Pharmacy and Poisons Board
Protocol No: ECCT/17/08/03 Date of Protocol: 14-02-2017
Study Title:
A Phase 2 interventional, multicenter, randomized open-label study to determine the effective and tolerable dose of KAF156 and Lumefantrine Solid Dispersion Formulation in combination, given once daily for 1, 2 and 3-days to adults and children with uncomplicated Plasmodium falciparum malaria.
 
 
Study Objectives:

Primary Objective

  • To determine the effective doses of KAF156 combined with LUM-SDF given daily over 1, 2 or 3 days for treatment of uncomplicated malaria caused by P.falciparum.

 

Secondary Objectives

  • To evaluate the safety and tolerability of KAF156/LUM-SDF.
  • To further assess the effect of treatment with KAF156/LUM-SDF by assessing uncorrected ACPR and corrected ACPR at additional time points, as well as fever- and parasite clearance times.
  • To assess the key PK parameters of KAF156 and lumefantrine.

 

Exploratory Objectives

  • To explore the effect of pharmacokinetic parameters on key efficacy and safety parameters.
  • To explore the effect of KAF156/LUM-SDF on gametocytes and transmission-blocking potential.
  • To further explore the effect of treatment with KAF156/LUM-SDF by assessing parasite reduction ratio and the parasite clearance estimator.
  • To examine the relationship between parasite genotypes of interest and parasite clearance kinetics/efficacy.
Laymans Summary:

A phase 2 interventional, multicentre, randomized open-label study to determine the effective and tolerable dose of KAF156 and Lumefantrine and 3-days to adults and children with uncomplicated plasmodium falciparum malaria
Abstract of Study:
Disease Burden
According to the WHO (2015) Malaria is one of the most important infectious diseases which threatens about 3.2 billion people; almost half of the world’s population. Plasmodium falciparum (P. falciparum) malaria is a major cause of morbidity and mortality in Africa. Siaya County in Western Kenya is holoendemic for malaria. At the Siaya Hospital outpatient department alone, data abstraction shows 2000-4000 cases of uncomplicated malaria seen at the facility annually.
 
Available remedies
Artemisinin-based combination therapies (ACTs) such as Coartem®/Riamet® and Eurartesim®, are current standard-of-care for P. falciparum malaria. 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.
 
Emergence of resistance
Recent studies showed that artemisinin resistance extends over more of Southeast Asia than had previously been known, and is now present close to the border with India (Menard et al 2016). If widespread artemisinin drug resistance was to occur, malaria pharmacotherapy would be severely impaired. This finding signifies that spread of resistance is inevitable, thus there is urgent need for new antimalarials with new mechanism of actions (Tun et al 2015).
 
Secondly, evidence suggests that compliance to this 3-day regimen is low, thereby reducing
Treatment effectiveness. New drug combinations are required. Particularly, effective single dose combination treatments will likely improve effectiveness; reduce likelihood of development of drug resistance.