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Trial record 1 of 39 for:    "primary progressive multiple sclerosis"
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Dimethyl Fumarate Treatment of Primary Progressive Multiple Sclerosis (FUMAPMS)

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ClinicalTrials.gov Identifier: NCT02959658
Recruitment Status : Recruiting
First Posted : November 9, 2016
Last Update Posted : December 5, 2016
Sponsor:
Collaborator:
Biogen
Information provided by (Responsible Party):
Helene Højsgaard Chow, Rigshospitalet, Denmark

Brief Summary:

This study aims to evaluate safety and efficacy of dimethyl fumarate treatment in patients with primary progressive multiple sclerosis (PPMS).

Half of the patients will receive dimethyl fumarate and the other half will receive placebo.


Condition or disease Intervention/treatment Phase
Primary Progressive Multiple Sclerosis Drug: Dimethyl Fumarate Drug: Placebo Oral Capsule Phase 2

Detailed Description:

Multiple sclerosis (MS) is a chronic, inflammatory disease of the central nervous system and is presumed to be caused by T cell-mediated autoimmune processes. PPMS has no registered treatment options only symptomatic treatment exists. Progressive forms of MS are characterized clinically by gradual symptom development with or without superimposed relapses.

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.


Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Dimethyl Fumarate Treatment of Primary Progressive Multiple Sclerosis
Study Start Date : November 2016
Estimated Primary Completion Date : December 2018
Estimated Study Completion Date : December 2019

Resource links provided by the National Library of Medicine

U.S. FDA Resources

Arm Intervention/treatment
Active Comparator: Active drug
Dimethyl fumarate, 240mg twice daily for 48 weeks
Drug: Dimethyl Fumarate
Other Name: Tecfidera
Placebo Comparator: Placebo
Placebo Oral Capsules, 2 tablets twice daily for 48 weeks
Drug: Placebo Oral Capsule
Manufactured to mimic Dimethyl Fumarate capsules



Primary Outcome Measures :
  1. Neuro filament light chain [ Time Frame: 0-48 weeks ]
    Changes in this measure is obtained over a course of 48 weeks. Patients will have a lumbar puncture performed at baseline and again at week 48.


Secondary Outcome Measures :
  1. Expanded Disability Status Scale (EDSS) [ Time Frame: 0-48 weeks ]
    Is assessed by neurostatus 03/09 by either the primary investigator or another medical doctor to whom the task has been delegated. The evaluation is performed at baseline and at week 48 and change is recorded.

  2. Timed 25-Foot Walk (T25FW) [ Time Frame: 0-48 weeks ]
    Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.

  3. Nine hole peg test (9HPT) [ Time Frame: 0-48 weeks ]
    Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.

  4. Symbol digit modalities test (SDMT) [ Time Frame: 0-48 weeks ]
    Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.

  5. Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS) [ Time Frame: 0-48 weeks ]
    Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.

  6. Low contrast visual acuity (LCVA) [ Time Frame: 0-48 weeks ]
    Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at baseline and at week 48 and change is recorded.

  7. Urinary distress inventory (UDI) [ Time Frame: 0-48 weeks ]
    Is assessed by questionnaire. The questionnaire is handed out at baseline and at week 48 and change is recorded.

  8. Fatigue Scale for Motor and Cognitive Functions (FSMC) [ Time Frame: 0-48 weeks ]
    Is assessed by questionnaire. The questionnaire is handed out at baseline and at week 48 and change is recorded.

  9. Multiple Sclerosis Impact Scale 29 (MSIS-29) [ Time Frame: 0-48 weeks ]
    Is assessed by questionnaire. The questionnaire is handed out at baseline and at week 48 and change is recorded.

  10. Cerebrospinal fluid cell count [ Time Frame: 0-48 weeks ]
    Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.

  11. Immunoglobulin type G index [ Time Frame: 0-48 weeks ]
    Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.

  12. Cerebrospinal fluid-serum albumin quotient [ Time Frame: 0-48 weeks ]
    Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.

  13. Chitinase 3 like 1 [ Time Frame: 0-48 weeks ]
    Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.

  14. matrix metalloproteinase 9 [ Time Frame: 0-48 weeks ]
    Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.

  15. C-X-C motif chemokine ligand 13 (CXCL13) [ Time Frame: 0-48 weeks ]
    Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.

  16. Myelin Basic protein [ Time Frame: 0-48 weeks ]
    Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded.

  17. Number of Gadolinium enhancing lesions on MRI [ Time Frame: 0-48 weeks ]
    Is assessed on MRI performed at baseline and at week 48. Change is recorded.

  18. Number of new or enlarged T2 lesions on MRI [ Time Frame: 0-48 weeks ]
    Is assessed on MRI performed at baseline and at week 48. Change is recorded.

  19. Percentage brain volume change [ Time Frame: 0-48 weeks ]
    Is assessed on MRI performed at baseline and at week 48. Change is recorded.

  20. Volume of T2 lesions, cortical grey matter (CGM), putamen, thalamus and normal-appearing white matter (NAWM) on MRI [ Time Frame: 0-48 weeks ]
    Is assessed on MRI performed at baseline and at week 48. Change is recorded.

  21. Magnetization transfer ratio of T2 lesions, putamen, thalamus, CGM and NAWM on MRI [ Time Frame: 0-48 weeks ]
    Is assessed on MRI performed at baseline and at week 48. Change is recorded.

  22. Diffusion tensor imaging measures (fractional anisotropy and mean diffusivity) of T2 lesions, putamen, thalamus, CGM and NAWM on MRI [ Time Frame: 0-48 weeks ]
    Is assessed on MRI performed at baseline and at week 48. Change is recorded.

  23. Cross sectional area at C2 level of the cervical spinal cord on MRI [ Time Frame: 0-48 weeks ]
    Is assessed on MRI performed at baseline and at week 48. Change is recorded.

  24. Circle drawing test at the time of the MRI [ Time Frame: 0-48 weeks ]
    Is assessed on MRI performed at baseline and at week 48. Change is recorded.


Other Outcome Measures:
  1. EDSS [ Time Frame: 48-96 weeks ]
    Is assessed by neurostatus 03/09 by either the primary investigator or another medical doctor to whom the task has been delegated. The evaluation is performed at week 48 and at week 96 and change is recorded.

  2. T25FW [ Time Frame: 48-96 weeks ]
    Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at week 48 and at week 96 and change is recorded.

  3. 9HPT [ Time Frame: 48-96 weeks ]
    Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at week 48 and at week 96 and change is recorded.

  4. SDMT [ Time Frame: 48-96 weeks ]
    Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at week 48 and at week 96 and change is recorded.

  5. BICAMS [ Time Frame: 48-96 weeks ]
    Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at week 48 and at week 96 and change is recorded.

  6. LCVA [ Time Frame: 48-96 weeks ]
    Is assessed by a trained research nurse, the primary investigator or another medical doctor to whom the task has been delegated. The test is performed at week 48 and at week 96 and change is recorded.

  7. UDI [ Time Frame: 48-96 weeks ]
    Is assessed by questionnaire. The questionnaire is handed out at week 48 and at week 96 and change is recorded.

  8. FSMC [ Time Frame: 48-96 weeks ]
    Is assessed by questionnaire. The questionnaire is handed out at week 48 and at week 96 and change is recorded.

  9. MSIS-29 [ Time Frame: 48-96 weeks ]
    Is assessed by questionnaire. The questionnaire is handed out at week 48 and at week 96 and change is recorded.

  10. Number of Gadolinium enhancing lesions on MRI [ Time Frame: 48-96 weeks ]
    Is assessed on MRI performed at week 48 and at week 96. Change is recorded.

  11. Number of new or enlarged T2 lesions on MRI [ Time Frame: 48-96 weeks ]
    Is assessed on MRI performed at week 48 and at week 96. Change is recorded.

  12. Percentage brain volume change [ Time Frame: 48-96 weeks ]
    Is assessed on MRI performed at week 48 and at week 96. Change is recorded.

  13. Volume of T2 lesions, cortical grey matter (CGM), putamen, thalamus and normal-appearing white matter (NAWM) on MRI [ Time Frame: 48-96 weeks ]
    Is assessed on MRI performed at week 48 and at week 96. Change is recorded.

  14. Magnetization transfer ratio of T2 lesions, putamen, thalamus, CGM and NAWM on MRI [ Time Frame: 48-96 weeks ]
    Is assessed on MRI performed at week 48 and at week 96. Change is recorded.

  15. Diffusion tensor imaging measures (fractional anisotropy and mean diffusivity) of T2 lesions, putamen, thalamus, CGM and NAWM on MRI [ Time Frame: 48-96 weeks ]
    Is assessed on MRI performed at week 48 and at week 96. Change is recorded.

  16. Cross sectional area at C2 level of the cervical spinal cord on MRI [ Time Frame: 48-96 weeks ]
    Is assessed on MRI performed at week 48 and at week 96. Change is recorded.

  17. Circle drawing test at the time of the MRI [ Time Frame: 48-96 weeks ]
    Is assessed on MRI performed at week 48 and at week 96. Change is recorded.



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.


Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age 18 to 60 years
  • 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:

  • Pregnancy or breast feeding
  • 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

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): NCT02959658


Contacts
Contact: Finn Sellebjerg, Professor finn.thorup.sellebjerg@regionh.dk

Locations
Denmark
Danish Multiple Sclerosis Center, Department of neurology Recruiting
Copenhagen, Denmark, 2100
Contact: Finn Sellebjerg, Professor       finn.thorup.sellebjerg@regionh.dk   
Contact: Helene Højsgaard Chow, MD       helene.hoejsgaard.jensen@regionh.dk   
Sponsors and Collaborators
Rigshospitalet, Denmark
Biogen
Investigators
Principal Investigator: Helene Højsgaard Chow, MD Rigshospitalet, Denmark

Responsible Party: Helene Højsgaard Chow, Principal Investigator, Rigshospitalet, Denmark
ClinicalTrials.gov Identifier: NCT02959658     History of Changes
Other Study ID Numbers: FUMAPMS2016
First Posted: November 9, 2016    Key Record Dates
Last Update Posted: December 5, 2016
Last Verified: December 2016
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Dimethyl Fumarate
Dermatologic Agents
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs