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)

Pneumococcal Infections Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03615482
• Other study ID #: V114-021
• Secondary ID: V114-021
• Status: Completed
• Phase: Phase 3
• Start date: September 14, 2018
• Est. completion date: June 24, 2019

Study information

• Verified date: July 2022
• Source: Merck Sharp & Dohme LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1200
• Est. completion date: June 24, 2019
• Est. primary completion date: June 24, 2019
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 50 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Pneumococcal Infections

Intervention

Biological:
• V114
Single 0.5 mL injection
• QIV
Single 0.5 mL injection
• Matching Placebo for V114
Single 0.5 mL injection

Locations

Country	Name	City	State
United States	Wellness Clinical Research Associates ( Site 0048)	Allen	Texas
United States	Heartland Research Associates, LLC ( Site 0031)	Augusta	Kansas
United States	Kentucky Pediatric/Adult Research Inc ( Site 0011)	Bardstown	Kentucky
United States	Achieve Clinical Research, LLC ( Site 0046)	Birmingham	Alabama
United States	Holston Medical Group ( Site 0003)	Bristol	Tennessee
United States	PMG Research Of Cary LLC ( Site 0035)	Cary	North Carolina
United States	Synexus Clinical Research US, Inc. ( Site 0039)	Chandler	Arizona
United States	Charlottesville Medical Research Center, LLC ( Site 0008)	Charlottesville	Virginia
United States	Synexus Clinical Research US, Inc./Colorado Springs Family Practice ( Site 0021)	Colorado Springs	Colorado
United States	Regional Clinical Research, Inc. ( Site 0029)	Endwell	New York
United States	Evanston Premier Healthcare & Research, LLC. ( Site 0012)	Evanston	Illinois
United States	Healthcare Research Network LLC ( Site 0006)	Flossmoor	Illinois
United States	Benchmark Research ( Site 0037)	Fort Worth	Texas
United States	Southland Clinical Research Center ( Site 0033)	Fountain Valley	California
United States	San Gabriel Clinical Research ( Site 0047)	Georgetown	Texas
United States	Healthcare Research Network LLC ( Site 0032)	Hazelwood	Missouri
United States	Indago Research & Health Center, Inc ( Site 0007)	Hialeah	Florida
United States	Research Centers of America, LLC ( Site 0036)	Hollywood	Florida
United States	Holston Medical Group ( Site 0028)	Kingsport	Tennessee
United States	Clinical Research Center of Neveda, LLC. ( Site 0022)	Las Vegas	Nevada
United States	Unity Clinical Research ( Site 0044)	Lindsay	Oklahoma
United States	Community Clinical Research Network (Marlboro, MA) ( Site 0030)	Marlborough	Massachusetts
United States	Synexus Clinical Research, US,Inc/Central Arizona Medical Associates, PC ( Site 0004)	Mesa	Arizona
United States	Alpha Science Research ( Site 0018)	Miami	Florida
United States	L&C Professional Medical Research Institute ( Site 0015)	Miami	Florida
United States	Suncoast Research Group, LLC ( Site 0020)	Miami	Florida
United States	Lakes Research LLC ( Site 0034)	Miami Lakes	Florida
United States	PMG Research Inc ( Site 0027)	Mount Pleasant	South Carolina
United States	Clinical Research Associates Inc. ( Site 0040)	Nashville	Tennessee
United States	Mid Hudson Medical Research ( Site 0024)	New Windsor	New York
United States	Heartland Research Associates, LLC ( Site 0016)	Newton	Kansas
United States	Valley Clinical Trials Inc. ( Site 0001)	Northridge	California
United States	Center for Clinical Trials, LLC ( Site 0025)	Paramount	California
United States	Clinical Research Partners, LLC. ( Site 0005)	Richmond	Virginia
United States	Rochester Clinical Research, Inc. ( Site 0009)	Rochester	New York
United States	Synexus Clinical Research US, Inc. ( Site 0019)	San Antonio	Texas
United States	Artemis Institute for Clinical Research ( Site 0026)	San Diego	California
United States	California Research Foundation ( Site 0002)	San Diego	California
United States	Southwest CARE Center ( Site 0013)	Santa Fe	New Mexico
United States	Synexus Clinical Research US, Inc. ( Site 0042)	Scottsdale	Arizona
United States	Springfield Clinic ( Site 0045)	Springfield	Illinois
United States	Bayview Research Group, LLC ( Site 0010)	Valley Village	California
United States	Omega Medical Research ( Site 0049)	Warwick	Rhode Island
United States	Allegiance Research Specialists ( Site 0017)	Wauwatosa	Wisconsin
United States	Clinical Research Center Of Reading LLP ( Site 0014)	Wyomissing	Pennsylvania

Sponsors (1)

Lead Sponsor	Collaborator
Merck Sharp & Dohme LLC

Country where clinical trial is conducted

United States, 

References & 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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)
Primary	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	Geometric Mean Concentration (GMC) of Pneumococcal Serotype-specific Immunoglobulin G (IgG)	Serotype-specific IgG GMC ratios (estimated) and GMC ratios with 95% confidence intervals (CIs) 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 GMC 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)
Secondary	Geometric Mean Fold Rise (GMFR) in Pneumococcal Serotype-Specific OPA	Activity for the 15 serotypes contained in V114 vaccine will be determined using a Multiplex Opsonophagocytic Assay. GMFR is the geometric mean of fold rise from baseline to postvaccination.	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)
Secondary	GMFR in Pneumococcal Serotype-Specific IgG	Immunoglobulin G for the 15 serotypes contained in V114 vaccine will be determined using an electrochemiluminescence assay. GMFR is the geometric mean of fold rise from baseline to postvaccination.	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)
Secondary	Percentage of Participants With GMFR =4 in Pneumococcal Serotype-specific OPA	Activity for the 15 serotypes contained in V114 vaccine will be determined using a Multiplex Opsonophagocytic Assay. GMFR is the geometric mean of fold rise from baseline to postvaccination. The percentage of participants who had = 4-fold rise in GMFR were calculated from baseline to postvaccination.	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)
Secondary	Percentage of Participants With GMFR =4 in Pneumococcal Serotype-specific IgG	Immunoglobulin G for the 15 serotypes contained in V114 vaccine will be determined using an electrochemiluminescence assay. GMFR is the geometric mean of fold rise from baseline to postvaccination. The percentage of participants who had = 4-fold rise in GMFR are calculated from baseline to postvaccination.	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)
Secondary	GMFR of Influenza Strain-Specific HAI	Activity for the 4 strains contained in QIV vaccine will be determined using an HAI assay. GMFR is the geometric mean of fold rise from baseline to postvaccination.	Baseline (Day 1) and Day 30
Secondary	Percentage of Participants With Influenza Strain-specific HAI Titer =1:40	Activity for the 4 strains contained in QIV vaccine will be determined using an HAI assay. Seroconversion is defined as achieving a 4-fold rise from baseline to postvaccination among participants who are seropositive at baseline (HAI titer = 1:10) or a titer of = 1:40 at postvaccination among participants who are seronegative at baseline (HAI titer < 1:10).	Day 30
Secondary	Percentage of Participants Who Seroconvert for Influenza Strain-specific HAI	Activity for the 4 strains contained in QIV vaccine will be determined using an HAI assay. Seroconversion for HAI responses is defined as achieving either 1) a 4-fold rise in influenza strain-specific HAI titer from Baseline to Day 30 among participants who are seropositive at Baseline (HAI titer =1:10) or 2) a influenza strain-specific HAI titer of =1:40 at Day 30 among participants who are seronegative at Baseline (HAI titer <1:10).	Baseline (Day 1) and Day 30