Trial of Imatinib for Hospitalized Adults With COVID-19

February 7, 2023 updated by: Ashkan Emadi, MD, PhD, University of Maryland, Baltimore

Randomized Double-Blind Placebo-Controlled Trial on the Safety and Efficacy of Imatinib for Hospitalized Adults With COVID-19

This study is a randomized Double-Blind Placebo-Controlled Trial on the Safety and Efficacy of Imatinib for Hospitalized Adults with COVID-19

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

Detailed Description

Coronavirus disease 2019 (COVID-19) is an ongoing global pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and at present with no approved or proven antiviral treatment.

Imatinib is a tyrosine kinase inhibitor that has been approved for treatment of many hematologic and solid neoplasm. Imatinib is a weak base that compared to the extracellular compartment is enriched over 1000-fold in the lysosome within several hours as a result of its lysosomotropic property. Imatinib as a weak base accumulates in lysosomes resulting in some antiviral activities by lysosomal alkalization required for virus/cell fusion.

Imatinib demonstrates in vitro activity against SARS-CoV viruses. Imatinib inhibit SARS-CoV and MERS-CoV with micromolar EC50s (range, 9.8 to 17.6 μM) with low toxicity. The mechanism of action studies suggested that ABL-1 tyrosine kinase regulates budding or release of poxviruses and Ebola virus, demonstrating that the c-ABL-1 kinase signaling pathways play an important role in the egress of these viruses. It is also reported that kinase signaling may also be important for replication of two members of the Coronaviridae family, SARS-CoV and MERS-CoV. In vivo studies performed in the mouse model of vaccinia virus infection showed that imatinib was effective in blocking dissemination of the virus.

Imatinib has anti-inflammatory activity including its effectiveness in a "two-hit" murine model of acute lung injury (ALI) caused by combined lipopolysaccharide (LPS) and ventilator-induced lung injury (VILI). Imatinib significantly decreased bronchoalveolar lavage protein, total cells, neutrophils, and TNFα levels in mice exposed to LPS plus VILI, indicating that it attenuates ALI in this clinically relevant model. In another experiment, imatinib attenuated ALI when given 4 hours after LPS, suggesting potential efficacy when given after the onset of injury. Overall, these results strongly suggest the therapeutic potential of imatinib against inflammatory vascular leak and a potential role of imatinib combination therapy for patients with acute respiratory distress syndrome (ARDS) on mechanical ventilation.

The investigators hypothesize that addition of imatinib to the best conventional care (BCC) improves the outcome of hospitalized adult patients with COVID-19. This hypothesis is on the bases of 1) intralysosomal entrapment of imatinib will increase endosomal pH and effectively decrease SARS-CoV-2/cell fusion, 2) kinase inhibitory activity of imatinib will interfere with budding/release or replication of SARS-CoV-2, and 3) because of the critical role of mechanical ventilation in the care of patients with ARDS, imatinib will have a significant clinical impact for patients with severe COVID-19 infection in Intensive Care Unit (ICU).

Study Type

Interventional

Enrollment (Anticipated)

204

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

  • Name: Ashkan Emadi, MD, PhD
  • Phone Number: 410-328-2596
  • Email: aemadi@umm.edu

Study Contact Backup

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • University of Maryland Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Patients may be included in the study only if they meet all of the following criteria:

  1. Ability to understand and willingness to sign a written informed consent document. Informed consent must be obtained prior to participation in the study. For patients who are too unwell to provide consent such as patients on invasive ventilator or ECMO, Legally Authorized Representative (LAR) can sign the informed consent.
  2. Hospitalized patients ≥ 18 years of age
  3. Positive RT-PCR assay for SARS-CoV-2 in the respiratory tract sample (oropharyngeal, nasopharyngeal or BAL) by Center for Disease Control or local laboratory within 7 days of randomization.

Exclusion Criteria

Patients meeting any of the following criteria are not eligible for the study:

  1. Patients receiving any other investigational agents in a clinical trial. Off-label use of agents such as hydroxychloroquine is not an exclusion criterion. Therapies that are shown to be effective but may not be licensed can be added as an exception to the exclusion criteria in order to allow for the most contemporary standard of care to include emergency use authorization treatments as they become available. Antivirals such as remdesivir will be permissible given the FDA authorized emergency use.
  2. Pregnant or breastfeeding women.

  3. Patients with significant liver or renal dysfunction function at screen as defined as:

    • Direct bilirubin > 2.5 mg/dL
    • AST, ALT, or alkaline phosphatase > 5 x upper limit of normal
    • eGFR ≤ 30 mL/min or requiring renal replacement therapy

  4. Patients with significant hematologic disorder at screen as defined as:

    • Absolute neutrophil count (ANC) < 500/μL
    • Platelet < 20,000/μL
    • Hemoglobin < 7 g/dL
  5. Uncontrolled undercurrent illness including, but not limited to, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled active seizure disorder, or psychiatric illness/social situations that per site Principal Investigator's judgment would limit compliance with study requirements.
  6. Known allergy to imatinib or its component products.
  7. Any other clinical conditions that in the opinion of the investigator would make the subject unsuitable for the study.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
EXPERIMENTAL: Imatinib
Imatinib oral 400 mg daily for 14 days.
Drug: Imatinib
Therapeutic
ACTIVE_COMPARATOR: Placebo
Placebo oral for 14 days
Drug: Placebo oral tablet
Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
The proportion of patients with a two-point change using the 8-category ordinal scale
Time Frame: Day 14 from baseline
The ordinal scale is an evaluation of the clinical status at the first assessment of a given study day. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO); 8) Death.
Day 14 from baseline

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
All-Cause mortality
Time Frame: Day 28 and Day 60 post baseline
All-cause mortality post baseline
Day 28 and Day 60 post baseline
Time to a 2-point clinical change
Time Frame: Up to 60 days post baseline
Time to a 2-point clinical change difference
Up to 60 days post baseline
Hospitalization
Time Frame: Up to 60 days post baseline
Duration of hospitalization
Up to 60 days post baseline
Duration of ECMO or invasive mechanical ventilation
Time Frame: Up to 60 days post baseline
For subjects who are on ECMO or mechanical ventilation at Day 1
Up to 60 days post baseline
Duration of ICU stay
Time Frame: Up to 60 days post baseline
For subjects who are in ICU at Day 1
Up to 60 days post baseline
SARS-CoV-2 negative
Time Frame: Up to 60 days post baseline
Time to SARS-CoV-2 negative by reverse transcriptase-polymerase chain reaction (RT-PCR)
Up to 60 days post baseline
Negative oropharyngeal or nasopharyngeal swab
Time Frame: Up to 28 days post baseline
Proportion of patients with negative oropharyngeal or nasopharyngeal swab for SARS-CoV-2 by quantitative RT PCR on days 5, 10, 14, 21, and 28 after starting treatment
Up to 28 days post baseline
Serious adverse events (SAEs)
Time Frame: Up to 60 days post baseline
Proportion of subjects with serious adverse events
Up to 60 days post baseline
Discontinuation due to adverse events
Time Frame: Up to 60 days post baseline
Proportion of subjects who discontinue study drug due to adverse events
Up to 60 days post baseline

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University of Maryland, Baltimore

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (ACTUAL)

June 2, 2020

Primary Completion (ANTICIPATED)

June 30, 2024

Study Completion (ANTICIPATED)

December 30, 2024

Study Registration Dates

First Submitted

May 8, 2020

First Submitted That Met QC Criteria

May 18, 2020

First Posted (ACTUAL)

May 19, 2020

Study Record Updates

Last Update Posted (ESTIMATE)

February 9, 2023

Last Update Submitted That Met QC Criteria

February 7, 2023

Last Verified

February 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2038GCCC

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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