phase iii trial to evaluate efficacy and safety of a tetravalent dengue vaccine

Conditions: Dengue

Summary: this is a randomized, multicenter, double-blind, placebo-controlled phase iii study that will evaluate efficacy and safety of a live attenuated, tetravalent, lyophilized dengue vaccine produced by butantan institute. the study will be carried out in multiple sites in brazil. the study will be community-based in select urban areas where there's dengue transmission. study's intervention will be a single dose of the tetravalent dengue vaccine or placebo in a ratio 2:1. for efficacy analysis will be considered all dengue cases occurring after 28 days post-vaccination in the entire population of 16944 participants. for safety analysis participants will be divided in three age groups: 18 to 59 ys, 7-17 ys and 2 to 6 ys. in each of these age groups there will be a minimum of 4992 participants. the age groups of 18 to 59 ys and 7 to 17 ys will start first. once safety data for the first 21 days after vaccination is analysed for 450 participants in 7-to17-ys age group, the following group, of 2 to 6 ys, will start. the study's hypothesis is that the vaccine under investigation and produced by butantan institute is safe and provides protection against dengue symptomatic disease of 80% or more with a lower bound of the 95% confidence interval of 25%. this way, the expected number of dengue cases virologically confirmed is 24 or more which will provide a response in terms of vaccine efficacy. all participants will be followed up for five years to verify dengue incidence, regardless severity.


Eligibility criteria:
inclusion criteria: 1. children who have completed 24 months of age, adolescents and adults who have not completed 60 years of age; 2. agree with periodic contacts, either/or by phone, electronic means, and home visits. 3. show voluntary intention to participate in the study, documented by the participant's or participant's legal representative's signature of the informed consent form. exclusion criteria: 1. for women: pregnancy (confirmed by positive beta-hcg test) or breastfeeding; 2. evidence of active neurological, cardiac, pulmonary, hepatic or renal disease as per clinical history and/or physical examination; 3. compromised immune system diseases including: decompensated diabetes mellitus, cancer (except basal cell carcinoma), congenital or acquired immune deficiencies and not controlled autoimmune, as per clinical history and/or physical examination; 4. behavioral, cognitive or psychiatric disease that in the opinion of the principal investigator or his representative physician, affects the participant ability to understand and cooperate with all study protocol requirements; 5. abusive usage of alcohol or drugs in the past 12 months that has caused medical, professional or family problems, indicated by clinical history; 6. history of severe allergic reactions or anaphylaxis to the vaccine or to components of the vaccine in study; 7. history of asplenia; 8. use of any investigational product within 28 days before or after receiving this study vaccination; 9. has participated in another clinical trial six months prior to inclusion in the study or planning to participate in another clinical trial within 2 years following inclusion; 10. use of immunosuppressant drugs such as: antineoplastic chemotherapy, radiation therapy, immunosuppressants to induce tolerance to transplants, and corticosteroids use (except topical or nasal). for this protocol will be considered for exclusion use of corticosteroids 3 months prior to the inclusion in the study and 6 months prior to the inclusion for the other therapies mentioned, and planned use of any immunosuppressant therapy within 2 years following inclusion in the study. it will be considered immunosuppressive dose of corticosteroids the equivalent to a dose ≥20 mg of prednisone per day for adults and the equivalent of prednisone at 2 mg/kg/day for children for over 7 days; 11. have received blood products in the past three months, including transfusions or immunoglobulin, or scheduled administration of blood products or immunoglobulin for the following 2 years after vaccination; 12. fever or suspected fever within 72 hours prior to vaccination or axillary temperature greater than 37,8°c on the day of vaccination (inclusion might be postponed until participant has completed 72 hours of no fever); 13. have received live virus vaccine within 28 days or killed virus vaccine in the last 14 days prior to vaccination, or have a scheduled immunization during the first 28 days after receiving the investigational product; 14. any other condition that might put in risk the safety/rights of a potential participant or hurdle his/her compliance with this protocol in investigator's opinion or his representative physician.