Safety, Tolerability and Activity Study of Ibudilast in Subjects With Progressive Multiple Sclerosis
This is a multicenter, randomized, double-blind, placebo-controlled, parallel-group study designed to evaluate the safety, tolerability and activity of ibudilast administered twice daily over a 96 week period in subjects with primary or secondary progressive multiple sclerosis who are currently untreated with long-term MS disease modifying therapy (DMT) or who are receiving either glatiramer acetate (GA) or interferon beta (IFNβ-1a [Avonex, Rebif] or IFNβ-1b [Betaseron Etavia]) treatment. Study drug will be administered as an adjunct to glatiramer or beta interferon treatment. A total of 250 male and female subjects from 21 to 65 years old, inclusive, are planned to be enrolled into two treatment groups. Randomization of subjects will be stratified by disease status (primary progressive multiple sclerosis or secondary progressive multiple sclerosis) and immunomodulating therapy status: current use of immunomodulating therapy or no current use of immunomodulating therapy.
The study will consist of a screening phase (up to 30 days) followed by a treatment phase (96 weeks) and a follow-up visit (1 month post Week 96 visit). Following the screening phase, subjects who continue to meet entry criteria will be randomly assigned to 1 of 2 treatment groups: doses up to ibudilast 100 mg/day or matching-placebo in a 1:1 ratio. Study drug will be administered twice daily (BID), e.g., ibudilast 50 mg or placebo taken in the morning and evening).
|Multiple Sclerosis, Primary Progressive Multiple Sclerosis, Secondary Progressive||Drug: ibudilast Drug: Placebo||Phase 2|
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Participant, Care Provider, Investigator
Primary Purpose: Treatment
|Official Title:||A Phase 2 Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety, Tolerability and Activity of Ibudilast (MN-166) in Subjects With Progressive Multiple Sclerosis|
- Covariate-adjusted mean rate of change in brain atrophy over 96 weeks as measured by brain parenchymal fraction (BPF). [ Time Frame: 36 months ]To evaluate the activity of ibudilast (100 mg/day) versus placebo at 96 weeks as measured by quantitative magnetic resonance imaging (MRI) analysis for whole brain atrophy using brain parenchymal fraction (BPF).
- Safety Measures: TEAEs (treatment-emergent adverse events), TESAEs (treatment-emergent serious adverse events), treatment discontinuations due to TEAEs, laboratory measures (chemistry, hematology, urinalysis), vital signs, electrocardiograms (ECGs). [ Time Frame: 36 months ]To evaluate the safety and tolerability of ibudilast (100 mg/day) versus placebo administered orally in subjects with primary progressive multiple sclerosis (PPMS) and secondary progressive multiple sclerosis (SPMS)
- Diffusion tensor imaging (DTI) in descending pyramidal white matter tracts [ Time Frame: 36 months ]
- Magnetization transfer ratio (MTR) imaging in normal-appearing brain tissue [ Time Frame: 36 months ]
- Retinal nerve fiber layer as measured by Optical coherence tomography (OCT) [ Time Frame: 36 months ]
- Cortical atrophy as measured by cortical longitudinal atrophy detection algorithm [CLADA] [ Time Frame: 36 months ]
- Inflammatory disease activity, as measured by T1 lesion volume, T2 lesion volume, and annualized relapse rate [ Time Frame: 36 months ]
- Disability, as measured by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: 36 months ]
- Quality of Life, as measured by Multiple Sclerosis Impact Scale (MSIS-29), EuroQol 5 Dimensions (EQ-5D), and Short Form-36 Health Survey (SF-36) [ Time Frame: 36 months ]
- Cognitive impairment, as measured by Symbol Digit Modalities Test (SDMT) and the Selective Reminding Test (SRT). [ Time Frame: 36 months ]
- Neuropathic pain, as measured by Brief Pain Inventory (BPI) [ Time Frame: 36 months ]
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||May 2017|
|Estimated Primary Completion Date:||May 2017 (Final data collection date for primary outcome measure)|
Subjects will receive up to 100 mg/d ibudilast for 96 weeks.
Other Name: MN-166
Placebo Comparator: Placebo
Subjects will receive placebo for 96 weeks.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01982942
Show 28 Study Locations
|Principal Investigator:||Robert J Fox, MD, FAAN||The Cleveland Clinic|