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)

Phase 2

Completed

• Conditions: Alagille Syndrome
• Interventions: Drug: LUM001 (Maralixibat)

• Registration Number: NCT02047318
• Lead Sponsor: Mirum Pharmaceuticals, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12-20
• Study First Submitted: 2014-01-23
• Study First Submitted QC: 2014-01-24
• Study First Posted: 2014-01-28
• Primary Completion: 2020-06-17
• Study Completion: 2020-06-17
• Results First Submitted: 2021-03-29
• Status Verified: 2021-11
• Results First Submitted QC: 2021-11-17
• Last Update Submitted: 2021-11-17
• Results First Posted: 2021-11-19
• Last Update Posted: 2021-11-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 19

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
LUM001 (Maralixibat)	LUM001 (Maralixibat)	LUM001 also known as Maralixibat (MRX) administered orally up to twice each day

Primary Outcome Measures

Name	Time	Method
Change From MRX Baseline to Week 48 in Fasting sBA Levels	MRX baseline to Week 48	The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level.

Secondary Outcome Measures

Name	Time	Method
Change From MRX Baseline Over Time in Fasting sBA Levels	MRX baseline to End of Treatment (maximum exposure was 336 weeks)	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.
Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score	MRX baseline to Week 48	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.
Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score	MRX baseline to End of Treatment (maximum exposure was 336 weeks)	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.
Change From MRX Baseline to Week 48 in Pruritus	MRX baseline to Week 48	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).
Change From MRX Baseline Over Time in Pruritus	MRX baseline to End of Treatment (maximum exposure was 336 weeks)	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.
Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase	MRX baseline to Week 48	This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALP.
Change From MRX Baseline Over Time in Alkaline Phosphatase	MRX baseline to end of treatment (maximum exposure was 336 weeks)	This secondary efficacy endpoint is the mean change from MRX baseline over time in ALP. Results reported here are the long-term results.
Change From MRX Baseline Over Time in Alanine Aminotransferase	MRX baseline to End of Treatment (maximum exposure was 336 weeks)	This secondary efficacy endpoint is the mean change from MRX baseline over time in ALT levels. Results reported here are the long-term results.
Change From MRX Baseline to Week 48 in Aspartate Aminotransferase	MRX baseline to Week 48	This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in AST levels.
Change From MRX Baseline Over Time in Aspartate Aminotransferase	MRX baseline to End of treatment (maximum exposure was 336 weeks)	This secondary efficacy endpoint is the mean change from MRX baseline over time in AST levels. Results reported here are the long-term results.
Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase	MRX baseline to Week 48	This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in GGT.
Change From MRX Baseline Over Time in Gamma Glutamyltransferase	MRX baseline to End of Treatment (maximum exposure was 336 weeks)	This secondary efficacy endpoint is the mean change from MRX baseline over time in GGT. Results reported here are the long-term results.
Change From MRX Baseline to Week 48 in Alanine Aminotransferase	MRX baseline to Week 48	This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALT.
Change From MRX Baseline to Week 48 in Total and Direct Bilirubin	MRX baseline to Week 48	This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in total bilirubin and direct bilirubin.
Change From MRX Baseline Over Time in Total and Direct Bilirubin	MRX baseline to End of Treatment (maximum exposure was 336 weeks)	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.

Trial Locations

Locations (3)

Leeds Teaching Hospital NHS Trust; 🇬🇧 Leeds, West Yorkshire, United Kingdom

Birmingham Children's Hospital; 🇬🇧 Birmingham, West Midlands, United Kingdom

Kings College Hospital; 🇬🇧 London, United Kingdom