Corona Virus Infection
Conditions
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
Interventions
DRUGSIR1-365
Route of administration: oral
DRUGMatching Placebo
Route of administration: oral
Sponsors
Sironax USA, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Blinded
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Patients With Any TEAEs During the Treatment Period Baseline to Day 14 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Secondary Safety Endpoint -2 : Proportion of Patients With Any SAEs During the Study Baseline to Day 14 | 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) |
| Secondary Safety Endpoint -3 : Number of Patients With Any SAEs During the Study Baseline to Day 28 | 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) |
| Secondary Safety Endpoint -4 : Number of Patients With Any Drug-Related TEAE During the Study Baseline to Day 14 | 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 |
| Secondary Safety Endpoint - 1 : Number of Patients With Any TEAEs During the Treatment Period Baseline to Day 28 | 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 |
| Secondary Efficacy Endpoint -1 : Change in Derived PaO2/FiO2 Ratio From Baseline | Baseline to EOT(Day 14) | 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) |
| Secondary Efficacy Endpoint -2 : Analysis of Number of Days Without Oxygen Use (Baseline to Day 14) | 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 |
| Secondary Efficacy Endpoint -3 : Analysis of Number of Days Without Oxygen Use (Baseline to Day 28) | 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 |
| Secondary Safety Endpoint -5 : Number of Patients With Any Drug-Related TEAE During the Study Baseline to Day 28 | 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 |
Countries
Mexico, Pakistan, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| SIR1-365 SIR1-365 dose 1 daily for 14 days
SIR1-365: Route of administration: oral | 23 |
| Matching Placebo Matching placebo dose 1 daily for 14 days
Matching Placebo: Route of administration: oral | 19 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 0 | 2 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Protocol Violation | 0 | 1 |
| Overall Study | Withdrawal by Subject | 4 | 2 |
Baseline characteristics
| Characteristic | SIR1-365 | Matching Placebo | Total |
|---|---|---|---|
| Age, Categorical Age <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Age >=65 years | 5 Participants | 3 Participants | 8 Participants |
| Age, Categorical Age Between 18 and 65 years | 18 Participants | 16 Participants | 34 Participants |
| Body Mass Index (BMI) | 29.75 kg/m^2 STANDARD_DEVIATION 6.92 | 30.76 kg/m^2 STANDARD_DEVIATION 6.786 | 30.20 kg/m^2 STANDARD_DEVIATION 6.795 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 12 Participants | 24 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 7 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 8 Participants | 6 Participants | 14 Participants |
| Race (NIH/OMB) Asian | 6 Participants | 4 Participants | 10 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) White | 6 Participants | 3 Participants | 9 Participants |
| Region of Enrollment Mexico | 10 participants | 11 participants | 21 participants |
| Region of Enrollment Pakistan | 6 participants | 4 participants | 10 participants |
| Region of Enrollment United States | 7 participants | 4 participants | 11 participants |
| Sex: Female, Male Female | 8 Participants | 5 Participants | 13 Participants |
| Sex: Female, Male Male | 15 Participants | 14 Participants | 29 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 23 | 0 / 19 |
| other Total, other adverse events | 7 / 23 | 11 / 19 |
| serious Total, serious adverse events | 3 / 23 | 5 / 19 |
Outcome results
Primary
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.
Time frame: Baseline to Day 14
Population: Safety Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SIR1-365 | Number of Patients With Any TEAEs During the Treatment Period Baseline to Day 14 | 5 Participants |
| Matching placebo | Number of Patients With Any TEAEs During the Treatment Period Baseline to Day 14 | 10 Participants |
Secondary
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)
Time frame: Baseline to EOT(Day 14)
Population: ITT Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SIR1-365 | Secondary Efficacy Endpoint -1 : Change in Derived PaO2/FiO2 Ratio From Baseline | 241 Ratio |
| Matching placebo | Secondary Efficacy Endpoint -1 : Change in Derived PaO2/FiO2 Ratio From Baseline | 193 Ratio |
Secondary
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
Time frame: Baseline to Day 14
Population: ITT Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SIR1-365 | Secondary Efficacy Endpoint -2 : Analysis of Number of Days Without Oxygen Use (Baseline to Day 14) | 0 Days |
| Matching placebo | Secondary Efficacy Endpoint -2 : Analysis of Number of Days Without Oxygen Use (Baseline to Day 14) | 0 Days |
Secondary
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
Time frame: Baseline to Day 28
Population: ITT Set
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| SIR1-365 | Secondary Efficacy Endpoint -3 : Analysis of Number of Days Without Oxygen Use (Baseline to Day 28) | 1.60 Days |
| Matching placebo | Secondary Efficacy Endpoint -3 : Analysis of Number of Days Without Oxygen Use (Baseline to Day 28) | 3 Days |
Secondary
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
Time frame: Baseline to Day 28
Population: Safety Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SIR1-365 | Secondary Safety Endpoint - 1 : Number of Patients With Any TEAEs During the Treatment Period Baseline to Day 28 | 7 Participants |
| Matching placebo | Secondary Safety Endpoint - 1 : Number of Patients With Any TEAEs During the Treatment Period Baseline to Day 28 | 11 Participants |
Secondary
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)
Time frame: Baseline to Day 14
Population: Safety Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SIR1-365 | Secondary Safety Endpoint -2 : Proportion of Patients With Any SAEs During the Study Baseline to Day 14 | 1 Participants |
| Matching placebo | Secondary Safety Endpoint -2 : Proportion of Patients With Any SAEs During the Study Baseline to Day 14 | 5 Participants |
Secondary
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)
Time frame: Baseline to Day 28
Population: Safety Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SIR1-365 | Secondary Safety Endpoint -3 : Number of Patients With Any SAEs During the Study Baseline to Day 28 | 3 Participants |
| Matching placebo | Secondary Safety Endpoint -3 : Number of Patients With Any SAEs During the Study Baseline to Day 28 | 5 Participants |
Secondary
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
Time frame: Baseline to Day 14
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SIR1-365 | Secondary Safety Endpoint -4 : Number of Patients With Any Drug-Related TEAE During the Study Baseline to Day 14 | 2 Participants |
| Matching placebo | Secondary Safety Endpoint -4 : Number of Patients With Any Drug-Related TEAE During the Study Baseline to Day 14 | 1 Participants |
Secondary
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
Time frame: Baseline to Day 28
Population: Safety Set
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| SIR1-365 | Secondary Safety Endpoint -5 : Number of Patients With Any Drug-Related TEAE During the Study Baseline to Day 28 | 2 Participants |
| Matching placebo | Secondary Safety Endpoint -5 : Number of Patients With Any Drug-Related TEAE During the Study Baseline to Day 28 | 1 Participants |