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

Corona Virus Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04622332
• Other study ID #: SIR365-US-101
• Status: Completed
• Phase: Phase 1
• Start date: December 18, 2020
• Est. completion date: November 27, 2021

Study information

• Verified date: March 2022
• Source: Sironax USA, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Description:

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: November 27, 2021
• Est. primary completion date: November 27, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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

Related Conditions & MeSH terms

• Corona Virus Infection
• Coronavirus Infections

Intervention

Drug:
• SIR1-365
Route of administration: oral
• Matching Placebo
Route of administration: oral

Locations

Country	Name	City	State
Mexico	Hospital Civil Fray Antonio Alcalde	Guadalajara	Jalisco
Mexico	Hospital Universitario "Dr. José Eleuterio González"	Monterrey	Nuevo León
Mexico	Media Sur - Medica Sur Tlalpan	Tlalpan
Pakistan	Aga Khan University Hospital	Karachi	Sindh
Pakistan	Dow University Hospital, Ojha Karachi	Karachi	Sindh
Pakistan	Sindh Infectious Disease Hospital	Karachi	Sindh
United States	Baptist Medical Center	Jackson	Mississippi
United States	OSF St. Francis Medical Center	Peoria	Illinois
United States	Triple O Research Institute	West Palm Beach	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sironax USA, Inc.

Countries where clinical trial is conducted

United States,  Mexico,  Pakistan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of patients with any TEAEs during the treatment period	Primary Safety Endpoint	Baseline to Day 14
Secondary	Proportion of patients with any AEs, SAEs and drug-related AEs during the study	Secondary Safety Endpoint	Baseline to Day 14 and Day 28
Secondary	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
Secondary	Change from Baseline to Day 7 and Day 14 in PaO2/FiO2 ratio	Clinical Efficacy Endpoint	Baseline to Day 7 and Day 14
Secondary	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
Secondary	Number of days without oxygen use during the study	Clinical Efficacy Endpoint	Baseline to Day 28
Secondary	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
Secondary	Number of days hospitalized during the study	Clinical Efficacy Endpoint	Baseline to Day 28
Secondary	Proportion of patients free of respiratory failure during the study	Clinical Efficacy Endpoint	Baseline to Day 28
Secondary	All-cause mortality rate during the study	Clinical Efficacy Endpoint	Baseline to Day 28
Secondary	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
Secondary	Time to reach 50% reduction from Baseline in plasma CRP level during the treatment period	Inflammatory Biomarker Measure	Baseline to Day 14
Secondary	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
Secondary	Change from Baseline to Day 7 and Day 14 in serum cytokine levels	Inflammatory Biomarker Measure	Baseline to Day 7 and Day 14
Secondary	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
Secondary	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
Secondary	Plasma drug levels	Assessment of PK profile	Baseline to Day 7 and Day 14