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)
- Conditions
- Pneumococcal Infections
- Interventions
- Biological: V114Biological: QIVBiological: Matching Placebo for V114
- Registration Number
- NCT03615482
- Lead Sponsor
- Merck Sharp & Dohme LLC
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1200
- 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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Concomitant Vaccination Matching Placebo for V114 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 Non-concomitant Vaccination Matching Placebo for V114 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 Concomitant Vaccination V114 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 Non-concomitant Vaccination V114 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 Concomitant Vaccination QIV 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 Non-concomitant Vaccination QIV 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
- Primary Outcome Measures
Name Time Method Percentage of Participants With a Vaccine-Related Serious Adverse Event Up to 7 months 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.
Geometric Mean Titer (GMT) Ratio of Pneumococcal Serotype-specific Opsonophagocytic Activity (OPA) 30 days after V114 vaccination (Day 30 for concomitant vaccination group and Day 60 for non-concomitant vaccination group) 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.
Percentage of Participants With a Solicited Systemic Adverse Event Up to Day 14 after any vaccination 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.
GMT of Influenza Strain-Specific Hemagglutination Inhibition Day 30 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.
Percentage of Participants With a Solicited Injection-site Adverse Event Up to Day 5 after vaccination 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.
- Secondary Outcome Measures
Name Time Method 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) 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.
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) 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.
Percentage of Participants Who Seroconvert for Influenza Strain-specific HAI Baseline (Day 1) and Day 30 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).
Percentage of Participants With Influenza Strain-specific HAI Titer ≥1:40 Day 30 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).
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) 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.
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) 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.
GMFR of Influenza Strain-Specific HAI Baseline (Day 1) and Day 30 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.
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) 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.
Trial Locations
- Locations (45)
Center for Clinical Trials, LLC ( Site 0025)
🇺🇸Paramount, California, United States
Bayview Research Group, LLC ( Site 0010)
🇺🇸Valley Village, California, United States
Community Clinical Research Network (Marlboro, MA) ( Site 0030)
🇺🇸Marlborough, Massachusetts, United States
Lakes Research LLC ( Site 0034)
🇺🇸Miami Lakes, Florida, United States
Synexus Clinical Research, US,Inc/Central Arizona Medical Associates, PC ( Site 0004)
🇺🇸Mesa, Arizona, United States
Research Centers of America, LLC ( Site 0036)
🇺🇸Hollywood, Florida, United States
Suncoast Research Group, LLC ( Site 0020)
🇺🇸Miami, Florida, United States
L&C Professional Medical Research Institute ( Site 0015)
🇺🇸Miami, Florida, United States
Alpha Science Research ( Site 0018)
🇺🇸Miami, Florida, United States
Evanston Premier Healthcare & Research, LLC. ( Site 0012)
🇺🇸Evanston, Illinois, United States
Holston Medical Group ( Site 0028)
🇺🇸Kingsport, Tennessee, United States
California Research Foundation ( Site 0002)
🇺🇸San Diego, California, United States
Clinical Research Associates Inc. ( Site 0040)
🇺🇸Nashville, Tennessee, United States
Synexus Clinical Research US, Inc. ( Site 0019)
🇺🇸San Antonio, Texas, United States
Synexus Clinical Research US, Inc./Colorado Springs Family Practice ( Site 0021)
🇺🇸Colorado Springs, Colorado, United States
Heartland Research Associates, LLC ( Site 0031)
🇺🇸Augusta, Kansas, United States
Heartland Research Associates, LLC ( Site 0016)
🇺🇸Newton, Kansas, United States
Southland Clinical Research Center ( Site 0033)
🇺🇸Fountain Valley, California, United States
Artemis Institute for Clinical Research ( Site 0026)
🇺🇸San Diego, California, United States
Valley Clinical Trials Inc. ( Site 0001)
🇺🇸Northridge, California, United States
Healthcare Research Network LLC ( Site 0006)
🇺🇸Flossmoor, Illinois, United States
Springfield Clinic ( Site 0045)
🇺🇸Springfield, Illinois, United States
Kentucky Pediatric/Adult Research Inc ( Site 0011)
🇺🇸Bardstown, Kentucky, United States
Healthcare Research Network LLC ( Site 0032)
🇺🇸Hazelwood, Missouri, United States
Southwest CARE Center ( Site 0013)
🇺🇸Santa Fe, New Mexico, United States
Regional Clinical Research, Inc. ( Site 0029)
🇺🇸Endwell, New York, United States
Mid Hudson Medical Research ( Site 0024)
🇺🇸New Windsor, New York, United States
PMG Research Of Cary LLC ( Site 0035)
🇺🇸Cary, North Carolina, United States
Rochester Clinical Research, Inc. ( Site 0009)
🇺🇸Rochester, New York, United States
Clinical Research Center Of Reading LLP ( Site 0014)
🇺🇸Wyomissing, Pennsylvania, United States
Omega Medical Research ( Site 0049)
🇺🇸Warwick, Rhode Island, United States
Wellness Clinical Research Associates ( Site 0048)
🇺🇸Allen, Texas, United States
Benchmark Research ( Site 0037)
🇺🇸Fort Worth, Texas, United States
San Gabriel Clinical Research ( Site 0047)
🇺🇸Georgetown, Texas, United States
Charlottesville Medical Research Center, LLC ( Site 0008)
🇺🇸Charlottesville, Virginia, United States
Synexus Clinical Research US, Inc. ( Site 0039)
🇺🇸Chandler, Arizona, United States
Synexus Clinical Research US, Inc. ( Site 0042)
🇺🇸Scottsdale, Arizona, United States
PMG Research Inc ( Site 0027)
🇺🇸Mount Pleasant, South Carolina, United States
Clinical Research Center of Neveda, LLC. ( Site 0022)
🇺🇸Las Vegas, Nevada, United States
Indago Research & Health Center, Inc ( Site 0007)
🇺🇸Hialeah, Florida, United States
Holston Medical Group ( Site 0003)
🇺🇸Bristol, Tennessee, United States
Allegiance Research Specialists ( Site 0017)
🇺🇸Wauwatosa, Wisconsin, United States
Achieve Clinical Research, LLC ( Site 0046)
🇺🇸Birmingham, Alabama, United States
Clinical Research Partners, LLC. ( Site 0005)
🇺🇸Richmond, Virginia, United States
Unity Clinical Research ( Site 0044)
🇺🇸Lindsay, Oklahoma, United States