Effectiveness of OZ439 as a Gametocytocidal and Transmission Blocking Agent

Summary

This is a single-centre, controlled, open label study using P. falciparum-induced blood stage malaria (IBSM) infection to assess the effectiveness of OZ439 as a gametocytocidal agent, as well as its treatment effects on gametocyte infectivity and development in vector mosquitoes. Previous clinical studies including one IBSM study have shown that in addition to effectively clearing replicating, asexual (pathogenic) life cycle stages of malaria, a single dose of piperaquine (480 mg) results in the production of gametocytes, as determined by gametocyte-specific transcript (pfs25) qPCR. The propensity of piperaquine to induce gametocytaemia will be employed in this study to assess the efficacy of OZ439 as a gametocytocidal and transmission blocking agent. Experimental mosquito feeding via both direct feeding on participants and artificial (indirect) membrane mosquito feeding will be performed. The study will be conducted in up to 3 cohorts where participants will be randomised into an experimental or a control group (n=2 per group) when peak gametocytemia occurs (approximately 15 days after administration of piperaquine).

Timeline

Start

2015-04

Primary completion

2016-09

Completion

2016-09

Publications

• Collins KA, Wang CY, Adams M, Mitchell H, Rampton M, Elliott S, Reuling IJ, Bousema T, Sauerwein R, Chalon S, Mohrle JJ, McCarthy JS. A controlled human malaria infection model enabling evaluation of transmission-blocking interventions. J Clin Invest. 2018 Apr 2;128(4):1551-1562. doi: 10.1172/JCI98012. Epub 2018 Mar 12.

Drugs

Indications