Flag of the European Union EU Clinical Trials Register Help

Clinical trials

The European Union Clinical Trials Register   allows you to search for protocol and results information on:
  • interventional clinical trials that were approved in the European Union (EU)/European Economic Area (EEA) under the Clinical Trials Directive 2001/20/EC
  • clinical trials conducted outside the EU/EEA that are linked to European paediatric-medicine development

    • EU/EEA interventional clinical trials approved under or transitioned to the Clinical Trial Regulation 536/2014 are publicly accessible through the
    Clinical Trials Information System (CTIS).

    The EU Clinical Trials Register currently displays   44334   clinical trials with a EudraCT protocol, of which   7366   are clinical trials conducted with subjects less than 18 years old.   The register also displays information on   18700   older paediatric trials (in scope of Article 45 of the Paediatric Regulation (EC) No 1901/2006).

    Phase 1 trials conducted solely on adults and that are not part of an agreed paediatric investigation plan (PIP) are not publicly available (see Frequently Asked Questions ).  
     
    Examples: Cancer AND drug name. Pneumonia AND sponsor name.
    How to search [pdf]
    Search Tips: Under advanced search you can use filters for Country, Age Group, Gender, Trial Phase, Trial Status, Date Range, Rare Diseases and Orphan Designation. For these items you should use the filters and not add them to your search terms in the text field.
    Advanced Search: Search tools
     

    < Back to search results

    Download PDF

    Clinical Trial Results:
    ILLUMINATE-A: A Phase 3 Randomized, Double-Blind, Placebo-Controlled Study with an Extended Dosing Period to Evaluate the Efficacy and Safety of Lumasiran in Children and Adults with Primary Hyperoxaluria Type 1

    Summary
    EudraCT number
    		 2018-001981-40
    Trial protocol
    		 GB   FR   DE   NL  
    Global end of trial date
    12 Jan 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    28 Jul 2024
    First version publication date
    28 Jul 2024
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    ALN-GO1-003
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03681184
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Alnylam Pharmaceuticals, Inc.
    Sponsor organisation address
    300 Third Street, Cambridge, United States, 02142
    Public contact
    Clinical Trial Information Line, Alnylam Pharmaceuticals, Inc., 001 877256 9526, clinicaltrials@alnylam.com
    Scientific contact
    Clinical Trial Information Line, Alnylam Pharmaceuticals, Inc., 001 877256 9526, clinicaltrials@alnylam.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002079-PIP01-16
    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
    12 Jan 2024
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    12 Jan 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The purpose of this study was to evaluate the efficacy and safety of lumasiran in children and adults with primary hyperoxaluria type 1 (PH1).
    Protection of trial subjects
    All subjects in this study were required to read and sign an Informed Consent Form (ICF).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    27 Nov 2018
    Long term follow-up planned
    Yes
    Long term follow-up rationale
    		 Safety
    Long term follow-up duration
    		 12 Months
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 5
    Country: Number of subjects enrolled
    United Kingdom: 7
    Country: Number of subjects enrolled
    France: 4
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Israel: 7
    Country: Number of subjects enrolled
    Switzerland: 1
    Country: Number of subjects enrolled
    United Arab Emirates: 1
    Country: Number of subjects enrolled
    United States: 13
    Worldwide total number of subjects
    39
    EEA total number of subjects
    10
    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)
    16
    Adolescents (12-17 years)
    6
    Adults (18-64 years)
    17
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

    		 Close Top of page
    Recruitment
    Recruitment details
    		 Subjects with PH1 were enrolled at sixteen sites in France, Germany, Israel, the Netherlands, Switzerland, the United Arab Emirates, the United Kingdom and the United States.

    Pre-assignment
    Screening details
    		 Subjects were treated with placebo or lumasiran during the 6-month Double-Blind Period. All subjects received lumasiran during the 3-Month Blinded Treatment Extension Period and 51-Month Open-Label Extension Period.

    Period 1
    Period 1 title
    6-Month Double-Blind Period
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo/Lumasiran
    Arm description
    		 Lumasiran-matching placebo (normal saline [0.9% NaCl]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Lumasiran-matching placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Placebo by SC injection

    Arm title
    		 Lumasiran/Lumasiran
    Arm description
    		 Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lumasiran
    Investigational medicinal product code
    Other name
    ALN-GO1
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Lumasiran by SC injection

    Number of subjects in period 1
    		Placebo/Lumasiran Lumasiran/Lumasiran
    Started
    13
    26
    Completed
    13
    25
    Not completed
    0
    1
         Parent/Caregiver Withdrew Consent
    -
    1
    Period 2
    Period 2 title
    3-Month Blinded Extension Period
    Is this the baseline period?
    		 No
    Allocation method
    Randomised - controlled
    Blinding used
    		 Single blind
    Roles blinded
    		 Subject

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo/Lumasiran
    Arm description
    		 Lumasiran-matching placebo (normal saline [0.9% NaCl]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) peri od.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Lumasiran
    Investigational medicinal product code
    Other name
    ALN-GO1
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Lumasiran by SC injection

    Arm title
    		 Lumasiran/Lumasiran
    Arm description
    		 Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lumasiran
    Investigational medicinal product code
    Other name
    ALN-GO1
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Lumasiran by SC injection

    Number of subjects in period 2 [1]
    		Placebo/Lumasiran Lumasiran/Lumasiran
    Started
    13
    24
    Completed
    13
    24
    Notes
    [1] - The number of subjects starting the period is not consistent with the number completing the preceding period. It is expected the number of subjects starting the subsequent period will be the same as the number completing the preceding period.
    Justification: 1 subject discontinued study drug and entered safety follow up after the DB period.
    Period 3
    Period 3 title
    Open-Label Extension Period
    Is this the baseline period?
    		 No
    Allocation method
    Not applicable
    Blinding used
    		 Not blinded

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo/Lumasiran
    Arm description
    		 Lumasiran-matching placebo (normal saline [0.9% NaCl]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) peri od.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Lumasiran
    Investigational medicinal product code
    Other name
    ALN-GO1
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Lumasiran by SC injection

    Arm title
    		 Lumasiran/Lumasiran
    Arm description
    		 Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lumasiran
    Investigational medicinal product code
    Other name
    ALN-GO1
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Lumasiran by SC injection

    Number of subjects in period 3
    		Placebo/Lumasiran Lumasiran/Lumasiran
    Started
    13
    24
    Completed
    13
    24

    Baseline characteristics

    		 Close Top of page
    Baseline characteristics reporting groups
    Reporting group title
    Placebo/Lumasiran
    Reporting group description
    		 Lumasiran-matching placebo (normal saline [0.9% NaCl]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period.

    Reporting group title
    Lumasiran/Lumasiran
    Reporting group description
    		 Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.

    Reporting group values
    		 Placebo/Lumasiran Lumasiran/Lumasiran Total
    Number of subjects
    		 13 26 39
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 17.0 ( 15.19 ) 18.7 ( 11.52 ) -
    Gender categorical
    Units: Subjects
        Female
    		 5 8 13
        Male
    		 8 18 26
    24-Hour Urinary Oxalate Excretion Corrected for BSA
    Units: mmol/24hr/1.73m^2
        arithmetic mean (standard deviation)
    		 1.7994 ( 0.6836 ) 1.836 ( 0.5966 ) -
    Estimated Glomerular Filtration Rate (eGFR)
    Units: mL/min/1.73m^2
        arithmetic mean (standard deviation)
    		 78.834 ( 29.9841 ) 82.967 ( 25.5499 ) -
    24-hour Urinary Oxalate:Creatinine Ratio
    Units: mmol/mmol
        arithmetic mean (standard deviation)
    		 0.231 ( 0.1306 ) 0.209 ( 0.1012 ) -

    End points

    		 Close Top of page
    End points reporting groups
    Reporting group title
    Placebo/Lumasiran
    Reporting group description
    		 Lumasiran-matching placebo (normal saline [0.9% NaCl]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) period.

    Reporting group title
    Lumasiran/Lumasiran
    Reporting group description
    		 Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
    Reporting group title
    Placebo/Lumasiran
    Reporting group description
    		 Lumasiran-matching placebo (normal saline [0.9% NaCl]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) peri od.

    Reporting group title
    Lumasiran/Lumasiran
    Reporting group description
    		 Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.
    Reporting group title
    Placebo/Lumasiran
    Reporting group description
    		 Lumasiran-matching placebo (normal saline [0.9% NaCl]) was administered subcutaneously (SC) at Day 1 and Months 1, 2 and 3 during the 6-Month Double-blind (DB) Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month Open-label Extension (OLE) peri od.

    Reporting group title
    Lumasiran/Lumasiran
    Reporting group description
    		 Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.

    Subject analysis set title
    DB Period: Placebo
    Subject analysis set type
    		 Safety analysis
    Subject analysis set description
    Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period.

    Primary: Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6

    		 Close Top of page
    End point title
    		 Percent Change in 24-hour Urinary Oxalate Excretion Corrected for Body Surface Area (BSA) From Baseline to Month 6
    End point description
    Percent change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average percent change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome. Full Analysis Set (FAS): All randomized subjects who received any amount of study drug.
    End point type
    Primary
    End point timeframe
    Baseline to Month 6
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    13
    26
    Units: percent change
        least squares mean (standard error)
    -11.8 ( 3.8 )
    -65.4 ( 2.9 )
    Statistical analysis title
    		 Percent Change in 24-hour urinary oxalate
    Comparison groups
    Placebo/Lumasiran v Lumasiran/Lumasiran
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 < 0.0001 [2]
    Method
    		 [MMRM]
    Parameter type
    		 Difference in Least Squares (LS) Mean
    Point estimate
    -53.546
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -62.314
         upper limit
    		 -44.778
    Variability estimate
    Standard error of the mean
    Dispersion value
    4.3224
    Notes
    [1] - The Mixed-Effect Model Repeated Measures (MMRM) includes fixed effects of treatment arms (lumasiran vs. placebo) and scheduled visits (months 3, 4, 5, and 6), baseline 24-hour urinary oxalate corrected for BSA as a continuous fixed covariate, and subject as a random effect. The variance-covariance matrix is assumed to be unstructured. Satterthwaite approximation is used to estimate denominator degrees of freedom.
    [2] - P=1.685E-14

    Secondary: Absolute Change in 24-hour Urinary Oxalate Corrected for BSA From Baseline to Month 6

    		 Close Top of page
    End point title
    		 Absolute Change in 24-hour Urinary Oxalate Corrected for BSA From Baseline to Month 6
    End point description
    Absolute change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average absolute change from baseline across Months 3 through 6. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome. FAS includes all randomized subjects who received any amount of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline to Month 6
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    13
    26
    Units: mmol/24hr/1.73m^2
        least squares mean (standard error)
    -0.27 ( 0.08 )
    -1.24 ( 0.06 )
    Statistical analysis title
    		 Absolute Change in 24-hour Urinary Oxalate
    Comparison groups
    Placebo/Lumasiran v Lumasiran/Lumasiran
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [3]
    P-value
    		 < 0.0001 [4]
    Method
    		 [MMRM]
    Parameter type
    		 Difference in Least Squares (LS) Mean
    Point estimate
    -0.975
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.177
         upper limit
    		 -0.772
    Variability estimate
    Standard error of the mean
    Dispersion value
    0.0998
    Notes
    [3] - The MMRM includes fixed effects of treatment arms (lumasiran vs. placebo) and scheduled visits (months 3, 4, 5, and 6), baseline 24-hour urinary oxalate corrected for BSA as a continuous fixed covariate, and subject as a random effect. The variance-covariance matrix is assumed to be unstructured. Satterthwaite approximation is used to estimate denominator degrees of freedom.
    [4] - P=1.225E-11

    Secondary: Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6

    		 Close Top of page
    End point title
    		 Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
    End point description
    Percent change in 24-hour urinary oxalate:creatinine ratio was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. FAS: All randomized subjects who received any amount of study drug.
    End point type
    Secondary
    End point timeframe
    Baseline to Month 6
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    13
    26
    Units: percent change
        least squares mean (standard error)
    -10.8 ( 5.4 )
    -62.5 ( 4.0 )
    Statistical analysis title
    		 Percent Change
    Statistical analysis description
    Percent Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline to Month 6
    Comparison groups
    Placebo/Lumasiran v Lumasiran/Lumasiran
    Number of subjects included in analysis
    39
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [5]
    P-value
    		 < 0.0001 [6]
    Method
    		 [MMRM]
    Parameter type
    		 Difference in Least Squares (LS) Mean
    Point estimate
    -51.7718
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -64.2653
         upper limit
    		 -39.2784
    Variability estimate
    Standard error of the mean
    Dispersion value
    6.16118
    Notes
    [5] - The MMRM includes fixed effects of treatment arms (lumasiran vs. placebo) and scheduled visits (months 3, 4, 5, and 6), baseline 24-hour urinary oxalate:creatinine ratio as a continuous fixed covariate, and subject as a random effect. The variance-covariance matrix is assumed to be unstructured. Satterthwaite approximation is used to estimate denominator degrees of freedom.
    [6] - P=5.032E-10

    Secondary: Percentage of Subjects With 24-hour Urinary Oxalate Level Corrected for BSA at or Below 1.5 x ULN at Month 6

    		 Close Top of page
    End point title
    		 Percentage of Subjects With 24-hour Urinary Oxalate Level Corrected for BSA at or Below 1.5 x ULN at Month 6
    End point description
    The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m^2 for 24-hour urinary oxalate excretion corrected for BSA. Subjects from the FAS (all randomized subjects who received any amount of study drug) for whom data are available. Number analysed is the number of subjects with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    13
    25
    Units: percentage of subjects
        number (not applicable)
    0
    84.0
    Statistical analysis title
    		 Percentage of Subjects
    Statistical analysis description
    The proportion of subjects (lumasiran vs. placebo) with 24-hour urinary oxalate ≤1.5 x ULN at Month 6 is analyzed using the Cochran–Mantel–Haenszel test, stratified by baseline 24-hour urinary oxalate corrected for BSA (≤1.70 mmol/24hr/1.73m^2 vs. >1.70 mmol/24hr/1.73m^2). The difference in proportion (lumasiran vs. placebo) and the corresponding 95% confidence interval are calculated using the Newcombe method, based on the Wilson score.
    Comparison groups
    Placebo/Lumasiran v Lumasiran/Lumasiran
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [7]
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Proportions
    Point estimate
    0.84
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.55
         upper limit
    		 0.94
    Notes
    [7] - P=8.341E-07

    Secondary: Percentage of Subjects With 24-hour Urinary Oxalate Level Corrected for BSA at or Below ULN at Month 6

    		 Close Top of page
    End point title
    		 Percentage of Subjects With 24-hour Urinary Oxalate Level Corrected for BSA at or Below ULN at Month 6
    End point description
    The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m^2 for 24-hour urinary oxalate excretion corrected for BSA. Subjects from the FAS (all randomized subjects who received any amount of study drug) for whom data are available. Number analysed is the number of subjects with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Month 6
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    13
    25
    Units: percentage of subjects
        number (not applicable)
    0
    52.0
    Statistical analysis title
    		 Percentage of Subjects
    Statistical analysis description
    The proportion of subjects (lumasiran vs. placebo) with 24-hour urinary oxalate ≤ULN at Month 6 is analyzed using the Cochran–Mantel–Haenszel test, stratified by baseline 24-hour urinary oxalate corrected for BSA (≤1.70 mmol/24hr/1.73m^2 vs. >1.70 mmol/24hr/1.73m^2). The difference in proportion (lumasiran vs. placebo) and the corresponding 95% confidence interval are calculated using the Newcombe method, based on the Wilson score.
    Comparison groups
    Placebo/Lumasiran v Lumasiran/Lumasiran
    Number of subjects included in analysis
    38
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.001
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Proportions
    Point estimate
    0.52
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 0.23
         upper limit
    		 0.7

    Secondary: Percentage Change in Plasma Oxalate From Baseline to Month 6

    		 Close Top of page
    End point title
    		 Percentage Change in Plasma Oxalate From Baseline to Month 6
    End point description
    Percent change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. Plasma Oxalate Analysis Set: all subjects who received any amount of study drug and had baseline plasma oxalate level >/=1.5 times lower limit of quantitation (LLOQ). LLOQ is 5.55 mcg/L. Number analysed is the number of subjects with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Baseline to Month 6
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    10
    23
    Units: percent change
        least squares mean (standard error)
    -0.3 ( 4.3 )
    -39.8 ( 2.9 )
    Statistical analysis title
    		 Percentage Change in Plasma Oxalate
    Statistical analysis description
    The MMRM includes fixed effects of treatment arms (lumasiran vs. placebo) and scheduled visits (months 3, 4, 5, and 6), baseline plasma oxalate as a continuous fixed covariate, and subject as a random effect. The variance-covariance matrix is assumed to be unstructured. Satterthwaite approximation is used to estimate denominator degrees of freedom.
    Comparison groups
    Placebo/Lumasiran v Lumasiran/Lumasiran
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 < 0.0001 [8]
    Method
    		 [MMRM]
    Parameter type
    		 Difference in Least Squares (LS) Mean
    Point estimate
    -39.48
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -50.1
         upper limit
    		 -28.87
    Variability estimate
    Standard error of the mean
    Dispersion value
    5.181
    Notes
    [8] - P=2.862E-08

    Secondary: Absolute Change in Plasma Oxalate From Baseline to Month 6

    		 Close Top of page
    End point title
    		 Absolute Change in Plasma Oxalate From Baseline to Month 6
    End point description
    Absolute change in plasma oxalate (umol/L) was estimated by an average percent change from baseline across Months 3 through 6. A negative change from Baseline indicates a favorable outcome. Plasma Oxalate Analysis Set: all subjects who received any amount of study drug and had baseline plasma oxalate level >/=1.5 times lower limit of quantitation (LLOQ). LLOQ is 5.55 mcg/L. Number analysed is the number of subjects with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Baseline to Month 6
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    10
    23
    Units: μmol/L
        least squares mean (standard error)
    1.3 ( 1.1 )
    -7.5 ( 0.8 )
    Statistical analysis title
    		 Absolute Change in Plasma Oxalate
    Comparison groups
    Placebo/Lumasiran v Lumasiran/Lumasiran
    Number of subjects included in analysis
    33
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [9]
    P-value
    		 < 0.0001 [10]
    Method
    		 [MMRM]
    Parameter type
    		 Difference in Least Squares (LS) Mean
    Point estimate
    -8.71
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -11.45
         upper limit
    		 -5.98
    Variability estimate
    Standard error of the mean
    Dispersion value
    1.338
    Notes
    [9] - The MMRM includes fixed effects of treatment arms (lumasiran vs. placebo) and scheduled visits (months 3, 4, 5, and 6), baseline plasma oxalate as a continuous fixed covariate, and subject as a random effect. The variance-covariance matrix is assumed to be unstructured. Satterthwaite approximation is used to estimate denominator degrees of freedom.
    [10] - P=3.893E-07

    Secondary: Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6

    		 Close Top of page
    End point title
    		 Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline to Week 2 and Months 1, 2, 3, 4, 5 and 6
    End point description
    eGFR is calculated from serum creatinine based on the Modification of Diet in Renal Disease formula for patients ≥18 years of age and the Schwartz Bedside Formula for patients >1 year to <18 years of age at screening. Change from baseline to Month 6 is reported. Subjects from the FAS (all randomized subjects who received any amount of study drug) for whom data are available. Number analysed is the number of subjects with data available for analysis.
    End point type
    Secondary
    End point timeframe
    Baseline, Week 2, Months 1, 2, 3, 4, 5 and 6
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    13
    25
    Units: mL/min/1.73m^2
    arithmetic mean (standard deviation)
        Week 2 (n= 13, 24)
    -5 ( 9 )
    -4 ( 9 )
        Month 1 (n= 12, 25)
    -6 ( 7 )
    -2 ( 12 )
        Month 2 (n= 13, 25)
    -5 ( 8 )
    -2 ( 15 )
        Month 3 (n= 13, 25)
    -3 ( 6 )
    0 ( 11 )
        Month 4 (n= 12, 25)
    -4 ( 8 )
    -4 ( 10 )
        Month 5 (n= 13, 25)
    -4 ( 7 )
    -6 ( 13 )
        Month 6 (n= 13, 25)
    0 ( 6 )
    -3 ( 11 )
    No statistical analyses for this end point

    Secondary: Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for BSA From Baseline in the Extension Period

    		 Close Top of page
    End point title
    		 Absolute Change in 24-hour Urinary Oxalate Excretion Corrected for BSA From Baseline in the Extension Period
    End point description
    Absolute change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average absolute change from baseline in the extension periods. Only valid urine samples without any non-protocol-related issues were included in the analysis. A negative change from Baseline indicates a favorable outcome. All Lumasiran Treated Set: All subjects who received any amount of lumasiran including subjects who took lumasiran during the 6-month double-blinded period and subjects who initially took placebo during the 6-month double-blinded period and then switched to lumasiran during the extension period. 999 indicates that data was not evaluable at given time point. Number analysed is the number of subjects with data available for analysis.
    End point type
    Secondary
    End point timeframe
    From Baseline to Month 54 and Month 60
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    6
    23
    Units: mmol/24hr/1.73m^2
    arithmetic mean (standard deviation)
        At Month 54 (n= 6, 23)
    -0.951 ( 0.6148 )
    -1.086 ( 0.7678 )
        At Month 60 (n= 0, 19)
    9999 ( 9999 )
    -1.129 ( 0.7581 )
    No statistical analyses for this end point

    Secondary: Percentage Change in 24-hour Urinary Oxalate Excretion Corrected by BSA From Baseline in the Extension Period

    		 Close Top of page
    End point title
    		 Percentage Change in 24-hour Urinary Oxalate Excretion Corrected by BSA From Baseline in the Extension Period
    End point description
    Percent change in 24-hour urinary oxalate excretion corrected for BSA was estimated by an average percent change from baseline in the extension periods. Only valid urine samples without any non-protocol-related issues were included in the analysis. All Lumasiran Treated Set: All subjects who received any amount of lumasiran including subjects who took lumasiran during the 6-month double-blinded period and subjects who initially took placebo during the 6-month double-blinded period and then switched to lumasiran during the extension period. A negative change from Baseline indicates a favorable outcome. 999 indicates that data was not evaluable at given time point. Number analysed is the number of subjects with data available for analysis.
    End point type
    Secondary
    End point timeframe
    From Baseline to Month 54 and Month 60
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    6
    23
    Units: percent change
    arithmetic mean (standard deviation)
        At Month 54 (n= 6, 23)
    -55.57 ( 11.903 )
    -53.87 ( 41.919 )
        At Month 60 (n= 0, 19)
    9999 ( 9999 )
    -53.98 ( 28.476 )
    No statistical analyses for this end point

    Secondary: Percentage of Time That 24-hour Urinary Oxalate is at or Below 1.5 × ULN During Lumasiran Treatment

    		 Close Top of page
    End point title
    		 Percentage of Time That 24-hour Urinary Oxalate is at or Below 1.5 × ULN During Lumasiran Treatment
    End point description
    The upper limit of normal (ULN) = 0.514 mmol/24hr/1.73m^2 for 24-hour urinary oxalate excretion corrected for BSA. All Lumasiran Treated Set: All subjects who received any amount of lumasiran including subjects who took lumasiran during the 6-month double-blinded period and subjects who initially took placebo during the 6-month double-blinded period and then switched to lumasiran during the extension period.
    End point type
    Secondary
    End point timeframe
    Up to Month 60
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    13
    26
    Units: percentage of time
        median (full range (min-max))
    89.44 (21.1 to 99.3)
    89.23 (1.7 to 98.6)
    No statistical analyses for this end point

    Secondary: Absolute Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline in the Extension Period

    		 Close Top of page
    End point title
    		 Absolute Change in 24-hour Urinary Oxalate:Creatinine Ratio From Baseline in the Extension Period
    End point description
    Absolute change in 24-hour urinary oxalate:creatine ratio was estimated by an average absolute change from baseline to the end of the OLE period at Month 54 and Month 60. A negative change from Baseline indicates a favorable outcome. All Lumasiran Treated Set: All subjects who received any amount of lumasiran including subjects who took lumasiran during the 6-month double-blinded period and subjects who initially took placebo during the 6-month double-blinded period and then switched to lumasiran during the extension period. 999 indicates that data was not evaluable at given time point. Number analysed is the number of subjects with data available for analysis.
    End point type
    Secondary
    End point timeframe
    From Baseline to Month 54 and Month 60
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    6
    24
    Units: mmol/mmol
    arithmetic mean (standard deviation)
        At Month 54 (n=6, 24)
    -0.145 ( 0.1242 )
    -0.127 ( 0.1063 )
        At Month 60 (n=0, 19)
    9999 ( 9999 )
    -0.138 ( 0.1162 )
    No statistical analyses for this end point

    Secondary: Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline in the Extension Period

    		 Close Top of page
    End point title
    		 Change in Estimated Glomerular Filtration Rate (eGFR) From Baseline in the Extension Period
    End point description
    eGFR is calculated from serum creatinine based on the Modification of Diet in Renal Disease formula for patients ≥18 years of age and the Schwartz Bedside Formula for patients >1 year to <18 years of age at screening. All Lumasiran Treated Set: All subjects who received any amount of lumasiran including subjects who took lumasiran during the 6-month double-blinded period and subjects who initially took placebo during the 6-month double-blinded period and then switched to lumasiran during the extension period. 999 indicates that data was not evaluable at given time point. Number analysed is the number of subjects with data available for analysis.
    End point type
    Secondary
    End point timeframe
    From Baseline to Month 54 and Month 60
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    6
    23
    Units: mL/min/1.73m^2
    arithmetic mean (standard deviation)
        At Month 54 (n= 6,23)
    -12.860 ( 9.5386 )
    -6.899 ( 12.9302 )
        At Month 60 (n= 0, 18)
    9999 ( 9999 )
    -2.892 ( 11.6544 )
    No statistical analyses for this end point

    Secondary: Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

    		 Close Top of page
    End point title
    		 Number of Subjects With Treatment Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
    End point description
    AE is any untoward medical occurrence in clinical investigational subject administered a medicinal product & which does not necessarily have a causal relationship with this treatment. SAE is any untoward medical occurrence that at any dose results in death, is life-threatening, requires in-patient hospitalization/prolongs existing hospitalization, results in persistent/significant disability/incapacity, is congenital anomaly/birth defect, is an important medical event that may not be immediately life-threatening or result in death/hospitalization but may jeopardize subject & may require intervention to prevent one of the outcomes listed above. Per the SAP, long-term safety of lumasiran was summarized by sequence (placebo/lumasiran & lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. Lumasiran/Lumasiran: lumasiran administered in both DB & Extension Period (EP) hence, safety data is reported together for DB & EP.
    End point type
    Secondary
    End point timeframe
    DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60).
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran DB Period: Placebo
    Number of subjects analysed
    13
    26
    13
    Units: subjects
    number (not applicable)
        Adverse Event (AE)
    12
    25
    9
        Serious Adverse Event (SAE)
    1
    5
    0
    No statistical analyses for this end point

    Other pre-specified: Rate of Renal Stone Events

    		 Close Top of page
    End point title
    		 Rate of Renal Stone Events
    End point description
    A renal stone event is defined as a subject-reported event that includes ≥1 of the following: visit to healthcare provider because of a renal stone; medication for renal colic; stone passage; macroscopic hematuria due to a renal stone. Lower rates indicate a favorable outcome. FAS: All randomized subjects who received any amount of study drug.
    End point type
    Other pre-specified
    End point timeframe
    12-Month Period prior to Informed Consent, 6-Month DB Period
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    13
    26
    Units: rate per person-year
    number (confidence interval 95%)
        12-Month Period prior to Informed Consent
    0.54 (0.26 to 1.13)
    3.19 (2.57 to 3.96)
        6-Month DB Period
    0.66 (0.25 to 1.76)
    1.09 (0.63 to 1.87)
    No statistical analyses for this end point

    Other pre-specified: Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound

    		 Close Top of page
    End point title
    		 Change From Baseline in Nephrocalcinosis as Assessed by Renal Ultrasound
    End point description
    Renal ultrasound data were used to grade medullary nephrocalcinosis findings (range: 0 to 3), where a higher grade indicates greater severity. Improving=if both sides improve, or one side improves and the other side has no change; No change=if both sides have no change; Worsening=if both sides worsen, or one side worsens and the other side has no change; Indeterminate=if one side improves and the other side worsens. Subjects from the FAS (all randomized subjects who received any amount of study drug) with both Baseline and Month 6 renal ultrasounds.
    End point type
    Other pre-specified
    End point timeframe
    Baseline, Month 6
    End point values
    		 Placebo/Lumasiran Lumasiran/Lumasiran
    Number of subjects analysed
    12
    22
    Units: subjects
    number (not applicable)
        Improving
    0
    3
        No Change
    11
    19
        Worsening
    1
    0
        Indeterminate
    0
    0
    No statistical analyses for this end point

    Adverse events

    		 Close Top of page
    Adverse events information
    Timeframe for reporting adverse events
    DB Period (Placebo): From first dose of study drug (Day 1) up to Month 6; Placebo/Lumasiran: From first dose of lumasiran (Month 6) up to end of study (Month 60); Lumasiran/Lumasiran: From first dose of lumasiran (Day 1) up to end of study (Month 60).
    Adverse event reporting additional description
    Per the SAP, long-term safety of lumasiran was summarized by sequence (placebo/lumasiran & lumasiran/lumasiran) using the All Lumasiran Treated Set. In this set, data is presented during lumasiran treatment only. Lumasiran/Lumasiran: lumasiran administered in both DB & Extension Period (EP) hence, safety data is reported together for DB & EP.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Placebo/Lumasiran
    Reporting group description
    		 Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg, at Months 6, 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.

    Reporting group title
    Lumasiran/Lumasiran
    Reporting group description
    		 Lumasiran was administered SC, 3.0 mg/kg, at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period, followed by lumasiran SC, 3.0 mg/kg at Month 6, and lumasiran-matching placebo SC at Months 7 and 8 during the 3-Month Blinded Treatment Extension Period, followed by lumasiran SC, 3.0 mg/kg, at Month 9 and then every three months during the 51-Month OLE period.

    Reporting group title
    Placebo
    Reporting group description
    		 Lumasiran-matching placebo was administered SC at Day 1 and Months 1, 2 and 3 during the 6-Month DB Period.

    Serious adverse events
    		 Placebo/Lumasiran Lumasiran/Lumasiran Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 13 (7.69%)
    5 / 26 (19.23%)
    0 / 13 (0.00%)
         number of deaths (all causes)
    0
    0
    0
         number of deaths resulting from adverse events
    0
    0
    0
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Follicular lymphoma
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Post procedural complication
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Abdominal pain
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 2
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal impairment
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Post procedural infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Urosepsis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 0%
    Non-serious adverse events
    		 Placebo/Lumasiran Lumasiran/Lumasiran Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    12 / 13 (92.31%)
    25 / 26 (96.15%)
    9 / 13 (69.23%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    4
    0
    White coat hypertension
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Pregnancy, puerperium and perinatal conditions
    Post abortion haemorrhage
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    General disorders and administration site conditions
    Asthenia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Catheter site extravasation
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Chest pain
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Fatigue
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    0
    5
    0
    Influenza like illness
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Injection site discomfort
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    0
    5
    0
    Injection site erythema
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 26 (11.54%)
    0 / 13 (0.00%)
         occurrences all number
    1
    10
    0
    Injection site pain
         subjects affected / exposed
    1 / 13 (7.69%)
    4 / 26 (15.38%)
    0 / 13 (0.00%)
         occurrences all number
    17
    37
    0
    Injection site reaction
         subjects affected / exposed
    5 / 13 (38.46%)
    9 / 26 (34.62%)
    0 / 13 (0.00%)
         occurrences all number
    17
    17
    0
    Oedema peripheral
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Peripheral swelling
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Pyrexia
         subjects affected / exposed
    2 / 13 (15.38%)
    3 / 26 (11.54%)
    0 / 13 (0.00%)
         occurrences all number
    5
    5
    0
    Vaccination site pain
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 26 (11.54%)
    0 / 13 (0.00%)
         occurrences all number
    0
    4
    0
    Vaccination site swelling
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Immune system disorders
    Hypersensitivity
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Immunisation reaction
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    6
    0
    Milk allergy
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Reproductive system and breast disorders
    Ovarian cyst
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Priapism
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Testicular pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    2
    0
    Nasal congestion
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Oropharyngeal pain
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 26 (11.54%)
    1 / 13 (7.69%)
         occurrences all number
    2
    3
    1
    Productive cough
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Rhinorrhoea
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Psychiatric disorders
    Anxiety
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    5
    0
    Attention deficit hyperactivity disorder
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Enuresis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Fear of injection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Irritability
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Separation anxiety disorder
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Investigations
    Aspartate aminotransferase increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Blood creatinine increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Cardiac murmur
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Electrocardiogram ST segment depression
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Electrocardiogram T wave inversion
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Hepatic enzyme increased
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Protein urine present
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Weight decreased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Weight increased
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Injury, poisoning and procedural complications
    Corneal abrasion
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Foot fracture
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Hand fracture
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Ligament sprain
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Nail injury
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Post-traumatic pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Procedural pain
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    2
    0
    Skin abrasion
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Skin laceration
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Sunburn
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Tibia fracture
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Traumatic haematoma
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Contusion
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 26 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Gastrostomy tube site complication
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 26 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Pain in extremity
         subjects affected / exposed
    0 / 13 (0.00%)
    0 / 26 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    0
    1
    Congenital, familial and genetic disorders
    Thalassaemia beta
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Cardiac disorders
    Arrhythmia supraventricular
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Nervous system disorders
    Disturbance in attention
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    3
    0
    Dizziness
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    0
    7
    0
    Headache
         subjects affected / exposed
    2 / 13 (15.38%)
    5 / 26 (19.23%)
    3 / 13 (23.08%)
         occurrences all number
    2
    10
    3
    Hypoaesthesia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Migraine
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Presyncope
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Restless legs syndrome
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Blood and lymphatic system disorders
    Iron deficiency anaemia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Thrombocytopenia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Ear and labyrinth disorders
    Ear pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Eye disorders
    Blepharitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Dacryostenosis acquired
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Eye pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Vision blurred
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Gastrointestinal disorders
    Abdominal discomfort
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Abdominal pain
         subjects affected / exposed
    1 / 13 (7.69%)
    8 / 26 (30.77%)
    0 / 13 (0.00%)
         occurrences all number
    6
    14
    0
    Abdominal pain lower
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    2
    2
    0
    Abdominal pain upper
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    4
    2
    0
    Abdominal tenderness
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    3
    0
    Constipation
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    0
    3
    0
    Diarrhoea
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    0
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Gingival hypertrophy
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Haemorrhoidal haemorrhage
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Nausea
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    2
    8
    0
    Vomiting
         subjects affected / exposed
    2 / 13 (15.38%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    3
    2
    0
    Hepatobiliary disorders
    Hepatomegaly
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Skin and subcutaneous tissue disorders
    Actinic cheilitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Alopecia
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 26 (11.54%)
    0 / 13 (0.00%)
         occurrences all number
    1
    3
    0
    Dermatitis atopic
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Dry skin
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Eczema
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Erythema
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Livedo reticularis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Pruritus
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Rash
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Rash erythematous
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Skin hyperpigmentation
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Skin lesion
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Renal and urinary disorders
    Dysuria
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 26 (11.54%)
    0 / 13 (0.00%)
         occurrences all number
    11
    10
    0
    Haematuria
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Hypertonic bladder
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Hypocitraturia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Microalbuminuria
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Nephrolithiasis
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Polyuria
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Proteinuria
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Renal cyst
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Renal impairment
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Renal pain
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 26 (11.54%)
    0 / 13 (0.00%)
         occurrences all number
    3
    5
    0
    Urinary incontinence
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Back pain
         subjects affected / exposed
    1 / 13 (7.69%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    1
    5
    0
    Flank pain
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 26 (11.54%)
    1 / 13 (7.69%)
         occurrences all number
    1
    3
    1
    Groin pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Musculoskeletal chest pain
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Pain in extremity
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Infections and infestations
    Asymptomatic COVID-19
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Bronchitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    COVID-19
         subjects affected / exposed
    4 / 13 (30.77%)
    4 / 26 (15.38%)
    0 / 13 (0.00%)
         occurrences all number
    7
    4
    0
    Cellulitis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Ear infection
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Fungal foot infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Fungal skin infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Furuncle
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Gastroenteritis
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    2
    1
    0
    Gastroenteritis viral
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Hand-foot-and-mouth disease
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Herpes simplex reactivation
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Herpes zoster
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Infected bite
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Influenza
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    0
    Nasopharyngitis
         subjects affected / exposed
    2 / 13 (15.38%)
    4 / 26 (15.38%)
    0 / 13 (0.00%)
         occurrences all number
    2
    7
    0
    Onychomycosis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Otitis media acute
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    1
    Pharyngitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Pharyngitis streptococcal
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Pneumonia
         subjects affected / exposed
    0 / 13 (0.00%)
    2 / 26 (7.69%)
    0 / 13 (0.00%)
         occurrences all number
    0
    2
    0
    Pyelitis
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    3
    0
    Pyelonephritis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Pyelonephritis acute
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Rhinitis
         subjects affected / exposed
    3 / 13 (23.08%)
    2 / 26 (7.69%)
    2 / 13 (15.38%)
         occurrences all number
    5
    6
    2
    Tonsillitis
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Tooth infection
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    1
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 13 (7.69%)
    3 / 26 (11.54%)
    2 / 13 (15.38%)
         occurrences all number
    1
    3
    2
    Urinary tract infection
         subjects affected / exposed
    0 / 13 (0.00%)
    3 / 26 (11.54%)
    0 / 13 (0.00%)
         occurrences all number
    0
    5
    0
    Viral infection
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Viral sinusitis
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0
    Metabolism and nutrition disorders
    Acidosis
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Gout
         subjects affected / exposed
    1 / 13 (7.69%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    1
    1
    0
    Hypercholesterolaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Hyperkalaemia
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    0
    Iron deficiency
         subjects affected / exposed
    1 / 13 (7.69%)
    0 / 26 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    1
    0
    1
    Vitamin D deficiency
         subjects affected / exposed
    2 / 13 (15.38%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    2
    2
    0
    Weight gain poor
         subjects affected / exposed
    0 / 13 (0.00%)
    1 / 26 (3.85%)
    0 / 13 (0.00%)
         occurrences all number
    0
    1
    0

    More information

    		 Close Top of page

    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    23 Jul 2018
    1. The primary purpose for this protocol amendment was to provide additional clarification about the subject caregiver surveys specific to subjects under the legal age of consent, and to make corrections to the open-label extension period Schedule of Assessments. 2. The visit schedule for the 12-lead ECG and renal ultrasound assessments through Year 5 in the open-label extension period was corrected from annually to Month 36 and Month 48 in addition to the EOS visit at Month 60.
    19 Mar 2019
    The primary purpose of Amendment 2 was to broaden the subject population by allowing enrollment of subjects with a glomerular filtration rate ≥30 mL/min/1.73 m2 and to align clinical objectives and endpoints across the Phase 3 program.
    06 May 2020
    1. The primary purpose of this protocol amendment was to incorporate Urgent Safety Measures (USMs) to assure the safety of study subjects while minimizing risks to study integrity amid the coronavirus 2019 (COVID-19) pandemic. 2. This protocol amendment also incorporated the changes that are not related to USMs. After ongoing review and assessment of the safety data from studies conducted with lumasiran, modifications are designed to enhance subject safety and reduce subject burden regarding blood sampling.

    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
    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.

    European Medicines Agency © 1995-Sat May 03 23:31:49 CEST 2025 | Domenico Scarlattilaan 6, 1083 HS Amsterdam, The Netherlands
    EMA HMA