Safety and Immunogenicity of Inactivated Influenza Virus Vaccine Among Healthy Children 6-12 Weeks of Age

Study Overview
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Brief Summary
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Study of the safety and immunogenicity (antibody producing capability) comparing inactivated influenza vaccine to placebo given to infants at 2 and 3 months of age. Infants will receive inactivated influenza vaccine at the same time as other vaccines on the routine immunization schedule. Infants will be randomized at enrollment to receive inactivated influenza vaccine or placebo at a 2:1 ratio. This study is double-blind, randomized, and placebo-controlled.

Detailed Description
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Methods: A double-blind, randomized, placebo-controlled trial was conducted in 1375 healthy US infants 6-12 weeks of age. Subjects received either 2 doses of trivalent inactivated influenza vaccine (TIV, Fluzone®, sanofi pasteur 2005-6 pediatric formulation) (N=915) or placebo (N=460) 1 month apart, along with indicated concomitant vaccines. Solicited adverse events were collected for 7 days following each vaccination, unsolicited adverse events for 28 days, and serious adverse events for 6 months. Hemagglutination inhibition antibodies to all 3 vaccine strains were measured following the second TIV/placebo dose. Results: No significant differences were seen between TIV and placebo groups for any safety outcomes. Fever ≥38oC rectal within 3 days of vaccination was seen in 11.2% vs 11.7% of TIV vs placebo recipients. Serious adverse events within 28 days of vaccine/placebo were reported in 1.9% of TIV and 1.5% of placebo recipients; only one (hypersensitivity reaction in a TIV recipient) was considered vaccine-related. Significantly increased antibody responses (p<0.001) were seen against all 3 strains in TIV recipients by titer ≥ 1:40 or geometric mean titer (GMT) (p<0.001). Altogether, 50% of infants had antibody titers ≥ 1:40 for H1N1, 86% for H3N2, and 11% for B compared with 7%, 10%, and 0.3% in the placebo group. The reciprocal GMT for influenza recipients was 33, 95, and 11 for H1N1, H3N2, and B vs. 7, 9, and 5 for placebo recipients. Over 90% of infants who received TIV had antibody ≥ 1:40 for at least one vaccine strain and 49.6% for 2 strains, vs. 16.4% and 0.9% in the placebo group. Conclusions: TIV administered to young infants beginning at 6-12 weeks of age is safe and immunogenic.

Official Title
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Safety and Immunogenicity of Fluzone Influenza Virus Vaccine (2005-2006 Formulation) Among Healthy Children 6 to 12 Weeks of Age

Conditions
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Inactivated Influenza Vaccine

Intervention / Treatment
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* Biological: 2005-2006 trivalent inactivated influenza vaccine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 42 to 84 days on the day of inclusion Full term (born at >=36 weeks with birth weight >=2.5 kg Considered to be in good health Parental consent obtained and available Available for the study duration (6 months) Exclusion Criteria: Reported allergy to egg proteins, chicken proteins Previous history of influenza vaccination or disease Receipt of any vaccine other than Hepatitis B prior to enrollment Acute illness with rectal temperature >= 38.0 (defer enrollment) Known bleeding disorder Participation in other interventional clinical trial within 30 days prior to enrollment

Ages Eligible for Study
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Minimum Age: 42 Days
Maximum Age: 84 Days

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 |
| --- | --- |
| Placebo Comparator: 1<br>0.25 ml normal saline placebo given as injection to infants at 2 and 3 months of age | Biological: 2005-2006 trivalent inactivated influenza vaccine<br>* Children enrolled at 6-12 weeks to receive first dose, 0.25 ml of trivalent inactivated influenza vaccine, 2005-6 pediatric Fluzone formulation (sanofi pastuer), with concomitant routine pediatric vaccines. Second dose administered 4 weeks later.<br>|
| Experimental: 2<br>2005-6 Fluzone, pediatric formulation of trivalent inactivated influenza vaccine (sanofi pasteur) administered to infants at 2 and 3 months of age | Biological: 2005-2006 trivalent inactivated influenza vaccine<br>* Children enrolled at 6-12 weeks to receive first dose, 0.25 ml of trivalent inactivated influenza vaccine, 2005-6 pediatric Fluzone formulation (sanofi pastuer), with concomitant routine pediatric vaccines. Second dose administered 4 weeks later.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| To demonstrate the safety of Fluzone vaccine administered to 2-month old children |  | within 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza vaccine, infants, safety, immunogenicity