An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of Odevixibat in Children With Biliary Atresia (BOLD-EXT)
Primary Purpose
Biliary Atresia
Status
Enrolling by invitation
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Odevixibat
Sponsored by
About this trial
This is an interventional treatment trial for Biliary Atresia
Eligibility Criteria
Inclusion Criteria:
- Completion of the 104-week Treatment Period of Study A4250-011
- Signed informed consent by caregiver
Exclusion Criteria:
- Patients who were not compliant with study drug treatment or procedures in Study A4250-011 as per the investigator's discretion
- Any conditions or abnormalities which, in the opinion of the investigator, may compromise the safety of the patient, or interfere with the patient participating in or completing the study
- Known hypersensitivity to any components of odevixibat
- Patients who are scheduled for a liver transplant or are likely to require a liver transplant in the immediate future based on the investigator's judgment
Sites / Locations
- Children's Hospital Colorado
- Children's Healhcare of Atlanta- Emory University school of medicine
- Indiana University school of Medicine
- Boston Children's Hospital
- The Childrens Hospital at Montefiore Albert Einstein School of Medicine
- Hassenfeld Children's Hospital at NYU Langone
- Columbia University Medical Center New York Presbyterian Morgan Stanley-Komansky Childrens Hospital
- UPMC Children's Hospital of Pittsburgh
- Seattle Children's Hospital
- Royal Children's Hospital
- CHU Sainte-Justine
- The Hospital for Sick Children
- Bicêtre Hospital
- Charité - Universitätsmedizin Berlin
- University Children´s Hospital Tuebingen
- ASST Papa Giovanni XXIII
- University Malaya Medical Centre
- University Medical Center Groningen
- Starship Child Health, Te Whatu Ora - Health New Zealand
- Instytut Pomnik-Centrum Zdrowia Dziecka
- Hospital Universitari Vall d'Hebron
- Akdeniz University Medical Faculty
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Odevixibat (A4250)
Arm Description
Capsules for oral administration once daily for 104 weeks.
Outcomes
Primary Outcome Measures
Proportion of patients who are alive and have not undergone liver transplant
Secondary Outcome Measures
Change in aspartate aminotransferase (AST) to platelet ratio index (APRI) score
The APRI (aspartate aminotransferase to platelet ratio index) score estimates the severity of liver fibrosis. A higher score indicates a greater amount of scarring (fibrosis) in the liver.
A score ≤ 0.5 indicates a low likelihood of fibrosis
A score ≥ 1.5 indicates a higher probability of fibrosis
Change in Fibrosis-4 (Fib-4) score
The Fib-4 score provides an estimate of the amount of scarring (fibrosis) in the liver. A higher score indicates a greater amount of scarring in the liver.
A score < 1.45 indicates a low likelihood of fibrosis
A score > 3.25 indicates a higher probability of fibrosis
Change in serum bile acids
Change in height
Change in weight
Change in mid-arm circumference
Measure of growth
Time to onset of any sentinel events
Change in pediatric end-stage liver disease (PELD) score
The PELD (pediatric end-stage liver disease) score is a measure of disease severity. PELD scores can range from a negative value (such as -10) to high numbers (such as 45). A higher score indicates more severe disease.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT05426733
Brief Title
An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of Odevixibat in Children With Biliary Atresia
Acronym
BOLD-EXT
Official Title
An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of Odevixibat (A4250) in Children With Biliary Atresia (BOLD-EXT)
Study Type
Interventional
2. Study Status
Record Verification Date
February 2023
Overall Recruitment Status
Enrolling by invitation
Study Start Date
July 5, 2022 (Actual)
Primary Completion Date
December 31, 2024 (Anticipated)
Study Completion Date
December 31, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Albireo
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of Odevixibat (A4250) in Children with Biliary Atresia
Detailed Description
This is a Phase 3, multi-center, open-label extension study to evaluate the long-term efficacy and safety of odevixibat in patients with Biliary Atresia (BA). Patients who completed treatment in the A4250-011 BOLD study and meet eligibility criteria for Study A4250-016 (BOLD-EXT) can participate. The duration of the treatment period is 104 weeks, followed by a 4-week Safety Follow-up Period. Patients who wish to continue receiving odevixibat after 104 weeks can remain on treatment in the optional extension period (OEP).
Up to 180 patients will be enrolled at approximately 70 sites in the North America, Europe, the Middle East and Asia-Pacific.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Biliary Atresia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
180 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Odevixibat (A4250)
Arm Type
Experimental
Arm Description
Capsules for oral administration once daily for 104 weeks.
Intervention Type
Drug
Intervention Name(s)
Odevixibat
Other Intervention Name(s)
A4250
Intervention Description
Odevixibat is a small molecule inhibitor of the ileal bile acid transporter (IBAT).
Primary Outcome Measure Information:
Title
Proportion of patients who are alive and have not undergone liver transplant
Time Frame
From baseline to Week 104
Secondary Outcome Measure Information:
Title
Change in aspartate aminotransferase (AST) to platelet ratio index (APRI) score
Description
The APRI (aspartate aminotransferase to platelet ratio index) score estimates the severity of liver fibrosis. A higher score indicates a greater amount of scarring (fibrosis) in the liver.
A score ≤ 0.5 indicates a low likelihood of fibrosis
A score ≥ 1.5 indicates a higher probability of fibrosis
Time Frame
From baseline to Week 104
Title
Change in Fibrosis-4 (Fib-4) score
Description
The Fib-4 score provides an estimate of the amount of scarring (fibrosis) in the liver. A higher score indicates a greater amount of scarring in the liver.
A score < 1.45 indicates a low likelihood of fibrosis
A score > 3.25 indicates a higher probability of fibrosis
Time Frame
From baseline to Week 104
Title
Change in serum bile acids
Time Frame
From Baseline to Weeks 26, 52, 78, and 104
Title
Change in height
Time Frame
From Baseline to Weeks 26, 52, 78 and 104
Title
Change in weight
Time Frame
From Baseline to Weeks 26, 52, 78 and 104
Title
Change in mid-arm circumference
Description
Measure of growth
Time Frame
From Baseline to Weeks 26, 52, 78 and 104
Title
Time to onset of any sentinel events
Time Frame
From Baseline to Week 104
Title
Change in pediatric end-stage liver disease (PELD) score
Description
The PELD (pediatric end-stage liver disease) score is a measure of disease severity. PELD scores can range from a negative value (such as -10) to high numbers (such as 45). A higher score indicates more severe disease.
Time Frame
From Baseline to Weeks 26, 52, 78 and 104
10. Eligibility
Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Completion of the 104-week Treatment Period of Study A4250-011
Signed informed consent by caregiver
Exclusion Criteria:
Patients who were not compliant with study drug treatment or procedures in Study A4250-011 as per the investigator's discretion
Any conditions or abnormalities which, in the opinion of the investigator, may compromise the safety of the patient, or interfere with the patient participating in or completing the study
Known hypersensitivity to any components of odevixibat
Patients who are scheduled for a liver transplant or are likely to require a liver transplant in the immediate future based on the investigator's judgment
Facility Information:
Facility Name
Children's Hospital Colorado
City
Aurora
State/Province
Colorado
ZIP/Postal Code
80045
Country
United States
Facility Name
Children's Healhcare of Atlanta- Emory University school of medicine
City
Atlanta
State/Province
Georgia
ZIP/Postal Code
30322
Country
United States
Facility Name
Indiana University school of Medicine
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
Boston Children's Hospital
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
The Childrens Hospital at Montefiore Albert Einstein School of Medicine
City
Bronx
State/Province
New York
ZIP/Postal Code
10467
Country
United States
Facility Name
Hassenfeld Children's Hospital at NYU Langone
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Columbia University Medical Center New York Presbyterian Morgan Stanley-Komansky Childrens Hospital
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
UPMC Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Royal Children's Hospital
City
Parkville
ZIP/Postal Code
3052
Country
Australia
Facility Name
CHU Sainte-Justine
City
Montréal
Country
Canada
Facility Name
The Hospital for Sick Children
City
Toronto
Country
Canada
Facility Name
Bicêtre Hospital
City
Le Kremlin-Bicêtre
Country
France
Facility Name
Charité - Universitätsmedizin Berlin
City
Berlin
Country
Germany
Facility Name
University Children´s Hospital Tuebingen
City
Tuebingen
Country
Germany
Facility Name
ASST Papa Giovanni XXIII
City
Bergamo
Country
Italy
Facility Name
University Malaya Medical Centre
City
Kuala Lumpur
ZIP/Postal Code
59100
Country
Malaysia
Facility Name
University Medical Center Groningen
City
Groningen
Country
Netherlands
Facility Name
Starship Child Health, Te Whatu Ora - Health New Zealand
City
Auckland
ZIP/Postal Code
1023
Country
New Zealand
Facility Name
Instytut Pomnik-Centrum Zdrowia Dziecka
City
Warsaw
Country
Poland
Facility Name
Hospital Universitari Vall d'Hebron
City
Barcelona
Country
Spain
Facility Name
Akdeniz University Medical Faculty
City
Antalya
Country
Turkey
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of Odevixibat in Children With Biliary Atresia
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