Evaluation of the Safety and Efficacy of Razuprotafib in Hospitalized Subjects With Coronavirus Disease 2019 (RESCUE)
Primary Purpose
COVID-19, Acute Respiratory Distress Syndrome (ARDS)
Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Razuprotafib Subcutaneous Solution
Placebo Subcutaneous Solution
Sponsored by
About this trial
This is an interventional treatment trial for COVID-19 focused on measuring COVID-19, ARDS, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
Eligibility Criteria
Inclusion Criteria:
- Ability to understand and provide informed consent;
- Males and non-pregnant females 18 years of age or older at the time of Screening;
- Laboratory-confirmed active SARS-CoV-2 infection within 72 hours prior to randomization, or (if testing results cannot be obtained) by evidence of progressive disease suggestive of ongoing SARS-CoV-2 infection;
- Females of childbearing potential must be willing to completely abstain or agree to use a highly effective method of contraception through Day 28; and have a negative urine pregnancy test during Screening;
- Currently hospitalized, receiving standard of care therapy for COVID-19, and meets the criteria for moderate or severe COVID-19, as follows: Moderate = symptoms of moderate illness with COVID-19, which could include any symptom of mild illness or shortness of breath with exertion and with respiratory rate at 20 or greater breaths/min, SpO2 >93% on room air at sea level, or heart rate at 90 or greater beats/min; Severe = symptoms suggestive of severe systemic illness with COVID-19, which could include any symptom of moderate illness, shortness of breath at rest, or respiratory distress, and respiratory rate at 30 or greater breaths/min, heart rate at 125 or greater beats/min, or SpO2 >93% on room air at sea level or PaO2:FiO2 <300.
Exclusion Criteria:
- Inability to initiate study drug within 12 hours after randomization;
- Female of childbearing potential who is unable or unwilling to forego breastfeeding through Day 28;
- Systolic blood pressure <100 mmHg;
- In shock or requiring pressor support;
- Respiratory failure, defined as subjects who are on mechanical ventilation; are receiving 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 of 0.5 or greater), noninvasive positive pressure ventilation, or extracorporeal membrane oxygenation (ECMO); or have a clinical diagnosis of respiratory failure (ie, clinical need for 1 of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation);
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × the upper limit of normal (ULN);
- Total bilirubin >2 × ULN;
- Estimated glomerular filtration rate <30 mL/min or receiving hemodialysis or hemofiltration;
- Moribund subject not expected to survive 24 hours in the opinion of the treating clinical team;
- Any concurrent serious medical condition (eg, active malignancies on chemotherapy, post organ transplant, end stage congestive heart failure) or not likely to respond to treatment;
- Decision to withhold life-sustaining treatment; Note: In the event of cardiac arrest, the decision to withhold cardiopulmonary resuscitation only does not fulfill this exclusion criterion.
- Use of cytochrome P450 (CYP) 2C8 substrates (eg, repaglinide, paclitaxel, or cerivastatin) or CYP3A4 substrates (eg, amlodipine, budesonide, dasabuvir, enzalutamide, imatinib, lopinavir, loperamide, saquinavir, sildenafil, midazolam, or montelukast);
- Use of CYP2C8 inhibitors (eg, gemfibrozil, fluvoxamine, or ketoconazole);
- Participation in another investigational study during the present study through the last visit (Day 28); or
- Previous randomization in this study.
Sites / Locations
- University of Southern California
- University of California- Irvine Medical Center
- MedStar Georgetown University Hospital
- Snake River Research
- University of Minnesota
- University of Cincinnati
- Rhode Island Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Placebo Comparator
Experimental
Arm Label
Razuprotafib 10 mg
Placebo
Razuprotafib 20 mg
Arm Description
Active Comparator
Placebo Comparator
Active Comparator
Outcomes
Primary Outcome Measures
Number and Percent of Subjects Who Were Alive and Free of Respiratory Failure Prior to Day 7 and Day 28
All results were summarized descriptively by treatment arm and expressed as proportions, along with corresponding 95%CI of the difference between response rates, and p-values using Cochran-Mantel-Haenszel (CMH). The 95% CI will be constructed using the normal approximation method. Respiratory failure was defined as subjects who were on invasive mechanical ventilation; received oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) noninvasive positive pressure ventilation or extracorporeal membrane oxygenation; or had a clinical diagnosis of respiratory failure (ie, clinical need for 1 of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation).Subjects who died prior to the study timepoint (Day 7 or Day 28) were imputed based on the worst outcome.
Secondary Outcome Measures
Summary of The Mean Change From Baseline in D-Dimer at Day 7 and 28
Mean Change from baseline in systemic biomarkers of vascular leakage and inflammation (ie, D-Dimer) at Day 7 and 28 in the Full Analysis Set
Summary of Change From Baseline in C-Reactive Protein (CRP) at Day 7 and 28
Change from baseline in systemic biomarkers of vascular leakage and inflammation (ie, CRP ) at Day 7 and 28 in the Full Analysis Set
Number of Participants Who Improve by at Least 2 Categories on the NIAID 8-point Ordinal Scale From Baseline to Day 7 and Baseline to Day 28
Analysis of the proportion of participants who improve by >=2 categories on the NIAID 8-point scale from baseline to Day 7. % = 100 x n/N', where N' = number of participants with a non-missing values at baseline and the specified post-baseline visit. Baseline is defined as the last measurement prior to the first dose of study drug.
Number of Participants Who Were Discharged and Free of Respiratory Failure Prior to Day 7 and Day 28
The number of participants who were discharged and free of respiratory failure at Day 7 and Day 28 were summarized by treatment arm and pooled razuprotafib (10 and 20 mg) group.
Number of Participants Alive and Not Requiring Invasive Mechanical Ventilation at Any Time
Analysis of Number of Participants Alive and Not Requiring Invasive Mechanical Ventilation at Any Time Through Day 28 in the Full Analysis Set
Time to Reach Grade 6, 7, or 8 on the NIAID 8-Point Ordinal Scale
The clinical status of the participants was assessed within 1 hr prior to each dose of study drug, using the NIAID 8-point ordinal scale until Day 28. After the treatment period, clinical status will be assessed once daily until Day 18, unless discharged. If the subject is discharged alive prior to Day 28, clinical status was assessed at the post-treatment observation period telephone visits only. Grade 6=hospitalized, not requiring oxygen and no longer requires ongoing medical care; Grade 7 = not hospitalized, limitation on activities and/or requiring home oxygen; and Grade 8 = not hospitalized, no limitations on activities.
Change in PaO2:FiO2 Ratio From Baseline to Day 7 and Baseline to Day 28
Analysis of the change in PaO2:FiO2 ratio from baseline to Day 7 (or discharge) and baseline to Day 28 (or discharge) in the intent-to-treat population. Baseline was defined as the last measurement prior to the first dose of study drug. Baseline PaO2;FiO2 ratio value was not provided for the pooled Razuprotafib group.
Length of Hospitalization and Not Requiring Invasive Mechanical Ventilation From Baseline to Day 7 and Day 28 (or Death)
Analysis of length of hospitalization and not requiring invasive mechanical ventilation from baseline to Day 7 and Day 28 in the intent-to-treat population. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the ITT Population. The summaries of the mean number of days from baseline included only those participants with available data. Baseline was defined as the last measurement prior to the first dose of study drug. Baseline values were not provided.The length of hospitalization was to include all days that the participant was admitted to the hospital. For participants who were discharged and readmitted to the hospital, the length of hospitalization was to include the days after readmission. Hospitalization days were counted in 24-hour periods; any partial days were counted as a whole day.
Length of Hospitalization From Baseline to Day 7 and Day 28 (or Death)
Analysis of length of hospitalization from baseline to day 7 and day 28 (or death) in the intent-to-treat population. Baseline was defined as the last measurement prior to the first dose of study drug. Baseline values were not provided. The length of hospitalization was to include all days that the participant was admitted to the hospital. For participants who were discharged and readmitted to the hospital, the length of hospitalization was to include the days after readmission. Hospitalization days were counted in 24-hour periods; any partial days were counted as a whole day.
Number of Participants Who Worsen by Greater Than or Equal to 2 Categories on The NIAID 8-point Ordinal Scale From Baseline to Day 7 and Day 28
Analysis of number of participants who worsen by >= 2 categories on the NIAID 8-point ordinal scale from baseline to Day 7 in the Full Analysis Population. % = 100 x n/N', where N' = number of participants with non-missing values at baseline and the specified post-baseline visit. Participants who died prior to the Day 7 or Day 28 were imputed as 1.
Number of Participants in Each Category of the NIAID 8-point Ordinal Scale at Day 7 and Day 28
Summary of number and percent of subjects in each category (ie, categories 1 to 8) of the NIAID 8-Point Ordinal Scale at baseline, Day 7 and Day 28. The NIAID 8-point ordinal scale includes the following grades:
Death;
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO);
Hospitalized, on noninvasive ventilation or high-flow oxygen devices;
Hospitalized, requiring supplemental oxygen;
Hospitalized, not requiring supplementation oxygen - requiring ongoing medical care (COVID-19 related or otherwise);
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;
Not hospitalized, limitation on activities and/or requiring home oxygen; and
Not hospitalized, no limitations on activities.
The Number and Percent of Participants Who Experienced All-Cause Mortality at Day 7 and Day 28
Analysis of the Number and Percent of Participants who Experienced All-Cause Mortality at Day 7 and Day 28 in the Full Analysis Set
Number of Participants Who Improve by Greater or Equal to 2 Categories on the NIAID 8-point Ordinal Scale From Baseline to Day 7 and Day 28
Analysis of number of participants who improve by >= 2 categories on the NIAID 8-point scale from baseline to Day 7 and Day 28 in the full analysis set.% = 100 x n/N', where N' = number of participants with non-missing values at baseline and the specified post-baseline visit. Participants who died prior to the Day 7 or Day 28 were imputed as 1.
Time to Return to Prehospitalization Oxygen Requirement
Summary of Time to Return to Prehospitalization Oxygen Requirement in the Intent-to-Treat Population
Full Information
NCT ID
NCT04511650
First Posted
August 7, 2020
Last Updated
June 6, 2023
Sponsor
EyePoint Pharmaceuticals, Inc.
1. Study Identification
Unique Protocol Identification Number
NCT04511650
Brief Title
Evaluation of the Safety and Efficacy of Razuprotafib in Hospitalized Subjects With Coronavirus Disease 2019
Acronym
RESCUE
Official Title
Phase 2, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Dose Escalation and Proof-of-Concept Study to Evaluate the Safety and Efficacy of Razuprotafib in Hospitalized Subjects With Coronavirus Disease 2019
Study Type
Interventional
2. Study Status
Record Verification Date
June 2023
Overall Recruitment Status
Terminated
Why Stopped
After completion of Step 1 Part 1, the Sponsor discontinued the study based on challenges associated with recruiting and monitoring patients in the current pandemic environment.
Study Start Date
October 21, 2020 (Actual)
Primary Completion Date
February 26, 2021 (Actual)
Study Completion Date
February 26, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
EyePoint Pharmaceuticals, Inc.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
This was a Phase 2, randomized, double-blind, placebo-controlled, parallel-group, multicenter, dose escalation and proof-of-concept study to evaluate the safety and efficacy of razuprotafib, administered 3 times daily (TID) (every 8 hours [Q8H]), in hospitalized subjects with moderate to severe Coronavirus disease 2019 (COVID-19) receiving standard of care therapy.
The study was planned to include 2 parts with Part 1 comprising the dose escalation period of the study and Part 2 comprising the proof-of-concept safety and efficacy period of the study.
Detailed Description
Part 1 was to be a 2-step dose escalation that included approximately 60 subjects. Part 1, Step 1 was to include 30 subjects, and Part 1, Step 2 was to include 30 subjects. Part 1 was designed to primarily focus on safety; however, efficacy data was to be collected and analyzed as well.
Despite the Data Review Committee (DRC) recommendation to continue the study, after completion of Part 1, Step 1, the Sponsor elected to discontinue the study due to business-related reasons. Recruitment challenges and slow site startup led to delays in completing the study in a practical timeframe, and were the primary reasons to discontinue the study. No further subjects were recruited after Part 1, Step 1 completion. A full analysis of the data from Part 1, Step 1 was conducted and is presented in this report.
Part 1, Step 2 and Part 2 was not conducted.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
COVID-19, Acute Respiratory Distress Syndrome (ARDS)
Keywords
COVID-19, ARDS, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2)
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Model Description
The study was planned to include 2 parts with Part 1 comprising the dose escalation period of the study and Part 2 comprising the proof-of-concept safety and efficacy period of the study. Although The Data Review Committee (DRC) recommended to continue with the study after the completion of Part 1, Step 1, the Sponsor elected to discontinue the study due to business-related reasons.
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
31 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Razuprotafib 10 mg
Arm Type
Experimental
Arm Description
Active Comparator
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Placebo Comparator
Arm Title
Razuprotafib 20 mg
Arm Type
Experimental
Arm Description
Active Comparator
Intervention Type
Drug
Intervention Name(s)
Razuprotafib Subcutaneous Solution
Other Intervention Name(s)
Razuprotafib 10 mg and 20 mg solution
Intervention Description
Up to 3 daily dose levels of Razuprotafib Subcutaneous Solution will be evaluated. Doses will be administered subcutaneously three times daily (Q8H) for 7 days.
Intervention Type
Drug
Intervention Name(s)
Placebo Subcutaneous Solution
Other Intervention Name(s)
Placebo comparator
Intervention Description
Matched vehicle-controlled placebo solution will be administered subcutaneously three times daily (Q8H) for 7 days
Primary Outcome Measure Information:
Title
Number and Percent of Subjects Who Were Alive and Free of Respiratory Failure Prior to Day 7 and Day 28
Description
All results were summarized descriptively by treatment arm and expressed as proportions, along with corresponding 95%CI of the difference between response rates, and p-values using Cochran-Mantel-Haenszel (CMH). The 95% CI will be constructed using the normal approximation method. Respiratory failure was defined as subjects who were on invasive mechanical ventilation; received oxygen delivered by high-flow nasal cannula (heated, humidified, oxygen delivered via reinforced nasal cannula at flow rates >20L/min with fraction of delivered oxygen ≥0.5) noninvasive positive pressure ventilation or extracorporeal membrane oxygenation; or had a clinical diagnosis of respiratory failure (ie, clinical need for 1 of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation).Subjects who died prior to the study timepoint (Day 7 or Day 28) were imputed based on the worst outcome.
Time Frame
Baseline up to Day 7 and Day 28
Secondary Outcome Measure Information:
Title
Summary of The Mean Change From Baseline in D-Dimer at Day 7 and 28
Description
Mean Change from baseline in systemic biomarkers of vascular leakage and inflammation (ie, D-Dimer) at Day 7 and 28 in the Full Analysis Set
Time Frame
at Day 7 and 28
Title
Summary of Change From Baseline in C-Reactive Protein (CRP) at Day 7 and 28
Description
Change from baseline in systemic biomarkers of vascular leakage and inflammation (ie, CRP ) at Day 7 and 28 in the Full Analysis Set
Time Frame
at Day 7 and 28
Title
Number of Participants Who Improve by at Least 2 Categories on the NIAID 8-point Ordinal Scale From Baseline to Day 7 and Baseline to Day 28
Description
Analysis of the proportion of participants who improve by >=2 categories on the NIAID 8-point scale from baseline to Day 7. % = 100 x n/N', where N' = number of participants with a non-missing values at baseline and the specified post-baseline visit. Baseline is defined as the last measurement prior to the first dose of study drug.
Time Frame
from baseline to Day 7 and baseline to Day 28
Title
Number of Participants Who Were Discharged and Free of Respiratory Failure Prior to Day 7 and Day 28
Description
The number of participants who were discharged and free of respiratory failure at Day 7 and Day 28 were summarized by treatment arm and pooled razuprotafib (10 and 20 mg) group.
Time Frame
Day 7 and Day 28
Title
Number of Participants Alive and Not Requiring Invasive Mechanical Ventilation at Any Time
Description
Analysis of Number of Participants Alive and Not Requiring Invasive Mechanical Ventilation at Any Time Through Day 28 in the Full Analysis Set
Time Frame
Baseline up to Day 28
Title
Time to Reach Grade 6, 7, or 8 on the NIAID 8-Point Ordinal Scale
Description
The clinical status of the participants was assessed within 1 hr prior to each dose of study drug, using the NIAID 8-point ordinal scale until Day 28. After the treatment period, clinical status will be assessed once daily until Day 18, unless discharged. If the subject is discharged alive prior to Day 28, clinical status was assessed at the post-treatment observation period telephone visits only. Grade 6=hospitalized, not requiring oxygen and no longer requires ongoing medical care; Grade 7 = not hospitalized, limitation on activities and/or requiring home oxygen; and Grade 8 = not hospitalized, no limitations on activities.
Time Frame
From Screening through the end of the study (up to 28 days)
Title
Change in PaO2:FiO2 Ratio From Baseline to Day 7 and Baseline to Day 28
Description
Analysis of the change in PaO2:FiO2 ratio from baseline to Day 7 (or discharge) and baseline to Day 28 (or discharge) in the intent-to-treat population. Baseline was defined as the last measurement prior to the first dose of study drug. Baseline PaO2;FiO2 ratio value was not provided for the pooled Razuprotafib group.
Time Frame
Baseline up to Day 7 and Day 28
Title
Length of Hospitalization and Not Requiring Invasive Mechanical Ventilation From Baseline to Day 7 and Day 28 (or Death)
Description
Analysis of length of hospitalization and not requiring invasive mechanical ventilation from baseline to Day 7 and Day 28 in the intent-to-treat population. Note: The overall number of participants analyzed represents the total number of participants in each treatment group for the ITT Population. The summaries of the mean number of days from baseline included only those participants with available data. Baseline was defined as the last measurement prior to the first dose of study drug. Baseline values were not provided.The length of hospitalization was to include all days that the participant was admitted to the hospital. For participants who were discharged and readmitted to the hospital, the length of hospitalization was to include the days after readmission. Hospitalization days were counted in 24-hour periods; any partial days were counted as a whole day.
Time Frame
Baseline up to Day 7 and Day 28
Title
Length of Hospitalization From Baseline to Day 7 and Day 28 (or Death)
Description
Analysis of length of hospitalization from baseline to day 7 and day 28 (or death) in the intent-to-treat population. Baseline was defined as the last measurement prior to the first dose of study drug. Baseline values were not provided. The length of hospitalization was to include all days that the participant was admitted to the hospital. For participants who were discharged and readmitted to the hospital, the length of hospitalization was to include the days after readmission. Hospitalization days were counted in 24-hour periods; any partial days were counted as a whole day.
Time Frame
From Baseline to Day 7 or Day 28 (or Death)
Title
Number of Participants Who Worsen by Greater Than or Equal to 2 Categories on The NIAID 8-point Ordinal Scale From Baseline to Day 7 and Day 28
Description
Analysis of number of participants who worsen by >= 2 categories on the NIAID 8-point ordinal scale from baseline to Day 7 in the Full Analysis Population. % = 100 x n/N', where N' = number of participants with non-missing values at baseline and the specified post-baseline visit. Participants who died prior to the Day 7 or Day 28 were imputed as 1.
Time Frame
From baseline to Day 7 and Day 28
Title
Number of Participants in Each Category of the NIAID 8-point Ordinal Scale at Day 7 and Day 28
Description
Summary of number and percent of subjects in each category (ie, categories 1 to 8) of the NIAID 8-Point Ordinal Scale at baseline, Day 7 and Day 28. The NIAID 8-point ordinal scale includes the following grades:
Death;
Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO);
Hospitalized, on noninvasive ventilation or high-flow oxygen devices;
Hospitalized, requiring supplemental oxygen;
Hospitalized, not requiring supplementation oxygen - requiring ongoing medical care (COVID-19 related or otherwise);
Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care;
Not hospitalized, limitation on activities and/or requiring home oxygen; and
Not hospitalized, no limitations on activities.
Time Frame
Baseline, Day 7, and Day 28
Title
The Number and Percent of Participants Who Experienced All-Cause Mortality at Day 7 and Day 28
Description
Analysis of the Number and Percent of Participants who Experienced All-Cause Mortality at Day 7 and Day 28 in the Full Analysis Set
Time Frame
Baseline up to Day 7 and Day 28
Title
Number of Participants Who Improve by Greater or Equal to 2 Categories on the NIAID 8-point Ordinal Scale From Baseline to Day 7 and Day 28
Description
Analysis of number of participants who improve by >= 2 categories on the NIAID 8-point scale from baseline to Day 7 and Day 28 in the full analysis set.% = 100 x n/N', where N' = number of participants with non-missing values at baseline and the specified post-baseline visit. Participants who died prior to the Day 7 or Day 28 were imputed as 1.
Time Frame
Baseline to Day 7 and Day 28
Title
Time to Return to Prehospitalization Oxygen Requirement
Description
Summary of Time to Return to Prehospitalization Oxygen Requirement in the Intent-to-Treat Population
Time Frame
up to 28 days
Other Pre-specified Outcome Measures:
Title
Summary of Razuprotafib Plasma Concentration
Description
A summary of plasma razuprotafib concentrations for samples collected on Day 1 and 6 in the pharmacokinetic population. All results were summarized descriptively by treatment group.
Time Frame
razuprotafib plasma concentrations 30 and 90 minutes post-dose on Days 1 and 6
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Ability to understand and provide informed consent;
Males and non-pregnant females 18 years of age or older at the time of Screening;
Laboratory-confirmed active SARS-CoV-2 infection within 72 hours prior to randomization, or (if testing results cannot be obtained) by evidence of progressive disease suggestive of ongoing SARS-CoV-2 infection;
Females of childbearing potential must be willing to completely abstain or agree to use a highly effective method of contraception through Day 28; and have a negative urine pregnancy test during Screening;
Currently hospitalized, receiving standard of care therapy for COVID-19, and meets the criteria for moderate or severe COVID-19, as follows: Moderate = symptoms of moderate illness with COVID-19, which could include any symptom of mild illness or shortness of breath with exertion and with respiratory rate at 20 or greater breaths/min, Peripheral capillary oxygen saturation (SpO2) >93% on room air at sea level, or heart rate at 90 or greater beats/min; Severe = symptoms suggestive of severe systemic illness with COVID-19, which could include any symptom of moderate illness, shortness of breath at rest, or respiratory distress, and respiratory rate at 30 or greater breaths/min, heart rate at 125 or greater beats/min, or SpO2 >93% on room air at sea level or (partial pressure of oxygen:fraction of inspired oxygen (PaO2:FiO2) <300.
Exclusion Criteria:
Inability to initiate study drug within 12 hours after randomization;
Female of childbearing potential who is unable or unwilling to forego breastfeeding through Day 28;
Systolic blood pressure <100 mmHg;
In shock or requiring pressor support;
Respiratory failure, defined as subjects who are on mechanical ventilation; are receiving 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 of 0.5 or greater), noninvasive positive pressure ventilation, or extracorporeal membrane oxygenation (ECMO); or have a clinical diagnosis of respiratory failure (ie, clinical need for 1 of the preceding therapies, but preceding therapies not able to be administered in setting of resource limitation);
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >3 × the upper limit of normal (ULN);
Total bilirubin >2 × ULN;
Estimated glomerular filtration rate <30 mL/min or receiving hemodialysis or hemofiltration;
Moribund subject not expected to survive 24 hours in the opinion of the treating clinical team;
Any concurrent serious medical condition (eg, active malignancies on chemotherapy, post organ transplant, end stage congestive heart failure) or not likely to respond to treatment;
Decision to withhold life-sustaining treatment; Note: In the event of cardiac arrest, the decision to withhold cardiopulmonary resuscitation only does not fulfill this exclusion criterion.
Use of cytochrome P450 (CYP) 2 subfamily C, polypeptide 8 (2C8) substrates (eg, repaglinide, paclitaxel, or cerivastatin) or CYP3A4 substrates (eg, amlodipine, budesonide, dasabuvir, enzalutamide, imatinib, lopinavir, loperamide, saquinavir, sildenafil, midazolam, or montelukast);
Use of CYP2C8 inhibitors (eg, gemfibrozil, fluvoxamine, or ketoconazole);
Participation in another investigational study during the present study through the last visit (Day 28); or
Previous randomization in this study.
Facility Information:
Facility Name
University of Southern California
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
University of California- Irvine Medical Center
City
Orange
State/Province
California
ZIP/Postal Code
92868
Country
United States
Facility Name
MedStar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Snake River Research
City
Idaho Falls
State/Province
Idaho
ZIP/Postal Code
83404
Country
United States
Facility Name
University of Minnesota
City
Minneapolis
State/Province
Minnesota
ZIP/Postal Code
55455
Country
United States
Facility Name
University of Cincinnati
City
Cincinnati
State/Province
Ohio
ZIP/Postal Code
45219
Country
United States
Facility Name
Rhode Island Hospital
City
Providence
State/Province
Rhode Island
ZIP/Postal Code
02905
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Evaluation of the Safety and Efficacy of Razuprotafib in Hospitalized Subjects With Coronavirus Disease 2019
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