Clinical trial NCT05321524: Obeticholic Acid in Pediatric Subjects With Biliary Atresia
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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
Conditions: Biliary Atresia
Keywords: Biliary Atresia
hepatoportoenterostomy (HPE)
Kasai portoenterostomy
Liver
Obeticholic Acid
Lead sponsor: Intercept Pharmaceuticals
Sponsor class: INDUSTRY
First posted: 2022-04-11
Enrollment: 7
Sex: ALL
Minimum age (years): 2
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety and tolerability as assessed by the incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs)
timeFrame: Day 1, 21, and 56.
measure: The plasma concentration of OCA and its conjugates (glyco-OCA and tauro-OCA)
timeFrame: Day 1, 21, and 56.
Secondary outcomes:
measure: Biomarkers of FXR-activation: change from baseline of the plasma value of Fibroblast Growth Factor-19 (FGF-19)
timeFrame: Day 1, 21, and 56
measure: Biomarkers of FXR-activation: change from baseline of the plasma value of 7-hydroxyl-4-cholesten-3-one (C4)
timeFrame: Day 1, 21, and 56
measure: Biomarkers of FXR-activation: change from baseline of the plasma value of Endogenous Bile Acids
timeFrame: Day 1, 21, and 56
measure: Biomarkers of hepatobiliary function: Alkaline Phosphatase (ALP)
timeFrame: Time Frame: Day 1, 21, and 56
measure: Biomarkers of hepatobiliary function: Aspartate Aminotransferase (AST)
timeFrame: Time Frame: Day 1, 21, and 56
measure: Biomarkers of hepatobiliary function: Alanine Aminotransferase (ALT)
timeFrame: Time Frame: Day 1, 21, and 56
measure: Biomarkers of hepatobiliary function: Gamma-Glutamyl Transpeptidase (GGT)
timeFrame: Time Frame: Day 1, 21, and 56
Other outcomes:
Locations:
city: Brussel
country: Belgium
facility: Clinques University Saint-Luc
city: Lille
country: France
facility: CHU Lille
state: ME
city: Marseille
country: France
facility: Hopital de la Timone
state: Paca
city: Paris
country: France
facility: APHP- Hopital Necker Enfants Malades
city: Toulouse
country: France
facility: CHU de Toulouse Purpan-Hopital des Enfants
city: Hannover
country: Germany
facility: Hannover Medical School, Children's Hospital, Paediatric Gastroenterology and Hepatology,
state: Lower Saxony
city: Beer Sheva
country: Israel
facility: Soroka University Medical Center
city: Jerusalem
country: Israel
facility: Shaare-Zedek Medical Center
city: Jerusalem
country: Israel
facility: Hadassah Medical Center
city: Petach Tikva
country: Israel
facility: Schneider Children's Medical Center
city: Bergamo
country: Italy
facility: Centre for Paediatric Hepatology
city: Turin
country: Italy
facility: Regina Margherita Children's Hospital
city: Groningen
country: Netherlands
facility: University Medical Center Gröningen-Beatrix, children's Hospital
city: Warsaw
country: Poland
facility: Instytut Pomnik-Centrum Zdrowia Dziecka
city: Barcelona
country: Spain
facility: Passeig Vall d'Hebron
city: Málaga
country: Spain
facility: Hospital Materno-Infantil de Malaga
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
state: West Midlands
Study officials:
affiliation: Intercept Pharmaceuticals
name: Lynda Szczech, MD
role: STUDY_DIRECTOR
References: