Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   43851   clinical trials with a EudraCT protocol, of which   7283   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Print Download

    Summary
    EudraCT Number:2019-001211-22
    Sponsor's Protocol Code Number:MRX-502
    National Competent Authority:Hungary - National Institute of Pharmacy
    Clinical Trial Type:EEA CTA
    Trial Status:Completed
    Date on which this record was first entered in the EudraCT database:2019-06-20
    Trial results View results
    Index
    A. PROTOCOL INFORMATION
    B. SPONSOR INFORMATION
    C. APPLICANT IDENTIFICATION
    D. IMP IDENTIFICATION
    D.8 INFORMATION ON PLACEBO
    E. GENERAL INFORMATION ON THE TRIAL
    F. POPULATION OF TRIAL SUBJECTS
    G. INVESTIGATOR NETWORKS TO BE INVOLVED IN THE TRIAL
    N. REVIEW BY THE COMPETENT AUTHORITY OR ETHICS COMMITTEE IN THE COUNTRY CONCERNED
    P. END OF TRIAL
    Expand All   Collapse All
    A. Protocol Information
    A.1Member State ConcernedHungary - National Institute of Pharmacy
    A.2EudraCT number2019-001211-22
    A.3Full title of the trial
    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.
    MRX 502: Randomizált, kettős vak, placebokontrollos, III. fázisú vizsgálat a maralixibat hatásosságának és biztonságosságának értékelésére progresszív familiáris intrahepaticus cholestasisos (PFIC) vizsgálati alanyok kezelésében – MARCH PFIC
    A.3.1Title of the trial for lay people, in easily understood, i.e. non-technical, language
    A Placebo-controlled study of Maralixibat in Subjects with Progressive Familial Intrahepatic Cholestasis (MARCH-PFIC).
    A.3.2Name or abbreviated title of the trial where available
    MARCH-PFIC
    A.4.1Sponsor's protocol code numberMRX-502
    A.5.2US NCT (ClinicalTrials.gov registry) numberNCT03905330
    A.7Trial is part of a Paediatric Investigation Plan Yes
    A.8EMA Decision number of Paediatric Investigation PlanP/409/2019
    B. Sponsor Information
    B.Sponsor: 1
    B.1.1Name of SponsorMirum Pharmaceuticals Inc.
    B.1.3.4CountryUnited States
    B.3.1 and B.3.2Status of the sponsorCommercial
    B.4 Source(s) of Monetary or Material Support for the clinical trial:
    B.4.1Name of organisation providing supportMirum Pharmaceuticals, Inc.
    B.4.2CountryUnited States
    B.5 Contact point designated by the sponsor for further information on the trial
    B.5.1Name of organisationMirum Pharmaceuticals, Inc.
    B.5.2Functional name of contact pointChief Scientific Officer
    B.5.3 Address:
    B.5.3.1Street Address950 Tower Lane, Suite 1050
    B.5.3.2Town/ cityFoster City California
    B.5.3.3Post codeCA 94404
    B.5.3.4CountryUnited States
    B.5.4Telephone number16506674085
    B.5.5Fax number16506674085
    B.5.6E-mailmedinfo@mirumpharma.com
    D. IMP Identification
    D.IMP: 1
    D.1.2 and D.1.3IMP RoleTest
    D.2 Status of the IMP to be used in the clinical trial
    D.2.1IMP to be used in the trial has a marketing authorisation No
    D.2.5The IMP has been designated in this indication as an orphan drug in the Community Yes
    D.2.5.1Orphan drug designation numberEU/3/13/1216
    D.3 Description of the IMP
    D.3.1Product nameMaralixibat (formerly SHP625 or LUM001)
    D.3.4Pharmaceutical form Oral solution
    D.3.4.1Specific paediatric formulation Yes
    D.3.7Routes of administration for this IMPOral use
    D.3.8 to D.3.10 IMP Identification Details (Active Substances)
    D.3.8INN - Proposed INNMARALIXIBAT CHLORIDE
    D.3.9.1CAS number 228113-66-4
    D.3.9.4EV Substance CodeSUB195693
    D.3.10 Strength
    D.3.10.1Concentration unit mg/ml milligram(s)/millilitre
    D.3.10.2Concentration typerange
    D.3.10.3Concentration number5 to 20
    D.3.11 The IMP contains an:
    D.3.11.1Active substance of chemical origin Yes
    D.3.11.2Active substance of biological/ biotechnological origin (other than Advanced Therapy IMP (ATIMP) No
    The IMP is a:
    D.3.11.3Advanced Therapy IMP (ATIMP) No
    D.3.11.3.1Somatic cell therapy medicinal product No
    D.3.11.3.2Gene therapy medical product No
    D.3.11.3.3Tissue Engineered Product No
    D.3.11.3.4Combination ATIMP (i.e. one involving a medical device) No
    D.3.11.3.5Committee on Advanced therapies (CAT) has issued a classification for this product No
    D.3.11.4Combination product that includes a device, but does not involve an Advanced Therapy No
    D.3.11.5Radiopharmaceutical medicinal product No
    D.3.11.6Immunological medicinal product (such as vaccine, allergen, immune serum) No
    D.3.11.7Plasma derived medicinal product No
    D.3.11.8Extractive medicinal product No
    D.3.11.9Recombinant medicinal product No
    D.3.11.10Medicinal product containing genetically modified organisms No
    D.3.11.11Herbal medicinal product No
    D.3.11.12Homeopathic medicinal product No
    D.3.11.13Another type of medicinal product No
    D.8 Information on Placebo
    D.8 Placebo: 1
    D.8.1Is a Placebo used in this Trial?Yes
    D.8.3Pharmaceutical form of the placeboOral solution
    D.8.4Route of administration of the placeboOral use
    E. General Information on the Trial
    E.1 Medical condition or disease under investigation
    E.1.1Medical condition(s) being investigated
    In patients with progressive familial intrahepatic cholestasis (PFIC),
    impairment of the egress of bile acids from the liver leads to cholestasis,
    hepatocellular injury and damage, and progressive liver disease that
    may ultimately lead to the need for liver transplantation. Itch is a
    common symptom associated with cholestasis, it can occur at all stages of cholestatic liver disease, with or without jaundice.
    E.1.1.1Medical condition in easily understood language
    PFIC is a long-term debilitating and life-threatening disease
    due to liver and heart problems.
    E.1.1.2Therapeutic area Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]
    MedDRA Classification
    E.1.2 Medical condition or disease under investigation
    E.1.2Version 20.0
    E.1.2Level PT
    E.1.2Classification code 10076033
    E.1.2Term Progressive familial intrahepatic cholestasis
    E.1.2System Organ Class 10010331 - Congenital, familial and genetic disorders
    E.1.3Condition being studied is a rare disease Yes
    E.2 Objective of the trial
    E.2.1Main objective of the trial
    To evaluate the efficacy of maralixibat vs placebo on the severity of pruritus in the primary cohort.
    E.2.2Secondary objectives of the trial
    •To evaluate the efficacy of maralixibat vs. placebo on the frequency of pruritus in the primary cohort
    •To evaluate the efficacy of maralixibat vs. placebo on total serum bile acid (sBA) levels in the primary cohort
    •To evaluate the safety, tolerability, and PK of maralixibat vs placebo
    E.2.3Trial contains a sub-study No
    E.3Principal inclusion criteria
    1.Informed consent and assent (as applicable) per Institutional Review Board/Ethics Committee (IRB/EC)
    2.Male or female subjects with a body weight ≥ 5 kg, who are ≥12 months and < 18 years of age at time of consent
    3.Cholestasis as manifested by total sBA ≥ 3× ULN
    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)
    6.6.Diagnosis of PFIC based on:
    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
    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 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
    E.4Principal exclusion criteria
    1. 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)
    2. Recurrent intrahepatic cholestasis, indicated by a history of sBA levels <3x ULN or intermittent pruritus
    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), and patients who have clinically significant renal disease per Investigator discretion, and patients with hepatorenal syndrome
    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 resected and fully excised 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 sodium phenylbutyrate during the screening period
    16. Administration of growth hormones at any time before or during the study
    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
    E.5 End points
    E.5.1Primary end point(s)
    •Mean change in the average morning ItchRO(Obs) severity score between baseline and Week 15 through Week 26
    E.5.1.1Timepoint(s) of evaluation of this end point
    The primary, secondary, and exploratory efficacy endpoints will be evaluated in the primary cohort, overall supplemental cohort, all cohorts combined, and the PFIC1 and PFIC3 sub-cohorts (separately) given sufficient sample size.
    The safety and tolerability, and other endpoints will be evaluated in the primary cohort, and all cohorts combined.
    E.5.2Secondary end point(s)
    •Mean change in the average morning ItchRO(Obs) frequency score between baseline and Week 15 through Week 26
    •Mean change in total sBA between baseline and Week 26
    E.5.2.1Timepoint(s) of evaluation of this end point
    These are measured throughout the trial by means of the subject eDiary
    and clinician scales and questionnaires.
    E.6 and E.7 Scope of the trial
    E.6Scope of the trial
    E.6.1Diagnosis No
    E.6.2Prophylaxis No
    E.6.3Therapy Yes
    E.6.4Safety Yes
    E.6.5Efficacy Yes
    E.6.6Pharmacokinetic Yes
    E.6.7Pharmacodynamic No
    E.6.8Bioequivalence No
    E.6.9Dose response Yes
    E.6.10Pharmacogenetic No
    E.6.11Pharmacogenomic No
    E.6.12Pharmacoeconomic No
    E.6.13Others No
    E.7Trial type and phase
    E.7.1Human pharmacology (Phase I) No
    E.7.1.1First administration to humans No
    E.7.1.2Bioequivalence study No
    E.7.1.3Other No
    E.7.1.3.1Other trial type description
    E.7.2Therapeutic exploratory (Phase II) No
    E.7.3Therapeutic confirmatory (Phase III) Yes
    E.7.4Therapeutic use (Phase IV) No
    E.8 Design of the trial
    E.8.1Controlled Yes
    E.8.1.1Randomised Yes
    E.8.1.2Open No
    E.8.1.3Single blind No
    E.8.1.4Double blind Yes
    E.8.1.5Parallel group Yes
    E.8.1.6Cross over No
    E.8.1.7Other No
    E.8.2 Comparator of controlled trial
    E.8.2.1Other medicinal product(s) No
    E.8.2.2Placebo Yes
    E.8.2.3Other No
    E.8.2.4Number of treatment arms in the trial2
    E.8.3 The trial involves single site in the Member State concerned No
    E.8.4 The trial involves multiple sites in the Member State concerned Yes
    E.8.4.1Number of sites anticipated in Member State concerned1
    E.8.5The trial involves multiple Member States Yes
    E.8.5.1Number of sites anticipated in the EEA20
    E.8.6 Trial involving sites outside the EEA
    E.8.6.1Trial being conducted both within and outside the EEA Yes
    E.8.6.2Trial being conducted completely outside of the EEA No
    E.8.6.3If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned
    Argentina
    Austria
    Belgium
    Brazil
    Canada
    Colombia
    France
    Germany
    Hungary
    Italy
    Lebanon
    Mexico
    Poland
    Singapore
    Turkey
    United Kingdom
    United States
    E.8.7Trial has a data monitoring committee Yes
    E.8.8 Definition of the end of the trial and justification where it is not the last visit of the last subject undergoing the trial
    LPLV
    E.8.9 Initial estimate of the duration of the trial
    E.8.9.1In the Member State concerned years1
    E.8.9.1In the Member State concerned months11
    E.8.9.1In the Member State concerned days9
    E.8.9.2In all countries concerned by the trial years1
    E.8.9.2In all countries concerned by the trial months11
    E.8.9.2In all countries concerned by the trial days9
    F. Population of Trial Subjects
    F.1 Age Range
    F.1.1Trial has subjects under 18 Yes
    F.1.1Number of subjects for this age range: 30
    F.1.1.1In Utero No
    F.1.1.2Preterm newborn infants (up to gestational age < 37 weeks) No
    F.1.1.3Newborns (0-27 days) No
    F.1.1.4Infants and toddlers (28 days-23 months) Yes
    F.1.1.4.1Number of subjects for this age range: 5
    F.1.1.5Children (2-11years) Yes
    F.1.1.5.1Number of subjects for this age range: 20
    F.1.1.6Adolescents (12-17 years) Yes
    F.1.1.6.1Number of subjects for this age range: 5
    F.1.2Adults (18-64 years) No
    F.1.2.1Number of subjects for this age range: 0
    F.1.3Elderly (>=65 years) No
    F.1.3.1Number of subjects for this age range: 0
    F.2 Gender
    F.2.1Female Yes
    F.2.2Male Yes
    F.3 Group of trial subjects
    F.3.1Healthy volunteers No
    F.3.2Patients Yes
    F.3.3Specific vulnerable populations Yes
    F.3.3.1Women of childbearing potential not using contraception No
    F.3.3.2Women of child-bearing potential using contraception Yes
    F.3.3.3Pregnant women No
    F.3.3.4Nursing women No
    F.3.3.5Emergency situation No
    F.3.3.6Subjects incapable of giving consent personally Yes
    F.3.3.6.1Details of subjects incapable of giving consent
    Children from ≥12 months and < 18 years old to be recruited. Assent and parent/caregiver consent will be obtained for those children not able to provide assent personally. Subjects signed assent at age 17 may turn to 18 during the study.
    F.3.3.7Others No
    F.4 Planned number of subjects to be included
    F.4.1In the member state3
    F.4.2 For a multinational trial
    F.4.2.1In the EEA 13
    F.4.2.2In the whole clinical trial 30
    F.5 Plans for treatment or care after the subject has ended the participation in the trial (if it is different from the expected normal treatment of that condition)
    Upon completion of protocol MRX-502 treatment patients will be offered to continue treatment in long term open label extension study MRX-503.
    Otherwise options for patients' treatment will be evaluated by the study doctor.
    G. Investigator Networks to be involved in the Trial
    N. Review by the Competent Authority or Ethics Committee in the country concerned
    N.Competent Authority Decision Authorised
    N.Date of Competent Authority Decision2019-08-15
    N.Ethics Committee Opinion of the trial applicationFavourable
    N.Ethics Committee Opinion: Reason(s) for unfavourable opinion
    N.Date of Ethics Committee Opinion2019-07-17
    P. End of Trial
    P.End of Trial StatusCompleted
    P.Date of the global end of the trial2022-09-01
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

    European Medicines Agency © 1995-Sat Apr 20 08:01:09 CEST 2024 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA