A Study to Evaluate the Efficacy and Safety of Maralixibat in Subjects With Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC)
NCT ID: NCT03905330
Last Updated: 2023-12-11
Study Results
Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.
View full resultsBasic Information
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COMPLETED
PHASE3
93 participants
INTERVENTIONAL
2019-07-09
2022-09-01
Brief Summary
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Detailed Description
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Conditions
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Keywords
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Study Design
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RANDOMIZED
PARALLEL
TREATMENT
QUADRUPLE
Study Groups
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Maralixibat
Participants will receive Maralixibat oral solution (up to 600 microgram per kilogram \[mcg/kg\]) orally twice daily for 26 weeks.
Maralixibat
Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.
Placebo
Participants will receive placebo matched to maralixibat oral solution twice daily for 26 weeks.
Placebo
Placebo matching to maralixibat orally twice daily for 26 weeks.
Interventions
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Maralixibat
Maralixibat oral solution (up to 600 mcg/kg) orally twice daily for 26 weeks.
Placebo
Placebo matching to maralixibat orally twice daily for 26 weeks.
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
2. Male or female subjects with a body weight ≥5 kg, who are ≥12 months and \<18 years of age at time of baseline
3. Cholestasis as manifested by total sBA ≥3× ULN (applies to primary cohort only)
4. An average AM ItchRO(Obs) score ≥1.5 during 4 consecutive weeks of the screening period, leading to the baseline visit (Visit 1)
5. 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)
6. 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.
7. 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
8. Access to email or phone for scheduled remote visits
9. Ability to read and understand the questionnaires (both caregivers and subjects above the age of assent)
10. Access to consistent caregiver(s) during the study
11. Subject and caregiver willingness to comply with all study visits and requirements.
2. Recurrent intrahepatic cholestasis, indicated by a history of sBA levels \<3x ULN or intermittent pruritus (applies to primary cohort only)
3. Current or recent history (\<1 year) of atopic dermatitis or other non-cholestatic diseases associated with pruritus.
4. History of surgical disruption of the enterohepatic circulation (applies to primary cohort only)
5. 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
6. Previous or need for imminent liver transplant
7. Decompensated cirrhosis (international normalized ratio \[INR\] \>1.5, albumin \<30 g/L, history or presence of clinically significant ascites, variceal hemorrhage, and/or encephalopathy)
8. ALT or total serum bilirubin (TSB) \>15× ULN at screening
9. Presence of other liver disease
10. 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
11. Possibly malignant liver mass on imaging, including screening ultrasound
12. Known diagnosis of human immunodeficiency virus (HIV) infection
13. Any prior cancer diagnosis (except for in situ carcinoma) within 5 years of the screening visit (Visit 0)
14. Any known history of alcohol or substance abuse
15. Administration of bile acids or lipid binding resins, or phenylbutyrates during the screening period
16. Criterion has been deleted as of Amendment 3
17. Administration of any investigational drug, biologic, or medical device during the screening period
18. Previous use of an ileal bile acid transporter inhibitor (IBATi)
19. 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
20. Known hypersensitivity to maralixibat or any of its excipients.
1 Year
17 Years
ALL
No
Sponsors
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Mirum Pharmaceuticals, Inc.
INDUSTRY
Responsible Party
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Locations
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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
Consultario de Joshue David Covarrubias Esquer
Zapopan, , Mexico
Instytut Pomnik Centrum Zdrowia Dziecka
Warsaw, , Poland
KK Women's and Children's Hospital
Singapore, , Singapore
Koc University Hospital
Istanbul, , Turkey (Türkiye)
Birmingham Children's Hospital
Birmingham, , United Kingdom
King's College Hospital NHS
London, , United Kingdom
Countries
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References
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Miethke AG, Moukarzel A, Porta G, Covarrubias Esquer J, Czubkowski P, Ordonez F, Mosca A, Aqul AA, Squires RH, Sokal E, D'Agostino D, Baumann U, D'Antiga L, Kasi N, Laborde N, Arikan C, Lin CH, Gilmour S, Mittal N, Chiou FK, Horslen SP, Huber WD, Jaecklin T, Nunes T, Lascau A, Longpre L, Mogul DB, Garner W, Vig P, Hupertz VF, Gonzalez-Peralta RP, Ekong U, Hartley J, Laverdure N, Ovchinsky N, Thompson RJ. Maralixibat in progressive familial intrahepatic cholestasis (MARCH-PFIC): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Gastroenterol Hepatol. 2024 Jul;9(7):620-631. doi: 10.1016/S2468-1253(24)00080-3. Epub 2024 May 6.
Provided Documents
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Document Type: Study Protocol
Document Type: Statistical Analysis Plan
Related Links
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Genetics Home Reference - PFIC
US FDA Resources
Mirum Pharmaceuticals homepage
Other Identifiers
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2019-001211-22
Identifier Type: EUDRACT_NUMBER
Identifier Source: secondary_id
MRX-502
Identifier Type: -
Identifier Source: org_study_id