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).

Mirum Pharmaceuticals, Inc.27 enrolled

Overview

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 \[PFIC\].

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

Study Type

INTERVENTIONAL

Allocation

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Progressive Familial Intrahepatic Cholestasis Alagille Syndrome Cholestatic Liver Disease

Interventions

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

Eligibility

Sex: ALLMin age: 0 DaysMax age: 364 Days

Medical Language ↔ Plain English

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

Locations (14)

Children Hospital LA

Los Angeles, California, United States

University of California - San Francisco

San Francisco, California, United States

Medstar Georgetown University Hospital

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

Ochsner Hospital for Children

New Orleans, Louisiana, United States

Children's Hospital of Pittsburgh

Pittsburgh, Pennsylvania, United States

Texas Children's Hospital

Houston, Texas, United States

Seattle Children's Hospital

Seattle, Washington, United States

Cliniques Universitaires Saint-Luc

Brussels, Belgium

Sociedade Beneficente de Senhoras - Hospital Sírio-Libanês

São Paulo, Brazil

Hôpital Kremlin Bicêtre

Le Kremlin-Bicêtre, France

...and 4 more locations

Outcomes

Primary Outcomes

Frequency of Treatment-emergent Adverse Events [TEAEs]

TEAEs = Treatment-emergent Adverse Events

Time frame: From Baseline through to Week 13

Secondary Outcomes

Change in Fasting Serum Bile Acid (sBA) Levels

sBA = serum bile acid

Time frame: From Baseline through to Week 13

To Evaluate the Effect on Liver Enzymes (ALT)

ALT= alanine aminotransferase.

Time frame: 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.

Time frame: 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.

Time frame: At Baseline, Week 6, Week 10, Week 13 or Early Termination Visit

To Evaluate the Effect on Liver Enzymes (AST)

AST= aspartate aminotransferase

Time frame: From Baseline through to Week 13.

To Evaluate the Effect on Bilirubin

Bilirubin

Time frame: 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

Time frame: 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.

Time frame: 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.

Time frame: At Baseline, Week 6, Week 10, Week 13 or Early Termination Visit