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.

Study Overview

• Status: Terminated
• Conditions: COVID-19 Infection
• Intervention / Treatment: Drug: Enzalutamide

• Study Type: Interventional
• Enrollment (Actual): 7
• Phase: Phase 2

Contacts and Locations

Study Locations

• Switzerland
  • Bellinzona, Switzerland, 6500
    • Oncology Institute of Southern Switzerland (IOSI)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Ricardo Pereira Mestre
• Collaborators: Oncology Institute of Southern Switzerland; Institute of Oncology Research; Institute for Research in Biomedicine

Study record dates

Study Major Dates

• Study Start (Actual): August 24, 2020
• Primary Completion (Actual): June 9, 2021
• Study Completion (Actual): June 9, 2021

Study Registration Dates

• First Submitted: July 1, 2020
• First Submitted That Met QC Criteria: July 1, 2020
• First Posted (Actual): July 2, 2020

Study Record Updates

• Last Update Posted (Actual): August 10, 2022
• Last Update Submitted That Met QC Criteria: August 7, 2022
• Last Verified: August 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19
• Other Study ID Numbers: COVID_ENZA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No