Efficacy and safety of proxalutamide (GT0918) in severe or critically ill patients with COVID-19: study protocol for a prospective, open-label, single-arm, single-center exploratory trial

Background: The rapid global spread of COVID-19 has presented a significant health challenge, with high mortality rates among patients who are severely or critically ill. Currently, there is no specific, effective therapy for these patient populations. Previous studies have indicated a potential link between androgen levels and susceptibility to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Proxalutamide, an androgen receptor antagonist, has demonstrated potential therapeutic effects in patients with COVID-19. Therefore, this trial aims to evaluate the efficacy and safety of proxalutamide in patients with severe or critical COVID-19.

Methods: This is a single-arm, open-label, single-center, prospective exploratory trial planned to enroll 64 patients with severe or critical COVID-19 in China. Recruitment began on May 16, 2022, and is expected to conclude on May 16, 2023. Patients will be followed for up to 60 days or until death, whichever occurs first. The primary outcome measure is 30-day all-cause mortality. Secondary outcomes include 60-day all-cause mortality, rate of clinical deterioration within 30 days post-treatment, time to sustained clinical recovery (assessed using an 8-point ordinal scale), mean change in Acute Physiology and Chronic Health Evaluation II scores, changes in oxygenation index, improvements in chest CT imaging, the proportion of patients testing negative for SARS-CoV-2 by nasopharyngeal swab, changes in SARS-CoV-2 cycle threshold (Ct) values, and safety outcomes. Study visits are scheduled for days 1 (baseline), 15 or 30, 22, and 60.

Discussion: This trial represents the first investigation into the efficacy and safety of proxalutamide in patients with severe or critical COVID-19. The findings from this study may contribute to the development of effective treatments for COVID-19 and provide robust evidence regarding the therapeutic potential and safety profile of proxalutamide in this patient population.

Trial registration: This study was registered on June 18, 2022, with the Chinese Clinical Trial Registry (ChiCTR2200061250).