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    Clinical Trial Results:
    An Open Label, Randomized, Phase 2 Study to Assess the Safety, Tolerability, and Efficacy of IONIS GHR-LRX, an Antisense Inhibitor of the Growth Hormone Receptor, Administered Monthly as Monotherapy in Patients with Acromegaly

    Summary
    EudraCT number
    		 2020-000675-20
    Trial protocol
    		 HU   LT   PL   LV   IT   RO  
    Global end of trial date
    04 May 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 May 2024
    First version publication date
    19 May 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    ISIS 766720-CS5
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04522180
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Ionis Pharmaceuticals, Inc.
    Sponsor organisation address
    2855 Gazelle Court, Carlsbad, CA, United States, 92010
    Public contact
    Ionis Clinical Trial Information, Ionis Pharmaceuticals, Inc., +1 760-603-2387, ClinicalTrials@ionisph.com
    Scientific contact
    Ionis Clinical Trial Information, Ionis Pharmaceuticals, Inc., +1 760-603-2387, ClinicalTrials@ionisph.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
    04 May 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    04 May 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The purpose of this study was to determine the safety, tolerability, and efficacy of IONIS-GHR-LRx subcutaneous (SC) injection as monotherapy in patients with acromegaly.
    Protection of trial subjects
    All participants in this study were required to read and sign an Informed Consent Form (ICF).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Jan 2021
    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
    Russian Federation: 13
    Country: Number of subjects enrolled
    Serbia: 1
    Country: Number of subjects enrolled
    United States: 4
    Country: Number of subjects enrolled
    Estonia: 5
    Country: Number of subjects enrolled
    Hungary: 1
    Country: Number of subjects enrolled
    Italy: 6
    Country: Number of subjects enrolled
    Lithuania: 2
    Country: Number of subjects enrolled
    Poland: 2
    Worldwide total number of subjects
    34
    EEA total number of subjects
    16
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    27
    From 65 to 84 years
    7
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were enrolled at 22 investigational sites in United States of America, Estonia, Hungary, Italy, Lithuania, Poland, Russia, and Serbia from 4 January 2021 to 18 Jan2022.

    Pre-assignment
    Screening details
    		 Participants with acromegaly were enrolled and assigned to receive an initial dose of GHR-LRX 120 mg or GHR-LRX 160 mg up to week 17 (when the first post-baseline IGF-1 results were available). After Week 17, patients may have received a higher dose up to 160 mg for efficacy, if necessary, up to 73 weeks.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 GHR-LRX 120 mg
    Arm description
    		 Participants received GHR-LRX 120 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3)
    Arm type
    		 Experimental

    Investigational medicinal product name
    ISIS 766720
    Investigational medicinal product code
    Other name
    GHR-LRX
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    120 mg of GHR-LRX was administered by SC injection.

    Arm title
    		 GHR-LRX 160 mg
    Arm description
    		 Participants received GHR-LRX 160 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3)
    Arm type
    		 Experimental

    Investigational medicinal product name
    ISIS 766720
    Investigational medicinal product code
    Other name
    GHR-LRX
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    160 mg of GHR-LRX was administered by SC injection.

    Number of subjects in period 1
    		GHR-LRX 120 mg GHR-LRX 160 mg
    Started
    18
    16
    Per Protocol Set (Initial Dose)
    18
    14
    Completed
    18
    13
    Not completed
    0
    3
         Reason Not specified
    -
    2
         Pregnancy
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    GHR-LRX 120 mg
    Reporting group description
    		 Participants received GHR-LRX 120 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3)

    Reporting group title
    GHR-LRX 160 mg
    Reporting group description
    		 Participants received GHR-LRX 160 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3)

    Reporting group values
    		 GHR-LRX 120 mg GHR-LRX 160 mg Total
    Number of subjects
    		 18 16
    Age Categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 57.0 ( 11.09 ) 48.3 ( 10.88 ) -
    Gender categorical
    Units: Subjects
        Male
    		 10 7 17
        Female
    		 8 9 17
    Race
    Units: Subjects
        White
    		 18 15 33
        Multiple Race
    		 0 1 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 0 0 0
        Not Hispanic or Latino
    		 18 16 34

    End points

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    End points reporting groups
    Reporting group title
    GHR-LRX 120 mg
    Reporting group description
    		 Participants received GHR-LRX 120 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3)

    Reporting group title
    GHR-LRX 160 mg
    Reporting group description
    		 Participants received GHR-LRX 160 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3)

    Subject analysis set title
    GHR-LRX 120 mg
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received initial dose of GHR-LRX 120 mg SC injection once every month for up to 73 weeks with a booster dose administered on Day 15 (Week 3)

    Subject analysis set title
    GHR-LRX 160 mg
    Subject analysis set type
    		 Per protocol
    Subject analysis set description
    Participants received initial dose of GHR-LRX 160 mg SC injection once every month for up to 73 weeks with a booster dose administered on Day 15 (Week 3)

    Subject analysis set title
    GHR-LRX Total
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Overall number of participants analyzed is the number of participants available for analyses. Total of all participants in the Per Protocol Set (received initial doses of 120 mg or 160 mg doses).

    Primary: Percent Change in Insulin-like Growth Factor I (IGF-1) from Baseline to Week 27

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    End point title
    		 Percent Change in Insulin-like Growth Factor I (IGF-1) from Baseline to Week 27 [1]
    End point description
    IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. Baseline of IGF-1 is defined as the average value of Screening and Day 1. A negative percent change from baseline indicated improvement.
    End point type
    Primary
    End point timeframe
    Baseline to Week 27
    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: Only descriptive analysis was planned for this endpoint.
    End point values
    		 GHR-LRX 120 mg GHR-LRX 160 mg GHR-LRX Total
    Number of subjects analysed
    16
    10
    26
    Units: percent change
    arithmetic mean (standard deviation)
        At Week 27
    -10.47 ( 11.418 )
    -1.68 ( 27.848 )
    -7.09 ( 19.402 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Serum IGF-1 Over Time

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    End point title
    		 Change From Baseline in Serum IGF-1 Over Time
    End point description
    IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative change from baseline indicated improvement. 
    End point type
    Secondary
    End point timeframe
    Baseline, Week 3, 5, 7, 9, 11, 13, 15, 17, 21, 23, 25, 27, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73
    End point values
    		 GHR-LRX 120 mg GHR-LRX 160 mg GHR-LRX Total
    Number of subjects analysed
    3 [2]
    29 [3]
    32
    Units: nanograms per millilitre (ng/mL)
    arithmetic mean (standard deviation)
        At Week 3 (n =3, 29, 32)
    -30.00 ( 44.908 )
    5.03 ( 49.932 )
    1.74 ( 49.896 )
        At Week 5 (n =3, 29, 32)
    -50.67 ( 101.186 )
    -45.53 ( 87.817 )
    -46.01 ( 87.341 )
        At Week 7 (n =3, 29, 32)
    -84.33 ( 133.829 )
    -39.46 ( 80.258 )
    -43.66 ( 84.558 )
        At Week 9 (n =3, 29, 32)
    -109.00 ( 111.959 )
    -25.28 ( 93.924 )
    -33.13 ( 96.909 )
        At Week 11(n =3, 29, 32)
    -157.67 ( 144.923 )
    -14.28 ( 64.463 )
    -27.73 ( 83.134 )
        At Week 13 (n =3, 29, 32)
    -89.67 ( 130.989 )
    -38.01 ( 68.885 )
    -42.85 ( 75.013 )
        At Week 15 (n =3, 27, 30)
    -112.00 ( 112.618 )
    -28.97 ( 79.942 )
    -37.28 ( 85.124 )
        At Week 17 (n =3, 29, 32)
    -89.33 ( 136.433 )
    -36.91 ( 88.212 )
    -41.82 ( 92.034 )
        At Week 21 (n =2, 24, 26)
    -123.25 ( 136.118 )
    -51.91 ( 92.746 )
    -57.39 ( 95.030 )
        At Week 25 (n =2, 24, 26)
    -99.75 ( 126.926 )
    -36.99 ( 78.236 )
    -41.82 ( 81.034 )
        At Week 27 (n =2, 24, 26)
    -58.75 ( 87.328 )
    -49.45 ( 112.579 )
    -50.16 ( 109.415 )
        At Week 29 (n =2, 23, 25)
    -90.25 ( 126.219 )
    -40.25 ( 80.174 )
    -44.25 ( 82.145 )
        At Week 33 (n =2, 23, 25)
    -75.25 ( 110.662 )
    -53.12 ( 72.494 )
    -54.89 ( 73.247 )
        At Week 37 (n =2, 23, 25)
    -98.75 ( 179.252 )
    -32.55 ( 107.499 )
    -37.85 ( 110.760 )
        At Week 41 (n =2, 23, 25)
    -93.25 ( 146.018 )
    -43.12 ( 97.911 )
    -47.13 ( 99.341 )
        At Week 45 (n =2, 21, 23)
    -86.75 ( 175.009 )
    -52.80 ( 110.595 )
    -55.75 ( 112.282 )
        At Week 49 (n =2, 19, 21)
    -81.75 ( 109.955 )
    -64.59 ( 105.493 )
    -66.23 ( 103.184 )
        At Week 53 (n =2, 18, 20)
    -90.25 ( 158.745 )
    -68.71 ( 81.822 )
    -70.86 ( 85.793 )
        At Week 57 (n =2, 17, 19)
    -73.75 ( 91.570 )
    -59.43 ( 90.080 )
    -60.93 ( 87.744 )
        At Week 61 (n =2, 15, 17)
    -125.75 ( 199.051 )
    -83.08 ( 112.428 )
    -88.10 ( 117.206 )
        At Week 65 (n =1, 11, 12)
    74.00 ( 99999 )
    -103.30 ( 102.760 )
    -88.52 ( 110.540 )
        At Week 69 (n =1, 8, 9)
    -22.00 ( 99999 )
    -85.59 ( 53.018 )
    -78.53 ( 53.934 )
        At Week 73 (n =1, 7, 8)
    -1.00 ( 99999 )
    -91.18 ( 79.166 )
    -79.91 ( 79.928 )
    Notes
    [2] - The standard deviation was not estimable for a single participant.
    [3] - The standard deviation was not estimable for a single participant.
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieved Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27)

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    End point title
    		 Percentage of Participants Who Achieved Normalized IGF-1 Levels to Within 1.0 Times Gender and Age Limits at Day 183 (Week 27)
    End point description
    Normalized IGF-1 level is defined as the ratio of the serum IGF-1 level and the participant’s ULN.
    End point type
    Secondary
    End point timeframe
    At Week 27
    End point values
    		 GHR-LRX 120 mg GHR-LRX 160 mg GHR-LRX Total
    Number of subjects analysed
    16
    10
    26
    Units: Percentage of participants
    number (confidence interval 95%)
        At Week 27
    0 (0.0 to 20.6)
    0 (0.0 to 30.8)
    0 (0.0 to 13.2)
    No statistical analyses for this end point

    Secondary: Percentage of Participants Who Achieved Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27)

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    End point title
    		 Percentage of Participants Who Achieved Normalized IGF-1 Levels to Within 1.2 Times Gender and Age Limits at Day 183 (Week 27)
    End point description
    Normalized IGF-1 level is defined as the ratio of the serum IGF-1 level and the participant’s upper limit of normal (ULN).
    End point type
    Secondary
    End point timeframe
    At Week 27 
    End point values
    		 GHR-LRX 120 mg GHR-LRX 160 mg GHR-LRX Total
    Number of subjects analysed
    16
    10
    26
    Units: percentage of participants
        number (confidence interval 95%)
    0 (0.0 to 20.6)
    0 (0.0 to 30.8)
    0 (0.0 to 13.2)
    No statistical analyses for this end point

    Secondary: Percent Change From Baseline in Serum IGF-1 Over Time

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    End point title
    		 Percent Change From Baseline in Serum IGF-1 Over Time
    End point description
    IGF-1 is a hormone that manages the effects of growth hormone (GH) in the body. A negative percent change from baseline indicated improvement. 
    End point type
    Secondary
    End point timeframe
    Baseline, Week 3, 5, 7, 9, 11, 13, 15, 17, 21, 25, 27, 29, 33, 37, 41, 45, 49, 53, 57, 61, 65, 69, 73
    End point values
    		 GHR-LRX 120 mg GHR-LRX 160 mg GHR-LRX Total
    Number of subjects analysed
    3 [4]
    29 [5]
    32
    Units: percent change
    arithmetic mean (standard deviation)
        At Week 3 (n =3, 29, 32)
    -3.73 ( 5.072 )
    2.64 ( 11.936 )
    2.04 ( 11.571 )
        At Week 5 (n =3, 29, 32)
    -5.67 ( 12.296 )
    -8.28 ( 18.158 )
    -8.04 ( 17.554 )
        At Week 7 (n =3, 29, 32)
    -9.57 ( 16.297 )
    -7.16 ( 16.637 )
    -7.39 ( 16.360 )
        At Week 9 (n=3,29,32)
    -17.43 ( 11.285 )
    -2.95 ( 16.995 )
    -4.31 ( 16.955 )
        At Week 11 (n =3, 29, 32)
    -26.56 ( 15.966 )
    -1.15 ( 16.235 )
    -3.54 ( 17.638 )
        At Week 13 (n =3, 29, 32)
    -10.32 ( 17.934 )
    -6.35 ( 16.837 )
    -6.72 ( 16.679 )
        At Week 15 (n =3, 27, 30)
    -17.81 ( 13.377 )
    -5.40 ( 21.168 )
    -6.64 ( 20.698 )
        At Week 17 (n =3, 29, 32)
    -9.36 ( 20.529 )
    -4.59 ( 20.631 )
    -5.04 ( 20.338 )
        At Week 21 (n =2, 24, 26)
    -19.07 ( 8.695 )
    -9.98 ( 22.994 )
    -10.68 ( 22.261 )
        At Week 25 (n =2, 24, 26)
    -13.28 ( 12.010 )
    -6.58 ( 16.164 )
    -7.10 ( 15.794 )
        At Week 27 (n =2, 24, 26)
    -6.20 ( 10.803 )
    -7.16 ( 20.100 )
    -7.09 ( 19.402 )
        At Week 29 (n =2, 23, 25)
    -10.55 ( 14.242 )
    -7.92 ( 18.173 )
    -8.13 ( 17.656 )
        At Week 33 (n =2, 23, 25)
    -8.10 ( 13.484 )
    -10.10 ( 16.351 )
    -9.94 ( 15.905 )
        At Week 37 (n =2, 23, 25)
    -6.25 ( 27.791 )
    -4.29 ( 25.161 )
    -4.45 ( 24.755 )
        At Week 41 (n =2, 23, 25)
    -8.89 ( 19.345 )
    -9.01 ( 23.250 )
    -9.00 ( 22.608 )
        At Week 45 (n =2, 21, 23)
    -3.24 ( 29.617 )
    -8.26 ( 23.791 )
    -7.82 ( 23.590 )
        At Week 49 (n =2, 19, 21)
    -10.12 ( 11.603 )
    -12.83 ( 22.932 )
    -12.57 ( 21.924 )
        At Week 53 (n =2, 18, 20)
    -6.37 ( 23.892 )
    -14.81 ( 19.811 )
    -13.97 ( 19.697 )
        At Week 57 (n =2, 17, 19)
    -10.11 ( 8.205 )
    -10.50 ( 19.795 )
    -10.46 ( 18.763 )
        At Week 61 (n =2, 15, 17)
    -11.72 ( 26.723 )
    -18.94 ( 25.675 )
    -18.09 ( 25.044 )
        At Week 65 (n =1, 11, 12)
    35.41 ( 99999 )
    -21.36 ( 25.392 )
    -16.63 ( 29.235 )
        At Week 69 (n =1, 8, 9)
    -10.53 ( 99999 )
    -23.32 ( 14.391 )
    -21.89 ( 14.120 )
        At Week 73 (n =1, 7, 8)
    -0.48 ( 99999 )
    -22.62 ( 20.556 )
    -19.85 ( 20.578 )
    Notes
    [4] - The standard deviation was not estimable for a single participant.
    [5] - The standard deviation was not estimable for a single participant.
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Day 1 up to the end of study follow-up (up to 121 week)
    Adverse event reporting additional description
    All participants who were randomized and received at least 1 dose of GHR-LRX. Data for all-cause mortality, serious and non-serious adverse events is reported as per the maximum dose received by participants per arm considering dose escalation was allowed in this study.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    GHR-LRX 120 mg
    Reporting group description
    		 Participants received GHR-LRX 120 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3)

    Reporting group title
    GHR-LRX 160 mg
    Reporting group description
    		 Participants received GHR-LRX 160 mg SC injection once every month for 73 weeks with a booster dose administered on Day 15 (Week 3)

    Reporting group title
    GHR-LRX Total (Per Protocol Set)
    Reporting group description
    		 Overall number of participants analyzed is the number of participants available for analyses. Total of all participants in the Per Protocol Set (received maximum doses of 120 mg or 160 mg doses).

    Serious adverse events
    		 GHR-LRX 120 mg GHR-LRX 160 mg GHR-LRX Total (Per Protocol Set)
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 31 (6.45%)
    3 / 34 (8.82%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Cardiac disorders
    Atrioventricular block second degree
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 31 (3.23%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholecystitis chronic
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    COVID-19 pneumonia
         subjects affected / exposed
    0 / 3 (0.00%)
    1 / 31 (3.23%)
    1 / 34 (2.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 GHR-LRX 120 mg GHR-LRX 160 mg GHR-LRX Total (Per Protocol Set)
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    3 / 3 (100.00%)
    26 / 31 (83.87%)
    29 / 34 (85.29%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    0 / 3 (0.00%)
    5 / 31 (16.13%)
    5 / 34 (14.71%)
         occurrences all number
    0
    7
    7
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    1 / 3 (33.33%)
    4 / 31 (12.90%)
    5 / 34 (14.71%)
         occurrences all number
    1
    4
    5
    Respiratory, thoracic and mediastinal disorders
    Pulmonary fibrosis
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    1
    Cough
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Psychiatric disorders
    Insomnia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Investigations
    Blood creatine phosphokinase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 31 (9.68%)
    3 / 34 (8.82%)
         occurrences all number
    0
    5
    5
    Weight increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Urine albumin/creatinine ratio increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Lipase increased
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Injury, poisoning and procedural complications
    Post procedural hypothyroidism
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    1
    Cardiac disorders
    Sinus bradycardia
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 31 (9.68%)
    3 / 34 (8.82%)
         occurrences all number
    0
    11
    11
    Nervous system disorders
    Paraesthesia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    5
    5
    Dysgeusia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    4
    4
    Dizziness
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 31 (9.68%)
    3 / 34 (8.82%)
         occurrences all number
    0
    3
    3
    Headache
         subjects affected / exposed
    0 / 3 (0.00%)
    11 / 31 (35.48%)
    11 / 34 (32.35%)
         occurrences all number
    0
    20
    20
    Tremor
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    1
    Blood and lymphatic system disorders
    Anaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 31 (6.45%)
    3 / 34 (8.82%)
         occurrences all number
    1
    2
    3
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    3
    3
    Eye disorders
    Vision blurred
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    1 / 3 (33.33%)
    4 / 31 (12.90%)
    5 / 34 (14.71%)
         occurrences all number
    1
    7
    8
    Dyspepsia
         subjects affected / exposed
    0 / 3 (0.00%)
    4 / 31 (12.90%)
    4 / 34 (11.76%)
         occurrences all number
    0
    5
    5
    Haemorrhoids
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 31 (3.23%)
    2 / 34 (5.88%)
         occurrences all number
    1
    1
    2
    Flatulence
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 31 (3.23%)
    2 / 34 (5.88%)
         occurrences all number
    1
    1
    2
    Haematochezia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Diverticulum intestinal
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Abdominal pain
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Diarrhoea
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 31 (9.68%)
    3 / 34 (8.82%)
         occurrences all number
    0
    11
    11
    Hepatobiliary disorders
    Hepatic steatosis
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    1
    Hepatic cyst
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    4
    4
    Hyperhidrosis
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Dermal cyst
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    1
    Rosacea
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    1
    Renal and urinary disorders
    Renal cyst
         subjects affected / exposed
    2 / 3 (66.67%)
    0 / 31 (0.00%)
    2 / 34 (5.88%)
         occurrences all number
    2
    0
    2
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    1
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    1
    Back pain
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Myalgia
         subjects affected / exposed
    1 / 3 (33.33%)
    2 / 31 (6.45%)
    3 / 34 (8.82%)
         occurrences all number
    1
    2
    3
    Arthralgia
         subjects affected / exposed
    1 / 3 (33.33%)
    3 / 31 (9.68%)
    4 / 34 (11.76%)
         occurrences all number
    1
    9
    10
    Infections and infestations
    Rhinitis
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Pyelonephritis chronic
         subjects affected / exposed
    1 / 3 (33.33%)
    0 / 31 (0.00%)
    1 / 34 (2.94%)
         occurrences all number
    1
    0
    1
    Upper respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    3
    3
    COVID-19
         subjects affected / exposed
    1 / 3 (33.33%)
    6 / 31 (19.35%)
    7 / 34 (20.59%)
         occurrences all number
    1
    6
    7
    Respiratory tract infection viral
         subjects affected / exposed
    1 / 3 (33.33%)
    3 / 31 (9.68%)
    4 / 34 (11.76%)
         occurrences all number
    1
    3
    4
    Urinary tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    4 / 31 (12.90%)
    4 / 34 (11.76%)
         occurrences all number
    0
    4
    4
    Nasopharyngitis
         subjects affected / exposed
    0 / 3 (0.00%)
    3 / 31 (9.68%)
    3 / 34 (8.82%)
         occurrences all number
    0
    4
    4
    Asymptomatic COVID-19
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Respiratory tract infection
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Metabolism and nutrition disorders
    Dyslipidaemia
         subjects affected / exposed
    0 / 3 (0.00%)
    2 / 31 (6.45%)
    2 / 34 (5.88%)
         occurrences all number
    0
    2
    2
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 3 (33.33%)
    1 / 31 (3.23%)
    2 / 34 (5.88%)
         occurrences all number
    2
    1
    3

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    07 Jul 2021
    1. Revised inclusion and exclusion criteria. 2. Revised the platelet count criterion from lower limit of normal (LLN) to < 125,000 cubic millimeters (mm^3).
    31 Jul 2021
    1) Updated patient eligibility criteria. 2) Updated ability to conduct home health care visits and patient contact. 3) Updated the Clinical Experience and Rationale for Dose and Schedule sections of the protocol with information from ongoing Phase 2 studies.
    12 Dec 2021
    1. Updated the subject randomization. 2. Clarified enrollment of treatment dose groups.

    Interruptions (globally)
    Were there any global interruptions to the trial? Yes
    Date
    Interruption
    Restart date
    04 May 2023
    The study was terminated early due to the Sponsor's decision. The amount of safety data accumulated on ISIS 766720 after all participants had completed 1 year of treatment was adequate and ended the study.
    -

    Limitations and caveats
    Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data.
    The study is terminated early due to the Sponsor's decision. The amount of safety data accumulated on ISIS 766720 after all participants had completed 1 year of treatment was adequate and ended the study.
    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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