A Phase 2, multi-center, randomized, open-label, doseescalation study to determine safety of single (QD) and multiple (3 QD) doses of KAE609, given to adults with uncomplicated Plasmodium falciparummalaria
Study period:Ongoing.
KAE609 is a novel spiroindolone class drug with potent and fast-acting schizonticidal activity, which acts by disrupting the malaria parasite Na+ homeostasis by inhibition of the ATPase PfATP4. KAE609 has been evaluated in healthy volunteers in single doses up to 300 mg and repeated doses up to 150 mg (3-day Once daily (QD)) without any significant safety and tolerability issue. In the initial patient study, a 3-dayQD treatment of 30 mg was well tolerated. In a subsequent patient study, at a single dose of 75 mg, transient Grade 2-3 LFT elevations were however observed in 5/11 patients. In a malaria challenge studywith healthy volunteers in Australia, transient Grade 3-4 LFT elevations were observed in 3/8 subjects following a single dose of 10 mg of KAE609. Following evaluation of these events, it was concluded that hepatic toxicity of KAE609 cannot be excluded, and that an additional safety dose escalation study should be performed before exploring safety and efficacy in a fixed-dose combination of KAE609 with a long acting anti-malarial.
Purpose : This Phase 2 study aims to determine the maximum safe dose of the investigational drug KAE609 in malaria patients. The study population consists of adult malaria patients (≥ 18 years, ≥ 45 kg bodyweight) with uncomplicated symptomatic malaria caused by Plasmodium (P.) falciparum. KAE609 will be evaluated primarily for hepatic safety following administration of single and multiple doses (once a day for 3 days) in sequential cohorts with escalatingdoses. In case that safety is acceptable for all consecutive cohorts, a protocol amendment could be considered to study additional higher dose(s).
Objectives:
- To evaluate overall safety and tolerability of KAE609.
- To assess key pharmacokinetic (PK)parameters following treatment with KAE609.
- To assess the efficacy of KAE609 in patients with uncomplicated falciparummalaria.
- To assess recrudescence after single and multiple doses of KAE609.
