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).

Study Overview
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Brief Summary
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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].

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

Official Title
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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

Conditions
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Progressive Familial Intrahepatic Cholestasis, Alagille Syndrome, Cholestatic Liver Disease

Intervention / Treatment
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* Drug: Maralixibat


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 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 Exclusion criteria: 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

Ages Eligible for Study
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Minimum Age: 0 Days
Maximum Age: 364 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Single group with 2 cohorts - ≥ 6 participants each from ALGS and PFIC.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maralixibat<br>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<br>* 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<br>* Other names: Formerly LUM001 and SHP625;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of treatment-emergent adverse events [TEAEs] |  | From Baseline through to Week 13 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PFIC, ALGS, Maralixibat, Bile Duct Diseases, Liver Diseases, Biliary Tract Diseases, Pediatric