Evaluation of a Recombinant Quadrivalent Influenza Vaccine Versus a Marketed Quadrivalent Inactivated Influenza Vaccine in Children 3 to 17.
Condition: Influenza, Human
MeSH terms: Influenza, Human
Study type: Interventional
Phase: Phase 3

Summary: 
      Multicentric study, Phase III; this study is a randomized, participant- and observer-blind,
      parallel group evaluation to evaluate the immunogenicity, relative efficacy, safety and
      reactogenicity of a recombinant quadrivalent hemagglutinin influenza vaccine versus an
      inactivated quadrivalent influenza vaccine in pediatric subjects and adolescents of 3-17
      years of age. Investigational vaccine is indicated for active immunization against influenza
      A and B for strains contained in the vaccine marketed in the United States for persons 18
      years of age or older.
    

Detailed description: 
      Abbreviated title Evaluation of immunogenicity, relative efficacy, safety and reactogenicity
      of Flublok Quadrivalent® in healthy children and adolescents aged 3 to17 years.

      Sponsor Product Identifiers Flublok® Quadrivalent of Laboratories Liomont, S.A. de C.V.

      Flublok Quadrivalent consists of 180 μg total recombinant hemagglutinins Study Phase Phase 3
      Study National multicentric Participating sites: Mexico: At least 10 research sites
      distributed in different states.

      Clinical indication Vaccine indicated for active immunization against influenza A and B for
      strains contained in the vaccine; authorized in the United States for persons 18 years of age
      or older.

      It will be evaluated in a population aged 3 to 17 years. Treatment Groups Flublok®
      Quadrivalent (research product) Fluzone® Quadrivalent (active comparator) Number of
      participants in the study 1,556 Estimated study duration: 25 months Duration of participation
      6 months Randomization ratio 1:1 Study visits Visit 1: It corresponds to the screening visit,
      baseline blood sampling and administration of the study vaccine that can be performed on Day
      0.

      Visit 1A and 2: Remote contacts on day 2 and 7 post-vaccination. Visit 3: i. Follow up and
      blood sampling (for the 1-dose group); ii. Visit 3A, follow-up and application of the second
      dose of the vaccine (for the corresponding group); iii. Visit 3B, follow-up and blood
      sampling for the 2-dose group. The visits occur on Day 28.

      Months 3, 4, 5: Remote Contacts for safety tracking Visit 4: Remote contact for study closure
      and safety tracking at Month 6. Statistical analysis plan • Primary efficacy analysis:
      Proportion of subjects in each age category and vaccine group who seroconvert, with
      seroconversion being defined as (a) a >4-fold rise in HAI antibody titer in those subjects
      seropositive (titer >10) at baseline or (b) achievement of an HAI titer of >40 in those
      seronegative at baseline. Seroconversion will be evaluated against each of the 4 vaccine
      antigens, on Study Day 28 (or Day 56 for 2-dose subjects), by category A and B separated

      • Geometric Mean Titer (GMT) of HAI antibody against each vaccine antigen in each age
      category and vaccine group 28 days after immunization (Day 56 for 2-dose subjects) by
      category A and B separated Secondary efficacy analysis. Efficacy analysis and analysis of
      safety results associated to reactogenicity and other adverse events.

      Final contribution of the study results The direct benefit for subjects, individually, is
      expected to be seasonal influenza protection with the expected degree of protection,
      specially among recipients of the IIV4 control vaccine, which is also approved for use in the
      age groups of the study population, evaluating in detail the comparative response of the
      research product.

      The results of the study are intended to evaluate the immunogenicity, efficacy and safety of
      Flublok Quadrivalent in this population age and in this way, support the use of Flublok
      Quadrivalent for children and adolescents 3-17 years of age.

      If the results are favorable and if the hypothesis is fulfilled, the extension of the
      indication to the evaluated age segment may result in greater protection of the child
      population so as, not to be unprotected by the limited resources in health, the shortage of
      vaccines in certain regions, and to improve the supply and accessibility of the population in
      general for influenza prevention.

      The hypothesis underlying the study design and sample size estimated for the trial population
      from 3 to 17 years of age is based on the immunogenicity of Flublok Tetravalent, considering
      that the haemagglutination inhibition (HAI) seroconversion titers and the geometric mean of
      post-vaccination titers for the four hemagglutinin antigens in the vaccines after completion
      of vaccination with Flublok Quadrivalent are not inferior to those titers observed in those
      vaccinated with IIV4.

      Statistical considerations. sample size is 330 subjects in each age cohort for each treatment
      group, reaching a power of 80% to detect a marginal difference of non-inferiority for the
      seroconversion rate between the groups of -0.1000. The seroconversion rate of the control
      group is 0.7000. The Flublok Quadrivalent seroconversion rate is assumed to be 0.6000 under
      the null hypothesis of inferiority. The power was estimated for the case that the relative
      seroconversion rate of Flublok Quadrivalent is 0.7000. The statistical test use is a one
      tailed Z test (unpooled). The significance level for the test was established in 0.0250.

      A total of 1,556 subjects (330 complete cases per treatment group in subjects from 3 to 17
      years of age) will be enrolled, considering possible losses up to a maximum of 15%.
    

Intervention name(s): Study group - quadrivalent recombinant hemagglutinin influenza vaccine; Control group - quadrivalent inactivated influenza vaccine
Intervention type(s): Biological; Biological
Intervention description(s): Eligible subjects will be randomized, 1:1, to receive one or two doses of same vaccine. Subjects will be categorized in two age groups: subjects 9 to 17 years will be allocated in Group A and will receive one dose; Subjects 3 to 8 will be allocated to group B and the ACIP/CDC algorithm will be applied to determine should one or two doses will be applied 28 days apart. Vaccinator will be non blind and will not participate in the clinical evaluation.; Eligible subjects will be randomized, 1:1, to receive one or two doses of same vaccine. Subjects will be categorized in two age groups: subjects 9 to 17 years will be allocated in Group A and will receive one dose; Subjects 3 to 8 will be allocated to group B and the ACIP/CDC algorithm will be applied to determine should one or two doses will be applied 28 days apart. Vaccinator will be non blind and will not participate in the clinical evaluation.
Intervention MeSH terms: Hemagglutinins; Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: Visit 1: screening visit, baseline blood sampling and administration of the study vaccine that can be performed on Day 0.
Visit 1A and 2: Remote follow up contacts on day 2 and 7 post-vaccination. Visit 3: i. Follow up and blood sampling (for the 1-dose group); ii. Visit 3A, follow-up and application of the second dose of the vaccine (for the corresponding group); iii. Visit 3B, follow-up and blood sampling for the 2-dose group. The visits occur on Day 28.
Months 3, 4, 5: Remote Contacts for safety tracking Visit 4: Remote contact for study closure and safety tracking at Month 6
Masking: Double (Participant, Investigator)
Primary purpose: Other
Keywords: hemagglutinin influenza vaccine; recombinant influenza vaccine