Now Available for Public Comment: Notice of Proposed Rulemaking (NPRM) for FDAAA 801 and NIH Draft Reporting Policy for NIH-Funded Trials

Efficacy Study of Two Influenza Vaccines and Placebo in Healthy Adult Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier:
NCT00630331
First received: February 28, 2008
Last updated: January 15, 2013
Last verified: January 2013
  Purpose

The present study will evaluate clinical efficacy, safety, tolerability and immunogenicity of both Novartis Vaccines' cell-derived influenza vaccine and egg-derived influenza vaccine in healthy adults 18 to 49 years of age.


Condition Intervention Phase
Influenza
Biological: Cell culture-derived influenza vaccine
Biological: Egg-derived influenza virus vaccine
Biological: Placebo
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, Observer-Blind, Placebo-Controlled, Multicenter Study to Assess Clinical Efficacy of a Cell-Derived Subunit Influenza Vaccine and an Egg-Derived Subunit Influenza Vaccine in the 2007-2008 Influenza Season in Healthy Adult Subjects

Resource links provided by NLM:


Further study details as provided by Novartis:

Primary Outcome Measures:
  • Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    The vaccine efficacy of CCI and IVV vaccines was estimated relative to Placebo group as the number of subjects prevented against virus-confirmed symptomatic influenza illness caused by each of three vaccine-like virus strains.


Secondary Outcome Measures:
  • Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    The vaccine efficacy of CCI and IVV vaccines was estimated relative to placebo group as the number of subjects prevented against virus-confirmed symptomatic influenza A or B illness caused by non-vaccine-like strains.

  • Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    The vaccine efficacy of CCI and IVV vaccines was estimated relative to placebo as the number of subjected prevented against virus-confirmed symptomatic influenza A or B illness caused by vaccine-like and non-vaccine-like strains.

  • Influenza-Associated Days in Bed, All Subjects [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    The number of subjects in this analysis included all subjects in the per protocol efficacy population.

  • Influenza-Associated Days in Bed, Subset of Subjects With Virus-Confirmed- Influenza [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza.

  • Number Of Medical Visits (Inpatient and Outpatient) Due to Influenza Illness or Symptoms of Influenza, All Subjects [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    The number of subjects in this analysis included all subjects in the per protocol efficacy population.

  • Number of Medical Visits (Inpatient and Outpatient), Subset of Subjects With Virus-Confirmed-Influenza [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza.

  • Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost Due to Influenza Disease, All Subjects [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    The number of subjects in this analysis included all subjects in the per protocol efficacy population.

  • Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost, Subset of Subjects With Virus-Confirmed-Influenza [ Time Frame: 6 Months ] [ Designated as safety issue: No ]
    The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza.

  • Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo [ Time Frame: Before vaccination (day 1) and three weeks after vaccination (day 22) ] [ Designated as safety issue: No ]
    Immunogenicity was measured as the percentage of subjects achieving HI titers ≥40 at baseline (day 1) and three weeks after (day 22) one vaccination of either cell-culture or egg-derived vaccine or placebo for each of the three influenza vaccine strains (A/H1N1, A/H3N2 and B), evaluated using hemagglutination inhibition (HI) egg-derived antigen assay. This criterion is met according to US (CBER) guideline if the lower limit of the two-sided 95% CI for the percentage of subjects achieving HI titers ≥40 is ≥70%.

  • Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo [ Time Frame: Three weeks after vaccination (day 22) ] [ Designated as safety issue: No ]
    As per the CBER guideline, seroconversion is defined as the percentage of subjects with a prevaccination HI titer <10, a postvaccination titer ≥40; or in subjects with prevaccination HI titer ≥10, a ≥4-fold increase in postvaccination HI antibody titer. According to CBER criteria, the lower limit of the two-sided 95% CI for the percentage of subjects achieving seroconversion for HI antibody titer at day 22 met exceeded 40%.

  • Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination [ Time Frame: Up to 7 days post vaccination ] [ Designated as safety issue: Yes ]
    The solicited local and systemic reactogenicity were collected up to 7 days after vaccination for all three vaccine groups.


Enrollment: 11404
Study Start Date: October 2007
Study Completion Date: July 2008
Primary Completion Date: July 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: CCI
Subjects received one dose of cell culture-derived influenza vaccine.
Biological: Cell culture-derived influenza vaccine
One dose (0.5 mL) of cell culture-derived influenza vaccine, administered in the deltoid muscle.
Experimental: IVV
Subjects received one dose of the trivalent egg-derived influenza vaccine.
Biological: Egg-derived influenza virus vaccine
One dose (0.5 mL) of the trivalent egg-derived influenza virus vaccine, administered in the deltoid muscle.
Placebo Comparator: Placebo
Subjects received one dose of phosphate buffered solution (PBS).
Biological: Placebo
One dose (0.5 mL) of phosphate buffered solution.

  Eligibility

Ages Eligible for Study:   18 Years to 49 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. subjects 18 to 49 years of age;
  2. in good health as determined by medical history and physical examination;
  3. able and willing to provide written informed consent prior to any study procedure;
  4. able to comply with all study procedures, including availability and willingness to be actively followed throughout the ensuing influenza season with weekly telephone calls and to comply with the need for prompt collection of nasal and throat specimens in the event of influenza symptoms.

Exclusion Criteria:

  1. history of anaphylaxis or serious reaction after administration of any vaccine, or hypersensitivity to eggs, egg protein, chicken feathers, influenza viral protein, neomycin, kanamycin, or any other vaccine component, chemically related substance, or component of the potential packaging materials;
  2. any health condition for which the inactivated vaccine is recommended by the Advisory Committee on Immunization Practices (ACIP) including chronic diseases of the pulmonary or cardiovascular systems (including asthma), chronic metabolic diseases (including diabetes), renal dysfunction, hemoglobinopathies, immune deficiency disease (including HIV infection) or on-going immunosuppressive therapy;
  3. employment in professions prone to influenza transmission to or from high-risk populations (this exclusion specifically includes nurses, physicians, all other healthcare workers with direct patient contact; and police, fire, and rescue personnel); or living in the same household as an immunocompromised person;
  4. history of Guillain-Barré syndrome;
  5. bleeding diathesis;
  6. receipt of another investigational agent within 90 days prior to enrollment in the study or before completion of the safety follow-up period in another study, whichever is longer, and unwilling to refuse participation in another clinical study through the end of the study;
  7. receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Visit 1;
  8. laboratory-confirmed influenza disease within 6 months prior to Visit 1;
  9. receipt of an influenza vaccine within 6 months prior to Visit 1 or plans to receive influenza vaccine outside of this study;
  10. experienced a temperature (≥100.0°F / ≥37.8°C) and/or any acute illness within 3 days prior to study vaccination;
  11. pregnant or breast-feeding female;
  12. if female of childbearing potential and sexually active, has not used any of the birth control methods detailed in the section entitled "Females of Childbearing Potential" for at least 2 months prior to study entry;
  13. if female of childbearing potential and sexually active, refusal to use a reliable contraceptive method as detailed in the section entitled "Females of Childbearing Potential" during the first 3 weeks after vaccination;
  14. research staff directly involved with the clinical study or family members or household members of research staff. Research staff are individuals with direct or indirect contact with study subjects, or study site personnel who have access to any study documents containing subject information. This would include receptionists, persons scheduling appointments or making screening calls, regulatory specialists, laboratory technicians, etc.;
  15. any condition which, in the opinion of the investigator, might interfere with the evaluation of the study objectives or with the safety of the study subject.
  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: NCT00630331

  Show 56 Study Locations
Sponsors and Collaborators
Novartis Vaccines
Investigators
Study Chair: Novartis Vaccines Novartis Vaccines
  More Information

Publications:
Responsible Party: Novartis ( Novartis Vaccines )
ClinicalTrials.gov Identifier: NCT00630331     History of Changes
Other Study ID Numbers: V58P13, 2007-002871-15, 11580
Study First Received: February 28, 2008
Results First Received: November 21, 2012
Last Updated: January 15, 2013
Health Authority: United States: Food and Drug Administration
Finland: Finnish Medicines Agency
Poland: Office for Registration of Medicinal Products, Medical Devices and Biocidal Products

Keywords provided by Novartis:
Influenza
Flu
Cell Culture-Derived
Egg-Derived
Healthy Adults
Efficacy
Safety
Immunogenicity
Trivalent
Inactivated
Influenza-Like Illness
Vaccination

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

ClinicalTrials.gov processed this record on November 24, 2014