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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 9 November 2020
Main ID:  EUCTR2013-005373-43-PL
Date of registration: 09/07/2014
Prospective Registration: Yes
Primary sponsor: Mirum Pharmaceuticals,Inc.
Public title: The purpose of this study is to evaluate a drug (LUM001 also known as SHP625) that may help treat the liver and control itching in Alagille Syndrome. In the Optional Follow-up Treatment Period (after Week 48), all eligible children treated in the LUM001-304 study will be offered to continue the study drug treatment until the subjects are eligible to enter another LUM001 study or LUM001 is available commercially, or the sponsor stops the program or development in this indication.
Scientific title: Long-Term, Open-Label Study with a Double-Blind, Placebo Controlled, Randomized Drug Withdrawal Period of LUM001, an Apical Sodium-Dependent Bile Acid Transporter Inhibitor (ASBTi), in Patients with Alagille Syndrome - ICONIC
Date of first enrolment:
Target sample size: 30
Recruitment status: Not Recruiting
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-005373-43
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: yes Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: yes Other trial design description: This trial also contains a double blind, placebo-controlled, randomized drug withdrawal period If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 2  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
Australia Belgium France Poland Spain United Kingdom
Contacts
Name: Chief Scientific Officer   
Address:  950 Tower Lane, Suite 1050 94404 Foster City, California United States
Telephone: 0016503255156
Email: medinfo@mirumpharma.com
Affiliation:  MirumPharmaceuticals, Inc.
Name: Chief Scientific Officer   
Address:  950 Tower Lane, Suite 1050 94404 Foster City, California United States
Telephone: 0016503255156
Email: medinfo@mirumpharma.com
Affiliation:  MirumPharmaceuticals, Inc.
Key inclusion & exclusion criteria
Inclusion criteria:
To participate in this study subjects must meet all of the following criteria:
1. Male or female between the ages of 12 months and 18 years inclusive.
2. Diagnosis of ALGS based on the diagnostic criteria.
3. Evidence of cholestasis (one or more of the following):
a. Total serum bile acid >3x ULN for age.
b. Conjugated bilirubin >1 mg/dL.
c. Fat soluble vitamin deficiency otherwise unexplainable.
d. GGT >3x ULN for age.
e. Intractable pruritus explainable only by liver disease.
4. Females of childbearing potential must have a negative serum pregnancy test during
Screening.
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 for 30 days following the last dose of study drug, must agree to use acceptable contraception during the trial.
6. Subject is expected to have a consistent caregiver(s) for the duration of the study.
7. Informed consent and assent (per IRB/IEC) as appropriate.
8. Access to phone for scheduled calls from study site.
9. Caregivers (and age appropriate subjects) must be willing and able to use an eDiary device during the study.
10. Caregivers (and age appropriate subjects) must digitally accept the licensing agreement
in the eDiary software.
11. 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 (maximum possible reports = 14 per week).
12. Average daily score >2 on the Itch Reported Outcome (ItchRO™) questionnaire (maximum possible daily score of 4) for two consecutive weeks in the screening period, prior to dosing. A daily score is the higher of the scores for the morning and evening ItchRO. The average daily score is the sum of all daily scores divided by the number of days the ItchRO was completed.

Inclusion Criteria for subjects with LUM001 dosing interruption <7 days, or =7 days are:
Subjects will be considered eligible for the long-term optional follow-up treatment period if they meet the following criteria:
1. The subject has either:
a. completed the protocol through the Week 48 visit with no major safety concerns
OR
b. discontinued due to safety reasons judged unrelated to the study drug, and
laboratory results have returned to levels acceptable for this patient population or individual and subject does not meet any of the protocol’s stopping rules at the time of entry into the follow-up period. The decision will be made by the investigator in consultation with the sponsor medical monitor. [Subjects who were discontinued for other reasons will be considered on an individual basis.]
2. Females of childbearing potential must have a negative urine or serum pregnancy test (ß-human chorionic gonadotropin [ß-hCG]) at the time of entry into the long term optional follow-up treatment period.
3. 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.
4. Informed consent and assent (per IRB/EC) as appropriate.
5. Access to phone for scheduled calls from study site.
6. Caregivers (and age appropriate subjects) must be willing and able to use an eDiary device during the study.
Are the trial subjects under 1

Exclusion criteria:
Subjects will be excluded from the study if they meet any of the following criteria:
1. Chronic diarrhea requiring ongoing intravenous fluid or nutritional intervention.
2. Surgical interruption of the enterohepatic circulation.
3. Previous liver transplant.
4. Decompensated cirrhosis (ALT >15 x ULN, INR >1.5 [unresponsive to vitamin K
therapy], albumin <3.0 g/dL, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy).
5. History or presence of other concomitant liver disease.
6. 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 (eg, inflammatory bowel disease).
7. History or presence of gallstones or kidney stones.
8. Known diagnosis of human immunodeficiency virus (HIV) infection.
9. Cancers, except for in situ carcinoma, or cancers treated at least 5 years prior to Screening with no evidence of recurrence.
10. Recent medical history or current status that suggests that the subject may be unable to complete the study.
11. Any female who is pregnant or lactating or who is planning to become pregnant during the study period.
12. Known history of alcohol or substance abuse.
13. Administration of bile acid or lipid binding resins within 28 days prior to screening and throughout the trial.
14. Known hypersensitivity to LUM001or any of its components.
15. Receipt of investigational drug, biologic, or medical device within 28 days prior to Screening, or 5 half-lives of the study agent, whichever is longer.
16. History of non-adherence to medical regimens, unreliability, mental instability or incompetence that could compromise the validity of informed consent or lead to nonadherence with the study protocol based upon investigator judgment.
17. 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.
18. Subjects weighing over 50 kg at screening

Exclusion Criteria for Subjects with LUM001 dosing interruption=7 days are:
All exclusion criteria mentioned for the core study apply upon entry into the long-term optional follow-up period, with the exception of exclusion criterion #18 (subjects weighing over 50 kg at screening).


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Alagille syndrome (ALGS) is an autosomal dominant with variable penetration genetic multisystem disorder. The clinical diagnosis is based on the presence of intrahepatic bile duct paucity on liver biopsy in association with at least three of the major clinical features: chronic cholestasis, cardiac disease, skeletal abnormalities, ocular abnormalities and characteristic facial features.
MedDRA version: 20.0 Level: PT Classification code 10053870 Term: Alagille syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
Intervention(s)

Product Name: LUM001
Product Code: LUM001
Pharmaceutical Form: Oral solution
INN or Proposed INN: Maralixibat chloride
CAS Number: 228113-66-4
Current Sponsor code: LUM001
Concentration unit: µg/kg microgram(s)/kilogram
Concentration type: up to
Concentration number: 800-
Pharmaceutical form of the placebo: Oral solution
Route of administration of the placebo: Oral use

Primary Outcome(s)
Main Objective: The objectives are to evaluate:
1. The long-term safety and tolerability of LUM001 in children with ALGS.
2. The effect of LUM001 on serum bile acid levels in children with ALGS.
3. The effect of LUM001 on biochemical markers of cholestasis and liver
disease in children with ALGS.
4. The effect of LUM001 on pruritus in children with ALGS.
5. The long-term effect of LUM001 in children with ALGS 48 weeks of treatment.

Additional objectives for the Optional Follow-up Treatment Period are:
1. To explore twice a day (BID) dosing regimen and higher daily dosing of LUM001;
2. Assessment of alpha-fetoprotein (AFP) levels, a marker of hepatocellular carcinoma;
3. Assessment of the palatability of the LUM001 formulation in all subjects, by-proxy in subjects <4 years old and by patient questionnaire in children =4 years old.
Primary end point(s): The primary efficacy endpoints will be the mean change from Week 18 to 22 of fasting serum bile acid levels in subjects who previously responded to LUM001 treatment, as defined by a reduction in sBA =50% from baseline to Week 12 or Week 18. A sensitivity analysis will also be conducted using subjects who experienced a reduction from baseline in serum bile acids of =50% at the Week 48 measurement.
Secondary Objective: Not applicable
Timepoint(s) of evaluation of this end point: Serum bile acid levels are measured at baseline, 12, 18, 22 and 48 weeks
Secondary Outcome(s)
Secondary end point(s): Secondary efficacy endpoints include mean change from Week 18 to Week 22 in liver enzymes (ALP, ALT, and bilirubin [total and direct]) and pruritus as measured by ItchRO (Observer ItchRO/patient ItchRO), in subjects who previously responded to LUM001 treatment, as defined by a reduction in ItchRO scale >1 point from baseline to Week 12 or Week 18.
Timepoint(s) of evaluation of this end point: These are measured throughout the trial by means of the subject eDiary and clinician scales and questionnaires.
Secondary ID(s)
2013-005373-43-ES
LUM001-304
Source(s) of Monetary Support
Mirum Pharmaceuticals,Inc.
Secondary Sponsor(s)
Ethics review
Status:
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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