Results of a Phase II Rheumatoid Arthritis Clinical Trial Using T-Cell Receptor Peptides

Summary

Restricted T-cell receptor gene use has been found in animal models of autoimmune disease. This observation has resulted in the successful use of T-cell receptor peptide therapy in animal studies. Initial phase I studies in patients with rheumatoid arthritis (RA) indicated that this therapy was safe and well tolerated. A double-blind, placebo-controlled, multicenter phase II rheumatoid arthritis clinical trial was undertaken using IR501 therapeutic vaccine, which consists of a combination of three peptides derived from T-cell receptors (Vβ3, Vβ14, Vβ17) in incomplete Freund’s adjuvant (IFA). These T-cell receptors were previously reported to be restricted in RA patients. A total of 99 patients received either 90μg (31 patients) or 300μg (35 patients) of IR501 therapeutic vaccine or IFA alone (33 patients) as a control. IR501 therapeutic vaccine was administered as a 1.0-ml intramuscular injection at weeks 0, 4, 8, and 20. Patients were followed for 32 weeks. The results of the trial indicated that the treatment was safe, with none of the patients discontinuing the trial because of treatment-related adverse events. No significant adverse events attributable to the study drug were observed. Patients in both dose groups treated with IR501 therapeutic vaccine showed improvement in disease condition. Most importantly, the 90-μg dose group showed a statistically significant improvement when compared to control patients after the third and fourth injections. More than 50% of the treated patients showed improvement compared to 19% of controls, as measured in accordance with the American College of Rheumatology definition for clinical response (ACR 20 criteria).