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

• ClinicalTrials.gov Identifier: NCT04168190
• Recruitment Status: Completed
• First Posted: November 19, 2019
• Results First Posted: August 2, 2022
• Last Update Posted: September 16, 2022
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Pneumonia, Pneumococcal	Biological: V116; Biological: Pneumovax™23	Phase 1; Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 600 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Prevention
• Official Title: A Phase 1/Phase 2, Randomized, Double-blind Study to Evaluate the Safety, Tolerability, and Immunogenicity of a Polyvalent Pneumococcal Conjugate Vaccine in Adults.
• Actual Study Start Date: December 6, 2019
• Actual Primary Completion Date: July 12, 2021
• Actual Study Completion Date: July 12, 2021

Arms and Interventions

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: Polyvalent pneumococcal conjugate vaccine (pPCV); Pneumococcal 21-valent Conjugate Vaccine
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: Polyvalent pneumococcal conjugate vaccine (pPCV); Pneumococcal 21-valent Conjugate Vaccine
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 Name: 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: Polyvalent pneumococcal conjugate vaccine (pPCV); Pneumococcal 21-valent Conjugate Vaccine
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 Name: PPSV23

Outcome Measures

Primary Outcome Measures :

1. Phase 1: Percentage of Participants With a Solicited Injection-site Adverse Event (AE) [ Time Frame: Up to 5 days post-vaccination ]
   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.
2. Phase 1: Percentage of Participants With a Solicited Systemic AE [ Time Frame: Up to 5 days post-vaccination ]
   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.
3. Phase 1: Percentage of Participants With Vaccine-related Serious Adverse Events (SAEs) [ Time Frame: Up to Day 195 ]
   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.
4. Phase 2: Percentage of Participants With a Solicited Injection-site AE [ Time Frame: Up to 5 days post-vaccination ]
   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.
5. Phase 2: Percentage of Participants With a Solicited Systemic AE [ Time Frame: Up to 5 days post-vaccination ]
   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.
6. Phase 2: Percentage of Participants With Vaccine-related SAEs [ Time Frame: Up to Day 293 ]
   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.
7. Phase 2: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the Common Serotypes in V116 and Pneumovax™23 [ Time Frame: 30 days post vaccination ]
   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.
8. Phase 2: Serotype-specific OPA GMTs for the Unique Serotypes in V116 [ Time Frame: 30 days post vaccination ]
   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.

Secondary Outcome Measures :

1. Phase 1: Serotype-specific Immunoglobin G (IgG) Geometric Mean Concentrations (GMCs) for the Common Serotypes in V116 and Pneumovax™23 [ Time Frame: 30 days post vaccination ]
   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.
2. Phase 1: Serotype-specific Immunoglobin G (IgG) Geometric Mean Concentrations (GMCs) for the Serotypes Unique to V116 [ Time Frame: 30 days post vaccination ]
   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.
3. Phase 1: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the Common Serotypes in V116 and Pneumovax™23 [ Time Frame: 30 days post vaccination ]
   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.
4. Phase 1: Serotype-specific Opsonophagocytic Activity (OPA) Geometric Mean Titers (GMTs) for the Unique Serotypes in V116 and Pneumovax™23 [ Time Frame: 30 days post vaccination ]
   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.
5. Phase 1: Geometric Mean Fold Rise (GMFR) From Baseline in GMTs of Serotype-specific OPA [ Time Frame: Baseline (Day 1) and 30 days 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 IgG serotype was calculated.
6. Phase 1: Geometric Mean Fold Rise (GMFR) From Baseline in GMCs of Serotype-specific IgG [ Time Frame: Baseline (Day 1) and 30 days post vaccination ]
   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.
7. Phase 2: Serotype-specific IgG GMCs for the Common Serotypes in V116 and Pneumovax™23 [ Time Frame: 30 days post vaccination ]
   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.
8. Phase 2: Serotype-specific IgG GMCs for the Serotypes Unique to V116 [ Time Frame: 30 days post vaccination ]
   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.
9. Phase 2: Geometric Mean Fold Rise (GMFR) From Baseline in GMTs of Serotype-specific OPA [ Time Frame: Baseline (Day 1) and 30 days post vaccination ]
   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.
10. Phase 2: GMFR From Baseline in GMCs of Serotype-specific IgG [ Time Frame: Baseline (Day 1) and 30 days post vaccination ]
    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.
11. 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 [ Time Frame: Baseline (Day 1) and 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.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

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

Contacts and Locations

Locations

United States, Alabama

Simon Williamson Clinic ( Site 0004)

Birmingham, Alabama, United States, 35211

United States, Arizona

Central Arizona Medical Associates ( Site 0003)

Mesa, Arizona, United States, 85206

United States, Florida

Clinical Research of South Florida ( Site 0008)

Coral Gables, Florida, United States, 33134

Indago Research & Health Center, Inc ( Site 0011)

Hialeah, Florida, United States, 33012

Research Centers of America, LLC ( Site 0001)

Hollywood, Florida, United States, 33024

QPS Miami Research Associates ( Site 0016)

Miami, Florida, United States, 33143

L&C Professional Medical Research Institute ( Site 0009)

Miami, Florida, United States, 33144

Advanced Medical Research Institute ( Site 0010)

Miami, Florida, United States, 33174

United States, Illinois

Optimal Research ( Site 0006)

Peoria, Illinois, United States, 61614

United States, Louisiana

Benchmark Research ( Site 0012)

Metairie, Louisiana, United States, 70006

United States, Michigan

Arcturus Healthcare , PLC, Troy Internal Medicine Research Division ( Site 0018)

Troy, Michigan, United States, 48098

United States, Nebraska

Meridian Clinical Research, LLC ( Site 0024)

Norfolk, Nebraska, United States, 68701

United States, Nevada

Wake Research Clinical Research Center of Nevada, LLC ( Site 0014)

Las Vegas, Nevada, United States, 89104

United States, New York

Meridian Clinical Research, LLC ( Site 0025)

Endwell, New York, United States, 13760

Rochester Clinical Research, Inc. ( Site 0002)

Rochester, New York, United States, 14609

United States, Ohio

PriMED Clinical Research ( Site 0021)

Dayton, Ohio, United States, 45419

Advanced Medical Research ( Site 0017)

Maumee, Ohio, United States, 43537

United States, Oregon

Kaiser Permanente Center for Health Research ( Site 0015)

Portland, Oregon, United States, 97227

United States, Texas

Diagnostics Research Group ( Site 0013)

San Antonio, Texas, United States, 78229

United States, Utah

Advanced Clinical Research ( Site 0022)

West Jordan, Utah, United States, 84088

Sponsors and Collaborators

Merck Sharp & Dohme LLC

Investigators

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

  Study Documents (Full-Text)

Documents provided by Merck Sharp & Dohme LLC:

Study Protocol and Statistical Analysis Plan  [PDF] May 11, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. 2023 Feb;23(2):233-246. doi: 10.1016/S1473-3099(22)00526-6. Epub 2022 Sep 15.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT04168190
• Other Study ID Numbers: pPCV-001; pPCV-001 ( Other Identifier: Merck Protocol Number ); V116-001 ( Other Identifier: Merck Protocol Number )
• First Posted: November 19, 2019
• Results First Posted: August 2, 2022
• Last Update Posted: September 16, 2022
• Last Verified: September 2022

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

Additional relevant MeSH terms:

Pneumonia, Pneumococcal; Pneumonia; Respiratory Tract Infections; Infections; Lung Diseases; Respiratory Tract Diseases; Pneumococcal Infections; Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Pneumonia, Bacterial; Vaccines; Heptavalent Pneumococcal Conjugate Vaccine; Immunologic Factors; Physiological Effects of Drugs