Safety and Efficacy Study of LUM001 in the Treatment of Cholestatic Liver Disease in Patients With Alagille Syndrome

Study Overview
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Brief Summary
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The study is a randomized, double-blind, placebo-controlled study to evaluate the safety and tolerability of LUM001. Efficacy will be assessed by evaluating the effect of LUM001 versus placebo on the biochemical markers and pruritus associated with Alagille Syndrome.

Official Title
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A Randomized, Double-blind, Placebo-controlled Study to Evaluate the Safety and Efficacy of LUM001, an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Paediatric Patients With Alagille Syndrome

Conditions
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Alagille Syndrome

Intervention / Treatment
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* Drug: LUM001
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Alagille Syndrome Evidence of cholestasis Moderate to severe pruritus Ability to understand and willingness to sign informed consent/assent prior to initiation of any study procedures Exclusion Criteria: Surgical disruption of the enterohepatic circulation Liver transplant History or presence of other concomitant liver disease Females who are pregnant or lactating Known HIV infection

Ages Eligible for Study
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Minimum Age: 12 Months
Maximum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LUM001<br>LUM001 administered orally once each day | Drug: LUM001<br> <br> |
| Placebo Comparator: Placebo<br>Placebo administered orally once each day | Drug: Placebo<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 13 (End of Treatment) in Fasting Serum Bile Acid Level | Participants were required to fast for at least 4 hours; only water was permitted prior to collection. A negative change from baseline indicates that the level of bile acid decreased. | Baseline to 13 weeks or end of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to Week 13 (End of Treatment) in Liver Enzymes | Analysis of liver enzymes included alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP). A negative change from baseline indicates that the level of that enzyme decreased. | Baseline to 13 weeks or end of treatment | 
| Change From Baseline to Week 13 (End of Treatment) in Pruritus as Measured by The Patient And Observer Itch Reported Outcome (ItchRO) Average Daily Scores | The ItchRO was administered as a twice daily electronic diary (eDiary). Children ≥9 years of age completed the patient ItchRO; those between the ages of 5 and 8 completed the patient ItchRO with the assistance of their caregiver. There was no patient report for subjects under the age of 5. ItchRO scores range from 0 to 4, with the higher score indicating increasing itch severity. ItchRO average daily scores were calculated as the sum of daily scores (ie, the maximum of morning and evening scores) divided by the number of days. The average daily score was calculated by using the 7 days pre-treatment for baseline, and the last 7 days of treatment for Week 13. A negative change from Baseline indicates that itch severity decreased. | Baseline to 13 weeks or end of treatment |