Efficacy and Safety of KAF156 in Combination With LUM-SDF in Adults and Children With Uncomplicated Plasmodium Falciparum Malaria

Summary

This study was designed 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 Plasmodium falciparum malaria. There 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.

Timeline

Start

2017-08-02

Primary completion

2021-06-14

Completion

2021-06-28

Outcome

Mixed primary results

paper The primary efficacy endpoint was PCR-corrected adequate clinical and parasitological response at day 29 PMID 37327809 ↗

paper was more than 80% for all treatment regimens in part A PMID 37327809 ↗

paper Only the 3-day regimen met the prespecified primary endpoint in paediatric patients PMID 37327809 ↗

Publications

• Sangana R, Ogutu B, Yeka A, Kusemererwa S, Tinto H, Toure AO, Kibuuka A, Lingani M, Lourenco C, Mombo-Ngoma G, Nduba V, Landry N'Guessan T, Nassa GJW, Nyantaro M, Tina LO, Anvikar A, Sinha A, Kaguthi G, Fofana B, Grobusch MP, Gaaloul ME, Marrast AC, Pathan R, Chikoto H, Csermak K, Risterucci C, Su G, Winnips C, Zhang J, Zack J. Pharmacokinetics of Ganaplacide and Lumefantrine in Adults, Adolescents, and Children with Plasmodium falciparum Malaria Treated with Ganaplacide Plus Lumefantrine Solid Dispersion Formulation: Analysis of Data from a Multinational Phase 2 Study. J Clin Pharmacol. 2025 Feb;65(2):179-189. doi: 10.1002/jcph.6138. Epub 2024 Sep 29.
• Ogutu B, Yeka A, Kusemererwa S, Thompson R, Tinto H, Toure AO, Uthaisin C, Verma A, Kibuuka A, Lingani M, Lourenco C, Mombo-Ngoma G, Nduba V, N'Guessan TL, Nassa GJW, Nyantaro M, Tina LO, Singh PK, El Gaaloul M, Marrast AC, Chikoto H, Csermak K, Demin I, Mehta D, Pathan R, Risterucci C, Su G, Winnips C, Kaguthi G, Fofana B, Grobusch MP. Ganaplacide (KAF156) plus lumefantrine solid dispersion formulation combination for uncomplicated Plasmodium falciparum malaria: an open-label, multicentre, parallel-group, randomised, controlled, phase 2 trial. Lancet Infect Dis. 2023 Sep;23(9):1051-1061. doi: 10.1016/S1473-3099(23)00209-8. Epub 2023 Jun 13.

Drugs

Evaluation	Drug	Modality	Dose	Route
Comparator	Coartem	Unknown	—	Oral
Subject	Ganaplacide	Small molecule	200 mg	Oral
Subject	Ganaplacide	Small molecule	400 mg	Oral
Subject	Ganaplacide	Small molecule	800 mg	Oral
Subject	lumefantrine	Small molecule	480 mg	Oral
Subject	lumefantrine	Small molecule	960 mg	Oral

Indications