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History of Changes for Study: NCT04446429
Anti-Androgen Treatment for COVID-19
Latest version (submitted December 8, 2021) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 June 23, 2020 None (earliest Version on record)
2 June 23, 2020 Study Description and Study Status
3 July 25, 2020 Recruitment Status, Study Status, Arms and Interventions, Contacts/Locations, Study Design and Oversight
4 July 28, 2020 Contacts/Locations and Study Status
5 December 10, 2020 Arms and Interventions and Study Status
6 December 29, 2020 Arms and Interventions, Outcome Measures, Eligibility, Study Design, Conditions, Study Description and Study Status
Show
Results Submission Events
7 January 29, 2021 Recruitment Status, Study Status, Contacts/Locations, Eligibility, Study Design, Document Section, Results and Outcome Measures
8 June 14, 2021 Adverse Events, Outcome Measures, Participant Flow, Document Section, Baseline Characteristics, Arms and Interventions, Study Status and Study Design
9 December 8, 2021 Study Status
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Changes (Side-by-Side) for Study: NCT04446429
December 10, 2020 (v5) -- December 29, 2020 (v6)

Changes in: Study Status, Study Description, Conditions, Study Design, Arms and Interventions, Outcome Measures, Eligibility

Open or close this module Study Identification
Unique Protocol ID: AB-DRUG-SARS-004 AB-DRUG-SARS-004
Brief Title: Anti-Androgen Treatment for COVID-19 Anti-Androgen Treatment for COVID-19
Official Title: Anti-Androgen Treatment for COVID-19 Anti-Androgen Treatment for COVID-19
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2020 July 2020
Overall Status: RecruitingRecruiting
Study Start: July 2, 2020 July 2, 2020
Primary Completion: December 31, 2020 [Anticipated] December 31, 2020 [Anticipated]
Study Completion: January 31, 2021 [Anticipated] January 31, 2021 [Anticipated]
First Submitted: June 22, 2020 June 22, 2020
First Submitted that
Met QC Criteria:
June 23, 2020 June 23, 2020
First Posted: June 24, 2020 [Actual] June 24, 2020 [Actual]
Last Update Submitted that
Met QC Criteria:
December 10, 2020 December 29, 2020
Last Update Posted: December 11, 2020 [Actual] December 31, 2020 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: Applied Biology, Inc. Applied Biology, Inc.
Responsible Party: Sponsor Sponsor
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: NoNo
U.S. FDA-regulated Device: NoNo
Data Monitoring: No No
Open or close this module Study Description
Brief Summary: This study is intended to explore the possible protective role of anti-androgens in SARS-CoV-2 infection This study is intended to explore the possible protective role of anti-androgens in SARS-CoV-2 infection
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.

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.

We have chosen the use of the novel second generation androgen receptor (AR) antagonist proxalutamide as a means for rapid reduction in AR activity. Proxalutamide (GT0918) demonstrates a dual mechanism of action. It is highly effective in inhibiting AR as well as exhibiting pharmacological effects of inducing the down-regulation of AR expression; the mechanism that is not present in bicalutamide and enzalutamide. Additionally, it has been reported that Proxalutamide lowers the expression of ACE2. Both would be beneficial for preventing SARS-CoV-2 entry into lung cells.

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.

Open or close this module Conditions
Conditions: COVID-19
SARS-CoV2
Androgenetic Alopecia
Prostate Cancer
Benign Prostatic Hyperplasia
SARS (Severe Acute Respiratory Syndrome)
COVID-19
SARS-CoV2
Androgenetic Alopecia
Prostate Cancer
Benign Prostatic Hyperplasia
SARS (Severe Acute Respiratory Syndrome)
Keywords: Anti-Androgen
Dutasteride
Anti-Androgen
Proxalutamide
Open or close this module Study Design
Study Type: InterventionalInterventional
Primary Purpose: TreatmentTreatment
Study Phase: Not ApplicableNot Applicable
Interventional Study Model: Parallel Assignment Parallel Assignment
This study is designed as a prospective, interventional, placebo controlled, double-blinded, randomized parallel assignment study. This study is designed as a prospective, interventional, placebo controlled, double-blinded, randomized parallel assignment study.
Number of Arms: 32
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Allocation: RandomizedRandomized
Enrollment: 381 [Anticipated] 254 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Experimental: Dutasteride + Standard Care
Nitazoxanide + Azythromycin + Dutasteride
Drug: Nitazoxanide
500 mg b.i.d
Drug: Azithromycin
500 mg q.d.
Drug: Dutasteride
0.5 mg q.d.
Active Comparator: Standard Care
Nitazoxanide + Azythromycin Standard of care as determined by the PI
Drug: Nitazoxanide
500 mg b.i.d
Drug: Azithromycin
500 mg q.d.
Standard of Care
Standard of care as determined by the PI
Experimental: Proxalutamide + Standard Care
Nitazoxanide + Azythromycin + Proxalutamide Proxalutamide + standard of care as determined by the PI
Drug: Nitazoxanide
500 mg b.i.d
Drug: Azithromycin
500 mg q.d.
Drug: Proxalutamide
200 mg q.d.
Open or close this module Outcome Measures
Primary Outcome Measures:
1. COVID-19 hospitalization
[ Time Frame: 30 days ]

Percentage of subjects hospitalized due to COVID-19
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
Open or close this module Eligibility
Minimum Age: 50 Years 50 Years
Maximum Age:
Sex: Male Male
Gender Based: Yes Yes
Accepts Healthy Volunteers: NoNo
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

Inclusion Criteria:

  1. Male
  2. Age ≥50 years old

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
Open or close this module Contacts/Locations
Central Contact Person: Flavio A Cadegiani, MD
Telephone: +5561996506111
Email: f.cadegiani@gmail.com
Flavio A Cadegiani, MD
Telephone: +5561996506111
Email: f.cadegiani@gmail.com
Central Contact Backup: Andy Goren, MD
Email: andyg@appliedbiology.com
Andy Goren, MD
Email: andyg@appliedbiology.com
Study Officials: Flavio A Cadegiani, MD
Principal Investigator
Corpometria Institute
Flavio A Cadegiani, MD
Principal Investigator
Corpometria Institute
Andy Goren, MD
Study Director
Applied Biology, Inc.
Andy Goren, MD
Study Director
Applied Biology, Inc.
Locations: BrazilBrazil
Corpometria Institute
[Recruiting]
Brasilia, Brazil, 70390-150
Contact:Contact: Flavio A Cadegiani, MD +5561996506111 f.cadegiani@gmail.com
Contact:Principal Investigator: Flavio A Cadegiani, MD
Contact:Sub-Investigator: Carlos Wambier, MD
Corpometria Institute
[Recruiting]
Brasilia, Brazil, 70390-150
Contact:Contact: Flavio A Cadegiani, MD +5561996506111 f.cadegiani@gmail.com
Contact:Principal Investigator: Flavio A Cadegiani, MD
Contact:Sub-Investigator: Carlos Wambier, MD
Open or close this module IPDSharing
Plan to Share IPD: No No
Open or close this module References
Citations: Goren A, McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Dhurat R, Washenik K, Lotti T. What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy. Dermatol Ther. 2020 Jul;33(4):e13365. doi: 10.1111/dth.13365. Epub 2020 Apr 8. PubMed 32237190Goren A, McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Dhurat R, Washenik K, Lotti T. What does androgenetic alopecia have to do with COVID-19? An insight into a potential new therapy. Dermatol Ther. 2020 Jul;33(4):e13365. doi: 10.1111/dth.13365. Epub 2020 Apr 8. PubMed 32237190
Goren A, Vaño-Galván S, Wambier CG, McCoy J, Gomez-Zubiaur A, Moreno-Arrones OM, Shapiro J, Sinclair RD, Gold MH, Kovacevic M, Mesinkovska NA, Goldust M, Washenik K. A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - A potential clue to the role of androgens in COVID-19 severity. J Cosmet Dermatol. 2020 Jul;19(7):1545-1547. doi: 10.1111/jocd.13443. Epub 2020 Apr 23. PubMed 32301221Goren A, Vaño-Galván S, Wambier CG, McCoy J, Gomez-Zubiaur A, Moreno-Arrones OM, Shapiro J, Sinclair RD, Gold MH, Kovacevic M, Mesinkovska NA, Goldust M, Washenik K. A preliminary observation: Male pattern hair loss among hospitalized COVID-19 patients in Spain - A potential clue to the role of androgens in COVID-19 severity. J Cosmet Dermatol. 2020 Jul;19(7):1545-1547. doi: 10.1111/jocd.13443. Epub 2020 Apr 23. PubMed 32301221
McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Sinclair R, Ramos PM, Washenik K, Andrade M, Herrera S, Goren A. Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19? J Cosmet Dermatol. 2020 Jul;19(7):1542-1543. doi: 10.1111/jocd.13455. Epub 2020 Jun 14. PubMed 32333494McCoy J, Wambier CG, Vano-Galvan S, Shapiro J, Sinclair R, Ramos PM, Washenik K, Andrade M, Herrera S, Goren A. Racial variations in COVID-19 deaths may be due to androgen receptor genetic variants associated with prostate cancer and androgenetic alopecia. Are anti-androgens a potential treatment for COVID-19? J Cosmet Dermatol. 2020 Jul;19(7):1542-1543. doi: 10.1111/jocd.13455. Epub 2020 Jun 14. PubMed 32333494
Wambier CG, Goren A, Vaño-Galván S, Ramos PM, Ossimetha A, Nau G, Herrera S, McCoy J. Androgen sensitivity gateway to COVID-19 disease severity. Drug Dev Res. 2020 Nov;81(7):771-776. doi: 10.1002/ddr.21688. Epub 2020 May 15. PubMed 32412125Wambier CG, Goren A, Vaño-Galván S, Ramos PM, Ossimetha A, Nau G, Herrera S, McCoy J. Androgen sensitivity gateway to COVID-19 disease severity. Drug Dev Res. 2020 Nov;81(7):771-776. doi: 10.1002/ddr.21688. Epub 2020 May 15. PubMed 32412125
Wambier CG, Vaño-Galván S, McCoy J, Gomez-Zubiaur A, Herrera S, Hermosa-Gelbard Á, Moreno-Arrones OM, Jiménez-Gómez N, González-Cantero A, Fonda-Pascual P, Segurado-Miravalles G, Shapiro J, Pérez-García B, Goren A. Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The "Gabrin sign". J Am Acad Dermatol. 2020 Aug;83(2):680-682. doi: 10.1016/j.jaad.2020.05.079. Epub 2020 May 22. PubMed 32446821Wambier CG, Vaño-Galván S, McCoy J, Gomez-Zubiaur A, Herrera S, Hermosa-Gelbard Á, Moreno-Arrones OM, Jiménez-Gómez N, González-Cantero A, Fonda-Pascual P, Segurado-Miravalles G, Shapiro J, Pérez-García B, Goren A. Androgenetic alopecia present in the majority of patients hospitalized with COVID-19: The "Gabrin sign". J Am Acad Dermatol. 2020 Aug;83(2):680-682. doi: 10.1016/j.jaad.2020.05.079. Epub 2020 May 22. PubMed 32446821
Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, Carbone GM, Cavalli A, Pagano F, Ragazzi E, Prayer-Galetti T, Alimonti A. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020 Aug;31(8):1040-1045. doi: 10.1016/j.annonc.2020.04.479. Epub 2020 May 6. PubMed 32387456Montopoli M, Zumerle S, Vettor R, Rugge M, Zorzi M, Catapano CV, Carbone GM, Cavalli A, Pagano F, Ragazzi E, Prayer-Galetti T, Alimonti A. Androgen-deprivation therapies for prostate cancer and risk of infection by SARS-CoV-2: a population-based study (N = 4532). Ann Oncol. 2020 Aug;31(8):1040-1045. doi: 10.1016/j.annonc.2020.04.479. Epub 2020 May 6. PubMed 32387456
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