Evaluation of LUM001 in the Reduction of Pruritus in Alagille Syndrome (ITCH)

The Evaluation of the Intestinal Bile Acid Transport (IBAT) Inhibitor LUM001 in the Reduction of Pruritus in Alagille Syndrome, a Cholestatic Liver Disease

The study is a randomized, double-blind, placebo-controlled study in children with Alagille Syndrome (ALGS). The study will investigate the effects of LUM001, compared to placebo, on pruritus, serum bile acids, liver enzymes, and other biochemical markers in patients with ALGS.

Study Overview

• Status: Completed
• Conditions: Alagille Syndrome
• Intervention / Treatment: Drug: Placebo; Drug: LUM001

• Study Type: Interventional
• Enrollment (Actual): 37
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5G 1X8
      • The Hospital for Sick Children
• United States
  • California
    • Los Angeles, California, United States, 90027
      • Children's Hospital Los Angeles
    • San Francisco, California, United States, 94143
      • University of California at San Francisco
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Children's Hospital Colorado
  • Georgia
    • Atlanta, Georgia, United States, 30322
      • Children's Healthcare of Atlanta
  • Illinois
    • Chicago, Illinois, United States, 60611
      • Ann & Robert H. Lurie Children's Hospital of Chicago
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Riley Hospital for Children
  • Ohio
    • Cincinnati, Ohio, United States, 45229
      • Cincinnati Children's Hospital Medical Center
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • The Children's Hospital of Philadelphia
    • Pittsburgh, Pennsylvania, United States, 15224
      • Children's Hospital of Pittsburgh of UPMC
  • Texas
    • Houston, Texas, United States, 77030
      • Baylor College of Medicine/Texas Children's Hospital
  • Utah
    • Salt Lake City, Utah, United States, 84113
      • University of Utah
  • Washington
    • Seattle, Washington, United States, 98105
      • Seattle Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 18 years (ADULT, CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Diagnosis of Alagille Syndrome
2. Evidence of cholestasis
3. Moderate to severe pruritus
4. Ability to understand and willingness to sign informed consent/assent prior to initiation of any study procedures

Exclusion Criteria:

1. Surgical disruption of the enterohepatic circulation
2. Liver transplant
3. History or presence of other concomitant liver disease
4. Females who are pregnant or lactating
5. Known HIV infection

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: TRIPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
PLACEBO_COMPARATOR: Placebo; Placebo administered orally once each day	Drug: Placebo; Placebo administered orally
EXPERIMENTAL: LUM001; LUM001 for oral administration	Drug: LUM001; LUM001 administered orally

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Endpoint (Week 13/Early Termination) in Pruritus	Pruritus was assessed using Itch report outcome measure (ItchRO[Obs]), administered as an electronic diary (eDiary) which was completed by the participants twice daily (morning and evening). ItchRO(Obs) score ranged from 0 to 4, with the higher score indicating increasing itch severity. The highest score between the morning and evening ItchRO(Obs) reports represented the daily score: a measure of the worst itching over the previous 24-hour period.	Baseline, Week 13/Early Termination

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline to Endpoint (Week 13/Early Termination) in Fasting Serum Bile Acid (sBA) Level	Fasting sBA level was measured by using a liquid chromatography mass spectrometry method.	Baseline, Week 13/Early Termination
Change From Baseline to Endpoint (Week 13/Early Termination) in Liver Enzyme Levels	Liver enzyme levels of alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase and gamma glutamyl transferase were reported here.	Baseline, Week 13/Early Termination
Change From Baseline to Endpoint (Week 13/Early Termination) in Total and Direct Bilirubin Concentrations	Liver enzyme levels of total bilirubin and direct bilirubin were reported here.	Baseline, Week 13/Early Termination

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 AE was any unfavorable and unintended sign (including a clinically significant abnormal laboratory finding, for example), symptom, or disease temporally associated with the study or use of investigational drug product, whether or not the AE was considered related to the investigational drug product. A serious adverse event (SAE) was 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 experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.TEAEs were defined as AEs/SAEs that started or worsened after the study drug treatment.	From the start of study drug administration up to Week 17

Collaborators and Investigators

• Sponsor: Mirum Pharmaceuticals, Inc.
• Collaborators: Childhood Liver Disease Research and Education Network

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 24, 2014
• Primary Completion (ACTUAL): November 16, 2016
• Study Completion (ACTUAL): November 16, 2016

Study Registration Dates

• First Submitted: February 5, 2014
• First Submitted That Met QC Criteria: February 5, 2014
• First Posted (ESTIMATE): February 7, 2014

Study Record Updates

• Last Update Posted (ACTUAL): March 26, 2019
• Last Update Submitted That Met QC Criteria: March 15, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Cardiovascular Diseases; Skin Diseases; Disease; Congenital Abnormalities; Liver Diseases; Genetic Diseases, Inborn; Skin Manifestations; Biliary Tract Diseases; Heart Defects, Congenital; Cardiovascular Abnormalities; Abnormalities, Multiple; Bile Duct Diseases; Cholestasis, Intrahepatic; Cholestasis; Syndrome; Pruritus; Alagille Syndrome
• Other Study ID Numbers: LUM001-301