Safety, Tolerability, and Immunogenicity of Two Formulations of V114 in Healthy Adults 50 Years of Age or Older (V114-006)

Study Overview
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Brief Summary
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The purpose of this study is to assess the safety, tolerability, and immunogenicity of a single dose of different formulations of V114 (V114-A and V114-B) and Prevnar 13® (pneumococcal 13-valent conjugate vaccine) in adult participants ≥50 years of age in good health.

Official Title
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A Multicenter, Double-Blind Study of the Safety, Tolerability, and Immunogenicity of V114 Compared to Prevnar 13™ in Healthy Pneumococcal Vaccine-Naïve Adults 50 Years of Age or Older

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: V114-A
* Biological: V114-B
* Biological: Prevnar 13®


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Good health; any underlying chronic illness must be documented to be in stable condition Highly unlikely to conceive through 6 weeks after administration of the study vaccine Exclusion Criteria: Prior administration of any pneumococcal vaccine History of invasive pneumococcal disease (IPD) [positive blood culture, positive cerebrospinal fluid culture, or other sterile site) or known history of other culture-positive pneumococcal disease Known hypersensitivity to any vaccine component Known or suspected impairment of immune function Received systemic corticosteroids for >=14 consecutive days and has not completed treatment <=30 days prior to study entry, or received systemic corticosteroids exceeding physiologic replacement doses within 14 days prior to study vaccination Coagulation disorder contraindicating intramuscular vaccination Receives immunosuppressive therapy, including chemotherapeutic agents used to treat cancer or other conditions, and treatments associated with organ or bone marrow transplantation, or autoimmune disease Received a blood transfusion or blood products, including immunoglobulins within the 6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product within 30 days of receipt of study vaccine. Autologous blood transfusions are not considered an exclusion criterion. Participated in another clinical study of an investigational product within 2 months before the beginning of or any time during the duration of the current clinical study Breast feeding User of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence

Ages Eligible for Study
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Minimum Age: 50 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: V114 Formulation A<br>Participants receive a single 0.5 mL intramuscular injection of V114 Formulation A on Day 1 | Biological: V114-A<br>* Formulation A of V114 contains 2 µg of pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, and 33F; 4 µg of serotype 6B; 32 µg of CRM197 protein carrier; and 125 µg of Aluminum Phosphate Adjuvant in each 0.5 mL dose (V114-A uses a unique excipient to improve stability of the vaccine against physical stress).<br>|
| Experimental: V114 Formulation B<br>Participants receive a single 0.5 mL intramuscular injection of V114 Formulation B on Day 1 | Biological: V114-B<br>* Formulation B of V114 contains 2 µg of pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19F, 19A, 22F, 23F, and 33F; 4 µg of serotype 6B; 32 µg of CRM197 protein carrier; and 125 µg of Aluminum Phosphate Adjuvant in each 0.5 mL dose (V114-B uses a unique excipient to improve stability of the vaccine against physical stress).<br>|
| Active Comparator: Prevnar 13®<br>Participants receive a single 0.5 mL intramuscular injection of Prevnar 13® on Day 1 | Biological: Prevnar 13®<br>* Pneumococcal capsular polysaccharide serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg each), and 6B (4.4 mcg) in each 0.5 mL dose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With an Adverse Event (AE) | The percentage of participants experiencing ≥1 AE(s) in each arm was determined. An AE is defined as any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which does not necessarily have to have a causal relationship with this treatment. | Up to 14 days after vaccination | 
| Percentage of Participants With a Solicited Injection-site Adverse Event (AE) | The percentage of participants experiencing ≥1 solicited injection-site AE(s) in each arm was determined. | Up to 14 days after vaccination | 
| Percentage of Participants With a Solicited Systemic Adverse Event (AE) | The percentage of participants experiencing ≥1 solicited systemic AE(s) in each arm was determined. | Up to 14 days after vaccination | 
| Percentage of Participants With a Serious Adverse Event (SAE) | The percentage of participants experiencing ≥1 SAE(s) in each arm was determined. | Up to 30 days after vaccination | 
| Percentage of Participants With Vaccine-Related Serious Adverse Event (SAE) | The percentage of participants experiencing ≥1 vaccine-related SAEs(s) in each arm was determined. | Up to 30 days after vaccination | 
| Geometric Mean Titers (GMTs) of Serotype-specific Opsonophagocytic Killing Activity (OPA) at One Month Post-Vaccination | The OPA GMTs of each common serotype (CS) and V114-specific serotype (VS) were determined in each arm. Titer levels were determined with the multiplexed opsonophagocytic assay (MOPA). | Day 30 (one month after vaccination) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentrations (GMCs) of Serotype-specific Immunoglobulin G (IgG) at One Month Post-Vaccination | The IgG GMCs of each common pneumococcal serotype (CS) and V114-specific pneumococcal serotype (VS) were determined for each arm. Concentrations were determined with pneumococcal electrochemiluminescence (PnECL). | Day 30 (one month after vaccination) | 
| Percentage of Participants With a ≥4-fold Rise From Baseline in Serotype-specific Opsonophagocytic Killing Activity (OPA) Geometric Mean Titers (GMTs) | The percentage of participants with ≥4-fold rise from baseline in OPA GMTs of each common serotype (CS) and V114-specific serotype (VS) were compared in the V114 and Prevnar® 13 arms. Estimated GMT, GMT ratio, 95% CI, and p-values were obtained from a constrained longitudinal data analysis (cLDA) model. | Baseline and Day 30 (one month after vaccination) | 
| Percentage of Participants With a ≥4-fold Rise From Baseline in Geometric Mean Concentrations (GMCs) of Serotype-specific Immunoglobulin G (IgG) Antibodies | The percentage of participants with ≥4-fold rise from baseline in IgG GMCs of each common serotype (CS) and V114-specific serotype (VS) were compared in the V114 and Prevnar® 13 arms. Estimated GMT, GMT ratio, 95% CI, and p-values were obtained from a constrained longitudinal data analysis (cLDA) model. | Baseline and Day 30 (one month after vaccination) |