Evaluation of Maralixibat in Biliary Atresia Response Post-Kasai (EMBARK)

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

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).

Study Overview

• Status: Completed
• Conditions: Biliary Atresia
• Intervention / Treatment: Drug: Maralixibat; Other: Placebo

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.

• Study Type: Interventional
• Enrollment (Actual): 75
• Phase: Phase 2

Contacts and Locations

Study Locations

• China
  • Shanghai, China, 201102
    • Children's Hospital of Fudan University
  • Shanghai, China, 200062
    • Children's Hospital of Shanghai
  • Beijing
    • Beijing, Beijing, China, 100020
      • Beijing Pediatric Research Institute
  • Guangdong
    • Guangzhou, Guangdong, China, 510623
      • Guangzhou Women and Children's Medical Center
  • Zhejiang
    • Hanzhou, Zhejiang, China, 310058
      • The Children's Hospital, Zhejiang University School of Medicine
• Germany
  • Hanover, Germany
    • Hannover Medical School
• Poland
  • Warsaw, Poland
    • Instytut Pomnik-Centrum Zdrowia Dziecka
• Singapore
  • Bukit Timah, Singapore, 229899
    • KK Women's and Children's Hospital
• Taiwan
  • Taichung, Taiwan, 407
    • Taichung Veterans General Hospital
  • Taoyuan, Taiwan, 333
    • Linkou Chang Gung Memorial Hospital
• United Kingdom
  • Birmingham, United Kingdom, B4 6NH
    • Birmingham Children's Hospital
  • London, United Kingdom
    • King's College Hospital NHS
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Phoenix Children's Division of Gastroenterology & Hepatology
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Children's Healthcare of Atlanta - Emory University School of Medicine
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center
    • New York, New York, United States, 10016
      • NYU Grossman school of Medicine
    • New York, New York, United States, 10032
      • New York-Presbyterian - Columbia University Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Children's Hospital of Philadelphia
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
• Vietnam
  • Hanoi, Vietnam, 115000
    • Vietnam National Children's Hospital
  • Ho Chi Minh City, Vietnam, 740500
    • Children's Hospital No. 1
  • Thừa Thiên Huế
    • Huế, Thừa Thiên Huế, Vietnam
      • Hue Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 3 weeks to 3 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Male or female subjects with body weight ≥2500 g, who are ≥21 days old and <90 days old at the time of HPE (Kasai)
2. HPE or Kasai Procedure within 3 weeks prior to randomization
3. Clinical diagnosis of biliary atresia

Exclusion Criteria:

1. Subjects with intractable chronic diarrhea at randomization
2. Subjects not tolerating enteral feeds at randomization
3. History of ileal resection
4. Diagnosis of biliary atresia splenic malformation syndrome or cystic biliary atresia
5. Evidence of another non-biliary atresia pathology involving the intrahepatic bile duct (e.g., paucity, sclerosing cholangitis)
6. Evidence of liver failure (e.g. significant ascites)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Double Blind - Maralixibat; The double-blind period comprised of 4-8 weeks of dose escalation followed by 18 - 22 weeks of stable dosing treatment, after which participants were transferred to the open-label arm.	Drug: Maralixibat; A small molecule inhibitor of the ileal bile acid transporter (IBAT); Other Names: Formerly LUM001 and SHP625
Placebo Comparator: Double Blind - Placebo; The double-blind period comprised of 4-8 weeks of dose escalation followed by 18 - 22 weeks of stable dosing treatment, after which participants were transferred to the open-label arm.	Other: Placebo; Identical to maralixibat except for the active drug substance
Experimental: Open Label - Maralixibat; The Open-Label period comprised of 4-8 weeks of dose escalation followed by 70 - 74 weeks of stable dosing treatment. During the OLE, all participants, regardless of treatment assignment in the double-blind period, received maralixibat.	Drug: Maralixibat; A small molecule inhibitor of the ileal bile acid transporter (IBAT); Other Names: Formerly LUM001 and SHP625

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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 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		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

Collaborators and Investigators

• Sponsor: Mirum Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2021
• Primary Completion (Actual): November 7, 2023
• Study Completion (Actual): February 7, 2024

Study Registration Dates

• First Submitted: August 20, 2020
• First Submitted That Met QC Criteria: August 20, 2020
• First Posted (Actual): August 24, 2020

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 10, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Congenital Abnormalities; Biliary Atresia; Kasai; Bile Duct Diseases; Biliary Tract Diseases
• Additional Relevant MeSH Terms: Digestive System Diseases; Biliary Tract Diseases; Congenital Abnormalities; Bile Duct Diseases; Digestive System Abnormalities; Biliary Atresia
• Other Study ID Numbers: MRX-701

Drug and device information, study documents

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