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

Study Overview
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Brief Summary
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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.

Official Title
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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

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: DZP
* Other: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Rescreening will be allowed once during the study in case there is new evidence for an inclusion criterion that was not fulfilled at the first screening or in case a study participant no longer meets an exclusion criterion or screening period exceeded the maximum duration due to delays in screening processes Study participant must be ≥16 years of age, unless restricted by local regulation, at the time of signing the Informed Consent form (ICF) Study participants who have moderate to severe disease activity due to either persisting active SLE or due to an acute worsening of SLE in the scope of frequent flaring/relapsing-remitting systemic lupus erythematosus (SLE) despite stable standard of care (SOC) medication defined as: a. Diagnosed with SLE at least 24 weeks before the Screening Visit (Visit 1) study entry by a qualified physician b. Classified by 2019 SLE European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria for SLE c. With serological evidence for SLE at Screening as demonstrated by at least 1 of the following: i) Evidence for anti-dsDNA (in central laboratory at Screening) ii) Either complement C3 < lower limit of normal (LLN) OR complement C4 <LLN OR elevated erythrocyte-bound complement C4d (where available) as measured by central laboratory iii) Antinuclear antibodies with a titer of at least 1:80 confirmed by central laboratory in combination with evidence of at least 1 of the following SLE typical autoantibodies: 1. Anti-Smith (anti-Sm) antibodies (central laboratory) 2. Anti-Sjögren's syndrome antibody A (Anti-SSA) (Ro)/Anti-Sjögren's syndrome antibody B (anti-SSB) (La) autoantibodies (central laboratory) 3. Historic evidence for anti-dsDNA antibodies d. Moderately to severely active defined as British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004) Grade B in ≥2 organ systems and/or a BILAG 2004 Grade A in ≥1 organ systems at Screening and Baseline Visit AND Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) ≥6 at Screening Visit AND SLEDAI-2K without labs ≥4 at Baseline Visit e. Receiving the following SOC medication at stable dose: Antimalarial treatment in combination with corticosteroids and/or immunosuppressants or as stand-alone treatment if justified OR Treatment with corticosteroids and/or immunosuppressants if anti-malarial treatment is not possible Exclusion Criteria: Study participant has any medical or psychiatric condition (including conditions due to neuropsychiatric systemic lupus erythematosus (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 Study participant has a history of malignancy, except the following treated cancers: cervical carcinoma in situ, basal cell carcinoma, or dermatological squamous cell carcinoma Study participant has an increased risk for thromboembolic events due to an ongoing heart disease or due to a medical device, including but not limited to vascular graft, valvular heart disease, atrial fibrillation, or a heart rhythm disorder Study participant has evidence of human immunodeficiency virus (HIV) infection, agammaglobulinemias, T-cell deficiencies, or human T-cell lymphotropic virus-1 infection Study participant had a reactivated latent infection (example, cytomegalovirus, herpes simplex virus, or herpes zoster infection) or opportunistic infection (including but not limited to, pneumocystis, cytomegalovirus, or severe herpes zoster infection) within 12 weeks prior to the first study medication infusion (Visit 2), or is currently receiving suppressive therapy for an opportunistic infection Study participants who have received live/live attenuated vaccines within 6 weeks prior to the first study medication infusion Study participant has clinically significant active or latent infection Study participant has a mixed connective tissue disease, scleroderma, and/or overlap syndrome of these diseases with SLE Study participant takes any protocol defined prohibited concomitant medication Study participant has previously been randomized within this study or participant has previously been assigned to treatment with dapirolizumab pegol (DZP) in a study evaluating DZP Study participant has participated in another study of an IMP within the previous 12 weeks or 5 half-lives of the investigational medicinal product (IMP) whatever is longer or is currently participating in another study of an IMP Study participant has chronic kidney failure stage 4, manifested by estimated glomerular filtration rate <30mL/min/1.73m^2, or serum creatinine >2.5 mg/dL, or participant has proteinuria >3 g/day, or protein: creatinine ratio >340 mg/mmol at the Screening Visit

Ages Eligible for Study
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Minimum Age: 16 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dapirolizumab pegol<br>Subjects will receive dapriolizumab pegol througout the Treatment Period. | Drug: DZP<br>* Subjects will receive dapirolizumab pegol at prespecified time-points.<br>* Other names: CDP7657;|
| Placebo Comparator: Placebo<br>Subjects will receive placebo througout the Treatment Period. | Other: Placebo<br>* Subjects will receive placebo at prespecified time-points.<br>* Other names: PBO;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of BICLA response at Week 48 | A study participant is considered to be a BILAG 2004-based Composite Lupus Assessment (BICLA) responder if all of the following is 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.); 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 ≤10mm increase on a 100mm 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. | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Achievement of BICLA response at Week 24 | A study participant is considered to be a BICLA responder if all of the following is 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.); 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 ≤10mm increase on a 100mm 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. | Week 24 | 
| Achievement of BICLA response at Week 12 | A study participant is considered to be a BICLA responder if all of the following is 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.); 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 ≤10mm increase on a 100mm 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. | Week 12 | 
| Achievement of prevention of severe BILAG flares (severe BILAG flare-free) through Week 48 | BILAG severe flare is defined as a British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004) Grade A in any system due to individual items that are new or worse and are qualifying for the Grade A (Isenberg et al, 2011). 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 (Yee et al, 2010). | During Treatment Period up to Week 48 | 
| Achievement of LLDAS in ≥50% of post-Baseline visits through Week 48 | Low lupus disease activity state (LLDAS) is defined as: No significant disease activity as per SLEDAI-2K and BILAG 2004 (SLEDAI-2K score ≤4 with no activity in major organ systems (renal, 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 PGA ≤33mm Prednisone equivalent systemic dose for systemic lupus erythematosus (SLE) indication ≤7.5mg per day Stable standard maintenance doses of immunosuppressive drugs as allowed by protocol | During Treatment Period up to Week 48 | 
| Change from Baseline in SLEDAI-2K at Week 48 | The SLEDAI-2K Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K; 30 days) measures disease activity. 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. | From Baseline (Day 1) to Week 48 | 
| Achievement of BILAG improvement without worsening at Week 48 | 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. | Week 48 | 
| Change from Baseline in PGA at Week 48 | Physician's Global Assessment of Disease (PGA) The Investigator will rate the overall status of the study participant. | From Baseline (Day 1) to Week 48 | 
| Achievement of SRI4 response at Week 48 | The Systemic Lupus Erythematosus Responder Index (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 study entry defined as ≤10mm increase on a 100mm visual analog scale | Week 48 | 
| Achievement of prevention of moderate/severe BILAG flares (moderate/severe BILAG flare-free) through Week 48 | BILAG severe flare is defined as a BILAG 2004 Grade A in any system due to individual items that are new or worse and are qualifying for the Grade A (Isenberg et al, 2011). 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 (Yee et al, 2010). BILAG moderate flare is defined as 2 or more BILAG 2004 Grade Bs due to individual items that are new or worse and are qualifying for the Grade B in any system (Isenberg et al, 2011). 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 (Yee et al, 2010) | During Treatment Period up to Week 48 | 
| Time to severe BILAG Flare through Week 48 | BILAG severe flare is defined as a BILAG 2004 Grade A in any system due to individual items that are new or worse and are qualifying for the Grade A (Isenberg et al, 2011). 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 (Yee et al, 2010). | During Treatment Period up to Week 48 | 
| Time to moderate/severe BILAG flare through Week 48 | BILAG severe flare is defined as a BILAG 2004 Grade A in any system due to individual items that are new or worse and are qualifying for the Grade A (Isenberg et al, 2011). 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 (Yee et al, 2010). BILAG moderate flare is defined as 2 or more BILAG 2004 Grade Bs due to individual items that are new or worse and are qualifying for the Grade B in any system (Isenberg et al, 2011). 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 (Yee et al, 2010) | During Treatment Period up to Week 48 | 
| Percentage of participants with treatment-emergent adverse events (TEAEs) during the study | Treatment-emergent adverse events (TEAEs) are any untoward medical incidence in a subject during administered study treatment, whether or not these events are related to study treatment. | From Baseline (Day 1) until Safety Follow-Up (up to Week 54) | 
| Percentage of participants with serious treatment-emergent adverse events during the study | A serious treatment-emergent adverse event (serious TEAE) is any untoward medical occurrence that at any dose: Results in death Is life-threatening Requires in patient hospitalisation or prolongation of existing hospitalisation Is a congenital anomaly or birth defect Is an infection that requires treatment with parenteral antibiotics Other important medical events which based on medical or scientific judgement may jeopardise the patients, or may require medical or surgical intervention to prevent any of the above | From Baseline (Day 1) until Safety Follow-Up (up to Week 54) | 
| Percentage of participants with treatment-emergent adverse events of special interest during the study | An adverse event of special interest 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 UCB product/compound. | From Baseline (Day 1) until Safety Follow-Up (up to Week 54) | 
| Percentage of participants with treatment-emergent adverse events of special monitoring during the study | An adverse event of special monitoring is a product-specific AEs, adverse reactions, or safety topics considered as requiring special monitoring by UCB. | From Baseline (Day 1) until Safety Follow-Up (up to Week 54) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic lupus erythematosus, Dapirolizumab pegol, SLE, DZP