RESCUE: A Study to Evaluate the Safety and Efficacy of Razuprotafib, a Novel Tie 2 Activator, in Hospitalized Subjects With Moderate to Severe Coronavirus Disease 2019 (COVID-19)

Sponsor

Aerpio Therapeutics (Industry)

Overall Status

Terminated

CT.gov ID

NCT04511650

Collaborator

Medical Technology Enterprise Consortium (MTEC) (Other)

Enrollment

Locations

Arms

4.2

Actual Duration (Months)

4.4

Patients Per Site

1.1

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This is 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 subcutaneously administered three times daily (TID) in hospitalized subjects with moderate to severe COVID-19. Part 1 of the study is a 2-step dose escalation period conducted in approximately 60 subjects. Part 2 is a safety and efficacy period evaluating razuprotafib doses selected from Part 1 and will be conducted in approximately 120 subjects. Subjects will receive razuprotafib or placebo TID for 7 days or until discharge from the hospital (or death) and will be evaluated for safety and efficacy through Day 28. The effects of razuprotafib on biomarkers of coagulation, inflammation and vascular leakage will also be evaluated.

Condition or Disease	Intervention/Treatment	Phase
COVID-19 Acute Respiratory Distress Syndrome	Drug: Razuprotafib Subcutaneous Solution Drug: Placebo Subcutaneous Solution	Phase 2

Study Design

Study Type:

Interventional

Actual Enrollment :

31 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Triple (Participant, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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 in Hospitalized Subjects With Moderate to Severe Coronavirus Disease 2019 (COVID-19) (RESCUE Study)

Actual Study Start Date :

Oct 21, 2020

Actual Primary Completion Date :

Feb 26, 2021

Actual Study Completion Date :

Feb 26, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Razuprotafib	Drug: Razuprotafib Subcutaneous Solution 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. Other Names: AKB-9778 Subcutaneous Solution
Placebo Comparator: Placebo	Drug: Placebo Subcutaneous Solution Matched vehicle-controlled placebo solution will be administered subcutaneously three times daily (Q8H) for 7 days

Arm

Intervention/Treatment

Experimental: Razuprotafib

Drug: Razuprotafib Subcutaneous Solution

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.

Other Names:

AKB-9778 Subcutaneous Solution

Placebo Comparator: Placebo

Drug: Placebo Subcutaneous Solution

Matched vehicle-controlled placebo solution will be administered subcutaneously three times daily (Q8H) for 7 days

Outcome Measures

Primary Outcome Measures

Proportion of subjects alive and free of respiratory failure at Day 7 [Baseline up to Day 7]
Proportion of subjects alive and free of respiratory failure at Day 28 [Baseline up to Day 28]
Length hospitalized and free of respiratory failure from baseline to Day 7 [Baseline up to Day 7]
Length hospitalized and free of respiratory failure from baseline to Day 28 [Baseline up to Day 28]
Length of hospitalization from baseline to Day 7 [Baseline up to Day 7]
Length of hospitalization from baseline to Day 28 [Baseline up to Day 28]
Proportion of subjects who improve by at least 2 categories on the NIAID 8-point ordinal scale from baseline to Day 7 [Baseline up to Day 7]
Proportion of subjects who improve by at least 2 categories on the NIAID 8-point ordinal scale from baseline to Day 28 [Baseline up to Day 28]
Proportion of subjects who worsen by at least 2 categories on the NIAID 8-point ordinal scale from baseline to Day 7 [Baseline up to Day 7]
Proportion of subjects who worsen by at least 2 categories on the NIAID 8-point ordinal scale from baseline to Day 28 [Baseline up to Day 28]
All-cause mortality at Day 7 [Baseline up to Day 7]
All-cause mortality at Day 28 [Baseline up to Day 28]
Length of ICU stay from baseline to Day 28 [Baseline up to Day 28]
Number of subjects in each category of the NIAID 8-point ordinal scale at Day 7 [Baseline up to Day 7]
Number of subjects in each category of the NIAID 8-point ordinal scale at Day 28 [Baseline up to Day 28]
Time to return to prehospitalization oxygen requirement [Baseline up to Day 28]
Proportion of subjects who were discharged and remained free of respiratory failure prior to Day 7 [Baseline up to Day 7]
Proportion of subjects who were discharged and remained free of respiratory failure prior to Day 28 [Baseline up to Day 28]
Change in PaO2:FiO2 ratio from baseline to Day 7 [Baseline up to Day 7]
Change in PaO2:FiO2 ratio from baseline to Day 28 [Baseline up to Day 28]

Secondary Outcome Measures

Number of participants with any serious adverse event from baseline to Day 7 [Baseline up to Day 7]
Number of participants with any treatment emergent adverse event from baseline to Day 28 [Baseline up to Day 28]
Number of participants with any treatment emergent adverse event from baseline to Day 7 [Baseline up to Day 7]
Number of participants with any serious adverse event from baseline to Day 28 [Baseline up to Day 28]

Other Outcome Measures

Change from baseline in systemic biomarkers of vascular leakage and inflammation (ie, Angpt 2, IL-6, IL-8, TNFα, HMGB-1, CRP and D-dimer); [Baseline up to Day 7]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Southern California	Los Angeles	California	United States	90033
2	University of California- Irvine Medical Center	Orange	California	United States	92868
3	MedStar Georgetown University Hospital	Washington	District of Columbia	United States	20007
4	Snake River Research	Idaho Falls	Idaho	United States	83404
5	University of Minnesota	Minneapolis	Minnesota	United States	55455
6	University of Cincinnati	Cincinnati	Ohio	United States	45219
7	Rhode Island Hospital	Providence	Rhode Island	United States	02905