Immunogenicity and safety

Prevnar 13®: Studied head-to-head versus Pneumovax® 23 in 2 comparative trials of immune response2
Primary end points
In both studies, Prevnar 13® demonstrated a noninferior immune response versus Pneumovax® 23 for the 12 shared serotypes

In a separate primary end point for serotype 6A, titer levels were statistically significantly greater after receiving Prevnar 13® than Pneumovax® 23
Secondary end points
Prevnar 13® demonstrated a statistically significantly greater immune response versus Pneumovax® 23 for 8 of 12 shared serotypes for vaccine-naive adults and 9 of 12 shared serotypes for previously vaccinated adults
  • The comparative efficacy of Prevnar 13® and Pneumovax® 23 has not been evaluated in randomized controlled studies
  • Never been vaccinated with Pneumovax® 23
  • Study subjects were given either Prevnar 13® or Pneumovax® 23
    Immune response compared between Prevnar 13® and Pneumovax® 23 in patients aged 60-64 years

  • This study recruited immunocompetent adults, including those with stable underlying conditions, such as:
Chronic cardiovascular disease
Renal disorders
Chronic liver disease
Smoking
Chronic pulmonary disease
Diabetes mellitus
Alcoholism

Study description
Clinical trials were conducted in adults not previously vaccinated with pneumococcal polysaccharide vaccine, Pneumovax® 23. In an active-controlled, modified double-blind* clinical trial (noninferiority study in Pneumovax® 23–unvaccinated adults) of Prevnar 13® in the United States:
  • Pneumovax® 23–unvaccinated adults aged 60 through 64 years received either Pneumovax® 23 (n=367-402) or Prevnar 13® (n=359-404), and adults aged 50 through 59 years received 1 dose of Prevnar 13® (open label, n=350-384)
  • Immune responses elicited by Prevnar 13® and Pneumovax® 23 were measured by an opsonophagocytic assay (OPA) for the 13 pneumococcal serotypes contained in Prevnar 13®. OPA quantifies the ability of immune sera to mediate the killing of Streptococcus pneumoniae by phagocytic cells
  • Serotype-specific OPA geometric mean titers (GMTs), measured 1 month after each vaccination, were used to calculate the geometric mean ratios (GMRs) comparing Prevnar 13® and Pneumovax® 23 (Prevnar 13®/Pneumovax® 23)
  • Study end points used GMRs to compare serotype-specific OPA responses of Prevnar 13® relative to those of Pneumovax® 23 for shared serotypes
  • Response to serotype 6A, which is contained in Prevnar 13® but not in Pneumovax® 23, was assessed by the proportion of subjects in each group who demonstrated a 4-fold increase in the specific OPA titer above preimmunization levels

*Modified double-blind means that the site staff dispensing and administering the vaccine were unblinded, but all other study personnel and subjects were blinded.

  • Previously vaccinated with Pneumovax® 23 at least 5 years prior
  • Study subjects were given either Prevnar 13® or Pneumovax® 23

  • This study recruited immunocompetent adults, including those with stable underlying conditions, such as:
Chronic cardiovascular disease
Renal disorders
Chronic liver disease
Smoking
Chronic pulmonary disease
Diabetes mellitus
Alcoholism

Study description
Clinical trials were conducted in adults previously vaccinated with Pneumovax® 23. In an active-controlled, modified double-blind* clinical trial (noninferiority study in Pneumovax® 23– prevaccinated adults) of Prevnar 13® in the United States and Sweden:
  • Pneumovax® 23–prevaccinated adults aged 70 years and older who had received 1 dose of Pneumovax® 23 at least 5 years prior received either Pneumovax® 23 (n=395-445) or Prevnar 13® (n=400-426)
  • Subjects were previously vaccinated with Pneumovax® 23 at least 5 years prior per CDC recommendations for adults aged 65 years and older
  • Immune responses elicited by Prevnar 13® and Pneumovax® 23 were measured by an opsonophagocytic assay (OPA) for the 13 pneumococcal serotypes contained in Prevnar 13®. OPA quantifies the ability of immune sera to mediate the killing of S. pneumoniae by phagocytic cells
  • Serotype-specific OPA geometric mean titers (GMTs), measured 1 month after each vaccination, were used to calculate the geometric mean ratios (GMRs) comparing Prevnar 13® and Pneumovax® 23 (Prevnar 13®/Pneumovax® 23)
  • Study end points used GMRs to compare serotype-specific OPA responses of Prevnar 13® relative to those of Pneumovax® 23 for shared serotypes
  • Response to serotype 6A, which is contained in Prevnar 13® but not in Pneumovax® 23, was assessed by the proportion of subjects in each group who demonstrated a 4-fold increase in the specific OPA titer above preimmunization levels

*Modified double-blind means that the site staff dispensing and administering the vaccine were unblinded, but all other study personnel and subjects were blinded.

  • Never been vaccinated with Pneumovax® 23
  • Study subjects were given Prevnar 13®
  • Immune response to Prevnar 13® was compared to that elicited by Prevnar 13® in vaccine-naive adults aged 60-64 years, for all 13 serotypes

  • This study recruited immunocompetent adults, including those with stable underlying conditions, such as:3
Chronic cardiovascular disease
Renal disorders
Chronic liver disease
Current smokers
Chronic pulmonary disease
Diabetes mellitus
Alcoholism

Study description3
This was a cohort analysis from a larger randomized, double-blind clinical trial that compared the immunogenicity, tolerability, and safety of Prevnar 13® and Pneumovax® 23 in Pneumovax® 23-naive adults. In this analysis, the immunogenicity, tolerability, and safety of Prevnar 13® in adult subjects 18-49 years of age was compared with adults 60-64 years of age.
  • Pneumovax® 23-naive adults were grouped by age into 2 cohorts: 18-49 years (n=899) and 60-64 years (n=417). All subjects received 1 dose of Prevnar 13®
  • Immunogenicity was assessed by an opsonophagocytic assay (OPA) for the 13 pneumococcal serotypes contained in Prevnar 13®. OPA quantifies the ability of immune sera to mediate the killing of S. pneumoniae by phagocytic cells
  • Serotype-specific OPA geometric mean titers (GMTs), measured 1 month after each vaccination, were used to calculate the GMT ratio comparing the 2 age cohorts
  • The primary immunogenicity objective of the study was to demonstrate the noninferiority of the immune response in the 18- to 49-year-old cohort to that of the 60- to 64-year-old cohort

In the 6 immunogenicity and safety studies (N=7097), in both pneumococcal vaccine–naive and previously vaccinated adults aged 18 years and older, the following adverse events were reported:2
Local adverse events
The most commonly reported local adverse events (>20%) in adults were:
  • pain at the injection site (>50%)
  • redness (>10%)
  • swelling (>10%)
  • limitation of arm movement (>10%)
Systemic adverse events
The most commonly reported systemic adverse events (>20%) in adults were:
  • fatigue (>30%)
  • headache (>20%)
  • muscle pain (>20%)
  • joint pain (>10%)
  • decreased appetite (>10%)
  • vomiting (>5%)
  • fever (>5%)
  • chills (>5%)
  • rash (>5%)
Incidence of fever
In clinical trials of Prevnar 13®, incidence of fever (defined as temperatures ≥100.4°F) was:
  • 1.5% to ~4.2% in vaccine-naive adults
  • 1.0% to ~1.1% in previously vaccinated adults

Solicited adverse reactions for Prevnar 13® in the safety and immunogenicity studies were monitored by subjects recording local adverse reactions and systemic reactions daily using an electronic diary for 14 consecutive days following vaccination. Unsolicited serious and nonserious adverse events were collected for 1 month after each vaccination.

*Number of subjects with known values.
Statistically significant difference, P<0.05. No adjustments for multiplicity.
Local adverse events within 14 days after vaccination in an open-label, noncomparator cohort of a randomized, double-blind comparator clinical trial.
*Number of subjects with known values.
Generalized pain.
Statistically significant difference, P<0.05. No adjustments for multiplicity.
§Systemic adverse events within 14 days after vaccination in an open-label, noncomparator cohort of a randomized, double-blind comparator clinical trial.
Percentage of subjects with fever within 14 days after vaccination with Prevnar 13® or Pneumovax® 23 in clinical trials
*Open-label administration of Prevnar 13®.
Number of subjects with known values.
Fevers >104.0°F were confirmed to be data entry errors.
Pneumovax is a registered trademark of Merck & Co., Inc.
ACIP=Advisory Committee on Immunization Practices; CDC=Centers for Disease Control and Prevention.
The safety of Prevnar 13® was evaluated in 6 safety and immunogenicity studies and 1 efficacy study2