Trial Outcomes & Findings for Efficacy and Safety of Dengue Vaccine in Healthy Children (NCT NCT00842530)

Study participants were enrolled from 05 February 2009 to 05 February 2010 at 1 clinical site in Thailand. A total of 4002 participants who met all of the inclusion criteria and none of the exclusion criteria were enrolled and randomized; however, only 3997 participants received the first vaccination.

Two-step enrollment approach was followed. Cohort 1 (100 participants \[CYD vaccine arm\] received CYD vaccine as Injection \[Inj.\] 1 and 50 \[control group arm\] received rabies vaccine as Inj. 1) was enrolled first. After 14 days review of Cohort 1 safety data in both arms, cohort 2 was enrolled (2569 participants in CYD group; 1283 in control group).

Efficacy and Safety of Dengue Vaccine in Healthy Children

Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature \>= 37.5 degree Celsius (°C) measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue non-structural protein-1 (NS1) enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk.

The severity of VCD cases was assessed by WHO 1999 severity assessment and IDMC clinical assessment. Dengue Hemorrhagic Fever (DHF) Grade I, II, III, and IV : Clinical Manifestations: a) Fever: acute onset, high and continuous, lasting 2-7 days, b) Any of hemorrhagic manifestations: petechiae, purpura, ecchymosis, epistaxis, gum bleeding, and hematemesis and/or melena, c) thrombocytopenia (platelet count=100 000/mm3 or less) d) Plasma leakage as shown by hemoconcentration (hematocrit increased by 20% or more) or pleural effusion and/or hypoalbuminemia. IDMC severity criteria: 1) Thrombocytopenia: platelet count \<= 50 000/mm\^3; 2) Hemorrhage that needs blood transfusion; 3) Objective evidence of capillary permeability 4) Signs of circulatory failure; 5) Visceral Manifestations. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk.

Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature \>= 37.5°C measured at least twice with an interval of at least 4 hours), confirmed by dengue reverse transcriptase-polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk.

GMT of antibodies against each serotype with the parental dengue virus strain were assessed by the plaque reduction neutralization test (PRNT).

GMTs of antibodies against each serotype with the parental dengue virus strain were assessed by the PRNT. Dengue immune participants were defined as those participants with titers \>= 10 (1/dilution) against at least one dengue serotype at baseline.

GMTs of antibodies against each serotype with the parental dengue virus strain were assessed by the PRNT. Dengue non-immune participants were defined as participants with titers \< 10 (1/dilution) against all four dengue serotypes at baseline.

Solicited Inj. site reactions: Pain, Erythema, and Swelling. Pain: - Grade 1: easily tolerated, Grade 2: sufficiently discomforting to interfere with normal behavior or activities, Grade 3: incapacitating, unable to perform usual activities. Erythema and Swelling: - Grade 1: \> 0.0 to \< 2.5 cm, Grade 2: \>= 2.5 to \< 5 cm, Grade 3: \>= 5 cm.

Solicited systemic reactions: Fever, Headache, Malaise, Myalgia, and Asthenia. Fever:- Grade 1: \>=37.5°C to \<=38.0°C, Grade 2: \>38.0°C to \<=39.0°C, Grade 3: \>39.0°C. Headache, malaise, myalgia and asthenia: - Grade 1: noticeable but does not interfere with daily activities, Grade 2: interferes with daily activities, Grade 3: prevents daily activities.

Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature \>=37.5°C measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. Vaccine efficacy was reported as density incidence (cases/100 person-years at risk). Density incidence was defined as the number of VCD cases divided by the cumulative person-years at risk.

Symptomatic VCD cases were defined as acute febrile illness with fever lasting for at least 1 day (temperature \>= 37.5°C measured at least twice with an interval of at least 4 hours), confirmed by reverse transcriptase-polymerase chain reaction and/or dengue NS1 enzyme-linked immunosorbent assay antigen test, and occurring more than 28 days after the third injection. VCD cases confirmed only by NS1 method were classified in the Not Identified category. Cases were defined as the number of participants with at least one symptomatic VCD episode more than 28 days after Inj. 3 (during the Active Phase).

Clinical signs and symptoms for VCD included the following: fever, clinical syndrome and hospitalization. Duration of each symptom (in days) is reported in this outcome measure.