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 Results 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 (3)

• 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 Outcomes (8)

• Percentage of Participants With Improvement in GGT and Direct Bilirubin (Composite Responder Endpoint)

  Up to Week 48

• Change From Baseline in GGT

  Baseline and up to Week 48

• Change From Baseline in Total and Direct (Conjugated) Bilirubin

  Baseline and up to Week 48

• Change From Baseline in Endogenous Bile Acids

  Baseline and up to Week 48

• Change From Baseline in Liver Stiffness as Assessed by Transient Elastography

  Baseline and up to Week 48

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, 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

Results Point of Contact

• Title: Medical Information
• Organization: Intercept Pharmaceuticals, Inc.

medinfo@interceptpharma.com

844-782-4278

Study Officials

• Lynda Szczech, MD

  Intercept Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

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: July 7, 2026
• Results First Posted: July 7, 2026

Record last verified: 2026-06

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)