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

Phase 3

Completed

• Conditions: Efficacy and Safety
• Interventions: Drug: Proxalutamide (GT0918); Drug: Placebo

• Registration Number: NCT04870606
• Lead Sponsor: Suzhou Kintor Pharmaceutical Inc,

Brief Summary

The purpose of this study is to assess the efficacy and safety of Proxalutamide (GT0918) as a treatment for outpatients COVID-19 subjects.

Detailed Description

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.

Study Timeline

• Study Start: 2021-03-05
• Study First Submitted: 2021-04-27
• Study First Submitted QC: 2021-04-29
• Study First Posted: 2021-05-03
• Primary Completion: 2022-01-24
• Study Completion: 2022-04-06
• Results First Submitted: 2023-08-14
• Status Verified: 2023-12
• Results First Submitted QC: 2023-12-11
• Last Update Submitted: 2023-12-11
• Results First Posted: 2024-01-02
• Last Update Posted: 2024-01-02

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 733

Inclusion Criteria

1. 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.

2. Understand and agree to comply with planned study procedures.

3. Male subjects with age ≥18 years of age at the time of randomization.

4. Are currently not hospitalized.

5. Have one or more mild or moderate symptom(s) COVID-19-related symptoms within 5 days of onset of symptoms onset

6. 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.

7. 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.

8. Agree to the collection of nasopharyngeal swabs and venous blood.

Exclusion Criteria

1. Have SpO2 ≤ 93% on room air at sea level or PaO2/FiO2 < 300, respiratory rate ≥30 per minute, heart rate ≥125 per minute

2. Estimated glomerular filtration rate (eGFR) < 30 ml/min

3. Serum total bilirubin > 1.5 x ULN (upper limit of normal) and AST and ALT >3x ULN

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. 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.

6. Have known allergies to any of the components used in the formulation of the interventions.

7. Have hemodynamic instability requiring use of vasopressors within 24 hours of randomization.

8. 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]).

9. Have any co-morbidity requiring surgery within <7 days, or that is considered life-threatening within 30 days.

10. Have any serious concomitant systemic disease, condition, or disorder that, in the opinion of the investigator, should preclude participation in this study.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
GT0918+ standard of care	Proxalutamide (GT0918)	Proxalutamide 200mg, oral, QD, for continuous 14 days, plus standard of care(n=334)
placebo+ standard of care	Placebo	Placebo 200mg, oral, QD, for continuous 14 days, plus standard of care(n=334)

Primary Outcome Measures

Name	Time	Method
Sensitivity Analysis to Evaluate Efficacy in Terms of Clinical Status Following Treatment With Pruxelutamide (GT0918) Compared to Placebo	28 days	In mITT (treatment period \>7 days) , percentage of subjects who do not experience any of the following events due to all causes by Day 28: * Hospitalization for ≥ 24 hours, or; * Supplemental oxygen for ≥24 hours in response to SpO2 ≤93%, or; * Death
Efficacy in Terms of Clinical Status Following Treatment With Pruxelutamide (GT0918) Compared to Placebo	28 days	In mITT (administrated at least one dose)，percentage of subjects who do not experience any of the following events due to all causes by Day 28: * Hospitalization for ≥ 24 hours, or; * Supplemental oxygen for ≥24 hours in response to SpO2 ≤93%, or; * Death

Secondary Outcome Measures

Name	Time	Method
Proportion of Subjects With Hospitalization by Day 28	28 days	Percentage of subjects who do experience any of the following events due to all causes by Day 28: * Hospitalization for ≥ 24 hours, or; * Supplemental oxygen for ≥24 hours in response to SpO2 ≤93%, or; * Death
Viral Load	at day 3,7,14,28	Changes from baseline in SARS-CoV-2 viral load at days 3, 7, 14, and 28.

Trial Locations

Locations (8)

Olivo Medical and Wellness Center; 🇺🇸 Chicago, Illinois, United States

Absolute Clinical Research; 🇺🇸 Phoenix, Arizona, United States

Long Beach Clinical Trials; 🇺🇸 Long Beach, California, United States

WR-Mount Vernon Clinical Research, LLC; 🇺🇸 Sandy Springs, Georgia, United States

Main Street Physician's Care; 🇺🇸 Little River, South Carolina, United States

Lotus Clinical Research; 🇺🇸 Houston, Texas, United States

Gtc Research; 🇺🇸 Shawnee Mission, Kansas, United States

Platinum Research Network, LLC; 🇺🇸 Metairie, Louisiana, United States