Study of BROdalumab in Primary Sclerosing Cholangitis

Phase 2

• Conditions: Primary sclerosing cholangitis; Digestive System

• Registration Number: ISRCTN15271834
• Lead Sponsor: orfolk and Norwich University Hospitals NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2023-10-27
• Last Update Posted: 21 May 2024
• Study Completion: 2025-09-30

Recruitment & Eligibility

• Status: Ongoing
• Sex: All
• Target Recruitment: 20

Inclusion Criteria

Current inclusion criteria as of 08/05/2024:
1. Age 18-75 years
2. Written informed consent
3. Established clinical diagnosis of large duct PSC-based on a standard disease definition (adopted from the British Society of Gastroenterology guidelines): i) cholestatic blood tests, ii) typical cholangiographic findings on endoscopic retrograde cholangiography (ERCP) or magnetic resonance cholangiography (MRCP), and absence of Anti-mitochondrial antibodies and causes of secondary cholangitis.
4. Participants may be recruited with OR without a confirmed diagnosis of inflammatory bowel disease (IBD). For those recruited with an established diagnosis of concomitant colonic inflammatory bowel disease (IBD), there must be a confirmed diagnosis of quiescent-mild disease established prior to enrolment (with endoscopy performed within 12 months of screening visit) by clinical, biochemical, AND endoscopic evidence corroborated by a histopathology report. Where there is a disparity in disease activity between the endoscopic and histological report- histology should be taken as the gold standard of actual disease activity. Note: enrolment of participants into the SABR-PSC study with mild disease, will be a phased 2 step process:
Phase 1: The initial 10 patients enrolled in the study will have QUIESCENT disease (UC or CD) clinically, biochemically and histologically. There will be a review by the safety committee after enrolment and treatment commencement of the 9th patient with regards to any IBD safety signals or adverse events. The safety committee will then advise the trial steering committee and CI of their views.
Phase 2: If the safety committee are satisfied that there are no significant safety concerns, the final 10 patients recruited may be recruited with either quiescent or mild disease.
Quiescent Crohns Disease (CD) is clinically defined by a Crohns Disease Activity Index (CDAI) of <150
Mild CD is clinically defined by a Crohns Disease Activity Index (CDAI) of 15-219
Quiescent Ulcerative Colitis (UC) is clinically defined by a partial Mayo score of <2
Mild Ulcerative Colitis (UC) is clinically defined by a partial Mayo score of 2-5
5. Participants with a diagnosis of IBD on maintenance therapy with 5-aminosalicylic acid (5-ASA) or thiopurine therapy must be taking a stable dose for at least 12 weeks prior to screening, with no dose changes and be expected to remain on the same dose and medication for the duration of the trial.
6. If pre-treated with ursodeoxycholic acid (UDCA)- UDCA therapy should remain at a stable dose for 12 weeks prior to screening, and not exceeding 20 mg/kg/day.
7. All patients with IBD must have had colorectal cancer screen within 12 months of the screening visit with no signs of malignancy or dysplasia- evidenced by a colonoscopy with segmental biopsies and histological confirmation of absence of dysplasia.
8. Female subjects of childbearing age must be on a highly effective contraceptive method from screening to at least 12 weeks after the last dose of the drug. All hormonal contraceptive methods must be supplemented by use of a male condom.

Previous inclusion criteria:
1. Age 18-75 years
2. Written informed consent
3. Established clinical diagnosis of large duct PSC-based on a standard disease definition (adopted from the British Society of Gastroenterology guidelines): i) cholestatic blood tests, ii) typical cholangiographic findings on endoscopic retrograde cholangiography (ERCP) or magnetic resonance cholangiogra

Exclusion Criteria

Current exclusion criteria as of 08/05/2024:
1. Gallbladder lesion or polyp (>5 mm diameter), cholangiocarcinoma mass lesion, or high suspicion of cholangiocarcinoma, as indicated on imaging such as ultrasound, computer tomography (CT), dynamic magnetic resonance imaging (MRI) or MRCP.
2. Evidence of any other concomitant liver disease including but not limited to overlap syndromes with autoimmune hepatitis, primary biliary cholangitis, alcohol-related liver disease, or clinically significant metabolic-associated fatty liver disease (at investigator's discretion).
3. Primary biliary cholangitis, or IgG4-Related cholangitis as judged by the investigator.
4. Has received a liver transplant, is listed for a liver transplant or in the opinion of the investigator, the participant has an anticipated need for liver transplantation within the next 12 months.
5. Had a total or subtotal colectomy or presence of an ileostomy or colostomy.
6. Has current or recent history of Crohn’s abscess, stricturing or fistulating disease.
7. Has had 1 or more interventional treatments for dominant biliary stricture (including stent placement/replacement) within 6 months prior to the screening visit, or a dominant bile duct stricture thought to need intervention in the next 6 months (i.e., stenting or dilatation).
8. Has evidence of cholangitis, requiring antibiotics or hospitalisation, within 3 months prior to the screening visit [short courses of antibiotics for no more than 5 days are allowed for stent placement or endoscopic retrograde cholangiopancreatography (ERCP) prophylaxis].
9. Has evidence of liver cirrhosis based on liver histology, ultrasound, or vibration-controlled transient elastography (VCTE) (KPa >14.4) or history of the presence of decompensated liver disease e.g., ascites, variceal bleed, hepatic encephalopathy, portal hypertension or hepatic hydrothorax.
10. Acceptable references for portal hypertension meeting study exclusion include: a recent gastroscopy with evidence or varices, platelets <150, and/or splenomegaly on recent imaging measuring >12 cm
11. Chronic alcohol consumption or participants consuming more than the recommended allowance of 14 units of alcohol per week (as set out by the Department of Health).
12. Any active malignant disease or history of malignancy within the past 5 years including high risk basal cell carcinoma.
13. Existing or intended pregnancy or breastfeeding during the study period.
14. Current or recent participation in any other clinical trial involving a CTIMP within the last 6 weeks prior to the screening period (to be reviewed on a case-by-case basis).
15. Have received any systemic corticosteroid or topical colonic corticosteroid including budesonide, or any disease-specific IBD treatment (outside of normal maintenance therapy) within the last 3 months prior to the screening visit.
16. Positive stool culture for Clostridium difficile or enteric pathogens within 12 weeks prior to the study visit.

Infectious disease exclusion criteria:
1. Has chronic hepatitis B virus (HBV), hepatitis C virus (HCV) or positive hepatitis B core antibody (anti-HBc) at screening.
2. Has evidence of an active infection (defined as infection of any organ or where antibiotics are required except minor skin infections not requiring antibiotics) within 28 days, or within 8 weeks if serious infection, of screening visit or known long term (chronic) infection.
3. Has proven previous history of systemic fungal sepsis- as defined by

Study & Design

• Study Type: Interventional
• Study Design: Not specified