Obeticholic Acid in Pediatric Subjects With Biliary Atresia

NCT05321524 | Terminated Phase 2 DMC

• 1 other identifier: 747-206
• Study Type: interventional
• Target: 7
• Locations: 9 countries
• Sites: 17

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.

Conditions

Biliary Atresia

Keywords

Biliary Atresia; hepatoportoenterostomy (HPE); Kasai portoenterostomy; Liver; Obeticholic Acid

Outcome Measures

Primary Outcomes (2)

• 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)

  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 Outcomes (7)

• 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 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: Aspartate Aminotransferase (AST)

  Time Frame: Day 1, 21, and 56

Study Arms (3)

SD (1.5mg adult-equivalent dose of OCA) + MD Low dose (1.5mg adult-equivalent dose of OCA)

EXPERIMENTAL

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.

Drug: OCA 0.1mg; Drug: OCA 1.5mg

SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA)

EXPERIMENTAL

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.

Drug: OCA 0.1mg; Drug: OCA 1.5mg; Drug: OCA 5mg

SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA)

EXPERIMENTAL

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.

Drug: OCA 0.1mg; Drug: OCA 1.5mg; Drug: OCA 5mg

Interventions

OCA 0.1mg DRUG

Tablets administered orally once daily.

Also known as: Obeticholic Acid, 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747

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)

OCA 1.5mg DRUG

Tablets administered orally once daily.

Also known as: 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747

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)

OCA 5mg DRUG

Tablets administered orally once daily.

Also known as: 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747

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)

Eligibility Criteria

• Age: 2 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Intercept Pharmaceuticals: lead

Study Sites (17)

Clinques University Saint-Luc

Brussels, 1200, Belgium

Location

CHU Lille

Lille, ME, 59037, France

Location

Hopital de la Timone

Marseille, PACA, 13385, France

Location

APHP- Hopital Necker Enfants Malades

Paris, 75015, France

Location

CHU de Toulouse Purpan-Hopital des Enfants

Toulouse, 31059, France

Location

Hannover Medical School, Children's Hospital, Paediatric Gastroenterology and Hepatology,

Hanover, Lower Saxony, 30625, Germany

Location

Soroka University Medical Center

Beersheba, 84101, Israel

Location

Shaare-Zedek Medical Center

Jerusalem, 9103102, Israel

Location

Hadassah Medical Center

Jerusalem, 91120, Israel

Location

Schneider Children's Medical Center

Petah Tikva, 4920235, Israel

Location

Centre for Paediatric Hepatology

Bergamo, 24127, Italy

Location

Regina Margherita Children's Hospital

Turin, 10126, Italy

Location

University Medical Center Gröningen-Beatrix, children's Hospital

Groningen, 9713 GZ, Netherlands

Location

Instytut Pomnik-Centrum Zdrowia Dziecka

Warsaw, Poland

Location

Passeig Vall d'Hebron

Barcelona, Spain

Location

Hospital Materno-Infantil de Malaga

Málaga, Spain

Location

Birmingham Children's Hospital

Birmingham, West Midlands, B4 6NH, United Kingdom

Location

MeSH Terms

Conditions

Biliary Atresia

Interventions

obeticholic acid

Condition Hierarchy (Ancestors)

Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Digestive System Abnormalities; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Study Officials

• Lynda Szczech, MD

  Intercept Pharmaceuticals

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 18, 2022
• First Posted: April 11, 2022
• Study Start: July 1, 2015
• Primary Completion: March 9, 2023
• Study Completion: March 9, 2023
• Last Updated: March 28, 2023

Record last verified: 2023-03

Locations

GB (1); IL (4); FR (4); PL (1); NL (1); BE (1); DE (1); IT (2); ES (2)