BRAVO Study: Laquinimod Double-blind Placebo-controlled Study in Participants With Relapsing-Remitting Multiple Sclerosis (RRMS) With a Rater Blinded Reference Arm of Interferon β-1a (Avonex®)

Inclusion Criteria

• Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria [Ann Neurol 2005: 58:840-846], with a relapsing-remitting disease course.
• Subjects must be ambulatory with converted Kurtzke EDSS score of 0-5.5.
• Subjects must be in a stable neurological condition between screening (month -1) and baseline visits (month 0).
• Subjects must have had experienced one of the following:
• At least one documented relapse in the 12 months prior to screening
• At least two documented relapses in the 24 months prior to screening
• One documented relapse between 12 and 24 months prior to screening with at least one documented T1-Gd enhancing lesion in an MRI performed within 12 months prior to screening.
• Subjects must be between 18 and 55 years of age, inclusive.
• Subjects must have disease duration of at least 6 months (from first symptom) prior to screening.
• Women of child-bearing potential must practice 2 acceptable methods of birth control [acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive, partner's vasectomy or double-barrier method (condom or diaphragm with spermicide)].
• Subjects must be willing and able to comply with the protocol requirements for the duration of the study.

Exclusion Criteria

• An onset of relapse or any treatment with corticosteroids (intravenous [iv], intramuscular [im] and/or per os [po]) or ACTH between month -1 (screening) and 0 (baseline).
• Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to screening.
• Use of immunosuppressive (including Mitoxantrone (Novantrone®) or cytotoxic agents within 6 months prior to the screening visit.
• Previous use of either of the following: natalizumab (Tysabri®), cladribine or laquinimod.
• Previous treatment with glatiramer acetate (Copaxone®) or IVIG within 3 months prior to screening visit.
• Previous treatment with Interferon beta-1a (Avonex® or Rebif®) or Interferon beta-1b (Betaseron®).
• Systemic corticosteroid treatment of ≥30 consecutive days duration within 2 months prior to screening visit.
• Previous total body irradiation or total lymphoid irradiation.
• Previous stem-cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
• A known history of tuberculosis.
• Acute infection 2 weeks prior to baseline visit.
• Major trauma or surgery 2 weeks prior to baseline visit.
• A history of vascular thrombosis (excluding catheter-site superficial venous thrombophlebitis).
• A carrier state of factor V Leiden mutation (either homo- or heterozygous) by history or as disclosed at screening.
• Positive screening test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV antibody as disclosed at screening visit.
• Use of potent inhibitors of CYP3A4 within 2 weeks prior to baseline visit (see detailed list of drugs in protocol) (1 month for fluoxetine).
• Use of amiodarone within 2 years prior to screening visit.
• Pregnancy or breastfeeding.
• Subjects with a clinically significant or unstable medical or surgical condition that would preclude safe and complete study participation, as determined by medical history, physical examinations, ECG, laboratory tests or chest X-ray. Such conditions may include:
• A cardiovascular or pulmonary disorder that cannot be well-controlled by standard treatment permitted by the study protocol.
• A gastrointestinal disorder that may affect the absorption of study medication.
• Renal, metabolic, endocrinological or hematological diseases.
• Any form of chronic liver disease, including known non-alcoholic steatohepatitis.
• A ≥2xULN serum elevation of either of the following at screening: ALT, AST or direct bilirubin.
• A QTc interval (obtained from either two ECG recordings at screeni