Clinical trial NCT03615482: A Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 When Administered Concomitantly With Influenza Vaccine in Healthy Adults 50 Years of Age or Older (V114-021/PNEU-FLU)
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 When Administered Concomitantly With Influenza Vaccine in Healthy Adults 50 Years of Age or Older (PNEU-FLU)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumococcal Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2018-08-03
Enrollment: 1200
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 was designed to evaluate the safety and tolerability of a single dose of V114 when administered concomitantly and non-concomitantly (i.e., 30 days after) with influenza vaccine. It also evaluated whether V114 can be administered concomitantly with influenza vaccine without impairing the antibody response to the 15 serotypes contained in V114 and to the 4 influenza viruses contained in the seasonal inactivated quadrivalent influenza vaccine (QIV). The primary hypotheses state that immune responses to V114 and to QIV are non-inferior when administered concomitantly as compared with non-concomitant administration as measured by serotype-specific opsonophagocytic activity (OPA) and hemagglutination inhibition (HAI) geometric mean titers (GMTs) at 30 days postvaccination. This study will also contribute to the overall safety database and immunogenicity data for V114 to support initial licensure in adults.


Eligibility criteria: Inclusion Criteria:

* In good health. Any underlying chronic illness must be documented to be in stable condition.
* A female participant is eligible to participate if she is not pregnant, not breastfeeding, and at least 1 of the following conditions applies: a) not a woman of childbearing potential (WOCBP) OR b) a WOCBP who agrees to use 1 of the contraceptive methods as defined in the protocol during the treatment period and for at least 6 weeks after the last dose of study intervention.

Exclusion Criteria:

* History of invasive pneumococcal disease (IPD, positive blood culture, positive cerebrospinal fluid culture, or positive culture at another sterile site) or known history of other culture-positive pneumococcal disease within 3 years before Visit 1 (Day 1)
* Known hypersensitivity to any component of pneumococcal polysaccharide vaccine, pneumococcal conjugate vaccine (PCV), or any diphtheria toxoid-containing vaccine
* Known hypersensitivity to any component of influenza vaccines, including egg protein, or following a previous dose of any influenza vaccine.
* Known or suspected impairment of immunological function
* Experienced Guillain-Barré syndrome within 6 weeks of receiving a previous influenza vaccination
* Coagulation disorder contraindicating intramuscular vaccinations.
* History of malignancy ≤5 years prior to signing informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer
* A WOCBP who has a positive urine or serum pregnancy test before the first vaccination at Visit 1 (Day 1)
* Prior administration of any PCV (e.g., Prevnar 13®) or is expected to receive any pneumococcal vaccine during the study outside of the protocol.
* Prior administration of PNEUMOVAX®23 ≤12 months before Visit 1 (Note: individuals who received PNEUMOVAX®23 \>12 months prior to Visit 1 are eligible for this study.)
* Previous receipt of influenza vaccine during the 2018/2019 flu season or expected to receive any influenza vaccine during the study outside of the protocol
* Received systemic corticosteroids (≥20 mg/day prednisone equivalent) 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).
* Receiving immunosuppressive therapy, including chemotherapeutic agents used to treat cancer or other conditions, and interventions associated with organ or bone marrow transplantation, or autoimmune disease
* Received a blood transfusion or blood products, including immunoglobulin within the 6 months before receipt of study vaccine or is scheduled to receive a blood transfusion or blood product within 30 days of receipt of study vaccine. Autologous blood transfusions are not considered an exclusion criterion.
* Is currently participating in or has participated in an interventional clinical study with an investigational compound or device within 2 months of participating in this current study.
* Is a user of recreational or illicit drugs or has had a recent history (within the last year) of drug or alcohol abuse or dependence as assessed by the study investigator.
* Is or has an immediate family member (e.g., spouse, parent/legal guardian, sibling, or child) who is investigational site or Sponsor staff directly involved with this study.

Primary outcomes:
measure: Percentage of Participants With a Solicited Injection-site Adverse Event
timeFrame: Up to Day 5 after vaccination
measure: Percentage of Participants With a Solicited Systemic Adverse Event
timeFrame: Up to Day 14 after any vaccination
measure: Percentage of Participants With a Vaccine-Related Serious Adverse Event
timeFrame: Up to 7 months
measure: Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA)
timeFrame: 30 days after V114 vaccination (Day 30 for concomitant vaccination group and Day 60 for non-concomitant vaccination group)
measure: GMT of Influenza Strain-Specific Hemagglutination Inhibition
timeFrame: Day 30
Secondary outcomes:
measure: Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG)
timeFrame: 30 days after V114 vaccination (Day 30 for concomitant vaccination group and Day 60 for non-concomitant vaccination group)
measure: Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA
timeFrame: Baseline and 30 days after V114 vaccination (Day 1 and Day 30 for concomitant vaccination group, and Day 30 and Day 60 for non-concomitant vaccination group, respectively)
measure: GMFR in Pneumococcal Serotype-Specific IgG
timeFrame: Baseline and 30 days after V114 vaccination (Day 1 and Day 30 for concomitant vaccination group, and Day 30 and Day 60 for non-concomitant vaccination group, respectively)
measure: Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA
timeFrame: Baseline and 30 days after V114 vaccination (Day 1 and Day 30 for concomitant vaccination group, and Day 30 and Day 60 for non-concomitant vaccination group, respectively)
measure: Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG
timeFrame: Baseline and 30 days after V114 vaccination (Day 1 and Day 30 for concomitant vaccination group, and Day 30 and Day 60 for non-concomitant vaccination group, respectively)
measure: GMFR of Influenza Strain-Specific HAI
timeFrame: Baseline (Day 1) and Day 30
measure: Percentage of Participants With Influenza Strain-specific HAI Titer ≥1:40
timeFrame: Day 30
measure: Percentage of Participants Who Seroconvert for Influenza Strain-specific HAI
timeFrame: Baseline (Day 1) and Day 30
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Achieve Clinical Research, LLC ( Site 0046)
state: Alabama
city: Chandler
country: United States
facility: Synexus Clinical Research US, Inc. ( Site 0039)
state: Arizona
city: Mesa
country: United States
facility: Synexus Clinical Research, US,Inc/Central Arizona Medical Associates, PC ( Site 0004)
state: Arizona
city: Scottsdale
country: United States
facility: Synexus Clinical Research US, Inc. ( Site 0042)
state: Arizona
city: Fountain Valley
country: United States
facility: Southland Clinical Research Center ( Site 0033)
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials Inc. ( Site 0001)
state: California
city: Paramount
country: United States
facility: Center for Clinical Trials, LLC ( Site 0025)
state: California
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research ( Site 0026)
state: California
city: San Diego
country: United States
facility: California Research Foundation ( Site 0002)
state: California
city: Valley Village
country: United States
facility: Bayview Research Group, LLC ( Site 0010)
state: California
city: Colorado Springs
country: United States
facility: Synexus Clinical Research US, Inc./Colorado Springs Family Practice ( Site 0021)
state: Colorado
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc ( Site 0007)
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America, LLC ( Site 0036)
state: Florida
city: Miami Lakes
country: United States
facility: Lakes Research LLC ( Site 0034)
state: Florida
city: Miami
country: United States
facility: Suncoast Research Group, LLC ( Site 0020)
state: Florida
city: Miami
country: United States
facility: L&C Professional Medical Research Institute ( Site 0015)
state: Florida
city: Miami
country: United States
facility: Alpha Science Research ( Site 0018)
state: Florida
city: Evanston
country: United States
facility: Evanston Premier Healthcare & Research, LLC. ( Site 0012)
state: Illinois
city: Flossmoor
country: United States
facility: Healthcare Research Network LLC ( Site 0006)
state: Illinois
city: Springfield
country: United States
facility: Springfield Clinic ( Site 0045)
state: Illinois
city: Augusta
country: United States
facility: Heartland Research Associates, LLC ( Site 0031)
state: Kansas
city: Newton
country: United States
facility: Heartland Research Associates, LLC ( Site 0016)
state: Kansas
city: Bardstown
country: United States
facility: Kentucky Pediatric/Adult Research Inc ( Site 0011)
state: Kentucky
city: Marlborough
country: United States
facility: Community Clinical Research Network (Marlboro, MA) ( Site 0030)
state: Massachusetts
city: Hazelwood
country: United States
facility: Healthcare Research Network LLC ( Site 0032)
state: Missouri
city: Las Vegas
country: United States
facility: Clinical Research Center of Neveda, LLC. ( Site 0022)
state: Nevada
city: Santa Fe
country: United States
facility: Southwest CARE Center ( Site 0013)
state: New Mexico
city: Endwell
country: United States
facility: Regional Clinical Research, Inc. ( Site 0029)
state: New York
city: New Windsor
country: United States
facility: Mid Hudson Medical Research ( Site 0024)
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc. ( Site 0009)
state: New York
city: Cary
country: United States
facility: PMG Research Of Cary LLC ( Site 0035)
state: North Carolina
city: Lindsay
country: United States
facility: Unity Clinical Research ( Site 0044)
state: Oklahoma
city: Wyomissing
country: United States
facility: Clinical Research Center Of Reading LLP ( Site 0014)
state: Pennsylvania
city: Warwick
country: United States
facility: Omega Medical Research ( Site 0049)
state: Rhode Island
city: Mount Pleasant
country: United States
facility: PMG Research Inc ( Site 0027)
state: South Carolina
city: Bristol
country: United States
facility: Holston Medical Group ( Site 0003)
state: Tennessee
city: Kingsport
country: United States
facility: Holston Medical Group ( Site 0028)
state: Tennessee
city: Nashville
country: United States
facility: Clinical Research Associates Inc. ( Site 0040)
state: Tennessee
city: Allen
country: United States
facility: Wellness Clinical Research Associates ( Site 0048)
state: Texas
city: Fort Worth
country: United States
facility: Benchmark Research ( Site 0037)
state: Texas
city: Georgetown
country: United States
facility: San Gabriel Clinical Research ( Site 0047)
state: Texas
city: San Antonio
country: United States
facility: Synexus Clinical Research US, Inc. ( Site 0019)
state: Texas
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center, LLC ( Site 0008)
state: Virginia
city: Richmond
country: United States
facility: Clinical Research Partners, LLC. ( Site 0005)
state: Virginia
city: Wauwatosa
country: United States
facility: Allegiance Research Specialists ( Site 0017)
state: Wisconsin
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Severance R, Schwartz H, Dagan R, Connor L, Li J, Pedley A, Hartzel J, Sterling TM, Nolan KM, Tamms GM, Musey LK, Buchwald UK. Safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, administered concomitantly with influenza vaccine in healthy adults aged >/=50 years: a randomized phase 3 trial (PNEU-FLU). Hum Vaccin Immunother. 2022 Dec 31;18(1):1-14. doi: 10.1080/21645515.2021.1976581. Epub 2021 Nov 2.