Ulinastatin for the Treatment of COVID-19 in Hospitalized Patients

Study Overview
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Brief Summary
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The primary objective of this study is to evaluate the safety and efficacy of intravenous (IV) infusion of ulinastatin compared to placebo with respect to time to recovery, disease severity, need for ventilator support, and mortality in patients with COVID 19.

Official Title
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A Multi-Center, Randomized, Double-Blind, Placebo Controlled Study of the Safety and Efficacy of Ulinastatin for the Treatment of COVID-19 in Hospitalized Patients

Conditions
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COVID-19

Intervention / Treatment
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* Drug: Ulinastatin
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Willing and able to provide written informed consent Signs and symptoms suggestive of COVID-19 infection Laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection ≤7 days before randomization Currently hospitalized or in an emergency department with planned hospitalization Peripheral capillary oxygen saturation (SpO2) <93% on room air at Screening Exclusion Criteria: Simultaneous participation in any other clinical study incompatible with this one Treatment with an antibody immunotherapy within 4 weeks of Screening Requirement for mechanical ventilation or ECMO at Screening Hypotension at Screening Severe liver injury defined as AST or ALT ≥5x the upper limit of normal Severe kidney failure defined as an estimated glomerular filtration rate (eGFR) <30 mL/min Pregnancy or breastfeeding > 120 hours between admission and signing consent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Ulinastatin<br>Patients will receive ulinastatin via IV infusion every 8 hours for up to 5 days or until hospital discharge (whichever is earlier). | Drug: Ulinastatin<br>* Ulinastatin administered via IV infusion (200,000/infusion)<br>|
| Placebo Comparator: Placebo<br>Patients will receive placebo to match ulinastatin via IV infusion every 8 hours for up to 5 days or until hospital discharge (whichever is earlier). | Drug: Placebo<br>* Placebo to match ulinastatin administered via IV infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to recovery | Time to recovery, defined as attaining a score of 6, 7, or 8 on the COVID-19 disease severity scale, an 8 point ordinal scale used in the NIH Adaptive COVID-19 Treatment Trial (ACTT; NCT04280705). = Death; = Hospitalized and on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); = Hospitalized and on non-invasive ventilation or high-flow oxygen devices; = Hospitalized and requiring supplemental oxygen; = Hospitalized and not requiring supplemental oxygen but requiring ongoing medical care (COVID-19-related or otherwise); = Hospitalized and not requiring supplemental oxygen and no longer requiring ongoing medical care; = Not hospitalized, limitation on activities and/or requiring home oxygen; = Not hospitalized, no limitation on activities | Up to 29 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| COVID-19 disease severity scale score on Day 8 | COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state). | Day 8 | 
| COVID-19 disease severity scale score on Day 15 | COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state). | Day 15 | 
| COVID-19 disease severity scale score on Day 22 | COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state). | Day 22 | 
| COVID-19 disease severity scale score on Day 29 | COVID-19 disease severity scale (range; 1-8, higher scores correspond to better health state). | Day 29 | 
| Incidence of mortality at Day 29 |  | 29 days | 
| Incidence of in-hospital mortality |  | Up to 29 days | 
| Number of days alive and not on mechanical ventilator or ECMO in the 28 days following first dose |  | Up to 29 days | 
| Number of patients with resolution of symptoms defined as score of 8 on the 8-point ordinal scale at Day 29 |  | Day 29 | 
| Number of patients alive and free of respiratory failure defined as score of 4, 5, 6, 7, or 8 on the 8-point ordinal scale at Day 29 |  | Day 29 | 
| Duration of mechanical ventilation | For patients requiring mechanical ventilation. | Up to 29 days | 
| Duration of ECMO | For patients requiring mechanical ECMO. | Up to 29 days | 
| Duration of noninvasive ventilation | For patients requiring non-invasive ventilation | Up to 29 days | 
| Duration of ICU stay | For patients admitted to ICU | Up to 29 days | 
| Duration of hospital stay |  | Up to 29 days | 
| Change in oxygen saturation |  | Between screening and 24 hours after last dose (up to 6 days) |