Abstract
Sevuparin in children with severe malaria: a phase I safety and dose-finding trial
Chaponda, M.
Gwasupika, J.
Connon, R.
Tshilab Kabwit, P.
Miti, S.
Obonyo, N.
Gibb, D. M.
Williams, T. N.
Day, N. P. J.
Dondorp, A. M.
Walker, A. S.
George, E. C.
Maitland, K.
Nat Commun. 2026; 17
Permanent descriptor
https://doi.org/10.1038/s41467-026-78536-3Mortality rates for African children with severe malaria remain high. Sevuparin, a heparin-like compound, as an adjunctive treatment, may improve outcomes due to its effects on Plasmodium falciparum-infected erythrocytes. A Phase I dose-finding trial in Kenyan and Zambian children with severe malaria aimed to identify the maximum tolerated dose (MTD) of sevuparin, given as three infusions (at 0, 8 and 16 h post-enrolment) using the continual reassessment method (ISRCTN32271864). The primary endpoint was dose limiting toxicity (DLT) defined as Activated Partial Thromboplastin Time (APTT) > 95 seconds (2.5x upper limit of normal) across 1.5-6 mg/kg doses. Secondary endpoints were lactate clearance, parasite half-life, APTT at 24 h and grade 3-4 serious adverse events. Twenty-three children were enroled; 20 were included in the primary analysis, across 10 cohorts. A data monitoring committee followed model recommendations, leading to dose escalation from 1.5 mg/kg through all doses to 6 mg/kg when 2 DLTs occurred. During de-escalation, DLTs occurred at 5 mg/kg and 4 mg/kg. The final dose was therefore 3 mg/kg. There was 1 death (1/23 (4.3%)), 1 readmission and 1 grade 3 non-DLT adverse event: all judged unrelated to sevuparin. MTD of 3 mg/kg sevuparin in each of three infusions at 0, 8 and 16 h was identified for future investigation.