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Anti-Androgen Treatment for COVID-19

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ClinicalTrials.gov Identifier: NCT04446429
Recruitment Status : Recruiting
First Posted : June 24, 2020
Last Update Posted : July 29, 2020
Sponsor:
Information provided by (Responsible Party):
Applied Biology, Inc.

Brief Summary:
This study is intended to explore the possible protective role of anti-androgens in SARS-CoV-2 infection

Condition or disease Intervention/treatment Phase
COVID-19 SARS-CoV2 Androgenetic Alopecia Prostate Cancer Benign Prostatic Hyperplasia SARS (Severe Acute Respiratory Syndrome) Drug: Dutasteride Drug: Ivermectin Drug: Azithromycin Drug: Proxalutamide Not Applicable

Detailed Description:

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. 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; thus, it is hypothesized that men with AGA would be more prone to severe COVID-19 disease. The investigators 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%.

Based on the scientific rationale combined with this preliminary observation, the investigators 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. Provided anti-androgens are effective in reducing the rate of COVID-19 hospitalization, subjects enrolled in this study may experience a lower rate of hospitalization.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 381 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: This study is designed as a prospective, interventional, placebo controlled, double-blinded, randomized parallel assignment study.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Anti-Androgen Treatment for COVID-19
Actual Study Start Date : July 2, 2020
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : January 31, 2021


Arm Intervention/treatment
Experimental: Dutasteride + Standard Care
Ivermectin+ Azythromycin + Dutasteride
Drug: Dutasteride
0.5 mg q.d.

Drug: Ivermectin
200 mcg/kg q.d

Drug: Azithromycin
500 mg q.d.

Active Comparator: Standard Care
Ivermectin + Azythromycin
Drug: Ivermectin
200 mcg/kg q.d

Drug: Azithromycin
500 mg q.d.

Experimental: Proxalutamide + Standard Care
Ivermectin+ Azythromycin + Proxalutamide
Drug: Ivermectin
200 mcg/kg q.d

Drug: Azithromycin
500 mg q.d.

Drug: Proxalutamide
200 mg q.d.




Primary Outcome Measures :
  1. COVID-19 hospitalization [ Time Frame: 30 days ]
    Percentage of subjects hospitalized due to COVID-19

  2. COVID-19 Ordinal Outcomes Scale [ Time Frame: 30 days ]

    COVID Ordinal Scale defined as:

    1. Death
    2. Hospitalized on invasive mechanical ventilation or ECMO ( extracorporeal membrane oxygenation)
    3. Hospitalized on non-invasive ventilation or high flow nasal cannula
    4. Hospitalized on supplemental oxygen
    5. Hospitalized not on supplemental oxygen
    6. Not hospitalized with limitation in activity (continued symptoms)
    7. Not hospitalized without limitation in activity (no symptoms)


Secondary Outcome Measures :
  1. Symptoms severity of COVID-19 [ Time Frame: 30 days ]
    Symptoms severity of COVID-19 using Brescia-COVID Respiratory Severity Scale (BCRSS)/Algorithm



Information from the National Library of Medicine

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Ages Eligible for Study:   50 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   Male
Gender Based Eligibility:   Yes
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Male
  2. Age ≥50 years old
  3. Presenting "Gabrin sign" i.e., androgenetic alopecia (Norwood-Hamilton grade ≥ III)
  4. Positive SARS-CoV-2 rtPCR test in the past 7 days
  5. Not hospitalized for acute respiratory symptoms
  6. Willing to provide informed consent

Exclusion Criteria:

  1. Subject enrolled in a study to investigate a COVID-19 drug
  2. Subject taking an anti-androgen
  3. Hypothyroidism
  4. Not willing to provide informed consent

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04446429


Contacts
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Contact: Flavio A Cadegiani, MD +5561996506111 f.cadegiani@gmail.com
Contact: Andy Goren, MD andyg@appliedbiology.com

Locations
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Brazil
Corpometria Institute Recruiting
Brasilia, Brazil, 70390-150
Contact: Flavio A Cadegiani, MD    +5561996506111    f.cadegiani@gmail.com   
Principal Investigator: Flavio A Cadegiani, MD         
Sub-Investigator: Carlos Wambier, MD         
Sponsors and Collaborators
Applied Biology, Inc.
Investigators
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Principal Investigator: Flavio A Cadegiani, MD Corpometria Institute
Study Director: Andy Goren, MD Applied Biology, Inc.
Publications:

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Responsible Party: Applied Biology, Inc.
ClinicalTrials.gov Identifier: NCT04446429    
Other Study ID Numbers: AB-DRUG-SARS-004
First Posted: June 24, 2020    Key Record Dates
Last Update Posted: July 29, 2020
Last Verified: July 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Applied Biology, Inc.:
Anti-Androgen
Dutasteride
Additional relevant MeSH terms:
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Severe Acute Respiratory Syndrome
Coronavirus Infections
Prostatic Hyperplasia
Alopecia
Hyperplasia
Prostatic Diseases
Pathologic Processes
Hypotrichosis
Hair Diseases
Skin Diseases
Pathological Conditions, Anatomical
Coronaviridae Infections
Nidovirales Infections
RNA Virus Infections
Virus Diseases
Respiratory Tract Infections
Respiratory Tract Diseases
Azithromycin
Ivermectin
Dutasteride
Anti-Bacterial Agents
Anti-Infective Agents
Antiparasitic Agents
5-alpha Reductase Inhibitors
Steroid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs