Clinical trial NCT01187433: Study of CYD Dengue Vaccine in Healthy Children and Adolescents in South America
Official title: Immunogenicity and Safety of CYD Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in South America
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dengue
Dengue Hemorrhagic Fever
Keywords: Dengue
Dengue hemorrhagic fever
CYD Dengue Vaccines
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2010-08-24
Enrollment: 150
Sex: ALL
Minimum age (years): 9
Maximum age (years): 16
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to generate immunogenicity and safety data in preparation for efficacy studies in Latin America.

Primary Objectives:

* To describe the immune response to dengue viruses before and after each vaccination with CYD dengue vaccine.
* To evaluate the safety of each vaccination with CYD dengue vaccine.

Detailed description: Participants in the Dengue Vaccine Group will receive 3 vaccinations with CYD Dengue vaccine. Participants in the Control Group will receive placebo vaccinations for the first 2 vaccinations, followed by tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine adsorbed (ADACEL®) (in Venezuela) or Meningococcal A+C vaccine (in Brazil) as a way of providing therapeutic benefit to the participants in the control group.

Eligibility criteria: Inclusion Criteria :

* Aged 9 to 16 years on the day of inclusion
* Participant in good health, based on medical history and physical examination
* Provision of assent form/informed consent form signed by the participant and by the parent(s) or another legally acceptable representative
* Participant and parent(s)/legally acceptable representative(s) able to attend all scheduled visits and to comply with all trial procedures
* For a female participant of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks prior to first vaccination until at least 4 weeks after the last vaccination

Exclusion Criteria :

* Personal or family history of thymic pathology (thymoma), thymectomy, or myasthenia
* For a female participant of child-bearing potential, known pregnancy or positive urine pregnancy test at Visit 1
* Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination
* Breast-feeding woman
* Planned participation in another clinical trial during the present trial period
* Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 months, or long-term systemic corticosteroids therapy
* Known systemic hypersensitivity to any of the components of any of the trial vaccines or history of a life-threatening reaction to any of the trial vaccines or to a vaccine containing any of the same substances
* Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator
* Current alcohol abuse or drug addiction that may interfere with the participant's ability to comply with trial procedures
* Receipt of blood or blood-derived products in the preceding 3 months that might interfere with the assessment of immune response
* Receipt of any vaccine in the 4 weeks preceding the first trial vaccination
* Planned receipt of any vaccine in the 4 weeks following the first trial vaccination
* Participant deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized without his/her consent
* Febrile illness (temperature ≥ 38.0 ºC) or moderate or severe acute illness/infection on the day of vaccination, according to Investigator judgment
* Thrombocytopenia, bleeding disorder or anticoagulants in the 3 weeks preceding inclusion contraindicating intramuscular vaccination
* Severe diseases with or without fever, convulsions or neurological abnormalities without treatment or in progression.

Primary outcomes:
measure: Percentage of Participants With Seropositivity Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo
timeFrame: Before and 28 days after each injection
measure: Percentage of Flavivirus Immune Participants With Seropositivity Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo
timeFrame: Before and 28 days after each injection
measure: Percentage of Flavivirus Naïve Subjects With Seropositivity Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo
timeFrame: Before and 28 Days after each injection
measure: Percentage of Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo
timeFrame: Before and 28 days after each injection
measure: Percentage of Flavivirus Immune Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo
timeFrame: Before and 28 days after each injection
measure: Percentage of Flavivirus Naïve Subjects With Seropositivity Against At Least 1, 2, 3, or 4 Parental Dengue Virus Serotypes Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo
timeFrame: Before and 28 days after each injection
measure: Geometric Mean Titer Ratios (GMTRs) Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo
timeFrame: Before and 28 days after each injection
measure: Geometric Mean Titers (GMTs) Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo
timeFrame: Before and 28 days after each injection
measure: Geometric Mean Titers (GMTs) of Flavivirus Immune Subjects Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo
timeFrame: Before and 28 days after each injection
measure: Geometric Mean Titer Ratios (GMTRs) of Flavivirus naïve Subjects Against Each Serotype With the Parental of Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo
timeFrame: Before and 28 days after each injection
measure: Percentage of Participants Reporting Solicited Injection-Site and Systemic Reactions Following Any and Each Vaccination With Either CYD Dengue Vaccine or a Placebo
timeFrame: Day 0 up to Day 14 post each vaccination
Secondary outcomes:
Other outcomes:
Locations:
city: Vitória
country: Brazil
Study officials:
affiliation: Sanofi Pasteur Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Dayan GH, Garbes P, Noriega F, Izoton de Sadovsky AD, Rodrigues PM, Giuberti C, Dietze R. Immunogenicity and safety of a recombinant tetravalent dengue vaccine in children and adolescents ages 9-16 years in Brazil. Am J Trop Med Hyg. 2013 Dec;89(6):1058-1065. doi: 10.4269/ajtmh.13-0304. Epub 2013 Nov 4.
citation: Coronel D, Garcia-Rivera EJ, Rivera DM, Arredondo-Garcia JL, Dietze R, Perroud AP, Cortes M, Bonaparte M, Wang H, Pagnon A, Jantet-Blaudez F, Penalosa LAR, Dayan G, Zambrano B, DiazGranados CA, Noriega F. Immune Response Persistence and Safety of a Booster Dose of the Tetravalent Dengue Vaccine in Adolescents and Adults Who Previously Completed the 3-dose Schedule 4-5 Years Earlier in Latin America: A Randomized Placebo-controlled Trial. Pediatr Infect Dis J. 2020 Oct;39(10):961-968. doi: 10.1097/INF.0000000000002830.