A Trial of BTT1023 in Patients With Primary Sclerosing Cholangitis

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT02239211
• Date of registration: 04/09/2014
• Prospective Registration: Yes
• Primary sponsor: University of Birmingham
• Public title: A Trial of BTT1023 in Patients With Primary Sclerosing Cholangitis BUTEO
• Scientific 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).
• Date of first enrolment: September 8, 2015
• Target sample size: 23
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT02239211
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 2

Countries of recruitment

United Kingdom

Contacts

• Name: Philip Newsome, MD
• Affiliation: University of Birmingham

Key inclusion & exclusion criteria

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 trial 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, (in line with the patient's standard of care; within 18 months) of stable
disease, without findings of high grade dysplasia

4. 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

5. Serum ALP greater than 1.5 x ULN

6. Stable serum ALP levels (levels must not change by more than 25% from Screening Visit
1 and Screening Visit 2)

7. 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

8. 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

9. 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

10. Patients must weigh = 40 kg

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 >3 x ULN or INR >1.3 in the absence of
anti-coagulants

4. Serum creatinine >130µmol/L or platelet count <50 x 109/L

5. Any evidence of hepatic decompensation past or present, including ascites, episodes of
hepatic encephalopathy or 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 >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

10. Diagnosed cholangiocarcinoma or high clinical suspicion of cholangiocarcinoma either
clinically or by imaging

11. 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

12. Presence of a percutaneous drain or bile duct stent

13. Major surgical procedure within 30 days of screening

14. Prior organ transplantation

15. Known hypersensitivity to the investigational product or any of its formulation
excipients

16. Unavailable for follow-up assessment or concern for subject's compliance

17. 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 trial
drug half-life is greater than 12 days

18. Any other condition that in the opinion of the Investigator renders the subject a poor
risk for inclusion into the trial

19. Positive screening test for tuberculosis (TB) (including T-SPOT.TB TB test), unless
respiratory review confirms false positive test results

20. Receipt of live vaccination within 6 weeks prior to Screening Visit 2

21. Known HIV positive status



Age minimum: 18 Years
Age maximum: 75 Years
Gender: All

Health Condition(s) or Problem(s) studied

Primary Sclerosing Cholangitis

Intervention(s)

Drug: BTT1023

Primary Outcome(s)

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

Secondary Outcome(s)

Calculation of any change (improvement or worsening) from baseline to Day 99 in Fibroscan measures [Time Frame: 99 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in Aspartate Transaminase (AST) [Time Frame: 99 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in Inflammatory Bowel Disease Diaries (if applicable) [Time Frame: 99 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire EQ-5D [Time Frame: 99 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in Bilirubin [Time Frame: 99 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire Pruritus Visual Analogue Score [Time Frame: 99 days]

Evaluate changes (improvement or worsening) in sVAP-1/SSAO as a biomarker of liver disease activity across the trial period [Time Frame: 120 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in Alanine Transaminase (ALT) [Time Frame: 99 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in Albumin [Time Frame: 99 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in Model for End Stage Liver Disease (MELD) Score [Time Frame: 99 days]

Adverse Event (AE) frequency [Time Frame: 120 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in Alkaline Phosphatase (ALP) [Time Frame: 99 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in Mayo PSC Risk Score [Time Frame: 99 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in the quality of life questionnaire Fatigue Severity Scale [Time Frame: 99 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in Gamma Glutamyl Transferase (GGT) [Time Frame: 99 days]

Treatment Compliance (including patient withdrawal) [Time Frame: 120 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in enhanced liver fibrosis test [Time Frame: 99 days]

Calculation of any change (improvement or worsening) from baseline to Day 99 in International Normalised Ratio (INR) [Time Frame: 99 days]

Serious Adverse Event (SAE) frequency [Time Frame: 120 days]

Secondary ID(s)

2014-002393-37

RG_13-027

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

University Hospital Birmingham

Biotie Therapies Corp.

National Institute for Health Research, United Kingdom