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

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 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 ade