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    Clinical Trial Results:
    A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of VIB7734 for the Treatment of Moderate to Severely Active Systemic Lupus Erythematosus (RECAST SLE)

    Summary
    EudraCT number
    		 2020-005528-12
    Trial protocol
    		 ES  
    Global end of trial date
    09 Jun 2023

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

    Trial information

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    Trial identification
    Sponsor protocol code
    VIB7734.P2.S1
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04925934
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    Amgen Inc.
    Sponsor organisation address
    One Amgen Center Drive, Thousand Oaks, United States,
    Public contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@amgen.com
    Scientific contact
    IHQ Medical Info-Clinical Trials, Amgen (EUROPE) GmbH, MedInfoInternational@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
    09 Jun 2023
    Is this the analysis of the primary completion data?
    No
    Global end of trial reached?
    Yes
    Global end of trial date
    09 Jun 2023
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    The main objective of the study was to evaluate the effect of daxdilimab compared to placebo in reducing SLE disease activity at week 48 in participants treated with standard-of-care therapy.
    Protection of trial subjects
    The final trial protocol and informed consent form (ICF) received written approval from an Institutional Review Board (IRB) or Independent Ethics Committee (IEC) before participant enrollment. The Investigator informed the IRB/IEC of any protocol amendments and obtained their approval, except in urgent safety cases. All advertising for participant recruitment was approved by the IRB/IEC. The protocol underwent IRB/IEC re-approval upon each amendment and annually as per local regulations. The Investigator ensured compliance with IRB/IEC requirements and provided reports, including serious adverse drug reactions, to the IRB/IEC. The Sponsor facilitated this process. The trial adhered to International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH)/Good Clinical Practice (GCP) standards, regulatory requirements, and the Sponsor's ethical policies. The Investigator obtained written informed consent from participants before trial commencement. Consent documentation complied with regulations and ICH E6(R2). Participants were informed of record review by relevant parties and given the opportunity to ask questions. Consent allowed for record access for at least 25 years. The Investigator retained the original signed and dated ICF, with a copy given to the participant. The Sponsor reserved the right to delay trial initiation at sites not meeting consent document standards. An external Safety Data Monitoring Committee (SDMC) oversaw participant safety and trial integrity by reviewing accumulating safety data. It provided recommendations to the Sponsor regarding trial conduct and participant management. The SDMC members were independent of the Sponsor and any collaborating organizations.
    Background therapy
    		 -
    Evidence for comparator
    		 -
    Actual start date of recruitment
    28 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
    Argentina: 34
    Country: Number of subjects enrolled
    Spain: 2
    Country: Number of subjects enrolled
    Greece: 4
    Country: Number of subjects enrolled
    India: 20
    Country: Number of subjects enrolled
    Mexico: 39
    Country: Number of subjects enrolled
    Poland: 32
    Country: Number of subjects enrolled
    Russian Federation: 5
    Country: Number of subjects enrolled
    Serbia: 19
    Country: Number of subjects enrolled
    Taiwan: 6
    Country: Number of subjects enrolled
    Ukraine: 7
    Country: Number of subjects enrolled
    United States: 46
    Worldwide total number of subjects
    214
    EEA total number of subjects
    38
    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)
    205
    From 65 to 84 years
    9
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 Participants with systemic lupus erythematosus (SLE) were enrolled at 68 sites in the United States, Argentina, Greece, India, Mexico, Poland, Serbia, Spain, Taiwan, Ukraine and Russia between May 2021 and June 2023.

    Pre-assignment
    Screening details
    		 Participants were randomized to take daxdilimab 200 mg Q4W subcutaneously (SC), daxdilimab 200 mg Q12W SC (plus 200 mg at Week 4) or placebo. Randomization was stratified by SLE Disease Activity Index 2000 (SLEDAI-2K) score at screening (≥ 10 or < 10) and prednisone or equivalent oral glucocorticoid dose at baseline (≥ 10 mg/day or < 10 mg/day).

    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 were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    SC Q4W

    Arm title
    		 Daxdilimab 200 mg Q4W
    Arm description
    		 Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daxdilimab
    Investigational medicinal product code
    Other name
    VIB7734
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    200 mg SC Q4W

    Arm title
    		 Daxdilimab 200 mg Q12W
    Arm description
    		 Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Daxdilimab
    Investigational medicinal product code
    Other name
    VIB7734
    Pharmaceutical forms
    Injection
    Routes of administration
    Subcutaneous use
    Dosage and administration details
    200 mg SC Q12W, with an additional 200 mg SC dose at Week 4

    Number of subjects in period 1
    		Placebo Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W
    Started
    71
    72
    71
    Completed
    51
    61
    57
    Not completed
    20
    11
    14
         Consent withdrawn by subject
    8
    5
    9
         Adverse Event
    1
    -
    -
         Other
    2
    2
    2
         Death
    -
    1
    -
         Eastern European Conflict
    7
    3
    2
         Lost to follow-up
    2
    -
    1

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.

    Reporting group title
    Daxdilimab 200 mg Q4W
    Reporting group description
    		 Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.

    Reporting group title
    Daxdilimab 200 mg Q12W
    Reporting group description
    		 Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.

    Reporting group values
    		 Placebo Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W Total
    Number of subjects
    		 71 72 71 214
    Age Categorical
    Units: Subjects
    Age Continuous
    Units: years
        arithmetic mean (standard deviation)
    		 41.0 ( 11.0 ) 44.5 ( 13.1 ) 45.3 ( 11.6 ) -
    Gender Categorical
    Units: Subjects
        Female
    		 67 67 66 200
        Male
    		 4 5 5 14
    Race (NIH/OMB)
    Units: Subjects
        American Indian or Alaskan Native
    		 2 2 0 4
        Asian
    		 9 7 10 26
        Black or African American
    		 4 8 6 18
        White
    		 54 49 51 154
        Other
    		 1 6 4 11
        Multiple categories checked
    		 1 0 0 1
    Ethnicity
    Units: Subjects
        Hispanic or Latino
    		 25 27 27 79
        Not Hispanic or Latino
    		 46 45 44 135
    Number of Participants Within Each OGC Stratification Dose Level
    OGC dose represents the baseline dose of prednisone or any equivalent corticosteroids.
    Units: Subjects
        < 10 mg/day
    		 36 35 36 107
        ≥ 10 mg/day
    		 35 37 35 107
    SLEDAI-2K Score
    The SLEDAI-2K assessment consists of 24 lupus-related items. It is a weighted instrument, in which descriptors are multiplied by an organ’s “weight”. For example, renal descriptors are multiplied by 4 and CNS descriptors by 8; these weighted organ manifestations are totalled into the final score. The scores range from 0 to 105, with higher scores indicating more severe disease activity.
    Units: Score
        arithmetic mean (standard deviation)
    		 9.9 ( 2.8 ) 10.6 ( 4.0 ) 10.1 ( 2.9 ) -
    Physician Global Assessment (PGA) Score
    The PGA takes into account various clinical factors, including the participant’s symptoms, physical examination findings, laboratory results, and the physician's judgment. The PGA is scored with a range 0 to 3 where higher scores indicate greater disease activity and severity.
    Units: Score
        arithmetic mean (standard deviation)
    		 1.89 ( 0.37 ) 1.96 ( 0.32 ) 1.90 ( 0.41 ) -
    British Isles Lupus Assessment Group (BILAG)-2004 Score
    The BILAG-2004 Index assesses lupus disease activity across various organ systems. Each organ system is graded from A (severe disease activity requiring urgent treatment) to E (system never involved).
    Units: Score
        arithmetic mean (standard deviation)
    		 19.2 ( 4.7 ) 19.5 ( 4.6 ) 19.8 ( 5.5 ) -

    End points

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    End points reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.

    Reporting group title
    Daxdilimab 200 mg Q4W
    Reporting group description
    		 Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.

    Reporting group title
    Daxdilimab 200 mg Q12W
    Reporting group description
    		 Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.

    Primary: Number of Participants Achieving a BILAG-2004 Index-based Combined Lupus Assessment (BICLA) Response and an OGC Dose ≤ 7.5 mg/day and ≤ Baseline Dose of Prednisone or Equivalent at Week 48

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    End point title
    		 Number of Participants Achieving a BILAG-2004 Index-based Combined Lupus Assessment (BICLA) Response and an OGC Dose ≤ 7.5 mg/day and ≤ Baseline Dose of Prednisone or Equivalent at Week 48
    End point description
    A BICLA response required improvement in all domains affected at baseline, assessed by the BILAG 2004, no worsening of other BILAG 2004 domains, no worsening of SLEDAI‐2K or PGA scores compared with baseline, no use of restricted medications beyond the protocol-allowed threshold, and no discontinuation of IP.
    End point type
    Primary
    End point timeframe
    Week 48
    End point values
    		 Placebo Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W
    Number of subjects analysed
    64
    69
    69
    Units: Participants
        Week 48
    25
    29
    27
    Statistical analysis title
    		 BICLA response at Week 48
    Statistical analysis description
    Adjusted response rate, rate difference and p-value are from logistic regression analysis with treatment and randomization stratification factors in the model.
    Comparison groups
    Placebo v Daxdilimab 200 mg Q12W
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.9942
    Method
    		 Regression, Logistic
    Parameter type
    		 Rate Difference
    Point estimate
    -0.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -14.2
         upper limit
    		 14.1
    Statistical analysis title
    		 BICLA response at Week 48
    Statistical analysis description
    Adjusted response rate, rate difference and p-value are from logistic regression analysis with treatment and randomization stratification factors in the model.
    Comparison groups
    Placebo v Daxdilimab 200 mg Q4W
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority [1]
    P-value
    		 = 0.7474
    Method
    		 Regression, Logistic
    Parameter type
    		 Rate Difference
    Point estimate
    2.8
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -11.4
         upper limit
    		 17
    Notes
    [1] - daxdilimab 200 mg Q4W versus placebo

    Secondary: Number of Participants With a Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) Score ≥ 10 at Baseline Achieving ≥ 50% Reduction From Baseline in CLASI-A Score at Week 12

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    End point title
    		 Number of Participants With a Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity (CLASI-A) Score ≥ 10 at Baseline Achieving ≥ 50% Reduction From Baseline in CLASI-A Score at Week 12
    End point description
    CLASI-A evaluates erythema (0-3 [higher scores indicate more severe redness]), scale/hypertrophy (0-2 [higher scores indicate more extensive scaling/thickening]), mucous membrane lesions (0 [absent] or 1 [present]), recent hair loss (0 [absent] or 1 [present]), and non-scarring alopecia (0-3 [(higher scores indicate more extensive hair loss without scarring]) at 13 anatomical sites on the skin. Total score is calculated by summing scores across all anatomical locations for each parameter. Higher total scores indicate greater disease activity and severity in SLE. Reduction of 50% in CLASI-A score was defined by meeting all following conditions: 1) A ≥ 50% reduction of CLASI-A score at Week 12 as compared to baseline. 2) No use of restricted medications beyond protocol-allowed threshold before assessment. 3) No discontinuation IP. FAS: included all randomized participants who received any dose of IP. Only participants with a CLASI-A score ≥ 10 at baseline were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 Placebo Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W
    Number of subjects analysed
    8
    10
    14
    Units: Participants
        Week 12
    1
    4
    5
    Statistical analysis title
    		 CLASI-A score reduction at Week 12
    Statistical analysis description
    Adjusted response rate, rate difference and p-value are from logistic regression analysis with treatment, randomization stratification factors and Baseline CLASI-A score in the model.
    Comparison groups
    Placebo v Daxdilimab 200 mg Q12W
    Number of subjects included in analysis
    22
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2873
    Method
    		 Regression, Logistic
    Parameter type
    		 Rate Difference
    Point estimate
    24.1
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -7.5
         upper limit
    		 55.8
    Statistical analysis title
    		 CLASI-A score reduction at Week 12
    Statistical analysis description
    Adjusted response rate, rate difference and p-value are from logistic regression analysis with treatment, randomization stratification factors and Baseline CLASI-A score in the model.
    Comparison groups
    Placebo v Daxdilimab 200 mg Q4W
    Number of subjects included in analysis
    18
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.1626
    Method
    		 Regression, Logistic
    Parameter type
    		 Rate Difference
    Point estimate
    37.2
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -0.3
         upper limit
    		 74.7

    Secondary: Number of Participants Achieving an SLE Responder Index (SRI)-4 Response and an OGC Dose ≤ 7.5 mg/day and ≤ Baseline Dose of Prednisone or Equivalent at Week 48

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    End point title
    		 Number of Participants Achieving an SLE Responder Index (SRI)-4 Response and an OGC Dose ≤ 7.5 mg/day and ≤ Baseline Dose of Prednisone or Equivalent at Week 48
    End point description
    The SRI-4 measures reduction in SLE disease activity and it is a composite measure that includes the SLEDAI-2K, BILAG-2004, and PGA. SRI responder was defined as meeting all of the following criteria: 1) Reduction of ≥4 points from baseline in SLEDAI-2K score; 2) no new BILAG A or no more than 1 new BILAG B disease activity scores and 3) no worsening (defined as an increase of ≥0.3 points [0-3 scale] from baseline) in the PGA.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 Placebo Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W
    Number of subjects analysed
    64
    69
    69
    Units: Participants
        Week 48
    26
    34
    30
    Statistical analysis title
    		 SRI-4 response at Week 48
    Statistical analysis description
    Adjusted response rate, rate difference and p-value are from logistic regression analysis with treatment and randomization stratification factors in the model.
    Comparison groups
    Placebo v Daxdilimab 200 mg Q12W
    Number of subjects included in analysis
    133
    Analysis specification
    Post-hoc
    Analysis type
    		 superiority
    P-value
    		 = 0.7364
    Method
    		 Regression, Logistic
    Parameter type
    		 Rate Difference
    Point estimate
    2.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -11.2
         upper limit
    		 17
    Statistical analysis title
    		 SRI-4 response at Week 48
    Statistical analysis description
    Adjusted response rate, rate difference and p-value are from logistic regression analysis with treatment and randomization stratification factors in the model.
    Comparison groups
    Placebo v Daxdilimab 200 mg Q4W
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.322
    Method
    		 Regression, Logistic
    Parameter type
    		 Rate Difference
    Point estimate
    8.6
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -5.6
         upper limit
    		 22.7

    Secondary: Number of Participants with an OGC Dose ≥ 10 mg/day of Prednisone or Equivalent at Baseline Who Maintained an OGC Dose ≤ 7.5 mg/day From Week 36 Through Week 48

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    End point title
    		 Number of Participants with an OGC Dose ≥ 10 mg/day of Prednisone or Equivalent at Baseline Who Maintained an OGC Dose ≤ 7.5 mg/day From Week 36 Through Week 48
    End point description
    Maintenance of OGC reduction from Week 36 to Week 48 was defined as meeting all the following criteria: 1) Achieved an OGC dose of ≤ 7.5 mg/day prednisone or equivalent at Week 36. 2) Maintained an OGC dose of ≤ 7.5 mg/day from Week 36 through Week 48. 3) No use of restricted medications beyond the protocol-allowed threshold before assessment. 4) No discontinuation of IP before assessment. FAS: included all randomized participants who received any dose of IP. Participants were analyzed according to the treatment randomized. Data excludes participants from Russia and Ukraine sites. Only participants with an OGC dose ≥ 10 mg/day of prednisone or equivalent at baseline were included in the analysis.
    End point type
    Secondary
    End point timeframe
    Week 36 to Week 48
    End point values
    		 Placebo Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W
    Number of subjects analysed
    30
    34
    34
    Units: Participants
    20
    27
    26
    Statistical analysis title
    		 Maintenance of OGC reduction Weeks 36 - 48
    Statistical analysis description
    Adjusted response rate, rate difference and p-value are from logistic regression analysis with treatment, stratification factors (SLEDAI-2K only) and Baseline OGC dose included in the model.
    Comparison groups
    Placebo v Daxdilimab 200 mg Q4W
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.2805
    Method
    		 Regression, Logistic
    Parameter type
    		 Rate Difference
    Point estimate
    11.7
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -6.1
         upper limit
    		 29.4
    Statistical analysis title
    		 Maintenance of OGC reduction Weeks 36 - 48
    Statistical analysis description
    Adjusted response rate, rate difference and p-value are from logistic regression analysis with treatment, stratification factors (SLEDAI-2K only) and Baseline OGC dose included in the model.
    Comparison groups
    Placebo v Daxdilimab 200 mg Q12W
    Number of subjects included in analysis
    64
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.3926
    Method
    		 Regression, Logistic
    Parameter type
    		 Rate Difference
    Point estimate
    9.4
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -8.6
         upper limit
    		 27.3

    Secondary: Number of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 48

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    End point title
    		 Number of Participants Achieving Lupus Low Disease Activity State (LLDAS) at Week 48
    End point description
    LLDAS was defined as meeting all the following: 1) SLEDAI-2K ≤ 4, with no activity in major organ systems (renal, central nervous system, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity measured as maintaining a D (no disease activity but suggests the system had previously been affected) or E (no current or previous disease activity) score in BILAG Gastrointestinal Body System 2) No new lupus disease activity compared with the previous 3) Physician's Global Assessment of Disease Activity ≤ 1 on a 3-point visual analog scale from no disease activity to severe disease activity 4) A current prednisolone (or equivalent) dose ≤ 7.5 mg daily 5) Well-tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents FAS: included all randomized participants who received any dose of IP. Participants were analyzed according to the treatment randomized.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 Placebo Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W
    Number of subjects analysed
    64
    69
    69
    Units: Participants
        Week 48
    11
    23
    15
    Statistical analysis title
    		 Achieving LLDAS at Week 48
    Statistical analysis description
    Adjusted response rate, rate difference and p-value are from logistic regression analysis with treatment and randomization stratification factors in the model.
    Comparison groups
    Placebo v Daxdilimab 200 mg Q12W
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.4939
    Method
    		 Regression, Logistic
    Parameter type
    		 Rate Difference
    Point estimate
    4.9
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 -6.7
         upper limit
    		 16.4
    Statistical analysis title
    		 Achieving LLDAS at Week 48
    Statistical analysis description
    Adjusted response rate, rate difference and p-value are from logistic regression analysis with treatment and randomization stratification factors in the model.
    Comparison groups
    Placebo v Daxdilimab 200 mg Q4W
    Number of subjects included in analysis
    133
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.037
    Method
    		 Regression, Logistic
    Parameter type
    		 Rate Difference
    Point estimate
    16.5
    Confidence interval
         level
    		 90%
         sides
    2-sided
         lower limit
    		 4
         upper limit
    		 29

    Secondary: Serum Concentration of Daxdilimab

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    End point title
    		 Serum Concentration of Daxdilimab [2]
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Week 8, Week 12, Week 16, Week 20, Week 24, Week 28, Week 32, Week 36, Week 40, Week 44, Week 48
    Notes
    [2] - 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: No additional statistical analysis was pre-specified for this endpoint.
    End point values
    		 Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W
    Number of subjects analysed
    72
    71
    Units: ug/mL
    arithmetic mean (standard deviation)
        Baseline (N = 72, 71)
    0.011 ( 0.026 )
    0.008 ( 0.004 )
        Week 4 (N = 71, 71)
    3.319 ( 1.972 )
    3.301 ( 1.718 )
        Week 8 (N = 72, 71)
    4.714 ( 3.079 )
    4.643 ( 2.708 )
        Week 12 (N = 70, 70)
    5.344 ( 3.624 )
    1.372 ( 1.189 )
        Week 16 (N = 68, 65)
    5.035 ( 3.377 )
    4.268 ( 2.720 )
        Week 20 (N = 66, 64)
    5.884 ( 4.451 )
    1.239 ( 1.097 )
        Week 24 (N = 63, 62)
    5.539 ( 4.224 )
    0.530 ( 0.922 )
        Week 28 (N = 65, 61)
    4.855 ( 3.743 )
    3.590 ( 2.522 )
        Week 32 (N = 65, 61)
    4.951 ( 4.047 )
    1.096 ( 1.151 )
        Week 36 (N = 63, 59)
    5.321 ( 4.309 )
    0.366 ( 0.471 )
        Week 40 (N = 65, 59)
    4.652 ( 3.426 )
    3.439 ( 2.534 )
        Week 44 (N = 64, 59)
    4.908 ( 3.780 )
    1.115 ( 1.378 )
        Week 48 (N = 60, 58)
    5.543 ( 4.637 )
    0.406 ( 0.585 )
    No statistical analyses for this end point

    Secondary: Number of Participants with Anti-drug Antibodies (ADA) to Daxdilimab

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    End point title
    		 Number of Participants with Anti-drug Antibodies (ADA) to Daxdilimab
    End point description
    A baseline ADA-positive participant was defined as a participant who had an ADA positive sample at baseline. ADA incidence is the number of the participants ADA positive post-Baseline only or who boosted their preexisting ADA (≥ 4 × Baseline level) during the trial. Persistent positive was defined as ADA positive at ≥ 2 post-Baseline assessments (with ≥ 16 weeks between first and last positive) or positive at last post-Baseline assessment. Transient positive was defined as ADA post-Baseline positive but did not fulfill the criteria of persistent positive. Safety analysis set (SAS): included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received.
    End point type
    Secondary
    End point timeframe
    Baseline to Week 56
    End point values
    		 Placebo Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W
    Number of subjects analysed
    71
    72
    71
    Units: Participants
        ADA not detected (negative) on trial
    47
    59
    56
        ADA incidence
    14
    6
    6
        Boosted ADA (≥ 4 × Baseline level)
    1
    2
    2
        ADA detected (positive) on trial: ADA prevalence
    24
    13
    15
        Only Baseline positive
    1
    5
    5
        Only post-Baseline positive
    13
    4
    4
        Both Baseline and post-Baseline positive
    10
    4
    6
        Persistent positive
    19
    8
    8
        Transient positive
    4
    0
    2
    No statistical analyses for this end point

    Secondary: Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood

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    End point title
    		 Change From Baseline in Plasmacytoid Dendritic Cell (pDCs) Expression in Blood
    End point description
    End point type
    Secondary
    End point timeframe
    Baseline, Week 4, Week 8, Week 12, Week 20, Week 24, Week 32, Week 36, Week 44, Week 48, Week 52, Week 56
    End point values
    		 Placebo Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W
    Number of subjects analysed
    43
    48
    46
    Units: cells/uL
    arithmetic mean (standard deviation)
        Baseline (N = 43, 48, 46)
    2.5068 ( 1.8486 )
    2.2960 ( 1.7457 )
    1.9195 ( 1.1990 )
        Week 4 (N = 33, 42, 41)
    -0.2324 ( 1.8194 )
    -1.4240 ( 1.9493 )
    -1.2903 ( 1.2201 )
        Week 8 (N = 32, 43, 38)
    -0.4608 ( 1.4125 )
    -1.5194 ( 1.7555 )
    -1.1486 ( 1.2090 )
        Week 12 (N = 33, 42, 39)
    0.0275 ( 1.7580 )
    -1.5164 ( 1.8180 )
    -1.1134 ( 1.5290 )
        Week 20 (N =32, 43, 35)
    285.1519 ( 1613.566 )
    -1.5131 ( 1.6837 )
    -1.0320 ( 1.1063 )
        Week 24 (N = 30, 40, 40)
    -0.3911 ( 1.7344 )
    -1.5974 ( 1.7705 )
    -0.5507 ( 1.3090 )
        Week 32 (N = 26, 40, 38)
    0.3513 ( 1.7855 )
    -1.3367 ( 1.5678 )
    -0.8496 ( 1.2403 )
        Week 36 (N = 26, 37, 33)
    -0.1274 ( 1.6962 )
    -1.4614 ( 1.7634 )
    -0.9131 ( 0.9845 )
        Week 44 (N = 28, 39, 33)
    -0.3194 ( 1.6347 )
    -1.6540 ( 1.6184 )
    -1.1322 ( 1.3782 )
        Week 48 (N = 28, 36, 36)
    0.1973 ( 2.4112 )
    -1.4608 ( 1.5647 )
    -0.7964 ( 1.0055 )
        Week 52 (N = 3, 3, 7)
    0.1483 ( 3.7955 )
    -0.4353 ( 0.5127 )
    0.0149 ( 0.7999 )
        Week 56 (N = 3, 3, 5)
    -2.0823 ( 3.9807 )
    -2.3137 ( 3.2514 )
    -0.7056 ( 0.6729 )
    No statistical analyses for this end point

    Secondary: Number of Participants who Experienced Treatment-emergent Adverse Events (TEAEs)

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    End point title
    		 Number of Participants who Experienced Treatment-emergent Adverse Events (TEAEs)
    End point description
    An adverse event (AE) is any untoward medical occurrence associated with the use of an intervention in humans whether or not it is considered intervention-related. TEAEs are AEs that started on or after the first dose of IP. An AE was considered serious (SAE) if it resulted in any of the following outcomes: death, a life-threatening AE, inpatient hospitalization or prolonged existing hospitalization, a persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions, a congenital abnormality/birth defect, or an important medical event. AE severity was rated according to the Common Terminology Criteria for Adverse Events (CTCAE) Version 5.0: grade 1 (mild), grade 2 (moderate), grade 3 (severe), grade 4 (life-threatening), grade 5 (death). SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received.
    End point type
    Secondary
    End point timeframe
    Up to Week 56
    End point values
    		 Placebo Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W
    Number of subjects analysed
    71
    72
    71
    Units: Participants
        TEAEs
    49
    49
    58
        Treatment-related TEAEs
    10
    17
    17
        AEs Grade 3 or higher
    5
    8
    9
        SAEs
    8
    9
    9
        Treatment-related SAEs
    0
    1
    0
        AEs Resulting in Death
    0
    1
    0
    No statistical analyses for this end point

    Secondary: Number of Participants who Experienced AEs of special interest (AESI)

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    End point title
    		 Number of Participants who Experienced AEs of special interest (AESI)
    End point description
    An AESI is an AE of scientific and medical interest specific to understanding of the IP and may require close monitoring and collection of additional information by the Investigator. AESIs for this study included: a. Hypersensitivity reaction, including anaphylaxis. b. Severe (Grade 3 or higher) viral infections/reactivations. c. Opportunistic infection. d. Malignancy (except non-melanoma skin cancer). SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received.
    End point type
    Secondary
    End point timeframe
    Up to Week 56
    End point values
    		 Placebo Daxdilimab 200 mg Q4W Daxdilimab 200 mg Q12W
    Number of subjects analysed
    71
    72
    71
    Units: Participants
        Hypersensitivity Reaction Including Anaphylaxis
    1
    0
    1
        Opportunistic infection
    1
    1
    1
        Viral infection/Reactivation
    10
    6
    7
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    Up to 56 weeks
    Adverse event reporting additional description
    SAS: included all participants who received any dose of IP. Participants were analyzed according to the treatment that they received. All-cause mortality is reported for all participants enrolled/randomized in the study. Serious adverse events and other adverse events are reported for all participants who received at least one dose of study drug.
    Assessment type
    		 Systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    Placebo
    Reporting group description
    		 Participants were randomized to receive matching placebo Q4W SC for a treatment period up to 48 weeks.

    Reporting group title
    Daxdilimab 200mg Q12W
    Reporting group description
    		 Participants were randomized to receive daxdilimab 200 mg Q12W (with an additional 200 mg SC dose at Week 4) for a treatment period up to 48 weeks.

    Reporting group title
    Daxdilimab 200mg Q4W
    Reporting group description
    		 Participants were randomized to receive daxdilimab 200 mg Q4W for a treatment period up to 48 weeks.

    Serious adverse events
    		 Placebo Daxdilimab 200mg Q12W Daxdilimab 200mg Q4W
    Total subjects affected by serious adverse events
         subjects affected / exposed
    8 / 71 (11.27%)
    9 / 71 (12.68%)
    9 / 72 (12.50%)
         number of deaths (all causes)
    0
    0
    1
         number of deaths resulting from adverse events
    Vascular disorders
    Peripheral artery occlusion
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Reproductive system and breast disorders
    Hydrosalpinx
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Uterine polyp
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pulmonary embolism
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Abortion induced incomplete
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Congenital, familial and genetic disorders
    Huntington's disease
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Cardiac disorders
    Pericardial effusion
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Ischaemic cardiomyopathy
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
    Angina pectoris
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Acute myocardial infarction
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Nervous system disorders
    Ischaemic stroke
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Loss of consciousness
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Blood and lymphatic system disorders
    Iron deficiency anaemia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Hiatus hernia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Duodenal ulcer haemorrhage
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Colitis
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Abdominal hernia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Renal and urinary disorders
    Acute kidney injury
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Fibromyalgia
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Intervertebral disc protrusion
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Osteoarthritis
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    1 / 71 (1.41%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Infections and infestations
    Appendicitis
         subjects affected / exposed
    2 / 71 (2.82%)
    0 / 71 (0.00%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 2
    0 / 0
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    1 / 72 (1.39%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Metabolism and nutrition disorders
    Hyponatraemia
         subjects affected / exposed
    0 / 71 (0.00%)
    1 / 71 (1.41%)
    0 / 72 (0.00%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 Placebo Daxdilimab 200mg Q12W Daxdilimab 200mg Q4W
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    17 / 71 (23.94%)
    29 / 71 (40.85%)
    30 / 72 (41.67%)
    Cardiac disorders
    Palpitations
         subjects affected / exposed
    0 / 71 (0.00%)
    0 / 71 (0.00%)
    4 / 72 (5.56%)
         occurrences all number
    0
    0
    4
    Nervous system disorders
    Headache
         subjects affected / exposed
    5 / 71 (7.04%)
    1 / 71 (1.41%)
    3 / 72 (4.17%)
         occurrences all number
    5
    1
    3
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
    4 / 72 (5.56%)
         occurrences all number
    1
    2
    4
    Dyspepsia
         subjects affected / exposed
    1 / 71 (1.41%)
    4 / 71 (5.63%)
    0 / 72 (0.00%)
         occurrences all number
    1
    4
    0
    Infections and infestations
    COVID-19
         subjects affected / exposed
    9 / 71 (12.68%)
    9 / 71 (12.68%)
    10 / 72 (13.89%)
         occurrences all number
    10
    10
    10
    Influenza
         subjects affected / exposed
    0 / 71 (0.00%)
    2 / 71 (2.82%)
    4 / 72 (5.56%)
         occurrences all number
    0
    2
    4
    Sinusitis
         subjects affected / exposed
    1 / 71 (1.41%)
    2 / 71 (2.82%)
    4 / 72 (5.56%)
         occurrences all number
    1
    2
    4
    Nasopharyngitis
         subjects affected / exposed
    4 / 71 (5.63%)
    2 / 71 (2.82%)
    3 / 72 (4.17%)
         occurrences all number
    5
    3
    3
    Urinary tract infection
         subjects affected / exposed
    4 / 71 (5.63%)
    8 / 71 (11.27%)
    7 / 72 (9.72%)
         occurrences all number
    4
    12
    7
    Upper respiratory tract infection bacterial
         subjects affected / exposed
    2 / 71 (2.82%)
    4 / 71 (5.63%)
    1 / 72 (1.39%)
         occurrences all number
    3
    4
    1

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    10 Feb 2022
    • Clarified, in inclusion criterion 8, that women of childbearing potential were to have negative serum pregnancy test at Screening and a negative urine pregnancy test at randomization and must refrain from egg retrieval and donation while receiving IP. • Clarified, in inclusion criterion 8, that if a change in birth control methods occurred during the trial the participant must employ a barrier method in addition to the highly effective method of contraception for at least 2 months, unless the participant was changing the method to complete abstinence. • Updated the definition of women of childbearing potential throughout the protocol. • Clarified, in exclusion criterion 2, that the Sponsor and Central Review Committee may also review a participant’s screening data and find reason not to allow participation in the trial. • Updated exclusion criterion 5 to standardize the amount of time that breastfeeding or pregnant women would be followed after receiving the last dose of IP. • Updated exclusion criterion 10 to add the mg/mmol exclusionary value as it is generally used at ex-United States sites. • Updated exclusion criterion 13 to clarify actions for indeterminate IFN-gamma release assay (IGRA) test results. • Removed the example of fever from exclusion criterion 18 as it can be a manifestation of lupus and thus possibly confusing. • Updated exclusion criterion 19 to clarify the definition of clinically significant cardiac disease. • Updated exclusion criterion 23 to include conventional anti-rheumatic doses for treatment of SLE. • Removed direct Coombs testing, as the specimen has limited stability that often does not allow testing to be performed by the central laboratory within the stability period due to courier transit time and is not needed on a routine basis.
    10 Feb 2022
    • Clarified that the Week 48 Visit was also considered an Early Termination Visit and that the Safety Follow-up Period was only for participants who completed the 48-week Treatment Period; specified that participants who permanently discontinued IP should be followed after final IP administration. • Removed PGI of Change on Day 1, as the PG of Change is designed to assess post-treatment change and, therefore, was assessed beginning with the first post-treatment visit. • Updated the 28-Joint Count section to align with the current SLEDAI-2K joint count arthritis definition. • Allowed for additional time at Week 24 for vital sign measurement, laboratory sample collection and ECG recording prior to dosing. • Clarified that tuberculosis (TB) assessments at Screening were to occur only at the central laboratory. • Clarified that if Baseline skin sample(s) were not collected (pre-dose), the subsequent visit samples should not be collected. • Clarified that if the Baseline DNA/epigenetic sample (for consenting participants) was not collected (pre-dose), the subsequent visit samples should still be collected. • Provided guidance on collection times and windows for the optional fecal microbiome sample. • Updated the Sponsor’s Quality Assurance contact information for reporting product complaints. • Removed the specific gauge size from the description of IP dose preparation, as specific needles could not be supplied at certain sites. • Clarified how anti-COVID therapeutic antibody treatment was to be handled. • Clarified limitations for the permitted use of as-needed nonsteroidal anti-inflammatory drug (NSAIDs). • Clarified that AESI for viral infection and reactivation only included those that were Grade 3 or higher and all cases of opportunistic infections listed in Appendix 3 of the protocol. • Clarified that AESIs only needed to be immediately reported after randomization and updated the contact information for immediate reporting.

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

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