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) (IMAGINE)

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

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.

Study Overview

• Status: Completed
• Conditions: Alagille Syndrome
• Intervention / Treatment: Drug: LUM001 (Maralixibat)

• Study Type: Interventional
• Enrollment (Actual): 19
• Phase: Phase 2

Contacts and Locations

Study Locations

• United Kingdom
  • London, United Kingdom, SE5 9RS
    • Kings College Hospital
  • West Midlands
    • Birmingham, West Midlands, United Kingdom, B4 6NH
      • Birmingham Children's Hospital
  • West Yorkshire
    • Leeds, West Yorkshire, United Kingdom, LS1 3EX
      • Leeds Teaching Hospital NHS Trust

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LUM001 (Maralixibat); LUM001 also known as Maralixibat (MRX) administered orally up to twice each day	Drug: LUM001 (Maralixibat); 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).

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Mirum Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): December 20, 2013
• Primary Completion (Actual): June 17, 2020
• Study Completion (Actual): June 17, 2020

Study Registration Dates

• First Submitted: January 23, 2014
• First Submitted That Met QC Criteria: January 24, 2014
• First Posted (Estimate): January 28, 2014

Study Record Updates

• Last Update Posted (Actual): November 19, 2021
• Last Update Submitted That Met QC Criteria: November 17, 2021
• Last Verified: November 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Disease; Congenital Abnormalities; Genetic Diseases, Inborn; Biliary Tract Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Abnormalities, Multiple; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Liver Diseases; Syndrome; Alagille Syndrome
• Other Study ID Numbers: LUM001-303; 2013-003832-54 (EudraCT Number)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No