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 < 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.