IMATINIB IN COVID-19 DISEASE IN AGED PATIENTS.

NCT04357613 | Unknown Phase 2 DMC

• 1 other identifier: P20/05_IMAGE19
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 2

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%.

Conditions

SARS Virus

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (9)

• To evaluate the feasibility of imatinib therapy.

  Day 14

• To evaluate safety of imatinib therapy

  3 months

• To evaluate the clinical evolution

  3 months

• To evaluate the progression rate to severe COVID-19 disease

  3 months

• To evaluate mortality

  14 days

Study Arms (2)

Expérimental ARM

EXPERIMENTAL

800mg/d IMATINIB during 14days

Drug: Experimental drug

Comparator ARM

NO INTERVENTION

Standard of care

Interventions

Experimental drug DRUG

Imatinib 800mg/d during 14days

Expérimental ARM

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• Versailles Hospital: lead

Study Sites (2)

CHU Bordeaux

Bordeaux, France

Location

CH de Versailles

Le Chesnay, France

Location

Related Publications (1)

• 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.

  PMID: 32999432 DERIVED

MeSH Terms

Conditions

Severe Acute Respiratory Syndrome

Interventions

Drugs, Investigational

Condition Hierarchy (Ancestors)

Respiratory Tract Infections; Infections; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• Philippe Rousselot

  CH Versailles

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laure Morisset

CONTACT

+33139239785; lmorisset@ch-versailles.fr

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: April 20, 2020
• First Posted: April 22, 2020
• Study Start: September 1, 2020
• Primary Completion: December 1, 2020
• Study Completion: December 1, 2021
• Last Updated: August 7, 2020

Record last verified: 2020-08

Locations

FR (2)