Multiple Sclerosis (MS) MedDRA version: 17.0 Level: PT Classification code 10063399 Term: Relapsing-remitting multiple sclerosis System Organ Class: 10029205 - Nervous system disorders
Conditions
Interventions
Trade Name: Tysabri®
Product Name: AN100226, BG00002
Pharmaceutical Form: Concentrate and solvent for solution for infusion
INN or Proposed INN: NATALIZUMAB
CAS Number: 189261-10-7
Concentration unit:
Sponsors
Biogen Idec Research Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion Criteria for MS Patients: - Must have a documented diagnosis of relapsing MS (McDonald 2010 Criteria [Polman 2011]) at study screening. - If the subject is on BRACE at study screening: • He/she must have been on therapy for at least 12 months, and • Experienced =1 relapse within the last 6 months prior to study screening with =1 new T1-Gd+ lesion or =2 new T2 lesions on a brain MRI scan performed =6 months prior to study screening, with comparison made to a T2 MRI scan performed up to 18 months before study screening. - If the subject is DMT naïve at study screening, he/she must have experienced =2 relapses in the 12 months prior to study screening. In addition, they must have had =1 new T1-Gd+ lesion or =2 new T2 lesions on a brain MRI scan performed =6 months prior to study screening, with comparison made to a T2 MRI scan performed up to 18 months prior to study screening. - Willing to take natalizumab or fingolimod as the only DMTs for the duration of the study. - Must have an EDSS score from 0 to 5.5 inclusive at study screening. Inclusion Criteria for Healthy Volunteers: - Subjects who are generally healthy as demonstrated by physical examination and by medical history, with no history or evidence of major illnesses, diseases, or disorders. 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 540 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: Exclusion Criteria for MS Patients: - History of or positive test result at study screening for human immunodeficiency virus (HIV). - History or positive test result at study screening for hepatitis C virus (HCV) antibody or current hepatitis B infection (defined as positive for hepatitis B surface antigen [HBsAg] and/or hepatitis B core antibody [HBcAb]). Subjects with immunity to hepatitis B from either active vaccination (defined as negative HBsAg, positive hepatitis B surface antibody [HBsAb] and negative HBcAb) or from previous natural infection (defined as negative HBsAg, positive HBsAb immunoglobulin G, and positive HBcAb) are eligible to participate in the study (definitions are based on the United States (US) Centers for Disease Control and Prevention [CDC]’s interpretation of the hepatitis B serology panel). - Prior treatment with natalizumab or fingolimod - Diagnosis of Primary Progressive Multiple Sclerosis [PPMS] and/or Secondary Progressive Multiple Sclerosis [SPMS] -Exclusion Criteria for Healthy Volunteers: - Claustrophobia sufficient to interfere with generating reliable MRI scans - History of other major illness including neurological disorders as determined by the Investigator - Presence of a metal device affected by MRI (e.g., any type of electronic, mechanical or magnetic implant, cardiac pacemaker, aneurysm clips, implanted cardiac defibrillator) or potential ferromagnetic foreign body (metal slivers, metal shavings, other metal objects), which would be a contraindication for MRI
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary objective of the study is to assess the effect of natalizumab compared to fingolimod on the evolution of new on-treatment T1-gadolinium-enhancing (Gd+) lesions to persistent black holes (PBH) over 52 weeks.;Secondary Objective: The secondary objectives of this study are to assess the effect of natalizumab compared to fingolimod on: • MRI measures of CNS tissue destruction as measured by the number of new T1-Gd+ lesions. • Various other MRI measures of disease activity. • No Evidence of Disease Activity (NEDA) • Relapse on treatment over 52 weeks. • The change in information processing speed as measured by the Symbol Digit Modalities Test (SDMT).;Primary end point(s): The primary endpoint of the study is the cumulative number of =6-month confirmed T1-hypointense lesions (i.e., PBH) arising from new on-treatment T1-Gd+ lesions.;Timepoint(s) of evaluation of this end point: Weeks 4, 8, 12, 16, 20, 24, 52 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The secondary endpoints of this study are the follwoing: • MRI endpoints: o Cumulative number of new T1-Gd+ lesions . o Change in total T1-hypointense and total T2-hyperintense lesion volumes. o Cumulative number of new or enlarging T2 lesions. • Proportion of subjects with NEDA according to the following definition: o No relapses. o No 12-week confirmed disability progression based on EDSS.* o No new T1-Gd+ lesions on brain MRI. o No new or enlarging T2-hyperintense lesions. • Time to first relapse, cumulative risk of relapses and time to complete recovery from first relapse. ** • Change in information processing speed as measured by the SDMT from baseline to Week 24 and Week 52. * Increase of 1.0 or more on the EDSS from a baseline score of 1.0 or more, or an increase of 1.5 or more from a baseline score of 0 that was sustained for 12 weeks (progression could not be confirmed during a relapse). ** 12-week confirmed complete Expanded Disability Status Scale (EDSS) recovery from first on-treatment relapse is defined as an EDSS score that is equal to or lower than the last pre-relapse EDSS score and sustained for at least 12 week;Timepoint(s) of evaluation of this end point: Weeks 4, 8, 12, 16, 20, 24, 52 | — |
Countries
Australia, Canada, Czech Republic, Denmark, France, Germany, Italy, Spain, Sweden, United Kingdom, United States
Outcome results
None listed