AVONEX® Combination Trial – “ACT”

Inclusion Criteria:

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.