AVONEX® Combination Trial - "ACT"

• Age 18 to 55, inclusive
• Diagnosis of MS
• A relapsing-remitting course
• Expanded Disability Status Scale (EDSS) score 0.0-5.5 inclusive at Baseline
• Currently receiving AVONEX® therapy
• Treated with AVONEX® for at least 6 consecutive months prior
• Breakthrough disease (clinical relapse or gadolinium-enhancing MRI lesion) during the prior 12 months, at least 6 months after initiating AVONEX therapy.

Exclusion Criteria:

• History of cirrhosis, chronic hepatitis, or currently active hepatitis
• History of poorly-controlled hypertension, diabetes mellitus, or peptic ulcer disease
• History of aseptic bone necrosis, osteoporosis, or osteoporosis-related bone fracture
• History of steroid-induced psychosis.
• History of or abnormal laboratory results indicating significant illness
• History of severe allergic or anaphylactic reactions or known drug hypersensitivity or intolerance to MTX, IVMP, or AVONEX®.
• History of allergy to albumin
• History of any episode of suicidal ideation or severe depression within 3 months of the Screening Visit.
• History of seizure within 3 months prior to the Screening Visit.
• Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS
• MS relapse with onset within 60 days prior to the Baseline Visit
• Any metallic or electronic material or device in the body, or condition that precludes the subject from undergoing MRI with gadolinium administration
• A clinically significant infectious illness (e.g., cellulitis, abscess, pneumonia, septicemia) within 30 days of the Screening Visit
• Abnormal blood tests, performed at the Screening Visit, which exceed any of the limits defined by the study.