A Phase 1/Phase 2 Study of Polyvalent Pneumococcal Conjugate Vaccine (V116) in Adults (V116-001)

A Phase 1/Phase 2, Randomized, Double-blind Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Polyvalent Pneumococcal Conjugate Vaccine in Adults.

This Phase 1 and Phase 2 study will evaluate the safety, tolerability and immunogenicity of V116 when administered to adults. Phase 1 has no formal hypothesis. The primary hypotheses for Phase 2 are: V116 is noninferior to Pneumovax™23 as measured by the serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) for the common serotypes at 30 days postvaccination and that the serotype-specific OPA GMTs for the unique serotypes in V116 at 30 days postvaccination are statistically significantly greater following vaccination with V116 than those following vaccination with Pneumovax™23.

Study Overview

• Status: Completed
• Conditions: Pneumonia, Pneumococcal
• Intervention / Treatment: Biological: V116; Biological: Pneumovax™23

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Simon Williamson Clinic ( Site 0004)
  • Arizona
    • Mesa, Arizona, United States, 85206
      • Central Arizona Medical Associates ( Site 0003)
  • Florida
    • Coral Gables, Florida, United States, 33134
      • Clinical Research of South Florida ( Site 0008)
    • Hialeah, Florida, United States, 33012
      • Indago Research & Health Center, Inc ( Site 0011)
    • Hollywood, Florida, United States, 33024
      • Research Centers of America, LLC ( Site 0001)
    • Miami, Florida, United States, 33143
      • QPS Miami Research Associates ( Site 0016)
    • Miami, Florida, United States, 33144
      • L&C Professional Medical Research Institute ( Site 0009)
    • Miami, Florida, United States, 33174
      • Advanced Medical Research Institute ( Site 0010)
  • Illinois
    • Peoria, Illinois, United States, 61614
      • Optimal Research ( Site 0006)
  • Louisiana
    • Metairie, Louisiana, United States, 70006
      • Benchmark Research ( Site 0012)
  • Michigan
    • Troy, Michigan, United States, 48098
      • Arcturus Healthcare , PLC, Troy Internal Medicine Research Division ( Site 0018)
  • Nebraska
    • Norfolk, Nebraska, United States, 68701
      • Meridian Clinical Research, LLC ( Site 0024)
  • Nevada
    • Las Vegas, Nevada, United States, 89104
      • Wake Research Clinical Research Center of Nevada, LLC ( Site 0014)
  • New York
    • Endwell, New York, United States, 13760
      • Meridian Clinical Research, LLC ( Site 0025)
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc. ( Site 0002)
  • Ohio
    • Dayton, Ohio, United States, 45419
      • PriMED Clinical Research ( Site 0021)
    • Maumee, Ohio, United States, 43537
      • Advanced Medical Research ( Site 0017)
  • Oregon
    • Portland, Oregon, United States, 97227
      • Kaiser Permanente Center for Health Research ( Site 0015)
  • Texas
    • San Antonio, Texas, United States, 78229
      • Diagnostics Research Group ( Site 0013)
  • Utah
    • West Jordan, Utah, United States, 84088
      • Advanced Clinical Research ( Site 0022)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria

• Phase 1:
• Male or female, from 18 years to 49 years of age inclusive
• Phase 2:
• Male or female ≥50 years of age Phase 1 and Phase 2
• Males: refrain from donating sperm, remain abstinent during study or agree to use condom
• Females: Not pregnant. If a woman of childbearing potential, agree to use contraception or remain abstinent

Exclusion Criteria

• History of invasive pneumococcal disease or known history of other culture-positive pneumococcal disease within 3 years of screening
• Known hypersensitivity to any component of the pPCV, or any diphtheria toxoid-containing vaccine
• 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
• Coagulation disorder contraindicating IM vaccination
• 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 within 72 hours of screening
• Known malignancy that is progressing or has required active treatment within 3 years.(Note: participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or carcinoma in situ [eg, breast carcinoma, cervical cancer in situ] that have undergone potentially curative therapy are not excluded)
• Pregnant
• Received any pneumococcal vaccine or is expected to receive any pneumococcal vaccine during the study, outside of the protocol.
• Receiving immunosuppressive therapy, including chemotherapeutic agents used to treat cancer or other conditions, and interventions associated with organ or bone marrow transplantation, or autoimmune disease
• Received a blood transfusion or blood products, including immunoglobulin, 6 months before study vaccination or is scheduled to receive a blood transfusion or blood product

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Phase 1: V116 0.5 mL; Participants will receive a single intramuscular (IM) 0.5 mL vaccination on Day 1 of Phase 1	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: Pneumococcal 21-valent Conjugate Vaccine; Polyvalent pneumococcal conjugate vaccine (pPCV)
Experimental: Phase 1: V116 1.0 mL; Participants will receive a single IM 1.0 mL vaccination on Day 1 of Phase 1	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: Pneumococcal 21-valent Conjugate Vaccine; Polyvalent pneumococcal conjugate vaccine (pPCV)
Active Comparator: Phase 1: Pneumovax™23; Participants will receive a single IM 0.5 mL vaccination on Day 1 of Phase 1	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 Names: PPSV23
Experimental: Phase 2: V116; Participants will receive a single IM 1.0 mL vaccination on Day 1 of Phase 2	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: Pneumococcal 21-valent Conjugate Vaccine; Polyvalent pneumococcal conjugate vaccine (pPCV)
Active Comparator: Phase 2: Pneumovax™23; Participants will receive a single IM 0.5 mL vaccination on Day 1 of Phase 2	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 Names: PPSV23

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Percentage of Participants With a Solicited Injection-site Adverse Event (AE)	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. Injection-site AEs solicited on the Vaccine Report Card (VRC) were redness/erythema, swelling, and tenderness/pain. The percentage of participants with one or more solicited injection-site AE was assessed.	Up to 5 days post-vaccination
Phase 1: Percentage of Participants With a Solicited Systemic AE	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. Systemic AEs solicited on the VRC were muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. The percentage of participants with one or more solicited systemic AE was assessed.	Up to 5 days post-vaccination
Phase 1: Percentage of Participants With Vaccine-related Serious Adverse Events (SAEs)	A serious adverse event (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. The percentage of participants with one or more SAE that were assessed by the investigator to be at least possibly related to the study vaccination were reported.	Up to Day 195
Phase 2: Percentage of Participants With a Solicited Injection-site AE	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. Injection-site AEs solicited on the Vaccine Report Card (VRC) were redness/erythema, swelling, and tenderness/pain. The percentage of participants with one or more solicited injection-site AE was assessed.	Up to 5 days post-vaccination
Phase 2: Percentage of Participants With a Solicited Systemic AE	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. Systemic AEs solicited on the VRC were muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. The percentage of participants with 1 or more solicited systemic AE was assessed.	Up to 5 days post-vaccination
Phase 2: Percentage of Participants With Vaccine-related SAEs	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. The percentage of participants who experienced at least one SAE that were assessed by the investigator to be at least possibly related to the study vaccination were reported.	Up to Day 293
Phase 2: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the Common Serotypes in V116 and Pneumovax™23	GMTs for the serotypes common to V116 and Pneumovax™23 were determined using the muliplex 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 CIs were not calculated.	30 days post vaccination
Phase 2: Serotype-specific OPA GMTs for the Unique Serotypes in V116	GMTs for the 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 CIs were not calculated.	30 days post vaccination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1: Serotype-specific Immunoglobin G (IgG) Geometric Mean Concentrations (GMCs) for the Common Serotypes in V116 and Pneumovax™23	Serotype-specific pneumococcal IgG antibodies were measured using pneumococcal electrochemiluminescence (PnECL). Serotype-specific pneumococcal IgG GMCs and GMC ratios with 95% confidence intervals were calculated using a cLDA model. Per protocol, within-group CIs were not calculated.	30 days post vaccination
Phase 1: Serotype-specific Immunoglobin G (IgG) Geometric Mean Concentrations (GMCs) for the Serotypes Unique to V116	Serotype-specific pneumococcal IgG antibodies were measured using PnECL. Serotype-specific pneumococcal IgG GMCs and GMC ratios with 95% confidence intervals were calculated using a cLDA model. Per protocol, within-group CIs were not calculated.	30 days post vaccination
Phase 1: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the Common Serotypes in V116 and Pneumovax™23	GMTs for the serotypes common to V116 and Pneumovax™23 were determined using the MOPA. Serotype-specific OPA GMTs and GMT ratios with 95% confidence intervals were calculated using a cLDA model. Per protocol, within-group CIs were not calculated.	30 days post vaccination
Phase 1: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the Unique Serotypes in V116 and Pneumovax™23	GMTs for the serotypes common to V116 and Pneumovax™23 were determined using the MOPA. Serotype-specific OPA GMTs and GMT ratios with 95% confidence intervals were calculated using a cLDA model. Per protocol, within-group CIs were not calculated.	30 days post vaccination
Phase 1: Geometric Mean Fold Rise (GMFR) From Baseline in GMTs of Serotype-specific OPA	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 IgG serotype was calculated.	Baseline (Day 1) and 30 days postvaccination
Phase 1: Geometric Mean Fold Rise (GMFR) From Baseline in GMCs of Serotype-specific IgG	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 IgG serotype was calculated.	Baseline (Day 1) and 30 days post vaccination
Phase 2: Serotype-specific IgG GMCs for the Common Serotypes in V116 and Pneumovax™23	Serotype-specific pneumococcal IgG antibodies were measured using PnECL. Serotype-specific pneumococcal IgG GMCs and GMC ratios with 95% confidence intervals were calculated using a cLDA model. Per protocol, within-group CIs were not calculated.	30 days post vaccination
Phase 2: Serotype-specific IgG GMCs for the Serotypes Unique to V116	Serotype-specific pneumococcal IgG antibodies were measured using PnECL. Serotype-specific pneumococcal IgG GMCs and GMC ratios with 95% confidence intervals were calculated using a cLDA model. Per protocol, within-group CIs were not calculated.	30 days post vaccination
Phase 2: Geometric Mean Fold Rise (GMFR) From Baseline in GMTs of Serotype-specific OPA	GMTs for the serotypes in V116 and Pneumovax™23 were determined using the MOPA at baseline and at 30 days post vaccination and derived from a cLDA model. The GMFR for each pneumococcal IgG serotype was calculated as Day 30 GMT/Day 1 GMT.	Baseline (Day 1) and 30 days post vaccination
Phase 2: GMFR From Baseline in GMCs of Serotype-specific IgG	GMCs for each serotype common in V116 and Pneumovax™23 were measured using PnECL at baseline and 30 days post vaccination and derived from a cLDA model. The GMFR for each pneumococcal IgG serotype was calculated as Day 30 GMC/Day 1 GMC.	Baseline (Day 1) and 30 days post vaccination
Phase 2: Percentage of Participants Who Achieve a ≥4-fold Increase in Serotype-specific OPA Responses From Prevaccination (Baseline [Day 1]) to 30 Days Post Vaccination	The percentage of participants with ≥4-fold rise from baseline (Day 1) to Day 30 in GMTs of each pneumococcal serotype was calculated. Titer levels were determined by the MOPA and derived from a cLDA model.	Baseline (Day 1) and 30 days post vaccination

Collaborators and Investigators

• Sponsor: Merck Sharp & Dohme LLC

Publications and helpful links

General Publications

• Platt H, Omole T, Cardona J, Fraser NJ, Mularski RA, Andrews C, Daboul N, Gallagher N, Sapre A, Li J, Polis A, Fernsler D, Tamms G, Xu W, Murphy R, Skinner J, Joyce J, Musey L. Safety, tolerability, and immunogenicity of a 21-valent pneumococcal conjugate vaccine, V116, in healthy adults: phase 1/2, randomised, double-blind, active comparator-controlled, multicentre, US-based trial. Lancet Infect Dis. 2022 Sep 15:S1473-3099(22)00526-6. doi: 10.1016/S1473-3099(22)00526-6. Online ahead of print.

Study record dates

Study Major Dates

• Study Start (Actual): December 6, 2019
• Primary Completion (Actual): July 12, 2021
• Study Completion (Actual): July 12, 2021

Study Registration Dates

• First Submitted: November 18, 2019
• First Submitted That Met QC Criteria: November 18, 2019
• First Posted (Actual): November 19, 2019

Study Record Updates

• Last Update Posted (Actual): September 16, 2022
• Last Update Submitted That Met QC Criteria: September 1, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia; Lung Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Streptococcal Infections; Gram-Positive Bacterial Infections; Pneumonia, Bacterial; Pneumococcal Infections; Pneumonia, Pneumococcal; Physiological Effects of Drugs; Immunologic Factors; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: pPCV-001 (Other Identifier: Merck Protocol Number); V116-001 (Other Identifier: Merck Protocol 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