Phase 2 Study to Evaluate LUM001 in Combination With Ursodeoxycholic Acid in Patients With Primary Biliary Cirrhosis

Study Overview
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Brief Summary
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The study is a randomized, double-blind, placebo-controlled, multicenter study. It is a 13-week Phase 2 study in adults with primary biliary cirrhosis designed to compare the effect of daily dosing with UDCA in combination with LUM001 or placebo.

Official Title
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A Phase 2, Randomized, Double-blind, Placebo-controlled Study to Evaluate LUM001, an Apical Sodium-dependent Bile Acid Transporter Inhibitor (ASBTi) in Combination With Ursodeoxycholic Acid (UDCA) in Patients With Primary Biliary Cirrhosis

Conditions
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PBC, Primary Biliary Cirrhosis

Intervention / Treatment
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* Drug: LUM001
* Drug: Placebo
* Drug: Ursodeoxycholic Acid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Primary Biliary Cirrhosis Moderate to severe pruritus Taking ursodeoxycholic acid (UDCA) for at least 6 months, or unable to tolerate UDCA Ability to understand and willingness to sign informed consent prior to initiation of any study procedures Exclusion Criteria: History or presence of other concomitant significant liver disease Liver transplant Known HIV infection Women who are pregnant or lactating

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LUM001 and Ursodeoxycholic Acid (UDCA)<br>Administered orally once daily | Drug: LUM001<br> <br> Drug: Ursodeoxycholic Acid<br> <br> * Other names: UDCA;|
| Placebo Comparator: Placebo and Ursodeoxycholic Acid (UDCA)<br>Administered orally once daily | Drug: Placebo<br> <br> Drug: Ursodeoxycholic Acid<br> <br> * Other names: UDCA;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pruritus Using Adult Itch Reported Outcome (ItchRO) Weekly Sum Score at Week 13/ Early Termination (ET) | Pruritus was assessed using ItchRO measure, administered as an electronic diary (eDiary) which was completed by the participants twice daily (morning and evening). (ItchRO) scores ranged from 0 to 10, with 0 representing no itch and 10 representing very severe itching. The highest score between the morning and evening ItchRO reports represented the daily score: a measure of the worst itching over the previous 24-hour period. The weekly sum score was calculated as the sum of the daily scores for the 7 days prior to the time point being reported: 7 days prior to randomization or 7 days prior to Week 13/ET visit. | Baseline and Week 13/ET | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline in Pruritus Using Adult ItchRO Weekly Sum Scores at Weeks 4, 8 and 13 | ItchRO scores had a range from 0 to 10, with 0 representing no itch and 10 representing very severe itching. The highest score between the morning and evening ItchRO reports represented the daily score: a measure of the worst itching over the previous 24-hour period. The weekly sum score was calculated as the sum of the daily scores for the 7 days prior to the time point being reported: 7 days prior to randomization or 7 days prior to Week 13/ET visit. | Baseline, Weeks 4, 8 and 13 | 
| Change From Baseline in Pruritus Using Adult ItchRO Average Daily Scores at Weeks 4, 8, 13, and Last Post-baseline Visit (Week 13/ET) | ItchRO scores had a range from 0 to 10, with 0 representing no itch and 10 representing very severe itching. The highest score between the morning and evening ItchRO reports represented the daily score: a measure of the worst itching over the previous 24-hour period. Adult ItchRO average daily score was the sum of daily scores divided by the number of days adult ItchRO was completed, using the 7 days prior to the reported visit date. | Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET) | 
| Change From Baseline in Alkaline Phosphatase (ALP) at Weeks 4, 8, 13, and Last Post-baseline Visit (Week 13/ET) | Laboratory serum ALP enzyme levels were evaluated using blood samples collected. | Baseline, Weeks 4, 8, 13 and Last Post-baseline (Week 13/ET) | 
| Change From Baseline in 5-D Itch Score at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET) | The 5-D itch (validated instrument to measure pruritus) scale was developed for the multidimensional quantification of pruritus that is sensitive to change over time. The 5-D itch scale included 5 domains (duration, degree, direction, disability, and distribution of pruritus). The total 5-D score was obtained by scoring each of the domains separately and then summing them together. 5-D total scores ranged between 5 (no pruritus) and 25 (most severe pruritus). | Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET) | 
| Change From Baseline in Fasting Serum Bile Acid Level at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET) | Laboratory serum bile acid level levels were evaluated using blood samples collected. | Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET) | 
| Change From Baseline in Bile Acid Synthesis as Measured by Serum 7 Alpha-Hydroxy-4-Cholesten-3-One C4 Level [7 Alpha C4]) at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET) | C4 7 alpha-hydroxy-4-cholesten-3-one is an intermediate in the biochemical synthesis of bile acids from cholesterol and its concentrations reflect the activity of the bile acid synthetic pathway. Elevated levels of C4 indicate bile acid malabsorption. Laboratory C4 levels were evaluated using blood samples collected. | Baseline, Weeks 4, 8, 13 and Last Post-baseline Visit (Week 13/ET) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PBC