Vaccine Information: Comirnaty (Page 2 of 5)

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.

Table 1: 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 Dose 1 N † =2899 n ‡ (%)	Placebo Dose 1 N † =2908 n ‡ (%)	COMIRNATY Dose 2 N † =2682 n ‡ (%)	Placebo Dose 2 N † =2684 n ‡ (%)
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.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded. † 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. ‡ n = Number of participants with the specified reaction. § Mild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm. ¶ Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
Redness §
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
Swelling §
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 site ¶
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

Table 2: 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 Dose 1 N † =2899 n ‡ (%)	Placebo Dose 1 N † =2908 n ‡ (%)	COMIRNATY Dose 2 N † =2682 n ‡ (%)	Placebo Dose 2 N † =2684 n ‡ (%)
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.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded. † 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. ‡ n = Number of participants with the specified reaction. § Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity. ¶ Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration. # Mild: 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. Þ Severity was not collected for use of antipyretic or pain medication.
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
Fatigue §
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)
Headache §
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)
Chills §
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)
Vomiting ¶
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
Diarrhea #
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 pain §
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 pain §
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 medication Þ	805 (27.8)	398 (13.7)	1213 (45.2)	320 (11.9)

Table 3: 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 Dose 1 N † =2008 n ‡ (%)	Placebo Dose 1 N † =1989 n ‡ (%)	COMIRNATY Dose 2 N † =1860 n ‡ (%)	Placebo Dose 2 N † =1833 n ‡ (%)
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.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded. † 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. ‡ n = Number of participants with the specified reaction. § Mild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm. ¶ Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
Redness §
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)
Swelling §
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 site ¶
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

Table 4: 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 Dose 1 N † =2008 n ‡ (%)	Placebo Dose 1 N † =1989 n ‡ (%)	COMIRNATY Dose 2 N † =1860 n ‡ (%)	Placebo Dose 2 N † =1833 n ‡ (%)
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.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. Participants with chronic, stable HIV infection were excluded. † 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. ‡ n = Number of participants with the specified reaction. § Mild: 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. ¶ Mild: 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. # Mild: 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. Þ Severity was not collected for use of antipyretic or pain medication.
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
Fatigue §
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
Headache §
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)
Chills §
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
Vomiting ¶
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
Diarrhea #
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 pain §
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 medication Þ	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.

Table 5: 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 Dose 1 N † =1127 n ‡ (%)	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.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. † N = Number of participants reporting at least 1 yes or no response for the specified reaction after the specified dose. ‡ n = Number of participants with the specified reaction. § Mild: >2.0 to ≤5.0 cm; Moderate: >5.0 to ≤10.0 cm; Severe: >10.0 cm. ¶ Mild: does not interfere with activity; Moderate: interferes with activity; Severe: prevents daily activity.
Redness §
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 site ¶
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)

Table 6: 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 Dose 1 N † =1127 n ‡ (%)	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.
* Randomized participants in the safety analysis population who received at least 1 dose of the study intervention. † N = Number of participants reporting at least 1 yes or no response for the specified event after the specified dose. ‡ n = Number of participants with the specified reaction. § Mild: does not interfere with activity; Moderate: some interference with activity; Severe: prevents daily activity. ¶ Mild: 1 to 2 times in 24 hours; Moderate: >2 times in 24 hours; Severe: requires intravenous hydration. # Mild: 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. Þ Severity was not collected for use of antipyretic or pain medication.
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)
Fatigue §
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)
Vomiting ¶
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)
Diarrhea #
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 medication Þ	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.