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
Overview
- Phase
- Phase 2
- Intervention
- ibudilast
- Conditions
- Multiple Sclerosis, Primary Progressive
- Sponsor
- MediciNova
- Enrollment
- 255
- Locations
- 28
- Primary Endpoint
- Covariate-adjusted Mean Rate of Change in Brain Atrophy Over 96 Weeks as Measured by Brain Parenchymal Fraction (BPF).
- Status
- Completed
- Last Updated
- 5 years ago
Overview
Brief Summary
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-1, any formulation (IFNβ-1A [Avonex, Rebif] or IFNβ-1B [Betaseron, Extavia]). Study drug or placebo will be administered to a total of 250 male and female subjects from 21 to 65 years old, inclusive, in 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).
Investigators
Eligibility Criteria
Inclusion Criteria
- •Written informed consent is obtained and willing and able to comply with the protocol in the opinion of the Investigator.
- •Male or female subjects ages 21 to 65, inclusive
- •Confirmed diagnosis of SPMS or primary progressive multiple sclerosis (PPMS) according to 2010 International Panel Criteria
- •Typical MS lesions on MRI according to Swanton's MRI Criteria (at least one lesion in two or more of the following regions: periventricular, juxtacortical, infratentorial \[brainstem/cerebellum\], spinal cord)
- •EDSS 3.0-6.5, inclusive
- •Clinical evidence of disability progression in the preceding two years, as measured by any of the following (excluding progression during clinical relapses):
- •worsening overall EDSS of at least 0.5 points (may be assessed retrospectively but cannot be during a clinical relapse) or
- •20% worsening in 25-foot walk (25-FW) or
- •20% worsening in 9-hole peg test (9-HPT) in either hand
- •Existing multiple sclerosis pharmacotherapy status may include interferon-beta or glatiramer acetate or none (i.e. untreated).
Exclusion Criteria
- •Progressive neurological disorder other than SPMS or PPMS
- •Relapse and/or systemic corticosteroid steroid treatment for multiple sclerosis within 3 months of screening. Inhaled or topical steroids are allowed.
- •Current use of intermittent systemic corticosteroids (i.e., monthly or bimonthly intravenous methylprednisolone)
- •Use of oral immunosuppressants (e.g. azathioprine, methotrexate, cyclosporine, teriflunomide \[Aubagio®\]) within 6 months of screening
- •Use of mitoxantrone, natalizumab, or IVIg within 6 months of screening
- •Use of fingolimod or dimethyl fumarate \[Tecfidera®\] within 3 months of screening
- •Use of rituximab or other B-cell therapy within 12 months of screening
- •Current use of other MS disease-modifying therapies (DMTs) besides glatiramer acetate, IFNβ-1 (any formulation), and the above listed medications.
- •Current use of cimetidine, cyclosporine, dronedarone, lopinavir, probenecid, quinidine (including Neudexta), ranolazine, rifampin, ritonavir, or tipranavir.
- •Clinically significant cardiovascular disease, including myocardial infarct within last 6 months, unstable ischemic heart disease, congestive heart failure or angina
Arms & Interventions
ibudilast
Subjects will receive up to 100 mg/d ibudilast for 96 weeks.
Intervention: ibudilast
Placebo Oral Capsule
Subjects will receive placebo for 96 weeks.
Intervention: Placebo oral capsule
Outcomes
Primary Outcomes
Covariate-adjusted Mean Rate of Change in Brain Atrophy Over 96 Weeks as Measured by Brain Parenchymal Fraction (BPF).
Time Frame: 96 weeks
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), calculated as the ratio of brain parenchymal tissue volume to the total volume contained within the brain surface contour.
Percentage of Participants With Adverse Events.
Time Frame: 96 weeks
Safety Measures: percentage of participants who experienced treatment-emergent adverse events, clinically significant abnormal laboratory and electrocardiogram results.
Secondary Outcomes
- Magnetization Transfer Ratio (MTR) Imaging in Normal-appearing Brain Tissue(96 weeks)
- Diffusion Tensor Imaging (DTI) in Descending Pyramidal White Matter Tracts(48 weeks)
- Retinal Nerve Fiber Layer as Measured by Optical Coherence Tomography (OCT).(96 weeks)