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

Phase 2

Terminated

• Conditions: COVID-19 Infection
• Interventions: Drug: Enzalutamide

• Registration Number: NCT04456049
• Lead Sponsor: Ricardo Pereira Mestre

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2020-07-01
• Study First Submitted QC: 2020-07-01
• Study First Posted: 2020-07-02
• Study Start: 2020-08-24
• Primary Completion: 2021-06-09
• Study Completion: 2021-06-09
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-07
• Last Update Posted: 2022-08-10

Recruitment & Eligibility

• Status: TERMINATED
• Sex: Male
• Target Recruitment: 7

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Enzalutamide (Xtandi®)	Enzalutamide	Interventional treatment
Standard of care (SOC)	Enzalutamide	Supportive treatment

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Oncology Institute of Southern Switzerland (IOSI); 🇨🇭 Bellinzona, Switzerland