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Proxalutamide Treatment for COVID-19 Female Outpatients

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04853134
Recruitment Status : Active, not recruiting
First Posted : April 21, 2021
Last Update Posted : July 21, 2021
Sponsor:
Information provided by (Responsible Party):
Applied Biology, Inc.

Tracking Information
First Submitted Date  ICMJE April 19, 2021
First Posted Date  ICMJE April 21, 2021
Last Update Posted Date July 21, 2021
Actual Study Start Date  ICMJE November 1, 2020
Estimated Primary Completion Date December 1, 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: April 19, 2021)
COVID-19 hospitalization [ Time Frame: 30 days ]
Percentage of subjects hospitalized due to COVID-19
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Proxalutamide Treatment for COVID-19 Female Outpatients
Official Title  ICMJE Proxalutamide Treatment for COVID-19 Female Outpatients
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 Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE 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
Condition  ICMJE
  • Covid19
  • SARS-CoV Infection
Intervention  ICMJE
  • Drug: Proxalutamide
    200 mg q.d.
  • Other: Standard of Care
    Standard of care as determined by the PI
Study Arms  ICMJE
  • Placebo Comparator: Standard Care
    Standard of care as determined by the PI
    Intervention: Other: Standard of Care
  • Active Comparator: Proxalutamide + Standard Care
    Proxalutamide + standard of care as determined by the PI
    Intervention: Drug: Proxalutamide
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: April 19, 2021)
200
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE December 1, 2021
Estimated Primary Completion Date December 1, 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Female age >=18 years old
  • Laboratory confirmed positive SARS-CoV-2 rtPCR test within 7 days prior to randomization
  • Clinical status on the NIAID COVID-19 Ordinal Scale of 1 or 2 (i.e., not requiring hospitalization)
  • Coagulation: INR<=1.5XULN, and APTT<=1.5XULN
  • Subject (or legally authorized representative) gives written informed consent prior to any study screening procedures
  • Subject (or legally authorized representative) agree that subject will not participate in another COVID-19 trial while participating in this study
  • Not Pregnant or breastfeeding

Exclusion Criteria:

  • Subject enrolled in a study to investigate a treatment for COVID-19 Page 17 of 40
  • Subject taking an anti-androgen of any type including: androgen depravation therapy, 5-alpha reductase inhibitors, etc...
  • Patients who are allergic to the investigational product or similar drugs (or any excipients)
  • 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
  • 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
  • Subjects with uncontrolled medical conditions that could compromise participation in the study (e.g. uncontrolled hypertension, hypothyroidism, diabetes mellitus)
  • Known diagnosis of human immunodeficiency virus (HIV) , hepatitis C, active hepatitis B, treponema pallidum (testing is not mandatory)
  • Alanine Transaminase (ALT) or Aspartate Transaminase (AST) > 5 times the upper limit of normal.
  • Estimated glomerular filtration rate (eGFR) < 30 ml/min
  • Severe kidney disease requiring dialysis
  • Subject unlikely to return for day 15 site visit for reasons other then remission
  • Subject (or legally authorized representative) not willing or unable to provide informed consent
  • Pregnant or breastfeeding
Sex/Gender  ICMJE
Sexes Eligible for Study: Female
Gender Based Eligibility: Yes
Gender Eligibility Description: This is a study in female subjects as an extension to NCT04446429 for male subjects
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT04853134
Other Study ID Numbers  ICMJE AB-DRUG-SARS-005
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Applied Biology, Inc.
Study Sponsor  ICMJE Applied Biology, Inc.
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Flavio Cadegiani, MD Corpometria Institute
Principal Investigator: Carlos Wambier, MD Applied Biology, Inc.
Study Director: Andy Goren, MD Applied Biology, Inc.
PRS Account Applied Biology, Inc.
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP