Safety Study of Single Dose Intravenous DON in Adults and Children With Cerebral Malaria

What this Trial Is About

Researchers are studying the safety and effects of a drug called 6-diazo-5-oxo-L-norleucine DON in healthy adults, adults with uncomplicated malaria, and children aged 12 months to 14 years with cerebral malaria. The study aims to evaluate the safety of a single intravenous dose of DON, understand how the drug moves through the body, and assess if DON improves brain blood flow, reduces brain swelling, and changes brain activity patterns in children with cerebral malaria. This is a Phase 12a dose-escalation safety study involving dose increases in adults and children. The study has two parts. In Part 1, healthy adults and adults with uncomplicated malaria will receive one dose of DON intravenously at increasing doses from 0.1 mgkg up to 10.0 mgkg. Adults also receive the anti-nausea drug ondansetron, and adults with malaria receive standard malaria treatment per local guidelines. Part 2 involves children with cerebral malaria, who will be randomly assigned to receive either DON at different doses or a placebo, along with anti-nausea medication and recommended malaria therapies. Pediatric enrollment spans multiple malaria seasons with dose escalation through cohorts. Participants will be closely monitored over six months. Adults receive ondansetron before and after the DON dose and are observed for safety. Children will have brain scans MRI, brain blood flow assessments transcranial Doppler, and brain activity tests EEG along with routine clinical evaluations. Researchers will track side effects, drug levels in the blood, and brain function to assess safety and effects. The studys main safety assessments occur within 14 days of dosing, and pharmacokinetic measurements are taken up to 18 hours after infusion.

DON in Pediatric Cerebral Malaria