A total of 188 patients are planned for the multi-center study. Upon enrollment, patients will be randomly assigned to one of four treatment group: placebo, methylprednisolone 1 gram IV daily for 3 days, Hu23F2G 1 mg/kg IV, or Hu23F2G 2 mg/kg IV. The subjects will be followed for one year after treatment in order to assess the early changes related to the acute exacerbation (Day 0 to Day 90) as well as the subsequent course (Day 91 to Day 365). The clinical response to treatment will be measured by a neurologic examination form which three numerical scores are derived: the Scripps score, the sum of the Functional System (FS), and modified Expanded Disability Status Scale (EDSS). The primary endpoint will be the change in Scripps score form Day 0 through Day 90. The Scripps score was selected as the primary outcome measure because we hypothesize that it will be more sensitive to change in the setting of an acute exacerbation than the other two scores. The change in the sum of the FS and EDSS form Day 0 through Day 90 will be secondary endpoints. MRI of the brain will be obtained prior to treatment and on Day 5. The change in the extent of abnormalities detected on the MRI form Day 0 to Day 5 will be a secondary endpoint. Since corticosteroid rescue will be available for patients deemed to have failed the assigned treatment, the time to corticosteroid rescue will be a secondary endpoint. The clinical course over the year following treatment will be assessed by determining the time to the next exacerbation and the EDSS on Day 365; these parameters will also be secondary endpoints. The in vitro biologic activity and in vivo efficacy of Hu23F2G in a nonhuman primate model of experimental allergic encephalomyelitis (EAE) support a potential application in the treatment of MS. The acute exacerbation component of MS will be studied under this protocol. The rationale is that the EAE model is associated with acute onset of neurologic deficits and new lesions in the central nervous system (CNS), events that are analogous to the acute MS exacerbation. In the acute exacerbation setting, a treatment commonly offered is three to five days of corticosteroids. This treatment duration is comparable to the duration of maximal pharmacodynamic effects observed after a single IV dose of 1 to 2 mg/kg of Hu23F2G in Phase 1 studies. Since corticosteroids therapy is currently used for many patients with acute exacerbations, in this study the effects of Hu23F2G treatment will be compared to a standard corticosteroid regimen along with placebo. Corticosteroid therapy will also be available for patients deemed to have failed the assigned treatment.
NIH ExPorter
NIH ExPorter