A phase II, double blind, placebo-controlled, randomized evaluation of the safety and efficacy of tafenoquine in patients with mild-moderate COVID-19 disease

Abstract

The safety and efficacy of tafenoquine administered as a 200 mg dose once per day on days 1, 2, 3, and 10 was evaluated over a 28-day period in mild-moderate COVID-19 patients. The primary endpoint was Day 14 clinical recovery from COVID-19 symptoms, defined as cough mild or absent, respiratory rate < 24 bpm, and no shortness of breath or fever. Following a successful futility analysis after n = 86 patients out of a target n = 275 were randomized, the study was terminated and unblinded early to facilitate planning for confirmatory studies. The proportion of patients not recovered on Day 14 was numerically decreased by 27% in the ITT population [8/45 v 10/42 not recovered in the tafenoquine and placebo arms, P = 0.60] and 47% in the PP population [5/42 v 9/41, P = 0.25]. Amongst individuals who recorded responses in an electronic diary at Day 28, all tafenoquine patients were recovered, whereas up to 12% of placebo patients exhibited lingering dyspnea. Time to clinical recovery from COVID-19 symptoms was accelerated in the tafenoquine arm by about 2-2.5 days. There were two COVID-19 related hospitalizations in the placebo arm and one in the tafenoquine arm. Mild, drug related adverse events occurred in 8.4% of individuals in the tafenoquine arm [v 2.4% in the placebo]. Although this trial was underpowered for the primary endpoint due to its early termination, the data are suggestive of a therapeutic benefit associated with tafenoquine administration in outpatients with mild to moderate COVID-19 disease, and larger studies are planned.

Keywords: COVID-19; Clinical Trial; FDA-Approved Regimen for Malaria Pophylaxis; Outpatients; Tafenoquine.

© 2022 The Author(s).

Figures

Fig. 1

Study flowchart.

Fig. 2

Recovery from symptoms comprising the composite primary endpoint in the PP population. Patients were included if they experience symptoms on any of Days 1-3 and considered recovered if the symptom was resolved for three consecutive days. IP refers to investigational product [tafenoquine or placebo]. The figure is truncated at Day 18 since only placebo subjects continued to experience symptoms through Day 28 [shortness of breath]. The two tafenoquine subjects experiencing shortness of breath at Day 18 were lost to follow-up thereafter. When all components of the primary endpoint were considered together, tafenoquine patients recovered 2.3 days faster than placebo patients in the PP population [P = 0.02, see Table 2].

Fig. 3

Effect of tafenoquine on 14 patient-reported COVID-19 symptoms in the ITT population. IP = investigational product. The lowest P value, on Day 5, was 0.059.