Covid19, SARS (Severe Acute Respiratory Syndrome)
Conditions
Keywords
Proxalutamide, Androgen, Anti-androgen
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.
Interventions
DRUGProxalutamide
Proxalutamide 300mg q.d
DRUGPlacebo
Placebo pill
Sponsors
Applied Biology, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Masking description
Double (Participant, Care Provider)
Intervention model description
This study is designed as a prospective, interventional, placebo controlled, double-blinded, randomized parallel assignment study.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 14 Day Recovery Rate | Day 14 | Recovery rate defined as those reaching scores 1 or 2 over 14 days after randomization on the COVID-19 ordinal scale. The ordinal scale is defined as follows: 8\. Death; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 6. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5. Hospitalized, requiring supplemental oxygen; 4. Hospitalized, not requiring supplemental oxygen- requiring ongoing medical care (COVID-19 related or otherwise; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2. Not hospitalized, limitation on activities; 1\. Not hospitalized, no limitations on activities |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 28 Day Recovery Rate | Day 28 | Recovery rate defined as those reaching scores 1 or 2 over 28 days after randomization on the COVID-19 ordinal scale. The ordinal scale is defined as follows: 8\. Death; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 6. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5. Hospitalized, requiring supplemental oxygen; 4. Hospitalized, not requiring supplemental oxygen- requiring ongoing medical care (COVID-19 related or otherwise; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2. Not hospitalized, limitation on activities; 1\. Not hospitalized, no limitations on activities |
| 28 Day Mortality Rate | 28 days | All-cause mortality rate over 28 days post randomization. |
| Post-Randomization Time to Recover (Alive Hospital Discharge) | 28 days | Number of day post-randomization required to achieve live hospital discharge. |
Countries
Brazil
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Proxalutamide + Usual Care Proxalutamide + usual care as determined by care provider
Proxalutamide: Proxalutamide 300mg q.d | 317 |
| Placebo + Usual Care Placebo + usual care as determined by care provider
Placebo: Placebo pill | 328 |
| Total | 645 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 4 | 5 |
| Overall Study | Other | 3 | 0 |
| Overall Study | Physician Decision | 7 | 7 |
| Overall Study | Protocol Violation | 10 | 4 |
| Overall Study | Transfer | 1 | 0 |
| Overall Study | Withdrawal by Subject | 4 | 20 |
Baseline characteristics
| Characteristic | Total | Placebo + Usual Care | Proxalutamide + Usual Care |
|---|---|---|---|
| 0 Coexisting conditions | 431 Participants | 227 Participants | 204 Participants |
| 1 Coexisting conditions | 124 Participants | 56 Participants | 68 Participants |
| 2+ Coexisting conditions | 90 Participants | 45 Participants | 45 Participants |
| Age, Continuous | 50 years | 49 years | 50 years |
| Body mass index over 30 kg/m2 | 53 Participants | 25 Participants | 28 Participants |
| Chronic kidney disease | 0 Participants | 0 Participants | 0 Participants |
| Chronic obstructive pulmonary disorder | 16 Participants | 8 Participants | 8 Participants |
| Hypertension | 175 Participants | 82 Participants | 93 Participants |
| Race and Ethnicity Not Collected | 0 Participants | — | — |
| Region of Enrollment Brazil | 645 participants | 328 participants | 317 participants |
| Sex: Female, Male Female | 279 Participants | 146 Participants | 133 Participants |
| Sex: Female, Male Male | 366 Participants | 182 Participants | 184 Participants |
| Type 2 diabetes mellitus | 79 Participants | 38 Participants | 41 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 35 / 317 | 162 / 328 |
| other Total, other adverse events | 51 / 317 | 11 / 328 |
| serious Total, serious adverse events | 38 / 317 | 170 / 328 |
Outcome results
Primary
14 Day Recovery Rate
Recovery rate defined as those reaching scores 1 or 2 over 14 days after randomization on the COVID-19 ordinal scale. The ordinal scale is defined as follows: 8\. Death; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 6. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5. Hospitalized, requiring supplemental oxygen; 4. Hospitalized, not requiring supplemental oxygen- requiring ongoing medical care (COVID-19 related or otherwise; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2. Not hospitalized, limitation on activities; 1\. Not hospitalized, no limitations on activities
Time frame: Day 14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proxalutamide + Usual Care | 14 Day Recovery Rate | 258 Participants |
| Placebo + Usual Care | 14 Day Recovery Rate | 117 Participants |
Secondary
28 Day Mortality Rate
All-cause mortality rate over 28 days post randomization.
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proxalutamide + Usual Care | 28 Day Mortality Rate | 35 Participants |
| Placebo + Usual Care | 28 Day Mortality Rate | 162 Participants |
Secondary
28 Day Recovery Rate
Recovery rate defined as those reaching scores 1 or 2 over 28 days after randomization on the COVID-19 ordinal scale. The ordinal scale is defined as follows: 8\. Death; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 6. Hospitalized, on non-invasive ventilation or high flow oxygen devices; 5. Hospitalized, requiring supplemental oxygen; 4. Hospitalized, not requiring supplemental oxygen- requiring ongoing medical care (COVID-19 related or otherwise; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 2. Not hospitalized, limitation on activities; 1\. Not hospitalized, no limitations on activities
Time frame: Day 28
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Proxalutamide + Usual Care | 28 Day Recovery Rate | 271 Participants |
| Placebo + Usual Care | 28 Day Recovery Rate | 155 Participants |
Secondary
Post-Randomization Time to Recover (Alive Hospital Discharge)
Number of day post-randomization required to achieve live hospital discharge.
Time frame: 28 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Proxalutamide + Usual Care | Post-Randomization Time to Recover (Alive Hospital Discharge) | 5 Days |
| Placebo + Usual Care | Post-Randomization Time to Recover (Alive Hospital Discharge) | 10 Days |