A Pilot Study to Assess Safety and Efficacy of SIR1-365 in Patients With Severe COVID-19
Study Details
Study Description
Brief Summary
Primary Objective:
• To evaluate overall safety and tolerability of SIR1-365 in patients with severe COVID-19
Secondary Objectives:
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To assess the clinical efficacy of SIR1-365 in patients with severe COVID-19
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To assess the effects of SIR1-365 on multiple inflammatory biomarker levels including C-reactive protein (CRP), ferritin, lymphocyte and neutrophil counts, cytokines, and chemokines
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To assess the effects of SIR1-365 on biomarkers indicative of target engagement in patients with severe COVID-19
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To assess the effects of SIR1-365 on biomarkers indicative of kidney injury in patients with severe COVID-19
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To assess the effects of SIR1-365 on biomarkers indicative of cardiovascular endothelial cell damage in patients with severe COVID-19
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To characterize plasma pharmacokinetics (PK) of SIR1-365 in patients with severe COVID-19
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Detailed Description
Study duration per participant is approximately 28 days including a 14-day treatment period
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: SIR1-365 SIR1-365 dose 1 daily for 14 days |
Drug: SIR1-365
Route of administration: oral
Other Names:
|
| Placebo Comparator: Matching placebo Matching placebo dose 1 daily for 14 days |
Drug: Matching Placebo
Route of administration: oral
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Proportion of patients with any TEAEs during the treatment period [Baseline to Day 14]
Primary Safety Endpoint
Secondary Outcome Measures
- Proportion of patients with any AEs, SAEs and drug-related AEs during the study [Baseline to Day 14 and Day 28]
Secondary Safety Endpoint
- Proportion of patients with clinically significant abnormality in clinical laboratory tests and ECG during the study [Baseline to Day 14 and Day 28]
Secondary Safety Endpoint
- Change from Baseline to Day 7 and Day 14 in PaO2/FiO2 ratio [Baseline to Day 7 and Day 14]
Clinical Efficacy Endpoint
- Time to improvement of oxygenation defined as oxygen saturation (pulse oximetry) >93% and increased ≥1% from Baseline breathing only room air in the 48 hours preceding the measurement during the study [Baseline to Day 28]
Clinical Efficacy Endpoint
- Number of days without oxygen use during the study [Baseline to Day 28]
Clinical Efficacy Endpoint
- Proportion of patients with clinical improvement defined as a reduction of 2 points in the WHO ordinal scale during the study [Baseline to Day 28]
Clinical Efficacy Endpoint
- Number of days hospitalized during the study [Baseline to Day 28]
Clinical Efficacy Endpoint
- Proportion of patients free of respiratory failure during the study [Baseline to Day 28]
Clinical Efficacy Endpoint
- All-cause mortality rate during the study [Baseline to Day 28]
Clinical Efficacy Endpoint
- Change from Baseline to Day 7 and to Day 14 in plasma CRP level [Baseline to Day 7 and to Day 14]
Inflammatory Biomarker Measure
- Time to reach 50% reduction from Baseline in plasma CRP level during the treatment period [Baseline to Day 14]
Inflammatory Biomarker Measure
- Number of the patients to reach 50% reduction from Baseline in plasma CRP level during the treatment period [Baseline to Day 14]
Inflammatory Biomarker Measure
- Change from Baseline to Day 7 and Day 14 in serum cytokine levels [Baseline to Day 7 and Day 14]
Inflammatory Biomarker Measure
- Change from Baseline to Day 7 and Day 14 in plasma pRIP1 and pMLKL levels [Baseline to Day 7 and Day 14]
Biomarker Assessment for Target Engagement
- Change from Baseline to Day 7 and Day 14 in urine NGAL and KIM-1 levels [Baseline to Day 7 and Day 14]
Biomarker Assessment for Kidney Injury
- Plasma drug levels [Baseline to Day 7 and Day 14]
Assessment of PK profile
Eligibility Criteria
Criteria
Inclusion Criteria:
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Hospitalized patient with clinical diagnosis of SARS-CoV-2 virus infection per World Health Organization criteria including positive nucleic acid test of any specimen (e.g., respiratory, blood, or other bodily fluid) within 2 weeks prior to screening.
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Symptoms suggestive of severe systemic illness with COVID-19, which could include any of the following symptoms: fever, cough, sore throat, malaise, headache, muscle pain, gastrointestinal symptoms, or shortness of breath at rest, or respiratory distress.
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Clinical signs indicative of severe systemic illness with COVID-19, which could include any of the following clinical signs: respiratory rate ≥ 30 per minutes, heart rate ≥ 125 per minute, SpO2 ≤ 93% on room air, or PaO2/FiO2 ratio < 300 mmHg.
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Men or women ≥18 but ≤80 years of age at the time of signing the informed consent.
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Patient is able to understand the purpose and risks of the study and provide signed and dated informed consent or have a legal representative provide consent and authorization to use protected health information (in accordance with national and local patient privacy regulations).
Exclusion Criteria:
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Patient requires endotracheal intubation and mechanical ventilation, oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20 L/min with fraction of delivered oxygen ≥ 0.5), noninvasive positive pressure ventilation, extracorporeal membrane oxygenation (ECMO), or clinical diagnosis of respiratory failure.
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Patient with shock defined by systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg or requiring vasopressor.
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Patient with multi-organ dysfunction or failure defined by an increase in the Sequential Organ Failure Assessment score of 2 points or more.
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Patient is unlikely to survive beyond 2 days at the discretion of Investigator.
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Patient has used chronic systemic corticosteroids within 2 weeks prior to screening.
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Patient with positive results for human immunodeficiency virus (HIV) or hepatitis B or C test.
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Patient has known active tuberculosis (TB), history of uncontrolled TB, suspected or known systemic bacterial or fungal infections within 4 weeks prior to screening.
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Patient has any other condition, which makes the patient unsuitable for study participation
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Triple O Research Institute | West Palm Beach | Florida | United States | 33407 |
| 2 | OSF St. Francis Medical Center | Peoria | Illinois | United States | 61637 |
| 3 | Baptist Medical Center | Jackson | Mississippi | United States | 39202 |
| 4 | Hospital Civil Fray Antonio Alcalde | Guadalajara | Jalisco | Mexico | 14050 |
| 5 | Hospital Universitario "Dr. José Eleuterio González" | Monterrey | Nuevo León | Mexico | 64460 |
| 6 | Media Sur - Medica Sur Tlalpan | Tlalpan | Mexico | 14050 | |
| 7 | Dow University Hospital, Ojha Karachi | Karachi | Sindh | Pakistan | 74200 |
| 8 | Sindh Infectious Disease Hospital | Karachi | Sindh | Pakistan | 74200 |
| 9 | Aga Khan University Hospital | Karachi | Sindh | Pakistan | 74800 |
Sponsors and Collaborators
- Sironax USA, Inc.
Investigators
- Study Director: Clare Qu, Sironax USA, Inc.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- SIR365-US-101