Clinical trial NCT04728802: Proxalutamide Treatment for Hospitalized COVID-19 Patients
Official title: Proxalutamide Treatment for Hospitalized COVID-19 Patients
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Covid19
SARS (Severe Acute Respiratory Syndrome)
Keywords: Proxalutamide
Androgen
Anti-androgen
Lead sponsor: Applied Biology, Inc.
Sponsor class: INDUSTRY
First posted: 2021-01-28
Enrollment: 645
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This study is designed as a prospective, interventional, placebo controlled, double-blinded, randomized parallel assignment study.
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to assess the efficacy and safety of Proxalutamide as a treatment for hospitalized COVID-19 male and female patients.


Eligibility criteria: Inclusion Criteria:

1. Admitted to the hospital with symptoms of COVID-19
2. Male and females age ≥18 years old
3. Laboratory confirmed positive SARS-CoV-2 rtPCR test within 7 days prior to randomization
4. Clinical status on the COVID-19 Ordinal Scale (defined in Section 5.1) of 3, 4, 5, or 6
5. Coagulation: INR ≤ 1.5×ULN, and APTT ≤ 1.5×ULN
6. Subject (or legally authorized representative) gives written informed consent prior to performing any study procedures
7. 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. Requires mechanical ventilation
3. Subject taking an anti-androgen of any type including: androgen depravation therapy, 5-alpha reductase inhibitors, etc...
4. Patients who are allergic to the investigational product or similar drugs (or any excipients);
5. 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
6. 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
7. Subjects with uncontrolled medical conditions that could compromise participation in the study(e.g. uncontrolled hypertension, hypothyroidism, diabetes mellitus)
8. Known diagnosis of human immunodeficiency virus(HIV) , hepatitis C, active hepatitis B, treponema pallidum (testing is not mandatory）
9. Alanine Transaminase (ALT) or Aspartate Transaminase (AST) \> 5 times the upper limit of normal.
10. Estimated glomerular filtration rate (eGFR) \< 30 ml/min
11. Severe kidney disease requiring dialysis
12. Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using highly effective contraception, as shown below, throughout the study and for 3 months after stopping GT0918 treatment. Highly effective contraception methods include:

    * Total Abstinence (when this is in line with the preferred and usual lifestyle of the patient. Periodic abstinence (e.g. calendar, ovulation, symptothermal, post-ovulation methods) and withdrawal are not acceptable methods of contraception, or
    * Use of one of the following combinations (a+b or a+c or b+c):

      1. Use of oral, injected or implanted hormonal methods of contraception or other forms of hormonal contraception that have comparable efficacy (failure rate \< 1%), for example hormone vaginal ring or transdermal hormone contraception.
      2. Placement of an intrauterine device (IUD) or intrauterine system (IUS) ;
      3. Barrier methods of contraception: Condom or Occlusive cap (diaphragm or cervical/vault caps) with spermicidal foam/gel/film/cream/vaginal suppository ;
    * Female sterilization (have had prior surgical bilateral oophorectomy with or without hysterectomy) or tubal ligation at least six weeks before taking study treatment. In case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow-up hormone level assessment ;
    * Male sterilization (at least 6 months prior to screening). For female patients on the study, the vasectomized male partner should be the sole partner for that patient;
    * In case of use of oral contraception women should have been stable for a minimum of 3 months before taking study treatment. Women are considered post-menopausal and not of child bearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g. age appropriate, history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy) or tubal ligation at least six weeks ago. In the case of oophorectomy alone, only when the reproductive status of the woman has been confirmed by follow up hormone level assessment, is she considered not of child bearing potential;
13. Sexually active males must use a condom during intercourse while taking the drug and for 3 months after stopping GT0918 treatment and should not father a child in this period. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid
14. Subject likely to transfer to another hospital within the next 28 days
15. Subject (or legally authorized representative) not willing or unable to provide informed consent

Primary outcomes:
measure: 14 Day Recovery Rate
timeFrame: Day 14
Secondary outcomes:
measure: 28 Day Recovery Rate
timeFrame: Day 28
measure: 28 Day Mortality Rate
timeFrame: 28 days
measure: Post-Randomization Time to Recover (Alive Hospital Discharge)
timeFrame: 28 days
Other outcomes:
Locations:
city: Itacoatiara
country: Brazil
facility: Hospital Regional José Mendes
state: Amazonas
city: Manacapuru
country: Brazil
facility: Hospital de Campanha de Manacapuru
state: Amazonas
city: Manaus
country: Brazil
facility: Hospital Oscar Nicolau
state: Amazonas
city: Manaus
country: Brazil
facility: Hospital Prontocord
state: Amazonas
city: Manaus
country: Brazil
facility: Hospital Samel
state: Amazonas
city: Manicore
country: Brazil
facility: Hospital Regional Dr. Hamilton Maia Cidae
state: Amazonas
city: Maues
country: Brazil
facility: Hospital Raimunda Francisca Dinelli da Silva
state: Amazonas
city: Parintins
country: Brazil
facility: Hospital Regional Jofre Cohen
state: Amazonas
Study officials:
affiliation: Applied Biology, Inc.
name: Flavio Cadegiani, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Applied Biology, Inc.
name: Andy Goren, MD
role: STUDY_DIRECTOR
References:
citation: 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. No abstract available.
citation: Goren A, Vano-Galvan 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.
citation: Wambier CG, Vano-Galvan S, McCoy J, Gomez-Zubiaur A, Herrera S, Hermosa-Gelbard A, Moreno-Arrones OM, Jimenez-Gomez N, Gonzalez-Cantero A, Fonda-Pascual P, Segurado-Miravalles G, Shapiro J, Perez-Garcia 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.
citation: 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.
citation: McCoy J, Cadegiani FA, Wambier CG, Herrera S, Vano-Galvan S, Mesinkovska NA, Ramos PM, Shapiro J, Sinclair R, Tosti A, Goren A. 5-alpha-reductase inhibitors are associated with reduced frequency of COVID-19 symptoms in males with androgenetic alopecia. J Eur Acad Dermatol Venereol. 2021 Apr;35(4):e243-e246. doi: 10.1111/jdv.17021. Epub 2020 Nov 22. No abstract available.
citation: McCoy J, Wambier CG, Herrera S, Vano-Galvan S, Gioia F, Comeche B, Ron R, Serrano-Villar S, Iwasiow RM, Tayeb MA, Cadegiani FA, Mesinkovska NA, Shapiro J, Sinclair R, Goren A. Androgen receptor genetic variant predicts COVID-19 disease severity: a prospective longitudinal study of hospitalized COVID-19 male patients. J Eur Acad Dermatol Venereol. 2021 Jan;35(1):e15-e17. doi: 10.1111/jdv.16956. Epub 2020 Oct 21. No abstract available.