A Trial of BTT1023 in Patients With Primary Sclerosing Cholangitis

NCT02239211 | Completed Phase 2 DMC

• 2 other identifiers: RG_13-0272014-002393-37
• Study Type: interventional
• Target: 23
• Locations: 1 country
• Sites: 6

Brief Summary

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).

Conditions

Primary Sclerosing Cholangitis

Keywords

BUTEO; Primary sclerosing cholangitis; PSC; VAP-1; BTT1023; Human monoclonal antibody

Outcome Measures

Primary Outcomes (1)

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

  99 days

Secondary Outcomes (19)

• Treatment Compliance (including patient withdrawal)

  120 days

• Serious Adverse Event (SAE) frequency

  120 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 EQ-5D

  99 days

• Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire Fatigue Severity Scale

  99 days

Study Arms (1)

BTT1023

EXPERIMENTAL

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

Drug: BTT1023

Interventions

BTT1023 DRUG

IV (in the vein) Investigational Medicinal Product (IMP)

BTT1023

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• Concurrent malignancies or invasive cancers diagnosed within past 3 years except for adequately treated basal cell and squamous cell carcinoma of the skin and in situ carcinoma of the uterine cervix
• Presence of a percutaneous drain or bile duct stent
• Major surgical procedure within 30 days of screening
• Prior organ transplantation
• Known hypersensitivity to the investigational product or any of its formulation excipients

Sponsors & Collaborators

• University of Birmingham: lead
• Biotie Therapies Corp.: collaborator
• University Hospital Birmingham: collaborator
• National Institute for Health Research, United Kingdom: collaborator

Study Sites (6)

Queens Medical Centre

Nottingham, Nottinghamshire, NG7 2UH, United Kingdom

Location

University Hospitals Birmingham NHS Foundation Trust

Birmingham, West Midlands, B15 2TH, United Kingdom

Location

Addenbrooke's Hospital

Cambridge, United Kingdom

Location

Royal Free Hospital

London, United Kingdom

Location

Royal Victoria Infirmary

Newcastle, United Kingdom

Location

John Radcliffe Hospital

Oxford, United Kingdom

Location

Related Publications (1)

• 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. 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. BMJ Open. 2017 Jul 3;7(6):e015081. doi: 10.1136/bmjopen-2016-015081.

  PMID: 28674140 DERIVED

MeSH Terms

Conditions

Cholangitis, Sclerosing

Interventions

timolumab

Condition Hierarchy (Ancestors)

Cholangitis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases

Study Officials

• Philip Newsome, MD

  University of Birmingham

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2014
• First Posted: September 12, 2014
• Study Start: September 8, 2015
• Primary Completion: October 23, 2018
• Study Completion: October 23, 2018
• Last Updated: May 3, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

GB (6)