Rebif Advanced Magnetic Resonance Imaging (MRI) and Immunology Pilot Trial

Study Overview
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Brief Summary
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The purpose of this trial is to evaluate the effects of Rebif® 44 mcg subcutaneous (sc) three times a week (tiw) on a) remyelination/demyelination, b) lesion and brain volume, c) central nervous system (CNS) iron deposition, and d) immune status in subjects with relapsing-remitting multiple sclerosis (RRMS) RRMS via several MRI techniques.

Official Title
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A Twenty-four Week, Two Arm, Pilot Trial to Evaluate Remyelination/ Demyelination, Gray Matter Volume and Iron Deposition in the Central Nervous System (CNS) and Immune Status of Subjects With Relapsing-remitting Multiple Sclerosis (RRMS) Treated With Rebif® 44 mcg Subcutaneously (sc) Three Times a Week (Tiw) Compared to a Healthy Control Group

Conditions
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Multiple Sclerosis

Intervention / Treatment
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* Drug: Rebif


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male and female subjects, 18-65 years of age, inclusive, at the time of informed consent signature RRMS diagnosed according to the McDonald criteria, treatment naïve or currently using any of the FDA-approved DMDs (excluding natalizumab (Tysabri®), mitoxantrone or Rebif®) Have a disease duration of up to twenty years Be willing and able to comply with the study procedures for the duration of the trial Have given written informed consent and signed Health Insurance Portability and Accountability Act (HIPAA) Authorization before any study- related activities are carried out Female subjects must not be either pregnant or breast-feeding and must lack childbearing potential, as defined by either: The following inclusion criteria must be fulfilled by the Healthy Control subjects: Male and female subjects, 18-65 years of age, inclusive, at the time of informed consent signature Be willing and able to comply with the study procedures for the duration of the trial Have given written informed consent and signed Health Insurance Portability and Accountability Act (HIPAA) Authorization before any study- related activities are carried out Female subjects must not be either pregnant or breast-feeding and must lack childbearing potential, as defined by either: Exclusion Criteria: Have received treatment within three months prior to Screening with interferon-beta-1a (Rebif®), IVIG or plasmapheresis Have received treatment within thirty days prior to screening with immunosuppressant agents (e.g. including but not limited to mitoxantrone, cyclophosphamide, cladribine, fludarabine, cyclosporine or total body irradiation) or any other concomitant immunomodulatory therapies (e.g., azathioprine, methotrexate, CellCept®, natalizumab, alemtuzumab/Campath and other immunomodulators/monoclonal agents) Have had a relapse within thirty days prior to the Screening Visit Have received steroid treatment within thirty days prior to the initial MRI scan date at Study Day 1 Have inadequate liver function, defined by a alanine aminotransferase (ALT) > 2.5x upper limit of normal (ULN), or alkaline phosphatase > 2.5x ULN, or total bilirubin > 1.5x ULN Have inadequate bone marrow reserve, defined as a total white blood cell count < 3.0x 109/L, platelet count < 75x109/L, hemoglobin < 100g/L Have complete transverse myelitis or simultaneous-onset bilateral optic neuritis Have a history of alcohol or drug abuse Have thyroid dysfunction Have moderate to severe renal impairment Have a major medical or psychiatric illness that in the opinion of the investigator creates undue risk to the subject or could affect compliance with the study protocol Have a history of seizures not adequately controlled by treatment Have serious or acute cardiac disease, such as uncontrolled dysrhythmias, uncontrolled angina pectoris, cardiomyopathy, or uncontrolled congestive heart failure Have, in the opinion of the investigator, any visual, physical or cognitive impairment that would preclude the subject from complying with the study protocol Have a known hypersensitivity or allergy to interferon-beta or any of the excipients Have received an investigational drug or experimental procedure within the past thirty days Are pregnant or attempting to conceive The following exclusion criteria must be fulfilled by the Healthy Control subjects: 1. Have met any of the above noted criteria

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Arm 1 MS Patients<br>Rebif 44 tiw | Drug: Rebif<br>* 44 mcg tiw<br>|
| No Intervention: Arm 2 Healthy Control<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Volume (in Millimeters Cubed) of Normal Appearing Brain Tissue (NABT) With Increasing (Indicative of Remyelination) Voxel-wise Magnetization Transfer Ratio (VW-MTR) From Baseline to 6 Months | To characterize the effect of Rebif on remyelination using VW-MTR dynamic mapping of NABT in subjects ith RRMS over 6 months of treatment compared to a group of healthy Control (HC). | Baseline to Month 6 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Volume (in Millimeters Cubed) of Normal Appearing Brain Tissue (NABT) With Decreasing (Indicative of Demyelination) Voxel-wise Magnetization Transfer Ratio (VW-MTR)From Baseline to 6 Months | To characterize the effect of Rebif on demyelination using VW-MTR dynamic mapping of NABT in subjects ith RRMS over 6 months of treatment compared to a group of healthy Control (HC). | Baseline to Month 6 |