Prevenar 20

The vaccine is a homogeneous white suspension.
1 dose (0.5 mL) contains: Pneumococcal polysaccharide serotype 1^*,† 2.2 μg; Pneumococcal polysaccharide serotype 3^*,† 2.2 μg; Pneumococcal polysaccharide serotype 4^*,† 2.2 μg; Pneumococcal polysaccharide serotype 5^*,† 2.2 μg; Pneumococcal polysaccharide serotype 6A^*,† 2.2 μg; Pneumococcal polysaccharide serotype 6B^*,† 4.4 μg; Pneumococcal polysaccharide serotype 7F^*,† 2.2 μg; Pneumococcal polysaccharide serotype 8^*,† 2.2 μg; Pneumococcal polysaccharide serotype 9V^*,† 2.2 μg; Pneumococcal polysaccharide serotype 10A^*,† 2.2 μg; Pneumococcal polysaccharide serotype 11A^*,† 2.2 μg; Pneumococcal polysaccharide serotype 12F^*,† 2.2 μg; Pneumococcal polysaccharide serotype 14^*,† 2.2 μg; Pneumococcal polysaccharide serotype 15B^*,† 2.2 μg; Pneumococcal polysaccharide serotype 18C^*,† 2.2 μg; Pneumococcal polysaccharide serotype 19A^*,† 2.2 μg; Pneumococcal polysaccharide serotype 19F^*,† 2.2 μg; Pneumococcal polysaccharide serotype 22F^*,† 2.2 μg; Pneumococcal polysaccharide serotype 23F^*,† 2.2 μg; Pneumococcal polysaccharide serotype 33F^*,† 2.2 μg.
^*Conjugated to CRM₁₉₇ carrier protein (approximately 51 μg per dose).
^†Adsorbed on aluminium phosphate (0.125 mg aluminium per dose).
Excipients/Inactive Ingredients: Aluminium phosphate, Succinic acid, Sodium chloride, Polysorbate 80, Water for injections.

Pharmacological class, therapeutic class: Vaccines (J07AL02).
Pharmacology: Pharmacodynamics: Mechanism of action: S. pneumoniae (pneumococcus) is a gram-positive diplococcus that can cause invasive disease including meningitis, sepsis, and pneumonia with bacteremia and noninvasive disease such as pneumonia without bacteremia and acute otitis media (AOM). Over 100 different serotypes of pneumococcus have been identified.
PREVENAR 20 contains 20 pneumococcal capsular polysaccharides all conjugated to CRM₁₉₇ carrier protein, which modifies the immune response to the polysaccharide from a T-cell independent response to a T-cell dependent response. The T-cell dependent response leads to a higher antibody response, and induces antibodies that enhance opsonization, phagocytosis and killing of pneumococci to protect against pneumococcal disease, as well as generation of memory B-cells, allowing for an anamnestic (booster) response on re-exposure to the bacteria.
Vaccination with PREVENAR 20 induces serum antibody production and immunologic memory against the serotypes contained within the vaccine. Antibodies to some polysaccharides may cross-react with related types and provide some protection against additional serotypes.
In adults, the levels of circulating antibodies, and in pediatric populations the serotype-specific levels, that correlate with protection against pneumococcal disease have not been clearly defined.
Disease burden for infants and children: Pneumonia: A substantial burden of bacteremic pneumonia including parapneumonic effusions and empyemas are caused by the PREVENAR 20 serotypes. While the serotype distribution of non-bacteremic pneumonia currently cannot be determined due to the lack of sensitive and specific diagnostic tests, evidence of the substantial proportion of bacteremic pneumonia due to the PREVENAR 20 serotypes and the impact of pneumococcal conjugate vaccines on all-cause pneumonia suggest PREVENAR 20 will likely help protect against childhood pneumonia.
Acute otitis media: AOM is a common infection in young children worldwide - one of the most common reasons for clinic visits and antimicrobial prescriptions in developed countries. The majority of AOM is due to bacteria, and among bacterial OM globally, S. pneumoniae is one of the most common causes, causing 24% and approximately 26% of cases as reported from studies in the USA and Israel, respectively, during the 13vPnC period. Studies in France, Germany, Israel, and USA during the 13vPnC period found that 12% to 31% of acute or complicated pneumococcal OM cases were caused by the 7 additional PREVENAR 20 serotypes not covered by 13vPnC. While mortality is rare, certain clinical presentations of OM, especially those caused by S. pneumoniae, are associated with significant morbidity given their severity, complexity, and propensity for sequelae including hearing loss.
Disease burden for adults: Pneumonia is the most common clinical presentation of pneumococcal disease in adults.
The reported incidence of CAP and IPD in Europe varies by country, increases with age from 50 years and is highest in individuals 65 years of age and older. S. pneumoniae is the most frequent bacterial cause of CAP and has been estimated to be responsible for approximately 30% of all CAP cases requiring hospitalization in adults in developed countries, with the majority of cases considered non-bacteremic.
Bacteremic pneumonia (approximately 80% of IPD in adults), bacteremia without a focus, and meningitis are the most common manifestations of IPD in adults. Based on surveillance data, in the context of established childhood pneumococcal conjugate vaccination programs, the pneumococcal serotypes in PREVENAR 20 may be responsible for at least 63% to 76% (depending on country) of IPD in older adults in Europe.
The risk for CAP and IPD in adults also increases with chronic underlying medical conditions, specifically, anatomical or functional asplenia, diabetes mellitus, asthma, chronic cardiovascular, pulmonary, kidney or liver disease, and it is highest in those who are immune-suppressed such as those with malignant hematological diseases or HIV infection.
PREVENAR 20 effectiveness: Effectiveness studies using PREVENAR 20 were not conducted.
The efficacy and effectiveness of 13vPnC are relevant to PREVENAR 20, since the vaccines are manufactured similarly and contain 13 of the same polysaccharide conjugates.
13vPnC effectiveness in children: Invasive pneumococcal disease: Four years after the introduction of 7vPnC as a two dose primary series plus booster dose in the second year of life and with a 94% vaccine uptake a 98% (95% CI 95; 99) reduction of disease caused by the 7 vaccine serotypes was reported in England and Wales. Subsequently, four years following the switch to 13vPnC, the additional reduction in incidence of IPD due to the 7 serotypes in 7vPnC ranged from 76% in children less than 2 years of age to 91% in children 5-14 years of age. The serotype specific reductions for each of the 5 additional serotypes in 13vPnC (no cases of serotype 5 IPD were observed) by age group are shown in Table 1 and ranged from 68% (serotype 3) to 100% (serotype 6A) for children less than 5 years of age. Significant incidence reductions were also observed in older age groups who had not been vaccinated with 13vPnC (indirect effect). (See Table 1.)


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Otitis media (OM): In a two dose primary series plus booster dose in the second year of life the impact of 13vPnC on OM was documented in a population-based active-surveillance system in Israel middle ear fluid collected via tympanocentesis from children less than 2 years of age with OM. Following the introduction of 7vPnC and subsequently 13vPnC there was a decline in incidence of 96% of OM for the 7vPnC serotypes plus serotype 6A and a decline in incidence of 85% for the additional serotypes 1, 3, 5, 7F, and 19A in 13vPnC.
In a prospective, population-based, long-term surveillance study conducted in Israel between 2004 and 2015 following the introduction of 7vPnC and subsequently 13vPnC, reductions of non-pneumococcal bacteria isolated from children <3 years of age with OM were 75% for all NTHi cases, and 81% and 62% for cases of OM due to M. catarrhalis and S. pyogenes, respectively.
Pneumonia: In a multicenter observational study in France comparing the periods before and after the switch from 7vPnC to 13vPnC, there was 16% reduction in all community-acquired pneumonia (CAP) cases in emergency departments in children 1 month to 15 years of age. Reductions were 53% (p<0.001) for CAP cases with pleural effusion and 63% (p<0.001) for microbiologically confirmed pneumococcal CAP cases. In the second year after the introduction of 13vPnC the total number of CAP cases due to the 6 additional vaccine serotypes in 13vPnC was reduced by 74% (27 to 7 isolates).
In an ongoing surveillance system (2002 to 2013) to document the impact of 7vPnC and subsequently 13vPnC on CAP in children less than 5 years in Southern Israel using a 2-dose primary series with a booster dose in the second year of life, there was a reduction of 68% (95% CI 73; 61) in outpatient visits and 32% (95% CI 39; 22) in hospitalizations for alveolar CAP following the introduction of 13vPnC when compared to the period before the introduction of 7vPnC was introduced.
Reduction of Antimicrobial Resistance (AMR): Following the introduction of 7vPnC and subsequently 13vPnC, a reduction in AMR has been shown as a result of direct reduction of serotypes and clones associated with AMR from the population (including 19A), reduction of transmission (herd effects), and reduction in the use of antimicrobial agents.
In a double-blind, randomized, controlled study in Israel comparing 7vPnC and 13vPnC that reported the acquisition of S. pneumoniae, reductions of serotypes 19A, 19F, and 6A not susceptible to either penicillin, erythromycin, clindamycin, penicillin plus erythromycin, or multiple drugs (≥3 antibiotics) ranged between 34% and 62% depending on serotype and antibiotic.
Analyses of data from the United States Centers for Disease Control and Prevention evaluated temporal trends for four antibiotic classes and showed that compared to 2009 (the last year of 7vPnC use in the US, following which it was replaced with 13vPnC), by 2013 the annual incidence of IPD due to pneumococci non-susceptible to macrolides, cephalosporins, penicillins, and tetracyclines had decreased by 63%, 81%, 83%, and 81% in children less than 5 years of age and 24%, 49%, 57%, and 53% in persons 65 years of age and older.
13vPnC Effect on Nasopharyngeal Carriage: In a surveillance study in France in children presenting with AOM, changes in nasopharyngeal (NP) carriage of pneumococcal serotypes were evaluated following the introduction of 7vPnC and subsequently 13vPnC. 13vPnC significantly reduced NP carriage of the 6 additional serotypes (and serotype 6C) combined and individual serotypes 6C, 7F, 19A when compared with 7vPnC. A reduction in carriage was also seen for serotype 3 (2.5% vs 1.1%; p=0.1). There was no carriage of serotypes 1 or 5 observed.
The effect of pneumococcal conjugate vaccination on NP carriage was studied in a randomized double-blind study (6096A1-3006) in which infants received either 13vPnC or 7vPnC at 2, 4, 6 and 12 months of age in Israel. 13vPnC significantly reduced newly identified NP acquisition of the 6 additional serotypes (and serotype 6C) combined and of individual serotypes 1, 6A, 6C, 7F, 19A when compared with 7vPnC. There was no reduction seen in serotype 3 and for serotype 5 the colonization was too infrequent to assess impact. For 6 of the remaining 7 common serotypes, similar rates of NP acquisition were observed in both vaccine groups; for serotype 19F a significant reduction was observed.
13vPnC efficacy study in adults 65 years of age and older: Efficacy against vaccine-type (VT) pneumococcal CAP and IPD was assessed in a large-scale, randomized, double-blind, placebo-controlled study (Community-Acquired Pneumonia Immunization Trial in Adults [CAPiTA]) in the Netherlands. A total of 84,496 participants 65 years of age and older received a single vaccination of either 13vPnC or placebo in a 1:1 randomization.
The CAPiTA study enrolled participants 65 years of age and older whose demographic and health characteristics may differ from those seeking vaccination. Chronic medical conditions (asthma, diabetes, heart, liver, and/or lung diseases) were reported in 42.3% of study participants at baseline.
A first episode of hospitalized, chest X-ray-confirmed pneumonia was identified in about 2% of this population (n=1814 participants) of which 329 cases were confirmed pneumococcal CAP and 182 cases were VT pneumococcal CAP in the per-protocol and modified intent-to-treat (mITT) populations.
Efficacy was demonstrated for the primary and secondary endpoints in the per-protocol population (see Table 2).


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The duration of protective efficacy against a first episode of VT pneumococcal CAP, NB/NI VT pneumococcal CAP, and VT-IPD extended throughout the 4-year study.
The study was not designed to demonstrate efficacy in subgroups, and the number of participants 85 years of age and older was not sufficient to demonstrate efficacy in this age group.
A post-hoc analysis was used to estimate the following public health outcomes against clinical CAP (as defined in the CAPiTA study, and based on clinical findings regardless of radiologic infiltrate or etiologic confirmation): VE, incidence rate reduction (IRR), and number needed to vaccinate (NNV) (Table 3).
IRR, also referred to as vaccine-preventable disease incidence, is the number of cases of vaccine-preventable disease per 100,000 person-years of observation.
In Table 3, NNV is a measure that quantifies the number of people that need to be vaccinated in order to prevent one clinical CAP case. (See Table 3.)


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PREVENAR 20 immunogenicity clinical studies in infants: Approval of PREVENAR 20 for the pediatric population was based on comparing the totality of the immune responses in infants after receiving PREVENAR 20 to the immune responses after receiving 13vPnC. The comparison, following the WHO guideline, included the percentage of participants with predefined IgG (immunoglobulin G) concentrations and IgG geometric mean concentrations (GMCs). The noninferiority criteria and other supportive data were agreed by the United States Food and Drug Administration (FDA) and Committee for Medicinal Products for Human Use (CHMP). This approach is largely based upon the observed relationship between immunogenicity and IPD efficacy from 3 placebo-controlled trials with either 7vPnC (see as previously mentioned for 13vPnC Effectiveness) or the investigational 9-valent CRM₁₉₇ conjugate polysaccharide vaccine conducted in Navajo and White Mountain Apache Indian infants (cluster randomized trial), infants in Soweto, South Africa, and infants in the Northern California Kaiser Permanente (NCKP) health organization. The predefined IgG concentration corresponding to 0.35 μg/mL in the WHO enzyme-linked immunosorbent assay (ELISA) is only applicable at the population level and cannot be used to predict individual or serotype-specific protection against IPD.
Immune responses elicited by PREVENAR 20 and 13vPnC in children were measured using a serotype-specific multiplex direct-binding Luminex immunoassay (dLIA), designed to determine the concentration of specific polysaccharide-binding IgG antibodies, and opsonophagocytic activity (OPA) assays to measure serotype-specific functional OPA titers. The Pfizer LUMINEX assay (dLIA) to measure IgG has been bridged to the standard ELISA assay.
PREVENAR 20 clinical trials in infants: Clinical studies evaluating the immunogenicity of PREVENAR 20 were conducted in infants following a 3-dose series at 2, 4 and 11 to 12 months of aged (2 infant doses and toddler dose) in a Phase 3 trial (Study 1012) or 4-dose series (3 infant doses and a toddler dose) at 2, 4, 6, and 12 to 15 months of age have been conducted in one randomized Phase 2 trial (Study 1003) and one Phase 3 trial (Study 1011) in USA/Puerto Rico.
The full infant immunization series for PREVENAR 20 consists of 3-dose with an alternative 4-dose immunization series.
Pneumococcal immune responses after 2 and 3 doses in a 3-dose vaccination series: In Study 1012, the immunogenicity of PREVENAR 20 was evaluated in infants when administered in a series of 2 infant doses and 1 toddler dose in infants enrolled from Europe and Australia. The study enrolled infants 2 months (≥42 to ≤112 days) of age and born at >36 weeks of gestation. Participants were randomized (1:1) to receive either PREVENAR 20 or 13vPnC with the first dose given at 42 to 112 days of age, a second dose given approximately 2 months later, and the third dose given at approximately 11 to 12 months of age. Participants received concomitant vaccines at these visits.
PREVENAR 20 elicited immune responses, as assessed by IgG GMCs, percentages of participants with predefined IgG concentrations, and OPA geometric mean titers (GMTs) for all 20 serotypes contained in the vaccine. The observed IgG GMCs and percentages of participants with predefined IgG concentrations 1 month after the third (last) dose of PREVENAR 20 were generally comparable to the 13vPnC group for the 13 matched serotypes and higher for the 7 additional serotypes (Table 4).
One month after the 2 infant doses, the observed IgG GMCs were generally comparable for most serotypes to the 13vPnC group and the percentages of participants with predefined IgG concentrations for the 13 matched serotypes were generally lower in the PREVENAR 20 group than the 13vPnC group (Table 5). The immune responses to the additional 7 serotypes were higher in the PREVENAR 20 group than the 13vPnC group after the 2^nd dose. (See Tables 4 and 5.)


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OPA responses after 2 and 3 doses in a 3-dose vaccination series: The OPA GMTs for the 13 matched serotypes at 1 month after Dose 2 and 1 month after Dose 3 in the PREVENAR 20 group were generally similar to the observed OPA GMTs in the 13vPnC group for most serotypes. The observed OPA GMTs were lower for serotype 6B after Dose 2 and serotype 1 after Dose 3 in the PREVENAR 20 group. OPA GMTs were higher after Dose 3 than after Dose 2 for all serotypes. The observed OPA GMTs for the 7 additional serotypes, both 1 month after the second dose and 1 month after the third dose were substantially higher in the PREVENAR 20 group than those in the 13vPnC group (see Table 6).


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Booster responses after the last dose in a 3-dose infant vaccination series: PREVENAR 20 immune responses show boosting in IgG GMCs and percentage of participants with a predefined IgG concentrations 1 month after Dose 3, that are higher than concentrations before Dose 3, and also increased relative to the levels 1 month after Dose 2, indicating that a memory response was elicited by the 2 infant doses (see Tables 4 and 5). For all serotypes, the OPA responses also show a generally similar pattern of boosting as observed with the IgG responses, with priming evidenced by the robust OPA responses geometric mean fold rise (GMFRs) and the percentages of participants with a ≥4-fold rise in OPA titers) from before to one month after Dose 3. In summary, PREVENAR 20 elicits immune responses that are comparable to 13vPnC for the 13 matched serotypes and the 7 additional serotypes after the third (toddler) dose.
The totality of data show that a 3-dose series of PREVENAR 20 elicited immune responses expected to provide children protection against pneumococcal disease similar to that of 13vPnC for all 20 vaccine serotypes.
Pneumococcal IgG immune responses after 3 and 4 doses in a 4-dose vaccination series: In Study 1011, healthy infants 2 months (≥42 to ≤98 days) of age at the time of consent and born at >36 weeks of gestation, were enrolled. Participants were randomized (1:1) to receive either PREVENAR 20 or 13vPnC at approximately 2, 4, 6, and 12 to 15 months of age. Routine pediatric vaccinations were administered concomitantly (see Interactions).
The IgG GMCs for PREVENAR 20 were noninferior for all 13 matched serotypes to 13vPnC one month after Dose 4, based on a 2-fold noninferiority criterion. The IgG GMCs for all 7 additional serotypes were noninferior to the lowest IgG GMC among 13vPnC serotypes (other than serotype 3) based on a 2-fold noninferiority criterion. This was also the case for the IgG GMCs for PREVENAR 20, 1 month after Dose 3. Noninferiority of the percentages of participants with predefined serotype-specific IgG concentrations one month after Dose 3 was met for 8 of the 13 serotypes and missed by small margins for 4 serotypes (serotypes 1, 4, 9V and 23F) based on a 10% noninferiority criterion. Six of the 7 additional serotypes met the noninferiority criterion; serotype 12F missed the statistical noninferiority criterion. At both 1 month after Dose 3 and 1 month after Dose 4, the IgG GMCs and percentages of participants with predefined IgG concentrations for all 7 additional serotypes, including serotype 12F, were much higher than the corresponding serotype responses in the 13vPnC group, consistent with statistically greater antibody levels based on the lower bounds of the nominal 2-sided 95% confidence limits (not adjusted for multiplicity). (See Tables 7 and 8.)


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Additional Important Measures of Immune Response: OPA responses after 3 and 4 doses of PREVENAR 20: The OPA GMTs for the 13 matched serotypes 1 month after Dose 3 and 1 month after Dose 4 in the PREVENAR 20 group were generally similar to the OPA GMTs in the 13vPnC group for most serotypes, and the observed OPA GMTs were substantially higher for the 7 additional serotypes at both timepoints in the PREVENAR 20 group than in the 13vPnC group.
PREVENAR 20 elicits OPA immune responses that are comparable to 13vPnC for the 13 matched serotypes and the 7 additional serotypes after 3 doses in infants and Dose 4 in toddlers. PREVENAR 20 also elicits functional antibody to all 20 serotypes that was observed 1 month after Dose 3 and 1 month after Dose 4. PREVENAR 20 immune responses also show boosting after Dose 4, indicating that a memory response was elicited by the 3 infant doses. (See Table 9.)


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Boosting responses after the last dose in a 4-dose infant vaccination series: PREVENAR 20 shows boosting of IgG and OPA responses after Dose 4, indicating that a memory response was elicited by the 3 infant doses (see Tables 7, 8, and 9).
In summary, PREVENAR 20 elicits immune responses that are comparable to 13vPnC for the 13 matched serotypes and the 7 additional serotypes after 3 doses in infants and a fourth dose in toddlers. PREVENAR 20 also elicits functional antibody and booster responses to all 20 serotypes from 1 month after Dose 3 and 1 month after Dose 4. Thus, the totality of data shows that a 4-dose series of PREVENAR 20 elicited immune responses expected to provide children protection against pneumococcal disease similar to that of 13vPnC for all 20 vaccine serotypes.
PREVENAR 20 clinical trials in adults: Three Phase 3 clinical trials, B7471006, B7471007 and B7471008 (Study 1006, Study 1007, and Study 1008, respectively), were conducted in the United States and Sweden evaluating the immunogenicity of PREVENAR 20 in different adult age groups and in individuals who were either pneumococcal vaccine-naïve or who were previously vaccinated with 13vPnC, PPSV23, or both.
Each study included healthy adults and immunocompetent adults with stable underlying conditions including chronic cardiovascular disease, chronic pulmonary disease, renal disorders, diabetes mellitus, chronic liver disease, and medical risk conditions and behaviors (e.g., smoking) that are known to increase the risk of serious pneumococcal pneumonia and IPD. A stable medical condition was defined as a medical condition not requiring significant change in therapy in the previous 6 weeks (i.e., change to new therapy category due to worsening disease) or any hospitalization for worsening disease within 12 weeks before receipt of the study vaccine.
In each study, immune responses elicited by PREVENAR 20 and the control pneumococcal vaccines were measured by an opsonophagocytic activity (OPA) assay. OPA assays measure functional antibodies to S. pneumoniae.
Comparison of immune responses of PREVENAR 20 to 13vPnC and PPSV23: In a randomized, active-controlled, double-blind noninferiority clinical trial (Study 1007) of PREVENAR 20 in the United States and Sweden, pneumococcal vaccine-naïve adults 18 years of age and older were enrolled into 1 of 3 cohorts based on their age at enrollment and randomized to receive either PREVENAR 20 or control. Participants 60 years of age and older were randomly assigned (1:1 ratio) to PREVENAR 20 followed 1 month later with saline placebo or to 13vPnC followed 1 month later with PPSV23.
Serotype-specific OPA GMTs were measured before the first vaccination and 1 month after each vaccination. Noninferiority of immune responses, OPA GMTs 1 month after vaccination, with PREVENAR 20 to a control vaccine for a serotype was declared if the lower bound of the 2-sided 95% confidence interval (CI) for the GMT ratio (PREVENAR 20/13vPnC; PREVENAR 20/PPSV23) for that serotype was greater than 0.5.
In adults 60 years of age and older, immune responses to all 13 matched serotypes elicited by PREVENAR 20 were noninferior to the immune responses to the serotypes elicited by 13vPnC 1 month after vaccination. Immune responses to 6 out of the 7 additional serotypes induced by PREVENAR 20 were noninferior to the immune responses to these same serotypes induced by PPSV23 one month after vaccination. The response to serotype 8 missed the pre-specified statistical noninferiority criterion by a small margin (the lower bound of the 2-sided 95% CI for the GMT ratio being 0.49 versus >0.50) (Table 10).
The GMFR in OPA titers indicated that the response to serotype 8 (GMFR of 22.1) was within the range observed for the 13 serotypes in the 13vPnC group (GMFRs of 5.8 to 42.6). The same trend was also observed both in the percentage of participants with a ≥4-fold rise in OPA titers: 77.8% for serotype 8 in the PREVENAR 20 group, within the range of 54.0% to 84.0% across the 13 serotypes in the 13vPnC group and the percentage of participants with OPA titers ≥lower limit of quantitation (LLOQ) at 1 month after vaccination: 92.9% for serotype 8 in the PREVENAR 20 group, within the range of 76.0% to 96.6% across the 13 serotypes in the 13vPnC group. (See Table 10.)


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Immunogenicity in adults 18 through 59 years of age: Two studies (Study 1007 and Study 1008) assessed immune responses in adults 18 through 59 years of age with no history of prior pneumococcal vaccination. In Study 1007, described previously, participants 50 through 59 years of age and participants 18 through 49 years of age were randomly assigned (3:1 ratio) to receive 1 vaccination with PREVENAR 20 or 13vPnC. Serotype-specific OPA GMTs were measured before vaccination and 1 month after vaccination. A noninferiority analysis of PREVENAR 20 in the younger age group versus PREVENAR 20 in adults 60 through 64 years of age for a serotype was performed to support the indication in adults 18 through 49 years of age and 50 through 59 years of age. Noninferiority was to be declared if the lower bound of the 2-sided 95% CI for the GMT ratio (PREVENAR 20 in participants 18 through 49 years of age/60 through 64 years of age and in 50 through 59 years of age/60 through 64 years of age) for the 20 serotypes was >0.5. PREVENAR 20 elicited immune responses to all 20 vaccine serotypes in both of the younger age groups that were noninferior to responses in adults 60 through 64 years of age 1 month after vaccination (see Table 11).


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Study 1008 was a randomized double-blind trial to evaluate immunogenicity of 3 separately manufactured lots of PREVENAR 20. It was conducted in the United States and enrolled adults 18 through 49 years of age. The 3 different lots of PREVENAR 20 elicited immune responses that met the objectives of the study.
Immunogenicity of PREVENAR 20 in adults previously vaccinated with pneumococcal vaccine: A Phase 3 randomized, open-label clinical trial (Study 1006) described immune responses to PREVENAR 20 in adults 65 years of age and older previously vaccinated with PPSV23 (≥1 to ≤5 years prior to enrollment), previously vaccinated with 13vPnC (≥6 months prior to enrollment), or previously vaccinated with 13vPnC followed by PPSV23 (with PPSV23 vaccination ≥1 year prior to enrollment). Participants in this study previously vaccinated with 13vPnC (13vPnC only or followed by PPSV23) were enrolled at sites in the United States and participants previously vaccinated with PPSV23 only were also enrolled from Swedish sites (35.5% in that category).
PREVENAR 20 elicited immune responses to all 20 vaccine serotypes in adults 65 years of age and older with prior pneumococcal vaccination (see Table 12).


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Concomitant vaccine administration: Infants and children: In Study 1012, the concomitant administration of Infanrix hexa (containing DTaP, HBV, IPV, and Hib antigens) with all 3 doses of PREVENAR 20 or 13vPnC and single doses of MMRVAXPRO and Varilrix vaccine (containing MMR and varicella antigens respectively) were also administered with the third dose and evaluated 1 month after the third (toddler) dose of PREVENAR 20 or 13vPnC. Noninferiority was demonstrated for immune responses to diphtheria, tetanus, acellular pertussis, hepatitis B, poliovirus, Hib, MMR, and varicella vaccine antigens co-administered with PREVENAR 20 compared with 13vPnC. The results from Study 1012 support co-administration of PREVENAR 20 with routine pediatric vaccines. No safety concerns were identified in this study.
In Study 1011, the concomitant administration of Pediarix (containing DTaP, HBV, IPV antigens) and Hiberix (Hib antigen) with each of the 3 infant doses of either PREVENAR 20 or 13vPnC were evaluated 1 month after the third dose. Concomitant administration of single doses of M-M-R II (MMR antigens) and VARIVAX (varicella antigens) with the fourth dose of either PREVENAR 20 or 13vPnC were evaluated 1 month following vaccination. Noninferiority was demonstrated for immune responses to the co-administered diphtheria, tetanus, acellular pertussis, hepatitis B virus, poliovirus, and Hib vaccine antigens 1 month after 3 infant doses and co-administered MMR, and varicella virus vaccine antigens after the fourth (toddler) dose of PREVENAR 20 compared with 13vPnC. The results from Study 1011 support co-administration of PREVENAR 20 with routine pediatric vaccines. No safety concerns were identified in this study
Influenza and rotavirus vaccines were permitted to be administered concomitantly at any time during these studies according to local or national recommendations.
Clinical trial in adults to assess PREVENAR 20 given with influenza vaccine, adjuvanted (Fluad Quadrivalent, [QIV]): In a double-blind, randomized study B7471004 (Study 1004), adults 65 years of age and older were randomized in a 1:1 ratio to receive PREVENAR 20 concomitantly administered with an influenza vaccine, adjuvanted (Fluad Quadrivalent, [QIV]) (Group 1, N=898) or PREVENAR 20 administered 1 month after receiving QIV (Group 2, N=898). Pneumococcal serotype-specific OPA GMTs were evaluated 1 month after PREVENAR 20 and influenza vaccine strain hemagglutinin inhibition assay (HAI) GMTs were evaluated 1 month after QIV. The noninferiority criteria for the comparisons of OPA GMTs (lower limit of the 2-sided 95% CI of the GMT ratio [Group 1/Group 2] >0.5, 2-fold noninferiority criterion) were met for all 20 pneumococcal serotypes in PREVENAR 20. The noninferiority criteria for the comparisons of HAI GMTs (lower limit of the 2-sided 95% CI for the GMT ratio [Group 1/Group 2] >0.67, 1.5-fold noninferiority criterion) were also met for all 4 influenza vaccine strains.
Clinical trial in adults to assess PREVENAR 20 given with a third (booster) dose of COVID-19 mRNA vaccine (nucleoside modified): In a double-blind, randomized descriptive study B7471026 (Study 1026), adults 65 years of age and older who had received 2 doses of COVID-19 mRNA vaccine (nucleoside modified) at least 6 months earlier, were randomized in a 1:1:1 ratio to receive PREVENAR 20 concomitantly administered with a third (booster) dose of COVID-19 mRNA vaccine (nucleoside modified) (N=190), PREVENAR 20 administered alone (N=191), or a third (booster) dose of COVID-19 mRNA vaccine (nucleoside modified) administered alone (N=189).
Immune responses to both vaccines were observed after co-administration of PREVENAR 20 and COVID-19 mRNA vaccine (nucleoside modified). OPA GMTs for the 20 pneumococcal serotypes were similar to PREVENAR 20 administered alone and IgG GMCs for the full-length S-binding protein were similar to COVID-19 mRNA vaccine (nucleoside modified) administered alone. A post-hoc analysis found the immune responses to all 20 serotypes elicited by PREVENAR 20 when co-administered with COVID-19 mRNA vaccine (nucleoside modified) would have met conventional 2-fold noninferiority criteria compared to PREVENAR 20 alone, and the full-length S-binding IgG GMC elicited by COVID-19 mRNA vaccine (nucleoside modified) would have met conventional 1.5-fold noninferiority criteria compared to COVID-19 mRNA vaccine (nucleoside modified) alone.
Pharmacokinetics: Not applicable.
Toxicology: Preclinical safety data: Nonclinical data revealed no special hazard for humans based on conventional studies of repeated dose toxicity and reproduction and developmental toxicity.

Active immunization for the prevention of invasive disease, pneumonia, and acute otitis media caused by Streptococcus pneumoniae in infants from 6 weeks to 15 months of age.
Active immunization for the prevention of invasive disease and pneumonia caused by Streptococcus pneumoniae in individuals 18-64 years of age.
See Precautions and Pharmacology: Pharmacodynamics under Actions for information on protection against specific pneumococcal serotypes.
The use of PREVENAR 20 should be determined on the basis of official recommendations taking into consideration the risk of invasive disease and pneumonia in different age groups, underlying comorbidities as well as the variability of serotype epidemiology in different geographical areas.

Posology: The immunisation schedules for PREVENAR 20 should be based on official recommendations.
Infants from 6 weeks to 15 months of age: It is recommended that infants who receive a first dose of PREVENAR 20 complete the vaccination course with PREVENAR 20.
Vaccination series: (See Table 13.)


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Pediatric population: The safety and efficacy of PREVENAR 20 in infants below 6 weeks of age have not been established. No data are available.
Special populations: There are no clinical data with PREVENAR 20 in special populations [adults and children at higher risk of pneumococcal infection including immunocompromised adults and children with human immunodeficiency virus (HIV) infection or hematopoietic stem cell transplant (HSCT), and children with sickle cell disease (SCD)].
Method of administration: For intramuscular use only.
PREVENAR 20 (0.5 mL) should be given by intramuscular injection. The preferred sites are the anterolateral aspect of the thigh (vastus lateralis muscle) in infants or the deltoid muscle of the upper arm in children and adults. PREVENAR 20 should be administered with care to avoid injection into or near nerves and blood vessels.
For instructions on the handling of the vaccine before administration, see Special precautions for disposal and other handling under Cautions for Usage.

Overdose with PREVENAR 20 is unlikely due to its presentation as a pre-filled syringe.

Hypersensitivity to the active substances, to any of the excipients listed in Description, or to diphtheria toxoid.

Do not inject PREVENAR 20 intravascularly.
Traceability: In order to improve the traceability of biological medicinal products, the name and the batch number of the administered product should be clearly recorded.
Hypersensitivity: As with all injectable vaccines, appropriate medical treatment and supervision must always be readily available in case of a rare anaphylactic event following the administration of the vaccine (see Adverse Reactions).
Concurrent illness: As with other vaccines, the administration of PREVENAR 20 should be postponed in individuals suffering from acute severe febrile illness. However, the presence of a minor infection, such as a cold, should not result in the deferral of vaccination.
Thrombocytopenia and coagulation disorders: As with all injectable vaccines, the vaccine must be administered with caution to individuals with thrombocytopenia or a bleeding disorder since bleeding may occur following an intramuscular administration.
The risk of bleeding in patients with coagulation disorders needs to be carefully evaluated before intramuscular administration of any vaccine, and subcutaneous administration should be considered if the potential benefit clearly outweighs the risks.
Protection against pneumococcal disease: PREVENAR 20 will only protect against Streptococcus pneumoniae serotypes included in the vaccine, and will not protect against other microorganisms that cause invasive disease, pneumonia or otitis media.
As with any vaccine, PREVENAR 20 may not protect all individuals receiving the vaccine from pneumococcal disease.
Immunocompromised individuals: Safety and immunogenicity data on PREVENAR 20 are not available for individuals in immunocompromised groups and vaccination should be considered on an individual basis.
Based on experience with pneumococcal vaccines, some individuals with altered immunocompetence may have reduced immune responses to PREVENAR 20.
Individuals with impaired immune responsiveness, whether due to the use of immunosuppressive therapy, a genetic defect, HIV infection, or other causes, may have reduced antibody response to active immunization. The clinical relevance of this is unknown.
Effects on ability to drive and use machines: PREVENAR 20 has no or negligible influence on the ability to drive and use machines. However, some of the effects mentioned under Adverse Reactions may temporarily affect the ability to drive or use machines.
Use in Children: As with all injectable pediatric vaccines, the potential risk of apnea should be considered when administering the primary immunization series to preterm infants. The need for monitoring for at least 48 hours after vaccination should be considered for every preterm infant born ≤28 weeks of gestation who remain hospitalized at the time of the recommended administration. As the benefit of vaccination is high in this group of infants, vaccination should not be withheld or delayed.

Pregnancy: Safety during pregnancy for PREVENAR 20 has not been established in humans.
Lactation: Safety during lactation for PREVENAR 20 has not been established in humans.
It is not known whether vaccine antigens or antibodies are excreted in human milk.
Fertility: No human data on the effect of PREVENAR 20 on fertility are available.
Animal studies do not indicate direct or indirect harmful effects with respect to female fertility or reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions).

Summary of the safety profile: Infants and children 6 weeks to less than 15 months of age: Clinical trials were conducted in healthy infants and children 6 weeks to less than 15 months of age using a 3-dose series (Phase 3 trial B7471012 [Study 1012]) or a 4-dose series (Phase 3 trials B7471011 and B7471013 [Studies 1011 and 1013] and the Phase 2 trial B7471003 [Study 1003]). In these 4 infant trials 5,156 participants received at least 1 dose of vaccine: 2,833 received PREVENAR 20 and 2,323 received 13vPnC. Overall, approximately 90% of participants in each group received all doses through the study-specified toddler dose. In all studies, local reactions and systemic events were collected after each dose, and adverse events were collected from the first dose through 1 month after the last infant vaccination and from the toddler dose through 1 month after vaccination in all studies. Serious adverse events were evaluated through 1 month after the last dose in Studies 1012 and 6 months after the last dose in Studies 1011, 1013, and 1003.
PREVENAR 20 was well tolerated when administered on a 3-dose and a 4-dose series, in the infant study populations with low rates of severe local reactions and systemic events, and most reactions resolving within 1 to 3 days. The percentages of participants with reactogenicity events after PREVENAR 20 were generally similar to those after 13vPnC. Based on the infant data, the most frequently reported local reactions and systemic events after any dose of PREVENAR 20 were irritability, drowsiness, and pain at injection site.
In these studies, PREVENAR 20 was co-administered or permitted to be administered with certain routine pediatric vaccines (see Interactions).
Study 1012 was a pivotal double-blind, active-controlled Phase 3 trial, in which 601 healthy infants, 2 months (≥42 to ≤112 days) of age and born at >36 weeks of gestation received PREVENAR 20 in a 3-dose series. The most frequently reported adverse reactions (>10%) after any dose of PREVENAR 20 were irritability (71.0% to 71.9%), drowsiness/increased sleep (50.9% to 61.2%), pain at injection site (22.8% to 42.4%), decreased appetite (24.7% to 39.3%), redness at the injection site (25.3% to 36.9%), swelling at the injection site (21.4% to 29.8%) and fever of ≥38.0℃ (8.9% to 24.3%). Most adverse reactions occurred within 1 to 2 days following vaccination and were mild to moderate in severity and of short duration (1 to 2 days).
Study 1011 was a pivotal double-blind, active-controlled Phase 3 trial, in which 1,001 healthy infants, 2 months (≥42 to ≤98 days) of age and born at >36 weeks of gestation received PREVENAR 20 in a 4-dose series. The most frequently reported adverse reactions (>10%) after any dose of PREVENAR 20 were irritability (61.0% to 71.6%), drowsiness/increased sleep (39.5% to 67.2%), pain at injection site (35.7% to 49.1%), decreased appetite (20.6% to 26.4%), redness (23.2% to 25.5%), swelling (14.9% to 17.1%) and fever of ≥38.0℃ (10.3% to 17.3%). Most adverse reactions were mild or moderate following vaccination and severe reactions were reported infrequently.
Study 1013 was a double-blind, active-controlled Phase 3 safety trial, in which 1,000 healthy infants, 2 months (≥42 to ≤98 days) of age and born at ≥34 weeks of gestation received PREVENAR 20 in a 4-dose series. The most frequently reported adverse reactions (>10%) after any dose of PREVENAR 20 were irritability (54.8% to 68.2%), drowsiness/increased sleep (35.3% to 64.8%), pain at injection site (24.7% to 40.5%), decreased appetite (23.6% to 28.4%), redness (21.2% to 23.5%), swelling (14.8% to 20.0%) and fever of ≥38.0℃ (9.3% to 18.0%). In Study 1013, the local reactions and systemic events in the preterm subgroup (111 infants born at 34 to less than 37 weeks of gestation) were similar to or lower than the term infants in the study. In the preterm subgroup the frequency of any reported local reaction (31.7% to 55.3% in the PREVENAR 20 group and 37.9% to 47.1% in the 13vPnC group) and systemic event (65.0% to 85.5% in the PREVENAR 20 group and 59.4% to 77.4% in the 13vPnC group).
Study 1003 was a double-blind, active-controlled Phase 2 trial, in which 231 infants, 2 months (≥42 to ≤98 days) of age and born at >36 weeks of gestation received PREVENAR 20 in a 4-dose series. The most frequently reported adverse reactions (>10%) after any dose of PREVENAR 20 were irritability (62.4% to 79.5%), drowsiness/increased sleep (32.8% to 68.1%), pain at injection site (35.5% to 51.1%), decreased appetite (23.3% to 30.8%), redness (24.7% to 26.9%), and swelling (12.7% to 17.9%).
The frequency and severity of the adverse reactions in all infant clinical trials were generally similar in the PREVENAR 20 and 13vPnC groups.
Adults 18 years of age and older: The safety profile presented is based on analysis of over 7,000 individuals 18 years of age and older, of which 4,552 were vaccinated with PREVENAR 20 in three Phase 1 and Phase 2 clinical trials and three Phase 3 clinical trials. In the Phase 3 trials, 4,263 participants received PREVENAR 20, which included 1,798 adults 18 through 49 years of age, 334 adults 50 through 59 years of age, and 2,132 adults 60 years of age and older (1,138 were 65 years of age and older). Of the Phase 3 PREVENAR 20 recipients, 3,639 adults were naïve to pneumococcal vaccines, 253 had previously received Pneumovax 23 (pneumococcal polysaccharide vaccine [23-valent]; PPSV23) only, 246 had previously received 13vPnC only, and 125 had previously received both PPSV23 and 13vPnC.
In participants 18 to 49 years of age, the most frequently reported adverse reactions were pain at injection site (79.2%), muscle pain (62.9%), fatigue (46.7%), headache (36.7%), and joint pain (16.2%). In participants 50 to 59 years of age, the most frequently reported adverse reactions were pain at injection site (72.5%), muscle pain (49.8%), fatigue (39.3%), headache (32.3%), and joint pain (15.4%). In participants ≥60 years of age, the most frequently reported adverse reactions were pain at injection site (55.4%), muscle pain (39.1%), fatigue (30.2%), headache (21.5%), and joint pain (12.6%).
Adverse reactions from clinical trials with PREVENAR 20: As PREVENAR 20 contains the same 13 serotype-specific capsular polysaccharide conjugates and the same vaccine excipients as 13vPnC, the adverse reactions already identified for 13vPnC have been adopted for PREVENAR 20.
Tabulated list of adverse reactions: Table 14 present adverse reactions reported in the Phase 2 infant trial, and Phase 3 trials in pediatric and adult populations, based on the highest frequency among adverse events, local reactions, or systemic events, after vaccination in a PREVENAR 20 group in a study or integrated dataset. The data from clinical trials in infants reflect PREVENAR 20 administered simultaneously with other routine childhood vaccines. In the case of adverse reactions reported in clinical trials of 13vPnC, but not reported in PREVENAR 20 trials, the frequency is not known. In clinical trials, the safety profile of PREVENAR 20 was similar to that of 13vPnC. (See Table 14.)


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Not all ARs reported in 13vPnC Phase 3 trials in adults were reported in the PREVENAR 20 trials. The following ARs were not reported in the PREVENAR 20 Phase 3 trials in adults: General disorders and administration site conditions: Limitation of arm movement (reported in 13vPnC clinical trials with Very Common frequency [≥1/10]).
Metabolism and nutrition disorders: Decreased appetite (reported in 13vPnC clinical trials with Very Common frequency [≥1/10]).
Safety with concomitant vaccine administration: Infants and children: The safety profile of PREVENAR 20 was acceptable, and similar to 13vPnC when administered concomitantly with routine pediatric vaccines containing diphtheria, tetanus, acellular pertussis, hepatitis B virus, poliovirus, and Haemophilus influenzae type b antigens (Infanrix hexa); measles, mumps, and rubella antigens (MMRVaxPro); and varicella antigens (Varilrix).
Adults: The safety profile was similar when PREVENAR 20 was administered with or without influenza vaccine, adjuvanted (Fluad Quadrivalent [QIV]).
PREVENAR 20 administered together with COVID-19 mRNA vaccine (nucleoside modified) was observed to have a tolerability profile similar to COVID-19 mRNA vaccine (nucleoside modified) administered alone, and an overall safety profile consistent with PREVENAR 20 or COVID-19 mRNA vaccine (nucleoside modified) given alone.
Adverse reactions from post marketing experience: The following adverse events have been reported through passive surveillance since market introduction of 13vPnC. Because these events 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 the vaccine. The following adverse events were included based on one or more of the following factors: severity, frequency of reporting, or strength of evidence for a causal relationship to 13vPnC and are, therefore, considered adverse reactions. Although these adverse reactions reported in the postmarketing experience of 13vPnC in pediatric and adult populations were not observed in the PREVENAR 20 clinical trials, they are considered adverse reactions for PREVENAR 20 as the components of 13vPnC are also contained in PREVENAR 20. (See Table 15.)


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Three events (angioedema, vaccination-site pruritus, vaccination-site urticaria) that had been reported as adverse reactions from the 13vPnC postmarketing experience were reported in the PREVENAR 20 Phase 3 adult clinical trials, so they are listed in Table 14 for the adult populations. Lymphadenopathy localized to the region of the vaccination site had been reported in both 13vPnC clinical trials and in the postmarketing period. Since the term lymphadenopathy was reported in Phase 3 adult clinical trials of PREVENAR 20, it is noted in Table 14 for the adult population.
Additional information in special populations in studies with 13vPnC: Adults with HIV infection had similar frequencies of adverse reactions as adults 18 years of age and older, except that fever and vomiting had a frequency category of very common (≥1/10) and nausea had a frequency category of common (≥1/1000 to <1/10).
Adults with HSCT have similar frequencies of adverse reactions as adults 18 years and older, except that fever, diarrhea and vomiting had a frequency category of very common (≥1/10).
Reporting of suspected adverse reactions: Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions via: https://e-meso.pom.go.id/ADR.

Different injectable vaccines should always be administered at different vaccination sites.
Do not mix PREVENAR 20 with other vaccines/products in the same syringe.
Pediatric population: In infants and children 6 weeks to 15 months of age, PREVENAR 20 can be administered concomitantly with any of the following vaccine antigens, either as monovalent or combination vaccines: diphtheria, tetanus, acellular pertussis, Haemophilus influenzae type b, inactivated poliomyelitis, hepatitis B, measles, mumps, rubella (MMR) and varicella vaccines. The vaccine has been safely administered with influenza and rotavirus vaccines.
Adults 18 years of age and older: PREVENAR 20 can be administered concomitantly with influenza vaccine, adjuvanted (Fluad Quadrivalent [QIV]) and COVID-19 mRNA vaccine (nucleoside modified) (see Pharmacology: Pharmacodynamics under Actions).
No data are currently available regarding concomitant use with other vaccines.

Incompatibilities: In the absence of compatibility studies, this vaccine must not be mixed with other medicinal products.
Special precautions for disposal and other handling: During storage, a white deposit and clear supernatant may be observed in the pre-filled syringe containing the suspension. Syringes should be stored horizontally to minimize the re-dispersion time.
Preparation for administration: Step 1. Vaccine resuspension: Hold the pre-filled syringe horizontally between the thumb and the forefinger and shake vigorously until the contents of the syringe are a homogeneous white suspension. Do not use the vaccine if it cannot be re-suspended.
Step 2. Visual inspection: Visually inspect the vaccine for large particulate matter and discoloration prior to administration. Do not use if large particulate matter or discoloration is found. If the vaccine is not a homogeneous white suspension, repeat steps 1 and 2.
Step 3. Remove syringe cap: Remove the syringe cap from the Luer lock adapter by slowly turning the cap counter-clockwise while holding the Luer lock adapter.
Note: Care should be taken to ensure that the extended plunger rod is not depressed while removing the syringe cap.
Step 4. Attach a sterile needle: Attach a needle appropriate for intramuscular administration to the pre-filled syringe by holding the Luer lock adapter and turning the needle clockwise.
Any unused product or waste material should be disposed of in accordance with local requirements.

Store in a refrigerator 2℃ to 8℃.
Syringes should be stored in the refrigerator horizontally to minimize the re-dispersion time.
Do not freeze. Discard if the vaccine has been frozen.
PREVENAR 20 should be administered as soon as possible after being removed from refrigeration.
PREVENAR 20 can be administered provided total (cumulative multiple excursions) time out of refrigeration (at temperatures between 8℃ and 25℃) does not exceed 96 hours. Cumulative multiple excursions between 0℃ and 2℃ are also permitted as long as the total time between 0℃ and 2℃ does not exceed 72 hours. These are not, however, recommendations for storage.

Vaccines, Antisera & Immunologicals

J07AL02 - pneumococcus, purified polysaccharides antigen conjugated ; Belongs to the class of pneumococcal bacterial vaccines.

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