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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Influenza

Intervention / Treatment
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* Biological: Cell culture-derived influenza vaccine
* Biological: Egg-derived influenza virus vaccine
* Biological: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: subjects 18 to 49 years of age; in good health as determined by medical history and physical examination; able and willing to provide written informed consent prior to any study procedure; 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: 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; 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; 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; history of Guillain-Barré syndrome; bleeding diathesis; 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; receipt of another vaccine within 2 weeks (for inactivated vaccines) or 4 weeks (for live vaccines) prior to Visit 1; laboratory-confirmed influenza disease within 6 months prior to Visit 1; receipt of an influenza vaccine within 6 months prior to Visit 1 or plans to receive influenza vaccine outside of this study; experienced a temperature (≥100.0°F / ≥37.8°C) and/or any acute illness within 3 days prior to study vaccination; pregnant or breast-feeding female; 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; 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; 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.; 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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 49 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CCI<br>Subjects received one dose of cell culture-derived influenza vaccine. | Biological: Cell culture-derived influenza vaccine<br>* One dose (0.5 mL) of cell culture-derived influenza vaccine, administered in the deltoid muscle.<br>|
| Experimental: IVV<br>Subjects received one dose of the trivalent egg-derived influenza vaccine. | Biological: Egg-derived influenza virus vaccine<br>* One dose (0.5 mL) of the trivalent egg-derived influenza virus vaccine, administered in the deltoid muscle.<br>|
| Placebo Comparator: Placebo<br>Subjects received one dose of phosphate buffered solution (PBS). | Biological: Placebo<br>* One dose (0.5 mL) of phosphate buffered solution.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Culture-Confirmed Influenza Illness Caused by Vaccine-like Strains | 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. | 6 Months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Culture-confirmed Influenza Illness Caused by Non-Vaccine Like Strains | 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. | 6 Months | 
| Number of Subjects With Influenza Caused by Vaccine-like and Non-vaccine-like Strains | 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. | 6 Months | 
| Influenza-Associated Days in Bed, All Subjects | The number of subjects in this analysis included all subjects in the per protocol efficacy population. | 6 Months | 
| Influenza-Associated Days in Bed, Subset of Subjects With Virus-Confirmed- Influenza | The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza. | 6 Months | 
| Number Of Medical Visits (Inpatient and Outpatient) Due to Influenza Illness or Symptoms of Influenza, All Subjects | The number of subjects in this analysis included all subjects in the per protocol efficacy population. | 6 Months | 
| Number of Medical Visits (Inpatient and Outpatient), Subset of Subjects With Virus-Confirmed-Influenza | The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza. | 6 Months | 
| Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost Due to Influenza Disease, All Subjects | The number of subjects in this analysis included all subjects in the per protocol efficacy population. | 6 Months | 
| Number of Days of Usual Activity (i.e. Job, School,Household/Family/Community Activities) Lost, Subset of Subjects With Virus-Confirmed-Influenza | The analysis was done among the subset of subjects in the per protocol efficacy population who had culture-confirmed influenza. | 6 Months | 
| Percentages of Subjects Who Achieved HI Titers ≥40 After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | 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%. | Before vaccination (day 1) and three weeks after vaccination (day 22) | 
| Percentages of Subjects Achieving Seroconversion After One Vaccination of Either Cell-culture Derived or Egg-derived Influenza Vaccine or Placebo | 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%. | Three weeks after vaccination (day 22) | 
| Number of Subjects Reported Solicited Local and Systemic Reactions up to 7 Days After Vaccination | The solicited local and systemic reactogenicity were collected up to 7 days after vaccination for all three vaccine groups. | Up to 7 days post vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Flu, Cell Culture-Derived, Egg-Derived, Healthy Adults, Efficacy, Safety, Immunogenicity, Trivalent, Inactivated, Influenza-Like Illness, Vaccination