A Trial of BTT1023 in Patients With Primary Sclerosing Cholangitis (BUTEO)
|Study Design:||Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
|Official Title:||A Single Arm, Two-stage, Multi-centre, Phase II Clinical Trial Investigating the Safety and Activity of the Use of BTT1023 Targeting Vascular Adhesion Protein (VAP-1), in the Treatment of Patients With Primary Sclerosing Cholangitis (PSC).|
- To determine the activity of the anti-Vap-1 antibody BTT1023 in patients with PSC as measured by a decrease in alkaline phosphatase levels (primary endpoint) with secondary endpoints to include various measures of liver injury and fibrosis. [ Time Frame: 99 days ]Vap-1 levels will be measured at multiple times from initiation of treatment, during treatment (78 days) and post treatment.
- To evaluate the safety and tolerability of BTT1023 in patients with PSC [ Time Frame: 120 days ]Biochemical blood tests will be measured throughout the study period, as well as additional cardiology assessments (ECG). The results of these tests will be contribute to the safety evaluation of BTT1023.
- To determine the mechanisms of action of BTT1023 through in vivo assessment of SSAO enzyme activity and immune cell function. [ Time Frame: 120 days ]SSAO and immune cell assay function will be performed throughout the entire period.
- To evaluate the potential of a novel MRI based assessment of liver fibrosis and biliary strictures for assessing therapeutic outcome in PSC. [ Time Frame: Baseline and day 120 ]MRI imaging of the liver will be performed at two time points (baseline, day 120). This imaging will be assessed using a novel analytical method.
- Assess the use of sVap-1 as a biomarker to monitor disease progression in PSC. [ Time Frame: 120 days ]Multiple measures of the known potential biomarker (sVAP-1) wiil be taken and correlated against clinical outcome throughout the period of the trial.
|Actual Study Start Date:||September 8, 2015|
|Estimated Study Completion Date:||March 2019|
|Estimated Primary Completion Date:||January 2019 (Final data collection date for primary outcome measure)|
BTT1023 8mg/kg IV infusion, every 14 days (total of 7 infusion). Duration 1-2 hours per infusion.
IV (in the vein) Investigational Medicinal Product (IMP)
Primary sclerosing cholangitis is a progressive immune mediated biliary disease characterised by bile duct inflammation and fibrosis, and accompanying hepatic fibrosis. For patients with elevated alkaline phosphatase (ALP) in particular, progressive disease is predicted, that currently results in a need for liver transplantation in the majority. No current medical therapy has as yet been shown to be effective in altering the natural history of disease. For this reason patients with PSC with elevated ALP values will be recruited to this study, to evaluate the impact of Vap-1 blockade by BTT1023, in an early phase study focused on biochemical efficacy and safety.
This is an early phase study of BTT1023 in immune mediated liver disease, with the rationale to identify biochemical efficacy of effect (reduction in ALP) and safety, in an orphan disease indication for PSC that presently lacks any other medical therapy. The study design therefore focuses on identifying early biochemical efficacy signals to justify larger scale, randomised controlled studies over longer duration.
Please refer to this study by its ClinicalTrials.gov identifier: NCT02239211
|Contact: Gideon Hirschfield, MD||+44 121 414 firstname.lastname@example.org|
|Contact: Anna Rowe, PhD||+44 121 371 email@example.com|
|Queens Medical Centre||Recruiting|
|Nottingham, Nottinghamshire, United Kingdom, NG7 2UH|
|Principal Investigator: Guruprasad Aithal, MD|
|University Hospitals Birmingham NHS Foundation Trust||Recruiting|
|Birmingham, West Midlands, United Kingdom, B15 2TH|
|Principal Investigator: Gideon Hirschfield, MD|
|Sub-Investigator: Prof David Adams, MD|
|Royal Victoria Infirmary||Recruiting|
|Newcastle, United Kingdom|
|Principal Investigator: Mark Hudson, MD|
|Oxford, United Kingdom|
|Principal Investigator: Ellie Barnes, MD|
|Principal Investigator:||Gideon Hirschfield, MD||University of Birmingham|