Trial reportMalaria journal2021
Hepatic safety and tolerability of cipargamin (KAE609), in adult patients with Plasmodium falciparum malaria: a randomized, phase II, controlled, dose-escalation trial in sub-Saharan Africa.
Trial report in Malaria journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03334747 (A Phase 2, Multi-center, Randomized, Open-label, Dose-escalation Study to Determine Safety of Single), which is not on this map. Cited by 12 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 2, Multi-center, Randomized, Open-label, Dose-escalation Study to Determine Safety of Single (QD) and Multiple (3 QD) Doses of KAE609, Given to Adults With Uncomplicated Plasmodium Falciparum Malaria.
Who cites it
12 citing papers in PubMed, 29 citations in OpenAlex.
- Rapid multiplexed nanopore amplicon sequencing to distinguish Plasmodium falciparum recrudescence from new infection in antimalarial drug trials.Scientific reports · 2025Trial
- First-in-human, randomized, double-blind, placebo-controlled, single and multiple ascending doses clinical study to assess the safety, tolerability, and pharmacokinetics of cipargamin administered intravenously in healthy adults.Antimicrobial agents and chemotherapy · 2024Trial
- Evaluation of a Bayesian hierarchical pharmacokinetic-pharmacodynamic model for predicting parasitological outcomes in Phase 2 studies of new antimalarial drugs.Antimicrobial agents and chemotherapy · 2024Trial
- Indole-2-carboxamides Optimization for Antiplasmodial Activity.ACS bio & med chem Au · 2025Article
- Identification of α-Azacyclic Acetamide-Based Inhibitors ofACS infectious diseases · 2025Article
- Article
- Malaria: past, present, and future.Signal transduction and targeted therapy · 2025Review
- Targeting Malaria's Achilles' Heels: A Review of Plasmodium Life Cycle Vulnerabilities for Drug Discovery.Current topics in medicinal chemistry · 2025Review
- Defining the next generation of severe malaria treatment: a target product profile.Malaria journal · 2024Review
- Antimalarial drug discovery: progress and approaches.Nature reviews. Drug discovery · 2023Review
- Novel Therapeutics for Malaria.Pharmaceutics · 2023Review
- Spirooxindole: A Versatile Biologically Active Heterocyclic Scaffold.Molecules (Basel, Switzerland) · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 10 institutions in 9 countries.
Funding
Abstract
backgroundThe novel anti-malarial cipargamin (KAE609) has potent, rapid activity against Plasmodium falciparum. Transient asymptomatic liver function test elevations were previously observed in cipargamin-treated subjects in two trials: one in malaria patients in Asia and one in volunteers with experimentally induced malaria. In this study, the hepatic safety of cipargamin given as single doses of 10 to 150 mg and 10 to 50 mg once daily for 3 days was assessed. Efficacy results, frequency of treatment-emerging mutations in the atp4 gene and pharmacokinetics have been published elsewhere. Further, the R561H mutation in the k13 gene, which confers artemisinin-resistance, was associated with delayed parasite clearance following treatment with artemether-lumefantrine in Rwanda in this study. This was also the first study with cipargamin to be conducted in patients in sub-Saharan Africa.
methodsThis was a Phase II, multicentre, randomized, open-label, dose-escalation trial in adults with uncomplicated falciparum malaria in five sub-Saharan countries, using artemether-lumefantrine as control. The primary endpoint was ≥ 2 Common Terminology Criteria for Adverse Events (CTCAE) Grade increase from baseline in alanine aminotransferase (ALT) or aspartate transaminase (AST) during the 4-week trial.
resultsOverall, 2/135 patients treated with cipargamin had ≥ 2 CTCAE Grade increases from baseline in ALT or AST compared to 2/51 artemether-lumefantrine patients, with no significant difference between any cipargamin treatment group and the control group. Cipargamin exposure was comparable to or higher than those in previous studies. Hepatic adverse events and general safety and tolerability were similar for all cipargamin doses and artemether-lumefantrine. Cipargamin was well tolerated with no safety concerns.
conclusionsThis active-controlled, dose escalation study was a detailed assessment of the hepatic safety of cipargamin, across a wide range of doses, in patients with uncomplicated falciparum malaria. Comparison with previous cipargamin trials requires caution as no clear conclusion can be drawn as to whether hepatic safety and potential immunity to malaria would differ with ethnicity, patient age and or geography. Previous concerns regarding hepatic safety may have been confounded by factors including malaria itself, whether natural or experimental infection, and should not limit the further development of cipargamin. Trial registration ClinicalTrials.gov number: NCT03334747 (7 Nov 2017), other study ID CKAE609A2202.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.