Safety and Immunogenicity of 3 Lots of Cell-derived Subunit Influenza Vaccine as Compared to 1 Lot to Egg-derived Subunit Influenza Vaccine in Healthy Adults (>=18 to <=60)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT00310804
First received: April 3, 2006
Last updated: January 18, 2013
Last verified: January 2013
  Purpose

The present study aims to evaluate safety, tolerability and immunogenicity of three lots of Chiron's cell-derived subunit influenza vaccine in healthy adult subjects as compared to a conventional egg-derived control vaccine licensed in Europe.


Condition Intervention Phase
Influenza
Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 1 (cTIV)
Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 2 (cTIV)
Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 3 (cTIV)
Biological: Egg-Derived Trivalent Subunit Influenza Vaccine (TIV)
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Subject)
Primary Purpose: Prevention
Official Title: A Phase III, Randomized, Controlled, Observer-Blind, Multi-Center Study to Evaluate Safety, Tolerability and Immunogenicity of a Single Intramuscular Dose of Three Lots of a Trivalent Subunit Influenza Vaccine Produced in Mammalian Cell Culture Or of a Trivalent Subunit Influenza Vaccine Produced in Embryonated Hen Eggs, in Healthy Adult Subjects Aged >=18 to <=60

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Geometric Mean Titers After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult Subjects [ Time Frame: Day 22 postvaccination ] [ Designated as safety issue: No ]

    The haemagglutinin Inhibition (HI) antibody titer response following

    1. one dose of cTIV for each of the three lots separately and
    2. one dose of cTIV (combined) compared to TIV is reported as Geometric mean titers (GMTs).

    The HI GMTs were evaluated using egg-derived antigen assay.


  • Geometric Mean Ratios After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine in Adult Subjects [ Time Frame: Day 22 postvaccination ] [ Designated as safety issue: No ]

    Immunogenicity was assessed in terms of Geometric Mean Ratio (GMR) following

    1. one dose of cTIV for each of the three vaccine lots separately and
    2. for one dose of cTIV (combined) compared to TIV, according to the CHMP criterion.

    The European licensure (CHMP) criterion is met if the mean geometric increase (GMR, day 22/day 1) in HI antibody titer is >2.5.


  • Percentage of Subjects With HI Titers ≥40 [ Time Frame: Day 22 postvaccination ] [ Designated as safety issue: No ]

    Immunogenicity was assessed in terms of percentage of adult subjects achieving HI titers ≥40, after

    1. one dose of cTIV for each of the three vaccine lots separately and
    2. for one dose of cTIV (combined) compared to TIV, according to the CHMP criterion.

    European Licensure (CHMP) criterion is met if the percentage of subjects achieving HI titers ≥40 is >70%.


  • Percentage of Subjects With Seroconversion or Significant Increase in HI Antibody Titers After One Dose of Either Cell-derived or Egg-derived Subunit Trivalent Influenza Vaccine [ Time Frame: Day 22 postvaccination ] [ Designated as safety issue: No ]

    Immunogenicity was assessed in terms of percentage of adult subjects showing seroconversion or significant increase in HI antibody titers after

    1. one dose of cTIV for each of the three vaccine lots separately and
    2. one dose of cTIV (combined) compared to TIV, according to the CHMP criterion.

    European Licensure (CHMP) criterion is met if the percentage of subjects achieving seroconversion or significant increase is >40%.

    As per European Licensure (CHMP) criterion seroconversion is defined as percentage of subjects with a prevaccination HI titer <10 to a postvaccination titer ≥40; whereas, significant increase is defined as HI titer ≥10 prevaccination and ≥4-fold Hi titer increase post-vaccination.



Secondary Outcome Measures:
  • Number of Subjects Reporting Solicited Adverse Events After One Dose of Cell Culture-derived or the Egg-derived Influenza Vaccine. [ Time Frame: Day 1 to Day 7 postvaccination ] [ Designated as safety issue: Yes ]

    To assess the safety and tolerability in terms of number of subjects reporting solicited adverse events following one injection of

    1. one dose of cTIV for each of the three vaccine lots separately and
    2. for one dose of cTIV (combined) compared to TIV.

  • Safety Data of Subjects Upto Six Months After One Dose of Cell Culture Derived or Egg-derived Influenza Vaccine [ Time Frame: Day 1 - Day 181 postvaccination ] [ Designated as safety issue: Yes ]
    Additional safety data from day 1 through day 181 after one dose of cTIV (combined) or TIV in terms of serious adverse events (SAEs), adverse events (AEs) necessitating a physician's visit and/or resulting in premature subject's withdrawal from study is reported.


Enrollment: 1200
Study Start Date: September 2005
Study Completion Date: April 2006
Primary Completion Date: October 2005 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: cTIV_lot 1 Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 1 (cTIV)
One single 0.5ml intramuscular injection of Cell Derived Trivalent Subunit Influenza Vaccine (cTIV) from Lot 1
Experimental: cTIV_lot 2 Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 2 (cTIV)
One single 0.5ml intramuscular injection of Cell Derived Trivalent Subunit Influenza Vaccine (cTIV) from Lot 2
Experimental: cTIV_lot 3 Biological: Cell-Derived Trivalent Subunit Influenza Vaccine Lot 3 (cTIV)
One single 0.5ml intramuscular injection of Cell Derived Trivalent Subunit Influenza Vaccine (cTIV) from Lot 3
Active Comparator: TIV group Biological: Egg-Derived Trivalent Subunit Influenza Vaccine (TIV)
One single 0.5ml intramuscular injection of Egg Derived Trivalent Subunit Influenza Vaccine (TIV).

  Eligibility

Ages Eligible for Study:   18 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. 18 to <61 years of age
  2. mentally competent to understand the nature, the scope and the consequences of the study
  3. able and willing to give written informed consent prior to study entry
  4. in good health as determined by:

    1. medical history,
    2. physical examination,
    3. clinical judgment of the Investigator.

Exclusion Criteria:

  1. unwilling or unable to give written informed consent to participate in the study
  2. participation in another clinical trial of an investigational agent within 90 days prior to Visit 1 and throughout the entire study
  3. currently experiencing an acute infectious disease
  4. any serious disease, such as, for example:

    1. cancer,
    2. autoimmune disease (including rheumatoid arthritis),
    3. advanced arteriosclerotic disease or complicated diabetes mellitus,
    4. chronic obstructive pulmonary disease (COPD) requiring oxygen therapy,
    5. acute or progressive hepatic disease,
    6. acute or progressive renal disease,
    7. congestive heart failure
  5. surgery planned during the study period
  6. bleeding diathesis
  7. history of hypersensitivity to any component of the study medication or chemically related substances
  8. history of any anaphylaxis, serious vaccine reactions, or allergy to any of the vaccine component
  9. known or suspected impairment/alteration of immune function, for example resulting from:

    1. receipt of immunosuppressive therapy (any corticosteroid therapy or cancer chemotherapy),
    2. receipt of immunostimulants,
    3. receipt of parenteral immunoglobulin preparation, blood products, and/or plasma derivates within 3 months prior to Visit 1 or planned during the full length of the study,
    4. high risk for developing an immunocompromising disease
  10. history of drug or alcohol abuse
  11. laboratory-confirmed influenza disease within 6 months prior to Visit 1
  12. receipt of influenza vaccine within 6 months prior to Visit 1
  13. receipt of another vaccine within 60 days prior to Visit 1, or planned vaccination within 3 weeks following study vaccination
  14. any acute respiratory disease or infections requiring systemic antibiotic or antiviral therapy (chronic antibiotic therapy for urinary tract prophylaxis is acceptable) or experienced fever (i.e., axillary temperature ≥ 38 degree C) within 5 days prior to Visit 1
  15. if female, pregnant or breastfeeding
  16. if female, refusal to use a reliable contraceptive method during the three weeks following vaccination
  17. planned relocation abroad during the study period
  18. any condition that, in the opinion of the Investigator, might interfere with the evaluation of the study objectives.
  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: NCT00310804

Locations
Lithuania
2nd Department of Internal Diseases, Panevezys Hospital,
Panevezys, Lithuania
Dept. Infectious Diseases and Microbiology of Vilnius University
Vilnius, Lithuania
Sponsors and Collaborators
Novartis Vaccines
Investigators
Study Chair: Novartis Vaccines Novartis Vaccines & Diagnostics
  More Information

Publications:
Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT00310804     History of Changes
Other Study ID Numbers: V58P9, EUDRACT: 2005-002257-47
Study First Received: April 3, 2006
Results First Received: December 11, 2012
Last Updated: January 18, 2013
Health Authority: Lithuania: State Medicine Control Agency - Ministry of Health

Keywords provided by Novartis:
Influenza
Flu
Cell-Derived
Egg-Derived
Healthy Adults
Safety
Immunogenicity
Vaccination

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

ClinicalTrials.gov processed this record on October 01, 2014