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

• ClinicalTrials.gov Identifier: NCT04357613
• Recruitment Status: Not yet recruiting
• First Posted: April 22, 2020
• Last Update Posted: August 7, 2020
• Sponsor: Versailles Hospital
• Information provided by (Responsible Party): Philippe ROUSSELOT, Versailles Hospital

Study Description

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%.

Condition or disease	Intervention/treatment	Phase
SARS Virus	Drug: Experimental drug	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 99 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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.
• Estimated Study Start Date: September 1, 2020
• Estimated Primary Completion Date: December 1, 2020
• Estimated Study Completion Date: December 1, 2021

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. To evaluate the benefit of early imatinib therapy to prevent severe COVID-19 disease in hospitalized aged patients. [ Time Frame: 30 days ]
   To evaluate the 30 days mortality rate in aged patients hospitalized with COVID-19

Secondary Outcome Measures :

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

Eligibility Criteria

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

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

Contacts and Locations

Contacts

Contact: Laure Morisset; +33139239785; lmorisset@ch-versailles.fr

Locations

France

CHU Bordeaux

Bordeaux, France

Contact: Malvy

CH de Versailles

Le Chesnay, France

Contact: Philippe Rousselot

Sponsors and Collaborators

Versailles Hospital

Investigators

• Principal Investigator: Philippe Rousselot; CH Versailles

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

• Responsible Party: Philippe ROUSSELOT, MD, Versailles Hospital
• ClinicalTrials.gov Identifier: NCT04357613
• Other Study ID Numbers: P20/05_IMAGE19
• First Posted: April 22, 2020
• Last Update Posted: August 7, 2020
• Last Verified: August 2020

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No