Safety and Immunogenicity of A/H1N1-SOIV (Swine Flu) Vaccine With and Without Adjuvant in Children (3 to < 9 Years)

Study Overview
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Brief Summary
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This study will evaluate the safety and immunogenicity of different combinations of A/H1N1 S-OIV (swine flu) vaccine in healthy young children.

Official Title
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A Pivotal Randomized, Single-Blind, Dose-Finding Study to Evaluate Immunogenicity, Safety and Tolerability of Different Formulations of an Adjuvanted and Non-Adjuvanted Egg-Derived, Inactivated Novel Swine Origin A/H1N1 Monovalent Subunit Influenza Virus Vaccine in Healthy Pediatric Subjects 3 to < 9 Years of Age

Conditions
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Influenza

Intervention / Treatment
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* Biological: MF59-eH1N1


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Children 3 to < 9 years of age in good health as determined by medical history, physical assessment and clinical judgement of the investigator and without influenza within the past 6 months. Exclusion Criteria: History of serious disease. History of serious reaction following administration of vaccine or hypersensitivity to vaccine components. Known or suspected impairment/alteration of immune function. Receipt or planned receipt of seasonal trivalent influenza vaccine within 1 week before or after each study vaccination. For additional entry criteria, please refer to protocol.

Ages Eligible for Study
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Minimum Age: 3 Years
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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 3.75_(50)MF59<br>3.75 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22 | Biological: MF59-eH1N1<br>* MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).<br>|
| Experimental: 7.5_(0) MF59<br>7.5 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22 | Biological: MF59-eH1N1<br>* MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).<br>|
| Experimental: 7.5_(50) MF59<br>7.5 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22 | Biological: MF59-eH1N1<br>* MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).<br>|
| Experimental: 7.5_(100) MF59<br>7.5 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22 | Biological: MF59-eH1N1<br>* MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).<br>|
| Experimental: 15_(0) MF59<br>15 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22 | Biological: MF59-eH1N1<br>* MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).<br>|
| Experimental: 15_(50)MF59<br>15 μg A/H1N1 antigen with 50% MF59 adjuvant administered on study day 1 and day 22 | Biological: MF59-eH1N1<br>* MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).<br>|
| Experimental: 15_(100) MF59<br>15 μg A/H1N1 antigen with 100% MF59 adjuvant administered on study day 1 and day 22 | Biological: MF59-eH1N1<br>* MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).<br>|
| Experimental: 30_(0) MF59<br>30 μg A/H1N1 antigen without MF59 adjuvant administered on study day 1 and day 22 | Biological: MF59-eH1N1<br>* MF59 adjuvanted with egg-derived A/H1N1 antigen. MF59-eH1N1 vaccine is the same vaccine as A/H1N1-SOIV (Swine Origin A/H1N1 Influenza Virus).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Antibody Responses According to the Hemagglutinin Inhibition (HI) Assay After the First and Second Vaccinations | HI antibody assay (used to assess immune responses in subjects following vaccination) according to the Center for Biologics Evaluation and Research (CBER) guidance for <65 years of age: The lower bound of the two-sided 95% Confidence Interval (CI) for the percentages of subjects achieving seroconversion for HI antibody should be ≥ 40% and the lower bound of the two-sided 95% CI for the percentages of subjects achieving an HI antibody titer ≥ 1:40 should be ≥ 70%. Both criteria (seroconversion and HI antibody titer ≥ 40) had to be fulfilled to establish immunogenicity. PPS Day 1-29 analysis set: N= 143, 149, 149, 146, 147, 147, 144, and 144 for Groups A, B, C, D, E, F,G,and H respectively. PPS Day 1-202 analysis set: N= 82, 85, 84, 84, 86, 87, 82, and 79 for Groups A, B, C, D, E, F, G, and H respectively. PPS Day 1-387 analysis set: N= 55, 63, 61, 58, 61, 65, 59, and 63 for Groups A, B, C, D, E, F, G, and H respectively. | Day 22, Day 29, Day 43, Day 202 and Day 387 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Geometric Mean Titer (GMT) After Each Vaccination by Vaccine Group | Immunogenicity was measured in terms of GMTs After each vaccination by vaccine Group. PPS Day1-29 analysis set: N=143, 149, 149, 146, 147, 147, 144, and 144 for Groups A, B, C, D, E, F, G, and H respectively. PPS Day 1-202 analysis set. N= 82, 85, 84, 84, 86, 87, 82, and 79 for Groups A, B, C, D, E, F, G, and H respectively. | Day 22, Day 29, Day 43, Day 202 and Day 387 | 
| Antibody Responses With and Without Seasonal Influenza Vaccination for Year 2009 to 2010. | HI antibody assay (used to assess immune responses in subjects following vaccination) according to the Committee for Medicinal Products for Human Use (CHMP) guidance: in adults ages 18 to 60 years are:The percentage of subjects with seroconversion or significant increase in HI antibody is > 40%.The percentage of subjects achieving an HI titer ≥ 40 is > 70% and The GMR is > 2.5. All 3 criteria (seroconversion/significant increase, HI antibody titer ≥ 40, and GMR) had to be fulfilled to establish immunogenicity.Subgroup analysis based on receipt of recent seasonal vaccination. Comparison between subjects previously vaccinated versus not vaccinated with seasonal influenza vaccines.Subgroups without recent seasonal flu vaccine:PPS Day1, Day 1-22 and Day1-43 analysis set. N= 141, 147, 150, 148, 146, 146, 150, and 146 for Groups A, B, C, D, E, F, G, and H respectively. PPS Day 1-29 analysis set. N= 132, 140, 143, 139, 138, 136, 139, and 138 for Groups A, B, C, D, E, F, G,and H respectively. | Day 22, Day 29, Day 43 | 
| Geometric Mean Titers (GMTs) With and Without Seasonal Influenza Vaccination for Year 2009 to 2010 | Immunogenicity was measured in terms of GMTs of Subgroups with receipt of recent seasonal vaccination. Comparison between subjects previously vaccinated versus not vaccinated with seasonal influenza vaccines Subgroups without recent seasonal flu vaccine: PPS Day 1, Day 1-22 and Day 1-43 analysis set. N= 141, 147, 150, 148, 146, 146, 150, and 146 for Groups A, B, C, D, E, F, G, and H respectively. PPS Day 1-29 analysis set. N= 132, 140, 143, 139, 138, 136, 139, and 138 for Groups A, B, C, D, E, F,G, and H respectively. Subgroups with recent seasonal flu vaccine:PPS Day 1-22 and Day 1-43 analysis set. N= 11, 9, 6, 8, 9, 11, 6, and 7 for Groups A, B, C, D, E, F, G,and H respectively. PPS Day 1-29 analysis set. N= 11, 9, 6, 7, 9, 11, 5, and 6 for Groups A, B, C, D, E, F, G, and H respectively | Day 1, Day 22, Day 29, Day 43 | 
| Antibody Response Based on Baseline Seropositivity | Subgroup analysis based on Subjects with seropositivity (pre-vaccination HI antibody titer < 1:10 and prevaccination HI antibody titer ≥ 1:10) at baseline. Subgroups with baseline HI titer < 1:10: PPS Day 1-29 analysis set. N= 104, 116, 111, 107, 109, 113,120, and 103 for Groups A, B, C, D, E, F, G, and H respectively. Subgroups with baseline HI titer ≥ 1:10: PPS Day 1-29 analysis set. N= 39, 33, 38, 39, 38, 34, 24, and 41 for Groups A, B, C, D, E, F, G, and H respectively. | Day 22, Day 29 and Day 43 | 
| Geometric Mean Titers (GMTs) Based on Baseline Seropositivity | Subgroup analysis based on Subjects with seropositivity (pre-vaccination HI antibody titer < 1:10 and prevaccination HI antibody titer ≥ 1:10) at baseline. Immunogenicity responses in subjects who are seropositive (A/H1N1 2009 HI titer ≥ 1:10) at Baseline [Day 1 (pre-vaccination)] as compared to those who are seronegative (HI titer < 1:10). | Day 1, Day 22, Day 29, Day 43 | 
| Number of Subjects Reporting Solicited Local and Systemic Symptoms After the First Vaccination | Solicited local and systemic reactions were assessed after the first vaccination by vaccine group. Source Vocabulary Name: MedDRA (13.1). | 7 days after first vaccination | 
| Number of Subjects Reporting Solicited Local and Systemic Symptoms After the Second Vaccination | Solicited local and systemic reactions were assessed after the second vaccination by vaccine group.Source Vocabulary Name: MedDRA (13.1) | 7 days after second vaccination | 
| Number of Participants Reporting Unsolicited Adverse Events (AEs) | Safety was measured in terms of the Number of Participants Reporting Unsolicited AEs. Source Vocabulary Name: MedDRA (13.1) | Safety monitoring periods were the Primary Period: Day 1 (1st vaccination) through ≤21 days post second vaccination, and the Follow-up Period: >21 Days post second vaccination to 12 months after second vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Adjuvant, Swine Flu, Flu, Vaccine, Children