Proxalutamide Significantly Accelerates Viral Clearance and Reduces Time to Clinical Remission in Patients with Mild to Moderate COVID-19: Results from a Randomized, Double-Blinded, Placebo-Controlled Trial

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-CoV-2 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). Results 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). Conclusion Proxalutamide significantly accelerated viral clearance on Day 7 in mild to moderate COVID-19 patients versus placebo. Further, the time to clinical remission was significantly reduced in patients treated with Proxalutamide versus placebo.

Proxalutamide Reduction of Mortality Rate in Hospitalized COVID-19 Patients Depends on Treatment Duration – an Exploratory Analysis of the Proxa-Rescue AndroCoV Trial

“…19 We have previously demonstrating that proxalutamide was effective to prevent hospitalization in COVID-19 male patients and to reduce viral shedding and inflammatory response, in a double-blind, placebo-controlled randomized clinical trial (RCT). 20,21 We have also demonstrated that proxalutamide was able to reduce mortality rate by 77.7% in moderate-to-severe hospitalized COVID-19 patients that were not on mechanical ventilation, and increased recovery speed by 128%, when compared to placebo, also in a double-blind, placebo-controlled RCT.…”

“…25 Unbalanced actives and placebo distribution across sites and minor protocol modifications were the major weaknesses of the present RCT, while the lack of any modification of the ITT analysis prevented additional biases. 21 Spontaneous erection (males) 4/329 (1.2%) 4/163 (2.5%) 0/166 0.70…”

WITHDRAWN: Proxalutamide (GT0918) Reduces the Rate of Hospitalization and Death in COVID-19 Male Patients: A Randomized Double-Blinded Placebo-Controlled Trial.

“…15 We have previously reported our preliminary analysis of the effects of proxalutamide 200mg per day in COVID-19 patients, which showed an overall 74% reduction in nasopharyngeal detection of SARS-CoV-2 on the 7 th day of treatment. 16 The objective of this study was to evaluate the e cacy of proxalutamide in preventing hospitalization in males diagnosed with COVID-19 in an outpatient setting.…”

Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial

“…The COVIDENZA trial led by the University of Gothenburg is an ongoing randomized trial of enzalutamide plus standard of care versus standard of care in hospitalized patients with COVID-19 [ 14 ]. A trial in the outpatient setting recently reported that antiandrogen treatment accelerated viral clearance as compared to placebo [ 15 ]. Whether or not AR antagonism should be considered as a therapeutic strategy for patients hospitalized with COVID-19 will depend on the results of this and related trials.…”