Immunogenicity and Safety of Sanofi Pasteur's CYD Dengue Vaccine in Healthy Children and Adolescents in Latin America

Study Overview
=================
Brief Summary
-----------------
Primary objectives: To describe the immune response to each dengue serotype before and after each vaccination with sanofi pasteur's CYD dengue vaccine. To evaluate the safety of each vaccination with sanofi pasteur's CYD dengue vaccine.

Detailed Description
-----------------
The antibody levels against each serotype will be measured before and after each vaccination. The subjects will be followed for 28 days after each vaccination for solicited and unsolicited safety parameters. Serious adverse events (SAEs) will be collected throughout the study.

Official Title
-----------------
Immunogenicity and Safety of Sanofi Pasteur's CYD Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in Latin America

Conditions
-----------------
Dengue, Dengue Hemorrhagic Fever, Dengue Virus, Dengue Fever

Intervention / Treatment
-----------------
* Biological: CYD Dengue Vaccine
* Biological: Tetanus Toxoid Reduced Diphtheria Toxoid Acellular Pertussis


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria : Aged 9 to 16 years on the day of inclusion Subject in good health, based on medical history and physical examination Provision of assent form/informed consent form signed by the subject and by the parent(s) or another legally acceptable representative Subject and parent(s)/legally acceptable representative(s) able to attend all scheduled visits and to comply with all trial procedures For a female subject 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 subject 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 subject'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 Subject deprived of freedom by administrative or court order, or in an emergency setting, or hospitalized without his/her consent Febrile illness (temperature ≥38.0°C) 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.

Ages Eligible for Study
-----------------
Minimum Age: 9 Years
Maximum Age: 16 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYD Dengue Vaccine Group<br>Sanofi pasteur's CYD Dengue vaccine group (Dengvaxia®) | Biological: CYD Dengue Vaccine<br>* 0.5 mL, Subcutaneous at Day 0, 6 and 12 months<br>* Other names: Dengvaxia®;|
| Sham Comparator: Control Vaccine Group<br> | Biological: Tetanus Toxoid Reduced Diphtheria Toxoid Acellular Pertussis<br>* NaCl: 0.5 mL, Intramuscular at Day 0 and 6 months; Adacel®: 0.5 mL, Intramuscular at 12 months<br>* Other names: NaCl;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Antibody Titers of ≥10 1/Dil Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). | Day 0 (pre-each vaccination) and Day 28 post-each vaccination | 
| Percentage of Flavi Virus-Immune Participants at Baseline With Antibody Titers ≥10 1/Dil Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavi virus (FV) immune participants at baseline are defined as those participants with ≥ 10 1/dil for at least one serotype with the parental dengue virus strain or for Yellow Fever titer. | Day 0 (pre-each vaccination) and Day 28 post-each vaccination | 
| Percentage of Flavi Virus-Naive Participants at Baseline With Antibody Titers ≥10 1/Dil Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavi virus (FV) naïve participants are defined as those participants with < 10 1/dil for all serotypes with parental dengue virus strains and for Yellow Fever titer. | Day 0 (pre-each vaccination) and Day 28 post-each vaccination | 
| Percentage of Participants With Antibody Titers of ≥10 1/Dil Against At Least 1, 2, 3, or 4 Serotypes With Parental Dengue Virus Strain Before and Following Each Injection With Either Sanofi Pasteur's CYD Dengue Vaccine or A Placebo Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). | Day 0 (before each vaccination) and Day 28 post each vaccination | 
| Percentage of Flavi Virus-Immune Participants With Antibody Titers of ≥10 1/Dil Against At Least 1, 2, 3, or 4 Serotypes With Parental Dengue Virus Strain Pre and Post-Injection With Either Sanofi Pasteur's CYD Dengue Vaccine or A Placebo Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). | Day 0 (before each vaccination) and Day 28 post each vaccination | 
| Percentage of Flavi Virus-Naive Participants With Antibody Titers of ≥10 1/Dil Against At Least 1, 2, 3, or 4 Serotypes With Parental Dengue Virus Strain Pre and Post-Injection With Either Sanofi Pasteur's CYD Dengue Vaccine or A Placebo Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). | Day 0 (before each vaccination) and Day 28 post each vaccination | 
| Summary of Geometric Mean Titers (GMTs) of Antibodies Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). | Day 0 (before each vaccination) and Day 28 post-each vaccination | 
| Summary of Geometric Mean Titers Ratios of Antibodies Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Geometric mean titer ratio is the geometric mean of individual post vaccination/pre vaccination titer of antibodies to each parental dengue virus serotype strain. | Day 0 (before each vaccination) and Day 28 post each vaccination | 
| Summary of Geometric Mean Titers (GMTs) of Antibodies in Flavivirus-Immune Participants at Baseline Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-immune subjects at baseline are defined as those participants with ≥ 10 1/dil for at least one serotype with the parental dengue virus strain or for Yellow Fever titer. | Day 0 (before each vaccination) and Day 28 post each vaccination | 
| Summary of Geometric Mean Titers Ratios of Antibodies in Flavivirus-Immune Participants at Baseline Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-immune subjects at baseline are defined as those participants with ≥ 10 1/dil for at least one serotype with the parental dengue virus strain or for Yellow Fever titer. Geometric mean titer ratio is the geometric mean of individual post vaccination/pre-vaccination titer of antibodies to each parental dengue virus serotype strain. | Day 0 (pre each vaccination) and Day 28 post each vaccination | 
| Summary of Geometric Mean Titers (GMTs) of Antibodies in Flavivirus-Naïve Participants at Baseline Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-naïve participants are defined as those participants with < 10 1/dilutions for all serotypes with parental dengue virus strains and for Yellow Fever titer. | Day 0 (pre-each vaccination) and Day 28 post-each vaccination | 
| Summary of Geometric Mean Titer Ratios of Antibodies in Flavivirus-Naive Participants at Baseline Against Each Parental Dengue Virus Serotype Strain Before and Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine | Neutralizing antibody levels against each of the 4 parental dengue virus strains of Sanofi Pasteur's CYD dengue vaccine constructs were measured using the dengue plaque reduction neutralization test (PRNT). Flavivirus-naïve participants are defined as those participants with < 10 1/dil for all serotypes with parental dengue virus strains and for Yellow Fever titer. Geometric mean titer ratio is the geometric mean of individual post-vaccination/pre-vaccination titer of antibodies to each parental dengue virus serotype strain. | Day 0 (pre-each vaccination) and Day 28 post-each vaccination | 
| Number of Participants Reporting a Solicited Injection-site or Systemic Reactions Following Each Injection With Sanofi Pasteur's CYD Dengue Vaccine | Solicited Injection-site reactions: Pain, Erythema, and Swelling. Solicited Systemic Reactions: Fever, (Temperature) Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited Injection-Site Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥ 5 cm. Grade 3 Solicited Systemic Reactions: Fever, ≥ 39˚C; Headache, Malaise, Myalgia, and Asthenia, Significant; prevents daily activity. | Day 0 up to Day 14 post-each vaccination | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Dengue, Dengue hemorrhagic fever, Dengue virus, Dengue fever, Sanofi pasteur's CYD Dengue vaccine