Obeticholic Acid in Pediatric Subjects With Biliary Atresia (CARE)

Intercept Pharmaceuticals

Status and phase: Terminated; Phase 2

Conditions: Biliary Atresia

Treatments: Drug: OCA 0.1mg; Drug: OCA 1.5mg; Drug: OCA 5mg

Study type: Interventional

Funder types: Industry

Identifiers

NCT05321524

747-206

Details and patient eligibility

About

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.

Enrollment: 7 patients

Sex: All

Ages: 2 to 17 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

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

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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7 participants in 3 patient groups

SD (1.5mg adult-equivalent dose of OCA) + MD Low dose (1.5mg adult-equivalent dose of OCA)

Experimental group

Description:

At Single Dose (SD) phase, eligible subjects will receive a 1.5 mg adult-equivalent, body weight-based single dose of OCA on Day 1. Enrollment in the Multiple Dose (MD) Phase will occur in a sequential fashion. At Day 28, the first 8 (±1) eligible subjects will be assigned to the Low Dose Cohort and will receive a 1.5 mg adult-equivalent dose of OCA daily for 4 weeks. The adult-equivalent dose is based on a 70-kg adult. 2 OCA tablet dose strength (0.1mg and 1.5mg) are available in the study and dose will be determined using weight based dosing chart.

Treatment:

Drug: OCA 1.5mg

Drug: OCA 0.1mg

SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA)

Experimental group

Description:

At Single Dose (SD) phase, eligible subjects will receive a 1.5 mg adult-equivalent, body weight-based single dose of OCA on Day 1. Upon safety and tolerability assessment in the Low Dose Cohort, 8 (±1) eligible subjects will be assigned to the Medium Dose Cohort and will receive a 5 mg adult-equivalent dose of OCA daily for 4 weeks. The adult-equivalent dose is based on a 70-kg adult. 3 OCA tablet dose strength (0.1mg, 1.5mg and 5mg tablets) are available in the study and dose will be determined using weight based dosing chart.

Treatment:

Drug: OCA 5mg

Drug: OCA 1.5mg

Drug: OCA 0.1mg

SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA)

Experimental group

Description:

At Single Dose (SD) phase, eligible subjects will receive a 1.5 mg adult-equivalent, body weight-based single dose of OCA on Day 1. Upon safety and tolerability assessment in the Medium Dose Cohort, 8 (±1) eligible subjects will be assigned to the High Dose Cohort and will receive a 10 mg adult-equivalent dose of OCA daily for 4 weeks. The adult-equivalent dose is based on a 70-kg adult. 3 OCA tablet dose strength (0.1mg, 1.5mg and 5mg tablets) are available in the study and dose will be determined using weight based dosing chart.

Treatment:

Drug: OCA 5mg

Drug: OCA 1.5mg

Drug: OCA 0.1mg