Safety and Efficacy of Orally Administered Laquinimod Versus Placebo for Treatment of Relapsing Remitting Multiple Sclerosis (RRMS)
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Intervention: Laquinimod; Placebo
Intervention description: Laquinimod 0.6 mg capsule, oral, once daily; oral, once daily, capsule
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Enrollment: 1106.0
Sex: All
Minimum age: 18 Years
Maximum age: 55 Years
Healthy volunteers: No
Keywords: Relapsing; Remitting

Summary:

      Determination the efficacy of daily oral treatment with laquinimod 0.6 mg capsules as
      compared to placebo in subjects with Relapsing Remitting Multiple Sclerosis (RRMS).
    

Eligibility criteria:

        Inclusion Criteria:

          1. 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.

          2. Subjects must be ambulatory with converted Kurtzke EDSS score of 0-5.5.

          3. Subjects must be in a stable neurological condition and free of corticosteroid
             treatment [intravenous (iv), intramuscular (im) and/or per os (po)] 30 days prior to
             screening (month -1).

          4. 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.

          5. Subjects must be between 18 and 55 years of age, inclusive.

          6. Subjects must have disease duration of at least 6 months (from the first symptom)
             prior to screening.

          7. Women of child-bearing potential must practice an acceptable method 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).

          8. Subjects must be able to sign and date a written informed consent prior to entering
             the study

          9. Subjects must be willing and able to comply with the protocol requirements for the
             duration of the study.

        Exclusion Criteria:

          1. Subjects with progressive forms of MS

          2. An onset of relapse, unstable neurological condition or any treatment with
             corticosteroids [intravenous (iv), intramuscular (im) and/or per os (po)] or ACTH
             between month -1 (screening) and 0 (baseline).

          3. Use of experimental or investigational drugs, and/or participation in drug clinical
             studies within the 6 months prior to screening.

          4. Use of immunosuppressive including Mitoxantrone (Novantrone®) or cytotoxic agents
             within 6 months prior to the screening visit.

          5. Previous use of either of the following: natalizumab (Tysabri®), cladribine,
             laquinimod.

          6. Previous treatment with glatiramer acetate (Copaxone®) Interferon-β (either 1a or 1b)
             or IVIG within 2 months prior to screening visit.

          7. Systemic corticosteroid treatment of ≥30 consecutive days duration within 2 months
             prior to screening visit.

          8. Previous total body irradiation or total lymphoid irradiation.

          9. Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone
             marrow transplantation.

         10. A known history of tuberculosis.

         11. Acute infection two weeks prior to baseline visit.

         12. Major trauma or surgery two weeks prior to baseline

         13. A history of vascular thrombosis (excluding catheter-site superficial venous
             thrombophlebitis).

         14. A carrier state of factor V Leiden mutation (either homo- or heterozygous) as
             disclosed at screening.

         15. Positive screening test for Hepatitis B surface antigen, Hepatitis C antibody, or HIV
             antibody as disclosed at screening visit.

         16. Use of potent inhibitors of CYP3A4 within 2 weeks prior to baseline visit (1 month for
             fluoxetine) see detailed list in Appendix 5

         17. Use of amiodarone within 2 years prior to screening visit.

         18. Pregnancy or breastfeeding.

         19. 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 or metabolic 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 2 ECG recordings at screening or from the
                  mean value calculated from 3 measurements at baseline visit) which is >450msec.

               -  A family history of Long- QT syndrome.

               -  A history of drug and/or alcohol abuse.

               -  Major psychiatric disorder.

         20. A known history of sensitivity to Gd.

         21. Inability to successfully undergo MRI scanning.

         22. Known drug hypersensitivity that would preclude administration of laquinimod, such as
             hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate.

        Exclusion Criteria:

          1. Subjects who suffer from any form of progressive MS.

          2. Any condition which the investigator feels may interfere with participation in the
             study.

          3. Subjects with a clinically significant or unstable medical or surgical condition that
             would preclude safe and complete study participation,

          4. Subjects who received any investigational medication, immunosuppressives or cytotoxic
             agents within 6 months prior to screening

          5. Previous treatment with immunomodulators within two months prior to screening

          6. Pregnancy or breastfeeding.