TREATMENT OF MULTIPLE-SCLEROSIS WITH THE MONOCLONAL ANTI-CD4 ANTIBODYCM-T412 - RESULTS OF A RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED, MR-MONITORED PHASE-II TRIAL

We report the results of a randomized, double-blind, placebo-controlle d exploratory trial of the chimeric monoclonal anti-CD4 antibody cM-T4 12 in 71 patients suffering from active relapsing-remitting and second ary progressive multiple sclerosis. Infusion of the antibody produced frequent but usually minor side effects and resulted in a long-lasting reduction of circulating CD4-positive T cells. There was no significa nt effect on the primary measure of efficacy, the number of active les ions on monthly gadolinium-enhanced MRI over 9 months. Further statist ical evaluation provided evidence that the degree of depletion of CD4- positive cells was important with regard to treatment efficacy; using CD4 counts as a covariate there was a statistically significant effect on the number of active lesions over 18 months (p = 0.04). There was a statistically significant reduction of 41% in the number of clinical relapses (a secondary efficacy parameter) after 9 months (p = 0.02), which was still present after 18 months, but this finding may be partl y due to physician unblinding. Other secondary efficacy parameters (Ex panded Disability Status Scale progression, number of courses of methy lprednisolone) were not influenced by anti-CD4 treatment. We conclude that intravenous treatment with the monoclonal antibody cM-T412 in the dosage we used results in a substantial and sustained reduction of th e number of circulating CD4-positive cells, but is not able to reduce MS activity as measured by monthly gadolinium-enhanced MRI, and is the refore unlikely to have a beneficial effect on the clinical disease co urse. We found preliminary evidence suggesting that more aggressive de pletion of CD4-positive cells might lead to a more substantial reducti on in MRI activity.