Eligibility: Ages Eligible for Study: 18 Years to 58 Years
Key Inclusion Criteria:
Key Exclusion Criteria:
- Onset of SPMS at least 1 to 2 years prior to randomization. SPMS is defined as relapsing-remitting disease followed by progression of disability independent of or not explained by relapses.
- Have documented confirmed evidence of disease progression independent of clinical relapses over the 1 year prior to randomization.
- Have EDSS score of 3.0 to 6.5, inclusive.
- Have an multiple sclerosis (MS) Severity Score of 4 or higher.
ClinicalTrials.gov identifier: NCT02430532
- Have a diagnosis of relapsing remitting multiple sclerosis (RRMS) or primary progressive MS as defined by the revised McDonald criteria.
- Had a recent clinical relapse (within 3 months) prior to randomization.
- Uncontrolled intercurrent illness including, but not limited to- ongoing or active infection; symptomatic congestive heart failure; unstable angina pectoris; cardiac arrhythmia; serious or acute liver, kidney, or bone marrow dysfunction; uncontrolled diabetes; serious or acute psychiatric illness that would limit compliance with study requirements.
Epub: Zhao et al. Dimethyl Fumarate Protects Brain From Damage Produced by Intracerebral Hemorrhage by Mechanism Involving Nrf2. Stroke. 2015 May 14. pii: STROKEAHA.115.009398.
BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) represents a devastating form of stroke for which there is no effective treatment. This preclinical study was designed to evaluate dimethyl fumarate (DMF), a substance recently approved for the treatment of multiple sclerosis, as therapy for ICH.
HYPOTHESIS: We hypothesized that DMF through activating the master regulator of cellular self-defense responses, transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), would act as effective treatment for ICH-mediated damage.
METHODS: Male rats and mice, including Nrf2 knockouts, were subjected to intracerebral injection of blood (to mimic ICH) and then treated with DMF. Neurological deficit, brain edema, gene induction profile and hematoma resolution were evaluated. Phagocytic functions of primary microglia in culture were used to study hematoma resolution.
RESULTS: Treatment with DMF induced Nrf2-target genes, improved hematoma resolution, reduced brain edema, and ultimately enhanced neurological recovery in rats and wild-type, but not Nrf2 knockout, mice. Most importantly, the treatment of ICH with DMF showed a 24 h window of therapeutic opportunity.
CONCLUSIONS: A clinically relevant dose of DMF demonstrates potent therapeutic efficacy and impressive 24 h therapeutic window of opportunity. This study merits further evaluation of this compound as potential treatment for ICH in humans.