Vaxneuvance

Description

VAXNEUVANCE (Pneumococcal 15-valent Conjugate Vaccine) is a sterile suspension of purified capsular polysaccharides from S. pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F individually conjugated to CRM₁₉₇. Each pneumococcal capsular polysaccharide is activated via sodium metaperiodate oxidation and then individually conjugated to CRM₁₉₇ carrier protein via reductive amination. CRM₁₉₇ is a non-toxic variant of diphtheria toxin (originating from Corynebacterium diphtheriae C7) expressed recombinantly in Pseudomonas fluorescens.

Each of the fifteen serotypes is manufactured independently using the same manufacturing steps with slight variations to accommodate for differences in strains, polysaccharides and process stream properties. Each S. pneumoniae serotype is grown in media containing yeast extract, dextrose, salts and soy peptone. Each polysaccharide is purified by a series of chemical and physical methods. Then each polysaccharide is chemically activated and conjugated to the carrier protein CRM₁₉₇ to form each glycoconjugate. CRM₁₉₇ is isolated from cultures grown in a glycerol-based, chemically-defined, salt medium and purified by chromatography and ultrafiltration. The final vaccine is prepared by blending the fifteen glycoconjugates with aluminum phosphate adjuvant in a final buffer containing histidine, polysorbate 20 and sodium chloride.

Each 0.5 mL dose contains 2.0 mcg each of S. pneumoniae polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F, and 4.0 mcg of polysaccharide serotype 6B, 30 mcg of CRM₁₉₇ carrier protein, 1.55 mg L-histidine, 1 mg of polysorbate 20, 4.50 mg sodium chloride, and 125 mcg of aluminum as aluminum phosphate adjuvant. VAXNEUVANCE does not contain any preservatives.

The tip cap and plunger stopper of the prefilled syringe are not made with natural rubber latex.

Indications

VAXNEUVANCE™ is indicated for active immunization for the prevention of invasive disease caused by Streptococcus pneumoniae serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F in individuals 6 weeks of age and older.

Dosage And Administration

For intramuscular injection only.

Dosage

Each dose of VAXNEUVANCE is 0.5 mL.

Administration

Hold the prefilled syringe horizontally and shake vigorously immediately prior to use to obtain an opalescent suspension. Do not use the vaccine if it cannot be resuspended. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. Do not use if particulate matter or discoloration is observed.

Vaccination Schedule

Children

Administer VAXNEUVANCE as a 4-dose series at 2, 4, 6 and 12 through 15 months of age (and at least 2 months after the third dose). The first dose may be given as early as 6 weeks of age.

The 4-dose series initiated with a lower valency pneumococcal conjugate vaccine can be completed with VAXNEUVANCE [see Clinical Studies].

Adults

Administer VAXNEUVANCE as a single dose in adults 18 years of age and older.

Catch-Up Vaccination Schedule In Children And Adolescents

Children 7 months through 17 years of age who have never received a pneumococcal conjugate vaccine may receive VAXNEUVANCE according to the schedule in Table 1:

Table 1: Catch-Up Vaccination Schedule for Individuals Initiating Vaccination at 7 Months Through 17 Years of Age

Children And Adolescents Previously Vaccinated With A Pneumococcal Conjugate Vaccine

Administer a single dose of VAXNEUVANCE to children and adolescents 2 years through 17 years of age who have received an incomplete series of another pneumococcal conjugate vaccine. At least 2 months should elapse between receipt of the last dose of another pneumococcal conjugate vaccine and administration of VAXNEUVANCE.

How Supplied

Dosage Forms And Strengths

VAXNEUVANCE is a suspension for intramuscular injection supplied in a 0.5 mL single-dose prefilled syringe.

Storage And Handling

VAXNEUVANCE is supplied as follows:

Carton of one 0.5 mL single-dose prefilled Luer Lock syringes with tip caps. NDC 0006-4329-02
Carton of ten 0.5 mL single-dose prefilled Luer Lock syringes with tip caps. NDC 0006-4329-03

Store refrigerated at 2°C to 8°C (36°F to 46°F).

Do not freeze. Protect from light.

The tip cap and plunger stopper of the prefilled syringe are not made with natural rubber latex.

Manufactured by: Merck Sharp & Dohme Corp., a subsidiary of MRCK & CO., INC., Whitehouse Station, NJ 08889, USA. Revised: Jun 2022

Side Effects

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

The most commonly reported solicited adverse reactions in individuals 18 through 49 years of age were: injection-site pain (75.8%), fatigue (34.3%), myalgia (28.8%), headache (26.5%), injection-site swelling (21.7%), injection-site erythema (15.1%) and arthralgia (12.7%).

The most commonly reported solicited adverse reactions in individuals 50 years of age and older were: injection-site pain (66.8%), myalgia (26.9%), fatigue (21.5%), headache (18.9%), injection-site swelling (15.4%), injection-site erythema (10.9%) and arthralgia (7.7%).

Safety Assessment In Clinical Studies

The safety of VAXNEUVANCE was assessed in 7 randomized, double-blind clinical studies conducted in the Americas, Europe and Asia Pacific, in which 5,630 adults 18 years of age and older received VAXNEUVANCE and 1,808 adults received Prevnar 13 [Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM₁₉₇ Protein)]. In Studies 1-3 (NCT03950622, NCT03950856, and NCT03480763), a total of 3,032 adults 50 years of age and older with no history of pneumococcal vaccination received VAXNEUVANCE and 1,154 participants received Prevnar 13. In Study 4 (NCT03547167), adults 18 through 49 years of age with no history of pneumococcal vaccination, including individuals with increased risk of developing pneumococcal disease, received VAXNEUVANCE (N=1,134) or Prevnar 13 (N=378), followed by PNEUMOVAX 23 six months later. In Study 5 (NCT02573181), adults 65 years of age and older previously vaccinated with PNEUMOVAX 23 (at least 1 year prior to study entry) received VAXNEUVANCE (N=127) or Prevnar 13 (N=126). In Study 6 (NCT03615482), adults 50 years of age and older received VAXNEUVANCE concomitantly with a seasonal inactivated quadrivalent influenza vaccine (Fluarix Quadrivalent; QIV) (Group 1, N=600) or nonconcomitantly 30 days after QIV (Group 2, N=585). In this study population, 20.9% of individuals had a history of prior vaccination with PNEUMOVAX 23. In Study 7 (NCT03480802), HIV-infected adults 18 years of age and older received VAXNEUVANCE (N=152) or Prevnar 13 (N=150), followed by PNEUMOVAX 23 two months later.

The clinical studies included adults with stable underlying medical conditions (e.g., diabetes mellitus, renal disorders, chronic heart disease, chronic liver disease, chronic lung disease including asthma) and/or behavioral risk factors (e.g., smoking, increased alcohol use) that are known to increase the risk of pneumococcal disease. Overall, the mean age of the participants was 58 years and 54.6% were female. The racial distribution was as follows: 72.3% were White, 9.9% were Asian, 8.1% were American Indian or Alaska Native, 7.4% were Black or African American, and 18.1% were of Hispanic or Latino ethnicity.

In all studies, safety was monitored using a Vaccination Report Card (VRC) for up to 14 days postvaccination. Study investigators reviewed the VRC with the participants 15 days postvaccination to ensure consistency with protocol definitions. The analyses presented in Tables 1-3 below reflect the information based on the final assessment by the study investigators. Oral body temperature and injection-site adverse reactions were solicited on Day 1 through Day 5 postvaccination. Systemic adverse reactions were solicited on Day 1 through Day 14 postvaccination. Unsolicited adverse events were reported on Day 1 through Day 14 postvaccination.

The duration of the safety follow-up period for serious adverse events postvaccination with VAXNEUVANCE was 1 month in Study 5; 2 months in Study 7; 6 months in Studies 1, 2, 4 and 6; and 12 months in Study 3.

Solicited Adverse Reactions

The percentage of participants with solicited adverse reactions that occurred within 5 or 14 days following administration of VAXNEUVANCE or Prevnar 13 in 3 studies are shown in Tables 1-3. The majority of solicited adverse reactions lasted ≤3 days.

Table 1: Percentage of Participants with Solicited Local and Systemic Adverse Reactions in Pneumococcal Vaccine-Naïve Adults 50 Years of Age and Older (Study 2)*

Table 2: Percentage of Participants with Solicited Local and Systemic Adverse Reactions in Pneumococcal Vaccine-Naïve Adults 18 to 49 Years of Age With or Without Risk Factors for Pneumococcal Disease (Study 4)*

Table 3: Percentage of Participants with Solicited Local and Systemic Adverse Reactions in Adults 65 Years of Age and Older with Previous Pneumococcal Vaccination (Study 5)*

Unsolicited Adverse Reactions

Across all studies, injection-site pruritus was reported to occur in up to 2.8% of adults vaccinated with VAXNEUVANCE.

Serious Adverse Events

Across all studies, among participants 18 years of age and older who received VAXNEUVANCE (excluding those who received QIV concomitantly; N=5,030) or Prevnar 13 (N=1,808), serious adverse events within 30 days postvaccination were reported by 0.4% of VAXNEUVANCE recipients and by 0.7% of Prevnar 13 recipients. In a subset of these studies, among those who received VAXNEUVANCE (N=4,751) and Prevnar 13 (N=1,532), serious adverse events within 6 months postvaccination were reported by 2.5% of VAXNEUVANCE recipients and by 2.4% of Prevnar 13 recipients.

There were no notable patterns or numerical imbalances between vaccination groups for specific categories of serious adverse events that would suggest a causal relationship to VAXNEUVANCE.

Safety With Concomitant Influenza Vaccine Administration

The safety profile was similar when VAXNEUVANCE was administered with or without inactivated quadrivalent influenza vaccine.

Drug Interactions

Immunosuppressive Therapies

Immunosuppressive therapies may reduce the immune response to this vaccine [see WARNINGS AND PRECAUTIONS].

WarningS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Management Of Allergic Reactions

Appropriate medical treatment to manage allergic reactions must be immediately available in the event an acute anaphylactic reaction occurs following administration of VAXNEUVANCE.

Altered Immunocompetence

Some individuals with altered immunocompetence, including those receiving immunosuppressive therapy, may have a reduced immune response to VAXNEUVANCE. [See Use In Specific Populations]

Apnea In Premature Infants

Apnea following intramuscular vaccination has been observed in some infants born prematurely. A decision about when to administer VAXNEUVANCE to infants born prematurely should be based on consideration of the individual infant’s medical status and the potential benefits and possible risks of vaccination.

Patient Counseling Information

Advise the patient, parent or guardian to read the FDA-approved patient labeling (PATIENT INFORMATION).

Discuss the following with the patient, parent or guardian:

• Provide the required vaccine information to the patient, parent or guardian.
• Inform the patient, parent or guardian of the benefits and risks associated with vaccination.
• Inform the patient, parent or guardian that vaccination with VAXNEUVANCE may not protect all vaccine recipients.
• Discuss the importance of completing the vaccination series unless contraindicated.
• Instruct the patient, parent or guardian to report any serious adverse reactions to their healthcare provider who in turn should report such events to the vaccine manufacturer or the U.S. Department of Health and Human Services through the Vaccine Adverse Event Reporting System (VAERS), 1-800- 822-7967, or report online at www.vaers.hhs.gov.

Nonclinical Toxicology

Carcinogenesis, Mutagenesis, Impairment Of Fertility

VAXNEUVANCE has not been evaluated for carcinogenic or mutagenic potential or for impairment of male fertility in animals. VAXNEUVANCE administered to female rats had no effect on fertility [see Use In Specific Populations].

Use In Specific Populations

Pregnancy

Risk Summary

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

There are no adequate and well-controlled studies of VAXNEUVANCE in pregnant women. Available data on VAXNEUVANCE administered to pregnant women are insufficient to inform vaccine-associated risks in pregnancy.

Developmental toxicity studies have been performed in female rats administered a human dose of VAXNEUVANCE on four occasions; twice prior to mating, once during gestation and once during lactation. These studies revealed no evidence of harm to the fetus due to VAXNEUVANCE [see Animal Data below].

Data

Animal Data

Developmental toxicity studies have been performed in female rats. In these studies, female rats received a human dose of VAXNEUVANCE by intramuscular injection on day 28 and day 7 prior to mating, and on gestation day 6 and on lactation day 7. No vaccine related fetal malformations or variations were observed. No adverse effect on pup weight up to post-natal day 21 was noted.

Lactation

Risk Summary

Human data are not available to assess the impact of VAXNEUVANCE on milk production, its presence in breast milk, or its effects on the breastfed child. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for VAXNEUVANCE and any potential adverse effects on the breastfed child from VAXNEUVANCE or from the underlying maternal condition. For preventive vaccines, the underlying condition is susceptibility to disease prevented by the vaccine.

Pediatric Use

The safety and effectiveness of VAXNEUVANCE have been established in individuals 6 weeks through 17 years of age [see ADVERSE REACTIONS and Clinical Studies]. The safety and effectiveness of VAXNEUVANCE in individuals younger than 6 weeks of age have not been established.

Geriatric Use

Of the 4,389 individuals aged 50 years and older who received VAXNEUVANCE, 2,478 (56.5%) were 65 years and older, and 479 (10.9%) were 75 years and older [see ADVERSE REACTIONS and Clinical Studies]. Overall, there were no clinically meaningful differences in the safety profile or immune responses observed in older individuals (65 to 74 years and 75 years of age and older) when compared to younger individuals.

Individuals At Increased Risk For Pneumococcal Disease

Infants Born Prematurely

The safety and immunogenicity of VAXNEUVANCE were evaluated in preterm infants (<37 weeks gestation at birth) who were randomized to receive a complete 4-dose series of either VAXNEUVANCE (N=142) or Prevnar 13 (N=144) within Study 8, Study 9, and Study 10. Participants in these studies may have received either US-licensed or non-US licensed concomitant vaccines according to the local recommended schedule. In descriptive analyses, serotype-specific immunoglobulin G (IgG) and opsonophagocytic activity (OPA) responses at 30 days postdose 3, predose 4 and at 30 days postdose 4 were numerically similar between vaccination groups for the 13 shared serotypes and higher in VAXNEUVANCE for the 2 unique serotypes. The safety profile of VAXNEUVANCE was similar to the safety profile of Prevnar 13. In addition, the immune responses and safety profile in preterm infants receiving a 4-dose series of VAXNEUVANCE were similar to those observed in term infants in these studies. The effectiveness of VAXNEUVANCE in infants born prematurely has not been established.

Children With Sickle Cell Disease

In a double-blind, descriptive study (Study 13, NCT03731182), the safety and immunogenicity of VAXNEUVANCE were evaluated in children 5 through 17 years of age with sickle cell disease. Participants were randomized 2:1 to receive a single dose of VAXNEUVANCE (N=70) or Prevnar 13 (N=34). Immune responses were assessed by serotype-specific IgG GMCs and OPA GMTs at 30 days postvaccination for all 15 serotypes contained in VAXNEUVANCE. For all vaccine serotypes included in VAXNEUVANCE, serotype-specific IgG GMCs and OPA GMTs were higher following vaccination compared to pre-vaccination. IgG GMCs and OPA GMTs were numerically similar between the two vaccination groups for the 13 shared serotypes and higher in VAXNEUVANCE for serotypes 22F and 33F. The safety profile of VAXNEUVANCE was similar to the safety profile of Prevnar 13. The effectiveness of VAXNEUVANCE in children with sickle cell disease has not been established.

Individuals With HIV Infection

Children With HIV Infection

In a double-blind, descriptive study (Study 14, NCT03921424), the safety and immunogenicity of VAXNEUVANCE were evaluated in HIV-infected children 6 through 17 years of age, with CD4+ T-cell count ≥200 cells per microliter and plasma HIV RNA value <50,000 copies/mL. Participants were randomized to receive a single dose of VAXNEUVANCE (N=203) or Prevnar 13 (N=204), followed by PNEUMOVAX 23 two months later. For all vaccine serotypes included in VAXNEUVANCE, serotype-specific IgG GMCs and OPA GMTs were higher following vaccination compared to pre-vaccination. Serotype-specific IgG GMCs and OPA GMTs were numerically similar for the 13 shared serotypes and higher for the 2 unique serotypes (22F and 33F) at 30 days following vaccination with VAXNEUVANCE or Prevnar 13 and were numerically similar for all 15 serotypes contained in VAXNEUVANCE at 30 days following subsequent vaccination with PNEUMOVAX 23. The safety profile of VAXNEUVANCE was similar to the safety profile of Prevnar 13. The effectiveness of VAXNEUVANCE in HIV-infected children has not been established.

Adults With HIV Infection

In a double-blind, descriptive study (Study 7), the safety and immunogenicity of VAXNEUVANCE were evaluated in pneumococcal vaccine-naïve HIV-infected adults 18 years of age and older, with CD4+ T-cell count ≥50 cells per microliter and plasma HIV RNA value <50,000 copies/mL. Participants were randomized to receive VAXNEUVANCE (N=152) or Prevnar 13 (N=150), followed by PNEUMOVAX 23 two months later [see ADVERSE REACTIONS]. Anti-pneumococcal opsonophagocytic activity (OPA) geometric mean antibody titers (GMTs) were higher after administration of VAXNEUVANCE, compared to pre-vaccination, for the 15 serotypes contained in VAXNEUVANCE. After sequential administration with PNEUMOVAX 23, OPA GMTs observed at 30 days after PNEUMOVAX 23 vaccination were numerically similar between the two vaccination groups for all 15 serotypes contained in VAXNEUVANCE. The safety profile of VAXNEUVANCE was similar to the safety profile of Prevnar 13. The effectiveness of VAXNEUVANCE in HIV-infected adults has not been established.

Overdose

No Information provided

Contraindications

Do not administer VAXNEUVANCE to individuals with a severe allergic reaction (e.g., anaphylaxis) to any component of VAXNEUVANCE or to diphtheria toxoid. [See DESCRIPTION]

Clinical Pharmacology

Mechanism Of Action

Protection against invasive disease is conferred mainly by antibodies (Immunoglobulin G [IgG] directed against capsular polysaccharides) and opsonophagocytic activity (OPA) against S. pneumoniae. VAXNEUVANCE induces IgG antibodies and OPA against the serotypes contained in the vaccine.

Clinical Studies

Immune responses elicited by VAXNEUVANCE and Prevnar 13 in children were measured by a pneumococcal electrochemiluminescence (Pn ECL) assay for total IgG and a multiplexed opsonophagocytic assay (MOPA) for opsonophagocytic killing for the 15 pneumococcal serotypes contained in VAXNEUVANCE postdose 3, predose 4 and postdose 4. In children, a serotype-specific Immunoglobulin G (IgG) antibody level corresponding to ≥0.35 mcg/mL using the WHO enzyme linked immunosorbent assay (ELISA) has been used as the threshold value for the clinical evaluation of pneumococcal conjugate vaccines. Immune responses elicited by VAXNEUVANCE and Prevnar 13 in adults were measured by MOPA and Pn ECL assays for the 15 pneumococcal serotypes contained in VAXNEUVANCE pre- and post-vaccination.

Clinical Trials In Children

Children Receiving A 4-Dose Series

In a double-blind, active comparator-controlled study (Study 8), participants were randomized to receive VAXNEUVANCE (N=860) or Prevnar 13 (N=860) in a 4-dose series; the first 3 doses were administered to infants at 2, 4, and 6 months of age and the fourth dose was administered to children 12 through 15 months of age. Pentacel (US participants) or a non-US-licensed DTaP-IPV-Hib vaccine (non-US participants), RECOMBIVAX HB, and RotaTeq were administered concomitantly with each of the 3 infant doses. VAQTA, M-M-R II, VARIVAX, and Hiberix were administered concomitantly with the fourth dose. [See ADVERSE REACTIONS and Clinical Studies]

Study 8 assessed serotype-specific IgG response rates, IgG geometric mean concentrations (GMCs), and opsonophagocytic activity (OPA) geometric mean titers (GMTs), for all 15 serotypes contained in VAXNEUVANCE. At 30 days postdose 3, VAXNEUVANCE was noninferior to Prevnar 13 for the 13 shared serotypes, as assessed by the proportion of participants meeting the serotype-specific IgG threshold value of ≥0.35 mcg/mL (response rate). VAXNEUVANCE was noninferior for the 2 unique vaccine serotypes, as assessed by the IgG response rates for serotypes 22F and 33F compared with the response rate for serotype 6B (the lowest response rate for any of the shared serotypes in Prevnar 13 among US participants, excluding serotype 3) at 30 days postdose 3 (Table 9).

Table 9: Proportions of US Participants with IgG Response Rates ≥0.35 mcg/mL at 30 Days Following Dose 3 in Infants Administered VAXNEUVANCE at 2, 4 and 6 Months of Age (Study 8)

At 30 days postdose 3, serotype-specific IgG GMCs in the VAXNEUVANCE group were noninferior to Prevnar 13 for 12 of the 13 shared serotypes, except for serotype 6A. The IgG response to serotype 6A missed the prespecified noninferiority criterion by a small margin (the lower bound of the 2-sided 95% CI for the GMC ratio [VAXNEUVANCE/Prevnar 13] being 0.48 versus >0.5). VAXNEUVANCE was noninferior to Prevnar 13 for the 2 unique serotypes, as assessed by serotype-specific IgG GMCs for serotypes 22F and 33F compared with the IgG GMCs for serotype 4 (the lowest IgG GMC for any of the shared serotypes in Prevnar 13 among US participants, excluding serotype 3) (Table 10).

Table 10: Serotype-Specific IgG GMCs at 30 Days Following Dose 3 in US Infants Administered VAXNEUVANCE at 2, 4 and 6 Months of Age (Study 8)

At 30 days postdose 4, serotype-specific IgG GMCs for VAXNEUVANCE were noninferior to Prevnar 13 for all 13 shared serotypes (the lower bound of the 2-sided 95% CI for the GMC ratio [VAXNEUVANCE/Prevnar 13] being >0.5) and for the 2 unique serotypes 22F and 33F as assessed by the IgG GMCs for serotypes 22F and 33F compared with the IgG GMCs for serotype 4 (the lowest IgG GMC for any of the shared serotypes in Prevnar 13 among US participants, excluding serotype 3) (Table 11).

Table 11: Serotype-Specific IgG GMCs at 30 Days Following Dose 4 in US Infants Administered VAXNEUVANCE at 2, 4, 6 and 12 to 15 Months of Age (Study 8)

Additionally, IgG response rates and IgG GMCs at 30 days postdose 3 and IgG GMCs at 30 days postdose 4 were statistically significantly greater for VAXNEUVANCE compared to Prevnar 13 for serotype 3 and the 2 unique serotypes (22F, 33F).

Serotype-specific OPA GMTs and response rates at 30 days postdose 3 and OPA GMTs at 30 days postdose 4 were descriptively evaluated in a subset of participants in Study 8. Serotype specific OPA GMTs and response rates were numerically similar across groups for the 13 shared serotypes and higher in the VAXNEUVANCE group for the 2 unique serotypes.

Children Receiving VAXNEUVANCE To Complete A 4-Dose Series Initiated With Prevnar 13

In a double-blind, active comparator-controlled, descriptive study (Study 9), participants were randomized in a 1:1:1:1:1 ratio to one of five vaccination groups. Two vaccination groups received a 4-dose series composed entirely of either VAXNEUVANCE (N=180) or Prevnar 13 (N=179). The remaining 3 study groups received either 1, 2, or 3 doses of Prevnar 13 followed by VAXNEUVANCE to complete the 4-dose series (N=180, 180, and 181, respectively). Participants also received other pediatric vaccines concomitantly [see ADVERSE REACTIONS and Clinical Studies]. Serotype-specific IgG GMCs for the 13 shared serotypes at 30 days postdose 4 were numerically similar for participants completing the vaccination series with VAXNEUVANCE compared to participants who received a complete series with Prevnar 13.

Children And Adolescents Receiving Catch-Up Vaccination

In a double-blind, active comparator-controlled, descriptive study (Study 12), participants were enrolled in three age cohorts (7 through 11 months of age, 12 through 23 months of age, and 2 through 17 years of age) and randomized to receive VAXNEUVANCE (N=303) or Prevnar 13 (N=303). Children in the two youngest age cohorts were pneumococcal vaccine-naïve at enrollment. Children in the oldest age cohort (2 through 17 years of age) were either pneumococcal vaccine naïve, not fully vaccinated, or had completed a dosing regimen with a lower valency pneumococcal conjugate vaccine (excluding Prevnar 13). Participants who were pneumococcal vaccine-naïve at enrollment received 1 to 3 doses of VAXNEUVANCE or Prevnar 13, depending on age at enrollment and according to the schedule shown in Table 1. All participants 2 through 17 years of age received one dose of VAXNEUVANCE. Catch-up vaccination with VAXNEUVANCE elicited immune responses, as assessed by serotype-specific IgG GMCs at 30 days following the last dose of vaccine, in children 7 months through 17 years of age that were numerically similar to Prevnar 13 for the shared serotypes and higher than Prevnar 13 for the unique serotypes 22F and 33F. Within each age cohort, serotype-specific IgG GMCs at 30 days following the last dose of vaccine were numerically similar between the vaccination groups for the 13 shared serotypes and higher in VAXNEUVANCE for the 2 unique serotypes.

Clinical Trials In Pneumococcal Vaccine-Naïve Adults

Study 1

Study 1 assessed serotype-specific opsonophagocytic activity (OPA) responses for each of the 15 serotypes contained in VAXNEUVANCE at 30 days postvaccination in a double-blind, active comparator-controlled study that enrolled pneumococcal vaccine-naïve participants 50 years of age and older. Participants were randomized to receive either VAXNEUVANCE (N=604) or Prevnar 13 (N=601) at sites in USA, Canada, Spain, Taiwan, and Japan. The mean age of participants was 66 years and 57.3% were female. The racial distribution was as follows: 67.7% were White, 25.1% were Asian, 6.1% were Black or African American and 22.0% were of Hispanic or Latino ethnicity.

Table 12 summarizes the OPA geometric mean antibody titers (GMTs) at 30 days postvaccination for the 15 serotypes contained in VAXNEUVANCE. The study demonstrated that VAXNEUVANCE is noninferior to Prevnar 13 for the 13 shared serotypes and induces statistically significantly greater OPA GMTs compared to Prevnar 13 for shared serotype 3 and for the 2 unique serotypes (22F, 33F).

Table 12: Serotype-Specific OPA GMTs in Pneumococcal Vaccine-Naïve Adults 50 Years of Age and Older (Study 1)

Study 3

In a double-blind, active comparator-controlled, descriptive study (Study 3), pneumococcal vaccine-naïve adults 50 years of age and older were randomized to receive either VAXNEUVANCE (N=327) or Prevnar 13 (N=325), followed by PNEUMOVAX 23 one year later.

Following vaccination with PNEUMOVAX 23, OPA GMTs were numerically similar between the two vaccination groups for the 15 serotypes in VAXNEUVANCE.

Study 4

In a double-blind, descriptive study (Study 4), adults 18 through 49 years of age, including individuals with increased risk of developing pneumococcal disease, were randomized to receive VAXNEUVANCE (N=1,135) or Prevnar 13 (N=380), followed by PNEUMOVAX 23 six months later [see ADVERSE REACTIONS]. Among those who received VAXNEUVANCE, 620 participants had one risk factor and 228 participants had two or more risk factors for pneumococcal disease.

Table 13 presents OPA GMTs in the overall study population for each of the 15 serotypes 30 days following vaccination with VAXNEUVANCE or Prevnar 13.

Table 13: Serotype-Specific OPA GMTs in Pneumococcal Vaccine-Naïve Adults 18 through 49 Years of Age With or Without Risk Factors for Pneumococcal Disease (Study 4)

Following vaccination with PNEUMOVAX 23, the OPA GMTs for the 15 serotypes in VAXNEUVANCE were numerically similar among subjects who had received VAXNEUVANCE or Prevnar 13 for the first vaccination.

Concomitant Vaccination

Children

In Study 8, the concomitant administration of Pentacel with each of the 3 infant doses of either VAXNEUVANCE (N=598) or Prevnar 13 (N=601) was evaluated 30 days following the third dose; concomitant administration of single doses of VAQTA, M-M-R II, VARIVAX and Hiberix with the fourth dose of either VAXNEUVANCE or Prevnar 13 was evaluated 30 days following vaccination. There was no evidence that VAXNEUVANCE, as compared to Prevnar 13, interfered with the immune responses to these concomitantly administered vaccines. The immune responses to the antigens in Pentacel following completion of the 4-dose series were not evaluated.

In Study 9, the concomitant administration of RECOMBIVAX HB with either VAXNEUVANCE (N=124) or Prevnar 13 (N=266) was evaluated 30 days following the third dose of pneumococcal conjugate vaccine. Most infants (97.2%) received a birth dose of hepatitis B vaccine, followed by two doses of RECOMBIVAX HB administered concomitantly with VAXNEUVANCE or Prevnar 13. There was no evidence that VAXNEUVANCE, as compared to Prevnar 13, interfered with the immune response to RECOMBIVAX HB.

Adults

In a double-blind, randomized study (Study 6), adults 50 years of age and older were randomized to receive VAXNEUVANCE concomitantly administered with a seasonal inactivated quadrivalent influenza vaccine (Fluarix Quadrivalent; QIV) (Group 1, N=600) or VAXNEUVANCE 30 days after receiving QIV (Group 2, N=600) [see ADVERSE REACTIONS]. Pneumococcal vaccine serotype OPA GMTs were evaluated 30 days after VAXNEUVANCE and influenza vaccine strain hemagglutinin inhibition assay (HAI) GMTs were evaluated 30 days after QIV. The noninferiority criteria for the comparisons of GMTs [lower limit of the 2-sided 95% confidence interval (CI) of the GMT ratio (Group 1/Group 2) >0.5] were met for the 15 pneumococcal serotypes in VAXNEUVANCE and for the 4 influenza vaccine strains tested.