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

A Phase 3 Randomized, Observer-Blind, Multi-center, Controlled Study to Evaluate Safety, Immunogenicity, and Lot-to-Lot Consistency of an Adjuvanted Cell Culture-Derived, H5N1 Subunit Influenza Virus Vaccine in Healthy Adult Subjects ≥18 Years of Age

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.

Study Overview

• Status: Completed
• Conditions: Avian Influenza
• Intervention / Treatment: Biological: aH5N1c; Biological: Placebo

• Study Type: Interventional
• Enrollment (Actual): 3196
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Huntsville, Alabama, United States, 35802
      • Optimal Research, LLC
  • Arizona
    • Chandler, Arizona, United States, 85224
      • Radiant Research
    • Tempe, Arizona, United States, 85283
      • Clinical Research Consortium Arizona
  • California
    • San Diego, California, United States, 92123
      • California Research Foundation
    • San Diego, California, United States, 92108
      • Optimal Research Site
  • Connecticut
    • Milford, Connecticut, United States, 06460
      • Clinical Research Consulting, LLC
  • Florida
    • Clearwater, Florida, United States, 33756
      • Innovative Research of West Florida, Inc.
    • Melbourne, Florida, United States, 32934
      • Optimal Research, LLC
  • Illinois
    • Chicago, Illinois, United States, 60640
      • Great Lakes Clinical Trials LLC
    • Peoria, Illinois, United States, 61614
      • Optimal Research
  • Kansas
    • Wichita, Kansas, United States, 67207
      • Heartland Research Associates
  • Maryland
    • Rockville, Maryland, United States, 20850
      • Optimal Research, LLC
  • Missouri
    • Kansas City, Missouri, United States, 64114
      • The Center for Pharmaceutical Research
    • Saint Louis, Missouri, United States, 63141
      • Sundance Clinical Research, LLC
  • New York
    • Binghamton, New York, United States, 13901
      • RCR/United Medical Associates, PC
    • Rochester, New York, United States, 14609
      • Rochester Clinical Research, Inc
  • North Carolina
    • Raleigh, North Carolina, United States, 60640
      • PMG Research of Raleigh
    • Winston-Salem, North Carolina, United States, 27609
      • PMG Research of Winston-Salem
  • Ohio
    • Columbus, Ohio, United States, 43213
      • Aventiv Research
  • South Carolina
    • Charleston, South Carolina, United States, 29407
      • Medical Research South
    • Spartanburg, South Carolina, United States, 29303
      • Spartanburg Medical Research
  • Texas
    • San Antonio, Texas, United States, 78229
      • Biogenics Research Institute
  • Utah
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc/Foothill Family Clinic South
    • Salt Lake City, Utah, United States, 84109
      • J. Lewis Research Inc.-Foothill Family Clinic
    • Salt Lake City, Utah, United States, 84121
      • J. Lewis Research, Inc. / FirstMed East
    • South Jordan, Utah, United States, 84095
      • J. Lewis Research, Inc/Jordan River Family Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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 Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group A; aH5N1c lot #1; receive 2 doses (on Day 1 and Day 22)	Biological: aH5N1c; Intramuscular (IM) administration, containing 7.5 mcg H5N1 hemagglutinin antigen (HA) + 0.25 mL MF59 (approximately 0.5 mL total volume).
Experimental: Group B; aH5N1c lot #2; receive 2 doses (on Day 1 and Day 22)	Biological: aH5N1c; Intramuscular (IM) administration, containing 7.5 mcg H5N1 hemagglutinin antigen (HA) + 0.25 mL MF59 (approximately 0.5 mL total volume).
Experimental: Group C; aH5N1c lot #3; receive 2 doses (on Day 1 and Day 22)	Biological: aH5N1c; Intramuscular (IM) administration, containing 7.5 mcg H5N1 hemagglutinin antigen (HA) + 0.25 mL MF59 (approximately 0.5 mL total volume).
Placebo Comparator: Group D; Placebo; receive 2 doses (on Day 1 and Day 22)	Biological: Placebo; Placebo: Saline injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Immunogenicity Endpoint: Geometric Mean Titer (GMT) at Day 43 by Lot	Hemagglutination Inhibition (HI) GMT was assessed at Day 1 and Day 43 for 3 consecutively produced lots.	Day 1, Day 43
Primary Immunogenicity Endpoint: Percentage of Subjects With Haemagglutination Inhibition (HI) Titer ≥ 1:40 at Day 43 by Age Cohort	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%.	Day 1, Day 43
Percentage of Subjects With Solicited Local, Solicited Systemic, and Other Adverse Events (AEs) as Measured for 7 Days (Inclusive) Following Each Vaccination	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.	Day 1 to Day 7
Percentages of Subjects With Any Unsolicited AEs Reported Through 21 Day After Vaccination	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.	Day 1 to Day 43
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.	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.	Day 1 to Day 387

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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).	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).	Day 1, Day 22, Day 43, and Day 183
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).	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%.	Day 1, Day 22, Day 43 and Day 183
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).	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).	Day 22, and Day 43
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)	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).	Day 1, Day 22, Day 43 and Day 183
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)	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%.	Day 1, Day 22, Day 43, and Day 183
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)	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)	Day 22, and Day 43
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)	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.	Day 1, Day 22, Day 43

Collaborators and Investigators

• Sponsor: Seqirus
• Collaborators: Biomedical Advanced Research and Development Authority

Publications and helpful links

General Publications

• Peterson J, Van Twuijver E, Versage E, Hohenboken M. Phase 3 Randomized, Multicenter, Placebo-Controlled Study to Evaluate Safety, Immunogenicity, and Lot-to-Lot Consistency of an Adjuvanted Cell Culture-Derived, H5N1 Subunit Influenza Virus Vaccine in Healthy Adult Subjects. Vaccines (Basel). 2022 Mar 23;10(4):497. doi: 10.3390/vaccines10040497.

Study record dates

Study Major Dates

• Study Start (Actual): July 11, 2016
• Primary Completion (Actual): October 4, 2017
• Study Completion (Actual): October 4, 2017

Study Registration Dates

• First Submitted: July 18, 2016
• First Submitted That Met QC Criteria: July 19, 2016
• First Posted (Estimate): July 20, 2016

Study Record Updates

• Last Update Posted (Actual): April 4, 2019
• Last Update Submitted That Met QC Criteria: April 2, 2019
• Last Verified: April 1, 2019

More Information

Terms related to this study

• Keywords: Influenza; Vaccine; H5N1; Flu; Pandemic; MF59; Avian
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Influenza in Birds
• Other Study ID Numbers: V89_18

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No