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    Clinical Trial Results:
    A Multicenter, Open-label, Non-comparative Study of Modigraf® (Tacrolimus Granules) to Evaluate the Pharmacokinetics and Long-term Safety and Efficacy in De Novo Pediatric Allograft Liver and Kidney Transplantation Recipients

    Summary
    EudraCT number
    		 2022-002350-68
    Trial protocol
    		 Outside EU/EEA  
    Global end of trial date
    06 Mar 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    14 Sep 2024
    First version publication date
    14 Sep 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    F506-CL-0405
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT05152628
    WHO universal trial number (UTN)
    		 -
    Other trial identifiers
    		 Chinese Clinical Trial Registry: CTR20212678
    Sponsors
    Sponsor organisation name
    Astellas Pharma China, Inc.
    Sponsor organisation address
    No.3 Jia 6 Road 10, Shenyang City, China,
    Public contact
    Clinical Trial Transparency, Astellas Pharma China, Inc., +86 (0)10-85216666, astellas.resultsdisclosure@astellas.com
    Scientific contact
    Clinical Trial Transparency, Astellas Pharma China, Inc., +86 (0)10-85216666, astellas.resultsdisclosure@astellas.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    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?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    06 Mar 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    06 Mar 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The primary objective of this study was to determine the pharmacokinetics of tacrolimus following oral administration of Modigraf, after the first oral dose and at steady state in pediatric participants undergoing de novo allograft liver or kidney transplantation.
    Protection of trial subjects
    This clinical study was written, conducted and reported in accordance with the protocol, International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH) Good Clinical Practice (GCP) Guidelines, and applicable local regulations, including the European Directive 2001/20/EC, on the protection of human rights, and with the ethical principles that have their origin in the Declaration of Helsinki. Astellas ensures that the use and disclosure of Protected Health Information (PHI) obtained during a research study complies with the federal, national and/or regional legislation related to the privacy and protection of personal information.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    11 Jan 2022
    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
    China: 55
    Worldwide total number of subjects
    55
    EEA total number of subjects
    0
    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)
    14
    Children (2-11 years)
    30
    Adolescents (12-17 years)
    11
    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
    		 Chinese pediatric participants who had de novo allograft liver or kidney transplantation were enrolled in the study.

    Pre-assignment
    Screening details
    		 Participants who met all inclusion criteria and none of the exclusion criteria were enrolled in the study.

    Period 1
    Period 1 title
    Overall study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Non-randomised - controlled
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Liver transplant
    Arm description
    		 Pediatric participants who underwent de novo allograft liver transplantation received initial daily dose of 0.2 milligram per kilogram (mg/kg) of body weight oral suspension of tacrolimus granules post-operatively for 12 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tacrolimus
    Investigational medicinal product code
    Other name
    Modigraf
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received oral suspension of tacrolimus granules.

    Arm title
    		 Kidney transplant
    Arm description
    		 Pediatric participants who underwent de novo allograft kidney transplantation received initial daily dose of 0.2 mg/kg of body weight oral suspension of tacrolimus granules post-operatively for 12 months.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Tacrolimus
    Investigational medicinal product code
    Other name
    Modigraf
    Pharmaceutical forms
    Granules
    Routes of administration
    Oral use
    Dosage and administration details
    Participants received oral suspension of tacrolimus granules.

    Number of subjects in period 1
    		Liver transplant Kidney transplant
    Started
    41
    14
    Completed
    33
    8
    Not completed
    8
    6
         Adverse event, serious fatal
    1
    -
         Consent withdrawn by subject
    -
    2
         Adverse event, non-fatal
    5
    4
         Medicine not sent due to city lockdown
    1
    -
         Lack of efficacy
    1
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Liver transplant
    Reporting group description
    		 Pediatric participants who underwent de novo allograft liver transplantation received initial daily dose of 0.2 milligram per kilogram (mg/kg) of body weight oral suspension of tacrolimus granules post-operatively for 12 months.

    Reporting group title
    Kidney transplant
    Reporting group description
    		 Pediatric participants who underwent de novo allograft kidney transplantation received initial daily dose of 0.2 mg/kg of body weight oral suspension of tacrolimus granules post-operatively for 12 months.

    Reporting group values
    		 Liver transplant Kidney transplant Total
    Number of subjects
    		 41 14 55
    Age Categorical
    Units: participants
        Infants and toddlers (28 days-23 months)
    		 14 0 14
        Children (2-11 years)
    		 24 6 30
        Adolescents (12-17 years)
    		 3 8 11
    Gender Categorical
    Units: participants
        Female
    		 23 3 26
        Male
    		 18 11 29
    Race
    Units: Subjects
        Asian
    		 41 14 55

    End points

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    End points reporting groups
    Reporting group title
    Liver transplant
    Reporting group description
    		 Pediatric participants who underwent de novo allograft liver transplantation received initial daily dose of 0.2 milligram per kilogram (mg/kg) of body weight oral suspension of tacrolimus granules post-operatively for 12 months.

    Reporting group title
    Kidney transplant
    Reporting group description
    		 Pediatric participants who underwent de novo allograft kidney transplantation received initial daily dose of 0.2 mg/kg of body weight oral suspension of tacrolimus granules post-operatively for 12 months.

    Primary: PK of tacrolimus granules in Whole Blood: AUCtau on Day 7

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    End point title
    		 PK of tacrolimus granules in Whole Blood: AUCtau on Day 7 [1]
    End point description
    AUCtau was recorded from the PK blood samples collected. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 7
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    30
    11
    Units: h*ng/mL
        arithmetic mean (standard deviation)
    104 ( 40.0 )
    121 ( 41.4 )
    No statistical analyses for this end point

    Primary: Pharmacokinetic (PK) of tacrolimus granules in Whole Blood: Area under the curve (AUCtau) on Day 1

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    End point title
    		 Pharmacokinetic (PK) of tacrolimus granules in Whole Blood: Area under the curve (AUCtau) on Day 1 [2]
    End point description
    AUCtau was recorded from the PK blood samples collected. The Extended Pharmacokinetic Set (EPKS) consisted of all participants from the Safety Analysis Set (SAF) population for whom sufficient plasma concentration data was available to facilitate derivation of at least one pharmacokinetic parameter. SAF population consisted of all participants who took at least one dose of study drug. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hours (hr) post dose on day 1
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    13
    Units: hour*nanograms per milliliter (h*ng/mL)
        arithmetic mean (standard deviation)
    124 ( 72.1 )
    107 ( 40.9 )
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Cmax on Day 7

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Cmax on Day 7 [3]
    End point description
    Cmax was recorded from the PK blood samples collected. Cmax is maximum concentration observed in an observation period. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 7
    Notes
    [3] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    30
    12
    Units: ng/mL
        arithmetic mean (standard deviation)
    16.1 ( 8.52 )
    24.6 ( 8.72 )
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Maximum Concentration (Cmax) on Day 1

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Maximum Concentration (Cmax) on Day 1 [4]
    End point description
    Cmax was recorded from the PK blood samples collected. Cmax is maximum concentration observed in an observation period. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 1
    Notes
    [4] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    13
    Units: ng/mL
        arithmetic mean (standard deviation)
    16.9 ( 9.72 )
    19.2 ( 7.43 )
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Time of Maximum Concentration (Tmax) on Day 1

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Time of Maximum Concentration (Tmax) on Day 1 [5]
    End point description
    Tmax was recorded from the PK blood samples collected. Tmax is time of maximum concentration in an observation period. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 1
    Notes
    [5] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    13
    Units: hr
        median (full range (min-max))
    1.97 (0.533 to 8.10)
    1.97 (0.467 to 2.03)
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Tmax on Day 7

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Tmax on Day 7 [6]
    End point description
    Tmax was recorded from the PK blood samples collected. Tmax is time of maximum concentration in an observation period. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 7
    Notes
    [6] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    30
    12
    Units: hr
        median (full range (min-max))
    1.93 (0.433 to 7.87)
    0.983 (0.433 to 2.00)
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Trough blood concentration (Ctrough) on Day 1

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Trough blood concentration (Ctrough) on Day 1 [7]
    End point description
    Ctrough was recorded from the PK blood samples collected. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Pre-dose on day 1
    Notes
    [7] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    13
    Units: ng/mL
        arithmetic mean (standard deviation)
    6.95 ( 5.30 )
    4.03 ( 2.17 )
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Ctrough on Day 7

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Ctrough on Day 7 [8]
    End point description
    Ctrough was recorded from the PK blood samples collected. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Pre-dose on day 7
    Notes
    [8] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    30
    12
    Units: ng/mL
        arithmetic mean (standard deviation)
    5.25 ( 2.00 )
    5.16 ( 2.19 )
    No statistical analyses for this end point

    Primary: Correlation between Ctrough and AUCtau of tacrolimus granules in Whole Blood on Day 1

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    End point title
    		 Correlation between Ctrough and AUCtau of tacrolimus granules in Whole Blood on Day 1 [9]
    End point description
    The correlation between Ctrough and AUCtau was assessed by Pearson’s coefficient at each sample time by visit. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 1
    Notes
    [9] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    13
    Units: Pearson Correlation Coefficient
        number (not applicable)
    0.90
    0.83
    No statistical analyses for this end point

    Primary: Correlation between Ctrough and AUCtau of tacrolimus granules in Whole Blood on Day 7

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    End point title
    		 Correlation between Ctrough and AUCtau of tacrolimus granules in Whole Blood on Day 7 [10]
    End point description
    The correlation between Ctrough and AUCtau was assessed by Pearson’s coefficient at each sample time by visit. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 7
    Notes
    [10] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    30
    11
    Units: Pearson Correlation Coefficient
        number (not applicable)
    0.83
    0.90
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Dose-normalized AUCtau on Day 1

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Dose-normalized AUCtau on Day 1 [11]
    End point description
    Dose-normalized AUCtau was AUCtau normalized with the dose just prior to blood sampling. Dose-normalized AUCtau was calculated as AUCtau/dose. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 1
    Notes
    [11] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    13
    Units: h*ng/mL/mg
        arithmetic mean (standard deviation)
    83.5 ( 46.6 )
    29.7 ( 14.9 )
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Dose-normalized AUCtau on Day 7

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Dose-normalized AUCtau on Day 7 [12]
    End point description
    Dose-normalized AUCtau was AUCtau normalized with the dose just prior to blood sampling. Dose-normalized AUCtau was calculated as AUCtau/dose. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 7
    Notes
    [12] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    30
    11
    Units: h*ng/mL/mg
        arithmetic mean (standard deviation)
    129 ( 78.9 )
    32.1 ( 15.0 )
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Dose-normalized Ctrough on Day 1

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Dose-normalized Ctrough on Day 1 [13]
    End point description
    Ctrough normalized with the dose just prior to blood sampling. Dose-normalized Ctrough was calculated as Ctrough/dose. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 1
    Notes
    [13] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    13
    Units: ng/mL/mg
        arithmetic mean (standard deviation)
    4.30 ( 2.82 )
    1.09 ( 0.687 )
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Dose-normalized Cmax on Day 7

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Dose-normalized Cmax on Day 7 [14]
    End point description
    Dose-normalized Cmax was Cmax normalized with the dose just prior to blood sampling. Dose-normalized Cmax was calculated as Cmax/dose. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 7
    Notes
    [14] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    30
    12
    Units: ng/mL/mg
        arithmetic mean (standard deviation)
    19.4 ( 12.6 )
    6.91 ( 3.44 )
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Dose-normalized Cmax at Day 1

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Dose-normalized Cmax at Day 1 [15]
    End point description
    Dose-normalized Cmax was Cmax normalized with the dose just prior to blood sampling. Dose-normalized Cmax was calculated as Cmax/dose. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 1
    Notes
    [15] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    13
    Units: ng/mL/mg
        arithmetic mean (standard deviation)
    12.1 ( 7.50 )
    5.59 ( 2.97 )
    No statistical analyses for this end point

    Primary: PK of tacrolimus granules in Whole Blood: Dose-normalized Ctrough on Day 7

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    End point title
    		 PK of tacrolimus granules in Whole Blood: Dose-normalized Ctrough on Day 7 [16]
    End point description
    Ctrough normalized with the dose just prior to blood sampling. Dose-normalized Ctrough was calculated as Ctrough/dose. EPKS population with available data were reported.
    End point type
    Primary
    End point timeframe
    Predose, 0.5, 1, 2, 8, 12 hr post dose on day 7
    Notes
    [16] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    30
    12
    Units: ng/mL/mg
        arithmetic mean (standard deviation)
    6.52 ( 3.79 )
    1.49 ( 0.946 )
    No statistical analyses for this end point

    Primary: Percentage of Participants With Acute Rejection (AR)

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    End point title
    		 Percentage of Participants With Acute Rejection (AR) [17]
    End point description
    AR is an immune response against the donor graft that causes tissue impairment and potential failure. The criteria for rejection was performed by the local histopathologist following the “Histological Grading of Liver Biopsies for Rejection”, the “Banff diagnostic categories for renal allograft biopsies”. The Full Analysis Set (FAS) consisted of all participants who took at least one dose of study drug.
    End point type
    Primary
    End point timeframe
    From first dose to month 12
    Notes
    [17] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    14
    Units: Percentage of participants
        number (confidence interval 95%)
    17.1 (7.2 to 32.1)
    0 (0.0 to 23.2)
    No statistical analyses for this end point

    Primary: Percentage of Participants With Biopsy-Proven Acute Rejections (BPAR)

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    End point title
    		 Percentage of Participants With Biopsy-Proven Acute Rejections (BPAR) [18]
    End point description
    AR is an immune response against the donor graft that causes tissue impairment and potential failure. The criteria for rejection was performed by the local histopathologist following the “Histological Grading of Liver Biopsies for Rejection”, the “Banff diagnostic categories for renal allograft biopsies”. A BPAR episode was defined as any AR episode confirmed by biopsy. FAS population.
    End point type
    Primary
    End point timeframe
    From first dose to month 12
    Notes
    [18] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    14
    Units: Percentage of participants
        number (confidence interval 95%)
    9.8 (2.7 to 23.1)
    0 (0.0 to 23.2)
    No statistical analyses for this end point

    Primary: Percentage of Participants With Clinically Suspected Rejection

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    End point title
    		 Percentage of Participants With Clinically Suspected Rejection [19]
    End point description
    AR is an immune response against the donor graft that causes tissue impairment and potential failure. The criteria for rejection was performed by the local histopathologist following the “Histological Grading of Liver Biopsies for Rejection”, the “Banff diagnostic categories for renal allograft biopsies”. An AR was clinically suspected in participants who experienced an increase in serum creatinine, after the exclusion of other causes of graft dysfunction (generally with biopsy). FAS population.
    End point type
    Primary
    End point timeframe
    From first dose to month 12
    Notes
    [19] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    14
    Units: Percentage of participants
        number (confidence interval 95%)
    7.3 (1.5 to 19.9)
    0 (0.0 to 23.2)
    No statistical analyses for this end point

    Primary: Number of Participants who Died

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    End point title
    		 Number of Participants who Died [20]
    End point description
    Number of participant who died was recorded during 12 months’ post-transplant; any cause of death was taken into account. FAS population.
    End point type
    Primary
    End point timeframe
    From first dose to month 12
    Notes
    [20] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    14
    Units: participants
    number (not applicable)
        Death by Acute liver failure
    1
    0
        Kidney tumor worsened; died of respiratory failure
    0
    1
    No statistical analyses for this end point

    Primary: Number of Participants with Graft Failure

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    End point title
    		 Number of Participants with Graft Failure [21]
    End point description
    Graft failure was defined as graft dysfunction, including re-transplantation, graft loss or death, during the study period. A graft dysfunction to permanent dialysis in kidney transplantation was also considered as graft failure. FAS population.
    End point type
    Primary
    End point timeframe
    From first dose to month 12
    Notes
    [21] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    14
    Units: participants
        number (not applicable)
    1
    1
    No statistical analyses for this end point

    Primary: Number of Dose Adjustments Throughout the Study Period

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    End point title
    		 Number of Dose Adjustments Throughout the Study Period [22]
    End point description
    The dose adjustments required for the organ transplant were reported. SAF population.
    End point type
    Primary
    End point timeframe
    From first dose to month 12
    Notes
    [22] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    14
    Units: dose adjustments
        arithmetic mean (standard deviation)
    9.0 ( 5.0 )
    13.8 ( 5.7 )
    No statistical analyses for this end point

    Primary: Number of Participants with Treatment Emergent Adverse Events (AEs)

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    End point title
    		 Number of Participants with Treatment Emergent Adverse Events (AEs) [23]
    End point description
    An AE is defined as any untoward medical occurrence in a participant given a study drug not necessarily linked to this treatment. An AE can be any unfavorable and unintended sign (e.g., abnormal laboratory finding; abnormal laboratory test result or other safety assessment, symptom, or disease temporally associated with the use of study drug whether or not considered related to the study drug. Treatment emergent adverse event (TEAE) is defined as AE observed after administering the study drug. SAF population.
    End point type
    Primary
    End point timeframe
    From first dose to month 12
    Notes
    [23] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    14
    Units: participants
        number (not applicable)
    36
    14
    No statistical analyses for this end point

    Primary: Whole Blood Trough Levels of Tacrolimus

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    End point title
    		 Whole Blood Trough Levels of Tacrolimus [24]
    End point description
    Tacrolimus whole blood trough levels were routinely monitored from whole blood samples, using a local assay method, for example EMITÒ or Liquid-Chromatography-Mass-Spectrometry-Mass-Spectrometry (LC-MS-MS) in the local laboratories. Mean trough levels of tacrolimus from day 1 through month 12 has been reported. SAF population.
    End point type
    Primary
    End point timeframe
    From day 1 through month 12 (predose)
    Notes
    [24] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Per protocol, statistical analysis was not planned for this endpoint.
    End point values
    		 Liver transplant Kidney transplant
    Number of subjects analysed
    41
    14
    Units: ng/mL
        arithmetic mean (standard deviation)
    7.80 ( 2.21 )
    8.13 ( 1.45 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From first dose to month 12
    Adverse event reporting additional description
    SAF population
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    v26.0
    Reporting groups
    Reporting group title
    Kidney Transplant
    Reporting group description
    		 Pediatric participants who underwent de novo allograft kidney transplantation received initial daily dose of 0.2 mg/kg of body weight oral suspension of tacrolimus granules post-operatively for 12 months.

    Reporting group title
    Liver Transplant
    Reporting group description
    		 Pediatric participants who underwent de novo allograft liver transplantation received initial daily dose of 0.2 mg/kg of body weight oral suspension of tacrolimus granules post-operatively for 12 months.

    Serious adverse events
    		 Kidney Transplant Liver Transplant
    Total subjects affected by serious adverse events
         subjects affected / exposed
    9 / 14 (64.29%)
    16 / 41 (39.02%)
         number of deaths (all causes)
    1
    1
         number of deaths resulting from adverse events
    1
    1
    Investigations
    Glucose urine present
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Transaminases increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Post transplant lymphoproliferative disorder
         subjects affected / exposed
    1 / 14 (7.14%)
    3 / 41 (7.32%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal neoplasm
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    Injury, poisoning and procedural complications
    Complications of transplanted kidney
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    2 / 3
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Post procedural bile leak
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Vascular disorders
    Embolism arterial
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lymphorrhoea
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Nervous system disorders
    Cauda equina syndrome
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epilepsy
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Acute hepatic failure
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Biliary fistula
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 41 (4.88%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Portal vein stenosis
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 41 (4.88%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatic artery embolism
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Hydronephrosis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Bacterial infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Biliary tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Central nervous system infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus hepatitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cytomegalovirus viraemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Epstein-Barr virus infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Febrile infection
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastroenteritis adenovirus
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hand-foot-and-mouth disease
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Liver abscess
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 14 (7.14%)
    3 / 41 (7.32%)
         occurrences causally related to treatment / all
    1 / 1
    3 / 3
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Sepsis
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 41 (4.88%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Septic shock
         subjects affected / exposed
    0 / 14 (0.00%)
    1 / 41 (2.44%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 14 (0.00%)
    2 / 41 (4.88%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Kidney Transplant Liver Transplant
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    14 / 14 (100.00%)
    33 / 41 (80.49%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Post transplant lymphoproliferative disorder
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Vascular disorders
    Jugular vein thrombosis
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    Lymphorrhoea
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    General disorders and administration site conditions
    Puncture site haemorrhage
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Pyrexia
         subjects affected / exposed
    3 / 14 (21.43%)
    14 / 41 (34.15%)
         occurrences all number
    6
    22
    Immune system disorders
    Hypogammaglobulinaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Reproductive system and breast disorders
    Gynaecomastia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 14 (7.14%)
    7 / 41 (17.07%)
         occurrences all number
    1
    9
    Epistaxis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    3
    0
    Psychiatric disorders
    Mood altered
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Enuresis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Investigations
    BK polyomavirus test positive
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 41 (0.00%)
         occurrences all number
    3
    0
    Bacterial test positive
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Blood lactate dehydrogenase increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Blood urea increased
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    4
    0
    Blood urine present
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Carbon dioxide combining power decreased
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    Fungal test positive
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Glucose urine present
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    4
    0
    Glycosylated haemoglobin increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    Lymphocyte count increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Neutrophil count increased
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    Platelet count increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Protein urine present
         subjects affected / exposed
    6 / 14 (42.86%)
    0 / 41 (0.00%)
         occurrences all number
    7
    0
    Red blood cells urine positive
         subjects affected / exposed
    4 / 14 (28.57%)
    0 / 41 (0.00%)
         occurrences all number
    5
    0
    SARS-CoV-2 test positive
         subjects affected / exposed
    2 / 14 (14.29%)
    15 / 41 (36.59%)
         occurrences all number
    2
    17
    Transaminases increased
         subjects affected / exposed
    5 / 14 (35.71%)
    0 / 41 (0.00%)
         occurrences all number
    10
    0
    Urinary occult blood positive
         subjects affected / exposed
    5 / 14 (35.71%)
    0 / 41 (0.00%)
         occurrences all number
    5
    0
    Urine leukocyte esterase positive
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    5
    0
    White blood cell count increased
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Arteriovenous fistula occlusion
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Complications of transplanted kidney
         subjects affected / exposed
    5 / 14 (35.71%)
    0 / 41 (0.00%)
         occurrences all number
    7
    0
    Delayed graft function
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Cardiac disorders
    Ectopic atrial rhythm
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Right atrial enlargement
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Dizziness
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Blood and lymphatic system disorders
    Granulocytopenia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Leukocytosis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Agranulocytosis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Leukopenia
         subjects affected / exposed
    5 / 14 (35.71%)
    0 / 41 (0.00%)
         occurrences all number
    8
    0
    Lymphopenia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    5
    0
    Neutropenia
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 41 (0.00%)
         occurrences all number
    8
    0
    Splenomegaly
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Ascites
         subjects affected / exposed
    0 / 14 (0.00%)
    4 / 41 (9.76%)
         occurrences all number
    0
    4
    Aphthous ulcer
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    Abdominal pain
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    Abdominal discomfort
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Diarrhoea
         subjects affected / exposed
    9 / 14 (64.29%)
    11 / 41 (26.83%)
         occurrences all number
    18
    26
    Nausea
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Toothache
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    4 / 14 (28.57%)
    4 / 41 (9.76%)
         occurrences all number
    4
    4
    Constipation
         subjects affected / exposed
    3 / 14 (21.43%)
    2 / 41 (4.88%)
         occurrences all number
    4
    4
    Hepatobiliary disorders
    Liver injury
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Hepatic steatosis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Hepatic function abnormal
         subjects affected / exposed
    2 / 14 (14.29%)
    10 / 41 (24.39%)
         occurrences all number
    2
    13
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Dermatitis
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    Eczema
         subjects affected / exposed
    0 / 14 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    0
    3
    Prurigo
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Urticaria
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Renal and urinary disorders
    Proteinuria
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    Albuminuria
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    3
    0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    4 / 14 (28.57%)
    0 / 41 (0.00%)
         occurrences all number
    4
    0
    Upper respiratory tract infection
         subjects affected / exposed
    5 / 14 (35.71%)
    13 / 41 (31.71%)
         occurrences all number
    10
    18
    Respiratory tract infection
         subjects affected / exposed
    1 / 14 (7.14%)
    3 / 41 (7.32%)
         occurrences all number
    1
    4
    Pneumonia mycoplasmal
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Pneumonia
         subjects affected / exposed
    0 / 14 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    0
    4
    Mycoplasma infection
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Gastroenteritis
         subjects affected / exposed
    1 / 14 (7.14%)
    1 / 41 (2.44%)
         occurrences all number
    1
    1
    Folliculitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Febrile infection
         subjects affected / exposed
    0 / 14 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    0
    5
    Epstein-Barr virus infection
         subjects affected / exposed
    0 / 14 (0.00%)
    22 / 41 (53.66%)
         occurrences all number
    0
    25
    Cytomegalovirus infection
         subjects affected / exposed
    4 / 14 (28.57%)
    11 / 41 (26.83%)
         occurrences all number
    4
    17
    Cytomegalovirus hepatitis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    COVID-19
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Bacterial infection
         subjects affected / exposed
    0 / 14 (0.00%)
    3 / 41 (7.32%)
         occurrences all number
    0
    3
    Anal abscess
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    3 / 14 (21.43%)
    0 / 41 (0.00%)
         occurrences all number
    5
    0
    Alkalosis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Hypercalcaemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    5
    0
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    Hyperphosphataemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    3
    0
    Hyperglycaemia
         subjects affected / exposed
    4 / 14 (28.57%)
    0 / 41 (0.00%)
         occurrences all number
    8
    0
    Hyperkalaemia
         subjects affected / exposed
    5 / 14 (35.71%)
    0 / 41 (0.00%)
         occurrences all number
    16
    0
    Hyperlipidaemia
         subjects affected / exposed
    10 / 14 (71.43%)
    0 / 41 (0.00%)
         occurrences all number
    17
    0
    Hypo HDL cholesterolaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Hyperuricaemia
         subjects affected / exposed
    11 / 14 (78.57%)
    0 / 41 (0.00%)
         occurrences all number
    22
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    Hypokalaemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0
    Hypomagnesaemia
         subjects affected / exposed
    7 / 14 (50.00%)
    1 / 41 (2.44%)
         occurrences all number
    9
    1
    Hypocalcaemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Hypochloraemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Vitamin D deficiency
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Metabolic acidosis
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    3
    0
    Hyponatraemia
         subjects affected / exposed
    1 / 14 (7.14%)
    0 / 41 (0.00%)
         occurrences all number
    1
    0
    Hypophosphataemia
         subjects affected / exposed
    2 / 14 (14.29%)
    0 / 41 (0.00%)
         occurrences all number
    2
    0

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    17 Dec 2020
    The study design was updated to ensure participants can continue Modigraf treatment before commercial drug available in China, these participants will continue treatment on study for 12 months. The safety and efficacy evaluation will be continued. A pooled analysis of F506-CL-0405 and F506-CL-0406 is planned to have efficacy and safety data of about 100 participants for analyses. An inclusion criterion was added as advised by authority. The exclusion criteria were updated based on the advice from Key Opinion Leaders (KOLs). The proportion of bilateral kidney transplantation was very small, and there was higher risk of post-operative complications. Same for the participants with a low body weight and severe primary diseases. The initial daily dose was updated as advised by KOLs. The safety endpoints were added as the study was aiming to accumulate safety and efficacy data from the very first Chinese pediatric patients who receive Modigraf. Flow chart and Schedule of assessments and consistency was maintained throughout the protocol as the study was extended to 12 months. Other administrative changes were made.

    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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