Efficacy, Safety and Tolerability of KLU156 in Adults and Children ≥ 5 kg Body Weight With Uncomplicated P. Falciparum Malaria
- Conditions
- Uncomplicated Plasmodium Falciparum Malaria
- Interventions
- Registration Number
- NCT05842954
- Lead Sponsor
- Novartis Pharmaceuticals
- Brief Summary
This study aims to confirm the efficacy, safety and tolerability of KLU156, a fixed dose combination of ganaplacide (KAF156) and a solid dispersion formulation of lumefantrine (lumefantrine-SDF), when administered once daily for three days in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated P. falciparum malaria (with or without other Plasmodium spp. co-infection).
In the Extension phase, the safety, tolerability and efficacy of repeated treatment with KLU156 will be assessed for a maximum of two years in patients who did not experience early treatment failure (ETF), who did not experience any study treatment-related SAE (Serious Adverse Event) previously and who gave informed consent to participate in the Extension phase.
- Detailed Description
The purpose of this study is to confirm the efficacy, safety and tolerability of KLU156 in patients with uncomplicated P. falciparum malaria (with or without other Plasmodium spp. co-infection) by demonstrating that KLU156 is non-inferior to Coartem.
* The study duration will be 43 days (Core phase) plus 24 months (Extension phase).
* The treatment duration will be 3 days for each malaria episode.
* The visit frequency will be Days 1-3 (hospitalized) and 5 follow-up visits (Days 4, 8, 22, 29 and 43) in the Core phase and Days 1-3 (hospitalized) and 3 follow-up visits (Days 4, 8 and 29) in the Extension phase.
Recruitment & Eligibility
- Status
- RECRUITING
- Sex
- All
- Target Recruitment
- 1500
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description KLU156 KLU156 KLU156 once daily (QD) for 3 days under fed conditions (light meal). Coartem Coartem Coartem twice a day (BID) for 3 days under fed conditions.
- Primary Outcome Measures
Name Time Method PCR-corrected adequate clinical and parasitological response (ACPR) Day 29 (i.e., 28 days post-first dose administration) To confirm the efficacy of KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) by demonstrating that KLU156 is non-inferior to Coartem (non-inferiority margin = 5%) based on the PCR-corrected ACPR at Day 29.
- Secondary Outcome Measures
Name Time Method Proportion of patients with parasitemia 12, 24, 48 and 72 hours after treatment For the parasitemia assessment, blood sampling can be done by means of a finger prick except when the timing for parasitology assessments coincides with time for clinical laboratory tests, in which case, blood sample can be taken from the venous blood collected for clinical laboratory analyses.
Gametocytemia From baseline up to Day 43 Disappearance or development of gametocytemia in patients with or without gametocytemia at baseline (pre-first dose administration), respectively
PCR-corrected and uncorrected ACPR Days 22 and 43 (i.e., 21 and 42 days post-first dose administration) To confirm the efficacy of KLU156 by assessing uncorrected and PCR-corrected ACPR at additional time points
Fever Clearance Time Up to Day 3 To confirm the efficacy of KLU156 by assessing fever clearance between the two treatment arms
Parasite Clearance Time Up to Day 3 To assess parasite clearance time between the two treatment arms
Extension phase: PCR-corrected and uncorrected ACPR Day 29 of malaria episode To evaluate efficacy over repeated treatment with KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) for a maximum of 2 years
Extension phase: Gametocyte carriage over time Up to 2 years To assess gametocyte carriage over time by malaria episode in the extension phase
Uncorrected ACPR Day 29 To further confirm the efficacy of KLU156 by demonstrating non-inferiority of KLU156 to Coartem (NI margin 7.5%) based on the uncorrected ACPR at Day 29
Incidence and severity of Adverse Events (AEs) and Serious Adverse Events (SAEs) Day 43 Incidence and severity of AEs and SAEs by treatment group, including changes in vital signs, electrocardiograms (ECGs), and laboratory results qualifying and reported as AEs.
Incidence rate of recrudescence and new infection Days 22, 29 and 43 Proportion of patients with recrudescence and new infections between the two treatment arms
Extension phase: KLU156-related AE/SAE incidence and severity by malaria episode Up to 2 years To assess the safety and tolerability over repeated treatment with KLU156 in adults and children ≥ 5 kg body weight and ≥ 2 months of age suffering from uncomplicated malaria caused by P. falciparum (with or without other Plasmodium spp. co-infection) for a maximum of 2 years
Trial Locations
- Locations (1)
Novartis Investigative Site
🇿🇲Ndola, Zambia