A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC)

Inclusion Criteria

• Informed consent and assent (as applicable) per Institutional Review Board/Ethics Committee (IRB/EC)
• Male or female subjects with a body weight ≥5 kg, who are ≥12 months and 6 months) pruritus in addition to biochemical abnormalities and/or pathological evidence of progressive liver disease and
• Primary Cohort: Subjects with genetic testing results consistent with biallelic disease-causing variation in ABCB11 (PFIC2), based on standard of care genotyping
• Supplemental Cohort: i. Subjects with genetic testing results consistent with biallelic disease-causing variation in ATP8B1 (PFIC1), ABCB4 (PFIC3), or TJP2 (PFIC4), based on standard of care genotyping. ii. Subjects with PFIC phenotype without a known mutation or with another known mutation not described above or with intermittent cholestasis as manifested by fluctuating sBA levels. iii. Subjects with PFIC after internal or external biliary diversion surgery or for whom internal or external biliary diversion surgery was reversed.
• Male 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 methods of 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
• Access to email or phone for scheduled remote visits
• Ability to read and understand the questionnaires (both caregivers and subjects above the age of assent)
• Access to consistent caregiver(s) during the study
• Subject and caregiver willingness to comply with all study visits and requirements.

Exclusion Criteria

• 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 (applies to primary cohort only). Subjects can enter the study in the Supplemental Cohort (under inclusion criteria 6.ii or 6.iii).
• Recurrent intrahepatic cholestasis, indicated by a history of sBA levels 1.5, albumin 15× ULN at screening
• Presence of other liver disease
• 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
• Possibly malignant liver mass on imaging, including screening ultrasound
• Known diagnosis of human immunodeficiency virus (HIV) infection
• Any prior cancer diagnosis (except for in situ carcinoma) within 5 years of the screening visit (Visit 0)
• Any known history of alcohol or substance abuse
• Administration of bile acids or lipid binding resins, or phenylbutyrates during the screening period
• Criterion has been deleted as of Amendment 3
• Administration of any investigational drug, biologic, or medical device during the screening period
• Previous use of an ileal bile acid transporter inhibitor (IBATi)
• 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 nonadherence with the study protocol or inability to conduct the study procedures
• Known hypersensitivity to maralixibat or any of its excipients.