COVID-19 PneumoniaPhase 1/2NCT05057221
Safety, Tolerability and Efficacy of Uproleselan (GMI-1271) in Patients With COVID-19 Pneumonia
A Phase 1/2 study testing Uproleselan in people with COVID-19 Pneumonia, run by Lena Napolitano, MD at 1 site in United States.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- COVID-19 Pneumonia
- What is being tested?
- Uproleselan
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- 12 Nov 2021to 9 Mar 2022
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
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- 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
Trial locations and contacts
1 site in 1 country.
United States1 site
The University of Michigan
Ann Arbor, Michigan, 48109
About this study
Official title: A Pilot Study to Assess the Safety, Tolerability and Efficacy of Selectin Inhibitor Uproleselan (GMI-1271) in Patients With COVID-19 Pneumonia
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.
Read the 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.
- Conditions
- COVID-19 Pneumonia
- Being tested
- Uproleselan
- Keywords
- Uproleselan, Selectin Inhibitor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
UproleselanDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Uproleselan | Experimental | Uproleselan injection is a sterile solution for IV administration, supplied in single-dose vials at a concentration of 50 mg/mL. Receives: Drug: Uproleselan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Safety of Uproleselan - as Measured by Serious Adverse Events
Descriptive statistics will be calculated for quantitative safety data
Measured: 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.
Measured: Up to 28 days
Secondary outcomes (12)
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.
Measured: 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
Measured: Up to 28 days
All-cause Mortality
All-cause hospital mortality
Measured: Up to 28 days
Time to Change Oxygenation
Number of days it took to reduce their oxygen requirements
Measured: during hospitalization; hospital stay ranged from 2 to 10 days
Number of Patients Requiring Mechanical Ventilation
Number of patients requiring mechanical ventilation
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: 6 Days
Participants Who Experienced Venous Thromboembolism (Deep Venous Thrombosis or Pulmonary Embolism)
Venous thromboembolism - DVT or PE
Measured: Enrollment, up to day 28
Number of Mechanical Ventilation and Vasopressor Days
Days of mechanical ventilation and days of vasopressors
Measured: Up to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2021
- Study start12 Nov 2021
- Primary completion9 Mar 2022
- Study completion9 Mar 2022
Why it stopped: No more eligible patients were available.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for COVID-19 PneumoniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- This is a prospective, interventional, single-arm, open label trial, with 1:1 matched de-identified retrospective control cohort.
- Masking
- None (open label)
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Lena Napolitano, MD
- Sponsor type
- University, hospital or other
- Collaborators
- GlycoMimetics Incorporated
- Responsible party
- Sponsor-investigator, Lena Napolitano, MD, University of Michigan
- Investigators
- Lena Napolitano, MD, Principal investigator, University of Michigan
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05057221
- Sponsor's protocol ID
- HUM00195034
- Status last verified
- Jun 2023
- First submitted
- 23 Sep 2021
- Last updated
- 10 Jul 2023
- Results posted
- Yes, on ClinicalTrials.gov
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Jul 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pilot Study to Assess the Safety, Tolerability and Efficacy of Selectin Inhibitor Uproleselan (GMI-1271) in Patients With COVID-19 Pneumonia
- ClinicalTrials.gov ID
- NCT05057221
- Acronym / sponsor ID
- HUM00195034
- Conditions
- COVID-19 Pneumonia
- Keywords
- Uproleselan, Selectin Inhibitor
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: No more eligible patients were available.
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Lena Napolitano, MDUniversity, hospital or other
- Collaborators
- GlycoMimetics Incorporated
- Study start
- 12 Nov 2021 (actual)
- Primary completion
- 9 Mar 2022 (actual)
- Study completion
- 9 Mar 2022 (actual)
- First posted
- 27 Sep 2021 (actual)
- Results
- Posted 10 Jul 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- This is a prospective, interventional, single-arm, open label trial, with 1:1 matched de-identified retrospective control cohort.
| Arm | Type | Receives |
|---|---|---|
| Uproleselan | Experimental | Drug: UproleselanUproleselan injection is a sterile solution for IV administration, supplied in single-dose vials at a concentration of 50 mg/mL. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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.
Key exclusion criteria (16 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| UproleselanUproleselan 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. | Drug | Uproleselan |
Primary outcome
Safety of Uproleselan - as Measured by Serious Adverse Events
Time frame: Up to 28 days
Descriptive statistics will be calculated for quantitative safety data
Safety of Uproleselan- as Measured by Frequency of Serious Adverse Events
Time frame: Up to 28 days
Frequency counts will be compiled for classification of qualitative safety data.
12 secondary outcomes
Change in the Progression to Acute Respiratory Failure for Patients With a Baseline PaO2/FiO2 >= 200
Time frame: Enrollment, 15 days
Number of Patients Alive Who Are Free of Respiratory Failure
Time frame: Up to 28 days
All-cause Mortality
Time frame: Up to 28 days
Time to Change Oxygenation
Time frame: during hospitalization; hospital stay ranged from 2 to 10 days
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
Time frame: Enrollment, day 28
Actual Duration of Hospitalization
Time frame: Up to 28 days
Actual Duration of ICU Care
Time frame: Up to 28 days
Participants Who Experienced Grade 3-4 Hemorrhagic Events
Time frame: Up to 28 days
Change in E-selectin Plasma Concentrations, as Shown by Values for Each of Those Days
Time frame: 6 Days
Participants Who Experienced Venous Thromboembolism (Deep Venous Thrombosis or Pulmonary Embolism)
Time frame: Enrollment, up to day 28
Number of Mechanical Ventilation and Vasopressor Days
Time frame: Up to Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Jul 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Lena Napolitano, MD principal investigator
University of Michigan
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Uproleselan in people with COVID-19 Pneumonia, run by Lena Napolitano, MD at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 10 Jul 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Jul 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Safety of Uproleselan - as Measured by Serious Adverse Events (time frame: Up to 28 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Jul 2023.