MRX-800: A Long-Term Safety Study of Maralixibat in the Treatment of Cholestatic Liver Disease in Subjects Who Previously Participated in a Maralixibat Study

Study Overview
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Brief Summary
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Evaluate the long-term safety of maralixibat (MRX) in subjects with cholestatic liver disease including, but not limited to, Alagille Syndrome (ALGS), Progressive Familial Intrahepatic Cholestasis (PFIC) and Biliary Atresia.

Detailed Description
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This is a multicenter, open-label study of maralixibat in subjects diagnosed with cholestatic liver disease (including, but not limited to ALGS, PFIC or Biliary Atresia) who have previously participated in a maralixibat clinical study. All subjects will receive maralixibat in this study.

Official Title
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MRX-800: A Long-Term Safety Study of Maralixibat, an Apical Sodium Dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Subjects Who Previously Participated in a Maralixibat Study

Conditions
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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 Subjects will need to meet all criteria below to be considered eligible for the study. Provide informed consent and assent (as applicable) per the Institutional Review Board/Ethics Committee (IRB/EC). Previously participated in a maralixibat study and with approval of the Medical Monitor. Previous participation is defined as: Having completed the EOT Visit, for subjects coming from the maralixibat Phase 2 studies. Having completed the entire duration of the study (i.e., core and extension, if applicable), for subjects coming from the maralixibat Phase 3 studies. At least 1 year of age Males, and females of non-childbearing potential. Males and non-pregnant, non-lactating females of childbearing potential who are sexually active must agree to use acceptable contraception during the study and 30 days following the last dose of the study medication. Females of childbearing potential must have a negative pregnancy test. Caregivers (and/or age appropriate subjects) must have access to email or phone for scheduled remote visits if applicable. Subject and caregiver willingness to comply with all study visits and requirements. Exclusion Criteria A subject will be excluded from the study if any of the following exclusion criteria are met: Experienced an AE or SAE related to maralixibat during the lead-in protocol that led to permanent discontinuation of the subject from maralixibat. Any conditions or abnormalities (including laboratory abnormalities) which, in the opinion of the Investigator or Medical Monitor may compromise the safety of the subject or interfere with the subject participating in or completing the study. History of non-adherence to medical regimens, unreliability, medical condition, mental instability or cognitive impairment that, in the opinion of the Investigator or Sponsor medical monitor, could compromise the validity of informed consent, compromise the safety of the subject, or lead to non-adherence with the study protocol or inability to conduct the study procedures.

Ages Eligible for Study
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Minimum Age: 12 Months

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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Maralixibat<br>Participants will all receive Maralixibat oral solution | Drug: Maralixibat<br>* Maralixibat chloride oral solution orally twice daily (up to 1200* mcg/kg/day), and according to indication. *equivalent to 1140 mcg/kg/day maralixibat<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 reported adverse events AEs | Treatment-emergent AEs (TEAEs) will be defined as AEs that start or deteriorate on or after the first dose of study medication and no later than 14 days following the last dose of study medication or reported through the End of Trial ( EOT/ET) Visit. In this study, all AEs will be considered TEAEs. | From baseline through study completion, up to approximately 3 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from maralixibat baseline over the course of the study in the weekly average morning ItchRO(Obs)™ severity score (ALGS and PFIC) |  | From baseline through study completion, up to approximately 3 years | 
| Change from maralixibat baseline over the course of the study in the weekly average morning ItchRO(Obs)™ frequency score (ALGS and PFIC) |  | From baseline through study completion, up to approximately 3 years | 
| Evaluate the long-term effect of maralixibat on pruritus severity using in the Clinician Scratch Scale (CSS) as change from baseline over the course of the study |  | From baseline through study completion, up to approximately 3 years | 
| Evaluate the long-term effect of maralixibat on serum bile acid levels |  | From baseline through study completion, up to approximately 3 years | 
| Evaluate the long-term effect of maralixibat on time to liver-associated outcomes reported as a mean change from baseline (i.e., partial external biliary diversion [PEBD] or liver transplantation) |  | From baseline to occurrence of liver associated event, up to approximately 3 years | 
| Evaluate the long-term effects of maralixibat on growth | Change from baseline in height and weight, summarized as a Z-score over the course of the study | Through study completion, up to approximately 3 years | 
| Change from maralixibat baseline over the course of the study in mean total serum bilirubin |  | Change from baseline through study completion, up to approximately 3 years | 

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