Safety and Immunogenicity of a Four Influenza Vaccines in Children Ages 6 Months Old to Less Than 48 Months Old

Study Overview
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Brief Summary
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To evaluate the safety and immunogenicity of four influenza vaccines in children 6 months to < 48 months of age

Official Title
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A Phase I/II, Randomized, Observer-Blind, Multicenter Study to Evaluate Immunogenicity and Safety of Four Influenza Vaccines in Healthy Pediatric Subjects 6 to < 48 Months of Age.

Conditions
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Influenza

Intervention / Treatment
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* Biological: Trivalent influenza vaccine (TIVc)
* Biological: Trivalent influenza vaccine-licensed


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy subject, male or female, 6 through < 48 months of age at the time of enrollment, who has never previously received an influenza vaccine Individual who has a parent or guardian that can give written informed consent after understanding the nature of the study and are available for follow-up Exclusion Criteria: Individuals recently vaccinated against influenza Subjects with contraindications to receive influenza vaccine

Ages Eligible for Study
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Minimum Age: 6 Months
Maximum Age: 48 Months

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: TIVc-High Dose<br>Subjects (6 to <48 months old) received two doses of 0.75 mL of TIVc vaccine | Biological: Trivalent influenza vaccine (TIVc)<br> <br> |
| Experimental: TIVc-Full Dose<br>Subjects(6 to <48 months old) received two doses of 0.50 mL of TIVc vaccine | Biological: Trivalent influenza vaccine (TIVc)<br> <br> |
| Experimental: TIVc- Half Dose<br>Subjects (6 to <48 months old)received two doses of 0.25 mL of TIVc vaccine | Biological: Trivalent influenza vaccine (TIVc)<br> <br> |
| Active Comparator: TIVe<br>Subjects (6 to <48 months old) received two doses of TIVe vaccine(IM/0.25mL -for ages 6 to <36 months and IM/ 0.5 mL -for ages 36 to <48 months) | Biological: Trivalent influenza vaccine-licensed<br>* Licensed influenza vaccine<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Ratios of Geometric Mean Titer (GMT) in Subjects (6 to <48 Months Old) After Receiving Two Doses of Either TIVc or TIVe Vaccine | Immunogenicity was assessed in terms of ratios of GMTs in subjects (6 to <48 months old), measured by hemagglutination inhibition (HI) assay, day 1 to day 50 after vaccination with two doses of either TIVc or TIVe vaccine | Day 50/Day 1 | 
| Percentages of Subjects (6 to <48 Months Old) Achieving Seroconversion or Significant Increase After Receiving Two Doses of Either TIVc or TIVe Vaccine | Immunogenicity was assessed in terms number (%) of subjects (6 to <48 months old) achieving seroconversion as measured by HI antibody titer, day 50 after vaccination with two doses of either TIVc or TIVe vaccine Seroconversion was defined as subjects with either a pre-vaccination (baseline) HI titer < 1:10 and post-vaccination HI titer ≥ 1:40 or with a pre-vaccination HI titer ≥ 1:10 and a ≥ 4-fold increase in post-vaccination HI antibody titer | Day 50 post vaccination | 
| Desirability Index Score of Subjects (6 to <48 Months Old) Reporting Severe Solicited Local and Systemic Reactions After Vaccination With Either TIVc or TIVe Vaccine | Differences in percentages of subjects (6 to <48 months old) with severe local solicited AEs and severe solicited systemic AEs, 3 days after vaccination with either TIVc or TIVe vaccine was assessed in terms of an individual desirability index score (High dose, Full dose, Half dose TIVc vs. TIVe vaccine). An individual desirability index score was assigned to each (non-transformed) safety value based on predefined functions. Each desirability index score is assigned a value between 0 and 1, wherein 0 is an undesirable response and 1 is a highly desirable response. | Day 1 to Day 3 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentages of Subjects (6 to <48 Months Old) Achieving Seroconversion or Significant Increase After Receiving Two Doses of Either TIVc or TIVe Vaccine | Immunogenicity was assessed in terms of number (%) of subjects (6 to <48 months old) achieving seroconversion as measured by HI assay, day 50 after vaccination with two doses of either TIVc or TIVe vaccine Seroconversion was defined as subjects with either a pre-vaccination (baseline) HI titer < 1:10 and post-vaccination HI titer ≥ 1:40 or with a pre-vaccination HI titer ≥ 1:10 and a ≥ 4-fold increase in post-vaccination HI antibody titer The Center for Biologics Evaluation, Research, and Review (CBER) criterion for pediatric population is that the lower bound of the two-sided 95% confidence interval (CI) for the percentage of subjects achieving seroconversion for HI antibody should meet or exceed 40% The Committee for Medicinal Products for Human Use (CHMP) criterion for pediatric population is that the percentage of subjects achieving seroconversion or significant increase in HI antibody titers >40% | Day 50 post vaccination | 
| Percentages of Subjects (6 to <48 Months Old) Achieving HI Titer ≥1:40 After Receiving Two Doses of Either TIVc or TIVe Vaccine | Immunogenicity was assessed in terms of number (%) of subjects (6 to <48 months old) achieving HI titer ≥1:40 as measured by HI assay, day 50 after vaccination with two doses of either TIVc or TIVe vaccine The CBER criterion for pediatric population is that the lower bound of the two-sided 95% CI for the percentage of subjects achieving an HI antibody titer ≥1:40 should meet or exceed 70% The CHMP criterion for pediatric population is that the percentage of subjects achieving HI antibody titers ≥1:40 should be >70% | Day 1, Day 50 post vaccination | 
| Geometric Mean Ratios (GMR) in Subjects (6 to <48 Months Old) After Receiving Two Doses of Either TIVc or TIVe Vaccine | Immunogenicity was assessed in terms of GMR in subjects (6 to <48 months old) as measured by HI assay, day 50 after vaccination with two doses of either TIVc or TIVe vaccine The CHMP criterion is mean geometric ratio (GMR) >2.5 | Day 50 post vaccination over day 1 | 
| Geometric Mean Ratios (GMR) in Subjects (6 to <48 Months Old) After Receiving Two Doses of Either TIVc or TIVe Vaccine | Immunogenicity was assessed in terms of GMR in subjects (6 to <48 months old) as measured by MN assay, day 50 after vaccination with two doses of either TIVc or TIVe vaccine | Day 50 post vaccination over day 1 | 
| Percentages of Subjects (6 to <48 Months Old) With High Post Vaccination HI Titers (i.e. HI Titers ≥1:110, ≥1:150, ≥1:330 and ≥1:629) After Receiving Two Doses of Either TIVc or TIVe Vaccine | Immunogenicity was assessed in terms of number (%) of subjects (6 to <48 months old) achieving post vaccination HI titers (i.e. HI titers ≥1:110, ≥1:150, ≥1:330 and ≥1:629) as measured by HI assay, day 50 after vaccination with two doses of either TIVc or TIVe vaccine | Day 1 and Day 50 post vaccination | 
| Percentages of Subjects (6 to <48 Months Old) Achieving MN Titer ≥1:20 After Receiving Two Doses of Either TIVc or TIVe Vaccine | Immunogenicity was assessed in terms of number (%) of subjects (6 to <48 months old) achieving MN titer ≥1:20 as measured by MN assay, day 50 after vaccination with two doses of either TIVc or TIVe vaccine Post-vaccination MN titer ≥1:20 was defined as for subjects with baseline (day 1) MN titer <1:10, or a minimum 2-fold increase in titer on day 50 for subjects with baseline titer ≥1:10 and corresponding 95% CI | Day 1 and Day 50 post vaccination | 
| Percentages of Subjects (6 to <48 Months Old) Achieving MN Titer ≥1:40 After Receiving Two Doses of Either TIVc or TIVe Vaccine | Immunogenicity was assessed in terms of number (%) of subjects (6 to <48 months old) achieving MN titer ≥1:40 as measured by MN assay, day 50 after vaccination with two doses of either TIVc or TIVe vaccine Post-vaccination MN titer ≥1:40 was defined as for subjects with baseline (day 1) MN titer <1:10, or a minimum 4-fold increase in titer on day 50 for subjects with baseline titer ≥1:10 and corresponding 95% CI | Day 1 and Day 50 post vaccination | 
| Number of Subjects (6 to <48 Months Old) Reporting Solicited Local (Grading Type I) and Systemic Adverse Events (AEs) After Two Doses of Either TIVc or TIVe Vaccine | Safety was assessed in terms of number of subjects (6 to <48 months old) reporting solicited local and systemic reactions, day 1 to day 7 after vaccination with two doses of either TIVc or TIVe vaccine (By Any Vaccination) | Day 1 to Day 7 | 
| Number of Subjects (6 to <48 Months Old) Reporting Unsolicited Adverse Events (AEs) After Two Doses of Either TIVc or TIVe Vaccine | Safety was assessed in terms of number of subjects (6 to <48 months old) reporting unsolicited reactions after Each /any Vaccination from Day 1 [Post Vaccination] to Day 29 [Pre Clinic Visit] and Day 29 [Post Vaccination] to Day 50 [Pre Clinic Visit] , Serious Adverse Events (SAEs), AEs leading to New Onset of Chronic Diseases (NOCD), AEs leading to withdrawal from the study and concomitant medications (day 1 to day 209) after vaccination with two doses of either TIVc or TIVe vaccine (By Any Vaccination) | Unsolicited AEs after Each/any Vaccination from Day 1 to Day 29 and Day 29 to Day 50 , Day 1 to Day 209 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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influenza, children, safety, tolerability, immunogenicity