Multiple Sclerosis (MS) MedDRA version: 17.1 Level: PT Classification code 10048393 Term: Multiple sclerosis relapse System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Tysabri®
Product Name: AN100226, BG00002
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: NATALIZUMAB
CAS Number: 189261-10-7
Concentration unit: mg/ml milli
Sponsors
Biogen Idec Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: - Subjects of childbearing potential must practice effective contraception from Day -1 and be willing and able to continue contraception for duration of the study. - Must have documented diagnosis of relapsing MS (McDonald 2010 Criteria [Polman 2011]) at Screening. - Must have been treated with Gilenya or BRACET for at least the 12 months prior to Screening with no interruption of treatment greater than 1 month. More than 1 prior disease-modifying therapy is allowed, as long as minimum treatment duration was cumulatively 12 months. Prior treatment with natalizumab is allowed; however, there must be a minimum 1 year since last natalizumab infusion and the Screening visit of this study, and if discontinuation of natalizumab in the past was not due to intolerance, anti-natalizumab antibodies, or efficacy loss. - Must have had disease activity in the 6 months prior to Screening while on Gilenya or BRACET (as defined by at least 1 Gd+ lesion OR at least 2 new T2 lesions (compared with an MRI done within 12 months of screening) OR clinical relapse, or EDSS progression of 1 point) - Must have an EDSS score from 0 to 5.5 inclusive at Screening. NOTE: Other protocol-defined inclusion criteria may apply 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 200 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: - History or positive test result at Screening for human immunodeficiency virus (HIV). Prior treatment with Tysabri (either commercially or through a clinical study) within 1 year of Day -1. - Contraindications to treatment with Tysabri as described in the Prescribing Information for each of the participating countries. - Known allergy to Tysabri or known to be anti-natalizumab antibody positive. - Diagnosis of primary progressive MS, secondary progressive MS, and/or progressive-relapsing MS. - An MS relapse that has occurred within the 30 days prior to Day -1 and/or the subject has not stabilized from a previous relapse prior to Day -1. - Known active malignancies (subjects with cutaneous basal cell carcinoma that has been completely excised prior to study entry remain eligible). - History of severe opportunistic infections (including PML) or any clinically significant cardiac, endocrinologic, hematologic, hepatic, immunologic, metabolic, urologic, pulmonary, neurologic, dermatologic, psychiatric, and renal, or other major disease, as determined by the Investigator - Females breastfeeding, pregnant, or planning to become pregnant; women who are not post-menopausal or surgically sterile who are unwilling to practice contraception; women who have a positive pregnancy test result at Day -1. - Prior history of immunosuppressant use (e.g., mitoxantrone, azathioprine, methotrexate, cyclophosphamide, mycophenolate, cladribine, rituximab) in the last 12 months prior to Screening. Prior history of alemtuzumab use at any point in the past. NOTE: Other protocol-defined exclusion criteria may apply
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to determine the efficacy of Tysabri in subjects with relapsing forms of MS who have failed Gilenya or BRACET as measured by the proportion of subjects with no evidence of disease activity (NEDA) at Year 1.;Secondary Objective: The secondary objectives in this study population are to determine: 1. Change in total T1 hypointense and total T2 hyperintense lesion volume 2. Proportion of subjects with NEDA at Year 2 3. Change in MS cognition composite battery (MS-Cog) 4. Evaluation of the impact of Tysabri on annualized relapse rate (ARR) 5. Change in Multiple Sclerosis Impact Scale 29 (MSIS-29) physical impact score;Primary end point(s): The primary endpoint of the study is the proportion of subjects who have NEDA, defined as follows: 1) No EDSS progression (12-week sustained) 2) No relapses 3) No Gd+ lesions 4) No new or enlarging T2 hyperintense lesions over 48 weeks after resetting the baseline at Week 8 to remove CUA lesions that occurred prior to Week 8 when Tysabri was not yet active;Timepoint(s) of evaluation of this end point: Week 48 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study in this study population are as follows: 1) Change in total T1 hypointense and total T2 hyperintense lesion volume from Baseline (Day -1) to Week 56 and from Reset Baseline (Week 8) to Week 56 2) Proportion of subjects with NEDA (as defined above) from Week 8 (Reset Baseline) to Week 104 (with no 12-week confirmed EDSS progression determined at Week 116) 3) Change from Baseline (Day -1) to Week 56 and Week 104 in cognitive function as measured by an MS cognitive composite battery (MS-Cog) comprising 2 tests of processing speed (PASAT-2, PASAT-3, and SDMT) and 2 tests of memory and learning (SRT for verbal memory and BVMTR for visual memory) 4) ARR from Week 8 to Week 56 (Year 1), from Week 56 to Week 104 (Year 2), and across the 2 years (Week 8 to Week 104) 5) Change in MSIS-29 physical impact from Baseline (Day -1) to Week 56 and to Week 104;Timepoint(s) of evaluation of this end point: Week 56 and Week 104 | — |
Countries
Germany, Italy, United States
Outcome results
None listed