Clinical trial NCT04456049: Randomized Open Label Phase II Study to Evaluate the Efficacy of Enzalutamide in High Risk Male Outpatients With COVID-1
Official title: COVID_ENZA Trial: Randomized Open Label Phase II Study to Evaluate the Efficacy of Enzalutamide in High Risk Male Outpatients With COVID-1
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: COVID-19 Infection
Lead sponsor: Ente Ospedaliero Cantonale, Bellinzona
Sponsor class: OTHER
Collaborators: name: Oncology Institute of Southern Switzerland
name: Institute of Oncology Research
name: Institute for Research in Biomedicine
First posted: 2020-07-02
Enrollment: 7
Sex: MALE
Minimum age (years): 50
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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.

Primary outcomes:
measure: Efficacy of Enzalutamide by decreasing SARS-CoV-2 viral expression
timeFrame: 28 days
Secondary outcomes:
measure: Tollerability of Enzalutamide by identifying Adverse Events
timeFrame: 28 days
measure: Disease progression by unresolved SARS-CoV-2 viral expression after treatment
timeFrame: 28 days
Other outcomes:
Locations:
city: Bellinzona
country: Switzerland
facility: Oncology Institute of Southern Switzerland (IOSI)
Study officials:
References: