Malaria remains a major public health with great impact on children and pregnant women. In 2015 World health Organization reported 212 million new cases and over 429,000 deaths. WHO currently recommends the use of artemisinin-based combination treatment (ACT) for uncomplicated P. falciparum malaria, administrated in a 3-day dose. However, there is already development of resistance to ACTs in South East Asia and there is worry that this will spread the rest of the world and there is need to develop new combinations treatment regimens for treatment of uncomplicated malaria. Therefore, Sanofi and Medicines for Malaria Venture (MMV) are co-developing a fixed dose combination (FDC) of FQ and artefenomel (OZ439) for a single dose treatment of uncomplicated malaria in adults and children. The study is going to be done in several countries where malaria is common and Kenya is one of them. The sample size will be140 patients with uncomplicated malaria. In Kenya the study will be conducted in Ahero and Siaya County hospitals. In Ahero we will recruit about 40 patients both males and females. The patients will have blood drawn from the arm to check the presence parasites in the blood, check the blood level, kidney, liver functions and drug blood level. The main outcome will be clearance of parasites and no recurrence of infection by 28 days after starting treatment. The potential risks are that this is a new drug and a patient can react to it but so far it has been safe in the previous studies. The other possible risks is that being a new it may not clear malaria infection but the patients will be followed up closely and in case of failure to respond to treatment they will be given rescue treatment. The study will be conducted in line with National and international guidelines for clinical trials. The study will be initiated once all the approvals have been obtained and the sponsor representatives initiates the study site. The data generated will be analysed as per the predesigned statistical analytical plan and will focus on the how well the drug clears malaria parasites from the patients’ blood, how the drug is safe and drug level in the patients’ blood. The results from this study will inform the development of this new treatment of uncomplicated malaria that is needed as there is already resistance to ACTs in Asia. The results from this study will be disseminated to stakeholders in Kisumu County, published in peer reviewed scientific journals, presented at Scientific conferences.

Plasmodium falciparum (P. falciparum) malaria remains a deadly endemic parasitic disease, with 212 million new cases and over 429,000 deaths reported in 2015. World Health Organization (WHO) guidelines recommend that artemisinin-based combination therapies (ACT) are used to treat uncomplicated P. falciparum malaria, which is administrated in a 3-day regimen. Sanofi and Medicines for Malaria Venture (MMV) are co-developing a fixed dose combination (FDC) of FQ and artefenomel (OZ439) for a single dose treatment of uncomplicated malaria in adults and children. Per Food and Drug Administration (FDA) guidance for co-development of 2 new investigational drugs for use in combination, it is recommended to demonstrate the contribution of each individual component to the effect of the combination. This phase 2a study will test clinical and parasiticidal activity, pharmacokinetics (PK) and safety of 3 doses of OZ439 associated with a fixed dose of FQ and FQ alone. This is a phase 2a, randomized, open label, parallel-group study, single-dose regimen, testing 3 dose levels of OZ439 given in combination with FQ and FQ alone in participants with uncomplicated P. falciparum malaria. The primary objective of the study is to show the contribution of OZ439 to the clinical and parasiticidal effect of OZ439/FQ combination by analyzing exposure-response of OZ439 measured by Day 28 polymerase chain reaction (PCR)-corrected adequate clinical and parasitological response (ACPR) for the effect and the area under the concentration time curve up to infinity (AUC) of OZ439 as PK predictor. Adults up to 69 years old and adolescents as of 14 years old will be included in 4 parallel arms in a 1:1:1:1 randomization ratio. Randomization will occur the day of or up to 1 day after screening procedures. Participants will receive one of the 4 treatments: FQ 400 mg alone or combined with OZ439 300 mg, 600 mg, or 1000 mg. Participants will be hospitalized for the first 48 hours or up to 4 days or longer upon investigator’s judgment. Participants will be screened sequentially as they present to the study facility to achieve 140 randomly assigned to study treatment and 120 evaluable participants for an estimated total of 30 evaluable participants per treatment group. Ahero site we will recruit about 40 patients both males and females. There will be 4 study groups receiving different doses of study drugs. The primary endpoint will be Day 28 PCR-corrected ACPR. The parasite clearance will be determined by microscopy and PK parameters will determined by chromatography techniques while safety parameters will be assessed by clinical evaluation during the study visits and clinical laboratory evaluations.