Study of a Booster Dose of a Tetravalent Dengue Vaccine in Subjects Who Previously Completed the 3-dose Schedule
Condition: Dengue Fever; Dengue Hemorrhagic Fever
MeSH terms: Dengue; Hemorrhagic Fevers, Viral; Severe Dengue; Fever; Hyperthermia
Intervention: CYD Dengue Vaccine (5-dose formulation); Placebo, NaCl 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)
Masking description: An observer-blind procedure was followed for the injection of the CYD Dengue Vaccine booster or placebo. Neither the observer Investigator, nor the Sponsor, nor the participant/participants' parent(s)/legally acceptable representative(s) knew which product was administered.
Enrollment: 251.0
Sex: All
Minimum age: 13 Years
Maximum age: 22 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 and describe the booster effect of a CYD dengue vaccine
      dose administered 4 to 5 years after the completion of a 3-dose vaccination schedule.

      Primary Objective

      - To demonstrate the non-inferiority, in terms of geometric mean of titer ratios (GMTRs), of
      a CYD dengue vaccine booster compared to the third CYD dengue vaccine injection in
      participants from CYD13 - NCT00993447 and CYD30 - NCT01187433 trials (participants from Group
      1 only).

      Secondary Objectives:

        -  If the primary objective of non-inferiority was achieved: To demonstrate the
           superiority, in terms of GMTRs, of a CYD dengue vaccine booster compared to the third
           CYD dengue vaccine injection in participants from CYD13 and CYD30 trials.

        -  To describe the immune responses elicited by a CYD dengue vaccine booster and placebo
           injection in participants who received 3 doses of the CYD dengue vaccine in the CYD13
           and CYD30 trials in all participants.

        -  To describe the neutralizing antibody levels of each dengue serotype post-dose 3 (CYD13
           and CYD30 participants) and immediately prior to booster or placebo injection in all
           participants.

        -  To describe the neutralizing antibody persistence 6 months, 1 year, and 2 years post
           booster or placebo injection in all participants.

        -  To evaluate the safety of booster vaccination with the CYD dengue vaccine in all
           participants.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Had been identified as a potential participant by the Sponsor and is included in the
             list provided to the Investigator (i.e., aged 9 to 16 years on the day of first
             vaccination of CYD dengue vaccine in CYD13/CYD30 and has a post-dose 3 serum sample
             available [at least 400 microliters of serum]).

          -  Participants were 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) attended all scheduled
             visits and complied with all trial procedures.

        Exclusion Criteria:

          -  Participant who received any other dengue vaccination that was not part of the CYD13
             or CYD30 trials.

          -  Participant was pregnant, or lactating, or of childbearing potential (to be considered
             of non childbearing potential, a female must be pre-menarche or post-menopausal for at
             least 1 year, surgically sterile, or using an effective method of contraception or
             abstinence from at least 4 weeks prior to vaccination until at least 4 weeks after
             vaccination).

          -  Participation at the time of study enrollment (or in the 4 weeks preceding the trial
             vaccination) or planned participation during the present trial period in another
             clinical trial investigating a vaccine, drug, medical device, or medical procedure.

          -  Receipt of any vaccine in the 4 weeks preceding the trial vaccination or planned
             receipt of any vaccine in the 4 weeks following the trial vaccination.

          -  Receipt of immune globulins, blood or blood-derived products in the past 3 months.

          -  Known 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).

          -  Known systemic hypersensitivity to any of the vaccine components, or history of a
             life-threatening reaction to the vaccines 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.

          -  Deprived of freedom by an administrative or court order, or in an emergency setting,
             or hospitalized involuntarily.

          -  Current alcohol abuse or drug addiction.

          -  Moderate or severe acute illness/infection (according to investigator judgment) on the
             day of vaccination or febrile illness (temperature >= 38.0°C). A prospective
             participant should not be included in the study until the condition had resolved or
             the febrile event had subsided.

          -  Identified as an Investigator or employee of the Investigator or study center with
             direct involvement in the proposed study, or identified as an immediate family member
             (i.e., parent, spouse, natural or adopted child) of the Investigator or employee with
             direct involvement in the proposed study.