Primary Progressive Multiple Sclerosis MedDRA version: 19.0 Level: PT Classification code 10063401 Term: Primary progressive multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Product Name: Laquinimod
Product Code: TV-5600
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: LAQUINIMOD
CAS Number: 248282-07-
Sponsors
Teva Pharmaceutical Industries Ltd.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients must have a confirmed and documented PPMS diagnosis as defined by the current valid McDonald criteria 2. Baseline magnetic resonance imaging (MRI) showing lesions consistent with PPMS in either or both brain and spinal cord 3. Patients must have an Expanded Disability Status Scale (EDSS) score of 3 to 6.5, inclusive, at both screening and baseline visits 4. Documented evidence of clinical disability progression in the 2 years prior to screening. 5. Functional System Score (FSS) of > or equal 2 for the pyramidal system or gait impairment due to lower extremity dysfunction 6. Patients must be between 25 to 55 years of age, inclusive 7. Women of child-bearing potential must practice an acceptable method of birth control for 30 days before taking the study drug, and 2 acceptable methods of birth control during all study duration and until 30 days after the last dose of treatment is administered. 8. Patients must sign and date a written informed consent prior to entering the study. 9. Patients 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 375 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Patients with history of any multiple sclerosis (MS) exacerbations or relapses, including any episodes of optic neuritis. 2. Progressive neurological disorder other than PPMS. 3. Any MRI record showing presence of cervical cord compression. 4. Baseline MRI showing other findings (including lesions that are atypical for PPMS) that may explain the clinical signs and symptoms. 5. Relevant history of vitamin B12 deficiency. 6. Positive human T-lymphotropic virus Type I and II (HTLV-I/II) serology. 7. Use of experimental or investigational drugs in a clinical study within 24 weeks prior to baseline. Use of a currently marketed drug in a clinical study within 24 weeks prior to baseline would not be exclusionary, provided no other exclusion criteria are met. 8. Use of immunosuppressive agents, or cytotoxic agents, including cyclophosphamide and azathioprine within 48 weeks prior to baseline. 9. Previous treatment with fingolimod (GILENYA®, Novartis), dimethyl fumarate (TECFIDERA®, Biogen Idec Inc), glatiramer acetate (COPAXONE®, Teva), interferon-ß (either 1a or 1b), intravenous immunoglobulin, or plasmapheresis within 8 weeks prior to baseline. 10. Use of teriflunomide (AUBAGIO®, Sanofi) within 2 years prior to baseline, except if active washout (with either cholestyramine or activated charcoal) was done 2 months or more prior to baseline. 11. Prior use of monoclonal antibodies ever, except for: a. natalizumab (TYSABRI®, Biogen Idec Inc), if given more than 24 weeks prior to baseline AND the patient is John Cunningham (JC) virus antibody test negative (as per medical history) b. rituximab, ocrelizumab, or ofatumumab, if B cell count (CD19, as per medical history) is higher than 80 cells/µL 12. Use of mitoxantrone (NOVANTRONE®, Immunex) within 5 years prior to screening. Use of mitoxantrone >5 years before screening is allowed in patients with normal ejection fraction and who did not exceed the total lifetime maximal dose. 13. Previous use of laquinimod. 14. Chronic (eg, more than 30 consecutive days or monthly dosing, with the intent of MS disease modification) systemic (intravenous, intramuscular or oral) corticosteroid treatment within 8 weeks prior to baseline. 15. Previous use of cladribine or alemtuzumab (LEMTRADA®, Sanofi). 16. Previous total body irradiation or total lymphoid irradiation. 17. Previous stem cell treatment, cell-based treatment, or bone marrow transplantation of any kind. 18. Patients who underwent endovascular treatment for chronic cerebrospinal venous insufficiency (CCSVI) within 12 weeks prior to baseline. 19. Use of moderate/strong inhibitors of cytochrome P450 (CYP) 3A4 within 2 weeks prior to baseline. 20. Use of inducers of CYP3A4 within 2 weeks prior to baseline. 21. Pregnancy or breastfeeding. 22. Serum levels =3× upper limit of the normal range (ULN) of either alanine aminotransferase (ALT) or aspartate aminotransferase (AST) at screening. 23. Serum direct bilirubin which is =2×ULN at screening. 24. Patients with a clinically significant or unstable medical or surgical condi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objectives of this study are to assess the efficacy, safety, and tolerability of a once daily oral dose of laquinimod (0.6 or 1.5 mg) compared to placebo in PPMS patients.;Secondary Objective: Not applicable;Primary end point(s): Brain atrophy (BA), defined as change in brain volume;Timepoint(s) of evaluation of this end point: Percentage in Brain Volume Change (PBVC) from baseline to week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): - Time to CDP (confirmed disability progression) defined by an increase in baseline EDSS - Time to CDP defined by an increase in baseline EDSS or at least a 20% worsening in the Timed 25 Foot Walk - The number of new T2 brain lesions - Change from baseline in the T25FW score ; Timepoint(s) of evaluation of this end point: -Time to confirmed disability progression (CDP), to be confirmed after at least 12 weeks -An increase from baseline in EDSS score confirmed after at least 12 weeks -An increase of at least 20% from baseline in T25FW score, confirmed after at least 12 weeks -The number of new T2 brain lesions at week 48 -Change from baseline to week 48 in the T25FW score | — |
Countries
Canada, Germany, Italy, Netherlands, Poland, Russian Federation, Spain, Ukraine, United Kingdom, United States
Contacts
Public ContactClinical Trial Information Desk
Teva GmbH
Outcome results
None listed