Multiple Sclerosis
Conditions
Brief summary
The purpose of this study is to explore whether DMF (Dimethyl Fumarate) or MMF (monomethyl fumarate) its main bioactive metabolite, is capable of entering the central nervous system in SPMS patients that are being treated with Tecfidera®. PK samples (pharmacokinetics - or the amount of study drug in blood) will be tested to compare with PK samples, the amount of study drug, in spinal fluid (CSF).
Interventions
DRUGBG00012 (DMF) (Tecfidera®.)
Subjects will take DMF 120 mg BID for the first 4 weeks of treatment followed by DMF 240 mg BID for 24 weeks.
Sponsors
Biogen
Multiple Sclerosis Center of Northeastern New York
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
25 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
(MS Population): To be eligible to participate in this study, candidates must meet the following eligibility criteria at screening, or at the timepoint specified in the individual eligibility criterion listed: 1. Ability to understand the purpose and risks of the study and provide signed and dated informed consent and authorization to use protected health information (PHI) in accordance with national and local patient privacy regulations. Subjects must provide separate informed consent to participate in this CSF study. 2. Aged 25 to 65 years-old, inclusive, at the time of informed consent. 3. Male of female subject with a confirmed diagnosis of SPMS. 4. EDSS score between 3 and 7, inclusive, at screening. 5. Weight should be between 130 and 200 lb.
Exclusion criteria
(MS Population) * Candidates will be excluded from study entry if any of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The primary objective of the study is to investigate the PK (drug level) of MMF( the primary metabolite of study drug) conjugate in plasma in subjects with SPMS. | treatment in week 6 | Concentration of MMF conjugate in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6 |
| The primary objective of the study is to investigate the PK (drug level) of DMF(study drug) in CSF with SPMS. | post-DMF treatment in Week 6 | Concentration of DMF in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6. |
| The primary objective of the study is to investigate the PK (drug level) of DMF(study drug) in plasma in subjects with SPMS. | treatment in week 6 | Concentration of DMF in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6 |
| The primary objective of the study is to investigate the PK (drug level) of MMF(the primary metabolite of study drug) in CSF with SPMS. | treatment in week 6 | Concentration of MMF in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6. |
| The primary objective of the study is to investigate the PK (drug level) of MMF( the primary metabolite of study drug) in plasma in subjects with SPMS. | treatment in week 6 | Concentration of MMF in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6 |
| The primary objective of the study is to investigate the PK (drug level) of DMF conjugate (study drug) in CSF with SPMS. | treatment in week 6 | Concentration of DMF conjugate in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6. |
| The primary objective of the study is to investigate the PK (drug level) of DMF conjugate (study drug) in plasma in subjects with SPMS. | treatment in week 6 | Concentration of DMF conjugate in plasma predose and at 2,3,5,6, 7 and 8 hours post-DMF treatment at Week 6 |
| The primary objective of the study is to investigate the PK (drug level) of MMF (the primary metabolite of study drug) conjugate in CSF with SPMS. | treatment in week 6 | Concentration of MMF conjugate in CSF predose and at 3, 5, 7 hours post DMF treatment in week 6. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| A secondary objective is to assess the effects of DMF on biomarkers of inflammation in the CSF of subjects with SPMS. | at 28 weeks | Biomarkers of inflammation (e.g., osteopontin, B cell activating factor, chemokines, and matrix metalloproteinase 9), which may reflect pathogenesis in SPMS. |
| A secondary objective is to assess the effects of DMF on biomarkers of neuroaxonal damage in the CSF of subjects with SPMS. | at 28 weeks | Biomarkers of neuroaxonal damage (e.g., neurofilament, myelin basic protein, glial fibrillary acidic protein, and neural cell adhesion molecule), which may reflect pathogenesis in SPMS. |
| A secondary objective is to assess the effects of DMF on biomarkers of oxidative stress in the CSF of subjects with SPMS. | at 28 weeks | Biomarkers of oxidative stress (e.g., myeloperoxidase, 8-Oxo-2'-deoxyguanosine and RNA biomarkers), which may reflect pathogenesis in SPMS |
| A secondary objective is to assess the effects of DMF on myelin lipid biomarkers in the CSF of subjects with SPMS. | at 28 weeks | Myelin lipid biomarkers (e.g., cholesterol, galactoceramide, sulfatides, and sphingomyelin), which may correlate with disability progression in MS patients. |
| A secondary objective is to assess the effects of DMF on pharmacogenomic biomarkers in the CSF of subjects with SPMS. | at 28 weeks | Pharmacogenomic biomarkers: DNA analysis from blood samples. |
| A secondary objective is to assess the effects of DMF on RNA samples from CSF cellular pellet for transcriptionomics in the CSF of subjects with SPMS. | at 28 weeks | RNA samples from CSF cellular pellet for transcriptionomics. |
| A secondary objective is to assess the effects of DMF on PD biomarkers downstream of Nrf2 in the CSF of subjects with SPMS. | at 28 weeks | PD biomarkers downstream of Nrf2, such as NAD(P)H hydrogenase \[quinone 1\], heme oxygenase-1, and aldo-keto reductase family 1 member B8 that have not been evaluated in CNS. |
Countries
United States
Outcome results
None listed