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

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

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.

Study Overview

• Status: Completed
• Conditions: Primary Biliary Cirrhosis; PBC
• Intervention / Treatment: Drug: Placebo; Drug: Ursodeoxycholic Acid; Drug: LUM001

• Study Type: Interventional
• Enrollment (Actual): 66
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • University Health Network, Toronto Western Hospital
• United Kingdom
  • London, United Kingdom, NW3 2QG
    • Royal Free Hospital
  • London, United Kingdom, W2 1NY
    • Imperial College London St Mary's Hospital
  • England
    • Birmingham, England, United Kingdom, B15 2TT
      • University of Birmingham
    • Liverpool, England, United Kingdom, L7 8XP
      • Royal Liverpool & Broadgreen University Hospital
    • Newcastle Upon Tyne, England, United Kingdom, NE1 4LP
      • Newcastle University
    • Oxford, England, United Kingdom, OX3 9DU
      • Oxford University Hospitals (John Radcliffe)
• United States
  • California
    • La Jolla, California, United States, 92037
      • Scripps Clinic
    • Sacramento, California, United States, 95817
      • University of California at Davis
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami
  • Illinois
    • Chicago, Illinois, United States, 60637
      • University of Chicago Medical Center
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University
  • Kentucky
    • Louisville, Kentucky, United States, 40202
      • University of Louisville
  • Michigan
    • Detroit, Michigan, United States, 48202
      • Henry Ford Health System
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic
    • Saint Paul, Minnesota, United States, 55114
      • Minnesota Gastroenterology
  • Missouri
    • Saint Louis, Missouri, United States, 63104
      • St. Louis University
  • New York
    • New York, New York, United States, 10021
      • Weill Cornell Medical College
  • Texas
    • Dallas, Texas, United States, 75390
      • University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • Advanced Liver Therapies at St. Lukes Episcopal Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84132
      • University of Utah Health Science Center
  • Virginia
    • Newport News, Virginia, United States, 23602
      • Liver Institute of Virginia
    • Richmond, Virginia, United States, 23249
      • Hunter Holmes McGuire VA Medical Center
  • Washington
    • Seattle, Washington, United States, 98104
      • University of Washington Harborview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: LUM001 and Ursodeoxycholic Acid (UDCA); Administered orally once daily	Drug: Ursodeoxycholic Acid; Other Names: UDCA; Drug: LUM001
Placebo Comparator: Placebo and Ursodeoxycholic Acid (UDCA); Administered orally once daily	Drug: Placebo; Drug: Ursodeoxycholic Acid; Other Names: UDCA

What is the study measuring?

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)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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)

Collaborators and Investigators

• Sponsor: Mirum Pharmaceuticals, Inc.

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: August 1, 2013
• Primary Completion (Actual): April 1, 2015
• Study Completion (Actual): April 1, 2015

Study Registration Dates

• First Submitted: July 17, 2013
• First Submitted That Met QC Criteria: July 17, 2013
• First Posted (Estimate): July 22, 2013

Study Record Updates

• Last Update Posted (Actual): March 27, 2019
• Last Update Submitted That Met QC Criteria: March 15, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: PBC
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Liver Diseases; Biliary Tract Diseases; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Fibrosis; Liver Cirrhosis; Liver Cirrhosis, Biliary; Gastrointestinal Agents; Cholagogues and Choleretics; Ursodeoxycholic Acid
• Other Study ID Numbers: LUM001-201; 2013-000482-36 (EudraCT Number)