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Clinical Trial
. 2017 Jul 3;7(6):e015081.
doi: 10.1136/bmjopen-2016-015081.

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

Katherine Arndtz  1   2 , Margaret Corrigan  1   2 , Anna Rowe  3 , Amanda Kirkham  4 , Darren Barton  3 , Richard P Fox  4 , Laura Llewellyn  5 , Amrita Athwal  3 , Manpreet Wilkhu  3 , Yung-Yi Chen  1   2 , Chris Weston  1   2 , Amisha Desai  6 , David H Adams  1   2 , Gideon M Hirschfield  1   2 ; BUTEO trial team
Affiliations
Clinical Trial

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

Katherine Arndtz et al. BMJ Open. .

Abstract

Introduction: 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.

Methods and analysis: 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.

Ethics and dissemination: 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.

Trial registration: 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.

Keywords: Clinical Trials; Hepatobiliary Disease; Hepatology; Immunology.

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Conflict of interest statement

Competing interests: CW and DHA report grants from NIHR MRC, during the conduct of thestudy; grants and non-financial support from Pharmaxis Inc, Australia,outside the submitted work; and have a patent "The use of VAP-1 inhibitors for treating fibroticconditions (WO 2011029996 A1)" issued. Other authors have no competing interests declared.

Figures

Figure 1
Figure 1
Flow diagram showing the trial decision guidelines for the run-in period of the trial design, incorporating a conventional 3+3 cohort design if dose escalation is required.
Figure 2
Figure 2
BUTEO trial schema.
See this image and copyright information in PMC

References

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