Obeticholic Acid in Pediatric Subjects With Biliary Atresia

Biliary Atresia Clinical Trial

— CARE  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT05321524
• Other study ID #: 747-206
• Status: Terminated
• Phase: Phase 2
• Start date: July 1, 2015
• Est. completion date: March 9, 2023

Study information

• Verified date: March 2023
• Source: Intercept Pharmaceuticals
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 7
• Est. completion date: March 9, 2023
• Est. primary completion date: March 9, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 2 Years to 17 Years

Eligibility

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

Related Conditions & MeSH terms

• Biliary Atresia

Intervention

Drug:
• OCA 0.1mg
Tablets administered orally once daily.
• OCA 1.5mg
Tablets administered orally once daily.
• OCA 5mg
Tablets administered orally once daily.

Locations

Country	Name	City	State
Belgium	Clinques University Saint-Luc	Brussel
France	CHU Lille	Lille	ME
France	Hopital de la Timone	Marseille	Paca
France	APHP- Hopital Necker Enfants Malades	Paris
France	CHU de Toulouse Purpan-Hopital des Enfants	Toulouse
Germany	Hannover Medical School, Children's Hospital, Paediatric Gastroenterology and Hepatology,	Hannover	Lower Saxony
Israel	Soroka University Medical Center	Beer Sheva
Israel	Hadassah Medical Center	Jerusalem
Israel	Shaare-Zedek Medical Center	Jerusalem
Israel	Schneider Children's Medical Center	Petach Tikva
Italy	Centre for Paediatric Hepatology	Bergamo
Italy	Regina Margherita Children's Hospital	Turin
Netherlands	University Medical Center Gröningen-Beatrix, children's Hospital	Groningen
Poland	Instytut Pomnik-Centrum Zdrowia Dziecka	Warsaw
Spain	Passeig Vall d'Hebron	Barcelona
Spain	Hospital Materno-Infantil de Malaga	Málaga
United Kingdom	Birmingham Children's Hospital	Birmingham	West Midlands

Sponsors (1)

Lead Sponsor	Collaborator
Intercept Pharmaceuticals

Countries where clinical trial is conducted

Belgium,  France,  Germany,  Israel,  Italy,  Netherlands,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability as assessed by the incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs)		Day 1, 21, and 56.
Primary	The plasma concentration of OCA and its conjugates (glyco-OCA and tauro-OCA)	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.	Day 1, 21, and 56.
Secondary	Biomarkers of FXR-activation: change from baseline of the plasma value of Fibroblast Growth Factor-19 (FGF-19)		Day 1, 21, and 56
Secondary	Biomarkers of FXR-activation: change from baseline of the plasma value of 7-hydroxyl-4-cholesten-3-one (C4)		Day 1, 21, and 56
Secondary	Biomarkers of FXR-activation: change from baseline of the plasma value of Endogenous Bile Acids		Day 1, 21, and 56
Secondary	Biomarkers of hepatobiliary function: Alkaline Phosphatase (ALP)		Time Frame: Day 1, 21, and 56
Secondary	Biomarkers of hepatobiliary function: Aspartate Aminotransferase (AST)		Time Frame: Day 1, 21, and 56
Secondary	Biomarkers of hepatobiliary function: Alanine Aminotransferase (ALT)		Time Frame: Day 1, 21, and 56
Secondary	Biomarkers of hepatobiliary function: Gamma-Glutamyl Transpeptidase (GGT)		Time Frame: Day 1, 21, and 56