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The Novavax COVID-19 Vaccine, Adjuvanted is a colorless-to-slightly yellow, clear-to-mildly opalescent suspension for intramuscular injection that is free from visible particles. Each 0.5 mL dose of the Novavax COVID-19 Vaccine, Adjuvanted contains 5 mcg of SARS-CoV-2 recombinant spike (rS) protein and 50 mcg Matrix-M adjuvant. The Matrix-M adjuvant is composed of Fraction-A (42.5 mcg) and Fraction-C (7.5 mcg) of saponin extracts from the soapbark tree, Quillaja saponaria Molina.
The rS protein is produced by recombinant DNA technology using a baculovirus expression system in an insect cell line that is derived from Sf9 cells of the Spodoptera frugiperda species.
Each dose of the Novavax COVID-19 Vaccine, Adjuvanted also contains the following ingredients: cholesterol, phosphatidylcholine, potassium dihydrogen phosphate (3.85 mcg), potassium chloride (2.25 mcg), disodium hydrogen phosphate dihydrate (14.7 mcg), disodium hydrogen phosphate heptahydrate (2.465 mg), sodium dihydrogen phosphate monohydrate (0.445 mg), sodium chloride (8.766 mg) and polysorbate 80 (0.050 mg), and Water for Injection. The pH is adjusted with sodium hydroxide or hydrochloric acid.
Each 0.5 mL dose of the Novavax COVID-19 Vaccine, Adjuvanted may also contain residual amounts of baculovirus and Sf9 cell proteins (≤ 0.96 mcg), baculovirus and cellular DNA (≤ 0.00016 mcg), lentil lectin (< 0.025 mcg), methyl-α-D-mannopyranoside (2 mcg), simethicone (<0.92 mcg), pluronic F-68 (< 2.19 mcg), Triton X-100 (< 0.025 mcg), and Tergitol (NP9) (< 0.05 mcg).
The Novavax COVID-19 Vaccine, Adjuvanted does not contain preservative.
The vial stoppers are not made with natural rubber latex.
The U.S. Food and Drug Administration (FDA) has issued an Emergency Use Authorization (EUA) for the emergency use of Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula) for active immunization to prevent coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in individuals 12 years of age and older.
Novavax COVID-19 Vaccine, Adjuvanted is not licensed for any use.
There is currently an outbreak of COVID-19 caused by SARS-CoV-2. The Secretary of the Department of Health and Human Services (HHS) has:
An EUA is an FDA authorization for the emergency use of an unapproved product or unapproved use of an approved product (i.e., drug, biological product, or device) in the United States under certain circumstances including, but not limited to, when the Secretary of HHS declares that the use of EUA authority is justified, based on a determination that there is a public health emergency, or a significant potential for a public health emergency, that affects or has a significant potential to affect, national security or the health and security of United States citizens living abroad, and that involves biological agent(s) or a disease or condition that may be attributable to such agent(s). Criteria for issuing an EUA include:
COMIRNATY (COVID-19 Vaccine, mRNA) and SPIKEVAX (COVID-19 Vaccine, mRNA) are FDA-approved vaccines to prevent COVID-19 caused by SARS-CoV-2. There may be clinical trials of other COVID-19 vaccines, including vaccines that contain or encode the spike protein of the Omicron variant XBB.1.5 of SARS-CoV-2.
For information on clinical studies of Novavax COVID-19 Vaccine, Adjuvanted and other vaccines for the prevention of COVID-19, see www.clinicaltrials.gov.
For intramuscular injection only.
Administer the Novavax COVID-19 Vaccine, Adjuvanted intramuscularly.
Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula) is administered intramuscularly as a single 0.5 mL dose at least 2 months after receipt of the last previous dose of COVID-19 vaccine.6
Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula) is administered intramuscularly as a series of two doses (0.5 mL each) 3 weeks apart.
For individuals with certain kinds of immunocompromise7, an additional dose of Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula) may be administered at least 2 months following the last dose of a COVID-19 vaccine (2023-2024 Formula).8 Additional doses of Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula) may be administered at the discretion of the healthcare provider, taking into consideration the individual’s clinical circumstances. The timing of the additional doses may be based on the individual’s clinical circumstances.
The Novavax COVID-19 Vaccine, Adjuvanted is a suspension for injection. A single dose is 0.5 mL.
The Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula) is supplied as:
Carton (NDC 80631-105-02) containing 2 multi-dose vials (NDC 80631-105-01). Each multi-dose vial contains 5 doses of 0.5 mL each.
Store the unpunctured multi-dose vaccine vial in a refrigerator between 2 to 8°C (36 to 46°F).
Do not freeze.
Protect from light.
After first puncture, hold the vial between 2 to 25°C (36 to 77°F) for up to 12 hours. Discard the vial 12 hours after the first puncture.
REFERENCES
4 See U.S. Department of Health and Human Services, Determination of a Public Health Emergency and Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3. February 4, 2020; https://www.federalregister.gov/documents/2020/02/07/2020-02496/determination-of-public-health-emergency. See also U.S. Department of Health and Human Services, Amended Determination of a Public Health Emergency or Significant Potential for a Public Health Emergency Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3(b). March 15, 2023 (“Amended Determination”); https://www.federalregister.gov/documents/2023/03/20/2023-05609/covid-19-emergency-use-authorization-declaration.
5 See U.S. Department of Health and Human Services, Declaration that Circumstances Exist Justifying Authorizations Pursuant to Section 564(b) of the Federal Food, Drug, and Cosmetic Act, 21 U.S.C. § 360bbb-3, 85 FR 18250 (April 1, 2020); https://www.federalregister.gov/documents/2020/04/01/2020-06905/emergency-use-authorization-declaration. See also Amended Determination (“The declarations issued pursuant to section 564(b)(1) of the FD&C Act that circumstances exist justifying the authorization of emergency use of certain in vitro diagnostics, personal respiratory protective devices, other medical devices and drugs and biological products, as set forth in those declarations, and that are based on the February 4, 2020 determination, remain in effect until those declarations are terminated in accordance with section 564 of the FD&C Act.”).
6 COVID-19 vaccine refers to the monovalent COVID-19 vaccines (original) and the bivalent COVID-19 vaccines (Original and Omicron BA.4/BA.5). Â
7 Certain kinds of immunocompromise refers to individuals who have undergone solid organ transplantation, or who are diagnosed with conditions that are considered to have an equivalent level of immunocompromise.
8 The last dose of a COVID-19 vaccine (2023-2024 Formula) refers to a dose with Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula), COMIRNATY (COVID-19 Vaccine, mRNA) (2023-2024 Formula), SPIKEVAX (COVID-19 Vaccine, mRNA) (2023-2024 Formula), Pfizer-BioNTech COVID-19 Vaccine (2023-2024 Formula), or Moderna COVID-19 Vaccine (2023-2024 Formula).
Manufactured for: Novavax, Inc., Gaithersburg, MD, 20878. Revised: Oct 2023
An overview of clinical studies contributing to the safety assessment of Novavax COVID-19 Vaccine, Adjuvanted in individuals 12 years of age and older is provided in Table 1. Participants in these clinical studies received a 2-dose initial series with a COVID-19 vaccine (referred to as a primary series) and some received one or more subsequent doses (referred to as a booster dose).
Table 1 : Clinical Studies
| Study | Age | Dosing Regimens | Vaccine Recipientsa |
| Study 1 (NCT04611802) | 18 years of age and older | Primary Series: 2 doses of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent)b 3 weeks apart | 26,106 |
| Booster Dose: Sinsle dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent)b | 12,777c,d | ||
| 12 years through 17 years of age | Primary Series: 2 doses of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent)b 3 weeks apart | 2,152 | |
| Booster Dose: Single dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent)b | 1,499c | ||
| Study 5 (NCT05372588) | 18 years through 64 years (Part 1) | Booster Dose: Single dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent)b | 274e |
| Booster Dose: Single dose of monovalent Vaccine (Omicron BA.1)f | 286e | ||
| Booster Dose: Single dose of Bivalent Vaccine (Original and Omicron BA.1)g | 269e | ||
| 18 years of age and older (Part 2) | Booster Dose: Single dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent)b | 251e | |
| Booster Dose: Single dose of monovalent Vaccine (Omicron BA.5)h | 254e | ||
| Booster Dose: Single dose of Bivalent Vaccine (Original and Omicron BA.5)i | 259e | ||
| COV-BOOST (ISRCTN737651 30) | 30 years of age and older | Booster Dose: Single dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent)b | 114j |
| Abbreviation: SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. a Receiving at least one dose of the intended dosing regimen. b Vaccine containing a recombinant spike protein of SARS-CoV-2 Wuhan-Hu 1 strain (Original). c Booster dose recipients are a subset of primary series. d Includes 39 participants who did not receive both primary series doses of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) prior to receiving a dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in the booster vaccination period. e Participants received at least 3 doses of an mRNA COVID-19 vaccine prior to inclusion in this study. fVaccine containing a recombinant spike protein of SARS-CoV-2 Omicron variant lineage BA.1 (Omicron BA.1), not authorized or approved in the U.S. gVaccine containing a recombinant spike protein of SARS-CoV-2 Wuhan-Hu 1 strain (Original) and Omicron variant lineage BA.1 (Omicron BA.1), not authorized or approved in the U.S. hVaccine containing a recombinant spike protein of SARS-CoV-2 Omicron variant lineage BA.5 (Omicron BA.5), not authorized or approved in the U.S. iVaccine containing a recombinant spike protein of SARS-CoV-2 Wuhan-Hu 1 strain (Original) and Omicron variant lineage BA.5 (Omicron BA.5), not authorized or approved in the U.S. j Restricted to participants previously vaccinated with Pfizer-BioNTech COVID-19 Vaccine. |
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The safety data accrued with the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) [no longer authorized for use in the U.S.] and from Novavax's adjuvanted monovalent COVID-19 vaccine (Omicron BA.1) [not authorized or approved in the U.S., hereafter referred to as monovalent vaccine (Omicron BA.1)], Novavax's adjuvanted monovalent COVID-19 vaccine (Omicron BA.5) [not authorized or approved in the U.S., hereafter referred to as monovalent vaccine (Omicron BA.5)], Novavax's adjuvanted bivalent vaccine (Original and Omicron BA.1) [not authorized or approved in the U.S, hereafter referred to as bivalent vaccine (Original and Omicron BA.1)] and Novavax's adjuvanted bivalent vaccine (Original and Omicron BA.5) [not authorized or approved in the U.S., hereafter referred to as bivalent vaccine (Original and Omicron BA.5)] are relevant to Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula) because these vaccines are manufactured using a similar process.
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a vaccine cannot be directly compared with rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.
Participants 18 Years Of Age And Older
Safety of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) was assessed in a clinical study conducted in the United States (US) and Mexico (NCT04611802; Study 1). In this study, 26,106 participants 18 years of age and older have received at least one dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent).
Adolescents 12 Through 17 Years Of Age
Safety of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in adolescents was assessed in the adolescent primary series expansion of Study 1 conducted in the US. In this study, 2,232 participants 12 through 17 years of age have received at least one dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) (n=1,487) or placebo (n=745).
In Study 1, an ongoing Phase 3, multicenter, randomized, observer-blinded, placebo-controlled study, participants 18 years of age and older have received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) (n=19,735) or placebo (n=9,847). Overall, 52.0% were male, 48.0% were female; 75.0% were White, 11.8% were Black or African American, 4.1% were Asian, 6.7% were American Indian (including Native Americans) or Alaskan Native, and 1.6% were multiple races; 21.9% were Hispanic/Latino. Demographic characteristics of participants were well balanced between the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and placebo groups. During the study, COVID-19 vaccines authorized for emergency use became available, and participants, when eligible for vaccination, were offered the opportunity to cross over from the originally assigned study treatment to the other study treatment (vaccine or placebo) in a blinded fashion (“blinded crossover”). In the post-crossover period, 6,416 participants received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent), and 15,298 participants received placebo. The demographic characteristics of participants in the pre- and post-crossover groups were comparable. Due to data quality issues at two study sites, a total of 289 additional participants were excluded from the safety analysis set.
Study 1 also included an adolescent primary series expansion. In the pre-crossover period, among adolescent participants who received at least one dose of vaccine (n=1487) or placebo (n=745), 52.5% were male, 47.5% were female; 74.4% were White, 13.9% were Black or African American, 3.4% were Asian, 2.1% were American Indian (including Native Americans) or Alaskan Native, and 5.3% were multiple races; 18.5% were Hispanic/Latino. Demographic characteristics were well balanced between the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and placebo groups. During the study, COVID-19 vaccines authorized for emergency use became available, and participants, when eligible for vaccination, were offered the opportunity to cross over from the originally assigned study treatment to the other study treatment (vaccine or placebo) in a blinded fashion (“blinded crossover”). In the post-crossover period, 665 participants received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent), and 1,353 participants received placebo. The demographic characteristics of participants in the pre- and post-crossover groups were comparable.
Study 1 was amended to include a booster dose in which 12,738 individuals 18 to 96 years of age received a booster dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) starting approximately 6 months after the two-dose primary series.
Solicited Adverse Reactions
During the pre-crossover period, local and systemic adverse reactions were solicited within 7 days following each dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) or placebo in participants using an electronic diary.
The reported frequency and severity of solicited local and systemic adverse reactions series are presented for participants 18 through 64 years of age in Table 2.
Table 2 Number and Percentage of Participants with Solicited Local and Systemic Adverse Reactions Starting within 7 Daysa After Each Dose in Participants 18 Years through 64 Years of Age (Solicited Safety Set,b Dose 1 and Dose 2)c
| Event | Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) | Placebod | ||
| Primary Series | Primary Series | |||
| Dose 1 N =15884 n (%) |
Dose 2 N =15148 n (%) |
Dose 1 N = 7868 n (%) |
Dose 2 N = 7361 n (%) |
|
| Local Adverse Reactions | ||||
| Pain/tenderness | ||||
| Any Grade | 9604 (60.5) | 12234 (80.8) | 1706 (21.7) | 1623 (22.0) |
| Grade 3e,f | 174 (1.1) | 951 (6.3) | 17 (0.2) | 20 (0.3) |
| Grade 4g | 0 | 5 (0.03) | 0 | 1 (0.01) |
| Redness (erythema) | ||||
| Any Grade | 151 (1.0) | 1040 (6.9) | 21 (0.3) | 26 (0.4) |
| Grade 3h | 3 (0.02) | 134 (0.9) | 0 | 2 (0.03) |
| Swelling | ||||
| Any Grade | 137 (0.9) | 943 (6.2) | 24 (0.3) | 22 (0.3) |
| Grade 3i | 7 (0.04) | 82 (0.5) | 3 (0.04) | 1 (0.01) |
| Systemic Adverse Reactions | ||||
| Fever | ||||
| Any Grade | 56 (0.4) | 941 (6.2) | 31 (0.4) | 16 (0.2) |
| Grade 3j | 7 (0.04) | 60 (0.4) | 7 (0.09) | 2 (0.03) |
| Grade 4k | 4 (0.03) | 2 (0.01) | 1 (0.01) | 0 |
| Headache | ||||
| Any Grade | 4158 (26.2) | 7128 (47.1) | 1866 (23.7) | 1492 (20.3) |
| Grade 3l | 132 (0.8) | 492 (3.2) | 58 (0.7) | 36 (0.5) |
| Grade 4m | 4 (0.03) | 5 (0.03) | 1 (0.01) | 2 (0.03) |
| Fatigue/malaise | ||||
| Any Grade | 4892 (30.8) | 8825 (58.3) | 2095 (26.6) | 1889 (25.7) |
| Grade 3n | 249 (1.6) | 1591 (10.5) | 113 (1.4) | 114 (1.5) |
| Grade 4m | 8 (0.05) | 7 (0.05) | 1 (0.01) | 3 (0.04) |
| Muscle pain (myalgia) | ||||
| Any Grade | 3827 (24.1) | 7682 (50.7) | 1073 (13.6) | 900 (12.2) |
| Grade 3n | 79 (0.5) | 805 (5.3) | 31 (0.4) | 28 (0.4) |
| Grade 4m | 2 (0.01) | 5 (0.03) | 1 (0.01) | 4 (0.05) |
| Joint pain (arthralgia) | ||||
| Any Grade | 1260 (7.9) | 3542 (23.4) | 522 (6.6) | 504 (6.8) |
| Grade 3n | 49 (0.3) | 393 (2.6) | 25 (0.3) | 22 (0.3) |
| Grade 4m | 1 (< 0.01) | 5 (0.03) | 0 | 2 (0.03) |
| Nausea or vomiting | ||||
| Any Grade | 1069 (6.7) | 1822 (12.0) | 466 (5.9) | 417 (5.7) |
| Grade 3o | 18 (0.1) | 26 (0.2) | 7 (0.09) | 7 (0.1) |
| Grade 4p | 4 (0.03) | 7 (0.05) | 2 (0.03) | 2 (0.03) |
| a 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (eDiary). b Solicited safety set includes participants who received at least one dose of study vaccine and completed their eDiary. c Absence of rows for Grade 4 adverse reactions indicates no events were reported. d Placebo was a saline solution. e Grade 3 pain: Defined as any use of narcotic pain reliever or prevents daily activity. f Grade 3 tenderness: Defined as significant discomfort at rest. g Grade 4 pain/ tenderness: Defined as Emergency Room (ER) visit or hospitalization. h Grade 3 redness (erythema): Defined as > 10 cm. i Grade 3 swelling: Defined as > 10 cm or prevents daily activity. j Grade 3 fever: Defined as 39.0 to 40°C (102.1 to 104°F). k Grade 4 fever: Defined as > 40°C (> 104°F). l Grade 3 headache: Defined as significant; any use of narcotic pain reliever or prevents daily activity. m Grade 4 headache, fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as ER visit or hospitalization. n Grade 3 fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as significant; prevents daily activity. o Grade 3 nausea or vomiting: Defined as prevents daily activity, requires outpatient IV hydration. p Grade 4 nausea or vomiting: Defined as ER visit or hospitalization for hypotensive shock. |
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The reported frequency and severity of solicited local and systemic adverse reactions are presented for participants 65 years of age and older in Table 3.
Table 3 : Number and Percentage of Participants with Solicited Local and Systemic Adverse Reactions Starting within 7 Daysa After Each Dose in Participants 65 Years of Age and Older (Solicited Safety Set,b Dose 1 and Dose 2)c
| Event | Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) | Placebod | ||
| Primary Series | Primary Series | |||
| Dose 1 N = 2251 n (%) |
Dose 2 N = 2048 n (%) |
Dose 1 N = 1114 n (%) |
Dose 2 N = 978 n (%) |
|
| Local Adverse Reactions | ||||
| Pain/tenderness | ||||
| Any Grade | 854 (37.9) | 1258 (61.4) | 175 (15.7) | 161 (16.5) |
| Grade 3e,f | 13 (0.6) | 43 (2.1) | 3 (0.3) | 1 (0.1) |
| Redness (erythema) | ||||
| Any Grade | 16 (0.7) | 99 (4.8) | 5 (0.4) | 4 (0.4) |
| Grade 3g | 0 | 7 (0.3) | 0 | 0 |
| Swelling | ||||
| Any Grade | 18 (0.8) | 111 (5.4) | 1 (0.09) | 4 (0.4) |
| Grade 3h | 1 (0.04) | 8 (0.4) | 0 | 1 (0.1) |
| Systemic Adverse Reactions | ||||
| Fever | ||||
| Any Grade | 8 (0.4) | 40 (2.0) | 3 (0.3) | 7 (0.7) |
| Grade 3i | 1 (0.04) | 2 (0.1) | 0 | 1 (0.1) |
| Headache | ||||
| Any Grade | 344 (15.3) | 502 (24.5) | 184 (16.5) | 144 (14.7) |
| Grade 3j | 12 (0.5) | 18 (0.9) | 4 (0.4) | 2 (0.2) |
| Grade 4k | 1 (0.04) | 1 (0.05) | 0 | 0 |
| Fatigue/malaise | ||||
| Any Grade | 444 (19.7) | 714 (34.9) | 202 (18.1) | 182 (18.6) |
| Grade 3l | 23 (1.0) | 68 (3.3) | 5 (0.4) | 13 (1.3) |
| Muscle pain (myalgia) | ||||
| Any Grade | 284 (12.6) | 561 (27.4) | 125 (11.2) | 102 (10.4) |
| Grade 3l | 3 (0.1) | 32 (1.6) | 4 (0.4) | 2 (0.2) |
| Joint pain (arthralgia) | ||||
| Any Grade | 139 (6.2) | 271 (13.2) | 71 (6.4) | 63 (6.4) |
| Grade 3l | 4 (0.2) | 16 (0.8) | 4 (0.4) | 2 (0.2) |
| Grade 4k | 0 | 1 (0.05) | 0 | 0 |
| Nausea/vomiting | ||||
| Any Grade | 81 (3.6) | 108 (5.3) | 32 (2.9) | 35 (3.6) |
| Grade 3m | 0 | 3 (0.1) | 0 | 0 |
| a 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (eDiary). b Solicited safety set includes participants who received at least one dose of study vaccine and completed their eDiary. c Absence of rows for Grade 4 adverse reactions indicates no events were reported. d Placebo was a saline solution. eGrade 3 pain: Defined as any use of narcotic pain reliever or prevents daily activity. fGrade 3 tenderness: Defined as significant discomfort at rest. gGrade 3 redness (erythema): Defined as > 10 cm. hGrade 3 swelling: Defined as > 10 cm or prevents daily activity. i Grade 3 fever: Defined as 39.0 to 40°C (102.1 to 104°F). j Grade 3 headache: Defined as significant; any use of narcotic pain reliever or prevents daily activity. kGrade 4 headache, joint pain (arthralgia): Defined as ER visit or hospitalization. l Grade 3 fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as significant; prevents daily activity. m Grade 3 nausea or vomiting: Defined as prevents daily activity, requires outpatient IV hydration. |
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In Study 1, participants were monitored for non-serious unsolicited adverse events from the first dose through 28 days after the second dose in both the pre- and post-crossover periods and for serious adverse events for the duration of study participation. Participants who only received the first dose in the pre- and post-crossover periods were monitored for non-serious unsolicited adverse events through 49 days after administration of vaccine or placebo and for serious adverse events for the duration of study participation. In the pre-crossover period 19,735 participants received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and 9,847 participants received placebo. In the post-crossover period, 6,416 participants received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and 15,298 received placebo. Of participants who received two doses of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in the pre-crossover period (n=19,111), 78% had a follow-up duration of at least 2 months (median = 2.5 months) after Dose 2. Of participants who received two doses of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in the post-crossover period (n=6,346), 99% had a follow-up duration of at least 2 months (median = 4.4 months) after the last dose.
From Dose 1 through 28 days following Dose 2 in the pre-crossover period, the overall frequency of non-serious unsolicited adverse events was similar in the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) group (11.6%) and the placebo group (11.2%). The most frequently reported unsolicited adverse reactions were chills (0.4% vaccine recipients vs. 0.1% placebo recipients), lymphadenopathy-related reactions (0.3% vaccine recipients vs. 0.1% placebo recipients), and injection site pruritus (0.1% vaccine recipients vs. 0.0% placebo recipients). Lymphadenopathy-related reactions included lymphadenopathy, lymphadenitis, lymph node pain, and axillary pain. All lymphadenopathy-related reactions occurred in participants 18 through 64 years of age.
In the pre-crossover period, serious adverse events were reported by 199 (1.0%) participants in the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) group and by 108 (1.1%) participants in the placebo group. In the post-crossover period, serious adverse events were reported by 88 (1.4%) participants who received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and by 178 (1.2%) participants who received placebo.
Within 7 days of any dose (including 26,151 Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) recipients and 25,145 placebo recipients in both the pre- and post-crossover periods), hypersensitivity reactions (including urticaria, hypersensitivity, angioedema, and swelling of the face, lips, ear, and/or eyelids) were reported by 26 participants after the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) (0.1%) and 8 participants after placebo (0.03%). Of these events, 1 reaction (generalized urticaria and facial angioedema with a duration of 2 days) was serious and occurred 2 days after Dose 1 of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent).
Within 28 days of any dose, the following numerical imbalances with more events in vaccine than placebo recipients (including 26,151 Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) recipients and 25,145 placebo recipients in both the pre- and post-crossover periods) were observed for the following serious and other adverse events of interest.
Events of uveitis (iritis, uveitis, iridocyclitis) were reported by 3 participants after Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) (0.01%) and 2 participants after placebo (0.01%). All events were non-serious. One participant had onset of uveitis after Dose 1 of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) which resolved and then recurred following Dose 2. The two placebo recipients with events appeared to have had a previous history of uveitis and one of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) recipients had a history of iritis. Currently available information on uveitis is insufficient to determine a causal relationship with the vaccine.
Solicited Adverse Reactions
During the pre-crossover period, local and systemic adverse reactions were solicited within 7 days following each dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) or placebo in participants using an electronic diary.
The reported frequency and severity of solicited local and systemic adverse reactions are presented for participants 12 through 17 years of age in Table 4.
Table 4 : Number and Percentage of Participants with Solicited Local and Systemic Adverse Reactions Starting within 7 Daysa After Each Dose in Participants 12 Years through 17 Years of Age (Solicited Safety Set,b Dose 1 and Dose 2)c
| Event | Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) | Placebod | ||
| Dose 1 N = 1448 n (%) |
Dose 2 N = 1394 n (%) |
Dose 1 N = 726 n (%) |
Dose 2 N = 686 n (%) |
|
| Local Adverse Reactions | ||||
| Pain/tenderness | ||||
| Any Grade | 945 (65.3) | 1045 (75.0) | 204 (28.1) | 141 (20.6) |
| Grade 3e,f | 22 (1.5) | 108 (7.7) | 4 (0.6) | 4 (0.6) |
| Redness (erythema) | ||||
| Any Grade | 15 (1.0) | 104 (7.5) | 5 (0.7) | 0 |
| Grade 3g | 0 | 10 (0.7) | 0 | 0 |
| Swelling | ||||
| Any Grade | 20 (1.4) | 111 (8.0) | 3 (0.4) | 1 (0.1) |
| Grade 3h | 0 | 8 (0.6) | 1 (0.1) | 0 |
| Systemic Adverse Reactions | ||||
| Fever | ||||
| Any Grade | 11 (0.8) | 235 (16.9) | 5 (0.7) | 1 (0.1) |
| Grade 3i | 1 (0.07) | 31 (2.2) | 0 | 0 |
| Grade 4j | 2 (0.1) | 0 | 0 | 0 |
| Headache | ||||
| Any Grade | 440 (30.4) | 793 (56.9) | 181 (24.9) | 119 (17.3) |
| Grade 3k | 13 (0.9) | 87 (6.2) | 12 (1.7) | 14 (2.0) |
| Grade 4l | 0 | 1 (0.07) | 0 | 0 |
| Fatigue/malaise | ||||
| Any Grade | 418 (28.9) | 807 (57.9) | 142 (19.6) | 113 (16.5) |
| Grade 3m | 33 (2.3) | 223 (16.0) | 13 (1.8) | 13 (1.9) |
| Muscle pain (myalgia) | ||||
| Any Grade | 492 (34.0) | 683 (49.0) | 114 (15.7) | 82 (12.0) |
| Grade 3m | 17 (1.2) | 104 (7.5) | 4 (0.6) | 6 (0.9) |
| Joint pain (arthralgia) | ||||
| Any Grade | 102 (7.0) | 226 (16.2) | 35 (4.8) | 21 (3.1) |
| Grade 3m | 6 (0.4) | 40 (2.9) | 1 (0.1) | 2 (0.3) |
| Nausea or vomiting | ||||
| Any Grade | 113 (7.8) | 277 (19.9) | 56 (7.7) | 33 (4.8) |
| Grade 3n | 2 (0.1) | 14 (1.0) | 3 (0.4) | 3 (0.4) |
| Grade 4o | 0 | 1 (0.07) | 0 | 0 |
| a 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (eDiary). b Solicited safety set includes participants who received at least one dose of study vaccine and completed their eDiary. c Absence of rows for Grade 4 adverse reactions indicates no events were reported. d Placebo was a saline solution. e Grade 3 pain: Defined as any use of narcotic pain reliever or prevents daily activity. f Grade 3 tenderness: Defined as significant discomfort at rest. g Grade 3 redness (erythema): Defined as > 10 cm. hGrade 3 swelling: Defined as > 10 cm or prevents daily activity. iGrade 3 fever: Defined as 39.0 to 40°C (102.1 to 104°F). j Grade 4 fever: Defined as > 40°C (> 104°F). kGrade 3 headache: Defined as significant; any use of narcotic pain reliever or prevents daily activity. l Grade 4 headache, fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as ER visit or hospitalization. m Grade 3 fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as significant; prevents daily activity. nGrade 3 nausea or vomiting: Defined as prevents daily activity, requires outpatient IV hydration. o Grade 4 nausea or vomiting: Defined as ER visit or hospitalization for hypotensive shock. |
||||
In Study 1, participants were monitored for non-serious unsolicited adverse events from the first dose through 28 days after the second dose in both the pre- and post-crossover periods and for serious adverse events for the duration of study participation. Participants who only received the first dose in the pre- and post-crossover periods were monitored for non-serious unsolicited adverse events through 49 days after administration of vaccine or placebo and for serious adverse events for the duration of study participation. In the pre-crossover period 1,487 participants received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and 745 participants received placebo. In the post-crossover period, 665 participants received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and 1,353 received placebo. Of participants who received two doses of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in the pre-crossover period (n=1,468), 86% had a follow-up duration of at least 2 months (median = 71 days) after Dose 2. Of participants who received two doses of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in the post-crossover period (n=638), 43% had a follow-up duration of at least 1 month (median = 30 days) after the last dose.
From Dose 1 through 28 days following Dose 2 in the pre-crossover period, the overall frequency of non-serious unsolicited adverse events was similar in the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) group (15.5%) and the placebo group (15.3%). The most frequently reported unsolicited adverse reactions were lymphadenopathy-related reactions (0.9% vaccine recipients vs. 0.0% placebo recipients), fatigue (0.5% vaccine recipients vs. 0.0% placebo recipients), decreased appetite (0.3% vaccine recipients vs. 0.0% placebo recipients), arthralgia (0.2% vaccine recipients vs. 0.0% placebo recipients), injection site pruritus (0.2% vaccine recipients vs. 0.0% placebo recipients), and myalgia (0.1% vaccine recipients vs. 0.0% placebo recipients). Lymphadenopathy-related reactions included lymphadenopathy, lymph node pain, and axillary pain.
In the pre-crossover period, serious adverse events were reported by 7 (0.5%) participants in the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) group and by 2 (0.3%) participants in the placebo group. In the post-crossover period, serious adverse events were reported by 3 (0.5%) participants who received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and by 2 (0.1%) participants who received placebo.
Within 28 days of any dose, one serious adverse event of interest of myocarditis was observed. The event was reported by a 16-year-old adolescent participant 2 days after Dose 2 of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent).
Study 2 was a randomized, placebo-controlled study that included a crossover design. Approximately 10,800 participants received at least one dose of a COVID-19 vaccine containing SARS-CoV-2 recombinant spike (rS) protein and Matrix-M adjuvant, manufactured by a different process than the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) evaluated in Study 1, and approximately 10,900 participants received at least one dose of placebo.
Serious events of myocarditis in a 19-year-old male and pericarditis in a 60-year-old female were reported within 10 days following administration of Dose 2 and Dose 1, respectively, of the vaccine. Both events were reported as resolved. No events of myocarditis or pericarditis were reported following administration of placebo.
A serious event of Guillain Barré syndrome was reported 9 days following administration of Dose 1 of the vaccine. No events of Guillain Barré syndrome were reported following administration of placebo.
In Studies 3 and 4, approximately 5,500 participants received at least one dose of a COVID-19 vaccine containing SARS-CoV-2 recombinant spike (rS) protein and Matrix-M adjuvant, manufactured by a different process than the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) evaluated in Study 1. No serious adverse events considered related to vaccination were reported in these studies. No events of myocarditis/pericarditis or Guillain Barré syndrome were reported in vaccine recipients in these studies.
Novavax COVID-19 Vaccine, Adjuvanted (Original Monovalent) Administered As A Booster Dose Following A Primary Series Of Novavax COVID-19 Vaccine, Adjuvanted (Original Monovalent) In Participants 18 Years Or Older
In an open label portion of Study 1, 12,738 participants 18 years of age and older (based on enrollment until March 26, 2022) received a single booster dose of Novavax COVID-19
Vaccine, Adjuvanted (Original monovalent) (0.5 mL) at least 6 months after the two-dose primary series (median of 11.0 months between completion of primary series and booster dose). Safety analyses included evaluation of solicited local and systemic adverse reactions within 7 days after a booster dose (n=238) and nonserious unsolicited adverse events within 28 days after a booster dose (n=298). Safety analysis also included evaluation of serious adverse events and adverse events of interest after a booster dose (n=12,738) with a median follow-up of 121 days post booster dose through data extraction of August 18, 2022. The safety follow-up is ongoing.
Among the 12,738 boosted participants, 84.3% were between 18 and 64 years of age and 15.7% were 65 years of age and older, 50.6% were male, 49.4% were female; 72.6% were White, 14.4% were Black or African American, 3.8% were Asian, 6.5% were American Indian (including Native Americans) or Alaskan Native, 0.2% were Native Hawaiian or Other Pacific Islander, and 1.7% were multiple races; 21.4% were Hispanic or Latino.
Local and systemic adverse reactions were solicited within 7 days following the third (booster) dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) using an electronic diary.
The reported frequency and severity of solicited local and systemic adverse reactions in participants 18 years of age and older are presented in Table 5.
Table 5 : Number and Percentage of Participants with Solicited Local and Systemic Adverse Reactions Starting within 7a Days After Booster Dose in Participants 18 Years of Age and Older (Booster Safety Analysis Set b) c
| Event | Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) N = 238 n (%) |
| Local Adverse Reactions | |
| Pain/tenderness | |
| Any Grade | 193 (81.1) |
| Grade 3d,e | 18 (7.6) |
| Redness (erythema) | |
| Any Grade | 15 (6.3) |
| Grade 3f | 1 (0.4) |
| Swelling | |
| Any Grade | 20 (8.4) |
| Grade 3g | 2 (0.8) |
| Systemic Adverse Reactions | |
| Fever | |
| Any Grade | 15 (6.3) |
| Grade 3h | 2 (0.8) |
| Headache | |
| Any Grade | 126 (52.9) |
| Grade 3i | 14 (5.9) |
| Fatigue/malaise | |
| Any Grade | 151 (63.4) |
| Grade 3j | 41 (17.2) |
| Grade 4k | 2 (0.8) |
| Muscle pain (myalgia) | |
| Any Grade | 150 (63.0) |
| Grade 3j | 20 (8.4) |
| Grade 4k | 2 (0.8) |
| Joint pain (arthralgia) | |
| Any Grade | 72 (30.3) |
| Grade 3j | 9 (3.8) |
| Nausea or vomiting | |
| Any Grade | 35 (14.7) |
| Grade 3l | 2 (0.8) |
| Grade 4m | 1 (0.4) |
| a 7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (eDiary). b The analysis included a total of 238 participants who received the booster dose who completed their eDiary cAbsence of rows for Grade 4 adverse reactions indicates no events were reported. d Grade 3 pain: Defined as any use of narcotic pain reliever or prevents daily activity. e Grade 3 tenderness: Defined as significant discomfort at rest. f Grade 3 redness (erythema): Defined as > 10 cm. g Grade 3 swelling: Defined as > 10 cm or prevents daily activity. h Grade 3 fever: Defined as 39.0 to 40°C (102.1 to 104°F). i Grade 3 headache: Defined as significant; any use of narcotic pain reliever or prevents daily activity. j Grade 3 fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as significant; prevents daily activity. k Grade 4 fatigue/malaise, muscle pain (myalgia): Defined as ER visit or hospitalization. l Grade 3 nausea or vomiting: Defined as prevents daily activity, requires outpatient IV hydration. m Grade 4 nausea or vomiting: Defined as ER visit or hospitalization for hypotensive shock. |
|
Participants were monitored through 28 days after the booster dose for unsolicited adverse events. Out of 12,738 total booster participants, data are available for 298 participants for non-serious unsolicited adverse events until May 19, 2022 (median follow-up post booster of 122 days). There were no unsolicited adverse events that occurred in more than one participant.
Additionally, data for serious adverse events and adverse events of interest, including but not limited to allergic, neurologic, inflammatory, vascular, and autoimmune disorders, are available for 12,738 participants until August 18, 2022 (median follow-up post booster of 121 days).
An event of myocarditis was reported by a 28-year-old male participant 3 days after a booster dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in Study 1. The event following the booster dose was adjudicated as a non-ST elevation myocardial infarction; however, clinical features were also consistent with myocarditis (chest pain and elevated troponin), and no cardiac catheterization or cardiac MRI was performed during the acute presentation.
A serious adverse event of autoimmune hepatitis was reported in a 57-year-old male participant approximately 12 days after a booster dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent). A year prior to vaccination, the participant had transient increases in alanine transferase (ALT), up to 3 times the upper limit of normal (ULN). From a normal baseline ALT prior to receipt of the first dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent), ALT increased to 4 times ULN following the second dose of the primary series. After the booster dose, a recurrent and higher ALT increase was observed (7 times ULN). Viral hepatitis tests were negative, and no alternative etiologies have been identified. The event has been ongoing for 8 months and is not resolved with azathioprine treatment. Currently available information for this event is insufficient to determine a causal relationship with the vaccine.
Two serious adverse events in the injected arm were reported, including muscle edema in a 51-year-old female with onset 7 days after booster vaccination and cellulitis of the injection site in a 58-year-old male with onset 3 days after booster vaccination. The cellulitis resolved following antibiotic and steroid treatment. The muscle edema was not responsive to non-steroidal anti-inflammatory agents and has been ongoing for 6 months and is not resolved. Available information for these events is insufficient to determine a causal relationship with the vaccine.
A serious adverse event of extensive left leg and pelvic deep vein thrombosis and pulmonary embolism was reported 7 and 10 days, respectively, post booster in a 35-year-old female participant receiving oral contraceptive therapy. She required surgical intervention, thrombolytic therapy, and needs prolonged anti-coagulation. Available information for these events is insufficient to determine a causal relationship with the vaccine.
Novavax COVID-19 Vaccine, Adjuvanted (Original Monovalent), Monovalent Vaccine (Omicron BA.1), Bivalent Vaccine (Original and Omicron BA.1) Administered as a Booster Dose Following Primary and Booster Vaccination with Another Authorized or Approved COVID-19 Vaccine in Individuals 18 through 64 Years of Age
The safety of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent), the monovalent vaccine (Omicron BA.1) and the bivalent vaccine (Original and Omicron BA.1) administered as a booster dose to individuals 18 through 64 years of age, previously vaccinated with three doses of an authorized or approved mRNA COVID-19 vaccine was assessed in a randomized, observer blind study (NCT05372588, Part 1 in Australia; Study 5).
The safety analysis set included 274 participants in the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) group, 286 participants in the monovalent vaccine (Omicron BA.1) group, and 269 participants in the bivalent vaccine (Original and Omicron BA.1) group. The median time since the last COVID-19 vaccination was 180.0 days. The median age of the population was 41 years (range 18-64); 727 (87.7%) participants were 18 through 54 years of age and 102 (12.3%) were 55 years and older. Overall, 46.1% were male, 53.9% were female, 2.4% were Hispanic or Latino, 80.6% were White, 0.2% were African American, 0.6% were Aboriginal Australian, 14.6% were Asian, 0.2% were Native Hawaiian or Pacific Islander, 2.7% were other races, and 1.1% were Multiracial. Demographic characteristics were similar across the three groups. Safety analysis included a median follow-up of 66 days post booster dose through data cutoff date of 01 September 2022. The safety follow-up is ongoing.
Local and systemic adverse reactions were solicited within 7 days following vaccination with Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent), the monovalent vaccine (Omicron BA.1), or the bivalent vaccine (Original and Omicron BA.1) using an electronic diary. The reported frequency and severity of solicited local and systemic adverse reactions are presented for participants 18 to 64 years of age in Table 6.
Table 6 : Number and Percentage of Participants with Solicited Local and Systemic Adverse Reactions Starting within 7a Days After Booster Dose in Participants 18 Years through 64 Years of Age Who Received Primary and Booster Vaccination with Another Authorized or Approved COVID-19 Vaccine (Safety Analysis Set)b
| Event | Monovalent Vaccine (Omicron BA.1) N = 283 |
Novavax COVID-19 Vaccine (Original monovalent) N = 272 |
Bivalent Vaccine (Original and Omicron BA.1) N = 268 |
| Local Adverse Reactions | |||
| Pain/tenderness | |||
| Any Grade | 196 (69.3) | 192 (70.6) | 173 (64.6) |
| Grade 3c,d | 5 (1.8) | 1 (0.4) | 2 (0.7) |
| Redness (erythema) | |||
| Any Grade | 7 (2.5) | 3 (1.1) | 3 (1.1) |
| Grade 3e | 0 | 0 | 1 (0.4) |
| Swelling | |||
| Any Grade | 7 (2.5) | 3 (1.1) | 4 (1.5) |
| Systemic Adverse Reactions | |||
| Fever | |||
| Any Grade | 5 (1.8) | 2 (0.7) | 1 (0.4) |
| Grade 3f | 1 (0.4) | 0 | 0 |
| Grade 4f | 1 (0.4) | 0 | 0 |
| Headache | |||
| Any Grade | 106 (37.5) | 95 (34.9) | 96 (35.8) |
| Grade 3g | 1 (0.4) | 3 (1.1) | 1 (0.4) |
| Fatigue/malaise | |||
| Any Grade | 127 (44.9) | 111 (40.8) | 121 (45.1) |
| Grade 3h | 15 (5.3) | 8 (2.9) | 7 (2.6) |
| Muscle pain (myalgia) | |||
| Any Grade | 71 (25.1) | 66 (24.3) | 64 (23.9) |
| Grade 3h | 5 (1.8) | 0 | 0 |
| Joint pain (arthralgia) | |||
| Any Grade | 27 (9.5) | 29 (10.7) | 16 (6.0) |
| Grade 3h | 2 (0.7) | 0 | 1 (0.4) |
| Nausea or vomiting | |||
| Any Grade | 21 (7.4) | 19 (7.0) | 23 (8.6) |
| Grade 3i | 0 | 1 (0.4) | 0 |
| a 7 days included day of vaccination and the subsequent 6 days. Events were collected in the electronic diary (eDiary). The analysis included a total of 823 participants who received the booster dose who completed their eDiary. b Absence of rows for Grade 3 or Grade 4 adverse reactions indicates no events were reported. c Grade 3 pain: Defined as any use of narcotic pain reliever or prevents daily activity. dGrade 3 tenderness: Defined as significant discomfort at rest. eGrade 3 redness (erythema): Defined as > 10 cm. fGrade 3 fever: Defined as 39.0 to 40°C (102.1 to 104°F). Grade 4 fever: Defined as >40°C (>104°F). gGrade 3 headache: Defined as significant; any use of narcotic pain reliever or prevents daily activity. hGrade 3 fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as significant; prevents daily activity. i Grade 3 nausea or vomiting: Defined as prevents daily activity or requires outpatient IV hydration. |
|||
Participants were monitored through 36 days after the booster dose for unsolicited adverse events. Additionally, data for serious adverse events and adverse events of interest, including but not limited to allergic, neurologic, inflammatory, vascular, and autoimmune disorders, are available for participants through the data extraction date of 01 September 2022.
Serious adverse events were reported by 3 participants (3/286, 1.0%) in the monovalent vaccine (Omicron BA.1) group, 2 participants (2/274, 0.7%) in the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) group, and 2 participants (2/269, 0.7%) in the bivalent vaccine (Original and Omicron BA.1) group. None of these serious adverse events were considered related to vaccination.
Novavax COVID-19 Vaccine, Adjuvanted (Original Monovalent), Monovalent Vaccine (Omicron BA.5), Bivalent Vaccine (Original and Omicron BA.5) Administered as a Booster Dose Following Primary and Booster Vaccination with Another Authorized or Approved COVID-19 Vaccine in Individuals 18 Years or Older
The safety of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent), the monovalent vaccine (Omicron BA.5), and the bivalent vaccine (Original and Omicron BA.5) administered as a booster dose to individuals 18 years of age and older previously vaccinated with three or more doses of an authorized or approved mRNA COVID-19 vaccine was assessed in a randomized, observer blind study (NCT05372588, Part 2 in Australia; Study 5).
The safety analysis set included 251 participants in the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) group, 254 participants in the monovalent vaccine (Omicron BA.5) group and 259 participants in the bivalent vaccine (Original and Omicron BA.5) group. The median time since the last COVID-19 vaccination was 352.5 days. The median age of the population was 43.0 years (range 18-83); 632 (82.7%) participants were 18 through 54 years of age and 132 (17.3%) were 55 years and older. Overall, 45.0% were male, 55.0% were female, 2.1% were Hispanic or Latino, 80.5% were White, 0.3% were African American, 2.0% were Aboriginal Australian, 12.3% were Asian, 0.7% were Native Hawaiian or Pacific Islander, 3.1% were other races, and 0.9% were Multiracial. Demographic characteristics were similar across the three groups. Safety analysis included a median follow-up of 70 days post booster dose through data extraction of 22 June 2023. The safety follow-up is ongoing.
Local and systemic adverse reactions were solicited within 7 days following vaccination with Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent), the monovalent vaccine (Omicron BA.5), or the bivalent vaccine (Original and Omicron BA.5) using an electronic diary. The reported frequency and severity of solicited local and systemic adverse reactions are presented for participants 18 years of age and older in Table 7.
Table 7 : Number and Percentage of Participants with Solicited Local and Systemic Adverse Reactions Starting within 7a Days After Booster Dose in Participants 18 Years of Age and Older Who Received Primary and Booster Vaccination with Another Authorized or Approved COVID-19 Vaccine (Safety Analysis Set)b
| Event | Monovalent Vaccine (Omicron BA.5) N = 252 |
Novavax COVID-19 Vaccine (Original monovalent) N = 251 |
Bivalent Vaccine (Original and Omicron BA.5) N = 259 |
| Local Adverse Reactions | |||
| Pain/tenderness | |||
| Any Grade | 153 (60.7) | 166 (66.1) | 169 (65.3) |
| Grade 3c,d | 4 (1.6) | 2 (0.8) | 2 (0.8) |
| Redness (erythema) | |||
| Any Grade | 5 (2.0) | 8 (3.2) | 6 (2.3) |
| Swelling | |||
| Any Grade | 8 (3.2) | 6 (2.4) | 6 (2.3) |
| Systemic Adverse Reactions | |||
| Fever | |||
| Any Grade | 2 (0.8) | 2 (0.8) | 4 (1.5) |
| Grade 3e | 0 | 0 | 1 (0.4) |
| Headache | |||
| Any Grade | 73 (29.0) | 73 (29.1) | 74 (28.6) |
| Grade 3f | 4 (1.6) | 2 (0.8) | 3 (1.2) |
| Fatigue/malaise | |||
| Any Grade | 106 (42.1) | 103 (41.0) | 97 (37.5) |
| Grade 3g | 3 (1.2) | 7 (2.8) | 8 (3.1) |
| Muscle pain (myalgia) | |||
| Any Grade | 59 (23.4) | 71 (28.3) | 67 (25.9) |
| Grade 3g | 1 (0.4) | 2 (0.8) | 2 (0.8) |
| Joint pain (arthralgia) | |||
| Any Grade | 18 (7.1) | 20 (8.0) | 19 (7.3) |
| Grade 3g | 0 | 1 (0.4) | 1 (0.4) |
| Nausea or vomiting | |||
| Any Grade | 19 (7.5) | 18 (7.2) | 19 (7.3) |
| Grade 3h | 1 (0.4) | 0 | 0 |
| a 7 days included day of vaccination and the subsequent 6 days. Events were collected in the electronic diary (eDiary). The analysis included a total of 762 participants who received the booster dose who completed their eDiary. b Absence of rows for Grade 3 or Grade 4 adverse reactions indicates no events were reported. cGrade 3 pain: Defined as any use of narcotic pain reliever or prevents daily activity. dGrade 3 tenderness: Defined as significant discomfort at rest. eGrade 3 fever: Defined as 39.0 to 40°C (102.1 to 104°F). fGrade 3 headache: Defined as significant; any use of narcotic pain reliever or prevents daily activity. gGrade 3 fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as significant; prevents daily activity. hGrade 3 nausea or vomiting: Defined as prevents daily activity or requires outpatient IV hydration. |
|||
Participants were monitored through 36 days after the booster dose for unsolicited adverse events. Additionally, data for serious adverse events and adverse events of interest, including but not limited to allergic, neurologic, inflammatory, vascular, and autoimmune disorders, were collected through the data extraction date of June 22, 2023 (median follow-up post booster of 70 days).
Serious adverse events were reported by 4 participants (4/254, 1.6%) in the monovalent vaccine (Omicron BA.5) group, 1 participant (1/251, 0.4%) in the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) group, and 2 participants (2/259, 0.8%) in the bivalent vaccine (Original and Omicron BA.5) group. Two participants reported serious adverse events of cranial nerve palsy, including a serious adverse event of fourth nerve cranial palsy with onset of symptoms 7 days post vaccination and a serious adverse event of sixth nerve palsy with onset of symptoms 14 days post vaccination. Both participants had predisposing risk factors, including diabetes, hypertension, hypercholesterolemia. Currently available information on cranial palsies is insufficient to determine a causal relationship with the vaccine. The remaining serious adverse events were not related to vaccination.
Additionally, the safety of a Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) booster dose in individuals who completed a primary vaccination with another authorized or approved COVID-19 vaccine (heterologous booster dose) is inferred from the report of an independent, multicenter, randomized, controlled, Phase 2, trial conducted in the United Kingdom (ISRCTN 73765130). This study was conducted in adults aged 30 years and older with no history of laboratory-confirmed SARS-CoV-2 infection. One study group (n=114 participants; median age 63 years) received Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) administered at least 84 days (median 105 days) after completion of the Pfizer-BioNTech COVID-19 Vaccine primary series. Reported adverse reactions through 28 days following a Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) booster dose did not identify any new safety concerns, as compared with adverse reactions reported following two doses of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) given as a primary series.
Novavax COVID-19 Vaccine, Adjuvanted (Original Monovalent), Administered as a Booster Dose Following a Primary Series of Novavax COVID-19 Vaccine, Adjuvanted (Original Monovalent) in Adolescents 12 Through 17 Years of Age
In an open label portion of Study 1, participants 12 years through 17 years of age (N=1,499) received a single booster dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) at least 5 months after the two-dose primary series (median of 10 months between completion of primary series and booster dose). Safety analyses included evaluation of solicited local and systemic adverse reactions within 7 days after a booster dose, nonserious unsolicited adverse events within 28 days after a booster dose, and serious adverse events for the duration of participation, with data available through a median follow-up of 6.6 months post booster dose through data extraction of November 12, 2022 (94.0% of participants had completed 6 months of safety follow-up).
Among the 1,499 participants, 53.8% were male, 46.2% were female; 73.1% were White, 14.6% were Black or African American, 3.5% were Asian, 2.7% were American Indian (including Native Americans) or Alaskan Native, 0.3% were Native Hawaiian or Other Pacific Islander, and 5.1% were multiple races; 18.4% were Hispanic or Latino.
Local and systemic adverse reactions were solicited within 7 days following the booster dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) using an electronic diary. The reported frequency and severity of solicited local and systemic adverse reactions for a randomly selected subset of 190 participants 12 through 17 years of age who completed their eDiary is presented in Table 8.
Table 8 : Number and Percentage of Participants with Solicited Local and Systemic Adverse Reactions Starting Within 7 Daysa After Booster Dose in Participants 12 Years through 17 Years of Age (Booster Safety Analysis Set b)c
| Event | Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) N = 190 n (%) |
| Local Adverse Reactions | |
| Pain/tenderness | |
| Any Grade | 153 (80.5) |
| Grade 3d,e | 20 (10.5) |
| Redness (erythema) | |
| Any Grade | 20 (10.5) |
| Grade 3f | 4 (2.1) |
| Swelling | |
| Any Grade | 19 (10.0) |
| Grade 3g | 2 (1.1) |
| Systemic Adverse Reactions | |
| Fever | |
| Any Grade | 44 (23.2) |
| Grade 3h | 12 (6.3) |
| Headache | |
| Any Grade | 130 (68.4) |
| Grade 3i | 25 (13.2) |
| Fatigue/malaise | |
| Any Grade | 132 (69.5) |
| Grade 3j | 55 (28.9) |
| Muscle pain (myalgia) | |
| Any Grade | 117 (61.6) |
| Grade 3j | 26 (13.7) |
| Joint pain (arthralgia) | |
| Any Grade | 43 (22.6) |
| Grade 3j | 9 (4.7) |
| Nausea or vomiting | |
| Any Grade | 50 (26.3) |
| Grade 3k | 5 (2.6) |
| a7 days included day of vaccination and the subsequent 6 days. Events and use of antipyretic or pain medication were collected in the electronic diary (eDiary). b The analysis included a total of 190 participants who received the booster dose who completed their eDiary c Absence of rows for Grade 4 adverse reactions indicates no events were reported. d Grade 3 pain: Defined as any use of narcotic pain reliever or prevents daily activity. e Grade 3 tenderness: Defined as significant discomfort at rest. f Grade 3 redness (erythema): Defined as > 10 cm. g Grade 3 swelling: Defined as > 10 cm or prevents daily activity. h Grade 3 fever: Defined as 39.0 to 40°C (102.1 to 104°F). i Grade 3 headache: Defined as significant; any use of narcotic pain reliever or prevents daily activity. j Grade 3 fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as significant; prevents daily activity. kGrade 3 nausea or vomiting: Defined as prevents daily activity or requires outpatient IV hydration. |
|
In Study 1, participants were monitored for non-serious unsolicited adverse events from the first dose through 28 days after the booster dose and for serious adverse events for the duration of study participation.
In a randomly selected subset of 220 participants 12 through 17 years of age, the overall frequency of non-serious unsolicited adverse events through 28 days following the booster dose was 5.0%, including 2 events of lymphadenopathy.
In this open label portion of Study 1, no related serious adverse events were reported in participants 12 years through 17 years of age (N=1,499) through a median safety follow-up of 6.6 months.
The following adverse reactions have been identified during post-authorization use of the Novavax COVID-19 Vaccine, Adjuvanted. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to vaccine exposure.
Cardiac Disorders: myocarditis, pericarditis
Immune System Disorders: anaphylaxis
Nervous System Disorders: paresthesia, hypoesthesia
Vaccination providers must report the listed events following administration of the Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula) to the Vaccine Adverse Event Reporting System (VAERS):
*Serious adverse events are defined as:
Vaccination providers should complete and submit a VAERS form to FDA using one of the following methods:
IMPORTANT: When reporting adverse events or vaccine administration errors to VAERS, please complete the entire form with detailed information. It is important that the information reported to the FDA be as detailed and as complete as possible. Information to include:
The following steps are highlighted to provide the necessary information for safety tracking:
Vaccination providers may report to VAERS other adverse events that are not required to be reported using the contact information above.
To the extent feasible, report adverse events to Novavax, Inc. using the contact information below or by providing a copy of the VAERS form to Novavax, Inc.
| Website | Fax number | Telephone number |
| www.NovavaxMedInfo.com | 1-888-988-8809 | 1-844-NOVAVAX (1-844-668-2829) |
There is no information on concomitant administration of the Novavax COVID-19 Vaccine, Adjuvanted with other vaccines.
Included as part of the PRECAUTIONS section.
Appropriate medical treatment to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of the Novavax COVID-19 Vaccine, Adjuvanted.
Monitor Novavax COVID-19 Vaccine, Adjuvanted recipients for the occurrence of immediate adverse reactions according to the Centers for Disease Control and Prevention guidelines (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/managing-anaphylaxis.html).
Clinical trials data provide evidence for increased risks of myocarditis and pericarditis following administration of Novavax COVID-19 Vaccine, Adjuvanted [see Clinical Trials Experience].
The CDC has published considerations related to myocarditis and pericarditis after vaccination, including for vaccination of individuals with a history of myocarditis or pericarditis (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/interim-considerations-us.html#myocarditis-pericarditis).
Syncope (fainting) may occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting.
Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the Novavax COVID-19 Vaccine, Adjuvanted.
The Novavax COVID-19 Vaccine, Adjuvanted may not protect all vaccine recipients.
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to the Novavax COVID-19 Vaccine, Adjuvanted during pregnancy. Women who are vaccinated with the Novavax COVID-19 Vaccine, Adjuvanted during pregnancy are encouraged to enroll in the registry by visiting https://c-viper.pregistry.com/.
All pregnancies have a risk of birth defect, loss, or other adverse outcomes. In the US general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Available data on the Novavax COVID-19 Vaccine, Adjuvanted administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.
A developmental toxicity study was performed in female rats administered a vaccine formulation containing the same quantity of SARS-CoV-2 recombinant spike (rS) protein and one-fifth the quantity of adjuvant and formulation buffer inactive ingredients included in Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) on four occasions, twice prior to mating and twice during gestation. This study revealed no evidence of harm to the fetus due to the vaccine. (see Animal Data)
Disease-Associated Maternal And/Or Embryo/Fetal Risk
Pregnant individuals infected with SARS-CoV-2 are at increased risk of severe COVID-19 compared with non-pregnant individuals.
Animal Data
In a developmental toxicity study, 0.1 mL of a vaccine formulation containing the same quantity of SARS-CoV-2 rS protein (5 mcg), one-fifth the quantity of adjuvant (10 mcg), and inactive ingredients which comprise the formulation buffer (25 mM sodium phosphate, 300 mM sodium chloride, and 0.01% (w/v) polysorbate 80) contained in a single dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) was administered to female rats by the intramuscular route on four occasions: 27 and 13 days prior to mating, and on gestational days 7 and 15. No vaccine-related adverse effects on female fertility, fetal development, or postnatal development were reported in the study.
It is not known whether Novavax COVID-19 Vaccine, Adjuvanted is excreted in human milk. Data are not available to assess the effects of the Novavax COVID-19 Vaccine, Adjuvanted on the breastfed infant or on milk production/excretion. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Novavax COVID-19 Vaccine, Adjuvanted and any potential adverse effects on the breastfed child from Novavax COVID-19 Vaccine, Adjuvanted from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.
Novavax COVID-19 Vaccine, Adjuvanted is authorized for use in individuals 12 through 17 years of age.
Novavax COVID-19 Vaccine, Adjuvanted is not authorized for use in individuals younger than 12 years of age.
Clinical studies that evaluated primary vaccination with the Novavax COVID-19 Vaccine, Adjuvanted included participants 65 years of age and older receiving vaccine or placebo, and their data contribute to the overall assessment of safety and efficacy. In an ongoing Phase 3 clinical study (Study 1), 12.6% (n=2,480 Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent), n=1,235 placebo) of participants were 65 years of age and older and 1.8% (n=361 Novavax COVID-19 Vaccine, Adjuvanted ([Original monovalent)], n=179 placebo) of participants were 75 years of age and older. Vaccine efficacy in participants 65 years of age and older was 78.6% (95% CI: -16.6%, 96.1%) relative to 90.7% (95% CI: 72.9%, 96.8%) in participants 50 through 64 years of age. [see Clinical Trial Results and Supporting Data for EUA]. Overall, there were no notable differences in the safety profiles observed between participants 65 years of age and older and younger participants. [see ADVERSE REACTIONS]
In a clinical study (Study 1) that evaluated a booster dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent), 15.7% (n=2006) of participants were 65 years of age and older and 2.6% (n=326) of participants were 75 years of age and older. Overall, there were no notable differences in the safety profiles observed between participants 65 years of age and older and younger participants. [see ADVERSE REACTIONS]
No Information provided
Do not administer the Novavax COVID-19 Vaccine, Adjuvanted to individuals with a known history of severe allergic reaction (e.g., anaphylaxis) to any component of the Novavax COVID-19 Vaccine, Adjuvanted or to individuals who had a severe allergic reaction (e.g., anaphylaxis) following a previous dose of a Novavax COVID-19 Vaccine, Adjuvanted. [see DESCRIPTION].
The Novavax COVID-19 Vaccine, Adjuvanted contains purified, full-length rS protein. The vaccine elicits an immune response to the rS protein, which protects against COVID-19.
The effectiveness of Novavax COVID-19 Vaccine, Adjuvanted (2023-2024 Formula) is based on effectiveness of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and the immunogenicity of the monovalent vaccine (Omicron BA.1) and monovalent vaccine (Omicron BA.5).
Study 1 is an ongoing Phase 3, multicenter, randomized, observer-blinded, placebo-controlled study in participants 18 years of age and older in United States and Mexico.
Upon enrollment, participants were stratified by age (18 through 64 years or 65 years of age and older). The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; had active cancer on chemotherapy; received chronic immunosuppressive therapy or received immunoglobulin or blood-derived products within 90 days; were pregnant or breastfeeding; or had a history of laboratory-confirmed diagnosed COVID-19. Participants with clinically stable underlying comorbidities were included as were participants with well-controlled human immunodeficiency virus (HIV) infection.
A total of 29,945 participants were randomized in a 2:1 ratio to receive two doses of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) or placebo 3 weeks apart. Assessments of safety and efficacy against COVID-19 are planned for up to 24 months after the second dose.
The primary efficacy analysis population (Per Protocol Efficacy [PP-EFF] Analysis Set) included 25,657 participants who received either the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) (n=17,272) or placebo (n=8,385), received two doses (Dose 1 on day 0; Dose 2 on day 21 median 21 days, range 14-60), did not experience an exclusionary protocol deviation, and did not have evidence of SARS-CoV-2 infection through 6 days after the second dose. In the PP-EFF Analysis Set, 48.5% were female; 21.5% were Hispanic or Latino; 75.9% were White, 11.0% were Black or African American, 6.2% were American Indian or Alaska Native, 4.4% were Asian, and 1.7% were multiracial. The median age of participants was 47 years (range 18-95 years) and 11.7% were 65 years of age and older. Of the study participants in the PP-EFF Analysis Set, 95.2% were at high risk for COVID-19 due to living or working conditions involving known frequent exposure to SARS-CoV-2, comorbidities (chronic lung disease, cardiovascular disease, chronic liver disease, severe obesity, and diabetes), or age ≥ 65 years. Between participants who received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and those who received placebo, there were no notable differences in demographics or pre-existing medical conditions. Participants in the PP-EFF Analysis Set were included in the primary efficacy analysis up until the time that they received their crossover vaccination. As of the September 27, 2021, data cutoff date, the PP-EFF Analysis Set had a median follow-up of 2.5 months post-Dose 2 during the pre-crossover period.
Vaccine efficacy in participants without evidence of SARS-CoV-2 infection through 6 days after the second dose is presented in Table 9. Based on data accrued through September 27, 2021, the efficacy of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) to prevent polymerase chain reaction (PCR)-confirmed symptomatic mild, moderate or severe COVID-19 from 7 days after Dose 2 was 90.4% (95% CI: 83.8%, 94.3%). In the PP-EFF Analysis Set, no cases of moderate or severe COVID-19 were reported in participants who had received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent), compared with nine cases of moderate COVID-19 and four cases of severe COVID-19 reported in participants who had received placebo.
Table 9 : Vaccine Efficacy Against PCR-confirmed COVID-19 with Onset from 7 Days After Second Vaccination1 (PP-EFF Analysis Set)
| Subgroup | Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) | Placebo | Vaccine Efficacy (95% CI) (%) | ||||
| Partici- pants N | COVID-19 Cases n (%) | Mean Incidence Rate Per 1,000 Person-Years2 | Partici- pants N | COVID-19 Cases n (%) | Mean Incidence Rate Per 1,000 Person-Years2 | ||
| Primary efficacy endpoint | |||||||
| All participants | 17,272 | 17 (0.1) | 5.59 | 8,385 | 79 (0.9) | 58.30 | 90.4 (83.8, 94.3) 3,4 |
| Mild | - | 17 (0.1) | - | - | 66 (0.8) | - | - |
| Moderate | - | 0 | - | - | 9 (0.1) | - | - |
| Severe | - | 0 | - | - | 4 (< 0.1) | - | - |
| 1 Vaccine efficacy (VE) evaluated in participants without major protocol deviations who are seronegative (for SARS-CoV-2) at baseline and do not have a laboratory confirmed current SARS-CoV-2 infection with symptom onset through 6 days after the second dose, and who have received two doses of vaccine or placebo as randomized. 2 Mean incidence rate per 1,000 person-years was estimated with weighting for age strata reflective of the distribution seen in the study population. 3 Based on log-linear model of PCR-confirmed COVID-19 infection incidence rate using Poisson regression with treatment group and age strata as fixed effects and robust error variance, where VE = 100 × (1 – ratio of incidence rate) (Zou 2004). 4 Met primary efficacy endpoint criterion for success with a lower bound confidence interval (LBCI) > 30% at the planned primary confirmatory analysis. |
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Descriptive analyses of efficacy showed efficacy point estimates similar to the estimate for the overall study population across genders and racial groups, and across participants with or without medical comorbidities associated with high risk of severe COVID-19. Vaccine efficacy in participants of Hispanic/Latino ethnicity was 77.0% (95% CI: 48.7%, 89.7%) relative to 94.2% (95% CI: 87.9%, 97.2%) in participants who were not Hispanic/Latino. Vaccine efficacy in participants 65 years of age and older was 78.6% (95% CI: -16.6%, 96.1%) relative to 90.7% (95% CI: 72.9%, 96.8%) in participants 50 through 64 years of age.
Effectiveness in adolescents 12 years through 17 years of age is based on a comparison of immune responses in this age group to adults 18 years through 25 years of age.
Study 1 is an ongoing Phase 3 multicenter, randomized, observer-blinded, placebo-controlled study that included 2,247 participants 12 through 17 years of age in the United States. Participants were randomized in a 2:1 ratio to receive two doses of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) or placebo 3 weeks apart. The study excluded participants who were significantly immunocompromised due to immunodeficiency disease; had active cancer on chemotherapy; had received chronic immunosuppressive therapy or had received immunoglobulin or blood-derived products within 90 days; were pregnant or breastfeeding; or had a history of laboratory-confirmed diagnosed COVID-19. Participants with clinically stable underlying comorbidities and participants with well-controlled HIV infection were included.
In Study 1, an analysis was conducted of SARS-CoV-2 neutralizing antibody titers 14 days after Dose 2 in a subset of adolescents 12 through 17 years of age and participants 18 through 25 years of age from the adult main study. Noninferior immune responses as assessed by geometric mean titers and seroconversion rates were demonstrated in a comparison of adolescents 12 through 17 years of age to participants 18 through 25 years of age (Table 10).
Table 10 : SARS-CoV-2 Neutralizing Antibody Geometric Mean Titer Ratio and Seroconversion Rate – Comparison of Adolescents 12 Years Through 17 Years of Age to Participants 18 Years through 25 Years of Age – Per-Protocol Immunogenicity Analysis Set
| Assay | Time Point | 12 Years Through 17 Years | 18 Years Through 25 Years | 12 Years Through 17 Years/ 18 Years Through 25 Years | |
| GMTa (95% CI) n=390 |
GMTa (95% CI) n=415 |
GMRb (95% CI) | Met Non inferiority Criteriac | ||
| SARS-CoV-2 wild-type microneutralization assay (1/dilution)d | 14 days after Dose 2 | 3859.6 (3422.8, 4352.1) | 2611.8 (2367.4, 2881.5) | 1.47 (1.26, 1.72)3 | Yes |
| SCR%e(95% CI) | SCR%e (95% CI) |
Difference in SCR%f | |||
| n=385 | n=414 | (95% CI) | |||
| 98.7 (97.0, 99.6) | 99.8 (98.7, 100.0) | -1.04 (-2.75, 0.20) | |||
| CI = Confidence interval; GMR = Geometric mean ratio; GMT = Geometric mean titer; SCR = Seroconversion rate a The 95% CI for GMT is calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. b GMR is defined as the ratio of two geometric mean titers for comparison of two age cohorts. An analysis of covariance (ANCOVA) with age cohort as main effect and baseline microneutralization assay neutralizing antibodies as covariate was performed to estimate the GMR. c Noninferiority was achieved if the following 3 pre-specified criteria were met simultaneously: 1) Lower bound of two-sided 95% CI for the ratio of GMTs (GMT12-17yo/GMT18-25yo) > 0.67; 2) Point estimate of the ratio of GMTs ≥ 0.82; and 3) Lower bound of the two-sided 95% CI for difference of SCRs (SCR12-17yo - SCR18-25yo) was > -10%. d Validated virus neutralizing assay (VNA) with wild-type virus (SARS-CoV-2 hCoV-19/Australia/VIC01/2020 [GenBank MT007544.1]; 360biolabs, Melbourne, Australia). The lower limit for quantification for this assay was a titer of 20, with titers below this level documented as 10. e SCR is defined as percentage of participants with a ≥ 4-fold difference in titers between Day 35 and Day 0. The 95% CI for SCR was calculated using the Clopper-Pearson exact method. f Difference in SCR in the adolescent primary series expansion (Study 1) for 12 years through 17 years of Study 1 minus SCR in Adult Main Study (Study 1) for 18 years through 25 years. The 95% CI for the difference of SCR between groups was calculated with the method of Miettinen and Nurminen. |
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A descriptive efficacy analysis evaluating PCR-confirmed symptomatic mild, moderate or severe COVID-19 cases was performed in 1,799 participants who were included in the per-protocol efficacy (PP-EFF) Analysis Set, which required receipt of two doses (Dose 1 on day 0; Dose 2 on day 21), no exclusionary protocol deviation(s), and no evidence of SARS-CoV-2 infection through 6 days after the second dose. In the PP-EFF Analysis Set, 47.2% were female; 15.8% were Hispanic or Latino; 76.1% were White, 12.9% were Black or African American, 1.1% were American Indian or Alaska Native, 3.6% were Asian, and 5.6% were multiracial. The median age of participants was 14 years (range 12-17 years). Of the study participants in the PP-EFF Analysis Set, 25.3% were obese. Between participants who received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and those who received placebo, there were no notable differences in demographics. The median interval between doses of study vaccine was 22 days (range 14-43). As of the August 9, 2021, data cutoff date, the PP-EFF Analysis Set had a median follow-up of 67 days post-Dose 2 during the pre-crossover period.
Vaccine efficacy in participants without evidence of SARS-CoV-2 infection through 6 days after the second dose is presented in Table 11. Based on data accrued through August 9, 2021, the efficacy of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) to prevent PCR-confirmed symptomatic mild, moderate or severe COVID-19 from 7 days after Dose 2 was 78.29% (95% CI: 37.55%, 92.45%). No cases of moderate or severe COVID-19 were reported in participants who had received the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) or placebo.
Table 11 : Vaccine Efficacy Against PCR-confirmed COVID-19 with Onset from 7 Days After Second Vaccination1 (PP-EFF Analysis Set)
| Subgroup | Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) | Placebo | Vaccine Efficacy (95% CI) (%) | ||||
| Partici- pants N | COVID-19 Cases3 n (%) | Mean Incidence Rate Per 100 Person-Years | Partici- pants N | COVID-19 Cases3 n (%) | Mean Incidence Rate Per 100 Person-Years | ||
| Primary efficacy endpoint | |||||||
| All participants | 1205 | 5 (0.4) | 2.69 | 594 | 11 (1.9) | 12.38 | 78.29 (37.55, 92.45) 2 |
| Mild | - | 5 (0.4) | - | - | 11 (1.9) | - | - |
| Moderate | - | 0 | - | - | 0 | - | - |
| Severe | - | 0 | - | - | 0 | - | - |
| 1 Vaccine efficacy (VE) evaluated in participants without major protocol deviations who were seronegative (for SARS-CoV-2) at baseline and did not have a laboratory confirmed current SARS-CoV-2 infection with symptom onset through 6 days after the second dose, and who had received two doses of vaccine or placebo as randomized. 2 Based on Modified Poisson regression with logarithmic link function and treatment group as fixed effect and robust error variance (Zou 2004). 3 All cases for which sequence data are available (vaccine n=2; placebo n=7) were due to the Delta variant. |
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Effectiveness of a booster dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) was based on assessment of neutralizing antibody titers (MN50) against the original SARS-CoV-2 strain (SARS-CoV-2 hCoV-19/Australia/VIC01/2020). Immunogenicity analyses compared the MN50 titers following the booster dose to the MN50 titers following the primary series.
In the open-label booster phase of Study 1, participants 18 years of age and older received a single booster dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) at least 6 months after completion of the primary series. A subset of 243 participants were included in the per-protocol immunogenicity (PP-IMM) analysis set, did not have serologic or virologic evidence (if available) of SARS-CoV-2 infection up to 28 days post booster dose. Among participants assessed for immunogenicity, 87.2% were 18-64 years of age, 12.8 % were 65 years of age and older, 51.0% were males, 49.0% were female; 15.6% were Hispanic or Latino; 81.5% were White, 11.1% were Black or African American, 0.4% were American Indian or Alaska Native, 4.9% were Asian, and 1.6% were multiracial. The median age of participants was 52 years (range 19-79 years).
Prespecified immunogenicity non-inferiority analyses included an assessment of MN50 geometric mean titer (GMT) ratio and difference in seroconversion rates. Seroconversion for a participant was defined as achieving a 4-fold rise in MN50 from baseline (before the booster dose and before the first dose of the primary series).
The analysis of the GMT ratio of MN50 following the booster dose compared with the primary series met the non-inferiority criteria for a booster response (lower limit of the 95% CI > 0.67 and point estimate > 0.83).
The lower limit of the two-sided 95% CI for the difference in seroconversion rates (percentage) was -14.4%, which did not meet the non-inferiority criteria for a booster response (lower limit of 95% CI for the percentage difference of ≥ -10%). These analyses are summarized in Table 12 and Table 13.
Table 12 : Neutralizing Antibody Geometric Titers (MN50) Against the Original SARS-CoV-2 Virus Strain (SARS CoV-2 hCoV-19/Australia/VIC01/2020) at 28 Days after a Booster Dose Versus 14 Days After Completion of the Primary Series, Participants 18 Years of Age and Older, PP-IMM Analysis Set1
| Booster Dose (N = 239)2 GMT (95% CI)3 |
Primary Series (N = 239) GMT (95% CI) 3 |
GMT Ratio (Booster/Primary Series) (95% CI)1 | Met Success Criteria |
| 5075.6 (4448.3, 5791.4) | 1505.7 (1244.1, 1822.3) | 3.4 (2.8, 4.0) | Lower limit of 95% CI > 0.67 and point estimate > 0.83 criteria: Yes |
| Abbreviations: CI = confidence interval; GMT = geometric mean titer; MN50 = microneutralization assay with an inhibitory concentration of 50%; PP-IMM = Per-Protocol Immunogenicity. 1 PP-IMM Analysis Set included participants who received two doses (0.5 mL 3 weeks apart) of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in the initial vaccination period or in the blinded crossover vaccination period, had an immunogenicity blood sample collected at Day 35, did not have serologic or virologic evidence (if available) of SARS-CoV-2 infection up to 28 days post booster dose, did not receive an emergency use authorized COVID-19 vaccine, received the booster dose, and remained blinded on study and without major protocol deviations until 7 days post-crossover Dose. 2 The analysis included a total of 239 participants of the PP-IMM analysis set who had immunogenicity data available for both the booster and primary series. 3 The 95% CI for GMT and GMT ratio were calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. Note: The median duration between the time of the second dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and the time of the booster dose was 10 months. |
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Table 13 : Seroconversion Rates (%) Against the Original SARS-CoV-2 Strain (SARS-CoV-2 hCoV-19/Australia/VIC01/2020) at 28 Days after a Booster Dose Versus 14 Days After Completion of the Primary Series, Participants 18 Years of Age and Older, PP-IMM Analysis Set1
| Booster Dose (N = 239)2 SCR % (n) (95% CI)3 |
Primary Series (N = 239) SCR %(n) (95% CI)3 |
Difference in SCR4 (Booster-Primary Series) (95% CI)5 | Met Success Criteria6 |
| 85.4 (204) (80.2, 89.6) |
94.6 (226) (90.9, 97.1) |
-9.2% (-14.4%, -4.5 %) | Lower limit of 95% CI > -10% criterion: No |
| Abbreviations: CI = confidence interval; PP-IMM = Per-Protocol Immunogenicity; SCR = seroconversion rate. 1 PP-IMM Analysis Set included participants who received two doses (0.5 mL 3 weeks apart) of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in the initial vaccination period or in the blinded crossover vaccination period, had an immunogenicity blood sample collected at Day 35, did not have serologic or virologic evidence (if available) of SARS-CoV-2 infection up to 28 days post booster dose, did not receive an emergency use authorized COVID-19 vaccine, received the booster dose, and remained blinded on study and without major protocol deviations until 7 days post-crossover Dose 2. 2 The analysis included a total of 239 participants of the PP-IMM analysis set who had immunogenicity data (microneutralization) available for both the booster and primary series 3 95% CI is based on the Clopper-Pearson method. 4 Based on the Tango method. 5 Comparison between SCR of 28 days post-booster relative to time of booster and SCR of 14 days after second dose of the primary series relative to time of first dose. 6 Non-inferiority of the single booster dose was achieved if the lower limit of the 95% CI for the difference of the proportion of participants with SCR at 28 days after a single booster dose relative to the time of booster vaccination versus at 14 days after the second dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) relative to the time of first vaccination was > -10%. Note: SCR was defined as the proportion of participants with post-vaccination levels ≥ 4-fold higher than the baseline levels. Note: The median duration between the time of the second dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and the time of the booster dose was 10 months. |
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An additional descriptive analysis evaluated seroconversion rates using baseline neutralizing antibody titers prior to Dose 1 of the primary series. As shown in Table 14, the booster dose seroconversion rate, with seroconversion defined as at least a 4-fold rise relative to the time of first dose, was 98.3%. The difference in seroconversion rates in this post-hoc analysis was 3.8% (95% CI: 2.0%, 7.0%).
Table 14 : Seroconversion Rates (%) Against the Original SARS-CoV-2 Strain (SARS CoV-2 hCoV-19/Australia/VIC01/2020) at 28 Days after a Booster Dose Versus 14 Days After Completion of the Primary Series, Participants 18 Years of Age and Older, PP-IMM Analysis Set1
| Booster Dose (N = 239)2 SCR n % (n) (95% CI)3 |
Primary Series (N = 239) SCR n % (n) (95% CI)3 |
Difference in SCR4 (Booster-Primary Series) (95% CI)5 |
| 98.3 (235) | 94.6 (226) | 3.8% |
| (95.8, 99.5) | (90.9, 97.1) | (2.0%, 7.0%) |
| Abbreviations: CI = confidence interval; PP-IMM = Per-Protocol Immunogenicity; SCR = seroconversion rate. 1 PP-IMM Analysis Set included all participants who received two doses (0.5 mL 3 weeks apart) of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in the initial vaccination period or in the blinded crossover vaccination period, had an immunogenicity blood sample collected at Day 35, did not have serologic or virologic evidence (if available) of SARS-CoV-2 infection up to 28 days post booster dose, did not receive an emergency use authorized COVID-19 vaccine, received the booster dose, and remained blinded on study and without major protocol deviations until 7 days post-crossover Dose 2. 2 The analysis included a total of 239 participants of the PP-IMM analysis set who had immunogenicity data (microneutralization) available for both the booster and primary series. 3 95% CI is based on the Clopper-Pearson method. 4 Based on the Tango method. 5 Comparison between SCR of 28 days post-booster relative to time of first dose and SCR of 14 days after second dose of the primary series relative to time of first dose. Note: SCR was defined as the proportion of participants with post-vaccination levels ≥ 4-fold higher than at the time of the first dose. Note: The median duration between the time of the second dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and the time of the booster dose was 10 months. |
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Effectiveness of a booster dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) was based on assessment of neutralizing antibody titers (MN50) against the original SARS-CoV-2 strain (SARSCoV-2 hCoV-19/Australia/VIC01/2020). Immunogenicity analyses compared the MN50 titers following the booster dose to the MN50 titers following the primary series in participants who had data at both time points.
In the open-label booster phase of Study 1, participants 12 through 17 years of age received a single booster dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) at least 5 months after completion of the primary series. A subset of 58 participants were included in the per-protocol immunogenicity (PP-IMM) analysis set, had immunogenicity blood samples collected at 14 days after the second dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and at 28 days after the booster dose, and did not have serologic or virologic evidence of SARS-CoV-2 infection on or before the booster dose. Among participants assessed for immunogenicity, 51.7% were males, 48.3% were female; 17.2% were Hispanic or Latino; 91.4% were White, 1.7% were Black or African American, 1.7% were Asian, and 5.2% were multiracial. The median age of participants was 14 years (range 12-17 years).
Prespecified immunogenicity non-inferiority analyses included an assessment of MN50 GMT ratio and percentage difference in seroconversion rates. Seroconversion for a participant was defined as achieving a 4-fold rise in MN50 from baseline (before the first dose of the primary series).
The analysis of the GMT ratio of MN50 following the booster dose compared with the primary series met the non-inferiority criteria for a booster response (lower limit of the 95% CI > 0.67 and point estimate > 0.83).
The lower limit of the two-sided 95% CI for the difference in seroconversion rates (percentage) was -6.8%, which did meet the non-inferiority criteria for a booster response (lower limit of 95% CI for the percentage difference of ≥ -10%). These analyses are summarized in Table 15 and Table 16.
Table 15 : Neutralizing Antibody Geometric Titers (MN50) Against the Original SARS-CoV-2 Virus Strain (SARS CoV-2 hCoV-19/Australia/VIC01/2020) at 28 Days after a Booster Dose Versus 14 Days After Completion of the Primary Series, Participants 12 Years through 17 Years of Age, PP-IMM Analysis Set1
|
Booster Dose |
Primary Series (N = 53) GMT (95% CI) 3 |
GMT Ratio (Booster/Primary Series) (95% CI)1 | Met Success Criteria |
| 11824.4 (8993.1, 15546.9) | 4434.0 (3658.0, 5374.5) | 2.7 (2.0, 3.5) | Lower limit of 95% CI > 0.67 and point estimate > 0.83 criteria: Yes |
| Abbreviations: CI = confidence interval; GMT = geometric mean titer; MN50 = microneutralization assay with an inhibitory concentration of 50%; PP-IMM = Per-Protocol Immunogenicity. 1 PP-IMM Analysis Set included participants who received two doses (0.5 mL 3 weeks apart) of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in the initial vaccination period or in the blinded crossover vaccination period, had an immunogenicity blood sample collected at Day 35 (primary series) and at 28 days after booster vaccination, did not have serologic or virologic evidence of SARS-CoV-2 infection on or before the booster dose, did not receive an emergency use authorized COVID-19 vaccine, received the booster dose, and remained blinded on study and without major protocol deviations until 7 days post-crossover Dose. 2 The analysis included a total of 53 participants of the PP-IMM analysis set who had immunogenicity data available for both the booster and primary series. 3 The 95% CI for GMT and GMT ratio were calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. Note: The median duration between the time of the second dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and the time of the booster dose was 10.6 months. |
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Table 16 : Seroconversion Rates (%) Against the Original SARS-CoV-2 Strain (SARS-CoV-2 hCoV-19/Australia/VIC01/2020) at 28 Days after a Booster Dose Versus 14 Days After Completion of the Primary Series, Participants 12 Years through 17 Years of Age, PP-IMM Analysis Set1
| Booster Dose (N = 53)2 SCR % (95% CI)3 |
Primary Series (N = 53) SCR % (95% CI)3 |
Difference in SCR4 (Booster-Primary Series) (95% CI)5 | Met Success Criterion6 |
| 100 (93.3, 100) | 100 (93.3, 100) | 0.0 (-6.8, 6.8) | LB of 95% CI > -10% criterion: Yes |
| Abbreviations: CI = confidence interval; PP-IMM = Per-Protocol Immunogenicity; SCR = seroconversion rate. 1 PP-IMM Analysis Set included participants who received two doses (0.5 mL 3 weeks apart) of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in the initial vaccination period or in the blinded crossover vaccination period, had an immunogenicity blood sample collected at Day 35 (primary series) and at 28 days after booster vaccination, did not have serologic or virologic evidence of SARS-CoV-2 infection on or before the booster dose, did not receive an emergency use authorized COVID-19 vaccine, received the booster dose, and remained blinded on study and without major protocol deviations until 7 days post-crossover Dose. 2 The analysis included a total of 53 participants of the PP-IMM analysis set who had immunogenicity data (microneutralization) available for both the booster and primary series 3 95% CI is based on the Clopper-Pearson method. 4 Based on the Tango method. 5 Comparison between SCR of 28 days post-booster relative to time of booster and SCR of 14 days after second dose of the primary series relative to time of first dose. 6 Non-inferiority of the single booster dose was achieved if the lower limit of the 95% CI for the difference of the proportion of participants with SCR at 28 days after a single booster dose relative to the time of first vaccination versus at 14 days after the second dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) relative to the time of first vaccination was > -10%. Note: SCR was defined as the proportion of participants with post-vaccination levels ≥ 4-fold higher than the baseline levels. Note: The median duration between the time of the second dose of the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) and the time of the booster dose was 10.6 months. |
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Effectiveness of a Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) booster dose in individuals who completed primary vaccination with another authorized or approved COVID-19 vaccine is inferred from immunogenicity data reported from an independent study conducted in the United Kingdom (ISRCTN 73765130). This multicenter, randomized, controlled Phase 2 trial investigated the immunogenicity of a single booster dose of Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) in participants who had received two doses of the Pfizer-BioNTech COVID-19 Vaccine as a primary vaccination series. Participants included adults aged 30 years and older with no history of laboratory-confirmed SARS-CoV-2 infection. The Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) was administered at least 84 days after completion of a Pfizer-BioNTech COVID-19 Vaccine primary series in 114 participants. Neutralizing antibody titers measured by a microneutralization assay were assessed prior to the booster dose and 28 days post-booster dose. A booster response to the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) was demonstrated.
In Study 5 Part 1, a subgroup of participants 18 to 64 years of age who previously received 3 doses of the Pfizer-BioNTech COVID-19 Vaccine or the Moderna COVID-19 Vaccine, received one of the following as a booster dose: Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) or monovalent vaccine (Omicron BA.1). The booster doses were administered at a median of 182 and 177 days after the last vaccination, respectively. Neutralizing antibody titers for the Omicron BA.1 virus, measured by a microneutralization assay [MN50], were evaluated at 14 days after vaccination. Participants included in the day 14 per protocol analysis set population (n=240) had no serologic or virologic evidence of SARS-CoV-2 infection prior to the booster dose.
Prespecified immunogenicity analyses included an assessment of MN50 GMT ratio and difference in seroresponse rates. Seroresponse rate was defined as the percentage of participants achieving a 4-fold rise in MN50 from baseline (before the first dose of the study vaccine).
The analysis of the GMT ratio following the booster dose with monovalent vaccine (Omicron BA.1) compared to the booster dose with Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) met the superiority criterion for success (lower limit of the 95% CI > 1.0).
The lower limit of the two-sided 95% CI for the difference in seroresponse rates (percentage) was 10.3%, which met the non-inferiority criterion for success (lower limit of 95% CI for the percentage difference of > -5%). These analyses are summarized in Table 17 and Table 18.
Table 17 : Summary of Geometric Mean Titers of Monovalent Vaccine (Omicron BA.1) Against the Omicron BA.1 Virus at 14 Days After a Booster Dose Versus the Novavax COVID-19 Vaccine, Adjuvanted (Original Monovalent) at 14 Days After a Booster Dose, Participants 18 Years through 64 Years of Age, PP Analysis Set1
| Monovalent vaccine (Omicron BA.1) (N = 124)2 GMT (95% CI)3 |
Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) (N = 116)2 GMT (95% CI)3 |
GMT Ratio4 [Monovalent vaccine (Omicron BA.1)/Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent)] (95% CI)4 | Met Success Criterion |
| 130.8 (109.2, 156.7) | 83.9 (69.6, 101.2) | 1.6 (1.33, 2.03) | Yes5 |
| Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; GMT = geometric mean titer; MN50 = microneutralization assay with an inhibitory concentration of 50%; PP = Per-Protocol; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. 1 PP Analysis Set included participants who received study vaccine according to protocol, did not have serologic or virologic evidence of SARS-CoV-2 infection on or before the booster dose, and had no major protocol violations that were considered clinically relevant to impact immunogenicity. 2 The analysis included participants of the PP analysis set who had immunogenicity data available at baseline and at 14 days post booster dose. 3 The 95% CI for GMT were calculated based on the t-distribution of the log-transformed values, then back transformed to the original scale for presentation. 4 An ANCOVA with vaccine group as fixed effect and baseline value as covariate was performed to estimate the GMT ratio. The mean difference between vaccine groups and the corresponding CI limits was then exponentiated to obtain the ratio of MN50 GMTs and the corresponding 95% CIs. 5 Success criterion is met if the lower bound of the two-sided 95% CI was above unity (ie, > 1). |
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Table 18 : Summary of Seroresponse Rate of Monovalent Vaccine (Omicron BA.1) Against the Omicron BA.1 Virus at 14 Days After a Booster Dose Versus the Novavax COVID-19 Vaccine, Adjuvanted (Original Monovalent) at 14 Days After a Booster Dose, Participants 18 Years through 64 Years of Age, PP Analysis Set1
| Monovalent vaccine (Omicron BA.1) (N = 124)2 SRR3 % (95% CI)4 |
Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) (N = 116)2 SRR3 % (95% CI)4 |
Difference in SRR [(Monovalent vaccine (Omicron BA.1) -Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent)] % (95% CI)5 | Met Success Criterion |
| 73.4 (64.7, 80.9) | 50.9 (41.4, 60.3) | 22.5 (10.3, 34.2) | Yes6 |
| Abbreviations: CI = confidence interval; MN50 = microneutralization assay with an inhibitory concentration of 50%; PP = Per-Protocol; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SRR = seroresponse rate. 1 PP Analysis Set included participants who received study vaccine according to protocol, did not have serologic or virologic evidence of SARS-CoV-2 infection on or before the booster dose, and had no major protocol violations that were considered clinically relevant to impact immunogenicity. 2 The analysis included participants of the PP analysis set who had immunogenicity data available at baseline and at 14 days post booster dose. 3 The SRR was defined as percentage of participants at each post vaccination visit with a titer ≥ 4-fold rise in MN50 level. 4 The 95% CI for SRR was calculated using the exact Clopper-Pearson method. 5 The 95% CI for the difference in SRR was calculated based on the method of Miettinen and Nurminen. 6 Success criterion is met if the lower bound of the two-sided 95% CI was above -5%. |
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In sensitivity analyses using a per protocol analysis set that did not exclude participants with serologic evidence of SARS-CoV-2 infection (PP2 Analysis Subset, n= 491), neutralizing antibody responses against the Omicron BA.1 virus induced by the monovalent vaccine (Omicron BA.1) were compared with neutralizing antibody responses against the Omicron BA.1 virus induced by the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) 14 days after study vaccination.
The GMTs were 318.2 (95% CI: 269.8, 375.3) in the monovalent vaccine (Omicron BA.1) group (n= 247) and 218.1 (95% CI: 186.0, 255.7) in the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) group (n= 244), resulting in an estimated GMT ratio of the monovalent vaccine (Omicron BA.1) versus the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) of 1.5 (95% CI: 1.36, 1.77).
The seroresponse rates (percentage) were 54.3% in the monovalent vaccine (Omicron BA.1) group and 32.0% in the Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) group, resulting in a difference in seroresponse rates (percentage) of 22.3% (95% CIs: 13.6%, 30.6%).
In Study 5 Part 2, a subgroup of participants 18 years of age and older who previously received at least 3 doses of the Pfizer-BioNTech COVID-19 Vaccine or the Moderna COVID-19 Vaccine, received one of the following as a booster dose: Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) or monovalent vaccine (Omicron BA.5). The booster doses were administered a median of 389 and 328 days after the last vaccination, respectively. Neutralizing antibody titers against a pseudovirus expressing the SARS-CoV-2 Spike protein from the Omicron BA.5 virus, measured by pseudovirus neutralization assay [ID50], were evaluated at 28 days after vaccination. Participants included in the day 28 per protocol analysis set population (n=462) had no virologic evidence of SARS-CoV-2 infection at time of the booster dose.
Exploratory immunogenicity analyses included an assessment of the ID50 GMT ratio and difference in seroresponse rates. Seroresponse rate was defined as the percentage of participants achieving a 4-fold rise in ID50 from baseline (before the first dose of the study vaccine).
The GMT ratio following the booster dose with monovalent vaccine (Omicron BA.5) compared with the booster dose with Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) was 2.5 (two-sided 95% confidence interval: 2.10, 2.94).
The difference in seroresponse rates (percentage) between the booster dose with monovalent vaccine (Omicron BA.5) and the booster dose with Novavax Vaccine, Adjuvanted (Original monovalent) was 33.2% (two-sided 95% confidence interval: 25.4%, 40.7%). These analyses are summarized in Table 19 and Table 20.
Table 19 : Summary of Geometric Mean Titers of Monovalent Vaccine (Omicron BA.5) Against a Pseudovirus Expressing the SARS-CoV-2 Spike Protein from Omicron BA.5 sublineage at 28 Days After a Booster Dose Versus the Novavax COVID-19 Vaccine, Adjuvanted (Original Monovalent) at 28 Days After a Booster Dose, Participants 18 Years of Age and Older, PP Analysis Set1
| Monovalent vaccine (Omicron BA.5) (N = 235)2 Adjusted GMT3 (95% CI)3 |
Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) (N = 227)2 Adjusted GMT3 (95% CI)3 |
GMT Ratio3 [Monovalent vaccine (Omicron BA.5)/ Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent)] (95% CI)3 |
| 1279.1 (1119.7, 1461.1) | 515.1 (450.4, 589.0) | 2.5 (2.10, 2.94) |
| Abbreviations: ANCOVA = analysis of covariance; CI = confidence interval; GMT = geometric mean titer; PP = Per-Protocol; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. 1 PP Analysis Set included participants who received study vaccine according to protocol, had serologic or virologic results for baseline and at Day 28, and had no major protocol violations that were considered clinically relevant to impact immunogenicity. 2 The analysis included participants of the PP analysis set who had immunogenicity data available at baseline and at 28 days post booster dose. 3 An ANCOVA with vaccine group and age group (18-54 years, ≥ 55 years) as fixed effects and baseline value (Day 0) as covariate is performed to estimate the adjusted GMT and GMT ratio. The mean difference between vaccine groups and the corresponding CI limits is then exponentiated to obtain the ratio of GMTs and the corresponding 95% CIs. |
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Table 20 : Summary of Seroresponse Rate of Monovalent Vaccine (Omicron BA.5) Against a Pseudovirus Expressing the SARS-CoV-2 Spike Protein from Omicron BA.5 sublineage at 28 Days After a Booster Dose Versus the Novavax COVID-19 Vaccine, Adjuvanted (Original Monovalent) at 28 Days After a Booster Dose, Participants 18 Years of Age and Older, PP Analysis Set1
| Monovalent vaccine (Omicron BA.5) (N = 235)2 SRR3 % (95% CI)4 |
Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent) (N = 227)2 SRR3 % (95% CI)4 |
Difference in SRR [(Monovalent vaccine (Omicron BA.1) -Novavax COVID-19 Vaccine, Adjuvanted (Original monovalent)] % (95% CI)5 |
| 45.5 (39.0, 52.1) | 12.3 (8.4, 17.3) | 33.2 (25.4, 40.7) |
| Abbreviations: CI = confidence interval; LLOQ = lower limit of quantitation; PP = Per-Protocol; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2; SRR = seroresponse rate. 1 PP Analysis Set included participants who received study vaccine according to protocol, had serologic or virologic results for baseline and at Day 28, and had no major protocol violations that were considered clinically relevant to impact immunogenicity. 2 The analysis included participants of the PP analysis set who had immunogenicity data available at baseline and at 28 days post booster dose. 3 The SRR is defined as ≥ 4-fold increase from baseline value if the baseline value is equal to or above LLOQ; or ≥ 4 times the LLOQ if the baseline value is below LLOQ. 4 The 95% CI for SRR is calculated using the exact Clopper-Pearson method. 5 The 95% CI for the difference in SRR was calculated based on the method of Miettinen and Nurminen. |
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Advise the recipient or caregiver to read the Fact Sheet for Recipients and Caregivers.
The vaccination provider must include vaccination information in the state/local jurisdictionImmunization Information System (IIS) or other designated system. Advise recipient or caregiver that more information about IISs can be found at: https://www.cdc.gov/vaccines/programs/iis/about.html.
