Comirnaty (COVID-19 Vaccine, mRNA) injection, suspension
Pfizer Laboratories Div Pfizer Inc
1 INDICATIONS AND USAGE
COMIRNATY is a vaccine indicated 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.
COMIRNATY is a vaccine indicated 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. (1)
2 DOSAGE AND ADMINISTRATION
For intramuscular injection only.
The storage, preparation, and administration information in this Prescribing Information apply to COMIRNATY supplied in:
- single dose vials with gray caps and labels with gray borders, and
- multiple dose vials with gray caps and labels with gray borders.
COMIRNATY supplied in vials with gray caps and labels with gray borders MUST NOT be diluted prior to use.
- COMIRNATY supplied in single dose vials or multiple dose vials with gray caps and labels with gray borders MUST NOT be diluted prior to use. (2.1)
- For intramuscular injection only. (2.2)
- COMIRNATY is administered intramuscularly as a series of 2 doses (0.3 mL each) 3 weeks apart. (2.3)
2.1 Preparation for Administration
- COMIRNATY vials with gray caps and labels with gray borders contain a frozen suspension without preservative. Each vial must be thawed prior to administration. DO NOT DILUTE prior to use.
- Vials may be thawed in the refrigerator [2ºC to 8ºC (35ºF to 46ºF)] or at room temperature [up to 25ºC (77ºF)].
- Refer to thawing and preparation instructions in the panels below.
| Preparation Instructions | |
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COMIRNATY Vial with Gray Cap and Label with Gray Border –
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✔ Gray cap and label with gray border. |
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Thawing Prior to Use |
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Store in the refrigerator for up to 10 weeks prior to use. |
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Gently × 10 |
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Preparation of Individual 0.3 mL Doses |
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Single Dose Vial
Multiple Dose Vial
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Withdraw 0.3 mL dose of vaccine. |
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Multiple Dose Vial – Record Date and Time of First Puncture |
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Record the date and time of first puncture.
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2.2 Administration Information
Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. The vaccine will be a white to off-white suspension. Do not administer if vaccine is discolored or contains particulate matter.
After withdrawing a single 0.3 mL dose of COMIRNATY, administer immediately.
2.3 Vaccination Schedule
COMIRNATY is administered intramuscularly as a series of 2 doses (0.3 mL each) 3 weeks apart.
There are no data available on the interchangeability of COMIRNATY with COVID-19 vaccines from other manufacturers to complete the vaccination series. Individuals who have received 1 dose of COMIRNATY should receive a second dose of COMIRNATY to complete the vaccination series.
3 DOSAGE FORMS AND STRENGTHS
COMIRNATY is a suspension for injection. Each dose of COMIRNATY supplied in vials with gray caps and labels with gray borders is 0.3 mL.
Suspension for injection. A single dose is 0.3 mL. (3)
4 CONTRAINDICATIONS
Do not administer COMIRNATY to individuals with known history of a severe allergic reaction (e.g., anaphylaxis) to any component of COMIRNATY [see Description (11)].
Known history of a severe allergic reaction (e.g., anaphylaxis) to any component of COMIRNATY. (4)
5 WARNINGS AND PRECAUTIONS
- Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose. (5.2)
- Syncope (fainting) may occur in association with administration of injectable vaccines, including COMIRNATY. Procedures should be in place to avoid injury from fainting. (5.4)
5.1 Management of Acute Allergic Reactions
Appropriate medical treatment used to manage immediate allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of COMIRNATY.
5.2 Myocarditis and Pericarditis
Postmarketing data demonstrate increased risks of myocarditis and pericarditis, particularly within 7 days following the second dose. The observed risk is higher among males under 40 years of age than among females and older males. The observed risk is highest in males 12 through 17 years of age. Although some cases required intensive care support, available data from short-term follow-up suggest that most individuals have had resolution of symptoms with conservative management. Information is not yet available about potential long-term sequelae. 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/myocarditis.html).
5.3 Syncope
Syncope (fainting) may occur in association with administration of injectable vaccines, including COMIRNATY. 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 COMIRNATY.
5.5 Limitation of Effectiveness
COMIRNATY may not protect all vaccine recipients.
6 ADVERSE REACTIONS
In clinical studies, the most commonly reported (≥10%) adverse reactions in participants 16 through 55 years of age following any dose were pain at the injection site (88.6%), fatigue (70.1%), headache (64.9%), muscle pain (45.5%), chills (41.5%), joint pain (27.5%), fever (17.8%), and injection site swelling (10.6%).
In clinical studies, the most commonly reported (≥10%) adverse reactions in participants 56 years of age and older following any dose were pain at the injection site (78.2%), fatigue (56.9%), headache, (45.9%), muscle pain (32.5%), chills (24.8%), joint pain (21.5%), injection site swelling (11.8%), fever (11.5%), and injection site redness (10.4%).
In a clinical study, the most commonly reported (≥8%) adverse reactions in adolescents 12 through 15 years of age following any dose were pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), and injection site redness (8.6%).
- In clinical studies of participants 16 through 55 years of age, the most commonly reported adverse reactions (≥10%) were pain at the injection site (88.6%), fatigue (70.1%), headache (64.9%), muscle pain (45.5%), chills (41.5%), joint pain (27.5%), fever (17.8%), and injection site swelling (10.6%). (6.1)
- In clinical studies of participants 56 years of age and older, the most commonly reported adverse reactions (≥10%) were pain at the injection site (78.2%), fatigue (56.9%), headache, (45.9%), muscle pain (32.5%), chills (24.8%), joint pain (21.5%), injection site swelling (11.8%), fever (11.5%), and injection site redness (10.4%). (6.1)
- In clinical studies of adolescents 12 through 15 years of age, the most commonly reported adverse reactions (≥8%) were pain at the injection site (90.5%), fatigue (77.5%), headache (75.5%), chills (49.2%), muscle pain (42.2%), fever (24.3%), joint pain (20.2%), injection site swelling (9.2%), and injection site redness (8.6%). (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Pfizer Inc. at 1-800-438-1985 or VAERS at 1-800-822-7967 or http://vaers.hhs.gov.
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 to rates in the clinical trials of another vaccine and may not reflect the rates observed in practice.
The safety of COMIRNATY was evaluated in participants 12 years of age and older in 2 clinical studies conducted in Germany (Study 1), United States, Argentina, Brazil, Turkey, South Africa, and Germany (Study 2). Study BNT162-01 (Study 1) was a Phase 1/2, 2-part, dose-escalation trial that enrolled 60 participants, 18 through 55 years of age and 36 participants, 56 through 85 years of age. Study C4591001 (Study 2) is a Phase 1/2/3 multicenter, multinational, randomized, saline placebo-controlled, double-blinded (Phase 2/3), dose-finding, vaccine candidate-selection and efficacy study that has enrolled approximately 46,000 participants 12 years of age or older. Of these, approximately 44,047 participants (22,026 COMIRNATY; 22,021 placebo) in Phase 2/3 are 16 years of age or older (including 378 and 376 participants 16 through 17 years of age in the COMIRNATY and placebo groups, respectively) and 2,260 adolescents are 12 through 15 years of age (1,131 and 1,129 in the COMIRNATY and placebo groups, respectively). Upon issuance of the Emergency Use Authorization for COMIRNATY, participants were unblinded to offer placebo participants COMIRNATY. Participants were unblinded in a phased manner over a period of months to offer placebo participants COMIRNATY. Study 2 also included 200 participants with confirmed stable human immunodeficiency virus (HIV) infection; HIV-positive participants are included in safety population disposition but are summarized separately in safety analyses. Confirmed stable HIV infection was defined as documented viral load <50 copies/mL and CD4 count >200 cells/mm3 within 6 months before enrollment, and on stable antiretroviral therapy for at least 6 months.
In Study 2, all participants 12 through 15 years of age, and 16 years and older in the reactogenicity subset were monitored for solicited local and systemic reactions and use of antipyretic medication after each vaccination in an electronic diary. Participants are being monitored for unsolicited adverse events, including serious adverse events, throughout the study [from Dose 1 through 1 month (all unsolicited adverse events) or 6 months (serious adverse events) after the last vaccination]. Tables 1 through 6 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following each dose of COMIRNATY and placebo.
Participants 16 Years of Age and Older
At the time of the analysis of the ongoing Study 2 with a data cutoff of March 13, 2021, there were 25,651 (58.2%) participants (13,031 COMIRNATY and 12,620 placebo) 16 years of age and older followed for ≥4 months after the second dose.
Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity among participants who received COMIRNATY and those who received placebo. Overall, among the total participants who received either COMIRNATY or placebo, 50.9% were male, 49.1% were female, 79.3% were 16 through 64 years of age, 20.7% were 65 years of age and older, 82.0% were White, 9.6% were Black or African American, 25.9% were Hispanic/Latino, 4.3% were Asian, and 1.0% were American Indian or Alaska Native.
Local and Systemic Adverse Reactions Solicited in the Study 2
In participants 16 through 55 years of age after receiving Dose 2, the mean duration of pain at the injection site was 2.5 days (range 1 to 70 days), for redness 2.2 days (range 1 to 9 days), and for swelling 2.1 days (range 1 to 8 days) for participants in the COMIRNATY group. In participants 56 years of age and older after receiving Dose 2, the mean duration of pain at the injection site was 2.4 days (range 1 to 36 days), for redness 3.0 days (range 1 to 34 days), and for swelling 2.6 days (range 1 to 34 days) for participants in the COMIRNATY group.
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COMIRNATY
Dose 1 N N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each reaction was the same, therefore, this information was included in the column header. =2899 n n = Number of participants with the specified reaction. (%) |
Placebo
Dose 1 N =2908 n (%) |
COMIRNATY
Dose 2 N =2682 n (%) |
Placebo
Dose 2 N =2684 n (%) |
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| Notes: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. No Grade 4 solicited local reactions were reported in participants 16 through 55 years of age. |
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RednessMild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm. |
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Any (>2.0 cm) |
156 (5.4) |
28 (1.0) |
151 (5.6) |
18 (0.7) |
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Mild |
113 (3.9) |
19 (0.7) |
90 (3.4) |
12 (0.4) |
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Moderate |
36 (1.2) |
6 (0.2) |
50 (1.9) |
6 (0.2) |
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Severe |
7 (0.2) |
3 (0.1) |
11 (0.4) |
0 |
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Swelling |
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Any (>2.0 cm) |
184 (6.3) |
16 (0.6) |
183 (6.8) |
5 (0.2) |
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Mild |
124 (4.3) |
6 (0.2) |
110 (4.1) |
3 (0.1) |
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Moderate |
54 (1.9) |
8 (0.3) |
66 (2.5) |
2 (0.1) |
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Severe |
6 (0.2) |
2 (0.1) |
7 (0.3) |
0 |
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Pain at the injection siteMild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity. |
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Any |
2426 (83.7) |
414 (14.2) |
2101 (78.3) |
312 (11.6) |
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Mild |
1464 (50.5) |
391 (13.4) |
1274 (47.5) |
284 (10.6) |
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Moderate |
923 (31.8) |
20 (0.7) |
788 (29.4) |
28 (1.0) |
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Severe |
39 (1.3) |
3 (0.1) |
39 (1.5) |
0 |
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COMIRNATY
Dose 1 N N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each reaction or use of antipyretic or pain medication was the same, therefore, this information was included in the column header. =2899 n n = Number of participants with the specified reaction. (%) |
Placebo
Dose 1 N =2908 n (%) |
COMIRNATY
Dose 2 N =2682 n (%) |
Placebo
Dose 2 N =2684 n (%) |
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| Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after each dose. No Grade 4 solicited systemic reactions were reported in participants 16 through 55 years of age. |
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Fever |
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≥38.0°C |
119 (4.1) |
25 (0.9) |
440 (16.4) |
11 (0.4) |
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≥38.0°C to 38.4°C |
86 (3.0) |
16 (0.6) |
254 (9.5) |
5 (0.2) |
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>38.4°C to 38.9°C |
25 (0.9) |
5 (0.2) |
146 (5.4) |
4 (0.1) |
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>38.9°C to 40.0°C |
8 (0.3) |
4 (0.1) |
39 (1.5) |
2 (0.1) |
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>40.0°C |
0 |
0 |
1 (0.0) |
0 |
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FatigueMild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity. |
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Any |
1431 (49.4) |
960 (33.0) |
1649 (61.5) |
614 (22.9) |
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Mild |
760 (26.2) |
570 (19.6) |
558 (20.8) |
317 (11.8) |
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Moderate |
630 (21.7) |
372 (12.8) |
949 (35.4) |
283 (10.5) |
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Severe |
41 (1.4) |
18 (0.6) |
142 (5.3) |
14 (0.5) |
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Headache |
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Any |
1262 (43.5) |
975 (33.5) |
1448 (54.0) |
652 (24.3) |
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Mild |
785 (27.1) |
633 (21.8) |
699 (26.1) |
404 (15.1) |
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Moderate |
444 (15.3) |
318 (10.9) |
658 (24.5) |
230 (8.6) |
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Severe |
33 (1.1) |
24 (0.8) |
91 (3.4) |
18 (0.7) |
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Chills |
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Any |
479 (16.5) |
199 (6.8) |
1015 (37.8) |
114 (4.2) |
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Mild |
338 (11.7) |
148 (5.1) |
477 (17.8) |
89 (3.3) |
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Moderate |
126 (4.3) |
49 (1.7) |
469 (17.5) |
23 (0.9) |
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Severe |
15 (0.5) |
2 (0.1) |
69 (2.6) |
2 (0.1) |
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VomitingMild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration. |
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Any |
34 (1.2) |
36 (1.2) |
58 (2.2) |
30 (1.1) |
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Mild |
29 (1.0) |
30 (1.0) |
42 (1.6) |
20 (0.7) |
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Moderate |
5 (0.2) |
5 (0.2) |
12 (0.4) |
10 (0.4) |
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Severe |
0 |
1 (0.0) |
4 (0.1) |
0 |
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DiarrheaMild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours. |
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Any |
309 (10.7) |
323 (11.1) |
269 (10.0) |
205 (7.6) |
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Mild |
251 (8.7) |
264 (9.1) |
219 (8.2) |
169 (6.3) |
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Moderate |
55 (1.9) |
58 (2.0) |
44 (1.6) |
35 (1.3) |
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Severe |
3 (0.1) |
1 (0.0) |
6 (0.2) |
1 (0.0) |
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New or worsened muscle pain |
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Any |
664 (22.9) |
329 (11.3) |
1055 (39.3) |
237 (8.8) |
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Mild |
353 (12.2) |
231 (7.9) |
441 (16.4) |
150 (5.6) |
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Moderate |
296 (10.2) |
96 (3.3) |
552 (20.6) |
84 (3.1) |
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Severe |
15 (0.5) |
2 (0.1) |
62 (2.3) |
3 (0.1) |
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New or worsened joint pain |
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Any |
342 (11.8) |
168 (5.8) |
638 (23.8) |
147 (5.5) |
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Mild |
200 (6.9) |
112 (3.9) |
291 (10.9) |
82 (3.1) |
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Moderate |
137 (4.7) |
55 (1.9) |
320 (11.9) |
61 (2.3) |
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Severe |
5 (0.2) |
1 (0.0) |
27 (1.0) |
4 (0.1) |
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Use of antipyretic or pain medicationSeverity was not collected for use of antipyretic or pain medication. |
805 (27.8) |
398 (13.7) |
1213 (45.2) |
320 (11.9) |
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COMIRNATY
Dose 1 N N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. The N for each reaction was the same, therefore, the information was included in the column header. =2008 n n = Number of participants with the specified reaction. (%) |
Placebo
Dose 1 N =1989 n (%) |
COMIRNATY
Dose 2 N =1860 n (%) |
Placebo
Dose 2 N =1833 n (%) |
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| Notes: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. No Grade 4 solicited local reactions were reported in participants 56 years of age and older. |
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RednessMild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm. |
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Any (>2.0 cm) |
106 (5.3) |
20 (1.0) |
133 (7.2) |
14 (0.8) |
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Mild |
71 (3.5) |
13 (0.7) |
65 (3.5) |
10 (0.5) |
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Moderate |
30 (1.5) |
5 (0.3) |
58 (3.1) |
3 (0.2) |
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Severe |
5 (0.2) |
2 (0.1) |
10 (0.5) |
1 (0.1) |
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Swelling |
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Any (>2.0 cm) |
141 (7.0) |
23 (1.2) |
145 (7.8) |
13 (0.7) |
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Mild |
87 (4.3) |
11 (0.6) |
80 (4.3) |
5 (0.3) |
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Moderate |
52 (2.6) |
12 (0.6) |
61 (3.3) |
7 (0.4) |
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Severe |
2 (0.1) |
0 |
4 (0.2) |
1 (0.1) |
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Pain at the injection siteMild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity. |
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Any (>2.0 cm) |
1408 (70.1) |
185 (9.3) |
1230 (66.1) |
143 (7.8) |
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Mild |
1108 (55.2) |
177 (8.9) |
873 (46.9) |
138 (7.5) |
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Moderate |
296 (14.7) |
8 (0.4) |
347 (18.7) |
5 (0.3) |
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Severe |
4 (0.2) |
0 |
10 (0.5) |
0 |
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COMIRNATY
Dose 1 N N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. N for each reaction or use of antipyretic or pain medication was the same, therefore was included in the column header. =2008 n n = Number of participants with the specified reaction. (%) |
Placebo
Dose 1 N =1989 n (%) |
COMIRNATY
Dose 2 N =1860 n (%) |
Placebo
Dose 2 N =1833 n (%) |
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| Notes: Reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after each dose. The only Grade 4 solicited systemic reaction reported in participants 56 years of age and older was fatigue. |
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Fever |
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≥38.0°C |
26 (1.3) |
8 (0.4) |
219 (11.8) |
4 (0.2) |
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≥38.0°C to 38.4°C |
23 (1.1) |
3 (0.2) |
158 (8.5) |
2 (0.1) |
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>38.4°C to 38.9°C |
2 (0.1) |
3 (0.2) |
54 (2.9) |
1 (0.1) |
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>38.9°C to 40.0°C |
1 (0.0) |
2 (0.1) |
7 (0.4) |
1 (0.1) |
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>40.0°C |
0 |
0 |
0 |
0 |
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FatigueMild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity; Grade 4 reactions were defined in the clinical study protocol as emergency room visit or hospitalization for severe fatigue, severe headache, severe chills, severe muscle pain, or severe joint pain. |
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Any |
677 (33.7) |
447 (22.5) |
949 (51.0) |
306 (16.7) |
|
Mild |
415 (20.7) |
281 (14.1) |
391 (21.0) |
183 (10.0) |
|
Moderate |
259 (12.9) |
163 (8.2) |
497 (26.7) |
121 (6.6) |
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Severe |
3 (0.1) |
3 (0.2) |
60 (3.2) |
2 (0.1) |
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Grade 4 |
0 |
0 |
1 (0.1) |
0 |
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Headache |
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Any |
503 (25.0) |
363 (18.3) |
733 (39.4) |
259 (14.1) |
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Mild |
381 (19.0) |
267 (13.4) |
464 (24.9) |
189 (10.3) |
|
Moderate |
120 (6.0) |
93 (4.7) |
256 (13.8) |
65 (3.5) |
|
Severe |
2 (0.1) |
3 (0.2) |
13 (0.7) |
5 (0.3) |
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Chills |
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Any |
130 (6.5) |
69 (3.5) |
435 (23.4) |
57 (3.1) |
|
Mild |
102 (5.1) |
49 (2.5) |
229 (12.3) |
45 (2.5) |
|
Moderate |
28 (1.4) |
19 (1.0) |
185 (9.9) |
12 (0.7) |
|
Severe |
0 |
1 (0.1) |
21 (1.1) |
0 |
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VomitingMild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration; Grade 4 emergency visit or hospitalization for severe vomiting. |
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Any |
10 (0.5) |
9 (0.5) |
13 (0.7) |
5 (0.3) |
|
Mild |
9 (0.4) |
9 (0.5) |
10 (0.5) |
5 (0.3) |
|
Moderate |
1 (0.0) |
0 |
1 (0.1) |
0 |
|
Severe |
0 |
0 |
2 (0.1) |
0 |
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DiarrheaMild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours; Grade 4: emergency room or hospitalization for severe diarrhea. |
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Any |
168 (8.4) |
130 (6.5) |
152 (8.2) |
102 (5.6) |
|
Mild |
137 (6.8) |
109 (5.5) |
125 (6.7) |
76 (4.1) |
|
Moderate |
27 (1.3) |
20 (1.0) |
25 (1.3) |
22 (1.2) |
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Severe |
4 (0.2) |
1 (0.1) |
2 (0.1) |
4 (0.2) |
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New or worsened muscle pain |
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Any |
274 (13.6) |
165 (8.3) |
537 (28.9) |
99 (5.4) |
|
Mild |
183 (9.1) |
111 (5.6) |
229 (12.3) |
65 (3.5) |
|
Moderate |
90 (4.5) |
51 (2.6) |
288 (15.5) |
33 (1.8) |
|
Severe |
1 (0.0) |
3 (0.2) |
20 (1.1) |
1 (0.1) |
|
New or worsened joint pain |
||||
|
Any |
175 (8.7) |
124 (6.2) |
353 (19.0) |
72 (3.9) |
|
Mild |
119 (5.9) |
78 (3.9) |
183 (9.8) |
44 (2.4) |
|
Moderate |
53 (2.6) |
45 (2.3) |
161 (8.7) |
27 (1.5) |
|
Severe |
3 (0.1) |
1 (0.1) |
9 (0.5) |
1 (0.1) |
|
Use of antipyretic or pain medicationSeverity was not collected for use of antipyretic or pain medication. |
382 (19.0) |
224 (11.3) |
688 (37.0) |
170 (9.3) |
In participants with chronic, stable HIV infection the frequencies of solicited local and systemic adverse reactions were similar to or lower than those observed for all participants 16 years of age and older.
Unsolicited Adverse Events
Overall, 11,253 (51.1%) participants in the COMIRNATY group and 11,316 (51.4%) participants in the placebo group had follow-up time between ≥4 months to <6 months after Dose 2 in the blinded placebo-controlled follow-up period with an additional 1,778 (8.1%) and 1,304 (5.9%) with ≥6 months of blinded follow-up time in the COMIRNATY and placebo groups, respectively.
A total of 12,006 (54.5%) participants originally randomized to COMIRNATY had ≥6 months total (blinded and unblinded) follow-up after Dose 2.
In an analysis of all unsolicited adverse events reported following any dose, through 1 month after Dose 2, in participants 16 years of age and older (N=43,847; 21,926 COMIRNATY group vs. 21,921 placebo group), those assessed as adverse reactions not already captured by solicited local and systemic reactions were nausea (274 vs. 87), malaise (130 vs. 22), lymphadenopathy (83 vs. 7), asthenia (76 vs. 25), decreased appetite (39 vs. 9), hyperhidrosis (31 vs. 9), lethargy (25 vs. 6), and night sweats (17 vs. 3).
In analyses of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date, 58.2% of study participants had at least 4 months of follow-up after Dose 2. Among participants 16 through 55 years of age who received at least 1 dose of study vaccine, 12,995 of whom received COMIRNATY and 13,026 of whom received placebo, unsolicited adverse events were reported by 4,396 (33.8%) participants in the COMIRNATY group and 2,136 (16.4%) participants in the placebo group. In a similar analysis in participants 56 years of age and older that included 8,931 COMIRNATY recipients and 8,895 placebo recipients, unsolicited adverse events were reported by 2,551 (28.6%) participants in the COMIRNATY group and 1,432 (16.1%) participants in the placebo group. Among participants with confirmed stable HIV infection that included 100 COMIRNATY recipients and 100 placebo recipients, unsolicited adverse events were reported by 29 (29%) participants in the COMIRNATY group and 15 (15%) participants in the placebo group. The higher frequency of reported unsolicited adverse events among COMIRNATY recipients compared to placebo recipients was primarily attributed to events that are consistent with adverse reactions solicited among participants in the reactogenicity subset (Table 3 and Table 4).
Throughout the placebo-controlled safety follow-up period, Bell's palsy (facial paralysis) was reported by 4 participants in the COMIRNATY group and 2 participants in the placebo group. Onset of facial paralysis was Day 37 after Dose 1 (participant did not receive Dose 2) and Days 3, 9, and 48 after Dose 2. In the placebo group the onset of facial paralysis was Day 32 and Day 102. Currently available information is insufficient to determine a causal relationship with the vaccine. In the analysis of blinded, placebo-controlled follow-up, there were no other notable patterns or numerical imbalances between treatment groups for specific categories of non-serious adverse events (including other neurologic or neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.
Serious Adverse Events
In Study 2, among participants 16 through 55 years of age who had received at least 1 dose of vaccine or placebo (COMIRNATY =12,995; placebo = 13,026), serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 103 (0.8%) COMIRNATY recipients and 117 (0.9%) placebo recipients. In a similar analysis, in participants 56 years of age and older (COMIRNATY = 8,931; placebo = 8,895), serious adverse events were reported by 165 (1.8%) COMIRNATY recipients and 151 (1.7%) placebo recipients who received at least 1 dose of COMIRNATY or placebo, respectively. In these analyses, 58.2% of study participants had at least 4 months of follow-up after Dose 2. Among participants with confirmed stable HIV infection serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 2 (2%) COMIRNATY recipients and 2 (2%) placebo recipients.
In the analysis of blinded, placebo-controlled follow-up, there were no notable patterns between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of serious adverse events that would suggest a causal relationship to COMIRNATY.
Adolescents 12 Through 15 Years of Age
In Study 2, 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 through 15 years of age. At the time of the analysis of the ongoing Study 2 with a data cutoff of September 2, 2021, there were 1,559 (69.0%) adolescents (786 COMIRNATY and 773 placebo) 12 through 15 years of age followed for ≥4 months after the second dose. The safety evaluation in Study 2 is ongoing.
Demographic characteristics in Study 2 were generally similar with regard to age, gender, race, and ethnicity among adolescents who received COMIRNATY and those who received placebo. Overall, among the adolescents who received COMIRNATY, 50.1% were male and 49.9% were female, 85.8% were White, 4.6% were Black or African American, 11.7% were Hispanic/Latino, 6.4% were Asian, and 0.4% were American Indian/Alaska Native.
Local and Systemic Adverse Reactions Solicited in Study 2
In adolescents 12 through 15 years of age after receiving Dose 2, the mean duration of pain at the injection site was 2.5 days (range 1 to 11 days), for redness 1.8 days (range 1 to 5 days), and for swelling 1.6 days (range 1 to 5 days) in the COMIRNATY group.
|
COMIRNATY
Dose 1 N N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. =1127 n n = Number of participants with the specified reaction. (%) |
Placebo
Dose 1 N =1127 n (%) |
COMIRNATY
Dose 2 N =1097 n (%) |
Placebo
Dose 2 N =1078 n (%) |
|
|---|---|---|---|---|
| Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. | ||||
|
RednessMild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm. |
||||
|
Any (>2 cm) |
65 (5.8) |
12 (1.1) |
55 (5.0) |
10 (0.9) |
|
Mild |
44 (3.9) |
11 (1.0) |
29 (2.6) |
8 (0.7) |
|
Moderate |
20 (1.8) |
1 (0.1) |
26 (2.4) |
2 (0.2) |
|
Severe |
1 (0.1) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
Swelling |
||||
|
Any (>2 cm) |
78 (6.9) |
11 (1.0) |
54 (4.9) |
6 (0.6) |
|
Mild |
55 (4.9) |
9 (0.8) |
36 (3.3) |
4 (0.4) |
|
Moderate |
23 (2.0) |
2 (0.2) |
18 (1.6) |
2 (0.2) |
|
Severe |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
Pain at the injection siteMild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity. |
||||
|
Any |
971 (86.2) |
263 (23.3) |
866 (78.9) |
193 (17.9) |
|
Mild |
467 (41.4) |
227 (20.1) |
466 (42.5) |
164 (15.2) |
|
Moderate |
493 (43.7) |
36 (3.2) |
393 (35.8) |
29 (2.7) |
|
Severe |
11 (1.0) |
0 (0.0) |
7 (0.6) |
0 (0.0) |
|
COMIRNATY
Dose 1 N N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose. =1127 n n = Number of participants with the specified reaction. (%) |
Placebo
Dose 1 N =1127 n (%) |
COMIRNATY
Dose 2 N =1097 n (%) |
Placebo
Dose 2 N =1078 n (%) |
|
|---|---|---|---|---|
| Note: Events and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from Day 1 to Day 7 after each dose. | ||||
|
Fever |
||||
|
≥38.0℃ |
114 (10.1) |
12 (1.1) |
215 (19.6) |
7 (0.6) |
|
≥38.0℃ to 38.4℃ |
74 (6.6) |
8 (0.7) |
107 (9.8) |
5 (0.5) |
|
>38.4℃ to 38.9℃ |
29 (2.6) |
2 (0.2) |
83 (7.6) |
1 (0.1) |
|
>38.9℃ to 40.0℃ |
10 (0.9) |
2 (0.2) |
25 (2.3) |
1 (0.1) |
|
>40.0℃ |
1 (0.1) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
FatigueMild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity. |
||||
|
Any |
677 (60.1) |
457 (40.6) |
726 (66.2) |
264 (24.5) |
|
Mild |
278 (24.7) |
250 (22.2) |
232 (21.1) |
133 (12.3) |
|
Moderate |
384 (34.1) |
199 (17.7) |
468 (42.7) |
127 (11.8) |
|
Severe |
15 (1.3) |
8 (0.7) |
26 (2.4) |
4 (0.4) |
|
Headache |
||||
|
Any |
623 (55.3) |
396 (35.1) |
708 (64.5) |
264 (24.5) |
|
Mild |
361 (32.0) |
256 (22.7) |
302 (27.5) |
170 (15.8) |
|
Moderate |
251 (22.3) |
131 (11.6) |
384 (35.0) |
93 (8.6) |
|
Severe |
11 (1.0) |
9 (0.8) |
22 (2.0) |
1 (0.1) |
|
Chills |
||||
|
Any |
311 (27.6) |
109 (9.7) |
455 (41.5) |
74 (6.9) |
|
Mild |
195 (17.3) |
82 (7.3) |
221 (20.1) |
53 (4.9) |
|
Moderate |
111 (9.8) |
25 (2.2) |
214 (19.5) |
21 (1.9) |
|
Severe |
5 (0.4) |
2 (0.2) |
20 (1.8) |
0 (0.0) |
|
VomitingMild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration. |
||||
|
Any |
31 (2.8) |
10 (0.9) |
29 (2.6) |
12 (1.1) |
|
Mild |
30 (2.7) |
8 (0.7) |
25 (2.3) |
11 (1.0) |
|
Moderate |
0 (0.0) |
2 (0.2) |
4 (0.4) |
1 (0.1) |
|
Severe |
1 (0.1) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
DiarrheaMild: 2 to 3 loose stools in 24 hours; Moderate: 4 to 5 loose stools in 24 hours; Severe: 6 or more loose stools in 24 hours. |
||||
|
Any |
90 (8.0) |
82 (7.3) |
65 (5.9) |
44 (4.1) |
|
Mild |
77 (6.8) |
72 (6.4) |
59 (5.4) |
39 (3.6) |
|
Moderate |
13 (1.2) |
10 (0.9) |
6 (0.5) |
5 (0.5) |
|
Severe |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
New or worsened muscle pain |
||||
|
Any |
272 (24.1) |
148 (13.1) |
355 (32.4) |
90 (8.3) |
|
Mild |
125 (11.1) |
88 (7.8) |
152 (13.9) |
51 (4.7) |
|
Moderate |
145 (12.9) |
60 (5.3) |
197 (18.0) |
37 (3.4) |
|
Severe |
2 (0.2) |
0 (0.0) |
6 (0.5) |
2 (0.2) |
|
New or worsened joint pain |
||||
|
Any |
109 (9.7) |
77 (6.8) |
173 (15.8) |
51 (4.7) |
|
Mild |
66 (5.9) |
50 (4.4) |
91 (8.3) |
30 (2.8) |
|
Moderate |
42 (3.7) |
27 (2.4) |
78 (7.1) |
21 (1.9) |
|
Severe |
1 (0.1) |
0 (0.0) |
4 (0.4) |
0 (0.0) |
|
Use of antipyretic or pain medicationSeverity was not collected for use of antipyretic or pain medication. |
413 (36.6) |
111 (9.8) |
557 (50.8) |
95 (8.8) |
Unsolicited Adverse Events
In Study 2, 2,260 adolescents (1,131 COMIRNATY; 1,129 placebo) were 12 through 15 years of age. Of these, 634 (56.1%) participants in the COMIRNATY group and 629 (55.7%) participants in the placebo group had follow-up time between ≥4 months to <6 months after Dose 2 in the blinded placebo-controlled follow-up period with an additional 152 (13.4%) and 144 (12.8%) with ≥6 months of blinded follow-up time in the COMIRNATY and placebo groups, respectively.
A total of 1,113 (98.4%) participants 12 through 15 years of age originally randomized to COMIRNATY had ≥6 months total (blinded and unblinded) follow-up after Dose 2.
An analysis of all unsolicited adverse events in Study 2 from Dose 1 up to the participant unblinding date was conducted. Among participants 12 through 15 years of age who received at least one dose of study vaccine, unsolicited adverse events were reported by 95 (8.4%) participants in the COMIRNATY group and 113 (10.0%) participants in the placebo group.
In an analysis of all unsolicited adverse events reported during blinded follow-up from Dose 1 through 1 month after Dose 2, in adolescents 12 to 15 years of age, those assessed as adverse reactions not already captured by solicited local and systemic reactions were lymphadenopathy (9 vs. 2), and nausea (5 vs. 2).
In the analysis of blinded, placebo-controlled follow-up, there were no other notable patterns or numerical imbalances between treatment groups for specific categories of unsolicited adverse events (including other neurologic or neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of non-serious adverse events that would suggest a causal relationship to COMIRNATY.
Serious Adverse Events
In Study 2, among participants 12 through 15 years of age who had received at least 1 dose of vaccine or placebo (COMIRNATY = 1,131; placebo = 1,129), serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up were reported by 10 (0.9%) COMIRNATY recipients and 2 (0.2%) placebo recipients. In these analyses, 69.0% of study participants had at least 4 months of follow-up after Dose 2. In the analysis of blinded, placebo-controlled follow-up, there were no notable patterns between treatment groups for specific categories of serious adverse events (including neurologic, neuro-inflammatory, and thrombotic events) that would suggest a causal relationship to COMIRNATY. In the analysis of unblinded follow-up, there were no notable patterns of specific categories of serious adverse events that would suggest a causal relationship to COMIRNATY.
6.2 Postmarketing Experience
The following adverse reactions have been identified during postmarketing use of COMIRNATY, including under Emergency Use Authorization. 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
Gastrointestinal Disorders: diarrhea, vomiting
Immune System Disorders: severe allergic reactions, including anaphylaxis, and other hypersensitivity reactions (e.g., rash, pruritus, urticaria, angioedema)
Musculoskeletal and Connective Tissue Disorders: pain in extremity (arm)
Nervous System Disorders: syncope, dizziness
8 USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to COMIRNATY during pregnancy. Women who are vaccinated with COMIRNATY during pregnancy are encouraged to enroll in the registry by visiting https://mothertobaby.org/ongoing-study/covid19-vaccines/.
Risk Summary
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 COMIRNATY administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.
A developmental toxicity study has been performed in female rats administered the equivalent of a single human dose of COMIRNATY on 4 occasions, twice prior to mating and twice during gestation. These studies revealed no evidence of harm to the fetus due to the vaccine (see Animal Data).
Data
Animal Data
In a developmental toxicity study, 0.06 mL of a vaccine formulation containing the same quantity of nucleoside-modified messenger ribonucleic acid (mRNA) (30 mcg) and other ingredients included in a single human dose of COMIRNATY was administered to female rats by the intramuscular route on 4 occasions: 21 and 14 days prior to mating, and on gestation days 9 and 20. No vaccine-related adverse effects on female fertility, fetal development, or postnatal development were reported in the study.
8.2 Lactation
Risk Summary
It is not known whether COMIRNATY is excreted in human milk. Data are not available to assess the effects of COMIRNATY 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 COMIRNATY and any potential adverse effects on the breastfed child from COMIRNATY or from the underlying maternal condition. For preventive vaccines, the underlying maternal condition is susceptibility to disease prevented by the vaccine.
8.4 Pediatric Use
Safety and effectiveness of COMIRNATY in individuals 12 through 17 years of age is based on safety and effectiveness data in this age group and in adults [see Adverse Reactions (6) and Clinical Studies (14.1)].
The safety and effectiveness of COMIRNATY in individuals younger than 12 years of age have not been established.
8.5 Geriatric Use
Of the total number of COMIRNATY recipients in Study 2 as of March 13, 2021 (N = 22,026), 20.7% (n = 4,552) were 65 years of age and older and 4.2% (n = 925) were 75 years of age and older [see Clinical Studies (14.1)]. No overall differences in safety or effectiveness were observed between these recipients and younger recipients.
11 DESCRIPTION
COMIRNATY (COVID-19 Vaccine, mRNA) is a sterile suspension for injection for intramuscular use. Each 0.3 mL dose of COMIRNATY contains 30 mcg of a nucleoside-modified messenger RNA (mRNA) encoding the viral spike (S) glycoprotein of SARS-CoV-2.
Each 0.3 mL dose of COMIRNATY supplied in vials with gray caps and labels with gray borders also includes the following ingredients: lipids (0.43 mg ((4-hydroxybutyl)azanediyl)bis(hexane-6,1-diyl)bis(2-hexyldecanoate), 0.05 mg 2-(polyethylene glycol 2000)-N,N-ditetradecylacetamide, 0.09 mg 1,2-distearoyl-sn-glycero-3-phosphocholine, and 0.19 mg cholesterol), 0.06 mg tromethamine, 0.4 mg tromethamine hydrochloride, and 31 mg sucrose.
COMIRNATY does not contain preservative.
The vial stoppers are not made with natural rubber latex.
12 CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
The nucleoside-modified mRNA in COMIRNATY is formulated in lipid particles, which enable delivery of the mRNA into host cells to allow expression of the SARS-CoV-2 S antigen. The vaccine elicits an immune response to the S antigen, which protects against COVID-19.
13 NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
COMIRNATY has not been evaluated for the potential to cause carcinogenicity, genotoxicity, or impairment of male fertility. In a developmental toxicity study in rats with COMIRNATY there were no vaccine-related effects on female fertility [see Use in Specific Populations (8.1)].
14 CLINICAL STUDIES
14.1 Efficacy in Participants 16 Years of Age and Older
Study 2 is an ongoing, multicenter, multinational, randomized, placebo-controlled, observer-blind, dose-finding, vaccine candidate–selection, and efficacy study in participants 12 years of age and older. Randomization was stratified by age: 12 through 15 years of age, 16 through 55 years of age, or 56 years of age and older, with a minimum of 40% of participants in the ≥56-year stratum. The study excluded participants who were immunocompromised and those who had previous clinical or microbiological diagnosis of COVID-19. Participants with preexisting stable disease, defined as disease not requiring significant change in therapy or hospitalization for worsening disease during the 6 weeks before enrollment, were included as were participants with known stable infection with HIV, hepatitis C virus (HCV), or hepatitis B virus (HBV).
In Study 2, based on data accrued through March 13, 2021, approximately 44,000 participants 12 years of age and older were randomized equally and received 2 doses of COMIRNATY or placebo. Participants are planned to be followed for up to 24 months, for assessments of safety and efficacy against COVID-19.
Overall, among the total participants who received COMIRNATY or placebo, 51.4% or 50.3% were male and 48.6% or 49.7% were female, 79.1% or 79.2% were 16 through 64 years of age, 20.9% or 20.8% were 65 years of age and older, 81.9% or 82.1% were White, 9.5% or 9.6% were Black or African American, 1.0% or 0.9% were American Indian or Alaska Native, 4.4% or 4.3% were Asian, 0.3% or 0.2% Native Hawaiian or other Pacific Islander, 25.6% or 25.4% were Hispanic/Latino, 73.9% or 74.1% were non-Hispanic/Latino, 0.5% or 0.5% did not report ethnicity, 46.0% or 45.7% had comorbidities [participants who have 1 or more comorbidities that increase the risk of severe COVID-19 disease: defined as subjects who had at least 1 of the Charlson comorbidity index category or body mass index (BMI) ≥30 kg/m2], respectively. The mean age at vaccination was 49.8 or 49.7 years and median age was 51.0 or 51.0 in participants who received COMIRNATY or placebo, respectively.
Efficacy Against COVID-19
The population for the analysis of the protocol pre-specified primary efficacy endpoint included 36,621 participants 12 years of age and older (18,242 in the COMIRNATY group and 18,379 in the placebo group) who did not have evidence of prior infection with SARS-CoV-2 through 7 days after the second dose. The population in the protocol pre-specified primary efficacy analysis included all participants 12 years of age and older who had been enrolled from July 27, 2020, and followed for the development of COVID-19 through November 14, 2020. Participants 18 through 55 years of age and 56 years of age and older began enrollment from July 27, 2020, 16 through 17 years of age began enrollment from September 16, 2020, and 12 through 15 years of age began enrollment from October 15, 2020.
For participants without evidence of SARS-CoV-2 infection prior to 7 days after Dose 2, vaccine efficacy against confirmed COVID-19 occurring at least 7 days after Dose 2 was 95.0% (95% credible interval: 90.3, 97.6), which met the pre-specified success criterion. The case split was 8 COVID-19 cases in the COMIRNATY group compared to 162 COVID-19 cases in the placebo group.
The population for the updated vaccine efficacy analysis included participants 16 years of age and older who had been enrolled from July 27, 2020, and followed for the development of COVID-19 during blinded placebo-controlled follow-up through March 13, 2021, representing up to 6 months of follow-up after Dose 2. There were 12,796 (60.8%) participants in the COMIRNATY group and 12,449 (58.7%) in the placebo group followed for ≥4 months after Dose 2 in the blinded placebo-controlled follow-up period.
SARS-CoV-2 variants of concern identified from COVID-19 cases for this age group from this data cutoff include B.1.1.7 (Alpha) and B.1.351 (Beta). Representation of identified variants among cases in vaccine versus placebo recipients did not suggest decreased vaccine effectiveness against these variants.
The updated vaccine efficacy information is presented in Table 7.
| Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting). | |||
|
First COVID-19 occurrence from 7 days after Dose 2 in participants without evidence of prior SARS-CoV-2 infection Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis. |
|||
|
Subgroup |
COMIRNATY
|
Placebo
Cases n1 Surveillance Time (n2 ) |
Vaccine Efficacy %
|
|
All participants |
77 |
833 |
91.1 |
|
16 through 64 years |
70 |
709 |
90.5 |
|
65 years and older |
7 |
124 |
94.5 |
|
First COVID-19 occurrence from 7 days after Dose 2 in participants with or without evidence of prior SARS-CoV-2 infection |
|||
|
Subgroup |
COMIRNATY
Cases n1 Surveillance Time (n2 ) |
Placebo
Cases n1 Surveillance Time (n2 ) |
Vaccine Efficacy %
|
|
All participants |
81 |
854 |
90.9 |
|
16 through 64 years |
74 |
726 |
90.2 |
|
65 years and older |
7 |
128 |
94.7 |
Subgroup analyses of vaccine efficacy (although limited by small numbers of cases in some subgroups) did not suggest meaningful differences in efficacy across genders, ethnic groups, geographies, or for participants with obesity or medical comorbidities associated with high risk of severe COVID-19.
Efficacy Against Severe COVID-19
Efficacy analyses of secondary efficacy endpoints supported benefit of COMIRNATY in preventing severe COVID-19. Vaccine efficacy against severe COVID-19 is presented only for participants with or without prior SARS-CoV-2 infection (Table 8) as the COVID-19 case counts in participants without prior SARS-CoV-2 infection were the same as those in participants with or without prior SARS-CoV-2 infection in both the COMIRNATY and placebo groups.
| Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting). | |||
|
Vaccine Efficacy – First Severe COVID-19 Occurrence |
|||
|
COMIRNATY
|
Placebo
Surveillance Time (n2 ) |
Vaccine Efficacy %
|
|
|
7 days after Dose 2 |
1 |
21 |
95.3 |
|
Vaccine Efficacy – First Severe COVID-19 Occurrence Based on CDC Definition |
|||
|
COMIRNATY
Surveillance Time (n2 ) |
Placebo
Surveillance Time (n2 ) |
Vaccine Efficacy %
|
|
|
7 days after Dose 2 |
0 |
31 |
100 |
14.2 Efficacy in Adolescents 12 Through 15 Years of Age
A descriptive efficacy analysis of Study 2 has been performed in 2,260 adolescents 12 through 15 years of age evaluating confirmed COVID-19 cases accrued up to a data cutoff date of September 2, 2021.
The vaccine efficacy information in adolescents 12 through 15 years of age is presented in Table 9.
| Note: Confirmed cases were determined by Reverse Transcription-Polymerase Chain Reaction (RT-PCR) and at least 1 symptom consistent with COVID-19 (symptoms included: fever; new or increased cough; new or increased shortness of breath; chills; new or increased muscle pain; new loss of taste or smell; sore throat; diarrhea; vomiting). | |||
|
First COVID-19 occurrence from 7 days after Dose 2 in adolescents 12 through 15 years of age without evidence of prior SARS-CoV-2 infection Participants who had no evidence of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit prior to 7 days after Dose 2 were included in the analysis. |
|||
|
COMIRNATY
|
Placebo
Cases n1 Surveillance Time (n2 ) |
Vaccine Efficacy %
|
|
|
Adolescents |
0 |
28 |
100.0 |
|
First COVID-19 occurrence from 7 days after Dose 2 in adolescents 12 through 15 years of age with or without evidence of prior SARS-CoV-2 infection |
|||
|
COMIRNATY
Cases n1 Surveillance Time (n2 ) |
Placebo
Cases n1 Surveillance Time (n2 ) |
Vaccine Efficacy %
|
|
|
Adolescents |
0 |
30The only SARS-CoV-2 variant of concern identified from COVID-19 cases in this age group from this data cutoff was B.1.1.7 (Alpha).
|
100.0 |
14.3 Immunogenicity in Adolescents 12 Through 15 Years of Age
In Study 2, an analysis of SARS-CoV-2 50% neutralizing titers (NT50) 1 month after Dose 2 in a randomly selected subset of participants demonstrated non-inferior immune responses (within 1.5-fold) comparing adolescents 12 through 15 years of age to participants 16 through 25 years of age who had no serological or virological evidence of past SARS-CoV-2 infection up to 1 month after Dose 2 (Table 10).
| Abbreviations: CI = confidence interval; GMR = geometric mean ratio; GMT = geometric mean titer; LLOQ = lower limit of quantitation; NAAT = nucleic-acid amplification test; NT50 = 50% neutralizing titer; SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. | ||||||
| Note: Participants who had no serological or virological evidence (up to 1 month after receipt of the last dose) of past SARS-CoV-2 infection (i.e., N-binding antibody [serum] negative at Visit 1 and SARS-CoV-2 not detected by NAAT [nasal swab] at Visits 1 and 2), and had negative NAAT (nasal swab) at any unscheduled visit up to 1 month after Dose 2 were included in the analysis. | ||||||
|
COMIRNATY |
||||||
|
12 Through 15 Years
|
16 Through 25 Years
|
12 Through 15 Years/
|
||||
|
Assay |
Time Point Protocol-specified timing for blood sample collection. |
GMT
GMTs and 2-sided 95% CIs were calculated by exponentiating the mean logarithm of the titers and the corresponding CIs (based on the Student t distribution). Assay results below the LLOQ were set to 0.5 × LLOQ.
|
GMT (95% CI ) |
GMR
GMRs and 2-sided 95% CIs were calculated by exponentiating the mean difference of the logarithms of the titers (Group 1 [12 through 15 years of age] – Group 2 [16 through 25 years of age]) and the corresponding CI (based on the Student t distribution).
|
Met Noninferiority Objective
Noninferiority is declared if the lower bound of the 2-sided 95% CI for the GMR is greater than 0.67.
|
|
|
SARS-CoV-2 neutralization assay - NT50 (titer)SARS-CoV-2 NT50 were determined using the SARS-CoV-2 mNeonGreen Virus Microneutralization Assay. The assay uses a fluorescent reporter virus derived from the USA_WA1/2020 strain and virus neutralization is read on Vero cell monolayers. The sample NT50 is defined as the reciprocal serum dilution at which 50% of the virus is neutralized. |
1 month after Dose 2 |
1253.6 |
708.1 |
1.77 |
Y |
|
16 HOW SUPPLIED/STORAGE AND HANDLING
Single Dose Vials: COMIRNATY is a suspension for intramuscular injection. Single dose vials with gray caps and labels with gray borders are supplied in a carton containing 10 single dose vials. One vial contains 1 dose of 0.3 mL.
- Carton of 10 single dose vials: NDC 0069-3125-10
- Single dose vial: NDC 0069-3125-01
Multiple Dose Vials: COMIRNATY is a suspension for intramuscular injection. Multiple dose vials with gray caps and labels with gray borders are supplied in a carton containing 10 multiple dose vials or 25 multiple dose vials.
One vial contains 6 doses of 0.3 mL.
- Carton of 10 multiple dose vials: NDC 0069-2025-10
- Carton of 25 multiple dose vials: NDC 0069-2025-25
- Multiple dose vial: NDC 0069-2025-01
During storage, minimize exposure to room light, and avoid exposure to direct sunlight and ultraviolet light.
Do not refreeze thawed vials.
Vial Storage Prior to Use
Cartons of COMIRNATY single dose vials and multiple dose vials with gray caps and labels with gray borders will arrive frozen at ultra-cold conditions in thermal containers with dry ice.
Once received, frozen vials may be immediately transferred to the refrigerator [2°C to 8°C (35°F to 46°F)], thawed and stored for up to 10 weeks. The 10-week refrigerated expiry date should be recorded on the carton at the time of transfer. A carton of 10 single dose vials may take up to 2 hours to thaw at this temperature. A carton of 10 multiple dose vials may take up to 6 hours to thaw at this temperature.
Alternatively, frozen vials may be stored in an ultra-low temperature freezer at -90°C to -60°C (-130°F to -76°F). Do not store vials at -25°C to -15°C (-13°F to 5°F). Once vials are thawed, they should not be refrozen.
If cartons of COMIRNATY single dose vials or multiple dose vials with gray caps and labels with gray borders are received at 2°C to 8°C, they should be stored at 2°C to 8°C. Check that the carton has been updated to reflect the 10-week refrigerated expiry date.
Regardless of storage condition, the vaccine should not be used after the expiration date printed on the vial and cartons.
Vial Storage During Use
If not previously thawed at 2°C to 8°C (35°F to 46°F), allow COMIRNATY single dose vials and multiple dose vials to thaw at room temperature [up to 25°C (77°F)] for 30 minutes.
DO NOT DILUTE SINGLE DOSE VIALS OR MULTIPLE DOSE VIALS PRIOR TO USE.
COMIRNATY single dose vials and multiple dose vials with gray caps and labels with gray borders may be stored at room temperature [8°C to 25°C (46°F to 77°F)] for a total of 12 hours prior to the first puncture. After first puncture, multiple dose vials should be held between 2°C to 25°C (35°F to 77°F). Multiple dose vials should be discarded 12 hours after first puncture.
Transportation of Vials
If local redistribution is needed, single dose vials and multiple dose vials may be transported at -90°C to -60°C (-130°F to -76°F), or at 2°C to 8°C (35°F to 46°F).