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    Clinical Trial Results:
    A Phase 2 Placebo-Controlled, Double-Blind, Multicenter Study to Evaluate the Efficacy, Safety, and Tolerability of DCR-PHXC Solution for Injection (Subcutaneous use) in Patients with Primary Hyperoxaluria

    Summary
    EudraCT number
    		 2018-003098-91
    Trial protocol
    		 FR   GB   DE   NL   ES   PL   IT   RO  
    Global end of trial date
    29 Jun 2021

    Results information
    Results version number
    		 v1(current)
    This version publication date
    15 Jul 2022
    First version publication date
    15 Jul 2022
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    DCR-PHXC-201
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03847909
    WHO universal trial number (UTN)
    		 U1111-1224-6881
    Sponsors
    Sponsor organisation name
    Dicerna Pharmaceuticals, Inc.
    Sponsor organisation address
    75 Hayden Avenue, Lexington, United States, MA 02421
    Public contact
    Sarb Shergill, Dicerna Pharmaceuticals INC., 001 617-621-8097, sshergill@dicerna.com
    Scientific contact
    Sarb Shergill , Dicerna Pharmaceuticals INC., 001 617-621-8097, sshergill@dicerna.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    Yes
    EMA paediatric investigation plan number(s)
    		 EMEA-002493-PIP01-18
    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
    29 Jun 2021
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    29 Jun 2021
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To assess the efficacy of DCR PHXC in reducing urinary oxalate burden in patients with primary hyperoxaluria (PH) (types 1 and 2)
    Protection of trial subjects
    This study was conducted in accordance with the protocol and with the following: Consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) International Ethical Guidelines, applicable ICH Good Clinical Practice (GCP) Guidelines and applicable laws and regulations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    01 Mar 2019
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    Yes
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 1
    Country: Number of subjects enrolled
    Spain: 5
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    France: 3
    Country: Number of subjects enrolled
    Germany: 2
    Country: Number of subjects enrolled
    Italy: 1
    Country: Number of subjects enrolled
    United States: 8
    Country: Number of subjects enrolled
    Canada: 2
    Country: Number of subjects enrolled
    Australia: 3
    Country: Number of subjects enrolled
    Japan: 2
    Country: Number of subjects enrolled
    Lebanon: 5
    Worldwide total number of subjects
    35
    EEA total number of subjects
    12
    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)
    5
    Adolescents (12-17 years)
    10
    Adults (18-64 years)
    20
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study was conducted at 19 sites in France, Spain, Italy, Netherlands, Germany, United Kingdom, Australia, United States, Canada, Lebanon, and Japan.

    Pre-assignment
    Screening details
    		 A total of 57 subjects were screened, of which 35 subjects were randomised: 23 to DCR-PHXC and 12 to placebo. All 35 randomised subjects received at least one dose of study drug.

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor
    Blinding implementation details
    Treatment assignment was blinded for the Investigators and any personnel (other than the unblinded pharmacist or designee) involved with the study conduct or evaluation at the investigational sites, the contract research organisation (CRO), and the Sponsor.

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 DCR-PHXC
    Arm description
    		 Subjects aged greater than or equal to (>=) 12 years weighing >=50 kilograms (kg) received nedosiran 170 milligram (mg) (160 milligrams per millilitre [mg/mL] free acid equivalent [FAE]); subjects >=12 year weighing less than (<) 50 kg received 136 mg (128 mg FAE); and subjects 6-11 years received 3.5 milligrams per kilogram (mg/kg) (3.3 mg/kg FAE) not exceeding 136 mg, subcutaneous (SC) injection into the abdomen or thigh on Days 1, 30, 60, 90, 120 and 150.
    Arm type
    		 Experimental

    Investigational medicinal product name
    DCR-PHXC
    Investigational medicinal product code
    Other name
    Nedosiran
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Nedosiran was administered as a SC injection into the abdomen or thigh at the following dose levels based on age and weight: 1) 170 mg (160 mg FAE) for >= 12 years and ≥ 50 kg: ; 2) 136 mg (128 mg FAE) for >= 12 years and weight < 50 kg: 3.5 mg/kg (3.3 mg/kg FAE), not to exceed 136 mg for 6-11 years. Subjects who began the study weighing less than 50 kg had their dose increased to the 170 mg dose when they reach the 50 kg threshold. Subjects receiving the 170 mg dose had not decreased their dose to the 136 mg dose if they fell below the 50 kg threshold. The total dose for 6 to 11 year-old subjects was based upon body weight recorded on study Day 1 and was constant throughout the study, regardless of any weight gain or loss or change in age.

    Arm title
    		 Placebo
    Arm description
    		 Subjects received the equivalent volume of nedosiran matching placebo SC injection into the abdomen or thigh on Days 1, 30, 60, 90, 120 and 150.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Subjects received nedosiran matching placebo (normal saline 0.9%) SC injection into the abdomen or thigh on Days 1, 30, 60, 90, 120 and 150.

    Number of subjects in period 1
    		DCR-PHXC Placebo
    Started
    23
    12
    Safety population
    23
    12
    Intent to treat (ITT) population
    23
    12
    Modified ITT (MITT) population
    22
    12
    Completed
    22
    11
    Not completed
    1
    1
         Consent withdrawn by subject
    1
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    DCR-PHXC
    Reporting group description
    		 Subjects aged greater than or equal to (>=) 12 years weighing >=50 kilograms (kg) received nedosiran 170 milligram (mg) (160 milligrams per millilitre [mg/mL] free acid equivalent [FAE]); subjects >=12 year weighing less than (<) 50 kg received 136 mg (128 mg FAE); and subjects 6-11 years received 3.5 milligrams per kilogram (mg/kg) (3.3 mg/kg FAE) not exceeding 136 mg, subcutaneous (SC) injection into the abdomen or thigh on Days 1, 30, 60, 90, 120 and 150.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received the equivalent volume of nedosiran matching placebo SC injection into the abdomen or thigh on Days 1, 30, 60, 90, 120 and 150.

    Reporting group values
    		 DCR-PHXC Placebo Total
    Number of subjects
    		 23 12 35
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0
        Newborns (0-27 days)
    		 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0
        Children (2-11 years)
    		 3 2 5
        Adolescents (12-17 years)
    		 6 4 10
        Adults (18-64 years)
    		 14 6 20
        From 65-84 years
    		 0 0 0
        85 years and over
    		 0 0 0
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 23.7 ( 11.95 ) 23.6 ( 11.48 ) -
    Gender categorical
    Units: Subjects
        Female
    		 12 6 18
        Male
    		 11 6 17

    End points

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    End points reporting groups
    Reporting group title
    DCR-PHXC
    Reporting group description
    		 Subjects aged greater than or equal to (>=) 12 years weighing >=50 kilograms (kg) received nedosiran 170 milligram (mg) (160 milligrams per millilitre [mg/mL] free acid equivalent [FAE]); subjects >=12 year weighing less than (<) 50 kg received 136 mg (128 mg FAE); and subjects 6-11 years received 3.5 milligrams per kilogram (mg/kg) (3.3 mg/kg FAE) not exceeding 136 mg, subcutaneous (SC) injection into the abdomen or thigh on Days 1, 30, 60, 90, 120 and 150.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received the equivalent volume of nedosiran matching placebo SC injection into the abdomen or thigh on Days 1, 30, 60, 90, 120 and 150.

    Subject analysis set title
    DCR-PHXC: Adults
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subject analysis set included all adult subjects (age >= 18 years) from DCR-PHXC arm who received 170 mg nedosiran.

    Subject analysis set title
    DCR-PHXC: Adolescents
    Subject analysis set type
    		 Sub-group analysis
    Subject analysis set description
    Subject analysis set included all adolescents (aged 12-17 years) from DCR-PHXC arm who received 170 mg nedosiran.

    Primary: Percentage of subjects with a reduction from baseline in 24-hour urinary oxalate excretion (Uox) of at least 70%, based on an area under the curve (AUC) and/or reaching normalization or near-normalization of 24-hour Uox on at least 2 consecutive visits

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    End point title
    		 Percentage of subjects with a reduction from baseline in 24-hour urinary oxalate excretion (Uox) of at least 70%, based on an area under the curve (AUC) and/or reaching normalization or near-normalization of 24-hour Uox on at least 2 consecutive visits
    End point description
    Percentage of subjects with a reduction from baseline in 24-hour Uox of at least 70%, based on an area under the curve (AUC) and/or reaching normalization or near-normalization of 24-hour Uox on at least 2 consecutive visits are presented. Normalization of Uox was defined as less than (<) 0.46 millimole per 24 hours (mmol/24 hours) and near-normalization was defined as greater than or equal to (>=) 0.46 to < 0.60 mmol/24 hours (values adjusted per 1.73 square metre [1.73 m^2] body surface area [BSA] in subjects aged < 18 years). Modified Intent-to-treat population (MITT) included all subjects in the intent-to-treat (ITT) population who had at least one efficacy assessment after the Day 90 dosing visit where ITT population included all subjects who were randomised and had at least one post-baseline efficacy assessment.
    End point type
    Primary
    End point timeframe
    From Day 90 to 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    12
    Units: Percentage of subjects
        number (not applicable)
    59.1
    0
    Statistical analysis title
    		 DCR-PHXC versus Placebo
    Comparison groups
    DCR-PHXC v Placebo
    Number of subjects included in analysis
    34
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0005
    Method
    		 Fisher exact
    Confidence interval

    Secondary: AUC from Day 90 to Day 180, based on percent change from baseline in 24-hour Uox

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    End point title
    		 AUC from Day 90 to Day 180, based on percent change from baseline in 24-hour Uox
    End point description
    AUC from Day 90 to Day 180 based on percent change from baseline in 24-hour Uox is presented. MITT population included all subjects in the ITT population who had at least one efficacy assessment after the Day 90 dosing visit, where the ITT population included all subjects who were randomized and had at least one post-baseline efficacy assessment. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 90 and 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    12
    Units: Percent change in 24-hour Uox AUC
        least squares mean (standard error)
    3507.4 ( 788.49 )
    -1664.4 ( 1189.96 )
    No statistical analyses for this end point

    Secondary: Percent change from baseline to Day 180 in the summed surface area of kidney stones

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    End point title
    		 Percent change from baseline to Day 180 in the summed surface area of kidney stones
    End point description
    Percent change from baseline to Day 180 in the summed surface area measured in millimetre square (mm^2) of kidney stones is presented. The ITT population included all subjects who were randomised and had at least one post-baseline efficacy assessment. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    16
    10
    Units: Percent change in summed surface area
        median (full range (min-max))
    -2.13 (-100.0 to 228.6)
    21.77 (-24.3 to 1500.0)
    No statistical analyses for this end point

    Secondary: Percent change from baseline to Day 180 in the number of kidney stones

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    End point title
    		 Percent change from baseline to Day 180 in the number of kidney stones
    End point description
    Percent change from baseline to Day 180 in the number of kidney stones is presented. The ITT population included all subjects who were randomised and had at least one post-baseline efficacy assessment. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    16
    10
    Units: Percent change in kidney stone numbers
        median (full range (min-max))
    0.00 (-100.0 to 200.0)
    0.00 (-94.1 to 100.0)
    No statistical analyses for this end point

    Secondary: Percent change from baseline to Day 180 in plasma oxalate (for adults only)

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    End point title
    		 Percent change from baseline to Day 180 in plasma oxalate (for adults only)
    End point description
    Percent change from baseline to Day 180 in plasma oxalate (for adults only) is presented. Analysis population included all adult subjects from ITT population who were randomised and had at least one post-baseline efficacy assessment. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    14
    5
    Units: Percent change in plasma oxalate
        median (full range (min-max))
    -25.00 (-61.9 to 22.2)
    -0.00 (-25.0 to 350.0)
    No statistical analyses for this end point

    Secondary: Rate of change in estimated glomerular filtration rate (eGFR) from baseline to Day 180

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    End point title
    		 Rate of change in estimated glomerular filtration rate (eGFR) from baseline to Day 180
    End point description
    Monthly rate of eGFR decline is presented. eGFR was calculated using Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and creatinine-based equation. The ITT population included all subjects who were randomised and had at least one post-baseline efficacy assessment. Number analysed (n) signifies subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    23
    12
    Units: mL/minute/1.73^2
        arithmetic mean (standard error)
    0.3533 ( 0.39610 )
    1.1008 ( 0.54849 )
    No statistical analyses for this end point

    Secondary: Number of treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)

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    End point title
    		 Number of treatment emergent adverse events (TEAEs) and treatment emergent serious adverse events (TESAEs)
    End point description
    Number of TEAEs and TESAEs are presented. An adverse event (AE) is any untoward medical occurrence in a patient or clinical study subject, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An SAE was defined as any untoward medical occurrence that, at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalisation, results in persistent disability/incapacity or is a congenital anomaly/birth defect. TEAE was defined as any AE with an onset date/time on or after administration (including any partial administration) of the first dose of study intervention and through the study completion date from the end of study CRF. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention.
    End point type
    Secondary
    End point timeframe
    From Baseline up to Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    23
    12
    Units: Events
    number (not applicable)
        TEAEs
    101
    54
        TESAEs
    1
    3
    No statistical analyses for this end point

    Secondary: Change from baseline in electrocardiogram (ECG): heart rate

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    End point title
    		 Change from baseline in electrocardiogram (ECG): heart rate
    End point description
    Change from baseline in heart rate is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    11
    Units: beats per minute (beats/min)
        arithmetic mean (standard deviation)
    0.4 ( 8.36 )
    -1.8 ( 9.18 )
    No statistical analyses for this end point

    Secondary: Change from baseline in ECG: PR interval, QRS duration, QT interval, QTcB interval, QTcF interval and RR interval

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    End point title
    		 Change from baseline in ECG: PR interval, QRS duration, QT interval, QTcB interval, QTcF interval and RR interval
    End point description
    Change from baseline in PR interval, QRS duration, QT interval, QTcB interval, QTcF interval and RR interval is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    11
    Units: milliseconds (msec)
    arithmetic mean (standard deviation)
        PR interval
    -0.5 ( 13.92 )
    1.3 ( 8.14 )
        QRS duration
    1.3 ( 6.01 )
    -1.5 ( 7.53 )
        QT interval
    -2.4 ( 23.73 )
    4.0 ( 22.97 )
        QTcB interval
    -0.8 ( 15.60 )
    -0.7 ( 17.31 )
        QTcF interval
    -1.1 ( 15.80 )
    1.2 ( 15.59 )
        RR interval
    -7.6 ( 99.35 )
    17.8 ( 109.73 )
    No statistical analyses for this end point

    Secondary: Number of subjects with most abnormal post-baseline shift in physical examination

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    End point title
    		 Number of subjects with most abnormal post-baseline shift in physical examination
    End point description
    Number of subjects who had most abnormal post-baseline shift in physical examination are presented. Physical examination shifts were categories into 4 categories: 1) missing; 2) normal; 3) abnormal-not clinically significant (NCS) and 4) abnormal-clinically significant (CS). Each category was presented according body systems including: 1) eyes, ears, nose and throat; 2) chest/respiratory; 3) heart/cardiovascular; 4) gastrointestinal/liver; 5) musculoskeletal/extremities; 6) dermatological/skin; 7) thyroid/neck; 8) lymph nodes; 9) neurological. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention.
    End point type
    Secondary
    End point timeframe
    Baseline up to Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    23
    12
    Units: Subjects
        Eyes, ears, nose and throat: missing
    1
    1
        Eyes, ears, nose and throat: normal
    21
    11
        Eyes, ears, nose and throat: abnormal-NCS
    1
    0
        Eyes, ears, nose and throat: abnormal-CS
    0
    0
        Chest/respiratory: missing
    0
    0
        Chest/respiratory: normal
    23
    12
        Chest/respiratory: abnormal-NCS
    0
    0
        Chest/respiratory: abnormal-CS
    0
    0
        Heart/cardiovascular: missing
    0
    0
        Heart/cardiovascular: normal
    22
    12
        Heart/cardiovascular: abnormal-NCS
    1
    0
        Heart/cardiovascular: abnormal-CS
    0
    0
        Gastrointestinal/liver: missing
    0
    0
        Gastrointestinal/liver: normal
    22
    8
        Gastrointestinal/liver: abnormal-NCS
    1
    4
        Gastrointestinal/liver: abnormal-CS
    0
    0
        Musculoskeletal/extremities: missing
    1
    1
        Musculoskeletal/extremities: normal
    22
    10
        Musculoskeletal/extremities: abnormal-NCS
    0
    1
        Musculoskeletal/extremities: abnormal-CS
    0
    0
        Dermatological/skin: missing
    0
    0
        Dermatological/skin: normal
    18
    8
        Dermatological/skin: abnormal-NCS
    4
    4
        Dermatological/skin: abnormal-CS
    1
    0
        Thyroid/neck: missing
    1
    1
        Thyroid/neck: normal
    22
    10
        Thyroid/neck: abnormal-NCS
    0
    1
        Thyroid/neck: abnormal-CS
    0
    0
        Lymph nodes: missing
    0
    1
        Lymph nodes: normal
    23
    10
        Lymph nodes: abnormal-NCS
    0
    1
        Lymph nodes: abnormal-CS
    0
    0
    No statistical analyses for this end point

    Secondary: Change from baseline in vital signs: height

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    End point title
    		 Change from baseline in vital signs: height
    End point description
    Change from baseline to Day 180 in height is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    11
    Units: centimetres (cm)
        arithmetic mean (standard deviation)
    0.70 ( 2.383 )
    1.08 ( 1.446 )
    No statistical analyses for this end point

    Secondary: Change from baseline in vital signs: weight

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    End point title
    		 Change from baseline in vital signs: weight
    End point description
    Change from baseline to Day 180 in weight is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    11
    Units: kilograms
        arithmetic mean (standard deviation)
    1.134 ( 3.4794 )
    1.350 ( 3.4330 )
    No statistical analyses for this end point

    Secondary: Change from baseline in vital signs: body mass index (BMI)

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    End point title
    		 Change from baseline in vital signs: body mass index (BMI)
    End point description
    Change from baseline to Day 180 in BMI is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    11
    Units: Kilograms per square meter (kg/m^2)
        arithmetic mean (standard deviation)
    0.23 ( 1.175 )
    0.14 ( 1.293 )
    No statistical analyses for this end point

    Secondary: Change from baseline in vital signs: oral body temperature

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    End point title
    		 Change from baseline in vital signs: oral body temperature
    End point description
    Change from baseline to Day 180 in oral body temperature is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    11
    Units: Degree Celsius (C)
        arithmetic mean (standard deviation)
    0.01 ( 0.399 )
    0.05 ( 0.446 )
    No statistical analyses for this end point

    Secondary: Change from baseline in vital signs: heart rate

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    End point title
    		 Change from baseline in vital signs: heart rate
    End point description
    Change from baseline to Day 180 in heart rate is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    11
    Units: beats/min
        arithmetic mean (standard deviation)
    0.8 ( 10.64 )
    -3.1 ( 6.35 )
    No statistical analyses for this end point

    Secondary: Change from baseline in vital signs: respiratory rate

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    End point title
    		 Change from baseline in vital signs: respiratory rate
    End point description
    Change from baseline to Day 180 in respiratory rate is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    10
    Units: Breaths per minute (breaths/min)
        arithmetic mean (standard deviation)
    -0.2 ( 3.02 )
    -1.1 ( 5.00 )
    No statistical analyses for this end point

    Secondary: Change from baseline in vital signs: systolic and diastolic blood pressure

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    End point title
    		 Change from baseline in vital signs: systolic and diastolic blood pressure
    End point description
    Change from baseline to Day 180 in systolic and diastolic blood pressure is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    11
    Units: millimetres of mercury (mmHg)
    arithmetic mean (standard deviation)
        Systolic blood pressure
    -2.0 ( 13.64 )
    -3.0 ( 9.82 )
        Diastolic blood pressure
    0.8 ( 9.20 )
    -2.6 ( 11.84 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical chemistry laboratory tests: alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, gamma glutamyl transferase, alkaline phosphatase, lactate dehydrogenase and creatine kinase

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    End point title
    		 Change from baseline in clinical chemistry laboratory tests: alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, gamma glutamyl transferase, alkaline phosphatase, lactate dehydrogenase and creatine kinase
    End point description
    Change from baseline to Day 180 in alanine aminotransferase, aspartate aminotransferase, glutamate dehydrogenase, gamma glutamyl transferase, alkaline phosphatase, lactate dehydrogenase and creatine kinase are presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data and number analysed (n) signifies subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    11
    Units: Units per litre (U/L)
    arithmetic mean (standard deviation)
        Alanine aminotransferase (n= 22, 11)
    1.0 ( 8.59 )
    -1.1 ( 4.59 )
        Aspartate aminotransferase (n= 22, 11)
    -0.2 ( 4.95 )
    -1.3 ( 4.73 )
        Glutamate dehydrogenase (n= 22, 11)
    -0.15 ( 1.913 )
    -0.38 ( 1.064 )
        Gamma glutamyl transferase (n= 22, 11)
    2.7 ( 4.12 )
    -0.2 ( 3.03 )
        Alkaline phosphatase (n= 22, 11)
    3.0 ( 29.11 )
    -16.8 ( 41.78 )
        Lactate dehydrogenase (n= 20, 10)
    4.1 ( 20.51 )
    1.0 ( 20.72 )
        Creatine kinase (n= 22, 11)
    7.5 ( 59.28 )
    -34.1 ( 160.46 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical chemistry laboratory tests: bilirubin, direct bilirubin and creatinine

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    End point title
    		 Change from baseline in clinical chemistry laboratory tests: bilirubin, direct bilirubin and creatinine
    End point description
    Change from baseline to Day 180 in bilirubin, direct bilirubin and creatinine are presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data and number analysed (n) signifies subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    11
    Units: micromoles per litre (umol/L)
    arithmetic mean (standard deviation)
        Bilirubin (n= 22, 11)
    1.0 ( 3.18 )
    0.4 ( 1.80 )
        Direct bilirubin (n= 22, 10)
    0.1 ( 1.32 )
    0.1 ( 0.32 )
        Creatinine (n= 22, 11)
    -1.2 ( 10.81 )
    4.3 ( 11.02 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical chemistry laboratory tests: protein, albumin

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    End point title
    		 Change from baseline in clinical chemistry laboratory tests: protein, albumin
    End point description
    Change from baseline to Day 180 in protein and albumin are presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    11
    Units: grams per litre (g/L)
    arithmetic mean (standard deviation)
        Protein
    0.4 ( 4.47 )
    1.5 ( 6.27 )
        Albumin
    0.5 ( 3.22 )
    1.2 ( 3.63 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical chemistry laboratory tests: sodium, chloride, potassium and urea

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    End point title
    		 Change from baseline in clinical chemistry laboratory tests: sodium, chloride, potassium and urea
    End point description
    Change from baseline to Day 180 in sodium, chloride, potassium and urea are presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data and number analysed (n) signifies subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    22
    11
    Units: mmol/L
    arithmetic mean (standard deviation)
        Sodium (n= 22, 11)
    0.4 ( 2.44 )
    0.2 ( 3.03 )
        Chloride (n= 22, 11)
    0.6 ( 3.30 )
    -0.4 ( 4.08 )
        Potassium (n= 21, 10)
    -0.04 ( 0.425 )
    0.05 ( 0.360 )
        Urea (n= 22, 11)
    0.01 ( 0.895 )
    0.40 ( 1.197 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical chemistry laboratory tests: vitamin B6

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    End point title
    		 Change from baseline in clinical chemistry laboratory tests: vitamin B6
    End point description
    Change from baseline to Day 180 in vitamin B6 is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    2
    3
    Units: nanomoles per litre (nmol/L)
        arithmetic mean (standard deviation)
    34.60 ( 99.278 )
    -215.73 ( 337.775 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical hematology laboratory tests: erythrocytes

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    End point title
    		 Change from baseline in clinical hematology laboratory tests: erythrocytes
    End point description
    Change from baseline to Day 180 in erythrocytes is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: 10^12 per litre (10^12/L)
        arithmetic mean (standard deviation)
    -0.04 ( 0.365 )
    0.02 ( 0.230 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical hematology laboratory tests: hemoglobin and erythrocytes mean corpuscular hemoglobin concentration

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    End point title
    		 Change from baseline in clinical hematology laboratory tests: hemoglobin and erythrocytes mean corpuscular hemoglobin concentration
    End point description
    Change from baseline to Day 180 in hemoglobin and erythrocytes mean corpuscular hemoglobin concentration are presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: g/L
    arithmetic mean (standard deviation)
        Hemoglobin
    -1.7 ( 8.90 )
    0.1 ( 6.62 )
        Ery. mean corpuscular hemoglobin concentration
    1.5 ( 15.10 )
    -4.8 ( 10.80 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical hematology laboratory tests: hematocrit

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    End point title
    		 Change from baseline in clinical hematology laboratory tests: hematocrit
    End point description
    Change from baseline to Day 180 in hematocrit is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: Litre/litre
        arithmetic mean (standard deviation)
    -0.004 ( 0.0271 )
    0.006 ( 0.0288 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical hematology laboratory tests: erythrocytes (ery.) mean corpuscular volume and mean platelet volume

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    End point title
    		 Change from baseline in clinical hematology laboratory tests: erythrocytes (ery.) mean corpuscular volume and mean platelet volume
    End point description
    Change from baseline to Day 180 in ery. mean corpuscular volume and mean platelet volume are presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: femtoliter (fL)
    arithmetic mean (standard deviation)
        Ery. mean corpuscular volume
    0.0 ( 2.31 )
    1.1 ( 3.57 )
        Mean platelet volume
    -0.03 ( 0.864 )
    0.61 ( 0.547 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical hematology laboratory tests: erythrocytes mean corpuscular hemoglobin

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    End point title
    		 Change from baseline in clinical hematology laboratory tests: erythrocytes mean corpuscular hemoglobin
    End point description
    Change from baseline to Day 180 in erythrocytes mean corpuscular hemoglobin is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: picogram (pg)
        arithmetic mean (standard deviation)
    -0.1 ( 1.37 )
    -0.1 ( 0.99 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical hematology laboratory tests: reticulocytes, platelets, leukocytes, lymphocytes, monocytes, eosinophils, basophils, neutrophils

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    End point title
    		 Change from baseline in clinical hematology laboratory tests: reticulocytes, platelets, leukocytes, lymphocytes, monocytes, eosinophils, basophils, neutrophils
    End point description
    Change from baseline to Day 180 in reticulocytes, platelets, leukocytes, lymphocytes, monocytes, eosinophils, basophils, neutrophils are presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data and number analysed (n) signifies subjects with available data for each specified category.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: 10^9/L
    arithmetic mean (standard deviation)
        Reticulocytes (n= 20, 9)
    0.2 ( 30.08 )
    -23.1 ( 32.21 )
        Platelets (n= 21, 10)
    -11.4 ( 54.50 )
    2.3 ( 53.30 )
        Leukocytes (n= 21, 10)
    0.18 ( 1.573 )
    -1.03 ( 1.931 )
        Lymphocytes (n= 21, 10)
    -0.03 ( 0.621 )
    0.06 ( 0.331 )
        Monocytes (n= 21, 10)
    0.07 ( 0.085 )
    -0.02 ( 0.103 )
        Eosinophils (n= 21, 10)
    0.03 ( 0.072 )
    0.04 ( 0.126 )
        Basophils (n= 21, 10)
    0.01 ( 0.062 )
    -0.04 ( 0.097 )
        Neutrophils (n= 21, 10)
    0.14 ( 1.195 )
    -1.07 ( 1.700 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical hematology laboratory tests: lymphocytes/leukocytes

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    End point title
    		 Change from baseline in clinical hematology laboratory tests: lymphocytes/leukocytes
    End point description
    Change from baseline to Day 180 in lymphocytes/leukocytes is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: Percentage of lymphocytes/leukocytes
        arithmetic mean (standard deviation)
    -1.3 ( 10.26 )
    5.1 ( 10.21 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical hematology laboratory tests: monocytes/leukocytes

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    End point title
    		 Change from baseline in clinical hematology laboratory tests: monocytes/leukocytes
    End point description
    Change from baseline to Day 180 in monocytes/leukocytes is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: Percentage of monocytes/leukocytes
        arithmetic mean (standard deviation)
    1.0 ( 2.04 )
    0.9 ( 2.51 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical hematology laboratory tests: eosinophils/leukocytes

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    End point title
    		 Change from baseline in clinical hematology laboratory tests: eosinophils/leukocytes
    End point description
    Change from baseline to Day 180 in eosinophils/leukocytes is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: Percentage of eosinophils/leukocytes
        arithmetic mean (standard deviation)
    0.4 ( 1.56 )
    0.9 ( 1.66 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical hematology laboratory tests: basophils/leukocytes

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    End point title
    		 Change from baseline in clinical hematology laboratory tests: basophils/leukocytes
    End point description
    Change from baseline to Day 180 in basophils/leukocytes is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: Percentage of basophils/leukocytes
        arithmetic mean (standard deviation)
    0.0 ( 0.77 )
    0.1 ( 0.74 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical hematology laboratory tests: neutrophils/leukocytes

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    End point title
    		 Change from baseline in clinical hematology laboratory tests: neutrophils/leukocytes
    End point description
    Change from baseline to Day 180 in neutrophils/leukocytes is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: Percentage of neutrophils/leukocytes
        arithmetic mean (standard deviation)
    -0.3 ( 11.45 )
    -7.1 ( 13.14 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical urinalysis laboratory tests: specific gravity

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    End point title
    		 Change from baseline in clinical urinalysis laboratory tests: specific gravity
    End point description
    Change from baseline to Day 180 in urine specific gravity is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: Ratio
        arithmetic mean (standard deviation)
    0.0000 ( 0.00872 )
    -0.0008 ( 0.00480 )
    No statistical analyses for this end point

    Secondary: Change from baseline in clinical urinalysis laboratory tests: pH

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    End point title
    		 Change from baseline in clinical urinalysis laboratory tests: pH
    End point description
    Change from baseline to Day 180 in urine pH is presented. The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data.
    End point type
    Secondary
    End point timeframe
    Baseline, Day 180
    End point values
    		 DCR-PHXC Placebo
    Number of subjects analysed
    21
    10
    Units: Units on a scale
        arithmetic mean (standard deviation)
    0.29 ( 1.067 )
    -0.10 ( 0.738 )
    No statistical analyses for this end point

    Secondary: Maximum observed plasma concentration (Cmax) of DCR-PHXC

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    End point title
    		 Maximum observed plasma concentration (Cmax) of DCR-PHXC
    End point description
    The Cmax was defined as the maximum observed plasma concentration during a dosing interval. The Pharmacokinetic (PK) population included all subjects in the safety population without major dosing violations, where safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data and number analysed (n) signifies subjects with available data for each specified category. Data for this endpoint is reported only for adults and adolescent subjects from PK population. Here ‘99999’ signifies data for adolescents group was not collected on Day 150.
    End point type
    Secondary
    End point timeframe
    For adults: Day 1 and 30: predose, 5, 15, and 30 minutes and 1, 2, 4, 6, 10, and 12 hours (hrs) postdose; Day 150: predose, 2, 6, and 12 hours postdose For adolescents: Days 1 and 30: predose, 30 minutes and 2 and 10 hours postdose
    End point values
    		 DCR-PHXC: Adults DCR-PHXC: Adolescents
    Number of subjects analysed
    12
    5
    Units: ng/mL
    geometric mean (geometric coefficient of variation)
        Day 1 (n= 12, 5)
    778 ( 35.7 )
    363 ( 76.7 )
        Day 30 (n= 11, 5)
    774 ( 46.1 )
    350 ( 48.6 )
        Day 150 (n= 8, 0)
    648 ( 55.5 )
    99999 ( 99999 )
    No statistical analyses for this end point

    Secondary: Area under the curve from time of administration to the last measurable concentration (AUC0-last) of of DCR-PHXC

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    End point title
    		 Area under the curve from time of administration to the last measurable concentration (AUC0-last) of of DCR-PHXC
    End point description
    AUC0-last was defined as the area under the curve from time of administration to the last measurable concentration. The PK population included all subjects in the safety population without major dosing violations, where safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. Number of subjects analysed signifies subjects with available data and number analysed (n) signifies subjects with available data for each specified category. Data for this endpoint is reported only for adults and adolescent subjects from PK population. Here ‘99999’ signifies data for adolescents group was not collected on Day 150.
    End point type
    Secondary
    End point timeframe
    For adults: Day 1 and 30: predose, 5, 15, and 30 minutes and 1, 2, 4, 6, 10, and 12 hours postdose; Day 150: predose, 2, 6, and 12 hours postdose For adolescents: Days 1 and 30: predose, 30 minutes and 2 and 10 hours postdose
    End point values
    		 DCR-PHXC: Adults DCR-PHXC: Adolescents
    Number of subjects analysed
    12
    5
    Units: hours*nanograms per millilitre (h*ng/mL)
    geometric mean (geometric coefficient of variation)
        Day 1 (n= 12, 5)
    12500 ( 29.3 )
    6450 ( 54.5 )
        Day 30 (n= 11, 5)
    12800 ( 38.4 )
    6400 ( 45.1 )
        Day 150 (n= 8, 0)
    6100 ( 46.2 )
    99999 ( 99999 )
    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 end of the study (Day 180)
    Adverse event reporting additional description
    The safety population included all subjects randomly assigned to study intervention and who took at least 1 partial or full dose of study intervention. All serious and non-serious adverse events presented here are treatment emergent adverse events.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    23.1
    Reporting groups
    Reporting group title
    DCR-PHXC
    Reporting group description
    		 Subjects aged >= 12 years weighing >=50 kg received nedosiran 170 mg (160 mg/mL FAE); subjects >=12 year weighing < 50 kg received 136 mg (128 mg FAE); and subjects 6-11 years received 3.5 kg/mg (3.3 mg/kg FAE) not exceeding 136 mg, SC injection into the abdomen or thigh on Days 1, 30, 60, 90, 120 and 150.

    Reporting group title
    Placebo
    Reporting group description
    		 Subjects received the equivalent volume of nedosiran matching placebo SC injection into the abdomen or thigh on Days 1, 30, 60, 90, 120 and 150.

    Serious adverse events
    		 DCR-PHXC Placebo
    Total subjects affected by serious adverse events
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 12 (16.67%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Cardiac disorders
    Tachycardia
         subjects affected / exposed
    1 / 23 (4.35%)
    0 / 12 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Blood creatinine increased
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal colic
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 DCR-PHXC Placebo
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    16 / 23 (69.57%)
    10 / 12 (83.33%)
    General disorders and administration site conditions
    Injection site erythema
         subjects affected / exposed
    5 / 23 (21.74%)
    0 / 12 (0.00%)
         occurrences all number
    11
    0
    Injection site pain
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 12 (0.00%)
         occurrences all number
    3
    0
    Fatigue
         subjects affected / exposed
    1 / 23 (4.35%)
    2 / 12 (16.67%)
         occurrences all number
    2
    2
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 12 (0.00%)
         occurrences all number
    6
    0
    Menstrual disorder
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Respiratory, thoracic and mediastinal disorders
    Oropharyngeal pain
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Cough
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Psychiatric disorders
    Depression
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Investigations
    Neutrophil count decreased
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Blood creatine phosphokinase increased
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Alanine aminotransferase increased
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Aspartate aminotransferase increased
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Glutamate dehydrogenase increased
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Injury, poisoning and procedural complications
    Adverse event following immunisation
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    2
    Meniscus injury
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    4 / 23 (17.39%)
    3 / 12 (25.00%)
         occurrences all number
    6
    3
    Sensory disturbance
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Gastrointestinal disorders
    Nausea
         subjects affected / exposed
    4 / 23 (17.39%)
    1 / 12 (8.33%)
         occurrences all number
    4
    1
    Abdominal pain
         subjects affected / exposed
    2 / 23 (8.70%)
    0 / 12 (0.00%)
         occurrences all number
    2
    0
    Abdominal pain upper
         subjects affected / exposed
    0 / 23 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    2
    Chronic gastritis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Diarrhoea
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Dyspepsia
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Gastrooesophageal reflux disease
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Skin and subcutaneous tissue disorders
    Dermatitis acneiform
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    2 / 23 (8.70%)
    2 / 12 (16.67%)
         occurrences all number
    3
    7
    Renal colic
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 12 (8.33%)
         occurrences all number
    1
    2
    Hydronephrosis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    2 / 23 (8.70%)
    1 / 12 (8.33%)
         occurrences all number
    4
    1
    Arthralgia
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    Neck pain
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 12 (8.33%)
         occurrences all number
    1
    3
    Arthritis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Back pain
         subjects affected / exposed
    0 / 23 (0.00%)
    2 / 12 (16.67%)
         occurrences all number
    0
    2
    Flank pain
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Intervertebral disc protrusion
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Osteoarthritis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Infections and infestations
    Upper respiratory tract infection
         subjects affected / exposed
    1 / 23 (4.35%)
    1 / 12 (8.33%)
         occurrences all number
    1
    1
    COVID-19
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Rhinitis
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Hypercholesterolaemia
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1
    Vitamin D deficiency
         subjects affected / exposed
    0 / 23 (0.00%)
    1 / 12 (8.33%)
         occurrences all number
    0
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    13 Jun 2019
    Principal changes included a change in the primary endpoint to a responder analysis and addition of a “key secondary” endpoint; a change in how the completeness of 24-hour urine collections will be assessed; addition of a subgroup of participants with very high baseline Uox levels; addition of a spot urine sample collection for Uox determination; expanded details regarding modeling and simulation of PK/PD data; expanded details regarding kidney assessments; addition of information for the calculation of eGFR; and updates to the statistical analyses.
    12 Mar 2020
    Principal changes included updates in the equations used to calculate eGFR, a change in the dose of DCR-PHXC to be administered in adults weighing less than 50 kg, changed laboratory testing requirements to limit blood loss in children, added additional immunogenicity testing, updated instructions for monitoring of liver injury, clarified the performance of an interim analysis, and specified that metabolites of DCR-PHXC will be included in pharmacokinetic analyses.
    13 Aug 2020
    Principal change was to include the dose of DCR-PHXC to be administered in children aged 6-to-11 years. An appendix detailing measures to be undertaken during the COVID-19 pandemic was added.

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

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