Evaluation of Maralixibat in Biliary Atresia Response Post-Kasai

Study Overview
=================
Brief Summary
-----------------
A study to evaluate the efficacy and safety of maralixibat in infants with Biliary Atresia (BA) after Hepatoportoenterostomy (HPE, also known as the Kasai procedure).

Detailed Description
-----------------
This is a double-blind randomized, placebo-controlled study in subjects with Biliary Atresia with a primary endpoint at Week 26 followed by long-term open-label period during which all subjects will receive maralixibat to Week 104.

Official Title
-----------------
Randomized, Double-Blind, Placebo-Controlled Phase 2 Study to Evaluate the Efficacy and Safety of Maralixibat in the Treatment of Subjects With Biliary Atresia After Hepatoportoenterostomy

Conditions
-----------------
Biliary Atresia

Intervention / Treatment
-----------------
* Drug: Maralixibat
* Other: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male or female subjects with body weight ≥2500 g, who are ≥21 days old and <90 days old at the time of HPE (Kasai) HPE or Kasai Procedure within 3 weeks prior to randomization Clinical diagnosis of biliary atresia Exclusion Criteria: Subjects with intractable chronic diarrhea at randomization Subjects not tolerating enteral feeds at randomization History of ileal resection Diagnosis of biliary atresia splenic malformation syndrome or cystic biliary atresia Evidence of another non-biliary atresia pathology involving the intrahepatic bile duct (e.g., paucity, sclerosing cholangitis) Evidence of liver failure (e.g. significant ascites)

Ages Eligible for Study
-----------------
Minimum Age: 21 Days
Maximum Age: 111 Days

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maralixibat<br>Maralixibat chloride oral solution administered twice daily, up to 600* microgram per kilogram, for 26 weeks and in the OLE for all patients. *equivalent to 570 mcg/kg/day maralixibat free base | Drug: Maralixibat<br>* A small molecule inhibitor of the ileal bile acid transporter (IBAT)<br>* Other names: Formerly LUM001 and SHP625;|
| Placebo Comparator: Placebo<br>Placebo oral solution for 26 weeks. All placebo participants who complete Week 26 and continue in the open label extension (OLE) will receive maralixibat after Week 26. | Other: Placebo<br>* Identical to maralixibat except for the active drug substance<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in total serum bilirubin levels |  | From baseline to Week 26 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean change in total serum bile acids |  | From baseline to Week 26 | 
| Proportion of participants with mean TSB levels <2 mg/dL through Week 26 |  | From baseline to Week 26 | 
| Proportion of participants observed to have a liver-related clinical event, including liver transplantation, liver decompensation, discontinuations due to liver related events, or death. | Liver decompensation (hepatic encephalopathy, variceal bleeding, new persistent ascites) | From Baseline to Week 26 | 
| Proportion of participants undergoing liver transplantation or death through Week 26 |  | From Baseline to Week 26 | 
| Proportion of participants observed to develop clinically evident portal hypertension defined as splenomegaly and thrombocytopenia (platelet count <150 x 109/L) or clinically evident ascites or endoscopic evidence of esophageal or gastric varices. | Splenomegaly => (spleen size >2 cm below the costal margin palpated on physical examination) | From Baseline to Week 26 | 
| Proportion of participants with mean TSB levels ≤1.2 mg/dL |  | From Baseline to Week 26 | 
| Proportion of participants with mean sBA levels ≤40 mmol/L |  | From Baseline to Week 26 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Biliary Atresia, Kasai, Bile Duct Diseases, Biliary Tract Diseases, Congenital Abnormalities