Safety, Tolerability, and Immunogenicity of a Polyvalent Pneumococcal Conjugate Vaccine (V116) in Japanese Adults (V116-002)

• ClinicalTrials.gov Identifier: NCT04665050
• Recruitment Status: Completed
• First Posted: December 11, 2020
• Results First Posted: July 7, 2023
• Last Update Posted: October 4, 2023
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: December 8, 2020
• First Posted Date: December 11, 2020
• Results First Submitted Date: August 4, 2022
• Results First Posted Date: July 7, 2023
• Last Update Posted Date: October 4, 2023
• Actual Study Start Date: February 4, 2021
• Actual Primary Completion Date: April 6, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: August 4, 2022)

• Percentage of Participants With a Solicited Injection-site Adverse Event (AE) [ Time Frame: Up to 5 days postvaccination ]
  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs included tenderness/pain, redness/erythema, and swelling. The percentage of participants with one or more solicited injection-site AE was reported for each arm.
• Percentage of Participants With a Solicited Systemic AE [ Time Frame: Up to 5 days postvaccination ]
  An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited systemic AEs included headache, muscle pain/myalgia, joint pain/arthralgia, and tiredness/fatigue. The percentage of participants with one or more solicited systemic AE was reported for each arm.
• Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE) [ Time Frame: Up to 62 days postvaccination ]
  An SAE is an AE that results in death, 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. SAEs that were reported by the investigator to be at least possibly related to the study vaccination were reported.

Original Primary Outcome Measures (submitted: December 8, 2020)

• Percentage of Participants With a Solicited Injection-site Adverse Event (AE) [ Time Frame: Up to 5 days postvaccination ]
  Solicited injection-site AEs include tenderness/pain, redness/erythema, and swelling.
• Percentage of Participants With a Solicited Systemic AE [ Time Frame: Up to 5 days postvaccination ]
  Solicited systemic AEs include headache, muscle pain/myalgia, joint pain/arthralgia, and tiredness/fatigue.
• Percentage of Participants With a Vaccine-related Serious Adverse Event (SAE) [ Time Frame: Up to 30 days postvaccination ]
  A vaccine-related SAE is an AE that results in death, 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.

Current Secondary Outcome Measures (submitted: August 4, 2022)

• Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the Common Serotypes in V116 and PNEUMOVAX™23 [ Time Frame: Day 30 postvaccination ]
  The serotype-specific OPA GMTs for serotypes common to V116 and PNEUMOVAX™23 were determined using the multiplex opsonophagocytic assay (MOPA). Serotype-specific OPA GMTs and GMT ratios with 95% confidence intervals (CIs) were calculated using a constrained longitudinal data analysis (cLDA) model. Per protocol, within-group measures of dispersion (MOD) were not calculated.
• Serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for the Common Serotypes in V116 and PNEUMOVAX™23 [ Time Frame: Day 30 postvaccination ]
  The GMCs for serotype-specific pneumococcal IgG antibodies were measured using pneumococcal electrochemiluminescence (PnECL). Serotype-specific pneumococcal IgG GMCs and GMC ratios with 95% CIs were calculated using a cLDA model. Per protocol, within-group MOD were not calculated.
• Serotype-specific OPA GMTs for the Unique Serotypes in V116 [ Time Frame: Day 30 postvaccination ]
  The serotype-specific OPA GMTs for serotypes unique to V116 were determined using the MOPA. Serotype-specific OPA GMTs and GMT ratios with 95% CIs were calculated using a cLDA model. Per protocol, within-group MOD were not calculated.
• Serotype-specific IgG GMCs for the Unique Serotypes in V116 [ Time Frame: Day 30 postvaccination ]
  The GMCs for serotype-specific pneumococcal IgG antibodies unique to V116 were measured using PnECL. Serotype-specific pneumococcal IgG GMCs and GMC ratios with 95% CIs were calculated using a cLDA model. Per protocol, within-group MOD were not calculated.
• Geometric Mean Fold Rise (GMFR) From Baseline in GMTs of Serotype-specific OPA [ Time Frame: Baseline (Day 1) and Day 30 postvaccination ]
  GMTs for the serotypes in V116 and PNEUMOVAX™23 were determined using the MOPA at baseline and 30 days post vaccination and derived from a cLDA model. The GMFR (Day 30 GMT/Day 1 GMT) from baseline (Day 1) to Day 30 of each pneumococcal serotype was calculated.
• GMFR From Baseline in Serotype-specific IgG GMCs [ Time Frame: Baseline (Day 1) and Day 30 postvaccination ]
  GMCs for the serotypes in V116 and PNEUMOVAX™23 were measured by PnECL at baseline and 30 days post vaccination and derived from a cLDA model. The GMFR (Day 30 GMC/Day 1 GMC) from baseline (Day 1) to Day 30 of each pneumococcal serotype was calculated.

Original Secondary Outcome Measures (submitted: December 8, 2020)

• Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the Common Serotypes in pPCV and Pneumovax™23 [ Time Frame: Day 30 postvaccination ]
  The GMTs for serotypes common to pPCV and PNEOMOVAX™23 will be determined using the muliplex opsonophagocytic assay (MOPA).
• Serotype-specific Immunoglobulin G (IgG) Geometric Mean Concentrations (GMCs) for the Common Serotypes in pPCV and Pneumovax™23 [ Time Frame: Day 30 postvaccination ]
  The GMCs for serotype-specific pneumococcal IgG antibodies will be determined using pneumococcal electrochemiluminescence (PnECL).
• Serotype-specific OPA GMTs for the Unique Serotypes in pPCV [ Time Frame: Day 30 postvaccination ]
  The GMTs for serotypes unique to pPCV will be determined using the MOPA.
• Serotype-specific IgG GMCs for the Unique Serotypes in pPCV [ Time Frame: Day 30 postvaccination ]
  The GMCs for serotype-specific pneumococcal IgG antibodies unique to pPCV will be determined using PnECL.
• Geometric Mean Fold Rise (GMFR) from Baseline in Serotype-specific OPA GMTs for the Common Serotypes in pPCV and Pneumovax™23 [ Time Frame: Baseline (Day 1) and Day 30 postvaccination ]
  The GMFR in GMTs from baseline to Day 30 of serotypes common to pPCV and PNEOMOVAX™23 will be determined using the MOPA.
• GMFR from Baseline in Serotype-specific IgG GMCs for the Common Serotypes in pPCV and Pneumovax™23 [ Time Frame: Baseline (Day 1) and Day 30 postvaccination ]
  The GMFR in GMCs from baseline to Day 30 of serotype-specific pneumococcal IgG antibodies will be determined using PnECL.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety, Tolerability, and Immunogenicity of a Polyvalent Pneumococcal Conjugate Vaccine (V116) in Japanese Adults (V116-002)
• Official Title: A Phase 1, Randomized, Double-blind, Active-Comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Polyvalent Pneumococcal Conjugate Vaccine in Healthy Japanese Adults.
• Brief Summary: The purpose of this study is to compare the safety, tolerability, and immunogenicity of a polyvalent pneumococcal conjugate vaccine (V116) with that of PNEUMOVAX™23 in healthy Japanese adults.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Pneumococcal Infection

Intervention

• Biological: V116
  Pneumococcal 21-valent conjugate vaccine with 2 μg of each of the following pneumococcal polysaccharides (PnPs) antigen: 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20A, 22F, 23A, 23B, 24F, 31, 33F, and 35B in each 0.5 mL sterile solution
  Other Names:

  • Polyvalent pneumococcal conjugate vaccine (pPCV)
  • Pneumococcal 21-valent Conjugate Vaccine
• Biological: PNEUMOVAX™23
  Pneumococcal 23-valent polyvalent vaccine with 25 μg of each of the following PnPs antigen: 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, and 33F in each 0.5 mL sterile solution
  Other Name: PPSV23

Study Arms

• Experimental: V116
  Participants receive a single 1.0 mL intramuscular (IM) injection of V116 on Day 1.
  Intervention: Biological: V116
• Active Comparator: PNEUMOVAX™23
  Participants receive a single 0.5 mL IM injection of PNEUMOVAX™23 on Day 1.
  Intervention: Biological: PNEUMOVAX™23

• Publications *: Haranaka M, Yono M, Kishino H, Igarashi R, Oshima N, Sawata M, Platt HL. Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in Japanese healthy adults: A Phase I study. Hum Vaccin Immunother. 2023 Aug 1;19(2):2228162. doi: 10.1080/21645515.2023.2228162.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: April 16, 2021): 102
• Original Estimated Enrollment (submitted: December 8, 2020): 100
• Actual Study Completion Date: April 6, 2021
• Actual Primary Completion Date: April 6, 2021 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• is a healthy Japanese male or female ≥20 years of age at time of randomization
• male participants must agree to be abstinent or use contraception during the intervention period and for ≥30 days after the last dose of study intervention
• female participants must not be pregnant or breastfeeding, and is either:
• not a woman of childbearing potential (WOCBP) or
• a WOCBP who agrees to remain abstinent or use contraception during the intervention period and for ≥30 days after the last dose of study intervention

Exclusion Criteria:

• has a history of invasive pneumococcal disease (IPD) within 3 years of Day 1
• has a known hypersensitivity to any vaccine components
• has impaired immunological function
• has a coagulation disorder
• had a recent febrile illness (axillary temperature ≥37.5°C or equivalent) within 72 hours before Day 1
• has a known malignancy that is progressing/requiring treatment
• has received, or is expected to receive, a pneumococcal vaccine outside the study protocol
• has received systemic corticosteroids (prednisone equivalent of ≥20 mg/day) for ≥14 consecutive days and has not completed the regimen for ≥30 days prior to Day 1
• is receiving immunosuppressive therapy
• has received any non-live vaccine from 14 days prior to Day 1 other than inactivated influenza vaccine
• has received any live vaccine from 30 days prior to Day 1
• has received a blood transfusion or blood products
• has participated in another clinical trial within 2 months of this study
• has clinically relevant drug or alcohol abuse
• has any condition that, in the opinion of the investigator, precludes participation in this study

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 20 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Japan

Administrative Information

• NCT Number: NCT04665050
• Other Study ID Numbers: pPCV-002; pPCV-002 ( Other Identifier: Merck ); jRCT2071200094 ( Registry Identifier: jRCT ); V116-002 ( Other Identifier: Merck )
• Has Data Monitoring Committee: No

U.S. FDA-regulated Product

• 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

IPD Sharing Statement

• Plan to Share IPD: Yes
• Plan Description: http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf
• URL: http://engagezone.msd.com/ds_documentation.php

• Current Responsible Party: Merck Sharp & Dohme LLC
• Original Responsible Party: Same as current
• Current Study Sponsor: Merck Sharp & Dohme LLC
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Director: Medical Director; Merck Sharp & Dohme LLC

• PRS Account: Merck Sharp & Dohme LLC
• Verification Date: September 2023