Abstract: Open Access Original Article DOI: 10.7759/cureus.13492 Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, DoubleBlinded, Placebo-Controlled Trial Flavio A. Cadegiani 1, 2 , John McCoy 3 , Carlos Gustavo Wambier 4 , Sergio Vaño-Galván 5 , Jerry Shapiro 6 , Antonella Tosti 7 , Ricardo A. Zimerman 8 , Andy Goren 9 1. Internal Medicine: Diabetes and Endocrinology, Applied Biology Inc, Irvine, USA 2. Clinical Endocrinology, Federal University of São Paulo, São Paulo, BRA 3. Research & Development, Applied Biology Inc, Irvine, USA 4. Dermatology, The Alpert Medical School of Brown University, Providence, USA 5. Dermatology, Ramon y Cajal Hospital, Madrid, ESP 6. Ronald O. Perelman Department of Dermatology, New York University, New York, USA 7. Dermatology, University of Miami Health System, Miami, USA 8. Infectious Diseases, Hospital da Brigada Militar, Porto Alegre, BRA 9. Dermatology, Applied Biology Inc, Irvine, USA Corresponding author: John McCoy, johnm@appliedbiology.com Abstract Background The entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into type II pneumocytes is dependent on a modification of viral spike proteins by transmembrane protease serine 2 (TMPRSS2) expressed on the surface of human cells. TMPRSS2 is regulated by the androgen receptor, hence, SARS-CoV2 infectivity is indirectly dependent on androgenic status and phenotype. Previously, we have reported that men affected by androgenetic alopecia (AGA) are overrepresented in severe coronavirus disease 2019 (COVID-19). Additionally, we have reported that men taking antiandrogenic drugs, e.g., 5-alpha-reductase inhibitors (5ARis), are less likely to have severe COVID-19. Here we aimed to test whether the androgen receptor antagonist, Proxalutamide, would be a beneficial treatment for subjects with SARS-CoV-2 infection. Methods Male and female subjects were recruited to a double-blinded, randomized, prospective, investigational study of Proxalutamide for the treatment of COVID-19. Mild to moderate, non-hospitalized subjects, who were confirmed positive for SARS-CoV-2, were treated with either Proxalutamide 200 mg/day or placebo. Endpoints for the study were remission time (days) and the percentage of subjects confirmed negative for SARS-CoV-2 on Day 7 after treatment. A negative SARS-CoV-2 test was defined by concentration-time (Ct)>40 determined by real-time reverse transcription-polymerase chain reaction (rtPCR). Review began 02/04/2021 Results Review ended 02/15/2021 Published 02/22/2021 © Copyright 2021 Cadegiani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 4.0., which permits unrestricted Two-hundred thirty-six (2360 subjects were included in the study (108 female, 128 male); 171 were randomized to the Proxalutamide arm and 65 were in the placebo group. On Day 7, SARS-CoV-2 became non-detectable with rtPCR (cT>40) in 82% of the subjects in the Proxalutamide group versus 31% in the placebo group (p < 0.001). The average clinical remission time for patients treated with Proxalutamide was 4.2 ±5.4 days versus 21.8 ±13.0 days in the placebo arm (p < 0.001). use, distribution, and reproduction in any medium, provided the original author and source are credited. Conclusion Proxalutamide significantly accelerated viral clearance on Day 7 in mild to moderate COVID-19..