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

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

High risk outpatient adult males with a confirmed SARS-CoV-2 infection will be included in the study.

Patients will be randomized to receive Enzalutamide with standard of care (SOC) or SOC alone. Enzalutamide will be administered daily p.o. from Day 1 to Day 28 or until confirmed negativization of Nasopharyngeal swap (NPS) Polymerase chain reaction (PCR) (2 consecutive negative samples), whichever occurs first.

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.