Long-Term Low-Intervention SafEty and Clinical Outcomes Clinical Study of LivmArli® in Patients With Alagille Syndrome or Progressive Familial Intrahepatic Cholestasis in the European Union (LEAP-EU)

NCT07290257 | Recruiting Phase 4

• 1 other identifier: MRX-803
• Study Type: interventional
• Target: 230
• Locations: 8 countries
• Sites: 15

Brief Summary

In patients with Alagille syndrome (ALGS), the key objectives are to evaluate the tolerability, long-term safety (including possible liver toxicity) and long-term efficacy of Livmarli treatment. In patients with Progressive Familial Intrahepatic Cholestasis (PFIC), the key objectives are to evaluate tolerability, long-term safety (including possible liver toxicity and potential impact of chronic exposure to propylene glycol (PG)), long-term efficacy, and growth and development.

Conditions

Alagille Syndrome; Progressive Familial Intrahepatic Cholestasis

Keywords

ALGS; Liver Diseases; Alagille Syndrome; Livmarli; Maralixibat; Cholestasis; Pruritus; Itching; IBAT inhibitor; PFIC

Outcome Measures

Primary Outcomes (7)

• Adverse Events (AEs)

  Number and proportion of participants with AEs.

  Up to 7 days after the last dose of Livmarli.

• Liver function tests (LFTs) - measuring enzyme activity or concentration

  Change in LFTs from Baseline: Total and direct bilirubin

  Once every 3-4 months, for 5 years.

• Liver function tests (LFTs) - measuring enzyme activity or concentration

  Change in LFTs from Baseline: Aminotransferases and GGT.

  Once every 3-4 months, for 5 years.

• Fat-Soluble Vitamins (FSV) Concentration

  Change in FSV levels (vitamins A, D, and E) from Baseline.

  Once every 3-4 months, for 5 years.

• International Normalized Ratio (INR)

  Change in INR level from Baseline.

  Once every 3-4 months, for 5 years.

• Long-Term Clinical Outcomes

  Number of participants with surgical biliary diversion, liver transplantation, liver transplant waitlist status change, clinically evident portal hypertension, complications of liver cirrhosis, liver carcinoma, liver decompensation, and death.

  Once every 3-4 months, for 5 years.

• Laboratory Test for Monitoring of Propylene Glycol Toxicity in Participants with PFIC

  Change in PG level from Baseline.

  Once every 3-4 months, for 5 years.

Study Arms (1)

Livmarli

EXPERIMENTAL

ALGS: Primary cohort with a minimum of 45 previously untreated (treatment naïve). Supplemental cohort of participants who have previously received Livmarli. PFIC: Patients with Progressive Familial Intrahepatic Cholestasis treated with Livmarli. The study will enroll a minimum of 130 patients with PFIC

Drug: Livmarli Oral Product

Interventions

Livmarli Oral Product DRUG

Participants will be treated according to standard of care for the duration of the study and Schedule of Assessments.

Also known as: Maralixibat

Livmarli

Eligibility Criteria

• Age: 2 Months+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Understand and execute an Informed consent and assent (as applicable)
• For participants with ALGS ≥2 months of age at Day 1
• For participants with PFIC, ≥3 months of age at Day 1
• A clinically and/or genetically confirmed ALGS diagnosis with pruritus secondary to chronic cholestasis, or a clinically and/or genetically confirmed PFIC diagnosis
• For the ALGS primary cohort: Initiation of Livmarli at the time of study entry
• For the ALGS supplemental cohort, : Actively using Livmarli prior to study entry
• For participants with PFIC: Prescribed Livmarli at the time of study entry or prior to study entry

You may not qualify if:

• History of Liver Transplant
• Any Livmarli contraindications (as per SmPC)
• Any condition or abnormality that, in the opinion of the investigator, may interfere with the participation in or completion of the study
• Received an investigational drug within 30 days before the first dose of Livmarli (Participation in previous maralixibat studies or expanded-access programs is acceptable.)
• Received another IBAT inhibitor within 7 days before the first dose of Livmarli
• Baseline data before start of treatment of Livmarli are unavailable (\<2 values before treatment) for key safety (LFTs, FSV laboratory results) and key efficacy (sBA, pruritus) parameter

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (15)

Cliniques Universitaires Saint Luc (UCLouvain)

Brussels, 1200, Belgium

RECRUITING

University Hospital Gent (UZ Gent)

Ghent, 9000, Belgium

RECRUITING

Hospices Civils de Lyon - Hopital Femme Mère Enfant

Bron, Auvergne-Rhône-Alpes, 69500, France

RECRUITING

CHU de Toulouse - Hôpital des Enfants

Toulouse, Occitanie, 31049, France

RECRUITING

Bicetre University Hospital

Le Kremlin-Bicêtre, Île-de-France Region, 94270, France

RECRUITING

Charite Berlin

Berlin, 13353, Germany

RECRUITING

Children's University Hospital Essen

Essen, 45149, Germany

RECRUITING

University Hospital Hamburg-Eppendorf

Hamburg, 20246, Germany

RECRUITING

2nd Paediatric Clinic P &A Kyriakou Children's Hospital

Athens, 11527, Greece

NOT YET RECRUITING

AO Ospedale PAPA GIOVANNI XXIII

Bergamo, Lombardy, 24126, Italy

RECRUITING

Istituto mediterraneo trapianti - ISMETT

Palermo, Sicily, 90127, Italy

RECRUITING

University Medical Center Groningen (UMCG)

Groningen, 9713GZ, Netherlands

RECRUITING

Unidade Local de Saude de Coimbra Paediatric Department Avenida Afonso Romăo

Coimbra, 3000-602, Portugal

NOT YET RECRUITING

Hospital Universitairo Vall D'Hebron

Barcelona, Catalonia, 08035, Spain

RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

RECRUITING

MeSH Terms

Conditions

Alagille Syndrome; Cholestasis, progressive familial intrahepatic 1; Liver Diseases; Cholestasis; Pruritus

Interventions

maralixibat

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn; Skin Diseases; Skin and Connective Tissue Diseases; Skin Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Central Study Contacts

Clinical Trials Mirum

CONTACT

+16506674085; clinicaltrials@mirumpharma.com

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: OTHER
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: This is a single-group, open-label study enrolling participants with ALGS and PFIC treated with Livmarli. For ALGS, the primary cohort will include at least 45 treatment-naïve participants. A supplemental ALGS cohort will include participants previously treated with Livmarli, with no enrollment limit. For PFIC, the study will enroll at least 130 participants across PFIC subtypes, and all participants enrolled for at least 1 year will be included in the interim analysis.

Study Record Dates

• First Submitted: September 17, 2025
• First Posted: December 18, 2025
• Study Start: September 25, 2025
• Primary Completion (Estimated): September 22, 2030
• Study Completion (Estimated): December 22, 2030
• Last Updated: June 23, 2026

Record last verified: 2026-06

Locations

NL (1); BE (2); GR (1); PT (1); ES (2); FR (3); DE (3); IT (2)