Safety, Tolerability and Activity Study of Ibudilast in Subjects With Progressive Multiple Sclerosis

Completed · Phase 2 · Has a placebo group

Conditions studied: Multiple Sclerosis, Primary Progressive, Multiple Sclerosis, Secondary Progressive

In brief

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).

Key facts

Study ID

NCT01982942

Run by

MediciNova

People needed

255

Starts

2013-11-01

Expected to finish

2017-12-01

Last updated by the study team

2020-07-28

Who can join

Age: 21 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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).
• Females of child-bearing potential must have a negative serum ß-hCG at screening and must be willing to use appropriate contraception (as defined by the investigator) for the duration of study treatment and 30 days after the last dose of study treatment.
• Males should practice contraception as follows: condom use and contraception by female partner.
• Subject is in good physical health on the basis of medical history, physical examination, and laboratory screening, as defined by the investigator.
• Subject is willing and able to comply with the protocol assessments and visits, in the opinion of the study nurse/coordinator and the Investigator.

You may not qualify if…

• 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
• Resting pulse < 50 bpm, sinoatrial (SA) or atrioventricular (AV) block, uncontrolled hypertension, or QTcF > 450 ms
• Clinically significant pulmonary conditions, including severe chronic obstructive pulmonary disease (COPD), fibrosis, or tuberculosis
• Evidence of acute hepatitis, clinically significant chronic hepatitis, or evidence of clinically significant impaired hepatic function through clinical and laboratory evaluation including ALP > 1.5x ULN; ALT or AST > 2x ULN; GGT > 3x ULN
• Immune system disease (other than multiple sclerosis and autoimmune thyroid disease)
• History of stomach or intestinal surgery or any other condition that could interfere with or is judged by the Investigator to interfere with absorption, distribution, metabolism, or excretion of study drug.
• Any significant laboratory abnormality which, in the opinion of the Investigator, may put the subject at risk and with the following laboratory abnormalities at screening:
• Creatinine: females > 0.95 mg/dL; males > 1.17 mg/dL
• WBCs < 3,000 mm3
• Lymphocytes < 800 mm3
• Platelets < 90,000 mm3
• History of malignancy < 5 years prior to signing the informed consent, except for adequately treated basal cell or squamous cell skin cancer or in situ cervical cancer.
• History of HIV (human immunodeficiency virus), clinically significant chronic hepatitis, or other active infection.
• Subject currently has a clinically significant medical condition (other than MS) including the following: neurological, psychiatric, metabolic, hepatic, renal, hematological, pulmonary, cardiovascular (including uncontrolled hypertension), gastrointestinal, urological disorder, or central nervous system (CNS) infection that would pose a risk to the subject if they were to participate in the study or that might confound the results of the study.
• Note: Active medical conditions that are minor or well-controlled are not exclusionary if, in the judgment of the Investigator, they do not affect risk to the subject or the study results. In cases in which the impact of the condition upon risk to the subject or study results is unclear, the Medical Safety Monitor should be consulted.
• Subjects with moderate to severe depression as determined by the Beck Depression Inventory-Fast Screen (BDI-FS).

Where it is running

• University of Alabama at Birmingham — Birmingham, Alabama, United States
• University of California Davis — Davis, California, United States
• University of California Los Angeles — Los Angeles, California, United States
• University of Colorado Denver — Denver, Colorado, United States
• University of Miami Miller School of Medicine — Miami, Florida, United States
• Emory University — Atlanta, Georgia, United States
• Northwestern University — Evanston, Illinois, United States
• University of Kansas Medical Center — Kansas City, Kansas, United States
• Massachusetts General Hospital — Boston, Massachusetts, United States
• Brigham and Women's Hospital — Boston, Massachusetts, United States
• Washington University School of Medicine in St Louis — St Louis, Missouri, United States
• University at Buffalo, The State University of New York — Buffalo, New York, United States
• Cornell Medical College — New York, New York, United States
• Columbia University Medical Center — New York, New York, United States
• University of Rochester — Rochester, New York, United States
• University at Stony Brook, The State University of New York — Stony Brook, New York, United States
• University at Upstate, The State University of New York — Syracuse, New York, United States
• Montefiore Medical Center — The Bronx, New York, United States
• University of Cincinnati, Department of Neurology — Cincinnati, Ohio, United States
• Cleveland Clinic — Cleveland, Ohio, United States
• Ohio State University — Columbus, Ohio, United States
• Oregon Health and Science University — Portland, Oregon, United States
• University of Pittsburgh — Pittsburgh, Pennsylvania, United States
• Vanderbilt University — Nashville, Tennessee, United States
• University of Texas Southwestern Medical Center — Dallas, Texas, United States

Full record on ClinicalTrials.gov

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