Clinical trial NCT00880893: Study of Sanofi Pasteur's CYD Dengue Vaccine in Healthy Subjects in Singapore
Official title: Immunogenicity and Large-Scale Safety of Tetravalent Dengue Vaccine in Healthy Subjects Aged 2 to 45 Years in Singapore
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Dengue Fever
Dengue Hemorrhagic Fever
Dengue Virus
Dengue Diseases
Keywords: Dengue virus
Dengue fever
Dengue Hemorrhagic fever
Dengue diseases
Sanofi Pasteur's CYD Dengue Vaccine
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2009-04-14
Enrollment: 1198
Sex: ALL
Minimum age (years): 2
Maximum age (years): 45
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Primary Objectives:

* To evaluate safety after each CYD Dengue vaccination in terms of injection site and systemic reactogenicity.
* To evaluate the occurrence of Serious Adverse Events (SAEs) throughout the trial period.
* To evaluate the humoral immune response to each CYD Dengue serotype after each vaccination in a subset of participants.

Secondary Objectives:

* To evaluate the persistence of the humoral immune response during 4 years after the last vaccination in a subset of participants.

Detailed description: This was a multicenter trial involving three vaccinations one each at 0, 6 and 12 months over a period of 1 year, and a 4-year follow-up following the last vaccination.

Eligibility criteria: Inclusion Criteria :

* Aged from 2 to 45 years on the day of inclusion.
* Participant in good health, based on medical history and physical examination.
* Provision of informed consent form (and assent form for participants aged 6 to 12 years) signed by the participant and by the parent(s) or another legally acceptable representative for participants aged less than 21 years.
* Participants and parent(s)/legally acceptable representative able to attend all scheduled visits and comply with all trial procedures.
* For a woman of child-bearing potential, avoid becoming pregnant (use of an effective method of contraception or abstinence) for at least 4 weeks before the first vaccination until 4 weeks after the last vaccination.

Exclusion Criteria :

* Febrile illness (temperature \>= 37.5°C) or moderate or severe acute illness/infection on the day of the first vaccination, according to Investigator judgment.
* For a woman of child-bearing potential, known pregnancy or positive urine pregnancy test on the day of inclusion.
* Breast-feeding woman.
* Known systemic hypersensitivity to any of the components of the trial vaccines (especially egg proteins or neomycin) or history of a life-threatening reaction to the trial vaccines or to a vaccine containing any of the same substances.
* Personal or family history of thymic pathology or myasthenia.
* Previous hepatitis A vaccination (for children only).
* Known or suspected congenital or acquired immunodeficiency, immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the past 6 months, or long-term systemic corticosteroid therapy.
* Chronic illness at a stage that could interfere with trial conduct or completion, in the opinion of the Investigator.
* Receipt of blood or blood-derived products in the past 3 months that might interfere with the assessment of immune response.
* Participation in another clinical trial investigating a vaccine, drug, medical device, or a medical procedure in the 4 weeks preceding the first trial vaccination.
* Planned participation in another clinical trial during the 18 coming months.
* 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 an administrative or court order, or in an emergency setting, or hospitalized without his/her consent.
* Current or past alcohol abuse or drug addiction that may interfere with the participants ability to comply with trial procedures.
* Participant who plans to move to another country within the 18 coming months.

Primary outcomes:
measure: Percentage of All Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Injection With CYD Dengue Vaccine or Placebo
timeFrame: Day 0 up to 14 days post-any and each injection
measure: Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Reporting Solicited Injection-site and Systemic Reactions Following Each Injection (Inj.) With CYD Dengue Vaccine or Placebo
timeFrame: Day 0 up to 14 days post-each injection
measure: Percentage of All Participants Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After Each Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3
measure: Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1 and 28 days Post-Injection 3
measure: Percentage of Participants by Age Group (2-11 Years, 12-17 Years, 18-45 Years) Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1 and 28 days Post-Injection 3
measure: Geometric Mean Titers (GMTs) of Antibodies in All Participants Against Each Serotype With the Parental Dengue Virus Strain Before and Following Each Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1, 2, and 3 and 28 days Post-Injection 1, 2, and 3
measure: GMTs of Antibodies by Age Groups (2-11 Years, 12-17 Years, 18-45 Years) Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine
timeFrame: Pre-Injection 1 and 28 days Post-Injection 3
Secondary outcomes:
measure: Percentage of Participants Aged 2 to 11 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: Percentage of Participants Aged 18 to 45 Years Who Achieved Seropositivity Against Each of the Dengue Virus Serotypes Before and up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: Percentage of Participants Aged 2 to 11 Years Old Who Achieved Seropositivity Against At Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: Percentage of Participants Aged 12 to 17 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: Percentage of Participants Aged 18 to 45 Years Old Who Achieved Seropositivity Against at Least 1, 2, 3, or 4 of the Dengue Virus Serotypes Before and After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: GMTs of Antibodies in Participants 2 to 11 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine
timeFrame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: GMTs of Antibodies in Participants 12 to 17 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: GMTs of Antibodies in Participants 18 to 45 Years Old Against Each Serotype With the Parental Dengue Virus Strain Before and Following the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: Pre-Injection 1, 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: Percentage of Participants (Aged 2 to 11 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: Percentage of Participants (Aged 2 to 11 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: Percentage of Participants (Aged 12 to 17 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: Percentage of Participants (Aged 12 to 17 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: Percentage of Participants (Aged 18 to 45 Years) Immune to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
measure: Percentage of Participants (Aged 18 to 45 Years) Naïve to Dengue at Baseline Who Are Seropositive for Each of the Dengue Virus Serotypes up to 4 Years After the Third Vaccination With CYD Dengue Vaccine or Placebo
timeFrame: 28 days Post-Injection 3, at 1 year follow up, 2 year follow up, 3 year follow up and 4 year follow up (assessed post-injection 3 during the follow up duration of 4 years)
Other outcomes:
Locations:
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Singapore
country: Singapore
city: Singapore
country: Singapore
Study officials:
affiliation: Sanofi Pasteur Inc.
name: Medical Director
role: STUDY_DIRECTOR
References:
citation: Harenberg A, Begue S, Mamessier A, Gimenez-Fourage S, Ching Seah C, Wei Liang A, Li Ng J, Yun Toh X, Archuleta S, Wilder-Smith A, Shek LP, Wartel-Tram A, Bouckenooghe A, Lang J, Crevat D, Caillet C, Guy B. Persistence of Th1/Tc1 responses one year after tetravalent dengue vaccination in adults and adolescents in Singapore. Hum Vaccin Immunother. 2013 Nov;9(11):2317-25. doi: 10.4161/hv.25562. Epub 2013 Jul 9.
citation: Leo YS, Wilder-Smith A, Archuleta S, Shek LP, Chong CY, Leong HN, Low CY, Oh ML, Bouckenooghe A, Wartel TA, Crevat D. Immunogenicity and safety of recombinant tetravalent dengue vaccine (CYD-TDV) in individuals aged 2-45 y: Phase II randomized controlled trial in Singapore. Hum Vaccin Immunother. 2012 Sep;8(9):1259-71. doi: 10.4161/hv.21224. Epub 2012 Aug 16.