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    Clinical Trial Results:
    Two part (double-blind inclisiran versus placebo [Year 1] followed by open-label inclisiran [Year 2]) randomized multicenter study to evaluate safety, tolerability, and efficacy of inclisiran in adolescents (12 to less than 18 years) with heterozygous familial hypercholesterolemia and elevated LDL-cholesterol (ORION-16)

    Summary
    EudraCT number
    		 2020-002757-18
    Trial protocol
    		 HU   NO   DE   SI   NL   GR   FR   IT   PL   HR   SK   CZ  
    Global end of trial date
    27 Nov 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Jun 2025
    First version publication date
    07 Jun 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    CKJX839C12301
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04652726
    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)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002214-PIP01-17
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    Yes
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    27 Nov 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    27 Nov 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the trial was to evaluate the efficacy, safety and tolerability of inclisiran in adolescents (aged 12 to <18 years) with heterozygous familial hypercholesterolaemia (HeFH). 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
    27 Jan 2021
    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
    Brazil: 10
    Country: Number of subjects enrolled
    Argentina: 1
    Country: Number of subjects enrolled
    Canada: 8
    Country: Number of subjects enrolled
    Czechia: 5
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 9
    Country: Number of subjects enrolled
    Greece: 1
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    Israel: 6
    Country: Number of subjects enrolled
    Italy: 8
    Country: Number of subjects enrolled
    Jordan: 5
    Country: Number of subjects enrolled
    Lebanon: 3
    Country: Number of subjects enrolled
    Malaysia: 1
    Country: Number of subjects enrolled
    Netherlands: 25
    Country: Number of subjects enrolled
    Norway: 5
    Country: Number of subjects enrolled
    Poland: 5
    Country: Number of subjects enrolled
    Russian Federation: 3
    Country: Number of subjects enrolled
    Slovakia: 1
    Country: Number of subjects enrolled
    Slovenia: 1
    Country: Number of subjects enrolled
    South Africa: 7
    Country: Number of subjects enrolled
    Spain: 11
    Country: Number of subjects enrolled
    Switzerland: 2
    Country: Number of subjects enrolled
    Taiwan: 1
    Country: Number of subjects enrolled
    Türkiye: 7
    Country: Number of subjects enrolled
    United Kingdom: 4
    Country: Number of subjects enrolled
    United States: 8
    Worldwide total number of subjects
    141
    EEA total number of subjects
    75
    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)
    141
    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
    		 Participants were randomized from 51 study centers:ARG (1), BRA (3), CAN (1), CZE (2), FRA (3), DEU (2), GRC (1), HUN (1), ISR (2), ITA (4), JOR (1), LBN (1), MYS (1), NLD (2), NOR (1), POL (2), RUS (2), SVK (1), SVN (1), ZAF (3), ESP(4), CHE (1), TWN (1), TUR (4), GBR (1), USA (5)

    Pre-assignment
    Screening details
    		 The study had an approximately 4-week screening/run-in period

    Period 1
    Period 1 title
    Part 1 (Double-blind period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Part 1- Inclisiran
    Arm description
    		 Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)
    Arm type
    		 Experimental

    Investigational medicinal product name
    Inclisiran
    Investigational medicinal product code
    KJX839
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Inclisiran sodium 300mg(equivalent to 284mginclisiran) in 1.5 mL solution

    Arm title
    		 Part 1 - Placebo
    Arm description
    		 Placebo sc injection (given at Day 1, 90 and 270)
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo formulation to the active drug formulation

    Number of subjects in period 1
    		Part 1- Inclisiran Part 1 - Placebo
    Started
    93
    48
    Completed
    91
    48
    Not completed
    2
    0
         Physician decision
    1
    -
         Participant/guardian decision
    1
    -
    Period 2
    Period 2 title
    Part 2 (Open-label period)
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Part 2 – Inclisiran (Total)
    Arm description
    		 Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360
    Arm type
    		 Experimental

    Investigational medicinal product name
    Inclisiran
    Investigational medicinal product code
    KJX839
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Inclisiran sodium 300mg(equivalent to 284mginclisiran) in 1.5 mLsolution

    Number of subjects in period 2
    		Part 2 – Inclisiran (Total)
    Started
    139
    Completed
    139

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Part 1- Inclisiran
    Reporting group description
    		 Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)

    Reporting group title
    Part 1 - Placebo
    Reporting group description
    		 Placebo sc injection (given at Day 1, 90 and 270)

    Reporting group values
    		 Part 1- Inclisiran Part 1 - Placebo Total
    Number of subjects
    		 93 48 141
    Age Categorical
    Units: participants
        <=18 years
    		 93 48 141
        Between 18 and 65 years
    		 0 0 0
        >=65 years
    		 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 15.2 ( 2.02 ) 14.9 ( 1.80 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 51 24 75
        Male
    		 42 24 66
    Race/Ethnicity, Customized
    Units: Subjects
        Asian
    		 4 0 4
        Black or African American
    		 5 0 5
        Other
    		 4 0 4
        White
    		 80 48 128

    End points

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    End points reporting groups
    Reporting group title
    Part 1- Inclisiran
    Reporting group description
    		 Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)

    Reporting group title
    Part 1 - Placebo
    Reporting group description
    		 Placebo sc injection (given at Day 1, 90 and 270)
    Reporting group title
    Part 2 – Inclisiran (Total)
    Reporting group description
    		 Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360

    Primary: Percentage change in LDL-C from baseline to Day 330 (Part 1/Year 1)

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    End point title
    		 Percentage change in LDL-C from baseline to Day 330 (Part 1/Year 1)
    End point description
    Percentage change in low-density lipoprotein cholesterol (LDL-C) from baseline to Day 330 (Year 1)
    End point type
    Primary
    End point timeframe
    Baseline and Day 330
    End point values
    		 Part 1- Inclisiran Part 1 - Placebo
    Number of subjects analysed
    93
    48
    Units: percent change in LDL-C
        least squares mean (confidence interval 95%)
    -27.14 (-32.04 to -22.24)
    1.40 (-3.97 to 6.78)
    Statistical analysis title
    		 Difference between Inclisiran and Placebo
    Comparison groups
    Part 1- Inclisiran v Part 1 - Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean
    Point estimate
    -28.54
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -35.81
         upper limit
    		 -21.27

    Secondary: Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Part 1/Year 1)

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    End point title
    		 Time-adjusted percent change in LDL-C from baseline after Day 90 and up to Day 330 (Part 1/Year 1)
    End point description
    Time-adjusted percent change in LDL-C (after Day 90 and up to Day 330), calculated as the average of percent changes from baseline to Days 150, 270 and 330
    End point type
    Secondary
    End point timeframe
    Baseline, after Day 90 up to Day 330
    End point values
    		 Part 1- Inclisiran Part 1 - Placebo
    Number of subjects analysed
    93
    48
    Units: Time-adjusted percent change in LDL-C
        least squares mean (confidence interval 95%)
    -26.04 (-30.11 to -21.98)
    3.26 (-2.37 to 8.89)
    Statistical analysis title
    		 Difference between Inclisiran and Placebo
    Comparison groups
    Part 1- Inclisiran v Part 1 - Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 MMRM
    Parameter type
    		 LS Mean
    Point estimate
    -29.3
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -36.24
         upper limit
    		 -22.36

    Secondary: Percent change in non-HDL-C from baseline up to Day 330 (Part 1/Year 1)

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    End point title
    		 Percent change in non-HDL-C from baseline up to Day 330 (Part 1/Year 1)
    End point description
    Percentage change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to Day 330.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 330
    End point values
    		 Part 1- Inclisiran Part 1 - Placebo
    Number of subjects analysed
    93
    48
    Units: Percent change in non-HDL-C
        least squares mean (confidence interval 95%)
    -25.04 (-29.68 to -20.41)
    1.76 (-3.25 to 6.77)
    Statistical analysis title
    		 Difference between Inclisiran and Placebo
    Comparison groups
    Part 1- Inclisiran v Part 1 - Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean
    Point estimate
    -26.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -33.63
         upper limit
    		 -19.97

    Secondary: Percent change in Lp(a) from baseline up to Day 330 (Part 1/Year 1)

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    End point title
    		 Percent change in Lp(a) from baseline up to Day 330 (Part 1/Year 1)
    End point description
    Percentage change in lipoprotein (a) [Lp(a)] from baseline to Day 330.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 330
    End point values
    		 Part 1- Inclisiran Part 1 - Placebo
    Number of subjects analysed
    93
    48
    Units: Percent change in Lp(a)
        least squares mean (confidence interval 95%)
    -5.04 (-14.21 to 4.13)
    1.14 (-5.48 to 7.77)
    Statistical analysis title
    		 Difference between Inclisiran and Placebo
    Comparison groups
    Part 1- Inclisiran v Part 1 - Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1419
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean
    Point estimate
    -6.18
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -17.48
         upper limit
    		 5.12

    Secondary: Percent change in Apo B from baseline up to Day 330 (Part 1/Year 1)

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    End point title
    		 Percent change in Apo B from baseline up to Day 330 (Part 1/Year 1)
    End point description
    Percentage change in apolipoprotein B (Apo B) from baseline to Day 330.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 330
    End point values
    		 Part 1- Inclisiran Part 1 - Placebo
    Number of subjects analysed
    93
    48
    Units: Percent change in Apo B
        least squares mean (confidence interval 95%)
    -21.46 (-25.59 to -17.33)
    4.24 (-0.07 to 8.56)
    Statistical analysis title
    		 Difference between Inclisiran and Placebo
    Comparison groups
    Part 1- Inclisiran v Part 1 - Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean
    Point estimate
    -25.7
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -31.68
         upper limit
    		 -19.73

    Secondary: Absolute change in LDL-C from baseline to up Day 330 (Part 1/Year 1)

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    End point title
    		 Absolute change in LDL-C from baseline to up Day 330 (Part 1/Year 1)
    End point description
    Absolute change in LDL-C from baseline to Day 330.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 330
    End point values
    		 Part 1- Inclisiran Part 1 - Placebo
    Number of subjects analysed
    93
    48
    Units: mg/dL
        least squares mean (confidence interval 95%)
    -50.54 (-59.22 to -41.86)
    -0.55 (-10.48 to 9.38)
    Statistical analysis title
    		 Difference between Inclisiran and Placebo
    Comparison groups
    Part 1- Inclisiran v Part 1 - Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean
    Point estimate
    -49.99
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -63.18
         upper limit
    		 -36.81

    Secondary: Percent change in total cholesterol from baseline up to Day 330 (Part 1/Year 1)

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    End point title
    		 Percent change in total cholesterol from baseline up to Day 330 (Part 1/Year 1)
    End point description
    Percentage change in total cholesterol from baseline to Day 330.
    End point type
    Secondary
    End point timeframe
    Baseline and Day 330
    End point values
    		 Part 1- Inclisiran Part 1 - Placebo
    Number of subjects analysed
    93
    48
    Units: Percent change in total cholesterol
        least squares mean (confidence interval 95%)
    -18.72 (-22.48 to -14.96)
    0.48 (-3.46 to 4.42)
    Statistical analysis title
    		 Difference between Inclisiran and Placebo
    Comparison groups
    Part 1- Inclisiran v Part 1 - Placebo
    Number of subjects included in analysis
    141
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 < 0.0001
    Method
    		 ANCOVA
    Parameter type
    		 LS Mean
    Point estimate
    -19.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -24.65
         upper limit
    		 -13.75

    Secondary: Percent change in LDL-C from baseline up to Day 720

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    End point title
    		 Percent change in LDL-C from baseline up to Day 720
    End point description
    Percentage change in LDL-C from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    93
    139
    48
    Units: Percent change in LDL-C
    arithmetic mean (standard deviation)
        DAY 90 (n=93,48,0)
    -23.9 ( 22.14 )
    999 ( 999 )
    -0.1 ( 20.16 )
        DAY 150 (n=92,48,0)
    -32.5 ( 21.47 )
    999 ( 999 )
    6.4 ( 28.83 )
        DAY 270 (n=92,48,0)
    -19.0 ( 28.31 )
    999 ( 999 )
    2.1 ( 22.44 )
        DAY 330 (n=90,48,0)
    -27.8 ( 22.95 )
    999 ( 999 )
    1.5 ( 20.59 )
        DAY 360 (n=90,48,0)
    -26.1 ( 22.71 )
    999 ( 999 )
    1.5 ( 30.56 )
        DAY 450 (n=0,0,139)
    999 ( 999 )
    -24.5 ( 26.45 )
    999 ( 999 )
        DAY 510 (n=0,0,139)
    999 ( 999 )
    -32.5 ( 22.80 )
    999 ( 999 )
        DAY 630 (n=0,0,139)
    999 ( 999 )
    -26.5 ( 24.33 )
    999 ( 999 )
        Day 720 (study completion) (n=0,0,139)
    999 ( 999 )
    -33.7 ( 23.98 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Absolute change in LDL-C from baseline up to Day 720

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    End point title
    		 Absolute change in LDL-C from baseline up to Day 720
    End point description
    Absolute change in LDL-C from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    93
    139
    48
    Units: mg/dL
    arithmetic mean (standard deviation)
        DAY 90 (n=93,48,0)
    -45.4 ( 45.26 )
    999 ( 999 )
    -3.0 ( 35.02 )
        DAY 150 (n=92,48,0)
    -61.0 ( 45.84 )
    999 ( 999 )
    6.6 ( 46.22 )
        DAY 270 (n=92,48,0)
    -38.4 ( 55.77 )
    999 ( 999 )
    1.0 ( 36.92 )
        DAY 330 (n=90,48,0)
    -51.9 ( 45.47 )
    999 ( 999 )
    -0.3 ( 38.04 )
        DAY 360 (n=90,48,0)
    -49.0 ( 44.49 )
    999 ( 999 )
    -2.9 ( 51.74 )
        DAY 450 (n=0,0,139)
    999 ( 999 )
    -46.3 ( 52.51 )
    999 ( 999 )
        DAY 510 (n=0,0,139)
    999 ( 999 )
    -60.8 ( 48.88 )
    999 ( 999 )
        DAY 630 (n=0,0,139)
    999 ( 999 )
    -50.9 ( 50.30 )
    999 ( 999 )
        Day 720 (study completion) (n=0,0,139)
    999 ( 999 )
    -64.1 ( 53.91 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Percent change in Apo B from baseline up to Day 720

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    End point title
    		 Percent change in Apo B from baseline up to Day 720
    End point description
    Percentage change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: Percent change in Apo B
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    -25.1 ( 18.18 )
    999 ( 999 )
    2.2 ( 20.77 )
        DAY 330 (n=90, 48, 0)
    -21.9 ( 19.51 )
    999 ( 999 )
    3.9 ( 18.13 )
        DAY 360 (n=90, 48, 0)
    -19.3 ( 21.36 )
    999 ( 999 )
    1.7 ( 22.70 )
        DAY 510 (n=0, 0, 138)
    999 ( 999 )
    -24.5 ( 21.77 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    -25.7 ( 21.71 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Absolute change in Apo B from baseline up to Day 720

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    End point title
    		 Absolute change in Apo B from baseline up to Day 720
    End point description
    Absolute change in apolipoprotein B (Apo B) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: mg/dL
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    -33.3 ( 28.20 )
    999 ( 999 )
    0.0 ( 27.38 )
        DAY 330 (n=90, 48, 0)
    -29.2 ( 28.04 )
    999 ( 999 )
    2.9 ( 23.47 )
        DAY 360 (n=90, 48, 0)
    -26.1 ( 29.59 )
    999 ( 999 )
    -0.6 ( 28.72 )
        DAY 510 (n=0, 0, 138)
    999 ( 999 )
    -33.5 ( 32.13 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    -35.4 ( 33.83 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Percent change in Lp(a) from baseline up to Day 720

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    End point title
    		 Percent change in Lp(a) from baseline up to Day 720
    End point description
    Percentage change in lipoprotein (a) [Lp(a)] from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: Percent change in Lp(a)
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    -13.4 ( 22.60 )
    999 ( 999 )
    5.4 ( 23.96 )
        DAY 330 (n=90, 48, 0)
    -7.2 ( 30.80 )
    999 ( 999 )
    1.1 ( 24.25 )
        DAY 360 (n=90, 48, 0)
    -9.3 ( 28.44 )
    999 ( 999 )
    3.6 ( 23.27 )
        DAY 510 (n=0, 0, 139)
    999 ( 999 )
    -13.3 ( 28.81 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    -4.2 ( 163.74 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Absolute change in Lp(a) from baseline up to Day 720

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    End point title
    		 Absolute change in Lp(a) from baseline up to Day 720
    End point description
    Absolute change in lipoprotein (a) [Lp(a)] from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: nmol/L
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    -12.5 ( 34.73 )
    999 ( 999 )
    3.2 ( 20.67 )
        DAY 330 (n=90, 48, 0)
    -9.5 ( 33.81 )
    999 ( 999 )
    5.3 ( 21.55 )
        DAY 360 (n=90, 48, 0)
    -10.2 ( 31.16 )
    999 ( 999 )
    4.4 ( 22.99 )
        DAY 510 (n=0, 0, 139)
    999 ( 999 )
    -10.1 ( 34.98 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    -9.0 ( 50.08 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Percent change in non-HDL-C from baseline up to Day 720

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    End point title
    		 Percent change in non-HDL-C from baseline up to Day 720
    End point description
    Percentage change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: Percent change in non-HDL-C
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    -29.0 ( 20.15 )
    999 ( 999 )
    5.1 ( 24.85 )
        DAY 330 (n=90, 48, 0)
    -25.7 ( 21.69 )
    999 ( 999 )
    1.8 ( 19.43 )
        DAY 360 (n=90, 48, 0)
    -24.0 ( 21.74 )
    999 ( 999 )
    1.2 ( 27.43 )
        DAY 510 (n=0, 0, 139)
    999 ( 999 )
    -29.9 ( 21.60 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    -31.0 ( 23.04 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Absolute change in non-HDL-C from baseline up to Day 720

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    End point title
    		 Absolute change in non-HDL-C from baseline up to Day 720
    End point description
    Absolute change in non-high density lipoprotein cholesterol (non-HDL-C) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: mg/dL
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    -60.2 ( 47.41 )
    999 ( 999 )
    5.7 ( 47.61 )
        DAY 330 (n=90, 48, 0)
    -52.6 ( 46.93 )
    999 ( 999 )
    0.5 ( 39.20 )
        DAY 360 (n=90, 48, 0)
    -49.7 ( 46.30 )
    999 ( 999 )
    -3.0 ( 52.75 )
        DAY 510 (n=0, 0, 139)
    999 ( 999 )
    -62.0 ( 51.09 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    -65.1 ( 56.16 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Percent change in total cholesterol from baseline up to Day 720

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    End point title
    		 Percent change in total cholesterol from baseline up to Day 720
    End point description
    Percentage change in total cholesterol from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: Percent change in total cholesterol
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    -22.6 ( 15.77 )
    999 ( 999 )
    4.4 ( 20.49 )
        DAY 330 (n=90, 48, 0)
    -19.2 ( 17.77 )
    999 ( 999 )
    0.6 ( 15.46 )
        DAY 360 (n=90, 48, 0)
    -18.5 ( 17.18 )
    999 ( 999 )
    0.6 ( 21.81 )
        DAY 510 (n=0, 0, 139)
    999 ( 999 )
    -23.0 ( 17.50 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    -23.7 ( 18.29 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Absolute change in total cholesterol from baseline up to Day 720

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    End point title
    		 Absolute change in total cholesterol from baseline up to Day 720
    End point description
    Absolute change in total cholesterol from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: mg/dL
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    -59.0 ( 47.79 )
    999 ( 999 )
    6.6 ( 48.08 )
        DAY 330 (n=90, 48, 0)
    -49.4 ( 47.77 )
    999 ( 999 )
    -0.9 ( 38.48 )
        DAY 360 (n=90, 48, 0)
    -48.2 ( 47.06 )
    999 ( 999 )
    -3.1 ( 52.66 )
        DAY 510 (n=0, 0, 139)
    999 ( 999 )
    -59.6 ( 51.06 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    -62.3 ( 55.05 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Percent change in triglycerides from baseline up to Day 720

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    End point title
    		 Percent change in triglycerides from baseline up to Day 720
    End point description
    Percentage change in triglycerides from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: Percent change in triglycerides
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    16.2 ( 78.18 )
    999 ( 999 )
    2.8 ( 37.44 )
        DAY 330 (n=90, 48, 0)
    1.8 ( 38.39 )
    999 ( 999 )
    9.7 ( 43.04 )
        DAY 360 (n=90, 48, 0)
    1.7 ( 40.03 )
    999 ( 999 )
    3.8 ( 35.76 )
        DAY 510 (n=0, 0, 139)
    999 ( 999 )
    3.4 ( 43.08 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    1.9 ( 41.84 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Absolute change in triglycerides from baseline up to Day 720

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    End point title
    		 Absolute change in triglycerides from baseline up to Day 720
    End point description
    Absolute change in triglycerides from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: mg/dL
    arithmetic mean (standard deviation)
        DAY 150 (n= 92, 48, 0)
    6.9 ( 64.67 )
    999 ( 999 )
    -4.8 ( 31.53 )
        DAY 330 (n= 90, 48, 0)
    -2.9 ( 35.01 )
    999 ( 999 )
    3.5 ( 35.55 )
        DAY 360 (n= 90, 48, 0)
    -3.1 ( 38.13 )
    999 ( 999 )
    -1.7 ( 28.47 )
        DAY 510 (n= 0, 0, 139)
    999 ( 999 )
    -4.2 ( 34.70 )
    999 ( 999 )
        Day 720 (study completion) (n= 0, 0, 139)
    999 ( 999 )
    -4.8 ( 36.21 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Percent change in HDL-C from baseline up to Day 720

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    End point title
    		 Percent change in HDL-C from baseline up to Day 720
    End point description
    Percentage change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: Percent change in HDL-C
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    3.6 ( 18.88 )
    999 ( 999 )
    3.6 ( 16.49 )
        DAY 330 (n=90, 48, 0)
    7.4 ( 19.15 )
    999 ( 999 )
    -1.9 ( 16.15 )
        DAY 360 (n=90, 48, 0)
    4.4 ( 19.54 )
    999 ( 999 )
    0.9 ( 12.39 )
        DAY 510 (n=0, 0, 139)
    999 ( 999 )
    6.6 ( 19.84 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    7.4 ( 20.40 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Absolute change in HDL-C from baseline up to Day 720

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    End point title
    		 Absolute change in HDL-C from baseline up to Day 720
    End point description
    Absolute change in high density lipoprotein cholesterol (HDL-C) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: mg/dL
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    1.2 ( 10.23 )
    999 ( 999 )
    0.9 ( 8.07 )
        DAY 330 (n=90, 48, 0)
    3.2 ( 9.57 )
    999 ( 999 )
    -1.4 ( 7.77 )
        DAY 360 (n=90, 48, 0)
    1.5 ( 9.59 )
    999 ( 999 )
    -0.1 ( 6.23 )
        DAY 510 (n=0, 0, 139)
    999 ( 999 )
    2.4 ( 9.32 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    2.8 ( 9.75 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Percent change in VLDL-C from baseline up to Day 720

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    End point title
    		 Percent change in VLDL-C from baseline up to Day 720
    End point description
    Percentage change in very low density lipoprotein cholesterol (VLDL-C) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: Percent change in VLDL-C
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    11.8 ( 60.04 )
    999 ( 999 )
    3.3 ( 38.25 )
        DAY 330 (n=90, 48, 0)
    0.6 ( 39.00 )
    999 ( 999 )
    10.0 ( 42.29 )
        DAY 360 (n=90, 48, 0)
    1.0 ( 40.15 )
    999 ( 999 )
    4.7 ( 35.65 )
        DAY 510 (n=0, 0, 139)
    999 ( 999 )
    1.4 ( 41.13 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    1.9 ( 42.20 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Absolut change in VLDL-C from baseline up to Day 720

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    End point title
    		 Absolut change in VLDL-C from baseline up to Day 720
    End point description
    Absolute change in very low density lipoprotein cholesterol (VLDL-C) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: mg/dL
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    0.7 ( 10.02 )
    999 ( 999 )
    -0.9 ( 6.37 )
        DAY 330 (n=90, 48, 0)
    -0.7 ( 7.04 )
    999 ( 999 )
    0.8 ( 7.07 )
        DAY 360 (n=90, 48, 0)
    -0.7 ( 7.63 )
    999 ( 999 )
    -0.2 ( 5.66 )
        DAY 510 (n=0, 0, 139)
    999 ( 999 )
    -1.2 ( 6.90 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    -1.0 ( 7.40 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Absolute change in Apo A1 from baseline up to Day 720

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    End point title
    		 Absolute change in Apo A1 from baseline up to Day 720
    End point description
    Absolute change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: mg/dL
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    3.3 ( 21.76 )
    999 ( 999 )
    0.0 ( 17.72 )
        DAY 330 (n=90, 48, 0)
    6.1 ( 21.16 )
    999 ( 999 )
    -2.8 ( 14.24 )
        DAY 360 (n=90, 48, 0)
    2.7 ( 21.87 )
    999 ( 999 )
    -2.6 ( 13.89 )
        DAY 510 (n=0, 0, 138)
    999 ( 999 )
    7.5 ( 22.24 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    5.4 ( 21.61 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Percent change in Apo A1 from baseline up to Day 720

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    End point title
    		 Percent change in Apo A1 from baseline up to Day 720
    End point description
    Percentage change in apolipoprotein A1 (Apo A1) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    92
    139
    48
    Units: Percent change in Apo A1
    arithmetic mean (standard deviation)
        DAY 150 (n=92, 48, 0)
    3.7 ( 15.40 )
    999 ( 999 )
    0.4 ( 13.22 )
        DAY 330 (n=90, 48, 0)
    5.2 ( 14.49 )
    999 ( 999 )
    -1.5 ( 10.58 )
        DAY 360 (n=90, 48, 0)
    3.0 ( 15.12 )
    999 ( 999 )
    -1.5 ( 9.98 )
        DAY 510 (n=0, 0, 138)
    999 ( 999 )
    6.3 ( 16.19 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 139)
    999 ( 999 )
    4.9 ( 15.56 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Percent change in PCSK9 from baseline up to Day 720

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    End point title
    		 Percent change in PCSK9 from baseline up to Day 720
    End point description
    Percentage change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    90
    136
    48
    Units: Percent change in PCSK9
    arithmetic mean (standard deviation)
        DAY 90 (n=89, 47, 0)
    -67.8 ( 15.17 )
    999 ( 999 )
    11.6 ( 46.61 )
        DAY 150 (n=90, 47, 0)
    -72.3 ( 11.37 )
    999 ( 999 )
    3.8 ( 36.95 )
        DAY 330 (n=89, 47, 0)
    -72.9 ( 12.12 )
    999 ( 999 )
    4.8 ( 34.50 )
        DAY 360 (n=89, 48, 0)
    -72.0 ( 10.47 )
    999 ( 999 )
    11.7 ( 57.77 )
        DAY 510 (n=0, 0, 136)
    999 ( 999 )
    -74.3 ( 10.46 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 136)
    999 ( 999 )
    -71.6 ( 13.42 )
    999 ( 999 )
    No statistical analyses for this end point

    Secondary: Absolut change in PCSK9 from baseline up to Day 720

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    End point title
    		 Absolut change in PCSK9 from baseline up to Day 720
    End point description
    Absolute change in proprotein convertase subtilisin/kexin type 9 (PCSK9) from baseline to each assessment time up to Day 720.
    End point type
    Secondary
    End point timeframe
    Baseline, up to Day 720
    End point values
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Number of subjects analysed
    90
    136
    48
    Units: ng/mL
    arithmetic mean (standard deviation)
        DAY 90 (n=89, 47, 0)
    -259.6 ( 121.5 )
    999 ( 999 )
    2.1 ( 223.16 )
        DAY 150 (n=90, 47, 0)
    -274.8 ( 116.2 )
    999 ( 999 )
    -27.7 ( 210.44 )
        DAY 330 (n=89, 47, 0)
    -278.2 ( 119.8 )
    999 ( 999 )
    -23.9 ( 210.85 )
        DAY 360 (n=89, 48, 0)
    -275.4 ( 117.2 )
    999 ( 999 )
    -9.1 ( 245.36 )
        DAY 510 (n=0, 0, 136)
    999 ( 999 )
    -288.1 ( 156.9 )
    999 ( 999 )
        Day 720 (study completion) (n=0, 0, 136)
    999 ( 999 )
    -279.5 ( 159.2 )
    999 ( 999 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Adverse events were reported from first dose of study treatment until end of study treatment plus 90 days post treatment or 30 days after last study visit, whichever was longer, up to a maximum duration of approximately 2 years.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    27.1
    Reporting groups
    Reporting group title
    Part 1- Inclisiran
    Reporting group description
    		 Inclisiran sodium 300 mg subcutaneous (sc) injection (given at Days 1, 90 and 270)

    Reporting group title
    Part 2 – Inclisiran (Total)
    Reporting group description
    		 Inclisiran sodium 300 mg sc injection (given at Days 450 and 630). In addition, participants assigned to placebo in Part 1 received inclisiran sodium 300 mg sc injection on Day 360, while participants assigned to inclisiran in Part 1 received placebo sc injection on Day 360

    Reporting group title
    Part 1 - Placebo
    Reporting group description
    		 Placebo sc injection (given at Day 1, 90 and 270)

    Serious adverse events
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 93 (3.23%)
    6 / 139 (4.32%)
    1 / 48 (2.08%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 139 (0.72%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Concussion
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 139 (0.72%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Vascular disorders
    Varicose vein
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 139 (0.72%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Supraventricular tachycardia
         subjects affected / exposed
    0 / 93 (0.00%)
    0 / 139 (0.00%)
    1 / 48 (2.08%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Status migrainosus
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 139 (0.00%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Syncope
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 139 (0.72%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Immune system disorders
    Anaphylactic reaction
         subjects affected / exposed
    1 / 93 (1.08%)
    1 / 139 (0.72%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 93 (0.00%)
    1 / 139 (0.72%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Dengue fever
         subjects affected / exposed
    1 / 93 (1.08%)
    0 / 139 (0.00%)
    0 / 48 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 3%
    Non-serious adverse events
    		 Part 1- Inclisiran Part 2 – Inclisiran (Total) Part 1 - Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    57 / 93 (61.29%)
    52 / 139 (37.41%)
    29 / 48 (60.42%)
    Injury, poisoning and procedural complications
    Ligament sprain
         subjects affected / exposed
    3 / 93 (3.23%)
    1 / 139 (0.72%)
    1 / 48 (2.08%)
         occurrences all number
    3
    1
    1
    Nervous system disorders
    Migraine
         subjects affected / exposed
    4 / 93 (4.30%)
    2 / 139 (1.44%)
    0 / 48 (0.00%)
         occurrences all number
    4
    2
    0
    Headache
         subjects affected / exposed
    12 / 93 (12.90%)
    6 / 139 (4.32%)
    3 / 48 (6.25%)
         occurrences all number
    14
    8
    3
    Syncope
         subjects affected / exposed
    5 / 93 (5.38%)
    1 / 139 (0.72%)
    0 / 48 (0.00%)
         occurrences all number
    5
    1
    0
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    4 / 93 (4.30%)
    0 / 139 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    4
    0
    2
    Influenza like illness
         subjects affected / exposed
    4 / 93 (4.30%)
    2 / 139 (1.44%)
    3 / 48 (6.25%)
         occurrences all number
    5
    2
    5
    Injection site pain
         subjects affected / exposed
    4 / 93 (4.30%)
    4 / 139 (2.88%)
    2 / 48 (4.17%)
         occurrences all number
    7
    7
    2
    Injection site reaction
         subjects affected / exposed
    8 / 93 (8.60%)
    5 / 139 (3.60%)
    1 / 48 (2.08%)
         occurrences all number
    10
    5
    2
    Malaise
         subjects affected / exposed
    0 / 93 (0.00%)
    0 / 139 (0.00%)
    2 / 48 (4.17%)
         occurrences all number
    0
    0
    2
    Gastrointestinal disorders
    Vomiting
         subjects affected / exposed
    5 / 93 (5.38%)
    0 / 139 (0.00%)
    1 / 48 (2.08%)
         occurrences all number
    8
    0
    1
    Nausea
         subjects affected / exposed
    4 / 93 (4.30%)
    4 / 139 (2.88%)
    1 / 48 (2.08%)
         occurrences all number
    4
    4
    2
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    3 / 93 (3.23%)
    6 / 139 (4.32%)
    2 / 48 (4.17%)
         occurrences all number
    3
    6
    2
    Infections and infestations
    COVID-19
         subjects affected / exposed
    17 / 93 (18.28%)
    7 / 139 (5.04%)
    12 / 48 (25.00%)
         occurrences all number
    17
    7
    12
    Gastroenteritis
         subjects affected / exposed
    4 / 93 (4.30%)
    3 / 139 (2.16%)
    1 / 48 (2.08%)
         occurrences all number
    4
    4
    1
    Influenza
         subjects affected / exposed
    10 / 93 (10.75%)
    11 / 139 (7.91%)
    6 / 48 (12.50%)
         occurrences all number
    11
    11
    8
    Nasopharyngitis
         subjects affected / exposed
    13 / 93 (13.98%)
    14 / 139 (10.07%)
    9 / 48 (18.75%)
         occurrences all number
    14
    18
    11
    Pharyngitis
         subjects affected / exposed
    4 / 93 (4.30%)
    1 / 139 (0.72%)
    2 / 48 (4.17%)
         occurrences all number
    4
    3
    2
    Upper respiratory tract infection
         subjects affected / exposed
    6 / 93 (6.45%)
    4 / 139 (2.88%)
    2 / 48 (4.17%)
         occurrences all number
    10
    5
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    28 Oct 2022
    The purpose of Amendment 1 was to reduce the sample size of the study from approximately 150 participants to a minimum of 102 participants. The revised sample size was based on a careful review of all existing evidence, including new important data available, i.e., the meanwhile well-established, favorable efficacy and safety profile of inclisiran in adults, the comprehensive, supportive non-clinical studies, new re-assuring study results in pediatric patients for drugs with a similar (i.e., PCSK9-directed) mechanism of action, and positive experience with inclisiran in adolescents from two ongoing studies. The revised sample size of at least 102 participants provides more than 90% power to assess the primary efficacy endpoint, under conservative assumptions of a 30% betweengroup difference and standard deviations of 30/40% for the inclisiran and placebo groups. However, the actual enrollment was 141 participants, which further increased the statistical power for the primary efficacy endpoint and contributed additional safety data.
    17 Feb 2023
    The purpose of Amendment 2 was to add an interim analysis (IA) for the PK data collected on Day 1.

    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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