Clinical trial • Phase IV • Rare Disease|Cardiology|Gastroenterology
Maralixibat for Progressive familial intrahepatic cholestasis|Alagille syndrome
Phase IV trial of Maralixibat for Progressive familial intrahepatic cholestasis|Alagille syndrome. open-label, none/not specified-controlled.
Overview
- Trial Therapeutic Area
- Rare Disease|Cardiology|Gastroenterology
- Trial Disease
- Progressive familial intrahepatic cholestasis|Alagille syndrome
- Trial Stage
- Phase IV
- Drug Modality
- Small molecule
- Paediatric Trial
- Yes
- Orphan Drug
- Yes
Key dates
- Initial CTIS Submission Date
- 20-12-2024
- First CTIS Authorization Date
- 21-04-2025
Trial design
open-label, none/not specified-controlled Phase IV trial across 14 sites in France, Italy, Spain and others.
- Open Label
- Yes
- Comparator
- None/Not specified
- Single Multiple Or Escalation Dose Combined
- Yes
- Target Sample Size
- 223
- Trial Duration For Participant
- 3652
Eligibility
Recruits 223 paediatric patients.
- Vulnerable Population
- Vulnerable populations are included (isVulnerablePopulationSelected = true). The study includes children (from ≥2 months for ALGS and ≥3 months for PFIC). Consent approach requires informed consent and assent as applicable (principal inclusion criterion: "Understand and execute an Informed consent and assent (as applicable)"). Age-specific consent/assent documents are provided (parent/guardian ICF and assent forms for age groups such as 3-5, 6-11, 12-17, and parent/guardian forms), with materials available in multiple languages as per submitted ICF documents.
Inclusion criteria
- {"criterion_text":"- Understand and execute an Informed consent and assent (as applicable)\n- A clinically and/or genetically confirmed ALGS diagnosis with pruritus secondary to chronic cholestasis (Saleh et al. 2016) or a clinically and/or genetically confirmed PFIC diagnosis (Hassan and Hertel 2022)\n- For the ALGS primary cohort: Initiation of Livmarli at the time of study entry\n- For the ALGS supplemental cohort: Actively using Livmarli prior to study entry\n- For participants with ALGS, ≥2 months of age at Day 1\n- For participants with PFIC, ≥3 months of age at Day 1\n- For participants with PFIC: Prescribed Livmarli at the time of study entry or prior to study entry"}
Exclusion criteria
- {"criterion_text":"- History of LT\n- Any Livmarli contraindications (as per SmPC)\n- Any condition or abnormality that, in the opinion of the investigator, may interfere with the participation in or completion of the study\n- Received an investigational drug within 30 days before the first dose of Livmarli (Participation in previous maralixibat studies or expanded access programs is acceptable)\n- Baseline data before start of treatment of Livmarli are unavailable for key safety (LFTs, FSV laboratory results) and key efficacy (sBA, pruritus) parameters\n- Received another IBAT inhibitor within 7 days before the first dose of Livmarli"}
Endpoints
Primary endpoints
- {"endpoint_text":"- Safety • AEs • The number and proportion of participants who experience an AE • Change in liver function tests from Baseline • Change in FSV levels and INR (as an estimate of vitamin K) from Baseline • For participants with PFIC PG toxicity will be monitored","definition_or_measurement_approach":"Safety endpoints include number and proportion of participants with adverse events (AEs); change from Baseline in liver function tests; change from Baseline in fat-soluble vitamin (FSV) levels and INR as an estimate of vitamin K. For PFIC participants, propylene glycol (PG) toxicity will be monitored."}
- {"endpoint_text":"- Efficacy • Change in pruritus severity from Baseline as measured by Clinician Scratch Scale (CSS) score • Change in serum bile acids (sBA) levels from Baseline • Frequency in the use of concomitant medications for the treatment of underlying liver disease, treatment of pruritus, or treatment of cholestasis • Frequency and timing of long-term clinical outcomes","definition_or_measurement_approach":"Pruritus severity measured by Clinician Scratch Scale (CSS) score (change from Baseline); change from Baseline in serum bile acids (sBA); frequency of concomitant medication use for liver disease/pruritus/cholestasis; frequency and timing of long-term clinical outcomes (e.g., SBD, LT, portal hypertension, complications)."}
- {"endpoint_text":"- Tolerability: Tolerability of starting dose and dose escalation will be assessed by summarizing AEs and/or any other safety information (as available) on starting dose and during dose escalation phase. The cases of dose reduction, treatment interruption, and treatment discontinuation due to AEs/poor tolerability will be also summarized over the whole treatment period.","definition_or_measurement_approach":"Tolerability assessed by summaries of AEs and other safety information at starting dose and during dose escalation; summaries of cases with dose reduction, treatment interruption, and treatment discontinuation due to AEs/poor tolerability over the treatment period."}
- {"endpoint_text":"- Growth: Growth, including height/length and weight, will be assessed as an endpoint. The endpoint will be assessed as change from Baseline in height/length and weight (absolute values and z-scores).","definition_or_measurement_approach":"Growth assessed by change from Baseline in height/length and weight (absolute values and z-scores)."}
- {"endpoint_text":"- Overdose, Dosing Errors, Misuse, and Abuse Frequencies of overdose and dosing errors/medication errors will be calculated.","definition_or_measurement_approach":"Frequencies of overdose, dosing errors, medication errors, misuse, and abuse will be calculated and summarized."}
Recruitment
- Digital Remote Recruitment
- Yes
- Planned Sample Size
- 223
- Recruitment Window Months
- 120
- Consent Approach
- Informed consent is required from participants or their parent/legal guardian as applicable; assent is required for minors where applicable (inclusion criterion: 'Understand and execute an Informed consent and assent (as applicable)'). Age-specific consent/assent documents are provided (parent/guardian ICF and assent forms for age groups such as 3-5, 6-11, 12-17, and versions for infants/toddlers). Consent and patient-facing materials are available in multiple languages (English, French, German, Italian, Dutch, Spanish) as indicated by the multiple country-specific ICF and patient-facing documents.
Methods
- Site-based recruitment through participating hospitals/clinics listed in each country (hospital sites are specified in the Part II submissions: e.g., pediatric hepatology/gastroenterology departments in Spain, France, Italy, Belgium, Germany, Netherlands).
- Digital recruitment/materials via Scout Clinical platform and materials: 'Scout Brochure', 'Reloadable ScoutPass Mailer', 'Reloadable ScoutPass FAQs' (documents present in submission indicate use of Scout-related digital materials and mailer).
- Email communication to potential participants (documents titled 'L2_SC_Email communication' and similar country-specific email communication files).
- Participant information materials and study brochures in multiple languages (documents titled 'Scout Brochure' and multiple PedsQL patient-facing questionnaires and ICFs in EN/FR/DE/IT/NL/ES).
- Participant expense reimbursement management (documents and third-party role: Scout Clinical - 'Expense reimbursment management for study participants').
Geography
- Total Number Of Sites
- 14
- Total Number Of Participants
- 223
France
- Earliest CTIS Part Ii Submission Date
- 21-03-2025
- Latest Decision Or Authorization Date
- 22-04-2025
- Processing Time Days
- 32
- Number Of Sites
- 3
- Number Of Participants
- 55
Sites
- Site Name
- Assistance Publique Hopitaux De Paris
- Department Name
- Pediatric Hepatology
- Principal Investigator Name
- Emmanuel Gonzales
- Principal Investigator Email
- Emmanuel.gonzales@aphp.fr
- Contact Person Name
- Emmanuel Gonzales
- Contact Person Email
- Emmanuel.gonzales@aphp.fr
- Site Name
- Hospices Civils De Lyon
- Department Name
- Pediatric Gastroenterology, Hepatology and Nutrition
- Principal Investigator Name
- Mathias Ruiz
- Principal Investigator Email
- mathias.ruiz@chu-lyon.fr
- Contact Person Name
- Mathias Ruiz
- Contact Person Email
- mathias.ruiz@chu-lyon.fr
- Site Name
- Hopital Des Enfants
- Department Name
- Gastro-entérologie, hépatologie, nutrition et maladies héréditaires du métabolisme
- Principal Investigator Name
- Nolwen Laborde
- Principal Investigator Email
- laborde.n@chu-toulouse.fr
- Contact Person Name
- Nolwen Laborde
- Contact Person Email
- laborde.n@chu-toulouse.fr
Italy
- Earliest CTIS Part Ii Submission Date
- 17-01-2025
- Latest Decision Or Authorization Date
- 22-04-2025
- Processing Time Days
- 95
- Number Of Sites
- 2
- Number Of Participants
- 44
Sites
- Site Name
- ISMETT (Istituto Mediterraneo per i Trapianti e Terapie ad Alta Specializzazione)
- Department Name
- Pediatrics Unit of Hepatology and Transplantation
- Principal Investigator Name
- Giusy Ranucci
- Principal Investigator Email
- granucci@ismett.edu
- Contact Person Name
- Giusy Ranucci
- Contact Person Email
- granucci@ismett.edu
- Site Name
- ASST Ospedale Papa Giovanni XXIII
- Department Name
- Pediatria
- Principal Investigator Name
- Lorenzo D' Antiga
- Principal Investigator Email
- ldantiga@asst-pg23.it
- Contact Person Name
- Lorenzo D' Antiga
- Contact Person Email
- ldantiga@asst-pg23.it
Spain
- Earliest CTIS Part Ii Submission Date
- 21-03-2025
- Latest Decision Or Authorization Date
- 21-04-2025
- Processing Time Days
- 31
- Number Of Sites
- 2
- Number Of Participants
- 38
Sites
- Site Name
- Hospital Universitario La Paz
- Department Name
- Hepatology
- Principal Investigator Name
- Esteban Frauca
- Principal Investigator Email
- esteban.frauca@salud.madrid.org
- Contact Person Name
- Esteban Frauca
- Contact Person Email
- esteban.frauca@salud.madrid.org
- Site Name
- Hospital Universitari Vall D Hebron
- Department Name
- Hepatology
- Principal Investigator Name
- Jesus Quintero
- Principal Investigator Email
- jesus.quintero@vallhebron.cat
- Contact Person Name
- Jesus Quintero
- Contact Person Email
- jesus.quintero@vallhebron.cat
Belgium
- Earliest CTIS Part Ii Submission Date
- 05-11-2025
- Latest Decision Or Authorization Date
- 18-11-2025
- Processing Time Days
- 13
- Number Of Sites
- 2
- Number Of Participants
- 34
Sites
- Site Name
- Cliniques Universitaires Saint-Luc
- Department Name
- Pediatric Department
- Principal Investigator Name
- Xavier Stephenne
- Principal Investigator Email
- xavier.stephenne@saintluc.uclouvain.be
- Contact Person Name
- Xavier Stephenne
- Contact Person Email
- xavier.stephenne@saintluc.uclouvain.be
- Site Name
- Universitair Ziekenhuis Gent
- Department Name
- Pediatric Gastroenterology Department
- Principal Investigator Name
- Ruth De Bruyne
- Principal Investigator Email
- ruth.debruyne@uzgent.be
- Contact Person Name
- Ruth De Bruyne
- Contact Person Email
- ruth.debruyne@uzgent.be
Germany
- Earliest CTIS Part Ii Submission Date
- 07-11-2025
- Latest Decision Or Authorization Date
- 15-12-2025
- Processing Time Days
- 38
- Number Of Sites
- 4
- Number Of Participants
- 36
Sites
- Site Name
- Charite Universitaetsmedizin Berlin KöR
- Department Name
- Department of Pediatric Gastroenterology, Nephrology and Metabolic Diseases
- Principal Investigator Name
- Philip Bufler
- Principal Investigator Email
- philip.bufler@charite.de
- Contact Person Name
- Philip Bufler
- Contact Person Email
- philip.bufler@charite.de
- Site Name
- University Medical Center Hamburg-Eppendorf
- Department Name
- Klinik und Poliklinik für Kinder-und Jungenmedizin
- Principal Investigator Name
- Sebastian Schulz-Jürgensen
- Principal Investigator Email
- s.schulz-juergensen@uke.de
- Contact Person Name
- Sebastian Schulz-Jürgensen
- Contact Person Email
- s.schulz-juergensen@uke.de
- Site Name
- Universitaetsklinikum Regensburg AöR
- Department Name
- Klinik und Poliklinik fur Kinder- und Jugendmedizin
- Principal Investigator Name
- Thomas Kehler
- Principal Investigator Email
- thomas.kehler@klinik.uni-regensburg.de
- Contact Person Name
- Thomas Kehler
- Contact Person Email
- thomas.kehler@klinik.uni-regensburg.de
- Site Name
- Universitaetsklinikum Essen AöR
- Department Name
- Kinderklinik II Gastroenterologie
- Principal Investigator Name
- Elke Lainka
- Principal Investigator Email
- elke.lainka@uk-essen.de
- Contact Person Name
- Elke Lainka
- Contact Person Email
- elke.lainka@uk-essen.de
Netherlands
- Earliest CTIS Part Ii Submission Date
- 07-11-2025
- Latest Decision Or Authorization Date
- 15-12-2025
- Processing Time Days
- 38
- Number Of Sites
- 1
- Number Of Participants
- 16
Sites
- Site Name
- Universitair Medisch Centrum Groningen
- Department Name
- Pediatrics
- Principal Investigator Name
- Hendrik Jan Verkade
- Principal Investigator Email
- h.j.verkade@umcg.nl
- Contact Person Name
- Hendrik Jan Verkade
- Contact Person Email
- h.j.verkade@umcg.nl
Sponsor
Primary sponsor
- Full Name
- Mirum Pharmaceuticals Inc.
- Organisation Type
- Pharmaceutical company
- Country Of Registered Address
- United States
Contract research organisations
- Name
- Ergomed Clinical Research Limited
- Responsibilities
- sponsorDuties codes: ["1","11","12","13","2","5"]
- Name
- Primevigilance USA Inc.
- Responsibilities
- sponsorDuties codes: ["8"] (pharmacovigilance)
Third parties
- {"country":"United States","full_name":"Edetek Inc.","duties_or_roles":"sponsorDuties codes: [\"10\"]","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Primevigilance USA Inc.","duties_or_roles":"sponsorDuties codes: [\"8\"]","organisation_type":"Pharmaceutical company"}
- {"country":"United Kingdom","full_name":"Ergomed Clinical Research Limited","duties_or_roles":"sponsorDuties codes: [\"1\",\"11\",\"12\",\"13\",\"2\",\"5\"]","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Sitero LLC","duties_or_roles":"sponsorDuties: [\"15\"] (Other - eCRF configuration, EDC hosting Data management E-data capture)","organisation_type":"Pharmaceutical company"}
- {"country":"United States","full_name":"Scout Clinical","duties_or_roles":"sponsorDuties: [\"15\"] (Expense reimbursment management for study participants)","organisation_type":"Hospital/Clinic/Other health care facility"}
Investigational products
- Investigational Product Name
- Livmarli 9.5 mg/mL oral solution
- Active Substance
- Maralixibat
- Modality
- Small molecule
- Routes Of Administration
- Oral
- Route
- oral
- Authorisation Status
- Authorised (EU marketing authorisation EU/1/22/1704/001)
- Orphan Designation
- Yes
- Maximum Dose
- 57 mg per day
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