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

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.

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

Study Overview

• Status: Completed
• Conditions: Influenza
• Intervention / Treatment: Biological: Trivalent influenza vaccine (TIVc); Biological: Trivalent influenza vaccine-licensed

• Study Type: Interventional
• Enrollment (Actual): 671
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Finland
  • Kuopio, Finland
    • Site 502
  • Tampere, Finland
    • Site 506
• Philippines
  • Manila, Philippines
    • Site 301
  • Muntinlupa, Philippines
    • Site 302
• Thailand
  • Bangkok, Thailand
    • Site 201
  • Bangkok, Thailand
    • Site 202
• United States
  • Arizona
    • Phoenix, Arizona, United States
      • Site 116
    • Tucson, Arizona, United States
      • Site 119
  • Arkansas
    • Little Rock, Arkansas, United States
      • Site 109
  • California
    • Long Beach, California, United States
      • Site 112
    • Ontario, California, United States
      • Site 113
    • San Diego, California, United States
      • Site 117
    • West Covina, California, United States
      • Site 114
  • Colorado
    • Thornton, Colorado, United States
      • Site 107
  • Florida
    • Miami, Florida, United States
      • Site 111
    • Miami Beach, Florida, United States
      • Site 108
  • Georgia
    • Gainesville, Georgia, United States
      • Site 121
  • Nebraska
    • Omaha, Nebraska, United States
      • Site 101
    • Omaha, Nebraska, United States
      • Site 104
    • Omaha, Nebraska, United States
      • Site 105
    • Omaha, Nebraska, United States
      • Site 106
  • Ohio
    • Youngstown, Ohio, United States
      • Site 103
  • South Carolina
    • Charleston, South Carolina, United States
      • Site 102
  • Texas
    • Houston, Texas, United States
      • Site 115
  • Utah
    • Saint George, Utah, United States
      • Site 118
    • Salt Lake City, Utah, United States
      • Site 110
  • Washington
    • Spokane, Washington, United States
      • Site 120

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 6 months to 4 years (Child)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TIVc-High Dose; Subjects (6 to <48 months old) received two doses of 0.75 mL of TIVc vaccine	Biological: Trivalent influenza vaccine (TIVc)
Experimental: TIVc-Full Dose; Subjects(6 to <48 months old) received two doses of 0.50 mL of TIVc vaccine	Biological: Trivalent influenza vaccine (TIVc)
Experimental: TIVc- Half Dose; Subjects (6 to <48 months old)received two doses of 0.25 mL of TIVc vaccine	Biological: Trivalent influenza vaccine (TIVc)
Active Comparator: TIVe; 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; Licensed influenza vaccine

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Seqirus
• Collaborators: Novartis Vaccines

Study record dates

Study Major Dates

• Study Start: December 1, 2013
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: January 7, 2014
• First Submitted That Met QC Criteria: January 13, 2014
• First Posted (Estimate): January 14, 2014

Study Record Updates

• Last Update Posted (Actual): July 10, 2018
• Last Update Submitted That Met QC Criteria: June 11, 2018
• Last Verified: June 1, 2018

More Information

Terms related to this study

• Keywords: tolerability; safety; children; influenza; immunogenicity
• Additional Relevant MeSH Terms: RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Orthomyxoviridae Infections; Influenza, Human; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: V58P16; 2013-002081-39 (EudraCT Number)