Clinical trial NCT03480763: 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)
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumococcal Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-03-29
Enrollment: 652
Sex: ALL
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.


Eligibility 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.

Primary outcomes:
measure: Percentage of Participants With Solicited Injection-site Adverse Events Following V114 or Prevnar 13™
timeFrame: Up to 5 days after Vaccination 1
measure: Percentage of Participants With Solicited Injection-site Adverse Events Following PNEUMOVAX™23
timeFrame: Up to 5 days after Vaccination 2
measure: Percentage of Participants With Solicited Systemic Adverse Events Following V114 or Prevnar 13™
timeFrame: Up to 14 days after Vaccination 1
measure: Percentage of Participants With Solicited Systemic Adverse Events Following PNEUMOVAX™23
timeFrame: Up to 14 days after Vaccination 2
measure: Percentage of Participants With Vaccine-related Serious Adverse Events Following V114 or Prevnar 13™
timeFrame: Up to 12 months after Vaccination 1
measure: Percentage of Participants With Vaccine-related Serious Adverse Events Following PNEUMOVAX™23
timeFrame: Month 12 to Month 13 (Up to 44 days after Vaccination 2)
measure: Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at 30 Days Following PNEUMOVAX™23
timeFrame: Month 13 (30 days after Vaccination 2)
Secondary outcomes:
measure: Geometric Mean Concentration of Serotype-specific Immunoglobulin G at 30 Days Following PNEUMOVAX™23
timeFrame: Month 13 (30 days after Vaccination 2)
measure: GMT of Serotype-specific OPA at Day 30
timeFrame: Day 30
measure: GMC of Serotype-specific IgG at Day 30
timeFrame: Day 30
measure: Geometric Mean Fold Rise in Serotype-specific OPA Day 1 to Day 30
timeFrame: Day 1 (Baseline) and Day 30
measure: GMFR in Serotype-specific IgG Day 1 to Day 30
timeFrame: Day 1 (Baseline) and Day 30
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Day 1 to Day 30
timeFrame: Day 1 (Baseline) and Day 30
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Day 1 to Day 30
timeFrame: Day 1 (Baseline) and Day 30
measure: GMT of Serotype-specific OPA at Month 12
timeFrame: Month 12
measure: GMC of Serotype-specific IgG at Month 12
timeFrame: Month 12
measure: GMFR in Serotype-specific OPA Day 1 to Month 12
timeFrame: Day 1 (Baseline) and Month 12
measure: GMFR in Serotype-specific IgG Day 1 to Month 12
timeFrame: Day 1 (Baseline) and Month 12
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Day 1 to Month 12
timeFrame: Day 1 (Baseline) and Month 12
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Day 1 to Month 12
timeFrame: Day 1 (Baseline) and Month 12
measure: GMFR in Serotype-specific OPA Day 1 to Month 13
timeFrame: Day 1 (Baseline) and Month 13
measure: GMFR in Serotype-specific IgG Day 1 to Month 13
timeFrame: Day 1 (Baseline) and Month 13
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Day 1 to Month 13
timeFrame: Day 1 (Baseline) and Month 13
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Day 1 to Month 13
timeFrame: Day 1 (Baseline) and Month 13
measure: GMFR in Serotype-specific OPA Month 12 to Month 13
timeFrame: Month 12 (Baseline) and Month 13
measure: GMFR in Serotype-specific IgG Month 12 to Month 13
timeFrame: Month 12 (Baseline) and Month 13
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer Month 12 to Month 13
timeFrame: Month 12 (Baseline) and Month 13
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration Month 12 to Month 13
timeFrame: Month 12 (Baseline) and Month 13
Other outcomes:
Locations:
city: Chandler
country: United States
facility: East Valley Family Physicians ( Site 0104)
state: Arizona
city: Phoenix
country: United States
facility: Central Phoenix Medical Clinic, LLC ( Site 0125)
state: Arizona
city: Spring Valley
country: United States
facility: Encompass Clinical Research ( Site 0118)
state: California
city: Walnut Creek
country: United States
facility: Diablo Clinical Research, Inc ( Site 0132)
state: California
city: Coral Gables
country: United States
facility: Clinical Research of South Florida ( Site 0126)
state: Florida
city: South Miami
country: United States
facility: QPS Miami Research Associates ( Site 0116)
state: Florida
city: Wichita
country: United States
facility: Heartland Research Associates, Llc ( Site 0115)
state: Kansas
city: Elkridge
country: United States
facility: Centennial Medical Group ( Site 0109)
state: Maryland
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc. ( Site 0119)
state: Ohio
city: Galveston
country: United States
facility: University of Texas Medical Branch at Galveston ( Site 0127)
state: Texas
city: Houston
country: United States
facility: Texas Center For Drug Development ( Site 0107)
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group ( Site 0100)
state: Texas
city: Salt Lake City
country: United States
facility: J Lewis Research Inc / Foothill Family Clinic ( Site 0123)
state: Utah
city: South Jordan
country: United States
facility: J Lewis Research Inc/Jordan River Family Medicine ( Site 0114)
state: Utah
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc. ( Site 0106)
state: Virginia
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital ( Site 0400)
city: Seoul
country: Korea, Republic of
facility: Korea University Guro Hospital ( Site 0401)
city: Centelles
country: Spain
facility: CAP Centelles ( Site 0303)
state: Barcelona
city: Alicante
country: Spain
facility: Instituto de Ciencias Medicas.ICM ( Site 0301)
city: Valencia
country: Spain
facility: Fundacion Oftalmologica del Mediterraneo ( Site 0300)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 0500)
city: Taiwan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 0502)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: 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-valent pneumococcal conjugate vaccine, followed by sequential PPSV23 vaccination in healthy adults aged >/=50 years: A randomized phase III trial (PNEU-PATH). Vaccine. 2021 Oct 15;39(43):6422-6436. doi: 10.1016/j.vaccine.2021.08.038. Epub 2021 Sep 4.