Dimethyl Fumarate Treatment of Primary Progressive Multiple Sclerosis

NCT02959658 | Completed Phase 2 DMC

• 1 other identifier: FUMAPMS2016
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Progressive Multiple Sclerosis

Outcome Measures

Primary Outcomes (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.

  0-48 weeks

Secondary Outcomes (17)

• Expanded Disability Status Scale (EDSS)

  0-48 weeks

• Timed 25-Foot Walk (T25FW)

  0-48 weeks

• Nine hole peg test (9HPT)

  0-48 weeks

• Symbol digit modalities test (SDMT)

  0-48 weeks

• CSF/Serum Immunoglobulin type G index

  0-48 weeks

Other Outcomes (14)

• BVMTR

  0-48 weeks & 48-96 weeks

• California Verbal Learning Test 2 (CVLT-II)

  0-48 weeks & 48-96 weeks

• UDI

  0-48 weeks & 48-96 weeks

Study Arms (2)

Active drug

ACTIVE COMPARATOR

Dimethyl fumarate, 240mg twice daily for 48 weeks

Drug: Dimethyl fumarate

Placebo

PLACEBO COMPARATOR

Placebo Oral Capsules, 2 tablets twice daily for 48 weeks

Drug: Placebo

Interventions

Dimethyl fumarate DRUG

Also known as: Tecfidera, BG-12

Active drug

Placebo DRUG

Manufactured to mimic Dimethyl Fumarate capsules

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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:
• point increase in EDSS score from screening to week 48 if screening EDSS \<6
• point increase in EDSS score from screening to week 48 if screening EDSS\>5.5
• point increase in a physical functional system
• Worsening in SDMT, 9HPT or T25FW \>20% from screening to week 48

You may not qualify if:

• Pregnancy or breast feeding
• Lack of effective contraception for women of child-bearing potential
• 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

Sponsors & Collaborators

• Rigshospitalet, Denmark: lead
• Biogen: collaborator

Study Sites (1)

Danish Multiple Sclerosis Center, Department of neurology

Copenhagen, 2100, Denmark

Location

Related Publications (2)

• 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.

  PMID: 37369602 DERIVED

• 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.

  PMID: 34429340 DERIVED

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

Dimethyl Fumarate

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Fumarates; Dicarboxylic Acids; Acids, Acyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• Jacob Lando Talbot, MD

  Rigshospitalet, Denmark

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 8, 2016
• First Posted: November 9, 2016
• Study Start: December 1, 2016
• Primary Completion: December 21, 2019
• Study Completion: December 9, 2020
• Last Updated: December 24, 2020

Record last verified: 2020-12

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)