Safety and Immunogenicity of V116 in Pneumococcal Vaccine-naïve Adults (V116-003, STRIDE-3)

• ClinicalTrials.gov Identifier: NCT05425732
• Recruitment Status: Completed
• First Posted: June 21, 2022
• Last Update Posted: June 5, 2023
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Tracking Information

• First Submitted Date: June 15, 2022
• First Posted Date: June 21, 2022
• Last Update Posted Date: June 5, 2023
• Actual Study Start Date: July 13, 2022
• Actual Primary Completion Date: May 18, 2023 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 1, 2023)

• 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 consisted of pain/tenderness, redness/erythema, and swelling.
• 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 headache, muscle aches/myalgia, and tiredness/fatigue.
• Percentage of participants with vaccine-related serious AE (SAE) [ Time Frame: Up to 194 days postvaccination ]
  A vaccine-related SAE is any untoward medical consequence 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.
• Serotype specific opsonophagocytic (OPA) geometric mean titers (GMTs) in Cohorts 1 and 2 for the 21 serotypes contained in V116 [ Time Frame: Day 30 postvaccination ]
  The serotype specific OPA GMTs for the 21 serotypes contained in V116 will be determined using the multiplex opsonophagocytic assay (MOPA).
• Percentage of participants with ≥4-fold rise from baseline in serotype specific OPAs in Cohort 1 for the 21 serotypes contained in V116 [ Time Frame: Baseline and Day 30 postvaccination ]
  The percentage of participants with ≥4-fold rise from baseline in serotype specific OPAs for the 21 serotypes contained in V116 will be determined.

Original Primary Outcome Measures (submitted: June 15, 2022)

• Percentage of participants with solicited injection-site 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 consisted of pain/tenderness, redness/erythema, and swelling.
• 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 headache, muscle aches/myalgia, and tiredness/fatigue.
• Percentage of participants with vaccine-related serious AE (SAE) [ Time Frame: Up to 194 days postvaccination ]
  A vaccine-related SAE is any untoward medical consequence 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.
• Serotype-specific opsonophagocytic (OPA) geometric mean titers (GMTs) in Cohort 1 for the 21 serotypes contained in V116 [ Time Frame: Day 30 postvaccination ]
  The serotype-specific OPA GMTs for the 21 serotypes contained in V116 will be determined using the multiplex opsonophagocytic assay (MOPA).
• Percentage of participants with ≥4-fold rise from baseline in serotype-specific OPAs in Cohort 1 for for the 21 serotypes contained in V116 [ Time Frame: Baseline and Day 30 postvaccination ]
  The percentage of participants with ≥4-fold rise from baseline in serotype-specific OPAs for the 21 serotypes contained in V116 will be determined.

Current Secondary Outcome Measures (submitted: June 1, 2023)

• Percentage of participants with ≥4-fold rise in serotype specific cross-reactive OPA responses in Cohorts 1 and 2 [ Time Frame: Baseline and Day 30 postvaccination ]
  The percentage of participants with ≥4-fold rise from baseline in serotype specific cross-reactive OPAs will be determined.
• Serotype specific cross-reactive OPA GMTs in Cohorts 1 and 2 [ Time Frame: Day 30 postvaccination ]
  The serotype specific OPA GMTs will be determined using MOPA.
• Serotype specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) in Cohort 1 [ Time Frame: Day 30 postvaccination ]
  The GMCs for serotype specific IgG antibodies will be determined using pneumococcal electrochemiluminescence (PnECL).
• Geometric mean fold rise (GMFR) from baseline in serotype specific OPA GMTs in Cohort 1 [ Time Frame: Baseline and Day 30 postvaccination ]
  The GMFR from baseline in serotype specific OPA GMTs will be determined using MOPA.
• GMFR from baseline in serotype specific IgG GMCs in Cohort 1 [ Time Frame: Baseline and Day 30 postvaccination ]
  The GMFR in GMCs for serotype specific IgG antibodies will be determined using PnECL.
• Percentage of participants with ≥4-fold rise from baseline in serotype specific IgG GMCs in Cohort 1 [ Time Frame: Baseline and Day 30 postvaccination ]
  The percentage of participants with ≥4-fold rise from baseline in GMCs for serotype specific IgG antibodies will be determined using PnECL.
• Percentage of participants with ≥4-fold rise from baseline in serotype specific OPA GMTs in Cohort 1 [ Time Frame: Baseline and Day 30 postvaccination ]
  The percentage of participants with ≥4-fold rise from baseline in serotype specific OPAs will be determined.

Original Secondary Outcome Measures (submitted: June 15, 2022)

• Serotype-specific OPA GMTs in Cohorts 1 and 2 [ Time Frame: Day 30 postvaccination ]
  The serotype-specific OPA GMTs will be determined using MOPA.
• Percentage of participants with ≥4-fold rise in serotype-specific cross-reactive OPA responses in Cohorts 1 and 2 [ Time Frame: Day 30 postvaccination ]
  The percentage of participants with ≥4-fold rise from baseline in serotype-specific cross-reactive OPAs will be determined.
• Serotype-specific cross-reactive OPA GMTs in Cohorts 1 and 2 [ Time Frame: Day 30 postvaccination ]
  The serotype-specific OPA GMTs will be determined using MOPA.
• Serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) in Cohort 1 [ Time Frame: Day 30 postvaccination ]
  The GMCs for serotype-specific IgG antibodies will be determined using pneumococcal electrochemiluminescence (PnECL).
• Geometric mean fold rise (GMFR) from baseline in serotype-specific OPA GMTs in Cohort 1 [ Time Frame: Baseline and Day 30 postvaccination ]
  The GMFR from baseline in serotype-specific OPA GMTs will be determined using MOPA.
• GMFR from baseline in serotype-specific IgG GMCs in Cohort 1 [ Time Frame: Baseline and Day 30 postvaccination ]
  The GMFR in GMCs for serotype-specific IgG antibodies will be determined using PnECL.
• Percentage of participants with ≥4-fold rise from baseline in serotype-specific IgG GMCs in Cohort 1 [ Time Frame: Baseline and Day 30 postvaccination ]
  The GMFR in GMCs for serotype-specific IgG antibodies will be determined using PnECL.
• Percentage of participants with ≥4-fold rise from baseline in serotype-specific OPA GMTs in Cohort 1 [ Time Frame: Baseline and Day 30 postvaccination ]
  The percentage of participants with ≥4-fold rise from baseline in serotype-specific OPAs will be determined.

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

Descriptive Information

• Brief Title: Safety and Immunogenicity of V116 in Pneumococcal Vaccine-naïve Adults (V116-003, STRIDE-3)
• 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 Adults
• Brief Summary: This is a phase 3, randomized, double-blind, active comparator-controlled study of the safety, tolerability, and immunogenicity of V116 compared to PCV20 (pneumococcal 20-valent conjugate vaccine ([Prevnar 20™ / APEXXNAR™]) in pneumococcal vaccine-naïve adults. It is hypothesized that V116 is noninferior to PCV20 for the common serotypes and superior to PCV20 for the unique serotypes as assessed by serotype specific opsonophagocytic activity (OPA) 30 days postvaccination. It is also hypothesized that V116 in participants 18 to 49 years of age immunobridges to V116 in participants 50 to 64 years of age as assessed by serotype specific OPA geometric mean titers (GMTs) 30 days postvaccination for all 21 serotypes in V116. Participants ≥50 years of age will be enrolled in Cohort 1, and participants 18 to 49 years of age will be enrolled in Cohort 2.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Double (Participant, Investigator); Primary Purpose: Prevention
• Condition: Pneumococcal Infection

Intervention

• Biological: V116
  0.5 mL injection solution in prefilled syringe containing 4 μg of each PnPs antigen (3, 6A, 7F, 8, 9N, 10A, 11A, 12F, 15A, 15C, 16F, 17F, 19A, 20, 22F, 23A, 23B, 24F, 31, 33F, and 35B) given by intramuscular (IM) injection.
  Other Name: Pneumococcal 21-valent Conjugate Vaccine
• Biological: PCV20
  0.5 mL injection suspension in prefilled syringe containing 2.2 μg of each PnPs antigen (1, 3, 4, 5, 6A, 7F, 8, 9V, 10A, 11A, 12F, 14, 15B, 18C, 19A, 19F, 22F, 23F, 33F) and 4.4 μg of PnPs antigen 6B.
  Other Names:

  • Prevnar 20™
  • APEXXNAR™

Study Arms

• Experimental: Cohort 1 V116
  Pneumococcal vaccine-naïve adult participants (≥50 years of age) receive a single dose of V116 on Day 1.
  Intervention: Biological: V116
• Active Comparator: Cohort 1 PCV20
  Pneumococcal vaccine-naïve adult participants (≥50 years of age) receive a single dose of PCV20 on Day 1.
  Intervention: Biological: PCV20
• Experimental: Cohort 2 V116
  Pneumococcal vaccine-naïve adult participants (18 to 49 years of age) receive a single dose of V116 on Day 1.
  Intervention: Biological: V116
• Active Comparator: Cohort 2 PCV20
  Pneumococcal vaccine-naïve adult participants (18 to 49 years of age) receive a single dose of PCV20 on Day 1.
  Intervention: Biological: PCV20

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 1, 2023): 2664
• Original Estimated Enrollment (submitted: June 15, 2022): 2600
• Actual Study Completion Date: May 18, 2023
• Actual Primary Completion Date: May 18, 2023 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• For females, is not pregnant or breastfeeding and is either not a woman of childbearing potential (WOCBP) or is a WOCBP and uses acceptable contraception/abstinence; and has medical, menstrual, and recent sexual activity history reviewed by the investigator to decrease the chance 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 PCV20, 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 administration (prior to age of 5 is acceptable) of any 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 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: Australia, Belgium, Chile, Germany, Korea, Republic of, New Zealand, Puerto Rico, Sweden, Taiwan, Turkey, United States

Administrative Information

• NCT Number: NCT05425732
• Other Study ID Numbers: V116-003; V116-003 ( Other Identifier: Merck ); 2022-000258-27 ( EudraCT Number )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

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: May 2023