A Dose-ranging Pediatric Study of an Adjuvanted Pandemic Influenza Vaccine

Study Overview
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Brief Summary
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The purpose/aim of this study is to evaluate responses to vaccination with different MF59 adjuvanted pandemic influenza vaccine formulations of an H5N1 vaccine in pediatric subjects. The data from this study are intended to provide information for health authorities to determine the best formulation for protection of children during the pandemic phase of a pandemic of a novel pandemic influenza strain (World Health Organization (WHO) 2013).

Official Title
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A Phase 2, Randomized, Observer-Blind, Multicenter Study to Evaluate the Immunogenicity and Safety of Several Doses of Antigen and MF59 Adjuvant Content in a Monovalent H5N1 Pandemic Influenza Vaccine in Healthy Pediatric Subjects 6 Months to < 9 Years of Age

Conditions
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Influenza, Human

Intervention / Treatment
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* Biological: H5N1 antigen combined with MF59 adjuvant


Participation Criteria
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Eligibility Criteria
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INCLUSION Healthy male and female subjects of 6 months through <9 years of age on the day of informed consent/assent. Documented consent provided by the subject's parent(s)/LAR(s) have voluntarily given written informed consent/assent after the nature of the study has been explained according to local regulatory requirements, prior to study entry. Subject's parent(s)/LAR(s) able to comprehend and comply with all study procedures, and available for all clinic visits and telephone contacts scheduled in the study. Subjects must provide a baseline blood sample within 10 days prior to the Day 1 vaccination. EXCLUSION Each subject must not have: Progressive, unstable or uncontrolled clinical conditions. Hypersensitivity, including allergy, to any component of vaccines, medicinal products or medical equipment whose use is foreseen in this study. Clinical conditions representing a contraindication to intramuscular vaccination and blood draws, ie, Subjects who have had a fever (body temperature measurement ≥ 38°C) within three days prior to vaccination. The subject may return for vaccination after they have been free of fever for three days. History of epilepsy or convulsions (excluding febrile convulsions). A subject who has any medical condition meeting the definition of AESI defined for the purposes of this trial (see appendix A). Subjects who have received antipyretic medication within the past 24 hours prior to vaccination. The subject may return for vaccination after a period of 24 hours has passed since the administration of an antipyretic. 4. Abnormal function of the immune system resulting from: Clinical conditions. Systemic administration of corticosteroids (PO/IV/IM) for more than 14 consecutive days within 90 days prior to informed consent/assent. Topical, inhaled and intranasal corticosteroids are permitted. Intermittent use (one dose in 30 days) of intra-articular corticosteroids are also permitted. Administration of antineoplastic and immunomodulating agents or radiotherapy from within 90 days prior to informed consent/assent. 5. Suspicion of pandemic influenza illness within past six months or have ever received previous pandemic H5N1 flu vaccination. 6. Received immunoglobulins or any blood products within 180 days prior to informed consent/assent. 7. Received an investigational or non-registered medicinal within 30 days prior to informed consent/assent. 8. Children of study site staff (this includes research or clinic staff) or children who are otherwise related to study site staff or have household members who are study site staff. Study site staff are employees with direct or indirect contact with study subjects and/or have access to any study documents containing subject information. This would include receptionists, persons scheduling appointments or making screening calls, regulatory specialists, laboratory technicians, medical assistants, document scanners, etc. study personnel as an immediate family or household member. 9. Any other clinical condition that, in the opinion of the investigator, might interfere with the results of the study or pose additional risk to the subject due to participation in the study. 10. Individuals who received any other vaccines within 14 days (for inactivated vaccines) or 28 days (for live vaccines) prior to enrolment in this study or who are planning to receive any vaccine prior to day 43. Following day 43 other vaccines may be administered, including seasonal flu.

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 8 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Lowest dose, less-adjuvanted vaccine<br>Two consecutive intramuscular (IM) administrations (Day 1 and Day 22) | Biological: H5N1 antigen combined with MF59 adjuvant<br>* Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart<br>* Other names: aH5N1;|
| Experimental: Low dose, less-adjuvanted vaccine<br>Two consecutive (IM) administrations (Day 1 and Day 22) | Biological: H5N1 antigen combined with MF59 adjuvant<br>* Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart<br>* Other names: aH5N1;|
| Experimental: Mid dose, less-adjuvanted vaccine<br>Two consecutive (IM) administrations (Day 1 and Day 22) | Biological: H5N1 antigen combined with MF59 adjuvant<br>* Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart<br>* Other names: aH5N1;|
| Experimental: Lowest dose, adjuvanted vaccine<br>Two consecutive (IM) administrations (Day 1 and Day 22) | Biological: H5N1 antigen combined with MF59 adjuvant<br>* Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart<br>* Other names: aH5N1;|
| Experimental: Low dose, adjuvanted vaccine<br>Two consecutive (IM) administrations (Day 1 and Day 22) | Biological: H5N1 antigen combined with MF59 adjuvant<br>* Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart<br>* Other names: aH5N1;|
| Experimental: Mid dose, adjuvanted vaccine<br>Two consecutive (IM) administrations (Day 1 and Day 22) | Biological: H5N1 antigen combined with MF59 adjuvant<br>* Eligible subjects will be stratified by age at the time of enrollment into one of 2 age cohorts and within each age cohort will be randomly assigned (equally) to 1 of 6 study vaccine groups. Subjects in each study vaccine group will be scheduled to receive 2 injections of aH5N1 vaccine 3 weeks apart<br>* Other names: aH5N1;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety Endpoint 1: Percentages of subjects with solicited local and systemic adverse events (AEs) |  | 7 days post-vaccination | 
| Safety Endpoint 2: Percentages of subjects with any unsolicited AEs |  | 21 days post-vaccination | 
| Safety Endpoint 3: Percentages of subjects reporting serious adverse events (SAEs), new-onset chronic disease (NOCD), adverse events of special interest (AESI),and AEs leading to vaccine and/or study withdrawal |  | 387 days post-vaccination | 
| Primary Immunogenicity Endpoint 1a: Geometric Mean Titers (GMT), as measured by Hemagglutination Inhibition (HI) and Microneutralization (MN) assay against the homologous H5N1 strain |  | 2 time points post-vaccination - baseline and Day 22 | 
| Primary Immunogenicity Endpoint 1b: (GMR), as measured by HI and MN assays against the homologous H5N1 strain |  | Measuring ratios at 2 time points post-vaccination - Day 22/Day 1 and Day 43/Day 1 | 
| Primary Immunogenicity Endpoint 1c: Percentage of subjects achieving Seroconversion (non-detectable to ≥1:40, or 4-fold increase from a detectable Day 1 titer) |  | 2 time points post-vaccination - Day 22 and Day 43 | 
| Primary Immunogenicity Endpoint 1d Percentage of subjects achieving seroconversion with a titer ≥ 1:40 |  | 2 time points post-vaccination - Day 22 and Day 43 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Secondary Immunogenicity Endpoint 1a: GMTs, as measured by HI and MN |  | 2 time points post-vaccination - Day 1 and Day 202 | 
| Secondary Immunogenicity Endpoint 1b: (GMR), as measured by MN |  | Measuring a ratio at a 1 time point - Day 202/Day 1 | 
| Secondary Immunogenicity Endpoint 1c: Percentage of subjects achieving seroconversion (non-detectable to ≥1:40, or 4- fold increase from a detectable Day 1 titer) |  | On Day 202 - from a detectable Day 1 titer | 
| Secondary Immunogenicity Endpoint 1d: Percentage of subjects achieving seroconversion with a titer ≥1:40 |  | On Day 202 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pandemic, Influenza, Vaccine, MF59, Adjuvant