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Efficacy of cipargamin (KAE609) in a randomized, Phase II dose-escalation study in adults in sub-Saharan Africa with uncomplicated Plasmodium falciparum malaria

August 25, 2021 - 16:35 -- Open Access
Schmitt EK, Ndayisaba G, Gandhi P, et al.
Clin Infect Dis. 2021 Aug 19:ciab716

Cipargamin (KAE609) is a potent antimalarial in Phase II. Here we report efficacy, pharmacokinetics, and resistance marker analysis across a range of cipargamin doses. These were secondary endpoints from a study primarily conducted to assess the hepatic safety of cipargamin (hepatic safety data are reported elsewhere).

Ex vivo susceptibility to new antimalarial agents differs among human-infecting Plasmodium species

July 28, 2021 - 14:30 -- Open Access
van Schalkwyk DA, Moon RW, Duffey M, Leroy D, Sutherland CJ
Int J Parasitol Drugs Drug Resist. 2021 Jul 24;17:5-11

Several promising antimalarial drugs are currently being tested in human trials, such as artefenomel, cipargamin, ferroquine and ganaplacide. Many of these compounds were identified using high throughput screens against a single species of human malaria, Plasmodium falciparum, under the assumption that effectiveness against all malaria species will be similar, as has been observed for other antimalarial drugs. However, using our in vitro adapted line, we demonstrated recently that P. knowlesi is significantly less susceptible than P. falciparum to some new antimalarial drugs (e.g., cipargamin and DSM265), and more susceptible to others (e.g., ganaplacide). There is, therefore, an urgent need to determine the susceptibility profile of all human malaria species to the current generation of antimalarial compounds.

Defining the antimalarial activity of cipargamin in healthy volunteers experimentally infected with blood stage Plasmodium falciparum

November 18, 2020 - 12:18 -- Open Access
McCarthy JS, Abd-Rahman AN, Collins KA, Marquart L, Griffin P, Kümmel A, Fuchs A, Winnips C, Mishra V, Csermak-Renner K, Jain JP, Gandhi P
Antimicrob Agents Chemother. 2020 Nov 16:AAC.01423-20

The spiroindolone cipargamin, a new antimalarial compound that inhibits Plasmodium ATP4, is currently in clinical development. This study aimed to characterize the antimalarial activity of cipargamin in healthy volunteers experimentally infected with blood-stage Plasmodium falciparum Eight subjects were intravenously inoculated with parasite-infected erythrocytes and received a single oral dose of 10 mg cipargamin 7 days later. Blood samples were collected to monitor the development and clearance of parasitemia, and plasma cipargamin concentrations.

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