Immunogenicity and Safety of a Tetravalent Dengue Vaccine Administered Concomitantly or Sequentially With Gardasil®
Condition: Dengue Fever; Dengue Hemorrhagic Fever; Human Papillomavirus Disease
MeSH terms: Dengue; Hemorrhagic Fevers, Viral; Severe Dengue; Fever; Hyperthermia
Study type: Interventional
Phase: Phase 3

Summary: 
      The aim of the study was to assess the safety and immunogenicity of the CYD dengue vaccine
      and Gardasil (Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine,
      Recombinant) when administered concomitantly or sequentially.

      Primary objectives:

        -  To demonstrate that the humoral immune response (in terms of geometric mean titers
           [GMTs]) to Gardasil after concomitant administration was non-inferior to sequential
           administration with the CYD dengue vaccine measured 28 days after the last dose of
           Gardasil.

        -  To demonstrate that the humoral immune response to the CYD dengue vaccine after
           concomitant administration was non-inferior to sequential administration with Gardasil
           measured 28 days after the last dose of the CYD dengue vaccine.

      Secondary Objectives:

        -  To demonstrate that the humoral immune response (in terms of seroconversion) to Gardasil
           vaccine after concomitant administration was non-inferior to sequential administration
           with the CYD dengue vaccine measured 28 days after the last dose of Gardasil.

        -  To describe the humoral immune response to Gardasil at baseline and after each dose of
           Gardasil in each and any group.

        -  To describe the humoral immune response to the CYD dengue vaccine at baseline and after
           each dose of the CYD dengue vaccine in each and any group.

        -  To describe the safety of Gardasil and the CYD dengue vaccine after each and any dose in
           each group.
    

Detailed description: 
      Participants received 3 doses of CYD dengue vaccine and 2 doses of Gardasil administered
      either concomitantly or sequentially.

      The study activities were put on hold for several months (up to 6 months for some
      participants) to obtain the approval of Protocol Amendment 1 by the competent authorities and
      completed the associated logistic tasks. Due to this protocol amendment as per Independent
      Data Monitoring Committee recommendation, only previously dengue immune participants
      (seropositive for dengue before vaccination) were eligible to complete the vaccination
      schedule. Dengue non-immune participants (seronegative for dengue before vaccination) did not
      receive any additional CYD dengue vaccine injections, but were followed for safety up to 6
      months after the last injection.

      Due to the change in amendment 1, the number of evaluable dengue immune participants at
      baseline did not meet the predefined number of participants that would have allowed for a
      global power of at least 80% for non-inferiority testing of Gardasil vaccine and CYD dengue
      vaccine (121 per group for the co-primary objectives and 194 per group for the secondary
      objectives).

      All participants were assessed for immunogenicity and safety. Safety assessments included
      solicited reactions within 7 or 14 days after each injection, unsolicited adverse events
      (AEs) within 28 days after each injection, non-serious AEs of Special Interests (AESIs)
      within 7 days after each injection, and serious adverse events including AESI and
      hospitalized virologically-confirmed dengue cases during the study period.
    

Intervention name(s): CYD Dengue Vaccine; CYD Dengue Vaccine; Human Papillomavirus Quadrivalent [Types 6, 11, 16, and 18] Vaccine, Recombinant.
Intervention type(s): Biological; Biological; Biological
Intervention description(s): 0.5 mL, SC injection at Day 0, Month 6 and 12, respectively.; 0.5 mL, SC injection at Month 1, 7 and 13, respectively.; 0.5 mL, IM injection at Day 0 and Month 6, respectively.
Other intervention name(s): Dengvaxia®; Dengvaxia®; Gardasil®
Intervention MeSH terms: Vaccines
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: Dengue Fever; Dengue Hemorrhagic Fever; Human Papillomavirus Disease; CYD Dengue Vaccine; Dengvaxia®; Gardasil®