A Phase 2 Clinical Study in Subjects With Primary Progressive Multiple Sclerosis to Assess the Efficacy, Safety and Tolerability of Two Oral Doses of Laquinimod Either of 0.6 mg/Day or 1.5mg/Day (Experimental Drug) as Compared to Placebo

Inclusion Criteria

• Patients must have a confirmed and documented PPMS diagnosis as defined by the 2010 Revised McDonald criteria
• Baseline magnetic resonance imaging (MRI) showing lesions consistent with PPMS in either or both brain and spinal cord
• Patients must have an Expanded Disability Status Scale (EDSS) score of 3 to 6.5, inclusive, at both screening and baseline visits
• Documented evidence of clinical disability progression in the 2 years prior to screening.
• Functional System Score (FSS) of > or equal 2 for the pyramidal system or gait impairment due to lower extremity dysfunction
• Patients must be between 25 to 55 years of age, inclusive
• Women of child-bearing potential must practice an acceptable method of birth control for 30 days before taking the study drug, and 2 acceptable methods of birth control during all study duration and until 30 days after the last dose of treatment is administered.
• Patients must sign and date a written informed consent prior to entering the study.
• Patients must be willing and able to comply with the protocol requirements for the duration of the study.

Exclusion Criteria

• Patients with history of any multiple sclerosis (MS) exacerbations or relapses, including any episodes of optic neuritis.
• Progressive neurological disorder other than PPMS.
• Any MRI record showing presence of cervical cord compression.
• Baseline MRI showing other findings (including lesions that are atypical for PPMS) that may explain the clinical signs and symptoms.
• Relevant history of vitamin B12 deficiency.
• Positive human T-lymphotropic virus Type I and II (HTLV-I/II) serology.
• Use of experimental or investigational drugs in a clinical study within 24 weeks prior to baseline. Use of a currently marketed drug in a clinical study within 24 weeks prior to baseline would not be exclusionary, provided no other exclusion criteria are met.
• Use of immunosuppressive agents, or cytotoxic agents, including cyclophosphamide and azathioprine within 48 weeks prior to baseline.
• Previous treatment with fingolimod (GILENYA®, Novartis), dimethyl fumarate (TECFIDERA®, Biogen Idec Inc), glatiramer acetate (COPAXONE®, Teva), interferon-β (either 1a or 1b), intravenous immunoglobulin, or plasmapheresis within 8 weeks prior to baseline.
• Use of teriflunomide (AUBAGIO®, Sanofi) within 2 years prior to baseline, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to baseline.
• Prior use of monoclonal antibodies ever, except for:
• natalizumab (TYSABRI®, Biogen Idec Inc), if given more than 24 weeks prior to baseline AND the patient is John Cunningham (JC) virus antibody test negative (as per medical history)
• rituximab, ocrelizumab, or ofatumumab, if B cell count (CD19, as per medical history) is higher than 80 cells/μL
• Use of mitoxantrone (NOVANTRONE®, Immunex) within 5 years prior to screening. Use of mitoxantrone >5 years before screening is allowed in patients with normal ejection fraction and who did not exceed the total lifetime maximal dose.
• Previous use of laquinimod.
• Chronic (eg, more than 30 consecutive days or monthly dosing, with the intent of MS disease modification) systemic (intravenous, intramuscular or oral) corticosteroid treatment within 8 weeks prior to baseline.
• Previous use of cladribine or alemtuzumab (LEMTRADA®, Sanofi).
• Previous total body irradiation or total lymphoid irradiation.
• Previous stem cell treatment, cell-based treatment, or bone marrow transplantation of any kind.
• Patients who underwent endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) within 12 weeks prior to baseline.
• Use of moderate/strong inhibitors of cytochrome P450 (CYP) 3A4 within 2 weeks prior to baseline.
• Use of inducers of CYP3A4 within 2 weeks prior to baseline.
• Pregnancy or breastfeeding.
• Serum levels ≥3× upper limit of the normal range (ULN) of either alan