A clinical study in subjects with relapsing-remitting multiple sclerosis(RRMS) consisting of two parts:First part is to assess the efficacy, safety and tolerability of two oral doses of laquinimod either of 0.6 mg/day or 1.2mg/day (experimental drug) as compared placebo. Second part (all subjects receiving active treatment) is to evaluate the efficacy, safety and tolerability of two oral doses of laquinimod 0.6 mg/day or 1.2 mg/day (experimental drug).

Phase 1

Conditions: Relapsing remitting multiple sclerosis
MedDRA version: 14.1Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]

Registration Number: EUCTR2012-003647-30-BE

Lead Sponsor: Teva Pharmaceutical Industries Ltd

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 2199

Inclusion Criteria

1. Subjects must have a confirmed and documented MS diagnosis as defined by the Revised McDonald criteria, with relapse onset disease or a relapsing-remitting disease course.
2. Subjects must be ambulatory with Kurtzke EDSS score of 0-5.5 in both screening and randomization visits.
3.Subjects must be in a stable neurological condition, relapse-free and free of any corticosteroid treatment [intravenous (IV), intramuscular (IM) and/or per os (PO)] or adrenocorticotrophic hormone (ACTH), 60 days prior to randomization.
4. Subjects must have experienced at least one documented relapse in the 12 months prior to randomization.
5. Subjects must be between 18 and 55 years of age at screening, inclusive.
6. Subjects must have disease duration of not more than 15 years.
7. Women of child-bearing potential must practice an acceptable method of birth control until 30 days after the last dose of treatment was administered.
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.
10. Subjects must meet one or more of the following conditions:
- Patients who cannot receive other treatments for RRMS;
- Patients who have been unresponsive to their RRMS treatments;
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 1800
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

1. Subjects with progressive forms of MS.
2. Subjects with Neuromyelitis Optica (NMO).
3. Use of experimental or investigational drugs (including dimethyl fumarate and Teriflunomide)and/or participation in drug clinical studies within 6 months prior to randomization.
4. Use of immunosuppressive agents, including fingolimod (Gilenya®) or cytotoxic agents, including Cyclophosphamide within 6 months prior to randomization.
5. Use of either of the following within 2 years prior to randomization: natalizumab (Tysabri®), rituximab, ocrelizumab, atacicept, belimumab, or ofatumumab.
6. Previous treatment with glatiramer acetate (Copaxone®) Interferon-ß (either 1a or 1b) or intravenous immunoglobulin (IVIG) within 2 months prior to randomization.
7. Chronic (more than 30 consecutive days) systemic (IV, IM or PO) corticosteroid treatment within 2 months prior to randomization.
8. Previous use of Mitoxantrone (Novantrone®), Cladribine, or alemtuzumab (CAMPATH-1H).
9. Previous use of laquinimod.
10. Previous total body irradiation or total lymphoid irradiation.
11. Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation.
12. Use of moderate/strong inhibitors of CYP3A4 within 2 weeks prior to randomization.
13. Use of inducers of CYP3A4 within 2 weeks prior to randomization.
14. Pregnancy or breastfeeding.
15. Serum levels =3xULN of either ALT or AST at screening.
16. Serum direct bilirubin which is =2xULN at screening.
17. Subjects with a clinically significant or unstable medical or surgical condition or any other condition that cannot be well-controlled by the allowed medications permitted in the study protocol that would preclude safe and complete study participation, as determined by medical history, physical examinations, ECG, laboratory tests MRI or chest X-ray.
18. A known history of sensitivity to gadolinium (Gd).
19. GFR = 60 mL/min at the screening visit.
20. Inability to successfully undergo MRI scanning.
21. Subjects who underwent endovascular treatment for Chronic Cerebrospinal Venous Insufficiency (CCSVI) within 3 months prior to randomization.
22. Known hypersensitivity that would preclude administration of laquinimod capsule, such as hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To assess the efficacy, safety and tolerability of a daily dose of 0.6 mg and 1.2 mg of laquinimod as compared to placebo in subjects with relapsing remitting multiple sclerosis (RRMS).;Secondary Objective: Not applicable;Primary end point(s): Time to Confirmed Disease Progression (CDP) during Period 1. <br>CDP is defined as an increase in EDSS of =1 point from baseline for subjects with baseline EDSS of =5.0, or an increase in EDSS of = 0.5 points from baseline for subjects with baseline EDSS of 5.5. Analysis will be performed at the completion of Period 1.;Timepoint(s) of evaluation of this end point: Evaluation will be performed at months -1 (screening), 0 (baseline) and every 3 months thereafter and until completion visit of Period 1

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -Brain atrophy as defined by the percent change in brain volume from baseline to month 15 <br><br>-The time to first confirmed relapse during Period 1.<br>;Timepoint(s) of evaluation of this end point: In terms of brain atrophy:<br><br>evaulation at baseline and at month 15<br><br>In terms relapse evaluation:<br><br>Evaluation will be done at each timepoint during the study once any symptoms suggestive of a relapse appear / are reported by any subject. <br>

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