Clinical trial NCT04622332: A Pilot Study to Assess Safety and Efficacy of SIR1-365 in Patients With Severe COVID-19
Official title: A Multicenter, Randomized, Double-Blinded, Placebo-Controlled Study to Assess Safety and Efficacy of SIR1-365 in Patients With Severe COVID-19
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Corona Virus Infection
Lead sponsor: Sironax USA, Inc.
Sponsor class: INDUSTRY
First posted: 2020-11-09
Enrollment: 45
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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

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

Eligibility criteria: 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

Primary outcomes:
measure: Proportion of patients with any TEAEs during the treatment period
timeFrame: Baseline to Day 14
Secondary outcomes:
measure: Proportion of patients with any AEs, SAEs and drug-related AEs during the study
timeFrame: Baseline to Day 14 and Day 28
measure: Proportion of patients with clinically significant abnormality in clinical laboratory tests and ECG during the study
timeFrame: Baseline to Day 14 and Day 28
measure: Change from Baseline to Day 7 and Day 14 in PaO2/FiO2 ratio
timeFrame: Baseline to Day 7 and Day 14
measure: 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
timeFrame: Baseline to Day 28
measure: Number of days without oxygen use during the study
timeFrame: Baseline to Day 28
measure: Proportion of patients with clinical improvement defined as a reduction of 2 points in the WHO ordinal scale during the study
timeFrame: Baseline to Day 28
measure: Number of days hospitalized during the study
timeFrame: Baseline to Day 28
measure: Proportion of patients free of respiratory failure during the study
timeFrame: Baseline to Day 28
measure: All-cause mortality rate during the study
timeFrame: Baseline to Day 28
measure: Change from Baseline to Day 7 and to Day 14 in plasma CRP level
timeFrame: Baseline to Day 7 and to Day 14
measure: Time to reach 50% reduction from Baseline in plasma CRP level during the treatment period
timeFrame: Baseline to Day 14
measure: Number of the patients to reach 50% reduction from Baseline in plasma CRP level during the treatment period
timeFrame: Baseline to Day 14
measure: Change from Baseline to Day 7 and Day 14 in serum cytokine levels
timeFrame: Baseline to Day 7 and Day 14
measure: Change from Baseline to Day 7 and Day 14 in plasma pRIP1 and pMLKL levels
timeFrame: Baseline to Day 7 and Day 14
measure: Change from Baseline to Day 7 and Day 14 in urine NGAL and KIM-1 levels
timeFrame: Baseline to Day 7 and Day 14
measure: Plasma drug levels
timeFrame: Baseline to Day 7 and Day 14
Other outcomes:
Locations:
city: West Palm Beach
country: United States
facility: Triple O Research Institute
state: Florida
city: Peoria
country: United States
facility: OSF St. Francis Medical Center
state: Illinois
city: Jackson
country: United States
facility: Baptist Medical Center
state: Mississippi
city: Guadalajara
country: Mexico
facility: Hospital Civil Fray Antonio Alcalde
state: Jalisco
city: Monterrey
country: Mexico
facility: Hospital Universitario "Dr. José Eleuterio González"
state: Nuevo León
city: Tlalpan
country: Mexico
facility: Media Sur - Medica Sur Tlalpan
city: Karachi
country: Pakistan
facility: Dow University Hospital, Ojha Karachi
state: Sindh
city: Karachi
country: Pakistan
facility: Sindh Infectious Disease Hospital
state: Sindh
city: Karachi
country: Pakistan
facility: Aga Khan University Hospital
state: Sindh
Study officials:
affiliation: Sironax USA, Inc.
name: Clare Qu
role: STUDY_DIRECTOR
References: