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

• ClinicalTrials.gov Identifier: NCT02035696
• Recruitment Status: Completed
• First Posted: January 14, 2014
• Results First Posted: June 27, 2017
• Last Update Posted: July 10, 2018
• Sponsor: Seqirus
• Collaborator: Novartis Vaccines
• Information provided by (Responsible Party): Seqirus

Tracking Information

• First Submitted Date: January 7, 2014
• First Posted Date: January 14, 2014
• Results First Submitted Date: August 19, 2015
• Results First Posted Date: June 27, 2017
• Last Update Posted Date: July 10, 2018
• Study Start Date: December 2013
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 22, 2017)

• Ratios of Geometric Mean Titer (GMT) in Subjects (6 to <48 Months Old) After Receiving Two Doses of Either TIVc or TIVe Vaccine [ Time Frame: Day 50/Day 1 ]
  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
• Percentages of Subjects (6 to <48 Months Old) Achieving Seroconversion or Significant Increase After Receiving Two Doses of Either TIVc or TIVe Vaccine [ Time Frame: Day 50 post vaccination ]
  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
• 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 [ Time Frame: Day 1 to Day 3 ]
  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.

Original Primary Outcome Measures (submitted: January 13, 2014)

• Key immunogenicty endpoints: GMR, seroconversion [ Time Frame: 21 days after last vaccination ]
  To select an optimal vaccine candidate from Groups A, B or C for pediatric subjects 6 to < 48 months of age based a scoring system that assigns a combined index score based on weighted measures of the presence of solicited adverse events and antibody responses
• Safety parameters: severe local and systemic adverse events [ Time Frame: 3 days after each vaccination ]

Current Secondary Outcome Measures (submitted: May 22, 2017)

• Percentages of Subjects (6 to <48 Months Old) Achieving Seroconversion or Significant Increase After Receiving Two Doses of Either TIVc or TIVe Vaccine [ Time Frame: Day 50 post vaccination ]
  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%
• Percentages of Subjects (6 to <48 Months Old) Achieving HI Titer ≥1:40 After Receiving Two Doses of Either TIVc or TIVe Vaccine [ Time Frame: Day 1, Day 50 post vaccination ]
  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%
• Geometric Mean Ratios (GMR) in Subjects (6 to <48 Months Old) After Receiving Two Doses of Either TIVc or TIVe Vaccine [ Time Frame: Day 50 post vaccination over day 1 ]
  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
• Geometric Mean Ratios (GMR) in Subjects (6 to <48 Months Old) After Receiving Two Doses of Either TIVc or TIVe Vaccine [ Time Frame: Day 50 post vaccination over day 1 ]
  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
• 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 [ Time Frame: Day 1 and Day 50 post vaccination ]
  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
• Percentages of Subjects (6 to <48 Months Old) Achieving MN Titer ≥1:20 After Receiving Two Doses of Either TIVc or TIVe Vaccine [ Time Frame: Day 1 and Day 50 post vaccination ]
  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
• Percentages of Subjects (6 to <48 Months Old) Achieving MN Titer ≥1:40 After Receiving Two Doses of Either TIVc or TIVe Vaccine [ Time Frame: Day 1 and Day 50 post vaccination ]
  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
• 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 [ Time Frame: Day 1 to Day 7 ]
  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)
• Number of Subjects (6 to <48 Months Old) Reporting Unsolicited Adverse Events (AEs) After Two Doses of Either TIVc or TIVe Vaccine [ Time Frame: Unsolicited AEs after Each/any Vaccination from Day 1 to Day 29 and Day 29 to Day 50 , Day 1 to Day 209 ]
  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)

Original Secondary Outcome Measures (submitted: January 13, 2014)

• Antibody responses by HI/MN assay for all vaccine strains as per CBER/CHMP criteria [ Time Frame: 21 days post last vaccination ]
  Antibody responses, safety and tolerability to the study vaccines in subjects 6 to < 48 months of age
• To evaluate safety and tolerability by measuring solicited reactions [ Time Frame: % of subjects with solicited reactions 7 days post each vaccination ]
• To evaluate safety and tolerability by measuring unsolicited reactions [ Time Frame: % of subjects with unsolicited reactions after each or any dose up to day 50 ]
• To evaluate safety and tolerability by measuring AEs, SAEs, and NOCDs [ Time Frame: % of subjects reporting SAEs, NOCDs and AEs through day 209 ]

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Safety and Immunogenicity of a Four Influenza Vaccines in Children Ages 6 Months Old to Less Than 48 Months Old
• Official Title: 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.
• Brief Summary: To evaluate the safety and immunogenicity of four influenza vaccines in children 6 months to < 48 months of age
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1; Phase 2
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Influenza

Intervention

• Biological: Trivalent influenza vaccine (TIVc)
• Biological: Trivalent influenza vaccine-licensed
  Licensed influenza vaccine

Study Arms

• Experimental: TIVc-High Dose
  Subjects (6 to <48 months old) received two doses of 0.75 mL of TIVc vaccine
  Intervention: 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
  Intervention: 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
  Intervention: 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)
  Intervention: Biological: Trivalent influenza vaccine-licensed

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: May 22, 2017): 671
• Original Estimated Enrollment (submitted: January 13, 2014): 672
• Actual Study Completion Date: December 2014
• Actual Primary Completion Date: June 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 6 Months to 48 Months (Child)
• Accepts Healthy Volunteers: Yes
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Finland, Philippines, Thailand, United States

Administrative Information

• NCT Number: NCT02035696
• Other Study ID Numbers: V58P16; 2013-002081-39 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: Seqirus
• Study Sponsor: Seqirus
• Collaborators: Novartis Vaccines
• Investigators: Not Provided
• PRS Account: Seqirus
• Verification Date: June 2018