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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)

Primary Purpose

Alagille Syndrome

Status
Completed
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
LUM001 (Maralixibat)
Sponsored by
Mirum Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Alagille Syndrome

Eligibility Criteria

12 Months - 18 Years (Child, Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Birmingham Children's Hospital
  • Leeds Teaching Hospital NHS Trust
  • Kings College Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

LUM001 (Maralixibat)

Arm Description

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.

Full Information

First Posted
January 23, 2014
Last Updated
November 17, 2021
Sponsor
Mirum Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT02047318
Brief Title
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)
Acronym
IMAGINE
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
Study Type
Interventional

2. Study Status

Record Verification Date
November 2021
Overall Recruitment Status
Completed
Study Start Date
December 20, 2013 (Actual)
Primary Completion Date
June 17, 2020 (Actual)
Study Completion Date
June 17, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mirum Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Alagille Syndrome

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LUM001 (Maralixibat)
Arm Type
Experimental
Arm Description
LUM001 also known as Maralixibat (MRX) administered orally up to twice each day
Intervention Type
Drug
Intervention Name(s)
LUM001 (Maralixibat)
Intervention Description
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 Outcome Measure Information:
Title
Change From MRX Baseline to Week 48 in Fasting sBA Levels
Description
The primary endpoint of this study was the mean change from MRX baseline to Week 48 in fasting sBA level.
Time Frame
MRX baseline to Week 48
Secondary Outcome Measure Information:
Title
Change From MRX Baseline Over Time in Fasting sBA Levels
Description
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.
Time Frame
MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Title
Change From MRX Baseline to Week 48 in Pruritus
Description
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).
Time Frame
MRX baseline to Week 48
Title
Change From MRX Baseline Over Time in Pruritus
Description
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.
Time Frame
MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Title
Change From MRX Baseline to Week 48 in Clinician Xanthoma Severity Score
Description
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.
Time Frame
MRX baseline to Week 48
Title
Change From MRX Baseline Over Time in Clinician Xanthoma Severity Score
Description
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.
Time Frame
MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Title
Secondary: Change From MRX Baseline to Week 48 in Alkaline Phosphatase
Description
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALP.
Time Frame
MRX baseline to Week 48
Title
Change From MRX Baseline Over Time in Alkaline Phosphatase
Description
This secondary efficacy endpoint is the mean change from MRX baseline over time in ALP. Results reported here are the long-term results.
Time Frame
MRX baseline to end of treatment (maximum exposure was 336 weeks)
Title
Change From MRX Baseline to Week 48 in Alanine Aminotransferase
Description
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in ALT.
Time Frame
MRX baseline to Week 48
Title
Change From MRX Baseline Over Time in Alanine Aminotransferase
Description
This secondary efficacy endpoint is the mean change from MRX baseline over time in ALT levels. Results reported here are the long-term results.
Time Frame
MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Title
Change From MRX Baseline to Week 48 in Aspartate Aminotransferase
Description
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in AST levels.
Time Frame
MRX baseline to Week 48
Title
Change From MRX Baseline Over Time in Aspartate Aminotransferase
Description
This secondary efficacy endpoint is the mean change from MRX baseline over time in AST levels. Results reported here are the long-term results.
Time Frame
MRX baseline to End of treatment (maximum exposure was 336 weeks)
Title
Change From MRX Baseline to Week 48 in Gamma Glutamyltransferase
Description
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in GGT.
Time Frame
MRX baseline to Week 48
Title
Change From MRX Baseline Over Time in Gamma Glutamyltransferase
Description
This secondary efficacy endpoint is the mean change from MRX baseline over time in GGT. Results reported here are the long-term results.
Time Frame
MRX baseline to End of Treatment (maximum exposure was 336 weeks)
Title
Change From MRX Baseline to Week 48 in Total and Direct Bilirubin
Description
This secondary efficacy endpoint is the mean change from MRX baseline to Week 48 in total bilirubin and direct bilirubin.
Time Frame
MRX baseline to Week 48
Title
Change From MRX Baseline Over Time in Total and Direct Bilirubin
Description
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.
Time Frame
MRX baseline to End of Treatment (maximum exposure was 336 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
12 Months
Maximum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Mirum
Official's Role
Study Director
Facility Information:
Facility Name
Birmingham Children's Hospital
City
Birmingham
State/Province
West Midlands
ZIP/Postal Code
B4 6NH
Country
United Kingdom
Facility Name
Leeds Teaching Hospital NHS Trust
City
Leeds
State/Province
West Yorkshire
ZIP/Postal Code
LS1 3EX
Country
United Kingdom
Facility Name
Kings College Hospital
City
London
ZIP/Postal Code
SE5 9RS
Country
United Kingdom

12. IPD Sharing Statement

Learn more about this trial

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)

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