| Protocol No: | ECCT/18/04/01 | 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. The primary efficacy endpoint is the polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR) at Day 29. Secondary Objectives 1: To evaluate the safety and tolerability of KAF156/LUM-SDF. 2: 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. 3: To assess key pharmacokinetic (PK) parameters of KAF156 and lumefantrine. |
| 3 | 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. The primary efficacy endpoint is the polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR) at Day 29. Secondary Objectives 1: To evaluate the safety and tolerability of KAF156/LUM-SDF. 2: 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. 3: To assess key pharmacokinetic (PK) parameters of KAF156 and lumefantrine. |
| Laymans Summary: | This was a study to test the new anti-malaria drug ganaplacide (KAF156) in combination with lumefantrine (LUM-SDF). This is a new drug that can also work in malaria parasites that are resistant to the drugs that are now used. It is also easier to use since it can be taken once daily. The study was done in patients with an acute malaria infection. Clinics and patients from several countries in Africa and Asia took part in the study. In total 524 patients: adults and children above 2 years of age. 48 of those patients received a control treatment (Coartem®) to see if the new drug would work the same, worse, or better. The goal of this study was to test how good this new drug works to remove the malaria parasite from the patient’s blood. Also, the side effects of the drug were recorded. Another purpose was to find the best possible dose of the medication. The results of the study showed that the new drug KAF156/LUM-SDF was effectively removing the malaria parasite in patients of all ages and cured the patients from the malaria infection. The best effect was seen when the drug was given for 3 days (one time per day). The effect was like the effect of the control drug Coartem®. The side effects of the drug KAF156/LUM-SDF were not very strong and like the control treatment Coartem®. Some patients complained of headache, vomiting, stomach pain and tiredness. These are also symptoms of the malaria infection. The blood tests and heart tests did not show any sign of danger for the new drug. Conclusion of the study is that the new drug ganaplacide + lumefantrine works well and is safe. It should be given for 3 days and will now be tested in other studies with more patients. If the results of these studies are also good, the drug will be made available to doctors and patients. |
| 3 | Malaria remains a major public health problem affecting about half of the world’s population with sub-Saharan Africa carrying the highest burden of malaria. This experiment or research study which is sponsored by a drug company called Novartis (the “Sponsor”) is being done to see if treatment with a new malaria medicine being tested called KAF156 (which is not yet approved for the treatment of people with malaria outside of a research study environment) and another malaria medicine called Lumefantrine Solid Dispersion Formulation (LUM-SDF) when given together can help treat patients with malaria. The reason for this study is to find out the right doses of these malaria medicines, to find out how long or how many days is required for treatment to be effective against malaria and how safe the medicine. Patients will take different doses of KAF156 and LUM-SDF for different number of days. The medicine that is usually used for treating malaria called Coartem® will be given to another group of patients. This is done to check if any safety problems or efficacy results observed in the experimental treatment groups are due to the new treatment. Approximately 110 people have been treated with KAF156 in clinical studies so far. Lumefantrine has been used in millions of people to treat malaria as part of Coartem® treatment. There is an unmet medical need for new malaria medicines that work in new ways just in case current malaria medicines start developing resistance. In addition, we are trying to see if we can reduce the number of days one needs to be on treatment and to reduce the number of tablets people need to swallow to make it easier to take medicines. This study will take place in several countries in Africa including Kenya and in several research sites including Kombewa Clinical Research Centre. KAF156-LUM-SDF combination, could offer a much needed new treatment for malaria, including in areas where resistance to current malaria medicines is becoming a problem. |
| Abstract of Study: | This study aims to determine the most effective and tolerable dose at the shortest dosing regimen of the investigational drug KAF156 in combination with a solid dispersion formulation of lumefantrine (LUM-SDF) in adult/adolescent and pediatric patients with uncomplicated P. falciparum malaria. is unmet medical need for anti-malarial treatment with new mechanism of action to reduce probability of developing resistance, and for duration shorter than 3 days of treatment and/or reduced pill burden. The primary objective of this study is 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. The primary efficacy endpoint is the polymerase chain reaction (PCR) corrected adequate clinical and parasitological response (ACPR) at Day 29. This will be a multicenter and open-label study with a single cohort PK Run-in Part followed by 2 randomized, parallel-group parts in adults and children with confirmed and uncomplicated P. falciparum malaria. The study population will consist of male and female patients (PK Run-in Part and Part A: ≥ 12 years old and ≥ 35.0 kg; Part B: 2 to <12 years old and ≥ 10.0 kg) with confirmed and uncomplicated P. falciparum malaria. The plan is to enroll and treat 12 patients in PK Run-in Part and randomize approximately 500 patients in Parts A and B (325 in Part A and up to 175 in Part B) in approximately 15 sites in Africa and Asia. |