IMATINIB IN COVID-19 DISEASE IN AGED PATIENTS.

SARS Virus Clinical Trial

— IMAGE-19  

Official title:

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.

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT04357613
• Other study ID #: P20/05_IMAGE19
• Status: Not yet recruiting
• Phase: Phase 2
• Start date: September 1, 2020
• Est. completion date: December 1, 2021

Study information

• Verified date: August 2020
• Source: Versailles Hospital
• Contact: Laure Morisset
• Phone: +33139239785
• Email: lmorisset[@]ch-versailles.fr
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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%.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 99
• Est. completion date: December 1, 2021
• Est. primary completion date: December 1, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 70 Years and older

Eligibility

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

Related Conditions & MeSH terms

• SARS Virus

Intervention

Drug:
• Experimental drug
Imatinib 800mg/d during 14days

Locations

Country	Name	City	State
France	CHU Bordeaux	Bordeaux
France	CH de Versailles	Le Chesnay

Sponsors (1)

Lead Sponsor	Collaborator
Versailles Hospital

Country where clinical trial is conducted

France, 

Outcome

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