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

NCT06121375 | Terminated Phase 2 DMC FDA Drug

• 1 other identifier: 747-308
• Study Type: interventional
• Target: 28
• Locations: 10 countries
• Sites: 24

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.

Conditions

Biliary Atresia

Keywords

Biliary Atresia; Placebo-controlled; Pharmacokinetics; Pharmacodynamics; Obeticholic Acid; Efficacy; Post-hepatoportoenterostomy

Outcome Measures

Primary Outcomes (1)

• Time to the First Occurrence of Composite Endpoint

  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)

  Up to Week 64

Secondary Outcomes (9)

• 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

• Change from Baseline in Gamma Glutamyl Transferase (GGT)

  Baseline and up to Week 64

• Change from Baseline in total and direct (conjugated) bilirubin

  Baseline and up to Week 64

• Change from Baseline in Fibroblast Growth Factor-19 (FGF-19)

  Baseline and up to Week 64

• Change from Baseline in 7-hydroxyl-4-cholesten-3-one (C4)

  Baseline and up to Week 64

Study Arms (2)

Participants receiving OCA

ACTIVE COMPARATOR

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

Participants receiving Matching placebo

PLACEBO COMPARATOR

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

Interventions

OCA DRUG

OCA will be administered.

Participants receiving OCA

Matching Placebo DRUG

Matching Placebo will be administered.

Participants receiving Matching placebo

Eligibility Criteria

• Age: 1 Day - 18 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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:
• Gastroesophageal varices and/or variceal bleeding
• Clinically evident ascites related to portal hypertension
• Hepatic encephalopathy
• Prior placement of portosystemic shunt
• Hepatopulmonary syndrome or portopulmonary hypertension
• Hepatorenal syndrome
• Any evidence of portal hypertension based on imaging (e.g., cavernous transformation of portal vein, abdominal varices, etc.)
• Hepatocellular carcinoma
• Childs-Pugh B or C

Sponsors & Collaborators

• Intercept Pharmaceuticals: lead

Study Sites (24)

Queensland Childrens Hospital

South Brisbane, Queensland, 4101, Australia

Location

Women's and Children's Hospital

North Adelaide, South Australia, 5006, Australia

Location

Royal Childrens Hospital

Parkville, Victoria, 3104, Australia

Location

Alberta Childrens Hospital

Calgary, Alberta, T3B 6A8, Canada

Location

Stollery Children's Hospital

Edmonton, Alberta, Canada

Location

Children's Hospital, Zhejiang University School of Medicine

Hangzhou, Zhejiang, 310006, China

Location

Guangzhou Women And Childrens Medical Center

Guangzhou, China

Location

Children's Hospital of Fudan University

Shanghai, China

Location

Childrens Hospital of Shanghai

Shanghai, China

Location

Children's Hospital of Shanxi

Taiyuan, China

Location

Queen Mary Hospital

Hong Kong, Hong Kong

Location

Hadassah Medical Center

Jerusalem, Israel

Location

Shaare-Zedek Medical Center

Jerusalem, Israel

Location

Hospital Raja Perempuan Azinab II

Kota Bharu, Kelantan, 15586, Malaysia

Location

University Malaya Medical Center

Kuala Lumpur, 59100, Malaysia

Location

Starship Child Health

Auckland, 1142, New Zealand

Location

KK Women's and Children's Hospital

Singapore, Singapore

Location

Taichung Veterans General Hospital

Taichung, Taiwan

Location

National Chen Kung University Hospital

Tainan, Taiwan

Location

National Taiwan University Hospital

Taipei, Taiwan

Location

Linkou Chang Gung Memorial Hospital

Taoyuan District, Taiwan

Location

Akdeniz Üniversitesi Tıp Fakültesi Hastanesi Pediatrik Gastroenteroloji

Konyaalti, Antalya, 07050, Turkey (Türkiye)

Location

Ege Üniversitesi Hastanesi Pediatrik Gastroenteroloji Bölümü

Bornova, İzmir, 35100, Turkey (Türkiye)

Location

Hacettepe Universitesi ihsan Dogramaci Cocuk Hastansesi

Ankara, 06230, Turkey (Türkiye)

Location

MeSH Terms

Conditions

Biliary Atresia

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Lynda Szczech, MD

  Intercept Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 2023
• First Posted: November 7, 2023
• Study Start: September 2, 2024
• Primary Completion: October 21, 2025
• Study Completion: October 21, 2025
• Last Updated: October 31, 2025

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

CA (2); TW (4); MY (2); CN (5); AU (3); HK (1); NZ (1); IL (2); SG (1); TU (3)