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).

University of Birmingham6 个研究点分布在 1 个国家目标入组 23 人2015年9月8日

适应症Primary Sclerosing Cholangitis

干预措施BTT1023

概览

阶段: 2 期
干预措施: BTT1023
疾病 / 适应症: Primary Sclerosing Cholangitis
发起方: University of Birmingham
入组人数: 23
试验地点: 6
主要终点: Response at Visit 10 (Day 99): a reduction in serum ALP by 25% or more from baseline to Visit 10 (Day 99)
状态: 已完成
最后更新: 7年前

概览研究者入排标准研究组 & 干预措施结局指标研究点相似试验

概览

简要总结

This is a phase II study to determine the safety and preliminary efficacy of a human monoclonal antibody (BTT1023) which targets the vascular adhesion protein (VAP-1) and its use in the treatment of patients with primary sclerosing cholangitis (PSC).

详细描述

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.

注册库

clinicaltrials.gov

开始日期

2015年9月8日

结束日期

2018年10月23日

最后更新

7年前

研究类型

Interventional

研究设计

Single Group

性别

All

研究者

发起方

University of Birmingham

责任方

Sponsor

入排标准

入选标准

•Males and females 18 - 75 years of age who are willing and able to provide informed, written consent and comply with all trial requirements
•Clinical diagnosis of PSC as evident by chronic cholestasis of more than six months duration with either a consistent MRI showing sclerosing cholangitis or a liver biopsy consistent with PSC in the absence of a documented alternative aetiology for sclerosing cholangitis
•In those with concomitant Inflammatory Bowel Disease, clinical and colonoscopic evidence, (in line with the patient's standard of care; within 18 months) of stable disease, without findings of high grade dysplasia
•In those on treatment with UDCA, therapy must be stable for at least 3 months, and at a dose not greater than 20 mg/kg/day. In those not on treatment with UDCA at the time of screening, a minimum of 8 weeks since the last dose of UDCA should be recorded
•Serum ALP greater than 1.5 x ULN
•Stable serum ALP levels (levels must not change by more than 25% from Screening Visit 1 and Screening Visit 2)
•Female subjects of childbearing potential must have a negative pregnancy test prior to starting trial treatment. For the purposes of this trial, a female subject of childbearing potential is a woman who has not had a hysterectomy, bilateral oophorectomy, or medically-documented ovarian failure. Women ≤ 50 years of age with amenorrhea of any duration will be considered to be of childbearing potential
•All sexually active women of childbearing potential must agree to use two forms of highly effective method of contraception from the Screening Visit throughout the trial period and for 99 days following the last dose of trial drug. If using hormonal agents the same method must have been used for at least 1 month before trial dosing and subjects must use a barrier method as the other form of contraception. Lactating women must agree to discontinue breast feeding before trial investigational medicinal product administration
•Men, if not vasectomised, must agree to use barrier contraception (condom plus spermicide) during heterosexual intercourse from screening through to trial completion and for 99 days from the last dose of trial investigational medicinal product
•Patients must weigh ≥ 40 kg

排除标准

•Presence of documented secondary sclerosing cholangitis on prior clinical investigations
•Presence of alternative causes of liver disease, that are considered by the Investigator to be the predominant active liver injury at the time of screening, including viral hepatitis, alcoholic liver disease, non-alcoholic steatohepatitis, primary biliary cirrhosis. Patients with possible overlap syndrome with autoimmune hepatitis are excluded if the Investigator considers autoimmune hepatitis as the predominant liver injury
•AST and ALT \>10 x ULN or bilirubin \>3 x ULN or INR \>1.3 in the absence of anti-coagulants
•Serum creatinine \>130μmol/L or platelet count \<50 x 109/L
•Any evidence of hepatic decompensation past or present, including ascites, episodes of hepatic encephalopathy or variceal bleeding
•Recent cholangitis within last 90 days or ongoing need for prophylactic antibiotics
•Pregnancy or breast feeding
•Harmful alcohol consumption as evaluated by the Investigator
•Flare in colitis activity within last 90 days requiring intensification of therapy beyond baseline maintenance treatment; use of oral prednisolone \>10 mg/day, biologics (i.e. monoclonal antibodies) and or hospitalisation for colitis within 90 days. Prior use of biologics is not a contraindication to screening
•Diagnosed cholangiocarcinoma or high clinical suspicion of cholangiocarcinoma either clinically or by imaging

研究组 & 干预措施

BTT1023

BTT1023 8mg/kg IV infusion, total of 7 infusions over 11 weeks. Duration 1-2 hours per infusion.

干预措施: BTT1023

结局指标

主要结局

Response at Visit 10 (Day 99): a reduction in serum ALP by 25% or more from baseline to Visit 10 (Day 99)

时间窗: 99 days

次要结局

Calculation of any change (improvement or worsening) from baseline to Day 99 in Aspartate Transaminase (AST)(99 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in Inflammatory Bowel Disease Diaries (if applicable)(99 days)
Adverse Event (AE) frequency(120 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire Pruritus Visual Analogue Score(99 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in Bilirubin(99 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in Albumin(99 days)
Serious Adverse Event (SAE) frequency(120 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire Fatigue Severity Scale(99 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire EQ-5D(99 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in enhanced liver fibrosis test(99 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in Fibroscan measures(99 days)
Treatment Compliance (including patient withdrawal)(120 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in Model for End Stage Liver Disease (MELD) Score(99 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in Alkaline Phosphatase (ALP)(99 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in Mayo PSC Risk Score(99 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in Alanine Transaminase (ALT)(99 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in Gamma Glutamyl Transferase (GGT)(99 days)
Calculation of any change (improvement or worsening) from baseline to Day 99 in International Normalised Ratio (INR)(99 days)
Evaluate changes (improvement or worsening) in sVAP-1/SSAO as a biomarker of liver disease activity across the trial period(120 days)