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

Study Overview
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Brief Summary
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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.

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

Conditions
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COVID-19 Infection

Intervention / Treatment
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* Drug: Enzalutamide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzalutamide (Xtandi®)<br>Interventional treatment | Drug: Enzalutamide<br>* 40 mg oral tablets once daily for a maximum of 28 days.<br>* Other names: XTANDI;|
| Active Comparator: Standard of care (SOC)<br>Supportive treatment | Drug: Enzalutamide<br>* 40 mg oral tablets once daily for a maximum of 28 days.<br>* Other names: XTANDI;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of Enzalutamide by decreasing SARS-CoV-2 viral expression | efficacy of Enzalutamide in decreasing the nasopharyngeal swap SARS-CoV-2 viral load until negativization | 28 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tollerability of Enzalutamide by identifying Adverse Events | Evaluation of Enzalutamide tolerability in terms of incidence and severity grade of side effects | 28 days | 
| Disease progression by unresolved SARS-CoV-2 viral expression after treatment | Efficacy of Enzalutamide in controlling disease progression of SARS-CoV-2 viral load | 28 days |