Description for Comirnaty
COMIRNATY (COVID-19 Vaccine, mRNA) is a sterile suspension for injection for intramuscular use. COMIRNATY is supplied as a frozen suspension in multiple dose vials; each vial must be diluted with 1.8 mL of sterile 0.9% Sodium Chloride Injection, USP prior to use to form the vaccine. Each 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 the COMIRNATY 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 0.2 mg cholesterol), 0.01 mg potassium chloride, 0.01 mg monobasic potassium phosphate, 0.36 mg sodium chloride, 0.07 mg dibasic sodium phosphate dihydrate, and 6 mg sucrose. The diluent (0.9% Sodium Chloride Injection, USP) contributes an additional 2.16 mg sodium chloride per dose.
COMIRNATY does not contain preservative.
The vial stoppers are not made with natural rubber latex.
ADVERSE REACTIONS
An overview of clinical studies contributing to the safety assessment of COMIRNATY is provided in Table 1 and Table 2. Participants in these clinical studies received a single dose or a 2-dose series administered 3 weeks apart (referred to as a primary series) and subsequent doses referred to as booster doses.
Table 1: Clinical Studies — Adults and Adolescents 12 Years of Age and Older
|
Study |
Age Group |
Vaccine Strain Composition |
Dosing |
Number of Participants |
|
Primary Series |
||||
|
Study 1 (NCT04380701) |
18 through 55 years of age |
Originala |
Primary series |
60 |
|
Study 2 (NCT04368728) |
16 years of age and older |
Originala |
Primary series |
22,026b |
|
12 through 15 years of age |
Originala |
Primary series |
1,131b |
|
|
Booster Dose |
||||
|
Study 4 (NCT04955626) |
16 years of age and older |
Originala |
1st booster |
5,081b |
|
Study 2 (NCT04368728) |
18 through 55 years of age |
Originala |
1st booster |
306 |
|
Study 4 (NCT04955626) |
12 through 17 years of age |
Originala |
1st booster |
65 |
|
Study 2 (NCT04368728) |
12 through 15 years of age |
Originala |
1st booster |
825 |
|
Study 5 (NCT05472038) |
12 years of age and older |
Original and Omicron BA.4/BA.5c |
2nd booster |
726 |
|
Concomitant Administration |
||||
|
Study 8 (NCT05310084) |
18 through 64 years of age |
Originala |
2nd booster administered alone or concomitantly with Influenza Vaccined |
1,128 |
|
Abbreviation: SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. |
||||
Table 2: Clinical Studies — Children 5 Years Through 11 Years of Age
|
Study |
Age Group |
Vaccine Strain Composition |
Dosing |
Number of Participants |
|
Primary Series |
||||
|
Study 3 (NCT04816643) |
5 through 11 years of age |
Originala |
Primary series |
3,109b |
|
Booster Dose |
||||
|
Study 3 (NCT04816643) |
5 through 11 years of age |
Originala |
1st booster |
2,408 |
|
Study 6 (NCT05543616) |
5 through 11 years of age |
Original and Omicron BA.4/BA.5c |
2nd booster |
113 |
|
Single Dose |
||||
|
Study 6 (NCT05543616) |
5 through 11 years of age |
Omicron XBB.1.5d |
Single dose |
310 |
|
Abbreviation: SARS-CoV-2 = severe acute respiratory syndrome coronavirus 2. |
||||
Participants 12 years of age and older: The most commonly reported adverse reactions (≥10%) after a dose of COMIRNATY were pain at the injection site (up to 90.5%), fatigue (up to 77.5%), headache (up to 75.5%), chills (up to 49.2%), muscle pain (up to 45.5%), joint pain (up to 27.5%), fever (up to 24.3%), injection site swelling (up to 11.8%), and injection site redness (up to 10.4%).
Participants 5 years through 11 years of age: The most commonly reported adverse reactions (≥5%) following any dose were pain at the injection site (up to 83.8%), fatigue (up to 51.9%), headache (up to 38.4%), injection site redness (up to 25.9%), injection site swelling (up to 20.0%), muscle pain (up to 18.1%), chills (up to 13.3%), fever (up to 7.8%), and joint pain (up to 7.6%).
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.
Adults and Adolescents 12 Years of Age and Older
Two-Dose Series (Original Monovalent) in Vaccine-Naïve Individuals 16 Years of Age and Older
The safety of a 2-dose primary series 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 2 was a Phase 1/2/3 multicenter, randomized, saline placebo-controlled, double-blinded (Phase 2/3), dose-finding, vaccine candidate-selection and efficacy study that enrolled approximately 44,000 participants 16 years of age or older (22,026 COMIRNATY; 22,021 placebo).
Study 2 included 200 participants with confirmed stable human immunodeficiency virus (HIV) infection. 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. HIV-positive participants are included in the safety population but are summarized separately in the safety analyses.
In Study 2, participants 16 years and older in the reactogenicity subset were monitored using an electronic diary for solicited local and systemic reactions and use of antipyretic medication after each vaccination. Participants were also monitored for unsolicited adverse events throughout the study (from Dose 1 through 1 month [all unsolicited adverse events] or through 6 months [serious adverse events] after the last vaccination). Tables 3 and 6 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following Dose 1 or Dose 2 of COMIRNATY.
At the time of the analysis of Study 2 with a data cutoff of March 13, 2021, there were 25,651 (58.2%) participants (13,031 COMIRNATY; 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, sex, 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 Solicited Adverse Reactions
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.
Table 3: Study 2 — Frequency and Percentages of Participants With Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose — Participants 16 Through 55 Years of Age — Reactogenicity Subset of the Safety Population*
|
COMIRNATY† |
Placebo |
COMIRNATY† |
Placebo |
|
|
Rednessc |
||||
|
Any (>2.0 cm) |
156 (5.4) |
28 (1.0) |
151 (5.6) |
18 (0.7) |
|
Mild |
113 (3.9) |
19 (0.7) |
90 (3.4) |
12 (0.4) |
|
Moderate |
36 (1.2) |
6 (0.2) |
50 (1.9) |
6 (0.2) |
|
Severe |
7 (0.2) |
3 (0.1) |
11 (0.4) |
0 |
|
Swellingc |
||||
|
Any (>2.0 cm) |
184 (6.3) |
16 (0.6) |
183 (6.8) |
5 (0.2) |
|
Mild |
124 (4.3) |
6 (0.2) |
110 (4.1) |
3 (0.1) |
|
Moderate |
54 (1.9) |
8 (0.3) |
66 (2.5) |
2 (0.1) |
|
Severe |
6 (0.2) |
2 (0.1) |
7 (0.3) |
0 |
|
Pain at the injection sited |
||||
|
Any |
2426 (83.7) |
414 (14.2) |
2101 (78.3) |
312 (11.6) |
|
Mild |
1464 (50.5) |
391 (13.4) |
1274 (47.5) |
284 (10.6) |
|
Moderate |
923 (31.8) |
20 (0.7) |
788 (29.4) |
28 (1.0) |
|
Severe |
39 (1.3) |
3 (0.1) |
39 (1.5) |
0 |
|
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. |
||||
Table 4: Study 2 — Frequency and Percentages of Participants With Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose — Participants 16 Through 55 Years of Age — Reactogenicity Subset of the Safety Population*
|
COMIRNATY† |
Placebo |
COMIRNATY† |
Placebo |
|
|
Fever |
||||
|
≥38.0°C |
119 (4.1) |
25 (0.9) |
440 (16.4) |
11 (0.4) |
|
≥38.0°C to 38.4°C |
86 (3.0) |
16 (0.6) |
254 (9.5) |
5 (0.2) |
|
>38.4°C to 38.9°C |
25 (0.9) |
5 (0.2) |
146 (5.4) |
4 (0.1) |
|
>38.9°C to 40.0°C |
8 (0.3) |
4 (0.1) |
39 (1.5) |
2 (0.1) |
|
>40.0°C |
0 |
0 |
1 (0.0) |
0 |
|
Fatiguec |
||||
|
Any |
1431 (49.4) |
960 (33.0) |
1649 (61.5) |
614 (22.9) |
|
Mild |
760 (26.2) |
570 (19.6) |
558 (20.8) |
317 (11.8) |
|
Moderate |
630 (21.7) |
372 (12.8) |
949 (35.4) |
283 (10.5) |
|
Severe |
41 (1.4) |
18 (0.6) |
142 (5.3) |
14 (0.5) |
|
Headachec |
||||
|
Any |
1262 (43.5) |
975 (33.5) |
1448 (54.0) |
652 (24.3) |
|
Mild |
785 (27.1) |
633 (21.8) |
699 (26.1) |
404 (15.1) |
|
Moderate |
444 (15.3) |
318 (10.9) |
658 (24.5) |
230 (8.6) |
|
Severe |
33 (1.1) |
24 (0.8) |
91 (3.4) |
18 (0.7) |
|
Chillsc |
||||
|
Any |
479 (16.5) |
199 (6.8) |
1015 (37.8) |
114 (4.2) |
|
Mild |
338 (11.7) |
148 (5.1) |
477 (17.8) |
89 (3.3) |
|
Moderate |
126 (4.3) |
49 (1.7) |
469 (17.5) |
23 (0.9) |
|
Severe |
15 (0.5) |
2 (0.1) |
69 (2.6) |
2 (0.1) |
|
Vomitingd |
||||
|
Any |
34 (1.2) |
36 (1.2) |
58 (2.2) |
30 (1.1) |
|
Mild |
29 (1.0) |
30 (1.0) |
42 (1.6) |
20 (0.7) |
|
Moderate |
5 (0.2) |
5 (0.2) |
12 (0.4) |
10 (0.4) |
|
Severe |
0 |
1 (0.0) |
4 (0.1) |
0 |
|
Diarrheae |
||||
|
Any |
309 (10.7) |
323 (11.1) |
269 (10.0) |
205 (7.6) |
|
Mild |
251 (8.7) |
264 (9.1) |
219 (8.2) |
169 (6.3) |
|
Moderate |
55 (1.9) |
58 (2.0) |
44 (1.6) |
35 (1.3) |
|
Severe |
3 (0.1) |
1 (0.0) |
6 (0.2) |
1 (0.0) |
|
New or worsened muscle painc |
||||
|
Any |
664 (22.9) |
329 (11.3) |
1055 (39.3) |
237 (8.8) |
|
Mild |
353 (12.2) |
231 (7.9) |
441 (16.4) |
150 (5.6) |
|
Moderate |
296 (10.2) |
96 (3.3) |
552 (20.6) |
84 (3.1) |
|
Severe |
15 (0.5) |
2 (0.1) |
62 (2.3) |
3 (0.1) |
|
New or worsened joint painc |
||||
|
Any |
342 (11.8) |
168 (5.8) |
638 (23.8) |
147 (5.5) |
|
Mild |
200 (6.9) |
112 (3.9) |
291 (10.9) |
82 (3.1) |
|
Moderate |
137 (4.7) |
55 (1.9) |
320 (11.9) |
61 (2.3) |
|
Severe |
5 (0.2) |
1 (0.0) |
27 (1.0) |
4 (0.1) |
|
Use of antipyretic or pain medicationf |
805 (27.8) |
398 (13.7) |
1213 (45.2) |
320 (11.9) |
|
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. |
||||
Table 5: Study 2 — Frequency and Percentages of Participants With Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose — Participants 56 Years of Age and Older — Reactogenicity Subset of the Safety Population*
|
COMIRNATY† |
Placebo |
COMIRNATY† |
Placebo |
|
|
Rednessc |
||||
|
Any (>2.0 cm) |
106 (5.3) |
20 (1.0) |
133 (7.2) |
14 (0.8) |
|
Mild |
71 (3.5) |
13 (0.7) |
65 (3.5) |
10 (0.5) |
|
Moderate |
30 (1.5) |
5 (0.3) |
58 (3.1) |
3 (0.2) |
|
Severe |
5 (0.2) |
2 (0.1) |
10 (0.5) |
1 (0.1) |
|
Swellingc |
||||
|
Any (>2.0 cm) |
141 (7.0) |
23 (1.2) |
145 (7.8) |
13 (0.7) |
|
Mild |
87 (4.3) |
11 (0.6) |
80 (4.3) |
5 (0.3) |
|
Moderate |
52 (2.6) |
12 (0.6) |
61 (3.3) |
7 (0.4) |
|
Severe |
2 (0.1) |
0 |
4 (0.2) |
1 (0.1) |
|
Pain at the injection sited |
||||
|
Any (>2.0 cm) |
1408 (70.1) |
185 (9.3) |
1230 (66.1) |
143 (7.8) |
|
Mild |
1108 (55.2) |
177 (8.9) |
873 (46.9) |
138 (7.5) |
|
Moderate |
296 (14.7) |
8 (0.4) |
347 (18.7) |
5 (0.3) |
|
Severe |
4 (0.2) |
0 |
10 (0.5) |
0 |
|
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. |
||||
Table 6: Study 2 — Frequency and Percentages of Participants With Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose — Participants 56 Years of Age and Older — Reactogenicity Subset of the Safety Population*
|
COMIRNATY† |
Placebo |
COMIRNATY† |
Placebo |
|
|
Fever |
||||
|
≥38.0°C |
26 (1.3) |
8 (0.4) |
219 (11.8) |
4 (0.2) |
|
≥38.0°C to 38.4°C |
23 (1.1) |
3 (0.2) |
158 (8.5) |
2 (0.1) |
|
>38.4°C to 38.9°C |
2 (0.1) |
3 (0.2) |
54 (2.9) |
1 (0.1) |
|
>38.9°C to 40.0°C |
1 (0.0) |
2 (0.1) |
7 (0.4) |
1 (0.1) |
|
>40.0°C |
0 |
0 |
0 |
0 |
|
Fatiguec |
||||
|
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) |
|
Severe |
3 (0.1) |
3 (0.2) |
60 (3.2) |
2 (0.1) |
|
Grade 4 |
0 |
0 |
1 (0.1) |
0 |
|
Headachec |
||||
|
Any |
503 (25.0) |
363 (18.3) |
733 (39.4) |
259 (14.1) |
|
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) |
|
Chillsc |
||||
|
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 |
|
Vomitingd |
||||
|
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 |
|
Diarrheae |
||||
|
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) |
|
Severe |
4 (0.2) |
1 (0.1) |
2 (0.1) |
4 (0.2) |
|
New or worsened muscle painc |
||||
|
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 painc |
||||
|
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 medicationf |
382 (19.0) |
224 (11.3) |
688 (37.0) |
170 (9.3) |
|
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. |
||||
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 16 years of age and older 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 5 and Table 6).
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
Participants 16 through 55 years of age in Study 2 who had received at least 1 dose of vaccine or placebo (COMIRNATY = 12,995; placebo = 13,026), reported serious adverse events from Dose 1 up to the participant unblinding date in ongoing follow-up as follows: 103 (0.8%) COMIRNATY recipients and 117 (0.9%) placebo recipients. In a similar analysis, in participants 56 years of age and older (8,931 COMIRNATY group and 8,895 placebo group), 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.
Two-Dose Series (Original Monovalent) in Vaccine-Naïve Adolescents 12 Through 15 Years of Age
Study 2 was a Phase 1/2/3 multicenter, randomized, saline placebo-controlled, double-blinded (Phase 2/3), dose-finding, vaccine candidate-selection and efficacy study. 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.
Demographic characteristics in Study 2 were generally similar with regard to age, sex, 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.
In Study 2, participants 12 through 15 years of age in the reactogenicity subset were monitored using an electronic diary for solicited local and systemic reactions and use of antipyretic medication after each vaccination. Participants were also monitored for unsolicited adverse events throughout the study (from Dose 1 through 1 month [all unsolicited adverse events] or through 6 months [serious adverse events] after the last vaccination). Tables 7 through 8 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following Dose 1 or Dose 2 of COMIRNATY.
Local and Systemic Solicited Adverse Reactions
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.
Table 7: Study 2 — Frequency and Percentages of Adolescents With Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose — Adolescents 12 Through 15 Years of Age — Safety Population*
|
COMIRNATY† |
Placebo |
COMIRNATY† |
Placebo |
|
|
Rednessc |
||||
|
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) |
|
Swellingc |
||||
|
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 sited |
||||
|
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) |
|
Note: Reactions were collected in the electronic diary (e-diary) from Day 1 to Day 7 after vaccination. |
||||
Table 8: Study 2 — Frequency and Percentages of Adolescents With Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose — Adolescents 12 Through 15 Years of Age — Safety Population*
|
COMIRNATY† |
Placebo |
COMIRNATY† |
Placebo |
|
|
Fever |
||||
|
≥38.0°C |
114 (10.1) |
12 (1.1) |
215 (19.6) |
7 (0.6) |
|
≥38.0°C to 38.4°C |
74 (6.6) |
8 (0.7) |
107 (9.8) |
5 (0.5) |
|
>38.4°C to 38.9°C |
29 (2.6) |
2 (0.2) |
83 (7.6) |
1 (0.1) |
|
>38.9°C to 40.0°C |
10 (0.9) |
2 (0.2) |
25 (2.3) |
1 (0.1) |
|
>40.0°C |
1 (0.1) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
Fatiguec |
||||
|
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) |
|
Headachec |
||||
|
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) |
|
Chillsc |
||||
|
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) |
|
Vomitingd |
||||
|
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) |
|
Diarrheae |
||||
|
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 painc |
||||
|
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 painc |
||||
|
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 medicationf |
413 (36.6) |
111 (9.8) |
557 (50.8) |
95 (8.8) |
|
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. |
||||
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 1 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.
Single Dose (Original Monovalent) in Vaccine-Experienced Individuals 12 Years of Age and Older
16 Years of Age and Older
In Study 4, a double-blind placebo-controlled booster study, 5,081 participants 16 years of age and older recruited from Study 2 received a booster dose of COMIRNATY 10.8 months (median time, range of 5.0 to 12.6 months) after completing the primary series of COMIRNATY series and had a median follow-up time of 2.9 months based on data up to the cutoff date of February 8, 2022. The median age of participants who received COMIRNATY or placebo was 53.0 years (range 16 through 87 years of age), 49.1% were male and 50.9% were female, 79.0% were White, 14.9% were Hispanic/Latino, 9.2% were Black or African American, 5.5% were Asian, and 1.7% were American Indian/Alaska Native.
Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 141 (2.8%) participants who received a booster dose of COMIRNATY and in 83 (0.4%) participants who received COMIRNATY as a primary series.
18 Years Through 55 Years of Age
A subset of 306 Study 2 Phase 2/3 participants 18 through 55 years of age received a booster dose of COMIRNATY 6.8 months (median time, range 4.8 to 8.0 months) after completing the primary series. These participants had a median follow-up time of 8.3 months up to a data cutoff date of November 22, 2021. Among the 306 participants, the median age was 42 years (range 19 through 55 years of age), 45.8% were male and 54.2% were female, 81.4% were White, 27.8% were Hispanic/Latino, 9.2% were Black or African American, 5.2% were Asian, and 0.7% were American Indian/Alaska Native.
Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 16 (5.2%) of participants who received a booster dose of COMIRNATY and 83 (0.4%) in participants who received COMIRNATY as a primary series.
12 Years Through 17 Years of Age
A subset of 65 Study 4 participants 12 through 17 years of age received a booster dose of COMIRNATY 13.3 months (median time, range 6.5 to 16.9 months) after completing the primary series and had a median follow-up time of 5.6 months up to a data cutoff date of July 14, 2022. The median age of participants was 14 years (range 12 through 17 years of age), 49.2% were male and 50.8% were female, 76.9% were White, 16.9% were Hispanic/Latino, 13.8% were Black or African American, 7.7% were Asian, and 1.5% were American Indian/Alaska Native.
Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. There were no cases of lymphadenopathy reported in participants who received a booster dose of COMIRNATY.
12 Years Through 15 Years of Age
A subset of 825 Study 2 Phase 2/3 participants 12 through 15 years of age received a booster dose of COMIRNATY 11.2 months (median time, range 6.3 to 20.1 months) after completing the primary series and had a median follow-up time of 9.5 months up to a data cutoff date of November 3, 2022. The median age of participants was 14.0 years (range 13 through 15 years of age), 49.3% were male and 50.7% were female, 83.5% were White, 10.8% were Hispanic/Latino, 4.6% were Black or African American, 7.5% were Asian, and 0.4% were American Indian/Alaska Native.
Adverse reactions reported in participants receiving a booster dose of COMIRNATY were similar to those previously observed in participants receiving COMIRNATY as part of the primary series. Lymphadenopathy occurred in 8 (1.0%) participants who received a booster dose of COMIRNATY and in 9 (0.8%) participants who received COMIRNATY as a primary series.
Single Dose (Bivalent Original and BA.4/BA.5) in Vaccine-Experienced Individuals 12 Years of Age and Older
A subset of 107 Study 5 Phase 2/3 participants 12 through 17 years of age, 313 participants 18 through 55 years of age and 306 participants 56 years of age and older previously vaccinated with a 2-dose primary series and 1 booster dose of COMIRNATY, went on to receive a second booster dose with Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
Participants received a second booster dose 11.1 months (median time; range 5.4 to 16.9 months) after receiving the first booster dose and had a median follow-up time of 1.5 months up to a data cutoff date of October 31, 2022. The median age was 48.0 years, 42.7% were male, 57.3% were female, 80.6% were White, 11.4% were Hispanic/Latino, 5.9% were Asian, and 11.4% were Black or African American.
Local and Systemic Solicited Adverse Reactions
Table 9 and Table 10 present the frequency and severity of reported solicited local reactions and systemic reactions, respectively, within 7 days of a second booster dose of Pfizer-BioNTech COVID-19 Vaccine, Bivalent.
In participants 12 years of age and older who received a second booster dose, the mean duration of injection site pain was 2.1 to 2.4 days (range 1 to 11 days), injection site redness was 1.5 to 2.5 days (range 1 to 4 days), and injection site swelling was 1.3 to 1.9 days (range 1 to 4 days), respectively.
Table 9: Study 5 — Frequency and Percentages of Participants With Solicited Local Reactions, by Maximum Severity, Within 7 Days After a Second Booster Dose — Participants 12 Years of Age and Older — Safety Population
|
Pfizer-BioNTech COVID-19 Vaccine, Bivalent* |
|||
|
12 Through 17 Years of Age |
18 Through 55 Years of Age |
56 Years of Age and Older
|
|
|
Rednessc |
|||
|
Any (>2 cm) |
6 (5.6) |
21 (6.8%) |
11 (3.7%) |
|
Mild |
4 (3.7) |
16 (5.2%) |
7 (2.3) |
|
Moderate |
2 (1.9) |
5 (1.6) |
4 (1.3%) |
|
Severe |
0 |
0 |
0 |
|
Swellingc |
|||
|
Any (>2 cm) |
8 (7.5) |
23 (7.4%) |
8 (2.7) |
|
Mild |
6 (5.6) |
19 (6.1%) |
5 (1.7) |
|
Moderate |
2 (1.9) |
4 (1.3) |
3 (1.0) |
|
Severe |
0 |
0 |
0 |
|
Pain at the injection sited |
|||
|
Any |
75 (70.1) |
236 (76.1) |
172 (57.1) |
|
Mild |
45 (42.1) |
178 (57.4) |
147 (48.8) |
|
Moderate |
29 (27.1) |
58 (18.7) |
24 (8.0) |
|
Severe |
1 (0.9) |
0 |
1 (0.3) |
|
Note: Adverse Reactions were collected in the electronic diary (e-diary) from day of vaccination (Day 1) through Day 7 after the study vaccination. |
|||
Table 10: Study 5 — Frequency and Percentages of Participants With Solicited Systemic Adverse Reactions, by Maximum Severity, Within 7 Days After a Second Booster Dose — Participants 12 Years of Age and Older — Safety Population
|
Pfizer-BioNTech COVID-19 Vaccine, Bivalent* |
|||
|
12 Through 17 Years of Age |
18 Through 55 Years of Age |
56 Years of Age and Older |
|
|
Fever |
|||
|
≥38.0°C |
10 (9.3) |
15 (4.9) |
14 (4.7) |
|
≥38.0°C to 38.4°C |
7 (6.5) |
9 (2.9) |
10 (3.3) |
|
>38.4°C to 38.9°C |
2 (1.9) |
6 (1.9) |
3 (1.0) |
|
>38.9°C to 40.0°C |
1 (0.9) |
0 |
0 |
|
>40.0°C |
0 |
0 |
0 |
|
Fatiguec |
|||
|
Any |
72 (67.3) |
189 (61.2) |
116 (38.5) |
|
Mild |
27 (25.2) |
83 (26.9) |
56 (18.6) |
|
Moderate |
45 (42.1) |
100 (32.4) |
56 (18.6) |
|
Severe |
0 |
6 (1.9) |
4 (1.3) |
|
Headachec |
|||
|
Any |
54 (50.5) |
144 (46.6) |
92 (30.7) |
|
Mild |
28 (26.2) |
87 (28.2) |
62 (20.7) |
|
Moderate |
26 (24.3) |
55 (17.8) |
30 (10.0) |
|
Severe |
0 |
2 (0.6) |
0 |
|
Chillsc |
|||
|
Any |
25 (23.4) |
68 (22.0) |
36 (12.0) |
|
Mild |
19 (17.8) |
38 (12.3) |
21 (7.0) |
|
Moderate |
6 (5.6) |
28 (9.1) |
14 (4.7) |
|
Severe |
0 |
2 (0.6) |
1 (0.3) |
|
Vomitingd |
|||
|
Any |
3 (2.8) |
6 (1.9) |
2 (0.7) |
|
Mild |
3 (2.8) |
5 (1.6) |
2 (0.7) |
|
Moderate |
0 |
1 (0.3) |
0 |
|
Severe |
0 |
0 |
0 |
|
Diarrheae |
|||
|
Any |
7 (6.5) |
33 (10.7) |
29 (9.6) |
|
Mild |
7 (6.5) |
27 (8.7) |
23 (7.6) |
|
Moderate |
0 |
5 (1.6) |
6 (2.0) |
|
Severe |
0 |
1 (0.3) |
0 |
|
New or worsened muscle painc |
|||
|
Any |
28 (26.2) |
94 (30.4) |
54 (18.0) |
|
Mild |
12 (11.2) |
47 (15.2) |
30 (10.0) |
|
Moderate |
16 (15.0) |
47 (15.2) |
24 (8.0) |
|
Severe |
0 |
0 |
0 |
|
New or worsened joint painc |
|||
|
Any |
13 (12.1) |
46 (14.9) |
36 (12.0) |
|
Mild |
9 (8.4) |
21 (6.8) |
20 (6.7) |
|
Moderate |
4 (3.7) |
25 (8.1) |
16 (5.3) |
|
Severe |
0 |
0 |
0 |
|
Use of antipyretic or pain medicationf |
36 (33.6) |
105 (34.0) |
74 (24.7) |
|
Note: Adverse reactions and use of antipyretic or pain medication were collected in the electronic diary (e-diary) from day of vaccination (Day 1) through Day 7 after the study vaccination. |
|||
Unsolicited Adverse Events
Among participants 12 years of age and older, unsolicited adverse events were reported by 48 (6.6%) participants who received a second booster dose through 1 month after the booster dose. Lymphadenopathy occurred in 7 (1.0%) participants.
Concomitant Administration of COMIRNATY (Original Monovalent) With Influenza Vaccine in Adults 18 Years Through 64 Years of Age
In Study 8, a Phase 3 study, participants 18 through 64 years of age who received COMIRNATY concomitantly administered with Influenza Vaccine (Afluria Quadrivalent) followed 1 month later by saline placebo (n = 564) were compared to participants who received influenza vaccine with saline placebo followed 1 month later by COMIRNATY (n = 564).
Demographic characteristics in Study 8 among the participants in the concomitant administration and separate administration groups were similar with regard to age, sex, race, and ethnicity. Among the 564 participants in the concomitant administration group, the median age was 39.0 years (range 18 through 64 years of age), 36.9% were male and 63.1% were female, 79.1% were White, 12.9% were Asian, and 0.9% were Hispanic/Latino.
Solicited local and systemic adverse reactions were reported more frequently by participants who received COMIRNATY concomitantly with influenza vaccine, compared to participants who received COMIRNATY alone. The most common adverse reactions reported in the concomitant administration group and after COMIRNATY alone were injection site pain (COMIRNATY injection site) (86.2% and 84.4%, respectively), fatigue (64.0% and 50.8%, respectively), and headache (47.2% and 37.8%, respectively).
Children 5 Years Through 11 Years of Age
Two-Dose Series (Original Monovalent) in Vaccine-Naïve Children 5 Years Through 11 Years of Age
Study 3 is a Phase 1/2/3 multicenter, randomized, dose-finding, open label (Phase 1) and multinational, placebo controlled (saline placebo), observer-blind, immunogenicity and efficacy (Phase 2/3) study that has evaluated 4,695 participants 5 through 11 years of age, of whom 3,109 participants received COMIRNATY and 1,538 participants received placebo in Phase 2/3.
Demographic characteristics were generally similar with regard to age, sex, race, and ethnicity among participants who received COMIRNATY and those who received placebo. Overall, among the 4,647 participants who received at least 1 dose of COMIRNATY or placebo, 51.4% were male and 48.6% were female, 77.5% were White, 6.0% were Black or African American, 17.0% were Hispanic/Latino, 8.1% were Asian, and 0.4% were American Indian/Alaska Native.
In an analysis of Study 3 (Phase 2/3), 4,632 participants 5 through 11 years of age who received a 2-dose primary series [3,100 COMIRNATY; 1,532 placebo] have been followed a median of 1.9 months (range 0.1 to 7.5 months) after the second dose in the blinded placebo-controlled follow-up period up to the cutoff date of May 20, 2022.
In Study 3, participants 5 years through 11 years of age in the reactogenicity subset were monitored using an electronic diary for solicited local and systemic adverse reactions and use of antipyretic medication after each vaccination. Participants were also monitored for unsolicited adverse events throughout the study (from Dose 1 through 1 month [all unsolicited adverse events] or through 6 months [serious adverse events] after the last vaccination). Tables 11 through 12 present the frequency and severity of solicited local and systemic reactions, respectively, within 7 days following Dose 1 or Dose 2 of COMIRNATY.
Solicited Local and Systemic Adverse Reactions
The mean duration of pain at the injection site after Dose 2 was 2.3 days (range 1 to 37 days), for redness 2.0 days (range 1 to 10 days), and for swelling 2.2 days (range 1 to 16 days) for children in the COMIRNATY group in the blinded placebo-controlled follow-up period up to the cutoff date of May 20, 2022.
Table 11: Study 3 — Frequency and Percentages of Participants With Solicited Local Reactions, by Maximum Severity, Within 7 Days After Each Dose — Children 5 Through 11 Years of Age — Safety Population*
|
COMIRNATY± |
Placebo |
COMIRNATY± |
Placebo |
|
|
Rednessc |
||||
|
Any (≥0.5 cm) |
434 (14.0) |
91 (5.9) |
575 (18.8) |
79 (5.2) |
|
Mild |
287 (9.3) |
78 (5.1) |
315 (10.3) |
57 (3.7) |
|
Moderate |
146 (4.7) |
11 (0.7) |
257 (8.4) |
20 (1.3) |
|
Severe |
1 (0.0) |
2 (0.1) |
3 (0.1) |
2 (0.1) |
|
Swellingc |
||||
|
Any (≥0.5 cm) |
320 (10.3) |
46 (3.0) |
450 (14.7) |
41 (2.7) |
|
Mild |
177 (5.7) |
28 (1.8) |
247 (8.1) |
30 (2.0) |
|
Moderate |
142 (4.6) |
18 (1.2) |
203 (6.6) |
11 (0.7) |
|
Severe |
1 (0.0) |
0 |
0 |
0 |
|
Pain at the injection sited |
||||
|
Any |
2258 (72.9) |
482 (31.5) |
2181 (71.2) |
434 (28.5) |
|
Mild |
1810 (58.5) |
434 (28.3) |
1642 (53.6) |
389 (25.6) |
|
Moderate |
442 (14.3) |
48 (3.1) |
533 (17.4) |
44 (2.9) |
|
Severe |
6 (0.2) |
0 |
6 (0.2) |
1 (0.1) |
|
Note: Reactions were collected in an electronic diary (e-diary) from Day 1 to Day 7 after vaccination. |
||||
Table 12: Study 3 — Frequency and Percentages of Participants With Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Each Dose — Children 5 Through 11 Years of Age — Safety Population*
|
COMIRNATY± |
Placebo |
COMIRNATY± |
Placebo |
|
|
Fever |
||||
|
≥38.0°C |
64 (2.1) |
21 (1.4) |
193 (6.3) |
21 (1.4) |
|
≥38.0°C to 38.4°C |
37 (1.2) |
10 (0.7) |
101 (3.3) |
13 (0.9) |
|
>38.4°C to 38.9°C |
22 (0.7) |
9 (0.6) |
70 (2.3) |
5 (0.3) |
|
>38.9°C to 40.0°C |
4 (0.1) |
2 (0.1) |
21 (0.7) |
3 (0.2) |
|
>40.0°C |
1 (0.0) |
0 |
1 (0.0) |
0 |
|
Fatiguec |
||||
|
Any |
1067 (34.5) |
496 (32.4) |
1200 (39.2) |
383 (25.2) |
|
Mild |
702 (22.7) |
323 (21.1) |
665 (21.7) |
230 (15.1) |
|
Moderate |
360 (11.6) |
171 (11.2) |
508 (16.6) |
149 (9.8) |
|
Severe |
5 (0.2) |
2 (0.1) |
27 (0.9) |
4 (0.3) |
|
Headachec |
||||
|
Any |
703 (22.7) |
372 (24.3) |
870 (28.4) |
284 (18.7) |
|
Mild |
530 (17.1) |
275 (18.0) |
576 (18.8) |
201 (13.2) |
|
Moderate |
170 (5.5) |
91 (5.9) |
286 (9.3) |
82 (5.4) |
|
Severe |
3 (0.1) |
6 (0.4) |
8 (0.3) |
1 (0.1) |
|
Chillsc |
||||
|
Any |
174 (5.6) |
84 (5.5) |
301 (9.8) |
66 (4.3) |
|
Mild |
138 (4.5) |
69 (4.5) |
205 (6.7) |
52 (3.4) |
|
Moderate |
36 (1.2) |
15 (1.0) |
94 (3.1) |
13 (0.9) |
|
Severe |
0 |
0 |
2 (0.1) |
1 (0.1) |
|
Vomitingd |
||||
|
Any |
63 (2.0) |
30 (2.0) |
62 (2.0) |
27 (1.8) |
|
Mild |
52 (1.7) |
28 (1.8) |
56 (1.8) |
22 (1.4) |
|
Moderate |
11 (0.4) |
2 (0.1) |
5 (0.2) |
5 (0.3) |
|
Severe |
0 |
0 |
1 (0.0) |
0 |
|
Diarrheae |
||||
|
Any |
198 (6.4) |
75 (4.9) |
166 (5.4) |
76 (5.0) |
|
Mild |
184 (5.9) |
72 (4.7) |
149 (4.9) |
70 (4.6) |
|
Moderate |
14 (0.5) |
3 (0.2) |
15 (0.5) |
6 (0.4) |
|
Severe |
0 |
0 |
2 (0.1) |
0 |
|
New or worsened muscle painc |
||||
|
Any |
289 (9.3) |
126 (8.2) |
368 (12.0) |
104 (6.8) |
|
Mild |
206 (6.7) |
96 (6.3) |
245 (8.0) |
68 (4.5) |
|
Moderate |
82 (2.6) |
30 (2.0) |
122 (4.0) |
36 (2.4) |
|
Severe |
1 (0.0) |
0 |
1 (0.0) |
0 |
|
New or worsened joint painc |
||||
|
Any |
106 (3.4) |
70 (4.6) |
159 (5.2) |
57 (3.7) |
|
Mild |
71 (2.3) |
56 (3.7) |
103 (3.4) |
42 (2.8) |
|
Moderate |
35 (1.1) |
14 (0.9) |
56 (1.8) |
15 (1.0) |
|
Severe |
0 |
0 |
0 |
0 |
|
Use of antipyretic or pain medicationf |
436 (14.1) |
135 (8.8) |
601 (19.6) |
111 (7.3) |
|
Note: Events and use of antipyretic or pain medication were collected in an electronic diary (e-diary) from Day 1 to Day 7 after each dose. |
||||
Unsolicited Adverse Events
In the following analyses of Study 3 in participants 5 through 11 years of age, 3,109 participants received COMIRNATY and 1,538 participants received placebo. Among those who received 2 doses of COMIRNATY or placebo, 1,185 participants in the COMIRNATY group and 575 participants in the placebo group had follow- up time ≥4 to <6 months and 296 participants in the COMIRNATY group and 150 participants in the placebo group had follow-up time of >6 months in the blinded placebo-controlled follow-up period.
Among participants who received at least 1 dose of study vaccine, unsolicited adverse events were reported by 333 (10.7%) participants in the COMIRNATY group and 150 (9.8%) participants in the placebo group.
In an analysis of all unsolicited adverse events reported following administration of Dose 1 to one month after administration of Dose 2, the adverse reactions (excluding reactions reported as solicited adverse reactions) in participants who received COMIRNATY compared with participants who received placebo were lymphadenopathy (n=23; 0.7% vs. n=4; 0.3%), nausea (n=7; 0.2% vs. n=3; 0.2%), decreased appetite (n=3; 0.1% vs. n=2; 0.1%), malaise (n=2; 0.1% vs. n=0), and night sweats (n=1; 0.0% vs. n=0).
Serious Adverse Events
Serious adverse events, from administration of Dose 1 to the participant unblinding date, were reported in 8 (0.3%) COMIRNATY recipients and in 2 (0.1%) placebo recipients. No serious adverse events were considered related to vaccination.
Single Dose (Original Monovalent) in Vaccine-Experienced Children 5 Years Through 11 Years of Age
In Phase 2/3 of Study 3, 2,408 participants 5 years through 11 years of age received a first booster dose of COMIRNATY at a median of 7.9 months (range 5.3 to 19.4 months) after completing the primary series. These participants had a median safety follow-up of 6.4 months from vaccination through the data cutoff date of February 28, 2023. The median age was 8.0 years (range 5 through 11 years of age), 50.5% were male and 49.5% were female, 76.3% were White, 5.9% were Black or African American, 16.9% were Hispanic/Latino, 8.2% were Asian, and 0.5% were American Indian/Alaska Native.
Solicited Local and Systemic Adverse Reactions
The frequency of solicited adverse reactions reported in participants receiving a booster dose of COMIRNATY were generally consistent with those reported in pediatric participants receiving COMIRNATY as part of the two-dose series.
Unsolicited Adverse Events
Lymphadenopathy occurred in 46 (1.9%) participants who received a booster dose of COMIRNATY and in 23 (0.7%) participants who received COMIRNATY as a primary series.
Serious Adverse Events
Serious adverse events from study vaccination through 6 months after study vaccination were reported by 10 (0.4%) COMIRNATY recipients. No serious adverse events were considered related to vaccination.
Single Dose (Bivalent Original and BA.4/BA.5) in Vaccine-Experienced Children 5 Years Through 11 Years of Age
In Study 6, 113 participants 5 years through 11 years of age previously vaccinated with a 2-dose primary series and 1 booster dose of COMIRNATY received a second booster (fourth dose) with Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and Omicron BA.4/BA.5). Participants received a second booster with Pfizer- BioNTech COVID-19, Bivalent 2.6 to 8.5 months after receiving their third dose with COMIRNATY and had a median follow-up time of 6.3 months (range 1.1 to 6.8 months) up to a data cutoff date of April 20, 2023. The median age of participants was 9 years (range 5 through 11 years of age), 50.4% were male and 49.6% were female, 58.4% were White, 20.4% were Hispanic/Latino, 19.5% were multiracial, 11.5% were Asian, and 8.0% were Black or African American.
Solicited Local and Systemic Adverse Reactions
The frequency of solicited adverse reactions reported in participants receiving a second booster dose of Pfizer- BioNTech COVID-19 Vaccine, Bivalent (Original and BA.4/BA.5) were generally consistent with those reported in pediatric participants receiving COMIRNATY.
Unsolicited Adverse Events
Lymphadenopathy was reported in 1 (0.9%) participant who received Pfizer-BioNTech COVID-19 Vaccine, Bivalent (Original and BA.4/BA.5).
Serious Adverse Events
No serious adverse events were reported.
Single Dose (Monovalent XBB.1.5) in Vaccine-Naïve Children 5 Years Through 11 Years of Age
In a subset of Study 6, the safety of a single dose of COMIRNATY (encoding the viral spike (S) glycoprotein of SARS-CoV-2 Omicron XBB.1.5) was evaluated in 310 COVID-19 vaccine-naïve participants 5 through 11 years of age. Participants had a median follow-up time of 6.4 months (range 1.7 to 6.9 months). The median age of participants was 7.0 years (range 5 through 11 years of age), 47.1% were male and 52.9% were female, 41.3% were White, 52.9% were Black or African American, 52.3% were Hispanic or Latino, 1.9% were Asian, and 0.3% were American Indian/Alaska Native.
Solicited Local and Systemic Adverse Reactions
The frequency of solicited adverse reactions reported in participants who received a single dose of COMIRNATY, monovalent (XBB.1.5) were generally consistent with those previously reported by participants receiving COMIRNATY.
Unsolicited Adverse Events
In an analysis of all unsolicited adverse events through 1 month after study vaccination, unsolicited adverse events were reported by 11 (3.5%) COMIRNATY recipients. The adverse reaction not already captured by solicited local and systemic reactions was decreased appetite (n=1; 0.3%).
Serious Adverse Events
Serious adverse events from study vaccination through 6 months after study vaccination were reported by 3 (1.0%) COMIRNATY recipients. No serious adverse events were considered related to vaccination.
Postmarketing Experience
The following adverse reactions have been identified during postmarketing use of COMIRNATY, Pfizer-BioNTech COVID-19 Vaccine and Pfizer-BioNTech COVID-19 Vaccine, Bivalent. 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, febrile seizures (in children 5 through 11 years of age)
Cardiovascular Outcomes in Patients Diagnosed With mRNA COVID-19 Vaccine-associated Myocarditis
In a longitudinal retrospective observational cohort study across 38 hospitals in the U.S., information on cardiovascular outcomes was collected on 333 patients 5 through 29 years of age who had been diagnosed with COVID-19 vaccine-associated myocarditis. Among these patients, 322 were confirmed to have received an mRNA COVID-19 vaccine encoding the S glycoprotein of the Original SARS-CoV-2. Of 331 patients, 278 had onset of symptoms following the second dose of a primary series, 33 following the first dose of a primary series, and 20 following a first booster dose1.
Among 307 patients who had been diagnosed with COVID-19 vaccine-associated myocarditis for whom follow-up information was available, 89 reported cardiac symptoms at a median follow-up of 91 days (interquartile range 25-186 days) post-vaccination1.
Initial gadolinium-enhanced cardiac magnetic resonance imaging (CMR) was performed on 216 patients, of whom 177 had late gadolinium enhancement (LGE), a marker of myocardial injury. Among 161 patients who had LGE on initial CMR and who had a follow-up gadolinium-enhanced CMR at a median follow-up of 159 days (interquartile range 78-253 days), 98 had persistence of LGE. Overall, the severity of LGE decreased during follow-up. The clinical and prognostic significance of these CMR findings is not known1.
Limitations of this study include potential selection bias towards patients with more severe myocarditis who are more likely to be hospitalized and have CMR, variability in diagnostic testing, and variability in follow-up1.
Drug Interactions for Comirnaty
No information provided.
Warnings for Comirnaty
Included as part of the PRECAUTIONS section.
Precautions for Comirnaty
Management Of Acute Allergic Reactions
Appropriate medical treatment must be immediately available to manage potential anaphylactic reactions following administration of COMIRNATY.
Myocarditis And Pericarditis
Postmarketing data with authorized or approved mRNA COVID-19 vaccines demonstrate increased risks of myocarditis and pericarditis, particularly within the first week following vaccination. For COMIRNATY, 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 Centers for Disease Control and Prevention (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).
Syncope
Syncope (fainting) may occur in association with administration of injectable vaccines, including COMIRNATY. Procedures should be in place to avoid injury from fainting.
Altered Immunocompetence
Immunocompromised persons, including individuals receiving immunosuppressant therapy, may have a diminished immune response to COMIRNATY [see Use In Specific Populations].
Limitation Of Effectiveness
COMIRNATY may not protect all vaccine recipients.
Patient Counseling Information
Advise the vaccine recipient or caregiver to read the FDA-approved patient labeling.
Inform the vaccine recipient or caregiver of the potential benefits and risks of vaccination with COMIRNATY.
Advise the vaccine recipient or caregiver to report any adverse events to their healthcare provider or to the Vaccine Adverse Event Reporting System at 1-800-822-7967 and www.vaers.hhs.gov.
This product’s labeling may have been updated. For the most recent prescribing information, please visit https://dailymed.nlm.nih.gov/dailymed/.
Nonclinical Toxicology
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 [encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu 1 strain (Original)] there were no vaccine-related effects on female fertility [see Use In Specific Populations].
Use In Specific Populations
Pregnancy
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 [encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu 1 strain (Original)] 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).
Clinical Considerations
Disease-Associated Maternal And/Or Embryo/Fetal Risk
Pregnant individuals infected with SARS-CoV-2 are at increased risk of severe COVID-19 compared with non-pregnant individuals.
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 [encoding the viral spike (S) glycoprotein of SARS-CoV-2 Wuhan-Hu 1 strain (Original)] 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.
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.
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 and Clinical Studies].
The safety and effectiveness of COMIRNATY in individuals younger than 12 years of age have not been established. Evidence from clinical studies in individuals 6 months through 4 years of age strongly suggests that a single dose of COMIRNATY would be ineffective in individuals younger than 6 months of age.
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]. In Study 4, of 5081 recipients who received COMIRNATY as the first booster dose, 23.1% (n = 1175) were 65 years of age and older and 5.2% (n = 265) were 75 years of age and older. In Study 5, of 726 recipients who received Pfizer-BioNTech COVID-19 Vaccine, Bivalent as the second booster dose, 21.9% (n = 159) were 65 years of age and older and 4.8% (n = 35) were 75 years of age and older. No overall differences in safety or effectiveness were observed between these recipients and younger recipients.
Immunocompromised Individuals
The Centers for Disease Control and Prevention has published considerations related to COVID-19 vaccination for individuals who are moderately to severely immunocompromised (https://www.cdc.gov/vaccines/covid-19/clinical-considerations/covid-19-vaccines-us.html).
OVERDOSES
No information provided.
Contraindications for Comirnaty
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)] or to individuals who had a severe allergic reaction (e.g., anaphylaxis) following a previous dose of a Pfizer-BioNTech COVID-19 vaccine.
Clinical Pharmacology for Comirnaty
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.
Patient Information for Comirnaty
Advise the vaccine recipient or caregiver to read the FDA-approved patient labeling.
Inform the vaccine recipient or caregiver of the potential benefits and risks of vaccination with COMIRNATY.
Advise the vaccine recipient or caregiver to report any adverse events to their healthcare provider or to the Vaccine Adverse Event Reporting System at 1-800-822-7967 and www.vaers.hhs.gov.
This product’s labeling may have been updated. For the most recent prescribing information, please visit https://dailymed.nlm.nih.gov/dailymed/.
Manufactured for:
BioNTech Manufacturing GmbH
An der Goldgrube 12
55131 Mainz, Germany
Manufactured by:
Pfizer Inc., New York, NY 10001
LAB-1490-15.0
US Govt. License No. 2229
From 
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