MERGE: 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

Sponsor

Mirum Pharmaceuticals, Inc. (Industry)

Overall Status

Active, not recruiting

CT.gov ID

NCT04168385

Collaborator

(none)

Enrollment

Locations

Arm

58.5

Anticipated Duration (Months)

3.1

Patients Per Site

0.1

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cholestatic Liver Disease	Drug: Maralixibat	Phase 2

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.

Study Design

Study Type:

Interventional

Actual Enrollment :

52 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

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

Actual Study Start Date :

Jan 16, 2019

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maralixibat Participants will all receive Maralixibat oral solution	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 Other Names: Formerly LUM001 and SHP625

Arm

Intervention/Treatment

Experimental: Maralixibat

Participants will all receive Maralixibat oral solution

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

Other Names:

Formerly LUM001 and SHP625

Outcome Measures

Primary Outcome Measures

Frequency of reported adverse events AEs [From baseline through study completion, up to approximately 3 years]
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.

Secondary Outcome Measures

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]
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]
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]
Evaluate the long-term effect of maralixibat on serum bile acid levels [From baseline through study completion, up to approximately 3 years]
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]
Evaluate the long-term effects of maralixibat on growth [Through study completion, up to approximately 3 years]
Change from baseline in height and weight, summarized as a Z-score over the course of the study
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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

12 Months and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Provide informed consent and assent (as applicable) per the Institutional Review Board/Ethics Committee (IRB/EC).
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.

At least 1 year of age
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.
Caregivers (and/or age appropriate subjects) must have access to email or phone for scheduled remote visits if applicable.
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:

Experienced an AE or SAE related to maralixibat during the lead-in protocol that led to permanent discontinuation of the subject from maralixibat.
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.
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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children'S Hospital Los Angeles	Los Angeles	California	United States	90027
2	Riley Hospital For Children	Indianapolis	Indiana	United States	46202
3	Children's Hospital of Philadelphia	Philadelphia	Pennsylvania	United States	19104
4	Children Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
5	Baylor College of Medicine/Texas Children's Hospital	Houston	Texas	United States	77030
6	Seattle Children's Hospital	Seattle	Washington	United States	98105
7	Children's Hospital Westmead	Westmead	New South Wales	Australia	2145
8	The Royal Children'S Hospital Melbourne	Parkville	Victoria	Australia	3052
9	Cliniques Universitaires Saint-Luc	Brussels		Belgium
10	Hospital for Sick Children	Toronto		Canada
11	Hopital Necker-Enfants Malades	Paris		France	75015
12	Hopital Kremlin Bicetre	Paris		France	94275
13	The Children's Memorial Health Institute	Warsaw		Poland	04-730
14	Hospital Universitario La Paz- Hospital Materno Infantil	Madrid		Spain	261
15	Birmingham Children's Hospital	Birmingham		United Kingdom
16	Leeds Teaching Hospital NHS Trust	Leeds		United Kingdom	LS1 3EX
17	Paediatric Liver Center, Kings College Hospital	London		United Kingdom	SE5 9RS