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Impact of Natalizumab versus Fingolimod on Central Nervous System (CNS) Tissue Damage and Recovery in Active Relapsing-Remitting Multiple Sclerosis (RRMS) Subjects

Conditions
Multiple Sclerosis (MS)
MedDRA version: 17.0Level: PTClassification code 10063399Term: Relapsing-remitting multiple sclerosisSystem Organ Class: 10029205 - Nervous system disorders
Therapeutic area: Diseases [C] - Nervous System Diseases [C10]
Registration Number
EUCTR2013-004622-29-IT
Lead Sponsor
Biogen Idec Research Limited
Brief Summary

Not available

Detailed Description

Not available

Recruitment & Eligibility

Status
ot Recruiting
Sex
All
Target Recruitment
540
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 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

Study & Design

Study Type
Interventional clinical trial of medicinal product
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Main Objective: The primary objective of the study is to assess the effect of natalizumab compared to fingolimod on the evolution of<br>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:<br>• MRI measures of CNS tissue destruction as measured by the number of new T1-Gd+ lesions.<br>• Various other MRI measures of disease activity.<br>• No Evidence of Disease Activity (NEDA)<br>• Relapse on treatment over 52 weeks.<br>• 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 Outcome Measures
NameTimeMethod
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