Safety and Immunogenicity of V116 in Vaccine-naïve Japanese Older Adults (V116-009, STRIDE-9)

• ClinicalTrials.gov Identifier: NCT05633992
• Recruitment Status: Completed
• First Posted: December 1, 2022
• Last Update Posted: May 31, 2023
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief Summary:

This is a phase 3, randomized, double-blind, active comparator-controlled study of the safety, tolerability, and immunogenicity of V116 in pneumococcal vaccine-naïve Japanese adults 65 years of age and older. The polyvalent (23-valent) pneumococcal vaccine, PPSV23, is the active comparator. In addition to studying safety/tolerability, it is hypothesized that, at 30 days postvaccination, the immunogenicity of V116 is noninferior to PPSV23 for the 12 common serotypes in V116 and PPSV23 and the cross-reactive serotype 15B in V116, and that the immunogenicity of V116 is superior to PPSV23 for the unique serotype 15C in V116. It is also hypothesized that V116 is superior to PPSV23 in the percentage of participants with ≥4-fold rise from baseline in the 8 unique V116 serotypes (except for 15C), as measured by serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs).

Condition or disease	Intervention/treatment	Phase
Pneumococcal Disease	Biological: V116; Biological: PPSV23	Phase 3

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 450 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase 3, Randomized, Double-blind, Active Comparator-controlled Clinical Study to Evaluate the Safety, Tolerability, and Immunogenicity of V116 in Pneumococcal Vaccine-naïve Japanese Adults 65 Years of Age or Older
• Actual Study Start Date: January 10, 2023
• Actual Primary Completion Date: May 24, 2023
• Actual Study Completion Date: May 24, 2023

Arms and Interventions

Arm	Intervention/treatment
Experimental: V116 Treatment; Participants receive a single intramuscular (IM) injection of V116 on Day 1.	Biological: V116; Sterile 0.5 mL solution in prefilled syringe containing 4 μg of each pneumococcal polysaccharide (PnPs) antigen 3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B.; Other Name: Pneumococcal 21-valent Conjugate Vaccine
Active Comparator: PPSV23 Treatment; Participants receive a single IM injection of PPSV23 on Day 1.	Biological: PPSV23; Sterile 0.5 mL solution in prefilled syringe containing 25 μg of each 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.; Other Name: PNEUMOVAX™23

Outcome Measures

Primary Outcome Measures :

1. Percentage of participants with solicited injection-site adverse events (AEs) [ 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 consist of pain/tenderness, redness/erythema, and swelling.
2. Percentage of participants with solicited systemic AEs [ 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 consist of muscle aches all over body/myalgia, headache, and tiredness/fatigue.
3. Percentage of participants with vaccine-related serious AEs (SAEs) [ Time Frame: Up to 30 days postvaccination ]
   An SAE is any untoward medical occurrence that results in death, is life-threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is an other important medical event. SAEs that were reported to be at least possibly related by the investigator to study vaccination will be summarized.
4. Serotype-specific opsonophagocytic (OPA) geometric mean titers (GMTs) [common serotypes] [ Time Frame: Day 30 postvaccination ]
   The serotype-specific OPA GMTs for the 12 common serotypes contained in V116 and PPSV23, the cross-reactive serotype 15B in V116, and the unique serotype 15C in V116, will be determined using the multiplex opsonophagocytic assay (MOPA).
5. Percentage of participants with ≥4-fold rise from baseline in serotype-specific OPAs (unique to V116) [ Time Frame: Baseline (Day 1) and Day 30 postvaccination ]
   The percentage of participants with ≥4-fold rise from baseline in serotype-specific OPAs for the 8 unique serotypes contained in V116 (except for 15C) will be determined.

Secondary Outcome Measures :

1. Serotype-specific OPA GMTs (unique serotypes) [ Time Frame: Day 30 postvaccination ]
   The serotype-specific OPA GMTs for the 8 unique serotypes contained in V116 (except for serotype 15C) and the cross-reactive serotype 6C in V116 will be determined using MOPA.
2. Serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) [ Time Frame: Day 30 postvaccination ]
   The GMCs for serotype-specific IgG antibodies will be determined using pneumococcal electrochemiluminescence (PnECL).
3. Percentage of participants with ≥4-fold rise from baseline in serotype-specific OPA GMTs (all serotypes) [ Time Frame: Baseline (Day 1) and Day 30 postvaccination ]
   The percentage of participants with ≥4-fold rise from baseline in serotype-specific OPA GMTs will be determined with MOPA.
4. Percentage of participants with ≥4-fold rise from baseline in serotype-specific IgG GMCs (all serotypes) [ Time Frame: Baseline (Day 1) and Day 30 postvaccination ]
   The percentage of participants with ≥4-fold rise from baseline in serotype-specific IgG GMCs will be determined with PnECL.
5. Serotype-specific geometric mean fold rise (GMFR) in OPA GMTs [ Time Frame: Baseline (Day 1) and Day 30 postvaccination ]
   The GMFR from baseline in serotype-specific OPA GMTs will be determined using MOPA.
6. Serotype-specific GMFR in IgG GMCs [ Time Frame: Baseline (Day 1) and Day 30 postvaccination ]
   The GMFR from baseline in GMCs for serotype-specific IgG antibodies will be determined using PnECL.

Eligibility Criteria

• Ages Eligible for Study: 65 Years and older (Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Is Japanese
• For females, is not pregnant or breastfeeding and is either not a participant of childbearing potential (POCBP) or is a POCBP and uses acceptable contraception/abstinence; has a negative highly sensitive pregnancy test (urine or serum) within 24 (urine) or 72 (serum) hours before the first dose of study intervention; and has medical, menstrual, and recent sexual activity history reviewed by the investigator to decrease the chance of inclusion of an early undetected pregnancy

Exclusion Criteria:

• Has a history of invasive pneumococcal disease (IPD) [positive blood culture, positive cerebrospinal fluid culture, or positive culture at another sterile site] or known history of other culture-positive pneumococcal disease within 3 years of Visit 1 (Day 1)
• Has a known hypersensitivity to any component of V116 or PPSV23, including diphtheria toxoid
• Has a known or suspected impairment of immunological function including, but not limited to, a history of congenital or acquired immunodeficiency, documented human immunodeficiency virus (HIV) infection, functional or anatomic asplenia, or history of autoimmune disease
• Has a coagulation disorder contraindicating IM vaccination
• Had a recent febrile illness (defined as oral or tympanic temperature ≥100.4°F [≥38.0°C] or axillary or temporal temperature ≥99.4°F [≥37.4°C]) or received antibiotic therapy for any acute illness occurring <72 hours before receipt of study vaccine
• Has a known malignancy that is progressing or has required active treatment <3 years before enrollment
• Received prior pneumococcal vaccine or is expected to receive any pneumococcal vaccine during the study outside the protocol
• Received systemic corticosteroids (prednisone equivalent of ≥20 mg/day) for ≥14 consecutive days and has not completed intervention ≥14 days before receipt of study vaccine
• Is currently receiving immunosuppressive therapy, including chemotherapeutic agents or other immunotherapies/immunomodulators used to treat cancer or other conditions, and interventions associated with organ or bone marrow transplantation, or autoimmune disease
• Received any nonlive vaccine ≤14 days before receipt of study vaccine or is scheduled to receive any nonlive vaccine ≤30 days after receipt of study vaccine (inactivated influenza and SARS-CoV2 vaccines may be acceptable)
• Received any live virus vaccine ≤30 days before receipt of study vaccine or is scheduled to receive any live virus vaccine ≤30 days after receipt of study vaccine
• Received a blood transfusion or blood products, including immunoglobulin ≤6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product until the Day 30 postvaccination blood draw is complete

Contacts and Locations

Locations

Japan

Medical Corporation Heishinkai OPHAC Hospital ( Site 1008)

Osaka-shi, Osaka, Japan, 532-0003

Medical Corporation Heishinkai OCROM Clinic ( Site 1003)

Suita-shi, Osaka, Japan, 565-0853

P-One Clinic ( Site 1001)

Hachioji, Tokyo, Japan, 192-0071

Heishinkai Medical Group ToCROM Clinic ( Site 1004)

Shinjuku-ku, Tokyo, Japan, 160-0008

Medical Corporation Shinanokai Shinanozaka Clinic ( Site 1006)

Shinjuku-ku, Tokyo, Japan, 160-0017

Medical Corporation Houeikai Sekino Clinical Pharmacology Clinic ( Site 1005)

Toshima, Tokyo, Japan, 171-0014

PS Clinic ( Site 1002)

Fukuoka, Japan, 812-0025

Nishikumamoto Hospital ( Site 1007)

Kumamoto, Japan, 861-4157

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

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

More Information

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT05633992
• Other Study ID Numbers: V116-009; jRCT2031220551 ( Registry Identifier: jRCT )
• First Posted: December 1, 2022
• Last Update Posted: May 31, 2023
• Last Verified: May 2023

Individual Participant Data (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

• 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

Additional relevant MeSH terms:

Pneumococcal Infections; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs