Lupus Erythematosus, Systemic
Conditions
Keywords
Atacicept, Placebo
Brief summary
This is a multi-center, double-blind, randomized, Phase 2b trial to evaluate the efficacy of atacicept in subjects with systemic lupus erythematosus (SLE).
Interventions
DRUGAtacicept 75 milligram (mg)
Atacicept 75 mg will be administered as subcutaneous injection once weekly for 24 weeks.
DRUGAtacicept 150 mg
Atacicept 150 mg will be administered as subcutaneous injection once weekly for 24 weeks.
DRUGPlacebo
Placebo matched to atacicept will be administered as subcutaneous injection once weekly for 24 weeks.
Sponsors
EMD Serono
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Screening Visit as Baseline | Week 24 | 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. |
| Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Day 1 as Baseline | Week 24 | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Screening in Prednisolone-Equivalent Corticosteroid (CS) Daily Dose at Week 24 | Screening and Week 24 | Change From screening visit to Week 24 of prednisolone-equivalent CS daily dose was presented. |
| Time From Randomization to First SRI Response During Treatment Period | Baseline up to 24 Weeks | 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. |
| 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 | Week 24 | 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. |
| Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Baseline up to 24 weeks after last dose of study drug (assessed up to maximum of 48 weeks) | 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. |
| Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Week 0 (Day 1) and 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. |
| Percentage of Subjects With British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response at Week 24 | 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. |
| Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | 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. |
Countries
Argentina, Brazil, Bulgaria, Chile, Czechia, Germany, Italy, Japan, Mexico, Peru, Philippines, Poland, Russia, South Africa, South Korea, Spain, United Kingdom, United States
Participant flow
Recruitment details
The study was conducted at 136 sites in 18 countries in Asia, Europe, North America, Central America, and South America.
Participants by arm
| Arm | Count |
|---|---|
| Atacicept 75 mg Subjects received atacicept 75 milligram (mg) as once-weekly subcutaneous injection for 24 weeks. | 102 |
| Atacicept 150 mg Subjects received atacicept 150 mg as once-weekly subcutaneous injection for 24 weeks. | 104 |
| Placebo Subjects received placebo matched to atacicept as once-weekly subcutaneous injection for 24 weeks. | 100 |
| Total | 306 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 6 | 5 |
| Overall Study | Lack of Efficacy | 0 | 1 | 2 |
| Overall Study | Lost to Follow-up | 1 | 0 | 0 |
| Overall Study | Other events | 3 | 0 | 0 |
| Overall Study | Protocol Violation | 1 | 2 | 2 |
| Overall Study | Withdrawal by Subject | 6 | 3 | 7 |
Baseline characteristics
| Characteristic | Atacicept 75 mg | Atacicept 150 mg | Placebo | Total |
|---|---|---|---|---|
| Age, Continuous | 37 years STANDARD_DEVIATION 11.2 | 39 years STANDARD_DEVIATION 11.6 | 40 years STANDARD_DEVIATION 13 | 39 years STANDARD_DEVIATION 11.9 |
| Sex: Female, Male Female | 93 Participants | 97 Participants | 90 Participants | 280 Participants |
| Sex: Female, Male Male | 9 Participants | 7 Participants | 10 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 83 / 102 | 84 / 104 | 72 / 100 |
| serious Total, serious adverse events | 9 / 102 | 6 / 104 | 12 / 100 |
Outcome results
Primary
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.
Time frame: Week 24
Population: mITT analysis set included all randomized subjects who had received at least 1 dose of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atacicept 75 mg | Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Day 1 as Baseline | 55.9 percentage of subjects |
| Atacicept 150 mg | Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Day 1 as Baseline | 55.8 percentage of subjects |
| Placebo | Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Day 1 as Baseline | 41.0 percentage of subjects |
p-value: 0.020295% CI: [1.11, 3.46]Logistic regression model
Primary
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.
Time frame: Week 24
Population: mITT analysis set included all randomized subjects who had received at least 1 dose of IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atacicept 75 mg | Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Screening Visit as Baseline | 57.8 percentage of subjects |
| Atacicept 150 mg | Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Screening Visit as Baseline | 53.8 percentage of subjects |
| Placebo | Percentage of Subjects With Systemic Lupus Erythematosus (SLE) Responder Index (SRI) Response at Week 24 Using Screening Visit as Baseline | 44.0 percentage of subjects |
p-value: 0.120895% CI: [0.89, 2.72]Logistic regression model
Secondary
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.
Time frame: Screening and Week 24
Population: mITT analysis set included all randomized subjects who had received at least 1 dose of IMP.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Atacicept 75 mg | Change From Screening in Prednisolone-Equivalent Corticosteroid (CS) Daily Dose at Week 24 | -2.64 mg per day | Standard Deviation 6.106 |
| Atacicept 150 mg | Change From Screening in Prednisolone-Equivalent Corticosteroid (CS) Daily Dose at Week 24 | -1.87 mg per day | Standard Deviation 4.653 |
| Placebo | Change From Screening in Prednisolone-Equivalent Corticosteroid (CS) Daily Dose at Week 24 | -1.89 mg per day | Standard Deviation 5.588 |
Secondary
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.
Time frame: Week 0 (Day 1) and Week 24
Population: mITT analysis set included all randomized subjects who had received at least 1 dose of IMP. Here Number Analyzed signifies those subjects who were evaluable for this outcome measure at specified categories.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Atacicept 75 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Physical Component Summary | 4.7 units on a scale | Standard Deviation 7.95 |
| Atacicept 75 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Mental Component Summary | 1.9 units on a scale | Standard Deviation 12.01 |
| Atacicept 75 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Physical Functioning | 3.5 units on a scale | Standard Deviation 9.3 |
| Atacicept 75 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Role-Physical | 4.3 units on a scale | Standard Deviation 10.26 |
| Atacicept 75 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Bodily Pain | 6.0 units on a scale | Standard Deviation 10.22 |
| Atacicept 75 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | General Health | 2.9 units on a scale | Standard Deviation 8.43 |
| Atacicept 75 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Vitality | 3.9 units on a scale | Standard Deviation 9.86 |
| Atacicept 75 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Social Functioning | 3.8 units on a scale | Standard Deviation 11.45 |
| Atacicept 75 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Role-Emotional | 2.5 units on a scale | Standard Deviation 12.71 |
| Atacicept 75 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Mental Health | 2.3 units on a scale | Standard Deviation 12.3 |
| Atacicept 150 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Role-Emotional | 1.0 units on a scale | Standard Deviation 10.43 |
| Atacicept 150 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Physical Component Summary | 3.4 units on a scale | Standard Deviation 7.57 |
| Atacicept 150 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | General Health | 3.0 units on a scale | Standard Deviation 7.72 |
| Atacicept 150 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Bodily Pain | 4.4 units on a scale | Standard Deviation 9.3 |
| Atacicept 150 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Mental Component Summary | 1.8 units on a scale | Standard Deviation 9.08 |
| Atacicept 150 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Mental Health | 2.8 units on a scale | Standard Deviation 8.87 |
| Atacicept 150 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Social Functioning | 2.2 units on a scale | Standard Deviation 10.06 |
| Atacicept 150 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Physical Functioning | 3.8 units on a scale | Standard Deviation 8.42 |
| Atacicept 150 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Vitality | 3.7 units on a scale | Standard Deviation 9.76 |
| Atacicept 150 mg | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Role-Physical | 2.3 units on a scale | Standard Deviation 8.64 |
| Placebo | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Social Functioning | 4.3 units on a scale | Standard Deviation 11.08 |
| Placebo | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Role-Physical | 3.9 units on a scale | Standard Deviation 9.51 |
| Placebo | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Bodily Pain | 5.6 units on a scale | Standard Deviation 10.72 |
| Placebo | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | General Health | 4.4 units on a scale | Standard Deviation 8 |
| Placebo | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Role-Emotional | 2.3 units on a scale | Standard Deviation 10.99 |
| Placebo | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Vitality | 3.5 units on a scale | Standard Deviation 9.57 |
| Placebo | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Physical Component Summary | 3.5 units on a scale | Standard Deviation 10.33 |
| Placebo | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Mental Health | 2.1 units on a scale | Standard Deviation 10.6 |
| Placebo | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Mental Component Summary | 0.7 units on a scale | Standard Deviation 11.44 |
| Placebo | Change From Week 0 (Day 1) in SF-36 Components at Week 24 | Physical Functioning | 3.3 units on a scale | Standard Deviation 8.62 |
Secondary
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.
Time frame: Week 24
Population: mITT analysis set included all randomized subjects who had received at least 1 dose of IMP. Here Number of Participants Analyzed signifies those subjects whose CS dose \>=10 mg at Screening.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atacicept 75 mg | 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 | 17.9 percentage of subjects |
| Atacicept 150 mg | 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 | 11.3 percentage of subjects |
| Placebo | 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 | 18.9 percentage of subjects |
Secondary
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.
Time frame: Week 24
Population: mITT analysis set included all randomized subjects who had received at least 1 dose of IMP. Here Number of Participants Analyzed signifies those subjects who were evaluable for this outcome measure.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atacicept 75 mg | Percentage of Subjects With British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response at Week 24 | 53.4 percentage of subjects |
| Atacicept 150 mg | Percentage of Subjects With British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response at Week 24 | 49.0 percentage of subjects |
| Placebo | Percentage of Subjects With British Isles Lupus Assessment Group (BILAG)-Based Combined Lupus Assessment (BICLA) Response at Week 24 | 45.2 percentage of subjects |
Secondary
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.
Time frame: Week 24
Population: mITT analysis set included all randomized subjects who had received at least 1 dose of IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atacicept 75 mg | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Very much or much improved | 57.8 percentage of subjects |
| Atacicept 75 mg | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Minimally improved or no change or minimally worse | 39.2 percentage of subjects |
| Atacicept 75 mg | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Much or very much worse | 2.0 percentage of subjects |
| Atacicept 75 mg | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Missing | 1.0 percentage of subjects |
| Atacicept 150 mg | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Missing | 1.0 percentage of subjects |
| Atacicept 150 mg | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Very much or much improved | 53.8 percentage of subjects |
| Atacicept 150 mg | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Much or very much worse | 1.0 percentage of subjects |
| Atacicept 150 mg | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Minimally improved or no change or minimally worse | 44.2 percentage of subjects |
| Placebo | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Missing | 2.0 percentage of subjects |
| Placebo | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Minimally improved or no change or minimally worse | 46.0 percentage of subjects |
| Placebo | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Much or very much worse | 6.0 percentage of subjects |
| Placebo | Percentage of Subjects With Patient Global Impression of Change (PGIC) Categories at Week 24 | Very much or much improved | 46.0 percentage of subjects |
Secondary
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.
Time frame: Baseline up to 24 weeks after last dose of study drug (assessed up to maximum of 48 weeks)
Population: Safety analysis set included all randomized subjects who received at least 1 dose of IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Atacicept 75 mg | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 81.4 percentage of subjects |
| Atacicept 75 mg | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 8.8 percentage of subjects |
| Atacicept 150 mg | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 80.8 percentage of subjects |
| Atacicept 150 mg | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 5.8 percentage of subjects |
| Placebo | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | TEAEs | 72.0 percentage of subjects |
| Placebo | Percentage of Subjects With Treatment-Emergent Adverse Events (TEAEs) and Serious TEAEs | Serious TEAEs | 12.0 percentage of subjects |
Secondary
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.
Time frame: Baseline up to 24 Weeks
Population: mITT analysis set included all randomized subjects who had received at least 1 dose of IMP.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Atacicept 75 mg | Time From Randomization to First SRI Response During Treatment Period | 12.4 weeks |
| Atacicept 150 mg | Time From Randomization to First SRI Response During Treatment Period | 16.1 weeks |
| Placebo | Time From Randomization to First SRI Response During Treatment Period | 16.1 weeks |
Post Hoc
High Disease Activity Subpopulation (SLEDAI-2K >=10 at Screening): Logistic Regression of Percentage of Subjects With SRI-6 Response at Week 24
SRI-6 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 (\>=) 6 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. Logistic regression of number of subjects with SRI-6 response was analyzed by using Logistic regression model.
Time frame: Week 24
Population: mITT\_HDA analysis set included mITT population with high disease activity (HDA) defined as screening SLE Disease Activity Index (SLEDAI) \>=10.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Atacicept 75 mg | High Disease Activity Subpopulation (SLEDAI-2K >=10 at Screening): Logistic Regression of Percentage of Subjects With SRI-6 Response at Week 24 | 43.6 percentage of subjects |
| Atacicept 150 mg | High Disease Activity Subpopulation (SLEDAI-2K >=10 at Screening): Logistic Regression of Percentage of Subjects With SRI-6 Response at Week 24 | 54.9 percentage of subjects |
| Placebo | High Disease Activity Subpopulation (SLEDAI-2K >=10 at Screening): Logistic Regression of Percentage of Subjects With SRI-6 Response at Week 24 | 28.8 percentage of subjects |
p-value: 0.004895% CI: [1.44, 7.61]Logistic regression model