Primary progressive multiple sclerosis (PPMS) MedDRA version: 21.1 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Tecfidera
Product Name: dimethyl fumarate
Product Code: dimethyl fumarate
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: dimethyl fumarate
CAS Number: 624-49-7
Other descriptive n
Sponsors
Finn Sellebjerg
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Age 18 to 60 years • PPMS according to the McDonald (2010) and Lublin (2014) criteria • Disease duration at least one year • Expanded Disability Status Scale (EDSS) under or equal to 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 cerebrospinal fluid (CSF) Neurofilament light chain (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 less than 6 • 0.5 point increase in EDSS score from screening to week 48 if screening EDSS is more than 5.5 • 2 point increase in a physical functional system • Worsening in Symbol Digit Modalities Test, 9 hole peg test or timed 25 foot walk test more than 20% from screening to week 48 Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 54 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
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 insuffiency or blood creatinine more than 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The trial investigates the use of dimethyl fumarate treatment in patients with primary progressive multiple sclerosis (PPMS).;Secondary Objective: Not applicable;Primary end point(s): The primary aim of the study is to assess whether 48 weeks of treatment with dimethyl fumarate can decrease neuroaxonal damage in PPMS as assessed by: • Difference in change in the CSF concentration of NFL from screening to week 48 in PPMS patients treated with dimethyl fumarate or placebo ;Timepoint(s) of evaluation of this end point: Evaluation of the primary endpoint is done after 48 weeks of treatment with either dimethyl fumarate or placebo | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • Clinical endpoints: comparison of change from screening to week 48 in patients treated with dimethyl fumarate and placebo for the following variables: ? Expanded Disability Status Scale (EDSS) ? Timed 25-Foot Walk (T25FW) ? Nine-Hole Peg Test (9HPT) ? Brief International Cognitive Assessment for MS (BICAMS) ? Symbol Digit Modalities Test (SDMT) • CSF endpoints: comparison of change from screening to week 48 in patients treated with dimethyl fumarate and placebo for the following variables: ? IgG-index ? CSF-serum albumin quotient ? Concentrations of: chitinase-3-like-1, sCD14, sCD27, BCMA (TNFRSF17) and myelin basic protein (MBP) • Magnetic resonance imaging (MRI) endpoints: comparison of change from screening to week 48 in patients treated with dimethyl fumarate and placebo for the following variables: ? Number of new or enlarged T2 lesions ? Fractional anisotropy (FA) in Normal Appearing White Matter (NAWM) ? Lesion volume ? Magnetization Transfer Ratio (MTR) in lesions ? Thalamic volume ? Percentage brain volume change (PBVC) ;Timepoint(s) of evaluation of this end point: Evaluation of the secondary endpoints are done after 48 weeks of treatment with either dimethyl fumarate or placebo | — |
Countries
Denmark
Contacts
Public ContactRigshospitalet
Helene Højsgaard Jensen
Outcome results
None listed