Long-Term SafEty and Clinical Outcomes of LivmArli in Patients in the United States (LEAP-US) (LEAP)

May 21, 2025 updated by: Mirum Pharmaceuticals, Inc.
The objective of this 5-year, prospective, observational cohort study is to evaluate the long-term safety and clinical outcomes of patients with Alagille syndrome (ALGS) or Progressive familial intrahepatic cholestasis (PFIC) treated with Livmarli.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Livmarli® is a novel, minimally absorbed, pharmacological product that inhibits the ileal bile acid transporter (IBAT) in the terminal ileum, leading to reduced levels of bile acids. Livmarli (maralixibat) has been developed by Mirum Pharmaceuticals and was the first treatment approved by the US Food and Drug Administration (FDA) for the treatment of cholestatic pruritus in patients 3 months of age and older with Alagille syndrome (ALGS). Subsequently, Livmarli was approved by the FDA for the treatment of cholestatic pruritus in patients 12 months of age and older with Progressive familial intrahepatic cholestasis (PFIC). To be eligible for the study, participants must meet the following criteria:

  • A clinically and/or genetically confirmed ALGS diagnosis or PFIC diagnosis
  • Prescribed Livmarli

Study Type

Observational

Enrollment (Estimated)

70

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 Locations

  • United States
    • California
      • Los Angeles, California, United States, 90027
        • Recruiting
        • Children's Hospital Los Angeles CHLA
        • Contact:
        • Contact:
          • George Yanni
        • Principal Investigator:
          • Chuan-Hao Lin
    • Colorado
      • Aurora, Colorado, United States, 80045
        • Recruiting
        • Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children's Hospital of Colorado and University of Colorado
        • Contact:
        • Principal Investigator:
          • Shikha S. Sundaram
    • Georgia
      • Atlanta, Georgia, United States, 30322
        • Recruiting
        • Children's Healthcare of Atlanta - Emory University School of Medicine
        • Contact:
        • Principal Investigator:
          • Chrissy Lopez
    • Missouri
      • Kansas City, Missouri, United States, 64108
        • Recruiting
        • Children's Mercy Kansas City, Department of Gastroenterology, Section of Hepatology
        • Contact:
        • Principal Investigator:
          • Ryan T. Fischer
    • Oregon
      • Portland, Oregon, United States, 97239
        • Recruiting
        • Oregon Health and Science University, Division of Pediatric Gastroenterology, Department of Pediatrics
        • Contact:
        • Principal Investigator:
          • Henry C. Lin
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19104
        • Recruiting
        • Children's Hospital of Philadelphia
        • Contact:
        • Principal Investigator:
          • Kathleen Loomes, MD
      • Pittsburgh, Pennsylvania, United States, 15260
        • Recruiting
        • Children Hospital of Pittsburgh
        • Contact:
        • Contact:
          • James E. Squires
        • Principal Investigator:
          • Simon Horslen
    • Utah
      • Salt Lake City, Utah, United States, 84112
        • Recruiting
        • University of Utah, Division of Pediatric Gastroenterology, Hepatology and Nutrition
        • Contact:
        • Principal Investigator:
          • M. Kyle Jensen

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

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Sampling Method

Non-Probability Sample

Study Population

All patients with ALGS and PFIC prescribed Livmarli at a participating study center and who consent/assent to participation (if required by the local IRB/IEC) will be included in the study at the discretion of the center investigator.

Description

Inclusion Criteria:

  • A clinically and/or genetically confirmed ALGS diagnosis or PFIC diagnosis
  • Participant prescribed Livmarli

Exclusion Criteria:

  • Refusal to provide informed consent/assent (if required by the local IRB)
  • Previously or currently on Livmarli through participation in a clinical study or expanded access program
  • Participants who have previously received an SBD or LT
  • Any condition or abnormalities that, in the opinion of the investigator, may interfere with the participant participating in or completing the study
  • Participants who have received an investigational drug within 30 days of the first dose of Livmarli

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

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Alagille syndrome (ALGS)
  • A clinically and/or genetically confirmed ALGS diagnosis
  • Participant prescribed Livmarli
Drug: Livmarli
The recommended dosage is 380 mcg/kg once daily.
Other Names:
  • Maralixibat
Drug: Livmarli
The recommended dosage us 570 mcg/kg twice daily.
Other Names:
  • Maralixibat
Progressive familial intrahepatic cholestasis (PFIC)
  • A clinically and/or genetically confirmed PFIC diagnosis
  • Prescribed Livmarli
Drug: Livmarli
The recommended dosage is 380 mcg/kg once daily.
Other Names:
  • Maralixibat
Drug: Livmarli
The recommended dosage us 570 mcg/kg twice daily.
Other Names:
  • Maralixibat

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Incidence of Long-Term Clinical Outcomes
Time Frame: Long-term clinical outcomes (SBD, LT, portal hypertension, all-cause mortality) up to 180 days after discontinuation of Livmarli will be recorded.
The dates, and reasons for the following first events (of this first endpoint) will be collected: Surgical Biliary Diversion (SBD), Liver Transplant (LT), and all-cause mortality. In addition, manifestations of clinically evident portal hypertension (CEPH) will be captured during each interval event assessments.
Long-term clinical outcomes (SBD, LT, portal hypertension, all-cause mortality) up to 180 days after discontinuation of Livmarli will be recorded.
Liver Transplant Indication and Waitlist Status
Time Frame: LT waitlist status will be collected at enrollment and every 6 months for 5 years.
LT waitlist status will be collected, including when placed on or removed from LT waitlist.
LT waitlist status will be collected at enrollment and every 6 months for 5 years.
Assessment of Growth and Development
Time Frame: Weight (kilograms) and height (centimeters) z-scores will be collected every year for 5 years.

Height and weight will be collected both at the time the participant started Livmarli and at the time of enrollment in the study. Subsequent weight will be collected for up to 5 years.

Weight z-score (kilograms) and height z-score (centimeters) will be assessed and reported every year for 5 years.
Weight (kilograms) and height (centimeters) z-scores will be collected every year for 5 years.
Incidence of Clinical Events Potentially Related to Fat-Soluble Vitamin Deficiencies and Their Long-Term Sequelae
Time Frame: The incidence of events will be assessed and reported every year for 5 years.
Bleeding events (including all gastrointestinal [GI] or non-GI bleeding requiring hospitalization, emergency department care, or transfusion) and fracture events will be reported.
The incidence of events will be assessed and reported every year for 5 years.

Collaborators and Investigators

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

Sponsor

Mirum Pharmaceuticals, Inc.

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

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)

September 21, 2023

Primary Completion (Estimated)

September 20, 2028

Study Completion (Estimated)

September 20, 2030

Study Registration Dates

First Submitted

December 11, 2023

First Submitted That Met QC Criteria

December 21, 2023

First Posted (Actual)

January 5, 2024

Study Record Updates

Last Update Posted (Actual)

May 25, 2025

Last Update Submitted That Met QC Criteria

May 21, 2025

Last Verified

May 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • MRX-310

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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