Clinical trial NCT03674099: Imatinib for Multiple Sclerosis (MS) Relapses
Official title: Imatinib for Multiple Sclerosis (MS) Relapses - a Phase II, Randomised Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Multiple Sclerosis
Keywords: Multiple Sclerosis relaps
Imatinib
Methylprednisolone
Lead sponsor: Karolinska Institutet
Sponsor class: OTHER
Collaborators: name: The Swedish Research Council
First posted: 2018-09-17
Enrollment: 200
Sex: ALL
Minimum age (years): 18
Maximum age (years): 55
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomized, single-blinded, controlled.
Primary purpose: TREATMENT

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.


Eligibility 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.

Primary outcomes:
measure: Functional system score (FSS) change in the most worsened FSS after 28 days due to the acute relapse
timeFrame: 28 days
Secondary outcomes:
measure: Functional system score (FSS) change between baseline and week 12 in the most worsened FSS due to the acute relapse
timeFrame: 12 weeks
measure: Mean expanded disability status scale (EDSS) change between baseline and day 28
timeFrame: 28 days
measure: Mean change in 9-hole peg test (evaluates upper limb function) between baseline and day 28
timeFrame: 28 days
measure: Mean change in timed 25- walk between baseline and day 28
timeFrame: 28 days
measure: Mean change in symbol digital modality test (SDMT) between baseline and day 28
timeFrame: 28 days
measure: Mean change in Multiple Sclerosis Impact Scale (MSIS-29; MS-specific quality of life (QoL) scale) between baseline and day 28
timeFrame: 28 days
measure: Mean change in EQ5D (EuroQol 5 dimensions) (general QoL) between baseline and day 28.
timeFrame: 28 days
measure: Any difference in number of new brain MRI lesions at day 14 with regards to the baseline, comparing the two drugs
timeFrame: 14 days
measure: Any difference in number of new brain MRI lesions at day 28 with regards to the baseline, comparing the two drugs
timeFrame: 28 days
Other outcomes:
Locations:
city: Copenhagen
country: Denmark
facility: Rigshospitalet
city: Hamburg
country: Germany
facility: Hamburg-Eppendorf
city: Kiel
country: Germany
facility: UKSH Campus Kiel
city: Köln
country: Germany
facility: Uniklinik Köln
city: Bergen
country: Norway
facility: Haukeland sjukhus
city: Lørenskog
country: Norway
facility: Akershus University Hospital
city: Oslo
country: Norway
facility: Rikshospitalet, Oslo
city: Oslo
country: Norway
facility: Ullevåls sjukhus
city: Huddinge
country: Sweden
facility: Karolinska Universityhospital, Huddinge
state: Stockholm
city: Göteborg
country: Sweden
facility: Neurology Sahlgrenska Hospital
city: Linköping
country: Sweden
facility: Linköping University Hospital
city: Stockholm
country: Sweden
facility: Akademiskt specialistcentrum
city: Stockholm
country: Sweden
facility: Karolinska Universitetssjukhuset, Solna
city: Uppsala
country: Sweden
facility: Uppsala University Hospital
Study officials:
References: