Immunogenicity and Safety of Different Vaccination Schedules of Tetravalent Dengue Vaccine in Healthy Subjects 9 to 50 Years of Age

Immunogenicity and Safety of Tetravalent Dengue Vaccine Given in 1-, 2-, or 3- Dose Schedules (STAGE I) Followed by a Single Booster Injection of the Same Vaccine (STAGE II) 1 or 2 Years After the Last Primary Dose in Healthy Subjects 9 to 50 Years of Age in Colombia and the Philippines

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.

Healthy participants aged between 9 and 50 year received CYD dengue vaccine in various schedules, in two sequential stages. In the first stage, participants received 1, 2 or 3 injections of CYD dengue vaccine over a 12-month period. In the second stage, participants were randomized to receive a booster dose of CYD dengue vaccine at either 12 months (Subgroup a) or 24 months (Subgroup b) after the third injection of study vaccine. During the conduction of this trial, the World Health Organization (WHO) indication about vaccinating only baseline seropositive participants was arisen; at this moment, STAGE I of the trial was completed. For STAGE II, only participants who were previously dengue exposed at baseline (dengue seropositive) were eligible to receive the booster dose.

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.