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    Clinical Trial Results:
    MRX-503: An Open-label Extension Study to Evaluate the Long-term Safety and Efficacy of Maralixibat in the Treatment of Subjects with Progressive Familial Intrahepatic Cholestasis (PFIC)

    Summary
    EudraCT number
    		 2019-003395-39
    Trial protocol
    		 DE   GB   BE   PL   FR   HU   AT   IT  
    Global end of trial date
    23 Apr 2025

    Results information
    Results version number
    		 v1(current)
    This version publication date
    09 Nov 2025
    First version publication date
    09 Nov 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    MRX-503
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04185363
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Mirum Pharmaceuticals Inc
    Sponsor organisation address
    989 E Hillsdale Blvd. Suite 300, Foster City, United States, 94404
    Public contact
    Chief Development Officer, Mirum Pharmaceuticals, Inc. , 1 6506674085, medinfo@mirumpharma.com
    Scientific contact
    Chief Development Officer, Mirum Pharmaceuticals, Inc., 1 6506674085, medinfo@mirumpharma.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-001475-PIP03-17
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    23 Apr 2025
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    23 Apr 2025
    Global end of trial reached?
    Yes
    Global end of trial date
    23 Apr 2025
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of the study is to evaluate the long-term safety and tolerability of maralixibat.
    Protection of trial subjects
    All study participants (caregivers as applicable) were required to read and sign an Informed Consent Form (ICF). Participants were re-consented to the most current version of the ICF(s) during their participation in the study.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    16 Dec 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Poland: 5
    Country: Number of subjects enrolled
    United Kingdom: 2
    Country: Number of subjects enrolled
    Austria: 2
    Country: Number of subjects enrolled
    Belgium: 2
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    Italy: 5
    Country: Number of subjects enrolled
    Argentina: 3
    Country: Number of subjects enrolled
    Brazil: 10
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Colombia: 5
    Country: Number of subjects enrolled
    Lebanon: 13
    Country: Number of subjects enrolled
    Mexico: 8
    Country: Number of subjects enrolled
    Singapore: 2
    Country: Number of subjects enrolled
    Türkiye: 2
    Country: Number of subjects enrolled
    United States: 18
    Worldwide total number of subjects
    84
    EEA total number of subjects
    19
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    18
    Children (2-11 years)
    62
    Adolescents (12-17 years)
    4
    Adults (18-64 years)
    0
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 A total of 84 participants were enrolled at 28 sites across 17 countries (Argentina, Austria, Belgium, Brazil, Canada, Colombia, France, Germany, Italy, Lebanon, Mexico, Poland, Singapore, Turkey, United Kingdom, United States)

    Pre-assignment
    Screening details
    		 MRX-503, screening starts after signing the ICF and confirming eligibility. It overlaps with the MRX-502 end-of-treatment (EOT) visit: if the MRX-503 baseline visit occurs the same day or within 30 days of the MRX-502 EOT visit, those prior evaluations count as the MRX-503 baseline assessments.

    Period 1
    Period 1 title
    Open-Label extension (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Open Label Extension
    Arm description
    		 This open-label, extension study comprised one continuous treatment period, including: - Dose-escalation (4-6 weeks) - Stable-dosing (until the sponsor or the subject terminates the study, discontinues/ transitions to commercial product) - Safety follow-up phases. Subjects were analyzed in two cohorts: - The Primary Cohort (non-truncated PFIC2) - The Secondary Cohort (other PFIC subtypes, including PFIC1, PFIC3, truncated PFIC2, or incomplete response after PEBD)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Maralixibat
    Investigational medicinal product code
    Other name
    LIVMARLI™
    Pharmaceutical forms
    Oral solution in bottle
    Routes of administration
    Oral use
    Dosage and administration details
    Maralixibat was administered orally as a ready-to-use oral solution (5, 10, 15, or 20 mg/mL) based on individual body weight, up to 600 µg/kg twice daily (BID). Dosing followed a weekly escalation schedule over 4–6 weeks as follows: • Week 1: 150 µg/kg BID • Week 2: 300 µg/kg BID • Week 3: 450 µg/kg BID • Week 4 and onward: 600 µg/kg BID (maximum tolerated dose) Doses were taken approximately 30 minutes before breakfast and the evening meal. Subjects unable to tolerate 150 µg/kg BID were discontinued. The maximum tolerated dose established by Week 6 was maintained for the Stable Dosing period until study termination or transition to commercial product.

    Number of subjects in period 1
    		Open Label Extension
    Started
    84
    Completed
    48
    Not completed
    36
         Consent withdrawn by subject
    7
         Physician decision
    3
         Disease progression
    2
         Adverse event, non-fatal
    5
         Rolled over under drug interruption.
    1
         Liver transplant
    17
         Lost to follow-up
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Open-Label extension
    Reporting group description
    		 -

    Reporting group values
    		 Open-Label extension Total
    Number of subjects
    		 84 84
    Age categorical
    Units: Subjects
        1 to <6 years
    		 55 55
        6 to <13 years
    		 25 25
        13 to 18 years
    		 4 4
    Gender categorical
    Units: Subjects
        Female
    		 48 48
        Male
    		 36 36
    Subject analysis sets

    Subject analysis set title
    Primary Cohort
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The Primary Cohort in MRX-503 includes subjects with non-truncated PFIC2 (nt-PFIC2) mutations previously enrolled in MRX-502.

    Subject analysis set title
    PFIC Cohort
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The PFIC (All PFIC) Cohort in MRX-503 combines the nt-PFIC2 primary cohort with other PFIC types to evaluate safety and efficacy across the wider PFIC population.

    Subject analysis set title
    Primary Cohort Baseline
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The Primary Cohort in MRX-503 includes subjects with non-truncated PFIC2 (nt-PFIC2) mutations previously enrolled in MRX-502.

    Subject analysis set title
    PFIC Cohort Baseline
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The PFIC (All PFIC) Cohort in MRX-503 combines the nt-PFIC2 primary cohort with other PFIC types to evaluate safety and efficacy across the wider PFIC population.

    Subject analysis sets values
    		 Primary Cohort PFIC Cohort Primary Cohort Baseline PFIC Cohort Baseline
    Number of subjects
    28
    60
    28
    60
    Age categorical
    Units: Subjects
        1 to <6 years
    17
    37
    17
    37
        6 to <13 years
    7
    19
    7
    19
        13 to 18 years
    4
    4
    4
    4
    Age continuous
    Units:
        
    ( )
    ( )
    ( )
    ( )
    Gender categorical
    Units: Subjects
        Female
    18
    33
    18
    33
        Male
    10
    27
    10
    27

    End points

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    End points reporting groups
    Reporting group title
    Open Label Extension
    Reporting group description
    		 This open-label, extension study comprised one continuous treatment period, including: - Dose-escalation (4-6 weeks) - Stable-dosing (until the sponsor or the subject terminates the study, discontinues/ transitions to commercial product) - Safety follow-up phases. Subjects were analyzed in two cohorts: - The Primary Cohort (non-truncated PFIC2) - The Secondary Cohort (other PFIC subtypes, including PFIC1, PFIC3, truncated PFIC2, or incomplete response after PEBD)

    Subject analysis set title
    Primary Cohort
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The Primary Cohort in MRX-503 includes subjects with non-truncated PFIC2 (nt-PFIC2) mutations previously enrolled in MRX-502.

    Subject analysis set title
    PFIC Cohort
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The PFIC (All PFIC) Cohort in MRX-503 combines the nt-PFIC2 primary cohort with other PFIC types to evaluate safety and efficacy across the wider PFIC population.

    Subject analysis set title
    Primary Cohort Baseline
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The Primary Cohort in MRX-503 includes subjects with non-truncated PFIC2 (nt-PFIC2) mutations previously enrolled in MRX-502.

    Subject analysis set title
    PFIC Cohort Baseline
    Subject analysis set type
    		 Intention-to-treat
    Subject analysis set description
    The PFIC (All PFIC) Cohort in MRX-503 combines the nt-PFIC2 primary cohort with other PFIC types to evaluate safety and efficacy across the wider PFIC population.

    Primary: Mean change from baseline over time in the average morning ItchRO(Obs) severity score

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    End point title
    		 Mean change from baseline over time in the average morning ItchRO(Obs) severity score
    End point description
    End point type
    Primary
    End point timeframe
    From Baseline to Weeks 75-78 (MRX-503)
    End point values
    		 Primary Cohort PFIC Cohort Primary Cohort Baseline PFIC Cohort Baseline
    Number of subjects analysed
    21
    42
    28
    60
    Units: ItchRO score (1-4)
        arithmetic mean (standard deviation)
    0.839 ( 1.0767 )
    0.943 ( 1.1075 )
    2.473 ( 1.1444 )
    2.537 ( 1.1096 )
    Statistical analysis title
    		 Primary Cohort: Change from Baseline Over Time
    Comparison groups
    Primary Cohort v Primary Cohort Baseline
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.613
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.275
         upper limit
    		 -0.95
    Variability estimate
    Standard deviation
    Dispersion value
    1.4936
    Statistical analysis title
    		 PFIC Cohort: Change from Baseline Over Time
    Comparison groups
    PFIC Cohort v PFIC Cohort Baseline
    Number of subjects included in analysis
    102
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.701
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.138
         upper limit
    		 -1.264
    Variability estimate
    Standard deviation
    Dispersion value
    1.4022

    Secondary: Maintenance of ItchRO(Obs) response (Weeks 15 – 26)

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    End point title
    		 Maintenance of ItchRO(Obs) response (Weeks 15 – 26)
    End point description
    Maintenance of treatment effect described as the proportion of participants in the MRX-MRX treatment group who obtain ItchRO(Obs) response from Week 15 to Week 26 in Study MRX-503 in the primary cohort and PFIC cohort.
    End point type
    Secondary
    End point timeframe
    Week 15 - 26
    End point values
    		 Primary Cohort PFIC Cohort
    Number of subjects analysed
    14
    33
    Units: %
    number (not applicable)
        Week 15 - 18
    71.4
    69.7
        Week 19-22
    64.3
    72.7
        Week 23-26
    64.3
    69.7
    No statistical analyses for this end point

    Secondary: Proportion of ItchRO(Obs) responders over time

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    End point title
    		 Proportion of ItchRO(Obs) responders over time
    End point description
    Proportion of ItchRO responders over time at each study visit using the 4-week study period prior to the visit as per ItchRO(Obs) responder definition.
    End point type
    Secondary
    End point timeframe
    Baseline to EOT
    End point values
    		 Primary Cohort PFIC Cohort
    Number of subjects analysed
    28
    60
    Units: %
    number (not applicable)
        Week 1-6
    57.1
    50
        Week 7-10
    67.9
    65
        Week 11-14
    67.9
    63.3
        Week 15-18
    75
    66.7
        Week 19-22
    67.9
    68.3
        Week 23-26
    64.3
    63.3
        Week 39-42
    78.6
    71.7
        Week 51-54
    71.4
    66.7
        Week 63-66
    57.1
    58.3
        Week 75-78
    57.1
    53.3
        Week 87-90
    50
    48.3
        Week 99-102
    57.1
    46.7
        Week 111-114
    21.4
    26.7
        Week 123-126
    14.3
    20
    No statistical analyses for this end point

    Secondary: Mean change from baseline over time in the average morning ItchRO(Obs) frequency score

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    End point title
    		 Mean change from baseline over time in the average morning ItchRO(Obs) frequency score
    End point description
    End point type
    Secondary
    End point timeframe
    From Baseline (MRX-502) to Weeks 75-78 (MRX-503)
    End point values
    		 Primary Cohort PFIC Cohort Primary Cohort Baseline PFIC Cohort Baseline
    Number of subjects analysed
    21
    41
    28
    60
    Units: Ordinal Scale (1-5)
        arithmetic mean (standard deviation)
    0.842 ( 0.8522 )
    0.878 ( 0.9447 )
    2.522 ( 1.1043 )
    2.525 ( 1.0973 )
    Statistical analysis title
    		 Primary Cohort Change from Baseline
    Comparison groups
    Primary Cohort v Primary Cohort Baseline
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.644
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.302
         upper limit
    		 -0.986
    Variability estimate
    Standard deviation
    Dispersion value
    1.4451
    Statistical analysis title
    		 PFIC Cohort Change from Baseline
    Comparison groups
    PFIC Cohort v PFIC Cohort Baseline
    Number of subjects included in analysis
    101
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 < 0.0001
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -1.598
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.036
         upper limit
    		 -1.159
    Variability estimate
    Standard deviation
    Dispersion value
    1.3893

    Secondary: Mean change from baseline over time in total serum bile acid (sBA) levels

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    End point title
    		 Mean change from baseline over time in total serum bile acid (sBA) levels
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline to week 70
    End point values
    		 Primary Cohort PFIC Cohort Primary Cohort Baseline PFIC Cohort Baseline
    Number of subjects analysed
    22
    46
    26
    58
    Units: umol/L
        arithmetic mean (standard deviation)
    128.822 ( 182.6239 )
    127.987 ( 159.9969 )
    312.932 ( 163.8795 )
    262.139 ( 145.9310 )
    Statistical analysis title
    		 Primary Cohort Change from Baseline
    Comparison groups
    Primary Cohort Baseline v Primary Cohort
    Number of subjects included in analysis
    48
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0054
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -150.064
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -250.1
         upper limit
    		 -50.029
    Variability estimate
    Standard deviation
    Dispersion value
    213.7437
    Statistical analysis title
    		 PFIC Cohort Change from Baseline
    Comparison groups
    PFIC Cohort v PFIC Cohort Baseline
    Number of subjects included in analysis
    104
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0003
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    -111.473
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -168.687
         upper limit
    		 -54.258
    Variability estimate
    Standard deviation
    Dispersion value
    188.188

    Secondary: Proportion of subjects who experience an sBA control over time from Week 18 to Week 26

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    End point title
    		 Proportion of subjects who experience an sBA control over time from Week 18 to Week 26
    End point description
    End point type
    Secondary
    End point timeframe
    From Week 18 to Week 26
    End point values
    		 Primary Cohort PFIC Cohort
    Number of subjects analysed
    28
    60
    Units: % of subjects
    number (not applicable)
        Week 18
    42.9
    40
        Week 22
    42.9
    38.3
        Week 26
    46.4
    43.3
        Average of Weeks 18,22,26
    42.9
    40
    No statistical analyses for this end point

    Secondary: Change from baseline in height z-score

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    End point title
    		 Change from baseline in height z-score
    End point description
    End point type
    Secondary
    End point timeframe
    From baseline to Week 70
    End point values
    		 Primary Cohort PFIC Cohort Primary Cohort Baseline PFIC Cohort Baseline
    Number of subjects analysed
    22
    47
    28
    60
    Units: Z-Score
        arithmetic mean (standard deviation)
    -1.425 ( 1.5057 )
    -1.671 ( 1.5503 )
    -2.061 ( 1.3016 )
    -2.107 ( 1.3061 )
    Statistical analysis title
    		 Primary Cohort Change from Baseline
    Comparison groups
    Primary Cohort v Primary Cohort Baseline
    Number of subjects included in analysis
    50
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0026
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.486
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.161
         upper limit
    		 0.782
    Variability estimate
    Standard deviation
    Dispersion value
    0.6665
    Statistical analysis title
    		 PFIC Cohort Change from Baseline
    Comparison groups
    PFIC Cohort v PFIC Cohort Baseline
    Number of subjects included in analysis
    107
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0006
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.335
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.152
         upper limit
    		 0.518
    Variability estimate
    Standard deviation
    Dispersion value
    0.6229

    Secondary: Change from baseline in weight z-score

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    End point title
    		 Change from baseline in weight z-score
    End point description
    End point type
    Secondary
    End point timeframe
    From Baseline to Week 70
    End point values
    		 Primary Cohort PFIC Cohort Primary Cohort Baseline PFIC Cohort Baseline
    Number of subjects analysed
    21
    46
    28
    60
    Units: Z-Score
        arithmetic mean (standard deviation)
    -0.364 ( 1.3123 )
    -1.051 ( 1.4540 )
    -1.127 ( 1.3173 )
    -1.459 ( 1.2806 )
    Statistical analysis title
    		 Primary Cohort Change from Baseline
    Comparison groups
    Primary Cohort v Primary Cohort Baseline
    Number of subjects included in analysis
    49
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0194
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.518
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.093
         upper limit
    		 0.944
    Variability estimate
    Standard deviation
    Dispersion value
    0.9349
    Statistical analysis title
    		 PFIC Cohort Change from Baseline
    Comparison groups
    PFIC Cohort v PFIC Cohort Baseline
    Number of subjects included in analysis
    106
    Analysis specification
    Pre-specified
    Analysis type
    		 other
    P-value
    		 = 0.0042
    Method
    		 t-test, 2-sided
    Parameter type
    		 Mean difference (final values)
    Point estimate
    0.33
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.109
         upper limit
    		 0.55
    Variability estimate
    Standard deviation
    Dispersion value
    0.7421

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From the first dose through 14 days after the last dose of maralixibat.
    Adverse event reporting additional description
    Adverse events were systematically collected from all participants at each scheduled visit and through continuous monitoring from first dose to 14 days after last dose. Investigators were required to actively elicit and record all new or worsening events, with assessment of severity, relationship, and outcome.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    22.1
    Reporting groups
    Reporting group title
    Open Label Extension
    Reporting group description
    		 This open-label, extension study comprised one continuous treatment period, including: - Dose-escalation (4-6 weeks) - Stable-dosing (until the sponsor or the subject terminates the study, discontinues/ transitions to commercial product) - Safety follow-up phases. Subjects were analyzed in two cohorts: - The Primary Cohort (non-truncated PFIC2) - The Secondary Cohort (other PFIC subtypes, including PFIC1, PFIC3, truncated PFIC2, or incomplete response after PEBD)

    Serious adverse events
    		 Open Label Extension
    Total subjects affected by serious adverse events
         subjects affected / exposed
    25 / 84 (29.76%)
         number of deaths (all causes)
    2
         number of deaths resulting from adverse events
    2
    Injury, poisoning and procedural complications
    Accidental exposure to product
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Accidental overdose
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Femur fracture
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Head injury
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Postoperative renal failure
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Stoma site haemorrhage
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 3
         deaths causally related to treatment / all
    0 / 0
    Congenital, familial and genetic disorders
    Progressive familial intrahepatic cholestasis
         subjects affected / exposed
    2 / 84 (2.38%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Vascular disorders
    Haematoma
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Surgical and medical procedures
    Biliary tract operation
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    General disorders and administration site conditions
    Disease progression
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Oedema peripheral
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Haematochezia
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Oesophageal varices haemorrhage
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatobiliary disorders
    Biliary colic
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholangitis
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Cholecystitis acute
         subjects affected / exposed
    2 / 84 (2.38%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Cholelithiasis
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatic function abnormal
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Jaundice
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Epistaxis
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nasal obstruction
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Respiratory distress
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 1
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Infections and infestations
    Adenovirus infection
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Bacterial translocation
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Coronavirus infection
         subjects affected / exposed
    2 / 84 (2.38%)
         occurrences causally related to treatment / all
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    Enterovirus infection
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Escherichia urinary tract infection
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    4 / 84 (4.76%)
         occurrences causally related to treatment / all
    0 / 5
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis rotavirus
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Gastroenteritis viral
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Hepatitis viral
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Nasopharyngitis
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Rhinovirus infection
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Septic shock
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Tonsillitis
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Viral infection
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Metabolism and nutrition disorders
    Dehydration
         subjects affected / exposed
    1 / 84 (1.19%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Open Label Extension
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    84 / 84 (100.00%)
    Investigations
    Activated partial thromboplastin time prolonged
         subjects affected / exposed
    5 / 84 (5.95%)
         occurrences all number
    9
    Alanine aminotransferase increased
         subjects affected / exposed
    14 / 84 (16.67%)
         occurrences all number
    27
    Aspartate aminotransferase increased
         subjects affected / exposed
    6 / 84 (7.14%)
         occurrences all number
    8
    Blood bilirubin increased
         subjects affected / exposed
    16 / 84 (19.05%)
         occurrences all number
    23
    International normalised ratio increased
         subjects affected / exposed
    11 / 84 (13.10%)
         occurrences all number
    14
    Prothrombin time prolonged
         subjects affected / exposed
    4 / 84 (4.76%)
         occurrences all number
    5
    Vitamin A increased
         subjects affected / exposed
    5 / 84 (5.95%)
         occurrences all number
    5
    Vitamin D decreased
         subjects affected / exposed
    14 / 84 (16.67%)
         occurrences all number
    28
    Vitamin E decreased
         subjects affected / exposed
    9 / 84 (10.71%)
         occurrences all number
    12
    Injury, poisoning and procedural complications
    Skin abrasion
         subjects affected / exposed
    5 / 84 (5.95%)
         occurrences all number
    5
    Nervous system disorders
    Headache
         subjects affected / exposed
    6 / 84 (7.14%)
         occurrences all number
    9
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    7 / 84 (8.33%)
         occurrences all number
    9
    Coagulopathy
         subjects affected / exposed
    4 / 84 (4.76%)
         occurrences all number
    10
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    4 / 84 (4.76%)
         occurrences all number
    4
    Pyrexia
         subjects affected / exposed
    40 / 84 (47.62%)
         occurrences all number
    77
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    23 / 84 (27.38%)
         occurrences all number
    37
    Abdominal pain upper
         subjects affected / exposed
    5 / 84 (5.95%)
         occurrences all number
    6
    Constipation
         subjects affected / exposed
    8 / 84 (9.52%)
         occurrences all number
    9
    Dental caries
         subjects affected / exposed
    4 / 84 (4.76%)
         occurrences all number
    5
    Diarrhoea
         subjects affected / exposed
    39 / 84 (46.43%)
         occurrences all number
    82
    Vomiting
         subjects affected / exposed
    13 / 84 (15.48%)
         occurrences all number
    20
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    5 / 84 (5.95%)
         occurrences all number
    6
    Jaundice
         subjects affected / exposed
    6 / 84 (7.14%)
         occurrences all number
    8
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    28 / 84 (33.33%)
         occurrences all number
    61
    Epistaxis
         subjects affected / exposed
    8 / 84 (9.52%)
         occurrences all number
    31
    Nasal congestion
         subjects affected / exposed
    5 / 84 (5.95%)
         occurrences all number
    7
    Oropharyngeal pain
         subjects affected / exposed
    6 / 84 (7.14%)
         occurrences all number
    8
    Rhinorrhoea
         subjects affected / exposed
    12 / 84 (14.29%)
         occurrences all number
    16
    Skin and subcutaneous tissue disorders
    Pruritus
         subjects affected / exposed
    21 / 84 (25.00%)
         occurrences all number
    35
    Rash
         subjects affected / exposed
    4 / 84 (4.76%)
         occurrences all number
    4
    Urticaria
         subjects affected / exposed
    5 / 84 (5.95%)
         occurrences all number
    6
    Infections and infestations
    Conjunctivitis
         subjects affected / exposed
    6 / 84 (7.14%)
         occurrences all number
    7
    Coronavirus infection
         subjects affected / exposed
    12 / 84 (14.29%)
         occurrences all number
    12
    Ear infection
         subjects affected / exposed
    11 / 84 (13.10%)
         occurrences all number
    12
    Gastroenteritis
         subjects affected / exposed
    11 / 84 (13.10%)
         occurrences all number
    17
    Gastrointestinal viral infection
         subjects affected / exposed
    4 / 84 (4.76%)
         occurrences all number
    4
    Influenza
         subjects affected / exposed
    16 / 84 (19.05%)
         occurrences all number
    23
    Nasopharyngitis
         subjects affected / exposed
    21 / 84 (25.00%)
         occurrences all number
    45
    Otitis media
         subjects affected / exposed
    9 / 84 (10.71%)
         occurrences all number
    10
    Otitis media acute
         subjects affected / exposed
    6 / 84 (7.14%)
         occurrences all number
    9
    Pharyngitis
         subjects affected / exposed
    8 / 84 (9.52%)
         occurrences all number
    11
    Respiratory tract infection
         subjects affected / exposed
    5 / 84 (5.95%)
         occurrences all number
    6
    Rhinitis
         subjects affected / exposed
    9 / 84 (10.71%)
         occurrences all number
    18
    Tonsillitis
         subjects affected / exposed
    6 / 84 (7.14%)
         occurrences all number
    8
    Upper respiratory tract infection
         subjects affected / exposed
    16 / 84 (19.05%)
         occurrences all number
    53
    Viral infection
         subjects affected / exposed
    7 / 84 (8.33%)
         occurrences all number
    9
    Viral upper respiratory tract infection
         subjects affected / exposed
    4 / 84 (4.76%)
         occurrences all number
    4
    Metabolism and nutrition disorders
    Vitamin A deficiency
         subjects affected / exposed
    6 / 84 (7.14%)
         occurrences all number
    6
    Vitamin D deficiency
         subjects affected / exposed
    10 / 84 (11.90%)
         occurrences all number
    10
    Vitamin E deficiency
         subjects affected / exposed
    4 / 84 (4.76%)
         occurrences all number
    5

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    15 Jun 2020
    This amendment clarified the study design and baseline transition from MRX-502 to MRX-503, refined dosing and packaging details, and aligned the safety-monitoring baseline with the previous study to ensure consistency. It introduced provisions for home or remote visits to maintain study conduct during COVID-19 restrictions and added the Work Productivity and Activity Impairment Questionnaire (WPAI:PFIC) to capture quality-of-life data. Secondary endpoints were expanded to include serum bile acid control and time to liver-associated events, and Appendix 9 was added to guide pandemic-related procedures. These changes were made to improve operational flexibility, maintain patient safety and data integrity during public-health disruptions, and refine the efficacy assessments based on emerging clinical experience and regulatory feedback.
    18 Nov 2021
    This amendment updated the protocol to reflect maralixibat’s approval and evolving regulatory standards. Terminology was revised from ASBT to IBAT, and background sections were aligned with the current Investigator’s Brochure. The stable dosing period was extended indefinitely to allow continued treatment until study termination or transition to commercial supply. A new “All PFIC” analysis cohort was introduced, and efficacy and safety sections were reorganized with updated endpoints and statistical methods. Electronic SAE reporting via the EDC system was implemented, safety monitoring and liver-function follow-up were strengthened, and new guidance for dose interruptions, PEBD, and COVID-19 vaccination was added. These updates were made to expand patient access, modernize safety oversight, and align the study with post-approval and electronic data-capture requirements.

    Interruptions (globally)
    Were there any global interruptions to the trial? No

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    None reported
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    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.

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