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)
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
  • Phase

    Phase 2
  • Study Type

    Interventional
  • Intervention/Treatment

    lum001 ...
  • Study Participants

    19
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 Started
Dec 20
2013
Primary Completion
Jun 17
2020
Study Completion
Jun 17
2020
Results Posted
Nov 19
2021
Last Update
Nov 19
2021

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).

LUM001 (Maralixibat) Experimental

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

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.

Summary

14 Microgram Per Kilogram Per Day (mcg/kg/Day)

35 Microgram Per Kilogram Per Day (mcg/kg/Day)

70 Microgram Per Kilogram Per Day (mcg/kg/Day)

140 Microgram Per Kilogram Per Day (mcg/kg/Day)

280 Microgram Per Kilogram Per Day (mcg/kg/Day)

420 Microgram Per Kilogram Per Day (mcg/kg/Day)

560 Microgram Per Kilogram Per Day (mcg/kg/Day)

LUM001 MRX Treatment

All Events

Event Type Organ System Event Term 14 Microgram Per Kilogram Per Day (mcg/kg/Day) 35 Microgram Per Kilogram Per Day (mcg/kg/Day) 70 Microgram Per Kilogram Per Day (mcg/kg/Day) 140 Microgram Per Kilogram Per Day (mcg/kg/Day) 280 Microgram Per Kilogram Per Day (mcg/kg/Day) 420 Microgram Per Kilogram Per Day (mcg/kg/Day) 560 Microgram Per Kilogram Per Day (mcg/kg/Day) LUM001 MRX Treatment

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.

Core Study Period: MRX Baseline Values

261.96
μmol/L (Mean)
Standard Deviation: 206.839

Core Study Period: Week 48 Values

128.32
μmol/L (Mean)
Standard Deviation: 101.742

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.

Core Study Period: MRX Baseline Value

261.96
μmol/L (Mean)
Standard Deviation: 206.839

Week 252 Values

118.32
μmol/L (Mean)
Standard Deviation: 76.140

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).

Core Study Period: MRX Baseline Value

2.435
scores on a scale (Mean)
Standard Deviation: 0.7952

Core Study Period: Week 48 Values

1.307
scores on a scale (Mean)
Standard Deviation: 0.6995

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.

Core Study Period: MRX Baseline Value

2.435
scores on a scale (Mean)
Standard Deviation: 0.7952

Week 278 Values

0.952
scores on a scale (Mean)
Standard Deviation: 0.4302

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.

Core Study Period: MRX Baseline Value

476.9
U/L (Mean)
Standard Deviation: 376.85

Week 252 Values

377.5
U/L (Mean)
Standard Deviation: 163.10

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.

Core Study Period: MRX Baseline Values

0.4
scores on a scale (Mean)
Standard Deviation: 0.55

Core Study Period: Week 48 Values

0.2
scores on a scale (Mean)
Standard Deviation: 0.73

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.

Core Study Period: MRX Baseline Value

0.4
scores on a scale (Mean)
Standard Deviation: 0.55

Week 252 Values

0.2
scores on a scale (Mean)
Standard Deviation: 0.41

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.

Core Study Period: MRX Baseline Value

601.5
U/L (Mean)
Standard Deviation: 232.54

Core Study Period: Week 48 Values

596.2
U/L (Mean)
Standard Deviation: 185.20

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.

Core Study Period: MRX Baseline Value

601.5
U/L (Mean)
Standard Deviation: 232.54

Week 252 Values

430.5
U/L (Mean)
Standard Deviation: 223.56

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.

Core Study Period: MRX Baseline Value

130.7
U/L (Mean)
Standard Deviation: 59.12

Core Study Period: Week 48 Values

174.5
U/L (Mean)
Standard Deviation: 97.28

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.

Core Study Period: MRX Baseline Value

130.7
U/L (Mean)
Standard Deviation: 59.12

Week 252 Values

175.3
U/L (Mean)
Standard Deviation: 101.17

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.

Core Study Period: MRX Baseline Values

127.6
U/L (Mean)
Standard Deviation: 60.03

Core Study Period: Week 48 Values

142.4
U/L (Mean)
Standard Deviation: 78.94

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.

Core Study Period: MRX Baseline Value

127.6
U/L (Mean)
Standard Deviation: 60.03

Week 252 Values

145.0
U/L (Mean)
Standard Deviation: 56.50

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.

Core Study Period: MRX Baseline Value

476.9
U/L (Mean)
Standard Deviation: 376.85

Core Study Period: Week 48 Values

440.5
U/L (Mean)
Standard Deviation: 230.60

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.

Core Study Period: MRX Baseline Value

Direct bilirubin

3.8
mg/dL (Mean)
Standard Deviation: 3.858

Total bilirubin

4.47
mg/dL (Mean)
Standard Deviation: 4.837

Core Study Period: Week 48 Values

Direct bilirubin

3.21
mg/dL (Mean)
Standard Deviation: 3.656

Total bilirubin

4.25
mg/dL (Mean)
Standard Deviation: 5.384

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.

Core Study Period: MRX Baseline Value

Direct bilirubin

3.8
mg/dL (Mean)
Standard Deviation: 3.858

Total bilirubin

4.47
mg/dL (Mean)
Standard Deviation: 4.837

Week 252 Values

Direct bilirubin

3.53
mg/dL (Mean)
Standard Deviation: 3.727

Total bilirubin

5.05
mg/dL (Mean)
Standard Deviation: 6.449

Age, Customized

Race (NIH/OMB)

Sex: Female, Male

Core Study Period

LUM001 (Maralixibat)

52-week Follow-up Treatment Period

LUM001 (Maralixibat)

Long-term Follow-up Treatment Period

LUM001 (Maralixibat)

Drop/Withdrawal Reasons

LUM001 (Maralixibat)