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


The purpose of this study is to determine if the investigational treatment (maralixibat) is safe and effective in pediatric participants with Progressive Familial Intrahepatic Cholestasis (PFIC).


  • Progressive Familial Intrahepatic Cholestasis (PFIC)


Eligible Ages
Between 1 Year and 17 Years
Eligible Genders
Accepts Healthy Volunteers

Inclusion Criteria

  • Informed consent and assent (as applicable) per Institutional Review Board/Ethics Committee (IRB/EC) - Male or female subjects with a body weight ≥ 5.0 kg, who are ≥ 12 months and < 18 years of age at time of baseline - Cholestasis as manifested by total sBA ≥ 3× Upper Limit of Normal (ULN) (applies to primary cohort only) - Moderate Pruritus - Diagnosis of PFIC based on: - Chronic cholestasis as manifested by persistent (>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 levelsiii. Subjects with PFIC after internal or external biliary diversion surgery or for whom internal or external biliary diversion surgery was reversed

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 <3x ULN or intermittent pruritus (applies to primary cohort only) - Current or recent history (<1 year) of atopic dermatitis or other non-cholestatic diseases associated with pruritus - History of surgical disruption of the enterohepatic circulation (applies to primary cohort only) - Chronic diarrhea requiring intravenous fluid or nutritional intervention for the diarrhea and/or its sequelae at screening or during the 6 months prior to screening - Previous or need for imminent liver transplant - Decompensated cirrhosis (international normalized ratio [INR] > 1.5, and/or albumin < 30 g/L, history or presence of clinically significant ascites, and/or variceal hemorrhage, and/or encephalopathy) - Alanine aminotransferase (ALT) or total serum bilirubin (TSB) > 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 phenylbutyrate during the screening period - 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.

Study Design

Phase 3
Study Type
Intervention Model
Parallel Assignment
Primary Purpose
Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Arm Groups

ArmDescriptionAssigned Intervention
Participants will be randomized to Maralixibat oral solution (up to 600 microgram per kilogram [mcg/kg]) orally twice daily for 26 weeks.
  • Drug: Maralixibat
    Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.
    Other names:
    • Formerly LUM001 and SHP625
Placebo Comparator
Participants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.
  • Other: Placebo
    Placebo matching to maralixibat orally twice daily for 26 weeks.

Recruiting Locations

University of Texas, Health Science Center San Antonio
San Antonio, Texas 78229
Naveen K Mittal, MD

More Details

Mirum Pharmaceuticals, Inc.

Study Contact

Clinical Trials Mirum

Detailed Description

This study will be conducted at multiple sites in North America, Europe, Asia, and South America.