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

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

Detailed Description
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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.

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

Conditions
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Biliary Atresia

Intervention / Treatment
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* Drug: Odevixibat


Participation Criteria
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Eligibility Criteria
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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
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

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

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 |