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    Clinical Trial Results:
    An open label, single arm, multiple dose study to assess efficacy, safety, pharmacokinetics and pharmacodynamics of LNP023 when administered in addition to Standard of Care (SoC) in patients with paroxysmal nocturnal hemoglobinuria (PNH) with signs of active hemolysis

    Summary
    EudraCT number
    2017-000888-33
    Trial protocol
    DE   FR   IT  
    Global end of trial date
    28 Feb 2022

    Results information
    Results version number
    v1(current)
    This version publication date
    08 Mar 2023
    First version publication date
    08 Mar 2023
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    CLNP023X2201
    Additional study identifiers
    ISRCTN number
    -
    US NCT number
    NCT03439839
    WHO universal trial number (UTN)
    -
    Sponsors
    Sponsor organisation name
    Novartis Pharma AG
    Sponsor organisation address
    Novartis Campus, Basel, Switzerland,
    Public contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.com
    Scientific contact
    Clinical Disclosure Office, Novartis Pharma AG, 41 613241111, Novartis.email@Novartis.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?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    28 Feb 2022
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    28 Feb 2022
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the effect of iptacopan on the reduction of chronic hemolysis in PNH patients when administered in addition to SoC (monoclonal antibody with anti C5 activity). Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.nov for complete trial results.
    Protection of trial subjects
    The study was in compliance with the ethical principles derived from the Declaration of Helsinki and the International Conference on Harmonization (ICH) Good Clinical Practice (GCP) guidelines. All the local regulatory requirements pertinent to safety of trial subjects were also followed during the conduct of the trial.
    Background therapy
    -
    Evidence for comparator
    -
    Actual start date of recruitment
    09 Apr 2018
    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
    France: 7
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Italy: 8
    Worldwide total number of subjects
    16
    EEA total number of subjects
    16
    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)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    15
    From 65 to 84 years
    1
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    Participants took part in 3 investigative sites in 3 countries: France (1), Italy (1) and Germany (1).

    Pre-assignment
    Screening details
    All patients needed to complete vaccinations against N. meningitidis, S. pneumoniae and H. influenzae at least 4 weeks prior to starting LNP023 treatment. If LNP023 treatment had to start earlier than 4 weeks post vaccination, prophylactic antibiotic treatment was initiated.

    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
    Cohort 1: LNP023 200mg bid + SoC
    Arm description
    Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.
    Arm type
    Experimental

    Investigational medicinal product name
    Iptacopan
    Investigational medicinal product code
    LNP023
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Oral iptacopan hard gelatin capsule 200 mg b.i.d

    Arm title
    Cohort 2: LNP023 50mg/200mg bid + SoC
    Arm description
    Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.
    Arm type
    Experimental

    Investigational medicinal product name
    Iptacopan
    Investigational medicinal product code
    LNP023
    Other name
    Pharmaceutical forms
    Capsule, hard
    Routes of administration
    Oral use
    Dosage and administration details
    Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.

    Number of subjects in period 1
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Started
    10
    6
    Completed
    7
    6
    Not completed
    3
    0
         Adverse event, serious fatal
    3
    -

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Cohort 1: LNP023 200mg bid + SoC
    Reporting group description
    Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.

    Reporting group title
    Cohort 2: LNP023 50mg/200mg bid + SoC
    Reporting group description
    Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.

    Reporting group values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC Total
    Number of subjects
    10 6 16
    Age Categorical
    Units: Participants
        <=18 years
    0 0 0
        Between 18 and 65 years
    9 6 15
        >=65 years
    1 0 1
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    44.4 ± 15.57 51.7 ± 9.83 -
    Sex: Female, Male
    Units: participants
        Female
    3 3 6
        Male
    7 3 10
    Race/Ethnicity, Customized
    Units: Subjects
        Unknown
    0 1 1
        White
    10 5 15

    End points

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    End points reporting groups
    Reporting group title
    Cohort 1: LNP023 200mg bid + SoC
    Reporting group description
    Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.

    Reporting group title
    Cohort 2: LNP023 50mg/200mg bid + SoC
    Reporting group description
    Orally administered iptacopan 50 mg b.i.d. for a minimum of 2 weeks in addition to SoC; this could be increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values.

    Subject analysis set title
    Cohort 2: LNP023 25mg bid + SoC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Orally administered iptacopan 25 mg b.i.d. at the respective visit due to dosing error

    Subject analysis set title
    Cohort 2: LNP023 50mg bid + SoC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Orally administered iptacopan 50 mg b.i.d. at the respective visit

    Subject analysis set title
    Cohort 2: LNP023 200mg bid + SoC
    Subject analysis set type
    Sub-group analysis
    Subject analysis set description
    Orally administered iptacopan 200 mg b.i.d. at the respective visit

    Primary: Percent change from baseline in lactate dehydrogenase (LDH) level at Day 92

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    End point title
    Percent change from baseline in lactate dehydrogenase (LDH) level at Day 92 [1]
    End point description
    Serum LDH was used as an intravascular hemolysis marker to assess the effect of iptacopan on the reduction of chronic hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) patients when administered in addition to SoC (monoclonal antibody with anti C5 activity) Baseline is defined as the mean of the last 3 measurements prior to dose administration. No statistical analysis was planned for this primary outcome.
    End point type
    Primary
    End point timeframe
    Baseline and Day 92
    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: No statistical analysis was planned for this outcome.
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Number of subjects analysed
    9
    5
    Units: Percentage of LDH
        arithmetic mean (confidence interval 90%)
    -53.59 (-61.38 to -45.79)
    -25.56 (-46.92 to -4.20)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline in Lactate dehydrogenase (LDH) level

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    End point title
    Absolute change from baseline in Lactate dehydrogenase (LDH) level
    End point description
    Serum LDH was used as an intravascular hemolysis marker to assess the effect of iptacopan on the reduction of chronic hemolysis in paroxysmal nocturnal hemoglobinuria (PNH) patients when administered in addition to SoC (monoclonal antibody with anti C5 activity) Baseline is defined as the mean of the last 3 measurements prior to dose administration.
    End point type
    Secondary
    End point timeframe
    Baseline, day 8, 15, 29, 57 and 92
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Number of subjects analysed
    10
    6
    Units: U/L
    arithmetic mean (confidence interval 90%)
        Day 8 (n= 10, 6)
    -272.57 (-349.07 to -196.07)
    -145.22 (-196.30 to -94.15)
        Day 15 (n= 10, 5)
    -353.97 (-486.36 to -221.57)
    -175.07 (-247.55 to -102.59)
        Day 29 (n= 10, 6)
    -368.17 (-510.15 to -226.18)
    -191.22 (-258.88 to -123.56)
        Day 57 (n= 10, 6)
    -317.07 (-459.11 to -175.03)
    -135.89 (-212.28 to -59.50)
        Day 92 (n= 9, 5)
    -330.52 (-488.02 to -173.01)
    -109.07 (-196.69 to -21.45)
    No statistical analyses for this end point

    Secondary: Absolute change from baseline in hemoglobin

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    End point title
    Absolute change from baseline in hemoglobin
    End point description
    Hemoglobin was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.
    End point type
    Secondary
    End point timeframe
    Baseline; day 1, 2, 8, 15, 22, 29, 36, 43, 57, 71, 85, 92, 113, 127, 141, 155, 169, 197, 225, 253, 281, 309, 337, 393, 449, 505, 561, 617, 673, 729, 785, 841, 897, 953, 1009, 1065, 1121, 1177, 1233
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Number of subjects analysed
    10
    6
    Units: g/L
    arithmetic mean (standard deviation)
        Day 1 (n= 10, 6)
    -4.05 ± 8.750
    -6.67 ± 7.218
        Day 2 (n= 10, 6)
    -3.65 ± 7.638
    -8.06 ± 6.830
        Day 8 (n= 10, 6)
    12.85 ± 9.228
    20.11 ± 13.475
        Day 15 (n= 10, 6)
    20.25 ± 10.122
    26.44 ± 10.047
        Day 22 (n= 10, 6)
    24.15 ± 11.898
    35.11 ± 11.065
        Day 29 (n= 10, 6)
    28.25 ± 13.131
    35.11 ± 10.141
        Day 36 (n= 10, 6)
    29.55 ± 12.166
    33.94 ± 10.062
        Day 43 (n= 10, 6)
    26.15 ± 12.571
    31.11 ± 7.428
        Day 57 (n= 10, 6)
    27.05 ± 10.855
    35.94 ± 10.804
        Day 71 (n= 8, 4)
    24.53 ± 12.259
    28.54 ± 8.080
        Day 85 (n= 10, 3)
    28.65 ± 15.722
    30.72 ± 15.008
        Day 92 (n= 10, 5)
    31.85 ± 14.543
    32.43 ± 14.584
        Day 113 (n= 9, 5)
    30.14 ± 14.831
    32.43 ± 11.092
        Day 127 (n= 9, 4)
    33.92 ± 16.882
    38.92 ± 13.519
        Day 141 (n= 10, 5)
    28.05 ± 17.088
    37.23 ± 15.802
        Day 155 (n= 8, 5)
    28.28 ± 17.370
    37.83 ± 12.287
        Day 169 (n= 10, 5)
    27.05 ± 17.253
    39.43 ± 11.174
        Day 197 (n= 10, 3)
    28.95 ± 15.429
    31.89 ± 16.385
        Day 225 (n= 10, 3)
    28.65 ± 17.258
    28.67 ± 7.147
        Day 253 (n= 10, 4)
    26.95 ± 18.015
    28.17 ± 12.039
        Day 281 (n= 9, 4)
    29.91 ± 18.351
    45.54 ± 16.168
        Day 309 (n= 9, 4)
    27.17 ± 15.152
    36.29 ± 9.866
        Day 337 (n= 9, 4)
    26.28 ± 16.733
    32.50 ± 10.700
        Day 393 (n= 9, 4)
    28.47 ± 18.801
    39.79 ± 12.930
        Day 449 (n= 8, 5)
    31.22 ± 18.573
    37.93 ± 10.547
        Day 505 (n= 7, 6)
    24.89 ± 13.435
    44.28 ± 18.271
        Day 561 (n= 6, 5)
    29.25 ± 18.665
    40.13 ± 11.653
        Day 617 (n= 7, 6)
    32.23 ± 18.335
    42.78 ± 17.771
        Day 673 (n= 5, 5)
    38.42 ± 13.407
    38.13 ± 15.418
        Day 729 (n= 8, 4)
    31.28 ± 15.366
    34.92 ± 11.357
        Day 785 (n= 4, 4)
    11.63 ± 22.691
    40.04 ± 26.752
        Day 841 (n= 7, 4)
    24.27 ± 18.109
    38.54 ± 23.649
        Day 897 (n= 7, 2)
    31.85 ± 17.303
    56.83 ± 20.035
        Day 953 (n= 6, 0)
    23.93 ± 14.964
    999 ± 999
        Day 1009 (n= 7, 0)
    23.99 ± 19.396
    999 ± 999
        Day 1065 (n= 6, 0)
    29.07 ± 17.334
    999 ± 999
        Day 1121 (n= 7, 0)
    27.27 ± 14.536
    999 ± 999
        Day 1177 (n= 5, 0)
    32.28 ± 11.180
    999 ± 999
        Day 1233 (n= 5, 0)
    33.08 ± 10.196
    999 ± 999
    No statistical analyses for this end point

    Secondary: Absolute change from baseline in free hemoglobin

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    End point title
    Absolute change from baseline in free hemoglobin
    End point description
    Free hemoglobin was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.
    End point type
    Secondary
    End point timeframe
    Baseline; day 1, 2, 8, 15, 22, 29, 36, 43, 57, 71, 85, 92, 113, 127, 141, 155, 169, 197, 225, 253, 281, 309, 337, 393, 449, 505, 561, 617, 673, 729, 785, 841, 897, 953, 1009, 1065, 1121, 1177, 1233
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Number of subjects analysed
    10
    6
    Units: mg/dL
    arithmetic mean (standard deviation)
        Day 1 (n= 10, 6)
    15.26 ± 36.879
    9.16 ± 15.310
        Day 2 (n= 10, 6)
    -26.73 ± 40.706
    -3.94 ± 6.785
        Day 8 (n= 9, 6)
    -24.03 ± 43.102
    -2.04 ± 6.725
        Day 15 (n= 10, 6)
    -23.16 ± 41.190
    14.21 ± 43.762
        Day 22 (n= 10, 6)
    -22.90 ± 39.726
    -0.66 ± 6.960
        Day 29 (n= 10, 6)
    -20.03 ± 42.349
    -1.21 ± 8.108
        Day 36 (n= 10, 6)
    -12.42 ± 47.495
    -2.56 ± 6.914
        Day 43 (n= 9, 6)
    -13.63 ± 24.961
    -0.54 ± 6.546
        Day 57 (n= 8, 6)
    1.71 ± 14.138
    -1.84 ± 6.662
        Day 71 (n= 9, 4)
    -17.92 ± 34.378
    0.18 ± 1.466
        Day 85 (n= 10, 4)
    -16.80 ± 47.407
    1.90 ± 2.338
        Day 92 (n= 8, 5)
    -25.12 ± 42.237
    -3.31 ± 6.295
        Day 113 (n= 9, 5)
    -24.00 ± 41.084
    16.09 ± 42.454
        Day 127 (n= 9, 5)
    -18.07 ± 52.791
    1.42 ± 2.945
        Day 141 (n= 10, 5)
    -24.03 ± 40.625
    -1.52 ± 8.137
        Day 155 (n= 9, 4)
    -20.58 ± 43.690
    -2.43 ± 8.741
        Day 169 (n= 9, 5)
    -1.00 ± 91.222
    10.24 ± 19.275
        Day 197 (n= 10, 4)
    14.93 ± 105.958
    3.19 ± 5.185
        Day 225 (n= 10, 3)
    10.64 ± 101.866
    15.89 ± 32.159
        Day 253 (n= 10, 4)
    -21.97 ± 40.320
    34.84 ± 61.838
        Day 281 (n= 10, 5)
    -24.19 ± 39.910
    -1.36 ± 7.326
        Day 309 (n= 10, 4)
    -21.57 ± 42.638
    -2.26 ± 9.656
        Day 337 (n= 10, 3)
    -20.69 ± 42.592
    31.39 ± 55.947
        Day 393 (n= 9, 3)
    -17.29 ± 42.263
    -2.11 ± 8.297
        Day 449 (n= 8, 5)
    -28.60 ± 44.210
    -3.93 ± 7.781
        Day 505 (n= 7, 6)
    -33.24 ± 41.787
    -1.69 ± 6.335
        Day 561 (n= 7, 4)
    -34.25 ± 43.692
    1.59 ± 2.372
        Day 617 (n= 7, 5)
    -34.68 ± 44.127
    -0.22 ± 6.960
        Day 673 (n= 5, 4)
    -37.43 ± 54.005
    2.39 ± 15.832
        Day 729 (n= 8, 4)
    -28.88 ± 38.550
    -3.99 ± 7.294
        Day 785 (n= 4, 2)
    -2.55 ± 4.388
    -0.67 ± 3.206
        Day 841 (n= 7, 4)
    -33.12 ± 43.462
    1.60 ± 4.485
        Day 897 (n= 4, 2)
    -12.98 ± 22.233
    4.77 ± 5.468
        Day 953 (n= 7, 0)
    -34.41 ± 46.196
    999 ± 999
        Day 1009 (n= 7, 0)
    8.39 ± 135.082
    999 ± 999
        Day 1065 (n= 7, 0)
    -34.10 ± 44.867
    999 ± 999
        Day 1121 (n= 7, 0)
    -33.45 ± 43.628
    999 ± 999
        Day 1177 (n= 3, 0)
    -16.30 ± 23.441
    999 ± 999
        Day 1233 (n= 3, 0)
    -12.27 ± 20.734
    999 ± 999
    No statistical analyses for this end point

    Secondary: Absolute change from baseline in reticulocytes count

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    End point title
    Absolute change from baseline in reticulocytes count
    End point description
    Reticulocytes count was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.
    End point type
    Secondary
    End point timeframe
    Baseline; day 1, 2, 8, 15, 22, 29, 36, 43, 57, 71, 85, 92, 113, 127, 141, 155, 169, 197, 225, 253, 281, 309, 337, 393, 449, 505, 561, 617, 673, 729, 785, 841, 897, 953, 1009, 1065, 1121, 1177, 1233
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Number of subjects analysed
    10
    6
    Units: 10^9/L
    arithmetic mean (standard deviation)
        Day 1 (n= 10, 5)
    4.44 ± 33.269
    1.62 ± 22.790
        Day 2 (n= 10, 6)
    8.61 ± 52.306
    4.39 ± 31.658
        Day 8 (n= 10, 6)
    -96.94 ± 69.179
    -104.55 ± 88.085
        Day 15 (n= 10, 6)
    -130.15 ± 80.335
    -130.40 ± 107.295
        Day 22 (n= 10, 6)
    -139.26 ± 78.206
    -147.70 ± 99.438
        Day 29 (n= 10, 6)
    -132.28 ± 76.822
    -169.68 ± 129.743
        Day 36 (n= 10, 6)
    -130.73 ± 72.017
    -167.51 ± 137.214
        Day 43 (n= 10, 6)
    -129.02 ± 64.301
    -160.05 ± 132.859
        Day 57 (n= 10, 6)
    -117.69 ± 65.394
    -149.53 ± 116.803
        Day 71 (n= 8, 4)
    -106.83 ± 62.973
    -146.87 ± 129.217
        Day 85 (n= 10, 3)
    -113.96 ± 65.278
    -167.16 ± 156.013
        Day 92 (n= 10, 5)
    -110.54 ± 62.638
    -150.02 ± 105.893
        Day 113 (n= 9, 5)
    -96.78 ± 66.366
    -147.06 ± 129.118
        Day 127 (n= 9, 4)
    -107.84 ± 57.904
    -149.92 ± 115.401
        Day 141 (n= 10, 5)
    -115.17 ± 70.942
    -108.39 ± 54.412
        Day 155 (n= 8, 5)
    -99.90 ± 62.273
    -98.67 ± 65.700
        Day 169 (n= 10, 5)
    -109.39 ± 63.159
    -84.57 ± 64.082
        Day 197 (n= 10, 3)
    -98.87 ± 85.280
    -152.09 ± 137.856
        Day 225 (n= 10, 3)
    -104.11 ± 72.206
    -143.68 ± 149.716
        Day 253 (n= 10, 4)
    -104.30 ± 64.401
    -139.05 ± 127.212
        Day 281 (n= 9, 4)
    -111.11 ± 60.896
    -121.06 ± 66.564
        Day 309 (n= 9, 4)
    -116.88 ± 51.145
    -114.06 ± 77.982
        Day 337 (n= 9, 4)
    -113.31 ± 61.144
    -170.89 ± 142.577
        Day 393 (n= 9, 4)
    -58.54 ± 152.003
    -183.20 ± 122.298
        Day 449 (n= 8, 5)
    -89.44 ± 77.782
    -152.66 ± 124.244
        Day 505 (n= 7, 6)
    -100.68 ± 64.132
    -135.80 ± 117.488
        Day 561 (n= 6, 5)
    -101.63 ± 67.525
    -163.34 ± 121.860
        Day 617 (n= 7, 6)
    -101.73 ± 54.916
    -132.40 ± 122.940
        Day 673 (n= 5, 5)
    -137.05 ± 63.373
    -150.14 ± 130.898
        Day 729 (n= 8, 4)
    -101.16 ± 63.442
    -179.15 ± 131.007
        Day 785 (n= 4, 4)
    -56.22 ± 26.739
    -134.60 ± 141.947
        Day 841 (n= 7, 4)
    -103.96 ± 60.469
    -145.80 ± 140.363
        Day 897 (n= 7, 2)
    -111.41 ± 58.641
    -81.27 ± 36.298
        Day 953 (n= 5, 0)
    -91.00 ± 52.203
    999 ± 999
        Day 1009 (n= 7, 0)
    -110.33 ± 61.354
    999 ± 999
        Day 1065 (n= 6, 0)
    -127.35 ± 61.501
    999 ± 999
        Day 1121 (n= 7, 0)
    -115.96 ± 55.981
    999 ± 999
        Day 1177 (n= 5, 0)
    -140.14 ± 73.898
    999 ± 999
        Day 1233 (n= 5, 0)
    -123.40 ± 70.558
    999 ± 999
    No statistical analyses for this end point

    Secondary: Absolute change from baseline in C3 fragment deposition on PNH RBC

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    End point title
    Absolute change from baseline in C3 fragment deposition on PNH RBC
    End point description
    C3 fragment deposition on PNH Red blood cell (RBC) was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as Day 1 pre-dose measurement.
    End point type
    Secondary
    End point timeframe
    Day 1 pre dose, day 8, 22, 29, 57, 92, 113, 141, 169, 253, 337, 505, 673, 785, 953, 1121, 1233
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Number of subjects analysed
    10
    5
    Units: % C3 fragment deposition on PNH RBC
    arithmetic mean (standard deviation)
        Day 8 (n= 10, 5)
    -5.59 ± 6.541
    -1.24 ± 4.510
        Day 22 (n= 8, 4)
    -8.02 ± 8.198
    -2.35 ± 5.620
        Day 29 (n= 8, 5)
    -11.64 ± 7.990
    -4.36 ± 2.662
        Day 57 (n= 8, 3)
    -8.90 ± 5.778
    -5.35 ± 2.357
        Day 92 (n= 7, 3)
    -8.70 ± 6.310
    -6.21 ± 0.866
        Day 113 (n= 7, 2)
    -13.65 ± 9.927
    -5.10 ± 2.478
        Day 141 (n= 6, 2)
    -13.18 ± 11.489
    -6.19 ± 4.818
        Day 169 (n= 7, 2)
    -11.06 ± 5.874
    -4.66 ± 3.175
        Day 253 (n= 9, 4)
    -10.08 ± 6.259
    -4.36 ± 1.538
        Day 337 (n= 7, 2)
    -11.21 ± 6.118
    -4.08 ± 3.340
        Day 505 (n= 3, 4)
    -16.04 ± 2.732
    -6.76 ± 2.650
        Day 673 (n= 4, 0)
    -15.19 ± 2.805
    999 ± 999
        Day 785 (n= 1, 0)
    -1.00 ± 999
    999 ± 999
        Day 953 (n= 2, 0)
    -15.28 ± 3.528
    999 ± 999
        Day 1121 (n= 1, 0)
    -0.94 ± 999
    999 ± 999
        Day 1233 (n= 1, 0)
    -12.74 ± 999
    999 ± 999
    No statistical analyses for this end point

    Secondary: Mean PNH clone size

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    End point title
    Mean PNH clone size
    End point description
    Mean PNH clone size was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.
    End point type
    Secondary
    End point timeframe
    Day 1 pre dose, day 8, 22, 29, 57, 92, 113, 141, 169, 253, 337, 505, 673, 785, 953, 1121, 1233
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Number of subjects analysed
    10
    6
    Units: PNH Red Blood Cells
    arithmetic mean (standard deviation)
        Day 1 pre dose (n= 10, 5)
    54.75 ± 32.536
    46.10 ± 31.436
        Day 8 (n= 9, 6)
    66.32 ± 29.570
    64.45 ± 27.711
        Day 22 (n= 8, 5)
    75.23 ± 23.458
    79.37 ± 20.270
        Day 29 (n= 8, 6)
    75.34 ± 20.837
    78.87 ± 17.642
        Day 57 (n= 9, 5)
    85.87 ± 15.660
    86.45 ± 12.576
        Day 92 (n= 8, 5)
    89.20 ± 16.861
    85.38 ± 12.939
        Day 113 (n= 8, 3)
    89.28 ± 18.936
    86.02 ± 9.626
        Day 141 (n= 8, 3)
    93.91 ± 6.105
    80.25 ± 6.638
        Day 169 (n= 8, 3)
    87.60 ± 19.644
    83.69 ± 11.187
        Day 253 (n= 9, 4)
    90.30 ± 18.176
    82.28 ± 12.649
        Day 337 (n= 8, 3)
    88.69 ± 20.381
    91.68 ± 11.905
        Day 505 (n= 3, 5)
    98.33 ± 1.738
    88.45 ± 10.419
        Day 673 (n= 4, 2)
    97.45 ± 2.370
    92.48 ± 6.626
        Day 785 (n= 2, 0)
    83.61 ± 9.327
    999 ± 999
        Day 953 (n= 2, 0)
    96.08 ± 3.825
    999 ± 999
        Day 1121 (n= 2, 0)
    93.74 ± 7.410
    999 ± 999
        Day 1233 (n= 3, 0)
    69.83 ± 43.045
    999 ± 999
    No statistical analyses for this end point

    Secondary: Mean Haptoglobin levels

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    End point title
    Mean Haptoglobin levels
    End point description
    Haptoglobin level was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.
    End point type
    Secondary
    End point timeframe
    Day 2, 8, 15, 22, 29, 36, 43, 57, 71, 85, 92, 113, 127, 141, 155, 169, 197, 225, 253, 281, 309, 337, 393, 449, 505, 561, 617, 673, 729, 785, 841, 897, 953, 1009, 1065, 1121, 1177, 1233
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Number of subjects analysed
    9
    4
    Units: g/L
    arithmetic mean (standard deviation)
        Day 2 (n= 2, 2)
    0.55 ± 0.071
    0.30 ± 0.141
        Day 8 (n= 7, 3)
    0.70 ± 0.548
    0.77 ± 0.306
        Day 15 (n= 9, 2)
    0.93 ± 0.960
    0.60 ± 0.141
        Day 22 (n= 8, 4)
    1.18 ± 1.387
    0.70 ± 0.483
        Day 29 (n= 7, 3)
    0.94 ± 0.896
    0.83 ± 0.586
        Day 36 (n= 5, 3)
    1.08 ± 0.779
    0.97 ± 0.503
        Day 43 (n= 5, 3)
    1.26 ± 1.401
    0.70 ± 0.520
        Day 57 (n= 3, 1)
    0.63 ± 0.416
    1.20 ± 999
        Day 71 (n= 4, 1)
    0.75 ± 0.473
    0.80 ± 999
        Day 85 (n= 3, 0)
    0.87 ± 0.611
    999 ± 999
        Day 92 (n= 2, 1)
    0.95 ± 0.495
    0.80 ± 999
        Day 113 (n= 3, 1)
    0.63 ± 0.493
    0.50 ± 999
        Day 127 (n= 3, 0)
    0.47 ± 0.208
    999 ± 999
        Day 141 (n= 3, 1)
    0.57 ± 0.306
    0.70 ± 999
        Day 155 (n= 1, 1)
    0.50 ± 999
    0.80 ± 999
        Day 169 (n= 3, 1)
    0.63 ± 0.577
    0.50 ± 999
        Day 197 (n= 3, 0)
    0.80 ± 0.700
    999 ± 999
        Day 225 (n= 4, 0)
    0.65 ± 0.705
    999 ± 999
        Day 253 (n= 4, 0)
    0.63 ± 0.519
    999 ± 999
        Day 281 (n= 2, 1)
    0.50 ± 0.283
    0.30 ± 999
        Day 309 (n= 2, 1)
    0.75 ± 0.071
    0.50 ± 999
        Day 337 (n= 1, 0)
    0.40 ± 999
    999 ± 999
        Day 393 (n= 2, 0)
    0.60 ± 0.283
    999 ± 999
        Day 449 (n= 1, 1)
    0.20 ± 999
    0.60 ± 999
        Day 505 (n= 2, 1)
    0.60 ± 0.141
    0.60 ± 999
        Day 561 (n= 1, 1)
    0.60 ± 999
    0.70 ± 999
        Day 617 (n= 2, 2)
    0.30 ± 0.141
    1.90 ± 1.838
        Day 673 (n= 1, 1)
    0.30 ± 999
    0.70 ± 999
        Day 729 (n= 2, 1)
    0.35 ± 0.071
    0.50 ± 999
        Day 785 (n= 1, 2)
    1.00 ± 999
    1.25 ± 0.919
        Day 841 (n= 3, 2)
    0.47 ± 0.153
    0.85 ± 0.212
        Day 897 (n= 3, 0)
    0.33 ± 0.058
    999 ± 999
        Day 953 (n= 2, 0)
    0.50 ± 0.141
    999 ± 999
        Day 1009 (n= 2, 0)
    0.45 ± 0.071
    999 ± 999
        Day 1065 (n= 2, 0)
    2.05 ± 1.768
    999 ± 999
        Day 1121 (n= 4, 0)
    1.00 ± 0.935
    999 ± 999
        Day 1177 (n= 2, 0)
    0.40 ± 0.000
    999 ± 999
        Day 1233 (n= 2, 0)
    0.95 ± 0.636
    999 ± 999
    No statistical analyses for this end point

    Secondary: Absolute change from baseline in total bilirubin

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    End point title
    Absolute change from baseline in total bilirubin
    End point description
    Bilirubin was used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan. Baseline is defined as the mean of all pre-dose measurements.
    End point type
    Secondary
    End point timeframe
    Baseline; day 1, 2, 8, 15, 22, 29, 36, 43, 57, 71, 85, 92, 113, 127, 141, 155, 169, 197, 225, 253, 281, 309, 337, 393, 449, 505, 561, 617, 673, 729, 785, 841, 897, 953, 1009, 1065, 1121, 1177, 1233
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Number of subjects analysed
    10
    6
    Units: umol/L
    arithmetic mean (standard deviation)
        Day 1 (n= 10, 6)
    2.94 ± 13.038
    1.36 ± 4.978
        Day 2 (n= 10, 6)
    -21.06 ± 15.647
    -25.47 ± 21.598
        Day 8 (n= 10, 6)
    -23.66 ± 16.081
    -25.97 ± 24.380
        Day 15 (n= 10, 6)
    -23.86 ± 16.538
    -26.97 ± 24.043
        Day 22 (n= 10, 6)
    -25.36 ± 15.403
    -25.14 ± 23.541
        Day 29 (n= 10, 6)
    -24.66 ± 15.026
    -26.14 ± 22.345
        Day 36 (n= 10, 6)
    -23.96 ± 15.945
    -25.31 ± 27.658
        Day 43 (n= 10, 6)
    -24.66 ± 14.552
    -25.14 ± 23.727
        Day 57 (n= 10, 6)
    -24.16 ± 13.946
    -22.81 ± 21.233
        Day 71 (n= 10, 4)
    -23.16 ± 15.154
    -27.92 ± 24.924
        Day 85 (n= 10, 4)
    -23.66 ± 14.595
    -28.42 ± 26.075
        Day 92 (n= 10, 5)
    -21.66 ± 13.985
    -27.87 ± 25.234
        Day 113 (n= 9, 5)
    -21.06 ± 15.026
    -26.87 ± 23.200
        Day 127 (n= 9, 4)
    -22.18 ± 13.357
    -27.79 ± 26.965
        Day 141 (n= 10, 5)
    -22.46 ± 14.404
    -18.23 ± 9.473
        Day 155 (n= 9, 5)
    -19.73 ± 12.376
    -16.23 ± 9.565
        Day 169 (n= 10, 5)
    -21.66 ± 13.383
    -14.83 ± 10.281
        Day 197 (n= 9, 4)
    -24.21 ± 13.678
    -23.71 ± 28.849
        Day 225 (n= 10, 3)
    -23.06 ± 12.410
    -30.06 ± 36.183
        Day 253 (n= 10, 4)
    -21.36 ± 12.192
    -24.21 ± 30.342
        Day 281 (n= 10, 4)
    -23.46 ± 12.150
    -16.54 ± 8.694
        Day 309 (n= 10, 4)
    -22.86 ± 12.078
    -11.21 ± 10.635
        Day 337 (n= 10, 4)
    -22.76 ± 13.248
    -28.71 ± 29.338
        Day 393 (n= 9, 4)
    -19.73 ± 15.644
    -28.00 ± 27.769
        Day 449 (n= 8, 5)
    -24.64 ± 13.021
    -23.50 ± 25.603
        Day 505 (n= 7, 6)
    -27.30 ± 12.450
    -25.81 ± 24.978
        Day 561 (n= 7, 5)
    -21.98 ± 14.718
    -21.10 ± 30.888
        Day 617 (n= 6, 6)
    -28.85 ± 11.516
    -23.47 ± 21.451
        Day 673 (n= 5, 5)
    -27.58 ± 13.453
    -24.50 ± 25.562
        Day 729 (n= 8, 4)
    -23.64 ± 12.971
    -32.13 ± 28.799
        Day 785 (n= 4, 4)
    -11.54 ± 5.370
    -26.67 ± 33.656
        Day 841 (n= 7, 4)
    -20.49 ± 12.006
    -29.42 ± 32.316
        Day 897 (n= 7, 2)
    -24.49 ± 13.627
    -16.00 ± 7.542
        Day 953 (n= 7, 0)
    -23.92 ± 14.707
    999 ± 999
        Day 1009 (n= 7, 0)
    -23.92 ± 14.204
    999 ± 999
        Day 1065 (n= 6, 0)
    -25.65 ± 13.844
    999 ± 999
        Day 1121 (n= 7, 0)
    -23.35 ± 14.363
    999 ± 999
        Day 1177 (n= 5, 0)
    -29.78 ± 11.559
    999 ± 999
        Day 1233 (n= 5, 0)
    -28.78 ± 12.328
    999 ± 999
    No statistical analyses for this end point

    Secondary: Pharmacokinetics profile: Maximum plasma concentration (Cmax)

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    End point title
    Pharmacokinetics profile: Maximum plasma concentration (Cmax) [2]
    End point description
    Cmax is the maximum (peak) observed plasma drug concentration after single dose administration (mass x volume-1). PK assessment parameters were determined using the actual recorded sampling times and non-compartmental methods. In Cohort 2, patients were supposed to be orally administered iptacopan 50 mg b.i.d. in addition to SoC; this was increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values. One patient in Cohort 2 was orally administered iptacopan 25 mg at day 1 due to a dosing error. No statistical analysis was planned for this outcome.
    End point type
    Secondary
    End point timeframe
    Day 1, 29, 169, 337
    Notes
    [2] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this outcome.
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 25mg bid + SoC Cohort 2: LNP023 50mg bid + SoC Cohort 2: LNP023 200mg bid + SoC
    Number of subjects analysed
    10
    1
    6
    3
    Units: ng/mL
    arithmetic mean (standard deviation)
        Day 1 (n= 10, 1, 5, 0)
    3400 ± 1060
    1610 ± 999
    1570 ± 366
    999 ± 999
        Day 29 (n= 10, 0, 6, 0)
    3500 ± 1340
    999 ± 999
    1770 ± 469
    999 ± 999
        Day 169 (n= 9, 0, 1, 3)
    3530 ± 853
    999 ± 999
    1180 ± 999
    3130 ± 824
        Day 337 (n= 9, 0, 1, 3)
    4030 ± 1140
    999 ± 999
    2470 ± 999
    4370 ± 1790
    No statistical analyses for this end point

    Secondary: Number of participants with on study transfusions from packed RBC units

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    End point title
    Number of participants with on study transfusions from packed RBC units
    End point description
    Number of participants with on study transfusions from packed RBC units was collected.
    End point type
    Secondary
    End point timeframe
    Up to 46 months
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Number of subjects analysed
    10
    6
    Units: Participants
    2
    2
    No statistical analyses for this end point

    Secondary: Pharmacokinetics profile: Area Under the Curve (AUC) tau

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    End point title
    Pharmacokinetics profile: Area Under the Curve (AUC) tau [3]
    End point description
    The AUCtau is the area under the plasma concentration-time curve calculated to the end of a dosing interval (tau) at steady-state. PK assessment parameters were determined using the actual recorded sampling times and non-compartmental methods. In Cohort 2, patients were supposed to be orally administered iptacopan 50 mg b.i.d. in addition to SoC; this was increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values. One patient in Cohort 2 was orally administered iptacopan 25 mg at day 1 due to a dosing error. No statistical analysis was planned for this outcome.
    End point type
    Secondary
    End point timeframe
    day 1, 29, 169, 337
    Notes
    [3] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this outcome.
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 25mg bid + SoC Cohort 2: LNP023 50mg bid + SoC Cohort 2: LNP023 200mg bid + SoC
    Number of subjects analysed
    10
    1
    6
    3
    Units: h*ng/mL
    arithmetic mean (standard deviation)
        Day 1 (n= 10, 1, 5, 0)
    18200 ± 6700
    9470 ± 999
    8620 ± 1310
    999 ± 999
        Day 29 (n= 10, 0, 6, 0)
    24400 ± 8720
    999 ± 999
    14800 ± 4100
    999 ± 999
        Day 169 (n= 9, 0, 1, 3)
    25600 ± 7570
    999 ± 999
    10700 ± 999
    23900 ± 5920
        Day 337 (n= 9, 0, 1, 3)
    26900 ± 7640
    999 ± 999
    16900 ± 999
    37800 ± 15500
    No statistical analyses for this end point

    Secondary: Pharmacokinetics profile: Time to reach maximum plasma concentration (Tmax)

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    End point title
    Pharmacokinetics profile: Time to reach maximum plasma concentration (Tmax) [4]
    End point description
    Tmax is the time to reach maximum (peak) plasma drug concentration after single dose administration (time). PK assessment parameters were determined using the actual recorded sampling times and non-compartmental methods. In Cohort 2, patients were supposed to be orally administered iptacopan 50 mg b.i.d. in addition to SoC; this was increased to iptacopan 200 mg b.i.d. at study day 15 or at any time later in the study if LDH was not within limit of normal or reduced by at least 60% as compared to baseline values. One patient in Cohort 2 was orally administered iptacopan 25 mg at day 1 due to a dosing error. No statistical analysis was planned for this outcome.
    End point type
    Secondary
    End point timeframe
    Day 1, 29, 169, 337
    Notes
    [4] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: No statistical analysis was planned for this outcome.
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 25mg bid + SoC Cohort 2: LNP023 50mg bid + SoC Cohort 2: LNP023 200mg bid + SoC
    Number of subjects analysed
    10
    1
    6
    3
    Units: hours
    median (full range (min-max))
        Day 1 (n= 10, 1, 5, 0)
    1.50 (1.00 to 6.00)
    2.00 (2.00 to 2.00)
    2.00 (2.00 to 2.00)
    999 (999 to 999)
        Day 29 (n= 10, 0, 6, 0)
    2.00 (1.00 to 2.00)
    999 (999 to 999)
    2.04 (2.00 to 4.00)
    999 (999 to 999)
        Day 169 (n= 9, 0, 1, 3)
    2.00 (1.00 to 4.00)
    999 (999 to 999)
    4.00 (4.00 to 4.00)
    2.00 (1.83 to 2.00)
        Day 337 (n= 9, 0, 1, 3)
    2.00 (1.00 to 2.00)
    999 (999 to 999)
    2.03 (2.03 to 2.03)
    2.00 (1.05 to 5.00)
    No statistical analyses for this end point

    Secondary: Red Blood Cell Count: Mean erythrocytes levels

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    End point title
    Red Blood Cell Count: Mean erythrocytes levels
    End point description
    Erythrocytes levels were used as a marker of intra and extravascular hemolysis when administered in addition to SoC (monoclonal antibody with anti C5 activity) to assess the effect of iptacopan.
    End point type
    Secondary
    End point timeframe
    Screening, Baseline, Day 2,8,15,22,29,36,43,57,71,85,92,113,127,141,155,169,197,225,253,281,309,337,393,449,505,561,617,673,729,729,785,841,897,953,1009,1065,1121,1177,1233
    End point values
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 50mg/200mg bid + SoC
    Number of subjects analysed
    10
    6
    Units: 10^12/L
    arithmetic mean (standard deviation)
        Screening (n = 9, 5)
    3.12 ± 0.887
    2.42 ± 0.427
        Baseline (n = 9, 5)
    2.73 ± 0.466
    2.40 ± 0.442
        Day 1 (n = 10, 5)
    2.67 ± 0.615
    2.16 ± 0.498
        Day 2 (n = 10, 6)
    2.70 ± 0.485
    2.17 ± 0.520
        Day 8 (n = 10, 6)
    3.17 ± 0.585
    3.00 ± 0.812
        Day 15 (n = 10, 6)
    3.43 ± 0.723
    3.23 ± 0.794
        Day 22 (n = 10, 6)
    3.58 ± 0.835
    3.57 ± 0.900
        Day 29 (n = 10, 6)
    3.72 ± 0.857
    3.62 ± 0.870
        Day 36 (n = 10, 6)
    3.75 ± 0.753
    3.62 ± 0.804
        Day 43 (n = 10, 6)
    3.67 ± 0.807
    3.55 ± 0.758
        Day 57 (n = 10, 6)
    3.69 ± 0.852
    3.72 ± 0.574
        Day 71 (n = 8, 4)
    3.50 ± 0.787
    3.48 ± 0.591
        Day 85 (n = 10, 3)
    3.65 ± 0.841
    3.60 ± 0.520
        Day 92 (n = 10, 5)
    3.76 ± 0.828
    3.56 ± 0.483
        Day 113 (n = 9, 5)
    3.58 ± 0.807
    3.58 ± 0.444
        Day 127 (n = 9, 4)
    3.69 ± 0.822
    3.75 ± 0.265
        Day 141 (n = 10, 5)
    3.64 ± 0.799
    3.44 ± 0.493
        Day 155 (n = 8, 5)
    3.53 ± 0.815
    3.52 ± 0.432
        Day 169 (n = 10, 5)
    3.62 ± 0.826
    3.54 ± 0.378
        Day 197 (n = 10, 3)
    3.68 ± 0.774
    3.77 ± 0.577
        Day 225 (n = 10, 3)
    3.70 ± 0.894
    3.43 ± 0.513
        Day 253 (n = 10, 4)
    3.62 ± 0.930
    3.45 ± 0.412
        Day 281 (n = 9, 4)
    3.81 ± 0.875
    3.73 ± 0.403
        Day 309 (n = 9, 4)
    3.50 ± 0.728
    3.58 ± 0.427
        Day 337 (n = 9, 4)
    3.50 ± 0.714
    3.75 ± 0.580
        Day 393 (n = 9, 4)
    3.63 ± 0.876
    4.00 ± 0.356
        Day 449 (n = 8, 5)
    3.80 ± 0.920
    3.94 ± 0.378
        Day 505 (n = 7, 6)
    3.63 ± 1.053
    3.92 ± 0.360
        Day 561 (n = 6, 5)
    3.47 ± 0.937
    3.92 ± 0.370
        Day 617 (n = 7, 6)
    3.80 ± 1.149
    3.85 ± 0.389
        Day 673 (n =5, 5)
    3.74 ± 0.716
    3.86 ± 0.270
        Day 729 (n = 8, 4)
    3.74 ± 1.021
    3.93 ± 0.150
        Day 785 (n = 4, 4)
    2.83 ± 0.618
    3.78 ± 0.263
        Day 841 (n = 7, 4)
    3.64 ± 1.081
    3.80 ± 0.294
        Day 897 (n = 7, 2)
    3.89 ± 1.123
    3.95 ± 0.071
        Day 953 (n = 6, 0)
    3.62 ± 1.196
    999 ± 999
        Day 1009 (n = 7, 0)
    3.61 ± 1.316
    999 ± 999
        Day 1065 (n = 6, 0)
    3.87 ± 1.073
    999 ± 999
        Day 1121 (n = 7, 0)
    3.69 ± 1.006
    999 ± 999
        Day 1177 (n = 5, 0)
    4.06 ± 0.829
    999 ± 999
        Day 1233 (n = 5, 0)
    4.14 ± 0.844
    999 ± 999
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    AEs were reported from first dose of study treatment until EoS treatment plus 14 days post treatment. SAEs were reported from first dose of study treatment until EoS treatment plus 30 days post treatment, up to a maximum duration of 189 weeks.
    Adverse event reporting additional description
    Consistent with EudraCT disclosure specifications, Novartis has reported under the Serious adverse events field “number of deaths resulting from adverse events” all those deaths, resulting from serious adverse events that are deemed to be causally related to treatment by the investigator.
    Assessment type
    Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    MedDRA
    Dictionary version
    24.1
    Reporting groups
    Reporting group title
    Cohort 1: LNP023 200mg bid + SoC
    Reporting group description
    Orally administered iptacopan 200 mg b.i.d. in Part 1 and Part 2 in addition to SoC.

    Reporting group title
    Cohort 2: LNP023 200mg bid + SoC
    Reporting group description
    Orally administered iptacopan 50 mg b.i.d. in Part 1 and iptacopan 50 mg b.i.d. or 200 mg b.i.d. in Part 2 in addition to SoC. This arm summarizes all events that started when treated with iptacopan 200 mg b.i.d. in Cohort 2. Total number at risk only includes patients who received LNP023 200mg bid.

    Reporting group title
    Total
    Reporting group description
    Total

    Reporting group title
    Cohort 2: LNP023 50mg bid + SoC
    Reporting group description
    Orally administered iptacopan 50 mg b.i.d. in Part 1 and iptacopan 50 mg b.i.d. or 200 mg b.i.d. in Part 2 in addition to SoC. This arm summarizes all events that started when treated with iptacopan 50 mg b.i.d. in Cophort 2

    Serious adverse events
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 200mg bid + SoC Total Cohort 2: LNP023 50mg bid + SoC
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 10 (40.00%)
    2 / 5 (40.00%)
    6 / 16 (37.50%)
    0 / 6 (0.00%)
         number of deaths (all causes)
    3
    0
    3
    0
         number of deaths resulting from adverse events
    1
    0
    1
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Basal cell carcinoma
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bladder transitional cell carcinoma
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Lymphoproliferative disorder
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    1 / 1
    0 / 0
    1 / 1
    0 / 0
    Squamous cell carcinoma of the oral cavity
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
    Squamous cell carcinoma of the tongue
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Penetrating aortic ulcer
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Haemorrhage intracranial
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Urinary bladder polyp
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Urinary tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Escherichia bacteraemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    Cohort 1: LNP023 200mg bid + SoC Cohort 2: LNP023 200mg bid + SoC Total Cohort 2: LNP023 50mg bid + SoC
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    10 / 10 (100.00%)
    5 / 5 (100.00%)
    16 / 16 (100.00%)
    4 / 6 (66.67%)
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Angiofibroma
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Vascular disorders
    Flushing
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Haematoma
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    2
    1
    Hot flush
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hypertension
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    0
    1
    2
    1
    General disorders and administration site conditions
    Medical device site pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Medical device site irritation
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Chest pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Asthenia
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    4 / 16 (25.00%)
    2 / 6 (33.33%)
         occurrences all number
    5
    0
    7
    2
    Non-cardiac chest pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Oedema peripheral
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Pyrexia
         subjects affected / exposed
    3 / 10 (30.00%)
    1 / 5 (20.00%)
    5 / 16 (31.25%)
    1 / 6 (16.67%)
         occurrences all number
    4
    1
    8
    3
    Social circumstances
    Andropause
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Reproductive system and breast disorders
    Genital discomfort
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Dysmenorrhoea
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Breast pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Vulvovaginal dryness
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Haematospermia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea exertional
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Cough
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    2
    1
    Dyspnoea
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Upper respiratory tract congestion
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    3 / 16 (18.75%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    3
    1
    Epistaxis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Psychiatric disorders
    Alcohol abuse
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Insomnia
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    3 / 16 (18.75%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    3
    1
    Nightmare
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Poor quality sleep
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Investigations
    SARS-CoV-2 test negative
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Gamma-glutamyltransferase increased
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Weight decreased
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Injury, poisoning and procedural complications
    Limb injury
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Foot fracture
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Contusion
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    2
    1
    Traumatic haematoma
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Vaccination complication
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    2
    3
    1
    Nervous system disorders
    Cervical radiculopathy
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Headache
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    5 / 16 (31.25%)
    2 / 6 (33.33%)
         occurrences all number
    2
    1
    5
    2
    Migraine
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Paraesthesia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Anosmia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Ageusia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Sciatica
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    3 / 16 (18.75%)
    0 / 6 (0.00%)
         occurrences all number
    4
    1
    5
    0
    Thrombocytopenia
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    3 / 16 (18.75%)
    0 / 6 (0.00%)
         occurrences all number
    2
    1
    3
    0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Aphthous ulcer
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Constipation
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Diarrhoea
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Dysphagia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Abdominal pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    2
    1
    Nausea
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    3
    2
    Tongue ulceration
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Vomiting
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    2
    1
    Hepatobiliary disorders
    Ocular icterus
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hepatic cytolysis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Actinic keratosis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Alopecia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Ecchymosis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Dry skin
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Dermatitis acneiform
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Eczema
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Onycholysis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Petechiae
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    2
    0
    Psoriasis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 5 (40.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Nocturia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Pollakiuria
         subjects affected / exposed
    1 / 10 (10.00%)
    1 / 5 (20.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    1
    1
    2
    0
    Dysuria
         subjects affected / exposed
    2 / 10 (20.00%)
    1 / 5 (20.00%)
    3 / 16 (18.75%)
    0 / 6 (0.00%)
         occurrences all number
    4
    1
    5
    0
    Urinary bladder polyp
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Endocrine disorders
    Hyperthyroidism
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Musculoskeletal and connective tissue disorders
    Osteopenia
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Joint swelling
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Chondropathy
         subjects affected / exposed
    0 / 10 (0.00%)
    2 / 5 (40.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    0
    2
    2
    0
    Back pain
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Arthralgia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    2
    1
    Spinal pain
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    1
    0
    2
    1
    Bronchitis
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Ear infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Nasopharyngitis
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Influenza
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    1 / 6 (16.67%)
         occurrences all number
    2
    0
    3
    1
    Pyelonephritis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Pharyngitis
         subjects affected / exposed
    0 / 10 (0.00%)
    1 / 5 (20.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    0
    1
    1
    0
    Periodontitis
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Oral herpes
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Fungal skin infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Herpes zoster
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    4
    0
    4
    0
    Rhinitis
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    2 / 16 (12.50%)
    0 / 6 (0.00%)
         occurrences all number
    4
    0
    4
    0
    Wound infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Vaginal infection
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 10 (0.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    1 / 6 (16.67%)
         occurrences all number
    0
    0
    1
    1
    Metabolism and nutrition disorders
    Hyperuricaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hypertriglyceridaemia
         subjects affected / exposed
    2 / 10 (20.00%)
    0 / 5 (0.00%)
    4 / 16 (25.00%)
    2 / 6 (33.33%)
         occurrences all number
    2
    0
    4
    2
    Hyperferritinaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0
    Vitamin B12 deficiency
         subjects affected / exposed
    1 / 10 (10.00%)
    0 / 5 (0.00%)
    1 / 16 (6.25%)
    0 / 6 (0.00%)
         occurrences all number
    1
    0
    1
    0

    More information

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    Substantial protocol amendments (globally)

    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    22 Dec 2017
    Eligibility criteria updated to exclude patients with hepatitis. Study stopping rules updated to state that the occurrence of one or more fatal or life-threatening severe reactions, considered by the Investigator as potentially related to iptacopan, would trigger a pause of enrollment and dosing of affected patient(s). Details on physical examination and SAE reporting (previously only available in Site Operations Manual) were added.
    23 Jan 2018
    Detail of DMC and DMC’s involvement in decisions regarding potential study stopping added
    24 Jul 2018
    Treatment duration prolonged beyond 13 weeks and up to 12 months for PNH patients enrolled in this study who have shown clinical benefits from iptacopan treatment. Upper limit of age was updated from 75 to 80 years old to facilitate recruitment.
    01 Feb 2019
    Treatment duration prolonged from approximately 1 year to 3 years. Detail on implementation of a down titration period and guidance for Investigators on how to monitor patients who discontinued iptacopan study treatment added. Detail on the implementation of Cohort 2 where the iptacopan start dose will be lowered to 50 mg b.i.d. with an option to up-titrate the dose to a maximum of 200 mg b.i.d. (original dose), in cases of persistent hemolysis, was added. Eligibility criteria updated to include Cohort 2 patients with LDH levels 1.25 × ULN, but in combination with a reduced hemoglobin level as another inclusion criterion. Detail on permitted eculizumab dose adjustment for stable patients without signs of active hemolysis who are at least for 6 months in the study and having received continued concomitant treatment with iptacopan and eculizumab added. Study endpoints were updated to include PNH-type RBCs and CH50
    26 Jul 2021
    Details on option to complete this phase 2 study after a minimum of 2 years of treatment and transition to the REP added (such patients no longer need to complete tapering down period) New wording added to describe Public Health Emergency (pandemic, epidemic or natural disaster) mitigation procedures to ensure patient safety and study integrity

    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.
    Due to EudraCT system limitations, which EMA is aware of, data using 999 as data points in this record are not an accurate representation of the clinical trial results. Please use https://www.novctrd.com/CtrdWeb/home.nov for complete trial results.
    For support, Contact us.
    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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