OP0004 RESULTS OF A PHASE II, DOUBLE-BLIND, RANDOMIZED STUDY OF A NONDEPLETING ANTI-CD4 MONOCLONAL ANTIBODY (CLENOLIXIMAB) GIVEN IN COMBINATION WITH METHOTREXATE (MTX) IN PATIENTS WITH MODERATE TO SEVERE RHEUMATOID ARTHRITIS (RA)
ME Luggen, J Schechtman, A Kivitz, M Greenwald, J Forstot, E Boling, J Aldworth, M Ingram, M Totoritis

The objective of this double blind, placebo-controlled study was to assess the safety and efficacy of a non-depleting anti-CD4 monoclonal antibody, clenoliximab, in patients with active rheumatoid arthritis (RA) in spite of treatment with methotrexate.

Methods: 134 patients with active RA received IV infusions of clenoliximab 350 mg or placebo once weekly for 8 weeks followed by 3 more doses given every 4 weeks (maintenance). Methotrexate (15-25 mg/week) was maintained throughout the study. ACR responses were measured at week 9 as the primary endpoint.

Results: 119 patients could be evaluated. Related adverse events and infections were similar in both groups, although a higher incidence of rashes was found in patients treated with clenoliximab. Three related serious adverse events occurred in the clenoliximab group and resolved without complication; asthmatic bronchitis, bilateral pneumonia, and a transient low CD4+ T cell count. However, significant T cell depletion did not occur in patients receiving clenoliximab. ACR responses are noted in the table below.

The response to clenoliximab was not sustained through week 24, the maintenance period. Serum clenoliximab concentrations were at steady state, CD4+ T cells were consistently coated with clenoliximab, and CD4 antigen density was reduced during the induction period only.

Conclusion: Weekly dosing of clenoliximab in combination with methotrexate is efficacious in this group of patients with moderate to severely active RA, but a longer dosing interval of 4 weeks between doses could not sustain the clinical response.

Editorial Comment: The high placebo ACR 20 response may reflect the small numbers of patients in the placebo arm. The results appear promising but only with weekly infusions thus compromising its practicality as a therapy. The high mg dose of antibody will also make subcutaneous injection difficult. However, this approach strengthens the concept of targeting the T cell in RA.

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