Ulinastatin for the Treatment of COVID-19 in Hospitalized Patients

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

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.

Study Overview

• Status: Withdrawn
• Conditions: COVID-19
• Intervention / Treatment: Drug: Ulinastatin; Drug: Placebo

• Study Type: Interventional
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Stanford University

Study record dates

Study Major Dates

• Study Start (Anticipated): February 1, 2022
• Primary Completion (Anticipated): August 1, 2022
• Study Completion (Anticipated): August 1, 2022

Study Registration Dates

• First Submitted: May 15, 2020
• First Submitted That Met QC Criteria: May 15, 2020
• First Posted (Actual): May 19, 2020

Study Record Updates

• Last Update Posted (Actual): March 3, 2022
• Last Update Submitted That Met QC Criteria: February 15, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Pneumonia, Viral; Pneumonia; Lung Diseases; COVID-19; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Serine Proteinase Inhibitors; Trypsin Inhibitors; Urinastatin
• Other Study ID Numbers: 56639

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: No plan to share data.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No