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Imatinib for Multiple Sclerosis (MS) Relapses

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ClinicalTrials.gov Identifier: NCT03674099
Recruitment Status : Recruiting
First Posted : September 17, 2018
Last Update Posted : August 14, 2019
Sponsor:
Collaborator:
The Swedish Research Council
Information provided by (Responsible Party):
Tomas Olsson, Karolinska Institutet

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

Condition or disease Intervention/treatment Phase
Multiple Sclerosis Drug: Imatinib Mesylate Drug: Methylprednisolone Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 200 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Randomized, single-blinded, controlled.
Masking: Single (Outcomes Assessor)
Masking Description: Treating physician not blinded, evaluating physician blinded.
Primary Purpose: Treatment
Official Title: Imatinib for Multiple Sclerosis (MS) Relapses - a Phase II, Randomised Study
Actual Study Start Date : October 1, 2018
Estimated Primary Completion Date : December 31, 2020
Estimated Study Completion Date : July 30, 2021


Arm Intervention/treatment
Experimental: Imatinib
Imatinib will be administered orally one tablet (400mg) twice daily, 800mg per day for 14 consecutive days.
Drug: Imatinib Mesylate
Tablets 400 mg

Active Comparator: Methylprednisolone
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.
Drug: Methylprednisolone
1 g tablets or infusion




Primary Outcome Measures :
  1. Functional system score (FSS) change in the most worsened FSS after 28 days due to the acute relapse [ Time Frame: 28 days ]
    The primary endpoint is mean change between baseline and day 28 in the most worsened FSS due to the acute relapse comparing MP and Imatinib. In case more than one domain is affected, priority of selected FSS should be in the following order: 1) Pyramidal, 2) Brain stem, 3) Cerebellar, 4) Visual, 5) Sensory. At least a two step deterioration due to neuroinflammatory bout should have occurred. Bowel and Cerebral domains will not be considered in the primary endpoints. The FSS is graded accordingly: 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 6. bowel/bladder function 7. Cerebral functions


Secondary Outcome Measures :
  1. Functional system score (FSS) change between baseline and week 12 in the most worsened FSS due to the acute relapse [ Time Frame: 12 weeks ]
    In case more than one domain is affected, priority of selected FSS should be in the following order: 1) Pyramidal, 2) Brain stem, 3) Cerebellar, 4) Visual, 5) Sensory. At least a two step deterioration due to neuroinflammatory bout should have occurred.

  2. Mean expanded disability status scale (EDSS) change between baseline and day 28 [ Time Frame: 28 days ]
    Calculation of EDSS summary score is based on the FSS score, from 0-5 with 0 representing normal neurological exam and 10 representing death by MS

  3. Mean change in 9-hole peg test (evaluates upper limb function) between baseline and day 28 [ Time Frame: 28 days ]
    Evaluates upper limb function

  4. Mean change in timed 25- walk between baseline and day 28 [ Time Frame: 28 days ]
  5. Mean change in symbol digital modality test (SDMT) between baseline and day 28 [ Time Frame: 28 days ]
    Evaluates cognitive function, with a score range of 0 to 110, with 110 representing the best cognitive function

  6. Mean change in Multiple Sclerosis Impact Scale (MSIS-29; MS-specific quality of life (QoL) scale) between baseline and day 28 [ Time Frame: 28 days ]
    The MISIS-29 consists of 29 items (composed of 20- item physical scale and a 9-item psychological scale), graded from 1-5 points with 5 indicating the most severe impact. The points for the two scales are individually summarized. The physical scale results in a sum with a range 20-100 , where 100 indicates the worse health. The psychological scale is similarly resulting in a range between to 9- 45, where 9 is the least and 45 is the worst.

  7. Mean change in EQ5D (EuroQol 5 dimensions) (general QoL) between baseline and day 28. [ Time Frame: 28 days ]
    EQ-5D is a standardized instrument developed by the EuroQol Group as a measure of health-related quality of life comprises five dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression

  8. Any difference in number of new brain MRI lesions at day 14 with regards to the baseline, comparing the two drugs [ Time Frame: 14 days ]
  9. Any difference in number of new brain MRI lesions at day 28 with regards to the baseline, comparing the two drugs [ Time Frame: 28 days ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03674099


Contacts
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Contact: Tomas Olsson, MD, Prof +46707213598 Tomas.Olsson@ki.se

Locations
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Denmark
Rigshospitalet Not yet recruiting
Copenhagen, Denmark, 2100
Contact: FinnThorup Sellebjerg, MD       finn.thorup.sellebjerg@regionh.dk   
Norway
Haukeland sjukhus Not yet recruiting
Bergen, Norway, 5021
Contact: Kjell Morten Myhr, MD       kjell-morten.myhr@helse-bergen.no   
Akershus University Hospital Recruiting
Lørenskog, Norway, 1478
Contact: Trygve Holmöy, MD       trygve.holmoy@medisin.uio.no   
Rikshospitalet, Oslo Not yet recruiting
Oslo, Norway, 0372
Contact: Hanne Flinstad Harbo, MD       h.f.harbo@medisin.uio.no   
Ullevåls sjukhus Not yet recruiting
Oslo, Norway, 0424
Contact: Elisabeth G Celius, MD       uxelgu@ous-hf.no   
Sweden
Karolinska Universityhospital, Huddinge Recruiting
Huddinge, Stockholm, Sweden, 14186
Contact: Katharina Fink, MD       Katharina.Fink@sll.se   
Neurology Sahlgrenska Hospital Recruiting
Göteborg, Sweden, 41345
Contact: Jan Lycke, MD       jan.lycke@neuro.gu.se   
Linköping University Hospital Not yet recruiting
Linköping, Sweden, 58185
Contact: Charlotte Dahle, MD       Charlotte.Dahle@regionostergotland.se   
Akademiskt specialistcentrum Recruiting
Stockholm, Sweden, 11341
Contact: Fredrik Piehl, MD    +46-851779840    Fredrik.Piehl@ki.se   
Karolinska Universitetssjukhuset, Solna Recruiting
Stockholm, Sweden, 17176
Contact: Tomas Olsson, MD    +46707213598    Tomas.Olsson@ki.se   
Uppsala University Hospital Not yet recruiting
Uppsala, Sweden, 75185
Contact: Joachim Burman, MD       joachim.burman@akademiska.se   
Sponsors and Collaborators
Tomas Olsson
The Swedish Research Council

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Responsible Party: Tomas Olsson, Professor, Karolinska Institutet
ClinicalTrials.gov Identifier: NCT03674099    
Other Study ID Numbers: Imatinib MS
First Posted: September 17, 2018    Key Record Dates
Last Update Posted: August 14, 2019
Last Verified: October 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Tomas Olsson, Karolinska Institutet:
Multiple Sclerosis relaps
Imatinib
Methylprednisolone
Additional relevant MeSH terms:
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Multiple Sclerosis
Sclerosis
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Methylprednisolone
Methylprednisolone Acetate
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone acetate
Imatinib Mesylate
Prednisolone hemisuccinate
Prednisolone phosphate
Antineoplastic Agents
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Anti-Inflammatory Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Gastrointestinal Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists