Safety and Immunogenicity of V114 in Healthy Adults (V114-019/PNEU-AGE)

NCT03950622 | Completed Phase 3 Results DMC FDA Drug

• 3 other identifiers: V114-0192018-004316-22194845
• Study Type: interventional
• Target: 1,205
• Locations: 5 countries
• Sites: 30

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.

Conditions

Pneumococcal Infections

Outcome Measures

Primary Outcomes (5)

• Percentage of Participants With a Solicited Injection-site Adverse Event

  An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. Solicited injection-site AEs consist of redness/erythema, swelling, and tenderness/pain.

  Up to Day 5 postvaccination

• Percentage of Participants With Solicited Systemic Adverse Events

  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 Day 14 postvaccination

• Percentage of Participants With a Vaccine-related Serious Adverse Event

  A serious adverse event (SAE) is any untoward medical occurrence that, at any dose, results in death, is life threatening, requires inpatient hospitalization or prolongs existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, or is another important medical event. SAEs that are reported to be at least possibly related by the investigator to study vaccination will be summarized.

  Up to Month 6

• Geometric Mean Titer of Serotype-specific Opsonophagocytic Activity at Day 30

  Serotype-specific opsonophagocytic activity (OPA) geometric mean titers (GMTs) (estimated) and GMT ratios with 95% CIs and 1-sided p-values 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) were determined using a multiplexed opsonophagocytic assay (MOPA). The measure type of "number" presented in the data table below for serotype-specific OPA titer is the geometric mean.

  Day 30

• Percentage of Participants With ≥4 Fold Rise in Serotype-specific OPA for 2 Unique V114 Serotypes

  Activity for the serotypes contained in Prevnar 13™ and V114 was determined using a multiplexed opsonophagocytic assay (MOPA). The percentage of participants who had ≥4-fold rise in OPA titers were calculated from baseline (Day 1) to 30 days postvaccination (Day 30) for OPA responses for the 2 unique serotypes in V114. The observed response percentage (m/n) included: m=the number of participants with the indicated response divided by n=the number of participants contributing to the analysis. Per the statistical analysis plan, the only CIs calculated were the between-group CIs (for the percentage point difference); within-group CIs were not calculated.

  Day 1 (Baseline) and Day 30

Secondary Outcomes (7)

• GMT of Serotype-specific OPA for Serotype 3 at Day 30

  Day 30

• Percentage of Participants With ≥4 Fold Rise in Serotype-specific OPA for Serotype 3 OPA Responses

  Day 1 (Baseline) and Day 30

• Geometric Mean Concentration of Serotype-specific IgG at Day 30

  Day 30

• Geometric Mean Fold Rise in Serotype-specific OPA

  Day 1 (Baseline) and Day 30

• Geometric Mean Fold Rise in Serotype-specific IgG

  Day 1 (Baseline) and Day 30

Study Arms (2)

V114

EXPERIMENTAL

Single intramuscular (IM) dose at 0.5 mL of V114 pneumococcal conjugate vaccine at Visit 1 (Day 1)

Biological: V114

Prevnar 13™

ACTIVE COMPARATOR

Single IM dose at 0.5 mL of Prevnar 13™ at Visit 1 (Day 1)

Biological: Prevnar 13®

Interventions

V114 BIOLOGICAL

15-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F, and 33F in each 0.5 mL dose.

V114

Prevnar 13® BIOLOGICAL

13-valent pneumococcal conjugate vaccine with serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F in each 0.5 mL dose.

Prevnar 13™

Eligibility Criteria

• Age: 50 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (30)

Synexus ( Site 1001)

Mesa, Arizona, 85206, United States

Location

Artemis Institute for Clinical Research ( Site 1012)

San Diego, California, 92103, United States

Location

Indago Research & Health Center, Inc ( Site 1002)

Hialeah, Florida, 33012, United States

Location

Research Centers of America, LLC ( Site 1014)

Hollywood, Florida, 33024, United States

Location

Advanced Medical Research Institute ( Site 0117)

Miami, Florida, 33174, United States

Location

Lakes Research LLC ( Site 1005)

Miami Lakes, Florida, 33014, United States

Location

Alliance for Multispecialty Research, LLC ( Site 1008)

Newton, Kansas, 67114, United States

Location

Wake Research Clinical Research Center of Nevada, LLC ( Site 1010)

Las Vegas, Nevada, 89104, United States

Location

Rapid Medical Research, Inc. ( Site 1011)

Cleveland, Ohio, 44122, United States

Location

Diagnostics Research Group ( Site 1000)

San Antonio, Texas, 78229, United States

Location

Synexus ( Site 1009)

San Antonio, Texas, 78229, United States

Location

J Lewis Research Inc / Foothill Family Clinic ( Site 1013)

Salt Lake City, Utah, 84109, United States

Location

Charlottesville Medical Research Center, LLC ( Site 1003)

Charlottesville, Virginia, 22911, United States

Location

Health Research of Hampton Roads, Inc. ( Site 1007)

Newport News, Virginia, 23606, United States

Location

Colchester Research Group ( Site 2002)

Truro, Nova Scotia, B2N 1L2, Canada

Location

Milestone Research ( Site 2003)

London, Ontario, N5W 6A2, Canada

Location

Bluewater Clinical Research Group Inc ( Site 2004)

Sarnia, Ontario, N7T 4X3, Canada

Location

Manna Research Inc.. ( Site 2007)

Toronto, Ontario, M9W 4L6, Canada

Location

Dynamik Research ( Site 2000)

Pointe-Claire, Quebec, H9R 3J1, Canada

Location

Q & T Research Sherbrooke Inc. ( Site 2001)

Sherbrooke, Quebec, J1J 2G2, Canada

Location

P-One Clinic, Keikokai Medical Corp. ( Site 0400)

Hachiōji, Tokyo, 192-0071, Japan

Location

Souseikai PS Clinic ( Site 0402)

Fukuoka, 812-0025, Japan

Location

Souseikai Nishikumamoto Hospital ( Site 0404)

Kumamoto, 861-4157, Japan

Location

Medical Corporation Heishinkai OPHAC Hospital ( Site 0401)

Osaka, 532-0003, Japan

Location

Medical Corporation Houeikai Sekino Clinical Pharmacology Clinic ( Site 0403)

Tokyo, 171-0014, Japan

Location

Hospital Universitario Quiron Madrid ( Site 0304)

Pozuelo de Alarcón, Madrid, 28223, Spain

Location

Instituto de Ciencias Medicas - ICM ( Site 0300)

Alicante, 03004, Spain

Location

CAP Centelles ( Site 0301)

Centelles, 08540, Spain

Location

National Cheng Kung University Hospital ( Site 0501)

Dawan, 704, Taiwan

Location

National Taiwan University Hospital ( Site 0500)

Taipei, 100, Taiwan

Location

Related Publications (1)

• 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.

  PMID: 34507861 DERIVED

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

13-valent pneumococcal vaccine

Condition Hierarchy (Ancestors)

Streptococcal Infections; Gram-Positive Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Results Point of Contact

• Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.

ClinicalTrialsDisclosure@merck.com

1-800-672-6372

Study Officials

• Medical Director

  Merck Sharp & Dohme LLC

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 13, 2019
• First Posted: May 15, 2019
• Study Start: June 13, 2019
• Primary Completion: March 30, 2020
• Study Completion: March 30, 2020
• Last Updated: April 26, 2021
• Results First Posted: March 18, 2021

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share

Locations

US (14); TW (2); CA (6); JP (5); ES (3)