An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of Odevixibat in Children With Biliary Atresia (BOLD-EXT)

An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of Odevixibat (A4250) in Children With Biliary Atresia (BOLD-EXT)

An Open-label Extension Study to Evaluate Long-term Efficacy and Safety of Odevixibat (A4250) in Children with Biliary Atresia

Study Overview

• Status: Enrolling by invitation
• Conditions: Biliary Atresia
• Intervention / Treatment: Drug: Odevixibat

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.

• Study Type: Interventional
• Enrollment (Estimated): 180
• Phase: Phase 3

Contacts and Locations

Study Locations

• Australia
  • Parkville, Australia, 3052
    • Royal Children's Hospital
• Canada
  • Montréal, Canada
    • CHU Sainte-Justine
  • Toronto, Canada
    • The Hospital for Sick Children
• France
  • Le Kremlin-Bicêtre, France
    • Bicetre Hospital
• Germany
  • Berlin, Germany
    • Charité - Universitätsmedizin Berlin
  • Tuebingen, Germany
    • University Children´s Hospital Tuebingen
• Italy
  • Bergamo, Italy
    • ASST Papa Giovanni XXIII
• Malaysia
  • Kuala Lumpur, Malaysia, 59100
    • University Malaya Medical Centre
• Netherlands
  • Groningen, Netherlands
    • University Medical Center Groningen
• New Zealand
  • Auckland, New Zealand, 1023
    • Starship Child Health, Te Whatu Ora - Health New Zealand
• Poland
  • Warsaw, Poland
    • Instytut Pomnik-Centrum Zdrowia Dziecka
• Spain
  • Barcelona, Spain
    • Hospital Universitari Vall d'Hebron
• Turkey
  • Ankara, Turkey
    • Hacettepe İhsan Doğramacı Children's Hospital
  • Antalya, Turkey
    • Akdeniz University Medical Faculty
  • Istanbul, Turkey
    • Istanbul University Istanbul Medical Faculty Hospital
• United States
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healhcare of Atlanta- Emory University school of medicine
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University School of Medicine
  • Massachusetts
    • Boston, Massachusetts, United States, 02115
      • Boston Children's Hospital
  • New York
    • Bronx, New York, United States, 10467
      • The Childrens Hospital at Montefiore Albert Einstein School of Medicine
    • New York, New York, United States, 10016
      • Hassenfeld Children's Hospital at NYU Langone
    • New York, New York, United States, 10032
      • Columbia University Medical Center New York Presbyterian Morgan Stanley-Komansky Childrens Hospital
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • UPMC Children's Hospital of Pittsburgh
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Odevixibat (A4250); Capsules for oral administration once daily for 104 weeks.	Drug: Odevixibat; Odevixibat is a small molecule inhibitor of the ileal bile acid transporter (IBAT).; Other Names: A4250

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of patients who are alive and have not undergone liver transplant	From baseline to Week 104

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	From baseline to Week 104
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	From baseline to Week 104
Change in serum bile acids		From Baseline to Weeks 26, 52, 78, and 104
Change in height		From Baseline to Weeks 26, 52, 78 and 104
Change in weight		From Baseline to Weeks 26, 52, 78 and 104
Change in mid-arm circumference	Measure of growth	From Baseline to Weeks 26, 52, 78 and 104
Time to onset of any sentinel events		From Baseline to Week 104
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.	From Baseline to Weeks 26, 52, 78 and 104

Collaborators and Investigators

• Sponsor: Albireo

Study record dates

Study Major Dates

• Study Start (Actual): July 5, 2022
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 13, 2022
• First Submitted That Met QC Criteria: June 16, 2022
• First Posted (Actual): June 22, 2022

Study Record Updates

• Last Update Posted (Actual): March 28, 2024
• Last Update Submitted That Met QC Criteria: March 27, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Congenital Abnormalities; Biliary Tract Diseases; Bile Duct Diseases; Digestive System Abnormalities; Biliary Atresia
• Other Study ID Numbers: A4250-016

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No