Enzalutamide Treatment in COVID-19 (COVIDENZA)

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

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.

Study Overview

• Status: Terminated
• Conditions: COVID-19; Corona Virus Infection
• Intervention / Treatment: Drug: Enzalutamide Pill

• Study Type: Interventional
• Enrollment (Actual): 42
• Phase: Phase 2

Contacts and Locations

Study Locations

• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska University Hospital
  • Linköping, Sweden
    • Linköping University Hospital
  • Sundsvall, Sweden
    • Sundsvall Region Hosptial
  • Umeå, Sweden
    • Umeå Univerisity Hospital
  • Skåne
    • Malmö, Skåne, Sweden
      • Anders Bjartell
  • Småland
    • Jönköping, Småland, Sweden
      • Ryhovs Hospital

Participation Criteria

Eligibility Criteria

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

Description

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

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+Standard of Care; Up to 5 days with 4x40 mg enzalutamide tablets orally once daily	Drug: Enzalutamide Pill; The once daily dose will be given only during hospitalization and stop if starting invasive mechanical ventilation or at discharge from hospital
No Intervention: Standard of Care; Standard of care

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Andreas Josefsson
• Collaborators: Göteborg University; Umeå University; Sahlgrenska University Hospital, Sweden; Sundsvall Hospital; Skane University Hospital; Jonkoping County Hospital; University Hospital, Umeå; Uppsala University Hospital; Astellas Pharma Europe Ltd.; Helsingborgs Hospital; Norrlands University Hospital
• Investigators: Principal Investigator: Andreas Josefsson, MdPhD, Norrlands University Hospital, Region Västerbotten

Publications and helpful links

General Publications

• Welen K, Overby AK, Ahlm C, Freyhult E, Robinsson D, Henningsson AJ, Stranne J, Bremell D, Angelin M, Lindquist E, Buckland R, Carlsson CT, Pauksens K, Bill-Axelsson A, Akre O, Ryden C, Wagenius M, Bjartell A, Nilsson AC, Styrke J, Repo J, Balkhed AO, Niward K, Gisslen M, Josefsson A. COVIDENZA - A prospective, multicenter, randomized PHASE II clinical trial of enzalutamide treatment to decrease the morbidity in patients with Corona virus disease 2019 (COVID-19): a structured summary of a study protocol for a randomised controlled trial. Trials. 2021 Mar 16;22(1):209. doi: 10.1186/s13063-021-05137-4.

Helpful Links

• Homepage of the trial
• Publication of the results

Study record dates

Study Major Dates

• Study Start (Actual): July 15, 2020
• Primary Completion (Actual): March 24, 2021
• Study Completion (Actual): May 29, 2021

Study Registration Dates

• First Submitted: June 8, 2020
• First Submitted That Met QC Criteria: July 16, 2020
• First Posted (Actual): July 17, 2020

Study Record Updates

• Last Update Posted (Actual): June 2, 2022
• Last Update Submitted That Met QC Criteria: May 30, 2022
• Last Verified: August 1, 2021

More Information

Terms related to this study

• Keywords: Randomized clinical trial; COVID-19; Enzalutamide; Sars-CoV2
• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Coronavirus Infections
• Other Study ID Numbers: COVIDENZA

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided
• IPD Plan Description: The extent of sharing will be regulated during the trial to consider the integrity of the data according GDPR and national laws

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No