Clinical study to Evaluate the Safety and Tolerability of Maralixibat in the Treatment of Infants with Progressive Familial Intrahepatic Cholestasis and Alagille Syndrome.

Phase 1

• Conditions: Progressive Familial Intrahepatic Cholestasis and Alagille Syndrome.; MedDRA version: 20.0Level: PTClassification code 10076033Term: Progressive familial intrahepatic cholestasisSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; MedDRA version: 20.0Level: PTClassification code 10053870Term: Alagille syndromeSystem Organ Class: 10010331 - Congenital, familial and genetic disorders; Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

• Registration Number: EUCTR2020-004628-40-PL
• Lead Sponsor: Mirum Pharmaceuticals Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2021-01-20
• Last Update Posted: 26 August 2024

Recruitment & Eligibility

• Status: A
• Sex: All
• Target Recruitment: 27

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. <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. For children born with
gestational age between 32 and 36 weeks, a postmenstrual age of
=36 weeks is required. Postmenstrual age is defined as the time
elapsed between the first day of the last menstrual period and birth
plus the time elapsed after birth.
5. Diagnosis of PFIC or ALGS based on the following:
PFIC: Participants with genetic testing results consistent with at least 1 disease-causing mutation associated with PFIC alongside clinical or biochemical evidence of cholestasis (as defined below).
ALGS: Participants meeting the ALGS diagnostic criteria outlined in the protocol alongside clinical or biochemical evidence of cholestasis (as defined below) Evidence of cholestasis (one or more of the following):
•Total serum BA >2× ULN for age
•Conjugated bilirubin >1 mg/dL
•LSV deficiency otherwise unexplainable
•Gamma-glutamyl transferase (GGT) > 3 × ULN for age
•Intractable pruritus explainable only by liver disease
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: 27
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. Predicted complete absence of bile salt excretion pump (BSEP)
function based on the type of ABCB11 mutation (PFIC2), as determined
by a standard-of-care genotyping.
2.History of surgical disruption of the enterohepatic circulation.
3. Chronic diarrhea requiring ongoing intravenous fluid or nutritional intervention at screening, during the screening period, or during the 30 days prior to screening
4. History of liver transplant or imminent need for liver transplant
5. 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)
6. ALT or total serum bilirubin (TSB) > 15× the upper limit of normal at screening
7. 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
8. 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
9. Liver mass on imaging, including screening ultrasound, suspected to be hepatocellular carcinoma
10. Presence of clinical or developmental preterm complications that
could impact safe participation in the study, as determined by the
investigator after evaluation.
11.Receipt of investigational drug, biologic, or medical device within 30 days or 5 half-lives (whichever is longer) prior to screening
12. Previous treatment with an IBAT inhibitor
13. Treatment with other medications containing propylene glycol (PG) or alcohol or any substrate for alcohol dehydrogenase (e.g., ethanol; forparticipants <1 month of age only).
14. Known hypersensitivity to maralixibat or any of its excipients
15. 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.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified