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.

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).