Phase IIb Study to Investigate the Efficacy of OZ439 & Piperaquine Phosphate Co-administered to Adults & Children With Uncomplicated Plasmodium Falciparum.

Uncomplicated Plasmodium Falciparum Malaria Clinical Trial

Official title: A Randomised, Double-blind, Phase IIb Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Artefenomel (OZ439) in Loose Combination With Piperaquine Phosphate in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria.

Status Completed

Clinical Trial Summary

A randomised, double-blind single-dose (loose combination) study in patients with uncomplicated Plasmodium falciparum malaria. The study will test for efficacy/futility through analyses, using Bayesian methodology. Adults and children will be included through progressive step-down in age following safety analyses.

This study investigates the efficacy exposure-response of OZ439/PQP combination in the target populations and if it meets its efficacy objectives, will inform dose setting for Phase III studies.

Clinical Trial Description

A randomised, double-blind single-dose (loose combination) study in patients spanning the age range greater than or equal to 6 months to less than 70 years, with uncomplicated Plasmodium falciparum malaria. Three OZ439/PQP treatment arms will be included (for patients > 35 kg), with doses scaled to target similar exposures in lighter patients.

The study aims to recruit predominantly patient populations with the highest probability of having 'lower immunity' to P. falciparum, while also including patients with a probability of having 'higher immunity'. Hence the study will recruit across a wide age range and across geographical regions (Africa, Asia and possibly Latin America). The underlying assumption is that children of 5 years or less in Africa and all ages in Asia/Latin America will have the lower immunity and hence potentially require the highest drug exposure to achieve effective treatment. For this reason, patients of 5 years or less in Africa will form the largest proportion of the population while patients of greater than 5 years in Africa will form the lowest proportion of the population.

The study will test for efficacy/futility at Day 28 (including data from patients discontinuing prior to Day 28) through interim analyses using Bayesian methodology. Only data from patients in Asia/Latin America and patients of 5 years or less in Africa (the 'lower immunity' population) will be included in the interim analyses. Interim assessment of efficacy and futility will occur after recruitment of approximately 50 evaluable patients per dose cohort and thereafter approximately every 25 patients.

Independently of the analyses for efficacy/futility, the safety of OZ439/PQP treatment arms will be assessed at scheduled time points by an Independent Safety Monitoring Board (ISMB).

Adults and children will be included through progressive step-down in age range following safety evaluation.

Following Screening and informed consent, patients will receive study drug and will 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). ;

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Malaria
• Malaria, Falciparum
• Uncomplicated Plasmodium Falciparum Malaria

• NCT number: NCT02083380
• Study type: Interventional
• Source: Medicines for Malaria Venture
• Status: Completed
• Phase: Phase 2/Phase 3
• Start date: July 2014
• Completion date: November 2015