6 ADVERSE REACTIONS
In adults 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 adults 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%).
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 a single dose of Prevnar 20 in adults 18 years of age and older was evaluated in five 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 6 trials, 4552 adults received Prevnar 20 and 2496 received active control vaccine.
Pneumococcal Vaccine Naïve Adults 18 Years of Age and Older
The safety of Prevnar 20 in adults 18 years of age and older with no history of pneumococcal vaccination was evaluated in five 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).
Adults ≥65 Years of Age Previously Immunized with a Pneumococcal Vaccine
The safety of Prevnar 20 in adults 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.
Demographics of Trial Participants
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 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%).
Solicited adverse reactions for Prevnar 20 in the three main trials 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 serious adverse events (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
Across all 6 clinical trials combined, performed in adults 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
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 adults naïve to pneumococcal vaccination (Study 1) and in adults with prior pneumococcal vaccination (Study 6) are shown in Table 1 and Table 2, 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 adults naïve to pneumococcal vaccination (Study 1) and in adults with prior pneumococcal vaccination (Study 6) are shown in Table 3 and Table 4, respectively.
|18–49 Years of Age||50–59 Years of Age||≥60 Years of Age|
|Pain at injection site‡|
|Any (>2.0 cm)§||11.6||12.5||8.8||10.8||7.5||8.0|
|Any (>2.0 cm)§||9.0||9.8||8.2||5.4||7.3||6.2|
|Any local reaction#||81.2||82.1||72.8||70.3||57.4||56.0|
|Prior Pneumococcal Vaccination Status‡|
|PPSV23||Prevnar 13||Prevnar 13 and PPSV23|
|Pain at the injection site¶|
|Any (>2.0 cm)#||9.9||6.6||9.4||14.3||4.0|
|Any (>2.0 cm)#||7.9||2.5||8.6||12.7||4.8|
|Any local reactionß||53.0||43.8||64.1||57.9||54.4|
|18 through 49 Years of Age||50 through 59 Years of Age||≥60 Years of Age|
|≥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|
|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|
|Prior Pneumococcal Vaccination Status‡|
|PPSV23||Prevnar 13||Prevnar 13 and PPSV23|
|≥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|
|Any systemic reactionÞ||51.8||43.8||50.2||59.5||52.8|
|Use of antipyretic or pain medicationß||15.8||14.9||17.1||19.8||17.6|
6.2 Postmarketing Experience With Prevnar 13
The postmarketing safety experience with Prevnar 13 is relevant to Prevnar 20 since the vaccines are manufactured and formulated similarly and contain 13 of the same polysaccharide conjugates. These adverse reactions are included based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to Prevnar 13 vaccine in adults. 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 product exposure. The following adverse reactions have been spontaneously reported during postapproval use of Prevnar 13 and may also be seen in postmarketing experience with Prevnar 20. Reactions reported in the postmarketing experience and which pertain only to pediatric populations are not included in this listing.
- Immune System Disorders: Anaphylactic/anaphylactoid reaction, including shock
- Skin and Subcutaneous Tissue Disorders: Angioneurotic edema, Erythema multiforme
- Blood and lymphatic system disorders: Lymphadenopathy localized to the region of the injection site
- General Disorders and Administration Site Conditions: Vaccination-site dermatitis, vaccination-site pruritus, vaccination-site urticaria