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Note: This record shows only 22 elements of the WHO Trial Registration Data Set. To view changes that have been made to the source record, or for additional information about this trial, click on the URL below to go to the source record in the primary register.
Register: EUCTR
Last refreshed on: 5 January 2021
Main ID:  EUCTR2020-004628-40-FR
Date of registration: 16/12/2020
Prospective Registration: Yes
Primary sponsor: Mirum Pharmaceuticals Inc
Public title: Clinical study to Evaluate the Safety and Tolerability of Maralixibat in the Treatment of Infants with Progressive Familial Intrahepatic Cholestasis and Alagille Syndrome.
Scientific 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. - Maralixibat Infant Safety Evaluation (RISE).
Date of first enrolment:
Target sample size: 12
Recruitment status: NA
URL:  https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2020-004628-40
Study type:  Interventional clinical trial of medicinal product
Study design:  Controlled: no Randomised: yes Open: yes Single blind: no Double blind: no Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: no Other: no Number of treatment arms in the trial: 2  
Phase:  Human pharmacology (Phase I): no Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no
Countries of recruitment
Belgium France Poland United Kingdom
Contacts
Name: Chief Scientific Officer   
Address:  950 Tower Lane, Suite 1050 CA 94404 Foster City California United States
Telephone: 16506674085
Email: medinfo@mirumpharma.com
Affiliation:  Mirum Pharmaceuticals Inc.
Name: Chief Scientific Officer   
Address:  950 Tower Lane, Suite 1050 CA 94404 Foster City California United States
Telephone: 16506674085
Email: medinfo@mirumpharma.com
Affiliation:  Mirum Pharmaceuticals Inc.
Key inclusion & exclusion criteria
Inclusion criteria:
1. Informed consent (by the legally authorized representative) per the Institutional Review Board/Ethics Committee
2. Body weight of =2.5 kg
3. =31 days and <12 months of age at the baseline visit (At least 3 participants in each cohort must be <9 months of age at the baseline visit)
4. Gestational age =36 weeks at birth
5. Diagnosis of PFIC or ALGS based on the following:
PFIC: Participants with genetic testing results consistent with at least one disease-causing mutation associated with PFIC alongside clinical or biochemical evidence of cholestasis
ALGS: Participants meeting the ALGS diagnostic criteria outlined in the protocol alongside clinical or biochemical evidence of cholestasis
6. Caregiver willingness to comply with all study visits and requirements, including ability to read and understand the questionnaires and, if applicable, capable of diluting maralixibat per investigator training and written instructions
7. Caregiver access to email or phone for remote participant contacts.
Are the trial subjects under 18? yes
Number of subjects for this age range: 12
F.1.2 Adults (18-64 years) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
1. History of surgical disruption of the enterohepatic circulation.
2. Chronic diarrhea requiring ongoing intravenous fluid or nutritional intervention at screening, during the screening period, or during the 30 days prior to screening
3. History of liver transplant or imminent need for liver transplant
4. Decompensated cirrhosis (international normalized ratio >1.5 despite vitamin K supplementation, albumin <30 g/L, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy)
5. ALT or TSB > 15× the upper limit of normal at screening
6. 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
7. 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
8. Liver mass on imaging, including screening ultrasound, suspected to be hepatocellular carcinoma
9. Receipt of investigational drug, biologic, or medical device within 30 days or 5 half-lives (whichever is longer) prior to screening
10. Previous treatment with an ASBT inhibitor
11. Known hypersensitivity to maralixibat or any of its excipients
12. Known caregiver history of unreliability, mental instability, or cognitive impairment that, in the opinion of the investigator or medical monitor, could compromise the validity of informed consent, compromise the safety of the participant, or lead to nonadherence with the study protocol or inability to conduct the study procedures.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes
Health Condition(s) or Problem(s) studied
Cholestatic Liver Diseases Including Progressive Familial Intrahepatic Cholestasis and Alagille Syndrome.
MedDRA version: 20.0 Level: PT Classification code 10076033 Term: Progressive familial intrahepatic cholestasis System Organ Class: 10010331 - Congenital, familial and genetic disorders
MedDRA version: 20.0 Level: PT Classification code 10053870 Term: Alagille syndrome System Organ Class: 10010331 - Congenital, familial and genetic disorders
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
Intervention(s)

Product Name: Maralixibat (formely SHP625 or LUM001)
Pharmaceutical Form: Oral solution
INN or Proposed INN: MARALIXIBAT CHLORIDE
CAS Number: 228113-66-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-

Product Name: Maralixibat (formely SHP625 or LUM001)
Pharmaceutical Form: Oral solution
INN or Proposed INN: MARALIXIBAT CHLORIDE
CAS Number: 228113-66-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 10-

Product Name: Maralixibat (formely SHP625 or LUM001)
Pharmaceutical Form: Oral solution
INN or Proposed INN: MARALIXIBAT CHLORIDE
CAS Number: 228113-66-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 15-

Product Name: Maralixibat (formely SHP625 or LUM001)
Pharmaceutical Form: Oral solution
INN or Proposed INN: MARALIXIBAT CHLORIDE
CAS Number: 228113-66-4
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 20-

Primary Outcome(s)
Main Objective: To evaluate the safety and tolerability of maralixibat in infant participants with cholestatic liver diseases including ALGS and PFIC.
Primary end point(s): Safety (incidence of treatment-emergent adverse events [TEAEs], including those that are serious, are related to maralixibat, that lead to withdrawal, are of special interest, along with TEAEs by severity and change from baseline in safety laboratory [including measurement of osmolality and osmolar gap] and physical examination findings, vital signs, and neurodevelopmental assessment) and tolerability.
Secondary Objective: • To evaluate the treatment effect of maralixibat on serum bile acid (sBA) levels
• To evaluate the effect on liver enzymes (ALT, AST) and bilirubin
• To evaluate the effect on lipid-soluble vitamins
• To evaluate the pharmacokinetics of maralixibat in infant participants
Timepoint(s) of evaluation of this end point: Throughout this study, the safety of participants will be closely monitored by an independent data monitoring committee (DMC). The DMC will comprise three disease experts (including pediatric hepatologists) and a biostatistician and will be governed by a DMC Charter. A Data Monitoring Committee will review safety and study data at specified intervals for the duration of the study.
Secondary Outcome(s)
Secondary end point(s): Secondary endpoints:
• Change from baseline to Week 13 in fasting sBA levels
• Change from baseline to Week 13 in liver enzymes (serum ALT, AST) and total serum bilirubin
• Change from baseline to Week 13 in vitamins A, D, E, and K
• Systemic maralixibat concentrations in plasma before dosing and 2.5 hours after morning dose at specified time points
Exploratory endpoints:
• Change from baseline in Clinician Scratch Scale (CSS) score
• Changes from baseline in height and weight and in midarm and head circumference
• Number of hospitalizations; emergency ward visits; and the length of stay for hospitalization, surgeries, and procedures related to the participant’s disease type;
• Number of days the caregiver misses from work.
Timepoint(s) of evaluation of this end point: Secondary and exploratory efficacy endpoints will be displayed by study
visit, using summary statistics including the number of observations, the
mean, median, standard deviation, and range for continuous measures
and counts and percentages for categorical measures. Actual values as
well as change from baseline will be presented.
Supportive and exploratory efficacy measures will be analyzed similarly
as above. Details of the analysis methods will be outlined in the
statistical analysis plan (SAP).
In addition, a responder analysis (based on change in serum bile acid
levels and bilirubin) will also be considered. The response definition and
its appropriate analysis methodology will be outlined in the SAP for the
study.
Secondary ID(s)
2020-004628-40-BE
MRX-801
Source(s) of Monetary Support
Mirum Pharmaceuticals, Inc.
Secondary Sponsor(s)
Ethics review
Status:
Approval date:
Contact:
Results
Results available:
Date Posted:
Date Completed:
URL:
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