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

March 7, 2024 updated by: Mirum Pharmaceuticals, Inc.

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

Intervention / Treatment

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

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

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
        • Huế Central Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

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

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Maralixibat

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
A small molecule inhibitor of the ileal bile acid transporter (IBAT)
Other Names:
  • Formerly LUM001 and SHP625
Placebo Comparator: Placebo
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
Identical to maralixibat except for the active drug substance

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Mean change in total serum bile acids
Time Frame: From baseline to Week 26
From baseline to Week 26
Proportion of participants with mean TSB levels <2 mg/dL through Week 26
Time Frame: From baseline to 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.
Time Frame: From Baseline to Week 26
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
Time Frame: From Baseline to 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.
Time Frame: From Baseline to Week 26
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
Time Frame: From Baseline to Week 26
From Baseline to Week 26
Proportion of participants with mean sBA levels ≤40 mmol/L
Time Frame: From Baseline to Week 26
From Baseline to Week 26

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mirum Pharmaceuticals, Inc.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

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 8, 2024

Last Update Submitted That Met QC Criteria

March 7, 2024

Last Verified

March 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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