Safety, Tolerability and Efficacy of Uproleselan (GMI-1271) in Patients With COVID-19 Pneumonia

  • STATUS
    Recruiting
  • End date
    Nov 15, 2023
  • participants needed
    15
  • sponsor
    Lena Napolitano, MD
Updated on 15 December 2021

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.

Description

Soluble E-selectin is a significant biomarker for 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.

Details
Condition COVID-19 Pneumonia
Treatment Uproleselan
Clinical Study IdentifierNCT05057221
SponsorLena Napolitano, MD
Last Modified on15 December 2021

Eligibility

Yes No Not Sure

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
Clear my responses

How to participate?

Step 1 Connect with a study center
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar

Primary Contact

site

0/250

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note