Randomized Open Label Phase II Study to Evaluate the Efficacy of Enzalutamide in High Risk Male Outpatients With COVID-1

• Enzalutamide (Drug), also known as XTANDI: 40 mg oral tablets once daily for a maximum of 28 days.

Primary outcomes

• Efficacy of Enzalutamide by decreasing SARS-CoV-2 viral expression [28 days]: efficacy of Enzalutamide in decreasing the nasopharyngeal swap SARS-CoV-2 viral load until negativization

Secondary outcomes

• Tollerability of Enzalutamide by identifying Adverse Events [28 days]: Evaluation of Enzalutamide tolerability in terms of incidence and severity grade of side effects
• Disease progression by unresolved SARS-CoV-2 viral expression after treatment [28 days]: Efficacy of Enzalutamide in controlling disease progression of SARS-CoV-2 viral load

Sex: Male, ages: 50 Years to any

Inclusion Criteria:

* Documented COVID-19 infection (confirmed by NPS positive PCR for SARS-CoV-2) with mild symptoms not requiring hospitalization
* First NPS ≤4 days (96 hours) since onset of symptoms
* Randomization ≤72 hours since first NPS
* Adult Males aged ≥ 50 years
* Indication for outpatient treatment but at high risk for complications, at least 1 risk factor (age ≥ 65 years, hypertension, diabetes, cardiovascular disease, active malignancy, COPD)
* WHO performance status 0-1
* Adequate hematologic values: haemoglobin ≥ 100 g/L, neutrophils ≥ 1.0 x 10(9)/L, platelets ≥ 150 x 10(9)/L.
* Adequate hepatic function: ALT and AST ≤ 2.5 x ULN, bilirubin ≤ 1.5 x ULN (exception if Gilbert's syndrome ≤ 2.5 x ULN)
* Adequate renal function: calculated creatinine clearance ≥ 50 mL/min according to the formula of Cockcroft-Gault
* Patient is able to swallow the trial drugs and to comply with trial requirements
* Patient agrees not to father a child during participation in the trial and for 3 months thereafter

Exclusion Criteria:

* Female sex
* Moderate to severe COVID-19 symptoms requiring hospitalization
* Patients requiring inpatient treatment
* Concurrent antiviral drugs or ongoing interventional clinical trial or any off label drug for COVID-19
* Patients with ongoing prostate cancer treatment
* Clinically significant cardiovascular disease including:

  * Myocardial infarction within 6 months prior to registration,
  * Uncontrolled angina within 3 months prior to registration,
  * Congestive heart failure NYHA class III or VI
  * QTc interval > 480 ms
  * History of clinically significant ventricular arrhythmias (e.g. ventricular tachycardia, ventricular fibrillation, torsades de pointes)
  * History of Mobitz II second or third degree heart block without a permanent pacemaker in place
  * Uncontrolled hypertension as indicated by systolic blood pressure > 170 mmHg or diastolic blood pressure > 105 mmHg
  * Deep venous thrombosis or pulmonary embolism within 6 months
  * History of cerebrovascular disease
* Severe concurrent disease, infection or co-morbidity that, in the judgment of the investigator, would make the patient inappropriate for enrolment.
* Known history of HIV, hepatitis B, hepatitis C
* Known history of seizures or any conditions that may predispose to seizure. History of loss of consciousness or ischemic cerebrovascular attack within 12 months prior to registration
* Concurrent anticoagulation with rivaroxaban or warfarin. Concomitant and continuous use of systemic corticosteroids exceeding 10 mg/day of prednisone or a dose equivalent corticosteroid within 14 days before registration.
* Known hypersensitivity to Enzalutamide or hypersensitivity to any of its components
* Any concomitant drugs contraindicated for use with Enzalutamide according to the Swissmedic approved product information
* Any psychological, familial, sociological or geographical condition potentially hampering compliance with the trial protocol and follow-up.