Phase II Efficacy Study of Artefenomel & Piperaquine in Adults & Children With P. Falciparum Malaria.
Condition: Uncomplicated Plasmodium Falciparum Malaria
MeSH terms: Malaria; Malaria, Falciparum
Study type: Interventional
Phase: Phase 2/Phase 3

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).
    

Intervention name(s): Artefenomel 800mg: piperaquine 640mg; Artefenomel 800mg: piperaquine 960mg; Artefenomel 800mg: piperaquine 1440mg
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Active, loose combination; Active, loose combination; Active, loose combination
Other intervention name(s): OZ439 ; PQP; OZ439 ; PQP; OZ439 ; PQP
Intervention MeSH terms: Piperaquine; Artefenomel
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Plasmodium falciparum malaria; malaria; OZ439; piperaquine; PQP