Obeticholic Acid in Pediatric Subjects With Biliary Atresia

A Multicenter, Open-Label, Single- and Multiple-Dose, Dose-Finding Study, With an Optional Open-Label Extension to Assess the Safety, Tolerability, and Pharmacokinetics of Obeticholic Acid in Pediatric Subjects With Biliary Atresia

This is a Phase 2, multicenter, open-label, single dose and multi-dose, dose-finding study with an optional open-label extension (OLE) to assess the safety, tolerability, and pharmacokinetics of obeticholic acid (OCA) in pediatric subjects with biliary atresia with successful hepatoportoenterostomy (HPE, also known as a Kasai portoenterosomy). The OLE will continue to evaluate safety, tolerability, pharmacodynamics, and efficacy of OCA. In addition, a change in vitamin A and D levels, and where possible the degree of change in liver stiffness, will be assessed during the OLE.

Key Inclusion Criteria:

1. Male or female pediatric subjects ≥2 to <18 years old
2. Diagnosis of biliary atresia
3. Demonstrated successful HPE (also known as Kasai portoenterostomy) as defined by total bilirubin <2 mg/dL (34.2 μmol/L) at least 3 months post-HPE procedure.
4. Able to swallow tablets (ie, tablet or mini-tablet formulation)

Key Exclusion Criteria:

1. Prior liver transplant or active status on transplant list

2. Conjugated (direct) bilirubin ≥ULN of site specific reference range

3. If conjugated bilirubin is not available: total bilirubin ≥2 mg/dL (34.2 μmol/L)

4. Platelets <150,000/μL

5. INR ≥1.5

6. Current or history of complications of decompensated chronic liver disease including:

   1. high-risk 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. Current intractable pruritus or requires systemic treatment for pruritus within 3 months of Screening (e.g., with bile acid sequestrants or rifampicin)

8. Height and weight Z-score <-2 per site specific ranges

9. Acholic (pale) stools

10. AST >4x ULN

11. ALT >4x ULN

12. GGT >500 U/L

13. Anticoagulation therapy

14. Albumin <3.5 g/dL

15. Ongoing current cholangitis

16. Choledochal cystic disease

17. Renal disease defined as serum creatinine >ULN for subject's age, prior to enrollment