Phase II multicenter clinical trial of a Ferroquine + MMV253 short regimen for the treatment of malaria (SINDOFO)

A simplified regimen, ideally a single-day cure, of uncomplicated malaria would be the magic bullet in the antimalarial armamentarium.

Improving treatment adherence is one of the key factors in reducing mortality and morbidity and also transmission of malaria, and such a regimen would substantially increase adherence. The two new compounds are ferroquine, (FQ) a next generation 4-aminoquinoline and MMV253, a triaminopyrimidine. Both compounds show unique features in terms of long half-life, and activity against current drug resistant strains.

The primary objective of the SINDOFO project is to assess the safety and efficacy of a FQ + MMV253 combination.

Clinical Study: The proposed study is a phase II, randomized, open label, trial, to assess the efficacy and safety of an oral formulation of FQ+MMV253 given in a short regimen (single dose, or two-day dose regimen on two consecutive days) in comparison with the standard of care in African adult and paediatric patients with uncomplicated Plasmodium falciparum malaria.

When safety and efficacy of a dose regimen in patients above 12-years has been established, an age step-down will be done, also including children below the age of five years, as they are the target population carrying the highest burden of disease. The trial will follow an adaptive study design.

The drug combination: Both compounds have independent mechanism of actions, with good activity against existing resistant parasites and excellent pharmacokinetic profiles.

FQ is a ferrocenyl 4-aminoquinoline derivative, a member of the chloroquine family, but with activity against chloroquine, amodiaquine and piperaquine resistant strains.

It has an active metabolite, N-monodemethyl-FQ, and these have a half-life in patients, of 30 days and 40 days, respectively, showing great potential for post-treatment prophylaxis.

MMV253 belongs to a novel compound class, the triaminopyrimidines that exhibit a rapid onset of action with a parasite reduction rate (PRR) similar to artesunate and a terminal half-life of 90 hours.

The SINDOFO consortium covers study sites representing different African regions with different patterns of malaria transmission.

Capacity building will be a major component of this project, in terms of capability to conduct clinical research following highest international standards and training of highly qualified staff in malaria endemic countries.