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)
- Conditions
- Pneumococcal Infections
- Interventions
- Biological: Prevnar 13™Biological: V114Biological: PNEUMOVAX™23
- Registration Number
- NCT03480763
- Lead Sponsor
- Merck Sharp & Dohme LLC
- Brief Summary
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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 652
- 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.
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description V114 PNEUMOVAX™23 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) Prevnar 13™ Prevnar 13™ 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) V114 V114 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) Prevnar 13™ PNEUMOVAX™23 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)
- Primary Outcome Measures
Name Time Method Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at 30 Days Following PNEUMOVAX™23 Month 13 (30 days after Vaccination 2) 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.
Percentage of Participants With Solicited Injection-site Adverse Events Following PNEUMOVAX™23 Up to 5 days after Vaccination 2 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.
Percentage of Participants With Vaccine-related Serious Adverse Events Following V114 or Prevnar 13™ Up to 12 months after Vaccination 1 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.
Percentage of Participants With Vaccine-related Serious Adverse Events Following PNEUMOVAX™23 Month 12 to Month 13 (Up to 44 days after Vaccination 2) 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.
Percentage of Participants With Solicited Injection-site Adverse Events Following V114 or Prevnar 13™ Up to 5 days after Vaccination 1 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.
Percentage of Participants With Solicited Systemic Adverse Events Following V114 or Prevnar 13™ Up to 14 days after Vaccination 1 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.
Percentage of Participants With Solicited Systemic Adverse Events Following PNEUMOVAX™23 Up to 14 days after Vaccination 2 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.
- Secondary Outcome Measures
Name Time Method GMFR in Serotype-specific OPA Day 1 to Month 12 Day 1 (Baseline) and 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.
GMC of Serotype-specific IgG at Day 30 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.
Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Day 1 to Day 30 Day 1 (Baseline) and 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.
GMT of Serotype-specific OPA at Month 12 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.
Geometric Mean Fold Rise in Serotype-specific OPA Day 1 to Day 30 Day 1 (Baseline) and 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.
Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Day 1 to Day 30 Day 1 (Baseline) and 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.
GMFR in Serotype-specific OPA Month 12 to Month 13 Month 12 (Baseline) and 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.
Geometric Mean Concentration of Serotype-specific Immunoglobulin G at 30 Days Following PNEUMOVAX™23 Month 13 (30 days after Vaccination 2) 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.
GMT of Serotype-specific OPA at Day 30 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.
GMFR in Serotype-specific IgG Day 1 to Day 30 Day 1 (Baseline) and 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.
GMC of Serotype-specific IgG at Month 12 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.
GMFR in Serotype-specific IgG Day 1 to Month 12 Day 1 (Baseline) and 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.
GMFR in Serotype-specific OPA Day 1 to Month 13 Day 1 (Baseline) and 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.
Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Day 1 to Month 12 Day 1 (Baseline) and 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.
Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Day 1 to Month 13 Day 1 (Baseline) and 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.
Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Day 1 to Month 12 Day 1 (Baseline) and 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.
Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Month 12 to Month 13 Month 12 (Baseline) and 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.
Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Day 1 to Month 13 Day 1 (Baseline) and 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.
GMFR in Serotype-specific IgG Month 12 to Month 13 Month 12 (Baseline) and 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.
GMFR in Serotype-specific IgG Day 1 to Month 13 Day 1 (Baseline) and 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.
Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Month 12 to Month 13 Month 12 (Baseline) and 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.
Trial Locations
- Locations (22)
Rapid Medical Research, Inc. ( Site 0119)
🇺🇸Cleveland, Ohio, United States
University of Texas Medical Branch at Galveston ( Site 0127)
🇺🇸Galveston, Texas, United States
Texas Center For Drug Development ( Site 0107)
🇺🇸Houston, Texas, United States
East Valley Family Physicians ( Site 0104)
🇺🇸Chandler, Arizona, United States
Central Phoenix Medical Clinic, LLC ( Site 0125)
🇺🇸Phoenix, Arizona, United States
Encompass Clinical Research ( Site 0118)
🇺🇸Spring Valley, California, United States
Diablo Clinical Research, Inc ( Site 0132)
🇺🇸Walnut Creek, California, United States
Clinical Research of South Florida ( Site 0126)
🇺🇸Coral Gables, Florida, United States
QPS Miami Research Associates ( Site 0116)
🇺🇸South Miami, Florida, United States
Centennial Medical Group ( Site 0109)
🇺🇸Elkridge, Maryland, United States
Heartland Research Associates, Llc ( Site 0115)
🇺🇸Wichita, Kansas, United States
J Lewis Research Inc / Foothill Family Clinic ( Site 0123)
🇺🇸Salt Lake City, Utah, United States
Diagnostics Research Group ( Site 0100)
🇺🇸San Antonio, Texas, United States
J Lewis Research Inc/Jordan River Family Medicine ( Site 0114)
🇺🇸South Jordan, Utah, United States
Health Research of Hampton Roads, Inc. ( Site 0106)
🇺🇸Newport News, Virginia, United States
Seoul National University Hospital ( Site 0400)
🇰🇷Seoul, Korea, Republic of
CAP Centelles ( Site 0303)
🇪🇸Centelles, Barcelona, Spain
Korea University Guro Hospital ( Site 0401)
🇰🇷Seoul, Korea, Republic of
Instituto de Ciencias Medicas.ICM ( Site 0301)
🇪🇸Alicante, Spain
National Taiwan University Hospital ( Site 0500)
🇨🇳Taipei, Taiwan
Fundacion Oftalmologica del Mediterraneo ( Site 0300)
🇪🇸Valencia, Spain
National Cheng Kung University Hospital ( Site 0502)
🇨🇳Taiwan, Taiwan