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Primary Progressive Multiple SclerosisPhase 2FUMAPMSNCT02959658

Dimethyl Fumarate Treatment of Primary Progressive Multiple Sclerosis

A Phase 2 study testing Dimethyl fumarate in people with Primary Progressive Multiple Sclerosis, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Primary Progressive Multiple Sclerosis
What is being tested?
Dimethyl fumarate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
54 participants
Where
1 siteDenmark
Study dates
Dec 2016to 9 Dec 2020
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Age 18 to 65 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
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  • 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

Who cannot join

  • 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
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  • 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

Trial locations and contacts

1 site in 1 country.

Denmark1 site

  • Danish Multiple Sclerosis Center, Department of neurology

    Copenhagen, 2100

Other trials in Denmark

About this study

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.

Read the 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.

Being tested
Dimethyl fumarate, Placebo
Medical subject headings
Multiple Sclerosis, Chronic Progressive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dimethyl fumarateDrug

    Also called Tecfidera, BG-12

  • PlaceboDrug

    Manufactured to mimic Dimethyl Fumarate capsules

Study groups in NCT02959658
Study groupRoleWhat they receive
Active drugActive comparatorDimethyl fumarate, 240mg twice daily for 48 weeks
Receives: Drug: Dimethyl fumarate
PlaceboPlacebo comparatorPlacebo Oral Capsules, 2 tablets twice daily for 48 weeks
Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Neurofilament light chain in the cerebrospinal fluid (CSF)

    CSF Neurofilament Light Chain (NFL) is measured twice over a course of 48 weeks. Patients will have a spinal tap performed at baseline and again at week 48.

    Measured: 0-48 weeks

Secondary outcomes (17)

  1. Expanded Disability Status Scale (EDSS)

    We will analyze the difference in EDSS change from screening visit to week 48 between the treatment and placebo group. EDSS is performed by a certified physician, primarily the PI.

    Measured: 0-48 weeks

  2. Timed 25-Foot Walk (T25FW)

    We will analyze the difference in T25FW change from screening visit to week 48 between the treatment and placebo group. T25FW is evaluated by the principal investigator or a delegated member of the study team.

    Measured: 0-48 weeks

  3. Nine hole peg test (9HPT)

    We will analyze the difference in 9HPT change from screening visit to week 48 between the treatment and placebo group. 9HPT is evaluated by the principal investigator or a delegated member of the study team.

    Measured: 0-48 weeks

  4. Symbol digit modalities test (SDMT)

    We will analyze the difference in the SDMT change from screening visit to week 48 between the treatment and placebo group using a general linear model with treatment allocation as factor and the screening SDMT value as covariate. SDMT is evaluated by the principal investigator or a delegated member of the study team.

    Measured: 0-48 weeks

  5. CSF/Serum Immunoglobulin type G index

    Is assessed from a sample of the cerebrospinal fluid at baseline and at week 48 and change is recorded. The analysis will be performed by the routine diagnostics department at the hospital where the spinal tap is performed.

    Measured: 0-48 weeks

  6. Cerebrospinal fluid-serum albumin quotient

    We will analyze the difference in change in CSF-serum albumin quotient from screening visit to week 48 between the treatment and placebo group. The analysis will be performed by the routine diagnostics department at the hospital where the spinal tap is performed.

    Measured: 0-48 weeks

  7. soluble CD14 (sCD14)

    We will analyze the difference in change in sCD14 concentration from screening visit to week 48 between the treatment and placebo group. The analysis is performed by a multiplex luminex assay (R\&D systems).

    Measured: 0-48 weeks

  8. soluble CD27 (sCD27)

    We will analyze the difference in change in sCD27 concentration from screening visit to week 48 between the treatment and placebo group. The analysis is performed by a multiplex luminex assay (R\&D systems).

    Measured: 0-48 weeks

  9. BCMA

    We will analyze the difference in change in BCMA concentration from screening visit to week 48 between the treatment and placebo group. The analysis is performed by a multiplex luminex assay (R\&D systems).

    Measured: 0-48 weeks

  10. Chitinase 3-like-1

    We will analyze the difference in change in CHI3L1 concentration from screening visit to week 48 visit between the treatment and placebo group. The analysis is performed by a multiplex luminex assay (R\&D systems).

    Measured: 0-48 weeks

  11. Myelin Basic protein (MBP)

    We will analyze the difference in change in MBP concentration from screening visit to week 48 between the treatment and placebo group. The analysis is performed by a enzyme-linked immunosorbent assay (ELISA) (R\&D DuoSet).

    Measured: 0-48 weeks

  12. Number of new or enlarged T2 lesions

    We will analyze the number of new or enlarging T2 lesions from screening visit to W48 between the treatment and placebo group. This analysis will be performed by our collaborator at Hvidovre Hospital (Danish Research Center for Magentic Resonance)

    Measured: 0-48 weeks

  13. Fractional anisotropy (FA) in Normal Appearing White Matter (NAWM)

    We will analyze the difference in change from screening to W48 of FA in NAWM between the treatment and placebo group. This analysis will be performed by our collaborator at Hvidovre Hospital (Danish Research Center for Magentic Resonance)

    Measured: 0-48 weeks

  14. Change in lesion volume

    We will analyze the change from screening to W48 in lesion volume. This analysis will be performed by our collaborator at Hvidovre Hospital (Danish Research Center for Magentic Resonance)

    Measured: 0-48 weeks

  15. Change from screening in in magnetization transfer ratio (MTR) of T2 lesions

    We will analyze the difference in change from screening to W48 in MTR of T2 lesions between the treatment and placebo group. This analysis will be performed by our collaborator at Hvidovre Hospital (Danish Research Center for Magentic Resonance).

    Measured: 0-48 weeks

  16. Thalamic volume

    We will analyze the difference in change from screening to W48 of thalamic volume between the treatment and placebo group. This analysis will be performed by our collaborator at Hvidovre Hospital (Danish Research Center for Magentic Resonance).

    Measured: 0-48 weeks

  17. Percent brain volume change (PBVC)

    We will analyze the difference in percentage change in brain volume from screening visit to week 48 between the treatment and placebo group. This analysis will be performed by our collaborator at Hvidovre Hospital (Danish Research Center for Magentic Resonance).

    Measured: 0-48 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Nov 2016 (estimated)
  2. Study startDec 2016
  3. Primary completion21 Dec 2019
  4. Study completion9 Dec 2020

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
54 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02959658
Sponsor's protocol ID
FUMAPMS2016
Acronym
FUMAPMS
Status last verified
Dec 2020
First submitted
8 Nov 2016
Last updated
24 Dec 2020
Results posted
No
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • 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.

    PubMed 37369602

  • 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.

    PubMed 34429340

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Dimethyl fumarate in people with Primary Progressive Multiple Sclerosis, run by Copenhagen University Hospital, Rigshospitalet at 1 site in Denmark.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 13 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 Dec 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Denmark. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Neurofilament light chain in the cerebrospinal fluid (CSF) (time frame: 0-48 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02959658, which also lists 2 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 Dec 2020.

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