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

Information source: MediciNova
ClinicalTrials.gov processed this data on August 20, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Multiple Sclerosis, Primary Progressive; Multiple Sclerosis, Secondary Progressive

Intervention: ibudilast (Drug); Placebo (Drug)

Phase: Phase 2

Status: Active, not recruiting

Sponsored by: MediciNova

Official(s) and/or principal investigator(s):
Robert J Fox, MD, FAAN, Principal Investigator, Affiliation: The Cleveland Clinic

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 (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: 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).

Clinical Details

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

Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome:

Covariate-adjusted mean rate of change in brain atrophy over 96 weeks as measured by 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).

Secondary outcome:

Diffusion tensor imaging (DTI) in descending pyramidal white matter tracts

Magnetization transfer ratio (MTR) imaging in normal-appearing brain tissue

Retinal nerve fiber layer as measured by Optical coherence tomography (OCT)

Cortical atrophy as measured by cortical longitudinal atrophy detection algorithm [CLADA]

Inflammatory disease activity, as measured by T1 lesion volume, T2 lesion volume, and annualized relapse rate

Disability, as measured by Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC)

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)

Cognitive impairment, as measured by Symbol Digit Modalities Test (SDMT) and the Selective Reminding Test (SRT).

Neuropathic pain, as measured by Brief Pain Inventory (BPI)

Eligibility

Minimum age: 21 Years. Maximum age: 65 Years. Gender(s): Both.

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.

Locations and Contacts

University of Alabama at Birmingham, Birmingham, Alabama 35294, United States

University of California Davis, Davis, California 95817, United States

Univeristy of California Los Angeles, Los Angeles, California 90095, United States

University of Colorado Denver, Denver, Colorado 80045, United States

University of Miami Miller School of Medicine, Miami, Florida 33136, United States

Emory University, Atlanta, Georgia 30322, United States

Northwestern University, Evanston, Illinois 60208, United States

University of Kansas Medical Center, Kansas City, Kansas 66160, United States

Brigham and Women's Hospital, Boston, Massachusetts 02445, United States

Massachusetts General Hospital, Boston, Massachusetts 02114, United States

Washington University School of Medicine in St Louis, St Louis, Missouri 63110, United States

Montefiore Medical Center, Bronx, New York 10467, United States

University at Buffalo, The State University of New York, Buffalo, New York 14260, United States

Columbia University Medical Center, New York City, New York 10032, United States

Cornell Medical College, New York City, New York 10021, United States

University of Rochester, Rochester, New York 14627, United States

University at Stony Brook, The State University of New York, Stony Brook, New York 11794, United States

University at Upstate, The State University of New York, Syracuse, New York 13210, United States

University of Cincinnati, Department of Neurology, Cincinnati, Ohio 45267, United States

Cleveland Clinic, Cleveland, Ohio 44195, United States

Ohio State University, Columbus, Ohio 43210, United States

Oregon Health and Science University, Portland, Oregon 97239, United States

University of Pittsburgh, Pittsburgh, Pennsylvania 15261, United States

Vanderbilt University, Nashville, Tennessee 37235, United States

University of Texas Southwestern Medical Center, Dallas, Texas 75390, United States

University of Utah, Salt Lake City, Utah 84112, United States

University of Virginia Charlottesville, Charlottesville, Virginia 22904, United States

Swedish Medical Center - Seattle, Seattle, Washington 98122, United States

Additional Information

Starting date: November 2013
Last updated: May 12, 2015

Page last updated: August 20, 2015

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