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

Primary Purpose

PBC, Primary Biliary Cirrhosis

Status
Completed
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
LUM001
Placebo
Ursodeoxycholic Acid
Sponsored by
Mirum Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for PBC focused on measuring PBC

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Scripps Clinic
  • University of California at Davis
  • University of Miami
  • University of Chicago Medical Center
  • Indiana University
  • University of Louisville
  • Henry Ford Health System
  • Mayo Clinic
  • Minnesota Gastroenterology
  • St. Louis University
  • Weill Cornell Medical College
  • University of Texas Southwestern Medical Center
  • Advanced Liver Therapies at St. Lukes Episcopal Hospital
  • University of Utah Health Science Center
  • Liver Institute of Virginia
  • Hunter Holmes McGuire VA Medical Center
  • University of Washington Harborview Medical Center
  • University Health Network, Toronto Western Hospital
  • University of Birmingham
  • Royal Liverpool & Broadgreen University Hospital
  • Newcastle University
  • Oxford University Hospitals (John Radcliffe)
  • Royal Free Hospital
  • Imperial College London St Mary's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

LUM001 and Ursodeoxycholic Acid (UDCA)

Placebo and Ursodeoxycholic Acid (UDCA)

Arm Description

Administered orally once daily

Administered orally once daily

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.
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).
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.
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.

Full Information

First Posted
July 17, 2013
Last Updated
March 15, 2019
Sponsor
Mirum Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT01904058
Brief Title
Phase 2 Study to Evaluate LUM001 in Combination With Ursodeoxycholic Acid in Patients With Primary Biliary Cirrhosis
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
March 2019
Overall Recruitment Status
Completed
Study Start Date
August 2013 (undefined)
Primary Completion Date
April 2015 (Actual)
Study Completion Date
April 2015 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mirum Pharmaceuticals, Inc.

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
PBC, Primary Biliary Cirrhosis
Keywords
PBC

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigator
Allocation
Randomized
Enrollment
66 (Actual)

8. Arms, Groups, and Interventions

Arm Title
LUM001 and Ursodeoxycholic Acid (UDCA)
Arm Type
Experimental
Arm Description
Administered orally once daily
Arm Title
Placebo and Ursodeoxycholic Acid (UDCA)
Arm Type
Placebo Comparator
Arm Description
Administered orally once daily
Intervention Type
Drug
Intervention Name(s)
LUM001
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Type
Drug
Intervention Name(s)
Ursodeoxycholic Acid
Other Intervention Name(s)
UDCA
Primary Outcome Measure Information:
Title
Change From Baseline in Pruritus Using Adult Itch Reported Outcome (ItchRO) Weekly Sum Score at Week 13/ Early Termination (ET)
Description
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.
Time Frame
Baseline and Week 13/ET
Secondary Outcome Measure Information:
Title
Change From Baseline in Pruritus Using Adult ItchRO Weekly Sum Scores at Weeks 4, 8 and 13
Description
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.
Time Frame
Baseline, Weeks 4, 8 and 13
Title
Change From Baseline in Pruritus Using Adult ItchRO Average Daily Scores at Weeks 4, 8, 13, and Last Post-baseline Visit (Week 13/ET)
Description
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.
Time Frame
Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET)
Title
Change From Baseline in Alkaline Phosphatase (ALP) at Weeks 4, 8, 13, and Last Post-baseline Visit (Week 13/ET)
Description
Laboratory serum ALP enzyme levels were evaluated using blood samples collected.
Time Frame
Baseline, Weeks 4, 8, 13 and Last Post-baseline (Week 13/ET)
Title
Change From Baseline in 5-D Itch Score at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET)
Description
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).
Time Frame
Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET)
Title
Change From Baseline in Fasting Serum Bile Acid Level at Weeks 4, 8, 13, and Last Post -Baseline Visit (Week 13/ET)
Description
Laboratory serum bile acid level levels were evaluated using blood samples collected.
Time Frame
Baseline, Weeks 4, 8, 13 and Last Post-baseline visit (Week 13/ET)
Title
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)
Description
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.
Time Frame
Baseline, Weeks 4, 8, 13 and Last Post-baseline Visit (Week 13/ET)
Other Pre-specified Outcome Measures:
Title
Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs)
Description
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.
Time Frame
From the first dose of study drug until the 13 weeks of treatment period (or ET) + 14 days (approximately 15 weeks)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Study Director
Organizational Affiliation
Mirum
Official's Role
Study Director
Facility Information:
Facility Name
Scripps Clinic
City
La Jolla
State/Province
California
ZIP/Postal Code
92037
Country
United States
Facility Name
University of California at Davis
City
Sacramento
State/Province
California
ZIP/Postal Code
95817
Country
United States
Facility Name
University of Miami
City
Miami
State/Province
Florida
ZIP/Postal Code
33136
Country
United States
Facility Name
University of Chicago Medical Center
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60637
Country
United States
Facility Name
Indiana University
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46202
Country
United States
Facility Name
University of Louisville
City
Louisville
State/Province
Kentucky
ZIP/Postal Code
40202
Country
United States
Facility Name
Henry Ford Health System
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48202
Country
United States
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States
Facility Name
Minnesota Gastroenterology
City
Saint Paul
State/Province
Minnesota
ZIP/Postal Code
55114
Country
United States
Facility Name
St. Louis University
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63104
Country
United States
Facility Name
Weill Cornell Medical College
City
New York
State/Province
New York
ZIP/Postal Code
10021
Country
United States
Facility Name
University of Texas Southwestern Medical Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75390
Country
United States
Facility Name
Advanced Liver Therapies at St. Lukes Episcopal Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
University of Utah Health Science Center
City
Salt Lake City
State/Province
Utah
ZIP/Postal Code
84132
Country
United States
Facility Name
Liver Institute of Virginia
City
Newport News
State/Province
Virginia
ZIP/Postal Code
23602
Country
United States
Facility Name
Hunter Holmes McGuire VA Medical Center
City
Richmond
State/Province
Virginia
ZIP/Postal Code
23249
Country
United States
Facility Name
University of Washington Harborview Medical Center
City
Seattle
State/Province
Washington
ZIP/Postal Code
98104
Country
United States
Facility Name
University Health Network, Toronto Western Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
Facility Name
University of Birmingham
City
Birmingham
State/Province
England
ZIP/Postal Code
B15 2TT
Country
United Kingdom
Facility Name
Royal Liverpool & Broadgreen University Hospital
City
Liverpool
State/Province
England
ZIP/Postal Code
L7 8XP
Country
United Kingdom
Facility Name
Newcastle University
City
Newcastle Upon Tyne
State/Province
England
ZIP/Postal Code
NE1 4LP
Country
United Kingdom
Facility Name
Oxford University Hospitals (John Radcliffe)
City
Oxford
State/Province
England
ZIP/Postal Code
OX3 9DU
Country
United Kingdom
Facility Name
Royal Free Hospital
City
London
ZIP/Postal Code
NW3 2QG
Country
United Kingdom
Facility Name
Imperial College London St Mary's Hospital
City
London
ZIP/Postal Code
W2 1NY
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
http://www.lumenapharma.com
Description
Related Info

Learn more about this trial

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

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