RISE: A Study to Evaluate the Safety and Tolerability of Maralixibat in Infant Participants With Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis (PFIC) and Alagille Syndrome (ALGS).

Sponsor

Mirum Pharmaceuticals, Inc. (Industry)

Overall Status

Recruiting

CT.gov ID

NCT04729751

Collaborator

(none)

Enrollment

Locations

Arm

22.7

Anticipated Duration (Months)

0.9

Patients Per Site

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study is designed to assess whether the investigational drug maralixibat, is safe and well tolerated in children <12 months of age with Alagille Syndrome [ALGS] or Progressive Familial Intrahepatic Cholestasis [PFIC].

Condition or Disease	Intervention/Treatment	Phase
Progressive Familial Intrahepatic Cholestasis Alagille Syndrome Cholestatic Liver Disease	Drug: Maralixibat	Phase 2

Detailed Description

This is an open label study where all participants will receive maralixibat treatment.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Intervention Model Description:

Single group with 2 cohorts - ≥ 6 participants each from ALGS and PFIC.Single group with 2 cohorts - ≥ 6 participants each from ALGS and PFIC.

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Open-Label, Phase 2 Study to Evaluate the Safety and Tolerability of Maralixibat in the Treatment of Infants With Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis and Alagille Syndrome

Actual Study Start Date :

Sep 9, 2021

Anticipated Primary Completion Date :

Mar 1, 2023

Anticipated Study Completion Date :

Aug 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Maralixibat Participants will receive up to 600 μg/kg twice daily (PFIC) or up to 400 μg/kg once daily (ALGS) over 13 weeks in the core study and for the duration of the Long Term Extension (LTE) where applicable.	Drug: Maralixibat Maralixibat chloride provided in the form of an oral solution (i.e., 5, 10, 15, and 20 mg/mL) 400 μg/kg maralixibat chloride is equivalent to 380 µg/kg maralixibat free base 600 μg/kg maralixibat chloride is equivalent to 570 µg/kg maralixibat free base Other Names: Formerly LUM001 and SHP625

Arm

Intervention/Treatment

Experimental: Maralixibat

Participants will receive up to 600 μg/kg twice daily (PFIC) or up to 400 μg/kg once daily (ALGS) over 13 weeks in the core study and for the duration of the Long Term Extension (LTE) where applicable.

Drug: Maralixibat

Maralixibat chloride provided in the form of an oral solution (i.e., 5, 10, 15, and 20 mg/mL) 400 μg/kg maralixibat chloride is equivalent to 380 µg/kg maralixibat free base 600 μg/kg maralixibat chloride is equivalent to 570 µg/kg maralixibat free base

Other Names:

Formerly LUM001 and SHP625

Outcome Measures

Primary Outcome Measures

Frequency of treatment-emergent adverse events [TEAEs] [From Baseline through to Week 13]

Secondary Outcome Measures

Change in fasting serum bile acid (sBA) levels [From Baseline through to Week 13]
To evaluate the effect on liver enzymes (ALT, AST) and bilirubin [From Baseline through to Week 13]
To evaluate the effect on LSVs [From Baseline through to Week 13]
To assess the plasma level of maralixibat in infant participants [At Baseline, Week 6, Week 10, Week 13 or Early Termination Visit]

Eligibility Criteria

Criteria

Ages Eligible for Study:

0 Days to 364 Days

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Body weight of ≥2.5 kg
<12 months of age at the baseline visit (ROW). >31 days and <12 months of age at the baseline visit (US).
Gestational age ≥36 weeks at birth. For children born with gestational age between 32 and 36 weeks, a postmenstrual age of ≥36 weeks is required.
Diagnosis of PFIC or ALGS

Exclusion criteria:

Predicted complete absence of bile salt excretion pump (BSEP) function
History of surgical disruption of the enterohepatic circulation
History of liver transplant or imminent need for liver transplant
Decompensated cirrhosis
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
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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Children Hospital LA	Los Angeles	California	United States	90027
2	University of California - San Francisco	San Francisco	California	United States	94158
3	Medstar Georgetown University Hospital	Washington	District of Columbia	United States	20007
4	Ochsner Hospital for Children	New Orleans	Louisiana	United States	70121
5	Children's Hospital of Pittsburgh	Pittsburgh	Pennsylvania	United States	15224
6	Texas Children's Hospital	Houston	Texas	United States	77030
7	Seattle Children's Hospital	Seattle	Washington	United States	98105
8	Cliniques Universitaires Saint-Luc	Brussels		Belgium
9	Sociedade Beneficente de Senhoras - Hospital Sírio-Libanês	São Paulo		Brazil	01308-000
10	Hôpital Kremlin Bicêtre	Le Kremlin-Bicêtre		France
11	Hopital Necker	Paris		France
12	Consultorio de Joshue David Covarrubias Esquer	Zapopan		Mexico	45050
13	Instytut Pomnik-Centrum Zdrowia Dziecka	Warsaw		Poland
14	King's College Hospital	London		United Kingdom