Alagille Syndrome, Progressive Familial Intrahepatic Cholestasis
Conditions
Keywords
ALGS, Liver Diseases, Alagille Syndrome, Livmarli, Maralixibat, Cholestasis, Pruritus, Itching, IBAT inhibitor, PFIC
Brief summary
In patients with Alagille syndrome (ALGS), the key objectives are to evaluate the tolerability, long-term safety (including possible liver toxicity) and long-term efficacy of Livmarli treatment. In patients with Progressive Familial Intrahepatic Cholestasis (PFIC), the key objectives are to evaluate tolerability, long-term safety (including possible liver toxicity and potential impact of chronic exposure to propylene glycol (PG)), long-term efficacy, and growth and development.
Detailed description
This is a multicenter, open-label, low-intervention clinical study in participants diagnosed with either ALGS with cholestatic pruritus or PFIC who are treated with Livmarli. Participants will be treated according to standard of care for the duration of the study.
Interventions
DRUGLivmarli Oral Product
Participants will be treated according to standard of care for the duration of the study and Schedule of Assessments.
Sponsors
Mirum Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
OTHER
Masking
NONE
Intervention model description
This is a single-group, open-label study enrolling participants with ALGS and PFIC treated with Livmarli. For ALGS, the primary cohort will include at least 45 treatment-naïve participants. A supplemental ALGS cohort will include participants previously treated with Livmarli, with no enrollment limit. For PFIC, the study will enroll at least 130 participants across PFIC subtypes, and all participants enrolled for at least 1 year will be included in the interim analysis.
Eligibility
Sex/Gender
ALL
Age
2 Months to No maximum
Healthy volunteers
No
Inclusion criteria
* Understand and execute an Informed consent and assent (as applicable) * For participants with ALGS ≥2 months of age at Day 1 * For participants with PFIC, ≥3 months of age at Day 1 * A clinically and/or genetically confirmed ALGS diagnosis with pruritus secondary to chronic cholestasis, or a clinically and/or genetically confirmed PFIC diagnosis * For the ALGS primary cohort: Initiation of Livmarli at the time of study entry * For the ALGS supplemental cohort, : Actively using Livmarli prior to study entry * For participants with PFIC: Prescribed Livmarli at the time of study entry or prior to study entry
Exclusion criteria
* History of Liver Transplant * Any Livmarli contraindications (as per SmPC) * Any condition or abnormality that, in the opinion of the investigator, may interfere with the participation in or completion of the study * Received an investigational drug within 30 days before the first dose of Livmarli (Participation in previous maralixibat studies or expanded-access programs is acceptable.) * Received another IBAT inhibitor within 7 days before the first dose of Livmarli * Baseline data before start of treatment of Livmarli are unavailable (\<2 values before treatment) for key safety (LFTs, FSV laboratory results) and key efficacy (sBA, pruritus) parameter
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse Events (AEs) | Up to 7 days after the last dose of Livmarli. | Number and proportion of participants with AEs. |
| Liver function tests (LFTs) - measuring enzyme activity or concentration | Once every 3-4 months, for 5 years. | Change in LFTs from Baseline: Total and direct bilirubin |
| Fat-Soluble Vitamins (FSV) Concentration | Once every 3-4 months, for 5 years. | Change in FSV levels (vitamins A, D, and E) from Baseline. |
| International Normalized Ratio (INR) | Once every 3-4 months, for 5 years. | Change in INR level from Baseline. |
| Long-Term Clinical Outcomes | Once every 3-4 months, for 5 years. | Number of participants with surgical biliary diversion, liver transplantation, liver transplant waitlist status change, clinically evident portal hypertension, complications of liver cirrhosis, liver carcinoma, liver decompensation, and death. |
| Laboratory Test for Monitoring of Propylene Glycol Toxicity in Participants with PFIC | Once every 3-4 months, for 5 years. | Change in PG level from Baseline. |
Countries
Belgium, France, Germany, Greece, Italy, Netherlands, Portugal, Spain
Contacts
CONTACTClinical Trials Mirum
Outcome results
None listed