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

Cholestatic Liver Disease Clinical Trial

— MERGE  

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

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT04168385
• Other study ID #: MRX-800
• Status: Active, not recruiting
• Phase: Phase 2
• Start date: January 16, 2020
• Est. completion date: July 2024

Study information

• Verified date: January 2024
• Source: Mirum Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 52
• Est. completion date: July 2024
• Est. primary completion date: July 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 12 Months and older

Eligibility

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.

Related Conditions & MeSH terms

• Cholestasis
• Cholestatic Liver Disease
• Liver Diseases

Intervention

Drug:
• Maralixibat
Maralixibat chloride oral solution orally twice daily (up to 1200* mcg/kg/day), and according to indication. *equivalent to 1140 mcg/kg/day maralixibat

Locations

Country	Name	City	State
Australia	The Royal Children'S Hospital Melbourne	Parkville	Victoria
Australia	Children's Hospital Westmead	Westmead	New South Wales
Belgium	Cliniques Universitaires Saint-Luc	Brussels
Canada	Hospital for Sick Children	Toronto
France	Hopital Kremlin Bicetre	Paris
France	Hopital Necker-Enfants Malades	Paris
Poland	The Children's Memorial Health Institute	Warsaw
Spain	Hospital Universitario La Paz- Hospital Materno Infantil	Madrid
United Kingdom	Birmingham Children's Hospital	Birmingham
United Kingdom	Leeds Teaching Hospital NHS Trust	Leeds
United Kingdom	Paediatric Liver Center, Kings College Hospital	London
United States	Baylor College of Medicine/Texas Children's Hospital	Houston	Texas
United States	Riley Hospital For Children	Indianapolis	Indiana
United States	Children'S Hospital Los Angeles	Los Angeles	California
United States	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania
United States	Children Hospital of Pittsburgh	Pittsburgh	Pennsylvania
United States	Seattle Children's Hospital	Seattle	Washington

Sponsors (1)

Lead Sponsor	Collaborator
Mirum Pharmaceuticals, Inc.

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  France,  Poland,  Spain,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Frequency of reported adverse events AEs	Treatment-emergent AEs (TEAEs) will be defined as AEs that start or deteriorate on or after the first dose of study medication and no later than 14 days following the last dose of study medication or reported through the End of Trial ( EOT/ET) Visit. In this study, all AEs will be considered TEAEs.	From baseline through study completion, up to approximately 3 years
Secondary	Change from maralixibat baseline over the course of the study in the weekly average morning ItchRO(Obs)™ severity score (ALGS and PFIC)		From baseline through study completion, up to approximately 3 years
Secondary	Change from maralixibat baseline over the course of the study in the weekly average morning ItchRO(Obs)™ frequency score (ALGS and PFIC)		From baseline through study completion, up to approximately 3 years
Secondary	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		From baseline through study completion, up to approximately 3 years
Secondary	Evaluate the long-term effect of maralixibat on serum bile acid levels		From baseline through study completion, up to approximately 3 years
Secondary	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)		From baseline to occurrence of liver associated event, up to approximately 3 years
Secondary	Evaluate the long-term effects of maralixibat on growth	Change from baseline in height and weight, summarized as a Z-score over the course of the study	Through study completion, up to approximately 3 years
Secondary	Change from maralixibat baseline over the course of the study in mean total serum bilirubin		Change from baseline through study completion, up to approximately 3 years

External Links

•   Genetics Home Reference - Alagille syndrome
•   Genetics Home Reference - PFIC
•   Mirum Pharmaceuticals homepage
•   US FDA Resources