Clinical trial NCT02083380
Conditions: Uncomplicated Plasmodium Falciparum Malaria
Keywords: Plasmodium falciparum malaria malaria OZ439 piperaquine PQP
Sponsor: Medicines for Malaria Venture
Start date: 2014-07-01; Completion date: 2015-11-01
Enrollment: 448 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A randomised, double-blind single-dose study to determine the efficacy, safety, tolerability and pharmacokinetics of OZ439 (artefenomel) in combination with piperaquine (PQP) in patients \> 0.5 years and \<= 70 years of age with uncomplicated Plasmodium falciparum malaria in Africa and Asia (Vietnam).

Interim analyses for futility were planned. Adults and children will be included through progressive step-down in age following safety review by an independent safety monitoring board (ISMB).

If the study were to meets its efficacy objectives, this will inform dose setting for Phase III studies.

Detailed description:
A randomised, double-blind single-dose (loose combination) study in the target patient population of children \> 0.5 years and \<= 5 years of age in Africa and patients of all ages in Asia (\> 0.5 years and \<= 70 years) with uncomplicated Plasmodium falciparum malaria. Patients \> 5 years in Africa were also to be recruited in a safety age step down procedure. The underlying assumption was that children of 5 years or less in Africa and all ages in Asia will have a higher probability of having lower immunity and hence potentially require higher drug exposure to achieve efficacy and hence the study aimed to recruit 60-80% African children \< = 5 years and 18-36% Asian patients (defined as the target population) and approximately 10% African patients \>5 years,

Three OZ439/PQP treatment arms were to be included for patients \>= 35 kg (800mg OZ439 in loose combination with PQP doses of either 640, 960, 1440 mg). Doses were scaled for patients \< 35kg based on the weight to achieve similar exposures in patients \>= 35kg.

The study was to test for futility and dose arms were to be dropped if the probability was \>30% that PCR-adjusted ACPR at Day 28 (ACPR28) was less than 90% (the target efficacy for the study was \>= 95% ACPR28). Only data from patients in Asia patients and Africa patients \< 5 years were to be included in the Interim analysis, although all patients were to be included in the final analysis. Interim analyses were to occur after recruitment of approximately 50 evaluable patients per dose cohort and thereafter approximately after every 25 patients.

In a separate process, the safety of OZ439/PQP treatment arms was to be assessed at scheduled time points by an ISMB and adults and children were included through progressive step-down in age range following safety evaluation

Following Screening and informed consent, patients were to receive study drug and were to be followed for clinical signs of malaria (parasitaemia and temperature), safety assessments and pharmacokinetics up to Day 42 following dosing (Day 63 at selected sites).

Arms: arm 1: One single dose of Artefenomel 800mg: Piperaquine phosphate 640mg loose combination arm 2: One single dose of Artefenomel 800mg: Piperaquine phosphate 960mg loose combination arm 3: One single dose of Artefenomel 800mg: Piperaquine phosphate 1440mg loose combination
Interventions: intervention 1: Artefenomel 800mg: piperaquine 640mg intervention 2: Artefenomel 800mg: piperaquine 960mg intervention 3: Artefenomel 800mg: piperaquine 1440mg
Intervention descriptions: intervention 1: Active, loose combination intervention 2: Active, loose combination intervention 3: Active, loose combination

Protocol documents: