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

NCT04622332 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: SIR365-US-101
• Study Type: interventional
• Target: 45
• Locations: 3 countries
• Sites: 9

Brief 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

Conditions

Corona Virus Infection

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (8)

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

  Baseline to Day 28

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

  Baseline to Day 14

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

  Baseline to Day 28

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

  Baseline to Day 14

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

  Baseline to Day 28

Study Arms (2)

SIR1-365

EXPERIMENTAL

SIR1-365 dose 1 daily for 14 days

Drug: SIR1-365

Matching placebo

PLACEBO COMPARATOR

Matching placebo dose 1 daily for 14 days

Drug: Matching Placebo

Interventions

SIR1-365 DRUG

Route of administration: oral

Also known as: Pharmaceutical form: tablets

SIR1-365

Matching Placebo DRUG

Route of administration: oral

Also known as: Pharmaceutical form: tablets

Matching placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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

Sponsors & Collaborators

• Sironax USA, Inc.: lead

Study Sites (9)

Triple O Research Institute

West Palm Beach, Florida, 33407, United States

Location

OSF St. Francis Medical Center

Peoria, Illinois, 61637, United States

Location

Baptist Medical Center

Jackson, Mississippi, 39202, United States

Location

Hospital Civil Fray Antonio Alcalde

Guadalajara, Jalisco, 14050, Mexico

Location

Media Sur - Medica Sur Tlalpan

Tlalpan, Mexico City, 14050, Mexico

Location

Hospital Universitario "Dr. José Eleuterio González"

Monterrey, Nuevo León, 64460, Mexico

Location

Dow University Hospital, Ojha Karachi

Karachi, Sindh, 74200, Pakistan

Location

Sindh Infectious Disease Hospital

Karachi, Sindh, 74200, Pakistan

Location

Aga Khan University Hospital

Karachi, Sindh, 74800, Pakistan

Location

Related Publications (1)

• 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.

  PMID: 39872839 DERIVED

MeSH Terms

Conditions

Coronavirus Infections

Condition Hierarchy (Ancestors)

Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections

Results Point of Contact

• Title: Lisa Fitzgerald, Senior Director Clinical Operation
• Organization: Sironax

Lisa.Fitzgerald@sironax.com

781-201-3892

Study Officials

• Clare Qu

  Sironax USA, Inc.

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Blinded
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2020
• First Posted: November 9, 2020
• Study Start: December 18, 2020
• Primary Completion: November 27, 2021
• Study Completion: November 27, 2021
• Last Updated: November 12, 2025
• Results First Posted: November 12, 2025

Record last verified: 2025-10

Locations

ME (3); US (3); PA (3)