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) (PNEU-PATH)
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| ClinicalTrials.gov Identifier: NCT03480763 |
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Recruitment Status :
Completed
First Posted : March 29, 2018
Results First Posted : January 6, 2021
Last Update Posted : November 2, 2021
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Sponsor:
Merck Sharp & Dohme LLC
Information provided by (Responsible Party):
Merck Sharp & Dohme LLC
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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.
| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Pneumococcal Infections | Biological: V114 Biological: Prevnar 13™ Biological: PNEUMOVAX™23 | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 652 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Prevention |
| Official Title: | 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) |
| Actual Study Start Date : | June 22, 2018 |
| Actual Primary Completion Date : | December 23, 2019 |
| Actual Study Completion Date : | December 23, 2019 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: 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)
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Biological: V114
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 Biological: PNEUMOVAX™23 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
Other Name: PPV23 |
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Active Comparator: 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)
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Biological: Prevnar 13™
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
Other Name: PCV13 Biological: PNEUMOVAX™23 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
Other Name: PPV23 |
Primary Outcome Measures :
- Percentage of Participants With Solicited Injection-site Adverse Events Following V114 or Prevnar 13™ [ Time Frame: 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 Injection-site Adverse Events Following PNEUMOVAX™23 [ Time Frame: 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 Solicited Systemic Adverse Events Following V114 or Prevnar 13™ [ Time Frame: 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 [ Time Frame: 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.
- Percentage of Participants With Vaccine-related Serious Adverse Events Following V114 or Prevnar 13™ [ Time Frame: 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 [ Time Frame: 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.
- Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at 30 Days Following PNEUMOVAX™23 [ Time Frame: 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.
Secondary Outcome Measures :
- Geometric Mean Concentration of Serotype-specific Immunoglobulin G at 30 Days Following PNEUMOVAX™23 [ Time Frame: 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 [ Time Frame: 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.
- GMC of Serotype-specific IgG at Day 30 [ Time Frame: 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.
- Geometric Mean Fold Rise in Serotype-specific OPA Day 1 to Day 30 [ Time Frame: 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.
- GMFR in Serotype-specific IgG Day 1 to Day 30 [ Time Frame: 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.
- Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Day 1 to Day 30 [ Time Frame: 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.
- Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Day 1 to Day 30 [ Time Frame: 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 [ Time Frame: 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.
- GMC of Serotype-specific IgG at Month 12 [ Time Frame: 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 OPA Day 1 to Month 12 [ Time Frame: 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.
- GMFR in Serotype-specific IgG Day 1 to Month 12 [ Time Frame: 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.
- Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Day 1 to Month 12 [ Time Frame: 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 IgG Concentration Day 1 to Month 12 [ Time Frame: 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.
- GMFR in Serotype-specific OPA Day 1 to Month 13 [ Time Frame: 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.
- GMFR in Serotype-specific IgG Day 1 to Month 13 [ Time Frame: 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 OPA Titer Day 1 to Month 13 [ Time Frame: 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 IgG Concentration Day 1 to Month 13 [ Time Frame: 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 OPA Month 12 to Month 13 [ Time Frame: 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.
- GMFR in Serotype-specific IgG Month 12 to Month 13 [ Time Frame: 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.
- Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Month 12 to Month 13 [ Time Frame: 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 Month 12 to Month 13 [ Time Frame: 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.
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| Ages Eligible for Study: | 50 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | Yes |
Criteria
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.
Information from the National Library of Medicine
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03480763
Locations
Show 22 study locations
Sponsors and Collaborators
Merck Sharp & Dohme LLC
Investigators
| Study Director: | Medical Director | Merck Sharp & Dohme LLC |
Study Documents (Full-Text)
Documents provided by Merck Sharp & Dohme LLC:
Documents provided by Merck Sharp & Dohme LLC:
Study Protocol and Statistical Analysis Plan [PDF] June 1, 2018
Publications of Results:
| Responsible Party: | Merck Sharp & Dohme LLC |
| ClinicalTrials.gov Identifier: | NCT03480763 |
| Other Study ID Numbers: |
V114-016 V114-016 ( Other Identifier: Merck Protocol Number ) 2017-004024-30 ( EudraCT Number ) |
| First Posted: | March 29, 2018 Key Record Dates |
| Results First Posted: | January 6, 2021 |
| Last Update Posted: | November 2, 2021 |
| Last Verified: | October 2021 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | http://engagezone.msd.com/doc/ProcedureAccessClinicalTrialData.pdf |
| URL: | http://engagezone.msd.com/ds_documentation.php |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Additional relevant MeSH terms:
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Pneumococcal Infections Streptococcal Infections Gram-Positive Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses |
Infections Heptavalent Pneumococcal Conjugate Vaccine Immunologic Factors Physiological Effects of Drugs |