Systemic Lupus Erythematosus
Conditions
Keywords
Systemic lupus erythematosus, Dapirolizumab pegol, SLE, DZP
Brief summary
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.
Interventions
DRUGDZP
Study participants will receive dapirolizumab pegol (DZP) at prespecified time-points.
OTHERPlacebo
Study participants will receive placebo at prespecified time-points.
Sponsors
UCB Biopharma SRL
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* 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) * Study participants who have moderate to severe disease activity due to either persisting active systemic lupus erythematosus (SLE) or due to an acute worsening of SLE in the scope of frequent relapsing-remitting SLE despite stable standard of care(SOC) medication defined as: a. Diagnosed with SLE at least 24 weeks before the Screening Visit 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 (defined as evidence for anti-dsDNA antibodies in central laboratory) ii) Either complement C3 \<lower limit of normal (LLN) OR complement C4 \<LLN 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 or source verifiable history) 2. Anti-Sjögren's syndrome antibody A (Anti-SSA) (Ro)/Anti-Sjögren's syndrome antibody B (anti-SSB) (La) autoantibodies (central laboratory) 3. Historical evidence for anti-dsDNA antibodies 4. Anti-ribonucleoprotein (RNP) autoantibodies (central laboratory) 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 the Screening Visit AND * SLEDAI-2K without labs ≥4 at Baseline Visit e. Receiving the following standard of care (SOC) medications at stable dose: * Antimalarial treatment in combination with glucocorticoids and/or immunosuppressants or as stand-alone treatment if justified OR * Treatment with glucocorticoids and/or immunosuppressants if antimalarial treatment is not appropriate (ie, there is documented intolerance in medical history, documented lack of efficacy, contraindications, or lack of availability)
Exclusion criteria
* 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 * Study participant has evidence of human immunodeficiency virus (HIV) infection, agammaglobulinemias, T-cell deficiencies, or human T-cell lymphotropic virus-1 infection at any time prior to or during the study * Study participant has clinically significant active or latent infection * Study participant had a reactivated latent infection (eg, 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 used the prohibited medications within the time frame (Wash-Out Period) listed in the Protocol * Study participant has previously been randomized within this study or has previously been assigned to treatment with dapirolizumab pegol (DZP) in a study evaluating DZP * Study participant has participated in another study of an investigational medicinal product (IMP) within the previous 12 weeks or 5 half-lives of the 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 (eGFR) \<30 mL/min/1.73m2, or serum creatinine \>2.5 mg/dL, or participant has proteinuria \>3g/day, or protein:creatinine ratio \>340 mg/mmol at the Screening Visit
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004)-based Composite Lupus Assessment (BICLA) response at Week 48 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Achievement of SRI 4 response at Week 48 | 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 | 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 | Week 40 to Week 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 | From Baseline to Week 48 | 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. |
| Percentage of participants having a reduction in glucocorticoid dose from >7.5mg/day prednisone-equivalent dose at Baseline to ≤7.5mg/day at Week 36 and maintained through Week 48 | From Baseline to Week 48 | 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. |
| Achievement of BILAG 2004 improvement without worsening at Week 48 | 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. |
| Change from Baseline in PGA at Week 48 | From Baseline to Week 48 | 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'. |
| Achievement of prevention of moderate/severe BILAG flares (moderate/severe BILAG flare-free) through Week 48 | During Treatment Period up to Week 48 | 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. |
| Change from Baseline in SLEDAI-2K at Week 48 | From Baseline to Week 48 | 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. |
| Change from Baseline in FACIT-Fatigue score at Week 48 | From Baseline to Week 48 | 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. |
| Percentage of participants with treatment-emergent adverse events (TEAEs) during the study | From Baseline until Safety Follow-Up (up to Week 54) | 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. |
| Percentage of participants with serious treatment-emergent adverse events during the study | From Baseline until Safety Follow-Up (up to Week 54) | A serious adverse event (SAE) is defined as any untoward medical occurrence that, at any dose: 1. Results in death 2. Is life-threatening 3. Requires inpatient hospitalization or prolongation of existing hospitalization 4. Results in persistent disability/incapacity 5. Is a congenital anomaly/birth defect 6. Is an Important medical event |
| Percentage of participants with treatment-emergent adverse events of special interest during the study | From Baseline until Safety Follow-Up (up to Week 54) | 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. |
| Percentage of participants with treatment-emergent adverse events of special monitoring during the study | From Baseline until Safety Follow-Up (up to Week 54) | 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. |
Countries
Argentina, Belgium, Canada, Chile, China, Denmark, France, Germany, Greece, Italy, Japan, Mexico, Netherlands, Peru, Poland, Puerto Rico, Serbia, South Korea, Spain, Taiwan, United Arab Emirates, United Kingdom, United States
Contacts
CONTACTUCB Cares
STUDY_DIRECTORUCB Cares
001 844 599 2273 (UCB)
Outcome results
None listed