Safety and Immunogenicity of Two Doses of aH5N1 Vaccine in Adult and Elderly Subjects With and Without Underlying Medical Conditions

Study Overview
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Brief Summary
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Evaluate the safety, immune response and reactogenicity of aH5N1 vaccination in adult (18 through 60 years of age) and elderly (≥61 years of age) subjects with and without underlying medical conditions.

Official Title
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Phase III, Stratified, Randomized, Controlled, Observer-Blind, Multicenter Study to Evaluate the Safety, Tolerability, and Immunogenicity of Two Doses of aH5N1 When Administered to Adult and Elderly Subjects With and Without Underlying Medical Conditions.

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: Novartis Investigational H5N1 vaccine
* Biological: Novartis Investigational H5N1 vaccine
* Biological: Novartis Seasonal Influenza Vaccine
* Biological: Novartis Seasonal Influenza Vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - Male and female individuals 18 years of age and older at the time of enrollment who are mentally competent, willing and able to understand the nature and risks of the proposed study, and able to sign the consent form prior to study entry; Individuals who are able to comply with all study procedures and requirements; Healthy volunteers and volunteers specifically with underlying COPD, cardiovascular disease, diabetes mellitus, peripheral vascular disease, or renal impairment may be eligible; Please contact the site for additional eligibility criteria. Exclusion Criteria: Individuals who are not able to follow all the required study procedures for the whole period of the study; Individuals with behavioral or cognitive impairment or psychiatric disease that, in the opinion of the Investigator, may interfere with the subject's ability to participate in the study; Please contact the site for additional eligibility criteria.

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: aH5N1 adult<br>aH5N1 healthy and non-healthy adults | Biological: Novartis Investigational H5N1 vaccine<br>* 2 doses of 0.5 ml, 3 weeks apart<br>|
| Experimental: Arm 2: aH5N1 elderly<br>aH5N1 healthy and non-healthy elderly | Biological: Novartis Investigational H5N1 vaccine<br>* 2 doses of 0.5 ml, 3 weeks apart<br>|
| Active Comparator: Arm 3: aTIV adult<br>aTIV healthy and non-healthy adults | Biological: Novartis Seasonal Influenza Vaccine<br>* 2 doses of 0.5 ml, 3 weeks apart<br>|
| Active Comparator: Arm 4: aTIV elderly<br>aTIV healthy and non-healthy elderly | Biological: Novartis Seasonal Influenza Vaccine<br>* 2 doses of 0.5 ml, 3 weeks apart<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of subjects achieving seroconversion | Seroconversion is defined as hemagglutination inhibition (HI) ≥1:40 for subjects who were seronegative at baseline [day 1 HI titer <1:10] or a minimum 4-fold increase in HI titer for subjects who were seropositive at baseline [day 1 HI titer ≥1:10]) | day 43 | 
| Geometric mean ratios (GMRs) as determined by HI assay |  | day 43 | 
| Percentage of subjects with an HI titer ≥1:40 |  | day 43 | 
| Solicited and unsolicited adverse events | In pooled age groups 18 years of age and older subjects who are healthy or with underlying medical condition who have received aTIV or aH5N1 vaccine. | day 202 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric mean titers (GMTs) as determined by HI | HI assay: homologous antibody responses to aH5N1 vaccine 3 weeks after first vaccination (day 22) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition | day 1 | 
| Geometric mean ratios (GMRs) as determined by SRH |  | day 22 | 
| Percentage of subjects with an HI titer ≥1:40 |  | day 22 | 
| Percentage of subjects achieving seroconversion | Seroconversion is defined as SRH area ≥25 mm2 for subjects who were seronegative at baseline [day 1 SRH area ≤3.997 mm2] or a significant increase [at least 50% increase] in SRH area for subjects who were seropositive at baseline [SRH area >3.997 mm2]) | day 22 | 
| Percentage of subjects with geometric mean area ≥25 mm2 |  | day 43 | 
| Percentage of subjects achieving seroconversion | Seroconversion is defined as HI ≥1:40 for subjects who were seronegative at baseline [day 1 HI titer <1:10] or a minimum 4-fold increase in HI titer for subjects who were seropositive at baseline [day 1 HI titer ≥1:10]) | day 22 | 
| GMTs as determined by SRH | Serial radial haemolysis (SRH) assay: homologous antibody responses to aH5N1 vaccine 3 weeks after first and second vaccinations (day 22 and day 43) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition | day 43 (3 weeks after the second vaccination) | 
| GMRs as determined by HI |  | day 22 | 
| Geometric mean titers (GMTs) as determined by HI | HI assay: homologous antibody responses to aH5N1 vaccine 3 weeks after first vaccination (day 22) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition | day 43 (3 weeks after the second vaccination) | 
| Geometric mean titers (GMTs) as determined by HI | HI assay: homologous antibody responses to aH5N1 vaccine 3 weeks after first vaccination (day 22) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition | day 22 (3 weeks after the first vaccination) | 
| GMRs as determined by SRH |  | day 43 | 
| Percentage of subjects with an HI titer ≥1:40 |  | day 1 | 
| Percentage of subjects with geometric mean area ≥25 mm2 |  | day 1 | 
| Percentage of subjects with geometric mean area ≥25 mm2 |  | day 22 | 
| Percentage of subjects achieving seroconversion | Seroconversion is defined as SRH area ≥25 mm2 for subjects who were seronegative at baseline [day 1 SRH area ≤3.997 mm2] or a significant increase [at least 50% increase] in SRH area for subjects who were seropositive at baseline [SRH area >3.997 mm2]) | day 43 | 
| GMTs as determined by SRH | Serial radial haemolysis (SRH) assay: homologous antibody responses to aH5N1 vaccine 3 weeks after first and second vaccinations (day 22 and day 43) according to CHMP immunogenicity criteria in adult and elderly subjects who are healthy or with underlying medical condition | day 1 | 
| Geometric mean ratios (GMRs) as determined by SRH |  | day 43 (3 weeks after the second vaccination) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, H5N1, aH5N1, H5N1 vaccine, Pandemic Influenza vaccine, MF59, Adjuvant, Avian flu, Underlying medical conditions, Underlying cardiovascular medical condition, Pandemic vaccine, Charlson Comorbidity Index (CCI), Adjuvanted vaccine