Anti-Androgen Treatment for COVID-19

Sponsor
Applied Biology, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04446429
Collaborator
(none)
268
Enrollment
1
Location
2
Arms
3
Actual Duration (Months)
88.7
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

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.

Study Design

Study Type:
Interventional
Actual Enrollment :
268 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.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 :
Oct 21, 2020
Actual Primary Completion Date :
Dec 24, 2020
Actual Study Completion Date :
Jan 21, 2021

Arms and Interventions

ArmIntervention/Treatment
Active Comparator: Usual Care

Usual care as determined by the PI

Other: Standard of Care
Standard of care as determined by the PI

Experimental: Proxalutamide + Usual Care

Proxalutamide + Usual care as determined by the PI

Drug: Proxalutamide
200 mg q.d.

Outcome Measures

Primary Outcome Measures

  1. COVID-19 Hospitalization [30 days]

    Percentage of subjects hospitalized due to COVID-19

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
Male
Accepts Healthy Volunteers:
No
Inclusion Criteria:
  1. Male age ≥18 years old

  2. Laboratory confirmed positive SARS-CoV-2 rtPCR test within 7 days prior to randomization

  3. Clinical status on the COVID-19 8-point Ordinal Scale of 1 or 2

  4. Coagulation: INR ≤ 1.5×ULN, and APTT ≤ 1.5×ULN

  5. Subject (or legally authorized representative) gives written informed consent prior to any study screening procedures

  6. Subject (or legally authorized representative) agree that subject will not participate in another COVID-19 trial while participating in this study

Exclusion Criteria:
  1. Subject enrolled in a study to investigate a treatment for COVID-19

  2. Subject taking an anti-androgen of any type including: androgen depravation therapy, 5-alpha reductase inhibitors, etc…

  3. Patients who are allergic to the investigational product or similar drugs (or any excipients);

  4. Subjects who have malignant tumors in the past 5 years, with the exception of completed resected basal cell and squamous cell skin cancer and completely resected carcinoma in situ of any type

  5. Subjects with known serious cardiovascular diseases, congenital long QT syndrome, torsade de pointes, myocardial infarction in the past 6 months, or arterial thrombosis, or unstable angina pectoris, or congestive heart failure which is classified as New York Heart Association (NYHA) class 3 or higher, or left ventricular ejection fraction (LVEF) < 50%, QTcF > 450 ms

  6. Subjects with uncontrolled medical conditions that could compromise participation in the study(e.g. uncontrolled hypertension, hypothyroidism, diabetes mellitus)

  7. Known diagnosis of human immunodeficiency virus(HIV) , hepatitis C, active hepatitis B, treponema pallidum (testing is not mandatory)

  8. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal.

  9. Estimated glomerular filtration rate (eGFR) < 30 ml/min

  10. Severe kidney disease requiring dialysis

  11. Subject unlikely to return for day 15 site visit for reasons other then remission

  12. Subject (or legally authorized representative) not willing or unable to provide informed consent

Contacts and Locations

Locations

SiteCityStateCountryPostal Code
1Corpometria InstituteBrasiliaBrazil70390-150

Sponsors and Collaborators

  • Applied Biology, Inc.

Investigators

  • Principal Investigator: Flavio A Cadegiani, MD, Corpometria Institute
  • Study Director: Andy Goren, MD, Applied Biology, Inc.

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
Applied Biology, Inc.
ClinicalTrials.gov Identifier:
NCT04446429
Other Study ID Numbers:
  • AB-DRUG-SARS-004
First Posted:
Jun 24, 2020
Last Update Posted:
Dec 10, 2021
Last Verified:
Dec 1, 2021
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Applied Biology, Inc.
Additional relevant MeSH terms:

Study Results

Participant Flow

Recruitment Details
Pre-assignment Detail
Arm/Group TitleUsual CareProxalutamide + Usual Care
Arm/Group DescriptionUsual care as determined by the PI Usualf Care: Care as determined by the PIProxalutamide + usual care as determined by the PI Proxalutamide: 200 mg q.d.
Period Title: Overall Study
STARTED134134
COMPLETED128134
NOT COMPLETED60

Baseline Characteristics

Arm/Group TitleUsual CareProxalutamide + Usual CareTotal
Arm/Group DescriptionUsual care as determined by the PI Usual Care: Care as determined by the PIProxalutamide + usual care as determined by the PI Proxalutamide: 200 mg q.d.Total of all reporting groups
Overall Participants134134268
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]
45
(10.8)
44.2
(14)
44.5
(7.7)
Sex: Female, Male (Count of Participants)
Female
0
0%
0
0%
0
0%
Male
134
100%
134
100%
268
100%
Race/Ethnicity, Customized (Count of Participants)
Mixed ethnicity (Brazil)
134
100%
134
100%
268
100%
Region of Enrollment (participants) [Number]
Brazil
134
100%
134
100%
268
100%
Coexisting conditions (Count of Participants)
Count of Participants [Participants]
20
14.9%
29
21.6%
49
18.3%

Outcome Measures

1. Primary Outcome
TitleCOVID-19 Hospitalization
DescriptionPercentage of subjects hospitalized due to COVID-19
Time Frame30 days

Outcome Measure Data

Analysis Population Description
All randomized patients were included. 6 patients from the placebo arm lost to follow-up were assumed to be non-hospitalized (COVID-19 8-point ordinal scale 1) and were included in the intention-to-treat analysis.
Arm/Group TitleUsual CareProxalutamide + Usual Care
Arm/Group DescriptionUsual care as determined by the PI Usual Care: Care as determined by the PIProxalutamide + usual care as determined by the PI Proxalutamide: 200 mg q.d.
Measure Participants134134
Count of Participants [Participants]
35
26.1%
3
2.2%

Adverse Events

Time Frame30 days
Adverse Event Reporting Description
Arm/Group TitleUsual CareProxalutamide + Usual Care
Arm/Group DescriptionUsual care as determined by the PI Usual Care: Care as determined by the PIProxalutamide + usual care as determined by the PI Proxalutamide: 200 mg q.d.
All Cause Mortality
Usual CareProxalutamide + Usual Care
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total2/134 (1.5%) 0/134 (0%)
Serious Adverse Events
Usual CareProxalutamide + Usual Care
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total35/134 (26.1%) 3/134 (2.2%)
Respiratory, thoracic and mediastinal disorders
Death2/134 (1.5%) 20/134 (0%) 0
Hospitalization35/134 (26.1%) 353/134 (2.2%) 3
Other (Not Including Serious) Adverse Events
Usual CareProxalutamide + Usual Care
Affected / at Risk (%)# EventsAffected / at Risk (%)# Events
Total78/134 (58.2%) 45/134 (33.6%)
Cardiac disorders
Tachycardia45/134 (33.6%) 6/134 (4.5%)
Gastrointestinal disorders
Diarrhea20/134 (14.9%) 39/134 (29.1%)
Nausea15/134 (11.2%) 21/134 (15.7%)
Abdominal pain or discomfort18/134 (13.4%) 22/134 (16.4%)
Dyspepsia or Heartburn6/134 (4.5%) 23/134 (17.2%)
General disorders
Fatigue71/134 (53%) 1/134 (0.7%)
Fever34/134 (25.4%) 2/134 (1.5%)
Disease progression43/134 (32.1%) 4/134 (3%)
Musculoskeletal and connective tissue disorders
Back pain36/134 (26.9%) 16/134 (11.9%)
Nervous system disorders
Ageusia23/134 (17.2%) 13/134 (9.7%)
Anosmia26/134 (19.4%) 14/134 (10.4%)
Headache12/134 (9%) 1/134 (0.7%)
Respiratory, thoracic and mediastinal disorders
Shortness of breath40/134 (29.9%) 4/134 (3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

Name/TitleDirector of Clinical Trials
OrganizationApplied Biology
Phone+1-949-387-4526
Emailmonican@appliedbiology.com
Responsible Party:
Applied Biology, Inc.
ClinicalTrials.gov Identifier:
NCT04446429
Other Study ID Numbers:
  • AB-DRUG-SARS-004
First Posted:
Jun 24, 2020
Last Update Posted:
Dec 10, 2021
Last Verified:
Dec 1, 2021