Condition category
Digestive System
Date applied
11/03/2015
Date assigned
11/03/2015
Last edited
11/03/2015
Prospective/Retrospective
Retrospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Primary sclerosing cholangitis (PSC) is an uncommon autoimmune chronic liver disease in which the bile ducts of the liver reduce in size over time as a result of inflammation and scarring (fibrosis). It often occurs in patients that have an inflammatory disease of the colon, for example, ulcerative colitis. Bile ducts are tubes which take bile (a liquid produced by the liver) to the intestines. Bile is like as detergent breaking up fat from the food we eat into small droplets that can then be absorbed into the body. It also allows us to absorb vitamins A, D, E and K from our diet. In people suffering from PSC, bile that is normally carried by these ducts builds up within the liver. This blockage to bile flow results in damage to liver cells, leading to inflammation and scarring. Over time, this scarring can affect the whole liver. The liver does have regenerative abilities and can usually re-grow without scarring when damaged. However, in PSC, this healing process does not work properly. A combination of scar tissue and irregular re-growth of the liver can lead eventually to cirrhosis. There are, at present, no treatments for patients with PSC and most patients with symptomatic disease eventually need a liver transplant. Here we want to test whether the antibody, BTT1023, which targets a protein involved in inflammation and scarring, is safe as well as effective in the treatment of PSC. BTT1023 targets a protein called VAP-1 and this enzyme has been studied in many autoimmune diseases including PSC, where our studies show it to be important. PSC is diagnosed by MRI scans usually but blood tests can be used to follow the disease, including in particular elevations in one particular marker of bile duct inflammation, alkaline phosphatase (ALP). We wish to see whether the study drug can be given safely to patients diagnosed with PSC and whether it reduces inflammation and scarring.

Who can participate?
Adults aged 18-75 diagnosed with PSC

What does the study involve?
Participants undergo an initial screening process to see whether they can take part in the study, involving two visits over a period of 8 weeks. They are then given 7 infusions of the BTT1023 drug over a period of 11 weeks. Participants are followed up though 2 visits over a 6 week period. Blood tests and scans are used to see whether the drug is working.

What are the possible benefits and risks of participating?
Not provided at time of registration

Where is the study run from?
The trial will be conducted at 3 hospital sites in England

When is the study starting and how long is it expected to run for?
February 2015 to February 2017

Who is funding the study?
National Institute for Health Research (UK)

Who is the main contact?
Mrs Manpreet Wilkhu

Trial website

Contact information

Type

Scientific

Primary contact

Mrs Manpreet Wilkhu

ORCID ID

Contact details

Cancer Research UK Clinical Trials Unit
School of Cancer Sciences
University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

Additional identifiers

EudraCT number

2014-002393-37

ClinicalTrials.gov number

NCT02239211

Protocol/serial number

18051

Study information

Scientific title

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 (VAP1), in the treatment of patients with primary sclerosing cholangitis (PSC)

Acronym

BUTEO

Study hypothesis

The aim of this trial is to assess whether the antibody, BTT1023, which targets a protein involved in inflammation and scarring, is safe as well as effective in the treatment of primary sclerosing cholangitis (PSC)

Ethics approval

14/EM/1272; First MREC approval date 06/01/2015

Study design

Non-randomised; Interventional; Design type: Not specified, Treatment

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Other

Trial type

Treatment

Patient information sheet

Not available in web format, please use contact details to request a patient information sheet

Condition

Topic: Hepatology; Subtopic: Hepatology; Disease: All Hepatology

Intervention

BTT1023 will be given to patients using intravenous infusion. With informed consent, patients who have been diagnosed with PSC and whose ALP is elevated, will be eligible to be screened to take part in the study. The trial will be conducted at 3 hospital sites in England and lasts approximately 25 weeks from the first day of screening through to the last follow up visit. The screening phase involves 2 visits over an 8 week period. The treatment phase of the trial lasts for 11 weeks and includes 7 infusions of the BTT1023 study drug. Blood tests and scans will be used to see if the drug is working.

Intervention type

Drug

Phase

Phase I/II

Drug names

Primary outcome measures

Alkaline phosphatase; Timepoint(s): Week 12

Secondary outcome measures

Safety; Timepoint(s): Throughout, week 1-week 12

Overall trial start date

01/02/2015

Overall trial end date

01/02/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Males and females 18-75 years of age who are willing and able to provide informed, written consent and comply with all study requirements.
2. 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.
3. In those with concomitant inflammatory bowel disease, clinical and colonoscopic evidence within the last year of stable disease, without dysplasia.
4. In those on treatment with Ursodeoxycholic acid (UDCA), therapy must be stable for at least 3 months, and at a dose not greater than 20mg/kg/day.
5. Serum ALP greater than 2xULN.
6. Female subjects of childbearing potential must have a negative serum pregnancy test prior to starting study treatment. For the purposes of this study, 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.
7. All sexually active women of childbearing potential must agree to use a highly effective method of contraception from the Screening Visit throughout the study period and for 105 days following the last dose of study drug. If using hormonal agents the same method must have been used for at least 1 month before study dosing and subjects must use a barrier method as the other form of contraception. Lactating women must agree to discontinue nursing before study investigational medicinal product administration.
8. Men, if not vasectomized, must agree to use barrier contraception (condom plus spermicide) during heterosexual intercourse from screening through to study completion and for 105 days from the last dose of study investigational medicinal product.

Participant type

Patient

Age group

Adult

Gender

Both

Target number of participants

Planned Sample Size: 59; UK Sample Size: 59

Participant exclusion criteria

1. Presence of documented secondary sclerosing cholangitis on prior clinical investigations.
2. 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.
3. AST and ALT > 10 x ULN or Bilirubin >3xULN or INR>1.3 in the absence of anti-coagulants.
4. Serum creatinine >130µmol/L or Platelet count <50x109/L.
5. Any evidence of hepatic decompensation past or present, including ascites, episodes of hepatic encephalopathy, variceal bleeding.
6. Recent cholangitis within last 90 days or ongoing need for prophylactic antibiotics.
7. Pregnancy or breast feeding.
8. Harmful alcohol consumption as evaluated by the investigator.
9. Flare in colitis activity within last 90 days requiring intensification of therapy beyond baseline maintenance treatment; use of oral prednisolone >10mg/day, biologics and or hospitalisation for colitis within 90 days.
10. Diagnosed cholangiocarcinoma or high clinical suspicion over dominant stricture.
11. Active malignancy (within 3 years of diagnosis), other than non-melanomatous skin cancer.
12. Presence of a percutaneous drain or bile duct stent.
13. Major surgical procedure within 30 days of screening or prior organ transplantation;
14. Known hypersensitivity to the investigational product or any of its formulation excipients; inability to receive simple anti-inflammatory
agents’ peri-infusion.
15. Unavailable for follow-up assessment or concern for subject’s compliance.
16. Participation in an investigational trial of a drug or device within 60 days of screening or 5 half-lives of the last dose of investigational drug, where the study drug half-life is greater than 12 days.
17. Any other condition that in the opinion of the investigator renders the subject a poor risk for inclusion into the study.
18. Positive screening test for tuberculosis (including T-SPOT.TB TB test), unless respiratory review confirms false positive test results
19. Receipt of live vaccination within 6 weeks prior to baseline visit.

Recruitment start date

01/02/2015

Recruitment end date

01/02/2017

Locations

Countries of recruitment

United Kingdom

Trial participating centre

Cancer Research UK Clinical Trials Unit
School of Cancer Sciences University of Birmingham Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor information

Organisation

University of Birmingham

Sponsor details

Edgbaston
Birmingham
B15 2TT
United Kingdom

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

National Institute for Health Research

Alternative name(s)

NIHR

Funding Body Type

government organisation

Funding Body Subtype

Federal/National Government

Location

United Kingdom

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes