To Evaluate Efficacy, Safety, Tolerability and PK of Intravenous Cipargamin in Participants With Severe Plasmodium Falciparum Malaria

Objectives

*Official Title: An Adaptive, Randomized, Active-controlled, Open-label, Sequential Cohort, Multicenter Study to Evaluate the Efficacy, Safety, Tolerability and Pharmacokinetics of Intravenous Cipargamin (KAE609) in Adult and Pediatric Participants With Severe Plasmodium Falciparum Malaria (KARISMA – KAE609’s Role In Severe Malaria)

The purpose of this study is to identify the safe and effective dose of intravenous cipargamin in participants with moderately severe and severe malaria. Precisely, to assess the efficacy of different doses of intravenous cipargamin vs artesunate by evaluating the proportion of participants with ≥ 90% reduction of parasitemia at 12 hours post administration of the first dose.

The study also intends to evaluate clinical treatment success using a novel clinical endpoint for drug development in severe malaria.

Primary objectives: 

1. This study is investigating the efficacy (parasite reduction and clinical outcome), safety, tolerability and pharmacokinetics of different injectable dose regimens of cipargamin in comparison to injectable artesunate.
2. The first cohort (Cohort 1) will be small and will include participants aged 12 years or over, diagnosed with moderately severe malaria and high parasitemia.
3. This cohort will be used the for initial evaluation of safety and parasite clearance rates before continuing
4. into Cohorts 2-5, which will include only severe malaria patients according to WHO criteria.
5. Progressively younger participants will be included with each new cohort from Cohort 2 onwards. This design aims at minimizing risks for pediatric participants < 12 years.

Secondary objectives:

1. To assess the clinical outcome as measured by the proportion of participants with clinical success at 48 hours.