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    Clinical Trial Results:
    A Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Study Participants With Moderately to Severely Active Systemic Lupus Erythematosus

    Summary
    EudraCT number
    		 2019-003406-27
    Trial protocol
    		 BE   PL   DE   BG   HU   ES   AT   GR   PT   GB   FR   CZ   IT   DK   RO  
    Global end of trial date
    04 Jun 2024

    Results information
    Results version number
    		 v1(current)
    This version publication date
    19 Apr 2025
    First version publication date
    19 Apr 2025
    Other versions

    Trial information

    		 Close Top of page
    Trial identification
    Sponsor protocol code
    SL0043
    Additional study identifiers
    ISRCTN number
    		 -
    US NCT number
    		 NCT04294667
    WHO universal trial number (UTN)
    		 -
    Sponsors
    Sponsor organisation name
    UCB Biopharma SRL
    Sponsor organisation address
    Allée de la Recherche 60, Brussels, Belgium, 1070
    Public contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.com
    Scientific contact
    Clin Trial Reg & Results Disclosure, UCB BIOSCIENCES GmbH, clinicaltrials@ucb.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
    23 Jul 2024
    Is this the analysis of the primary completion data?
    Yes
    Primary completion date
    22 May 2024
    Global end of trial reached?
    Yes
    Global end of trial date
    04 Jun 2024
    Was the trial ended prematurely?
    No
    General information about the trial
    Main objective of the trial
    To evaluate the ability of DZP as an add-on treatment to SOC medication to achieve clinically relevant long-term improvement of moderate to severe disease activity
    Protection of trial subjects
    During the conduct of the study all participants were closely monitored.
    Background therapy
    		 Background therapy as permitted in the protocol.
    Evidence for comparator
    		 Not applicable.
    Actual start date of recruitment
    12 Aug 2020
    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: 12
    Country: Number of subjects enrolled
    Australia: 1
    Country: Number of subjects enrolled
    Austria: 1
    Country: Number of subjects enrolled
    Belgium: 3
    Country: Number of subjects enrolled
    Bulgaria: 11
    Country: Number of subjects enrolled
    Canada: 11
    Country: Number of subjects enrolled
    Chile: 7
    Country: Number of subjects enrolled
    Colombia: 30
    Country: Number of subjects enrolled
    Czechia: 4
    Country: Number of subjects enrolled
    Germany: 17
    Country: Number of subjects enrolled
    Greece: 6
    Country: Number of subjects enrolled
    Hungary: 11
    Country: Number of subjects enrolled
    Italy: 7
    Country: Number of subjects enrolled
    Mexico: 21
    Country: Number of subjects enrolled
    Peru: 25
    Country: Number of subjects enrolled
    Philippines: 2
    Country: Number of subjects enrolled
    Poland: 40
    Country: Number of subjects enrolled
    Romania: 2
    Country: Number of subjects enrolled
    Serbia: 12
    Country: Number of subjects enrolled
    Korea, Republic of: 4
    Country: Number of subjects enrolled
    Spain: 12
    Country: Number of subjects enrolled
    Taiwan: 17
    Country: Number of subjects enrolled
    United States: 65
    Worldwide total number of subjects
    321
    EEA total number of subjects
    114
    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)
    1
    Adults (18-64 years)
    307
    From 65 to 84 years
    13
    85 years and over
    0

    Subject disposition

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    Recruitment
    Recruitment details
    		 The study started to enroll participants in August 2020 and concluded in June 2024.

    Pre-assignment
    Screening details
    		 Participant flow refers to the Randomized Set (RS).

    Period 1
    Period 1 title
    Overall Study (overall period)
    Is this the baseline period?
    		 Yes
    Allocation method
    Randomised - controlled
    Blinding used
    		 Double blind
    Roles blinded
    		 Subject, Investigator, Carer, Assessor

    Arms
    Are arms mutually exclusive
    Yes

    Arm title
    		 PBO+SOC
    Arm description
    		 Participants received placebo (PBO) as an intravenous (iv) infusion every 4 weeks (Q4W) in combination with Standard of Care (SOC) during 48 weeks Treatment Period.
    Arm type
    		 Placebo

    Investigational medicinal product name
    Placebo
    Investigational medicinal product code
    Other name
    PBO
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received placebo at prespecified time-points.

    Arm title
    		 DZP+SOC
    Arm description
    		 Participants received Dapirolizumab pegol (DZP) 24 milligrams/kilogram (mg/kg) as an iv infusion Q4W in combination with SOC during 48 weeks Treatment Period.
    Arm type
    		 Experimental

    Investigational medicinal product name
    Dapriolizumab pegol
    Investigational medicinal product code
    Other name
    CDP7657, DZP
    Pharmaceutical forms
    Infusion
    Routes of administration
    Intravenous use
    Dosage and administration details
    Participants received Dapirolizumab pegol at prespecified time-points.

    Number of subjects in period 1
    		PBO+SOC DZP+SOC
    Started
    108
    213
    Completed
    91
    192
    Not completed
    17
    21
         Subject Decision due to Personal Reason
    -
    1
         Adverse event, serious fatal
    -
    1
         PI closed Site – Subject Early Withdrawal
    -
    1
         Consent Withdrawal by Study Participant
    9
    7
         Adverse event, non-fatal
    3
    4
         Patient has a Renal Flare
    1
    -
         SLE Worsening
    -
    1
         Subject Moved to Another State
    -
    1
         Subject Withdrew due to Personal Reason
    -
    1
         Lack of efficacy
    4
    4

    Baseline characteristics

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    Baseline characteristics reporting groups
    Reporting group title
    PBO+SOC
    Reporting group description
    		 Participants received placebo (PBO) as an intravenous (iv) infusion every 4 weeks (Q4W) in combination with Standard of Care (SOC) during 48 weeks Treatment Period.

    Reporting group title
    DZP+SOC
    Reporting group description
    		 Participants received Dapirolizumab pegol (DZP) 24 milligrams/kilogram (mg/kg) as an iv infusion Q4W in combination with SOC during 48 weeks Treatment Period.

    Reporting group values
    		 PBO+SOC DZP+SOC Total
    Number of subjects
    		 108 213 321
    Age Categorical
    Units: participants
        12 to <18 Years
    		 0 1 1
        18 to <65 Years
    		 106 201 307
        65 to <85 Years
    		 2 11 13
    Age Continuous
    Units: Years
        arithmetic mean (standard deviation)
    		 41.5 ( 12.3 ) 43.8 ( 12.4 ) -
    Sex: Female, Male
    Units: participants
        Female
    		 101 198 299
        Male
    		 7 15 22

    End points

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    End points reporting groups
    Reporting group title
    PBO+SOC
    Reporting group description
    		 Participants received placebo (PBO) as an intravenous (iv) infusion every 4 weeks (Q4W) in combination with Standard of Care (SOC) during 48 weeks Treatment Period.

    Reporting group title
    DZP+SOC
    Reporting group description
    		 Participants received Dapirolizumab pegol (DZP) 24 milligrams/kilogram (mg/kg) as an iv infusion Q4W in combination with SOC during 48 weeks Treatment Period.

    Primary: Percentage of Participants with Achievement of BILAG 2004-based Composite Lupus Assessment (BICLA) response at Week 48

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    End point title
    		 Percentage of Participants with Achievement of BILAG 2004-based Composite Lupus Assessment (BICLA) response at Week 48
    End point description
    Participants were considered to be BILAG 2004-BICLA responder if all of following were fulfilled: • BILAG 2004 improvement without worsening (A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and less than or equal to [≤] 1 new B.); Here, score A (“Active”): Severely active disease; score B (“Beware”): Moderately active disease; score C (“Contentment”): Mild stable disease; score D (“Discount”): Inactive now but previously active; and • No worsening in the SLEDAI-2K total score compared to Baseline Visit (defined as no increase in SLEDAI-2K total score); and • No worsening in the Physician's Global Assessment of Disease (PGA) compared to Baseline Visit defined as ≤ 10 millimeter (mm) increase on a 100 mm visual analog scale (VAS). Full Analysis Set (FAS) consisted of all study participants randomized into the study except 6 participants excluded from FAS due to persistent GCP non-compliance at the site enrolling them.
    End point type
    Primary
    End point timeframe
    Week 48
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: percentage of participants
        number (not applicable)
    34.6
    49.5
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The difference in proportion responding between SOC+DZP 24mg/kg and SOC+PBO was estimated and tested using the Cochran-Mantel-Haenszel (CMH) risk difference estimate controlling for the randomization stratification factors, Pooled Region (North America vs Western Europe/Asia-Pacific vs Latin America/Eastern Europe), Screening disease activity (chronic active vs acute flaring) and Screening SLEDAI score (<10 vs >=10).
    Comparison groups
    DZP+SOC v PBO+SOC
    Number of subjects included in analysis
    315
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.011
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Proportions (%)
    Point estimate
    14.6
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 3.3
         upper limit
    		 25.8

    Secondary: Percentage of Participants with Achievement of BICLA response at Week 24

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    End point title
    		 Percentage of Participants with Achievement of BICLA response at Week 24
    End point description
    Study participants were considered to be a BICLA responder if all of the following were fulfilled: • British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004) improvement without worsening (A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and ≤ 1 new B.); Here, score A (“Active”): Severely active disease; score B (“Beware”): Moderately active disease; score C (“Contentment”): Mild stable disease; score D (“Discount”): Inactive now but previously active; and • No worsening in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score compared to Baseline Visit (defined as no increase in SLEDAI-2K total score); and • No worsening in the PGA compared to Baseline Visit defined as ≤ 10 mm increase on a 100 mm VAS. The FAS consisted of all study participants randomized into the study except 6 participants excluded from FAS due to persistent GCP non-compliance at the site enrolling them.
    End point type
    Secondary
    End point timeframe
    Week 24
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: percentage of participants
        number (not applicable)
    38.3
    46.6
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The difference in proportion responding between SOC+DZP 24mg/kg and SOC+PBO was estimated and tested using the CMH risk difference estimate controlling for the randomization stratification factors, Pooled Region (North America vs Western Europe/Asia-Pacific vs Latin America/Eastern Europe), Screening disease activity (chronic active vs acute flaring) and Screening SLEDAI score (<10 vs >=10).
    Comparison groups
    PBO+SOC v DZP+SOC
    Number of subjects included in analysis
    315
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1776
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Proportions (%)
    Point estimate
    7.9
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -3.6
         upper limit
    		 19.4

    Secondary: Percentage of Participants with Achievement of BICLA response at Week 12

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    End point title
    		 Percentage of Participants with Achievement of BICLA response at Week 12
    End point description
    Study participants were considered to be a BICLA responder if all of the following were fulfilled: • BILAG 2004 improvement without worsening (A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and less than or equal to [≤] 1 new B.); Here, score A (“Active”): Severely active disease; score B (“Beware”): Moderately active disease; score C (“Contentment”): Mild stable disease; score D (“Discount”): Inactive now but previously active and • No worsening in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score compared to Baseline Visit (defined as no increase in SLEDAI-2K total score); and • No worsening in the PGA compared to Baseline Visit defined as ≤ 10 mm increase on a 100 mm VAS. The FAS consisted of all study participants randomized into the study except 6 participants excluded from FAS due to persistent GCP non-compliance at the site enrolling them.
    End point type
    Secondary
    End point timeframe
    Week 12
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: percentage of participants
        number (not applicable)
    29.0
    39.9
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The difference in proportion responding between SOC+DZP 24mg/kg and SOC+PBO was estimated and tested using the CMH risk difference estimate controlling for the randomization stratification factors, Pooled Region (North America vs Western Europe/Asia-Pacific vs Latin America/Eastern Europe), Screening disease activity (chronic active vs acute flaring) and Screening SLEDAI score (<10 vs >=10).
    Comparison groups
    PBO+SOC v DZP+SOC
    Number of subjects included in analysis
    315
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0518
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Proportions (%)
    Point estimate
    10.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -0.1
         upper limit
    		 21.7

    Secondary: Percentage of Participants with Achievement of prevention of severe British Isles Lupus Assessment Group (BILAG) flares (severe BILAG flare-free) through Week 48

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    End point title
    		 Percentage of Participants with Achievement of prevention of severe British Isles Lupus Assessment Group (BILAG) flares (severe BILAG flare-free) through Week 48
    End point description
    A severe BILAG flare was defined as a british isles lupus assessment group disease activity index 2004 (BILAG 2004) Grade A in any system due to individual items that were new or worse qualifying for the Grade A. Determination of items that were new or worse and were qualifying for the Grade A were according to the supplementary information for the numerical scoring of the BILAG-2004 index. Here, Grade A (“Active”): Severely active disease (sufficient to require systemic immunosuppressant or anticoagulant therapy. The FAS consisted of all study participants randomized into the study except 6 participants excluded from FAS due to persistent GCP non-compliance at the site enrolling them.
    End point type
    Secondary
    End point timeframe
    During Treatment Period up to Week 48
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: percentage of participants
        number (not applicable)
    76.6
    88.4
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The difference in proportion responding between SOC+DZP 24mg/kg and SOC+PBO was estimated and tested using the CMH risk difference estimate controlling for the randomization stratification factors, Pooled Region (North America vs Western Europe/Asia-Pacific vs Latin America/Eastern Europe), Screening disease activity (chronic active vs acute flaring) and Screening SLEDAI score (<10 vs >=10).
    Comparison groups
    PBO+SOC v DZP+SOC
    Number of subjects included in analysis
    315
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0257
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Proportions (%)
    Point estimate
    11.5
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 1.4
         upper limit
    		 21.6

    Secondary: Percentage of Participants with Achievement of Lupus Low Disease Activity State (LLDAS) in ≥50% of post-Baseline visits through Week 48

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    End point title
    		 Percentage of Participants with Achievement of Lupus Low Disease Activity State (LLDAS) in ≥50% of post-Baseline visits through Week 48
    End point description
    The LLDAS includes domains that capture the absence of organ-threatening disease activity and harmful treatment burden. The LLDAS is defined as: • SLEDAI-2K score was ≤4 with no activity in major organ systems. • No new and/or worsening disease activity defined as no SLEDAI-2K component documented as present that was not documented present at the previous visit. • PGA ≤ 33 mm. • Prednisone equivalent systemic dose for systemic lupus erythematosus (SLE) indication ≤ 7.5 mg per day. • Stable standard maintenance doses of immunosuppressive drugs as allowed by protocol, defined as no increase in dose in the past 12 weeks and no dose higher than allowed as per protocol. The FAS consisted of all study participants randomized into the study except 6 participants excluded from FAS due to persistent GCP non-compliance at the site enrolling them.
    End point type
    Secondary
    End point timeframe
    During Treatment Period up to Week 48
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: percentage of participants
        number (not applicable)
    15.9
    23.6
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The difference in proportion responding between SOC+DZP 24mg/kg and SOC+PBO was estimated and tested using the Cochran-Mantel-Haenszel (CMH) risk difference estimate controlling for the randomization stratification factors, Pooled Region (North America vs Western Europe/Asia-Pacific vs Latin America/Eastern Europe), Screening disease activity (chronic active vs acute flaring) and Screening SLEDAI score (<10 vs >=10).
    Comparison groups
    PBO+SOC v DZP+SOC
    Number of subjects included in analysis
    315
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.1042
    Method
    		 Cochran-Mantel-Haenszel
    Parameter type
    		 Difference in Proportions (%)
    Point estimate
    7.2
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -1.5
         upper limit
    		 16

    Secondary: Change from Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) at Week 48

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    End point title
    		 Change from Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) at Week 48
    End point description
    The SLEDAI-2K is a global index which includes 24 clinical and laboratory variables such as antibodies, renal, and hematological components measured 30 days before, and at the timepoint of assessment. The variables were weighted by the type of manifestation, but not by severity or dynamic of the individual item. The SLEDAI-2K includes scoring for antibodies (anti-dsDNA positive or negative) and low complement, as well as some renal and hematologic parameters. The total score falls between 0 and 105, with higher scores representing increased disease activity. Mixed effects models for repeated measurements (MMRM). The FAS consisted of all study participants randomized into the study except 6 participants excluded from FAS due to persistent GCP non-compliance at the site enrolling them.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day 1) to Week 48
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: score on a scale
        least squares mean (standard error)
    -4.2 ( 0.39 )
    -6.1 ( 0.26 )
    Statistical analysis title
    		 Statistical Analysis 1
    Statistical analysis description
    The Least Squares (LS) Mean, the difference (DZP+SOC versus PBO+SOC), and the 95% CIs was computed from the MMRM.
    Comparison groups
    PBO+SOC v DZP+SOC
    Number of subjects included in analysis
    315
    Analysis specification
    Pre-specified
    Analysis type
    P-value
    		 = 0.0001
    Method
    		 MMRM
    Parameter type
    		 Difference of Change(DZP+SOC vs PBO+SOC)
    Point estimate
    -1.8
    Confidence interval
         level
    		 95%
         sides
    2-sided
         lower limit
    		 -2.7
         upper limit
    		 -0.9

    Secondary: Percentage of Participants with Achievement of BILAG improvement without worsening at Week 48

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    End point title
    		 Percentage of Participants with Achievement of BILAG improvement without worsening at Week 48
    End point description
    The BILAG improvement without worsening defined as A scores at Baseline improved to B, C or D; B scores improved to C or D; no new A scores and ≤1 new B Score. Here, score A (“Active”): Severely active disease (sufficient to require systemic immunosuppressant or anticoagulant therapy; score B (“Beware”): Moderately active disease (requires low dose or local immunosuppressant therapy or symptomatic therapy; score C (“Contentment”): Mild stable disease (no indication for changes in treatment); score D (“Discount”): Inactive now but previously active. The FAS consisted of all study participants randomized into the study except 6 participants excluded from FAS due to persistent GCP non-compliance at the site enrolling them.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: percentage of participants
        number (not applicable)
    34.6
    49.5
    No statistical analyses for this end point

    Secondary: Change from Baseline in Physician’s Global Assessment (PGA) at Week 48

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    End point title
    		 Change from Baseline in Physician’s Global Assessment (PGA) at Week 48
    End point description
    The PGA is a measure of systemic lupus erythematosus (SLE) signs and symptoms by the physician using a visual analog scale of 0 to 100mm, Where 0 indicate “very good”, asymptomatic, and no limitation of normal activity and 100 indicate “severe disease”. The FAS consisted of all study participants randomized into the study except 6 participants excluded from FAS due to persistent GCP non-compliance at the site enrolling them.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day 1) to Week 48
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: score on a scale
        least squares mean (standard error)
    -33.4 ( 1.99 )
    -39.6 ( 1.36 )
    No statistical analyses for this end point

    Secondary: Time to severe BILAG Flare through Week 48

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    End point title
    		 Time to severe BILAG Flare through Week 48
    End point description
    Time to severe BILAG flare (the event) through Week 48 was defined as the time from randomization until the start of the event. A severe BILAG flare was defined as a BILAG 2004 Grade A in any system due to individual items that were new or worse qualifying for the Grade A. Determination of items that were new or worse and were qualifying for the Grade A, according to the supplementary information for the numerical scoring of the BILAG-2004 index. Here, Grade A (“Active”): Severely active disease. The FAS consisted of all study participants randomized into the study except 6 participants excluded from FAS due to persistent GCP non-compliance at the site enrolling them. Here, 99999 indicates the time to flare estimate of the 25 percentile, median, 75 percentile time could not be calculated and presented due to the low number of events (less than 25%, 50%, 75% participants respectively had flare events in both arms).
    End point type
    Secondary
    End point timeframe
    During Treatment Period up to Week 48
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: weeks
        median (inter-quartile range (Q1-Q3))
    99999 (99999 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    PBO+SOC v DZP+SOC
    Number of subjects included in analysis
    315
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0111
    Method
    		 Logrank
    Confidence interval

    Secondary: Percentage of Participants with Achievement of prevention of moderate/severe BILAG flares (moderate/severe BILAG flare-free) through Week 48

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    End point title
    		 Percentage of Participants with Achievement of prevention of moderate/severe BILAG flares (moderate/severe BILAG flare-free) through Week 48
    End point description
    Achievement of prevention of moderate/severe BILAG flares through Week 48 was defined as % of participants with no moderate or severe flare through Week 48. Severe BILAG flare: BILAG 2004 Grade A in any system due to individual items that were new or worse qualifying for Grade A. Determination of items that were new or worse and were qualifying for Grade A, according to supplementary information for numerical scoring of BILAG-2004 index. A moderate BILAG flare: 2 or more BILAG 2004 Grade B due to individual items that were new or worse and were qualifying for Grade B in any system. Determination of items that were new or worse qualifying for Grade B, according to supplementary information for numerical scoring of BILAG- 2004 index. Here, Grade A (Active): Severely active disease; Grade B (Beware):Moderately active disease. FAS consisted of all study participants randomized into study except 6 participants excluded from FAS due to persistent GCP non-compliance at site enrolling them.
    End point type
    Secondary
    End point timeframe
    During Treatment Period up to Week 48
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: percentage of participants
        number (not applicable)
    63.0
    78.6
    No statistical analyses for this end point

    Secondary: Percentage of Participants with Achievement of Systemic Lupus Erythematosus Responder Index response - 4 (SRI-4) response at Week 48

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    End point title
    		 Percentage of Participants with Achievement of Systemic Lupus Erythematosus Responder Index response - 4 (SRI-4) response at Week 48
    End point description
    The SRI-4 define responders as meeting all of the following criteria: • Reduction in SLEDAI-2K score of ≥ 4. • No shift from BILAG 2004 Grade B, C, D, or E to A post-Baseline. Here, Grade A (“Active”): Severely active disease; Grade B (“Beware”): Moderately active disease; Grade C (“Contentment”): Mild stable disease; Grade D (“Discount”): Inactive now but previously active; Grade E (“Excluded”): Never affected. • No more than 1 shift from BILAG 2004 Grade C, D, or E to B post-Baseline. • No worsening in the PGA compared to study entry defined as ≤ 10 mm increase on a 100 mm visual analog scale, equivalent to less than a 10 mm increase in the PGA compared to study entry score. The FAS consisted of all study participants randomized into the study except 6 participants excluded from FAS due to persistent GCP non-compliance at the site enrolling them.
    End point type
    Secondary
    End point timeframe
    Week 48
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: percentage of participants
        number (not applicable)
    41.1
    60.1
    No statistical analyses for this end point

    Secondary: Time to moderate/severe BILAG flare through Week 48

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    End point title
    		 Time to moderate/severe BILAG flare through Week 48
    End point description
    Time to moderate/severe BILAG flare (event): time from randomization until start of event. Moderate BILAG flare: as 2 or more BILAG 2004 Grade B due to individual items that were new or worse and were qualifying for Grade B in any system. Determination of items that were new or worse qualifying for Grade B, as per supplementary information for numerical score of BILAG-2004. Severe BILAG flare: as BILAG 2004 Grade A in any system due to individual items that were new/worse qualifying for Grade A. Determination of items that were new/worse and are qualifying for Grade A, as per supplementary information for numerical score of BILAG-2004. Here, Grade A (Active): Severely active disease; Grade B (Beware): Moderately active disease. FAS was used. 99999: indicates that time to flare estimate of 25 percentile, median, 75 percentile time could not be calculated and presented in case of low number of events (less than 25%, 50%, 75% participants respectively had flare events).
    End point type
    Secondary
    End point timeframe
    During Treatment Period up to Week 48
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    107
    208
    Units: weeks
        median (inter-quartile range (Q1-Q3))
    99999 (36.1 to 99999)
    99999 (99999 to 99999)
    Statistical analysis title
    		 Statistical Analysis 1
    Comparison groups
    PBO+SOC v DZP+SOC
    Number of subjects included in analysis
    315
    Analysis specification
    Pre-specified
    Analysis type
    		 superiority
    P-value
    		 = 0.0228
    Method
    		 Logrank
    Confidence interval

    Secondary: Percentage of participants with treatment-emergent adverse events of special interest during the study

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    End point title
    		 Percentage of participants with treatment-emergent adverse events of special interest during the study
    End point description
    An adverse event of special interest (AESIs) is any AE that a regulatory authority has mandated be reported on an expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the administration of a product/compound. The SS consisted of all study participants who were randomized and had received at least 1 dose (any amount) of study medication.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    108
    213
    Units: percentage of participants
        number (not applicable)
    0.9
    0
    No statistical analyses for this end point

    Secondary: Percentage of participants with serious treatment-emergent adverse events during the study

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    End point title
    		 Percentage of participants with serious treatment-emergent adverse events during the study
    End point description
    A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: Results in death; Is life-threatening, Requires in patient hospitalization or prolongation of existing hospitalization; Results in persistent disability/incapacity; Is a congenital anomaly/birth defect; and Other important medical events which based on medical or scientific judgement may jeopardize the patients, or may require medical or surgical intervention to prevent any of the above. Treatment-emergent AEs were those with onset date on or after the first administration of study drug, and up to 60 days after last dose. The SS consisted of all study participants who were randomized and had received at least 1 dose (any amount) of study medication.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    108
    213
    Units: percentage of participants
        number (not applicable)
    14.8
    9.9
    No statistical analyses for this end point

    Secondary: Percentage of participants with treatment-emergent adverse events (TEAEs) during the study

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    End point title
    		 Percentage of participants with treatment-emergent adverse events (TEAEs) during the study
    End point description
    An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of investigational medicinal product (IMP), whether or not considered related to the IMP. An AE could therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of IMP. Treatment-emergent AEs were those with onset date on or after the first administration of study drug, and up to 60 days after last dose. The SS consisted of all study participants who were randomized and had received at least 1 dose (any amount) of study medication.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    108
    213
    Units: percentage of participants
        number (not applicable)
    75.0
    82.6
    No statistical analyses for this end point

    Secondary: Percentage of participants with treatment-emergent adverse events of special monitoring during the study

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    End point title
    		 Percentage of participants with treatment-emergent adverse events of special monitoring during the study
    End point description
    An AE of special monitoring is a product-specific AEs, adverse reactions, or safety topics considered as requiring special monitoring by UCB. The SS consisted of all study participants who were randomized and had received at least 1 dose (any amount) of study medication.
    End point type
    Secondary
    End point timeframe
    From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
    End point values
    		 PBO+SOC DZP+SOC
    Number of subjects analysed
    108
    213
    Units: percentage of participants
        number (not applicable)
    24.1
    36.6
    No statistical analyses for this end point

    Adverse events

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    Adverse events information
    Timeframe for reporting adverse events
    From Baseline (Day 1) until Safety Follow-Up (up to Week 54)
    Adverse event reporting additional description
    Treatment-emergent AEs were those with onset date on or after the first administration of study drug, and up to 60 days after last dose. The SS consisted of all study participants who were randomized and had received at least 1 dose (any amount) of study medication.
    Assessment type
    		 Non-systematic
    Dictionary used for adverse event reporting
    Dictionary name
    		 MedDRA
    Dictionary version
    24.0
    Reporting groups
    Reporting group title
    PBO+SOC
    Reporting group description
    		 Participants received placebo (PBO) as an intravenous (iv) infusion every 4 weeks (Q4W) in combination with Standard of Care (SOC) during 48 weeks Treatment Period.

    Reporting group title
    DZP+SOC
    Reporting group description
    		 Participants received Dapirolizumab pegol (DZP) 24 milligrams/kilogram (mg/kg) as an iv infusion Q4W in combination with SOC during 48 weeks Treatment Period.

    Serious adverse events
    		 PBO+SOC DZP+SOC
    Total subjects affected by serious adverse events
         subjects affected / exposed
    16 / 108 (14.81%)
    21 / 213 (9.86%)
         number of deaths (all causes)
    0
    1
         number of deaths resulting from adverse events
    0
    1
    Neoplasms benign, malignant and unspecified (incl cysts and polyps)
    Metastases to central nervous system
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lung adenocarcinoma
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    General disorders and administration site conditions
    Chest pain
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Respiratory, thoracic and mediastinal disorders
    Pleural effusion
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Shrinking lung syndrome
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Asthma
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Psychiatric disorders
    Suicidal ideation
    Additional description: The AE of suicidal ideation occurred before administration of the first dose of study treatment. Only for technical reasons it was listed in the analysis as “treatment emergent” as the onset date was the day of first study treatment.
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Drug abuse
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Anxiety
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Injury, poisoning and procedural complications
    Limb injury
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infusion related reaction
         subjects affected / exposed
    0 / 108 (0.00%)
    2 / 213 (0.94%)
         occurrences causally related to treatment / all
    0 / 0
    2 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tendon rupture
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Tibia fracture
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Humerus fracture
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Cardiac disorders
    Acute myocardial infarction
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Lupus myocarditis
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Mitral valve incompetence
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ear and labyrinth disorders
    Vertigo
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gastrointestinal disorders
    Lupus enteritis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Hepatobiliary disorders
    Cholelithiasis
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Skin and subcutaneous tissue disorders
    Cutaneous vasculitis
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Renal and urinary disorders
    Nephrolithiasis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Musculoskeletal and connective tissue disorders
    Musculoskeletal chest pain
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Systemic lupus erythematosus
         subjects affected / exposed
    1 / 108 (0.93%)
    3 / 213 (1.41%)
         occurrences causally related to treatment / all
    0 / 1
    1 / 4
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Infections and infestations
    Diverticulitis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Appendicitis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacteraemia
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia respiratory syncytial viral
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Pneumonia
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    1 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bronchitis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Herpes zoster
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Bacterial colitis
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Gangrene
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 1
    Cellulitis
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Diverticulitis intestinal perforated
         subjects affected / exposed
    1 / 108 (0.93%)
    0 / 213 (0.00%)
         occurrences causally related to treatment / all
    0 / 1
    0 / 0
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Joint tuberculosis
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    1 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Urinary tract infection
         subjects affected / exposed
    0 / 108 (0.00%)
    1 / 213 (0.47%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 1
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Ophthalmic herpes zoster
    Additional description: The two events were reported as “herpes zoster over left eyelid and forehead, V1” and “left herpes zoster ophthlamicus (dermatome V1/V2)”.
         subjects affected / exposed
    0 / 108 (0.00%)
    2 / 213 (0.94%)
         occurrences causally related to treatment / all
    0 / 0
    0 / 2
         deaths causally related to treatment / all
    0 / 0
    0 / 0
    Frequency threshold for reporting non-serious adverse events: 5%
    Non-serious adverse events
    		 PBO+SOC DZP+SOC
    Total subjects affected by non serious adverse events
         subjects affected / exposed
    47 / 108 (43.52%)
    109 / 213 (51.17%)
    Nervous system disorders
    Headache
         subjects affected / exposed
    7 / 108 (6.48%)
    15 / 213 (7.04%)
         occurrences all number
    8
    24
    Gastrointestinal disorders
    Diarrhoea
         subjects affected / exposed
    10 / 108 (9.26%)
    15 / 213 (7.04%)
         occurrences all number
    12
    15
    Nausea
         subjects affected / exposed
    6 / 108 (5.56%)
    9 / 213 (4.23%)
         occurrences all number
    9
    9
    Infections and infestations
    COVID-19
         subjects affected / exposed
    17 / 108 (15.74%)
    44 / 213 (20.66%)
         occurrences all number
    18
    44
    Herpes zoster
         subjects affected / exposed
    6 / 108 (5.56%)
    4 / 213 (1.88%)
         occurrences all number
    7
    4
    Bronchitis
         subjects affected / exposed
    5 / 108 (4.63%)
    11 / 213 (5.16%)
         occurrences all number
    6
    13
    Upper respiratory tract infection
         subjects affected / exposed
    8 / 108 (7.41%)
    20 / 213 (9.39%)
         occurrences all number
    9
    23
    Nasopharyngitis
         subjects affected / exposed
    13 / 108 (12.04%)
    18 / 213 (8.45%)
         occurrences all number
    19
    23
    Urinary tract infection
         subjects affected / exposed
    9 / 108 (8.33%)
    28 / 213 (13.15%)
         occurrences all number
    10
    36
    Oral herpes
         subjects affected / exposed
    6 / 108 (5.56%)
    4 / 213 (1.88%)
         occurrences all number
    8
    4

    More information

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    Substantial protocol amendments (globally)
    Were there any global substantial amendments to the protocol? Yes
    Date
    Amendment
    14 Oct 2020
    Protocol Amendment 1 was dated 14 Oct 2020: • Updated the planned analysis. • Added exploratory biomarker analysis on the immune response to infectious antigens (eg, severe acute respiratory syndrome coronavirus 2 [SARS-CoV-2]). • Clarified the handling of protocol-defined criteria and actions related to the SARS-CoV-2 pandemic. • Clarified unclear or misinterpretable text and inconsistencies between different sections.
    14 Jan 2022
    Protocol Amendment 3 was dated 14 Jan 2022: • Provided recommendations for contraception during mycophenolate treatment. • Added additional guidance on COVID-19 vaccinations in immunosuppressed participants.
    16 Mar 2023
    Protocol Amendment 4 was dated 16 Mar 2023: • Reduced the sample size and consequently removed the interim analysis.

    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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