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

A study participant is a BICLA responder if all of the following is fulfilled: a. BILAG 2004 improvement without worsening, defined as BILAG 2004 Grade As at Baseline improved to B/C/D, BILAG 2004 Grade Bs at Baseline improved to C/D, and no BILAG 2004 worsening in other BILAG 2004 organ systems (that had BILAG 2004 Grade C/D/E at Baseline) such that there are no new BILAG 2004 Grades A nor greater than 1 new BILAG 2004 Grade(s) B; and b. No worsening in the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI- 2K) total score compared to Baseline (defined as no increase in SLEDAI-2K total score); and c. No worsening in the Physician's Global Assessment of Disease (PGA) compared to Baseline defined as ≤10 mm increase on a 100 mm visual analog scale Escape treatment intervention as indicated by investigator until the assessment time point will be defined as an intercurrent event for the primary endpoint leading to non-response from the day after the event onward.

The Systemic Lupus Erythematosus Responder Index-4 (SRI 4) define responders as (ie, all criteria must be met):

• Reduction in SLEDAI-2K score of ≥4
• No shift from BILAG 2004 Grade B, C, D, or E to A post-Baseline
• No more than 1 shift from BILAG 2004 Grade C, D, or E to B post-Baseline
• No worsening in the PGA compared to Baseline score; "no worsening" is defined as either no worsening or worsening <10% of the full 100 mm visual analog scale (VAS).

Severe BILAG flare is defined as a BILAG 2004 Grade A in any system due to individual items that are new or worse qualifying for the Grade A.

Determination of items that are new or worse qualifying for the Grade A will be according to the supplementary information for the numerical scoring of the BILAG-2004 index.

Low lupus disease activity state (LLDAS) is defined as:

• No significant disease activity as per Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K); SLEDAI-2K score ≤4 with no activity in major organ systems (renal, central nervous system (CNS), cardiopulmonary, vasculitis, fever)
• No new and/or worsening disease activity defined as no SLEDAI-2K component documented as present that was not documented present at previous visit
• Physician's Global Assessment of Disease (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

The FATIGUE-PRO (Fatigue patient-reported outcome) is a PRO instrument measuring fatigue, a core symptom of SLE, developed using qualitative and quantitative research conducted in patients with SLE. It is composed of 31 items covering 3 domains: Physical Fatigue (items 1-9), Mental and Cognitive Fatigue (items 10-20), and Susceptibility to Fatigue (items 21-31). The study participant is asked to score each fatigue item based on how frequently they experienced the item during the past 7 days using the following response options: 1=none of the time; 2=a little of the time; 3=some of the time; 4=most of the time; 5=all of the time.

The achievement of a reduction in glucocorticoid dose from >7.5mg/day prednisone equivalent dose at Baseline to ≤7.5mg/day prednisone equivalent at Week 36 and maintained through Week 48 will be assessed.

BILAG 2004 improvement without worsening can be 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.

Physician's Global Assessment of Disease (PGA), the investigator will rate the overall status of the study participant. The PGA of disease activity used will be a 100 mm linear scale without anchors. The very far left end is 'very good, asymptomatic and no limitation of normal activities'; the very far right end indicates 'severe disease'.

A BILAG severe flare is defined as a BILAG 2004 Grade A in any system due to individual items that are new or worse qualifying for the Grade A. Determination of items that are new or worse qualifying for the Grade A will be according to the supplementary information for the numerical scoring of the BILAG-2004 index.

A BILAG moderate flare is defined as 2 or more BILAG 2004 Grade Bs due to individual items that are new or worse since previous visit and are qualifying for the Grade B in any system. Determination of items that are new or worse qualifying for the Grade B will be according to the supplementary information for the numerical scoring of the BILAG-2004 index.

SLEDAI-2K measures disease activity. Disease activity in the 30 days prior to and at the time point of the assessment shall be considered. It is a global index and includes 24 clinical symptoms and laboratory variables that are weighted by the type of manifestation, but not by severity or dynamic of the individual item. The total score falls between 0 and 105, with higher scores representing increased disease activity.

The FACIT (Functional Assessment of Chronic Illness Therapy)-Fatigue scale is a patient-reported outcome (PRO) measure assessing symptoms and impacts of fatigue originally developed in patients with cancer (Cella et al, 2002). It is composed of 13 items, all scored from 0 (Not at all) to 4 (Very much), and uses a recall period of the past 7 days. The FACIT-Fatigue score ranges from 0 to 52 with 0 being the worst possible score and 52 being the best possible score (lowest level of fatigue). To obtain a score from 0 to 52, all negatively worded questions have to be recoded, so that responses range from worst (0) to the best (4) outcome.

An adverse event (AE) is any untoward medical occurrence in a patient or clinical study participant, temporally associated with the use of study medication, whether or not considered related to the study medication.

A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose:

• Results in death
• Is life-threatening
• Requires inpatient hospitalization or prolongation of existing hospitalization
• Results in persistent disability/incapacity
• Is a congenital anomaly/birth defect
• Is an Important medical event

An adverse event of special interest is any adverse event (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 UCB product/compound.

An adverse event of special monitoring is a product-specific adverse event (AE), adverse reaction, or safety topic considered as requiring special monitoring by UCB.