EAT-DUTA AndroCoV Trial

NCT04729491 | Completed Phase 2

• 1 other identifier: CORPO-AB-DRUG-SARS-004B
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief Summary

During the continuing SARS-CoV-2 (COVID-19) pandemic, several studies have reported a significant difference in the rate of severe cases between adult females and adult males (42% vs 58%). Among children under the age of 14, the rate of severe cases was reported to be extremely low. To explain this difference, several theories have been proposed including cigarette smoking and lifestyle habits. However, no theory fits both the gender difference in severe cases as well as reduced risk in pre-pubescent children. Our past research on male androgenetic alopecia (AGA) has led us to investigate an association between androgens and COVID-19 pathogenesis. In normal subjects, androgen expression demonstrates significant variation between men and women as well as between adults and pre-pubescent children. SARS-CoV-2 primarily infects type II pneumocytes in the human lung. SARS-CoV-2 enters pneumocytes, by anchoring to the ACE2 cell surface receptor. Prior to receptor binding, viral spike proteins undergo proteolytic priming by the transmembrane protease, serine 2 (TMPRSS2). TMPRSS2 inhibition or knock down reduces ability of SARS-CoV-1 (a related virus to SARS-CoV-2) to infect cells in vitro. Additionally, TMPRSS2 also facilitates entry of influenza A and influenza B into primary human airway cells and type II pneumocytes. The human TMPRSS2 gene has a 15 bp androgen response element and in humans, androgens are the only known transcription promoters for the TMPRSS2 gene. In a study of androgen-stimulated prostate cancer cells (LNCaP), TMPRSS2 mRNA expression increase was mediated by the androgen receptor.10 Further, the ACE2 receptor, also critical for SARS-CoV-2 viral infectivity, is affected by male sex hormones with higher activity found in males. Androgenetic alopecia (AGA), often referred to as male pattern hair loss, is the most common form of hair loss among men. The development of androgenetic alopecia is androgen mediated and is dependent on genetic variants found in the androgen receptor gene located on the X chromosome. We hypothesized that men with AGA would be more prone to severe COVID-19 disease. We conducted a preliminary observational study of hospitalized COVID-19 patients at two Spanish tertiary hospitals between March 23-April 6, 2020 to test this theory. In total, 41 Caucasian males admitted to the hospitals with a diagnosis of bilateral SARS-CoV-2 pneumonia were analyzed. The mean age of patients was 58 years (range 23-79). Among them, 29 (71%) were diagnosed with AGA (16 (39%) were classified as severe AGA (Hamilton IV or above)) and 12 (29%) did not present clinical signs of AGA. The diagnosis of AGA was performed clinically by a dermatologist. The precise prevalence of AGA among otherwise healthy Spanish Caucasian males is unknown; however, based on published literature, the expected prevalence of a similar age-matched Caucasian population is approximately 31-53%. Further, according to the European Center for Disease Control and Prevention (https://www.ecdc.europa.eu/sites/default/files/documents/covid-19-rapid-risk-assessment-coronavirus-disease-2019-eighth-update-8-april-2020.pdf): "Of the confirmed cases in China, 3.8% (1 716/44 672) were healthcare workers. Of those, 14.8% were severely or critically ill and 5% of the severe cases died. Latest figures reported from Italy show that 9% of COVID-19 cases are healthcare workers, with Lombardy region reporting up to 20% of cases in healthcare workers. In Spain, the latest COVID-19 situation overview from the Ministry of Health reports that 26% of COVID-19 cases are in healthcare workers. In a Dutch study, healthcare workers were tested voluntarily for COVID-19 and 6% tested positive. In a report on 30 cases in healthcare workers in China, all cases had a history of direct contact (distance within 1 metre) with COVID-19 patients, with an average number of 12 contacts, and the average cumulative contact time being two hours (1.5, 2.7). In the Dutch study, only 3% of the healthcare workers reported being exposed to hospital patients with COVID-19 prior onset of symptoms and 63% had worked while asymptomatic. Based on the scientific rationale combined with this preliminary observation, we propose to test an anti-androgen as a treatment for patients recently diagnosed with COVID-19. This study is intended to explore the possible protective role of anti-androgens in SARS-CoV-2 infection, including reduction of virological duration and disease severity.

Conditions

Covid19

Keywords

SARS-CoV-2; Dutasteride

Outcome Measures

Primary Outcomes (1)

• Positivity rate of rtPCR-SARS-CoV-2 (qualitative analysis)

  Treatment efficacy of dutasteride relative to placebo arm as assessed by viral load measured by positivity rate (% of positive, detected rtSARS-CoV-2)

  Day 7

Secondary Outcomes (42)

• World Health Organization (WHO) Clinical Progression Scale [0 to 10; 0 = uninfected; 10 = death]

  Day 14

• World Health Organization (WHO) COVID=19 Ordinal Scale for Clinical Improvement [1 to 8; 1 = not hospitalized, no limitation on activities; 8 = death]

  Day 7

• Time-to-recovery

  Day 28

• SARS-CoV-2 viral load

  Day 5

• Duration of fatigue

  Day 14

Study Arms (2)

Dutasteride

ACTIVE COMPARATOR

Dutasteride 0.5mg/day q.d. for 30 days or until COVID-19 remission (defined as full remission of symptoms plus viral clearance through rtPCR-SARS-CoV-2)

Drug: Dutasteride 0.5 mg; Drug: Azithromycin; Drug: Nitazoxanide

Placebo

PLACEBO COMPARATOR

Placebo q.d. for 30 days or until COVID-19 remission (defined as full remission of symptoms plus viral clearance through rtPCR-SARS-CoV-2)

Drug: Azithromycin; Drug: Nitazoxanide; Drug: Placebo

Interventions

Dutasteride 0.5 mg DRUG

Use of dutasteride 0.5mg/day q.d. for 30 days or until COVID-19 remission, in recently diagnosed COVID-19 subjects.

Dutasteride

Azithromycin DRUG

Azithromycin 500mg/day for 05 days

Dutasteride; Placebo

Nitazoxanide DRUG

500mg twice daily for 06 days

Dutasteride; Placebo

Placebo DRUG

Use of placebo q.d. for 30 days or until COVID-19 remission, in recently diagnosed COVID-19 subjects.

Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male
• ≥18 years old
• Laboratory confirmed positive SARS-CoV-2 rtPCR test within 7 days prior to randomization
• Clinical status on the COVID-19 Ordinal Scale (defined in Section 5.1) of 1 to 3
• Subject (or legally authorized representative) gives written informed consent prior to performing any study procedures
• Subject (or legally authorized representative) agree that subject will not participate in another COVID-19 trial while participating in this study

You may not qualify if:

• Subject enrolled in a study to investigate a treatment for COVID-19
• Require oxygen use, hospitalization or mechanical ventilation
• Tachycardia (HR \> 150 bpm) or hypotension (BP \< 90/60 mmHg)
• Patients who are allergic to the investigational product or similar drugs (or any excipients);
• Subjects with QTcF \> 450 ms
• Subjects with uncontrolled medical conditions that could compromise participation in the study - uncontrolled hypertension (BP \> 220/120 mmHg), uncontrolled hypothyroidism (TSH \> 10 iU/L), uncontrolled diabetes mellitus (HbA1c \> 12%)
• Alanine Transaminase (ALT) or Aspartate Transaminase (AST) \> 5 times the upper limit of normal.
• Estimated glomerular filtration rate (eGFR) \< 30 ml/min or requiring dialysis
• Subject (or legally authorized representative) not willing or unable to provide informed consent
• Not willing to provide informed consent

Sponsors & Collaborators

• Corpometria Institute: lead

Study Sites (1)

Corpometria Institute

Brasília, Federal District, 70390-150, Brazil

Location

MeSH Terms

Conditions

COVID-19

Interventions

Dutasteride; Azithromycin; nitazoxanide

Condition Hierarchy (Ancestors)

Pneumonia, Viral; Pneumonia; Respiratory Tract Infections; Infections; Virus Diseases; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Azasteroids; Steroids, Heterocyclic; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Carlos G. Wambier, MD, Ph.D.

  Alpert School of Medicine - Brown University

  STUDY DIRECTOR

• Flavio A. Cadegiani, MD, MSc, Ph.D.

  Corpometria Institute

  PRINCIPAL INVESTIGATOR

• Andy Goren, MD

  Applied Biology

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: January 28, 2021
• Study Start: June 30, 2020
• Primary Completion: September 15, 2020
• Study Completion: October 7, 2020
• Last Updated: January 28, 2021

Record last verified: 2020-06

Data Sharing

• IPD Sharing: Will not share

Locations

BR (1)