Proxalutamide (GT0918) Reduces the Rate of Hospitalization in mild-to-moderate COVID-19 Female Patients: A Randomized Double-Blinded Placebo-Controlled Two-Arm Parallel Trial

Background: Antiandrogens were shown to be effective in mild-tomoderate COVID-19 male patients, supported by the SARS-CoV-2 dependency on transmembrane protease, serine 2 (TMPRSS2), which is solely modulated by androgens, for cell entry. While women with hyperandrogenism experiment more symptoms in COVID-19 compared to women without hyperandrogenism, and the chronic use of an antiandrogen seemed to mitigate these symptoms, whether the benefits would be observed in overall females is unknown. The objective of this study is to evaluate the efficacy of proxalutamide as a treatment for mild-to-moderate COVID-19 in females. Methods: This was a randomized, double-blind, placebo-controlled, two-arm, parallel study on COVID-19 female outpatients, that compared the use of proxalutamide versus placebo. The primary outcome was hospitalization rates throughout 30 days after randomization. Patients with laboratory confirmed COVID-19 not hospitalized were recruited in two sites in Brasilia, Brazil, between January 4 and February 28, 2021, were randomized on a 2:3 ratio between proxalutamide and placebo, and were administered proxalutamide 200mg/day or placebo for seven days, in addition to usual care. Results: A total of 177 women were randomized, including 75 in the proxalutamide arm and 102 patients in the placebo arm. None of the patients lost follow-up or discontinued treatment. The 30-day hospitalization rate was 2.7% in the proxalutamide arm and 18.6% in the placebo arm (p<0.001), with a hospitalization risk ratio (RR) of 0.14 [95% confidence interval (CI), 0.03-0.59]. Conclusions: These findings suggest that treatment of COVID-19 patients with proxalutamide in combination with standard of care was reduced hospitalization rate by 86% (p < 0.001), with no safety concerns. (Clinicaltrials.gov: NCT04853134)