- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02057718
Open Label Study to Evaluate Efficacy and Long Term Safety of LUM001 (Maralixibat) in the Treatment of Cholestatic Liver Disease in Patients With Progressive Familial Intrahepatic Cholestasis (INDIGO)
Open Label Study of the Efficacy and Long Term Safety of LUM001 (Maralixibat), an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Pediatric Patients With Progressive Familial Intrahepatic Cholestasis
Study Overview
Status
Intervention / Treatment
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
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Bron, France, 69677
- Hôpital Femme Mère Enfant de Lyon
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Warsaw, Poland, 04-730
- The Children's Memorial Health Institute
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Leeds, United Kingdom, LS1 3EX
- Leeds Teaching Hospital NHS Trust
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London, United Kingdom, SE5 9RS
- Kings College Hospital
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West Midlands
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Birmingham, West Midlands, United Kingdom, B4 6NH
- Birmingham Children's Hospital
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California
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Los Angeles, California, United States, 90027
- Children's Hospital Los Angeles
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Colorado
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Aurora, Colorado, United States, 80045
- Children's Hospital Colorado
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Ohio
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Cincinnati, Ohio, United States, 45229
- Cincinnati Children's Hospital Medical Center
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Pennsylvania
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Philadelphia, Pennsylvania, United States, 19104
- The Children's Hospital of Philadelphia
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Pittsburgh, Pennsylvania, United States, 15224
- Children's Hospital of Pittsburgh of UPMC
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria
1. Male or female subjects between the ages of 12 months and 18 years inclusive.
2. Diagnosis of PFIC based on:
- Intrahepatic cholestasis manifest by total serum bile acid >3x upper limit of normal (ULN) for age and, b or c:
- Two documented mutant alleles in ATP8B1, or ABCB11.
Evidence of chronic liver disease, excluding those listed in (see Section 16.3), with one or more of the following criteria:
- Duration of biochemical or clinical abnormalities of >6 months, or
- Pathologic evidence of progressive liver disease, or
- Sibling of known individual affected by PFIC (predicted to be chronic).
3. GGTP <100 IU/L at screening. 4. Females of childbearing potential must have a negative urine or serum pregnancy test [β human chorionic gonadotropin (β-hCG)] during screening and a negative urine pregnancy test at the Baseline (Day 0) visit.
5. Males and females of child-bearing potential who are sexually active, or are not currently sexually active during the study, but become sexually active during the period of the study and 30 days following the last dose of study drug, must agree and use acceptable contraception during the trial, as described in Section 8.7.1. of the protocol 6. Informed consent and assent (per IRB/EC) as appropriate. 7. Access to phone for scheduled calls from study site. 8. Caregivers and children above the age of assent must have the ability to read and understand one of the following languages: English, Spanish, US Spanish, French, German or Polish.
9. Subjects expected to have a consistent caregiver(s) for the duration of the first 13 weeks of the study.
10. Caregivers (and age appropriate subjects) must be willing and able to use an eDiary device as required by the study. To accommodate potential cultural restrictions within the FIC1 affected population a paper version of the ItchRO diary will be made available.
11. Caregivers (and age appropriate subjects) using the eDiary must digitally accept the licensing agreement in the eDiary software at the outset of the study.
12. Caregivers (and age appropriate subjects) must complete at least 10 eDiary reports (morning or evening) during each of two consecutive weeks of the screening period, prior to assignment (maximum possible reports = 14 per week). Subjects using a paper diary must complete the same number of reports within the same timeframe
Exclusion Criteria
- Chronic diarrhea requiring specific intravenous fluid or nutritional intervention for the diarrhea and/or its sequelae.
- Surgical disruption of the enterohepatic circulation at the time at screening. Subjects who have undergone reversal of a prior surgical procedure intended to disrupt enterohepatic circulation and who and have a permanently restored flow of bile acids from the liver to the terminal ileum may be eligible for the study upon consultation with the Medical Monitor.
- Liver transplant.
- Decompensated cirrhosis [international normalized ratio (INR) > 1.5, albumin < 30 g/L, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy].
- ALT >15×ULN at screening.
- History or presence of other liver disease (see Section 16.3).
- History or presence of any other disease or condition known to interfere with the absorption, distribution, metabolism or excretion of drugs, including bile salt metabolism in the intestine (e.g., inflammatory bowel disease).
- Liver mass on imaging.
- Known diagnosis of human immunodeficiency virus (HIV) infection.
- Cancers except for in situ carcinoma, or cancers treated at least 5 years prior to screening with no evidence of recurrence.
- Any female who is pregnant or lactating or who is planning to become pregnant within 20 weeks of assignment.
- Any known history of alcohol or substance abuse.
- Administration of bile acid or lipid binding resins within 30 days prior to Baseline / Day 0 and throughout the trial.
- Administration of sodium phenylbutyrate within 30 days prior to Baseline / Day 0 and throughout the trial.
- Investigational drug, biologic, or medical device within 30 days prior to screening, or 5 half-lives of the study agent, whichever is longer.
- History of non-adherence to medical regimens, unreliability, mental instability or incompetence that could compromise the validity of informed consent or lead to non-adherence with the study protocol based on Investigator judgment.
- Any other conditions or abnormalities which, in the opinion of the Investigator or Medical monitor, may compromise the safety of the subject, or interfere with the subject participating in or completing the study
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Experimental: LUM001 (Maralixibat)
Participants will receive LUM001, also known as Maralixibat (MRX) twice a day (BID).
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LUM001 also known as Maralixibat (MRX) oral dose up to twice a day (BID).
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Change From Baseline to Endpoint (Week 13) in Fasting sBA Level
Time Frame: Baseline (Day 0) to Week 13
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Baseline (Day 0) to Week 13
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
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Change From Baseline to Week 13/ET in Pruritus as Measured by ItchRO(Obs)
Time Frame: Baseline (Day 0) to Week 13
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This secondary efficacy endpoint is the change from baseline to Week 13 in pruritus as measured by ItchRO(Obs) weekly average morning score.
ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe).
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Baseline (Day 0) to Week 13
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Change From Baseline to Week 13/ET in Pruritus as Measured by ItchRO(Pt)
Time Frame: Baseline (Day 0) to Week 13
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This secondary efficacy endpoint is the change from baseline to Week 13 in pruritus as measured by ItchRO(Pt) weekly average morning score.
ItchRO scores range from 0 to 4; the higher score indicates increasing itch severity (0 = none; 4 = very severe).
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Baseline (Day 0) to Week 13
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Change From Baseline to Week 13/ET in ALT
Time Frame: Baseline (Day 0) to Week 13
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Baseline (Day 0) to Week 13
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Change From Baseline to Week 13/ET in Total Bilirubin
Time Frame: Baseline (Day 0) to Week 13
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Baseline (Day 0) to Week 13
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Change From Baseline to Week 13/ET in Direct Bilirubin
Time Frame: Baseline (Day 0) to Week 13
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Baseline (Day 0) to Week 13
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Study Director, Mirum
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- LUM001-501
- 2013-003833-14 (EudraCT Number)
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Progressive Familial Intrahepatic Cholestasis (PFIC)
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Mirum Pharmaceuticals, Inc.CompletedProgressive Familial Intrahepatic Cholestasis (PFIC)Italy, United States, Argentina, France, Singapore, United Kingdom, Austria, Brazil, Mexico, Lebanon, Germany, Turkey, Poland, Belgium, Canada, Colombia, Hungary
-
TakedaActive, not recruitingProgressive Familial Intrahepatic Cholestasis (PFIC)Japan
-
Mirum Pharmaceuticals, Inc.Active, not recruitingProgressive Familial Intrahepatic Cholestasis (PFIC)United States, Argentina, France, Singapore, United Kingdom, Belgium, Turkey, Austria, Brazil, Canada, Colombia, Germany, Italy, Lebanon, Mexico, Poland
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Mirum Pharmaceuticals, Inc.WithdrawnProgressive Familial Intrahepatic Cholestasis (PFIC)
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Institute of Liver and Biliary Sciences, IndiaKEM Hospital Research Centre; Apollo Hospital, New Delhi, India; Jaslok Hospital... and other collaboratorsRecruitingProgressive Familial Intrahepatic CholestasisIndia
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University Medical Center GroningenEnrolling by invitationProgressive Familial Intrahepatic CholestasisNetherlands
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AlbireoActive, not recruitingProgressive Familial Intrahepatic CholestasisUnited States, Spain, Netherlands, United Kingdom, Turkey, Canada, Italy, Germany, France, Israel, Australia, Belgium, Poland, Saudi Arabia, Sweden
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AlbireoApproved for marketingProgressive Familial Intrahepatic CholestasisUnited States
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National Liver Institute, EgyptUnknownProgressive Familial Intrahepatic CholestasisEgypt
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Mirum Pharmaceuticals, Inc.CompletedAlagille Syndrome | Progressive Familial Intrahepatic CholestasisUnited States, Canada
Clinical Trials on LUM001 (Maralixibat)
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Mirum Pharmaceuticals, Inc.CompletedAlagille SyndromeFrance, Belgium, Poland, Australia, Spain, United Kingdom
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Mirum Pharmaceuticals, Inc.Completed
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Mirum Pharmaceuticals, Inc.Lumena Pharmaceuticals, Inc.; Childhood Liver Disease Research and Education...Completed
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Mirum Pharmaceuticals, Inc.Active, not recruitingCholestatic Liver Disease | Alagille Syndrome | Progressive Familial Intrahepatic CholestasisUnited States, United Kingdom, France, Belgium, Poland, Brazil, Mexico
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Mirum Pharmaceuticals, Inc.CompletedBiliary AtresiaUnited States, United Kingdom, China, Taiwan, Germany, Poland, Singapore, Vietnam
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Mirum Pharmaceuticals, Inc.CompletedProgressive Familial Intrahepatic Cholestasis (PFIC)Italy, United States, Argentina, France, Singapore, United Kingdom, Austria, Brazil, Mexico, Lebanon, Germany, Turkey, Poland, Belgium, Canada, Colombia, Hungary
-
Mirum Pharmaceuticals, Inc.Completed
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Mirum Pharmaceuticals, Inc.Active, not recruitingCholestatic Liver DiseaseUnited States, France, United Kingdom, Canada, Belgium, Poland, Australia, Spain
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TakedaActive, not recruiting
-
TakedaActive, not recruitingProgressive Familial Intrahepatic Cholestasis (PFIC)Japan