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)

Pneumococcal Infections Clinical Trial

— PNEU-PATH  

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03480763
• Other study ID #: V114-016
• Secondary ID: V114-0162017-004
• Status: Completed
• Phase: Phase 3
• Start date: June 22, 2018
• Est. completion date: December 23, 2019

Study information

• Verified date: October 2021
• Source: Merck Sharp & Dohme Corp.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 652
• Est. completion date: December 23, 2019
• Est. primary completion date: December 23, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pneumococcal Infections

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Korea, Republic of	Korea University Guro Hospital ( Site 0401)	Seoul
Korea, Republic of	Seoul National University Hospital ( Site 0400)	Seoul
Spain	Instituto de Ciencias Medicas.ICM ( Site 0301)	Alicante
Spain	CAP Centelles ( Site 0303)	Centelles	Barcelona
Spain	Fundacion Oftalmologica del Mediterraneo ( Site 0300)	Valencia
Taiwan	National Taiwan University Hospital ( Site 0500)	Taipei
Taiwan	National Cheng Kung University Hospital ( Site 0502)	Taiwan
United States	East Valley Family Physicians ( Site 0104)	Chandler	Arizona
United States	Rapid Medical Research, Inc. ( Site 0119)	Cleveland	Ohio
United States	Clinical Research of South Florida ( Site 0126)	Coral Gables	Florida
United States	Centennial Medical Group ( Site 0109)	Elkridge	Maryland
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	Health Research of Hampton Roads, Inc. ( Site 0106)	Newport News	Virginia
United States	Central Phoenix Medical Clinic, LLC ( Site 0125)	Phoenix	Arizona
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	QPS Miami Research Associates ( Site 0116)	South Miami	Florida
United States	Encompass Clinical Research ( Site 0118)	Spring Valley	California
United States	Diablo Clinical Research, Inc ( Site 0132)	Walnut Creek	California
United States	Heartland Research Associates, Llc ( Site 0115)	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme Corp.

Countries where clinical trial is conducted

United States,  Korea, Republic of,  Spain,  Taiwan, 

References & Publications (1)

Song JY, Chang CJ, Andrews C, Diez-Domingo J, Oh MD, Dagan R, Hartzel J, Pedley A, Li J, Sterling T, Tamms G, Chiarappa JA, Lutkiewicz J, Musey L, Tu Y, Buchwald UK; V114-016 (PNEU-PATH) study group. Safety, tolerability, and immunogenicity of V114, a 15- — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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)
Primary	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	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)
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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