Biliary Atresia
Conditions
Keywords
Biliary Atresia, Placebo-controlled, Pharmacokinetics, Pharmacodynamics, Obeticholic Acid, Efficacy, Post-hepatoportoenterostomy
Brief summary
This study will evaluate the efficacy, safety and tolerability, as well as PK/PD of OCA in eligible pediatric participants with biliary atresia with successful hepatoportoenterostomy (HPE, also known as a Kasai portoenterostomy). The double-blind period comprises of 2 phases: dose titration phase and age expansion treatment phase.
Interventions
DRUGOCA
OCA will be administered.
DRUGMatching Placebo
Matching Placebo will be administered.
Sponsors
Intercept Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
1 Days to 18 Years
Healthy volunteers
No
Inclusion criteria
* Male or female pediatric participants from birth to \<18 years old. Note: Participants aged \<2 years old will not be enrolled until after review of safety data during the planned interim analysis and agreement from the Data Safety Monitoring Board (DSMB) that there is sufficient safety data to enroll this age group. * Diagnosis of non-syndromic biliary atresia. * Demonstrated successful HPE as defined by total bilirubin \<2 milligrams per deciliter (mg/dL) (34.2 micromoles per liter \[μmol/L\]) at least 3 months post-HPE procedure.
Exclusion criteria
* Prior liver transplant or active status on transplant list. * Participants diagnosed with biliary atresia splenic malformation (BASM). * Conjugated (direct) bilirubin ≥ upper limit of normal (ULN) of site-specific reference range. If conjugated bilirubin is not available: total bilirubin ≥2 mg/dL (34.2 mol/L). * Platelets \<120,000/μL * International normalized ratio (INR) ≥1.5. * Current or history of complications of decompensated chronic liver disease including: 1. Gastroesophageal varices and/or variceal bleeding 2. Clinically evident ascites related to portal hypertension 3. Hepatic encephalopathy 4. Prior placement of portosystemic shunt 5. Hepatopulmonary syndrome or portopulmonary hypertension 6. Hepatorenal syndrome 7. Any evidence of portal hypertension based on imaging (e.g., cavernous transformation of portal vein, abdominal varices, etc.) 8. Hepatocellular carcinoma 9. Childs-Pugh B or C * Height and weight Z-score \<-2 per site-specific reference ranges. * Acholic (pale) stools. * Aspartate aminotransferase (AST) \>4x ULN. * Alanine aminotransferase \>4x ULN * GGT \>500 Units per Liter (U/L) * On anticoagulation therapy * Albumin \<3.5 grams per deciliter (g/dL). * Inability to swallow tablets (i.e., tablet or mini-tablet formulations).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Time to the First Occurrence of Composite Endpoint | Up to Week 64 | To evaluate the effect of OCA compared to placebo in conjunction with established local standard of care on clinical outcomes in participants with biliary atresia who have had a successful Kasai procedure as measured by time to first occurrence of any of the following adjudicated events, derived as composite event endpoint of all-cause death, liver transplant, Pediatric end-stage liver disease (PELD) score ≥17/model of end-stage liver disease (MELD)≥15, Hospitalization (as defined by a stay of 24 hours or greater) for new onset or recurrence of Variceal bleed, hepatic encephalopathy (as defined by a West Haven score of ≥2), Spontaneous bacterial peritonitis (confirmed by diagnostic paracentesis) and Clinically evident ascites related to poral hypertension (diuretic-resistant ascites requiring therapeutic paracentesis at a frequency of at least twice in a month) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change from Baseline in Gamma Glutamyl Transferase (GGT) | Baseline and up to Week 64 | Blood samples will be calculated to assess GGT levels. |
| Change from Baseline in total and direct (conjugated) bilirubin | Baseline and up to Week 64 | Blood samples will be calculated to assess total and direct (conjugated) bilirubin levels. |
| Change from Baseline in Fibroblast Growth Factor-19 (FGF-19) | Baseline and up to Week 64 | Blood samples will be calculated to assess FGF-19 |
| Change from Baseline in 7-hydroxyl-4-cholesten-3-one (C4) | Baseline and up to Week 64 | Blood samples will be calculated to assess C4 |
| Plasma concentration of unconjugated OCA (parent), glyco-OCA, tauro-OCA, and total OCA (molar sum of OCA and its active conjugates) | Up to Week 64 | Plasma concentrations of OCA and its conjugates (glyco-OCA and tauro-OCA) will be determined using validated liquid-chromatography mass spectrometry/mass spectrometry methods |
| Change from Baseline in liver stiffness as assessed by transient elastography | Baseline and up to Week 64 | — |
| Change from Baseline in plasma levels of fat-soluble vitamins (D and K) | Baseline and up to Week 64 | Blood samples will be calculated to assess plasma levels of fat-soluble vitamins (D and K) |
| Safety and tolerability as assessed by the incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs) | Up to Week 64 | — |
| Change from Baseline in endogenous bile acids | Baseline and up to Week 64 | Blood samples will be calculated to assess endogenous bile acids |
Countries
Australia, Canada, China, Hong Kong, Israel, Malaysia, New Zealand, Singapore, Taiwan, Turkey (Türkiye)
Outcome results
None listed