Tafenoquine for radical cure of Plasmodium vivax malaria: a randomized, double-blind, double-dummy, comparative, multicenter Phase III study (“GATHER”).

Background: Tafenoquine (TQ) is an 8-aminoquinoline (8-AQ) in development by GlaxoSmithKline and Medicines for Malaria Venture as a single-dose radical cure (relapse prevention) for Plasmodium vivax malaria. GATHER (TAF116564, NCT02216123) was an actively controlled Phase III safety study conducted from April 2014 to November 2016 in subjects aged 16-years or older with microscopy-confirmed parasitaemia. Materials and Methods: Subjects were screened for glucose-6-phosphate dehydrogenase (G6PD) deficiency at baseline. Males with G6PD activity at least 70% and females with at least 40% of the site median were eligible. Subjects were randomised to tafenoquine 300mg or primaquine 15mg daily for 14 days in a ratio of 2:1, given concomitantly with three days of chloroquine. Subjects were recruited from 7 centres in 5 countries (Brazil, Peru, Colombia, Vietnam and Thailand). Clinical and parasitological assessments were made on Days 1, 2, 3, and on 10 subsequent follow-up visits until Day 180. The primary endpoint was clinically relevant haemolysis, defined as a haemoglobin decline of >30g/L or ≥30% from baseline, or an absolute fall to <60g/L. Secondary endpoints included evaluation of clinical laboratory tests, electrocardiograms, vital signs and adverse events. Other outcomes included relapse-free efficacy at 4 and 6 months post-dosing, time to relapse, parasite, fever, and gametocyte clearance times, incidence of genetically homologous and genetically heterologous P. vivax, and incidence of P. falciparum. Results & conclusions A total of 251 subjects (167 males; 84 females) were randomised. Conclusions: Efficacy and safety data will be presented along with interpretation and conclusions.