Sevuparin in children with severe malaria: a phase I safety and dose-finding trial.

In 30 seconds

This phase I dose-finding trial assessed sevuparin safety and tolerability in Kenyan and Zambian children with severe malaria. Sevuparin was administered in three infusions at 0, 8 and 16 hours, with doses evaluated from 1.5 to 6 mg/kg. Among 23 enrolled children, 20 were included in the primary analysis. Dose-limiting toxicities occurred during escalation and de-escalation; the trial identified a maximum tolerated dose of 3 mg/kg per infusion. One child died, but the death, readmission and grade 3 adverse event were judged unrelated to sevuparin.

Key findings

• The identified maximum tolerated dose was 3 mg/kg in each of three infusions at 0, 8 and 16 hours.
• Twenty-three children were enrolled; 20 contributed to the primary analysis across 10 cohorts.
• One death occurred (1/23 (4.3%)); the death, one readmission and one grade 3 non-dose-limiting adverse event were judged unrelated to sevuparin.

Why it matters

Severe malaria in African children remains associated with high mortality, and this trial provides an initial safety and dose-finding basis for investigating sevuparin as an adjunctive treatment. The findings establish a dose for future study, but do not show that sevuparin improves clinical outcomes.

What to keep in mind

This was a phase I dose-finding trial with 23 enrolled children and no reported comparison group; it was not designed to establish efficacy.