Relapsing Multiple Sclerosis
Conditions
Brief summary
A multinational, multicenter, randomized, double-blind, parallel-group, placebo-controlled study to assess the safety, tolerability and efficacy of two daily doses of oral laquinimod (0.6mg or 1.2mg) in adjunct to glatiramer acetate (GA) or interferon-beta (IFN-B) in relapsing remitting multiple sclerosis (RRMS) subjects
Interventions
DRUGLaquinimod 0.6
Laquinimod 0.6 capsule
DRUGLaquinimod 1.2
Placebo
OTHERGlatiramer Acetate or interferon-beta+ Placebo
GA 20 mg/1mL or IFN-B (Avonex®, Betaseron®/Betaferon®, Rebif® or Extavia®) + oral daily placebo
Sponsors
Teva Branded Pharmaceutical Products R&D, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
No
Inclusion criteria
1. Subjects must have a documented MS diagnosis as defined by the Revised McDonald criteria \[Ann Neurol 2011: 69:292-302\], with a relapsing-remitting disease course. 2. Subjects must be ambulatory with an EDSS score of 1-5.5 (inclusive) at the baseline visit. 3. Subjects must be relapse-free and in a stable neurological condition and free of corticosteroid treatment \[intravenous (IV), intramuscular (IM) and/or oral\] 30 days prior to screening (month -1). 4. Subjects must be treated with either Copaxone® or an IFN-B preparation (Avonex®, Betaseron®/Betaferon®, Rebif® or Extavia®), at a stable dose for at least 6 months prior to the screening visit (switching between IFN-B preparations during the 6 months prior to screening is allowed; switching between any IFN-B preparation and GA, or vice versa, is exclusionary). 5. Subjects must have had experienced at least one documented relapse in the 36 weeks prior to randomization, with an incomplete recovery of the neurological functions as compared to pre-relapse status. 6. Subjects must be between 18 and 55 years of age, inclusive. 7. Women of child-bearing potential must practice an acceptable method of birth control \[acceptable methods of birth control in this study include: surgical sterilization, intrauterine devices, oral contraceptive, contraceptive patch, long-acting injectable contraceptive or double-barrier method (condom or diaphragm with spermicide)\]. 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. An onset of a relapse between Month -1 (Screening) and 0 (Baseline), unstable neurological condition or any treatment with corticosteroids \[intravenous (IV), intramuscular (IM) and/or oral\] or Adrenocorticotropic hormone. 2. Use of experimental or investigational drugs, and/or participation in drug clinical studies within the 6 months prior to Screening. 3. Use of immunosuppressive including Mitoxantrone (Novantrone®) or cytotoxic agents within 6 months prior to the screening visit. 4. Previous use of either of the following: natalizumab (Tysabri®), cladribine, laquinimod, and fingolimod (Gilenya®). 5. Previous treatment with intravenous immunoglobulin (IVIG) within 2 months prior to screening visit. 6. Systemic corticosteroid treatment of ≥30 consecutive days duration within 2 months prior to screening visit. 7. Previous total body irradiation or total lymphoid irradiation. 8. Previous stem cell treatment, autologous bone marrow transplantation or allogenic bone marrow transplantation. 9. Use of moderate/strong inhibitors of cytochrome P450 CYP3A4 within 2 weeks prior to the screening visit. 10. Use of inducers of CYP3A4 within 2 weeks prior to the screening visit. 11. Use of amiodarone within 2 years prior to screening visit. 12. Pregnancy or breastfeeding. 13. A ≥3xULN serum elevation of either alanine transaminase (ALT) or aspartate transaminase (AST) at screening. 14. Serum direct bilirubin which is ≥2x upper limit of normal (ULN) at screening. 15. Subjects with a potentially 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 (but are not limited to): * 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 acute or chronic liver disease * Known human immunodeficiency virus (HIV) positive status * A history of drug and/or alcohol abuse * An unstable psychiatric disorder. * A known history of tuberculosis. * Unstable psychiatric disorder * Any malignancies, excluding basal cell carcinoma (BCC), in the last 5 years. 16. A glomerular filtration rate less than 60 ml/min at screening visit. 17. A known history of sensitivity to gadolinium (Gd). 18. Inability to successfully undergo MRI scanning. 19. Previous endovascular treatment for Chronic Cerebrospinal Venous Insufficiency (CCSVI). 20. Known drug hypersensitivity that would preclude administration of laquinimod, such as hypersensitivity to: mannitol, meglumine or sodium stearyl fumarate.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and efficacy | 10 months | To assess the safety, tolerability and efficacy of laquinimod in RRMS |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Tolerability | 10 months | To assess the safety, tolerability and efficacy of laquinimod in RRMS as compared to placebo, subjects treated with GA or an IFN-B preparation (Avonex®, Betaseron®/Betaferon®, Rebif® or Extavia®). |
Outcome results
None listed