Study to Assess Efficacy, Safety, Tolerability, Pharmacokinetics (PK), and Pharmacodynamics (PD) of Obeticholic Acid (OCA) Compared to Placebo in Pediatric Participants With Biliary Atresia, Post-hepatoportoenterostomy

A Randomized, Double-blind, Placebo-controlled, Phase 2/3 Study to Assess the Efficacy, Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of Obeticholic Acid Compared to Placebo in Pediatric Subjects With Biliary Atresia, Post-hepatoportoenterostomy

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.

Study Overview

• Status: Terminated
• Conditions: Biliary Atresia
• Intervention / Treatment: Drug: OCA; Drug: Matching Placebo

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Australia
  • Queensland
    • South Brisbane, Queensland, Australia, 4101
      • Queensland Childrens Hospital
  • South Australia
    • North Adelaide, South Australia, Australia, 5006
      • Women's and Children's Hospital
  • Victoria
    • Parkville, Victoria, Australia, 3104
      • Royal Childrens Hospital
• Canada
  • Alberta
    • Calgary, Alberta, Canada, T3B 6A8
      • Alberta Childrens Hospital
    • Edmonton, Alberta, Canada
      • Stollery Children's Hospital
• China
  • Guangzhou, China
    • Guangzhou Women And Childrens Medical Center
  • Shanghai, China
    • Children's Hospital of Fudan University
  • Shanghai, China
    • Childrens Hospital of Shanghai
  • Taiyuan, China
    • Children's Hospital of Shanxi
  • Zhejiang
    • Hangzhou, Zhejiang, China, 310006
      • Children's Hospital, Zhejiang University School of Medicine
• Hong Kong
  • Hong Kong, Hong Kong
    • Queen Mary Hospital
• Israel
  • Jerusalem, Israel
    • Hadassah Medical Center
  • Jerusalem, Israel
    • Shaare-Zedek Medical Center
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Center
  • Kelantan
    • Kota Bharu, Kelantan, Malaysia, 15586
      • Hospital Raja Perempuan Azinab II
• New Zealand
  • Auckland, New Zealand, 1142
    • Starship Child Health
• Singapore
  • Singapore, Singapore
    • KK Women's and Children's Hospital
• Taiwan
  • Taichung, Taiwan
    • Taichung Veterans General Hospital
  • Tainan, Taiwan
    • National Chen Kung University Hospital
  • Taipei, Taiwan
    • National Taiwan University Hospital
  • Taoyuan, Taiwan
    • Linkou Chang Gung Memorial Hospital
• Turkey (Türkiye)
  • Ankara, Turkey (Türkiye), 06230
    • Hacettepe Universitesi ihsan Dogramaci Cocuk Hastansesi
  • Antalya
    • Konyaalti, Antalya, Turkey (Türkiye), 07050
      • Akdeniz Üniversitesi Tıp Fakültesi Hastanesi Pediatrik Gastroenteroloji
  • İzmir
    • Bornova, İzmir, Turkey (Türkiye), 35100
      • Ege Üniversitesi Hastanesi Pediatrik Gastroenteroloji Bölümü

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult
• Accepts Healthy Volunteers: No

Description

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).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Participants receiving OCA; Participants will be randomized to receive OCA (starting at 1.5 milligrams [mg] adult equivalent dose [AED]) orally, with water, once daily. Dose will be titrated every 2 weeks in a stepwise manner for the first 6 weeks, starting at 1.5 mg AED and titrating through 3 mg AED to a maximum of 5 mg AED, as tolerated; a discussion with the Medical Monitor is encouraged when determining uptitration if considerable signs or symptoms have arisen. Following the 6-week dose titration phase, participants will continue at the tolerated dose for approximately 24 months in Age Expansion Treatment Phase.	Drug: OCA; OCA will be administered.
Placebo Comparator: Participants receiving Matching placebo; Participants will be randomized to receive matching placebo orally, with water, once daily. Dose will be titrated every 2 weeks in a stepwise manner for the first 6 weeks, starting at 1.5 mg AED and titrating through 3 mg AED to a maximum of 5 mg AED, as tolerated; a discussion with the Medical Monitor is encouraged when determining uptitration if considerable signs or symptoms have arisen. Following the 6-week dose titration phase, participants will continue at the tolerated dose for approximately 24 months in Age Expansion Treatment Phase.	Drug: Matching Placebo; Matching Placebo will be administered.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Composite Liver-Related Clinical Events	Number of participants experiencing any of the following: All-cause death; Liver transplantation; Hospitalization (≥24 hours) for variceal bleeding, hepatic encephalopathy, or spontaneous bacterial peritonitis; Clinically relevant ascites requiring therapeutic paracentesis have been presented. No clinical outcome events were reported at the time of the study termination; hence It was not possible to conduct the planned primary efficacy analysis.	Up to Week 48
Change From Baseline in Pediatric End-stage Liver Disease (PELD) Score	The Pediatric End-stage Liver Disease (PELD) score is a scale used to assess the severity of chronic liver disease in pediatric participants younger than 12 years of age. The total PELD score ranges from negative values to positive values, with no absolute minimum or maximum, with higher scores indicating more severe liver disease and greater urgency for liver transplantation. The score is calculated using total bilirubin, international normalized ratio (INR), albumin, age at listing, and growth failure. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was calculated as the last post-baseline value minus the baseline value. A negative change from baseline indicates improvement, while a positive change indicates worsening.	Baseline and up to Week 48
Change From Baseline in Model of End-stage Liver Disease With Sodium (MELD-NA) Score	The Model of End-stage Liver Disease with Sodium (MELD-Na) score is a scale used to assess the severity of chronic liver disease in participants 12 years of age and older, ranging from 6 (less ill) to 40 (gravely ill). Higher scores indicate more severe liver disease and greater urgency for liver transplantation. The score is derived from total bilirubin, serum creatinine, INR, and serum sodium. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was calculated as the last post-baseline value minus the baseline value. A negative change from baseline indicates improvement, while a positive change indicates worsening.	Baseline and up to Week 48

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Percentage of Participants With Improvement in GGT and Direct Bilirubin (Composite Responder Endpoint)	Participants were considered responders if both of the following criteria were met at EOS: ≥40% reduction from baseline in Gamma Glutamyl Transferase (GGT), and ≥25% reduction from baseline in direct (conjugated) bilirubin. Participants with missing values were considered non-responders.	Up to Week 48
Change From Baseline in GGT	Blood samples were collected to assess GGT levels. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.	Baseline and up to Week 48
Change From Baseline in Total and Direct (Conjugated) Bilirubin	Blood samples were collected to assess direct bilirubin levels. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.	Baseline and up to Week 48
Change From Baseline in Endogenous Bile Acids	Plasma samples were collected to assess endogenous bile acids. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.	Baseline and up to Week 48
Change From Baseline in Liver Stiffness as Assessed by Transient Elastography	Liver stiffness was measured using ultrasound elastography. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.	Baseline and up to Week 48
Number of Participants Reporting Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs	TEAEs were defined as adverse events that were reported or worsened on or after the first dose of study treatment. Serious adverse events are adverse events resulting in death, are immediately life threatening, requires in-patient hospitalization or prolongation of existing hospitalization, or results in persistent or significant disability/incapacity.	Up to Week 48
Change From Baseline in Plasma Levels of Fat-Soluble Vitamin D	Plasma samples were collected to assess levels of fat-soluble vitamins D. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.	Baseline and Week 48
Change From Baseline in Plasma Levels of Fat-Soluble Vitamin K	Plasma samples were collected to assess levels of fat-soluble vitamin K. Baseline was defined as the last assessment prior to first study drug administration. Change from baseline was computed by subtracting the baseline value from the post-baseline value, with a positive change indicating improvement.	Baseline and Week 48

Collaborators and Investigators

• Sponsor: Intercept Pharmaceuticals
• Investigators: Study Director: Lynda Szczech, MD, Intercept Pharmaceuticals

Study record dates

Study Major Dates

• Study Start (Actual): September 2, 2024
• Primary Completion (Actual): October 21, 2025
• Study Completion (Actual): October 21, 2025

Study Registration Dates

• First Submitted: November 2, 2023
• First Submitted That Met QC Criteria: November 2, 2023
• First Posted (Actual): November 7, 2023

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: June 16, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Efficacy; Pharmacokinetics; Placebo-controlled; Pharmacodynamics; Biliary Atresia; Obeticholic Acid; Post-hepatoportoenterostomy
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Congenital Abnormalities; Bile Duct Diseases; Digestive System Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Biliary Atresia
• Other Study ID Numbers: 747-308

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes