Biliary Atresia
Conditions
Keywords
Biliary Atresia, hepatoportoenterostomy (HPE), Kasai portoenterostomy, Liver, Obeticholic Acid
Brief summary
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.
Interventions
DRUGOCA 0.1mg
Tablets administered orally once daily.
DRUGOCA 1.5mg
Tablets administered orally once daily.
DRUGOCA 5mg
Tablets administered orally once daily.
Sponsors
Intercept Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
2 Years to 17 Years
Healthy volunteers
No
Inclusion 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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. | Change in plasma concentrations of unconjugated OCA and its conjugates (glyco-OCA and tauro-OCA) will be quantitated, and total OCA concentration will be calculated in the SD and MD Phase. |
Secondary
| Measure | Time frame |
|---|---|
| Biomarkers of FXR-activation: change from baseline of the plasma value of Endogenous Bile Acids | Day 1, 21, and 56 |
| Biomarkers of hepatobiliary function: Alkaline Phosphatase (ALP) | Time Frame: Day 1, 21, and 56 |
| Biomarkers of FXR-activation: change from baseline of the plasma value of Fibroblast Growth Factor-19 (FGF-19) | Day 1, 21, and 56 |
| Biomarkers of hepatobiliary function: Alanine Aminotransferase (ALT) | Time Frame: Day 1, 21, and 56 |
| Biomarkers of hepatobiliary function: Gamma-Glutamyl Transpeptidase (GGT) | Time Frame: Day 1, 21, and 56 |
| Biomarkers of hepatobiliary function: Aspartate Aminotransferase (AST) | Time Frame: Day 1, 21, and 56 |
| Biomarkers of FXR-activation: change from baseline of the plasma value of 7-hydroxyl-4-cholesten-3-one (C4) | Day 1, 21, and 56 |
Countries
Belgium, France, Germany, Israel, Italy, Netherlands, Poland, Spain, United Kingdom
Outcome results
None listed