IMATINIB IN COVID-19 DISEASE IN AGED PATIENTS. (IMAGE-19)

A RANDOMIZED NON-COMPARATIVE PHASE 2 PILOT STUDY TESTING THE VALUE OF IMATINIB MESYLATE AS AN EARLY TREATMENT OF COVID-19 DISEASE IN AGED HOSPITALIZED PATIENTS.

High-throughput screening studies identified Abl kinase inhibitors (including imatinib) as inhibitors of coronaviruses SARS and MERS. The SARS-CoV-2 coronavirus depend on Abl2 kinase activity to fuse and enter into the cells. Pharmacokinetic studies demonstrated that IC50 of imatinib for ABL1, BCR-ABL1 and ABL2 kinase inhibition is less than 1 microM (around 0.3 microM) below the expected trough plasmatic concentrations of imatinib 400 mg/day (1.7 microM). The EC50 of imatinib for the inhibition of the virus is under investigation but we now have a first estimates with EC50 close to 2.5 microM. This plasmatic concentration is achievable with imatinib 800 mg/d. We hypothesize that clinically achievable imatinib concentration will block the first round of cell to cell virus infection and therefore stop or prevent from SARS-CoV-2 infection in human. Based on our 20 years' experience of prescribing imatinib in patients, we expect that most of the adverse events and pharmacological interactions of imatinib can be anticipated and corrected. The eligible population will be aged (>70y) patients hospitalized for a non-severe COVID-19 disease for less than 7 days. Patients will be randomized 1/1 between standard of care and imatinib 800 mg per day during 14 days. The primary endpoint will be the death rate by 30 days. Secondary endpoint will include progression to severe CIVID-19 disease, safety, outcome at 3 months. We plan to randomize 90 patients in order to show a 10% benefit in term of death rate reduction from 16% to 6%.

Study Overview

• Status: Unknown
• Conditions: SARS Virus
• Intervention / Treatment: Drug: Experimental drug

• Study Type: Interventional
• Enrollment (Anticipated): 99
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • Chu Bordeaux
  • Le Chesnay, France
    • CH de Versailles

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 70 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:. Patient aged > 70y 2. Patient with a documented COVID-19 disease by SARS-CoV-2 RT-PCR (if no test is available, suspected COVID-19 disease on CT SCAN).

3. Initial phase (≤ 7 days) of COVID-19 disease 4. Non severe COVID-19 disease 5. Signed informe consent

Exclusion Criteria:

1. Patient in palliative care
2. Severe COVID-19 disease (SpO2 ≤ 94% with O2 ≥ 5 l/min)
3. Contra-indication to imatinib
4. Therapy with Warfarin (Heparin allowed)
5. Stage II to IV congestive heart failure (CHF) as determined by the New York Heart Association (NYHA)
6. Peripheral edema grade > 2
7. Known HBV, HBC or HIV infection
8. Known hepatic failure
9. Patient under legal protection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Expérimental ARM; 800mg/d IMATINIB during 14days	Drug: Experimental drug; Imatinib 800mg/d during 14days
No Intervention: Comparator ARM; Standard of care

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the benefit of early imatinib therapy to prevent severe COVID-19 disease in hospitalized aged patients.	To evaluate the 30 days mortality rate in aged patients hospitalized with COVID-19	30 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
To evaluate the feasibility of imatinib therapy.	Drop out rate of imatinib mesylate therapy	Day 14
To evaluate safety of imatinib therapy	Adverse events related to imatinib mesylate therapy	3 months
To evaluate the clinical evolution	Clinical (WHO COVID scale) and geriatric scores (GIR, ADL and IADL) modification	3 months
To evaluate the progression rate to severe COVID-19 disease	Clinical (WHO COVID scale) and geriatric scores (GIR, ADL and IADL) modification	3 months
To evaluate mortality	number of death	14 days
To evaluate mortality	number of death	60 days
To evaluate mortality	number of death	90 days
To evaluate viral load	Viral load by SARS-CoV-2 PCR	14 days
To evaluate plasmatic levels of imatinib	Imatinib trough level	14 days

Collaborators and Investigators

• Sponsor: Versailles Hospital
• Investigators: Principal Investigator: Philippe Rousselot, CH Versailles

Publications and helpful links

General Publications

• Zhao H, Mendenhall M, Deininger MW. Imatinib is not a potent anti-SARS-CoV-2 drug. Leukemia. 2020 Nov;34(11):3085-3087. doi: 10.1038/s41375-020-01045-9. Epub 2020 Sep 30. No abstract available.

Study record dates

Study Major Dates

• Study Start (Anticipated): September 1, 2020
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2021

Study Registration Dates

• First Submitted: April 20, 2020
• First Submitted That Met QC Criteria: April 20, 2020
• First Posted (Actual): April 22, 2020

Study Record Updates

• Last Update Posted (Actual): August 7, 2020
• Last Update Submitted That Met QC Criteria: August 6, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: P20/05_IMAGE19

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No