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

Study Overview
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Brief Summary
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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.

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

Conditions
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Pneumonia, Pneumococcal

Intervention / Treatment
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* Biological: V116
* Biological: Pneumovax™23


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Phase 1: V116 0.5 mL<br>Participants will receive a single intramuscular (IM) 0.5 mL vaccination on Day 1 of Phase 1 | Biological: V116<br>* 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<br>* Other names: Pneumococcal 21-valent Conjugate Vaccine;|
| Experimental: Phase 1: V116 1.0 mL<br>Participants will receive a single IM 1.0 mL vaccination on Day 1 of Phase 1 | Biological: V116<br>* 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<br>* Other names: Pneumococcal 21-valent Conjugate Vaccine;|
| Active Comparator: Phase 1: Pneumovax™23<br>Participants will receive a single IM 0.5 mL vaccination on Day 1 of Phase 1 | Biological: Pneumovax™23<br>* 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<br>* Other names: PPSV23;|
| Experimental: Phase 2: V116<br>Participants will receive a single IM 1.0 mL vaccination on Day 1 of Phase 2 | Biological: V116<br>* 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<br>* Other names: Pneumococcal 21-valent Conjugate Vaccine;|
| Active Comparator: Phase 2: Pneumovax™23<br>Participants will receive a single IM 0.5 mL vaccination on Day 1 of Phase 2 | Biological: Pneumovax™23<br>* 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<br>* Other names: PPSV23;|

What is the study measuring?
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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 |