Efficacy and Safety of Odevixibat in Children With Biliary Atresia Who Have Undergone a Kasai HPE (BOLD)

Study Overview
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Brief Summary
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Double-blind, randomized, placebo-controlled, Phase 3 study to investigate the efficacy and safety of odevixibat compared to placebo in children with biliary atresia who have undergone a Kasai hepatoportoenterostomy.

Detailed Description
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Up to 70 sites will be initiated for this study in North America, Europe, Middle East, and Asia Pacific.

Official Title
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A Double-Blind, Randomized, Placebo-Controlled Study to Evaluate the Efficacy and Safety of Odevixibat (A4250) in Children With Biliary Atresia Who Have Undergone a Kasai Hepatoportoenterostomy

Conditions
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Biliary Atresia

Intervention / Treatment
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* Drug: Odevixibat
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: A male or female patient with a clinical diagnosis of BA Age at Kasai HPE ≤90 days Eligible to start study treatment within 3 weeks post-Kasai HPE Key Exclusion Criteria: Patients with intractable ascites Ileal resection surgery ALT ≥10× upper limit of normal (ULN) at screening Patients reliant only on total parenteral nutrition, or not able to take study medication orally, at randomization Acute ascending cholangitis (patients may be randomized after resolution of acute ascending cholangitis) Choledochal cystic disease INR >1.6 (the patient may be treated with Vitamin K intravenously; sample may be redrawn and if INR is ≤1.6 at resampling the patient may be randomized) Any other conditions or abnormalities, including congenital abnormalities, major cardiac surgery, hepatic, biliary, or GI disease which, in the opinion of the Investigator or Medical Monitor, may compromise the safety of the patient, the integrity of study results, or patient compliance with study requirements Weight <3.5kg at randomization

Ages Eligible for Study
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Maximum Age: 111 Days

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


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 and selective inhibitor of IBAT.<br>|
| Placebo Comparator: Placebo<br>Capsules for oral administration (to match active) once daily for 104 weeks. | Drug: Placebo<br>* Placebo identical in appearance to experimental drug (odevixibat).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients with liver transplant | Proportion of patients who are alive and have not undergone a liver transplant after 104 weeks of study treatment. | From baseline to Week 104 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to onset of any sentinel events | Time to onset of any sentinel events | From baseline to Week 104 | 
| Time to pediatric end-stage liver disease (PELD) score >15 | Time to pediatric end-stage liver disease (PELD) score >15 | From baseline to Week 104 | 
| Total bilirubin levels | Total bilirubin level after 13, 26, 52, and 104 weeks of study treatment | From baseline to Weeks 13, 26, 52 and 104 | 
| Serum bile acid levels | Serum bile acid level after 13, 26, 52, and 104 weeks of study treatment | From baseline to Weeks 13, 26, 52 and 104 | 
| Percentage of participants experiencing Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. | From baseline to Week 104 | 
| Percentage of participants with clinically significant changes in Physical Examination | Percentage of participants with clinically significant changes in physical examination findings will be reported. The clinical significance will be graded by the investigator. | From baseline to Week 104 | 
| Percentage of participants with clinically significant changes in Laboratory Parameters (blood chemistry, hematology and coagulation) | Percentage of participants with clinically significant change in laboratory parameters (blood chemistry, hematology and coagulation) will be reported. The clinical significance will be decided by the investigator. | From baseline to Week 104 | 
| Percentage of participants with clinically significant changes in Abdominal Ultrasound findings | Percentage of participants with clinically significant change in Abdominal Ultrasound findings will be reported. The clinical significance will be decided by the investigator. | From baseline to Week 26 and Week 104 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kasai