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    Clinical Trial Results:
    A Phase 2b Dose Ranging Study to Evaluate the Efficacy and Safety of Efavaleukin Alfa in Subjects With Active Systemic Lupus Erythematosus With Inadequate Response to Standard of Care Therapy (VIOLET)

    Summary
    EudraCT number
    		 2020-003509-72
    Trial protocol
    		 FR   GR   PL   AT   BG   ES   IT  
    Global end of trial date
    24 May 2023

    Results information
    Results version number
    		 v1(current)
    This version publication date
    07 Jun 2024
    First version publication date
    07 Jun 2024
    Other versions

    Trial information

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    Trial identification
    Sponsor protocol code
    20200234
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04680637
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, CA, United States,
    Public contact
    Study Director, Amgen Inc., +1 8665726436, medinfo@amgen.com
    Scientific contact
    Study Director, Amgen Inc., +1 8665726436, medinfo@amgen.com
    Paediatric regulatory details
    Is trial part of an agreed paediatric investigation plan (PIP)
    No
    Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial?
    No
    Results analysis stage
    Analysis stage
    Final
    Date of interim/final analysis
    24 May 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    24 May 2023
    Was the trial ended prematurely?
    Yes
    General information about the trial
    Main objective of the trial
    The main objective of the trial was to evaluate the efficacy of efavaleukin alfa at Week 52, as measured by the Systemic Lupus Erythematosus Responder Index 4 (SRI-4) response.
    Protection of trial subjects
    This study was conducted in accordance with International Council for Harmonisation (ICH) Good Clinical Practice (GCP) and with consensus ethical principles derived from international guidelines including the Declaration of Helsinki and Council for International Organizations of Medical Sciences International Ethical Guidelines.
    Background therapy
    		 Participants were permitted to receive immunosuppressants/immunomodulators, oral corticosteroids, topical corticosteroids and topical calcineurin inhibitors, non-steroidal anti-inflammatory drugs (NSAIDS) and other analgesic therapies and anti-proteinuria agents, as outlined in the protocol and based upon clinical judgment of the investigator.
    Evidence for comparator
    		 -
    Actual start date of recruitment
    06 May 2021
    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
    Bulgaria: 17
    Country: Number of subjects enrolled
    Chile: 14
    Country: Number of subjects enrolled
    Colombia: 12
    Country: Number of subjects enrolled
    Greece: 6
    Country: Number of subjects enrolled
    Italy: 2
    Country: Number of subjects enrolled
    Japan: 10
    Country: Number of subjects enrolled
    Mexico: 21
    Country: Number of subjects enrolled
    Poland: 14
    Country: Number of subjects enrolled
    Russian Federation: 2
    Country: Number of subjects enrolled
    Spain: 3
    Country: Number of subjects enrolled
    Switzerland: 5
    Country: Number of subjects enrolled
    Taiwan: 9
    Country: Number of subjects enrolled
    United States: 53
    Worldwide total number of subjects
    168
    EEA total number of subjects
    42
    Number of subjects enrolled per age group
    In utero
    0
    Preterm newborn - gestational age < 37 wk
    0
    Newborns (0-27 days)
    0
    Infants and toddlers (28 days-23 months)
    0
    Children (2-11 years)
    0
    Adolescents (12-17 years)
    0
    Adults (18-64 years)
    160
    From 65 to 84 years
    8
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants were enrolled at 73 centers in 13 countries (Bulgaria, Chile, Colombia, Greece, Italy, Japan, Mexico, Poland, Russian Federation, Spain, Switzerland, Taiwan, and the United States) between 06 May 2021 and 24 May 2023.

    Pre-assignment
    Screening details
    		 A total of 464 participants were screened, of which 168 participants were enrolled and received efavaleukin alfa.

    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

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 Placebo
    Arm description
    		 Participants received placebo matching efavaleukin alfa every two weeks (Q2W) through a subcutaneous (SC) injection for up to 52 weeks.
    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
    Placebo matching efavaleukin alfa Q2W for up to 52 weeks.

    Arm title
    		 Efavaleukin Alfa Low Dose
    Arm description
    		 Participants received low dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Efavaleukin Alfa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Low dose Q2W for up to 52 weeks.

    Arm title
    		 Efavaleukin Alfa Medium Dose
    Arm description
    		 Participants received medium dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Efavaleukin Alfa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    Medium dose Q2W for up to 52 weeks.

    Arm title
    		 Efavaleukin Alfa High Dose
    Arm description
    		 Participants received high dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Efavaleukin Alfa
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Solution for injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    High dose Q2W for up to 52 weeks.

    Number of subjects in period 1
    		Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Started
    41
    35
    34
    58
    Received Study Treatment
    41
    35
    34
    58
    Completed
    12
    9
    10
    10
    Not completed
    29
    26
    24
    48
         Adverse event, serious fatal
    1
    -
    -
    -
         Consent withdrawn by subject
    7
    10
    17
    15
         Decision by Sponsor
    21
    15
    7
    32
         Lost to follow-up
    -
    1
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo matching efavaleukin alfa every two weeks (Q2W) through a subcutaneous (SC) injection for up to 52 weeks.

    Reporting group title
    Efavaleukin Alfa Low Dose
    Reporting group description
    		 Participants received low dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.

    Reporting group title
    Efavaleukin Alfa Medium Dose
    Reporting group description
    		 Participants received medium dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.

    Reporting group title
    Efavaleukin Alfa High Dose
    Reporting group description
    		 Participants received high dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.

    Reporting group values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose Total
    Number of subjects
    		 41 35 34 58 168
    Age categorical
    Units: Subjects
        In utero
    		 0 0 0 0 0
        Preterm newborn infants (gestational age < 37 wks)
    		 0 0 0 0 0
        Newborns (0-27 days)
    		 0 0 0 0 0
        Infants and toddlers (28 days-23 months)
    		 0 0 0 0 0
        Children (2-11 years)
    		 0 0 0 0 0
        Adolescents (12-17 years)
    		 0 0 0 0 0
        Adults (18-64 years)
    		 39 31 33 57 160
        From 65-84 years
    		 2 4 1 1 8
        85 years and over
    		 0 0 0 0 0
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 48.1 ( 10.3 ) 46.1 ( 12.8 ) 40.3 ( 12.2 ) 42.3 ( 11.2 ) -
    Sex: Female, Male
    Units:
        Female
    		 38 31 33 56 158
        Male
    		 3 4 1 2 10
    Ethnicity (NIH/OMB)
    Units: Subjects
        Hispanic or Latino
    		 14 11 12 22 59
        Not Hispanic or Latino
    		 27 24 22 36 109
        Unknown or Not Reported
    		 0 0 0 0 0
    Race/Ethnicity, Customized
    Units: Subjects
        American Indian or Alaska Native
    		 4 2 3 5 14
        Asian
    		 6 2 5 6 19
        Black (or African American)
    		 5 8 1 9 23
        Multiple
    		 0 0 1 0 1
        White
    		 25 20 20 29 94
        Other
    		 1 3 4 9 17

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo matching efavaleukin alfa every two weeks (Q2W) through a subcutaneous (SC) injection for up to 52 weeks.

    Reporting group title
    Efavaleukin Alfa Low Dose
    Reporting group description
    		 Participants received low dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.

    Reporting group title
    Efavaleukin Alfa Medium Dose
    Reporting group description
    		 Participants received medium dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.

    Reporting group title
    Efavaleukin Alfa High Dose
    Reporting group description
    		 Participants received high dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.

    Primary: Number of Participants Who Achieved an SRI-4 Response at Week 52

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    End point title
    		 Number of Participants Who Achieved an SRI-4 Response at Week 52 [1]
    End point description
    A participant achieved an SRI-4 response if all the following criteria were met: - ≥ 4-point reduction from baseline in Hybrid Systemic Lupus Erythematosus Disease Activity Index (hSLEDAI) score (scale 0-105, with higher scores indicating more disease activity). - No new British-Isles Lupus Assessment Group (BILAG) A score and no > 1 new BILAG B organ domain scores compared with baseline. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present). - < 0.3-points deterioration from baseline in Physician Global Assessment (PGA) visual analogue (VAS) score (scale 0 to 3, with higher scores indicating more severe disease). Participants were considered non-responders for using more than protocol-permitted therapies. Full Analysis Set: Included all participants randomized in the study.
    End point type
    Primary
    End point timeframe
    Week 52
    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: No statistical analysis was planned for this endpoint.
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    15 [2]
    16 [3]
    17 [4]
    14 [5]
    Units: participants
    8
    4
    6
    5
    Notes
    [2] - Participants who completed visit by date of termination decision communication were included.
    [3] - Participants who completed visit by date of termination decision communication were included.
    [4] - Participants who completed visit by date of termination decision communication were included.
    [5] - Participants who completed visit by date of termination decision communication were included.
    No statistical analyses for this end point

    Secondary: Number of Participants Who Achieved a BILAG-based Composite Lupus Assessment (BICLA) Response at Week 52

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    End point title
    		 Number of Participants Who Achieved a BILAG-based Composite Lupus Assessment (BICLA) Response at Week 52
    End point description
    A participant achieved a BICLA response if all the following criteria were met: - At least 1 gradation of improvement in baseline BILAG domain scores in all body systems with moderate or severe disease activity at entry and no > 1 BILAG B domain scores compared with baseline. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present). - No worsening of the hSLEDAI score from baseline (scale 0-105, with higher scores indicating more disease activity). - < 0.3-points deterioration from baseline in PGA VAS (scale 0 to 3, with higher scores indicating more severe disease). - No initiation of non-protocol treatment. Full Analysis Set: Included all participants randomized in the study. Participants were considered non-responders for using more than protocol-permitted therapies.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    15 [6]
    16 [7]
    17 [8]
    14 [9]
    Units: participants
    6
    2
    4
    4
    Notes
    [6] - Participants who completed visit by date of termination decision communication were included.
    [7] - Participants who completed visit by date of termination decision communication were included.
    [8] - Participants who completed visit by date of termination decision communication were included.
    [9] - Participants who completed visit by date of termination decision communication were included.
    No statistical analyses for this end point

    Secondary: Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) Response at Week 52

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    End point title
    		 Number of Participants Who Achieved a Lupus Low Disease Activity State (LLDAS) Response at Week 52
    End point description
    A participant achieved an LLDAS response if all the following criteria were met: - hSLEDAI ≤ 4 (scale 0-105, higher scores indicating more disease activity) with no activity in major organ systems (renal, central nervous system, cardiopulmonary, vasculitis and fever) & no hemolytic anemia or gastrointestinal activity in BILAG. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active) to E (never present). - No new lupus disease activity compared with previous assessment defined as no new descriptor scores in hSLEDAI. - A score of < 1 in PGA VAS score (scale 0 to 3, with higher scores indicating more severe disease). - Current prednisolone dose ≤ 7.5 mg daily. - No increase or initiation of immunosuppressive drugs. Participants were considered non-responders for using more than protocol-permitted therapies.
    End point type
    Secondary
    End point timeframe
    Week 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    15 [10]
    16 [11]
    17 [12]
    14 [13]
    Units: participants
    2
    3
    3
    1
    Notes
    [10] - FAS: Participants who completed visit by date of termination decision communication were included.
    [11] - FAS: Participants who completed visit by date of termination decision communication were included.
    [12] - FAS: Participants who completed visit by date of termination decision communication were included.
    [13] - FAS: Participants who completed visit by date of termination decision communication were included.
    No statistical analyses for this end point

    Secondary: Number of Participants with a Reduction of Oral Corticosteroids (OCS) to ≤ 7.5 mg/day by Week 44 and Sustained Through Week 52 in Participants with a Baseline OCS Dose ≥ 10 mg/day

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    End point title
    		 Number of Participants with a Reduction of Oral Corticosteroids (OCS) to ≤ 7.5 mg/day by Week 44 and Sustained Through Week 52 in Participants with a Baseline OCS Dose ≥ 10 mg/day
    End point description
    Participants taking OCS could begin tapering OCS after the Week 12 assessment up to the Week 44 assessment with initiation of tapering based upon clinical judgement of the treating physician. The tapering schedule was at the discretion of the investigator but should not have been tapered more than 20% of the prior dose per week. Tapering OCS before Week 12 was not encouraged but may have been allowed based upon investigator’s judgement. Between Weeks 44 and 52, the OCS dosing must again have remained stable. Full Analysis Set: Included all participants randomized in the study. Only participants with a baseline OCS dose ≥ 10 mg/day and had the opportunity to complete the visit by the date of the study termination decision being communicated to sites were included.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    9
    9
    8
    7
    Units: participants
    0
    1
    2
    0
    No statistical analyses for this end point

    Secondary: Number of Participants Who Achieved a SRI-4 Response at Week 24

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    End point title
    		 Number of Participants Who Achieved a SRI-4 Response at Week 24
    End point description
    A participant achieved an SRI-4 response if all the following criteria were met: - ≥ 4-point reduction from baseline in hSLEDAI score (scale 0-105, with higher scores indicating more disease activity). - No new BILAG A score and no > 1 new BILAG B organ domain scores compared with baseline. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present). - < 0.3-points deterioration from baseline in PGA VAS score (scale 0 to 3, with higher scores indicating more severe disease). Participants were considered non-responders for using more than protocol-permitted therapies. Full Analysis Set: Included all participants randomized in the study. Only participants who had the opportunity to complete the visit by the date of the study termination decision being communicated to sites were included.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    34
    29
    31
    44
    Units: participants
    20
    13
    13
    21
    No statistical analyses for this end point

    Secondary: Number of Participants Who Achieved a BICLA Response at Week 24

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    End point title
    		 Number of Participants Who Achieved a BICLA Response at Week 24
    End point description
    A participant achieved a BICLA response if all the following criteria were met: - At least 1 gradation of improvement in baseline BILAG domain scores in all body systems with moderate or severe disease activity at entry and no > 1 BILAG B domain scores compared with baseline. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present). - No worsening of the hSLEDAI score from baseline (scale 0-105, with higher scores indicating more disease activity). - < 0.3-points deterioration from baseline in PGA VAS (scale 0 to 3, with higher scores indicating more severe disease). - No initiation of non-protocol treatment. Full Analysis Set: Included all participants randomized in the study.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    34 [14]
    29 [15]
    31 [16]
    44 [17]
    Units: participants
    17
    12
    5
    17
    Notes
    [14] - Participants who completed visit by date of termination decision communication were included.
    [15] - Participants who completed visit by date of termination decision communication were included.
    [16] - Participants who completed visit by date of termination decision communication were included.
    [17] - Participants who completed visit by date of termination decision communication were included.
    No statistical analyses for this end point

    Secondary: Number of Participants with a hSLEDAI Response at Week 24 and Week 52

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    End point title
    		 Number of Participants with a hSLEDAI Response at Week 24 and Week 52
    End point description
    The hSLEDAI is a global index that evaluates disease activity and includes both laboratory and clinical parameters. The score ranges from 0 to 105, with higher scores indicating more disease activity. A participant achieved a hSLEDAI response if there was a ≥ 4-point reduction in hSLEDAI from baseline. Full Analysis Set: Included all participants randomized in the study. Only participants who had the opportunity to complete the visit by the date of the study termination decision being communicated to sites were included.
    End point type
    Secondary
    End point timeframe
    Week 24 and Week 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    34 [18]
    29 [19]
    31 [20]
    44 [21]
    Units: participants
        Week 24
    23
    14
    13
    23
        Week 52
    8
    4
    7
    6
    Notes
    [18] - Week 52 N = 15
    [19] - Week 52 N = 16
    [20] - Week 52 N = 17
    [21] - Week 52 N = 14
    No statistical analyses for this end point

    Secondary: Number of Participants with an Improvement From Baseline in Tender and Swollen Joint Count ≥ 50% at Weeks 8, 12, 24, 36, and 52 in Participants with ≥ 6 Tender and Swollen Joints in Hands and Wrists

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    End point title
    		 Number of Participants with an Improvement From Baseline in Tender and Swollen Joint Count ≥ 50% at Weeks 8, 12, 24, 36, and 52 in Participants with ≥ 6 Tender and Swollen Joints in Hands and Wrists
    End point description
    The swollen and tender join count assessments were performed at the site by an experienced independent and blinded joint evaluator. Each joint in hands and wrists were scored for the simultaneous presence (1) or absence (0) of swelling and tenderness. Scores ranged from 0-28. A higher score indicates more severe disease. Full Analysis Set: Full Analysis Set: Included all participants randomized in the study. Only participants who had ≥ 6 tender and swollen joints involving hands and wrists at baseline and the opportunity to complete the visit by the date of the study termination decision being communicated to sites were included.
    End point type
    Secondary
    End point timeframe
    Weeks 8, 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    22 [22]
    16 [23]
    20 [24]
    27 [25]
    Units: participants
        Week 8
    16
    8
    8
    13
        Week 12
    16
    7
    7
    13
        Week 24
    13
    9
    9
    11
        Week 36
    11
    8
    8
    3
        Week 52
    2
    1
    7
    3
    Notes
    [22] - Week 12 N = 22 Week 24 N = 19 Week 36 N = 26 Week 52 N = 8
    [23] - Week 12 N = 14 Week 24 N = 13 Week 36 N = 13 Week 52 N = 7
    [24] - Week 12 N = 19 Week 24 N = 18 Week 36 N = 17 Week 52 N = 12
    [25] - Week 12 N = 25 Week 24 N = 20 Week 36 N = 8 Week 52 N = 4
    No statistical analyses for this end point

    Secondary: Number of Participants with an Improvement from Baseline in Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Activity Score ≥ 50% at Week 8, 12, 24, 36, and 52 in Participants with a CLASI Activity Score ≥ 8 at Baseline

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    End point title
    		 Number of Participants with an Improvement from Baseline in Cutaneous Lupus Erythematosus Area and Severity Index (CLASI) Activity Score ≥ 50% at Week 8, 12, 24, 36, and 52 in Participants with a CLASI Activity Score ≥ 8 at Baseline
    End point description
    The CLASI consists of 2 scores, the first summarizes the activity of the disease while the second is a measure of the damage done by the disease. Activity is scored based on erythema, scale/hyperkeratosis, mucous membrane involvement, acute hair loss and non-scarring alopecia. The total score ranges from 0-70, with higher scores indicating more severe disease. Full Analysis Set: Included all participants randomized in the study. Only participants who had a CLASI activity score ≥ 8 at baseline and the opportunity to complete the visit by the date of the study termination decision being communicated to sites were included.
    End point type
    Secondary
    End point timeframe
    Weeks 8, 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    18 [26]
    8 [27]
    14 [28]
    17 [29]
    Units: participants
        Week 8
    2
    1
    5
    9
        Week 12
    6
    2
    5
    7
        Week 24
    4
    4
    5
    6
        Week 36
    5
    5
    4
    5
        Week 52
    3
    0
    3
    3
    Notes
    [26] - Week 12 N = 18 Week 24 N = 16 Week 36 N = 11 Week 52 N = 6
    [27] - Week 12 N = 8 Week 24 N = 8 Week 36 N = 8 Week 52 N = 4
    [28] - Week 12 N = 12 Week 24 N = 12 Week 36 N = 10 Week 52 N = 9
    [29] - Week 12 N = 17 Week 24 N = 12 Week 36 N = 8 Week 52 N = 6
    No statistical analyses for this end point

    Secondary: Change from Baseline in Fatigue Standardized Score Using the Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a Instrument at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in Fatigue Standardized Score Using the Patient-Reported Outcome Measurement Information System (PROMIS) Fatigue Short Form (SF) 7a Instrument at Week 12, 24, 36 and 52
    End point description
    The PROMIS Fatigue SF 7a assesses the experience of fatigue as well as its impact on physical, mental and social activities. The score ranges from 7 to 35, with higher scores indicating more fatigue. A negative change from baseline indicates a reduction in fatigue. Efficacy data collected after the study termination decision date were censored and excluded from analyses for that particular visit. Full Analysis Set: Included all participants randomized in the study and had observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    37 [30]
    27 [31]
    24 [32]
    46 [33]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    -4.12 ( 7.91 )
    -5.52 ( 5.04 )
    -5.78 ( 8.39 )
    -4.74 ( 9.60 )
        Week 24
    -5.24 ( 8.05 )
    -4.95 ( 8.72 )
    -4.62 ( 8.03 )
    -7.17 ( 7.01 )
        Week 36
    -3.20 ( 10.70 )
    -5.77 ( 7.09 )
    -5.32 ( 8.90 )
    -5.34 ( 10.61 )
        Week 52
    -3.29 ( 7.64 )
    -8.44 ( 4.21 )
    -6.97 ( 14.20 )
    -5.47 ( 13.97 )
    Notes
    [30] - Week 24 N = 32 Week 36 N = 23 Week 52 N = 8
    [31] - Week 24 N = 24 Week 36 N = 21 Week 52 N = 7
    [32] - Week 24 N = 22 Week 36 N = 14 Week 52 N = 11
    [33] - Week 24 N = 23 Week 36 N = 19 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Annualized Flare Rate Over 52 Weeks

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    End point title
    		 Annualized Flare Rate Over 52 Weeks
    End point description
    A flare was defined as a BILAG score designation of “worse” or “new” resulting in a B score in ≥ 2 organs or an A score in ≥ 1 organ. The BILAG index evaluates disease activity in 9 separate organ systems. Each of the organ systems are allocated an alphabetical score of A (most active), B (moderate activity), C (minor activity), D (stable) or E (never present). The annualized flare rate was calculated as the number of flares divided by the flare exposure time. Full Analysis Set: Included all participants randomized in the study.
    End point type
    Secondary
    End point timeframe
    Up to 52 weeks
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    41
    35
    34
    58
    Units: Ratio
        number (not applicable)
    0.3
    0.5
    0.7
    0.4
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Physical Component Score of the Medical Outcomes Short Form-36 Questionnaire Version 2 (SF-36V2) at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Physical Component Score of the Medical Outcomes Short Form-36 Questionnaire Version 2 (SF-36V2) at Week 12, 24, 36 and 52
    End point description
    The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: All randomized participants with observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    37 [34]
    27 [35]
    24 [36]
    46 [37]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    4.349 ( 7.526 )
    6.016 ( 7.854 )
    6.450 ( 6.701 )
    2.615 ( 7.622 )
        Week 24
    6.709 ( 7.520 )
    5.544 ( 7.624 )
    4.726 ( 7.058 )
    5.136 ( 8.351 )
        Week 36
    5.391 ( 9.040 )
    6.576 ( 6.331 )
    7.524 ( 8.988 )
    3.648 ( 8.269 )
        Week 52
    3.678 ( 2.958 )
    6.206 ( 4.144 )
    8.724 ( 9.159 )
    6.252 ( 12.226 )
    Notes
    [34] - Week 24 N = 32 Week 36 N = 23 Week 52 N = 8
    [35] - Week 24 N = 24 Week 36 N = 21 Week 52 N = 7
    [36] - Week 24 N = 22 Week 36 N = 14 Week 52 N = 11
    [37] - Week 24 N = 33 Week 36 N = 19 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Mental Component Score of the SF-36V2 at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Mental Component Score of the SF-36V2 at Week 12, 24, 36 and 52
    End point description
    The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: All randomized participants with observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    37 [38]
    27 [39]
    24 [40]
    46 [41]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    5.079 ( 11.395 )
    0.080 ( 10.789 )
    3.087 ( 11.651 )
    1.867 ( 9.092 )
        Week 24
    6.510 ( 12.498 )
    0.498 ( 10.902 )
    1.585 ( 9.032 )
    3.959 ( 9.220 )
        Week 36
    5.587 ( 14.482 )
    -0.118 ( 10.560 )
    3.129 ( 12.141 )
    0.564 ( 13.586 )
        Week 52
    4.781 ( 8.485 )
    1.106 ( 9.633 )
    -1.813 ( 16.608 )
    -2.163 ( 13.023 )
    Notes
    [38] - Week 24 N = 32 Week 36 N = 23 Week 52 N = 8
    [39] - Week 24 N = 24 Week 36 N = 21 Week 52 N = 7
    [40] - Week 24 N = 22 Week 36 N = 14 Week 52 N = 11
    [41] - Week 24 N = 33 Week 36 N = 19 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Physical Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Physical Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52
    End point description
    The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: All randomized participants with observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    37 [42]
    27 [43]
    24 [44]
    46 [45]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    14.460 ( 21.532 )
    7.963 ( 15.888 )
    14.165 ( 22.489 )
    5.761 ( 22.034 )
        Week 24
    20.469 ( 23.048 )
    6.876 ( 20.998 )
    14.545 ( 21.816 )
    10.607 ( 24.036 )
        Week 36
    13.477 ( 26.261 )
    10.713 ( 20.078 )
    16.786 ( 29.910 )
    9.736 ( 29.603 )
        Week 52
    8.750 ( 14.083 )
    15.714 ( 13.973 )
    18.183 ( 28.919 )
    15.001 ( 31.622 )
    Notes
    [42] - Week 24 N = 32 Week 36 N = 23 Week 52 N = 8
    [43] - Week 24 N = 24 Week 36 N = 21 Week 52 N = 7
    [44] - Week 24 N = 22 Week 36 N = 14 Week 52 N = 11
    [45] - Week 24 N = 33 Week 36 N = 19 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Social Role Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Social Role Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52
    End point description
    The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: All randomized participants with observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    37 [46]
    27 [47]
    24 [48]
    46 [49]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    15.54 ( 29.82 )
    9.72 ( 22.29 )
    7.81 ( 26.79 )
    2.17 ( 21.46 )
        Week 24
    21.88 ( 33.15 )
    13.02 ( 23.16 )
    3.98 ( 24.52 )
    9.47 ( 25.39 )
        Week 36
    13.04 ( 38.71 )
    8.93 ( 26.26 )
    16.96 ( 32.75 )
    1.32 ( 29.14 )
        Week 52
    10.94 ( 28.69 )
    21.43 ( 20.04 )
    5.68 ( 35.95 )
    -1.25 ( 36.54 )
    Notes
    [46] - Week 24 N = 32 Week 36 N = 23 Week 52 N = 8
    [47] - Week 24 N = 24 Week 36 N = 21 Week 52 N = 7
    [48] - Week 24 N = 22 Week 36 N = 14 Week 52 N = 11
    [49] - Week 24 N = 33 Week 36 N = 19 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Physical Role Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Physical Role Functioning Domain Score of the SF-36V2 at Week 12, 24, 36 and 52
    End point description
    The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: All randomized participants with observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    37 [50]
    27 [51]
    24 [52]
    46 [53]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    12.838 ( 24.516 )
    15.509 ( 26.081 )
    13.802 ( 22.571 )
    6.929 ( 21.899 )
        Week 24
    18.359 ( 22.221 )
    14.323 ( 26.290 )
    9.091 ( 20.479 )
    15.909 ( 23.804 )
        Week 36
    11.685 ( 26.935 )
    14.881 ( 26.917 )
    15.179 ( 24.966 )
    7.895 ( 29.377 )
        Week 52
    11.719 ( 15.468 )
    18.750 ( 14.878 )
    19.318 ( 25.381 )
    6.875 ( 35.041 )
    Notes
    [50] - Week 24 N = 32 Week 36 N = 23 Week 52 N = 8
    [51] - Week 24 N = 24 Week 36 N = 21 Week 52 N = 7
    [52] - Week 24 N = 22 Week 36 N = 14 Week 52 N = 11
    [53] - Week 24 N = 33 Week 36 N = 19 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Bodily Pain Domain Score of the SF-36V2 at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Bodily Pain Domain Score of the SF-36V2 at Week 12, 24, 36 and 52
    End point description
    The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: All randomized participants with observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    37 [54]
    27 [55]
    24 [56]
    46 [57]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    13.6 ( 25.1 )
    13.7 ( 23.0 )
    18.8 ( 22.6 )
    10.2 ( 23.0 )
        Week 24
    20.4 ( 26.6 )
    14.3 ( 21.5 )
    13.8 ( 23.1 )
    18.4 ( 26.6 )
        Week 36
    22.0 ( 26.3 )
    19.5 ( 20.7 )
    24.6 ( 33.0 )
    15.4 ( 23.3 )
        Week 52
    10.4 ( 7.7 )
    11.1 ( 17.1 )
    17.9 ( 29.7 )
    16.7 ( 37.1 )
    Notes
    [54] - Week 24 N = 32 Week 36 N = 23 Week 52 N = 8
    [55] - Week 24 N = 24 Week 36 N = 21 Week 52 N = 7
    [56] - Week 24 N = 22 Week 36 N = 14 Week 52 N = 11
    [57] - Week 24 N = 33 Week 36 N = 19 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Mental Health Domain Score of the SF-36V2 at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Mental Health Domain Score of the SF-36V2 at Week 12, 24, 36 and 52
    End point description
    The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: All randomized participants with observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    37 [58]
    27 [59]
    24 [60]
    46 [61]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    8.2 ( 19.3 )
    1.3 ( 18.7 )
    9.4 ( 22.5 )
    5.2 ( 17.4 )
        Week 24
    12.0 ( 21.2 )
    3.8 ( 22.4 )
    7.5 ( 19.6 )
    9.4 ( 17.8 )
        Week 36
    9.6 ( 23.2 )
    -1.9 ( 18.4 )
    6.4 ( 22.6 )
    6.6 ( 24.3 )
        Week 52
    7.5 ( 16.7 )
    -2.1 ( 22.7 )
    0.5 ( 33.0 )
    1.5 ( 28.5 )
    Notes
    [58] - Week 24 N = 32 Week 36 N = 23 Week 52 N = 8
    [59] - Week 24 N = 24 Week 36 N = 21 Week 52 N = 7
    [60] - Week 24 N = 22 Week 36 N = 14 Week 52 N = 11
    [61] - Week 24 N = 33 Week 36 N = 19 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Emotional Role Domain Score of the SF-36V2 at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Emotional Role Domain Score of the SF-36V2 at Week 12, 24, 36 and 52
    End point description
    The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: All randomized participants with observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    37 [62]
    27 [63]
    24 [64]
    46 [65]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    13.964 ( 27.781 )
    -3.704 ( 23.036 )
    4.514 ( 26.236 )
    3.804 ( 23.812 )
        Week 24
    16.926 ( 29.820 )
    -5.208 ( 23.417 )
    3.031 ( 23.223 )
    8.333 ( 25.769 )
        Week 36
    17.028 ( 35.129 )
    5.952 ( 24.029 )
    6.548 ( 29.810 )
    -0.440 ( 33.847 )
        Week 52
    9.375 ( 18.057 )
    8.334 ( 14.433 )
    -2.273 ( 33.144 )
    -9.168 ( 32.972 )
    Notes
    [62] - Week 24 N = 32 Week 36 N = 23 Week 52 N = 8
    [63] - Week 24 N = 24 Week 36 N = 21 Week 52 N = 7
    [64] - Week 24 N = 22 Week 36 N = 14 Week 52 N = 11
    [65] - Week 24 N = 33 Week 36 N = 19 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Vitality Domain Score of the SF-36V2 at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Vitality Domain Score of the SF-36V2 at Week 12, 24, 36 and 52
    End point description
    The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: All randomized participants with observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    37 [66]
    27 [67]
    24 [68]
    46 [69]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    10.642 ( 20.405 )
    12.037 ( 21.225 )
    15.365 ( 23.384 )
    7.609 ( 20.536 )
        Week 24
    13.477 ( 23.283 )
    8.333 ( 23.936 )
    8.523 ( 20.912 )
    12.879 ( 19.884 )
        Week 36
    11.685 ( 26.935 )
    6.548 ( 19.811 )
    14.732 ( 23.718 )
    5.592 ( 22.812 )
        Week 52
    15.625 ( 19.480 )
    4.464 ( 22.160 )
    9.659 ( 28.141 )
    13.750 ( 26.484 )
    Notes
    [66] - Week 24 N = 32 Week 36 N = 23 Week 52 N = 8
    [67] - Week 24 N = 24 Week 36 N = 21 Week 52 N = 7
    [68] - Week 24 N = 22 Week 36 N = 14 Week 52 N = 11
    [69] - Week 24 N = 33 Week 36 N = 19 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the General Health Domain Score of the SF-36V2 at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the General Health Domain Score of the SF-36V2 at Week 12, 24, 36 and 52
    End point description
    The SF-36v2 contains 36 items and yields assessments of 8 domains of health-related quality of life: 1) Limitations in physical activities because of health problems 2) Limitations in social activities because of physical or emotional problems 3) Limitations in usual role activities because of physical health problems 4) Bodily pain 5) General mental health (psychological distress and well-being) 6) Limitations in usual role activities because of emotional problems 7) Vitality (energy and fatigue) 8) General health perceptions The scores from the 8 domains will be evaluated independently and aggregated into 2 norm-based summary component measures of physical and mental health. The recall period is the past 7 days. The score ranges from 0-100 for the summary components and for each domain, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: All randomized participants with observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    37 [70]
    27 [71]
    24 [72]
    46 [73]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    5.2 ( 15.8 )
    6.1 ( 17.7 )
    10.6 ( 15.9 )
    2.6 ( 16.2 )
        Week 24
    9.2 ( 17.7 )
    6.2 ( 19.0 )
    3.8 ( 16.2 )
    5.6 ( 15.3 )
        Week 36
    10.7 ( 16.1 )
    5.6 ( 14.9 )
    7.2 ( 17.2 )
    -2.1 ( 16.6 )
        Week 52
    7.5 ( 8.9 )
    2.4 ( 5.9 )
    6.7 ( 19.0 )
    0.5 ( 29.5 )
    Notes
    [70] - Week 24 N = 32 Week 36 N = 23 Week 52 N = 8
    [71] - Week 24 N = 24 Week 36 N = 21 Week 52 N = 7
    [72] - Week 24 N = 22 Week 36 N = 14 Week 52 N = 11
    [73] - Week 24 N = 33 Week 36 N = 19 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Physical Health Domain Score of the Lupus Quality of Life (LupusQoL) at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Physical Health Domain Score of the Lupus Quality of Life (LupusQoL) at Week 12, 24, 36 and 52
    End point description
    The LupusQoL is a systemic lupus erythematosus (SLE)-specific health-related QoL instrument and consists of 8 domains: 1) Physical health. 2) Pain. 3) Planning. 4) Intimate relationships. 5) Burden to others. 6) Emotional health. 7) Body image. 8) Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: Included all participants randomized in the study and had observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    34 [74]
    26 [75]
    22 [76]
    42 [77]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    13.7868 ( 20.5586 )
    12.6202 ( 18.9259 )
    13.7784 ( 18.3909 )
    11.5327 ( 22.3595 )
        Week 24
    15.5172 ( 23.7770 )
    9.5109 ( 25.1501 )
    15.4688 ( 17.7205 )
    13.8542 ( 25.3834 )
        Week 36
    11.3636 ( 20.6738 )
    13.4375 ( 20.2549 )
    18.7500 ( 24.4404 )
    5.7292 ( 24.3304 )
        Week 52
    9.3750 ( 11.8114 )
    20.8333 ( 21.1640 )
    15.6250 ( 27.0994 )
    10.6250 ( 29.5437 )
    Notes
    [74] - Week 24 N = 29 Week 36 N = 22 Week 52 N = 8
    [75] - Week 24 N = 23 Week 36 N = 20 Week 52 N = 6
    [76] - Week 24 N = 20 Week 36 N = 13 Week 52 N = 11
    [77] - Week 24 N = 30 Week 36 N = 18 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Pain Domain Score of the LupusQoL at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Pain Domain Score of the LupusQoL at Week 12, 24, 36 and 52
    End point description
    The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1) Physical health. 2) Pain. 3) Planning. 4) Intimate relationships. 5) Burden to others. 6) Emotional health. 7) Body image. 8) Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: Included all participants randomized in the study and had observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    34 [78]
    25 [79]
    22 [80]
    42 [81]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    17.892 ( 22.392 )
    16.333 ( 23.873 )
    17.424 ( 23.975 )
    13.294 ( 24.072 )
        Week 24
    21.264 ( 28.311 )
    14.773 ( 25.708 )
    11.667 ( 23.939 )
    11.944 ( 28.339 )
        Week 36
    12.879 ( 25.423 )
    17.105 ( 21.956 )
    16.667 ( 30.238 )
    5.556 ( 28.296 )
        Week 52
    14.583 ( 18.767 )
    16.667 ( 8.333 )
    8.333 ( 27.639 )
    11.667 ( 27.833 )
    Notes
    [78] - Week 24 N = 29 Week 36 N = 22 Week 52 N = 8
    [79] - Week 24 N = 22 Week 36 N = 19 Week 52 N = 5
    [80] - Week 24 N = 20 Week 36 N = 13 Week 52 N = 11
    [81] - Week 24 N = 30 Week 36 N = 18 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Planning Domain Score of the LupusQoL at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Planning Domain Score of the LupusQoL at Week 12, 24, 36 and 52
    End point description
    The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1) Physical health. 2) Pain. 3) Planning. 4) Intimate relationships. 5) Burden to others. 6) Emotional health. 7) Body image. 8) Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: Included all participants randomized in the study and had observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    34 [82]
    25 [83]
    22 [84]
    42 [85]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    9.804 ( 23.071 )
    17.000 ( 23.259 )
    13.636 ( 23.925 )
    7.143 ( 23.825 )
        Week 24
    11.494 ( 29.915 )
    14.015 ( 28.334 )
    15.833 ( 22.926 )
    14.722 ( 22.391 )
        Week 36
    12.500 ( 30.834 )
    9.211 ( 23.553 )
    13.462 ( 23.457 )
    5.093 ( 29.861 )
        Week 52
    15.625 ( 29.693 )
    15.000 ( 18.066 )
    10.606 ( 25.025 )
    12.500 ( 27.287 )
    Notes
    [82] - Week 24 N = 29 Week 36 N = 22 Week 52 N = 8
    [83] - Week 24 N = 22 Week 36 N = 19 Week 52 N = 5
    [84] - Week 24 N = 20 Week 36 N = 13 Week 52 N = 11
    [85] - Week 24 N = 30 Week 36 N = 18 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Intimate Relationship Domain Score of the LupusQoL at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Intimate Relationship Domain Score of the LupusQoL at Week 12, 24, 36 and 52
    End point description
    The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1) Physical health. 2) Pain. 3) Planning. 4) Intimate relationships. 5) Burden to others. 6) Emotional health. 7) Body image. 8) Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: Included all participants randomized in the study and had observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    21 [86]
    18 [87]
    16 [88]
    29 [89]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    17.26 ( 27.52 )
    3.47 ( 22.61 )
    14.29 ( 35.65 )
    11.21 ( 31.04 )
        Week 24
    10.83 ( 35.00 )
    1.56 ( 26.57 )
    19.53 ( 28.86 )
    13.16 ( 29.01 )
        Week 36
    10.94 ( 33.81 )
    -1.67 ( 30.20 )
    11.36 ( 30.34 )
    12.50 ( 15.99 )
        Week 52
    6.25 ( 51.08 )
    0.00 ( 8.84 )
    9.38 ( 35.83 )
    8.33 ( 31.29 )
    Notes
    [86] - Week 24 N = 15 Week 36 N = 16 Week 52 N = 6
    [87] - Week 24 N = 16 Week 36 N = 15 Week 52 N = 5
    [88] - Week 24 N = 16 Week 36 N = 11 Week 52 N = 8
    [89] - Week 24 N = 19 Week 36 N = 12 Week 52 N = 6
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Burden to Others Domain Score of the LupusQoL at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Burden to Others Domain Score of the LupusQoL at Week 12, 24, 36 and 52
    End point description
    The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1) Physical health. 2) Pain. 3) Planning. 4) Intimate relationships. 5) Burden to others. 6) Emotional health. 7) Body image. 8) Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: Included all participants randomized in the study and had observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    34 [90]
    25 [91]
    22 [92]
    42 [93]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    10.784 ( 28.169 )
    14.333 ( 17.099 )
    17.803 ( 30.134 )
    6.944 ( 29.673 )
        Week 24
    20.115 ( 31.459 )
    5.682 ( 24.719 )
    12.083 ( 23.798 )
    12.778 ( 29.093 )
        Week 36
    14.773 ( 30.530 )
    10.088 ( 22.149 )
    21.795 ( 22.448 )
    18.519 ( 26.438 )
        Week 52
    16.667 ( 22.713 )
    38.333 ( 19.185 )
    21.212 ( 23.677 )
    18.333 ( 28.273 )
    Notes
    [90] - Week 24 N = 29 Week 36 N = 22 Week 52 N = 8
    [91] - Week 24 N = 22 Week 36 N = 19 Week 52 N = 5
    [92] - Week 24 N = 20 Week 36 N = 13 Week 52 N = 11
    [93] - Week 24 N = 30 Week 36 N = 18 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Emotional Health Domain Score of the LupusQoL at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Emotional Health Domain Score of the LupusQoL at Week 12, 24, 36 and 52
    End point description
    The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1) Physical health. 2) Pain. 3) Planning. 4) Intimate relationships. 5) Burden to others. 6) Emotional health. 7) Body image. 8) Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: Included all participants randomized in the study and had observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    34 [94]
    25 [95]
    22 [96]
    42 [97]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    9.681 ( 21.729 )
    10.667 ( 19.021 )
    14.962 ( 28.425 )
    5.258 ( 21.465 )
        Week 24
    13.218 ( 26.495 )
    7.765 ( 19.974 )
    11.458 ( 20.894 )
    9.722 ( 21.283 )
        Week 36
    10.038 ( 25.994 )
    6.798 ( 18.799 )
    20.192 ( 24.641 )
    3.704 ( 30.178 )
        Week 52
    4.167 ( 20.534 )
    13.333 ( 21.123 )
    15.530 ( 27.518 )
    -5.000 ( 25.595 )
    Notes
    [94] - Week 24 N = 29 Week 36 N = 22 Week 52 N = 8
    [95] - Week 24 N = 22 Week 36 N = 19 Week 52 N = 5
    [96] - Week 24 N = 20 Week 36 N = 13 Week 52 N = 11
    [97] - Week 24 N = 30 Week 36 N = 18 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Body Image Domain Score of the LupusQoL at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Body Image Domain Score of the LupusQoL at Week 12, 24, 36 and 52
    End point description
    The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1) Physical health. 2) Pain. 3) Planning. 4) Intimate relationships. 5) Burden to others. 6) Emotional health. 7) Body image. 8) Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: Included all participants randomized in the study and had observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    34 [98]
    25 [99]
    22 [100]
    42 [101]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    9.6 ( 26.5 )
    9.0 ( 18.7 )
    4.1 ( 34.0 )
    4.6 ( 26.6 )
        Week 24
    11.6 ( 30.6 )
    2.3 ( 25.5 )
    3.0 ( 28.2 )
    5.2 ( 29.6 )
        Week 36
    6.1 ( 25.6 )
    14.7 ( 21.4 )
    18.8 ( 41.2 )
    6.1 ( 28.0 )
        Week 52
    12.5 ( 33.3 )
    17.0 ( 22.5 )
    7.7 ( 37.4 )
    5.5 ( 36.6 )
    Notes
    [98] - Week 24 N = 29 Week 36 N = 22 Week 52 N = 8
    [99] - Week 24 N = 22 Week 36 N = 19 Week 52 N = 5
    [100] - Week 24 N = 20 Week 36 N = 13 Week 52 N = 11
    [101] - Week 24 N = 30 Week 36 N = 18 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Change from Baseline in the Fatigue Domain Score of the LupusQoL at Week 12, 24, 36 and 52

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    End point title
    		 Change from Baseline in the Fatigue Domain Score of the LupusQoL at Week 12, 24, 36 and 52
    End point description
    The LupusQoL is a SLE-specific health-related QoL instrument and consists of 8 domains: 1) Physical health. 2) Pain. 3) Planning. 4) Intimate relationships. 5) Burden to others. 6) Emotional health. 7) Body image. 8) Fatigue. The score for each domain ranges from 0-100, with higher scores indicating better outcomes. A positive change from baseline indicates an improvement in outcomes. Full Analysis Set: Included all participants randomized in the study and had observed data.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 12, 24, 36 and 52
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    34 [102]
    25 [103]
    22 [104]
    42 [105]
    Units: score on a scale
    arithmetic mean (standard deviation)
        Week 12
    8.456 ( 23.329 )
    9.750 ( 15.104 )
    15.909 ( 21.368 )
    8.185 ( 21.273 )
        Week 24
    10.776 ( 24.600 )
    7.670 ( 23.059 )
    13.750 ( 20.135 )
    13.542 ( 20.108 )
        Week 36
    5.966 ( 29.345 )
    10.526 ( 17.561 )
    12.019 ( 26.695 )
    4.514 ( 23.853 )
        Week 52
    10.938 ( 15.580 )
    25.000 ( 4.419 )
    15.341 ( 26.274 )
    16.250 ( 28.596 )
    Notes
    [102] - Week 24 N = 29 Week 36 N = 22 Week 52 N = 8
    [103] - Week 24 N = 22 Week 36 N = 19 Week 52 N = 5
    [104] - Week 24 N = 20 Week 36 N = 13 Week 52 N = 11
    [105] - Week 24 N = 30 Week 36 N = 18 Week 52 N = 10
    No statistical analyses for this end point

    Secondary: Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)

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    End point title
    		 Number of Participants Who Experienced a Treatment-emergent Adverse Event (TEAE)
    End point description
    A TEAE was defined as any untoward medical occurrence irrespective of a causal relationship with the study treatment and had emerged or worsened during treatment. A serious TEAE was defined as any untoward medical occurrence that, met at least 1 of the following criteria: - Resulted in death (fatal). - Was immediately life-threatening. - Required in-patient hospitalization or prolongation of existing hospitalization. - Resulted in persistent or significant disability/incapacity. - Was a congenital anomaly/birth defect. - Was any other medically important serious event. Clinically significant changes from baseline in laboratory values and vital signs were also recorded as TEAEs. Safety Analysis Set: All randomized participants who received at least 1 dose of investigational product. After randomization, 1 participant received more than their planned medium dose of efavaleukin alfa in error, therefore the participant is also counted in the efavaleukin alfa high dose arm.
    End point type
    Secondary
    End point timeframe
    Day 1 to Week 56
    End point values
    		 Placebo Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    41
    35
    33
    58 [106]
    Units: participants
        TEAE
    29
    29
    33
    55
        Serious TEAE
    4
    3
    4
    3
    Notes
    [106] - N = 59
    No statistical analyses for this end point

    Secondary: Serum Efavaleukin Alfa Concentrations by Timepoint

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    End point title
    		 Serum Efavaleukin Alfa Concentrations by Timepoint [107]
    End point description
    Serum efavaleukin alfa concentrations by timepoint after multiple dose subcutaneous administration of efavaleukin alfa to participants with active systemic lupus erythematosus. Lower limit of quantification= 0.100 ng/mL. The PK Concentration Analysis Set is defined as the subset of participants in the Safety Analysis Set who had at least 1 evaluable serum concentration (including results below the level of detection) of investigational product. PK concentration data will be analyzed according to the actual treatment received.
    End point type
    Secondary
    End point timeframe
    Day 1: 6-24 and 48-96 hrs, Day 29, Day 43: 6-24 and 48-96 hrs, Day 85, Day 169, Day 253, Day 309, and Day 365
    Notes
    [107] - The end point is not reporting statistics for all the arms in the baseline period. It is expected all the baseline period arms will be reported on when providing values for an end point on the baseline period.
    Justification: Endpoint is only applicable to participants receiving Efavaleukin Alfa.
    End point values
    		 Efavaleukin Alfa Low Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa High Dose
    Number of subjects analysed
    34
    30
    53
    Units: ng/mL
    arithmetic mean (standard error)
        Day 1: 6-24 hrs n= 34, 29, 53
    5.46 ( 5.18 )
    12.8 ( 12.3 )
    27.4 ( 25.7 )
        Day 1: 48-96 hrs n= 34, 30, 49
    2.34 ( 2.52 )
    5.93 ( 6.45 )
    21.8 ( 30.5 )
        Day 29 n= 26, 24, 39
    0.0201 ( 0.0649 )
    0.0179 ( 0.0496 )
    0.0699 ( 0.173 )
        Day 43: 6-24 hrs n= 21, 21, 39
    4.34 ( 5.55 )
    13.9 ( 11.7 )
    25.0 ( 22.6 )
        Day 43: 48-96 hrs n= 23, 21, 41
    2.80 ( 4.39 )
    12.7 ( 17.2 )
    18.1 ( 19.0 )
        Day 85 n= 15, 17, 27
    0.0577 ( 0.223 )
    0.00712 ( 0.0293 )
    0.191 ( 0.316 )
        Day 169 n= 14, 12, 17
    0.349 ( 1.10 )
    0.0588 ( 0.133 )
    0.140 ( 0.178 )
        Day 253 n= 18, 7, 11
    0.530 ( 1.48 )
    0.155 ( 0.221 )
    0.458 ( 0.71 )
        Day 309 n= 9, 9, 3
    0.252 ( 0.502 )
    0.0558 ( 0.167 )
    0.308 ( 0.533 )
        Day 365 n= 5, 4, 3
    0.00 ( 0.00 )
    0.00 ( 0.00 )
    0.136 ( 0.236 )
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    All-cause mortality: From enrollment until the end of study; median (min, max) time on study was 38.23 (0.28, 62.93) weeks. Serious TEAEs and other TEAEs: Day 1 to Week 56.
    Adverse event reporting additional description
    All-cause mortality reported for all enrolled participants. Treatment-emergent SAEs/TEAEs reported for participants who received at least one dose of study drug. After randomization, 1 participant received more than planned medium dose of efavaleukin alfa in error, therefore the participant is also counted in the efavaleukin alfa high dose arm.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    26.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants received placebo matching efavaleukin alfa Q2W through a SC injection for up to 52 weeks.

    Reporting group title
    Efavaleukin alfa High Dose
    Reporting group description
    		 Participants received high dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.

    Reporting group title
    Efavaleukin Alfa Medium Dose
    Reporting group description
    		 Participants received medium dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.

    Reporting group title
    Efavaleukin Alfa Low Dose
    Reporting group description
    		 Participants received low dose efavaleukin alfa Q2W through a SC injection for up to 52 weeks.

    Serious adverse events
    		 Placebo Efavaleukin alfa High Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa Low Dose
    Total subjects affected by serious adverse events
         subjects affected / exposed
    4 / 41 (9.76%)
    3 / 59 (5.08%)
    4 / 33 (12.12%)
    3 / 35 (8.57%)
         number of deaths (all causes)
    1
    0
    0
    0
         number of deaths resulting from adverse events
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Anal squamous cell carcinoma
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    0 / 33 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Contusion
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 59 (1.69%)
    0 / 33 (0.00%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Transient ischaemic attack
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 59 (0.00%)
    0 / 33 (0.00%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Stroke in evolution
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 59 (1.69%)
    0 / 33 (0.00%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Headache
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    0 / 33 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Brain stem infarction
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 59 (1.69%)
    0 / 33 (0.00%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Pyrexia
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 59 (0.00%)
    0 / 33 (0.00%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Colitis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 59 (0.00%)
    0 / 33 (0.00%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary alveolar haemorrhage
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    1 / 33 (3.03%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Pulmonary hypertension
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    1 / 33 (3.03%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Arthritis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    1 / 33 (3.03%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Sepsis
         subjects affected / exposed
    2 / 41 (4.88%)
    1 / 59 (1.69%)
    0 / 33 (0.00%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    0 / 33 (0.00%)
    1 / 35 (2.86%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    COVID-19
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    1 / 33 (3.03%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Bartholin's abscess
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    1 / 33 (3.03%)
    0 / 35 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Efavaleukin alfa High Dose Efavaleukin Alfa Medium Dose Efavaleukin Alfa Low Dose
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    18 / 41 (43.90%)
    48 / 59 (81.36%)
    33 / 33 (100.00%)
    27 / 35 (77.14%)
    Nervous system disorders
    Tension headache
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 59 (0.00%)
    0 / 33 (0.00%)
    3 / 35 (8.57%)
         occurrences all number
    2
    0
    0
    4
    Headache
         subjects affected / exposed
    4 / 41 (9.76%)
    5 / 59 (8.47%)
    5 / 33 (15.15%)
    4 / 35 (11.43%)
         occurrences all number
    5
    6
    9
    4
    Blood and lymphatic system disorders
    Lymphadenopathy
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 59 (3.39%)
    0 / 33 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    1
    2
    0
    5
    General disorders and administration site conditions
    Administration site inflammation
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    0 / 33 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    0
    0
    8
    Chest discomfort
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    2 / 33 (6.06%)
    0 / 35 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Injection site discolouration
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 59 (1.69%)
    3 / 33 (9.09%)
    0 / 35 (0.00%)
         occurrences all number
    0
    2
    7
    0
    Pain
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 59 (5.08%)
    0 / 33 (0.00%)
    0 / 35 (0.00%)
         occurrences all number
    1
    3
    0
    0
    Injection site inflammation
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 59 (1.69%)
    2 / 33 (6.06%)
    0 / 35 (0.00%)
         occurrences all number
    0
    43
    23
    0
    Injection site oedema
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 59 (5.08%)
    0 / 33 (0.00%)
    1 / 35 (2.86%)
         occurrences all number
    0
    4
    0
    1
    Injection site pain
         subjects affected / exposed
    1 / 41 (2.44%)
    10 / 59 (16.95%)
    10 / 33 (30.30%)
    4 / 35 (11.43%)
         occurrences all number
    11
    26
    43
    7
    Injection site pruritus
         subjects affected / exposed
    1 / 41 (2.44%)
    17 / 59 (28.81%)
    16 / 33 (48.48%)
    7 / 35 (20.00%)
         occurrences all number
    2
    125
    146
    39
    Injection site rash
         subjects affected / exposed
    0 / 41 (0.00%)
    13 / 59 (22.03%)
    7 / 33 (21.21%)
    4 / 35 (11.43%)
         occurrences all number
    0
    52
    33
    18
    Injection site reaction
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 59 (1.69%)
    0 / 33 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    0
    4
    0
    4
    Injection site swelling
         subjects affected / exposed
    0 / 41 (0.00%)
    9 / 59 (15.25%)
    6 / 33 (18.18%)
    6 / 35 (17.14%)
         occurrences all number
    0
    68
    71
    23
    Injection site urticaria
         subjects affected / exposed
    0 / 41 (0.00%)
    2 / 59 (3.39%)
    4 / 33 (12.12%)
    0 / 35 (0.00%)
         occurrences all number
    0
    9
    6
    0
    Injection site warmth
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 59 (5.08%)
    3 / 33 (9.09%)
    0 / 35 (0.00%)
         occurrences all number
    0
    5
    13
    0
    Injection site erythema
         subjects affected / exposed
    0 / 41 (0.00%)
    32 / 59 (54.24%)
    22 / 33 (66.67%)
    16 / 35 (45.71%)
         occurrences all number
    0
    200
    234
    108
    Pyrexia
         subjects affected / exposed
    1 / 41 (2.44%)
    6 / 59 (10.17%)
    2 / 33 (6.06%)
    1 / 35 (2.86%)
         occurrences all number
    1
    7
    4
    1
    Gastrointestinal disorders
    Abdominal pain upper
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 59 (3.39%)
    3 / 33 (9.09%)
    0 / 35 (0.00%)
         occurrences all number
    1
    2
    3
    0
    Constipation
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 59 (0.00%)
    2 / 33 (6.06%)
    0 / 35 (0.00%)
         occurrences all number
    2
    0
    2
    0
    Vomiting
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 59 (5.08%)
    2 / 33 (6.06%)
    0 / 35 (0.00%)
         occurrences all number
    1
    5
    2
    0
    Nausea
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 59 (3.39%)
    3 / 33 (9.09%)
    1 / 35 (2.86%)
         occurrences all number
    1
    2
    4
    1
    Gastritis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 59 (0.00%)
    0 / 33 (0.00%)
    2 / 35 (5.71%)
         occurrences all number
    1
    0
    0
    2
    Diarrhoea
         subjects affected / exposed
    2 / 41 (4.88%)
    2 / 59 (3.39%)
    4 / 33 (12.12%)
    1 / 35 (2.86%)
         occurrences all number
    2
    2
    10
    1
    Skin and subcutaneous tissue disorders
    Rash
         subjects affected / exposed
    1 / 41 (2.44%)
    2 / 59 (3.39%)
    1 / 33 (3.03%)
    3 / 35 (8.57%)
         occurrences all number
    1
    2
    2
    4
    Urticaria
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 59 (5.08%)
    3 / 33 (9.09%)
    2 / 35 (5.71%)
         occurrences all number
    1
    3
    4
    2
    Musculoskeletal and connective tissue disorders
    Pain in extremity
         subjects affected / exposed
    3 / 41 (7.32%)
    0 / 59 (0.00%)
    2 / 33 (6.06%)
    0 / 35 (0.00%)
         occurrences all number
    3
    0
    2
    0
    Myalgia
         subjects affected / exposed
    1 / 41 (2.44%)
    3 / 59 (5.08%)
    4 / 33 (12.12%)
    1 / 35 (2.86%)
         occurrences all number
    2
    3
    7
    1
    Back pain
         subjects affected / exposed
    1 / 41 (2.44%)
    1 / 59 (1.69%)
    2 / 33 (6.06%)
    0 / 35 (0.00%)
         occurrences all number
    1
    1
    2
    0
    Arthralgia
         subjects affected / exposed
    6 / 41 (14.63%)
    2 / 59 (3.39%)
    4 / 33 (12.12%)
    2 / 35 (5.71%)
         occurrences all number
    8
    12
    5
    2
    Arthritis
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 59 (5.08%)
    3 / 33 (9.09%)
    1 / 35 (2.86%)
         occurrences all number
    0
    5
    4
    1
    Infections and infestations
    Bronchitis
         subjects affected / exposed
    2 / 41 (4.88%)
    0 / 59 (0.00%)
    2 / 33 (6.06%)
    3 / 35 (8.57%)
         occurrences all number
    2
    0
    2
    3
    COVID-19
         subjects affected / exposed
    2 / 41 (4.88%)
    6 / 59 (10.17%)
    5 / 33 (15.15%)
    4 / 35 (11.43%)
         occurrences all number
    2
    6
    5
    4
    Gastroenteritis
         subjects affected / exposed
    0 / 41 (0.00%)
    1 / 59 (1.69%)
    2 / 33 (6.06%)
    1 / 35 (2.86%)
         occurrences all number
    0
    1
    2
    1
    Influenza
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 59 (5.08%)
    1 / 33 (3.03%)
    0 / 35 (0.00%)
         occurrences all number
    0
    3
    1
    0
    Nasopharyngitis
         subjects affected / exposed
    0 / 41 (0.00%)
    3 / 59 (5.08%)
    2 / 33 (6.06%)
    2 / 35 (5.71%)
         occurrences all number
    0
    3
    7
    3
    Oral candidiasis
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 59 (0.00%)
    2 / 33 (6.06%)
    1 / 35 (2.86%)
         occurrences all number
    2
    0
    2
    1
    Pharyngitis
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    2 / 33 (6.06%)
    2 / 35 (5.71%)
         occurrences all number
    0
    0
    4
    2
    Respiratory tract infection
         subjects affected / exposed
    1 / 41 (2.44%)
    0 / 59 (0.00%)
    2 / 33 (6.06%)
    0 / 35 (0.00%)
         occurrences all number
    1
    0
    2
    0
    Upper respiratory tract infection
         subjects affected / exposed
    3 / 41 (7.32%)
    4 / 59 (6.78%)
    1 / 33 (3.03%)
    4 / 35 (11.43%)
         occurrences all number
    4
    7
    1
    7
    Upper respiratory tract infection bacterial
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    3 / 33 (9.09%)
    0 / 35 (0.00%)
         occurrences all number
    0
    0
    3
    0
    Urinary tract infection
         subjects affected / exposed
    3 / 41 (7.32%)
    5 / 59 (8.47%)
    5 / 33 (15.15%)
    1 / 35 (2.86%)
         occurrences all number
    5
    6
    5
    2
    Urinary tract infection bacterial
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    2 / 33 (6.06%)
    0 / 35 (0.00%)
         occurrences all number
    0
    0
    2
    0
    Metabolism and nutrition disorders
    Decreased appetite
         subjects affected / exposed
    0 / 41 (0.00%)
    0 / 59 (0.00%)
    2 / 33 (6.06%)
    0 / 35 (0.00%)
         occurrences all number
    0
    0
    2
    0

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    25 Aug 2021
    The following updates were made: • The efficacy analysis set was updated to include all participants randomized in the study and not those who have received at least 1 dose of investigation product. • Added the 2019 European League Against Rheumatism (EULAR)/ACR criteria, lupus narrative and prior history of BILAG domains to the Schedule of Activities (SoA). • Updated BILAG reference and scoring. • Added exploratory endpoint. • Removed PGIC baseline assessment from SoA. • Added blinded samples to protocol. • Added study adjudication language. • Updated the first data monitoring committee (DMC) meeting for safety to occur after the first 20 participants completed the Week 12 visit. • Added a subsection (Risk Assessment) to include guidance to sites regarding coronavirus disease 2019 (COVID-19). • Updated eligibility criteria. • Changed numbering of rescreening attempts from 2 to 3. • Included guidance on which adverse events lead to withholding or permanently discontinuing efavaleukin alfa. • Updated vital signs section. • Provided clarification for "decision by sponsor" as a reason to remove participant from study. • Included guidance for the investigator to repeat any labs that are considered to be clinically significant to rule out laboratory error. • Removed the Phadia assay being used on anti-double stranded DNA (anti-dsDNA) to determine eligibility. • Included required alignments with current Amgen protocol template. • Administrative and editorial changes.
    01 Sep 2022
    The following updates were made: • Removed requirement for a separate blinded joint assessor. • Clarified that the same assessor must perform efficacy assessments at every time point for a given participant. • Improved clarity of the definition of SRI-4 response and BICLA response. • Clarified that for arthritis to be scored, affected joints must have involved small joints in hands, wrists or a combination of joints in hands and wrists. • Endpoints were updated. • SoA was updated. • Clarified blood collection timepoints. • Updated statistical hypothesis. • Human Exposure and Risk Assessment were updated. • Clarified that prior to randomization, the investigator must have confirmed disease activity and compliance and stability of SLE treatment. • Updated justification for Investigational Product Dose. • Updated eligibility assessment order. • Updated end of study definition. • Clarified safety follow-up. • Provided instructions for scheduling early termination visit. • Updated interim analysis language. • Added biomarker discovery section. • Updated inclusion and exclusion criteria. • Updated information collected for screen failure. • Updated list of excluded medications/treatment. • Included a footnote in Analyte Listing table. • Described that individuals who did not meet criteria for participation could be rescreened up to 3 times. • Clarified lab retests required during screening should be approved by the sponsor. • Removed instruction that participants who screen failed should wait before being rescreened. • Provided specific instructions for capturing in injection site reaction as an adverse event. • Antibody Testing Procedures were updated. • Updated language for safety collection and reporting of serious adverse events. • Removed organ involvement as a baseline covariate on treatment effect. • Incorporated abbreviated study name. • Administrative and editorial changes.
    21 Oct 2022
    The following updates were made: • Added back the requirement for an independent blinded joint evaluator to conduct joint count assessments (number of tender and swollen joints). • Incorporated administrative and editorial changes.

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

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