Status:Not yet recruiting
Keywords:Multiple sclerosis , Ibudilast , Progressive multiple sclerosis
Sub Specialty:Multiple Sclerosis
Despite recent improvements in pharmacotherapy for relapsing remitting multiple sclerosis (RRMS), there are no therapies with demonstrated efficacy in progressive multiple sclerosis (MS) in the absence of relapses. The few studies showing efficacy of anti-inflammatory therapies in progressive forms of MS were likely driven by the anti-inflammatory effect of the therapies. There is great need for a safe, effective, and conveniently-administered therapy for progressive MS without overt inflammation. This phase 2 study is to evaluate the safety and activity of Ibudilast.
1. To evaluate the activity of ibudilast (MN-166)) (100 mg/day) versus placebo at 96 weeks as measured by quantitative non-contrast magnetic resonance imaging (MRI) analysis for whole brain atrophy using brain parenchymal fraction (BPF).
2. To evaluate the safety and tolerability of ibudilast (MN-166) (100 mg/day) versus placebo administered orally in subjects with primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS).
To evaluate the activity if ibudilast (MN-166) as measured at 96 weeks versus placebo as measured by the following:
1. Diffusion tensor imaging (DTI) in descending pyramidal white matter tracts
2. Magnetization transfer ratio (MTR) imaging in normal-appearing brain tissue
3. Retinal nerve fiber layer as measured by ocular coherence tomography (OCT)
4. Cortical atrophy as measured by cortical longitudinal atrophy detection algorithm [CLADA]
Additional secondary outcomes to measure activity of ibudilast versus placebo are as follows:
1. Inflammatory disease activity as measured by T1 lesion volume, T2 lesion volume and annualized relapse rate
2. Disability as measured by the expanded Disability Status scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC)
3. Cognitive Impairment using the Symbol Digit Modalities Test and the Selective Reminding Test
4. Quality of Life as measured by Multiple Sclerosis Impact Scale (MSIS-29), EuroQol
5. Dimensions (EQ5D) and Short Form-36 Health Survey (SF-36)
6. Neuropathic pain, as measured by Brief Pain Inventory (BPI)
Exploratory objectives include the evaluation of the pharmacokinetics of ibudilast (MN-166) and correlations of cerebrospinal fluid, serum, and PBMC biomarkers with imaging and clinical measures of progressive disability.