A placebo-controlled Phase 2 trial of E6011, anti-human fractalkine monoclonal antibody, in primary biliary cholangitis

Abstract

Background

While ursodeoxycholic acid (UDCA) remains the first-line therapy for primary biliary cholangitis (PBC), the autoimmune nature of PBC underscores the need for treatments targeting immunological pathways that may achieve a cure. E6011, a novel humanized anti-fractalkine monoclonal antibody, has emerged as a potential therapeutic option for PBC. We conducted a randomized, placebo-controlled, double-blind study to evaluate the efficacy and safety of E6011 in patients with PBC with an incomplete response to UDCA.

Methods

The study was composed of 12-week Double-Blind Phase (placebo, E6011 10 mg/kg/month, 15 mg/kg/month, or 10 mg/kg/every other week [eow]) followed by a 52-week Open-Label Phase. The primary endpoint was the percent change in alkaline phosphatase (ALP) at Week 12.

Results

A total of 29 patients were enrolled. Histological evaluation at screening revealed that 83 % of the enrolled patients were classified as Stage 4 according to the Nakanuma Classification. The mean percent changes in ALP at Week 12 were +0.45 % in the placebo, +0.65 % in the 10 mg/kg/month, +1.23 % in the 15 mg/kg/month and +1.19 % in the 10 mg/kg/eow, with no observed trends toward ALP reduction in the E6011 treatment. Based on the interim analysis, the study was discontinued due to a lack of the efficacy. E6011 was generally safe and well tolerated.

Conclusion

This study of E6011 failed to meet the primary endpoint in patients with PBC with an incomplete response to UDCA. The advanced histological severity present in more than 80 % of patients at baseline may have contributed to these findings.