Vaccine Information: NOVAVAX COVID-19 Vaccine, Adjuvanted (Page 3 of 8)

5 WARNINGS AND PRECAUTIONS

5.1 Management of Acute Allergic Reactions

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 the 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).

5.2 Myocarditis and Pericarditis

Clinical trials data provide evidence for increased risks of myocarditis and pericarditis following administration of Novavax COVID-19 Vaccine, Adjuvanted [see Clinical Trials Experience (6.1)].

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).

5.3 Syncope

Syncope (fainting) may occur in association with administration of injectable vaccines. Procedures should be in place to avoid injury from fainting.

5.4 Altered Immunocompetence

Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to the Novavax COVID-19 Vaccine, Adjuvanted.

5.5 Limitations of Vaccine Effectiveness

The Novavax COVID-19 Vaccine, Adjuvanted may not protect all vaccine recipients.

6 OVERALL SAFETY SUMMARY

It is MANDATORY for vaccination providers to report to the Vaccine Adverse Event Reporting System (VAERS) all vaccine administration errors, all serious adverse events, cases of myocarditis, cases of pericarditis, cases of Multisystem Inflammatory Syndrome (MIS) in adults and children, and hospitalized or fatal cases of COVID-19 following vaccination with the Novavax COVID-19 Vaccine, Adjuvanted. To the extent feasible, provide a copy of the VAERS form to Novavax, Inc. Please see the REQUIREMENTS AND INSTRUCTIONS FOR REPORTING ADVERSE EVENTS AND VACCINE ADMINISTRATION ERRORS section for details on reporting to VAERS and Novavax, Inc.

Adverse Reactions in Clinical Trials

Primary Series

In a clinical trial, among participants 18 through 64 years of age, solicited adverse reactions (ARs) following administration of any dose of the Novavax COVID-19 Vaccine, Adjuvanted were injection site pain/tenderness (82.2%), fatigue/malaise (62.0%), muscle pain (54.1%), headache (52.9%), joint pain (25.4%), nausea/vomiting (15.6%), injection site redness (7.0%), injection site swelling (6.3%), and fever (6.0%). In participants ≥65 years of age, solicited ARs following administration of any dose of the Novavax COVID-19 Vaccine, Adjuvanted were injection site pain/tenderness (63.4%), fatigue/malaise (39.2%), muscle pain (30.2%), headache (29.2%), joint pain (15.4%), nausea/vomiting (7.3%), injection site swelling (5.3%), injection site redness (4.8%), and fever (2.0%).

In a clinical trial, among participants 12 through 17 years of age, solicited ARs following administration of any dose of the Novavax COVID-19 Vaccine, Adjuvanted were injection site pain/tenderness (79.8%), headache (63.3%), fatigue/malaise (61.6%), muscle pain (56.9%), nausea/vomiting (23.1%), joint pain (19.5%), fever (16.7%), injection site swelling (8.5%), and injection site redness (7.7%).

Myocarditis, pericarditis, chills, injection site pruritus, hypersensitivity reactions, lymphadenopathy-related reactions, and decreased appetite have been reported following administration of the Novavax COVID-19 Vaccine, Adjuvanted.

Booster Dose

In a clinical trial, among participants 18 years of age and older, solicited ARs following administration of a booster dose of the Novavax COVID-19 Vaccine, Adjuvanted were injection site pain/tenderness (81.1%), fatigue/malaise (63.4%), muscle pain (63.0%), headache (52.9%), joint pain (30.3%), nausea/vomiting (14.7%), injection site swelling (8.4%), injection site redness (6.3%), and fever (6.3%).

6.1 Clinical Trials Experience

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.

Two-Dose Primary Series

Participants 18 years of age and older

Safety of the Novavax COVID-19 Vaccine, Adjuvanted 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. Additional safety data are available from three other clinical trials in the United Kingdom (NCT04583995; Study 2), South Africa (NCT04533399; Study 3), and Australia (NCT04368988, Parts 1 and 2 in Australia and the US; Study 4) which evaluated a COVID-19 vaccine containing the SARS-CoV-2 recombinant spike (rS) protein and Matrix-M adjuvant but manufactured by a different process.

Adolescents 12 Through 17 Years of Age

Safety of the Novavax COVID-19 Vaccine, Adjuvanted 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 (n=1,487) or placebo (n=745).

Safety Data from Study 1

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 (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 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, 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 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, 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 starting approximately 6 months after the two-dose primary series.

Participants 18 years of age and older

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 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 1.

Table 1 Number and Percentage of Participants with Solicited Local and Systemic Adverse Reactions Starting within 7 Days * After Each Dose in Participants 18-64 Years (Solicited Safety Set, Dose 1 and Dose 2)
Event Novavax COVID-19 Vaccine, Adjuvanted Placebo §
Primary Series Primary Series
Dose 1N = 15884n (%) Dose 2N = 15148n (%) Dose 1N = 7868n (%) Dose 2N = 7361n (%)
*
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).
Solicited safety set includes participants who received at least one dose of study vaccine and completed their eDiary.
Absence of rows for Grade 4 adverse reactions indicates no events were reported.
§
Placebo was a saline solution.
Grade 3 pain: Defined as any use of narcotic pain reliever or prevents daily activity.
#
Grade 3 tenderness: Defined as significant discomfort at rest.
Þ
Grade 4 pain/ tenderness: Defined as Emergency Room (ER) visit or hospitalization.
ß
Grade 3 redness (erythema): Defined as > 10 cm.
à
Grade 3 swelling: Defined as > 10 cm or prevents daily activity.
è
Grade 3 fever: Defined as 39.0 to 40°C (102.1 to 104°F).
ð
Grade 4 fever: Defined as > 40°C (> 104°F).
ø
Grade 3 headache: Defined as significant; any use of narcotic pain reliever or prevents daily activity.
ý
Grade 4 headache, fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as ER visit or hospitalization.
£
Grade 3 fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as significant; prevents daily activity.
¥
Grade 3 nausea or vomiting: Defined as prevents daily activity, requires outpatient IV hydration.
Œ
Grade 4 nausea or vomiting: Defined as ER visit or hospitalization for hypotensive shock.
Local Adverse Reactions
Pain/tenderness
Any Grade 9604 (60.5) 12234 (80.8) 1706 (21.7) 1623 (22.0)
Grade 3, # 174 (1.1) 951 (6.3) 17 (0.2) 20 (0.3)
Grade 4Þ 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 3ß 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 3à 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 3è 7 (0.04) 60 (0.4) 7 (0.09) 2 (0.03)
Grade 4ð 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 3ø 132 (0.8) 492 (3.2) 58 (0.7) 36 (0.5)
Grade 4ý 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 3£ 249 (1.6) 1591 (10.5) 113 (1.4) 114 (1.5)
Grade 4ý 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 3£ 79 (0.5) 805 (5.3) 31 (0.4) 28 (0.4)
Grade 4ý 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 3£ 49 (0.3) 393 (2.6) 25 (0.3) 22 (0.3)
Grade 4ý 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 3¥ 18 (0.1) 26 (0.2) 7 (0.09) 7 (0.1)
Grade 4Π4 (0.03) 7 (0.05) 2 (0.03) 2 (0.03)

The reported frequency and severity of solicited local and systemic adverse reactions are presented for participants 65 years of age and older in Table 2.

Table 2 Number and Percentage of Participants with Solicited Local and Systemic Adverse Reactions Starting within 7 Days * After Each Dose in Participants 65 Years and Older (Solicited Safety Set, Dose 1 and Dose 2)
Event Novavax COVID-19 Vaccine, Adjuvanted Placebo §
Primary Series Primary Series
Dose 1N = 2251n (%) Dose 2N = 2048n (%) Dose 1N = 1114n (%) Dose 2N = 978n (%)
*
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).
Solicited safety set includes participants who received at least one dose of study vaccine and completed their eDiary.
Absence of rows for Grade 4 adverse reactions indicates no events were reported.
§
Placebo was a saline solution.
Grade 3 pain: Defined as any use of narcotic pain reliever or prevents daily activity.
#
Grade 3 tenderness: Defined as significant discomfort at rest.
Þ
Grade 3 redness (erythema): Defined as > 10 cm.
ß
Grade 3 swelling: Defined as > 10 cm or prevents daily activity.
à
Grade 3 fever: Defined as 39.0 to 40°C (102.1 to 104°F).
è
Grade 3 headache: Defined as significant; any use of narcotic pain reliever or prevents daily activity.
ð
Grade 4 headache, joint pain (arthralgia): Defined as ER visit or hospitalization.
ø
Grade 3 fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as significant; prevents daily activity.
ý
Grade 3 nausea or vomiting: Defined as prevents daily activity, requires outpatient IV hydration.
Local Adverse Reactions
Pain/tenderness
Any Grade 854 (37.9) 1258 (61.4) 175 (15.7) 161 (16.5)
Grade 3, # 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 3Þ 0 7 (0.3) 0 0
Swelling
Any Grade 18 (0.8) 111 (5.4) 1 (0.09) 4 (0.4)
Grade 3ß 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 3à 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 3è 12 (0.5) 18 (0.9) 4 (0.4) 2 (0.2)
Grade 4ð 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 3ø 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 3ø 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 3ø 4 (0.2) 16 (0.8) 4 (0.4) 2 (0.2)
Grade 4ð 0 1 (0.05) 0 0
Nausea/vomiting
Any Grade 81 (3.6) 108 (5.3) 32 (2.9) 35 (3.6)
Grade 3ý 0 3 (0.1) 0 0

Unsolicited Adverse Events (non-serious and serious)

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 and 9,847 participants received placebo. In the post-crossover period, 6,416 participants received the Novavax COVID-19 Vaccine, Adjuvanted and 15,298 received placebo. Of participants who received two doses of the Novavax COVID-19 Vaccine, Adjuvanted 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 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 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 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 and by 178 (1.2%) participants who received placebo.

Within 7 days of any dose (including 26,151 Novavax COVID-19 Vaccine, Adjuvanted 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 (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.

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 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.

  • Myocarditis and/or pericarditis were reported by two participants after the Novavax COVID-19 Vaccine, Adjuvanted (0.01%) and no participants after placebo. One serious event was reported by a 67-year-old male 28 days after Dose 1, associated with concomitant COVID-19, and one non-serious event was reported by a 20-year-old male 10 days after Dose 1. Among the two reported events, one was reported as resolved and one did not have follow-up available. Reports of myocarditis and/or pericarditis from Study 1 and Study 2 (see Safety Data from Study 2) provide evidence for increased risks of myocarditis and pericarditis following administration of the Novavax COVID-19 Vaccine, Adjuvanted.
  • Events of cardiomyopathy or cardiac failure were reported by eight participants after the Novavax COVID-19 Vaccine, Adjuvanted (0.03%) and one participant after placebo (<0.01%). All events were serious. Additionally, an event of congestive cardiac failure was reported after the Novavax COVID-19 Vaccine, Adjuvanted by a participant who was excluded from the safety analysis set. Currently available information on cardiomyopathy or cardiac failure is insufficient to determine a causal relationship with the vaccine.
  • Events of acute cholecystitis were reported by six participants after the Novavax COVID-19 Vaccine, Adjuvanted (0.02%) and two participants after placebo (0.01%). All events were serious. Currently available information on cholecystitis is insufficient to determine a causal relationship with the vaccine.
  • A total of 12 non-cardiac, non-neurovascular thrombotic and embolic events were reported by 11 participants after the Novavax COVID-19 Vaccine, Adjuvanted (0.04%) and a total of seven events were reported by six participants after placebo (0.02%). Events following the Novavax COVID-19 Vaccine, Adjuvanted included pulmonary embolism (n=5), deep vein thrombosis (n=2), thrombosis (n=2), and portal vein thrombosis, mesenteric artery thrombosis, and peripheral arterial occlusive disease (n=1 each); six of the events were serious, including pulmonary embolism (n=5) and deep vein thrombosis (n= 1). Events following placebo included pulmonary embolism (n=3), and deep vein thrombosis and peripheral arterial occlusive disease (n=2 each), all of which were serious except deep vein thrombosis and peripheral arterial occlusive disease (n= 1 each). Currently available information on non-cardiac, non-neurovascular thrombotic and embolic events is insufficient to determine a causal relationship with the vaccine.

Events of uveitis (iritis, uveitis, iridocyclitis) were reported by 3 participants after Novavax COVID-19 Vaccine, Adjuvanted (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 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 recipients had a history of iritis. Currently available information on uveitis is insufficient to determine a causal relationship with the vaccine.

Adolescents 12 Through 17 Years of Age

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 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 3.

Table 3 Number and Percentage of Participants with Solicited Local and Systemic Adverse Reactions Starting within 7 Days * After Each Dose in Participants 12-17 Years (Solicited Safety Set, Dose 1 and Dose 2)
Event Novavax COVID-19 Vaccine, Adjuvanted Placebo §
Dose 1N = 1448n (%) Dose 2N = 1394n (%) Dose 1N = 726n (%) Dose 2N = 686n (%)
*
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).
Solicited safety set includes participants who received at least one dose of study vaccine and completed their eDiary.
Absence of rows for Grade 4 adverse reactions indicates no events were reported.
§
Placebo was a saline solution.
Grade 3 pain: Defined as any use of narcotic pain reliever or prevents daily activity.
#
Grade 3 tenderness: Defined as significant discomfort at rest.
Þ
Grade 3 redness (erythema): Defined as > 10 cm.
ß
Grade 3 swelling: Defined as > 10 cm or prevents daily activity.
à
Grade 3 fever: Defined as 39.0 to 40°C (102.1 to 104°F).
è
Grade 4 fever: Defined as > 40°C (> 104°F).
ð
Grade 3 headache: Defined as significant; any use of narcotic pain reliever or prevents daily activity.
ø
Grade 4 headache, fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as ER visit or hospitalization.
ý
Grade 3 fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as significant; prevents daily activity.
£
Grade 3 nausea or vomiting: Defined as prevents daily activity, requires outpatient IV hydration.
¥
Grade 4 nausea or vomiting: Defined as ER visit or hospitalization for hypotensive shock.
Local Adverse Reactions
Pain/tenderness
Any Grade 945 (65.3) 1045 (75.0) 204 (28.1) 141 (20.6)
Grade 3, # 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 3Þ 0 10 (0.7) 0 0
Swelling
Any Grade 20 (1.4) 111 (8.0) 3 (0.4) 1 (0.1)
Grade 3ß 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 3à 1 (0.07) 31 (2.2) 0 0
Grade 4è 2 (0.1) 0 0 0
Headache
Any Grade 440 (30.4) 793 (56.9) 181 (24.9) 119 (17.3)
Grade 3ð 13 (0.9) 87 (6.2) 12 (1.7) 14 (2.0)
Grade 4ø 0 1 (0.07) 0 0
Fatigue/malaise
Any Grade 418 (28.9) 807 (57.9) 142 (19.6) 113 (16.5)
Grade 3ý 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 3ý 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 3ý 6 (0.4) 40 (2.9) 1 (0.1) 2 (0.3)
Nausea/vomiting
Any Grade 113 (7.8) 277 (19.9) 56 (7.7) 33 (4.8)
Grade 3£ 2 (0.1) 14 (1.0) 3 (0.4) 3 (0.4)
Grade 4¥ 0 1 (0.07) 0 0

Unsolicited Adverse Events (non-serious and serious)

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 and 745 participants received placebo. In the post-crossover period, 665 participants received the Novavax COVID-19 Vaccine, Adjuvanted and 1,353 received placebo. Of participants who received two doses of the Novavax COVID-19 Vaccine, Adjuvanted 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 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 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 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 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.

Safety Data from Other Studies with Primary Series

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 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 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.

Booster Dose Following a Primary Series of Novavax COVID-19 Vaccine, Adjuvanted 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 (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.

Solicited Adverse Reactions

Local and systemic adverse reactions were solicited within 7 days following the third (booster) dose of the Novavax COVID-19 Vaccine, Adjuvanted 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 4.

Table 4 Number and Percentage of Participants with Solicited Local and Systemic Adverse Reactions Starting within 7* Days After Booster Dose in Participants 18 Years and Older (Booster Safety Analysis Set )
Event Novavax COVID-19 Vaccine, Adjuvanted Booster N = 238n (%)
*
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).
The analysis included a total of 238 participants who received the booster dose who completed their eDiary
Absence of rows for Grade 4 adverse reactions indicates no events were reported.
§
Grade 3 pain: Defined as any use of narcotic pain reliever or prevents daily activity.
Grade 3 tenderness: Defined as significant discomfort at rest.
#
Grade 3 redness (erythema): Defined as > 10 cm.
Þ
Grade 3 swelling: Defined as > 10 cm or prevents daily activity.
ß
Grade 3 fever: Defined as 39.0 to 40°C (102.1 to 104°F).
à
Grade 3 headache: Defined as significant; any use of narcotic pain reliever or prevents daily activity.
è
Grade 3 fatigue/malaise, muscle pain (myalgia), joint pain (arthralgia): Defined as significant; prevents daily activity.
ð
Grade 4 fatigue/malaise, muscle pain (myalgia): Defined as ER visit or hospitalization.
ø
Grade 3 nausea or vomiting: Defined as prevents daily activity, requires outpatient IV hydration.
ý
Grade 4 nausea or vomiting: Defined as ER visit or hospitalization for hypotensive shock.
Local Adverse Reactions
Pain/tenderness
Any Grade 193 (81.1)
Grade 3§, 18 (7.6)
Redness (erythema)
Any Grade 15 (6.3)
Grade 3# 1 (0.4)
Swelling
Any Grade 20 (8.4)
Grade 3Þ 2 (0.8)
Systemic Adverse Reactions
Fever
Any Grade 15 (6.3)
Grade 3ß 2 (0.8)
Headache
Any Grade 126 (52.9)
Grade 3à 14 (5.9)
Fatigue/malaise
Any Grade 151 (63.4)
Grade 3è 41 (17.2)
Grade 4ð 2 (0.8)
Muscle pain (myalgia)
Any Grade 150 (63.0)
Grade 3è 20 (8.4)
Grade 4ð 2 (0.8)
Joint pain (arthralgia)
Any Grade 72 (30.3)
Grade 3è 9 (3.8)
Nausea or vomiting
Any Grade 35 (14.7)
Grade 3ø 2 (0.8)
Grade 4ý 1 (0.4)

Unsolicited Adverse Events (non-serious and serious)

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 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. 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, 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.

Booster Dose Following Primary Vaccination with Another Authorized or Approved COVID-19 Vaccine

The safety of a Novavax COVID-19 Vaccine, Adjuvanted 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 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 booster dose did not identify any new safety concerns, as compared with adverse reactions reported following two doses of Novavax COVID-19 Vaccine, Adjuvanted given as a primary series.

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