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
  • Jalisco
    • Guadalajara, Jalisco, Mexico, 14050
      • Hospital Civil Fray Antonio Alcalde
  • Mexico City
    • Tlalpan, Mexico City, Mexico, 14050
      • Media Sur - Medica Sur Tlalpan
  • 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

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
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.	Baseline to Day 14

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	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)	Baseline to Day 14
Secondary Safety Endpoint -3 : Number of Patients With Any SAEs During the Study Baseline to Day 28	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 28 (inclusive)	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	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	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)	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	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	Baseline to Day 28

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Chavez-Tapia N, Sayeed MA, Luxmi S, Kasper DJ, Xue F, Shen Y, Fan W, Yuan W, Du B. Safety and efficacy of selective RIPK1 inhibitor SIR1-365 in hospitalized patients with severe COVID-19: A multicenter, randomized, double-blind, phase 1b trial. J Intensive Med. 2024 Sep 12;5(1):70-78. doi: 10.1016/j.jointm.2024.07.003. eCollection 2025 Jan.

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): November 12, 2025
• Last Update Submitted That Met QC Criteria: October 28, 2025
• Last Verified: October 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Infections; RNA Virus Infections; Virus Diseases; Coronaviridae Infections; Nidovirales 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