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

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

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 Overview

• Status: Completed
• Conditions: Corona Virus Infection
• Intervention / Treatment: Drug: SIR1-365; Drug: Matching Placebo

Detailed Description

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

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 1

Contacts and Locations

Study Locations

• Mexico
  • Tlalpan, Mexico, 14050
    • Media Sur - Medica Sur Tlalpan
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 14050
      • Hospital Civil Fray Antonio Alcalde
  • Nuevo León
    • Monterrey, Nuevo León, Mexico, 64460
      • Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
• Pakistan
  • Sindh
    • Karachi, Sindh, Pakistan, 74800
      • Aga Khan University Hospital
    • Karachi, Sindh, Pakistan, 74200
      • Dow University Hospital, Ojha Karachi
    • Karachi, Sindh, Pakistan, 74200
      • Sindh Infectious Disease Hospital
• United States
  • Florida
    • West Palm Beach, Florida, United States, 33407
      • Triple O Research Institute
  • Illinois
    • Peoria, Illinois, United States, 61637
      • OSF St. Francis Medical Center
  • Mississippi
    • Jackson, Mississippi, United States, 39202
      • Baptist Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Sironax USA, Inc.
• Investigators: Study Director: Clare Qu, Sironax USA, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2020
• Primary Completion (Actual): November 27, 2021
• Study Completion (Actual): November 27, 2021

Study Registration Dates

• First Submitted: November 3, 2020
• First Submitted That Met QC Criteria: November 6, 2020
• First Posted (Actual): November 9, 2020

Study Record Updates

• Last Update Posted (Actual): March 24, 2022
• Last Update Submitted That Met QC Criteria: March 23, 2022
• Last Verified: March 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Coronavirus Infections
• Other Study ID Numbers: SIR365-US-101

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No