Vaccine Information: PREVNAR 20 (Page 2 of 6)

6 ADVERSE REACTIONS

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.

In individuals 2, 4, 6, and 12 through 15 months of age vaccinated with a 4-dose schedule, the most commonly reported solicited adverse reactions >10% were irritability (>60%), pain at the injection site (>30%), drowsiness (>30%), decreased appetite and injection site redness (>20%), injection site swelling (>10%), and fever (>10%).

In individuals 15 months through 17 years of age vaccinated with a single dose, the most commonly reported solicited adverse reactions >10% were irritability (>60% in individuals less than 2 years of age), pain at the injection site (>50%), drowsiness (>40% in individuals less than 2 years of age), fatigue and muscle pain (>20% in individuals 2 years of age and older), decreased appetite (>20% in individuals less than 2 years of age), injection site swelling and injection site redness (>10%), headache (>10% in individuals 5 years of age and older), and fever (>10% in individuals less than 2 years of age).

In individuals 18 through 59 years of age, the most commonly reported solicited adverse reactions >10% were pain at the injection site (>70%), muscle pain (>50%), fatigue (>40%), headache (>30%), and arthralgia and injection site swelling (>10%).

In individuals 60 years of age and older, the most commonly reported solicited adverse reactions >10% were pain at the injection site (>50%), muscle pain and fatigue (>30%), headache (>20%), and arthralgia (>10%).

Clinical Trial Experience in Individuals 6 Weeks Through 17 Years of Age

The safety of Prevnar 20 in individuals from 6 weeks through 17 years of age was evaluated in 3 randomized, double-blind, active-controlled, clinical trials and one single-arm clinical trial. Across the 4 pediatric trials (Studies 8, 9, 10, and 11; NCT04382326, NCT04379713, NCT03512288, and NCT04642079, respectively) conducted in the Americas and Europe, 3063 participants received at least one dose of Prevnar 20, and 1720 participants received at least one dose of Prevnar 13.

Safety Assessment in Individuals Receiving a 4-Dose Series (Studies 8 through 10)

The safety of Prevnar 20 was assessed in 3 randomized, double-blind, active-controlled, clinical trials in participants (Studies 8, 9, and 10). Globally, 2232 participants who received at least one dose of a 4-dose series of Prevnar 20 and 1717 participants who received at least one dose of a 4-dose series of Prevnar 13 were included in the safety analysis. In the United States (US) (including the US territory of Puerto Rico [PR]), 1567 participants received at least one dose of a 4-dose series of Prevnar 20 and 1376 participants received at least one dose of a 4-dose series of Prevnar 13. Study 8 was a double-blind, active-controlled trial of safety and immunogenicity in participants randomized 1:1 to receive a 4-dose series of either Prevnar 20 (N=1001) or Prevnar 13 (N=990) at 2, 4, 6, and 12 through 15 months of age, conducted in the US and PR. Study 9 was a double-blind trial of tolerability and safety in participants randomized 2:1 to receive a 4-dose series of either Prevnar 20 (N=1000) or Prevnar 13 (N=503) at 2, 4, 6, and 12 through 15 months of age, conducted in countries in Europe, South America, and North America, including the US and PR. Study 10 was a double-blind, active-controlled multicenter trial of safety and immunogenicity in participants randomized 1:1 to receive a 4-dose series of either Prevnar 20 (N=231) or Prevnar 13 (N=227) at 2, 4, 6, and 12 months of age, conducted in the US.

Across the 3 infant trials, there were similar percentages of male (51.7% and 50.1%) and female (48.3% and 49.9%) participants among the Prevnar 20 and Prevnar 13 recipients respectively. Participant age at the first dose (median age: 64.0 days, range: 42 to 98 days; median age: 64.0 days, range 43 to 97 days) and last dose (median age: 372.0 days, range 365 to 460 days; median age: 372.0 days, range 366 to 455 days) in the Prevnar 20 and Prevnar 13 groups, respectively, was similar. The racial and ethnic distribution of the US/PR infant safety population was as follows: 73.8% of Prevnar 20 recipients were White, 12.1% Black, 1.9% Asian, and 7.5% multi-racial; 29.7% were Hispanic) with similar distribution among Prevnar 13 recipients. In the multi-country infant trial, Study 9, the participants were predominantly White (87.4%). This study also included 111 late preterm infants (>34 to <37 weeks gestational age) among the total study population 77 were in the Prevnar 20 group, and 34 in the Prevnar 13 group.

In Study 8, Pediarix [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Hepatitis B (Recombinant) and Inactivated Poliovirus Vaccine Combined] (DTaP-HBV-IPV) and Hiberix [(Haemophilus influenzae type b Conjugate vaccine) [Hib] (Tetanus Toxoid conjugate)] were administered concomitantly with Prevnar 20 or Prevnar 13 at 2, 4, and 6 months of age; M-M-R II [Measles, Mumps, and Rubella Virus Vaccine Live] (MMR) and VARIVAX [Varicella virus vaccine live] were administered concomitantly with Prevnar 20 or Prevnar 13 at 12 through 15 months of age. In Study 10, Pediarix was administered concomitantly with Prevnar 20 or Prevnar 13 at 2, 4, and 6 months of age. In Studies 8 and 10, influenza and rotavirus vaccines were also permitted to be co-administered with Prevnar 20 or Prevnar 13 according to recommendations. The proportion of participants receiving a concomitant influenza vaccine and the proportions of participants receiving a concomitant rotavirus vaccine were similar across the two study groups in Studies 8 and 10. In Study 8, 65.8% to 87.3% of participants received a rotavirus vaccine with each of the first 3 doses of Prevnar 20; 11.7% and 10.1% of participants received an influenza vaccine with Dose 3 and Dose 4 of Prevnar 20, respectively. In Study 10, 65.3% to 94.8% of participants received a rotavirus vaccine with each of the first 3 doses of Prevnar 20; 21.4% of participants received an influenza vaccine with Dose 3 of Prevnar 20. In Study 9, US-licensed or non-US licensed routine pediatric vaccines were permitted to be given during the study, including with Prevnar 20 or Prevnar 13, according to local or national recommendations.

Across the infant trials, solicited local and systemic adverse reactions were recorded daily by parents/guardians using an electronic diary for 7 consecutive days following each vaccination. Adverse events (AEs) were reported from administration of the first dose until one month after the third dose, and from the fourth dose through one month after the fourth dose. Serious adverse events (SAEs) and newly diagnosed chronic medical conditions (NDCMCs) were reported from administration of the first dose through 6 months after the last dose.

Solicited Adverse Events in Individuals Receiving a 4-Dose Series (Study 8)

The percentage of participants in Study 8 with solicited local and systemic adverse reactions that occurred within 7 days following vaccination are shown in Tables 2 and 3. The median day of onset for local and systemic reactions was between Day 1 and Day 2 (Day 1 was the day of vaccination), and reactions resolved with a median duration between 1 to 2 (local reactions) or 3 days (systemic reactions).

Table 2. Percentage of Participants at 2, 4, 6, and 12 Through 15 Month of Age With Solicited Local Adverse Reactions Within 7 Days After Each Vaccination – Study 8*
Note: Local reactions were collected in the e-diary from Day 1 through Day 7 after each dose. If a severe reaction was identified by the investigator as a Grade 4 reaction at a follow-up assessment, it was also reported as an adverse reaction.
*
Study 8 was conducted in the United States and the territory of Puerto Rico (NCT04382326).
N = number of participants with any e-diary data reported after the specified dose. This value is the denominator for the percentage calculations.
Mild: hurts if gently touched; moderate: hurts if gently touched with crying; severe: causes limitation of limb movement.
§
Any includes all participants who reported a reaction as mild, moderate, or severe during Day 1 to Day 7 after vaccination
Mild: >0.0 to 2.0 cm; moderate: >2.0 to 7.0 cm; severe: >7.0 cm.
#
Any local reaction includes all participants who reported any injection site reaction (pain, swelling, or redness) as mild, moderate, or severe during Day 1 to Day 7 after vaccination.

Dose 1

Dose 2

Dose 3

Dose 4

Vaccine Group

Prevnar 20

(N =993)

%

Prevnar 13

(N =974)

%

Prevnar 20

(N =940)

%

Prevnar 13

(N =924)

%

Prevnar 20

(N =914)

%

Prevnar 13

(N =901)

%

Prevnar 20

(N =826)

%

Prevnar 13

(N =815)

%

Local Reaction

Pain at injection site

Any §

49.1

45.3

44.0

41.7

38.6

39.0

35.7

35.8

Mild

30.6

30.4

29.3

27.7

25.7

25.5

24.1

27.1

Moderate

18.4

14.9

14.8

14.0

12.9

13.4

11.3

8.7

Severe

0.1

0

0

0

0

0

0.4

0

Redness

Any §

25.5

24.6

23.2

26.4

25.4

27.2

23.5

26.6

Mild

21.5

22.3

21.2

23.1

21.1

23.5

19.6

22.0

Moderate

4.0

2.4

2.0

3.4

4.3

3.7

3.9

4.7

Severe

0

0

0

0

0

0

0

0

Swelling

Any §

16.4

18.8

15.5

17.3

17.1

17.6

14.9

17.3

Mild

11.5

14.7

11.5

13.5

12.5

13.8

10.7

13.6

Moderate

4.8

4.1

4.0

3.8

4.6

3.8

4.2

3.7

Severe

0.1

0

0

0

0

0.1

0

0

Any local reaction #

59.8

56.5

53.1

52.7

50.8

49.1

44.8

45.9

Table 3. Percentage of Participants at 2, 4, 6, and 12 Through 15 Months of Age With Solicited Systemic Adverse Reactions Within 7 Days After Each Vaccination – Study 8*
Note: Systemic reactions and use of antipyretic/pain medication were collected in the e-diary from Day 1 through Day 7 after each dose. If a severe reaction was identified by the investigator as a Grade 4 reaction at a follow-up assessment, it was also reported as an adverse reaction.
*
Study 8 was conducted in the United States and the territory of Puerto Rico (NCT04382326).
N = number of participants with any e-diary data reported after the specified dose. This value is the denominator for the percentage calculations.
Mild: easily consolable; moderate: requiring increased attention; severe: inconsolable; crying cannot be comforted.
§
Any includes all participants who reported a reaction as mild, moderate, or severe during Day 1 to Day 7 after vaccination
Mild: increased or prolonged sleeping bouts; moderate: slightly subdued interfering with daily activity; severe: disabling not interested in usual daily activity.
#
Mild: decreased interest in eating; moderate: decreased oral intake; severe: refusal to feed.
Þ
Any systemic reaction: includes all participants who reported any fever ≥38.0°C or any other systemic reaction (irritability, drowsiness or decreased appetite) as mild, moderate, or severe during Day 1 to Day 7 after vaccination. The route of temperature measurement was to be rectal.
ß
Severity was not collected for use of antipyretic or pain medication. The numbers listed reflect yes responses (i.e., number of events reported).

Dose 1

Dose 2

Dose 3

Dose 4

Vaccine Group

Prevnar 20

(N =993)

%

Prevnar 13

(N =974)

%

Prevnar 20

(N =940)

%

Prevnar 13

(N =924)

%

Prevnar 20

(N =914)

%

Prevnar 13

(N =901)

%

Prevnar 20

(N =826)

%

Prevnar 13

(N =815)

%

Systemic Events

Irritability

Any §

70.9

71.7

71.6

68.8

64.4

63.0

61.0

61.1

Mild

23.4

21.6

22.9

21.2

25.2

21.6

23.4

21.8

Moderate

43.0

46.2

44.7

43.4

37.5

39.2

35.0

37.9

Severe

4.5

3.9

4.0

4.2

1.8

2.2

2.7

1.3

Drowsiness

Any §

67.2

66.0

54.7

55.6

44.1

44.1

39.5

39.5

Mild

50.2

49.3

37.0

36.9

31.1

30.1

27.8

28.2

Moderate

16.1

15.6

16.9

17.9

12.5

13.1

11.0

10.7

Severe

0.9

1.1

0.7

0.9

0.5

0.9

0.6

0.6

Decreased Appetite #

Any §

24.4

23.9

26.4

23.5

20.6

22.4

24.8

25.2

Mild

14.5

16.1

16.4

15.3

13.5

13.9

15.9

16.1

Moderate

9.7

7.5

9.8

7.7

6.7

8.2

8.6

8.3

Severe

0.2

0.3

0.2

0.5

0.4

0.3

0.4

0.7

Fever Þ

≥38.0℃

10.3

7.5

17.3

16.3

12.6

13.7

14.5

14.0

≥38.0℃ to 38.4°C

7.3

6.3

10.9

10.0

7.7

7.9

6.5

7.7

>38.4℃ to 38.9°C

2.2

0.9

4.0

4.2

3.4

3.9

5.1

3.2

38.9℃ to 40.0°C

0.7

0.3

2.2

2.2

1.4

1.9

2.7

2.9

>40.0°C

0.1

0

0.2

0

0.1

0

0.2

0.1

Any systemic reaction Þ

85.9

84.5

82.0

80.5

74.0

72.6

70.8

71.2

Use of antipyretic or pain ß

35.1

33.8

40.7

41.0

36.3

36.1

37.5

36.7

Unsolicited Serious and Non-Serious Adverse Events in Individuals Receiving a 4-Dose Series (Studies 8 through 10)

Globally, across the 3 infant trials, the proportion of participants reporting 1 or more SAEs within 6 months after the fourth dose of Prevnar 20 was 4.5% (101 of 2232 participants). This was similar to the proportion of participants with SAEs after vaccination with Prevnar 13 3.7% (64 of 1717 participants). The proportions of SAEs observed from the first dose to 1 month after the third dose were 1.1% and 1.2% for Prevnar 20 and Prevnar 13, and from the fourth dose to 1 month after the fourth dose were 0.7% and 0.5% respectively. Participants in these studies may have received other US-licensed (Studies 8, 9, and 10) or non-US-licensed concomitant (Study 9) vaccines according to their local recommended schedule. In the Prevnar 20 group, two febrile seizures considered possibly related to vaccination with Prevnar 20 were reported. One case was serious and occurred 14 days after the fourth dose given with MMR and varicella vaccine. One case was non-serious and occurred 7 days after the fourth dose of Prevnar 20 in an individual with diagnosis of COVID-19 infection.

One participant experienced isolated injection site hypersensitivity (redness) within approximately 30 minutes of Prevnar 20 after each of the first 3 doses resolving on the same day, this was not observed after the fourth dose.

There were no notable patterns or imbalances between vaccine groups for specific categories of SAEs that would suggest a causal relationship to Prevnar 20.

Safety Assessment in Individuals 15 Months Through 17 Years of Age Receiving Catch-Up Vaccination (Study 11)

The safety of Prevnar 20 in individuals (15 months through 17 years of age) was assessed in a single-arm trial of safety and immunogenicity of a single dose of Prevnar 20 conducted in the United States (Study 11) (NCT 04642079). A total of 831 participants received a single dose of Prevnar 20 among the 4 age groups (≥15 to <24 months, ≥2 to <5 years, ≥5 to <10 years, and ≥10 to <18 years). Participants <5 years of age were eligible if they had received at least 3 prior doses of Prevnar 13. Routine pediatric vaccines including DTaP vaccines, Hib, hepatitis A, and influenza vaccines were permitted to be co-administered with Prevnar 20, if not feasible to separate from Prevnar 20 by 14 days. There were similar percentages of male and female participants, with the exception of a higher percentage of male than female participants (approximately 56% males) in the age groups ≥15 months to <24 months of age and ≥10 to <18 years of age. Participants were predominantly White (80.1% to 86.6%), with nearly all the other participants being Black or African American (8.3% to 12.4%) and multiracial (2.5% to 6.0%); 15.4% to 21.0% were Hispanic.

The safety assessment was consistent with that used in studies 8 through 10, with the exception of that age-applicable systemic adverse reactions were recorded. The types of solicited systemic events collected in the participants ≥15 months to <2 years of age were consistent with those collected in participants 6 weeks through 15 months of age (i.e., irritability, decreased appetite, drowsiness/increased sleep and fever), while the solicited systemic events in participants ≥2 years of age required verbal communication by the participant (i.e., fatigue, headache, muscle pain, joint pain and fever).

Solicited Adverse Reactions in Individuals 15 Months Through 17 Years of Age Receiving Catch-Up Vaccination (Study 11)

After a single dose of Prevnar 20, most local and systemic adverse reaction in individuals 15 months through 17 years of age were mild or moderate in severity and resolved within 1 to 2 days. The most frequently reported local reaction was pain at injection site (52.5%, 66.0%, 82.9%, 82.0% in individuals ≥15 months to <24 months, ≥2 to <5 years, ≥5 to <10 years, and ≥10 to <18 years respectively), followed by redness and swelling. Most local reactions were mild or moderate in severity.

The most frequently reported solicited systemic reactions in individuals ≥15 months to <2 years of age were irritability (61.8%), followed by drowsiness and increased sleep (41.7%), and decreased appetite (25.0%). Fever ≥38.0°C was reported by 11.8% of individuals; fever >38.4°C was reported infrequently.

The most frequently reported systemic events in participants ≥2 to <18 years of age varied by age group. Fatigue was most frequently reported in individuals ≥2 to <5 years of age, and muscle pain was most frequently reported in participants ≥5 to <10 years and ≥10 to <18 years of age. Fever was reported infrequently (in ≤3.3% of individuals ≥2 to <5 years of age and only 1 participant, 0.5% ≥5 to <10 years of age).

Serious Adverse Events in Individuals 15 Months Through 17 Years of Age (Study 11)

In Study 11, five participants reported SAEs within 6 months after vaccination (2 participants [1.0%] ≥15 to <24 months of age and 3 participants [1.5%] ≥10 to <18 years of age). One participant (0.5%) ≥15 to <24 months of age reported an SAE within 1 month after vaccination. No SAEs were considered related to the vaccination.

Unsolicited Adverse Reactions Following the Use of Prevnar and Prevnar 13

Events observed in clinical trials with Prevnar (Pneumococcal 7-valent Conjugate Vaccine [Diphtheria CRM197 Protein]) or Prevnar 13 in individuals 6 weeks through 15 months of age are relevant to Prevnar 20 since the vaccines are manufactured and formulated similarly and contain 7 and 13 of the same polysaccharide conjugates, respectively.

Reactions occurring in greater than 1% of infants and toddlers following administration of Prevnar 13: diarrhea, vomiting, and rash.

Reactions occurring in less than 1% of infants and toddlers following administration of Prevnar 13: crying, hypersensitivity reaction (including face edema, dyspnea, and bronchospasm), seizures (including febrile seizures), and urticaria or urticaria-like rash.

Among 6,839 participants who received at least 1 dose of Prevnar 13 in clinical trials conducted globally, there was 1 hypotonic-hyporesponsive episode adverse reaction reported (0.015%). Among 4,204 participants who received at least 1 dose of Prevnar in clinical trials conducted globally, there were 3 hypotonic-hyporesponsive episode adverse reactions reported (0.071%). All 4 events occurred in a single clinical trial in Brazil in which participants received whole cell pertussis vaccine at the same time as Prevnar 13 or Prevnar.

Clinical Trials Experience With Prevnar 20 in Individuals 18 Years of Age and Older

The safety of a single dose of Prevnar 20 in individuals 18 years of age and older was evaluated in 6 randomized, active-controlled, multicenter clinical trials and one open-label, multicenter clinical trial. All of the trials were conducted in the United States and 2 of the trials also enrolled participants (N=172) in Sweden. Across the 7 trials, 6343 individuals received Prevnar 20 and 2496 received active control vaccine.

Safety Assessments in Pneumococcal Vaccine Naïve Participants 18 Years of Age and Older (Studies 1 through 5)

The safety of Prevnar 20 in individuals 18 years of age and older with no history of pneumococcal vaccination was evaluated in 5 studies (Studies 1–5). In the main cohort of Study 1 (NCT03760146) and in Study 2 (NCT03313037), participants ≥60 years of age and participants 60 through 64 years of age, respectively, received a single dose of Prevnar 20 followed 1 month later with administration of saline placebo or received a single dose of Prevnar 13 followed 1 month later with a dose of PNEUMOVAX® 23 (PPSV23). The 2 other cohorts of Study 1, participants 50 through 59 years of age and participants 18 through 49 years of age, received a single vaccination with Prevnar 20 or Prevnar 13. In Study 3 (NCT03828617), participants 18 through 49 years of age received a single vaccination with Prevnar 20 or Prevnar 13. In Studies 4 (NCT02955160) and 5 (NCT03642847), which were smaller studies conducted early in the clinical development of Prevnar 20, participants 18 through 49 years of age received a single dose of Prevnar 20 or an active control (Tdap or Prevnar 13).

Safety Assessments in Participants ≥65 Years of Age (Pneumococcal Vaccine Naïve or Previously Immunized with a Pneumococcal Vaccine) (Studies 6 and 7)

The safety of Prevnar 20 in individuals 65 years of age and older with pneumococcal vaccination given as routine care prior to enrollment was assessed in Study 6 (NCT03835975). Participants were enrolled into 1 of 3 cohorts based on their prior pneumococcal vaccination history (PPSV23 only ≥1 to ≤5 years prior to enrollment, Prevnar 13 only ≥6 months prior to enrollment, or Prevnar 13 followed by PPSV23 [with PPSV23 given ≥1 year prior to enrollment]). Participants in 2 of the cohorts received a single vaccination with Prevnar 20 or control pneumococcal vaccine (Prevnar 13), and the other cohort received a single vaccination with Prevnar 20. only.

The safety of Prevnar 20 in individuals 65 years of age and older when coadministered with Influenza Vaccine, Adjuvanted (Fluad Quadrivalent) was assessed in Study 7 (NCT 04526574). Randomization was stratified by prior pneumococcal vaccine status (no previous pneumococcal vaccine, receipt of at least 1 dose of PPSV23 only, receipt of at least 1 dose of Prevnar 13 only, or receipt of at least 1 dose each of PPSV23 and Prevnar 13). Participants were randomized in a 1:1 ratio to receive Prevnar 20 concomitantly administered with Fluad Quadrivalent (Group 1) or Fluad Quadrivalent followed approximately one month later by Prevnar 20 (Group 2).

Demographics of Trial Participants 18 Years of Age and Older (Studies 1, 3, 6 and 7)

In the three main trials (Studies 1, 3, and 6), participants were predominantly female (52.0% to 65.9%) across groups defined by age and prior pneumococcal vaccination status within the Prevnar 20 and control vaccine groups. Across all 3 trials combined, 59.8% of participants were 60 years of age and older, 6.9% were 50 through 59 years of age, and 33.3% were 18 through 49 years of age. In Studies 1 and 3, participants were 80.7% White, 14.2% Black, 2.1% Asian, and 10.3% Hispanic. In Study 6, participants were predominantly White (92.4%). Participants were primarily from the United States; however a portion of participants 65 years of age and older were enrolled from Sweden in Study 1 (5.7% of participants 60 years of age and older in that study) and also in Study 6 (35.5% of participants with prior PPSV23 only). In Study 7, 54.7% of participants were female. The mean age of participants was 72 years (range 65–103 years). Participants were 90.6% White, 6.9% Black, 1.2% Asian, and 9.4% Hispanic.

In the three main trials, participants with pre-existing underlying diseases were enrolled if the medical condition was stable (did not require a significant change in therapy in the 6 weeks before receipt of study vaccine or any hospitalization for worsening disease within 12 weeks before receipt of study vaccine). In Study 1, approximately one-third of all participants had risk factors that placed them at increased risk for serious pneumococcal disease, including smoking (12.9%), stable medical conditions of chronic cardiovascular disease (5.5%), chronic pulmonary disease including asthma (8.7%), chronic liver disease (0.4%), and diabetes mellitus (13.9%).

Safety Monitoring

Solicited adverse reactions for Prevnar 20 in the three main trials and Study 7 were monitored in participants recording daily into an electronic diary their local adverse reactions for 10 consecutive days and systemic reactions for 7 consecutive days following vaccination. Across all trials, serious and nonserious adverse events were collected for 1 month after each vaccination. Safety follow-up of SAEs continued through 6 months after vaccination with Prevnar 20 or Prevnar 13 (or other appropriate control vaccine), as applicable. Newly diagnosed chronic medical conditions occurring within 6 months after vaccination were also collected via telephone contact.

Serious Adverse Events in Participants 18 Years of Age and Older (Studies 1 through 6)

Across studies 1 through 6, performed in individuals of all ages, naïve to and with prior pneumococcal vaccination, the proportion of participants reporting 1 or more SAEs within 6 months after vaccination with Prevnar 20 was 1.5% (67 of 4552 participants). This was similar to the proportion of participants with SAEs after vaccination with Prevnar 13 or other applicable control vaccine (1.8%, 44 of 2496). The proportions of participants with SAEs occurring within 1 month after vaccination with Prevnar 20 or with Prevnar 13 or other applicable control vaccine were both 0.4% (19 of 4552 participants and 11 of 2496 participants, respectively). There were no notable patterns or imbalances between vaccine groups for specific categories of serious adverse events that would suggest a causal relationship to Prevnar 20.

Solicited Adverse Reactions in Participants 18 Years of Age and Older (Studies 1 and 6)

The frequency and severity of the local adverse reactions (redness, swelling, and pain at the injection site) prompted daily in the 10 days after Prevnar 20 vaccination in individuals naïve to pneumococcal vaccination (Study 1) and in individuals with prior pneumococcal vaccination (Study 6) are shown in Table 4 and Table 5, respectively. The frequency and severity of the systemic adverse reactions (fever, fatigue, headache, muscle pain, and joint pain) prompted daily in the 7 days after Prevnar 20 vaccination in individuals naïve to pneumococcal vaccination (Study 1) and in individuals with prior pneumococcal vaccination (Study 6) are shown in Table 6 and Table 7, respectively.

Table 4. Percentage of Participants With Solicited Local Adverse Reactions, by Maximum Severity, Within 10 Days After Vaccination in Pneumococcal Vaccine-Naïve Individuals — Study 1*
*
Study 1 was conducted in the United States and in Sweden (NCT03760146).
N = number of participants with any e-diary data reported after vaccination (after Vaccination 1 [Prevnar 20 or Prevnar 13] for Study 1 participants 60 years of age and older). This value is the denominator for the percentage calculations.
Diameters were measured in caliper units of whole numbers from 1 to 21 or 21+. One caliper unit = 0.5 cm. Measurements were rounded up to the nearest whole number. Intensity of redness and swelling were then characterized as follows: mild is >2.0 to 5.0 cm; moderate is >5.0 to 10.0 cm; severe is >10.0 cm.
§
“Any” includes all participants who reported a reaction as “mild”, “moderate”, or “severe” during Day 1 to Day 10 after vaccination.
Mild = does not interfere with activity; moderate = interferes with activity; severe = prevents daily activity.
#
“Any local reaction” includes all participants who reported any injection site reaction (pain, swelling, or redness) as “mild”, “moderate”, or “severe” during Day 1 to Day 10 after vaccination.

18–49 Years of Age

50–59 Years of Age

≥60 Years of Age

Vaccine Group

Prevnar 20 (N =335) %

Prevnar 13 (N =112) %

Prevnar 20 (N =331) %

Prevnar 13 (N =111) %

Prevnar 20/Saline (N =1505) %

Prevnar 13/PPSV23 (N =1483) %

Local Reaction

Pain at injection site

Any §

81.2

82.1

72.5

69.4

55.4

54.1

Mild

42.7

52.7

53.5

52.3

45.3

44.6

Moderate

38.2

28.6

17.8

16.2

9.9

9.2

Severe

0.3

0.9

1.2

0.9

0.2

0.3

Swelling

Any (>2.0 cm)§

11.6

12.5

8.8

10.8

7.5

8.0

Mild

7.2

8.9

5.7

7.2

4.8

4.9

Moderate

4.5

3.6

3.0

3.6

2.4

2.8

Severe

0

0

0

0

0.3

0.3

Redness

Any (>2.0 cm)§

9.0

9.8

8.2

5.4

7.3

6.2

Mild

3.0

5.4

5.1

2.7

3.7

3.8

Moderate

5.4

4.5

2.7

2.7

2.8

2.2

Severe

0.6

0

0.3

0

0.8

0.2

Any local reaction #

81.2

82.1

72.8

70.3

57.4

56.0

Table 5. Percentage of Participants With Solicited Local Adverse Reactions, by Maximum Severity, Within 10 Days After Vaccination in Individuals 65 Years of Age and Older With Prior Pneumococcal Vaccination – Study 6*,
*
Study 6 was conducted in the United States and in Sweden (NCT03835975)
Open-label administration of Prevnar 20.
Includes participants who previously received either PPSV23 ≥1 to ≤5 years before enrollment (PPSV23), Prevnar 13 ≥6 months before enrollment (Prevnar 13), or Prevnar 13 followed by PPSV23 ≥1 year before enrollment (Prevnar 13 and PPSV23) in the study.
§
N = number of participants with any e-diary data reported after vaccination. This value is the denominator for the percentage calculations.
Mild = does not interfere with activity; moderate = interferes with activity; severe = prevents daily activity.
#
“Any” includes all participants who reported a reaction as “mild”, “moderate”, or “severe” during Day 1 to Day 10 after vaccination.
Þ
Diameters were measured in caliper units of whole numbers from 1 to 21 or 21+. One caliper unit = 0.5 cm. Measurements were rounded up to the nearest whole number. Intensity of redness and swelling were then characterized as follows: mild is >2.0 to 5.0 cm; moderate is >5.0 to 10.0 cm; severe is >10.0 cm.
ß
“Any local reaction” includes all participants who reported any injection site reaction (pain, swelling, or redness) as “mild”, “moderate”, or “severe” during Day 1 to Day 10 after vaccination.

Prior Pneumococcal Vaccination Status

PPSV23

Prevnar 13

Prevnar 13 and PPSV23

Vaccine Group

Prevnar 20 (N § =253) %

Prevnar 13 (N § =121) %

Prevnar 20 (N § =245) %

PPSV23 (N § =126) %

Prevnar 20 (N § =125) %

Local Reaction

Pain at the injection site

Any #

50.2

43.0

61.2

56.3

52.8

Mild

45.8

38.8

54.7

40.5

47.2

Moderate

4.3

3.3

6.1

14.3

5.6

Severe

0

0.8

0.4

1.6

0

Swelling Þ

Any (>2.0 cm)#

9.9

6.6

9.4

14.3

4.0

Mild

5.1

6.6

5.7

6.3

1.6

Moderate

3.6

0

3.7

7.1

2.4

Severe

1.2

0

0

0.8

0

Redness Þ

Any (>2.0 cm)#

7.9

2.5

8.6

12.7

4.8

Mild

3.6

1.7

2.9

4.8

1.6

Moderate

3.2

0.8

5.3

7.1

3.2

Severe

1.2

0

0.4

0.8

0

Any local reaction ß

53.0

43.8

64.1

57.9

54.4

Table 6. Percentage of Participants With Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Vaccination in Pneumococcal Vaccine-Naïve Individuals – Study 1*
*
Study 1 was conducted in the United States and in Sweden (NCT03760146).
N = number of participants with any e-diary data reported after vaccination (after Vaccination 1 [Prevnar 20 or Prevnar 13] for Study 1 participants 60 years of age and older). This value is the denominator for the percentage calculations.
Mild = does not interfere with activity; moderate = some interference with activity; severe = prevents daily activity.
§
“Any” includes all participants who reported a reaction as “mild”, “moderate”, or “severe” during Day 1 to Day 7 after vaccination.
“Any systemic reaction” includes all participants who reported any fever ≥38.0°C or any other systemic reaction (fatigue, headache, joint pain, or muscle pain) as “mild”, “moderate”, or “severe” during Day 1 to Day 7 after vaccination.
#
Severity was not collected for use of antipyretic or pain medication. The numbers listed reflect “yes” responses (i.e., number of reactions reported).

18 through 49 Years of Age

50 through 59 Years of Age

≥60 Years of Age

Vaccine Group

Prevnar 20 (N =335) %

Prevnar 13 (N =112) %

Prevnar 20 (N =331) %

Prevnar 13 (N =111) %

Prevnar 20/Saline (N =1505) %

Prevnar 13/PPSV23 (N =1483) %

Systemic Reaction

Muscle pain

Any §

66.6

74.1

49.8

49.5

39.1

37.3

Mild

36.4

42.0

33.8

31.5

28.9

26.8

Moderate

29.0

31.3

15.4

17.1

9.8

10.0

Severe

1.2

0.9

0.6

0.9

0.4

0.5

Fatigue

Any §

42.7

43.8

39.3

36.0

30.2

30.7

Mild

18.8

20.5

21.1

18.0

16.1

17.5

Moderate

22.1

19.6

17.2

15.3

12.8

11.9

Severe

1.8

3.6

0.9

2.7

1.2

1.2

Headache

Any §

38.8

33.9

32.3

36.0

21.5

23.3

Mild

21.5

16.1

20.5

21.6

15.5

17.0

Moderate

14.6

17.0

10.9

13.5

5.4

5.9

Severe

2.7

0.9

0.9

0.9

0.7

0.3

Joint pain

Any §

13.4

17.9

15.4

20.7

12.6

13.7

Mild

6.3

8.9

10.6

12.6

6.9

7.1

Moderate

7.2

8.0

4.8

7.2

5.4

6.3

Severe

0

0.9

0

0.9

0.3

0.2

Fever

≥38.0°C

1.2

1.8

1.5

0.9

0.9

0.8

≥38.0°C to 38.4°C

0.6

0

0.6

0.9

0.3

0.4

>38.4°C to 38.9°C

0.3

0

0.3

0

0.3

0.2

>38.9°C to 40.0°C

0.3

1.8

0.3

0

0

0

>40.0°C

0

0

0.3

0

0.3

0.2

Any systemic reaction

79.4

83.0

69.5

67.6

55.2

55.4

Use of antipyretic or pain medication #

25.7

23.2

24.5

27.9

18.5

20.4

Table 7. Percentage of Participants With Solicited Systemic Reactions, by Maximum Severity, Within 7 Days After Vaccination in Individuals 65 Years of Age and Older With Prior Pneumococcal Vaccination – Study 6*,
*
Study 6 was conducted in the United States and in Sweden (NCT03835975).
Open-label administration of Prevnar 20.
Includes participants who previously received either PPSV23 ≥1 to ≤5 years before enrollment (PPSV23), Prevnar 13 ≥6 months before enrollment (Prevnar 13), or Prevnar 13 followed by PPSV23 ≥1 year before enrollment (Prevnar 13 and PPSV23) in the study.
§
N = number of participants with any e-diary data reported after vaccination. This value is the denominator for the percentage calculations.
Mild = does not interfere with activity; moderate = interferes with activity; severe = prevents daily activity.
#
“Any” includes all participants who reported a reaction as “mild”, “moderate”, or “severe” during Day 1 to Day 7 after vaccination.
Þ
“Any systemic reaction” includes all participants who reported any fever ≥38.0°C or any other systemic reaction (fatigue, headache, joint pain, or muscle pain) as “mild”, “moderate”, or “severe” during Day 1 to Day 7 after vaccination.
ß
Severity was not collected for use of antipyretic or pain medication. The numbers listed reflect “yes” responses (i.e., number of reactions reported).

Prior Pneumococcal Vaccination Status

PPSV23

Prevnar 13

Prevnar 13 and PPSV23

Vaccine Group

Prevnar 20 (N § =253) %

Prevnar 13 (N § =121) %

Prevnar 20 (N § =245) %

PPSV23 (N § =126) %

Prevnar 20 (N § =125) %

Systemic Reaction

Muscle pain

Any #

32.0

31.4

33.9

46.0

37.6

Mild

26.1

24.0

25.3

31.7

28.0

Moderate

5.5

5.0

8.6

11.9

8.8

Severe

0.4

2.5

0

2.4

0.8

Fatigue

Any #

28.9

22.3

31.0

33.3

32.8

Mild

17.8

9.9

19.6

19.8

19.2

Moderate

11.1

9.9

10.2

13.5

12.0

Severe

0

2.5

1.2

0

1.6

Headache

Any #

17.8

18.2

13.5

21.4

19.2

Mild

12.6

12.4

9.8

20.6

12.8

Moderate

4.7

5.8

3.7

0.8

5.6

Severe

0.4

0

0

0

0.8

Joint pain

Any #

6.7

10.7

11.8

15.9

16.8

Mild

4.7

5.0

7.8

10.3

12.8

Moderate

2.0

5.0

4.1

5.6

4.0

Severe

0

0.8

0

0

0

Fever

≥38.0°C

0.8

0

0

1.6

0

≥38.0°C to 38.4°C

0.8

0

0

0.8

0

>38.4°C to 38.9°C

0

0

0

0.8

0

>38.9°C to 40.0°C

0

0

0

0

0

>40.0°C

0

0

0

0

0

Any systemic reaction Þ

51.8

43.8

50.2

59.5

52.8

Use of antipyretic or pain medication ß

15.8

14.9

17.1

19.8

17.6

Safety with Concomitant Vaccine Administration in Participants ≥65 years of age (Study 7)

In Study 7, the rates of local reactions at the Prevnar 20 injection site within 10 days after vaccination were similar between participants who received Prevnar 20 and Fluad Quadrivalent concomitantly (Group 1) or separately (Group 2). The rates of systemic reactions within 7 days following administration of Prevnar 20 were generally numerically higher in Group 1 compared to Group 2; however, overall, fever in both groups was uncommon (<1.5%) and other systemic reactions (fatigue, headache, muscle, or joint pain) were primarily mild to moderate (≤0.9% were severe). The proportions of participants with SAEs occurring within 1 month after vaccination with Prevnar 20 were 1.1% for Group 1 and 1.7% in Group 2. No SAEs occurring within 1 month after vaccination with Prevnar 20 were considered related to vaccination.

VxLabels.com provides trustworthy package insert and label information about marketed drugs and vaccines as submitted by manufacturers to the U.S. Food and Drug Administration. Package information is not reviewed or updated separately by VxLabels.com. Every individual vaccine label and package insert entry contains a unique identifier which can be used to secure further details directly from the U.S. National Institutes of Health and/or the FDA.

Vaccine Sections

Vaccine Information by RSS

As the leading independent provider of trustworthy vaccine information, our database comes directly from the FDA's central repository of drug labels and package inserts under the Structured Product Labeling standard. VxLabels.com provides the full vaccine subset of the FDA's repository. Vaccine information provided here is not intended as a substitute for direct consultation with a qualified health professional.

Terms of Use | Copyright © 2024. All Rights Reserved.