Investigators selected a 3 mg/kg maximum tolerated dose of sevuparin for further study in children hospitalized with severe malaria in Zambia and Kenya. In a small Phase I trial using a continual reassessment method, dose-limiting coagulation abnormalities occurred at 4–6 mg/kg but not at 3 mg/kg, supporting the safety-based next step as severe malaria remains a major cause of pediatric death in the WHO African Region.