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

NCT01982942 | Completed Phase 2 Results DMC

• 3 other identifiers: NN102 SPRINT - MS1U01NS082329-01A1RG 4778-A-6
• Study Type: interventional
• Target: 255
• Locations: 1 country
• Sites: 28

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).

Conditions

Multiple Sclerosis, Primary Progressive; Multiple Sclerosis, Secondary Progressive

Outcome Measures

Primary Outcomes (2)

• Covariate-adjusted Mean Rate of Change in Brain Atrophy Over 96 Weeks as Measured by Brain Parenchymal Fraction (BPF).

  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.

  96 weeks

• Percentage of Participants With Adverse Events.

  Safety Measures: percentage of participants who experienced treatment-emergent adverse events, clinically significant abnormal laboratory and electrocardiogram results.

  96 weeks

Secondary Outcomes (3)

• Diffusion Tensor Imaging (DTI) in Descending Pyramidal White Matter Tracts

  48 weeks

• Magnetization Transfer Ratio (MTR) Imaging in Normal-appearing Brain Tissue

  96 weeks

• Retinal Nerve Fiber Layer as Measured by Optical Coherence Tomography (OCT).

  96 weeks

Other Outcomes (1)

• New T1 Lesions Since Baseline

  96 weeks

Study Arms (2)

ibudilast

EXPERIMENTAL

Subjects will receive up to 100 mg/d ibudilast for 96 weeks.

Drug: ibudilast

Placebo Oral Capsule

PLACEBO COMPARATOR

Subjects will receive placebo for 96 weeks.

Drug: Placebo oral capsule

Interventions

ibudilast DRUG

Subjects randomly assigned to the ibudilast (MN-166) cohort will receive up to 100 mg/day for 96 weeks.

Also known as: MN-166

ibudilast

Placebo oral capsule DRUG

Subjects randomly assigned to the placebo cohort will receive placebo oral capsule for 96 weeks.

Placebo Oral Capsule

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

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
• % worsening in 25-foot walk (25-FW) or
• % 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.

Sponsors & Collaborators

• MediciNova: lead
• National Institutes of Health (NIH): collaborator
• National Institute of Neurological Disorders and Stroke (NINDS): collaborator
• National Multiple Sclerosis Society: collaborator

Study Sites (28)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

University of California Davis

Davis, California, 95817, United States

Location

University of California Los Angeles

Los Angeles, California, 90095, United States

Location

University of Colorado Denver

Denver, Colorado, 80045, United States

Location

University of Miami Miller School of Medicine

Miami, Florida, 33136, United States

Location

Emory University

Atlanta, Georgia, 30322, United States

Location

Northwestern University

Evanston, Illinois, 60208, United States

Location

University of Kansas Medical Center

Kansas City, Kansas, 66160, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Brigham and Women's Hospital

Boston, Massachusetts, 02445, United States

Location

Washington University School of Medicine in St Louis

St Louis, Missouri, 63110, United States

Location

University at Buffalo, The State University of New York

Buffalo, New York, 14260, United States

Location

Cornell Medical College

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

University of Rochester

Rochester, New York, 14627, United States

Location

University at Stony Brook, The State University of New York

Stony Brook, New York, 11794, United States

Location

University at Upstate, The State University of New York

Syracuse, New York, 13210, United States

Location

Montefiore Medical Center

The Bronx, New York, 10467, United States

Location

University of Cincinnati, Department of Neurology

Cincinnati, Ohio, 45267, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Ohio State University

Columbus, Ohio, 43210, United States

Location

Oregon Health and Science University

Portland, Oregon, 97239, United States

Location

University of Pittsburgh

Pittsburgh, Pennsylvania, 15261, United States

Location

Vanderbilt University

Nashville, Tennessee, 37235, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Utah

Salt Lake City, Utah, 84112, United States

Location

University of Virginia Charlottesville

Charlottesville, Virginia, 22904, United States

Location

Swedish Medical Center - Seattle

Seattle, Washington, 98122, United States

Location

Related Publications (6)

• Krijnen EA, Bruijn AM, Eloyan A, Schoonheim MM, Fox RJ, Klawiter EC. Evaluation of cortical pathology in primary-progressive multiple sclerosis: a post hoc analysis of the SPRINT-MS trial. BMJ Neurol Open. 2026 Jan 5;8(1):e001335. doi: 10.1136/bmjno-2025-001335. eCollection 2026.

  PMID: 41509523 DERIVED

• Novak A, Harvey T, Wojdala A, Teunissen C, Fox R. Effect of Ibudilast vs Placebo on GFAP and Contactin levels in a phase 2 clinical trial in progressive multiple sclerosis. Neurol Open Access. 2025 Dec;1(4):10.1212/wn9.0000000000000040. doi: 10.1212/wn9.0000000000000040. Epub 2025 Nov 21.

  PMID: 41342004 DERIVED

• Singh V, Zheng Y, Ontaneda D, Mahajan KR, Holloman J, Fox RJ, Nakamura K, Trapp BD. Disability independent of cerebral white matter demyelination in progressive multiple sclerosis. Acta Neuropathol. 2024 Aug 31;148(1):34. doi: 10.1007/s00401-024-02796-w.

  PMID: 39217272 DERIVED

• Nakamura K, Zheng Y, Mahajan KR, Cohen JA, Fox RJ, Ontaneda D. Effect of ibudilast on thalamic magnetization transfer ratio and volume in progressive multiple sclerosis. Mult Scler. 2023 Sep;29(10):1257-1265. doi: 10.1177/13524585231187289. Epub 2023 Aug 3.

  PMID: 37537928 DERIVED

• Bermel RA, Fedler JK, Kaiser P, Novalis C, Schneebaum J, Klingner EA, Williams D, Yankey JW, Ecklund DJ, Chase M, Naismith RT, Klawiter EC, Goodman AD, Coffey CS, Fox RJ. Optical coherence tomography outcomes from SPRINT-MS, a multicenter, randomized, double-blind trial of ibudilast in progressive multiple sclerosis. Mult Scler. 2021 Aug;27(9):1384-1390. doi: 10.1177/1352458520964409. Epub 2020 Oct 15.

  PMID: 33054533 DERIVED

• Fox RJ, Coffey CS, Conwit R, Cudkowicz ME, Gleason T, Goodman A, Klawiter EC, Matsuda K, McGovern M, Naismith RT, Ashokkumar A, Barnes J, Ecklund D, Klingner E, Koepp M, Long JD, Natarajan S, Thornell B, Yankey J, Bermel RA, Debbins JP, Huang X, Jagodnik P, Lowe MJ, Nakamura K, Narayanan S, Sakaie KE, Thoomukuntla B, Zhou X, Krieger S, Alvarez E, Apperson M, Bashir K, Cohen BA, Coyle PK, Delgado S, Dewitt LD, Flores A, Giesser BS, Goldman MD, Jubelt B, Lava N, Lynch SG, Moses H, Ontaneda D, Perumal JS, Racke M, Repovic P, Riley CS, Severson C, Shinnar S, Suski V, Weinstock-Guttman B, Yadav V, Zabeti A; NN102/SPRINT-MS Trial Investigators. Phase 2 Trial of Ibudilast in Progressive Multiple Sclerosis. N Engl J Med. 2018 Aug 30;379(9):846-855. doi: 10.1056/NEJMoa1803583.

  PMID: 30157388 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Multiple Sclerosis, Chronic Progressive

Interventions

ibudilast

Condition Hierarchy (Ancestors)

Multiple Sclerosis; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Nervous System Diseases; Demyelinating Diseases; Autoimmune Diseases; Immune System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Director, Medical Writing
• Organization: Medicinova Inc

makhay@medicinova.com

8582468680

Study Officials

• Robert J Fox, MD, FAAN

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 29, 2013
• First Posted: November 13, 2013
• Study Start: November 1, 2013
• Primary Completion: May 1, 2017
• Study Completion: December 1, 2017
• Last Updated: July 28, 2020
• Results First Posted: July 28, 2020

Record last verified: 2020-07

Locations

US (28)