An Early Phase 2 Double-Blind, Placebo-Controlled Study of E6011, a Novel Anti-Fractalkine Antibody, in Patients with Crohn's Disease.

Introduction: E6011 is a newly developed humanized monoclonal antibody that binds to and neutralizes fractalkine with high specificity and affinity. In a previous phase 1, open-label study, E6011 demonstrated good tolerability and preliminary efficacy in Japanese patients with mild to moderate active Crohn's disease (CD). Methods: In this early phase 2, double-blind, placebo-controlled study, we examined the efficacy and safety of E6011 in patients with moderate to severe active CD in a 12-week, double-blind period and the long-term efficacy and safety of E6011 in a subsequent open-label period for a maximum of 52 weeks. The primary efficacy endpoint was the percentage of patients who achieved a decrease in the CD activity index (CDAI) by ≥100 points from baseline at week 12. Results: Of the planned 40 participants, enrollment was closed after 25 had been enrolled, primarily because of the delay in patient enrollment during the COVID-19 pandemic. A decrease in CDAI by ≥100 points was achieved in 33.3% (4/12) in the E6011 group and 23.1% (3/13) in the placebo group at week 12, resulting in a posterior difference of 9.6% (95% credible interval -23.7% to 42.7%). The probability of the difference between groups being ≥25% was 18.3%, which did not exceed the prespecified threshold of 50%. E6011 was safe and well tolerated in the 12-week, double-blind period. No new safety issues were reported in patients treated until week 40. Conclusion: E6011 was safe and well tolerated in patients with moderate to severe active CD. Owing to the small sample size in this study, further studies are necessary to accurately evaluate its efficacy.