A Pilot Study to Assess Safety and Efficacy of SIR1-365 in Patients With Severe COVID-19

Study Overview
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Brief Summary
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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
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Study duration per participant is approximately 28 days including a 14-day treatment period

Official Title
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A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study to Assess Safety and Efficacy of SIR1-365 in Patients With Severe COVID-19

Conditions
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Corona Virus Infection

Intervention / Treatment
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* Drug: SIR1-365
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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). Exclusion Criteria: 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: SIR1-365<br>SIR1-365 dose 1 daily for 14 days | Drug: SIR1-365<br>* Route of administration: oral<br>* Other names: Pharmaceutical form: tablets;|
| Placebo Comparator: Matching placebo<br>Matching placebo dose 1 daily for 14 days | Drug: Matching Placebo<br>* Route of administration: oral<br>* Other names: Pharmaceutical form: tablets;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with any TEAEs during the treatment period | Primary Safety Endpoint | Baseline to Day 14 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with any AEs, SAEs and drug-related AEs during the study | Secondary Safety Endpoint | Baseline to Day 14 and Day 28 | 
| Proportion of patients with clinically significant abnormality in clinical laboratory tests and ECG during the study | Secondary Safety Endpoint | Baseline to Day 14 and Day 28 | 
| Change from Baseline to Day 7 and Day 14 in PaO2/FiO2 ratio | Clinical Efficacy Endpoint | Baseline to Day 7 and Day 14 | 
| 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 | Clinical Efficacy Endpoint | Baseline to Day 28 | 
| Number of days without oxygen use during the study | Clinical Efficacy Endpoint | Baseline to Day 28 | 
| Proportion of patients with clinical improvement defined as a reduction of 2 points in the WHO ordinal scale during the study | Clinical Efficacy Endpoint | Baseline to Day 28 | 
| Number of days hospitalized during the study | Clinical Efficacy Endpoint | Baseline to Day 28 | 
| Proportion of patients free of respiratory failure during the study | Clinical Efficacy Endpoint | Baseline to Day 28 | 
| All-cause mortality rate during the study | Clinical Efficacy Endpoint | Baseline to Day 28 | 
| Change from Baseline to Day 7 and to Day 14 in plasma CRP level | Inflammatory Biomarker Measure | Baseline to Day 7 and to Day 14 | 
| Time to reach 50% reduction from Baseline in plasma CRP level during the treatment period | Inflammatory Biomarker Measure | Baseline to Day 14 | 
| Number of the patients to reach 50% reduction from Baseline in plasma CRP level during the treatment period | Inflammatory Biomarker Measure | Baseline to Day 14 | 
| Change from Baseline to Day 7 and Day 14 in serum cytokine levels | Inflammatory Biomarker Measure | Baseline to Day 7 and Day 14 | 
| Change from Baseline to Day 7 and Day 14 in plasma pRIP1 and pMLKL levels | Biomarker Assessment for Target Engagement | Baseline to Day 7 and Day 14 | 
| Change from Baseline to Day 7 and Day 14 in urine NGAL and KIM-1 levels | Biomarker Assessment for Kidney Injury | Baseline to Day 7 and Day 14 | 
| Plasma drug levels | Assessment of PK profile | Baseline to Day 7 and Day 14 |