Enzalutamide Treatment in COVID-19

Study Overview
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Brief Summary
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COVID-19 is a disease with high rate of morbidity if symptomatic. There is a great need of treatments to decrease the severity. The vast majority of patients needing intensive care are men, and this may be due to the androgens, either by regulation of TMPRSS2, necessary for virus internalization, or other mechanisms. Enzalutamide is an antiandrogen inhibiting the expression of androgen regulated proteins, such as TMPRSS2. The aim of this trial is to evaluate a possible beneficial effect of short-term enzalutamide treatment of COVID-19 patients.

Official Title
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A Prospective, Multicenter, Randomized PHASE II Clinical Trial of Enzalutamide Treatment to Decrease the Morbidity in Patients With Corona Virus Disease 2019 (COVID-19)

Conditions
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COVID-19, Corona Virus Infection

Intervention / Treatment
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* Drug: Enzalutamide Pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive COVID-19 test Mild to severe symptoms of COVID-19 Hospitalization WHO performance status 0-3 Age above or equal to 50 years Can understand all the requirements of the study, provide informed consent, and provide authorization of use and disclosure of personal health information. Estimated expected survival of 1 year (excluding symptoms due to COVID-19) Exclusion Criteria: Severe allergy to Enzalutamide Pregnant or breast-feeding women Need of immediate mechanical ventilation Current medication includes enzalutamide treatment Stroke or Transitory Ischemic attack in medical history Treatment for HIV Treatment with tamoxifen Treatment with immunosuppressive agents Severe immunosuppressive disease Treatment with warfarin or NOAC (Non-vitamin K-antagonist anticoagulants) Previous seizure in medical history Other serious illness or medical condition Unstable cardiovascular disease

Ages Eligible for Study
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Minimum Age: 50 Years

Sexes Eligible for Study
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All

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
Interventional Model Description: Prospective, randomized (2:1), open, multicentre, clinical controlled trial
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Enzalutamide+Standard of Care<br>Up to 5 days with 4x40 mg enzalutamide tablets orally once daily | Drug: Enzalutamide Pill<br>* The once daily dose will be given only during hospitalization and stop if starting invasive mechanical ventilation or at discharge from hospital<br>|
| No Intervention: Standard of Care<br>Standard of care | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to worsening of disease | Clinical worsening to invasive mechanical ventilation or death as assessed by the 7-point ordinal scale | Up to 30 days after inclusion | 
| Time to improvement of disease | Time to discharge from hospital assessed by the 7-point ordinal scale | Up to 30 days after inclusion | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adverse events | Safety evaluation, as measured by AEs | Up to 6 months | 
| Duration of supplemental oxygen (days) | Total days of extra oxygen | Up to 30 days | 
| Admission to ICU | Frequence of admission to ICU | Up to 30 days and up to 6 months | 
| Laboratory assessment of Hemoglobin concentration day 0, 2, 4 and 6 | Changes of laboratory parameters: Hb | Up to 30 days | 
| Virus load assessment day 0, 2, 4 and 6 | PCR based SARS-CoV-2 measurement from upper respiratory tract | UP to 7 days | 
| Hospital stay (days) | Total number of days evaluated at 30 days and 6 months | Up to30 days and 6 months | 
| Re-admission to hospital due to rebound COVID-19 | If admitted to hospital due to COVID-19 disease after discharge from hospital | Evaluated for 30 days and after 6 months | 
| Mortality at 6 months | Death due to any cause | up to 30 days and up to 6 months respectively | 
| Laboratory assessment of CRP concentration day 0, 2, 4 and 6 | Changes of laboratory parameters: CRP | Up to 30 days | 
| Laboratory assessment of liver function day 0, 2, 4 and 6 | Changes of laboratory parameters: ALAT, ASTA and/or ALP | Up to 30 days | 
| Laboratory assessment of creatinine concentration day 0, 2, 4 and 6 | Changes of laboratory parameters: Createnin | Up to 30 days | 
| Laboratory assessment of D-dimer concentration day 0, 2, 4 and 6 | Changes of laboratory parameters: D-dimer | Up to 30 days | 
| Laboratory assessment of platelets concentration day 0, 2, 4 and 6 | Changes of laboratory parameters: TPK | Up to 30 days | 
| Laboratory assessment of IL-6 concentration day 0, 2, 4 and 6 | Changes of laboratory parameters: IL-6 | Up to 30 days | 
| Laboratory assessment of B- and T-lyphocytes concentration day 0, 2, 4 and 6 | Changes of laboratory parameters: Differentiate count of leucocytes | Up to 30 days | 
| Pharmacokinetic interaction of enzalutamide with steroids | Maximum Plasma Concentration [Cmax] of steroids in blood | Up to 30 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Enzalutamide, Randomized clinical trial, COVID-19, Sars-CoV2