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Trial record 98 of 112 for:    mf59

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02839330
Recruitment Status : Completed
First Posted : July 20, 2016
Results First Posted : April 4, 2019
Last Update Posted : April 4, 2019
Sponsor:
Collaborator:
Biomedical Advanced Research and Development Authority
Information provided by (Responsible Party):
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.

Condition or disease Intervention/treatment Phase
Avian Influenza Biological: aH5N1c Biological: Placebo Phase 3

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 3196 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
Official Title: 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
Actual Study Start Date : July 11, 2016
Actual Primary Completion Date : October 4, 2017
Actual Study Completion Date : October 4, 2017

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. Primary Immunogenicity Endpoint: Geometric Mean Titer (GMT) at Day 43 by Lot [ Time Frame: Day 1, Day 43 ]
    Hemagglutination Inhibition (HI) GMT was assessed at Day 1 and Day 43 for 3 consecutively produced lots.

  2. Primary Immunogenicity Endpoint: Percentage of Subjects With Haemagglutination Inhibition (HI) Titer ≥ 1:40 at Day 43 by Age Cohort [ Time Frame: 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%.

  3. Percentage of Subjects With Solicited Local, Solicited Systemic, and Other Adverse Events (AEs) as Measured for 7 Days (Inclusive) Following Each Vaccination [ Time Frame: 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.

  4. Percentages of Subjects With Any Unsolicited AEs Reported Through 21 Day After Vaccination [ Time Frame: 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.

  5. 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. [ Time Frame: 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 :
  1. 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). [ Time Frame: 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).

  2. 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). [ Time Frame: 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%.


  3. 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). [ Time Frame: 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).

  4. 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) [ Time Frame: 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).

  5. 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) [ Time Frame: 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%.

  6. 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) [ Time Frame: 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)

  7. 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) [ Time Frame: 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.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02839330


  Show 26 Study Locations
Sponsors and Collaborators
Seqirus
Biomedical Advanced Research and Development Authority
Investigators
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Study Director: Clinical Program Director Seqirus
  Study Documents (Full-Text)

Documents provided by Seqirus:
Study Protocol  [PDF] March 15, 2016
Statistical Analysis Plan  [PDF] November 15, 2017


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Responsible Party: Seqirus
ClinicalTrials.gov Identifier: NCT02839330     History of Changes
Other Study ID Numbers: V89_18
First Posted: July 20, 2016    Key Record Dates
Results First Posted: April 4, 2019
Last Update Posted: April 4, 2019
Last Verified: April 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Seqirus:
Influenza
Vaccine
Flu
Avian
Pandemic
H5N1
MF59

Additional relevant MeSH terms:
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Influenza, Human
Influenza in Birds
Orthomyxoviridae Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Vaccines
Immunologic Factors
Physiological Effects of Drugs