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

Completed · Phase 3 · Has a placebo group

Conditions studied: Progressive Familial Intrahepatic Cholestasis (PFIC)

In brief

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

Key facts

Study ID

NCT03905330

Run by

Mirum Pharmaceuticals, Inc.

People needed

93

Starts

2019-07-09

Expected to finish

2022-09-01

Last updated by the study team

2023-12-11

Who can join

Age: 1 and older, up to 17. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• 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 baseline
• Cholestasis as manifested by total sBA ≥3× ULN (applies to primary cohort only)
• An average AM ItchRO(Obs) score ≥1.5 during 4 consecutive weeks of the screening period, leading to the baseline visit (Visit 1)
• Completion of at least 21 valid* morning ItchRO(Obs) entries during 4 consecutive weeks of the screening period, leading to the baseline visit (Visit 1) (*valid = completed and not answered as "I don't know"; maximum allowed invalid reports = 7, no more than 2 invalid reports during the last 7 days before randomization)
• Diagnosis of PFIC based on the following:
• 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 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.

You may not qualify if…

• 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, 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
• 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.

Where it is running

• Children's Hospital Los Angeles CHLA — Los Angeles, California, United States
• Medstar Georgetown University Hospital — Washington D.C., District of Columbia, United States
• Advent Health — Orlando, Florida, United States
• The Children's Hospital at Montefiore Yeshiva University - Montefiore Medical Center — New York, New York, United States
• Cincinnati Children's Hospital — Cincinnati, Ohio, United States
• Cleveland Clinic - Pediatric Institute — Cleveland, Ohio, United States
• UPMC Children's Hospital of Pittsburgh — Pittsburgh, Pennsylvania, United States
• Medical University of South Carolina — Charleston, South Carolina, United States
• University of Texas - UT Southwestern Medical Center — Dallas, Texas, United States
• University of Texas, Health Science Center San Antonio — San Antonio, Texas, United States
• Seattle Children's Hospital — Seattle, Washington, United States
• Hospital Italiano de Buenos Aires — Buenos Aires, Argentina
• Medizinische Universität Wien, Universitätsklinik für Kinder- und Jugendheilkunde — Vienna, Austria
• Universite Catholique de Louvain (UCLouvain) - Cliniques Universitaires Saint-Luc — Brussels, Belgium
• Sociedade Beneficente de Senhoras Hospital Sírio-Libanês — São Paulo, Brazil
• University of Alberta - Women and Children's Health Research Institute — Edmonton, Canada
• Fundacion Cardioinfantil - Departamento de Investigaciones — Bogotá, Colombia
• Hospices Civils de Lyon - Hopital Femme Mere Enfant Service de Gastroenterologie, Hepatologie et Nutrition — Lyon, France
• CHU de Marseille, Hôpital de la Timone — Marseille, France
• CHU de Toulouse - Hôpital des Enfants — Toulouse, France
• Medizinische Hochschule Hannover — Hanover, Germany
• Semmelweis Egyetem - Altalanos Orvostudomanyi Kar (SE AOK) — Budapest, Hungary
• Hospital Papa Giovanni XXIII / Unità di Pediatria — Bergamo, Italy
• Ospedale Pediatrico Bambino Gesu — Roma, Italy
• Hotel Dieu de France — Beirut, Lebanon

Full record on ClinicalTrials.gov

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