Efficacy and Safety of Dengue Vaccine in Healthy Children

Dengue Fever Clinical Trial

Official title: Efficacy and Safety of Dengue Vaccine in Healthy Children Aged 4 to 11 Years in Thailand

Status Completed

Clinical Trial Summary

The primary objective of the study was to assess the efficacy of CYD dengue vaccine after three injections in preventing symptomatic virologically-confirmed dengue (VCD) cases, regardless of the severity, due to any of the four serotypes in children aged 4 to 11 years at the time of inclusion.

Secondary objectives included to assess:

• Vaccine efficacy against severe VCD cases

• Vaccine efficacy against VCD cases following at least two injections with CYD dengue vaccine

• Immune response to CYD dengue vaccine

• Safety profile of CYD dengue vaccine. Safety assessments include solicited reactions within 7 or 14 days after each injection, unsolicited adverse events within 28 days after each injection, and serious adverse events during the study period.

Other objectives included:

• Vaccine efficacy against VCD cases following at least one injection with CYD dengue vaccine

• Vaccine efficacy against VCD cases due to each serotype

• Participants with clinical signs and symptoms for VCD

Clinical Trial Description

Participants (both cohort 1 and 2) received 3 injections of CYD dengue vaccine. Participants (Cohort 1) received rabies vaccine at Month 0 and placebo at 6 and 12 months. Participants (cohort 2) received placebo at 0, 6, and 12 months.

Dengue cases were collected for assessment of efficacy during the Active Phase from first injection until at least 13 months after the third injection. A subset of participants were also evaluated for reactogenicity and immunogenicity.

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 non-structural protein 1 (NS1) enzyme-linked immunosorbent assay antigen test, and occurring >28 days after the third injection.

Dengue hemorrhagic fever (DHF) Grade I, II, III, and IV according to the 1999 World Health Organization (WHO) definition:

Clinical Manifestations: a) Fever: acute onset, high and continuous, lasting 2 to 7 days. b) Any of the following hemorrhagic manifestations (including at least a positive tourniquet test): petechiae, purpura, ecchymosis, epistaxis, gum bleeding, and hematemesis and/or melena.

Laboratory Findings: 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 (seen on chest X-ray) and/or hypoalbuminemia.

DHF was graded as follows: Grade I: Fever accompanied by non-specific constitutional symptoms; the only hemorrhagic manifestation is a positive tourniquet test. Grade II: Spontaneous bleeding in addition to the manifestations of Grade I participants, usually in the form of skin and/or other hemorrhages. Grade III: Circulatory failure manifested by rapid and weak pulse, narrowing of pulse pressure (20 mmHg or less) or hypotension, with the presence of cold clammy skin and restlessness. Grade IV: Profound shock with undetectable blood pressure and pulse.

Independent Data Monitoring Committee (IDMC) severity criteria:- 1) Thrombocytopenia:

platelet count ≤ 50 000/mm^3 ; 2) Any hemorrhage that needs blood transfusion; 3) Objective evidence of capillary permeability documented by one or several of the following: a) Increase in hematocrit by >= 20 percent (%) compared to normal for age, or [(Maximum hematocrit - minimum hematocrit)/min]*100% >= 20%, b) Pleural or abdominal (ascites) effusion (diagnosed either by clinical signs or radiography or other imaging method), c) Hypoproteinemia; 4) Signs of circulatory failure manifested by: a) Narrow pulse pressure <20mm Hg, or hypotension for age (as defined by systolic pressure <80 mm Hg in children <5 years and systolic pressure < 90 mm Hg in children >= 5 years), and b) Rapid and weak pulse, and c) Signs of poor capillary perfusion (cold and clammy extremities, delayed capillary refill); 5) Visceral Manifestations such as: a) Neurological symptoms (convulsions or change in level of consciousness), b) Hepatic failure or elevation of hepatic enzyme (>5-fold normal level), c) Metabolic (hypoglycemia) or electrolyte (hyponatremia, hypocalcemia) disturbances or volume overload (acute pulmonary edema or congestive heart failure), d) Other visceral manifestations such as cardiomyopathy, acute renal failure, acute respiratory failure, cholecystitis. ;

Related Conditions & MeSH terms

• Dengue
• Dengue Diseases
• Dengue Fever
• Dengue Hemorrhagic Fever
• Dengue Virus
• Fever
• Hyperthermia
• Severe Dengue

• NCT number: NCT00842530
• Study type: Interventional
• Source: Sanofi
• Status: Completed
• Phase: Phase 2
• Start date: February 2009
• Completion date: February 2014