An Extension Study to Evaluate the Long-Term Safety and Durability of Effect of LUM001 in the Treatment of Cholestatic Liver Disease in Subjects With Alagille Syndrome (ALGS)

Study Overview
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Brief Summary
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The purpose of this extension study is to determine the long-term safety and tolerability of an investigational treatment (LUM001 also known as Maralixibat) in children with ALGS who have completed participation in a core LUM001 treatment protocol. Efficacy will be assessed by evaluating the effect of LUM001 on pruritus, biochemical markers of pruritus, as well as biochemical markers of cholestasis and liver disease.

Official Title
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A Multicentre Extension Study to Evaluate the Long-Term Safety and Durability of the Therapeutic Effect of LUM001 Also Known as Maralixibat (MRX), an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Pediatric Subjects With Alagille Syndrome

Conditions
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Alagille Syndrome

Intervention / Treatment
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* Drug: LUM001 (Maralixibat)


Participation Criteria
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Eligibility Criteria
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Participation for an individual patient is expected to be approximately 72 weeks. Patients who complete 72 weeks of treatment may be eligible to receive treatment for up to 52 weeks during the follow-up treatment period and patients who completed the 124 weeks of treatment may be eligible to enter the additional long-term follow-up period.

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 18 Years

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: LUM001 (Maralixibat)<br>LUM001 also known as Maralixibat (MRX) administered orally up to twice each day | Drug: LUM001 (Maralixibat)<br>* Dosing of LUM001 also known as Maralixibat (MRX) with the objective of achieving optimal control of pruritus at a dose level that is tolerated by the participant and up to a maximum daily dose of 560 micrograms per kilogram (mcg/kg).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From MRX Baseline to Week 48 in Fasting sBA Levels | The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level. | MRX baseline to Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From MRX Baseline Over Time in Fasting sBA Levels | This secondary efficacy endpoint is the mean change from MRX baseline over time in fasting sBA levels. Results reported here are the long-term results. | MRX baseline to End of Treatment (maximum exposure was 336 weeks) | 
| Change From MRX Baseline to Week 48 in Pruritus | This secondary efficacy endpoint is the change from MRX baseline to Week 48 in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe). | MRX baseline to Week 48 | 
| Change From MRX Baseline Over Time in Pruritus | This secondary efficacy endpoint is the change from MRX baseline over time in pruritus as measured by ItchRO(Obs) weekly average morning severity score. ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe). Results reported here are the long-term results. | MRX baseline to End of Treatment (maximum exposure was 336 weeks) | 
| Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the participant's lesions interfere or limit his or her activities. Clinician xanthoma severity scores range from 0 to 4, with a xanthoma score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants who were assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented. | MRX baseline to Week 48 | 
| Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score | This secondary efficacy endpoint is the mean change from MRX baseline over time (with Week 252 chosen as the end point, as the last analysis visit with at least 6 participants) in clinician xanthoma severity scores. It is based on a 0-4 scale to rate the number of lesions present and the degree to which the lesions interfere or limit activities. Clinician xanthoma severity scores range from 0 to 4, with a score of zero representing no evidence of xanthomatosis and a score of 4 representing xanthoma so severe that it is disabling. Clinician xanthoma severity scores were not assessed in Study LUM001-302 so mean clinician xanthoma severity score at MRX baseline was calculated from the 5 participants assigned to placebo in Study LUM001-302, and analysis of change from MRX baseline is not presented. Results reported here are the long-term results. | MRX baseline to End of Treatment (maximum exposure was 336 weeks) | 
| Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALP. | MRX baseline to Week 48 | 
| Change From MRX Baseline Over Time in Alkaline Phosphatase | This secondary efficacy endpoint is the mean change from MRX baseline over time in ALP. Results reported here are the long-term results. | MRX baseline to end of treatment (maximum exposure was 336 weeks) | 
| Change From MRX Baseline to Week 48 in Alanine Aminotransferase | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALT. | MRX baseline to Week 48 | 
| Change From MRX Baseline Over Time in Alanine Aminotransferase | This secondary efficacy endpoint is the mean change from MRX baseline over time in ALT levels. Results reported here are the long-term results. | MRX baseline to End of Treatment (maximum exposure was 336 weeks) | 
| Change From MRX Baseline to Week 48 in Aspartate Aminotransferase | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in AST levels. | MRX baseline to Week 48 | 
| Change From MRX Baseline Over Time in Aspartate Aminotransferase | This secondary efficacy endpoint is the mean change from MRX baseline over time in AST levels. Results reported here are the long-term results. | MRX baseline to End of treatment (maximum exposure was 336 weeks) | 
| Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in GGT. | MRX baseline to Week 48 | 
| Change From MRX Baseline Over Time in Gamma Glutamyltransferase | This secondary efficacy endpoint is the mean change from MRX baseline over time in GGT. Results reported here are the long-term results. | MRX baseline to End of Treatment (maximum exposure was 336 weeks) | 
| Change From MRX Baseline to Week 48 in Total and Direct Bilirubin | This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in total bilirubin and direct bilirubin. | MRX baseline to Week 48 | 
| Change From MRX Baseline Over Time in Total and Direct Bilirubin | This secondary efficacy endpoint is the mean change from MRX baseline over time in total bilirubin and direct bilirubin. Results reported here are the long-term results. | MRX baseline to End of Treatment (maximum exposure was 336 weeks) |