Investigating the safety and activity of the use of BTT1023 (Timolumab), in the treatment of patients with primary sclerosing cholangitis (BUTEO): A single-arm, two-stage, open-label, multi-centre, phase II clinical trial protocol.
Investigating the safety and activity of the use of BTT1023 (Timolumab), in the treatment of patients with primary sclerosing cholangitis (BUTEO): A single-arm, two-stage, open-label, multi-centre, phase II clinical trial protocol.
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DOI：
10.1136/bmjopen-2016-015081
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发表时间：
2017-07-03
期刊：
影响因子：
2.9
通讯作者：
BUTEO trial team
中科院分区：
文献类型：
--
作者：
Arndtz K;Corrigan M;Rowe A;Kirkham A;Barton D;Fox RP;Llewellyn L;Athwal A;Wilkhu M;Chen YY;Weston C;Desai A;Adams DH;Hirschfield GM;BUTEO trial team
原发性硬化性胆管炎（PSC）是一种进行性炎症性肝病，其特征是持续的肝纤维化和对新疗法的高度未满足的需求。预防纤维化是重要新药开发中的一个重要领域。血管粘附蛋白-1 (VAP-1) 会导致肝脏疾病中的炎症，而针对 VAP-1 的抗体可抑制小鼠肝损伤模型中的纤维化。 BUTEO 是一项单臂、两阶段、开放标签、多中心、II 期临床试验。多达 59 名患者将在 78 天的治疗期内接受抗 VAP 单克隆抗体 BTT1023 的治疗。患有 PSC 且血清碱性磷酸酶 (ALP) 至少为正常上限 1.5 倍的成人也将包括在内。我们的主要结局指标是从基线到第 99 天，ALP 降低了 25% 以上。次要结局指标包括安全性和耐受性、治疗前/治疗后循环血清 VAP-1 的变化以及影像学结果。第一位患者参与者于 2015 年 9 月 8 日招募。该方案已获得研究伦理委员会批准（REC，参考号 14/EM/1272）。第一次 REC 批准日期为 2015 年 1 月 6 日，随后批准了三项修订。本文参考 2016 年 3 月 16 日的协议 V3.0。结果将通过同行评审出版物和国际会议上的演示进行传播。该试验已在欧洲药品管理局 (EudraCT: 2014-002393-37)、国家健康研究所 (Portfolio ID: 18051) 和 ISRCTN: 11233255 注册。ClinicalTrials.gov 标识符为 NCT02239211。预结果。
Primary sclerosing cholangitis (PSC) is a progressive inflammatory liver disease characterised by relentless liver fibrosis and a high unmet need for new therapies. Preventing fibrosis represents an important area of interest in the development of vital new drugs. Vascular adhesion protein-1 (VAP-1) drives inflammation in liver disease, and provision of an antibody against VAP-1 blunts fibrosis in murine models of liver injury. BUTEO is a single-arm, two-stage, open-label, multi-centre, phase II clinical trial. Up to 59 patients will receive treatment with anti-VAP monoclonal antibody, BTT1023, over a 78-day treatment period. Adults with PSC and a serum alkaline phosphatase (ALP) of at least 1.5 times the upper limit of normal will be included. Our primary outcome measure is a reduction in ALP by >25% from baseline to Day 99. Secondary outcome measures include safety and tolerability, changes pre therapy/post therapy in circulating serum VAP-1 as well as imaging findings. The first patient participant was recruited on 08 September 2015. This protocol has been approved by the Research Ethics Committee (REC, reference 14/EM/1272). The first REC approval date was 06 January 2015 with three subsequent approved amendments. This article refers to protocol V3.0, dated 16 March 2016. Results will be disseminated via peer-reviewed publication and presentation at international conferences. The trial is registered with the European Medicines agency (EudraCT: 2014-002393-37), the National Institute for Health Research (Portfolio ID: 18051) and ISRCTN: 11233255. The clinicaltrials.gov identifier is NCT02239211. Pre-results.
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