Clinical trial NCT03950622: Safety and Immunogenicity of V114 in Healthy Adults (V114-019/PNEU-AGE)
Official title: A Phase 3, Multicenter, Randomized, Double-blind, Active Comparator-controlled Study to Evaluate the Safety, Tolerability, and Immunogenicity of V114 in Healthy Adults 50 Years of Age or Older (PNEU-AGE)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Pneumococcal Infections
Lead sponsor: Merck Sharp & Dohme LLC
Sponsor class: INDUSTRY
First posted: 2019-05-15
Enrollment: 1205
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 purpose of this study is to 1) evaluate the safety and tolerability of V114 and 2) to compare the immune responses of the 15 serotypes contained in V114 with V114 versus Prevnar 13™. The primary hypotheses are that 1) V114 is noninferior to Prevnar 13™ as measured by the serotype specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) for 13 shared serotypes at 30 days postvaccination and that 2) V114 is superior to Prevnar 13™ as measured by serotype-specific OPA GMTs for 2 unique 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.
* Male or female ≥50 years of age at the time of signing the informed consent. (For Japan only: Is male or female ≥65 years of age at the time of signing the informed consent)
* 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.
* Provides written informed consent for the study. The participant may also provide consent for future biomedical research. However, the participant may participate in the main study without participating in future biomedical research.

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 (IM) 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.
* 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.
* 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 postvaccination
measure: Percentage of Participants With Solicited Systemic Adverse Events
timeFrame: Up to Day 14 postvaccination
measure: Percentage of Participants With a Vaccine-related Serious Adverse Event
timeFrame: Up to Month 6
measure: Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at Day 30
timeFrame: Day 30
measure: Percentage of Participants With ≥4 Fold Rise in Serotype-specific OPA for 2 Unique V114 Serotypes
timeFrame: Day 1 (Baseline) and Day 30
Secondary outcomes:
measure: GMT of Serotype-specific OPA for Serotype 3 at Day 30
timeFrame: Day 30
measure: Percentage of Participants With ≥4 Fold Rise in Serotype-specific OPA for Serotype 3 OPA Responses
timeFrame: Day 1 (Baseline) and Day 30
measure: Geometric Mean Concentration of Serotype-specific IgG at Day 30
timeFrame: Day 30
measure: Geometric Mean Fold Rise in Serotype-specific OPA
timeFrame: Day 1 (Baseline) and Day 30
measure: Geometric Mean Fold Rise in Serotype-specific IgG
timeFrame: Day 1 (Baseline) and Day 30
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific OPA Titer
timeFrame: Day 1 (Baseline) and Day 30
measure: Percentage of Participants With ≥4-Fold Rise in Serotype-specific IgG Concentration
timeFrame: Day 1 (Baseline) and Day 30
Other outcomes:
Locations:
city: Mesa
country: United States
facility: Synexus ( Site 1001)
state: Arizona
city: San Diego
country: United States
facility: Artemis Institute for Clinical Research ( Site 1012)
state: California
city: Hialeah
country: United States
facility: Indago Research & Health Center, Inc ( Site 1002)
state: Florida
city: Hollywood
country: United States
facility: Research Centers of America, LLC ( Site 1014)
state: Florida
city: Miami Lakes
country: United States
facility: Lakes Research LLC ( Site 1005)
state: Florida
city: Miami
country: United States
facility: Advanced Medical Research Institute ( Site 0117)
state: Florida
city: Newton
country: United States
facility: Alliance for Multispecialty Research, LLC ( Site 1008)
state: Kansas
city: Las Vegas
country: United States
facility: Wake Research Clinical Research Center of Nevada, LLC ( Site 1010)
state: Nevada
city: Cleveland
country: United States
facility: Rapid Medical Research, Inc. ( Site 1011)
state: Ohio
city: San Antonio
country: United States
facility: Diagnostics Research Group ( Site 1000)
state: Texas
city: San Antonio
country: United States
facility: Synexus ( Site 1009)
state: Texas
city: Salt Lake City
country: United States
facility: J Lewis Research Inc / Foothill Family Clinic ( Site 1013)
state: Utah
city: Charlottesville
country: United States
facility: Charlottesville Medical Research Center, LLC ( Site 1003)
state: Virginia
city: Newport News
country: United States
facility: Health Research of Hampton Roads, Inc. ( Site 1007)
state: Virginia
city: Truro
country: Canada
facility: Colchester Research Group ( Site 2002)
state: Nova Scotia
city: London
country: Canada
facility: Milestone Research ( Site 2003)
state: Ontario
city: Sarnia
country: Canada
facility: Bluewater Clinical Research Group Inc ( Site 2004)
state: Ontario
city: Toronto
country: Canada
facility: Manna Research Inc.. ( Site 2007)
state: Ontario
city: Pointe-Claire
country: Canada
facility: Dynamik Research ( Site 2000)
state: Quebec
city: Sherbrooke
country: Canada
facility: Q & T Research Sherbrooke Inc. ( Site 2001)
state: Quebec
city: Hachioji
country: Japan
facility: P-One Clinic, Keikokai Medical Corp. ( Site 0400)
state: Tokyo
city: Fukuoka
country: Japan
facility: Souseikai PS Clinic ( Site 0402)
city: Kumamoto
country: Japan
facility: Souseikai Nishikumamoto Hospital ( Site 0404)
city: Osaka
country: Japan
facility: Medical Corporation Heishinkai OPHAC Hospital ( Site 0401)
city: Tokyo
country: Japan
facility: Medical Corporation Houeikai Sekino Clinical Pharmacology Clinic ( Site 0403)
city: Pozuelo de Alarcon
country: Spain
facility: Hospital Universitario Quiron Madrid ( Site 0304)
state: Madrid
city: Alicante
country: Spain
facility: Instituto de Ciencias Medicas - ICM ( Site 0300)
city: Centelles
country: Spain
facility: CAP Centelles ( Site 0301)
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital ( Site 0500)
city: Taiwan
country: Taiwan
facility: National Cheng Kung University Hospital ( Site 0501)
Study officials:
affiliation: Merck Sharp & Dohme LLC
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Platt HL, Cardona JF, Haranaka M, Schwartz HI, Narejos Perez S, Dowell A, Chang CJ, Dagan R, Tamms GM, Sterling T, Morgan L, Shi Y, Pedley A, Musey LK, Buchwald UK. A phase 3 trial of safety, tolerability, and immunogenicity of V114, 15-valent pneumococcal conjugate vaccine, compared with 13-valent pneumococcal conjugate vaccine in adults 50 years of age and older (PNEU-AGE). Vaccine. 2022 Jan 3;40(1):162-172. doi: 10.1016/j.vaccine.2021.08.049. Epub 2021 Sep 8.