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)

• ClinicalTrials.gov Identifier: NCT02047318
• Recruitment Status: Completed
• First Posted: January 28, 2014
• Results First Posted: November 19, 2021
• Last Update Posted: November 19, 2021
• Sponsor: Mirum Pharmaceuticals, Inc.
• Information provided by (Responsible Party): Mirum Pharmaceuticals, Inc.

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Alagille Syndrome	Drug: LUM001 (Maralixibat)	Phase 2

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 19 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: 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
• Actual Study Start Date: December 20, 2013
• Actual Primary Completion Date: June 17, 2020
• Actual Study Completion Date: June 17, 2020

Arms and Interventions

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).

Outcome Measures

Primary Outcome Measures :

1. Change From MRX Baseline to Week 48 in Fasting sBA Levels [ Time Frame: 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 :

1. Change From MRX Baseline Over Time in Fasting sBA Levels [ Time Frame: 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.
2. Change From MRX Baseline to Week 48 in Pruritus [ Time Frame: 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).
3. Change From MRX Baseline Over Time in Pruritus [ Time Frame: 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.
4. Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score [ Time Frame: 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.
5. Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score [ Time Frame: 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.
6. Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase [ Time Frame: MRX baseline to Week 48 ]
   This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALP.
7. Change From MRX Baseline Over Time in Alkaline Phosphatase [ Time Frame: 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.
8. Change From MRX Baseline to Week 48 in Alanine Aminotransferase [ Time Frame: MRX baseline to Week 48 ]
   This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALT.
9. Change From MRX Baseline Over Time in Alanine Aminotransferase [ Time Frame: 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.
10. Change From MRX Baseline to Week 48 in Aspartate Aminotransferase [ Time Frame: MRX baseline to Week 48 ]
    This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in AST levels.
11. Change From MRX Baseline Over Time in Aspartate Aminotransferase [ Time Frame: 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.
12. Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase [ Time Frame: MRX baseline to Week 48 ]
    This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in GGT.
13. Change From MRX Baseline Over Time in Gamma Glutamyltransferase [ Time Frame: 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.
14. Change From MRX Baseline to Week 48 in Total and Direct Bilirubin [ Time Frame: 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.
15. Change From MRX Baseline Over Time in Total and Direct Bilirubin [ Time Frame: 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.

Eligibility Criteria

• Ages Eligible for Study: 12 Months to 18 Years (Child, Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

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.

Contacts and Locations

Locations

United Kingdom

Birmingham Children's Hospital

Birmingham, West Midlands, United Kingdom, B4 6NH

Leeds Teaching Hospital NHS Trust

Leeds, West Yorkshire, United Kingdom, LS1 3EX

Kings College Hospital

London, United Kingdom, SE5 9RS

Sponsors and Collaborators

Mirum Pharmaceuticals, Inc.

Investigators

• Study Director: Study Director; Mirum

  Study Documents (Full-Text)

Documents provided by Mirum Pharmaceuticals, Inc.:

Study Protocol  [PDF] February 8, 2019

Statistical Analysis Plan  [PDF] April 10, 2020

More Information

• Responsible Party: Mirum Pharmaceuticals, Inc.
• ClinicalTrials.gov Identifier: NCT02047318
• Other Study ID Numbers: LUM001-303; 2013-003832-54 ( EudraCT Number )
• First Posted: January 28, 2014
• Results First Posted: November 19, 2021
• Last Update Posted: November 19, 2021
• Last Verified: November 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:

Liver Diseases; Alagille Syndrome; Syndrome; Disease; Pathologic Processes; Digestive System Diseases; Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Abnormalities, Multiple; Congenital Abnormalities; Genetic Diseases, Inborn