Summary

for people ages 1-17 (full criteria)
at San Francisco, California and other locations
study started
estimated completion

Description

Summary

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).

Official Title

MRX-502: Randomized Double-blind Placebo-controlled Phase 3 Study to Evaluate the Efficacy and Safety of Maralixibat in the Treatment of Subjects With Progressive Familial Intrahepatic Cholestasis (PFIC) - MARCH-PFIC

Details

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

Keywords

Progressive Familial Intrahepatic Cholestasis (PFIC) Cholestasis Maralixibat Mutation PFIC PFIC2 Bile Duct Diseases Liver Diseases Biliary Tract Diseases Digestive System Diseases Pediatric Cholestasis, Intrahepatic

Eligibility

For people ages 1-17

Key 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 < 18 years of age at time of consent
  • Cholestasis as manifested by total serum Bile Acids ≥ 3× ULN
  • An average morning Itch Observer Reported Outcome (ItchRO[Obs]) score ≥ 1.5 during 4 consecutive weeks of the screening period, leading to the baseline visit (Visit 1)
  • Diagnosis of PFIC based on the following:
  • Chronic cholestasis as manifested by persistent (>6 months) pruritus, biochemical abnormalities 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 iii. Subjects with PFIC after internal or external biliary diversion surgery or for whom internal or external biliary diversion surgery was reversed

Key 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)
  • 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 planned liver transplant
  • Decompensated cirrhosis (international normalized ratio [INR] > 1.5, albumin < 30 g/L, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy)
  • 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
  • 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)
  • Administration of growth hormones at any time before or during the study
  • 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

Locations

  • UCSF Medical Center not yet accepting patients
    San Francisco California 94143 United States
  • Children Hospital LA not yet accepting patients
    Los Angeles California 90027 United States

Details

Status
accepting new patients
Start Date
Completion Date
(estimated)
Sponsor
Mirum Pharmaceuticals, Inc.
Links
Genetics Home Reference - PFIC
Mirum Pharmaceuticals homepage
ID
NCT03905330
Phase
Phase 3
Study Type
Interventional
Last Updated