Tanaka Atsushi, Abe Masanori, Namisaki Tadashi, Shimoda Shinji, Zeniya Mikio, Ido Akio, Yoshiji Hitoshi, Ohira Hiromasa, Harada Kenichi, Kakuda Yuko, Umeda Atsushi, Kamiya Yuki, Higashine Yukari, Hojo Seiichiro, Imai Toshio, Kawano Tetsu, Nakanuma Yasuni, Tsubouchi Hirohito
Department of Medicine, Teikyo University School of Medicine, Tokyo, Japan.
Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan.
J Transl Autoimmun. 2025 Mar 20;10:100283. doi: 10.1016/j.jtauto.2025.100283. eCollection 2025 Jun.
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.
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.
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.
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.
虽然熊去氧胆酸（UDCA）仍然是原发性胆汁性胆管炎（PBC）的一线治疗药物，但PBC的自身免疫性质突出了针对可能实现治愈的免疫途径进行治疗的必要性。E6011是一种新型人源化抗 fractalkine 单克隆抗体，已成为PBC的一种潜在治疗选择。我们进行了一项随机、安慰剂对照、双盲研究，以评估E6011在对UDCA反应不完全的PBC患者中的疗效和安全性。
该研究包括为期12周的双盲阶段（安慰剂、E6011 10毫克/千克/月、15毫克/千克/月或10毫克/千克/每隔一周[eow]），随后是为期52周的开放标签阶段。主要终点是第12周时碱性磷酸酶（ALP）的变化百分比。
共纳入29例患者。筛查时的组织学评估显示，根据中沼分类，83%的纳入患者被分类为4期。第12周时，安慰剂组ALP的平均变化百分比为+0.45%，10毫克/千克/月组为+0.65%，15毫克/千克/月组为+1.23%，10毫克/千克/eow组为+1.19%，在E6011治疗中未观察到ALP降低的趋势。基于中期分析，由于缺乏疗效，该研究提前终止。E6011总体上安全且耐受性良好。
这项关于E6011的研究未能在对UDCA反应不完全的PBC患者中达到主要终点。基线时超过80%的患者存在的高级组织学严重程度可能导致了这些结果。
