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).

NCT04729751 | Completed Phase 2 DMC FDA Drug

• 2 other identifiers: MRX-8012020-004628-40
• Study Type: interventional
• Target: 27
• Locations: 7 countries
• Sites: 14

Brief Summary

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 \[PFIC\].

Conditions

Progressive Familial Intrahepatic Cholestasis; Alagille Syndrome; Cholestatic Liver Disease

Keywords

PFIC; ALGS; Maralixibat; Bile Duct Diseases; Liver Diseases; Biliary Tract Diseases; Pediatric

Outcome Measures

Primary Outcomes (1)

• Frequency of treatment-emergent adverse events [TEAEs]

  From Baseline through to Week 13

Secondary Outcomes (4)

• Change in fasting serum bile acid (sBA) levels

  From Baseline through to Week 13

• To evaluate the effect on liver enzymes (ALT, AST) and bilirubin

  From Baseline through to Week 13

• To evaluate the effect on LSVs

  From Baseline through to Week 13

• To assess the plasma level of maralixibat in infant participants

  At Baseline, Week 6, Week 10, Week 13 or Early Termination Visit

Study Arms (1)

Maralixibat

EXPERIMENTAL

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

Interventions

Maralixibat DRUG

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

Also known as: Formerly LUM001 and SHP625

Maralixibat

Eligibility Criteria

• Age: 0 Days - 364 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Body weight of ≥2.5 kg
• \<12 months of age at the baseline visit (ROW). \>31 days and \<12 months of age at the baseline visit (US).
• 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.
• Diagnosis of PFIC or ALGS

You may not qualify if:

• Predicted complete absence of bile salt excretion pump (BSEP) function
• History of surgical disruption of the enterohepatic circulation
• History of liver transplant or imminent need for liver transplant
• Decompensated cirrhosis
• 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
• 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

Sponsors & Collaborators

• Mirum Pharmaceuticals, Inc.: lead

Study Sites (14)

Children Hospital LA

Los Angeles, California, 90027, United States

Location

University of California - San Francisco

San Francisco, California, 94158, United States

Location

Medstar Georgetown University Hospital

Washington D.C., District of Columbia, 20007, United States

Location

Ochsner Hospital for Children

New Orleans, Louisiana, 70121, United States

Location

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, 15224, United States

Location

Texas Children's Hospital

Houston, Texas, 77030, United States

Location

Seattle Children's Hospital

Seattle, Washington, 98105, United States

Location

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Location

Sociedade Beneficente de Senhoras - Hospital Sírio-Libanês

São Paulo, 01308-000, Brazil

Location

Hôpital Kremlin Bicêtre

Le Kremlin-Bicêtre, France

Location

Hopital Necker

Paris, France

Location

Consultorio de Joshue David Covarrubias Esquer

Zapopan, 45050, Mexico

Location

Instytut Pomnik-Centrum Zdrowia Dziecka

Warsaw, Poland

Location

King's College Hospital

London, United Kingdom

Location

Related Links

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

MeSH Terms

Conditions

Cholestasis, progressive familial intrahepatic 1; Alagille Syndrome; Bile Duct Diseases; Liver Diseases; Biliary Tract Diseases

Interventions

maralixibat

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Digestive System Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Abnormalities, Multiple; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Genetic Diseases, Inborn

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Single group with 2 cohorts - ≥ 6 participants each from ALGS and PFIC.

Study Record Dates

• First Submitted: January 25, 2021
• First Posted: January 28, 2021
• Study Start: September 9, 2021
• Primary Completion: December 17, 2024
• Study Completion: December 17, 2024
• Last Updated: February 6, 2025

Record last verified: 2025-02

Locations

BR (1); ME (1); FR (2); PL (1); US (7); BE (1); GB (1)