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    Clinical Trial Results:
    An Open-Label, Single-Arm, Multicenter Pilot Study to Evaluate Safety, Tolerability, and Efficacy of ALN-PCSSC in Subjects with Homozygous Familial Hypercholesterolemia

    Summary
    EudraCT number
    		 2016-003376-49
    Trial protocol
    		 NL  
    Global end of trial date
    08 Oct 2018

    Results information
    Results version number
    		 v1(current)
    This version publication date
    16 Nov 2019
    First version publication date
    16 Nov 2019
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    MDCO-PCS-16-02
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT02963311
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    The Medicines Company
    Sponsor organisation address
    8 Sylvan Way, Parsippany, United States, NJ 07054
    Public contact
    Global Health Science Center, The Medicines Company, +1 9732906000, medical.information@themedco.com
    Scientific contact
    Global Health Science Center, The Medicines Company, +1 9732906000, medical.information@themedco.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
    08 Oct 2019
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    08 Oct 2018
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To characterize the effect of 90 and 180 days of subcutaneous ALN-PCSSC (inclisiaran) on the percentage change from Day 1 in low-density lipoprotein cholesterol (LDL-C) in subjects with homozygous familial hypercholesterolemia.
    Protection of trial subjects
    The study was conducted in accordance with the ethical principles that have their origins in the Declaration of Helsinki and in compliance with Good Clinical Practice (GCP) for protection of subjects, as required by the applicable governmental regulations, directives, and guidelines in operation at the time of the study. The study protocol and amendments and informed consent form (ICF) were reviewed and approved by the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) at each participating site. Prior to initiation of any study-related procedures, the nature of the study was fully explained to all subjects and the ICF was signed by the subject. Consent was captured on an ICF form approved by the IEC/IRB and included the elements required by the International Conference on Harmonization and GCP guidelines.
    Background therapy
    		 Subjects taking part in this clinical study received guideline recommended standard of care as background therapy (including maximally-tolerated statin therapy and/or other LDL-C lowering therapies) when administered inclisiran.
    Evidence for comparator
    		 N/A
    Actual start date of recruitment
    13 Dec 2016
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    South Africa: 3
    Worldwide total number of subjects
    4
    EEA total number of subjects
    1
    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)
    4
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Not applicable

    Pre-assignment
    Screening details
    		 Subjects enrolled must have a bodyweight of 40 kg or greater. Subjects were excluded if they had low density lipoprotein (LDL) or plasma apheresis within 8 weeks prior to the screening visit, used Mipomersen or Lomitapide therapy within 5 months or had previous treatment with monoclonal antibodies directed towards PCSK9 within 8 weeks of screening.

    Pre-assignment period milestones
    Number of subjects started
    		 9 [1]
    Number of subjects completed
    		 4

    Pre-assignment subject non-completion reasons
    Reason: Number of subjects
    		 Consent withdrawn by subject: 1
    Reason: Number of subjects
    		 Physician decision: 4
    Notes
    [1] - The number of subjects reported to have started the pre-assignment period are not the same as the worldwide number enrolled in the trial. It is expected that these numbers will be the same.
    Justification: Nine subjects were screened; four subjects failed screening and five were consented into the study. One subject withdrew consent prior to treatment. Therefore, four subjects were treated with inclisiran.
    Period 1
    Period 1 title
    Overall trial (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Arm title
    		 Single arm
    Arm description
    		 A Phase II, open label, single-arm, multicenter pilot study designed to test the efficacy and duration of effect of inclisiran sodium 300 mg in subjects with Homozygous Familial Hypercholesterolemia (HoFH).
    Arm type
    		 Experimental

    Investigational medicinal product name
    Inclisiran
    Investigational medicinal product code
    ALN-60212
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    200 mg/ml

    Number of subjects in period 1
    		Single arm
    Started
    4
    Completed
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Overall trial
    Reporting group description
    		 -

    Reporting group values
    		 Overall trial Total
    Number of subjects
    		 4 4
    Age categorical
    Units: Subjects
        In utero
    		 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0
        Newborns (0-27 days)
    		 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0
        Children (2-11 years)
    		 0 0
        Adolescents (12-17 years)
    		 0 0
        Adults (18-64 years)
    		 4 4
        From 65-84 years
    		 0 0
        85 years and over
    		 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 37.0 ( 13.04 ) -
    Gender categorical
    Units: Subjects
        Female
    		 2 2
        Male
    		 2 2

    End points

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    End points reporting groups
    Reporting group title
    Single arm
    Reporting group description
    		 A Phase II, open label, single-arm, multicenter pilot study designed to test the efficacy and duration of effect of inclisiran sodium 300 mg in subjects with Homozygous Familial Hypercholesterolemia (HoFH).

    Primary: Percentage change from Day 1 to Day 90 in LDL-C

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    End point title
    		 Percentage change from Day 1 to Day 90 in LDL-C [1]
    End point description
    300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Primary
    End point timeframe
    Day 1, Day 90
    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: Due to the small number of subjects, and the fact that the data are not normally distributed, the data are presented as descriptive statistics with no inferential and limited summary statistics presented.
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: percent change
        arithmetic mean (confidence interval 95%)
    -12.26 (-43.75 to 19.24)
    No statistical analyses for this end point

    Primary: Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C

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    End point title
    		 Percentage Change From Day 1 to Day 180 (or Final Visit) in LDL-C [2]
    End point description
    300 milligrams (mg) administered subcutaneous (SC) on Day 1. Participants with a mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies
    End point type
    Primary
    End point timeframe
    Day 1 to Day 180
    Notes
    [2] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Due to the small number of subjects, and the fact that the data are not normally distributed, the data are presented as descriptive statistics with no inferential and limited summary statistics presented.
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percent change
        arithmetic mean (confidence interval 95%)
    -20.96 (-49.97 to 8.05)
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 90 in LDL-C

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    End point title
    		 Absolute Change From Day 1 to Day 90 in LDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -56.3 ( 115.18 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 180 (or Final Visit) in LDL-C

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    End point title
    		 Absolute Change From Day 1 to Day 180 (or Final Visit) in LDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180 (or Final Visit)
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -105.3 ( 116.44 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 60 in PCSK9

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    End point title
    		 Percentage Change From Day 1 to Day 60 in PCSK9
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 60
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: percentage
        arithmetic mean (standard deviation)
    -64.9 ( 18.33 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 90 in PCSK9

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    End point title
    		 Percentage Change From Day 1 to Day 90 in PCSK9
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: percentage
        arithmetic mean (standard deviation)
    -59.0 ( 16.46 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 60 in PCSK9

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    End point title
    		 Absolute Change From Day 1 to Day 60 in PCSK9
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 60
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: ng/mL
        arithmetic mean (standard deviation)
    -654.1 ( 564.67 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 90 in PCSK9

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    End point title
    		 Absolute Change From Day 1 to Day 90 in PCSK9
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: ng/mL
        arithmetic mean (standard deviation)
    602.3 ( 559.61 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 90 in Total Cholesterol

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    End point title
    		 Percentage Change From Day 1 to Day 90 in Total Cholesterol
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: percent change
        arithmetic mean (standard deviation)
    -13.9 ( 14.84 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 180 (or Final Visit) in Total Cholesterol

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    End point title
    		 Percentage Change From Day 1 to Day 180 (or Final Visit) in Total Cholesterol
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180 (or final visit)
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: percent change
        arithmetic mean (standard deviation)
    -19.8 ( 13.68 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 90 in Total Cholesterol

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    End point title
    		 Absolute Change From Day 1 to Day 90 in Total Cholesterol
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    77.8 ( 103.41 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 180 (or Final Visit) in Total Cholesterol

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    End point title
    		 Absolute Change From Day 1 to Day 180 (or Final Visit) in Total Cholesterol
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -118.0 ( 103.52 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 90 in Triglycerides

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    End point title
    		 Percentage Change From Day 1 to Day 90 in Triglycerides
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percent change
        arithmetic mean (standard deviation)
    -21.0 ( 30.99 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 180 (or Final Visit) in Triglycerides

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    End point title
    		 Percentage Change From Day 1 to Day 180 (or Final Visit) in Triglycerides
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    11.67 ( 20.3 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 90 in Triglycerides

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    End point title
    		 Absolute Change From Day 1 to Day 90 in Triglycerides
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -35.5 ( 38.76 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 Day 180 (or Final Visit) in Triglycerides

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    End point title
    		 Absolute Change From Day 1 Day 180 (or Final Visit) in Triglycerides
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -26.3 ( 24.64 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 90 in HDL-C

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    End point title
    		 Percentage Change From Day 1 to Day 90 in HDL-C
    End point description
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    -12.1 ( 17.98 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 180 (or Final Visit) in HDL-C

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    End point title
    		 Percentage Change From Day 1 to Day 180 (or Final Visit) in HDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    -19.8 ( 11.78 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 90 in HDL-C

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    End point title
    		 Absolute Change From Day 1 to Day 90 in HDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -6.0 ( 9.13 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 180 (or Final Visit) in HDL-C

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    End point title
    		 Absolute Change From Day 1 to Day 180 (or Final Visit) in HDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -9.5 ( 4.73 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 90 in Non-HDL-C

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    End point title
    		 Percentage Change From Day 1 to Day 90 in Non-HDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    -13.9 ( 14.78 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 180 (or Final Visit) in Non-HDL-C

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    End point title
    		 Percentage Change From Day 1 to Day 180 (or Final Visit) in Non-HDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    -19.7 ( 13.93 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 90 in Non-HDL-C

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    End point title
    		 Absolute Change From Day 1 to Day 90 in Non-HDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -71.8 ( 97.70 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 180 (or Final Visit) in Non-HDL-C

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    End point title
    		 Absolute Change From Day 1 to Day 180 (or Final Visit) in Non-HDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -108.5 ( 99.38 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 90 in VLDL-C

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    End point title
    		 Percentage Change From Day 1 to Day 90 in VLDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    8.5 ( 65.28 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 180 (or Final Visit) in VLDL-C

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    End point title
    		 Percentage Change From Day 1 to Day 180 (or Final Visit) in VLDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    55.5 ( 131.92 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 90 in VLDL-C

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    End point title
    		 Absolute Change From Day 1 to Day 90 in VLDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -15.5 ( 28.41 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 180 (or Final Visit) in VLDL-C

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    End point title
    		 Absolute Change From Day 1 to Day 180 (or Final Visit) in VLDL-C
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -3.3 ( 37.32 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 90 in Apolipoprotein A1

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    End point title
    		 Percentage Change From Day 1 to Day 90 in Apolipoprotein A1
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    -8.3 ( 12.95 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 180 (or Final Visit) in Apolipoprotein A1

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    End point title
    		 Percentage Change From Day 1 to Day 180 (or Final Visit) in Apolipoprotein A1
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    -14.2 ( 14.44 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 90 in Apolipoprotein A1

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    End point title
    		 Absolute Change From Day 1 to Day 90 in Apolipoprotein A1
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -11.5 ( 17.52 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 180 (or Final Visit) in Apolipoprotein A1

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    End point title
    		 Absolute Change From Day 1 to Day 180 (or Final Visit) in Apolipoprotein A1
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -19.8 ( 19.00 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 90 in Apolipoprotein B

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    End point title
    		 Percentage Change From Day 1 to Day 90 in Apolipoprotein B
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    -26.6 ( 14.98 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 180 (or Final Visit) in Apolipoprotein B

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    End point title
    		 Percentage Change From Day 1 to Day 180 (or Final Visit) in Apolipoprotein B
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    -25.0 ( 14.50 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 90 in Apolipoprotein B

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    End point title
    		 Absolute Change From Day 1 to Day 90 in Apolipoprotein B
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -95.3 ( 78.16 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 180 (or Final Visit) in Apolipoprotein B

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    End point title
    		 Absolute Change From Day 1 to Day 180 (or Final Visit) in Apolipoprotein B
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -86.3 ( 72.02 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 90 in Lipoprotein-a

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    End point title
    		 Percentage Change From Day 1 to Day 90 in Lipoprotein-a
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    -3.5 ( 15.70 )
    No statistical analyses for this end point

    Secondary: Percentage Change From Day 1 to Day 180 (or Final Visit) in Lipoprotein-a

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    End point title
    		 Percentage Change From Day 1 to Day 180 (or Final Visit) in Lipoprotein-a
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: Percentage change
        arithmetic mean (standard deviation)
    -11.8 ( 15.15 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 90 in Lipoprotein-a

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    End point title
    		 Absolute Change From Day 1 to Day 90 in Lipoprotein-a
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 90
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    13.5 ( 21.92 )
    No statistical analyses for this end point

    Secondary: Absolute Change From Day 1 to Day 180 (or Final Visit) in Lipoprotein-a

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    End point title
    		 Absolute Change From Day 1 to Day 180 (or Final Visit) in Lipoprotein-a
    End point description
    All subjects received open label inclisiran on Day 1. The dosing interval was determined by PCSK9 level at Day 60 or 90 or rate of change of PCSK9 levels between Days 60 and 90. If a second dose of study drug was deemed necessary (if mean serum proprotein convertase subtilisin/kexin type 9 (PCSK9) levels not suppressed by >70% at Day 60 or Day 90, as compared to baseline, subjects will receive a second dose at Day 90 or Day 104, respectively, based on PCSK9 levels from the previous visit. Participants also received standard of care as background therapy. Inclisiran: Inclisiran is a small interfering ribonucleic acid (siRNA) that inhibits PCSK9 synthesis and is given as SC injections. Standard of Care: Included maximally-tolerated statin therapy and/or other low density lipoprotein-cholesterol (LDL-C)-lowering therapies.
    End point type
    Secondary
    End point timeframe
    Day 1 to Day 180
    End point values
    		 Single arm
    Number of subjects analysed
    4
    Units: mg/dL
        arithmetic mean (standard deviation)
    -23.8 ( 52.73 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    18 months
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    10.0
    Reporting groups
    Reporting group title
    Inclisiran
    Reporting group description
    		 -

    Serious adverse events
    		 Inclisiran
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 4 (25.00%)
         number of deaths (all causes)
    0
         number of deaths resulting from adverse events
    0
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences causally related to treatment / all
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Inclisiran
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 4 (75.00%)
    Injury, poisoning and procedural complications
    Limb injury
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    Road traffic accident
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    Cardiac disorders
    Angina unstable
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    Nervous system disorders
    Paraesthesia
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    General disorders and administration site conditions
    Influenza like illness
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    Respiratory, thoracic and mediastinal disorders
    Dyspnoea
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    Musculoskeletal and connective tissue disorders
    Musculoskeletal pain
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    Pain in extremity
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    Infections and infestations
    Cystitis
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1
    Nasopharyngitis
         subjects affected / exposed
    1 / 4 (25.00%)
         occurrences all number
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Nov 2016
    Amend 01
    18 Aug 2017
    Amendment 2

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

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