Clinical trial NCT04357613: IMATINIB IN COVID-19 DISEASE IN AGED PATIENTS.
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.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: SARS Virus
Lead sponsor: Versailles Hospital
Sponsor class: OTHER
First posted: 2020-04-22
Enrollment: 99
Sex: ALL
Minimum age (years): 70
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief 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%.


Eligibility criteria: 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

Primary outcomes:
measure: To evaluate the benefit of early imatinib therapy to prevent severe COVID-19 disease in hospitalized aged patients.
timeFrame: 30 days
Secondary outcomes:
measure: To evaluate the feasibility of imatinib therapy.
timeFrame: Day 14
measure: To evaluate safety of imatinib therapy
timeFrame: 3 months
measure: To evaluate the clinical evolution
timeFrame: 3 months
measure: To evaluate the progression rate to severe COVID-19 disease
timeFrame: 3 months
measure: To evaluate mortality
timeFrame: 14 days
measure: To evaluate mortality
timeFrame: 60 days
measure: To evaluate mortality
timeFrame: 90 days
measure: To evaluate viral load
timeFrame: 14 days
measure: To evaluate plasmatic levels of imatinib
timeFrame: 14 days
Other outcomes:
Locations:
city: Bordeaux
country: France
facility: CHU Bordeaux
city: Le Chesnay
country: France
facility: CH de Versailles
Study officials:
affiliation: CH Versailles
name: Philippe Rousselot
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.