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

Phase 2
Completed
Conditions
Primary Biliary Cirrhosis
PBC
Interventions
Registration Number
NCT01904058
Lead Sponsor
Mirum Pharmaceuticals, Inc.
Brief 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.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
66
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Placebo and Ursodeoxycholic Acid (UDCA)PlaceboAdministered orally once daily
LUM001 and Ursodeoxycholic Acid (UDCA)LUM001Administered orally once daily
LUM001 and Ursodeoxycholic Acid (UDCA)Ursodeoxycholic AcidAdministered orally once daily
Placebo and Ursodeoxycholic Acid (UDCA)Ursodeoxycholic AcidAdministered orally once daily
Primary Outcome Measures
NameTimeMethod
Change From Baseline in Pruritus Using Adult Itch Reported Outcome (ItchRO) Weekly Sum Score at Week 13/ Early Termination (ET)Baseline and Week 13/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.

Secondary Outcome Measures
NameTimeMethod
Change From Baseline in Fasting Serum Bile Acid Level at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET)Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET)

Laboratory serum bile acid level levels were evaluated using blood samples collected.

Change From Baseline in Pruritus Using Adult ItchRO Weekly Sum Scores at Weeks 4, 8 and 13Baseline, 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.

Change From Baseline in Pruritus Using Adult ItchRO Average Daily Scores at Weeks 4, 8, 13, and Last Post-baseline Visit (Week 13/ET)Baseline, 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.

Change From Baseline in Alkaline Phosphatase (ALP) at Weeks 4, 8, 13, and Last Post-baseline Visit (Week 13/ET)Baseline, Weeks 4, 8, 13 and Last Post-baseline (Week 13/ET)

Laboratory serum ALP enzyme levels were evaluated using blood samples collected.

Change From Baseline in 5-D Itch Score at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET)Baseline, 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).

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)Baseline, 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.

Trial Locations

Locations (24)

Minnesota Gastroenterology

🇺🇸

Saint Paul, Minnesota, United States

Henry Ford Health System

🇺🇸

Detroit, Michigan, United States

Scripps Clinic

🇺🇸

La Jolla, California, United States

University of California at Davis

🇺🇸

Sacramento, California, United States

University of Miami

🇺🇸

Miami, Florida, United States

Indiana University

🇺🇸

Indianapolis, Indiana, United States

Mayo Clinic

🇺🇸

Rochester, Minnesota, United States

University of Chicago Medical Center

🇺🇸

Chicago, Illinois, United States

University of Louisville

🇺🇸

Louisville, Kentucky, United States

Royal Liverpool & Broadgreen University Hospital

🇬🇧

Liverpool, England, United Kingdom

Liver Institute of Virginia

🇺🇸

Newport News, Virginia, United States

University of Birmingham

🇬🇧

Birmingham, England, United Kingdom

St. Louis University

🇺🇸

Saint Louis, Missouri, United States

Weill Cornell Medical College

🇺🇸

New York, New York, United States

Advanced Liver Therapies at St. Lukes Episcopal Hospital

🇺🇸

Houston, Texas, United States

University of Texas Southwestern Medical Center

🇺🇸

Dallas, Texas, United States

University of Utah Health Science Center

🇺🇸

Salt Lake City, Utah, United States

Hunter Holmes McGuire VA Medical Center

🇺🇸

Richmond, Virginia, United States

Newcastle University

🇬🇧

Newcastle Upon Tyne, England, United Kingdom

University Health Network, Toronto Western Hospital

🇨🇦

Toronto, Ontario, Canada

Oxford University Hospitals (John Radcliffe)

🇬🇧

Oxford, England, United Kingdom

Royal Free Hospital

🇬🇧

London, United Kingdom

Imperial College London St Mary's Hospital

🇬🇧

London, United Kingdom

University of Washington Harborview Medical Center

🇺🇸

Seattle, Washington, United States

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