Imatinib for Multiple Sclerosis (MS) Relapses

NCT03674099 | Unknown Phase 2 DMC

• 1 other identifier: Imatinib MS
• Study Type: interventional
• Target: 200
• Locations: 4 countries
• Sites: 14

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.

Conditions

Multiple Sclerosis

Keywords

Multiple Sclerosis relaps; Imatinib; Methylprednisolone

Outcome Measures

Primary Outcomes (1)

• Functional system score (FSS) change in the most worsened FSS after 28 days due to the acute relapse

  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

  28 days

Secondary Outcomes (9)

• Functional system score (FSS) change between baseline and week 12 in the most worsened FSS due to the acute relapse

  12 weeks

• Mean expanded disability status scale (EDSS) change between baseline and day 28

  28 days

• Mean change in 9-hole peg test (evaluates upper limb function) between baseline and day 28

  28 days

• Mean change in timed 25- walk between baseline and day 28

  28 days

• Mean change in symbol digital modality test (SDMT) between baseline and day 28

  28 days

Study Arms (2)

Imatinib

EXPERIMENTAL

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

Drug: Imatinib Mesylate

Methylprednisolone

ACTIVE COMPARATOR

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

Interventions

Imatinib Mesylate DRUG

Tablets 400 mg

Imatinib

Methylprednisolone DRUG

1 g tablets or infusion

Methylprednisolone

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• 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:
• Combined (estrogen and progestogen containing hormonal contraception associated with inhibition of ovulation.
• oral
• intravaginal
• transdermal
• progestogen-only hormonal contraception associated with inhibition of ovulation
• oral
• injectable
• implantable
• intrauterine device (IUD)
• intrauterine hormone-releasing system (IUS)
• bilateral tubal occlusion

You may not qualify if:

• 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
• Patients with a positive Hepatitis B-DNA test result or serology indicating latent infection.

Sponsors & Collaborators

• Tomas Olsson: lead
• The Swedish Research Council: collaborator

Study Sites (14)

Rigshospitalet

Copenhagen, 2100, Denmark

NOT YET RECRUITING

Uniklinik Köln

Cologne, 50937, Germany

RECRUITING

Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

UKSH Campus Kiel

Kiel, 24105, Germany

RECRUITING

Haukeland sjukhus

Bergen, 5021, Norway

NOT YET RECRUITING

Akershus University Hospital

Lørenskog, 1478, Norway

NOT YET RECRUITING

Rikshospitalet, Oslo

Oslo, 0372, Norway

NOT YET RECRUITING

Ullevåls sjukhus

Oslo, 0424, Norway

NOT YET RECRUITING

Karolinska Universityhospital, Huddinge

Huddinge, Stockholm County, 14186, Sweden

RECRUITING

Neurology Sahlgrenska Hospital

Gothenburg, 41345, Sweden

RECRUITING

Linköping University Hospital

Linköping, 58185, Sweden

RECRUITING

Akademiskt specialistcentrum

Stockholm, 11341, Sweden

RECRUITING

Karolinska Universitetssjukhuset, Solna

Stockholm, 17176, Sweden

RECRUITING

Uppsala University Hospital

Uppsala, 75185, Sweden

RECRUITING

MeSH Terms

Conditions

Multiple Sclerosis

Interventions

Imatinib Mesylate; Methylprednisolone

Condition Hierarchy (Ancestors)

Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Central Study Contacts

Tomas Olsson, MD, Prof

CONTACT

+46707213598; Tomas.Olsson@ki.se

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Treating physician not blinded, evaluating physician blinded.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Model Details: Randomized, single-blinded, controlled.

Study Record Dates

• First Submitted: September 14, 2018
• First Posted: September 17, 2018
• Study Start: October 1, 2018
• Primary Completion: December 31, 2022
• Study Completion: July 30, 2023
• Last Updated: August 2, 2021

Record last verified: 2021-07

Data Sharing

• IPD Sharing: Will not share

Locations

DE (3); DK (1); SE (6); NO (4)