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

Sironax USA, Inc.45 enrolled

Overview

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

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

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

QUADRUPLE

Enrollment

Conditions

Corona Virus Infection

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 80 Years

Medical Language ↔ Plain English

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

Locations (9)

Triple O Research Institute

West Palm Beach, Florida, United States

OSF St. Francis Medical Center

Peoria, Illinois, United States

Baptist Medical Center

Jackson, Mississippi, United States

Hospital Civil Fray Antonio Alcalde

Guadalajara, Jalisco, Mexico

Media Sur - Medica Sur Tlalpan

Tlalpan, Mexico City, Mexico

Hospital Universitario "Dr. José Eleuterio González"

Monterrey, Nuevo León, Mexico

Dow University Hospital, Ojha Karachi

Karachi, Sindh, Pakistan

Sindh Infectious Disease Hospital

Karachi, Sindh, Pakistan

Aga Khan University Hospital

Karachi, Sindh, Pakistan

Outcomes

Primary Outcomes

Number of Patients With Any TEAEs During the Treatment Period Baseline to Day 14

Number of participants who experienced at least one treatment-emergent adverse event (TEAE), defined as any adverse event with an onset date on or after the first dose of study drug and up to and including Day 14 post-baseline, regardless of causality. TEAEs are reported per standard MedDRA terminology and severity grading. This is a safety endpoint assessed in the safety population.

Time frame: Baseline to Day 14

Secondary Outcomes

Secondary Safety Endpoint - 1 : Number of Patients With Any TEAEs During the Treatment Period Baseline to Day 28

This secondary safety endpoint assesses the overall tolerability of the study intervention by counting the number of participants who experienced one or more treatment-emergent adverse events (TEAEs) during the specified treatment period

Time frame: Baseline to Day 28

Secondary Safety Endpoint -2 : Proportion of Patients With Any SAEs During the Study Baseline to Day 14

This secondary safety endpoint evaluates the proportion of patients in the study population who experienced one or more serious adverse events (SAEs), as defined by regulatory standards (e.g., resulting in death, life-threatening events, hospitalization, persistent disability, or other medically significant conditions), occurring from baseline (Day 0) through Day 14 (inclusive)

Time frame: Baseline to Day 14

Secondary Safety Endpoint -3 : Number of Patients With Any SAEs During the Study Baseline to Day 28

Time frame: Baseline to Day 28

Secondary Safety Endpoint -4 : Number of Patients With Any Drug-Related TEAE During the Study Baseline to Day 14

This secondary safety endpoint assesses the incidence of any TEAE deemed related to the study drug (investigator-assessed causality) from baseline (Day 1, pre-dose) through Day 14 (inclusive). TEAEs are defined as adverse events (AEs) with an onset date on or after the first dose of study drug, regardless of severity or seriousness

Time frame: Baseline to Day 14

Secondary Safety Endpoint -5 : Number of Patients With Any Drug-Related TEAE During the Study Baseline to Day 28

This secondary safety endpoint assesses the incidence of any TEAE deemed related to the study drug (investigator-assessed causality) from baseline (Day 1, pre-dose) through Day 28 (inclusive). TEAEs are defined as adverse events (AEs) with an onset date on or after the first dose of study drug, regardless of severity or seriousness

Time frame: Baseline to Day 28

Secondary Efficacy Endpoint -1 : Change in Derived PaO2/FiO2 Ratio From Baseline

The PaO2/FiO2 ratio is a clinical measure of oxygenation efficiency, calculated as the arterial partial pressure of oxygen (PaO2, in mmHg) divided by the fraction of inspired oxygen (FiO2, expressed as a decimal between 0 and 1). The endpoint assesses the absolute change in this ratio from baseline (defined as the value at randomization or study entry, typically within 24 hours prior to intervention) to the specified post-baseline time point(s) (e.g., Day 7, End of Treatment, or as per protocol)

Time frame: Baseline to EOT(Day 14)

Secondary Efficacy Endpoint -2 : Analysis of Number of Days Without Oxygen Use (Baseline to Day 14)

This secondary efficacy endpoint quantifies the cumulative number of days, from baseline (defined as the start of study intervention or randomization) through Day 14 (inclusive), during which participants did not require supplemental oxygen therapy

Time frame: Baseline to Day 14

Secondary Efficacy Endpoint -3 : Analysis of Number of Days Without Oxygen Use (Baseline to Day 28)

This secondary efficacy endpoint quantifies the cumulative number of days, from baseline (defined as the start of study intervention or randomization) through Day 28 (inclusive), during which participants did not require supplemental oxygen therapy

Time frame: Baseline to Day 28