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

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by MediciNova
Sponsor:
Collaborators:
National Multiple Sclerosis Society
Information provided by (Responsible Party):
MediciNova
ClinicalTrials.gov Identifier:
NCT01982942
First received: October 29, 2013
Last updated: July 25, 2014
Last verified: July 2014
  Purpose

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).


Condition Intervention Phase
Multiple Sclerosis, Primary Progressive
Multiple Sclerosis, Secondary Progressive
Drug: ibudilast
Drug: Placebo
Phase 2

Study Type: Interventional
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

Resource links provided by NLM:


Further study details as provided by MediciNova:

Primary Outcome Measures:
  • 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)


Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 250
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)
Arms Assigned Interventions
Experimental: ibudilast
Subjects will receive 100 mg/d ibudilast for 96 weeks.
Drug: ibudilast
Other Name: MN-166
Placebo Comparator: Placebo
Subjects will receive placebo for 96 weeks.
Drug: Placebo

  Eligibility

Ages Eligible for Study:   21 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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).
  • 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.

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
  • 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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01982942

  Hide Study Locations
Locations
United States, Alabama
University of Alabama at Birmingham Recruiting
Birmingham, Alabama, United States, 35294
Contact: Kerry Howard    205-934-1885    kdhoward@uab.edu   
Principal Investigator: Khurram Bashir, MD         
United States, California
University of California Davis Recruiting
Davis, California, United States, 95817
Contact: Janelle Butters, RN    916-734-6276    Janelle.butters@ucdmc.ucdavis.edu   
Contact: Randev Sandhu, CCRP       rssandhu@ucdavis.edu   
Principal Investigator: Mark Agius, MD         
Univeristy of California Los Angeles Recruiting
Los Angeles, California, United States, 90095
Contact: Catherine Canamar       CCanamar@mednet.ucla.edu   
Contact: Jenny Bardens       JBardens@mednet.ucla.edu   
Principal Investigator: Barbara Giesser, MD         
Sub-Investigator: Callene Momtazee         
United States, Colorado
University of Colorado Denver Recruiting
Denver, Colorado, United States, 80045
Contact: Kathryn Connelly    303-724-5128    kathryn.connelly@ucdenver.edu   
Contact: AJ Stein    303-724-6346    alexander.stein@ucdenver.edu   
Principal Investigator: Augusto Miravalle, MD         
United States, Florida
University of Miami Miller School of Medicine Recruiting
Miami, Florida, United States, 33136
Contact: Gloria Rodriguez    305-243-8052    GRodriguez13@med.miami.edu   
Principal Investigator: Silvia Delgado, MD         
United States, Georgia
Emory University Recruiting
Atlanta, Georgia, United States, 30322
Contact: Kanoa Folami    404-778-3444    kfolami@emory.edu   
Principal Investigator: Neil Lava, MD         
United States, Illinois
Northwestern University Recruiting
Evanston, Illinois, United States, 60208
Contact: Pat Casey, MS    312-695-0774    Pcasey1@nmff.org   
Contact: Bartosz Jacher    312-695-8636    bartosz.jacher@northwestern.edu   
Principal Investigator: Joy Derwenskus, MD         
United States, Kansas
University of Kansas Medical Center Recruiting
Kansas City, Kansas, United States, 66160
Contact: Lisa Schmidt, LPN    913-588-3968    lschmidt@kumc.edu   
Principal Investigator: Sharon Lynch, MD         
United States, Massachusetts
Brigham and Women's Hospital Recruiting
Boston, Massachusetts, United States, 02445
Contact: Sandra Cook, RN    617-525-6585    scook@partners.org   
Principal Investigator: Christopher A Severson, MD         
Massachusetts General Hospital Recruiting
Boston, Massachusetts, United States, 02114
Contact: Courtney Miller    617-726-5585    cortizmiller@partners.org   
Principal Investigator: Eric Klawiter, MD         
United States, Missouri
Washington University School of Medicine in St Louis Recruiting
St Louis, Missouri, United States, 63110
Contact: Mengesha Teshome       teshomem@neuro.wustl.edu   
Contact: Susan Fox    314-362-2017    foxs@neuro.wustl.edu   
Principal Investigator: Robert Naismith, MD         
United States, New York
Montefiore Medical Center Recruiting
Bronx, New York, United States, 10467
Contact: Donna Patch, RN    718-920-6690    donna.patch@einstein.yu.edu   
Principal Investigator: Caorey A McGraw, MD         
University at Buffalo, The State University of New York Recruiting
Buffalo, New York, United States, 14260
Contact: Kara Patrick    716-859-7510    Kpatrick@buffalo.edu   
Contact: Karen Zakalik       kzakalik@buffalo.com   
Principal Investigator: Bianca Weinstock-Gutman, MD         
Cornell Medical College Recruiting
New York City, New York, United States, 10021
Contact: Nancy Olowo    212-746-9882    nao2012@med.cornell.edu   
Principal Investigator: Jai Perumal, MD         
Columbia University Medical Center Recruiting
New York City, New York, United States, 10032
Contact: Gabriella E Tosto       gmt2115@cumc.columbia.edu   
Principal Investigator: Claire S Riley, MD         
University of Rochester Recruiting
Rochester, New York, United States, 14627
Contact: Eileen Scheid    585-275-6673    Eileen_scheid@urmc.rochester.edu   
Principal Investigator: Andrew Goodman, MD         
University at Stony Brook, The State University of New York Recruiting
Stony Brook, New York, United States, 11794
Contact: Traci Bower       Traci.Bower@stoneybrookmedicine.edu   
Principal Investigator: Patricia Coyle, MD         
University at Upstate, The State University of New York Recruiting
Syracuse, New York, United States, 13210
Contact: Andrea McGlond    315-464-5302    mcglonda@upstate.edu   
Principal Investigator: Burk Jubelt, MD         
United States, Ohio
University of Cincinnati, Department of Neurology Recruiting
Cincinnati, Ohio, United States, 45267
Contact: Alecia Boehl    513-846-1905    alecia.boehl@uc.edu   
Principal Investigator: Aram Zabeti, MD         
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: John Mays    216-445-6339    maysj1@ccf.org   
Principal Investigator: Daniel Ontaneda, MD         
Ohio State University Recruiting
Columbus, Ohio, United States, 43210
Contact: amy Bartlett    614-314-0616    amy.bartlett@osumc.edu   
Contact: erin Marshall    614-366-3752    erin.marshall@osumc.edu   
Principal Investigator: Aaron Boster, MD         
United States, Oregon
Oregon Health and Science University Recruiting
Portland, Oregon, United States, 97239
Contact: Debbie Griffith    503-494-5759    griffide@ohsu.edu   
Principal Investigator: Vijayshree Yadav, MD         
United States, Pennsylvania
University of Pittsburgh Recruiting
Pittsburgh, Pennsylvania, United States, 15261
Contact: Kerry Oddis    412-692-4918    kmoddis@upmc.edu   
Principal Investigator: Galen Mitchell, MD         
United States, Tennessee
Vanderbilt University Recruiting
Nashville, Tennessee, United States, 37235
Contact: Jennifer Scott, RN    615-322-4085    Jennifer.I.scott@vanderbilt.edu   
Principal Investigator: Harold Moses, MD         
United States, Texas
University of Texas Southwestern Medical Center Recruiting
Dallas, Texas, United States, 75390
Contact: William thayer       william.thayer@utsouthwestern.edu   
Principal Investigator: Angela Flores, MD         
United States, Utah
University of Utah Recruiting
Salt Lake City, Utah, United States, 84112
Contact: Tammy Floore, RN    801-585-5227    Tammy.floore@hsc.utah.edu   
Contact: Sara Woltz       sara.woltz@hsc.utah.edu   
Principal Investigator: Dana DeWitt, MD         
United States, Virginia
University of Virginia Charlottesville Recruiting
Charlottesville, Virginia, United States, 22904
Contact: Stephanie Lowenhaupt, RN       SAL3Q@hscmail.mcc.virginia.edu   
Principal Investigator: Myla Goldman, MD         
United States, Washington
Swedish Medical Center - Seattle Recruiting
Seattle, Washington, United States, 98122
Contact: Becky Wood       Becky.Wood@swedish.org   
Contact: Beena Gangadharan       beena.gangadharan@swedish.org   
Principal Investigator: Pavle Repovic, MD, PhD         
Sponsors and Collaborators
MediciNova
National Multiple Sclerosis Society
Investigators
Principal Investigator: Robert J Fox, MD, FAAN The Cleveland Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: MediciNova
ClinicalTrials.gov Identifier: NCT01982942     History of Changes
Other Study ID Numbers: NN102 SPRINT - MS, 1U01NS082329-01A1, RG 4778-A-6
Study First Received: October 29, 2013
Last Updated: July 25, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Sclerosis
Multiple Sclerosis
Multiple Sclerosis, Chronic Progressive
Pathologic Processes
Demyelinating Autoimmune Diseases, CNS
Autoimmune Diseases of the Nervous System
Nervous System Diseases
Demyelinating Diseases
Autoimmune Diseases
Immune System Diseases
Ibudilast
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Hematologic Agents
Vasodilator Agents
Cardiovascular Agents

ClinicalTrials.gov processed this record on September 18, 2014