Efficacy and Safety
Conditions
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.
Interventions
DRUGProxalutamide (GT0918)
Proxalutamide (GT0918)+Standard of care determined by PI and local regulatory
DRUGPlacebo
Placebo+Standard of care determined by PI and local regulatory
Sponsors
Suzhou Kintor Pharmaceutical Inc,
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Recruitment details
A total of 865 subjects were screened, of whom 132 subjects failed at screening. A total of 733 subjects were randomized in this study
Pre-assignment details
733 subjects were randomized. 366 subjects were assigned to receive Pruxelutamide arm and 367 subjects were assigned to receive placebo arm. All randomized subjects were included in the ITT population. 730 subjects, which included 365 subjects from each of the Pruxelutamide and placebo groups, were randomized and received at least one dose of treatment. These subjects were included in both the mITT and SS populations.
Participants by arm
| Arm | Count |
|---|---|
| GT0918+ Standard of Care Proxalutamide (GT0918): Proxalutamide (GT0918)+Standard of care determined by PI and local regulatory | 366 |
| Placebo+ Standard of Care Placebo: Placebo+Standard of care determined by PI and local regulatory | 367 |
| Total | 733 |
Baseline characteristics
| Characteristic | GT0918+ Standard of Care | Placebo+ Standard of Care | Total |
|---|---|---|---|
| Age, Continuous | 41 years STANDARD_DEVIATION 13.82 | 40.9 years STANDARD_DEVIATION 13.45 | 41 years STANDARD_DEVIATION 13.63 |
| BMI | 29.02 kg/m^2 STANDARD_DEVIATION 5.817 | 29.03 kg/m^2 STANDARD_DEVIATION 6.625 | 29.02 kg/m^2 STANDARD_DEVIATION 6.04 |
| COVID-19 Test Type Antigen (Rapid) Test | 137 Participants | 127 Participants | 264 Participants |
| COVID-19 Test Type Molecular (RNA or PCR) Test | 228 Participants | 236 Participants | 464 Participants |
| COVID-19 Test Type Unknown | 1 Participants | 4 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 322 Participants | 325 Participants | 647 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 44 Participants | 42 Participants | 86 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 4 Participants |
| Race (NIH/OMB) Black or African American | 25 Participants | 33 Participants | 58 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 16 Participants | 13 Participants | 29 Participants |
| Race (NIH/OMB) White | 323 Participants | 316 Participants | 639 Participants |
| Sex: Female, Male Female | 183 Participants | 185 Participants | 368 Participants |
| Sex: Female, Male Male | 183 Participants | 182 Participants | 365 Participants |
| Vaccination Status Fully Vaccinated | 140 Participants | 152 Participants | 292 Participants |
| Vaccination Status Non Vaccinated | 210 Participants | 194 Participants | 404 Participants |
| Vaccination Status Partially Vaccinated | 14 Participants | 16 Participants | 30 Participants |
| Vaccination Status Unknown | 2 Participants | 5 Participants | 7 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 365 | 1 / 365 |
| other Total, other adverse events | 19 / 365 | 11 / 365 |
| serious Total, serious adverse events | 0 / 365 | 0 / 365 |
Outcome results
Primary
Efficacy in Terms of Clinical Status Following Treatment With Pruxelutamide (GT0918) Compared to Placebo
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
Time frame: 28 days
Population: In mITT (administrated at least one dose)
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GT0918+ Standard of Care | Efficacy in Terms of Clinical Status Following Treatment With Pruxelutamide (GT0918) Compared to Placebo | 361 Participants |
| Placebo+ Standard of Care | Efficacy in Terms of Clinical Status Following Treatment With Pruxelutamide (GT0918) Compared to Placebo | 357 Participants |
Primary
Sensitivity Analysis to Evaluate Efficacy in Terms of Clinical Status Following Treatment With Pruxelutamide (GT0918) Compared to Placebo
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
Time frame: 28 days
Population: mITT (treatment period \>7 days) The mITT was defined as patients treated at least one dose. The primary outcome was analyzed based on mITT set.~At the same time, the sponsor did some sensitive analysis based on another mITT set, defined as patients treated longer than 7 days, to support the primary outcome analysis.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GT0918+ Standard of Care | Sensitivity Analysis to Evaluate Efficacy in Terms of Clinical Status Following Treatment With Pruxelutamide (GT0918) Compared to Placebo | 348 Participants |
| Placebo+ Standard of Care | Sensitivity Analysis to Evaluate Efficacy in Terms of Clinical Status Following Treatment With Pruxelutamide (GT0918) Compared to Placebo | 339 Participants |
p-value: 0.0181Cochran-Mantel-Haenszel
Secondary
Proportion of Subjects With Hospitalization by Day 28
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
Time frame: 28 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| GT0918+ Standard of Care | Proportion of Subjects With Hospitalization by Day 28 | 4 Participants |
| Placebo+ Standard of Care | Proportion of Subjects With Hospitalization by Day 28 | 8 Participants |
p-value: 0.1223Chi-squared
Secondary
Viral Load
Changes from baseline in SARS-CoV-2 viral load at days 3, 7, 14, and 28.
Time frame: at day 3,7,14,28
Population: The patient enrolled by local laboratory-confirmed SARS-CoV-2 infection; at the same time, Quantitative RT-qPCR done in the central laboratory was to determine the viral load change from different time points. Only the patients with positive dd-PCR test results, Limit of Detection with 59.9 copies/mL, were included in the viral load analysis, 277 patients in GT0918 group and 272 patients in placebo group.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| GT0918+ Standard of Care | Viral Load | Days28 | -5.4 log10 copies/mL | Standard Error 0.1 |
| GT0918+ Standard of Care | Viral Load | Days14 | -4.8 log10 copies/mL | Standard Error 0.11 |
| GT0918+ Standard of Care | Viral Load | Days 7 | -3.6 log10 copies/mL | Standard Error 0.12 |
| GT0918+ Standard of Care | Viral Load | Days 3 | -2.0 log10 copies/mL | Standard Error 0.12 |
| Placebo+ Standard of Care | Viral Load | Days 3 | -1.5 log10 copies/mL | Standard Error 0.12 |
| Placebo+ Standard of Care | Viral Load | Days28 | -4.9 log10 copies/mL | Standard Error 0.1 |
| Placebo+ Standard of Care | Viral Load | Days 7 | -3.4 log10 copies/mL | Standard Error 0.13 |
| Placebo+ Standard of Care | Viral Load | Days14 | -4.5 log10 copies/mL | Standard Error 0.12 |
p-value: 0.0038t-test, 2 sided