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

Biliary Atresia Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT06121375
• Other study ID #: 747-308
• Status: Not yet recruiting
• Phase: Phase 2/Phase 3
• Start date: March 2024
• Est. completion date: December 2027

Study information

• Verified date: November 2023
• Source: Intercept Pharmaceuticals
• Contact: Scott Birnbaum
• Phone: +1 6197572331
• Email: scott.birnbaum[@]interceptpharma.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 144
• Est. completion date: December 2027
• Est. primary completion date: December 2027
• Accepts healthy volunteers: No
• Gender: All
• Age group: 1 Day to 18 Years

Eligibility

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).

Related Conditions & MeSH terms

• Biliary Atresia

Intervention

Drug:
• OCA
OCA will be administered.
• Matching Placebo
Matching Placebo will be administered.

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Intercept Pharmaceuticals

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Plasma concentration of unconjugated OCA (parent), glyco-OCA, tauro-OCA, and total OCA (molar sum of OCA and its active conjugates)	Plasma concentrations of OCA and its conjugates (glyco-OCA and tauro-OCA) will be determined using validated liquid-chromatography mass spectrometry/mass spectrometry methods	Up to Week 64
Secondary	Change from Baseline in Gamma Glutamyl Transferase (GGT)	Blood samples will be calculated to assess GGT levels.	Baseline and up to Week 64
Secondary	Change from Baseline in total and direct (conjugated) bilirubin	Blood samples will be calculated to assess total and direct (conjugated) bilirubin levels.	Baseline and up to Week 64
Secondary	Change from Baseline in Fibroblast Growth Factor-19 (FGF-19)	Blood samples will be calculated to assess FGF-19	Baseline and up to Week 64
Secondary	Change from Baseline in 7-hydroxyl-4-cholesten-3-one (C4)	Blood samples will be calculated to assess C4	Baseline and up to Week 64
Secondary	Change from Baseline in endogenous bile acids	Blood samples will be calculated to assess endogenous bile acids	Baseline and up to Week 64
Secondary	Change from Baseline in liver stiffness as assessed by transient elastography		Baseline and up to Week 64
Secondary	Change from Baseline in plasma levels of fat-soluble vitamins (D and K)	Blood samples will be calculated to assess plasma levels of fat-soluble vitamins (D and K)	Baseline and up to Week 64
Secondary	Safety and tolerability as assessed by the incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs)		Up to Week 64