Safety and Immunogenicity of Two Doses of H5N1 Influenza Vaccine in Elderly Subjects

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT01766921
First received: January 10, 2013
Last updated: July 14, 2015
Last verified: July 2015
  Purpose

Evaluate Safety, Tolerability and Immune response of adjuvanted H5N1 cell culture derived influenza vaccine in elderly subjects


Condition Intervention Phase
Pandemic H5N1 Influenza
Biological: Adjuvanted H5N1 pandemic influenza vaccine
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Prevention
Official Title: A Phase II, Randomized, Observer-Blind, Multi-Center, Study to Evaluate Safety, Tolerability and Immunogenicity of an Adjuvanted Cell Culture-Derived H5N1 Subunit Influenza Virus Vaccine at Two Different Formulations in Healthy Elderly Subjects.

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • The Percentages Of Subjects Achieving Hemagglutination Inhibition (HI) Titers ≥40 Against A/H5N1 Strain. [ Time Frame: Baseline (day 1) and Three weeks after 2nd vaccination (day 43) ] [ Designated as safety issue: No ]

    The optimal aH5N1c vaccine formulation was evaluated in terms of percentages of subjects achieving HI titers ≥40 against homologous A/H5N1 strain, three weeks after second vaccination with either low dose or high dose of aH5N1c vaccine, according to the Center for Biologics Evaluation and Research (CBER) criterion.

    The CBER criterion for the elderly population is met if the lower limit of the two-sided 95% confidence interval (CI) for the percentages of subjects achieving HI titer ≥40 meets or exceeds 60%.


  • The Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain. [ Time Frame: Three weeks after 2nd vaccination (day 43) ] [ Designated as safety issue: No ]

    Immunogenicity was measured in terms of the percentages of subjects achieving seroconversion or significant increase in HI titer against the vaccine strain, three weeks after receiving two injections of low dose or high dose of aH5N1c vaccine according to the CBER criterion.

    Seroconversion is defined as, a postvaccination titer ≥40 in subjects with a prevaccination HI titer <10; or in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer.

    The CBER criterion for the elderly population is met if the lower limit of the two-sided 95% CI for the percentages of subjects achieving seroconversion for HI antibody titer meets or exceeds 30%.


  • Number of Subjects Reporting Solicited Local and Systemic Adverse Events, After Any Vaccination. [ Time Frame: From day 1 through day 7 after any vaccination. ] [ Designated as safety issue: No ]
    Safety was assessed as the number of subjects who reported solicited local and systemic adverse events following vaccination with either low or high dose of aH5N1c vaccine.

  • Number of Subjects Reporting Unsolicited Adverse Events After Any Vaccination. [ Time Frame: Day 1 through day 387 after any vaccination ] [ Designated as safety issue: No ]
    Safety was assessed using the number of subjects who reported any unsolicited adverse events, adverse events possibly or probably related to study vaccine, serious adverse events (SAEs), new onset of chronic diseases (NOCDs), medically attended AEs, AEs of special interest (AESIs), AEs leading to withdrawal from study following vaccination with aH5N1c vaccine


Secondary Outcome Measures:
  • Geometric Mean Ratios (GMR) Against A/H5N1 Strain Following 2-dose Vaccination Schedule of Either Low Dose or High Dose aH5N1c Vaccine. [ Time Frame: Day 1; day 22; day 43 and day 387 ] [ Designated as safety issue: No ]

    Immunogenicity was measured as the GMR. The ratio of postvaccination to prevaccination HI geometric mean titers (GMTs) is reported.

    The criterion is met according to the European Committee for Medicinal Products for Human Use (CHMP) criterion if the geometric mean increase GMR (day 43/day 1) in HI antibody titer is >2.0 for subjects >60 years of age.


  • Percentages Of Subjects With HI Titers ≥40 Against A/H5N1 Strain [ Time Frame: Day 1, day 22, day 43 and day 387. ] [ Designated as safety issue: No ]

    Immunogenicity was assessed in terms of percentage of subjects achieving HI titers >40, three weeks after second vaccination with aH5N1c according to the CHMP criterion.

    The European Licensure (CHMP) criterion is met if the percentage of subjects achieving HI titers ≥40 is >60%.


  • The Percentages Of Subjects Achieving Seroconversion Against A/H5N1 Strain [ Time Frame: Day 22, day 43 and day 387 ] [ Designated as safety issue: No ]

    Immunogenicity was assessed in terms of percentages of subjects achieving seroconversion in HI titers, three weeks after receiving two injections of either low dose or high dose aH5N1c vaccine according to the CHMP criterion.

    Seroconversion is defined as a postvaccination titer ≥40 in subjects with a prevaccination HI titer <10; or in subjects with prevaccination HI titer ≥10, a minimum four-fold rise in postvaccination HI antibody titer.

    The criterion is met according to the European (CHMP) guideline if the percentage of subjects achieving seroconversion is >30%.



Enrollment: 1393
Study Start Date: January 2013
Study Completion Date: July 2014
Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: aH5N1c - High dose Biological: Adjuvanted H5N1 pandemic influenza vaccine
Comparison of two doses of aH5N1c vaccine
Experimental: aH5N1c - Low dose Biological: Adjuvanted H5N1 pandemic influenza vaccine
Comparison of two doses of aH5N1c vaccine

  Eligibility

Ages Eligible for Study:   65 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. Healthy elderly subjects ≥65 years,
  2. Individuals willing to provide written informed consent,
  3. Individuals in good health,
  4. Individuals willing to allow for their serum samples to be stored beyond the study period.

Exclusion Criteria:

  1. Individuals not able to understand and follow study procedures,
  2. History of any significant illness,
  3. History of any serious chronic medical condition or progressive disease,
  4. Presence of medically significant cancer,
  5. Known or suspected impairment/alteration of immune function,
  6. Presence of any progressive or severe neurologic disorder,
  7. Presence of any bleeding disorders or conditions that prolongs bleeding time,
  8. History of allergy to vaccine components,
  9. Receipt of any other investigational product within 30 days prior to entry into the study,
  10. History of previous H5N1 vaccination,
  11. Receipt of any other type of seasonal vaccination within 2 months prior to entry into the study,
  12. Receipt of any other vaccine within 2 weeks prior to entry into the study
  13. Body temperature ≥38°C.0 (≥100.4° F) and/or acute illness within 3 days of intended study vaccination,
  14. Body mass index (BMI) ≥ 35 kg/m2,
  15. History of drug or alcohol abuse,
  16. Any planned surgery during study period,
  17. Individuals conducting the study and their immediate family members,
  18. Individuals with behavioral or cognitive impairment or psychiatric diseases.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01766921

Locations
United States, Arizona
1 Tatum Highlands Med Ass PLLC
Phoenix, Arizona, United States, 85253
United States, Florida
5 Broward Research Group Pembroke Pines
Florida, Florida, United States, 33206
United States, Kansas
7 Heartland Rsrch Ass LLC
Wichita, Kansas, United States, 67207
9 Heartland Research Associates
Wichita, Kansas, United States, 67207
United States, Missouri
3 Saint Louis University
St Louis, Missouri, United States, 63141
2 Mercy Health Research
St. Louis, Missouri, United States, 63141
United States, New York
6 Regional Clinical Research Endwell,
Endwell, New York, United States, 13760
United States, Texas
4 Benchmark Medical Research
Austin, Texas, United States, 78705
12 Tekton Research
Georgetown, Texas, United States, 78745
United States, Utah
8 J. Lewis Research Inc.
Salt Lake City, Utah, United States, 84121
10 Foothill Family Clinic
South Cottonwood Heights, Utah, United States, 84121
11 Jordan River Family Medicine
South Jordan, Utah, United States, 84095
Australia, New South Wales
42 Hunter Clinical Research
Newcastle, New South Wales, Australia, 2292
Australia, Queensland
44 Wesley Research Institute Clinical Trials Center
Auchenflower, Queensland, Australia, 4066
Australia, South Australia
40 CMAX
Adelaide, South Australia, Australia, 5000
Australia, Western Australia
41 Linear Clinical Research
Nedlands, Western Australia, Australia, 6009
45 Childrens Clin Rsrch Facility
Perth, Western Australia, Australia, 6872
New Zealand
50 Southern Clinical Trials
Beckenham, Christchurch, New Zealand, 8244
51 Riccarton Clinic
Riccarton, Christchurch, New Zealand, 8041
Thailand
71 Phramongkutklao Hospital
Bangkok, Thailand, 10400
72 Faculty of Medicine, Chulalongkorn University - Queen Saovabha Memorial Institute
Bangkok, Thailand, 10330
73 Siriraj Clinical Research Ctr
Bangkok, Thailand, 10700
74 Chiang Mai Uni Hospital Clinical Trial Center
Bangkok, Thailand, 50200
Sponsors and Collaborators
Novartis Vaccines
Investigators
Study Chair: Novartis vaccines and Diagnostics Novartis Vaccines
  More Information

No publications provided

Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT01766921     History of Changes
Other Study ID Numbers: V89_13
Study First Received: January 10, 2013
Results First Received: May 5, 2015
Last Updated: July 14, 2015
Health Authority: United States: Food and Drug Administration and Department of Health and Human Services
Thailand: Food and Drug Administration
Australia: Department of Health and Ageing Therapeutic Goods Administration
New Zealand: Medsafe

Keywords provided by Novartis:
Influenza, Pandemic, H5N1, Elderly adults

Additional relevant MeSH terms:
Influenza in Birds
Influenza, Human
Orthomyxoviridae Infections
RNA Virus Infections
Respiratory Tract Diseases
Respiratory Tract Infections
Virus Diseases

ClinicalTrials.gov processed this record on September 01, 2015