Safety Study of Combination Therapy With Intramuscular Avonex and Oral Cellcept in Patients With Multiple Sclerosis
Condition: Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Sclerosis
Study type: Interventional
Phase: Phase 2/Phase 3

Summary: 
      1. To determine the safety and tolerability of oral Cellcept when used in combination with
           weekly intramuscular Avonex in early MS.

        2. To document changes in exacerbation frequency,

        3. To document the incidence of mild, moderate, and severe exacerbations in the treated
           groups (categorical analysis),

        4. To document changes in the level of sustained disability as measured by the expanded
           disability status score (EDSS) and ambulation index (AI),

        5. To document changes in quality of life measures,

        6. To assess fatigue with the validated fatigue assessment inventory,

        7. Neuroimmunological studies:At baseline, 6 and 12 months after treatment
    

Detailed description: 
      Design: Uni-center, double-blind, randomized, placebo-controlled study of Avonex + placebo vs
      Avonex + Cellcept

      Rationale: A number of immunopathogenic mechanisms have been hypothesized to figure
      prominently in the processes that culminate in the characteristic plaque lesion. These
      include the role of cytokines, chemokines, excitatory amino acids, free radicals,
      superoxides, and nitric oxide synthetase products. Recognizing that the disease process in MS
      involves a cascade of biological events, sets the stage for strategically targeting specific
      immunopathogenetic steps through rational combination therapy regimens. We now propose a
      combination clinical trial utilizing Avonex and mycophenolate mofetil (MMF), a novel agent
      with a broad spectrum of anti- inflammatory mechanisms.

        -  Study population: MS patients who have been diagnosed with clinically definite,
           laboratory supported definite, or monosymptomatic MS meeting CHAMPS criteria ref , of
           either sex, who are between the ages of 21 and 50 inclusive.

        -  Treatment Groups: 12 patients in each group, ALL patients on Intramuscular Avonex.
           Cellcept/Placebo will be started at 250mg bid for one week and then escalated by 250mg
           bid until a target dose of 1000mg bid is achieved and Avonex 30 mcg IM q week

      Patients also see an examining physician every three months, have brain MRI scans done every
      other month and donate WBCs through a procedure called leukapheresis (done every six months).

        -  Efficacy Parameters/Evaluations: EDSS, PSAT, MSFC and MRI, relapse rate and safety
           measures

        -  Safety Parameters/Evaluations: Safety will be assessed by virtue of changes in T2/FLAIR
           lesions (number and volume) and in gadolinium enhancements (measured at 6 and 12 months
           after treatment initiation) compared to baseline measurements derived from one
           pretreatment run- in scan. In addition, a variety of clinical assessments will be
           performed for the period of 12 months of treatment. We will enroll 12 patients in each
           group (24 total)
    

Intervention name(s): Mycophenolate Mofetil (cellcept)
Intervention type(s): Drug
Intervention MeSH terms: Mycophenolic Acid
Allocation: Randomized
Intervention model: Single Group Assignment
Masking: Double
Primary purpose: Treatment