MS

Trial Status: Open

Protocol: ACT: Avonex Combination Trial
Principle Investigator: Mark Janicki
Sub Investigators: Charles Simchak Jeffrey Hilburn
Synopsis: Will test the effectivness of Avonex combination with Methyltrexate vs combinatioin with Methylprednisilone is more effective at preventing MS exacerbations.

Inclusion

To be eligible for entry into this study, a subject must meet the following eligibility criteria at the time points specified:

1. Age 18 to 55, inclusive at the Baseline (randomization) Visit.
2. Diagnosis of MS, as defined by McDonald, et al.(100) A relapsing-remitting course (RR-MS).(1)
3. Currently receiving AVONEX® therapy and treated with AVONEX® for at least 6 consecutive months prior to the Screening Visit.
4. Breakthrough disease during the 12 months prior to the Screening Visit, defined as subjects who have experienced the following, after >6 consecutive months of AVONEX® therapy:
   • >1 documented clinical relapse. For eligibility, a pre-study relapse is defined as neurologic symptoms and signs documented by review of the history with the subject or in the medical record, of sufficient severity and duration to be determined by the site investigator as consistent with an acute MS relapse. The relapse does not need to have been treated to qualify. The timing of the relapse is defined based on the onset of symptoms.
     OR
   • >1 documented Gd-enhancing lesion on cranial or spinal MRI. The presence of a Gd-enhancing lesion must be documented either by a report in the medical record or review of the films by the site investigator.

The subject does not need to have been treated solely or continuously with AVONEX® subsequently, but if AVONEX® therapy was discontinued, it must have been restarted, and he/she must have been treated with AVONEX® 30 mcg IM weekly for >6 consecutive months prior to the Screening Visit.

Exclusion

Candidates will be excluded from study entry if any of the following exclusion criteria exist. These criteria refer to the Screening Visit unless otherwise specified:

1. History of cirrhosis, chronic hepatitis, or currently active hepatitis.
2. History of poorly-controlled hypertension, diabetes mellitus, or peptic ulcer disease, as defined by the site investigator.
3. History of aseptic bone necrosis, osteoporosis (prior T score <-2.5 on DEXA scan), or osteoporosis-related bone fracture.
4. History of steroid-induced psychosis.
5. History of, or abnormal laboratory results indicative of any other significant cardiac, endocrinologic, hematologic, hepatic, immunologic, infectious, metabolic, urologic, pulmonary, gastrointestinal, dermatologic, psychiatric (including major depression), renal, or other major disease, that, in the opinion of the site investigator, would preclude the safe administration of MTX, IVMP, or AVONEX® for 24 months.
6. History of severe allergic or anaphylactic reactions or known drug hypersensitivity or intolerance to MTX, IVMP, or AVONEX®.
7. History of allergy to albumin.
8. History of any episode of suicidal ideation or severe depression within 3 months of the Screening Visit. Severe depression is defined as any episode of depression that requires hospitalization.
9. History of seizure within 3 months prior to the Screening Visit.
10. Diagnosis of primary progressive, secondary progressive, or progressive relapsing MS as defined by Lublin and Reingold(1) at the Screening Visit. These conditions require the presence of continuous clinical disease worsening over a period of at least 3 consecutive months. Subjects with SP-MS may have superimposed relapses but are distinguished from RR-MS subjects by the presence of progression between relapses.
11. MS relapse with onset within 60 days prior to the Baseline Visit or the subject has not stabilized from a previous relapse, in the opinion of the site investigator, at the time of the Baseline Visit.
12. Any metallic or electronic material or device in the body, or condition that precludes the subject from undergoing MRI.
13. Current enrollment in any other investigational study or prior treatment with any other investigational drug for MS within the last year unless approved by the Steering Committee.
14. Prior treatment with any of the following medications:
    • Methotrexate.
    • Total lymphoid irradiation.
    • Cladribine.
    • T-cell or T-cell receptor vaccination.
    • Natalizumab or any other therapeutic monoclonal antibody.
15. Treatment with any of the following medications within 1 year prior to the Screening Visit:
    • Cyclophosphamide.
    • Novantrone® (mitoxantrone).
    • Cyclosporine.
    • CellCept® (mycophenolate mofetil)
16. Treatment with any of the following medications or procedures within 6 months prior to the Screening Visit:
    • Copaxone® (subcutaneous glatiramer acetate).
    • Imuran® (azathioprine).
    • Intravenous immunoglobulin (IVIG).
    • Plasmapheresis or cytapheresis.
17. Treatment with any of the following medications within 60 days prior to the Screening Visit:
    • IV or oral corticosteroid treatment.
    • 4-Aminopyridine.
    • Oral glatiramer acetate.
18. Subjects with prior documented anti-IFN NAb serum titer >1:5.
19. History of alcohol or drug abuse (as defined by the site investigator) within 2 years prior to the Screening Visit.
20. Female subjects who are not postmenopausal for at least 1 year, not surgically sterile, or not willing to practice effective contraception (as defined by the site investigator) during the study and for 3 months after discontinuation of oral study drug. The rhythm method is not to be used as the sole method of contraception.
21. Nursing mothers, pregnant women, and women planning to become pregnant while on study.
22. Male subjects who are not willing to practice effective contraception (as defined by the site investigator) during the study and for 3 months after discontinuation of oral study drug.
23. Previous participation in this study.