Study of CYD Dengue Vaccine in Healthy Children and Adolescents in South America

Study Overview
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Brief Summary
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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
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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.

Official Title
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Immunogenicity and Safety of CYD Dengue Vaccine in Healthy Children and Adolescents Aged 9 to 16 Years in South America

Conditions
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Dengue, Dengue Hemorrhagic Fever

Intervention / Treatment
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* Biological: Live, attenuated, recombinant dengue serotype 1 , 2, 3 , and 4 virus
* Biological: NaCl 0.9%
* Biological: Tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine adsorbed
* Biological: Meningococcal A+C vaccine


Participation Criteria
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Eligibility Criteria
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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.

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

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dengue Vaccine Group<br>Participants will receive Live, attenuated, recombinant dengue serotype 1 , 2, 3 , and 4 virus vaccine | Biological: Live, attenuated, recombinant dengue serotype 1 , 2, 3 , and 4 virus<br>* 0.5 mL, Subcutaneous (SC)<br>* Other names: CYD Dengue Vaccine;|
| Placebo Comparator: Control Group<br>Participants will receive a placebo, NaCl 0.9%. | Biological: NaCl 0.9%<br>* 0.5 mL, Subcutaneous<br>Biological: Tetanus toxoid, reduced diphtheria toxoid, acellular pertussis vaccine adsorbed<br>* 0.5 mL, Intramuscular<br>* Other names: ADACEL®;Biological: Meningococcal A+C vaccine<br>* 0.5 mL, Intramuscular<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). | Before and 28 days after each injection | 
| 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 | Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer. | Before and 28 days after each injection | 
| 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 | Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus naïve subjects at baseline are defined as those subjects with <10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer. | Before and 28 Days after each injection | 
| 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 | Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). | Before and 28 days after each injection | 
| 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 | Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer. | Before and 28 days after each injection | 
| 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 | Seropositivity was defined as participants achieving neutralizing antibody titers ≥10 (1/dil) against each serotype and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus naïve subjects at baseline are defined as those subjects with <10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer. | Before and 28 days after each injection | 
| 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 | Geometric mean titer ratios were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). | Before and 28 days after each injection | 
| 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 | Geometric mean titers were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). | Before and 28 days after each injection | 
| 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 | Geometric mean titers were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus immune subjects at baseline are defined as those subjects with ≥10 (1/dil) for at least 1 serotype with the parental dengue virus strain or for the yellow fever titer. | Before and 28 days after each injection | 
| 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 | Geometric mean titers were assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). Flavivirus naïve subjects at baseline are defined as those subjects with <10 (1/dil) for all serotypes with parental dengue virus strains and for yellow fever titer. | Before and 28 days after each injection | 
| Percentage of Participants Reporting Solicited Injection-Site and Systemic Reactions Following Any and Each Vaccination With Either CYD Dengue Vaccine or a Placebo | Injection-site reactions: Pain, Erythema, and Swelling. Systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Injection-site reactions (9 to 11 years): Pain, Incapacitating, unable to perform usual activities; Erythema and Swelling, ≥5 cm. Grade 3 Injection site reactions (≥12 years): Pain, Significant; prevents daily activity; Erythema and Swelling, >10 cm. Grade 3 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
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Keywords Provided by Centre Hospitalier Valida
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Dengue, Dengue hemorrhagic fever, CYD Dengue Vaccines