CLINICAL AND IMMUNOLOGICAL EFFECTS OF A PRIMATIZED(R) ANTI-CD4 MONOCLONAL-ANTIBODY IN ACTIVE RHEUMATOID-ARTHRITIS - RESULTS OF A PHASE-I, SINGLE-DOSE, DOSE ESCALATING TRIAL

Objective. The goal of this single infusion, dose escalation study was to evaluate the safety of the PRIMATIZED(R) anti-CD4 monoclonal antib ody (Mab), IDEC-CE9.1, in patients with rheumatoid arthritis (RA;). Me thods. Twenty-five patients received single infusions of IDEC-CE9.1 in dose escalation form (0.03 to 4 mg/kg). Cohorts consisted of 3 patien ts each with seropositive RA. Following treatment, patients were monit ored for 2 weeks before initiation of treatment of the next cohort. Pe ripheral blood samples were taken during and after treatment to measur e immune function. Flow cytometry of peripheral blood mononuclear cell s and in vitro proliferative responses to antigens and recall antigens were assessed pre and post-treatment. Cell surface markers CD3, CD4 ( OKT4 and Leu 3a), CD8, CD20, CD25, CD45Ro, CD45Ra and DR were analyzed , and proliferation to mitogens and recall antigens was measured. Resu lts, No infusion related adverse events were noted and other drug rela ted adverse events were mild. Reduction in peripheral CD4 T cell numbe r was brief (3 to 7 days) and not associated with infection. CD4 cell surface antigen downmodulation was observed postinfusion. Suppression of CD25 expression was associated with a positive clinical response. I n vitro proliferative responses to mitogens and antigen were Inhibited for up to one month with no association to positive clinical response . Conclusion, IDEC-CE9.1 appears to have a benign safety profile and m ay modulate immune function rather than deplete CD4+ T cells.