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

Recruiting

• Conditions: Alagille Syndrome; Progressive Familial Intrahepatic Cholestasis
• Interventions: Drug: Livmarli

• Registration Number: NCT06193928
• Lead Sponsor: Mirum Pharmaceuticals, Inc.

Brief Summary

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.

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 Timeline

• Study Start: 2023-09-21
• Study First Submitted: 2023-12-11
• Study First Submitted QC: 2023-12-21
• Study First Posted: 2024-01-05
• Status Verified: 2025-05
• Last Update Submitted: 2025-05-21
• Last Update Posted: 2025-05-25
• Primary Completion: 2028-09-20
• Study Completion: 2030-09-20

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 70

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 & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Alagille syndrome (ALGS)	Livmarli	* A clinically and/or genetically confirmed ALGS diagnosis * Participant prescribed Livmarli
Progressive familial intrahepatic cholestasis (PFIC)	Livmarli	* A clinically and/or genetically confirmed PFIC diagnosis * Prescribed Livmarli

Primary Outcome Measures

Name	Time	Method
Incidence of Long-Term Clinical Outcomes	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.
Liver Transplant Indication and Waitlist Status	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.
Assessment of Growth and Development	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.
Incidence of Clinical Events Potentially Related to Fat-Soluble Vitamin Deficiencies and Their Long-Term Sequelae	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.

Trial Locations

Locations (8)

Children's Hospital Los Angeles CHLA; 🇺🇸 Los Angeles, California, United States

Section of Gastroenterology, Hepatology and Nutrition, Department of Pediatrics and the Digestive Health Institute, Children's Hospital of Colorado and University of Colorado; 🇺🇸 Aurora, Colorado, United States

Children's Healthcare of Atlanta - Emory University School of Medicine; 🇺🇸 Atlanta, Georgia, United States

Children's Mercy Kansas City, Department of Gastroenterology, Section of Hepatology; 🇺🇸 Kansas City, Missouri, United States

Oregon Health and Science University, Division of Pediatric Gastroenterology, Department of Pediatrics; 🇺🇸 Portland, Oregon, United States

Children's Hospital of Philadelphia; 🇺🇸 Philadelphia, Pennsylvania, United States

Children Hospital of Pittsburgh; 🇺🇸 Pittsburgh, Pennsylvania, United States

University of Utah, Division of Pediatric Gastroenterology, Hepatology and Nutrition; 🇺🇸 Salt Lake City, Utah, United States