Clinical trial
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
Name
747-206
Description
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.
Trial arms
Trial start
2015-07-01
Estimated PCD
2023-03-09
Trial end
2023-03-09
Status
Terminated
Phase
Early phase I
Treatment
OCA 0.1mg
Tablets administered orally once daily.
Arms:
SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA), SD (1.5mg adult-equivalent dose of OCA) + MD Low dose (1.5mg adult-equivalent dose of OCA), SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA)
Other names:
Obeticholic Acid, 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747
OCA 1.5mg
Tablets administered orally once daily.
Arms:
SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA), SD (1.5mg adult-equivalent dose of OCA) + MD Low dose (1.5mg adult-equivalent dose of OCA), SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA)
Other names:
6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747
OCA 5mg
Tablets administered orally once daily.
Arms:
SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA), SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA)
Other names:
6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747
Size
7
Primary endpoint
Safety and tolerability as assessed by the incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs)
Day 1, 21, and 56.
The plasma concentration of OCA and its conjugates (glyco-OCA and tauro-OCA)
Day 1, 21, and 56.
Eligibility 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
Protocol
{'studyType': 'INTERVENTIONAL', 'phases': ['PHASE2'], 'designInfo': {'allocation': 'NON_RANDOMIZED', 'interventionModel': 'SEQUENTIAL', 'primaryPurpose': 'TREATMENT', 'maskingInfo': {'masking': 'NONE'}}, 'enrollmentInfo': {'count': 7, 'type': 'ACTUAL'}}
Updated at
2023-03-28
1 organization
1 product
1 indication
Organization
Intercept PharmaceuticalsProduct
OCAIndication
Biliary Atresia