Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants (V114-033)

Study Overview
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Brief Summary
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The purpose of this clinical study is to evaluate the safety and immunogenicity of a 4-dose schedule (3-dose primary series followed by a toddler dose) of V114 compared with Pneumococcal 13-valent Conjugate Vaccine (PCV13). The hypotheses are that: 1) V114 is non-inferior to PCV13 for the 13 shared serotypes between V114 and PCV13 based on the response rates at 30 days following dose 3; 2) V114 is non-inferior to PCV13 for the 2 unique V114 serotypes based on the response rate of the 2 unique V114 serotypes at 30 days following dose 3; 3) V114 is non-inferior to PCV13 for the 13 shared serotypes between V114 and PCV13 based on anti-pneumococcal polysaccharide (PnPs) serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) at 30 days following dose 3.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Active-Comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Japanese Infants

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: V114
* Biological: PCV13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Japanese male or female Exclusion Criteria: Has a history of invasive pneumococcal disease (IPD) Has a known hypersensitivity to any component of the pneumococcal conjugate vaccine (PCV), or any diphtheria toxoid containing vaccine Has a known or suspected impairment of immunological function Has a history of congenital or acquired immunodeficiency Has or his/her mother has a documented human immunodeficiency virus (HIV) infection Has or his/her mother has a documented hepatitis B surface antigen-positive test Has known or history of functional or anatomic asplenia Has a history of autoimmune disease Has a known neurologic or cognitive behavioral disorder Has received a dose of any pneumococcal vaccine prior to study entry Has received a blood transfusion or blood products, including immunoglobulins

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 6 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: V114<br>Participants will receive a single 0.5 mL subcutaneous injection of V114 administered at 2 to 6 months of age, and second and third dose is administered at an interval of ≥27 days from the prior dose. The fourth dose is administered at 12 to 15 months of age. | Biological: V114<br>* 15-valent pneumococcal conjugate vaccine containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) present in PCV13 plus 2 additional serotypes (22F, 33F) in each subcutaneous 0.5 mL single dose.<br>* Other names: Pneumococcal 15-Valent Conjugate Vaccine;|
| Active Comparator: Pneumococcal 13-valent Conjugate Vaccine (PCV13)<br>Participants will receive a single 0.5 mL subcutaneous injection of PCV13 administered at 2 to 6 months of age, and second and third dose is administered at an interval of ≥27 days from the prior dose. The fourth dose is administered at 12 to 15 months of age. | Biological: PCV13<br>* 13-valent pneumococcal conjugate vaccine containing 13 serotypes (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 23F) in each subcutaneous 0.5 mL single dose.<br>* Other names: Prevnar 13™;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Solicited Injection-Site Adverse Events | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any injection with either V114 or PCV13 the percentage of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs were erythema, induration, pain, and swelling. | Day 1 to Day 14 post any vaccination, up to a total of 13.5 months | 
| Percentage of Participants With Solicited Systemic Adverse Events | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following any of the injections with either V114 or PCV13, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were decreased appetite, irritability, somnolence, and urticaria. | Day 1 to Day 14 post any vaccination, up to a total of 13.5 months | 
| Percentage of Participants With Vaccine-Related Serious Adverse Events | A serious adverse event (SAE) is an AE that is life-threatening, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. The percentage of participants with a vaccine-related SAE following dose 1 (with either V114 or PCV13) was reported. Vaccine-related SAEs were counted starting after vaccine dose 1 through completion of study. |  1 month after Dose 4, up to a total of 14 months | 
| Percentage of Participants Meeting the Serotype Specific Immunoglobulin G Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 3 | The anti-pneumococcal polysaccharide (PnPs) serotype-specific immunoglobulin G (IgG) response rates (percentage of participants meeting serotype-specific IgG threshold value of ≥0.35 μg/mL of participants administered V114 versus participants administered PCV13) for the 15 serotypes contained in V114 were determined using an electrochemiluminescence assay. | 30 Days after Dose 3, up to a total of 11 months | 
| Geometric Mean Concentration of Serotype-Specific IgG for the 13 Shared Serotypes in V114 and PCV13 After Dose 3 | The anti-PnPs serotype-specific IgG Geometric Mean Concentrations (GMCs) of participants administered V114 versus participants administered PCV13 for the 13 serotypes shared in V114 and PCV13 were determined using an electrochemiluminescence assay. | 30 Days after Dose 3, up to a total of 11 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| GMC of Serotype-Specific IgG for the 2 Unique V114 Serotypes After Dose 3 | The anti-PnPs serotype-specific IgG GMCs of participants administered V114 versus participants administered PCV13 for the 2 unique V114 serotypes was determined using an electrochemiluminescence assay. | 30 days after Dose 3, up to a total of 11 months | 
| Percentage of Participants Meeting the Serotype Specific IgG Threshold Value of ≥0.35 μg/mL for Each Serotype in V114 After Dose 4 | The anti-PnPs serotype-specific IgG response rates (percentage of participants meeting serotype-specific IgG threshold value of ≥0.35 μg/mL of participants administered V114 versus participants administered PCV13) for the 15 serotypes contained in V114 were determined using an electrochemiluminescence assay. | 30 Days after Dose 4, up to a total of 14 months | 
| GMC of Serotype-Specific IgG for Each Serotype in V114 After Dose 4 | The anti-PnPs serotype-specific IgG GMCs of participants administered V114 versus participants administered PCV13 for the 15 serotypes contained in V114 was determined using an electrochemiluminescence assay. | 30 Days after Dose 4, up to a total of 14 months | 
| Geometric Mean Titer of Serotype-Specific Opsonophagocytic Activity for Each Serotype in V114 After Dose 3 | The anti-PnPs serotype-specific opsonophagocytic activity (OPA) and geometric mean titers (GMTs) of participants administered V114 versus participants administered PCV13 for the 15 serotypes contained in V114 was determined using a multiplexed opsonophagocytic assay. | 30 Days after Dose 3, up to a total of 11 months | 
| GMT of Serotype-Specific OPA for Each Serotype in V114 After Dose 4 | The anti-PnPs serotype-specific opsonophagocytic activity (OPA) and geometric mean titers (GMTs) of participants administered V114 versus participants administered PCV13 for the 15 serotypes contained in V114 was determined using a multiplexed opsonophagocytic assay. | 30 Days after Dose 4, up to a total of 14 months |