The study is looking at patients with primary sclerosing cholangitis and co-existant inflammatory bowel disease. Digestive System
Conditions
Interventions
Yaq-001, commercially known as CARBALIVE, is a highly adsorbent activated carbon with tailored pore size distribution. The study will be investigating the safety and tolerability of two different dose
therefore, randomisation is not applicable. The first 6 participants enrolled will receive the 8g dose, and the subsequent 6 will receive the 12g dose.
Sponsors
Yaqrit Limited
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Written informed consent 2. Men and women age =/>16 years 3. Participants must be able to understand and comply with the purpose and procedures that are involved in the trial 4. An established diagnosis of colonic inflammatory bowel disease, with evident willingness to participate in an annual colonoscopic surveillance program, as per the routine standard of care 5. An established clinical diagnosis of large duct PSC, with compatible features as assessed by magnetic resonance cholangiopancreatography (MRCP) or endoscopic retrograde cholangiopancreatography (ERCP) 6. Evidence of moderate to advanced stage liver fibrosis, as suspected by any of the following: 6.1. Median vibration-controlled transient elastography score (VCTE) score of >9.5Pa, with an interquartile range =30% 6.2. Previous liver biopsy indicating at least moderate fibrosis (Ishak fibrosis stage >III, or equivalent) 6.3. Serum enhanced liver fibrosis score (ELF) >7.7 6.4. Presence of portal hypertension (investigator discretion) 6.5. A colonoscopy showing no evidence of dysplasia/neoplasia within 24 months before screening 6.6. No evidence of active colitis, as evidenced by a Partial Mayo Score of =4, with a score of <2 on the rectal bleeding domain at screening 7. Individuals with IBD who are receiving treatment with biologics, immunosuppression or corticosteroids must be taking a stable dose for at least twelve weeks before screening, and be expected to remain on the same medication/same dose for the duration of the trial
Exclusion criteria
Exclusion criteria: 1. Secondary causes of sclerosing cholangitis including, but not limited to, IgG4-related cholangitis, cholangiopathy due to acquired immunodeficiency syndrome, drug-induced sclerosing cholangitis, trauma, ischaemic cholangiopathy, choledocholithiasis (investigator discretion), or sclerosing cholangiopathy as a sequela of hepatopancreatobiliary resection. 2. Other causes of liver disease, including, but not limited to, IgG4-related disease; viral hepatitis; alcohol-related liver disease; metabolic dysfunction-associated steatotic liver disease; drug-induced liver disease; autoimmune hepatitis; hereditary haemochromatosis; alpha-1-antitrypsin disease; primary biliary cholangitis; Wilson disease; Budd-Chiari Syndrome; or primary or secondary hepatopancreatobiliary cancer. 3. Presence of a clinically significant dominant stricture based on the combination of radiological, biochemical and clinical features. Patients can be included in the trial with a dominant extrahepatic stenosis if it has been stable for 6 months or more (as evidenced on imaging and also clinically), and one of the following are satisfied: 3.1. The principal investigator (PI) does not plan for any biliary intervention (endoscopic, percutaneous or surgical) for the duration of the trial OR 3.2. The PI decides that they do not wish to perform any biliary intervention (endoscopic, percutaneous or surgical) on the dominant stenosis for clinical reasons of stability/patient choice 4. Presence of a percutaneous drain or bile duct stent 5. Evidence of hepatic decompensation within twelve weeks prior to screening. Hepatic decompensation defined as a variceal haemorrhage, ascites, hepatic hydrothorax, or hepatic encephalopathy 6. Biochemical/laboratory evidence of very advanced hepatic dysfunction, as evidenced by a serum bilirubin value >55 µmol/L (or conjugated hyperbilirubinaemia >45 µmol/L) or Child-Turcotte-Pugh (CTP) score >B7 7. Ascending cholangitis as assessed clinically within twelve weeks of screening 8. Use of antibiotics within twelve weeks of screening 9. Participant already listed for liver transplantation 10. Small duct PSC 11. Significant renal dysfunction as evidenced by an estimated glomerular filtration rate of 21 units per week for men, and >14 units per week for women 19. Ongoing recreational substance misuse. Those with a prior history must have a negative urine drug screen at screening 20. Positive stool test for Clostridioides difficile toxin or microscopy/culture positivi
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Occurrence of adverse events as measured by CTCAE v5.0, alongside the incidence of adverse events of special interest: acute cholangitis flares (including those that are resistant to a single course of antibiotic treatment), acute colitis flares and episodes/time to hepatic decompensation over the 12-week treatment period. | — |
Secondary
| Measure | Time frame |
|---|---|
| The following secondary outcome measures will analyse the effects of CARBALIVE on markers of disease activity and severity throughout the course of the trial as measured at week 1, 6 and 12: 1. Liver function tests, including serum alkaline phosphatase (ALP), alanine transaminase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase, bilirubin, albumin and C-reactive protein 2. Surrogate biomarkers of liver fibrosis measured using the serum enhanced liver fibrosis score 3. Immune response indicators measured using circulating white blood cell count and platelet count 4. Patient-reported outcome (PRO) measures, using the following scores: simple cholestatic complaints score (SCCS), 5D itch, partial Mayo colitis score and SIBDQ 5. PSC-specific prognostic score measured using the Amsterdam-Oxford PSC score 6. IBD activity assessed using faecal calprotectin 7. Incidence of trial endpoint events, by recording the incidence of the following events: cholangiocarcinoma/hepatopancreatobiliary malignancy, referral for liver transplantation, colonic resection or colorectal cancer, and/or mortality | — |
Countries
England, United Kingdom
Contacts
Public ContactPalak Trivedi
Outcome results
None listed