Immunogenicity and Safety of Different Vaccination Schedules of Tetravalent Dengue Vaccine in Healthy Subjects 9 to 50 Years of Age
Condition: Dengue Fever; Dengue Hemorrhagic Fever
MeSH terms: Dengue; Hemorrhagic Fevers, Viral; Severe Dengue; Fever; Hyperthermia
Intervention: CYD Dengue Vaccine; Placebo (Sodium chloride 0.9%)
Intervention description: 0.5 mL, Subcutaneous; 0.5 mL, Subcutaneous
Phase: Phase 2
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1050.0
Sex: All
Minimum age: 9 Years
Maximum age: 50 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: Dengue Fever; Dengue virus; Dengue Hemorrhagic Fever; CYD Dengue Vaccine

Summary:

      The aim of the study was to assess the immune response and the safety of different
      vaccination schedules of CYD dengue vaccine.

      The primary objectives of the study were:

        -  To demonstrate the non-inferiority of the immune response elicited against each dengue
           serotype by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the
           immune response elicited by CYD dengue vaccine given as a 3-dose schedule (Group 1), in
           previously dengue exposed participants 28 days after the last injection.

        -  To demonstrate the non-inferiority of the immune response elicited against each dengue
           serotype by CYD dengue vaccine given as a 2-dose schedule (Group 2) compared to the
           immune response elicited by CYD vaccine given as a 3-dose schedule (Group 1) in
           previously dengue exposed participants, 1 year after the last injection.

        -  To demonstrate the non-inferiority of the immune response elicited against each dengue
           serotype elicited by a booster dose of CYD dengue vaccine one year or two years after
           the last injection in the primary series in previously dengue exposed participants,
           compared to the immune response post dose 3 in Group 1.

      The secondary objectives of the study were:

        -  To demonstrate the superiority of the immune response elicited by CYD dengue vaccine
           given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD
           dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed
           participants, 28 days after the last injection.

        -  To demonstrate the superiority of the immune response elicited by CYD dengue vaccine
           given as a 2-dose schedule (Group 2) compared to the immune response elicited by CYD
           dengue vaccine given as a 3-dose schedule (Group 1), in previously dengue exposed
           participants, one year after the last injection.

        -  To describe the neutralizing antibody levels of each dengue serotype at 28 days
           post-injection 3 to the antibody levels immediately before receiving a booster dose, by
           baseline dengue serostatus.

        -  To describe the neutralizing antibody levels of each dengue serotype at 28 days
           post-injection 2 and 28 days post-injection 3 from Group 1 in a primary series schedule
           by baseline dengue serostatus.

        -  To demonstrate the superiority of the immune response elicited against each dengue
           serotype 28 days after administration of a booster dose of CYD dengue vaccine, in
           previously dengue exposed participants, at one year or two years after last injection in
           the primary series.

        -  To describe the seroconversion rate 28 days post-booster injection in all 3 groups.

        -  To describe all hospitalized virologically confirmed dengue (VCD) cases during the
           study.

        -  To evaluate the safety profile of CYD after each and any injection during the trial.
           Safety assessments include solicited reactions within 7 or 14 days after each injection,
           unsolicited adverse events within 28 days after each injection, and serious adverse
           events during the study period.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Aged 9 to 50 years on the day of enrollment.

          -  Participant in good health, based on medical history and physical examination.

          -  Assent form or informed consent form (ICF) had been signed and dated by the
             participant (based on local regulations), and ICF had been signed and dated by the
             parent(s) or another legally acceptable representative (and by an independent witness
             if required by local regulations).

          -  Participant and parent(s)/legally acceptable representative(s) were able to attend all
             scheduled visits and to comply with all trial procedures.

        Exclusion Criteria:

          -  Participant was pregnant, or lactating, or of childbearing potential (to be considered
             of non-childbearing potential, a female must be pre-menarche, surgically sterile, or
             using an effective method of contraception or abstinence from at least 4 weeks prior
             to the first vaccination until at least 4 weeks after the last vaccination).

          -  Participation at the time of study enrollment (or in the 4 weeks preceding the first
             trial vaccination) or planned participation during the present trial period in another
             clinical trial investigating a vaccine, drug, medical device or medical procedure.

          -  Self-reported or suspected congenital or acquired immunodeficiency; or receipt of
             immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within
             the preceding 6 months; or long-term systemic corticosteroid therapy (prednisone or
             equivalent for more than 2 consecutive weeks within the past 3 months).

          -  Self-reported systemic hypersensitivity to any of the vaccine components, or history
             of a life-threatening reaction to the vaccine used in the trial or to a vaccine
             containing any of the same substances.

          -  Chronic illness that, in the opinion of the investigator, was at a stage where it
             might interfere with trial conduct or completion.

          -  Receipt of blood or blood-derived products in the past 3 months, which might interfere
             with assessment of the immune response.

          -  Planned receipt of any vaccine in the 4 weeks following any trial vaccination.

          -  Previous vaccination against dengue disease with either the trial vaccine or another
             vaccine.

          -  Deprived of freedom by an administrative or court order, or in an emergency setting,
             or hospitalized involuntarily.

          -  Current alcohol abuse or drug addiction that, based on investigator's judgment, might
             interfere with the participant's ability to comply with trial procedures.

          -  Identified as a site employee of the Investigator, with direct involvement in the
             proposed study or other studies under the direction of that Investigator or study
             center, as well as family members (i.e., immediate, husband, wife, and their children,
             adopted or natural) of the employees or the Investigator.

          -  A prospective participant must not be included in the study until the following
             conditions and/or symptoms were resolved:

               -  Febrile illness (temperature greater than or equal to [>=] 38.0 degree Celsius)
                  or moderate or severe acute illness/infection (according to Investigator's
                  judgment) on the day of vaccination.

               -  Receipt of any vaccine in the 4 weeks preceding the first trial vaccination.