Clinical trial NCT04168385: MRX-800: A Long-Term Safety Study of Maralixibat in the Treatment of Cholestatic Liver Disease in Subjects Who Previously Participated in a Maralixibat Study
Official title: MRX-800: A Long-Term Safety Study of Maralixibat, an Apical Sodium Dependent Bile Acid Transporter Inhibitor (ASBTi), in the Treatment of Cholestatic Liver Disease in Subjects Who Previously Participated in a Maralixibat Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Cholestatic Liver Disease
Keywords: PFIC
ALGS
Maralixibat
Bile Duct Diseases
Liver Diseases
Biliary Tract Diseases
Digestive System Diseases
Pediatric
Lead sponsor: Mirum Pharmaceuticals, Inc.
Sponsor class: INDUSTRY
First posted: 2019-11-19
Enrollment: 52
Sex: ALL
Minimum age (years): 12
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Evaluate the long-term safety of maralixibat (MRX) in subjects with cholestatic liver disease including, but not limited to, Alagille Syndrome (ALGS), Progressive Familial Intrahepatic Cholestasis (PFIC) and Biliary Atresia.

Detailed description: This is a multicenter, open-label study of maralixibat in subjects diagnosed with cholestatic liver disease (including, but not limited to ALGS, PFIC or Biliary Atresia) who have previously participated in a maralixibat clinical study. All subjects will receive maralixibat in this study.

Eligibility criteria: Inclusion Criteria Subjects will need to meet all criteria below to be considered eligible for the study.

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.
   * Having completed the entire duration of the study (i.e., core and extension, if applicable), for subjects coming from the maralixibat Phase 3 studies.
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.

Exclusion Criteria

A subject will be excluded from the study if any of the following exclusion criteria are met:

1. Experienced an AE or 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 non-adherence with the study protocol or inability to conduct the study procedures.

Primary outcomes:
measure: Frequency of reported adverse events AEs
timeFrame: From baseline through study completion, up to approximately 3 years
Secondary outcomes:
measure: Change from maralixibat baseline over the course of the study in the weekly average morning ItchRO(Obs)™ severity score (ALGS and PFIC)
timeFrame: From baseline through study completion, up to approximately 3 years
measure: Change from maralixibat baseline over the course of the study in the weekly average morning ItchRO(Obs)™ frequency score (ALGS and PFIC)
timeFrame: From baseline through study completion, up to approximately 3 years
measure: Evaluate the long-term effect of maralixibat on pruritus severity using in the Clinician Scratch Scale (CSS) as change from baseline over the course of the study
timeFrame: From baseline through study completion, up to approximately 3 years
measure: Evaluate the long-term effect of maralixibat on serum bile acid levels
timeFrame: From baseline through study completion, up to approximately 3 years
measure: Evaluate the long-term effect of maralixibat on time to liver-associated outcomes reported as a mean change from baseline (i.e., partial external biliary diversion [PEBD] or liver transplantation)
timeFrame: From baseline to occurrence of liver associated event, up to approximately 3 years
measure: Evaluate the long-term effects of maralixibat on growth
timeFrame: Through study completion, up to approximately 3 years
measure: Change from maralixibat baseline over the course of the study in mean total serum bilirubin
timeFrame: Change from baseline through study completion, up to approximately 3 years
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children'S Hospital Los Angeles
state: California
city: Indianapolis
country: United States
facility: Riley Hospital For Children
state: Indiana
city: Philadelphia
country: United States
facility: Children's Hospital of Philadelphia
state: Pennsylvania
city: Pittsburgh
country: United States
facility: Children Hospital of Pittsburgh
state: Pennsylvania
city: Houston
country: United States
facility: Baylor College of Medicine/Texas Children's Hospital
state: Texas
city: Seattle
country: United States
facility: Seattle Children's Hospital
state: Washington
city: Westmead
country: Australia
facility: Children's Hospital Westmead
state: New South Wales
city: Parkville
country: Australia
facility: The Royal Children'S Hospital Melbourne
state: Victoria
city: Brussels
country: Belgium
facility: Cliniques Universitaires Saint-Luc
city: Toronto
country: Canada
facility: Hospital for Sick Children
city: Paris
country: France
facility: Hopital Necker-Enfants Malades
city: Paris
country: France
facility: Hopital Kremlin Bicetre
city: Warsaw
country: Poland
facility: The Children's Memorial Health Institute
city: Madrid
country: Spain
facility: Hospital Universitario La Paz- Hospital Materno Infantil
city: Birmingham
country: United Kingdom
facility: Birmingham Children's Hospital
city: Leeds
country: United Kingdom
facility: Leeds Teaching Hospital NHS Trust
city: London
country: United Kingdom
facility: Paediatric Liver Center, Kings College Hospital
Study officials:
References: