Long-term safety study with Maralixibat, in treatment of subjects with cholestatic liver disease including, but not limited to, Alagille syndrome (ALGS) and Progressive Familial Intrahepatic Cholestasis (PFIC) and Biliary Atresia. 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 syndro
Conditions
Sponsors
Mirum Pharmaceuticals Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Provide informed consent and assent (as applicable) per the Institutional Review Board/Ethics Committee (IRB/EC). 2.Previously participated in a maralixibat study and with approval of the Medical Monitor. Previous participation is defined as: •Having completed the EOT Visit, for subjects coming from the maralixibat Phase 2 studies (LUM001-303, LUM001-304, and LUM001-305 in ALGS and LUM001-501 in PFIC). •Having completed the entire duration of the study (i.e., core and extension, if applicable), for subjects coming from other maralixibat studies (e.g., MRX 503, MRX-701 and other open-label maralixibat studies). •Previously early terminated from a maralixibat study for reasons other than safety, and received permission from the Medical Monitor to enroll, after completing all screening procedures and confirmation of eligibility •Having reached the stable-dose phase of maralixibat in the open-label extension of a previous study and are =1 year of age 3. At least 1 year of age 4.Males, and females of non-childbearing potential. Males and non-pregnant, non lactating females of childbearing potential who are sexually active must agree to use acceptable contraception during the study and 30 days following the last dose of the study medication. Females of childbearing potential must have a negative pregnancy test. 5.Caregivers (and/or age appropriate subjects) must have access to email or phone for scheduled remote visits if applicable. 6.Subject and caregiver willingness to comply with all study visits and requirements. Are the trial subjects under 18? yes Number of subjects for this age range: 104 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 5 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range 0
Exclusion criteria
Exclusion criteria: 1.Experienced an adverse event (AE) or serious adverse event (SAE) related to maralixibat during the lead-in protocol that led to permanent discontinuation of the subject from maralixibat. 2.Any conditions or abnormalities (including laboratory 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. 3.History of non-adherence to medical regimens, unreliability, medical condition, mental instability or cognitive impairment that, in the opinion of the Investigator or Sponsor medical monitor, could compromise the validity of informed consent, compromise the safety of the subject, or lead to nonadherence with the study protocol or inability to conduct the study procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: Evaluate the long-term safety of maralixibat in subjects with cholestatic liver disease including, but not limited to, ALGS and PFIC and Biliary Atresia.;Secondary Objective: •Evaluate the long-term effect of maralixibat on pruritus •Evaluate the long-term effect of maralixibat on serum bile acid levels •Evaluate the long-term effect of maralixibat on total serum bilirubin •Evaluate the long-term effect of maralixibat on time to liver-associated outcomes (i.e., partial external biliary diversion (PEBD) or liver transplantation) •Evaluate the long-term effects of maralixibat on growth ;Primary end point(s): The following safety and tolerability endpoints will be assessed: •AEs including serious, non-serious, related, non-related AEs •Clinical laboratory tests (hematology, chemistry, urinalysis; serum pregnancy test, if appropriate) •Vital signs (temperature, systolic and diastolic blood pressure, heart rate, respiratory rate, weight and height assessments) •Physical examination •Concomitant treatment/medication usage •Change from maralixibat baseline in neurodevelopmental assessment (biliary atresia);Timepoint(s) of evaluation of this end point: A Data Monitoring Committee (DMC) will review safety and study data at specified intervals for the duration of the study. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The efficacy endpoints: •Change from maralixibat baseline over the course of the study in the weekly average morning ItchRO(Obs)™ severity score (ALGS and PFIC) •Change from maralixibat baseline over the course of the study in the weekly average morning ItchRO(Obs)™ frequency score (ALGS and PFIC) •Change from maralixibat baseline over the course of the study in the Clinician Scratch Scale Score •Change from maralixibat baseline over the course of the study in sBA levels •Change from maralixibat baseline over the course of the study in mean total serum bilirubin •Time from maralixibat baseline to liver-associated outcomes (PEBD surgery, listing for liver transplantation, liver decompensation [hepatic encephalopathy, variceal bleeding, ascites, and spontaneous bacterial peritonitis] events, hepatocellular carcinoma, death from a liver associated event). •Comparison between treatment responders (defined as sBA normalization/= 70% change from maralixibat baseline (CFMB) AND = 1.0 CFMB ItchRO(Obs)™) and partial/non-responder (PFIC) •Comparison between treatment responders (defined as sBA = 50% CFMB (change from maralixibat baseline) AND =1.0 CFMB ItchRO(Obs)™) and partial/non-responder (ALGS) •Proportion of days at or below 1.0 point on the weekly morning ItchRO(Obs)™ severity score (ALGS and PFIC) •Durability of treatment response •Change from maralixibat baseline in height and weight Z-score over the course of the study •Change from maralixibat baseline in triceps skinfold, head circumference (until age 2 years), and mid arm circumference z-score over the course of the study (for subjects with biliary atresia) •Change from maralixibat baseline in xanthomas over the course of the study, as measured by the Clinician Xanthoma Scale (ALGS) ;Timepoint(s) of evaluation of this end point: All such analyses will be interpreted cautiously and not used for formal inference, although inferential statistics may be used as part of the data | — |
Countries
Australia, Belgium, Canada, France, Poland, Spain, United Kingdom, United States
Contacts
Public ContactChief Scientific Officer
Mirum Pharmaceuticals Inc.
Outcome results
None listed