A Study to Evaluate the Efficacy and Safety of Proxalutamide (GT0918) in Hospitalized COVID-19 Subjects

• Status: Recruiting
• Trial end date: 2022-11-01
• Target enrollment: 0
• Participant gender: All

Summary

This study is an adaptive Phase III randomized double-blind placebo-controlled trial to evaluate the efficacy and safety of Proxalutamide (GT0918) in hospitalized adults diagnosed with COVID-19. The study is a multicenter trial that will be conducted at approximately 80 sites globally. The study will compare GT0918 plus standard of care (SOC) with the placebo plus SOC. Approximately 1030 subjects will be randomized in a 1:1 ratio to either GT0918 plus SOC or placebo plus SOC group.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Suzhou Kintor Pharmaceutical Inc,
• Collaborator: IQVIA Biotech

Criteria

Inclusion Criteria:

1. Subject (or legally authorized representative) provides informed consent prior to initiation of any study procedures.

2. Subject (or legally authorized representative) understands and agrees to comply with planned study procedures.

3. Male and non-pregnant female subjects with age ≥18 years of age at the time of randomization.

4. Admitted to a hospital with symptoms suggestive of COVID-19.

5. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or other commercial or public health assay in any specimen, as documented by either of the following:

• PCR positive in sample collected < 72 hours prior to randomization; OR

• PCR positive in sample collected ≥ 72 hours prior to randomization, documented inability to obtain a repeat sample (e.g. due to lack of testing supplies, limited testing capacity, results taking > 24 hours, etc) AND progressive disease suggestive of ongoing SARS-CoV-2 infection.

6. Illness of any duration, and at least one of the following:

• Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR

• SpO2 ≤ 93% on room air, OR

• Requiring supplemental oxygen

7. 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 subjects on the study, the vasectomized male partner should be the sole partner for that subject;

• 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 childbearing 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 childbearing potential;

8. Regardless of their fertility status, male subjects must agree to either remain abstinent (if this is their preferred and usual lifestyle) or use condoms as well as one additional highly effective method of contraception (less than 1% failure rate) or effective method of contraception with nonpregnant women of childbearing potential partners for the duration of the study and until 90 days after the last dose. A condom is required to be used also by vasectomized men in order to prevent delivery of the drug via seminal fluid.

9. Agree not to participate in another clinical trial for the treatment of COVID-19 through Day 60 after first dose.

Exclusion Criteria:

Subjects are excluded from the study if any of the following criteria apply:

1. ALT/AST > 3 times the upper limit of normal.

2. Serum total bilirubin > 1.5 x ULN (upper limit of normal)

3. Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receiving hemodialysis or hemofiltration).

4. Subjects with significant cardiovascular disease as following:

i. heart failure NYHA class ≥3 ii. left ventricular ejection fraction <50% iii. those with a history of cardiac arrhythmias, including long QT syndrome.

5. Neutropenia (absolute neutrophil count <1000 cells/μL) (<1.0 x 10^3/μL).

6. Lymphopenia (absolute lymphocyte count <200 cells/μL) (<0.20 x 10^3/μL)

7. Pregnancy or breast feeding

8. Anticipated discharge from the hospital or transfer to another hospital which is not a study site within 72 hours.

9. Allergy to any study medication.

10. Received convalescent plasma or intravenous immunoglobulin [IVIg]) for COVID-19.

11. Has received or is receiving corticosteroids at high doses (i.e., dexamethasone > 6mg per day or equivalent) within 2 weeks of screening.

12. Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product.

13. Have a history of VTE (deep vein thrombosis [DVT] or pulmonary embolism [PE]) within 12 weeks prior to screening or have a history of recurrent (>1) VTE (DVT/PE).

14. Subject taking or had taken an anti-androgen of any type including androgen depravation therapy, 5-alpha reductase inhibitors, etc. within 3 months before dosing.

15. Have participated, within the last 30 days before dosing, in a clinical study involving an investigational intervention. If the previous investigational intervention has a long half-life, 5 half-lives or 30 days, whichever is longer, should have passed.

16. Subjects with myopathy

17. Is admitted to Intensive Care Units at randomization