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Completed

NCT Number: NCT02047318

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)

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.

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Key information

Conditions

Alagille Syndrome Abnormalities, Multiple Bile Duct Diseases Biliary Tract Diseases Cardiovascular Abnormalities Cardiovascular Diseases Cholestasis Cholestasis, Intrahepatic Congenital Abnormalities Congenital, Hereditary, and Neonatal Diseases and Abnormalities Digestive System Diseases Genetic Diseases, Inborn Heart Defects, Congenital Liver Diseases

Age range

12 month–18 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Birmingham Children's Hospital, Birmingham, West Midlands, United Kingdom

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Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

LUM001 (Maralixibat)

Drug

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).

Primary outcomes

  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 outcomes

  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.

Sponsors and collaborators

Lead sponsor

Mirum Pharmaceuticals, Inc.

Industry

Registry information

Official study 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

Acronym: IMAGINE

Important dates

Study start
2013
Primary completion
2020
Study completion
2020
First posted
Jan 28, 2014
Registry last updated
Nov 19, 2021

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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