Long-Term Safety and Clinical Outcomes of Livmarli in Patients With Alagille Syndrome (LEAP)

Alagille Syndrome Clinical Trial

— LEAP  

Official title:

Long-Term Safety and Clinical Outcomes of Livmarli in Patients With Alagille Syndrome (LEAP)

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06193928
• Other study ID #: MRX-310
• Status: Recruiting
• Start date: September 21, 2023
• Est. completion date: September 20, 2028

Study information

• Verified date: March 2024
• Source: Mirum Pharmaceuticals, Inc.
• Contact: Clinical Trials Mirum
• Phone: +16506674085
• Email: Clinical Trials [@]mirumpharma.com>;
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

The goal of this observational study is to evaluate the long-term safety and clinical outcomes of Livmarli prescribed to patients with Alagille Syndrome (ALGS).

Description:

Livmarli® is a novel, minimally absorbed, pharmacological treatment for the treatment of cholestatic pruritus in patients with Alagille syndrome (ALGS), a rare, genetic, autosomal dominant, complex multisystem disorder characterized by the presence of cholestasis (typically presenting as jaundice in the neonatal period) due to intrahepatic bile duct paucity. Livmarli inhibits the ileal bile acid transporter (IBAT) in the terminal ileum, leading to reduced levels of bile acids, thereby improving clinical manifestations and symptoms of cholestasis. Livmarli has been developed by Mirum Pharmaceuticals and approved by the US Food and Drug Administration (FDA) for the treatment of cholestatic pruritus in patients with ALGS who are 3 months of age and older.

To be eligible for the study, participants must meet the following criteria:

• A clinically and/or genetically confirmed ALGS diagnosis

• Participant prescribed Livmarli

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 50
• Est. completion date: September 20, 2028
• Est. primary completion date: September 20, 2028
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A and older

Eligibility

Inclusion Criteria:

• A clinically and/or genetically confirmed ALGS 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

Related Conditions & MeSH terms

• Alagille Syndrome
• Syndrome

Intervention

Drug:
• Maralixibat
The recommended dosage is 380 mcg/kg once daily.

Locations

Country	Name	City	State
United States	Children's Healthcare of Atlanta - Emory University School of Medicine	Atlanta	Georgia
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 Mercy Kansas City, Department of Gastroenterology, Section of Hepatology	Kansas City	Missouri
United States	Children's Hospital Los Angeles CHLA	Los Angeles	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University, Division of Pediatric Gastroenterology, Department of Pediatrics	Portland	Oregon
United States	University of Utah, Division of Pediatric Gastroenterology, Hepatology and Nutrition	Salt Lake City	Utah

Sponsors (1)

Lead Sponsor	Collaborator
Mirum Pharmaceuticals, Inc.

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Long-term clinical outcome events	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 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.
Primary	Liver Transplant Waitlist Status	LT waitlist status will be collected, including when placed on or removed from an LT waitlist.	LT waitlist status will be collected at enrollment and every 6 months for 5 years.
Primary	Assessment of Height	Height will be collected both at the time the participant started Livmarli and at the time of enrollment in the study. Subsequent height will be collected for up to 5 years.; Height z-score (centimeters) will be assessed and reported every year for 5 years.	Height z-score (centimeters) will be collected every year for 5 years.
Primary	Assessment of Weight	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) will be assessed and reported every year for 5 years.	Weight z-score (kilograms) will be collected every year for 5 years.
Primary	Incidence of Clinical Events Potentially Related to Fat-Soluble Vitamin Deficiencies	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.

External Links

•   Genetics Home Reference - ALGS
•   Mirum Pharmaceuticals homepage
•   US FDA Resources