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)

NCT03615482 | Completed Phase 3 Results DMC FDA Drug

• 1 other identifier: V114-021
• Study Type: interventional
• Target: 1,200
• Locations: 1 country
• Sites: 45

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.

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 clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Solicited injection-site AEs included injection-site erythema /redness, pain /tenderness, swelling.

  Up to Day 5 after vaccination

• Percentage of Participants With a Solicited Systemic Adverse Event

  An adverse event (AE) is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. Solicited systemic AEs included myalgia/muscle pain, arthralgia/joint pain, headache, and fatigue/tiredness.

  Up to Day 14 after any vaccination

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

  A serious adverse event (SAE) is an AE that results in death, requires or prolongs an existing hospitalization, results in persistent or significant disability or incapacity, is a congenital anomaly or birth defect, or is another important medical event deemed such by medical or scientific judgment. Relatedness of an SAE to the study vaccine was determined by the investigator.

  Up to 7 months

• Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA)

  Serotype-specific OPA GMTs (estimated) and GMT ratios with 95% confidence intervals (CIs) and 1-sided p-values were calculated using a constrained longitudinal data analysis (cLDA) method 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.

  30 days after V114 vaccination (Day 30 for concomitant vaccination group and Day 60 for non-concomitant vaccination group)

• GMT of Influenza Strain-Specific Hemagglutination Inhibition

  Activity for the 4 strains contained in QIV vaccine was determined using an hemagglutination inhibition (HAI) assay. Serotype-specific HAI GMTs (estimated) and GMT ratios with 95% confidence intervals (CIs) and 1-sided p-values were calculated using a constrained longitudinal data analysis (cLDA) method 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.

  Day 30

Secondary Outcomes (8)

• Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG)

  30 days after V114 vaccination (Day 30 for concomitant vaccination group and Day 60 for non-concomitant vaccination group)

• Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA

  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)

• GMFR in Pneumococcal Serotype-Specific IgG

  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)

• Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific OPA

  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)

• Percentage of Participants With GMFR ≥4 in Pneumococcal Serotype-specific IgG

  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)

Study Arms (2)

Concomitant Vaccination

EXPERIMENTAL

Participants will receive a single 0.5 mL intramuscular (IM) injection of V114 and a single 0.5 mL IM injection of QIV on Day 1 and a single 0.5 mL injection of placebo on Day 30

Biological: V114; Biological: QIV; Biological: Matching Placebo for V114

Non-concomitant Vaccination

EXPERIMENTAL

Participants will receive a single 0.5 mL IM injection of QIV and a single 0.5 mL IM injection of placebo on Day 1 and a single 0.5 mL injection of V114 on Day 30

Biological: V114; Biological: QIV; Biological: Matching Placebo for V114

Interventions

V114 BIOLOGICAL

Single 0.5 mL injection

Concomitant Vaccination; Non-concomitant Vaccination

QIV BIOLOGICAL

Single 0.5 mL injection

Also known as: Quadrivalent influenza vaccine (seasonal inactivated), Fluarix Quadrivalent (Influenza Vaccine)

Concomitant Vaccination; Non-concomitant Vaccination

Matching Placebo for V114 BIOLOGICAL

Single 0.5 mL injection

Concomitant Vaccination; Non-concomitant Vaccination

Eligibility Criteria

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

You may qualify if:

• 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.

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 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
• 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.

Sponsors & Collaborators

• Merck Sharp & Dohme LLC: lead

Study Sites (45)

Achieve Clinical Research, LLC ( Site 0046)

Birmingham, Alabama, 35216, United States

Location

Synexus Clinical Research US, Inc. ( Site 0039)

Chandler, Arizona, 85224, United States

Location

Synexus Clinical Research, US,Inc/Central Arizona Medical Associates, PC ( Site 0004)

Mesa, Arizona, 85206, United States

Location

Synexus Clinical Research US, Inc. ( Site 0042)

Scottsdale, Arizona, 85251, United States

Location

Southland Clinical Research Center ( Site 0033)

Fountain Valley, California, 92708, United States

Location

Valley Clinical Trials Inc. ( Site 0001)

Northridge, California, 91325, United States

Location

Center for Clinical Trials, LLC ( Site 0025)

Paramount, California, 90723, United States

Location

Artemis Institute for Clinical Research ( Site 0026)

San Diego, California, 92103, United States

Location

California Research Foundation ( Site 0002)

San Diego, California, 92123, United States

Location

Bayview Research Group, LLC ( Site 0010)

Valley Village, California, 91607, United States

Location

Synexus Clinical Research US, Inc./Colorado Springs Family Practice ( Site 0021)

Colorado Springs, Colorado, 80909, United States

Location

Indago Research & Health Center, Inc ( Site 0007)

Hialeah, Florida, 33012, United States

Location

Research Centers of America, LLC ( Site 0036)

Hollywood, Florida, 33024, United States

Location

Suncoast Research Group, LLC ( Site 0020)

Miami, Florida, 33135, United States

Location

L&C Professional Medical Research Institute ( Site 0015)

Miami, Florida, 33144, United States

Location

Alpha Science Research ( Site 0018)

Miami, Florida, 33186, United States

Location

Lakes Research LLC ( Site 0034)

Miami Lakes, Florida, 33014, United States

Location

Evanston Premier Healthcare & Research, LLC. ( Site 0012)

Evanston, Illinois, 60201, United States

Location

Healthcare Research Network LLC ( Site 0006)

Flossmoor, Illinois, 60422, United States

Location

Springfield Clinic ( Site 0045)

Springfield, Illinois, 62703, United States

Location

Heartland Research Associates, LLC ( Site 0031)

Augusta, Kansas, 67010, United States

Location

Heartland Research Associates, LLC ( Site 0016)

Newton, Kansas, 67114, United States

Location

Kentucky Pediatric/Adult Research Inc ( Site 0011)

Bardstown, Kentucky, 40004, United States

Location

Community Clinical Research Network (Marlboro, MA) ( Site 0030)

Marlborough, Massachusetts, 01752, United States

Location

Healthcare Research Network LLC ( Site 0032)

Hazelwood, Missouri, 63042, United States

Location

Clinical Research Center of Neveda, LLC. ( Site 0022)

Las Vegas, Nevada, 89104, United States

Location

Southwest CARE Center ( Site 0013)

Santa Fe, New Mexico, 87505, United States

Location

Regional Clinical Research, Inc. ( Site 0029)

Endwell, New York, 13760, United States

Location

Mid Hudson Medical Research ( Site 0024)

New Windsor, New York, 12553, United States

Location

Rochester Clinical Research, Inc. ( Site 0009)

Rochester, New York, 14609, United States

Location

PMG Research Of Cary LLC ( Site 0035)

Cary, North Carolina, 27518, United States

Location

Unity Clinical Research ( Site 0044)

Lindsay, Oklahoma, 73052, United States

Location

Clinical Research Center Of Reading LLP ( Site 0014)

Wyomissing, Pennsylvania, 19610, United States

Location

Omega Medical Research ( Site 0049)

Warwick, Rhode Island, 02886, United States

Location

PMG Research Inc ( Site 0027)

Mt. Pleasant, South Carolina, 29464, United States

Location

Holston Medical Group ( Site 0003)

Bristol, Tennessee, 37620, United States

Location

Holston Medical Group ( Site 0028)

Kingsport, Tennessee, 37660, United States

Location

Clinical Research Associates Inc. ( Site 0040)

Nashville, Tennessee, 37203, United States

Location

Wellness Clinical Research Associates ( Site 0048)

Allen, Texas, 75013, United States

Location

Benchmark Research ( Site 0037)

Fort Worth, Texas, 76135, United States

Location

San Gabriel Clinical Research ( Site 0047)

Georgetown, Texas, 78626, United States

Location

Synexus Clinical Research US, Inc. ( Site 0019)

San Antonio, Texas, 78229, United States

Location

Charlottesville Medical Research Center, LLC ( Site 0008)

Charlottesville, Virginia, 22911, United States

Location

Clinical Research Partners, LLC. ( Site 0005)

Richmond, Virginia, 23220, United States

Location

Allegiance Research Specialists ( Site 0017)

Wauwatosa, Wisconsin, 53226, United States

Location

Related Publications (1)

• 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.

  PMID: 34726574 BACKGROUND

MeSH Terms

Conditions

Pneumococcal Infections

Interventions

Influenza Vaccines

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

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: July 31, 2018
• First Posted: August 3, 2018
• Study Start: September 14, 2018
• Primary Completion: June 24, 2019
• Study Completion: June 24, 2019
• Last Updated: May 22, 2024
• Results First Posted: June 29, 2020

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share

Locations

US (45)