Relapsing remitting multiple sclerosis MedDRA version: 16.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Laquinimod capsules 0.6 mg
Product Code: TV-5600
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LAQUINIMOD
CAS Number: 248281-84-7
Current Sponsor code: TV-5600
Other descriptiv
Sponsors
Teva Pharmaceutical Industries, Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Subjects must have a confirmed and documented RRMS diagnosis as defined by the Revised McDonald criteria, with relapse onset disease or a relapsing-remitting disease course. 2. Subjects must be ambulatory with an Kurtzke EDSS score of 0 5.5 at both at Screening and Baseline (randomization) visits. 3. Subjects must be in a stable neurological condition, relapse-free and free of any corticosteroid treatment or adrenocorticotrophic hormone (ACTH), 60 days prior to randomization. 4. Subjects must have experienced at least 1 documented relapse in the last year prior to randomization or 2 relapses in the last 3 years prior to randomization. 5. Subjects must be between 18 and 55 years of age at screening, inclusive. 6. Women of child-bearing potential must practice an acceptable method of birth control until 30 days after the last dose of treatment was administered. 7. Subjects must be able to sign and date a written informed consent prior to entering the study. 8. Subjects must be willing and able to comply with the protocol requirements for the duration of the study. 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 600 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1. Subjects with progressive forms of MS. 2. Subjects with Neuromyelitis Optica (NMO). 3. Use of experimental or investigational drugs and/or participation in drug clinical studies within 6 months prior to Baseline visit (randomization). 4. Use of immunosuppressive agents, or cytotoxic agents, including cyclophosphamide and azatioprine within 12 months prior to Baseline. 5. Prior use of monoclonal antibodies ever, except for: - Natalizumab (Tysabri®) if given more than 6 months prior to randomization AND the subject is John Cunningham (JC) virus antibody test negative at Screening. - Previous use of Rituximab, ocrelizumab, or ofatumumab is allowed if the B cell count (CD19) is higher than 80 cells /µL. 6. Previous treatment with glatiramer acetate (Copaxone® ), fingolimod (Gilenya®), BG-12 (Tecfidera), Teriflunomide (Aubagio®) or intravenous immunoglobulin (IVIG) within 2 months prior to Baseline. 7. Use of mitoxantrone (Novantrone) within 5 years prior to Screening. Use of mitoxantrone (Novantrone) >5 years before screening is allowed in subjects with normal ejection fraction and who did not exceed the total lifetime maximal dose. 8. Chronic systemic (IV, IM or PO) corticosteroid treatment within 2 months prior to Baseline. 9. Previous use of cladribine. 10. Previous use of laquinimod or Avonex® IM. 11. Treatment with other Interferon-ß (either 1a subcutaneous [SC] or 1b SC) within 60 days before baseline (earlier treatment will be allowed if the reason for discontinuation was not treatment failure or for Interferon-ß related safety reasons. This decision will be taken by the investigator). 12. Previous total body irradiation or total lymphoid irradiation. 13. Previous stem cell treatment, autologous bone marrow transplantation, or allogenic bone marrow transplantation. 14. Acute infection within 2 weeks prior to Baseline visit. 15. Major trauma or surgery within 2 weeks prior to Baseline visit. 16. Use of moderate/strong inhibitors of CYP3A4 within 2 weeks prior to Baseline. 17. Use of inducers of CYP3A4 within 2 weeks prior to Baseline 18. Pregnancy or breast feeding. 19. Serum levels =3 times (x) upper limit of normal (ULN) of either ALT or AST at Screening. 20. Serum direct bilirubin =2xULN at Screening. 21. 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. months prior to randomization. 22. Twenty or more gadolinium (Gd)- enhancing (E) lesions on baseline MRI. 23. A known history of sensitivity to gadolinium (Gd). 24. GFR = 60 mL/min at the screening visit. 25. Inability to successfully/safely undergo MRI scanning. 26. Subjects who underwent endovascular treatment for Chronic Cerebrospinal Venous Insufficiency (CCSVI). 27. Known hypersensitivity that would preclude administration of laquinimod capsule, such as hypersensitivity to: mannitol, meglumine, or sodium stearyl fumarate. 28. A known history of hypersensitivity to natural or recombinant interferon ß, human albumin, or any other component of the formulation of Avonex® 29. Employees of the clinical study site or any other individuals involved with the conduct of the study, or immediate family members of such individuals
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The overall study objective is to assess the efficacy, safety, and tolerability of 2 laquinimod doses, 0.6 mg/day or 1.2 mg daily (QD), in a double-blind design compared to Avonex® (rater blinded) once weekly (QW) Study objectives: • To evaluate the effect of 2 laquinimod doses (0.6 mg/day or 1.2 mg/day) compared to Avonex® QW on brain atrophy. • To evaluate the effect of 2 laquinimod doses (0.6 mg/day or 1.2 mg/day) on new T2 lesions. ;Secondary Objective: • To assess the effect of 2 laquinimod doses (0.6 mg/day or 1.2 mg/day) compared to Avonex® on the following patient reported outcomes (PRO): - Physical and psychological well-being (Multiple Sclerosis Impact Scale; MSIS-29) - General health status (36-Item Short Form Health Survey; SF 36) - Treatment satisfaction (Treatment Satisfaction Questionnaire for Medication; TSQM-9) - Cognitive performance (Symbol Digit Modalities Test; SDMT) - Disability (Patient-Determined Disease Step; PDDS) - Effect on work (Work Productivity and Activities Impairment – General Health; WPAI-GH) • To assess - the rate of influenza-like symptoms in the 2 laquinimod doses compared to Avonex® - the effect of 2 laquinimod doses compared to Avonex® on thalamic volume, cortical volume, and white matter (WM) volume - the dose-response effect of 2 laquinimod doses on magnetic resonance imaging (MRI) and clinical parameters - the safety and tolerability of 2 laquinimod doses;Primary end point(s): Change in whole brain atrophy as defined by the percent change in total brain volume between laquinimod 0.6 mg versus Avonex® and laquinimod 1.2 mg versus Avonex®. ;Timepoint(s) of evaluation of this end point: Change in whole brain atrophy from Month 0 (Baseline) to Month 12. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): • The cumulative number of influenza-like symptoms experienced on the 2 doses of laquinimod (0.6 mg and 1.2 mg) versus Avonex® • The cumulative number of new T2 lesions between the 2 laquinimod doses ;Timepoint(s) of evaluation of this end point: • The cumulative number of influenza-like symptoms experienced from baseline to Month 3 on each dose of laquinimod (0.6 mg and 1.2 mg) versus Avonex® • The cumulative number of new T2 lesions measured at Month 6 and Month 12 between the 2 laquinimod doses | — |
Countries
Belgium, Denmark, Finland, France, Germany, Ireland, Italy, Netherlands, Norway, Spain, Sweden, Switzerland, United Kingdom
Contacts
Public ContactClinical Trial Information Desk
Teva Pharma GmbH
Outcome results
None listed