A Study To Evaluate the Long-Term Safety, Tolerability and Effect on Disease Course

• Tolerability [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  Proportion of subjects who prematurely discontinue and time to withdrawal.
• Long-term effect on disease course [ Time Frame: 3 years ] [ Designated as safety issue: No ]
  Long-term effect on disease course as measured by number of relapses and progression of physical disability

• Tolerability: proportion of subjects (%) reason for discontinuation [ Time Frame: 3 years ] [ Designated as safety issue: No ]
• Long-term effect on disease course as measured by number of relapses and progression of physical disability [ Time Frame: 3 years ] [ Designated as safety issue: No ]

The purpose of this study is to make laquinimod 0.6 mg available for all subjects who completed the placebo-controlled MS-LAQ-301 study according to the protocol and to evaluate the long-term safety, tolerability and effect on disease course of daily oral laquinimod 0.6 mg in subjects with relapsing multiple sclerosis.

Inclusion Criteria:

1. Subjects must have completed the Termination visit of MS-LAQ-301 (completion of all Termination visit activities) according to the MS-LAQ-301 protocol.
2. Women of child-bearing potential must practice an acceptable method of birth control [acceptable methods of birth control in this open label extension phase include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch (or hormone-releasing vaginal ring), long-acting injectable contraceptive, partner's vasectomy or double-barrier method (condom or diaphragm with spermicide)] during the study and up to 30 days after the last dose of the study drug..
3. Subjects must be willing and able to comply with the protocol requirements for the duration of the study.
4. Subjects must be able to comprehend, sign and date a written informed consent prior to entering the MS-LAQ-301E study.

Exclusion Criteria:

1. Premature discontinuation from the MS-LAQ-301 study, for any reason.
2. Pregnancy [according to urine dipstick β-HCG test performed at Baseline (Month 0E) visit] or breastfeeding.
3. Subjects with clinically significant or unstable medical or surgical condition detected or worsened during the MS-LAQ-301 study, which preclude safe participation and completion of the MS-LAQ-301E study. Acute exacerbation of MS will not exclude participation in the MS-LAQ-301E study.
4. Use of inhibitors of CYP3A4 within 2 weeks prior to baseline visit (V0E, Month 0E).

One capsule containing 0.6 mg laquinimod to be administered orally once daily.

-To assess the long-term safety and tolerability of daily oral laquinimod 0.6 mg in subjects with relapsing multiple sclerosis.

Safety and Tolerability Outcome Measures:

Safety:

• Adverse events
• Vital signs
• ECG findings
• Clinical laboratory parameters

Tolerability:

• Proportion of subjects (%) who prematurely discontinued from the study, reason of discontinuation and the time to withdrawal.
• Proportion of subjects (%) who prematurely discontinued from the study due to AEs and the time to withdrawal
• To assess the long-term effect of laquinimod 0.6 mg on disease course, as assessed by several parameters:
• Number of confirmed relapses
• Progression of disability as measured by the EDSS score (including FS and AI)
• Progression of disability as measured by the MSFC score
• Binocular low-contrast visual acuity using the 100%, 2.5% and 1.25% contrast level charts [Sloan letter (Appendix 9) or Tumbling-E (Appendix 10)]
• Subject-reported fatigue as assessed by the Modified Fatigue Impact Scale (MFIS)