Dimethyl Fumarate Treatment of Primary Progressive Multiple Sclerosis
NCT ID: NCT02959658
Last Updated: 2020-12-24
Study Results
The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.
Basic Information
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COMPLETED
PHASE2
54 participants
INTERVENTIONAL
2016-12-31
2020-12-09
Brief Summary
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Half of the patients will receive dimethyl fumarate and the other half will receive placebo.
Detailed Description
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Fumarates have long been known to have disease-attenuating effects in psoriasis. They have been in routine use in dermatology in Germany for several decades. Dimethyl fumarate has the interesting property of combining immunological effects, at least partly mediated by interference with nuclear factor kappa B and other transcription factors, and also anti-oxidative and neuroprotective effects mediated by activation of the transcription factor Nuclear factor (erythroid-derived 2)-Related Factor 2 (NRF2). Dimethyl fumarate is currently approved for treatment of relapsing-remitting MS by the European medicines Agency in a dose of 240 mg twice per day.
Neurofilament light chain (NFL) is a treatment responsive biomarker of neuronal and axonal death when appearing in the cerebrospinal fluid (CSF) and it has been associated with long-term prognosis in MS. The concentration is often elevated in progressive MS patients. Treatment effect is measured by measuring changes in neurofilament light chain concentration over the course of 48 weeks of treatment with either active drug or placebo.
Conditions
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Active drug
Dimethyl fumarate, 240mg twice daily for 48 weeks
Dimethyl fumarate
Placebo
Placebo Oral Capsules, 2 tablets twice daily for 48 weeks
Placebo
Manufactured to mimic Dimethyl Fumarate capsules
Interventions
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Dimethyl fumarate
Placebo
Manufactured to mimic Dimethyl Fumarate capsules
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* PPMS according to the McDonald (2010) and Lublin (2014) criteria
* Disease duration at least one year
* EDSS ≤ 6.5
* Written informed consent to study participation
* No other signs of significant disease judged by the investigator
* Eligible for randomization to active treatment or placebo as assessed by CSF NFL levels above 380ng/L
* Not eligible for randomization as assessed by CSF biomarker studies but accepts follow-up and open-label treatment per protocol
* Patients not eligible for randomization due to low NFL concentrations in CSF at screening can be followed up after 48 weeks, and are eligible for open-label treatment if they fulfil one of the following clinical criteria of disease progression:
* 1 point increase in EDSS score from screening to week 48 if screening EDSS \<6
* 0.5 point increase in EDSS score from screening to week 48 if screening EDSS\>5.5
* 2 point increase in a physical functional system
* Worsening in SDMT, 9HPT or T25FW \>20% from screening to week 48
Exclusion Criteria
* Lack of effective contraception for women of child-bearing potential
* Relapse within 6 months of inclusion
* Methylprednisolone treatment within 3 months of inclusion
* Treatment with interferon-beta, glatiramer acetate, immunoglobulin G or other immunomodulatory treatment within 6 months of inclusion
* Treatment with mitoxantrone, cyclophosphamide, azathioprine or other immunosuppressive treatment within 6 months of inclusion
* Findings on the screening MRI judged to preclude participation by the treating physician
* Other diseases associated with immunodeficiency
* Other diseases judged to be relevant by the treating physician
* Anticoagulant therapy other than platelet inhibitors
* Active malignant disease in the previous 5 years
* Renal insufficiency or blood creatinine \> 150 μmol/l
* Present or chronic infection with hepatitis B virus, hepatitis C virus, HIV (tested in the screening blood samples) or other infections found to be relevant by the treating physician.
* Psychiatric disorders or other disorders impairing the patient's ability to participate in the trial
* Contraindication to MRI
* Known allergy or hypersensitivity to dimethyl fumarate
18 Years
65 Years
ALL
No
Sponsors
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Biogen
INDUSTRY
Rigshospitalet, Denmark
OTHER
Responsible Party
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Jacob L Talbot
Principal Investigator
Principal Investigators
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Jacob Lando Talbot, MD
Role: PRINCIPAL_INVESTIGATOR
Rigshospitalet, Denmark
Locations
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Danish Multiple Sclerosis Center, Department of neurology
Copenhagen, , Denmark
Countries
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References
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von Essen MR, Talbot J, Hansen RHH, Chow HH, Lundell H, Siebner HR, Sellebjerg F. Intrathecal CD8+CD20+ T Cells in Primary Progressive Multiple Sclerosis. Neurol Neuroimmunol Neuroinflamm. 2023 Jun 27;10(5):e200140. doi: 10.1212/NXI.0000000000200140. Print 2023 Sep.
Hojsgaard Chow H, Talbot J, Lundell H, Gobel Madsen C, Marstrand L, Lange T, Mahler MR, Buhelt S, Holm Hansen R, Blinkenberg M, Romme Christensen J, Soelberg Sorensen P, Rode von Essen M, Siebner HR, Sellebjerg F. Dimethyl Fumarate Treatment in Patients With Primary Progressive Multiple Sclerosis: A Randomized, Controlled Trial. Neurol Neuroimmunol Neuroinflamm. 2021 Aug 24;8(5):e1037. doi: 10.1212/NXI.0000000000001037. Print 2021 Sep.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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FUMAPMS2016
Identifier Type: -
Identifier Source: org_study_id