A Pilot Study to Assess Safety and Efficacy of SIR1-365 in Patients With Severe COVID-19
- Registration Number
- NCT04622332
- Lead Sponsor
- Sironax USA, Inc.
- Brief Summary
Primary Objective:
• To evaluate overall safety and tolerability of SIR1-365 in patients with severe COVID-19
Secondary Objectives:
* To assess the clinical efficacy of SIR1-365 in patients with severe COVID-19
* 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
* To assess the effects of SIR1-365 on biomarkers indicative of target engagement in patients with severe COVID-19
* To assess the effects of SIR1-365 on biomarkers indicative of kidney injury in patients with severe COVID-19
* To assess the effects of SIR1-365 on biomarkers indicative of cardiovascular endothelial cell damage in patients with severe COVID-19
* To characterize plasma pharmacokinetics (PK) of SIR1-365 in patients with severe COVID-19
- Detailed Description
Study duration per participant is approximately 28 days including a 14-day treatment period
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 45
- 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.
- 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.
- 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.
- Men or women ≥18 but ≤80 years of age at the time of signing the informed consent.
- 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).
- 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.
- Patient with shock defined by systolic blood pressure < 90 mm Hg, or diastolic blood pressure < 60 mm Hg or requiring vasopressor.
- Patient with multi-organ dysfunction or failure defined by an increase in the Sequential Organ Failure Assessment score of 2 points or more.
- Patient is unlikely to survive beyond 2 days at the discretion of Investigator.
- Patient has used chronic systemic corticosteroids within 2 weeks prior to screening.
- Patient with positive results for human immunodeficiency virus (HIV) or hepatitis B or C test.
- Patient has known active tuberculosis (TB), history of uncontrolled TB, suspected or known systemic bacterial or fungal infections within 4 weeks prior to screening.
- Patient has any other condition, which makes the patient unsuitable for study participation
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Matching placebo Matching Placebo Matching placebo dose 1 daily for 14 days SIR1-365 SIR1-365 SIR1-365 dose 1 daily for 14 days
- Primary Outcome Measures
Name Time Method Proportion of patients with any TEAEs during the treatment period Baseline to Day 14 Primary Safety Endpoint
- Secondary Outcome Measures
Name Time Method 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
Plasma drug levels Baseline to Day 7 and Day 14 Assessment of PK profile
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
Trial Locations
- Locations (9)
Triple O Research Institute
🇺🇸West Palm Beach, Florida, United States
Baptist Medical Center
🇺🇸Jackson, Mississippi, United States
Hospital Universitario "Dr. José Eleuterio González"
🇲🇽Monterrey, Nuevo León, Mexico
Sindh Infectious Disease Hospital
🇵🇰Karachi, Sindh, Pakistan
Aga Khan University Hospital
🇵🇰Karachi, Sindh, Pakistan
Hospital Civil Fray Antonio Alcalde
🇲🇽Guadalajara, Jalisco, Mexico
Dow University Hospital, Ojha Karachi
🇵🇰Karachi, Sindh, Pakistan
Media Sur - Medica Sur Tlalpan
🇲🇽Tlalpan, Mexico
OSF St. Francis Medical Center
🇺🇸Peoria, Illinois, United States