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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). (RISE)

Primary Purpose

Progressive Familial Intrahepatic Cholestasis, Alagille Syndrome, Cholestatic Liver Disease

Status
Active
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Maralixibat
Sponsored by
Mirum Pharmaceuticals, Inc.
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Progressive Familial Intrahepatic Cholestasis focused on measuring PFIC, ALGS, Maralixibat, Bile Duct Diseases, Liver Diseases, Biliary Tract Diseases, Pediatric

Eligibility Criteria

0 Days - 364 Days (Child)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  1. Body weight of ≥2.5 kg
  2. <12 months of age at the baseline visit (ROW). >31 days and <12 months of age at the baseline visit (US).
  3. 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.
  4. Diagnosis of PFIC or ALGS

Exclusion criteria:

  1. Predicted complete absence of bile salt excretion pump (BSEP) function
  2. History of surgical disruption of the enterohepatic circulation
  3. History of liver transplant or imminent need for liver transplant
  4. Decompensated cirrhosis
  5. 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
  6. 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

Sites / Locations

  • Children Hospital LA
  • University of California - San Francisco
  • Medstar Georgetown University Hospital
  • Ochsner Hospital for Children
  • Children's Hospital of Pittsburgh
  • Texas Children's Hospital
  • Seattle Children's Hospital
  • Cliniques Universitaires Saint-Luc
  • Sociedade Beneficente de Senhoras - Hospital Sírio-Libanês
  • Hôpital Kremlin Bicêtre
  • Hopital Necker
  • Consultorio de Joshue David Covarrubias Esquer
  • Instytut Pomnik-Centrum Zdrowia Dziecka
  • King's College Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Maralixibat

Arm Description

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.

Outcomes

Primary Outcome Measures

Frequency of treatment-emergent adverse events [TEAEs]

Secondary Outcome Measures

Change in fasting serum bile acid (sBA) levels
To evaluate the effect on liver enzymes (ALT, AST) and bilirubin
To evaluate the effect on LSVs
To assess the plasma level of maralixibat in infant participants

Full Information

First Posted
January 25, 2021
Last Updated
September 5, 2023
Sponsor
Mirum Pharmaceuticals, Inc.
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1. Study Identification

Unique Protocol Identification Number
NCT04729751
Brief Title
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).
Acronym
RISE
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
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
September 9, 2021 (Actual)
Primary Completion Date
August 22, 2023 (Actual)
Study Completion Date
May 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Mirum Pharmaceuticals, Inc.

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. 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].
Detailed Description
This is an open label study where all participants will receive maralixibat treatment.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Progressive Familial Intrahepatic Cholestasis, Alagille Syndrome, Cholestatic Liver Disease
Keywords
PFIC, ALGS, Maralixibat, Bile Duct Diseases, Liver Diseases, Biliary Tract Diseases, Pediatric

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Single group with 2 cohorts - ≥ 6 participants each from ALGS and PFIC.
Masking
None (Open Label)
Allocation
N/A
Enrollment
12 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Maralixibat
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Maralixibat
Other Intervention Name(s)
Formerly LUM001 and SHP625
Intervention Description
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
Primary Outcome Measure Information:
Title
Frequency of treatment-emergent adverse events [TEAEs]
Time Frame
From Baseline through to Week 13
Secondary Outcome Measure Information:
Title
Change in fasting serum bile acid (sBA) levels
Time Frame
From Baseline through to Week 13
Title
To evaluate the effect on liver enzymes (ALT, AST) and bilirubin
Time Frame
From Baseline through to Week 13
Title
To evaluate the effect on LSVs
Time Frame
From Baseline through to Week 13
Title
To assess the plasma level of maralixibat in infant participants
Time Frame
At Baseline, Week 6, Week 10, Week 13 or Early Termination Visit

10. Eligibility

Sex
All
Minimum Age & Unit of Time
0 Days
Maximum Age & Unit of Time
364 Days
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
Children Hospital LA
City
Los Angeles
State/Province
California
ZIP/Postal Code
90027
Country
United States
Facility Name
University of California - San Francisco
City
San Francisco
State/Province
California
ZIP/Postal Code
94158
Country
United States
Facility Name
Medstar Georgetown University Hospital
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20007
Country
United States
Facility Name
Ochsner Hospital for Children
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70121
Country
United States
Facility Name
Children's Hospital of Pittsburgh
City
Pittsburgh
State/Province
Pennsylvania
ZIP/Postal Code
15224
Country
United States
Facility Name
Texas Children's Hospital
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Seattle Children's Hospital
City
Seattle
State/Province
Washington
ZIP/Postal Code
98105
Country
United States
Facility Name
Cliniques Universitaires Saint-Luc
City
Brussels
Country
Belgium
Facility Name
Sociedade Beneficente de Senhoras - Hospital Sírio-Libanês
City
São Paulo
ZIP/Postal Code
01308-000
Country
Brazil
Facility Name
Hôpital Kremlin Bicêtre
City
Le Kremlin-Bicêtre
Country
France
Facility Name
Hopital Necker
City
Paris
Country
France
Facility Name
Consultorio de Joshue David Covarrubias Esquer
City
Zapopan
ZIP/Postal Code
45050
Country
Mexico
Facility Name
Instytut Pomnik-Centrum Zdrowia Dziecka
City
Warsaw
Country
Poland
Facility Name
King's College Hospital
City
London
Country
United Kingdom

12. IPD Sharing Statement

Links:
URL
https://ghr.nlm.nih.gov/condition/progressive-familial-intrahepatic-cholestasis
Description
Genetics Home Reference - PFIC
URL
https://mirumpharma.com
Description
Mirum Pharmaceuticals homepage
URL
https://ghr.nlm.nih.gov/condition/alagille-syndrome
Description
Genetics Home Reference - ALGS
URL
https://clinicaltrials.gov/ct2/info/fdalinks
Description
US FDA Resources

Learn more about this trial

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).

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