Immunome Research
Open Access

Abstract

Therapeutic Effect of Oral CF101 in Patients with Rheumatoid Arthritis: A Randomized, Double-blind, Placebo-controlled Phase II Study

Rumen M Stoilov, Rodina N Licheva, Mariyana K Mihaylova, Tatiana Reitblat, Emil A Dimitrov, Krasimira M Shimbova, Girish Bhatia, Ameet Pispati, Alexandra Gurman- Balbir, BR Bagaria, Boytcho Aleksandrov Oparanov, Sari Fishman, Zivit Harpaz, Motti Farbstein, Shira Cohen, David Bristol, Michael H Silverman and Pnina Fishman

Background: CF101, an orally bioavailable A3 adenosine receptor (A3AR) agonist, demonstrated very good safety and anti-inflammatory effect in Phase II clinical studies in patients with rheumatoid arthritis (RA) and psoriasis. A3AR expression level in peripheral blood mononuclear cells has been defined as a biological predictive marker, based on a significant correlation found in a former RA Phase II study between its over expression at baseline and positive patients’ response to CF101 treatment.
Methods: 79 patients were enrolled to a phase II, multicenter, randomized, double-blind, Placebo controlled, parallel-group study designed to assess the efficacy and safety of CF101 1mg vs. placebo, administered orally twice daily to patients with active RA for 12 weeks. Primary efficacy endpoint was ACR20 response at week 12 and secondary efficacy included ACR 50/70. Patients were enrolled based on A3AR mRNA expression level, utilized as an inclusion criterion. (NCT # NCT01034306)
Results: CF101 was found to be safe and well tolerated. CF101 achieved ACR20 of 48.6%, statistically
significantly higher than that of the placebo group (25.0%) at week 12 (P=0.0352). CF101 showed superiority in ACR50 and ACR70 values vs. placebo. Interestingly, ACR20, ACR50 and ACR70 response rate at week 12 in a subpopulation with no prior systemic therapy was impressively higher (ACR20 75%) compared to the response of the whole patient population treated with CF101.
Conclusions: CF101 reached the primary endpoint in the current study demonstrating clear evidence of
efficacy and safety when given orally as monotherapy for 12 weeks in patients with active RA.