A Study to Evaluate Safety, Immunogenicity, and Lot-to-Lot Consistency of H5N1 Subunit Influenza Virus Vaccine in Healthy Adult Subjects ≥18 Years of Age
- Conditions
- Avian Influenza
- Interventions
- Biological: aH5N1cBiological: Placebo
- Registration Number
- NCT02839330
- Lead Sponsor
- Seqirus
- Brief Summary
This Phase 3 study evaluates the safety, immunogenicity and lot-to lot consistency of 3 lots of aH5N1c vaccine for pandemic avian influenza, in approximately 2394 healthy adults ≥18 years of age receiving the vaccine and 797 healthy adults receiving placebo. Subjects were randomized in a 3:1 ratio to receive either aH5N1c vaccine or saline placebo. Enrollment was stratified by age: 18 to \<65 years of age and ≥65 years of age, to allow adequate safety assessment of the entire age spectrum.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 3196
- Subjects ≥ 18 years of age, mentally competent, in good health as determined by medical history, physical examination and clinical judgment by the Investigator; able to comply with all study procedures, to be contacted, and to be available for study visits according to the protocol.
- Individuals who are pregnant or breastfeeding. Female subjects of childbearing potential must have a negative pregnancy test prior to study vaccines being administered.
- Females of childbearing potential who refuse to use an acceptable method of birth control from Day 1 (1st vaccination) to 3 weeks after the second study vaccination, and, if sexually active, who have not used a reliable birth control method for at least two months prior to study entry.
- Individuals with a body temperature ≥38.0 °C (≥100.4 °F) or any acute illness within 3 days of intended study vaccination.
- Individuals who received any type of influenza vaccine (e.g., "seasonal") within 7 days prior to enrolment in this study or who are planning to receive any type of influenza vaccine within 7 days (before or after) from the study vaccines.
- Individuals who received any other licensed vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrollment in this study or who are planning to receive any (non-influenza) vaccine within 28 days (before or after) from the study vaccines.
- Individuals with known or suspected impairment of the immune system.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A aH5N1c aH5N1c lot #1; receive 2 doses (on Day 1 and Day 22) Group B aH5N1c aH5N1c lot #2; receive 2 doses (on Day 1 and Day 22) Group D Placebo Placebo; receive 2 doses (on Day 1 and Day 22) Group C aH5N1c aH5N1c lot #3; receive 2 doses (on Day 1 and Day 22)
- Primary Outcome Measures
Name Time Method Primary Immunogenicity Endpoint: Geometric Mean Titer (GMT) at Day 43 by Lot Day 1, Day 43 Hemagglutination Inhibition (HI) GMT was assessed at Day 1 and Day 43 for 3 consecutively produced lots.
Percentage of Subjects With Solicited Local, Solicited Systemic, and Other Adverse Events (AEs) as Measured for 7 Days (Inclusive) Following Each Vaccination Day 1 to Day 7 Percentages of subjects with solicited local, solicited systemic, and other AEs as measured for 7 days (inclusive) following each vaccination (first and second) and any (first or second) vaccination, by treatment group and calculated for several time intervals after vaccination : 30 minutes, 1 to 3 days (without 30 minutes), 4 to 7 days, and 1 to 7 days (without 30 minutes), and 1 to 3 days (including 30 minutes) and 1 to 7 days (including 30 minutes). Analysis for intervals of the first 30 minutes, days 1 to 3, and days 4 to 7 was not performed.
Percentages of Subjects With Any Unsolicited AEs Reported Through 21 Day After Vaccination Day 1 to Day 43 Percentages of subjects with any unsolicited AEs reported through 21 days after each (first and second) and any (first or second) vaccination by treatment group.
Primary Immunogenicity Endpoint: Percentage of Subjects With Haemagglutination Inhibition (HI) Titer ≥ 1:40 at Day 43 by Age Cohort Day 1, Day 43 Percentage of subjects with HI titer ≥ 1:40 at Day 43 was assessed by age cohort (18 to \<65 years of age and ≥65 years of age) for the pooled lots. Center for Biologics Evaluation and Research (CBER) criterion for subjects aged 18 to \<65 years: The lower bound of the 2-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 70%. CBER criterion for subjects aged ≥65 years: The lower bound of the 2-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 60%.
Percentages of Subjects Reporting SAEs, AESIs, NOCD, AEs Leading to Vaccine/Study Withdrawal, and Medically Attended AEs, and Concomitant Medications Associated With These Events as Collected From Day 1 to Day 387, by Vaccine Group. Day 1 to Day 387 Percentages of subjects with any adverse events (AE), adverse events of special interest (AESI), new onset of chronic disease (NOCD), and serious adverse event (SAE) through study termination by treatment group.
- Secondary Outcome Measures
Name Time Method Secondary Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion on Day 22, and Day 43 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <60 Years of Age and ≥60 Years of Age) Day 22, and Day 43 Percentage of subjects achieving seroconversion (defined as: HI titer ≥1:40 for subjects negative at baseline \[HI titer \<1:10\]; or a minimum 4-fold increase in HI titer for subjects positive at baseline \[HI titer ≥1:10\]) on Day 22, and Day 43 by vaccine group (aH5N1c or placebo) and by age cohort (18 to \<60 years of age and ≥60 years of age)
Secondary Immunogenicity Endpoint: Geometric Mean Titer (GMT) at Day 1, Day 22, Day 43, and Day 183 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <65 Years of Age and ≥65 Years of Age). Day 1, Day 22, Day 43, and Day 183 Estimates of hemagglutination inhibition (HI) GMTs, and their associated 95% CIs at Day 1, Day 22, Day 43 and Day 183 were computed using ANCOVA with factors for treatment (active treatment groups or placebo), center and a covariate for the effect defined by the log-transformed prevaccination antibody titer (Day 1).
Secondary Immunogenicity Endpoint: Percentage of Subjects With Haemagglutination Inhibition (HI) Titer ≥ 1:40 on Day 1, Day 22, Day 43 and Day 183 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <65 Years of Age and ≥65 Years of Age). Day 1, Day 22, Day 43 and Day 183 The percentage of subjects with HI titer ≥1:40 data over time by vaccine group and age cohort are presented. CBER criterion for subjects aged 18 to \<65 years: The lower bound of the 2-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 70%.
CBER criterion for subjects aged ≥65 years: The lower bound of the 2-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 60%.Secondary Immunogenicity Endpoint: Geometric Mean Titer (GMT) at Day 1, Day 22, Day 43 and Day 183 by Vaccine Group (aH5N1c or Placebo) and By Age Cohort (18 to <60 Years of Age and ≥60 Years of Age) Day 1, Day 22, Day 43 and Day 183 Hemagglutination inhibition (HI) GMTs were assessed over time for the vaccine group and age cohort. Adjusted estimates of GMTs, and their associated 95% CIs at Day 1, Day 22, Day 43 and Day 183 were computed using ANCOVA with factors for treatment (active treatment groups or placebo), center and a covariate for the effect defined by the log-transformed prevaccination antibody titer (Day 1).
Secondary Immunogenicity Endpoint: Percentage of Subjects Achieving Seroconversion on Day 22, and Day 43 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <65 Years of Age and ≥65 Years of Age). Day 22, and Day 43 Percentage of subjects achieving seroconversion (defined as: HI titer ≥1:40 for subjects negative at baseline \[HI titer \<1:10\]; or a minimum 4-fold increase in HI titer for subjects positive at baseline \[HI titer ≥1:10\]) on Day 22, and Day 43 by vaccine group (aH5N1c or placebo) and by age cohort (18 to \<65 years of age and ≥65 years of age).
Secondary Immunogenicity Endpoint: Percentage of Subjects With Haemagglutination Inhibition (HI) Titer ≥ 1:40 on Day 1, Day 22, Day 43, and Day 183 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <60 Years of Age and ≥60 Years of Age) Day 1, Day 22, Day 43, and Day 183 The percentage of subjects with HI titer ≥1:40 data over time by vaccine group and age cohort. Committee for Medicinal Products for Human Use (CHMP) criterion for subjects aged 18 to \<60 years: The percentage of subjects achieving an HI titer ≥1:40 is \>70%. CHMP criterion for subjects aged ≥60 years: The percentage of subjects achieving an HI titer ≥1:40 is \>60%.
Secondary Immunogenicity Endpoint: Geometric Mean Ratio (GMR) of Haemagglutination Inhibition (HI) Titer: Day 22/Day 1, Day 43/Day 1 by Vaccine Group (aH5N1c or Placebo) and by Age Cohort (18 to <60 Years of Age and ≥60 Years of Age) Day 1, Day 22, Day 43 The GMR of HI titers (Day 22/Day 1, Day 43/Day 1) is presented for the vaccine groups and age cohort. CHMP criterion for subjects aged 18 to \<60 years: GMR is \>2.5. CHMP criterion for subjects aged ≥60 years: GMR is \>2.0.
Trial Locations
- Locations (24)
Innovative Research of West Florida, Inc.
🇺🇸Clearwater, Florida, United States
Great Lakes Clinical Trials LLC
🇺🇸Chicago, Illinois, United States
Aventiv Research
🇺🇸Columbus, Ohio, United States
J. Lewis Research Inc.-Foothill Family Clinic
🇺🇸Salt Lake City, Utah, United States
Optimal Research Site
🇺🇸San Diego, California, United States
California Research Foundation
🇺🇸San Diego, California, United States
J. Lewis Research, Inc. / FirstMed East
🇺🇸Salt Lake City, Utah, United States
J. Lewis Research, Inc/Foothill Family Clinic South
🇺🇸Salt Lake City, Utah, United States
Optimal Research, LLC
🇺🇸Rockville, Maryland, United States
Clinical Research Consortium Arizona
🇺🇸Tempe, Arizona, United States
Optimal Research
🇺🇸Peoria, Illinois, United States
Clinical Research Consulting, LLC
🇺🇸Milford, Connecticut, United States
The Center for Pharmaceutical Research
🇺🇸Kansas City, Missouri, United States
Heartland Research Associates
🇺🇸Wichita, Kansas, United States
Rochester Clinical Research, Inc
🇺🇸Rochester, New York, United States
Sundance Clinical Research, LLC
🇺🇸Saint Louis, Missouri, United States
RCR/United Medical Associates, PC
🇺🇸Binghamton, New York, United States
Medical Research South
🇺🇸Charleston, South Carolina, United States
Spartanburg Medical Research
🇺🇸Spartanburg, South Carolina, United States
PMG Research of Winston-Salem
🇺🇸Winston-Salem, North Carolina, United States
PMG Research of Raleigh
🇺🇸Raleigh, North Carolina, United States
Biogenics Research Institute
🇺🇸San Antonio, Texas, United States
J. Lewis Research, Inc/Jordan River Family Medicine
🇺🇸South Jordan, Utah, United States
Radiant Research
🇺🇸Chandler, Arizona, United States