Clinical trial NCT03950856: Lot-to-Lot Consistency of V114 in Healthy Adults (V114-020)
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled, Lot-to-Lot Consistency Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Adults 50 Years of Age or Older (PNEU-TRUE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumococcal Infections
Pneumonia, Pneumococcal
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-05-15
Enrollment: 2340
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: The primary objectives are to evaluate the safety and tolerability of V114 and to compare the serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) across 3 different lots of V114. The primary hypothesis is that all 3 lots of V114 are equivalent as measured by the serotype-specific OPA GMTs for 15 serotypes in V114 at 30 days postvaccination.


Eligibility criteria: Inclusion Criteria:

* Participant has good health in the opinion of the investigator. Any underlying chronic condition must be documented to be in stable condition according to the investigator's judgment.
* Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
* Female participant is eligible to participate if she is not pregnant, not breastfeeding, and is not a woman of childbearing potential (WOCBP) OR a WOCBP who agrees to use agreed upon contraception 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 of Visit 1 (Day 1).
* Known hypersensitivity to any component of pneumococcal polysaccharide vaccine, pneumococcal conjugate vaccine (PCV), or any diphtheria toxoid-containing vaccine.
* Known or suspected impairment of immunological function including, but not limited to, a history of congenital or acquired immunodeficiency, documented human immunodeficiency virus (HIV) infection, functional or anatomic asplenia, or history of autoimmune disease.
* Coagulation disorder contraindicating intramuscular vaccinations.
* Recent febrile illness (defined as oral or tympanic temperature ≥100.4°F \[≥38.0°C\] or axillary or temporal temperature ≥99.4°F \[≥37.4°C\]) or received antibiotic therapy for any acute illness occurring within 72 hours before receipt of study vaccine.
* 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).
* Has received any pneumococcal vaccine or is expected to receive any pneumococcal vaccine during the study outside of the protocol.
* Has 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.
* Has 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).
* Is 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.
* Has received any non-live vaccine within the 14 days before receipt of any study vaccine or is scheduled to receive any non-live vaccine within 30 days following receipt of any study vaccine. (Exception: Inactivated influenza vaccine may be administered but must be given at least 7 days before receipt of any study vaccine or at least 15 days after receipt of any study vaccine.)
* Has received any live vaccine within 30 days before receipt of any study vaccine or is scheduled to receive any live vaccine within 30 days following receipt of any study vaccine. If this exclusion criterion is met, then Day 1 Visit may be rescheduled for a time when criterion is not met.
* Has 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.
* 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.
* In the opinion of the investigator, has a history of clinically relevant drug or alcohol use that would interfere with participation in protocol-specified activities.
* History or current evidence of any condition, therapy, laboratory abnormality, or other circumstance that might expose the participant to risk by participating in the study, confound the results of the study, or interfere with the participant's participation for the full duration of the study.
* 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 Following Vaccination With Separate V114 Lots
timeFrame: Up to Day 5
measure: Percentage of Participants With a Solicited Injection-site Adverse Event Following Vaccination: Combined Lots of V114 or Prevnar 13™
timeFrame: Up to Day 5
measure: Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination With Separate V114 Lots
timeFrame: Up to Day 14
measure: Percentage of Participants With a Solicited Systemic Adverse Event Following Vaccination: Combined Lots of V114 or Prevnar 13™
timeFrame: Up to Day 14
measure: Percentage of Participants With a Vaccine-related Serious Adverse Event Following Vaccination With Separate V114 Lots
timeFrame: Up to Month 6
measure: Percentage of Participants With a Vaccine-related Serious Adverse Event Following Vaccination: Combined Lots of V114 or Prevnar 13™
timeFrame: Up to Month 6
measure: Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity (OPA) Following Vaccination With Separate V114 Lots
timeFrame: Day 30
Secondary outcomes:
measure: Geometric Mean Concentration of Serotype-specific Immunoglobulin G (IgG) Following Vaccination With Separate V114 Lots
timeFrame: Day 30
measure: Geometric Mean Concentration of Serotype-specific IgG Following Vaccination: Combined Lots of V114 or Prevnar 13™
timeFrame: Day 30
measure: Geometric Mean Fold Rise (GMFR) in Serotype-specific OPA Following Vaccination With Separate V114 Lots
timeFrame: Day 1 (Baseline) and Day 30
measure: GMFR in Serotype-specific IgG Following Vaccination With Separate V114 Lots
timeFrame: Day 1 (Baseline) and Day 30
measure: Percentage of Participants With ≥4 Fold Change in Serotype-specific OPA Following Vaccination With Separate V114 Lots
timeFrame: Day 1 (Baseline) and Day 30
measure: Percentage of Participants With ≥4 Fold Change in Serotype-specific IgG Following Vaccination With Separate V114 Lots
timeFrame: Day 1 (Baseline) and Day 30
Other outcomes:
Locations:
city: Chandler
country: United States
facility: Synexus Clinical Research US, Inc. ( Site 1031)
state: Arizona
city: Mesa
country: United States
facility: Synexus ( Site 1043)
state: Arizona
city: Fountain Valley
country: United States
facility: Southland Clinical Research Center ( Site 1027)
state: California
city: Northridge
country: United States
facility: Valley Clinical Trials Inc. ( Site 1003)
state: California
city: Paramount
country: United States
facility: Center for Clinical Trials, LLC ( Site 1019)
state: California
city: San Diego
country: United States
facility: California Research Foundation ( Site 1006)
state: California
city: San Marcos
country: United States
facility: Artemis Institute for Clinical Research ( Site 1041)
state: California
city: Simi Valley
country: United States
facility: Alta California Medical Group ( Site 1020)
state: California
city: Coral Gables
country: United States
facility: Alliance for Multispecialty Research, LLC ( Site 1029)
state: Florida
city: DeLand
country: United States
facility: Accel Research Sites-DeLand Clinical Research Unit ( Site 1026)
state: Florida
city: Jacksonville
country: United States
facility: Jacksonville Center for Clinical Research ( Site 1014)
state: Florida
city: Miami
country: United States
facility: L&C Professional Medical Research Institute ( Site 1012)
state: Florida
city: Miami
country: United States
facility: Alpha Science Research ( Site 1015)
state: Florida
city: South Miami
country: United States
facility: QPS Miami Research Associates ( Site 1035)
state: Florida
city: Metairie
country: United States
facility: Benchmark Research ( Site 1040)
state: Louisiana
city: Elkridge
country: United States
facility: Centennial Medical Group ( Site 1010)
state: Maryland
city: Marlborough
country: United States
facility: Community Clinical Research Network (Marlboro, MA) ( Site 1025)
state: Massachusetts
city: Las Vegas
country: United States
facility: Wake Research Clinical Research Center of Nevada, LLC ( Site 1044)
state: Nevada
city: Santa Fe
country: United States
facility: Southwest CARE Center ( Site 1011)
state: New Mexico
city: Corning
country: United States
facility: Corning Center For Clinical Research ( Site 1033)
state: New York
city: Endwell
country: United States
facility: Regional Clinical Research, Inc. ( Site 1024)
state: New York
city: Rochester
country: United States
facility: Rochester Clinical Research, Inc. ( Site 1039)
state: New York
city: Winston-Salem
country: United States
facility: PMG Research of Winston Salem ( Site 1037)
state: North Carolina
city: Lindsay
country: United States
facility: Unity Clinical Research ( Site 1036)
state: Oklahoma
city: Mount Pleasant
country: United States
facility: Coastal Carolina Research Center ( Site 1034)
state: South Carolina
city: Allen
country: United States
facility: Wellness Clinical Research Associates ( Site 1038)
state: Texas
city: San Antonio
country: United States
facility: Diagnostics Research Group ( Site 1042)
state: Texas
city: Murray
country: United States
facility: Synexus ( Site 1000)
state: Utah
city: West Jordan
country: United States
facility: Advanced Clinical Research ( Site 1028)
state: Utah
city: Wauwatosa
country: United States
facility: Allegiance Research Specialists ( Site 1013)
state: Wisconsin
city: Blacktown
country: Australia
facility: Paratus Clinical Pty Ltd - Blacktown Clinic ( Site 6006)
state: New South Wales
city: Maroubra
country: Australia
facility: Australian Clinical Research Network ( Site 6000)
state: New South Wales
city: Box Hill
country: Australia
facility: Box Hill Hospital ( Site 6001)
state: Victoria
city: Murdoch
country: Australia
facility: Trialswest ( Site 6004)
state: Western Australia
city: Santiago
country: Chile
facility: Clinica Alemana de Santiago Adolescencia ( Site 2000)
state: Región Metropolitana
city: Santiago
country: Chile
facility: CESFAM Colina ( Site 2002)
state: RM
city: Santiago
country: Chile
facility: Instituto Nacional del Torax ( Site 2004)
city: Santiago
country: Chile
facility: Centro de Investigacion Clinica UC CICUC ( Site 2001)
city: Temuco
country: Chile
facility: Hospital Dr. Hernan Henriquez Aravena ( Site 2003)
city: Aalborg
country: Denmark
facility: Aalborg University Hospital ( Site 3003)
city: Aarhus N
country: Denmark
facility: Aarhus Universitets hospital ( Site 3004)
city: Ballerup
country: Denmark
facility: CCBR. Center for Clinical and Basic Research ( Site 3000)
city: Copenhagen
country: Denmark
facility: Rigshospitalet ( Site 3005)
city: Hvidovre
country: Denmark
facility: Hvidovre Hospital ( Site 3002)
city: Odense
country: Denmark
facility: Odense Universitetshospital ( Site 3001)
city: Helsinki
country: Finland
facility: Tampereen yliopisto Etela-Helsingin Rokotetutkimusklinikka ( Site 4006)
city: Jarvenpaa
country: Finland
facility: Jarvenpaan rokotetutkimuskeskus ( Site 4005)
city: Kokkola
country: Finland
facility: Kokkolan rokotetutkimusklinikka ( Site 4002)
city: Oulu
country: Finland
facility: Tampereen yliopisto Oulun rokotetutkimusklinikka ( Site 4001)
city: Pori
country: Finland
facility: Tampereen yliopisto Porin rokotetutkimusklinikka ( Site 4004)
city: Tampere
country: Finland
facility: Tampereen yliopisto - Tampereen rokotetutkimusklinikka ( Site 4000)
city: Turku
country: Finland
facility: Turun rokotetutkimuskeskus ( Site 4003)
city: Corby
country: United Kingdom
facility: Medinova Lakeside Dedicated Research Centre ( Site 5004)
state: Northamptonshire
city: Harrow
country: United Kingdom
facility: GP Direct ( Site 5000)
city: Liverpool
country: United Kingdom
facility: Vauxhall Primary Health Care ( Site 5002)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Simon JK, Staerke NB, Hemming-Harlo M, Layle S, Dagan R, Shekar T, Pedley A, Jumes P, Tamms G, Sterling T, Musey L, Buchwald UK; V114-020 PNEU-TRUE study group. Lot-to-lot consistency, safety, tolerability, and immunogenicity of V114, a 15-valent pneumococcal conjugate vaccine, in healthy adults aged >/=50 years: A randomized phase 3 trial (PNEU-TRUE). Vaccine. 2022 Feb 23;40(9):1342-1351. doi: 10.1016/j.vaccine.2021.12.067. Epub 2022 Jan 14.