A Study to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Study Participants With Moderately to Severely Active Systemic Lupus Erythematosus

Study participants were considered to be a BILAG 2004-based Composite Lupus Assessment (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 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 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).

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 ≤ 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 PGA compared to Baseline Visit defined as ≤ 10 mm increase on a 100 mm VAS.

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 ≤ 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 PGA compared to Baseline Visit defined as ≤ 10 mm increase on a 100 mm VAS.

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 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 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 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 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 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.

Achievement of prevention of moderate/severe BILAG flares through Week 48 was defined as the percentage of participants with no moderate or severe flare through Week 48. 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. A moderate BILAG flare was defined as 2 or more BILAG 2004 Grade B due to individual items that were new or worse and were qualifying for the Grade B in any system. Determination of items that were new or worse qualifying for the Grade B, according to the supplementary information for the numerical scoring of the BILAG- 2004 index. Here, Grade A ("Active"): Severely active disease; Grade B ("Beware"): Moderately active disease.

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.

Time to moderate/severe BILAG flare (the event) through Week 48 was defined as the time from randomization until the start of the event. Moderate BILAG flare was defined as 2 or more BILAG 2004 Grade B due to individual items that were new or worse and were qualifying for the Grade B in any system. Determination of items that were new or worse qualifying for the Grade B, according to the supplementary information for the numerical scoring of the BILAG-2004 index. 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 are 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; Grade B ("Beware"): Moderately active disease.

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.

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.

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.

An AE of special monitoring is a product-specific AEs, adverse reactions, or safety topics considered as requiring special monitoring by UCB.