Imatinib for Multiple Sclerosis (MS) Relapses

Tomas Olsson

Status and phase: Unknown; Phase 2

Conditions: Multiple Sclerosis

Treatments: Drug: Methylprednisolone; Drug: Imatinib Mesylate

Study type: Interventional

Funder types: Other

Identifiers

NCT03674099

Imatinib MS

Details and patient eligibility

About

To investigate if treatment with Imatinib results in a better outcome than standard care in form of Methylprednisolone(MP) after MS-associated relapses.

Enrollment: 200 estimated patients

Sex: All

Ages: 18 to 55 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• An acute exacerbation, relapse, in persons with RRMS, either newly diagnosis or on treatment with one of the long-term immunomodulatory drugs, or possible MS where the diagnosis is supported by typical MRI or cerebrospinal fluid changes typical of MS (this enables inclusion of persons with a first neuroinflammatory bout, with high risk of developing MS before fulfilling the McDonald criteria for definite MS, or high risk for developing MS in the category clinically isolated syndrome (CIS)/possible MS with supporting MRI lesions and/or cerebrospinal fluid aberrations suggesting intra-thecal immunoglobulin synthesis with oligoclonal bands/and/or increased free Kappa Light chains. The relapse should be deemed to require relapse treatment by the investigator and affect a functional domain with a minimum of grade 2.

• 18-55 years of age

• Affection of any of the following EDSS sub-domains representing the targeted neurological deficit: 1. Visual function. grade 0-6, 2. Brain stem function grade 0-5. 3. Pyramidal function, grade 0-6. 4. Cerebellar function, grade 0-5. 5. Sensory function grade 0-6, and deterioration at least one step in any of these EDSS domains

• EDSS ≤ 6 before the acute exacerbation

• Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, if they are using effective methods of contraception during the study. Acceptable birth control methods are those with a failure rate of less than 1% per year when used consistently and correctly according to CTFG, September 2014 "Recommendations related to contraception and pregnancy testing in clinical trials". Such methods include:

  1. Combined (estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation.

     • oral
     • intravaginal
     • transdermal

  2. progestogen-only hormonal contraception associated with inhibition of ovulation

     • oral
     • injectable
     • implantable

  3. intrauterine device (IUD)

  4. intrauterine hormone-releasing system (IUS)

  5. bilateral tubal occlusion

  6. total abstinence or vasectomized partner.

Exclusion criteria

• A pseudo-relapse should be excluded, as deemed by the experienced treating neurologist, and as evidenced by an active infection, likely with fever, with reappearing new signs and symptoms in a previously affected neurological function.
• Inability to provide informed consent
• Concomitant medication with drugs which may increase the plasma concentration of Imatinib - ketoconazole, itraconazole , erythromycin and clarithromycin
• Concomitant medication with drugs which may decrease the plasma concentration of Imatinib: dexamethasone, phenytoin, carbamazepin, rifampicin, phenobarbital, fosphenytoin, primidon, Hypericum perforatum (St John's wort).
• Female patients with childbearing potential, if pregnancy cannot be excluded by pregnancy test (urine point-of-care pregnancy test).
• Patient is participating in other interventional study
• General infection or any other condition judged by the treating neurologist to contra-indicate Imatinib
• Any laboratory deviation of general bodily functions such as kidney, or renal function judged to be of clinical significance by the treating neurologist constitutes an exclusion criteria.
• Patients with a positive Hepatitis B-DNA test result or serology indicating latent infection.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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200 participants in 2 patient groups

Imatinib

Experimental group

Description:

Imatinib will be administered orally one tablet (400mg) twice daily, 800mg per day for 14 consecutive days.

Treatment:

Drug: Imatinib Mesylate

Methylprednisolone

Active Comparator group

Description:

Methylprednisolone will be administered once a day either in tablets; Medrol 1g per day or iv; Solumedrol 1000 mg per day, both for three consecutive days.

Treatment:

Drug: Methylprednisolone