A Phase 1/2 interventional study of Uproleselan in COVID-19 Pneumonia, sponsored by Lena Napolitano, MD. Terminated at 1 site in United States. Open to participants aged 18 Years to 75 Years. Per ClinicalTrials.gov, last updated 2023-07-10.
Sponsored by Lena Napolitano, MD · Phase 1/2, Interventional, and Treatment
The purpose of this study is to find out whether the drug uproleselan can help patients with severe COVID-19 pneumonia. Investigators will study both the side effects of the drug and assess if the drug will help patients recover more quickly and slow down the progression of acute respiratory failure.
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.
Exploratory Objectives:
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.
7,640 studies on the registry are indexed under COVID-19; 488 are open to participants now.
This study's enrollment of 6 is below the median of 100 across 4,099 interventional studies indexed under COVID-19.
Browse COVID-19 studies →This is the only study on the registry with Lena Napolitano, MD as lead sponsor.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria:
Uproleselan injection is a sterile solution for IV administration, supplied in single-dose vials at a concentration of 50 mg/mL.
Drug: 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.
Safety of Uproleselan - as Measured by Serious Adverse Events
Descriptive statistics will be calculated for quantitative safety data
Time frame: 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.
Time frame: Up to 28 days
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: 1. severe gas transfer deficit (PaO2/FiO2 \< 200); 2. 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.
Time frame: Enrollment, 15 days
Number of Patients Alive Who Are Free of Respiratory Failure
Number of patients alive and free of acute respiratory failure which required initiation of mechanical ventilation
Time frame: Up to 28 days
All-cause Mortality
All-cause hospital mortality
Time frame: Up to 28 days
Time to Change Oxygenation
Number of days it took to reduce their oxygen requirements
Time frame: during hospitalization; hospital stay ranged from 2 to 10 days
Number of Patients Requiring Mechanical Ventilation
Number of patients requiring mechanical ventilation
Time frame: Up to 28 days
Change in the World Health Organization (WHO) COVID-19, "8-point Ordinal Scale" as Shown by Presenting Selected Time Points Through Day 28
WHO COVID-19, "8-point ordinal scale" has a range of 1-8 with higher numbers indicating a more severe disease.
Time frame: Enrollment, day 28
Actual Duration of Hospitalization
Duration of hospitalization - number of inpatient hospital days. Participants were planned to be followed for up to 28 days, although the longest actual hospital stay for a participant was 10 days.
Time frame: Up to 28 days
Actual Duration of ICU Care
Duration of ICU stay - number of ICU days. Participants were planned to be followed for up to 28 days, although the longest actual hospital stay for a participant was 10 days.
Time frame: Up to 28 days
Participants Who Experienced Grade 3-4 Hemorrhagic Events
Number of participants who experienced a Grade 3 or Grade 4 hemorrhagic event based on the World Health Organization's (WHO) Bleeding Scale. On the scale, a Grade 3 event means gross blood loss, and a Grade 4 event means debilitating blood loss.
Time frame: Up to 28 days
Change in E-selectin Plasma Concentrations, as Shown by Values for Each of Those Days
Changes in E-selectin plasma concentrations measured each day for 6 days.
Time frame: 6 Days
Participants Who Experienced Venous Thromboembolism (Deep Venous Thrombosis or Pulmonary Embolism)
Venous thromboembolism - DVT or PE
Time frame: Enrollment, up to day 28
Number of Mechanical Ventilation and Vasopressor Days
Days of mechanical ventilation and days of vasopressors
Time frame: Up to Day 28
| Milestone | Uproleselan |
|---|---|
| Started | 6 |
| Completed | 6 |
| Not completed | 0 |
Descriptive statistics will be calculated for quantitative safety data
| Serious Adverse Events | Uproleselan |
|---|---|
| Safety of Uproleselan - as Measured by Serious Adverse Events | 0 |
Frequency counts will be compiled for classification of qualitative safety data.
| daily events | Uproleselan |
|---|---|
| Safety of Uproleselan- as Measured by Frequency of Serious Adverse Events | 0 |
Patients with a baseline PaO2/FiO2 \>= 200: progression of respiratory failure is defined by: 1. severe gas transfer deficit (PaO2/FiO2 \< 200); 2. 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.
| Participants | Uproleselan |
|---|---|
| Change in the Progression to Acute Respiratory Failure for Patients With a Baseline PaO2/FiO2 >= 200 | 0 |
Number of patients alive and free of acute respiratory failure which required initiation of mechanical ventilation
| Participants | Uproleselan |
|---|---|
| Number of Patients Alive Who Are Free of Respiratory Failure | 6 |
All-cause hospital mortality
| Participants | Uproleselan |
|---|---|
| All-cause Mortality | 0 |
Number of days it took to reduce their oxygen requirements
| Days | Uproleselan |
|---|---|
| Time to Change Oxygenation | 2 ± 1 |
Number of patients requiring mechanical ventilation
| Participants | Uproleselan |
|---|---|
| Number of Patients Requiring Mechanical Ventilation | 0 |
WHO COVID-19, "8-point ordinal scale" has a range of 1-8 with higher numbers indicating a more severe disease.
| score on a scale | Uproleselan |
|---|---|
| Day 1 | 4.67 ± 0.42 |
| Day 3 | 2.8 ± 0.74 |
| Day 15 | 1.17 ± 0.16 |
| Day 28 | 1.20 ± 0.2 |
Duration of hospitalization - number of inpatient hospital days. Participants were planned to be followed for up to 28 days, although the longest actual hospital stay for a participant was 10 days.
| days | Uproleselan |
|---|---|
| Actual Duration of Hospitalization | 4.67 ± 2.56 |
Duration of ICU stay - number of ICU days. Participants were planned to be followed for up to 28 days, although the longest actual hospital stay for a participant was 10 days.
| days | Uproleselan |
|---|---|
| Actual Duration of ICU Care | 1.33 ± 1.89 |
Number of participants who experienced a Grade 3 or Grade 4 hemorrhagic event based on the World Health Organization's (WHO) Bleeding Scale. On the scale, a Grade 3 event means gross blood loss, and a Grade 4 event means debilitating blood loss.
| Participants | Uproleselan |
|---|---|
| Participants Who Experienced Grade 3-4 Hemorrhagic Events | 0 |
Changes in E-selectin plasma concentrations measured each day for 6 days.
| Nanograms divided by milliliter | Uproleselan |
|---|---|
| Day 1 | 19.19 ± 9.783 |
| Day 2 | 15.15 ± 6.524 |
| Day 3 | 18.15 ± 9.660 |
| Day 4 | 18.09 ± 7.239 |
| Day 5 | 27.04 ± 0.000 |
| Day 6 | 26.85 ± 0.000 |
Venous thromboembolism - DVT or PE
| Participants | Uproleselan |
|---|---|
| Participants Who Experienced Venous Thromboembolism (Deep Venous Thrombosis or Pulmonary Embolism) | 0 |
Days of mechanical ventilation and days of vasopressors
| days | Uproleselan |
|---|---|
| Days of mechanical ventilation | 0 |
| vasopressor days | 0 |
Collected over 28 days. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Uproleselan | 0/6 (0%) | 0/6 (0%) | 3/6 (50%) |
| Event | Uproleselan |
|---|---|
| bilateral leg edemaBlood and lymphatic system disorders | 1/6 |
| dizzinessEar and labyrinth disorders | 1/6 |
| mild diarrhea and indigestionGastrointestinal disorders | 1/6 |
| bruising from clinical blood drawsBlood and lymphatic system disorders | 1/6 |
Adults with confirmed severe COVID-19 pneumonia (WHO definition) requiring supplemental oxygen
| Age, Continuous(years) | Uproleselan |
|---|---|
| Mean | 56.5 ± 13.7 |
| Sex: Female, Male(Participants) | Uproleselan |
|---|---|
| Female | 2 |
| Male | 4 |
| Race and Ethnicity Not Collected(Participants) | Uproleselan |
|---|
| Region of Enrollment(participants) | Uproleselan |
|---|---|
| United States | 6 |
| Body Mass Index (BMI(Kg/m^2) | Uproleselan |
|---|---|
| Mean | 37.21 ± 10.36 |
| E-selectin Plasma Concentrations(nanograms divided by milliliters) | Uproleselan |
|---|---|
| Mean | 15.83 ± 6.479 |
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