Study of a Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 11 Years in Malaysia

Study Overview
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Brief Summary
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The purpose of this study was to evaluate the safety and immunogenicity of Phase III lots of the CYD dengue vaccine in a pediatric population in Malaysia. Primary Objectives: To describe the safety (in terms of solicited and unsolicited adverse events) of the CYD dengue vaccine in all participants after each injection. To describe the antibody response to each dengue virus serotype post-injection 2 and post-injection 3.

Detailed Description
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Healthy participants aged 2 to 11 years received 3 vaccinations at pre-determined schedules and were followed-up for at least 6 months after the last vaccination.

Official Title
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Safety and Immunogenicity of a Tetravalent Dengue Vaccine in Healthy Children Aged 2 to 11 Years in Malaysia

Conditions
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Dengue Fever, Dengue Hemorrhagic Fever

Intervention / Treatment
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* Biological: Live, attenuated, recombinant dengue serotypes 1, 2, 3, and 4 virus
* Biological: Placebo: NaCl 0.9%


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 2 to 11 years on the day of inclusion Assent form was signed and dated by the participant (for participants ≥ 7 years) and informed consent form was signed and dated by the parent(s) or another legally accepted representative, and by an independent witness if the two parents or legally accepted representative were illiterate Participant and parent/legally accepted representative were able to attend all scheduled visits to comply with all trial procedures Participants in good health, based on medical history and physical examination For a female participant of childbearing potential, use of an effective method of contraception or abstinence for at least 4 weeks prior to the first vaccination, until at least 4 weeks after the last vaccination Exclusion Criteria: Known pregnancy, or a positive urine pregnancy test (for female participant of child-bearing potential only) 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 the trial first vaccination, except for pandemic influenza vaccination 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 months; or long-term systemic corticosteroid therapy (prednisone or equivalent for more than 2 consecutive weeks within the past 3 months) Seropositivity for human immunodeficiency virus (HIV) reported by the parent/legally acceptable representative Known systemic hypersensitivity to any of the vaccine components, or history of a life-threatening reaction to the vaccine(s) used in the trial or to a vaccine containing any of the same substances Chronic illness that, in the opinion of the investigator, was at a stage where it might interfere with trial conduct or completion Participants who plan to move to another country/region within the 18 coming months Identified as a child (adopted or natural) of the Investigator or of site 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.

Ages Eligible for Study
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Minimum Age: 2 Years
Maximum Age: 11 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CYD Dengue vaccine group<br>Participants received 3 injections of the CYD dengue vaccine, 1 injection each at 0, 6, and 12 months. | Biological: Live, attenuated, recombinant dengue serotypes 1, 2, 3, and 4 virus<br>* 0.5 mL (at 0, 6, and 12 months), Subcutaneous suspension<br>* Other names: CYD Dengue vaccine;|
| Placebo Comparator: Placebo Group<br>Participants received 3 injections of placebo, 1 injection each at 0, 6, and 12 months. | Biological: Placebo: NaCl 0.9%<br>* 0.5 mL (at 0, 6, and 12 months), Subcutaneous suspension<br>* Other names: Saline;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Reporting Solicited Injection-site and Systemic Reactions Following Any and Each Vaccination With Either CYD Dengue Vaccine or a Placebo | Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Grade 3 Solicited injection site reactions: Pain: Incapacitating, unable to perform usual activities; Erythema and Swelling: >=50 millimeter (mm). Grade 3 Solicited systemic reactions: Fever: >=39°Degree Celsius (C); Headache, Malaise, Myalgia, and Asthenia: Significant: Prevents daily activity. | Day 0 up to Day 14 post-any and each vaccination | 
| Percentage of Flavivirus-Immune Participants Reporting Solicited Injection Site and Systemic Reactions Following Each Vaccination With CYD Dengue Vaccine or Placebo Vaccine | Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Flavivirus-Immune participants were defined as participants with quantified antibodies against Japanese encephalitis and/or against at least 1 serotype with parental dengue virus strains (serotype 1, 2, 3, and 4) in the baseline sample. | Day 0 up to Day 14 post-each vaccination | 
| Percentage of Flavivirus-Naïve Participants Reporting Solicited Injection-site and Systemic Reactions Following Each Vaccination With CYD Dengue Vaccine or a Placebo Vaccine | Solicited injection site reactions: Pain, Erythema, and Swelling. Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Flavivirus-Naive participants were defined as participants without quantified antibodies against Japanese encephalitis and without antibody quantified against all serotypes (1, 2, 3, and 4) with parental dengue virus strains in the baseline sample. | Day 0 up to Day 14 post-each vaccination | 
| 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/dilution) against each dengue serotype (1,2, 3 and 4) and was assessed using the Dengue Plaque Reduction Neutralization Test (PRNT). | Pre-Injection 1 and Post-Injections 2 and 3 | 
| Percentage of Participants With Seropositivity Against at Least One, Two, Three, or the Four 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/dilution) against each dengue serotype (1, 2, 3, and 4) and was assessed using the dengue PRNT. | Pre-Injection 1 and Post-Injections 2 and 3 | 
| Geometric Mean Titers (GMTs) Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo | GMTs of antibodies against the dengue virus serotypes (1, 2, 3, and 4) were assessed using the dengue PRNT. | Pre-Injection 1 and Post-Injections 2 and 3 | 
| 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: Flavivirus-Immune Participants | Seropositivity was defined as participants achieving neutralizing antibody titers >=10 (1/dilution) against each serotype (1, 2, 3, and 4) and was assessed using the Dengue PRNT. Flavivirus-Immune participants were defined as participants with quantified antibodies against Japanese encephalitis and/or against at least 1 serotype (1, 2, 3, and 4) with parental dengue virus strains in the baseline sample. | Pre-Injection 1 and Post-Injections 2 and 3 | 
| 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: Flavivirus-Naive Participants | Seropositivity was defined as participants achieving neutralizing antibody titers >=10 (1/dilution) against each serotype (1, 2, 3, and 4) and was assessed using the Dengue PRNT. Flavivirus naïve participants were defined as participants without quantified antibodies against Japanese encephalitis and without quantified antibodies against all serotypes (1, 2, 3, and 4) with parental dengue virus strains in the baseline sample. | Pre-Injection 1 and Post-Injections 2 and 3 | 
| GMTs of Flavivirus-Immune Participants Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo | GMTs of antibodies against the dengue virus serotypes (1, 2, 3, and 4) were assessed using the Dengue PRNT. Flavivirus-Immune participants were defined as participants with quantified antibodies against Japanese encephalitis and/or against at least 1 serotype (1, 2, 3, and 4) with parental dengue virus strains in the baseline sample. | Pre-Injection 1 and Post-Injections 2 and 3 | 
| GMT of Flavivirus-Naïve Participants Against Each Serotype With the Parental Dengue Virus Strains Before and After Vaccinations With Either CYD Dengue Vaccine or a Placebo | GMTs of antibodies against the dengue virus serotypes (1, 2, 3, and 4) were assessed using the Dengue PRNT. Flavivirus-Naive participants were defined as participants without quantified antibodies against Japanese encephalitis and without antibody quantified against all serotypes (1, 2, 3, and 4) with parental dengue virus strains in the baseline sample. | Pre-Injection 1 and Post- Injections 2 and 3 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Dengue fever, Dengue hemorrhagic fever, CYD dengue vaccine