Sevuparin in children with severe malaria: a phase I safety and dose-finding trial
Abstract
Mortality 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.
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BibTeX
@article{chaponda2026sevuparin,
title = {{Sevuparin in children with severe malaria: a phase I safety and dose-finding trial}},
author = {Mike Chaponda and Jonathan Gwasupika and Roisin Connon and Patrick Tshilab Kabwit and Sam Miti and Nchafatso Obonyo and Diana M. Gibb and Thomas N. Williams and Nicholas P. J. Day and Arjen M. Dondorp and A. Sarah Walker and Elizabeth C. George and Kathryn Maitland},
journal = {Nature Communications},
year = {2026},
month = oct,
doi = {10.1038/s41467-026-78536-3},
url = {https://www.nature.com/articles/s41467-026-78536-3},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Sevuparin in children with severe malaria: a phase I safety and dose-finding trial
AU - Mike Chaponda
AU - Jonathan Gwasupika
AU - Roisin Connon
AU - Patrick Tshilab Kabwit
AU - Sam Miti
AU - Nchafatso Obonyo
AU - Diana M. Gibb
AU - Thomas N. Williams
AU - Nicholas P. J. Day
AU - Arjen M. Dondorp
AU - A. Sarah Walker
AU - Elizabeth C. George
AU - Kathryn Maitland
PY - 2026
DA - 2026/10/21
JO - Nature Communications
DO - 10.1038/s41467-026-78536-3
UR - https://www.nature.com/articles/s41467-026-78536-3
AB - Mortality 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.
SN - 2041-1723
ER -