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

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

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.

Study Overview

• Status: Completed
• Conditions: Pneumococcal Infections
• Intervention / Treatment: Biological: V114; Biological: PCV13

• Study Type: Interventional
• Enrollment (Actual): 694
• Phase: Phase 3

Contacts and Locations

Study Locations

• Japan
  • Fukui, Japan, 910-0833
    • Fukui Aiiku Hospital ( Site 3315)
  • Fukui, Japan, 918-8503
    • Fukui-ken Saiseikai Hospital ( Site 3314)
  • Fukuoka, Japan, 814-0121
    • Shindo Children's Clinic ( Site 3325)
  • Fukuoka, Japan, 815-0033
    • Kurokawa Michiko Pediatric Clinic ( Site 3319)
  • Fukuoka, Japan, 819-0002
    • Shimomura Pediatrics Clinic ( Site 3320)
  • Fukuoka, Japan, 819-0041
    • INAMITSU Children's Clinic ( Site 3321)
  • Kumamoto, Japan, 862-0920
    • Nagamine Soyokaze Clinic ( Site 3348)
  • Nagano, Japan, 388-8004
    • Minaminagano Medical Center Shinonoi General Hospital ( Site 3344)
  • Osaka, Japan, 536-0001
    • Saiseikai Noe Hospital ( Site 3330)
  • Osaka, Japan, 544-0033
    • Kubota Children's Clinic ( Site 3334)
  • Osaka, Japan, 553-0001
    • Sano Kids Clinic ( Site 3341)
  • Osaka, Japan, 556-0005
    • Aizenbashi Hospital ( Site 3317)
  • Shizuoka, Japan, 420-0853
    • Japanese Red Cross Shizuoka Hospital ( Site 3322)
  • Shizuoka, Japan, 424-8636
    • Shizuoka City Shimizu Hospital ( Site 3347)
  • Tokyo, Japan, 112-0001
    • Hosaka Children's Clinic ( Site 3307)
  • Tokyo, Japan, 130-8587
    • The Fraternity Memorial Hospital ( Site 3333)
  • Tokyo, Japan, 146-0095
    • Okawa Children & Family Clinic ( Site 3305)
  • Toyama, Japan, 939-8511
    • Toyama City Hospital ( Site 3328)
  • Aichi
    • Kasugai, Aichi, Japan, 486-0836
      • Morinaga Maternity Clinic ( Site 3345)
    • Nagoya, Aichi, Japan, 457-8511
      • Social Medical Corporation Koujunkai Daido Clinic ( Site 3326)
  • Chiba
    • Funabashi, Chiba, Japan, 274-0063
      • Kyoritsu Narashinodai Hospital ( Site 3332)
    • Isumi, Chiba, Japan, 299-4503
      • Sotobo Children's Clinic ( Site 3323)
  • Fukuoka
    • Kasuga, Fukuoka, Japan, 816-0801
      • Yokoyama Children's Clinic ( Site 3309)
  • Hiroshima
    • Kure, Hiroshima, Japan, 737-0193
      • Chugoku Rosai Hospital ( Site 3340)
  • Ibaraki
    • Tsuchiura, Ibaraki, Japan, 300-0028
      • Tsuchiura Kyodo General Hospital ( Site 3327)
  • Kagoshima
    • Hioki, Kagoshima, Japan, 899-2503
      • Kagoshima Children's Hospital ( Site 3342)
  • Kanagawa
    • Kawasaki, Kanagawa, Japan, 210-0013
      • Kawasaki Municipal Hospital ( Site 3302)
    • Sagamihara, Kanagawa, Japan, 252-0392
      • National Hospital Organization Sagamihara National Hospital ( Site 3303)
    • Yokohama, Kanagawa, Japan, 222-0036
      • JOHAS Yokohama Rosai Hospital ( Site 3343)
  • Mie
    • Tsu, Mie, Japan, 514-1101
      • National Hospital Organization Mie Chuo Medical Center ( Site 3308)
  • Miyagi
    • Sendai, Miyagi, Japan, 983-8520
      • National Hospital Organization Sendai Medical Center ( Site 3311)
  • Nagano
    • Ina, Nagano, Japan, 396-8555
      • Ina Central Hospital ( Site 3346)
    • Matsumoto, Nagano, Japan, 390-8510
      • Aizawa Hospital ( Site 3313)
  • Osaka
    • Izumisano, Osaka, Japan, 598-0043
      • Taniguchi Hospital ( Site 3310)
    • Sakai, Osaka, Japan, 591-8023
      • Medical corporation Waffle GunGunkids Clinic ( Site 3329)
    • Suita, Osaka, Japan, 564-8567
      • Suita Municipal Hospital ( Site 3338)
    • Takatsuki, Osaka, Japan, 569-1192
      • Takatsuki General Hospital ( Site 3318)
  • Saitama
    • Kawagoe, Saitama, Japan, 350-0001
      • Aiwa Hospital ( Site 3336)
    • Kawaguchi, Saitama, Japan, 332-8558
      • Saiseikai Kawaguchi General Hospital ( Site 3304)
    • Tokorozawa, Saitama, Japan, 359-1141
      • Hara Children's Clinic ( Site 3339)
    • Wako, Saitama, Japan, 351-0102
      • National Hospital Organization Saitama Hospital ( Site 3312)
  • Shiga
    • Ritto, Shiga, Japan, 520-3046
      • Saiseikai Shiga Hospital ( Site 3349)
  • Shizuoka
    • Fujieda, Shizuoka, Japan, 426-0067
      • Kobayashi Pediatric Clinic ( Site 3301)
  • Tokyo
    • Tachikawa, Tokyo, Japan, 190-0002
      • Saiwai Kodomo Clinic ( Site 3331)
    • Tama, Tokyo, Japan, 206-0025
      • Nishida Kodomo Clinic ( Site 3306)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 2 months to 6 months (Child)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: V114; 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; 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.; Other Names: VAXNEUVANCE™; Pneumococcal 15-Valent Conjugate Vaccine
Active Comparator: Pneumococcal 13-valent Conjugate Vaccine (PCV13); 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; 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.; Other Names: Prevnar 13™

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC
• Investigators: Study Director: Medical Director, Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Suzuki H, Fujita H, Iwai K, Kuroki H, Taniyama K, Shizuya T, Kishino H, Igarashi R, Shirakawa M, Sawata M. Safety and immunogenicity of 15-valent pneumococcal conjugate vaccine in Japanese healthy infants: A phase III study (V114-033). Vaccine. 2023 Jul 31;41(34):4933-4940. doi: 10.1016/j.vaccine.2023.05.064. Epub 2023 Jun 19.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Actual): December 1, 2021
• Study Completion (Actual): December 1, 2021

Study Registration Dates

• First Submitted: May 11, 2020
• First Submitted That Met QC Criteria: May 11, 2020
• First Posted (Actual): May 12, 2020

Study Record Updates

• Last Update Posted (Actual): July 28, 2023
• Last Update Submitted That Met QC Criteria: July 20, 2023
• Last Verified: July 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumococcal Infections; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: V114-033 (Other Identifier: Merck); 205287 (Registry Identifier: JAPIC-CTI); 2019-003644-68 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes