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Multiple Sclerosis, Primary ProgressivePhase 2NCT01982942

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

A Phase 2 study testing ibudilast in people with Multiple Sclerosis, Primary Progressive and Multiple Sclerosis, Secondary Progressive, run by MediciNova at 28 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial 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… Read more about this study

Who is it for?
Ages 21 to 65 years
What is being tested?
ibudilast
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
255 participants
Where
28 sitesUnited States
Study dates
Nov 2013to Dec 2017
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 21 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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):
Show all 14Show fewer
  • 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.

Who cannot join

  • 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
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  • 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).
  • Subject has a history of alcohol or substance abuse (DSM-IV-TR criteria) within 3 months prior to screening or alcohol or substance dependence (DSM-IV-TR criteria) within 12 months prior to screening. The only exceptions include caffeine or nicotine abuse/dependence.
  • Subject has poor peripheral venous access that will limit the ability to draw blood as judged by the Investigator.
  • Subject is currently participating, or has participated in, a study with an investigational or marketed compound or device within 3 months prior to signing the informed consent.
  • Subject is unable to cooperate with any study procedures, unlikely to adhere to the study procedures and keep appointments, in the opinion of the Investigator, or was planning to relocate during the study.
  • Subject is unable to undergo MRI imaging because of having an artificial heart valve, metal plate, pin, or other metallic objects (including gun shots or shrapnel) in their body or is unable to complete all the five MRI scans required for this study.

Trial locations and contacts

28 sites in 1 country.

28 sites in 1 country

United States28 sites

  • Emory University

    Atlanta, Georgia, 30322

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Massachusetts General Hospital

    Boston, Massachusetts, 02114

  • Brigham and Women's Hospital

    Boston, Massachusetts, 02445

  • University at Buffalo, The State University of New York

    Buffalo, New York, 14260

  • University of Virginia Charlottesville

    Charlottesville, Virginia, 22904

  • University of Cincinnati, Department of Neurology

    Cincinnati, Ohio, 45267

  • Cleveland Clinic

    Cleveland, Ohio, 44195

  • Ohio State University

    Columbus, Ohio, 43210

  • University of Texas Southwestern Medical Center

    Dallas, Texas, 75390

  • University of California Davis

    Davis, California, 95817

  • University of Colorado Denver

    Denver, Colorado, 80045

  • Northwestern University

    Evanston, Illinois, 60208

  • University of Kansas Medical Center

    Kansas City, Kansas, 66160

  • University of California Los Angeles

    Los Angeles, California, 90095

  • University of Miami Miller School of Medicine

    Miami, Florida, 33136

  • Vanderbilt University

    Nashville, Tennessee, 37235

  • Cornell Medical College

    New York, New York, 10021

  • Columbia University Medical Center

    New York, New York, 10032

  • University of Pittsburgh

    Pittsburgh, Pennsylvania, 15261

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • University of Rochester

    Rochester, New York, 14627

  • University of Utah

    Salt Lake City, Utah, 84112

  • Swedish Medical Center - Seattle

    Seattle, Washington, 98122

  • Washington University School of Medicine in St Louis

    St Louis, Missouri, 63110

  • University at Stony Brook, The State University of New York

    Stony Brook, New York, 11794

  • University at Upstate, The State University of New York

    Syracuse, New York, 13210

  • Montefiore Medical Center

    The Bronx, New York, 10467

Other trials in United States

About this study

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

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).

Being tested
ibudilast, Placebo oral capsule
Medical subject headings
Multiple Sclerosis, Chronic Progressive

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ibudilastDrug

    Also called MN-166

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

  • Placebo oral capsuleDrug

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

Study groups in NCT01982942
Study groupRoleWhat they receive
ibudilastExperimentalSubjects will receive up to 100 mg/d ibudilast for 96 weeks.
Receives: Drug: ibudilast
Placebo Oral CapsulePlacebo comparatorSubjects will receive placebo for 96 weeks.
Receives: Drug: Placebo oral capsule

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 96 weeks

  2. Percentage of Participants With Adverse Events.

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

    Measured: 96 weeks

Secondary outcomes (3)

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

    Diffusion tensor imaging estimates the three-dimensional diffusion of water in brain tissue and has been explored as an outcome in MS.

    Measured: 48 weeks

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

    A magnetization transfer MRI as a marker of brain myelin content including the cerebral cortex could be useful. MT imaging provides access to the restricted protons, which are located in biologically interesting tissue regions.Cortical and normal appearing grey matter MTR correlates strongly with measures of disability such as the multiple sclerosis functional composite score and can show treatment effects.

    Measured: 96 weeks

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

    Mean retinal nerve fiber layer thickness from baseline measured by Optical coherence tomography (OCT), a non-invasive imaging technique used to obtain high-resolution cross-sectional images of the retina. Increase in thickness is considered improvement.

    Measured: 96 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted13 Nov 2013 (estimated)
  2. Study startNov 2013
  3. Primary completionMay 2017
  4. Study completionDec 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Triple blind
Who is masked
Participant, Care provider, Investigator
Enrolment
255 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01982942
Sponsor's protocol ID
NN102 SPRINT - MS
Other IDs
1U01NS082329-01A1, RG 4778-A-6
Status last verified
Jul 2020
First submitted
29 Oct 2013
Last updated
28 Jul 2020
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 41509523

  • 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.

    PubMed 41342004

  • 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.

    PubMed 39217272

  • 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.

    PubMed 37537928

  • 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.

    PubMed 33054533

  • 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.

    PubMed 30157388

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing ibudilast in people with Multiple Sclerosis, Primary Progressive and Multiple Sclerosis, Secondary Progressive, run by MediciNova at 28 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 14 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 28 Jul 2020. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 28 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 28 Jul 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Covariate-adjusted Mean Rate of Change in Brain Atrophy Over 96 Weeks as Measured by Brain Parenchymal Fraction (BPF). (time frame: 96 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01982942, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2020.

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