A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by PNEUMOVAX™23 in Healthy Adults 50 Years of Age or Older (V114-016/PNEU-PATH)

Study Overview
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Brief Summary
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This study is designed 1) to evaluate the safety, tolerability, and immunogenicity of V114 and Prevnar 13™, 2) to describe the safety of sequential administration of V114 or Prevnar 13™ followed by PNEUMOVAX™23, and 3) to evaluate the immune responses to the 15 serotypes contained in V114 when PNEUMOVAX™23 is given approximately 12 months after receipt of either V114 or Prevnar 13™ in healthy adults 50 years of age or older. There was no formal hypothesis testing.

Official Title
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A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 Followed by Administration of PNEUMOVAX™23 One Year Later in Healthy Adults 50 Years of Age or Older (PNEU-PATH)

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Biological: V114
* Biological: Prevnar 13™
* Biological: PNEUMOVAX™23


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female in good health Female participant: not pregnant, not breastfeeding and 1) not of childbearing potential, or 2) of childbearing potential and agrees to practice contraception through 6 weeks after administration of last study vaccine. Exclusion Criteria History of invasive pneumococcal disease Known hypersensitivity to any component of pneumococcal polysaccharide vaccine, pneumococcal conjugate vaccine, or any diphtheria toxoid-containing vaccine. Known or suspected impairment of immune function Coagulation disorder contraindicating intramuscular vaccination History of malignancy ≤5 years before enrollment, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer Female participant: positive urine or serum pregnancy test Prior administration of any pneumococcal vaccine Received systemic corticosteroids (prednisone equivalent of ≥20 mg/day) for ≥14 consecutive days and has not completed intervention at least 30 days before study entry. Received systemic corticosteroids exceeding physiologic replacement doses (approximately 5 mg/day prednisone equivalent) within 14 days before vaccination. (Note: Topical, ophthalmic, intra-articular or soft-tissue [e.g., bursa, tendon steroid injections], and inhaled/nebulized steroids are permitted). Received immunosuppressive therapy Received a blood transfusion or blood products within 6 months of enrollment Participated in another clinical study of an investigational product within 2 months of enrollment Current user of recreational or illicit drugs or history 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<br>Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 on Day 1 (Vaccination 1) and a single 0.5 mL IM injection of PNEUMOVAX™23 at Month 12 (Vaccination 2) | Biological: V114<br>* 15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, 33F (2 mcg each), serotype 6B (4 mcg) and Merck Aluminum Phosphate Adjuvant (125 mcg) in each 0.5 mL dose<br>Biological: PNEUMOVAX™23<br>* 23-valent pneumococcal polysaccharide vaccine with serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F (25 mcg each) in each 0.5 mL dose<br>* Other names: PPV23;|
| Active Comparator: Prevnar 13™<br>Participants will receive a single 0.5 mL IM injection of Prevnar 13™ on Day 1 (Vaccination 1) and a single 0.5 mL IM injection of PNEUMOVAX™23 at Month 12 (Vaccination 2) | Biological: Prevnar 13™<br>* 13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 7F, 9V, 14, 18C, 19A, 19F, 23F (2.2 mcg) and 6B (4.4 mcg) and aluminum phosphate adjuvant (125 mcg) in each 0.5 mL dose<br>* Other names: PCV13;Biological: PNEUMOVAX™23<br>* 23-valent pneumococcal polysaccharide vaccine with serotypes 1, 2, 3, 4, 5, 6B, 7F, 8, 9N, 9V, 10A, 11A, 12F, 14, 15B, 17F, 18C, 19A, 19F, 20, 22F, 23F, 33F (25 mcg each) in each 0.5 mL dose<br>* Other names: PPV23;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Solicited Injection-site Adverse Events Following V114 or Prevnar 13™ | An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following vaccination with V114 or Prevnar 13™, the percentage of participants with solicited injection-site AEs was assessed. The solicited injection-site AEs assessed were redness/erythema, swelling, and tenderness/pain. | Up to 5 days after Vaccination 1 | 
| Percentage of Participants With Solicited Injection-site Adverse Events Following PNEUMOVAX™23 | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following vaccination with PNEUMOVAX™23, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. | Up to 5 days after Vaccination 2 | 
| Percentage of Participants With Solicited Systemic Adverse Events Following V114 or Prevnar 13™ | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following vaccination with V114 or Prevnar 13™, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. | Up to 14 days after Vaccination 1 | 
| Percentage of Participants With Solicited Systemic Adverse Events Following PNEUMOVAX™23 | An AE is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. Following vaccination with PNEUMOVAX™23, the percentage of participants with solicited systemic AEs was assessed. The solicited systemic AEs assessed were muscle pain/myalgia, joint pain/arthralgia, headache, and tiredness/fatigue. | Up to 14 days after Vaccination 2 | 
| Percentage of Participants With Vaccine-related Serious Adverse Events Following V114 or Prevnar 13™ | A serious adverse event (SAE) is an AE that 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. Relatedness of an SAE to the study vaccine will be determined by the investigator. Following vaccination with V114 or Prevnar 13™, the percentage of participants with vaccine-related serious adverse events was assessed. | Up to 12 months after Vaccination 1 | 
| Percentage of Participants With Vaccine-related Serious Adverse Events Following PNEUMOVAX™23 | A serious adverse event (SAE) is an AE that 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. Relatedness of an SAE to the study vaccine will be determined by the investigator. Following vaccination with PNEUMOVAX™23, the percentage of participants with vaccine-related serious adverse events was assessed. | Month 12 to Month 13 (Up to 44 days after Vaccination 2) | 
| Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at 30 Days Following PNEUMOVAX™23 | Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) (estimated) and GMT ratios with 95% confidence intervals (CIs) were calculated using a constrained longitudinal data analysis (cLDA) model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMT ratios); within-group CIs were not calculated. OPA for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using a Multiplexed Opsonophagocytic Assay. | Month 13 (30 days after Vaccination 2) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Concentration of Serotype-specific Immunoglobulin G at 30 Days Following PNEUMOVAX™23 | Serotype-specific Immunoglobulin G (IgG) geometric mean concentrations (GMCs) (estimated) and GMC ratios with 95% confidence intervals (CIs) were calculated using a constrained longitudinal data analysis (cLDA) model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMC ratios); within-group CIs were not calculated. IgG for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using an electrochemiluminescence assay. | Month 13 (30 days after Vaccination 2) | 
| GMT of Serotype-specific OPA at Day 30 | Serotype-specific OPA GMTs (estimated) and GMT ratios with 95% CIs were calculated using a constrained longitudinal data analysis (cLDA) model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMT ratios); within-group CIs were not calculated. OPA for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using a Multiplexed Opsonophagocytic Assay. | Day 30 | 
| GMC of Serotype-specific IgG at Day 30 | Serotype-specific IgG GMC (estimated) and GMC ratios with 95% CIs were calculated using a constrained longitudinal data analysis (cLDA) model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMC ratios); within-group CIs were not calculated. IgG for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using an electrochemiluminescence assay. | Day 30 | 
| Geometric Mean Fold Rise in Serotype-specific OPA Day 1 to Day 30 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a Multiplexed Opsonophagocytic Assay. Geometric mean fold rise (GMFR) is the geometric mean of fold rise from baseline to postvaccination. | Day 1 (Baseline) and Day 30 | 
| GMFR in Serotype-specific IgG Day 1 to Day 30 | Activity for the serotypes contained in Prevnar 13™ and V114 and (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. GMFR is the geometric mean of fold rise from baseline to postvaccination. | Day 1 (Baseline) and Day 30 | 
| Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Day 1 to Day 30 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using a Multiplexed Opsonophagocytic Assay. The percentage of participants who had ≥4-fold rise in OPA titers were calculated from baseline to postvaccination. | Day 1 (Baseline) and Day 30 | 
| Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Day 1 to Day 30 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using an electrochemiluminescence assay. The percentage of participants who had ≥ 4-fold rise in IgG concentration are calculated from baseline to postvaccination. | Day 1 (Baseline) and Day 30 | 
| GMT of Serotype-specific OPA at Month 12 | Serotype-specific OPA GMTs (estimated) and GMT ratios with 95% CIs were calculated using a constrained longitudinal data analysis (cLDA) model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMT ratios); within-group CIs were not calculated. OPA for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using a Multiplexed Opsonophagocytic Assay. | Month 12 | 
| GMC of Serotype-specific IgG at Month 12 | Serotype-specific IgG GMC (estimated) and GMC ratios with 95% CIs were calculated using a constrained longitudinal data analysis (cLDA) model utilizing data from both vaccination groups. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the GMC ratios); within-group CIs were not calculated. IgG for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using an electrochemiluminescence assay. | Month 12 | 
| GMFR in Serotype-specific OPA Day 1 to Month 12 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a Multiplexed Opsonophagocytic Assay. Geometric mean fold rise (GMFR) is the geometric mean of fold rise from baseline to postvaccination. | Day 1 (Baseline) and Month 12 | 
| GMFR in Serotype-specific IgG Day 1 to Month 12 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. GMFR is the geometric mean of fold rise from baseline to postvaccination. | Day 1 (Baseline) and Month 12 | 
| Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Day 1 to Month 12 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using a Multiplexed Opsonophagocytic Assay. The percentage of participants who had ≥4-fold rise in OPA titers were calculated from baseline to postvaccination. | Day 1 (Baseline) and Month 12 | 
| Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Day 1 to Month 12 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using an electrochemiluminescence assay. The percentage of participants who had ≥ 4-fold rise in IgG concentration are calculated from baseline to postvaccination. | Day 1 (Baseline) and Month 12 | 
| GMFR in Serotype-specific OPA Day 1 to Month 13 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a Multiplexed Opsonophagocytic Assay. Geometric mean fold rise (GMFR) is the geometric mean of fold rise from baseline to postvaccination. | Day 1 (Baseline) and Month 13 | 
| GMFR in Serotype-specific IgG Day 1 to Month 13 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. GMFR is the geometric mean of fold rise from baseline to postvaccination. | Day 1 (Baseline) and Month 13 | 
| Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Day 1 to Month 13 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using a Multiplexed Opsonophagocytic Assay. The percentage of participants who had ≥4-fold rise in OPA titers were calculated from baseline to postvaccination. | Day 1 (Baseline) and Month 13 | 
| Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Day 1 to Month 13 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using an electrochemiluminescence assay. The percentage of participants who had ≥ 4-fold rise in IgG concentration are calculated from baseline to postvaccination. | Day 1 (Baseline) and Month 13 | 
| GMFR in Serotype-specific OPA Month 12 to Month 13 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using a Multiplexed Opsonophagocytic Assay. Geometric mean fold rise (GMFR) is the geometric mean of fold rise from baseline to postvaccination. | Month 12 (Baseline) and Month 13 | 
| GMFR in Serotype-specific IgG Month 12 to Month 13 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) was determined using an electrochemiluminescence assay. GMFR is the geometric mean of fold rise from baseline to postvaccination. | Month 12 (Baseline) and Month 13 | 
| Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Month 12 to Month 13 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using a Multiplexed Opsonophagocytic Assay. The percentage of participants who had ≥4-fold rise in OPA titers were calculated from baseline to postvaccination. | Month 12 (Baseline) and Month 13 | 
| Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Month 12 to Month 13 | Activity for the serotypes contained in Prevnar 13™ and V114 (13 serotypes shared with Prevnar 13™ and 2 serotypes unique to V114) will be determined using an electrochemiluminescence assay. The percentage of participants who had ≥ 4-fold rise in IgG concentration are calculated from baseline to postvaccination. | Month 12 (Baseline) and Month 13 |