Ischemic Cholangiopathy, Liver Transplant; Complications
Conditions
Brief summary
A prospective, open-label, single-arm, investigator-initiated study (SELIC) to evaluate the efficacy and safety of seladelpar in adult liver transplant recipients with Ischemic cholangiopathy (IC).
Detailed description
Ischemic cholangiopathy (IC) is a serious complication after liver transplantation, particularly in recipients of donation after circulatory death grafts, and is associated with cholestasis, biliary strictures, and graft dysfunction. No approved pharmacologic therapies currently exist. Seladelpar, a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist recently approved for primary biliary cholangitis, reduces bile acid synthesis and inflammation and has demonstrated antifibrotic activity, making it a promising candidate for IC. We designed a prospective, open-label, single-arm, investigator-initiated study (SELIC) to evaluate the efficacy and safety of seladelpar in adult liver transplant recipients with IC. Ten patients will receive seladelpar 10 mg orally once daily for 52 weeks. Outcomes will be compared to historical controls identified from the same institution. The primary endpoint is percent change in serum alkaline phosphatase (ALP) from baseline to Week 26. Additional outcomes include ERCP utilization, liver allograft loss, and safety assessed by adverse event and laboratory monitoring and drug discontinuation rates. This pilot study will provide the first prospective data on seladelpar in IC and may establish preliminary evidence for a novel therapeutic approach to reduce cholestasis, improve symptoms, and preserve graft function in this high-risk population.
Interventions
DRUGSeladelpar
Seladelpar is a selective peroxisome proliferator-activated receptor delta (PPAR-δ) agonist
Sponsors
University of California, San Diego
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
1. Adult, age ≥ 18 and \< 80 years 2. Diagnosis of ischemic cholangiopathy defined as non-anastomotic biliary strictures confirmed by imaging (ERCP, MRI, percutaneous cholangiogram) 3. Cholestasis noted by elevated alkaline phosphatase (ALP) and gamma glutamyl transferase (GGT) 4. Imaging and clinical findings present at least 4 weeks after but within 12 months of liver transplantation 5. No recent hospitalization within 2 weeks before enrollment to ensure clinical stability
Exclusion criteria
1. Decompensated liver disease, including but not limited to ascites requiring paracentesis, hepatic encephalopathy, or variceal bleeding. 2. Pregnancy or breastfeeding. 3. Current or recent (within 30 days) use of other investigational agents or fenofibrate. 4. Current or recent (within 30 days) use of cyclosporine 5. Known hypersensitivity or contraindication to seladelpar or its excipients. 6. Severe concomitant illness (renal, cardiac, or other systemic condition) that, in the investigator's judgment, would interfere with study participation or interpretation of results. 7. ALT \> 150 IU/L. 8. AST \> 150 IU/L. 9. Total bilirubin \> 5 mg/dL at screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| serum alkaline phosphatase (ALP) | 26 weeks | Determine the effect of seladelpar on serum alkaline phosphatase (ALP) from baseline to week 26 |
Contacts
CONTACTMedical Director of Liver Transplantation, MD
Outcome results
None listed