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 sponsorstops the program or development in this indication.

Phase 1

• Conditions: 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: 20.0Level: PTClassification code 10053870Term: Alagille syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2013-005373-43-GB
• Lead Sponsor: Mirum Pharmaceuticals, Inc.

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2015-02-06
• Last Update Posted: 13 October 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 30

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 18? yes
Number of subjects for th

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).

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified