Back to resultsObeticholic Acid in Pediatric Subjects With Biliary Atresia (CARE)
Primary Purpose
Biliary Atresia
Status
Terminated
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
OCA 0.1mg
OCA 1.5mg
OCA 5mg
Sponsored by
About this trial
This is an interventional treatment trial for Biliary Atresia focused on measuring Biliary Atresia, hepatoportoenterostomy (HPE), Kasai portoenterostomy, Liver, Obeticholic Acid
Eligibility Criteria
Key Inclusion Criteria:
- 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 Exclusion Criteria:
- 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
Sites / Locations
- Clinques University Saint-Luc
- CHU Lille
- Hopital de la Timone
- APHP- Hopital Necker Enfants Malades
- CHU de Toulouse Purpan-Hopital des Enfants
- Hannover Medical School, Children's Hospital, Paediatric Gastroenterology and Hepatology,
- Soroka University Medical Center
- Shaare-Zedek Medical Center
- Hadassah Medical Center
- Schneider Children's Medical Center
- Centre for Paediatric Hepatology
- Regina Margherita Children's Hospital
- University Medical Center Gröningen-Beatrix, children's Hospital
- Instytut Pomnik-Centrum Zdrowia Dziecka
- Passeig Vall d'Hebron
- Hospital Materno-Infantil de Malaga
- Birmingham Children's Hospital
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
Experimental
Experimental
Arm Label
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)
SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA)
Arm Description
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.
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.
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.
Outcomes
Primary Outcome Measures
Safety and tolerability as assessed by the incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs)
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.
Secondary Outcome Measures
Biomarkers of FXR-activation: change from baseline of the plasma value of Fibroblast Growth Factor-19 (FGF-19)
Biomarkers of FXR-activation: change from baseline of the plasma value of 7-hydroxyl-4-cholesten-3-one (C4)
Biomarkers of FXR-activation: change from baseline of the plasma value of Endogenous Bile Acids
Biomarkers of hepatobiliary function: Alkaline Phosphatase (ALP)
Biomarkers of hepatobiliary function: Aspartate Aminotransferase (AST)
Biomarkers of hepatobiliary function: Alanine Aminotransferase (ALT)
Biomarkers of hepatobiliary function: Gamma-Glutamyl Transpeptidase (GGT)
Full Information
NCT ID
NCT05321524
First Posted
March 18, 2022
Last Updated
March 24, 2023
Sponsor
Intercept Pharmaceuticals
1. Study Identification
Unique Protocol Identification Number
NCT05321524
Brief Title
Obeticholic Acid in Pediatric Subjects With Biliary Atresia
Acronym
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
Study Type
Interventional
2. Study Status
Record Verification Date
March 2023
Overall Recruitment Status
Terminated
Why Stopped
After extensive efforts to improve recruitment, it is deemed not feasible to enroll the requisite number of subjects to generate data needed to meet the study objectives. EMA Paediatric Committee agreed with the Sponsor to terminate this study.
Study Start Date
July 1, 2015 (Actual)
Primary Completion Date
March 9, 2023 (Actual)
Study Completion Date
March 9, 2023 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Intercept Pharmaceuticals
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Biliary Atresia
Keywords
Biliary Atresia, hepatoportoenterostomy (HPE), Kasai portoenterostomy, Liver, Obeticholic Acid
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
7 (Actual)
8. Arms, Groups, and Interventions
Arm Title
SD (1.5mg adult-equivalent dose of OCA) + MD Low dose (1.5mg adult-equivalent dose of OCA)
Arm Type
Experimental
Arm Description
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.
Arm Title
SD (1.5mg adult-equivalent dose of OCA) + MD Medium dose (5mg adult-equivalent dose of OCA)
Arm Type
Experimental
Arm Description
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.
Arm Title
SD (1.5mg adult-equivalent dose of OCA) + MD High dose (10mg adult-equivalent dose of OCA)
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
OCA 0.1mg
Other Intervention Name(s)
Obeticholic Acid, 6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747
Intervention Description
Tablets administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
OCA 1.5mg
Other Intervention Name(s)
6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747
Intervention Description
Tablets administered orally once daily.
Intervention Type
Drug
Intervention Name(s)
OCA 5mg
Other Intervention Name(s)
6alpha-ethylchenodeoxycholic acid (6-ECDCA), INT-747
Intervention Description
Tablets administered orally once daily.
Primary Outcome Measure Information:
Title
Safety and tolerability as assessed by the incidence of treatment-emergent adverse events (TEAEs) including serious adverse events (SAEs)
Time Frame
Day 1, 21, and 56.
Title
The plasma concentration of OCA and its conjugates (glyco-OCA and tauro-OCA)
Description
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.
Time Frame
Day 1, 21, and 56.
Secondary Outcome Measure Information:
Title
Biomarkers of FXR-activation: change from baseline of the plasma value of Fibroblast Growth Factor-19 (FGF-19)
Time Frame
Day 1, 21, and 56
Title
Biomarkers of FXR-activation: change from baseline of the plasma value of 7-hydroxyl-4-cholesten-3-one (C4)
Time Frame
Day 1, 21, and 56
Title
Biomarkers of FXR-activation: change from baseline of the plasma value of Endogenous Bile Acids
Time Frame
Day 1, 21, and 56
Title
Biomarkers of hepatobiliary function: Alkaline Phosphatase (ALP)
Time Frame
Time Frame: Day 1, 21, and 56
Title
Biomarkers of hepatobiliary function: Aspartate Aminotransferase (AST)
Time Frame
Time Frame: Day 1, 21, and 56
Title
Biomarkers of hepatobiliary function: Alanine Aminotransferase (ALT)
Time Frame
Time Frame: Day 1, 21, and 56
Title
Biomarkers of hepatobiliary function: Gamma-Glutamyl Transpeptidase (GGT)
Time Frame
Time Frame: Day 1, 21, and 56
10. Eligibility
Sex
All
Minimum Age & Unit of Time
2 Years
Maximum Age & Unit of Time
17 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Key Inclusion Criteria:
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 Exclusion Criteria:
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Lynda Szczech, MD
Organizational Affiliation
Intercept Pharmaceuticals
Official's Role
Study Director
Facility Information:
Facility Name
Clinques University Saint-Luc
City
Brussel
ZIP/Postal Code
1200
Country
Belgium
Facility Name
CHU Lille
City
Lille
State/Province
ME
ZIP/Postal Code
59037
Country
France
Facility Name
Hopital de la Timone
City
Marseille
State/Province
Paca
ZIP/Postal Code
13385
Country
France
Facility Name
APHP- Hopital Necker Enfants Malades
City
Paris
ZIP/Postal Code
75015
Country
France
Facility Name
CHU de Toulouse Purpan-Hopital des Enfants
City
Toulouse
ZIP/Postal Code
31059
Country
France
Facility Name
Hannover Medical School, Children's Hospital, Paediatric Gastroenterology and Hepatology,
City
Hannover
State/Province
Lower Saxony
ZIP/Postal Code
30625
Country
Germany
Facility Name
Soroka University Medical Center
City
Beer Sheva
ZIP/Postal Code
84101
Country
Israel
Facility Name
Shaare-Zedek Medical Center
City
Jerusalem
ZIP/Postal Code
9103102
Country
Israel
Facility Name
Hadassah Medical Center
City
Jerusalem
ZIP/Postal Code
91120
Country
Israel
Facility Name
Schneider Children's Medical Center
City
Petach Tikva
ZIP/Postal Code
4920235
Country
Israel
Facility Name
Centre for Paediatric Hepatology
City
Bergamo
ZIP/Postal Code
24127
Country
Italy
Facility Name
Regina Margherita Children's Hospital
City
Turin
ZIP/Postal Code
10126
Country
Italy
Facility Name
University Medical Center Gröningen-Beatrix, children's Hospital
City
Groningen
ZIP/Postal Code
9713 GZ
Country
Netherlands
Facility Name
Instytut Pomnik-Centrum Zdrowia Dziecka
City
Warsaw
Country
Poland
Facility Name
Passeig Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Hospital Materno-Infantil de Malaga
City
Málaga
Country
Spain
Facility Name
Birmingham Children's Hospital
City
Birmingham
State/Province
West Midlands
ZIP/Postal Code
B4 6NH
Country
United Kingdom
12. IPD Sharing Statement
Learn more about this trial
Obeticholic Acid in Pediatric Subjects With Biliary Atresia
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