Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis and Alagille Syndrome. MedDRA version: 20.0 Level: PT Classification code 10076033 Term: Progressive familial intrahepatic cholestasis System Organ Class: 10010331 - Congenital, familial and genetic disorders MedDRA version: 20.0 Level: PT Classification code 10053870 Term: Alagille syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Conditions
Sponsors
Mirum Pharmaceuticals Inc
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Informed consent (by the legally authorized representative) per the Institutional Review Board/Ethics Committee 2. Body weight of =2.5 kg 3. =31 days and =65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. History of surgical disruption of the enterohepatic circulation. 2. Chronic diarrhea requiring ongoing intravenous fluid or nutritional intervention at screening, during the screening period, or during the 30 days prior to screening 3. History of liver transplant or imminent need for liver transplant 4. Decompensated cirrhosis (international normalized ratio >1.5 despite vitamin K supplementation, albumin 15× the upper limit of normal at screening 6. 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), per investigator discretion 7. Presence of other significant liver disease or any other conditions or abnormalities which, in the opinion of the investigator or medical monitor, may compromise the safety of the participant or interfere with the participant’s participation in or completion of the study 8. Liver mass on imaging, including screening ultrasound, suspected to be hepatocellular carcinoma 9. Receipt of investigational drug, biologic, or medical device within 30 days or 5 half-lives (whichever is longer) prior to screening 10. Previous treatment with an ASBT inhibitor 11. Known hypersensitivity to maralixibat or any of its excipients 12. Known caregiver history of unreliability, mental instability, or cognitive impairment that, in the opinion of the investigator or medical monitor, could compromise the validity of informed consent, compromise the safety of the participant, or lead to nonadherence with the study protocol or inability to conduct the study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the safety and tolerability of maralixibat in infant participants with cholestatic liver diseases including ALGS and PFIC.;Secondary Objective: • To evaluate the treatment effect of maralixibat on serum bile acid (sBA) levels • To evaluate the effect on liver enzymes (ALT, AST) and bilirubin • To evaluate the effect on lipid-soluble vitamins • To evaluate the pharmacokinetics of maralixibat in infant participants;Primary end point(s): Safety (incidence of treatment-emergent adverse events [TEAEs], including those that are serious, are related to maralixibat, that lead to withdrawal, are of special interest, along with TEAEs by severity and change from baseline in safety laboratory [including measurement of osmolality and osmolar gap] and physical examination findings, vital signs, and neurodevelopmental assessment) and tolerability.;Timepoint(s) of evaluation of this end point: Throughout this study, the safety of participants will be closely monitored by an independent data monitoring committee (DMC). The DMC will comprise three disease experts (including pediatric hepatologists) and a biostatistician and will be governed by a DMC Charter. A Data Monitoring Committee will review safety and study data at specified intervals for the duration of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints: • Change from baseline to Week 13 in fasting sBA levels • Change from baseline to Week 13 in liver enzymes (serum ALT, AST) and total serum bilirubin • Change from baseline to Week 13 in vitamins A, D, E, and K • Systemic maralixibat concentrations in plasma before dosing and 2.5 hours after morning dose at specified time points Exploratory endpoints: • Change from baseline in Clinician Scratch Scale (CSS) score • Changes from baseline in height and weight and in midarm and head circumference • Number of hospitalizations; emergency ward visits; and the length of stay for hospitalization, surgeries, and procedures related to the participant’s disease type; • Number of days the caregiver misses from work.;Timepoint(s) of evaluation of this end point: Secondary and exploratory efficacy endpoints will be displayed by study visit, using summary statistics including the number of observations, the mean, median, standard deviation, and range for continuous measures and counts and percentages for categorical measures. Actual values as well as change from baseline will be presented. Supportive and exploratory efficacy measures will be analyzed similarly as above. Details of the analysis methods will be outlined in the statistical analysis plan (SAP). In addition, a responder analysis (based on change in serum bile acid levels and bilirubin) will also be considered. The response definition and its appropriate analysis methodology will be outlined in the SAP for the study. | — |
Countries
Belgium, France, Poland, United Kingdom
Contacts
Public ContactChief Scientific Officer
Mirum Pharmaceuticals Inc.
Outcome results
None listed