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

Sponsor
Sironax USA, Inc. (Industry)
Overall Status
Completed
CT.gov ID
NCT04622332
Collaborator
(none)
45
Enrollment
9
Locations
2
Arms
11.3
Actual Duration (Months)
5
Patients Per Site
0.4
Patients Per Site Per Month

Study Details

Study Description

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

Condition or DiseaseIntervention/TreatmentPhase
Phase 1

Detailed Description

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

Study Design

Study Type:
Interventional
Actual Enrollment :
45 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Masking Description:
Blinded
Primary Purpose:
Treatment
Official Title:
A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study to Assess Safety and Efficacy of SIR1-365 in Patients With Severe COVID-19
Actual Study Start Date :
Dec 18, 2020
Actual Primary Completion Date :
Nov 27, 2021
Actual Study Completion Date :
Nov 27, 2021

Arms and Interventions

ArmIntervention/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
  • Outcome Measures

    Primary Outcome Measures

    1. Proportion of patients with any TEAEs during the treatment period [Baseline to Day 14]

      Primary Safety Endpoint

    Secondary Outcome Measures

    1. Proportion of patients with any AEs, SAEs and drug-related AEs during the study [Baseline to Day 14 and Day 28]

      Secondary Safety Endpoint

    2. Proportion of patients with clinically significant abnormality in clinical laboratory tests and ECG during the study [Baseline to Day 14 and Day 28]

      Secondary Safety Endpoint

    3. Change from Baseline to Day 7 and Day 14 in PaO2/FiO2 ratio [Baseline to Day 7 and Day 14]

      Clinical Efficacy Endpoint

    4. 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 [Baseline to Day 28]

      Clinical Efficacy Endpoint

    5. Number of days without oxygen use during the study [Baseline to Day 28]

      Clinical Efficacy Endpoint

    6. Proportion of patients with clinical improvement defined as a reduction of 2 points in the WHO ordinal scale during the study [Baseline to Day 28]

      Clinical Efficacy Endpoint

    7. Number of days hospitalized during the study [Baseline to Day 28]

      Clinical Efficacy Endpoint

    8. Proportion of patients free of respiratory failure during the study [Baseline to Day 28]

      Clinical Efficacy Endpoint

    9. All-cause mortality rate during the study [Baseline to Day 28]

      Clinical Efficacy Endpoint

    10. Change from Baseline to Day 7 and to Day 14 in plasma CRP level [Baseline to Day 7 and to Day 14]

      Inflammatory Biomarker Measure

    11. Time to reach 50% reduction from Baseline in plasma CRP level during the treatment period [Baseline to Day 14]

      Inflammatory Biomarker Measure

    12. Number of the patients to reach 50% reduction from Baseline in plasma CRP level during the treatment period [Baseline to Day 14]

      Inflammatory Biomarker Measure

    13. Change from Baseline to Day 7 and Day 14 in serum cytokine levels [Baseline to Day 7 and Day 14]

      Inflammatory Biomarker Measure

    14. Change from Baseline to Day 7 and Day 14 in plasma pRIP1 and pMLKL levels [Baseline to Day 7 and Day 14]

      Biomarker Assessment for Target Engagement

    15. Change from Baseline to Day 7 and Day 14 in urine NGAL and KIM-1 levels [Baseline to Day 7 and Day 14]

      Biomarker Assessment for Kidney Injury

    16. Plasma drug levels [Baseline to Day 7 and Day 14]

      Assessment of PK profile

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years to 80 Years
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    SiteCityStateCountryPostal Code
    1Triple O Research InstituteWest Palm BeachFloridaUnited States33407
    2OSF St. Francis Medical CenterPeoriaIllinoisUnited States61637
    3Baptist Medical CenterJacksonMississippiUnited States39202
    4Hospital Civil Fray Antonio AlcaldeGuadalajaraJaliscoMexico14050
    5Hospital Universitario "Dr. José Eleuterio González"MonterreyNuevo LeónMexico64460
    6Media Sur - Medica Sur TlalpanTlalpanMexico14050
    7Dow University Hospital, Ojha KarachiKarachiSindhPakistan74200
    8Sindh Infectious Disease HospitalKarachiSindhPakistan74200
    9Aga Khan University HospitalKarachiSindhPakistan74800

    Sponsors and Collaborators

    • Sironax USA, Inc.

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Sironax USA, Inc.
    ClinicalTrials.gov Identifier:
    NCT04622332
    Other Study ID Numbers:
    • SIR365-US-101
    First Posted:
    Nov 9, 2020
    Last Update Posted:
    Mar 24, 2022
    Last Verified:
    Mar 1, 2022
    Studies a U.S. FDA-regulated Drug Product:
    Yes
    Studies a U.S. FDA-regulated Device Product:
    No
    Additional relevant MeSH terms:

    Study Results

    No Results Posted as of Mar 24, 2022