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

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Intercept Pharmaceuticals Inc.

Participant type

Pediatric, Patients

Age range

0-17 years, 18-64 years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

completed 21 Oct 2025

Decision date (initial)

2024-04-16

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

Yes

External identifiers

EU CT number

2023-503926-37-00

ClinicalTrials.gov

NCT06121375

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others, Safety, Pharmacodynamic, Efficacy, Pharmacokinetic

To evaluate the effect of OCA compared to placebo in conjunction with established local standard of care on
clinical outcomes in subjects with biliary atresia who have had a successful Kasai procedure as measured by
time to first occurrence of any component of a composite endpoint comprised of the following adjudicated
events:
• Death (all-cause)
• 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)
• Clinically evident ascites related to portal hypertension (diuretic-resistant ascites requiring
therapeutic paracentesis at a frequency of at least twice in a month)

Secondary objectives 6

1. To evaluate the: Pharmacokinetics (PK) of OCA as measured by unconjugated plasma OCA (parent), glyco-OCA, tauro-OCA, and total OCA (molar sum of OCA and its active conjugates)
2. Pharmacodynamics (PD) of OCA as measured by: Biomarkers of farnesoid X receptor (FXR) activation: plasma fibroblast growth factor 19 (FGF-19), 7-hydroxy-4-cholesten-3-one (C4), and endogenous bile acids
3. Biomarkers of hepatobiliary function: gamma-glutamyl transferase (GGT), total and direct (conjugated) bilirubin)
4. Effect of OCA on liver stiffness by transient elastography (if available at site)
5. Disease progression as measured by plasma levels of fat-soluble vitamins (Vitamins D and K)
6. Safety and tolerability of OCA

Conditions and MedDRA coding

Biliary Atresia, Post-hepatoportoenterostomy

Study design 2 periods

Regulatory references

EMA paediatric investigation plan (PIP)

EMEA-001304-PIP02-13

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Male or female pediatric subjects from birth to <18 years old Note: Subjects aged <2 years old will not be enrolled until after review of safety data during the planned interim analysis and agreement from the DSMB that there is sufficient safety data to enroll this age group.
2. Diagnosis of non-syndromic biliary atresia
3. Demonstrated successful HPE as defined by total bilirubin <2 mg/dL (34.2 μmol/L) at least 3 months post-HPE procedure.
4. Female subjects of childbearing potential must use ≥1 highly effective method (≤1% failure rate) of contraception from the initiation of Screening and until at least 20 days (5 half-lives), after the last dose of investigational product. Highly effective methods of contraception are considered to be those listed below: • Surgical sterilization (bilateral tubal occlusion, etc.) • Placement of an intrauterine device (IUD) or intrauterine system (e.g., intrauterine hormone-releasing system [IUS]). • Combined (estrogen and progesterone containing) hormonal contraceptive associated with inhibition of ovulation: − Oral − Intravaginal − Transdermal • Progesterone-only hormonal contraception associated with inhibition of ovulation: − Oral − Injectable − Implantable • In the context of this study, the goal of using a highly effective contraception method is to avoid the potential embryofetal risks from exposure to investigational medicinal products. Sexual abstinence, as a form of highly effective contraception, is defined as avoiding all types of sexual activity that could result in pregnancy during the entire period of the study treatment until at least 20 days (5 half-lives), after the last dose of investigational product. The reliability of sexual abstinence needs to be evaluated in relation to the duration of the clinical study.
5. Male subjects who are sexually active with female partners of childbearing potential must agree to use a condom with spermicide and to use one other approved method of highly effective contraception from the time of initiation of the investigational product administration and until at least 20 days (5 half-lives), after the last dose of investigational product.
6. Male subjects, if permitted to donate sperm per local regulations, must refrain from sperm donation from Screening through at least 20 days (5 half-lives) after the last dose of investigational product.
7. Parent or guardian is willing to provide written informed consent and when appropriate, the subject is willing to assent and agree to comply with the study protocol.

Exclusion criteria 18

1. Prior liver transplant or active status on transplant list
2. Alanine aminotransferase >4x ULN
3. GGT >500 U/L
4. Anticoagulation therapy
5. Albumin <3.5 g/dL
6. Inability to swallow tablets (i.e., tablet or mini-tablet formulations)
7. Subjects diagnosed with biliary atresia splenic malformation (BASM)
8. 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 μmol/L)
9. Platelets <120,000/μL
10. International normalized ratio (INR) ≥1.5
11. Current or history of complications of decompensated chronic liver disease including: a.) gastroesophageal varices and/or variceal bleeding; b.) clinically evident ascites related to portal hypertension; c.) hepatic encephalopathy; d.) prior placement of portosystemic shunt; e.) hepatopulmonary syndrome or portopulmonary hypertension; f.) hepatorenal syndrome; g.) any evidence of portal hypertension based on imaging (e.g., cavernous transformation of portal vein, abdominal varices, etc.); h.) Hepatocellular carcinoma; i.) Childs-Pugh B or C
12. Height and weight Z-score <-2 per site-specific reference ranges
13. Acholic (pale) stools
14. Aspartate aminotransferase (AST) >4x ULN
15. History of known or suspected clinically significant hypersensitivity to OCA or any of its excipients
16. If female, known pregnancy, or has a positive urine pregnancy test (confirmed by a positive serum pregnancy test), or lactating
17. Subjects who are committed to an institution by virtue of an order issued either by the judicial or administrative authorities per local regulations
18. Subjects who are children of or related to investigational site staff members, site staff members otherwise supervised by the investigator, or sponsor employees directly involved in the conduct of the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 6

1. Time to the first occurrence of any of the following clinical events.
2. Time to first occurrence of: Death
3. Liver transplant
4. PELD score ≥17/MELD ≥15
5. 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)
6. Clinically evident ascites related to poral hypertension (diuretic-resistant ascites requiring therapeutic paracentesis at a frequency of at least twice in a month)

Secondary endpoints 6

1. PK exposure of OCA: Plasma unconjugated OCA (parent), glyco-OCA, tauro-OCA, and total OCA
2. Biomarkers of hepatobiliary function: GGT, total and direct (conjugated) bilirubin
3. Biomarkers of FXR activation (PD): Plasma FGF-19, C4, endogenous bile acids
4. Noninvasive assessment of liver stiffness (if available at site): Transient elastography
5. Disease progression: Plasma levels of fat-soluble vitamins (D and K)
6. Safety and tolerability of OCA: Treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs), electrocardiogram (ECG), physical exam, clinical laboratory results, and vital signs

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Intercept Pharmaceuticals Inc.

Sponsor organisation

Intercept Pharmaceuticals Inc.

Address

305 Madison Avenue

City

Morristown

Postcode

07960-6117

Country

United States

Scientific contact point

Organisation

Intercept Pharmaceuticals Inc.

Contact name

General Information

Public contact point

Organisation

Intercept Pharmaceuticals Inc.

Contact name

General Information

Third parties 9

Locations

7 EU/EEA countries · 9 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 57 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications