| Protocol No: | ECCT/15/11/05 | Date of Protocol: | 20-11-2014 |
| Study Title: |
A Randomized, Double-blind, Phase IIb Study to Investigate the Efficacy, Safety, Tolerability and Pharmacokinetics of a Single Dose Regimen of Ferroquine (FQ) with Artefenomel (OZ439) in Adults and Children with Uncomplicated Plasmodium falciparum Malaria.
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| Study Objectives: | Primary Objective To determine whether a single dose combination of OZ439/FQ is an efficacious treatment for uncomplicated Plasmodium falciparum (P. falciparum) malaria in adults and children
Secondary Objectives
m. To explore the relationship between Kelch-13 genotype and parasite clearance kinetics |
| Laymans Summary: | Malaria is responsible for considerable morbidity and mortality, particularly in Western Kenya. Malaria is best treated with a combination of drugs as this prevents development of drug resistance. Currently, uncomplicated malaria is treated with a three day course of treatment which is associated with considerable defaulting-many patients do not complete the three day dose. This is a proposed phase IIb trial of a single dose treatment of ferroquine and artefenomel in the treatment of uncomplicated malaria. Patients will be entered into the trial based on their age groups, beginning with older patients. All patients will receive the same dose (or a weight adjusted dose) of Artefenomel 800mg, but will be randomly assigned to varying doses of Ferroquine. The objective is to determine safety, tolerability and efficacy of the combination of treatment. |
| Abstract of Study: |
Plasmodium falciparum (P. falciparum) malaria is a major cause of morbidity and mortality in Africa. Siaya County in Western Kenya is holoendemic for malaria(1). At the Siaya Hospital outpatient department alone, data abstraction shows 2000-4000 cases of uncomplicated malaria seen at the facility annually.
Concurrent with preventive measures, World Health Organization (WHO) guidelines recommend artemisinin-based combination therapies (ACT) are used to treat uncomplicated P. falciparum malaria to prevent development of resistance and to improve treatment outcome.
Artemisinin produces rapid clearance of parasitemia and resolution of symptoms by reducing parasite number by 100- to 1000-fold per asexual cycle of the parasite. Artemisinin and its derivatives are rapidly eliminated. It is therefore given in combination with 4-aminoquinoline drugs which have a longer half-life. This requires a three day course of treatment. Evidence suggests that compliance to this 3-day regimen is low, thereby reducing treatment effectiveness. In addition, emergence of resistance to artemisinin may become a considerable problem in the coming years(2). New drug combinations are required. Particularly, effective single dose combination treatments will likely improve effectiveness.
A fixed dose combination of two therapeutic agents Ferroquine (FQ) and Artefenomel (OZ439) will be evaluated as single day-single dose treatment of uncomplicated malaria. This will be a Phase IIb safety, tolerability, pharmacokinetic and efficacy trial. The target population will be adults <70 years old and children >6months with uncomplicated malaria.
Patients will be randomized to up to four treatment arms containing both FQ and OZ439. The dose of OZ439 will be fixed at 800mg in each arm. However the dose of FQ will vary with each arm receiving a higher dose than the previous cohort. The primary outcome will be PCR-adjusted Adequate Clinical and Parasitological Response (ACPR) at day 28. Total follow up time per patient will be at least 67 days from study entry to close out. Safety endpoints will be based on clinical and laboratory identified adverse events.
If this combination proves to be effective and safe in areas where artemisinin-resistant P. falciparum is absent or rare complementary trials may be performed to determine whether a similar clinical benefit exists in locations where resistance to artemisinin and chloroquine have developed.
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