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: ibudilast 100 mg/day or matching-placebo in a 1:1 ratio. Study drug will be administered twice daily (BID), i.e., ibudilast 50 mg or placebo taken in the morning and evening).
Multiple Sclerosis, Primary Progressive
Multiple Sclerosis, Secondary Progressive
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, 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 ] [ Designated as safety issue: No ]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 ] [ Designated as safety issue: Yes ]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 ] [ Designated as safety issue: No ]
- Magnetization transfer ratio (MTR) imaging in normal-appearing brain tissue [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Retinal nerve fiber layer as measured by Optical coherence tomography (OCT) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Cortical atrophy as measured by cortical longitudinal atrophy detection algorithm [CLADA] [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Inflammatory disease activity, as measured by T1 lesion volume, T2 lesion volume, and annualized relapse rate [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Disability, as measured by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- 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 ] [ Designated as safety issue: No ]
- Cognitive impairment, as measured by Symbol Digit Modalities Test (SDMT) and the Selective Reminding Test (SRT). [ Time Frame: 36 months ] [ Designated as safety issue: No ]
- Neuropathic pain, as measured by Brief Pain Inventory (BPI) [ Time Frame: 36 months ] [ Designated as safety issue: No ]
|Study Start Date:||November 2013|
|Estimated Study Completion Date:||March 2017|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Subjects will receive 100 mg/d ibudilast for 96 weeks.
Other Name: MN-166
Placebo Comparator: Placebo
Subjects will receive placebo for 96 weeks.
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|Principal Investigator:||Robert J Fox, MD, FAAN||The Cleveland Clinic|