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

Exclusion Criteria

• •1. Patients with history of any multiple sclerosis (MS) exacerbations or relapses, including any episodes of optic neuritis.
• •2. Progressive neurological disorder other than PPMS.
• •3. Any MRI record showing presence of cervical cord compression.
• •4. Baseline MRI showing other findings (including lesions that are atypical for PPMS) that may explain the clinical signs and symptoms.
• •5. Relevant history of vitamin B12 deficiency.
• •6. Positive human T-lymphotropic virus Type I and II (HTLV-I/II) serology.
• •8. Use of immunosuppressive agents, or cytotoxic agents, including cyclophosphamide and azathioprine within 48 weeks prior to baseline.
• •9. 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.
• •10. 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.
• •11. Prior use of monoclonal antibodies ever, except for:
• •1. 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)
• •2. rituximab, ocrelizumab, or ofatumumab, if B cell count (CD19, as per medical history) is higher than 80 cells/μL
• •12. 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.
• •13. Previous use of laquinimod.
• •14. 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.
• •15. Previous use of cladribine or alemtuzumab (LEMTRADA®, Sanofi).
• •16. Previous total body irradiation or total lymphoid irradiation.
• •17. Previous stem cell treatment, cell-based treatment, or bone marrow transplantation of any kind.
• •18. Patients who underwent endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) within 12 weeks prior to baseline.
• •19. Use of moderate/strong inhibitors of cytochrome P450 (CYP) 3A4 within 2 weeks prior to baseline.
• •20. Use of inducers of CYP3A4 within 2 weeks prior to baseline.
• •21. Pregnancy or breastfeeding.
• •22. Serum levels ≥3× upper limit of the normal range (ULN) of either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at screening.
• •23. Serum direct bilirubin which is ≥2×ULN at screening.
• •24. Patients with a clinically significant or unstable medical or surgical condition that (in the opinion of the Investigator) would preclude safe and complete study participation, as determined by medical history, physical examinations, electrocardiogram (ECG), laboratory tests or chest X-ray.
• •25. A known history of hypersensitivity to gadolinium (Gd).
• •26. Glomerular filtration rate (GFR) \< or equal 60 mL/min at screening visit.
• •27. Inability to successfully undergo MRI scanning, including claustrophobia.
• •28. Known drug hypersensitivity that would preclude administration of laquinimod, such as hypersensitivity to mannitol, meglumine or sodium stearyl fumarate.