Compared with placebo, single-dose tafenoquine lowered risk for Plasmodium vivax malaria relapse significantly at 6 months in people with normal glucose-6-phosphate dehydrogenase (G6PD) activity, according to a study published in the New England Journal of Medicine.
In this phase 2b-3, double-blind, parallel group trial (ClinicalTrials.gov identifier: NCT01376167), investigators enrolled 522 people from 8 centers in 6 countries. All participants had microscopically confirmed P vivax malaria (>100 to <100,000 parasites/μL) and normal G6PD activity (defined as ≥70% of the median value determined at each trial site in 36 healthy male volunteers who were otherwise not involved in the trial). Participants were randomly assigned in a 2:1:1 ratio to receive tafenoquine, primaquine, or placebo.
Patients in the tafenoquine group (n=260) received a single 300-mg dose of tafenoquine on day 1 or 2, and participants in the primaquine group (n=129) received 15 mg of primaquine once daily for 14 days. The placebo group (n=133) received tafenoquine-matched and primaquine-matched dosing to maintain masking. In addition, all patients received a 3-day course of chloroquine (600 mg on day 1 and day 2, and 300 mg on day 3).
The primary outcome was the percentage of patients who were free from P vivax recurrence at 6 months.
In the intention-to-treat population, 62.4% of patients in the tafenoquine group (95% CI, 54.9-69.0), 27.7% in the placebo group (95% CI, 19.6-36.6), and 69.6% in the primaquine group (95% CI, 60.2-77.1) were free from recurrence of P vivax parasitemia at 6 months. Compared with placebo, the hazard ratio for risk of recurrence was 0.30 (95% CI, 0.22-0.40) with tafenoquine and 0.26 (95% CI, 0.18-0.39) with primaquine (P <.001 for both).
Results from the primary analysis were consistent in the per-protocol population and at 4 months as well as in a categorical analysis in which patients with missing data were considered to have had recurrence.
There were no withdrawals from the trial because of adverse events. Decreased hemoglobin level was more common in the tafenoquine group compared with the placebo group but resolved without intervention.
“Given the need to reduce the global burden of P vivax malaria, GlaxoSmithKline will make tafenoquine available at an affordable price in countries in which malaria is endemic to improve access to those who need it most,” noted the researchers. However, reliable quantitative point-of-care G6PD testing will be needed if tafenoquine use is expanded.
Disclosures: GlaxoSmithKline, in part, sponsored this trial and managed the conduct of the trial, collected and managed the data, monitored the trial staff, conducted the statistical analysis, and provided all the drugs used in the trial. Multiple authors disclosed affiliations with pharmaceutical companies. See the reference for complete disclosure information.
Lacerda MVG, Llanos-Cuentas A, Krudsood S, et al. Single-dose tafenoquine to prevent relapse of Plasmodium vivax malaria. N Engl J Med. 2019;380(3):215-228.