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Clinical Trial Summary

The purpose of this study is to assess the efficacy and safety of Proxalutamide as a treatment for COVID-19 patients in the intensive care unit


Clinical Trial Description

During the continuing SARS-CoV-2 (COVID-19) pandemic, several studies have reported a significant difference in the rate of severe cases between adult females and adult males (42% vs 58%). Among children under the age of 14, the rate of severe cases was reported to be extremely low. To explain this difference, several theories have been proposed including cigarette smoking and lifestyle habits. However, no theory fits both the gender difference in severe cases as well as reduced risk in pre-pubescent children. Our past research on male androgenetic alopecia (AGA) has led us to investigate an association between androgens and COVID-19 pathogenesis. In normal subjects, androgen expression demonstrates significant variation between men and women as well as between adults and pre-pubescent children. SARS-CoV-2 primarily infects type II pneumocytes in the human lung. SARS-CoV-2 enters pneumocytes, by anchoring to the ACE2 cell surface receptor. Prior to receptor binding, viral spike proteins undergo proteolytic priming by the transmembrane protease, serine 2 (TMPRSS2). TMPRSS2 inhibition or knock down reduces ability of SARS-CoV-1 (a related virus to SARS-CoV-2) to infect cells in vitro.Additionally, TMPRSS2 also facilitates entry of influenza A and influenza B into primary human airway cells and type II pneumocytes. The human TMPRSS2 gene has a 15 bp androgen response element and in humans, androgens are the only known transcription promoters for the TMPRSS2 gene. In a study of androgen-stimulated prostate cancer cells (LNCaP), TMPRSS2 mRNA expression increase was mediated by the androgen receptor. Further, the ACE2 receptor, also critical for SARS-CoV-2 viral infectivity, is affected by male sex hormones with higher activity found in males. Previously, the investigators have reported the results from two retrospective cohort analysis demonstrating the protective effect of 5-alpha-reductase inhibitors (5ARi) for men with COVID-19. In a study of 77 men hospitalized with COVID-19 the investigators found among men taking 5ARis, 8% were admitted to the ICU compared to 58% of men not taking 5ARis (P = 0.0015). In the cohort, 5ARis were associated with reduced risk for ICU admissions RR 0.14 (95% CI: 0.02-0.94).Similarly, the investigators have demonstrated that the frequency of COVID-19 symptoms was drastically reduced for men using 5ARis in an outpatient setting. A statistically significant (p<0.05) reduction in the frequency of 20 of the 29 clinical symptoms was observed in AGA men using 5ARis compared to AGA men not using 5ARis. For example, 38% and 2% of men presented with low-grade fever, 60% and 6% with dry cough, and 88% and 15% reported anosmia in the non-5ARi and 5ARi groups, respectively.18 One limitation of 5ARis is the time course required to achieve systemic DHT reductions. As such, the investigators explored the use of a novel second generation androgen receptor antagonist Proxalutamide as a means for rapid reduction in AR activity. Proxalutamide (GT0918) demonstrates a dual mechanism of action. It is highly effective in inhibiting AR as well as exhibiting pharmacological effects of inducing the down-regulation of AR expression; the mechanism that is not present in bicalutamide and enzalutamide. Because of the dual mechanism of action, it is expected to be a more effective and less toxic second-generation anti-androgen drug therapy. Clinical evidence has demonstrated that Proxalutamide lowers AR expression and activity. Additionally, it has been reported that Proxalutamide lowers the expression of ACE2. Both would be beneficial for preventing SARS-CoV-2 entry into lung cells. In addition, none of the 5ARis currently approved by the US FDA have been tested in phase I studies in women. As such, thet are not recommended for women. Phase I studies for Proxalutamide have been successfully completed in both men and women. In December 2020, the investigators completed a double-blinded, randomized, prospective, investigational study of Proxalutamide Treatment for Non-Hospitalized COVID-19 Male Patients (NCT04446429). The length of the study was 30 days. Proxalutamide was administered 200mg q.d. for 15 days. Men enrolled in the study were 50 years and older. Two hundred and sixty two men completed the study. 134 men were assigned to the Proxalutamide group and 128 men were assigned to the control group. Thirty five subjects were hospitalized in the control group compared to zero in the Proxalutamide group. The proportion of COVID-19 patients hospitalized was significantly different between the Proxalutamide and control arms; χ2 (1) = 42.051, p<.0001. The difference in proportions was 27.30% with a 95%CI: [19.79%, 35.59%]. No subject receiving Proxalutamide died compared to 2 (1.56%) in the control group. There were no treatment related adverse event reported during the course of the study. Based on the results of the Proxalutamide Treatment for Non-Hospitalized COVID-19 Male Patients study (NCT04446429), the purpose of this study is to assess the efficacy and safety of Proxalutamide as a treatment for COVID-19 patients in the intensive care unit ;


Study Design


Related Conditions & MeSH terms

  • Covid19
  • SARS (Severe Acute Respiratory Syndrome)
  • Severe Acute Respiratory Syndrome

NCT number NCT04853927
Study type Interventional
Source Applied Biology, Inc.
Contact Daniel Fonseca, MD
Phone +55 92 8415-1870
Email [email protected]
Status Recruiting
Phase Phase 3
Start date February 8, 2021
Completion date December 31, 2021

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