Obeticholic Acid in Pediatric Subjects With Biliary Atresia
- Conditions
- Biliary Atresia
- Interventions
- Drug: OCA 0.1mgDrug: OCA 1.5mgDrug: OCA 5mg
- Registration Number
- NCT05321524
- Lead Sponsor
- Intercept Pharmaceuticals
- 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.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 7
- Male or female pediatric subjects ≥2 to <18 years old
- Diagnosis of biliary atresia
- 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.
- Able to swallow tablets (ie, tablet or mini-tablet formulation)
Key
-
Prior liver transplant or active status on transplant list
-
Conjugated (direct) bilirubin ≥ULN of site specific reference range
-
If conjugated bilirubin is not available: total bilirubin ≥2 mg/dL (34.2 μmol/L)
-
Platelets <150,000/μL
-
INR ≥1.5
-
Current or history of complications of decompensated chronic liver disease including:
- high-risk gastroesophageal varices and/or variceal bleeding
- clinically evident ascites related to portal hypertension
- hepatic encephalopathy
- prior placement of portosystemic shunt
- hepatopulmonary syndrome or portopulmonary hypertension
- hepatorenal syndrome
-
Current intractable pruritus or requires systemic treatment for pruritus within 3 months of Screening (e.g., with bile acid sequestrants or rifampicin)
-
Height and weight Z-score <-2 per site specific ranges
-
Acholic (pale) stools
-
AST >4x ULN
-
ALT >4x ULN
-
GGT >500 U/L
-
Anticoagulation therapy
-
Albumin <3.5 g/dL
-
Ongoing current cholangitis
-
Choledochal cystic disease
-
Renal disease defined as serum creatinine >ULN for subject's age, prior to enrollment
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- SEQUENTIAL
- Arm && Interventions
Group Intervention Description SD (1.5mg adult-equivalent dose of OCA) + MD Low dose (1.5mg adult-equivalent dose of OCA) OCA 0.1mg 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. SD (1.5mg adult-equivalent dose of OCA) + MD Low dose (1.5mg adult-equivalent dose of OCA) OCA 1.5mg 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. SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA) OCA 1.5mg 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. SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA) OCA 0.1mg 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. SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA) OCA 5mg 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. SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA) OCA 5mg 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. SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA) OCA 1.5mg 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. SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA) OCA 0.1mg 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.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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 FXR-activation: change from baseline of the plasma value of 7-hydroxyl-4-cholesten-3-one (C4) Day 1, 21, and 56 Biomarkers of hepatobiliary function: Aspartate Aminotransferase (AST) Time Frame: Day 1, 21, and 56 Biomarkers of hepatobiliary function: Alanine Aminotransferase (ALT) Time Frame: Day 1, 21, and 56 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 hepatobiliary function: Gamma-Glutamyl Transpeptidase (GGT) Time Frame: Day 1, 21, and 56
Trial Locations
- Locations (17)
University Medical Center Gröningen-Beatrix, children's Hospital
🇳🇱Groningen, Netherlands
Hannover Medical School, Children's Hospital, Paediatric Gastroenterology and Hepatology,
🇩🇪Hannover, Lower Saxony, Germany
Soroka University Medical Center
🇮🇱Beer Sheva, Israel
Shaare-Zedek Medical Center
🇮🇱Jerusalem, Israel
Schneider Children's Medical Center
🇮🇱Petach Tikva, Israel
Hadassah Medical Center
🇮🇱Jerusalem, Israel
Clinques University Saint-Luc
🇧🇪Brussel, Belgium
Instytut Pomnik-Centrum Zdrowia Dziecka
🇵🇱Warsaw, Poland
CHU de Toulouse Purpan-Hopital des Enfants
🇫🇷Toulouse, France
CHU Lille
🇫🇷Lille, ME, France
Hopital de la Timone
🇫🇷Marseille, Paca, France
APHP- Hopital Necker Enfants Malades
🇫🇷Paris, France
Regina Margherita Children's Hospital
🇮🇹Turin, Italy
Centre for Paediatric Hepatology
🇮🇹Bergamo, Italy
Passeig Vall d'Hebron
🇪🇸Barcelona, Spain
Hospital Materno-Infantil de Malaga
🇪🇸Málaga, Spain
Birmingham Children's Hospital
🇬🇧Birmingham, West Midlands, United Kingdom