A Study of Different Formulations of an A/H1N1 Pandemic Vaccine in Healthy Children Aged 6 Months to 9 Years

Study Overview
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Brief Summary
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The purpose of the study is to evaluate different doses of the Influenza A/H1N1 pandemic vaccine in toddlers and children. Primary Objectives: To describe the immunogenicity of the candidate vaccines after each injection. To describe the safety of the candidate vaccines after each injection.

Detailed Description
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Participants will receive two injections of their randomized vaccine on Day 0 and Day 21, respectively.

Official Title
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Immunogenicity and Safety of Multiple Formulations of an A/H1N1 Pandemic Vaccine in Healthy Subjects Aged 6 Months to 9 Years

Conditions
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Influenza, Swine-origin A/H1N1 Influenza

Intervention / Treatment
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* Biological: Monovalent Subvirion A/H1N1 Influenza vaccine
* Biological: Monovalent Subvirion A/H1N1 Influenza vaccine
* Biological: Normal saline solution (placebo)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria : All subjects: Provision of Informed Consent Form signed by the subject's parent(s)/legal representative (and by an independent witness if required by local regulations). In addition, provision of Assent Form signed by subjects aged 7 to 9 years Subject and parent/guardian are able to attend all scheduled visits and to comply with all trial procedures Subjects aged 3 to 9 years: Healthy children aged 3 to 9 years on the day of inclusion Subjects aged 6 to 35 months: Healthy infants and toddlers aged 6 to 35 months on the day of inclusion Born at full term of pregnancy (≥ 37 weeks) and with a birth weight ≥ 2.5 kg Exclusion Criteria : Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination Planned participation in another clinical trial during the present trial period Receipt of any vaccine in the 4 weeks preceding the trial vaccination Planned receipt of any vaccine prior to the Day 42 blood sample Receipt of blood or blood-derived products in the past 3 months which might interfere with the assessment of immune response Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) Self-reported seropositivity for Human Immunodeficiency Virus (HIV), Hepatitis B surface antigen, or Hepatitis C Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances Self reported thrombocytopenia contraindicating intramuscular (IM) vaccination Bleeding disorder or receipt of anticoagulants in the 3 weeks preceding inclusion contraindicating IM vaccination Deprived of freedom by an administrative or court order, or in an emergency setting, or hospitalized involuntarily Chronic illness that in the opinion of the investigator, is at a stage where it might interfere with trial conduct or completion Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator. Any confirmed case of influenza (including swine-origin A/H1N1 Influenza) since March 2009 Personal or family history of Guillain-Barré syndrome Active neoplastic disease or a history of any hematologic malignancy Known seizure/epilepsy history and/or taking anti-seizure medication Receipt of psychiatric drugs. Subjects receiving a single antidepressant drug and stable for at least 3 months prior to enrollment, without decompensating symptoms will be allowed to enroll in the study Febrile illness (temperature ≥ 100.4°F [≥ 38.0°C]) or moderate or severe acute illness/infection (according to investigator judgment) on the day of vaccination

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 9 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: A/H1N1 Vaccine Group 1<br>Participants will receive A/H1N1 vaccine formulation 1 | Biological: Monovalent Subvirion A/H1N1 Influenza vaccine<br>* 0.5 mL, Intramuscular Day 0 and Day 21 (3 to 9 years); 0.25 mL, Intramuscular on Day 0 and Day 21 (6 months to 35 Months)<br>|
| Experimental: A/H1N1 Vaccine Group 2<br>Participants will receive A/H1N1 vaccine formulation 2 | Biological: Monovalent Subvirion A/H1N1 Influenza vaccine<br>* 0.5 mL, Intramuscular Day 0 and Day 21 (3 to 9 years); 0.25 mL, Intramuscular on day 0 and Day 21 (6 months to 35 Months)<br>|
| Placebo Comparator: Placebo Group<br>Participants will receive a placebo vaccine | Biological: Normal saline solution (placebo)<br>* 0.5 mL, Intramuscular Day 0 and Day 21 (3 to 9 years); 0.25 mL, Intramuscular on day 0 and Day 21 (6 months to 35 Months)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Antibody Titers ≥ 10 1/Dilution (1/Dil) Against A/California (H1N1 Vaccine) Strain - Age 6 to 35 Months | Pre- and post-vaccination antibody titers were determined by the hemagglutination inhibition (HAI) test. | Pre-vaccination (Day 0) and 21 days post-vaccination | 
| Number of Participants With Antibody Titers ≥ 40 1/Dilution (1/Dil) Against A/California (H1N1 Vaccine) Strain - Age 6 to 35 Months | Seroprotection: Antibody titer of ≥ 40 1/dil. Antibody titers were determined by the hemagglutination inhibition (HAI) test. | Pre-vaccination (Day 0) and Day 21 post-vaccination | 
| Geometric Mean Titers (GMT) of Antibodies Against A/California (H1N1 Vaccine) Strain - Age 6 to 35 Months | Pre-vaccination and post-vaccination antibody titers were determined by the hemagglutination inhibition (HAI) test. | Pre-vaccination (Day 0) and 21 days post-vaccination | 
| Number of Participants With Antibody Titers ≥ 10 1/Dilution (1/Dil) Against A/California (H1N1 Vaccine) Strain - Age 3 to 9 Years | Pre-vaccination and post-vaccination antibody titers were determined by the hemagglutination inhibition (HAI) test. | Pre-vaccination (Day 0) and 21 days post-vaccination | 
| Number of Participants With Antibody Titers ≥ 40 1/Dilution (1/Dil) Against A/California (H1N1 Vaccine) Strain - Age 3 to 9 Years | Seroprotection: Antibody titer ≥ 40 1/dil. Antibody titers were determined by the hemagglutination inhibition (HAI) test. | Pre-vaccination (Day 0) and Day 21 post-vaccination | 
| Geometric Mean Titers (GMT) of Antibodies Against A/California (H1N1 Vaccine) Strain - Age 3 to 9 Years | Pre-vaccination and post-vaccination antibody titers were determined by the hemagglutination inhibition (HAI) test. | Pre-vaccination (Day 0) and Day 21 post-vaccination | 
| Number of Participants With At Least One Solicited Injection Site or Systemic Reaction Following Vaccination - Age 6 to 23 Months | Solicited Injection Site Reactions: Tenderness, erythema (redness), swelling, induration (hardening), ecchymosis (bruising). Solicited systemic reactions: Fever (temperature), vomiting, crying abnormal, drowsiness, appetite lost, irritability. | Days 0 to 7 post-vaccination | 
| Number of Participants With At Least One Solicited Injection Site or Systemic Reaction Following Vaccination - Age 24 to 35 Months | Solicited Injection Site Reactions: Pain, erythema (redness), swelling, induration (hardening), ecchymosis (bruising). Solicited systemic reactions: Fever (temperature), headache, malaise (feeling unwell), myalgia (muscle aches and pains), shivering. | Days 0 to 7 post-vaccination | 
| Number of Participants With At Least One Solicited Injection Site or Systemic Reaction Following Vaccination - Age 3 to 9 Years | Solicited Injection Site Reactions: Pain, erythema (redness), swelling, induration (hardening), ecchymosis (bruising). Solicited systemic reactions: Fever (temperature), headache, malaise (feeling unwell), myalgia (muscle aches and pains), shivering. | Days 0 to 7 post vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Influenza, Pandemic Flu, Swine-origin A/H1N1 Influenza, Children