A single arm, two-stage, multi-centre, phase II clinical trial investigating the safety and activity of the use of BTT1023, a human monoclonal antibody targeting vascular adhesion protein (VAP-1), in the treatment of patients with primary sclerosing cholangitis (PSC) (BUTEO)
4th September 2015 - ongoing
Team: Professor Guruprasad Aithal.
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 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 of a longer duration
End-stage liver disease, regardless of aetiology, is characterised by hepatic fibrosis culminating in liver cirrhosis and accompanying increasing risks of liver cancer, liver failure, portal hypertension and death. Preventing progressive liver fibrosis represents an important area of interest in the development of new drugs suitable for all patients with liver disease. Primary sclerosing cholangitis (PSC) is a prime example of a progressive inflammatory liver disease characterised by relentless liver fibrosis and a high unmet need for new therapies. PSC has an incidence of 1.3/100,000 annually, with a prevalence of 16.2 per 100,000. It affects men and women with a median age of 41 and in 80% is associated with inflammatory bowel disease (IBD). More than 50% of patients require liver transplantation within 10-15 years of symptomatic presentation reflecting the failure of medical therapies to make any impact on the clinical outcome. The progression of PSC to scarring, cirrhosis and hepatobiliary cancer is driven by a chronic inflammatory response and immune cell mediated destruction of bile ducts . Our research implicates vascular adhesion protein-1 (VAP-1) in the inflammation that drives fibrogenesis in liver disease and we have shown levels of sVAP-1 in serum are elevated in chronic liver diseases and correlate with histological fibrosis[3, 4]. These observations underpin our proposal that VAP-1 has an important role in the progression of liver fibrosis. We now plan to test the hypothesis that inhibiting VAP-1 with a neutralising antibody (BTT1023) will reverse or delay fibrogenesis in patients with the progressive, autoimmune, fibrosing liver disease PSC and to investigate the potential of VAP-1 as a biomarker in liver disease.