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

Pneumonia, Pneumococcal Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04168190
• Other study ID #: pPCV-001
• Secondary ID: pPCV-001V116-001
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: December 6, 2019
• Est. completion date: July 12, 2021

Study information

• Verified date: September 2022
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 600
• Est. completion date: July 12, 2021
• Est. primary completion date: July 12, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Pneumonia, Pneumococcal

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
• 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

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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