Proxalutamide (GT0918) Treatment for Outpatients With Mild or Moderate COVID-19 Illness

This is a Phase 3, randomized, double-blind, placebo-controlled, multicenter study to evaluate the safety and efficacy of Proxalutamide (GT0918) in adult outpatients diagnosed with mild to moderate COVID-19. The study will be 2-arm comparison against matched placebo. The study will be conducted in around 100 sites in the USA and other countries. This study utilizes an adaptive design that maximizes our efficiency in identifying a safe and efficacious therapeutic agent for COVID-19 during the current outbreak. There will be an interim analysis after 334 subjects complete Day 28 after the first dose to allow early stopping for futility, efficacy, or safety. The study population will be subjects with mild to moderate COVID-19 illness chosen to evaluate if early intervention with anti-androgen therapy prior to respiratory compromise can effectively prevent progression to the severe form of COVID-19 illness. Randomization is essential for establishing efficacy of these new therapeutic agents.

The blood samples for PK analysis need to be collected for at least 200 subjects, whom will also be randomized into the interventional treatment or placebo group with 1:1 ratio.

Inclusion criteria

• The subject or legally authorized representative give signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.
• Understand and agree to comply with planned study procedures.
• Male subjects with age ≥18 years of age at the time of randomization.
• Are currently not hospitalized.
• Have one or more mild or moderate symptom(s) COVID-19-related symptoms within 5 days of onset of symptoms onset
• Must have first positive SARS-CoV-2 viral infection determination (has laboratory-confirmed SARS-CoV-2 infection as determined by PCR, or other commercial or public health assay in any specimen) ≤3 days prior to start of the first dose.
• 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.

Use an acceptable method of contraception such as:

• Highly effective methods of contraception (less than 1% failure rate) comprise, but are not limited to

• combination oral contraceptives
• implanted contraceptives, or
• intrauterine devices.
• Effective methods of contraception comprise but are not limited to

• diaphragms with spermicide or cervical sponges.
• men and their partners may choose to use a double-barrier method of contraception that must include use of a spermicide.
• Agree to the collection of nasopharyngeal swabs and venous blood.

Exclusion criteria

• Have SpO2 ≤ 93% on room air at sea level or PaO2/FiO2 < 300, respiratory rate ≥30 per minute, heart rate ≥125 per minute
• Estimated glomerular filtration rate (eGFR) < 30 ml/min
• Serum total bilirubin > 1.5 x ULN (upper limit of normal) and AST and ALT >3x ULN
• 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.

• Has been admitted to a hospital prior to randomization, or is hospitalized (inpatient) at randomization, due to COVID-19 or requires treatment with supplemental oxygen.
• Have known allergies to any of the components used in the formulation of the interventions.
• Have hemodynamic instability requiring use of vasopressors within 24 hours of randomization.
• Suspected or proven serious, active bacterial, fungal, viral, or other infection (except COVID-19) that in the opinion of the investigator could constitute a risk when taking intervention (i.e. known history of human immunodeficiency virus [HIV]).
• Have any co-morbidity requiring surgery within <7 days, or that is considered life-threatening within 30 days.
• Have any serious concomitant systemic disease, condition, or disorder that, in the opinion of the investigator, should preclude participation in this study.