Combination Therapy Using Mycophenolate Mofetil (CellCept) and Human Interferon beta1a (Rebif) in Early Treatment of Multiple Sclerosis

A total of 30 patients will be studied, fifteen in each arm. Proportional analysis for sample size estimation could not be done since the proportion of MxA positive patients at 1 year in the Rebif® treatment arm is unknown. Nevertheless, a sample size of 15 patients per arm will allow the detection of a suitable difference between the treatment groups as outlined below:

For purposes of this study an MxA non-producer will be designated as a "treatment failure" irrespective of the clinical status. The definition of an MxA non-producer is a patient who is producing 1 year into treatment; MxA transcripts at a level 2 SD below his/her mean baseline value at entry. Accordingly, patients will be compared to their own initial response to Rebif® at entry into the study. In the following examples the proportion of MxA non-producers in each group will be used for comparisons.

At the end of 1 year, the incidence of neutralizing antibodies in patients receiving Rebif® 44 micrograms SC tiw is approximately 20%. For purposes of calculation of sample size, a proportion of 40% (0.4) was chosen for the MxA non-producers in the Rebif® arm, since the proportion of patients that fail to produce MxA at 1 year is higher than the proportion that show neutralizing antibodies. In other words, mechanisms other than neutralizing antibodies are the basis of interferon unresponsiveness in most patients, an important phenomenon that is lost to detection if the sole focus is restricted to neutralizing antibodies. Assuming that the combination will be effective in maintaining biological activity of interferon at 1 year in most or all of the patients, the following scenarios can be identified.

Patients will be randomly assigned to either receive Rebif with or without CellCept. The randomization process will utilize a computer program designed specifically for randomizing patients. Patients will have an equal chance of being randomized to receive Rebif with or without CellCept therapy.

Each subject must meet the following eligibility criteria (i.e., all of the Inclusion criteria and not of the Exclusion criteria) before enrollment in to the study: