Safety, Tolerability and Efficacy of Uproleselan (GMI-127... | NCT05057221

NCT05057221

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
GlycoMimetics Incorporated	INDUSTRY

Description Module

Detailed Description

Soluble E-selectin is a significant biomarker for adult respiratory distress syndrome (ARDS). Soluble E-selectin also has pro-inflammatory properties further releasing cytokines and promoting its synthesis and the continued influx of neutrophils. Small molecule glycomimetic antagonists of E-selectin (rivipansel and uproleselan) are 500- to 1000-fold more potent inhibitors of E-selectin and have shown activity and no measurable toxicity in human clinical trials for other indications. Treatment with these E-selectin inhibitors reduced the levels of soluble E-selectin in the bloodstream which occurs during recovery of ARDS. Thus, antagonists of E-selectin which include glycomimetic antagonists and more specifically, rivipansel (GMI-1070) and uproleselan (GMI-1271), may be used to treat COVID-19 patients with respiratory symptoms that may lead to ARDS

Primary Objective:

Safety of uproleselan in patients with severe COVID-19 pneumonia.

Secondary Objectives:

To evaluate if treatment with uproleselan administered intravenously in addition to the best available therapy according to institutional guidelines is able to reduce the progression of acute respiratory failure, in patients with severe COVID-19 pneumonia.

To evaluate proportion of patients alive and free of respiratory failure through Day 28
To evaluate overall survival and all-cause mortality at day 15 and 28.
To evaluate changes in the COVID ordinal outcomes scale.
To assess adverse events to evaluate the safety of uproleselan.
To assess ventilator-free days, ICU-free days, oxygen, vasopressor free days.
To evaluate changes in D-dimer.

Exploratory Objectives:

To examine the correlation of plasma soluble E-selectin concentrations with clinical outcomes.
To examine the correlations of other biomarkers of interest with clinical outcome.

Previous versions of this record mistakenly suggested the trial would assess the number of participants who experienced a Grade 3-5 hemorrhagic event. The outcome title has been corrected to state the number of participants with a Grade 3-4 hemorrhagic event were assessed, as the scale used does not go to Grade 5.

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Uproleselan	Experimental	Uproleselan injection is a sterile solution for IV administration, supplied in single-dose vials at a concentration of 50 mg/mL.	Drug: Uproleselan

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Uproleselan	Drug	Uproleselan 20 mg/kg BID up to maximum dose of 2500 mg, infused IV over 20 minutes on days 1-7 or until hospital discharge. It should be administered intravenously (IV) into a peripheral line, a central catheter, or a peripherally inserted central line catheter (PICC). Infusion should take place at a steady rate over a period of 20 minutes ±2 minutes using a syringe pump or IV pump.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Safety of Uproleselan - as Measured by Serious Adverse Events	Descriptive statistics will be calculated for quantitative safety data	Up to 28 days
Safety of Uproleselan- as Measured by Frequency of Serious Adverse Events	Frequency counts will be compiled for classification of qualitative safety data.	Up to 28 days

Secondary Outcomes

Measure	Description	Time Frame
Change in the Progression to Acute Respiratory Failure for Patients With a Baseline PaO2/FiO2 >= 200	Patients with a baseline PaO2/FiO2 >= 200: progression of respiratory failure is defined by: severe gas transfer deficit (PaO2/FiO2 < 200); persistent respiratory distress while receiving oxygen (persistent marked dyspnea, use of accessory respiratory muscles, paradoxical respiratory movements); The rate will be calculated as the proportion of patients who experienced at least one of the events above by day+15 from treatment start.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Documented COVID-19 pneumonia: defined as upper respiratory tract specimen (nasopharyngeal swab (NPS) or viral throat swab) positive for COVID-19 and/or imaging at computed tomography scan suggestive of COVID-19 pneumonia.
Confirmed coronavirus (SARS-CoV-2) (positive real-time reverse transcription polymerase chain reaction test (RT-PCR) for SARS-CoV-2 within 72 hours) enrolled ≤ 48 hours of need for supplemental oxygen.
Currently hospitalized requiring supplemental oxygen.
Have severe COVID-19 according to the World Health Organization (WHO) Interim Guidance with confirmation by real-time RT-PCR assay. The enrollment criteria with one of the following: respiratory distress, respiratory rate (RR) ≥30 beats/min; oxygen saturation level less than 93% in resting state; or partial pressure of oxygen (PaO2)/oxygen concentration (FiO2) ≤ 300 mmHg.
Willing and able to participate in all required evaluations and procedures.

Exclusion Criteria:

In the opinion of at least two investigators, unlikely to survive for >48 hours from screening.
Severe chronic respiratory disease (e.g. Chronic obstructive pulmonary disease or other) requiring supplemental oxygen and/or having required mechanical ventilation pre-COVID-19 infection.
Concurrent enrollment in a COVID related interventional drug trial. Use of remdesivir, steroids, and convalescent plasma are permitted along with other standard of care therapies for COVID.37
Currently on invasive mechanical ventilation.
Hypotension defined as systolic blood pressure < 90 mmHg on two sequential readings at least 4 hours apart.
Total Bilirubin ≤ 3 x upper limit of normal (ULN), Creatinine Clearance ≥ 30 mL/min/1.73m2.
Pregnant or breastfeeding.
Known diagnosis of an acute thrombosis on admission.
Concurrent dual antithrombotic therapy (aspirin or P2Y12 inhibitor plus anticoagulation to treat deep venous thrombosis or pulmonary embolism (single antiplatelet or anticoagulant agent at prophylactic dose is permitted).
Concomitant use of thrombolytic therapy.
Concomitant therapeutic systemic anticoagulant therapy (e.g. heparin, warfarin, direct thrombin inhibitors and direct factor Xa inhibitors). As per NIH Guidelines: Hospitalized adults with COVID-19 should receive Venous thromboembolism (VTE) prophylaxis per the standard of care for other hospitalized adults (AIII). Anticoagulant or antiplatelet therapy should not be used to prevent arterial thrombosis outside of the usual standard of care for patients without COVID-19 (AIII); https://www.covid19treatmentguidelines.nih.gov/therapeutic-management/
History of recent major bleeding, defined in accordance with the criteria of the International Society on Thrombosis and Hemostasis (ISTH).
History of bleeding disorder thought to impose excessive bleeding risk as per investigator discretion
Hemodynamic instability, defined as inability to maintain mean arterial pressure.
Hypersensitivity to the active substance or to any of the excipients of uproleselan.
Any physical examination findings and/or history of any illness that, in the opinion of the investigator, might confound the results of the study or pose an additional risk to the patient by their participation in the study

Name	Affiliation	Role
Lena Napolitano, MD	University of Michigan	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
The University of Michigan		Ann Arbor	Michigan	48109	United States

ID	Title	Description
FG000	Uproleselan	Uproleselan injection is a sterile solution for IV administration, supplied in single-dose vials at a concentration of 50 mg/mL. Uproleselan: Uproleselan 20 mg/kg BID up to maximum dose of 2500 mg, infused IV over 20 minutes on days 1-7 or until hospital discharge. It should be administered intravenously (IV) into a peripheral line, a central catheter, or a peripherally inserted central line catheter (PICC). Infusion should take place at a steady rate over a period of 20 minutes ±2 minutes using a syringe pump or IV pump.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Uproleselan	Uproleselan injection is a sterile solution for IV administration, supplied in single-dose vials at a concentration of 50 mg/mL. Uproleselan: Uproleselan 20 mg/kg BID up to maximum dose of 2500 mg, infused IV over 20 minutes on days 1-7 or until hospital discharge. It should be administered intravenously (IV) into a peripheral line, a central catheter, or a peripherally inserted central line catheter (PICC). Infusion should take place at a steady rate over a period of 20 minutes ±2 minutes using a syringe pump or IV pump.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Continuous			Mean

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Safety of Uproleselan - as Measured by Serious Adverse Events

Descriptive statistics will be calculated for quantitative safety data

Posted

Number

Serious Adverse Events

Up to 28 days

ID	Title	Description
OG000	Uproleselan	Uproleselan injection is a sterile solution for IV administration, supplied in single-dose vials at a concentration of 50 mg/mL. Uproleselan: Uproleselan 20 mg/kg BID up to maximum dose of 2500 mg, infused IV over 20 minutes on days 1-7 or until hospital discharge. It should be administered intravenously (IV) into a peripheral line, a central catheter, or a peripherally inserted central line catheter (PICC). Infusion should take place at a steady rate over a period of 20 minutes ±2 minutes using a syringe pump or IV pump.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Uproleselan	Uproleselan injection is a sterile solution for IV administration, supplied in single-dose vials at a concentration of 50 mg/mL. Uproleselan: Uproleselan 20 mg/kg BID up to maximum dose of 2500 mg, infused IV over 20 minutes on days 1-7 or until hospital discharge. It should be administered intravenously (IV) into a peripheral line, a central catheter, or a peripherally inserted central line catheter (PICC). Infusion should take place at a steady rate over a period of 20 minutes ±2 minutes using a syringe pump or IV pump.