A Study to Evaluate the Safety and Tolerability of Maralixibat in Infant Participants With Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille Syndrome (ALGS). (RISE)

Open-Label, Phase 2 Study to Evaluate the Safety and Tolerability of Maralixibat in the Treatment of Infants With Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis and Alagille Syndrome

This study is designed to assess whether the investigational drug maralixibat, is safe and well tolerated in children <12 months of age with Alagille Syndrome [ALGS] or Progressive Familial Intrahepatic Cholestasis [PFIC].

Study Overview

• Status: Completed
• Conditions: Cholestatic Liver Disease; Alagille Syndrome; Progressive Familial Intrahepatic Cholestasis
• Intervention / Treatment: Drug: Maralixibat

Detailed Description

This is an open label study where all participants will receive maralixibat treatment.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• Belgium
  • Brussels, Belgium
    • Cliniques Universitaires Saint-Luc
• Brazil
  • São Paulo, Brazil, 01308-000
    • Sociedade Beneficente de Senhoras - Hospital Sírio-Libanês
• France
  • Le Kremlin-Bicêtre, France
    • Hôpital Kremlin Bicêtre
  • Paris, France
    • Hopital Necker
• Mexico
  • Zapopan, Mexico, 45050
    • Consultorio de Joshue David Covarrubias Esquer
• Poland
  • Warsaw, Poland
    • Instytut Pomnik-Centrum Zdrowia Dziecka
• United Kingdom
  • London, United Kingdom
    • King's College Hospital
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children Hospital LA
    • San Francisco, California, United States, 94158
      • University of California - San Francisco
  • District of Columbia
    • Washington D.C., District of Columbia, United States, 20007
      • MedStar Georgetown University Hospital
  • Louisiana
    • New Orleans, Louisiana, United States, 70121
      • Ochsner Hospital for Children
  • Pennsylvania
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh
  • Texas
    • Houston, Texas, United States, 77030
      • Texas Children's Hospital
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 11 months (Child)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Body weight of ≥2.5 kg
2. <12 months of age at the baseline visit (ROW). >31 days and <12 months of age at the baseline visit (US).
3. Gestational age ≥36 weeks at birth. For children born with gestational age between 32 and 36 weeks, a postmenstrual age of ≥36 weeks is required.
4. Diagnosis of PFIC or ALGS

Exclusion criteria:

1. Predicted complete absence of bile salt excretion pump (BSEP) function
2. History of surgical disruption of the enterohepatic circulation
3. History of liver transplant or imminent need for liver transplant
4. Decompensated cirrhosis
5. Presence of any other disease or condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, including bile salt metabolism in the intestine (e.g., inflammatory bowel disease), per investigator discretion
6. Presence of other significant liver disease or any other conditions or abnormalities which, in the opinion of the investigator or medical monitor, may compromise the safety of the participant or interfere with the participant's participation in or completion of the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Maralixibat; Participants will receive up to 600 μg/kg twice daily (PFIC) or up to 400 μg/kg once daily (ALGS) over 13 weeks in the core study and for the duration of the Long Term Extension (LTE) where applicable.	Drug: Maralixibat; Maralixibat chloride provided in the form of an oral solution (i.e., 5, 10, 15, and 20 mg/mL); 400 μg/kg maralixibat chloride is equivalent to 380 µg/kg maralixibat free base; 600 μg/kg maralixibat chloride is equivalent to 570 µg/kg maralixibat free base; Other Names: Formerly LUM001 and SHP625

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Frequency of Treatment-emergent Adverse Events [TEAEs]	TEAEs = Treatment-emergent Adverse Events	From Baseline through to Week 13

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Fasting Serum Bile Acid (sBA) Levels	sBA = serum bile acid	From Baseline through to Week 13
To Evaluate the Effect on Liver Enzymes (ALT)	ALT= alanine aminotransferase.	From Baseline through to Week 13
Change From Baseline to Week 13 in Lipid-Soluble Vitamins (LSVs) - Vitamin E	Change from baseline to Week 13 in vitamin E.	From Baseline through to Week 13
Maximum Level of Maralixibat Concentration in Plasma From Baseline to Week 13 for ALGS	BID=twice daily; QD=once daily. Systemic concentrations of maralixibat in plasma were determined at the following visits: Approximately 2.5 hours after the morning dose at Week 0/Day 1 of dosing; Before dosing and ~2.5 hours after the morning dose at Week 6, Week 10, and Week 13 Stable dosing occurred at 400 μg/kg QD for ALGS or at the highest tolerated dose. Note: The values added in section Measured Values are for maralixibat dose of 400 µg/kg QD.	At Baseline, Week 6, Week 10, Week 13 or Early Termination Visit
To Evaluate the Effect on Liver Enzymes (AST)	AST= aspartate aminotransferase	From Baseline through to Week 13.
To Evaluate the Effect on Bilirubin	Bilirubin	From Baseline through to Week 13
Change From Baseline to Week 13 in Lipid-Soluble Vitamins (LSVs) - Vitamin A	Change from baseline to Week 13 in vitamin A	From Baseline through to Week 13
Change From Baseline to Week 13 in Lipid-Soluble Vitamins (LSVs) - Vitamins D and K	Change from baseline to Week 13 in vitamins D and K.	From Baseline through to Week 13
Maximum Level of Maralixibat Concentration in Plasma From Baseline to Week 13 for PFIC	BID=twice daily; QD=once daily. Systemic concentrations of maralixibat in plasma were determined at the following visits: Approximately 2.5 hours after the morning dose at Week 0/Day 1 of dosing; Before dosing and ~2.5 hours after the morning dose at Week 6, Week 10, and Week 13 Stable dosing occurred at 300 μg/kg QD, 300 μg/kg BID and 600 μg/kg BID for PFIC or at the highest tolerated dose. Note: The values added in section Measured Values are for maralixibat dose of 600 µg/kg BID.	At Baseline, Week 6, Week 10, Week 13 or Early Termination Visit

Collaborators and Investigators

• Sponsor: Mirum Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

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

Study record dates

Study Major Dates

• Study Start (Actual): September 9, 2021
• Primary Completion (Actual): December 17, 2024
• Study Completion (Actual): December 17, 2024

Study Registration Dates

• First Submitted: January 25, 2021
• First Submitted That Met QC Criteria: January 27, 2021
• First Posted (Actual): January 28, 2021

Study Record Updates

• Last Update Posted (Actual): June 2, 2026
• Last Update Submitted That Met QC Criteria: June 1, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Keywords: Pediatric; Liver Diseases; Maralixibat; PFIC; Bile Duct Diseases; Biliary Tract Diseases; ALGS
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Genetic Diseases, Inborn; Digestive System Diseases; Congenital Abnormalities; Cardiovascular Abnormalities; Heart Defects, Congenital; Abnormalities, Multiple; Cholestasis, Intrahepatic; Cholestasis; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Alagille Syndrome; Cholestasis, progressive familial intrahepatic 1; maralixibat
• Other Study ID Numbers: MRX-801; 2020-004628-40 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No