The purpose of this study is to evaluate the ability of dapirolizumab pegol (DZP) as an add-on treatment to standard of care (SOC) medication to achieve clinically relevant long term improvement of moderate to severe disease activity.
Study participant must be ≥16 years of age, (≥18 years of age for China), unless restricted by local regulation, at the time of signing the Informed Consent form (ICF)
Anti-Smith (anti-Sm) antibodies (central laboratory or source verifiable history)
Anti-Sjögren's syndrome antibody A (Anti-SSA) (Ro)/Anti-Sjögren's syndrome antibody B (anti-SSB) (La) autoantibodies (central laboratory)
Historical evidence for anti-dsDNA antibodies
Study participant has any medical or psychiatric condition (including conditions due to neuropsychiatric SLE) that, in the opinion of the Investigator, could jeopardize or would compromise the study participant's ability to participate in this study. This includes study participants with a life-threatening condition
Study participant has a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies. This includes systemic reactions due to latex allergy
Study participant has a history of malignancy, except the following treated cancers: cervical carcinoma in situ (after complete resection [eg, curettage, electrodesiccation] not later than 4 weeks prior to the Screening Visit [V1]), basal cell carcinoma, or dermatological squamous cell carcinoma
Study participant has a mixed connective tissue disease, scleroderma, and/or overlap syndrome of these diseases with SLE
Parallel
DZP
DrugStudy participants will receive dapirolizumab pegol (DZP) at prespecified time-points.
Placebo
Other interventionStudy participants will receive placebo at prespecified time-points.
Achievement of British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004)-based Composite Lupus Assessment (BICLA) response at Week 48
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.
Achievement of SRI 4 response at Week 48
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).
Achievement of prevention of severe BILAG flares (severe BILAG flare-free) through Week 48
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.
Achievement of LLDAS at Week 40 and maintaining LLDAS at Weeks 44 and 48
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
Change from Baseline to Week 48 in the FATIGUE-PRO Total score
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.
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