Efficacy and Safety of Atacicept in Systemic Lupus Erythematosus

Study Overview
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Brief Summary
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This is a multi-center, double-blind, randomized, Phase 2b trial to evaluate the efficacy of atacicept in subjects with systemic lupus erythematosus (SLE).

Official Title
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A Phase IIb, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, Multidose, 24-Week Study to Evaluate the Efficacy and Safety of Atacicept in Subjects With Systemic Lupus Erythematosus (SLE)

Conditions
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Lupus Erythematosus, Systemic

Intervention / Treatment
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* Drug: Atacicept 75 milligram (mg)
* Drug: Atacicept 150 mg
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Eligible male and female subjects, aged 18 years or older Must have at least moderately active SLE, as defined as SLE Disease Activity Index-2000 (SLEDAI-2K) score greater than or equal to [>=] 6 at screening visit At least 4 of the 11 American college of rheumatology (ACR) classification criteria for SLE (diagnosed >= 6 months prior to the screening visit) Be seropositive for anti-nuclear antibodies (ANA) and/or anti-double-stranded deoxyribonucleic acid (anti-dsDNA) antibodies Other protocol defined inclusion criteria could apply Exclusion Criteria: Subjects have demyelinating disorder Severe central nervous system SLE Use of cyclophosphamide within 3 months of the screening visit Urine protein:creatinine ratio (UPCr) >= 2 milligram per milligram (mg/mg) per day Other protocol defined exclusion criteria could apply

Ages Eligible for Study
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Minimum Age: 18 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Atacicept 75 mg<br> | Drug: Atacicept 75 milligram (mg)<br>* Atacicept 75 mg will be administered as subcutaneous injection once weekly for 24 weeks.<br>|
| Experimental: Atacicept 150 mg<br> | Drug: Atacicept 150 mg<br>* Atacicept 150 mg will be administered as subcutaneous injection once weekly for 24 weeks.<br>|
| Placebo Comparator: Placebo<br> | Drug: Placebo<br>* Placebo matched to atacicept will be administered as subcutaneous injection once weekly for 24 weeks.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Screening Visit as Baseline | SRI response, a composite measure of reduced SLE disease activity, was defined as a reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (>=) 4 points; no significant worsening in Physician's Global Assessment (PGA) score (<10 % increase, defined as <0.3 point increase for statistical analyses); no new British Isles Lupus Assessment Group (BILAG) A organ domain scores and <=1 (defined as no more than one) new BILAG B organ domain score. | Week 24 | 
| Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Day 1 as Baseline | SRI response, a composite measure of reduced SLE disease activity, was defined as a reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (>=) 4 points; no significant worsening in Physician's Global Assessment (PGA) score (<10 % increase, defined as <0.3 point increase for statistical analyses); no new British Isles Lupus Assessment Group (BILAG) A organ domain scores and <=1 (defined as no more than one) new BILAG B organ domain score. | Week 24 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Subjects at Week 24 Whose Prednisone-Equivalent Corticosteroid (CS) Dose Reduced From Screening by >=25% and to a Dose of =<7.5mg/Day, and no British Isles Lupus Assessment Group (BILAG) A or 2B Flare in Disease Activity | BILAG A or 2B flare is defined by 1 new BILAG A organ domain score and/or 2 new BILAG B organ domain scores compared to the Screening Visit. The BILAG disease activity index evaluates systemic lupus erythematosus (SLE) activity in 8 organ systems, using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Disease sufficiently active requiring disease-modifying treatment (prednisone >20 mg daily or immunosuppressants); BILAG B: moderate disease activity requiring treatment with systemic low-dose oral glucocorticoids, intramuscular or intra-articular or soft tissue CS injection, topical CS or immunosuppressants, or symptomatic therapy such as antimalarials or NSAIDs. BILAG C: mild disease; BILAG D: system previously affected but now inactive and BILAG E: system never involved. | Week 24 | 
| Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | The PGIC is self-rated scale that asks the subject to describe the change in activity limitations, symptoms, emotions, and overall Quality of life (QoL) related to the subject's painful condition on the following scale: 1 (very much improved), 2 (much improved), 3 (minimally improved), 4 (no change), 5 (minimally worse), 6 (much worse) and 7 (very much worse). Percentage of subjects in the PGIC categories of very much or much improved (1 or 2), minimally improved or no change or minimally worse (3 or 4 or 5) and much or very much worse (6 or 7) at Week 24 were presented. | Week 24 | 
| Change From Screening in Prednisolone-Equivalent Corticosteroid (CS) Daily Dose at Week 24 | Change From screening visit to Week 24 of prednisolone-equivalent CS daily dose was presented. | Screening and Week 24 | 
| Time From Randomization to First SRI Response During Treatment Period | SRI response, a composite measure of reduced SLE disease activity, was defined as a reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) disease activity score of greater than or equal to (>=) 4 points; no significant worsening in Physician's Global Assessment (PGA) score (<10 % increase, defined as <0.3 point increase for statistical analyses); no new British Isles Lupus Assessment Group (BILAG) A organ domain scores and <=1 (defined as no more than one) new BILAG B organ domain score. Time to first SRI response during treatment period was presented. | Baseline up to 24 Weeks | 
| Percentage of Subjects With British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response at Week 24 | The BICLA response is defined as BILAG-2004 improvement (all screening visit BILAG A improving to B/C/D, all screening visit BILAG B to C/D, and <=1 new BILAG B and no new BILAG A); no deterioration in SLEDAI total score; PGA increase by <10% (defined as <0.3 point increase for the statistical analyses) and no nonpermitted medication/treatment. | Week 24 | 
| Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | An AE was defined as any unfavourable and unintended sign (including an abnormal laboratory finding), symptom, or disease temporally associated with the use of study drug, whether or not considered related to the study drug. A serious AE was an AE that resulted in any of the following outcomes: death; life threatening; persistent/significant disability/incapacity; initial or prolonged inpatient hospitalization; congenital anomaly/birth defect or was otherwise considered medically important. Treatment-emergent are events between first dose of study drug and up to 48 weeks. TEAEs include both Serious TEAEs and non-serious TEAEs. | Baseline up to 24 weeks after last dose of study drug (assessed up to maximum of 48 weeks) | 
| Change From Week 0 (Day 1) in SF-36 Components at Week 24 | The 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well being: physical and social functioning, physical and emotional role limitations, bodily pain, general health, vitality, mental health. These 8 aspects can also be summarized as physical and mental component summary scores. Total of 10 variables were analyzed (8 aspects, 2 component summary scores). The score for each of the 8 aspects and 2 component summary scores was scaled from 0 to 100, where 0 = lowest level of functioning and 100 = highest level of functioning. | Week 0 (Day 1) and Week 24 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atacicept, Placebo