Clinical trial NCT01436396: Study of Yellow Fever Vaccine Administered With Tetravalent Dengue Vaccine in Healthy Toddlers
Official title: Immunogenicity and Safety of Yellow Fever Vaccine (Stamaril®) Administered Concomitantly With Tetravalent Dengue Vaccine in Healthy Toddlers at 12-13 Months of Age in Colombia and Peru
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Dengue
Dengue Hemorrhagic Fever
Yellow Fever
Keywords: Dengue
Dengue Hemorrhagic Fever
CYD Dengue Vaccines
Yellow Fever
Stamaril®
Flavivirus Infections
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2011-09-19
Enrollment: 792
Sex: ALL
Minimum age (years): 12
Maximum age (years): 13
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The study was designed to evaluate whether the first CYD dengue vaccination can be administered concomitantly with Stamaril® yellow fever vaccine during the same day and visit, but at 2 different sites of administration.

Primary Objective:

* To demonstrate the non-inferiority of the immune response against Yellow Fever (YF) in flavivirus (FV) non-immune subjects at baseline receiving one dose of Stamaril vaccine administered concomitantly with the first dose of CYD dengue vaccine compared to participants receiving one dose of Stamaril vaccine concomitantly with placebo.

Secondary Objectives:

* To assess the non-inferiority of YF immune response 28 days post-Stamaril vaccination based on seroconversion rates regardless of the FV status of participants at baseline.
* To describe the YF immune response 28 days post-Stamaril vaccination in both groups.
* To describe the antibody (Ab) response to each dengue virus serotype 28 days post CYD dengue vaccine (Visit \[V\] 05 and V07), following CYD dengue vaccine Dose 1 and Dose 2 from Group 2 versus following CYD dengue vaccine Dose 2 and Dose 3 for Group 1 (effect of YF vaccination).
* To describe the safety of Stamaril vaccine administered concomitantly with the first dose of CYD dengue vaccine, or Stamaril administered concomitantly with placebo.
* To describe the safety of CYD dengue vaccine after the first dose of CYD dengue vaccine administered concomitantly with Stamaril vaccine or CYD vaccine administered alone.
* To describe the safety of the CYD dengue vaccine in all participants after each dose.

Detailed description: All participants received a total of 9 injections during the study. Vaccine immunogenicity assessments for dengue neutralizing antibodies was performed in a randomized subset of participants. All participants were followed-up for safety during the study and for 6 months after the last CYD dengue vaccination.

Eligibility criteria: Inclusion Criteria:

* Aged 12 to 13 months on the day of inclusion.
* Born at full term of pregnancy (\>=37 weeks) and with a birth weight \>=2.5 kg as reported by the parent/legally acceptable representative.
* Participant in good health, based on medical history and physical examination.
* Participant had completed his/her vaccination schedule according to the official immunization calendar of Colombia and/or Peru, respectively.
* Informed consent form had been signed and dated by the parent(s) or other legally acceptable representative (and by 2 independent witnesses if required by local regulations).
* Participant and parent/legally acceptable representative/tutor able to attend all scheduled visits and to comply with all trial procedures.

Exclusion Criteria:

* Participation in another clinical trial investigating a vaccine, drug, medical device, or medical procedure in the 4 weeks preceding the first trial vaccination.
* Planned participation in another clinical trial during the present trial period.
* Planned receipt of any vaccine in the 4 weeks following first trial vaccination.
* Previous vaccination against YF, hepatitis A, or measles, mumps and rubella.
* Receipt of blood or blood-derived products in the past 3 months which might interfere with assessment of the immune response.
* Known or suspected congenital or acquired immunodeficiency; or receipt of immunosuppressive therapy such as anti-cancer chemotherapy or radiation therapy within the preceding 6 weeks or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months).
* Personal known seropositivity for human immunodeficiency virus (HIV) as reported by the parent/legally acceptable representative.
* History of previous maternal vaccination against YF as reported by the parent/legally acceptable representative.
* Personal history of YF or dengue infection/disease as reported by the parent/legally acceptable representative.
* Known systemic hypersensitivity to any of the vaccine components of the vaccines that were used in the trial, or history of a life-threatening reaction to the vaccines used in the trial or to vaccines containing any of the same substances.
* History of contraindication to receipt of vaccines containing components of Stamaril® (yellow fever vaccine), measles, mumps and rubella vaccine, hepatitis A vaccine, pneumococcal conjugated vaccine or of diphtheria (D) toxoid, tetanus (T) toxoid, pertussis toxoid (PT), filamentous hemagglutinin (FHA), polyribosylribitol phosphate (PRP) and polio or other diphtheria, tetanus and pertussis vaccine (e.g., DTwP).
* Thrombocytopenia, as reported by the parent/legally acceptable representative.
* Bleeding disorder, or receipt of anticoagulants in the 3 weeks preceding inclusion, contraindicating intramuscular (IM) vaccination.
* History of central nervous system disorder or disease, including seizures.
* Personal history of thymic pathology (e.g., thymoma), and/or thymectomy.
* Chronic illness that, in the opinion of the Investigator, is at a stage where it might interfere with trial conduct or completion.
* Identified as a child (adopted or natural) of the Investigator or of employees of the Investigator or study center, with direct involvement in the proposed study or other studies under the direction of that Investigator or study center.

Primary outcomes:
measure: Percentage of Flavi Virus (FV) Non-immune Participants With Seroconversion Against YF Antigen After Vaccination With Yellow Fever (YF) Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: 28 days Post-Injection 1
Secondary outcomes:
measure: Percentage of All Participants With Seroconversion Against YF Antigen After Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: 28 days Post-Injection 1
measure: Geometric Mean Titers (GMTs) of YF Antibodies in All Participants Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Pre-Injection 1 and 28-days Post-Injection 1
measure: Geometric Mean Titer Ratios (GMTRs) of YF Antibodies in All Participants Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Pre-Injection 1 and 28- days Post-Injection 1
measure: Percentage of All Participants With YF Antibody Titers of >=10 (1/Dil) Before and After Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Pre-Injection 1 and 28-days Post-Injection 1
measure: GMTs of Dengue Virus Antibodies Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Pre-Injection 1 and 28-days Post-Injections 2 and 3
measure: GMTRs of Dengue Virus Antibodies Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Pre-Injection 1 and 28-days Post-Injections 2 and 3
measure: Percentage of Participants With Antibody Titer >= 10 (1/Dil) Against Each Serotype With Parental Dengue Virus Strains After Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Pre-Injection 1 and 28-days Post-Injections 2 and 3
measure: Percentage of Participants With Antibody Titer >= 10 (1/Dil) Against at Least 1, 2, 3, or 4 Serotypes With Parental Dengue Virus Strains After YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Pre-Injection 1 and 28 days Post-Injections 2 and 3
measure: GMTs of Dengue Virus Antibodies of FV Immune Participants Following Vaccination With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Pre-Injection 1 and 28 days Post-Injections 2 and 3
measure: GMTs of Dengue Virus Antibodies of FV-Non Immune (Naïve) Participants Following Vaccination With YF Vaccine Non Immune (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Pre-Injection 1 and 28 days Post-Injections 2 and 3
measure: Percentage of FV-immune Participants With Antibody Titer >= 10 (1/Dil) Against Each Serotype With Parental Dengue Virus Strains After YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Pre-Injection 1 and 28 days Post-Injections 2 and 3
measure: Percentage of FV Non-immune (Naïve) Participants With Antibody Titer >= 10 (1/Dil) Against Each Serotype With the Parental Dengue Virus Strains After YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Pre-Injection 1 and 28 days Post-Injections 2 and 3
measure: Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following Any and Each Injection With YF Vaccine (Stamaril®) Concomitantly With Either CYD Dengue Vaccine or a Placebo
timeFrame: Day 0 up to 14 days post any Inj., Post Inj. 1, Post Inj. 2 and Post Inj. 3
Other outcomes:
Locations:
city: Cali
country: Colombia
city: Lima
country: Peru
Study officials:
affiliation: Sanofi Pasteur Inc.
name: Medical Director
role: STUDY_DIRECTOR
References: