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    Clinical Trial Results:
    A Phase 2, Multicenter, Open-Label, Extension Study to Evaluate the Long-Term Administration of ALN-GO1 in Patients with Primary Hyperoxaluria Type 1

    Summary
    EudraCT number
    		 2016-003134-24
    Trial protocol
    		 DE   GB   NL   FR  
    Global end of trial date
    07 Feb 2023

    Results information
    Results version number
    		 v2(current)
    This version publication date
    21 Apr 2024
    First version publication date
    23 Aug 2023
    Other versions
    		 v1
    Version creation reason
    • New data added to full data set
    Certain data fields need to be updated.

    Trial information

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    Trial identification
    Sponsor protocol code
    ALN-GO1-002
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT03350451
    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., +1 8772569526, clinicaltrials@alnylam.com
    Scientific contact
    Clinical Trial Information Line, Alnylam Pharmaceuticals, Inc., +1 8772569526, 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
    07 Feb 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    07 Feb 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of this study was to evaluate the long-term safety of multiple doses of ALN-GO1 in subjects with primary hyperoxaluria type 1 (PH1).
    Protection of trial subjects
    All study subjects were required to read and sign an Informed Consent Form (ICF).
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    04 Apr 2018
    Long term follow-up planned
    No
    Independent data monitoring committee (IDMC) involvement?
    No
    Population of trial subjects
    Number of subjects enrolled per country
    Country: Number of subjects enrolled
    Netherlands: 2
    Country: Number of subjects enrolled
    United Kingdom: 3
    Country: Number of subjects enrolled
    France: 7
    Country: Number of subjects enrolled
    Germany: 1
    Country: Number of subjects enrolled
    Israel: 7
    Worldwide total number of subjects
    20
    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)
    10
    Adolescents (12-17 years)
    6
    Adults (18-64 years)
    4
    From 65 to 84 years
    0
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Subjects took part in the study at 9 study centers in France, Germany, Israel, Netherlands, and the United Kingdom from 04 April 2018 to 07 February 2023. A total of 20 subjects previously treated in Study 001B (2015-004407-23) were enrolled and treated within this study.

    Pre-assignment
    Screening details
    		 The cumulative dose of lumasiran administered over 6 months was the same for both 1 mg/kg QM & 3 mg/kg Q3M, these subjects were pooled into one arm as recommended by the Safety Review Committee (SRC). As pre-specified in the SAP, subjects who began treatment at 1 mg/kg QM, then transitioned to 3 mg/kg Q3M were to be summarised as a single group.

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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M
    Arm description
    		 Subjects enrolling from study 001B, received lumasiran, subcutaneous (SC) injection, at a starting dose of 1.0 milligrams per kilograms (mg/kg) once monthly (QM) or 3.0 mg/kg once every 3 months (Q3M) from Day 1 up to a maximum of Month 6. By Month 6, all subjects were approved to change dose and/or dosing regimen to receive lumasiran, SC injection at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. All 3 subjects who began treatment at 1 mg/kg QM transitioned to 3 mg/kg Q3M regimen by Month 6. As the cumulative dose administered over 6 months was the same for both 1 mg/kg QM & 3 mg/kg Q3M, these subjects were pooled into one arm as recommended by the SRC.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lumasiran
    Investigational medicinal product code
    ALN-GO1
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Lumasiran, SC injection, administered at a starting dose of 1.0 mg/kg, QM or 3.0 mg/kg Q3M from Day 1 up to a maximum of Month 6. By Month 6, lumasiran, SC injection was administered at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period.

    Arm title
    		 Lumasiran (ALN-GO1): 3.0 mg/kg QM
    Arm description
    		 Subjects enrolling from study 001B, received lumasiran, SC injection, at a starting dose of 3.0 mg/kg, QM, from Day 1 up to a maximum of Month 21. By Month 21, all subjects were approved to change dosing regimen to receive lumasiran, SC injection, at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Lumasiran
    Investigational medicinal product code
    ALN-GO1
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Lumasiran, SC injection, administered at a starting dose of 3.0 mg/kg, QM, from Day 1 up to a maximum of Month 21. By Month 21, lumasiran, SC injection, was administered at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period.

    Number of subjects in period 1
    		Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M Lumasiran (ALN-GO1): 3.0 mg/kg QM
    Started
    13
    7
    Safety Analysis Set
    13
    7
    Pharmacodynamic Analysis Set
    13
    7
    Completed
    13
    7

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M
    Reporting group description
    		 Subjects enrolling from study 001B, received lumasiran, subcutaneous (SC) injection, at a starting dose of 1.0 milligrams per kilograms (mg/kg) once monthly (QM) or 3.0 mg/kg once every 3 months (Q3M) from Day 1 up to a maximum of Month 6. By Month 6, all subjects were approved to change dose and/or dosing regimen to receive lumasiran, SC injection at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. All 3 subjects who began treatment at 1 mg/kg QM transitioned to 3 mg/kg Q3M regimen by Month 6. As the cumulative dose administered over 6 months was the same for both 1 mg/kg QM & 3 mg/kg Q3M, these subjects were pooled into one arm as recommended by the SRC.

    Reporting group title
    Lumasiran (ALN-GO1): 3.0 mg/kg QM
    Reporting group description
    		 Subjects enrolling from study 001B, received lumasiran, SC injection, at a starting dose of 3.0 mg/kg, QM, from Day 1 up to a maximum of Month 21. By Month 21, all subjects were approved to change dosing regimen to receive lumasiran, SC injection, at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period.

    Reporting group values
    		 Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M Lumasiran (ALN-GO1): 3.0 mg/kg QM Total
    Number of subjects
    		 13 7 20
    Age categorical
    Units: Subjects
    Age continuous
    Units: years
        arithmetic mean (standard deviation)
    		 16.1 ( 12.31 ) 12.6 ( 3.95 ) -
    Gender categorical
    Units: Subjects
        Female
    		 9 4 13
        Male
    		 4 3 7
    Ethnicity
    Units: Subjects
        Not Hispanic or Latino
    		 13 7 20
    Race
    Units: Subjects
        Asian
    		 2 2 4
        White
    		 10 5 15
        Other
    		 1 0 1

    End points

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    End points reporting groups
    Reporting group title
    Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M
    Reporting group description
    		 Subjects enrolling from study 001B, received lumasiran, subcutaneous (SC) injection, at a starting dose of 1.0 milligrams per kilograms (mg/kg) once monthly (QM) or 3.0 mg/kg once every 3 months (Q3M) from Day 1 up to a maximum of Month 6. By Month 6, all subjects were approved to change dose and/or dosing regimen to receive lumasiran, SC injection at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. All 3 subjects who began treatment at 1 mg/kg QM transitioned to 3 mg/kg Q3M regimen by Month 6. As the cumulative dose administered over 6 months was the same for both 1 mg/kg QM & 3 mg/kg Q3M, these subjects were pooled into one arm as recommended by the SRC.

    Reporting group title
    Lumasiran (ALN-GO1): 3.0 mg/kg QM
    Reporting group description
    		 Subjects enrolling from study 001B, received lumasiran, SC injection, at a starting dose of 3.0 mg/kg, QM, from Day 1 up to a maximum of Month 21. By Month 21, all subjects were approved to change dosing regimen to receive lumasiran, SC injection, at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period.

    Primary: Number of Subjects With at Least One Adverse Event (AE)

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    End point title
    		 Number of Subjects With at Least One Adverse Event (AE) [1]
    End point description
    AE is any untoward medical occurrence in a subject or clinical investigational participant administered a medicinal product and which does not necessarily have a causal relationship with this treatment. Safety analysis set included all subjects who received any amount of study drug. The cumulative dose of lumasiran administered over 6 months was the same for both 1 mg/kg QM & 3 mg/kg Q3M, these subjects were pooled into one arm as recommended by the SRC. As pre-specified in the SAP, subjects who began treatment at 1 mg/kg QM, then transitioned to 3 mg/kg Q3M were to be summarized as a single group. All 3 subjects who began treatment at 1 mg/kg QM transitioned to 3 mg/kg Q3M regimen by Month 6.
    End point type
    Primary
    End point timeframe
    Baseline (Day -1) up to 54 months
    Notes
    [1] - No statistical analyses have been specified for this primary end point. It is expected there is at least one statistical analysis for each primary end point.
    Justification: Only descriptive analysis was planned for this outcome measure.
    End point values
    		 Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M Lumasiran (ALN-GO1): 3.0 mg/kg QM
    Number of subjects analysed
    13
    7
    Units: subjects
    13
    7
    No statistical analyses for this end point

    Secondary: Change From Baseline in 24-hour Urinary Oxalate Corrected for Body Surface Area (BSA) at 54 Months

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    End point title
    		 Change From Baseline in 24-hour Urinary Oxalate Corrected for Body Surface Area (BSA) at 54 Months
    End point description
    Oxalate produced by liver is the key toxic metabolite driving disease pathology in subjects with PH1. Risk of disease complications increase as oxalate levels increase. 24-hour (urinary oxalate (millimole [mmol]/ 24 hour [h]/1.73 meters squared [m^2]) corrected for BSA at each visit per subject was calculated. Baseline=derived baseline value from lumasiran treated period of Study ALN-GO1-001. Negative change from baseline indicated favorable outcome. Pharmacodynamic (PD) analysis set included all subjects who received any amount of study drug & had at least 1 post-dose urine sample for PD. Overall number analysed = number of subjects with data available for analysis. The cumulative dose of lumasiran administered over 6 months was the same for both 1 mg/kg QM & 3 mg/kg Q3M, these subjects were pooled into one arm as recommended by the SRC. As pre-specified in the SAP, subjects who began treatment at 1 mg/kg QM, then transitioned to 3 mg/kg Q3M were to be summarised as a single group.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -1) up to 54 months
    End point values
    		 Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M Lumasiran (ALN-GO1): 3.0 mg/kg QM
    Number of subjects analysed
    12
    6
    Units: mmol/24hr/1.73m^2
        arithmetic mean (standard error)
    -1.425 ( 0.2188 )
    -2.126 ( 0.5528 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in 24-hour Urinary Oxalate:Creatinine Ratio at 54 Months

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    End point title
    		 Change From Baseline in 24-hour Urinary Oxalate:Creatinine Ratio at 54 Months
    End point description
    Baseline is the derived baseline value from the lumasiran treated period of Study ALN-GO1-001. A negative change from baseline indicates a favorable outcome. PD analysis set included all subjects who received any amount of study drug and who had at least 1 post-dose urine sample for PD. The cumulative dose of lumasiran administered over 6 months was the same for both 1 mg/kg QM & 3 mg/kg Q3M, these subjects were pooled into one arm as recommended by the SRC. As pre-specified in the SAP, subjects who began treatment at 1 mg/kg QM, then transitioned to 3 mg/kg Q3M were to be summarized as a single group. All 3 subjects who began treatment at 1 mg/kg QM transitioned to 3 mg/kg Q3M regimen by Month 6.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -1) up to 54 months
    End point values
    		 Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M Lumasiran (ALN-GO1): 3.0 mg/kg QM
    Number of subjects analysed
    13
    7
    Units: mmol/mmol
        arithmetic mean (standard error)
    -0.2175 ( 0.03880 )
    -0.2480 ( 0.04047 )
    No statistical analyses for this end point

    Secondary: Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at 54 Months

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    End point title
    		 Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at 54 Months
    End point description
    Baseline was defined as last measurement prior to the first dose of lumasiran in the ALN-GO1-001 study. eGFR was calculated based on Modification of Diet in Renal Disease (MDRD) formula for subjects ≥18 years of age at enrollment & Schwartz Bedside formula for subjects <18 years of age at enrollment. eGFR per MDRD formula was calculated as follows: eGFR (mL/min/1.73 m^2) = 175 × (serum creatinine {SCr} [μmol/deciliter(dL)]/88.4)-1.154 × (age)-0.203 × (0.742, if female), or × (1.212, if African American) or based on Schwartz formula: eGFR (mL/min/1.73m2) = (36.2 × height [cm])/ SCr (μmol /dL). Safety analysis set included all subjects who received any amount of study drug. Cumulative dose of lumasiran administered over 6 months was the same for both 1 mg/kg QM & 3 mg/kg Q3M, these subjects were pooled into one arm as recommended by the SRC. As pre-specified in the SAP, subjects who began treatment at 1 mg/kg QM, then transitioned to 3 mg/kg Q3M were to be summarised as a single group.
    End point type
    Secondary
    End point timeframe
    Baseline (Day -1) up to 54 months
    End point values
    		 Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M Lumasiran (ALN-GO1): 3.0 mg/kg QM
    Number of subjects analysed
    13
    7
    Units: mL/min/1.73m^2
        arithmetic mean (standard error)
    0.674 ( 3.7970 )
    -12.026 ( 3.6369 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Baseline (Day -1) up to 54 months
    Adverse event reporting additional description
    Safety analysis set. The cumulative dose of lumasiran administered over 6 months was the same for both 1 mg/kg QM & 3 mg/kg Q3M, these subjects were pooled into one arm as recommended by the SRC. As pre-specified in the SAP, subjects who began treatment at 1 mg/kg QM, then transitioned to 3 mg/kg Q3M were to be summarised as as a single group.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    25.0
    Reporting groups
    Reporting group title
    Lumasiran (ALN-GO1): 3.0 mg/kg QM
    Reporting group description
    		 Subjects enrolling from study 001B, received lumasiran, SC injection, at a starting dose of 3.0 mg/kg, QM, from Day 1 up to a maximum of Month 21. By Month 21, all subjects were approved to change dosing regimen to receive lumasiran, SC injection, at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period.

    Reporting group title
    Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M
    Reporting group description
    		 Subjects enrolling from study 001B, received lumasiran, SC injection, at a starting dose of 1.0 mg/kg QM or 3.0 mg/kg Q3M from Day 1 up to a maximum of Month 6. By Month 6, all subjects were approved to change dose and/or dosing regimen to receive lumasiran, SC injection at a dose of 3.0 mg/kg, Q3M, up to Month 51 of the treatment period. All 3 subjects who began treatment at 1 mg/kg QM transitioned to 3 mg/kg Q3M regimen by Month 6. As the cumulative dose administered over 6 months was the same for both 1 mg/kg QM & 3 mg/kg Q3M, these subjects were pooled into one arm as recommended by the SRC.

    Serious adverse events
    		 Lumasiran (ALN-GO1): 3.0 mg/kg QM Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M
    Total subjects affected by serious adverse events
         subjects affected / exposed
    3 / 7 (42.86%)
    4 / 13 (30.77%)
         number of deaths (all causes)
    0
    0
         number of deaths resulting from adverse events
    0
    0
    Investigations
    Glomerular Filtration Rate Decreased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Bone Contusion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Craniocerebral Injury
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Surgical and medical procedures
    Renal Stone Removal
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Thyroid Operation
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         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 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ureterolithiasis
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 13 (15.38%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Endocrine disorders
    Thyroid Mass
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Pyelonephritis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Lumasiran (ALN-GO1): 3.0 mg/kg QM Lumasiran (ALN-GO1): 1.0 mg/kg QM or 3.0 mg/kg Q3M
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    7 / 7 (100.00%)
    13 / 13 (100.00%)
    Vascular disorders
    Hypertension
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    Orthostatic Hypotension
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    Surgical and medical procedures
    Gastrostomy Closure
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Tooth Extraction
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Wisdom Teeth Removal
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    General disorders and administration site conditions
    Fatigue
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Feeling Cold
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Influenza Like Illness
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Injection Site Reaction
         subjects affected / exposed
    4 / 7 (57.14%)
    4 / 13 (30.77%)
         occurrences all number
    6
    7
    Non-cardiac Chest Pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    4
    0
    Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Pyrexia
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 13 (7.69%)
         occurrences all number
    5
    1
    Vaccination Site Pain
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 13 (7.69%)
         occurrences all number
    2
    2
    Vessel Puncture Site Haematoma
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Immune system disorders
    Immunisation Reaction
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 13 (7.69%)
         occurrences all number
    4
    1
    Seasonal Allergy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Reproductive system and breast disorders
    Dysmenorrhoea
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Genital Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Heavy Menstrual Bleeding
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    3
    0
    Respiratory, thoracic and mediastinal disorders
    Cough
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 13 (7.69%)
         occurrences all number
    3
    3
    Epistaxis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Nasal Congestion
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Oropharyngeal Pain
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    Upper-airway Cough Syndrome
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Psychiatric disorders
    Affective Disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Nightmare
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Sleep Disorder
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Product issues
    Device Breakage
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    Investigations
    Bilirubin Conjugated Increased
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Blood Bilirubin Increased
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 13 (23.08%)
         occurrences all number
    0
    3
    Blood Creatinine Increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    3
    0
    Electrocardiogram QRS Complex Prolonged
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Glycolic Acid Increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    SARS-CoV-2 Test Positive
         subjects affected / exposed
    0 / 7 (0.00%)
    3 / 13 (23.08%)
         occurrences all number
    0
    3
    Ultrasound Breast Abnormal
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Ultrasound Kidney Abnormal
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Weight Increased
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Injury, poisoning and procedural complications
    Fall
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Head Injury
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Ligament Sprain
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    2
    Limb Injury
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 13 (15.38%)
         occurrences all number
    1
    2
    Skin Abrasion
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    Skin Wound
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Stoma Site Pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    Thermal Burn
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Tibia Fracture
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Cardiac disorders
    Atrioventricular Block
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Nervous system disorders
    Headache
         subjects affected / exposed
    1 / 7 (14.29%)
    3 / 13 (23.08%)
         occurrences all number
    2
    4
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 13 (7.69%)
         occurrences all number
    2
    1
    Ear and labyrinth disorders
    Ear Pain
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Hyperacusis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Hypoacusis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Eye disorders
    Eye Allergy
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Periorbital Swelling
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Gastrointestinal disorders
    Abdominal Discomfort
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Abdominal Pain
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Abdominal Pain Upper
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    Dental Caries
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Diverticulum Intestinal
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Dyspepsia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Food Poisoning
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Large Intestine Polyp
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Nausea
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 13 (0.00%)
         occurrences all number
    2
    0
    Toothache
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Vomiting
         subjects affected / exposed
    4 / 7 (57.14%)
    2 / 13 (15.38%)
         occurrences all number
    6
    3
    Skin and subcutaneous tissue disorders
    Acne
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Alopecia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Blister
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Hyperhidrosis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Renal and urinary disorders
    Haematuria
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Nephrolithiasis
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 13 (7.69%)
         occurrences all number
    3
    4
    Renal Cyst
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Renal Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Endocrine disorders
    Thyroid Mass
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Musculoskeletal and connective tissue disorders
    Arthralgia
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Back Pain
         subjects affected / exposed
    2 / 7 (28.57%)
    1 / 13 (7.69%)
         occurrences all number
    4
    2
    Flank Pain
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    3
    Infections and infestations
    Asymptomatic COVID-19
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    COVID-19
         subjects affected / exposed
    3 / 7 (42.86%)
    6 / 13 (46.15%)
         occurrences all number
    3
    6
    Conjunctivitis
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Cystitis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Cystitis Escherichia
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    1
    Ear Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Gastroenteritis
         subjects affected / exposed
    1 / 7 (14.29%)
    1 / 13 (7.69%)
         occurrences all number
    1
    1
    Gastroenteritis Viral
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    2
    Influenza
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    2
    Nasopharyngitis
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 13 (15.38%)
         occurrences all number
    1
    2
    Pharyngitis
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    3
    Pyelonephritis
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Rhinitis
         subjects affected / exposed
    1 / 7 (14.29%)
    2 / 13 (15.38%)
         occurrences all number
    1
    3
    Tinea Versicolour
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    3
    0
    Upper Respiratory Tract Infection
         subjects affected / exposed
    2 / 7 (28.57%)
    0 / 13 (0.00%)
         occurrences all number
    3
    0
    Urinary Tract Infection
         subjects affected / exposed
    0 / 7 (0.00%)
    2 / 13 (15.38%)
         occurrences all number
    0
    4
    Metabolism and nutrition disorders
    Gout
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2
    Increased Appetite
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Iron Deficiency
         subjects affected / exposed
    1 / 7 (14.29%)
    0 / 13 (0.00%)
         occurrences all number
    1
    0
    Vitamin D Deficiency
         subjects affected / exposed
    3 / 7 (42.86%)
    0 / 13 (0.00%)
         occurrences all number
    7
    0
    Weight Gain Poor
         subjects affected / exposed
    0 / 7 (0.00%)
    1 / 13 (7.69%)
         occurrences all number
    0
    2

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    27 Aug 2019
    The primary purpose for this protocol amendment was to extend the study duration from up to 2 years to up to 54 months. In addition, the amendment: • Updated adverse event of clinical interest (AECI) • Added liver function test (LFT) criteria for withholding, monitoring, and stopping study drug dosing to align with other studies of lumasiran • Provided dosing information for subjects who progress to end-stage renal disease (ESRD) and require dialysis, a potential occurrence in PH1 subjects.
    04 May 2020
    The primary purpose for this protocol amendment was to incorporate urgent safety measures (USMs) that were communicated to investigators in a Dear Investigator Letter to assure the safety of study subjects while minimizing risks to study integrity amid the Coronavirus disease 2019 (COVID-19) pandemic. Changes not related to USMs were also incorporated. • Permitted lumasiran administration at locations other than study center that had undergone appropriate training • Allowed assessment of AEs and concomitant medication to be conducted offsite • Expanded study assessment window to ±28 days at Month 12 and ±14 days thereafter • Allowed, after 12 months, renal ultrasound and ECG assessments to be completed up to 9 months after intended time point. • Removed quality of life (QOL) questionnaire and assessment as part of the exploratory objective and endpoint.

    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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    The status and protocol content of GB trials is no longer updated since 1 January 2021. For the UK, as of 31 January 2021, EU Law applies only to the territory of Northern Ireland (NI) to the extent foreseen in the Protocol on Ireland/NI. Legal notice
    As of 31 January 2023, all EU/EEA initial clinical trial applications must be submitted through CTIS . Updated EudraCT trials information and information on PIP/Art 46 trials conducted exclusively in third countries continues to be submitted through EudraCT and published on this website.

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