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

Primary Biliary Cirrhosis Clinical Trial

— CLARITY  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01904058
• Other study ID #: LUM001-201
• Secondary ID: 2013-000482-36
• Status: Completed
• Phase: Phase 2
• Start date: August 2013
• Est. completion date: April 2015

Study information

• Verified date: March 2019
• Source: Mirum Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 66
• Est. completion date: April 2015
• Est. primary completion date: April 2015
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

Inclusion Criteria:

1. Diagnosis of Primary Biliary Cirrhosis

2. Moderate to severe pruritus

3. Taking ursodeoxycholic acid (UDCA) for at least 6 months, or unable to tolerate UDCA

4. Ability to understand and willingness to sign informed consent prior to initiation of any study procedures

Exclusion Criteria:

1. History or presence of other concomitant significant liver disease

2. Liver transplant

3. Known HIV infection

4. Women who are pregnant or lactating

Related Conditions & MeSH terms

• Fibrosis
• Liver Cirrhosis
• Liver Cirrhosis, Biliary
• PBC
• Primary Biliary Cirrhosis

Intervention

Drug:
• LUM001

• Placebo

• Ursodeoxycholic Acid

Locations

Country	Name	City	State
Canada	University Health Network, Toronto Western Hospital	Toronto	Ontario
United Kingdom	University of Birmingham	Birmingham	England
United Kingdom	Royal Liverpool & Broadgreen University Hospital	Liverpool	England
United Kingdom	Imperial College London St Mary's Hospital	London
United Kingdom	Royal Free Hospital	London
United Kingdom	Newcastle University	Newcastle Upon Tyne	England
United Kingdom	Oxford University Hospitals (John Radcliffe)	Oxford	England
United States	University of Chicago Medical Center	Chicago	Illinois
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Advanced Liver Therapies at St. Lukes Episcopal Hospital	Houston	Texas
United States	Indiana University	Indianapolis	Indiana
United States	Scripps Clinic	La Jolla	California
United States	University of Louisville	Louisville	Kentucky
United States	University of Miami	Miami	Florida
United States	Weill Cornell Medical College	New York	New York
United States	Liver Institute of Virginia	Newport News	Virginia
United States	Hunter Holmes McGuire VA Medical Center	Richmond	Virginia
United States	Mayo Clinic	Rochester	Minnesota
United States	University of California at Davis	Sacramento	California
United States	St. Louis University	Saint Louis	Missouri
United States	Minnesota Gastroenterology	Saint Paul	Minnesota
United States	University of Utah Health Science Center	Salt Lake City	Utah
United States	University of Washington Harborview Medical Center	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Mirum Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Canada,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)	An adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of an investigational product, whether or not considered related to the product. A serious adverse event (SAE) was defined as an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged in-patient hospitalization; life-threatening; persistent or significant disability/incapacity; congenital anomaly or birth defect; an important medical event that did not meet any of the above criteria but jeopardized the participant or required medical or surgical intervention to prevent one of the outcomes listed above. A TEAE was defined as any AE that occurred during the study, from the start of investigational product dosing through the end of the study (13 weeks of treatment period (or ET) + 14 days ]), or that worsened since the start of dosing.	From the first dose of study drug until the 13 weeks of treatment period (or ET) + 14 days (approximately 15 weeks)
Primary	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	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
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)
Secondary	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)

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