T-CELL RECEPTOR PEPTIDE VACCINATION IN RHEUMATOID-ARTHRITIS - A PLACEBO-CONTROLLED TRIAL USING A COMBINATION OF V(BETA)3, V(BETA)14, AND V(BETA)17 PEPTIDES

Objective. Restricted T cell receptor (TCR) gene usage has been demons trated in animal models of autoimmune disease and has resulted in the successful use of TCR peptide therapy in animal studies, This clinical trial was undertaken to determine the safety and efficacy of a combin ation of V(beta)3, V(beta)14, and V(beta)17 TCR peptides in Freund's i ncomplete adjuvant (IFA) in patients with rheumatoid arthritis (RA). M ethods. A double-blind, placebo-controlled, multicenter, phase II clin ical trial was undertaken using IR501 therapeutic vaccine, which consi sts of a combination of 3 peptides derived from TCRs (V(beta)3, V(beta )14, and V(beta)17) in IFA. A total of 99 patients with active RA rece ived either 90 mu g (n = 31) or 300 mu g (n = 35) of IR501 or IFA alon e (n = 33) as a control. The study medication and placebo were adminis tered as a single intramuscular injection (1 ml) at weeks 0, 4, 8, and 20. Results. Treatment with IR501 was safe and well tolerated. None o f the patients discontinued the trial because of treatment-related adv erse events. Efficacy was measured according to the American College o f Rheumatology 20% improvement criteria. Using these criteria, patient s in both IR501 dosage groups showed improvement in disease activity. In the most conservative analysis used to evaluate efficacy, an intent -to-treat analysis including all patients who enrolled, the 90-mu g do sage group showed a statistically significant improvement compared wit h control patients at the 20-week time point after the third injection . Trends toward improvement were shown in both the 90-mu g and the 300 -mu g dosage groups at week 24 after the fourth injection. Conclusion. IR501 therapeutic vaccine therapy was safe and well tolerated, immuno genic, and demonstrated clinical improvement in RA patients. Additiona l clinical trials are planned to confirm and extend these observations .