Trial Outcomes & Findings for Long-term Safety and Tolerability of Atacicept (Long-term Follow-Up of Participant Who Participated in ADDRESS II) (NCT NCT02070978)

NCT ID: NCT02070978

Last Updated: 2019-03-21

Results Overview

An Adverse event (AE) was defined as any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease associated with the use of study drug, whether or not considered related to the study drug or worsening of pre-existing medical condition, whether or not related to study drug. A serious adverse event (SAE) 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. An AE was considered as 'treatment emergent' if it occurred after the first drug administration of each period or if it was present prior to drug administration but exacerbated after the drug administration. Treatment- Emergent adverse events (TEAEs) during the treatment period exclude those ongoing at the time of study entry into 024 LTE Day 1 and exclude the safety follow-up period.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

253 participants

Primary outcome timeframe

Baseline (LTE Day 1) up to maximum treatment duration of 143.7 weeks

Results posted on

2019-03-21

Participant Flow

Participants who completed 24-week of the ADDRESS II core study (NCT01972568) and didn't meet any discontinuation criteria were enrolled in this long-term extension (LTE) study NCT02070978. The study was conducted at 81 sites in 17 countries in Asia, Europe, North America, Central America, and South America.

Participants who received placebo in core study ADDRESS II were switched to receive atacicept 150 milligram (mg) as once-weekly subcutaneous injections in LTE study. Participants who received atacicept 75 mg or 150 mg in core study ADDRESS II continued to receive the respective randomized dosage as once-weekly subcutaneous injections in LTE study.

Participant milestones

Participant milestones
Measure	Placebo/Atacicept 150 mg Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Overall Study STARTED	83	82	88
Overall Study COMPLETED	36	29	35
Overall Study NOT COMPLETED	47	53	53

Reasons for withdrawal

Reasons for withdrawal
Measure	Placebo/Atacicept 150 mg Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Overall Study Adverse Event	6	2	0
Overall Study Lost to Follow-up	1	3	4
Overall Study Withdrawal by Subject	3	5	3
Overall Study Protocol Violation	1	0	3
Overall Study Lack of Efficacy	0	1	0
Overall Study Death	0	0	2
Overall Study Un-specified	3	2	2
Overall Study Terminated by Sponsor	33	40	39

Baseline Characteristics

Long-term Safety and Tolerability of Atacicept (Long-term Follow-Up of Participant Who Participated in ADDRESS II)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.	Total n=253 Participants Total of all reporting groups
Age, Continuous	41 Years STANDARD_DEVIATION 13.0 • n=5 Participants	37 Years STANDARD_DEVIATION 10.7 • n=7 Participants	38 Years STANDARD_DEVIATION 11.5 • n=5 Participants	39 Years STANDARD_DEVIATION 11.8 • n=4 Participants
Sex: Female, Male Female	74 Participants n=5 Participants	75 Participants n=7 Participants	82 Participants n=5 Participants	231 Participants n=4 Participants
Sex: Female, Male Male	9 Participants n=5 Participants	7 Participants n=7 Participants	6 Participants n=5 Participants	22 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	48 Participants n=5 Participants	43 Participants n=7 Participants	40 Participants n=5 Participants	131 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	35 Participants n=5 Participants	39 Participants n=7 Participants	48 Participants n=5 Participants	122 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	4 Participants n=5 Participants	3 Participants n=7 Participants	3 Participants n=5 Participants	10 Participants n=4 Participants
Race (NIH/OMB) Asian	7 Participants n=5 Participants	13 Participants n=7 Participants	13 Participants n=5 Participants	33 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	3 Participants n=7 Participants	7 Participants n=5 Participants	13 Participants n=4 Participants
Race (NIH/OMB) White	64 Participants n=5 Participants	58 Participants n=7 Participants	55 Participants n=5 Participants	177 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	4 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants	19 Participants n=4 Participants

PRIMARY outcome

Timeframe: Baseline (LTE Day 1) up to maximum treatment duration of 143.7 weeks

Population: The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Number of Participants With at Least One Serious Adverse Event (SAE) During the Treatment Period	13 Participants	10 Participants	9 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1 of Core study) up to maximum duration of 167.7 weeks

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Number of Participants Who Prematurely Discontinued the Treatment Due to Adverse Event (AE)	9 Participants	4 Participants	5 Participants

SECONDARY outcome

Timeframe: Baseline: Day 1 (Core Study), Day 1 (LTE Study), Week 24, Week 48, Week 72 and Week 96

Population: Modified intent-to-treat (mITT) analysis set was defined as all enrolled participants in the LTE study. Efficacy analyses were performed on the mITT analysis set according to randomized treatment. Here "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified categories.

SLICC/ACR score or damage index evaluates cumulative damage in Systemic Lupus Erythematosus (SLE). These changes may or may not be related to SLE. Most items are scored only if they have been present for at least 6 months. Scores range from 0 to 47 points, with higher scores indicating greater cumulative damage. Baseline was defined as Day 1 of Core study.

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Organ Damage Scores Change at LTE Week 24	0 Units on a scale Standard Deviation 0.1	0 Units on a scale Standard Deviation 0.1	0 Units on a scale Standard Deviation 0.2
Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Organ Damage Scores Baseline; Day 1 (Core Study)	1 Units on a scale Standard Deviation 1.0	1 Units on a scale Standard Deviation 1.2	0 Units on a scale Standard Deviation 0.8
Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Organ Damage Scores Change at LTE Day 1	0 Units on a scale Standard Deviation 0.0	0 Units on a scale Standard Deviation 0.1	0 Units on a scale Standard Deviation 0.0
Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Organ Damage Scores Change at LTE Week 48	0 Units on a scale Standard Deviation 0.2	0 Units on a scale Standard Deviation 0.2	0 Units on a scale Standard Deviation 0.3
Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Organ Damage Scores Change at LTE Week 72	0 Units on a scale Standard Deviation 0.3	0 Units on a scale Standard Deviation 0.3	0 Units on a scale Standard Deviation 0.2
Change From Baseline in Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index Organ Damage Scores Change at LTE Week 96	0 Units on a scale Standard Deviation 0.3	0 Units on a scale Standard Deviation 0.3	0 Units on a scale Standard Deviation 0.0

SECONDARY outcome

Timeframe: Baseline: Core study Screening, LTE Day 1, Week 24, Week 48, Week 72 and Week 96

Population: mITT analysis set was defined as all enrolled participants in the LTE study. Efficacy analyses were performed on the mITT analysis set according to randomized treatment. Here "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified categories.

BILAG Disease Activity Index evaluates systemic lupus erythematosus (SLE) activity in 8 organ system domains: General, mucocutaneous, neurological, musculoskeletal, cardiorespiratory, vasculitis, renal, and hematologic using a separate alphabetic score (A to E) assigned to each organ system defined as follows. BILAG A: Severe disease activity; BILAG B: moderate disease activity; BILAG C: mild disease; BILAG D: system previously affected but now inactive; BILAG E: system never involved. BILAG evaluated by scoring each of a list of signs and symptoms as: improving (1); same (2); worse (3); new (4); not present (0); not done (ND). The total BILAG score is the sum of the scores of the 8 domains where A=9, B=3, C=1, D=0, and E=0. The total score ranges from 0 to 72 with a higher score indicating greater lupus activity.

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Change From Baseline in Disease Activity as Measured by British Isles Lupus Assessment Group (BILAG) 2004 Score Baseline: Core study Screening	15 Units on a scale Standard Deviation 7.1	14 Units on a scale Standard Deviation 7.2	16 Units on a scale Standard Deviation 6.1
Change From Baseline in Disease Activity as Measured by British Isles Lupus Assessment Group (BILAG) 2004 Score Change at LTE Day 1	-8 Units on a scale Standard Deviation 6.9	-9 Units on a scale Standard Deviation 7.2	-10 Units on a scale Standard Deviation 6.8
Change From Baseline in Disease Activity as Measured by British Isles Lupus Assessment Group (BILAG) 2004 Score Change at LTE Week 24	-8 Units on a scale Standard Deviation 8.3	-10 Units on a scale Standard Deviation 7.5	-12 Units on a scale Standard Deviation 7.2
Change From Baseline in Disease Activity as Measured by British Isles Lupus Assessment Group (BILAG) 2004 Score Change at LTE Week 48	-9 Units on a scale Standard Deviation 7.7	-8 Units on a scale Standard Deviation 7.5	-11 Units on a scale Standard Deviation 7.4
Change From Baseline in Disease Activity as Measured by British Isles Lupus Assessment Group (BILAG) 2004 Score Change at LTE Week 72	-9 Units on a scale Standard Deviation 7.9	-10 Units on a scale Standard Deviation 6.2	-11 Units on a scale Standard Deviation 8.2
Change From Baseline in Disease Activity as Measured by British Isles Lupus Assessment Group (BILAG) 2004 Score Change at LTE Week 96	-14 Units on a scale Standard Deviation 12.9	-8 Units on a scale Standard Deviation 6.3	-12 Units on a scale Standard Deviation 6.8

SECONDARY outcome

Timeframe: Baseline: Screening Visit (Core Study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96

Population: mITT analysis set was defined as all enrolled participants in the LTE study. Efficacy analyses were performed on the mITT analysis set according to randomized treatment. Here, "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified categories.

SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms). Baseline was defined as core study screening visit.

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Change From Baseline in Disease Activity as Measured by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score Baseline: Screening Visit (Core Study)	10 Units on a scale Standard Deviation 2.9	10 Units on a scale Standard Deviation 3.4	10 Units on a scale Standard Deviation 3.0
Change From Baseline in Disease Activity as Measured by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score Change at LTE Day 1	-4 Units on a scale Standard Deviation 4.1	-5 Units on a scale Standard Deviation 4.5	-5 Units on a scale Standard Deviation 3.9
Change From Baseline in Disease Activity as Measured by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score Change at LTE Week 24	-5 Units on a scale Standard Deviation 4.3	-6 Units on a scale Standard Deviation 4.1	-6 Units on a scale Standard Deviation 3.9
Change From Baseline in Disease Activity as Measured by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score Change at LTE Week 48	-6 Units on a scale Standard Deviation 3.4	-6 Units on a scale Standard Deviation 4.6	-7 Units on a scale Standard Deviation 4.3
Change From Baseline in Disease Activity as Measured by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score Change at LTE Week 72	-5 Units on a scale Standard Deviation 3.8	-6 Units on a scale Standard Deviation 3.7	-7 Units on a scale Standard Deviation 3.9
Change From Baseline in Disease Activity as Measured by Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) Score Change at LTE Week 96	-7 Units on a scale Standard Deviation 5.0	-6 Units on a scale Standard Deviation 4.9	-8 Units on a scale Standard Deviation 2.7

SECONDARY outcome

Timeframe: Baseline: Screening Visit (Core Study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96

Population: Data was not collected for this endpoint as the results from ADDRESS II core study (700461-023; NCT01972568) for SRI-50 were not significant. Therefore, data collection for the SRI-50 for current study (700461-024; NCT02070978) was halted and no analysis was conducted for endpoint.

SRI-50 index was derived from SLEDAI-2K and could capture 50% or better improvement in each descriptor between any 2 visits in systemic lupus erythematosus (SLE) participants when there was incomplete resolution. The new assigned scores for the descriptors of SRI-50 were derived by dividing the score of each SLEDAI-2K descriptor by 2. SLEDAI-2K was an activity index that measured disease activity and records feature of active lupus as present or not present. SLEDAI-2K used a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present was assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranged from 0 points (no symptoms) to 105 points (presence of all defined symptoms).

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline: Screening Visit (Core Study); LTE Day1, Week 24, Week 48, Week 72 and Week 96

The PGA was used to quantify disease activity and was measured using an anchored visual analog scale (VAS). The participant's current disease activity assessed by investigator in the score range of 0 to 3. Where 0=none; 1=mild; 2=moderate; 3=severe. The assessment made relative not to the participant's most severe state, but the most severe state of systemic lupus erythematosus (SLE) per the investigator's assessment. Baseline was defined as core study screening visit.

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Change From Baseline in Disease Activity as Measured by Physician's Global Assessment (PGA) Score Baseline: Screening Visit (Core Study)	1.56 Units on a scale Standard Deviation 0.424	1.46 Units on a scale Standard Deviation 0.509	1.47 Units on a scale Standard Deviation 0.460
Change From Baseline in Disease Activity as Measured by Physician's Global Assessment (PGA) Score Change at LTE Day 1	-0.76 Units on a scale Standard Deviation 0.559	-0.77 Units on a scale Standard Deviation 0.559	-0.77 Units on a scale Standard Deviation 0.614
Change From Baseline in Disease Activity as Measured by Physician's Global Assessment (PGA) Score Change at LTE Week 24	-0.91 Units on a scale Standard Deviation 0.620	-0.85 Units on a scale Standard Deviation 0.555	-0.94 Units on a scale Standard Deviation 0.547
Change From Baseline in Disease Activity as Measured by Physician's Global Assessment (PGA) Score Change at LTE Week 48	-1.01 Units on a scale Standard Deviation 0.647	-0.86 Units on a scale Standard Deviation 0.522	-0.99 Units on a scale Standard Deviation 0.557
Change From Baseline in Disease Activity as Measured by Physician's Global Assessment (PGA) Score Change at LTE Week 72	-0.90 Units on a scale Standard Deviation 0.758	-0.84 Units on a scale Standard Deviation 0.503	-1.03 Units on a scale Standard Deviation 0.580
Change From Baseline in Disease Activity as Measured by Physician's Global Assessment (PGA) Score Change at LTE Week 96	-1.17 Units on a scale Standard Deviation 0.518	-0.72 Units on a scale Standard Deviation 0.579	-1.21 Units on a scale Standard Deviation 0.411

SECONDARY outcome

Timeframe: Baseline: Core study Screening; LTE Day 1, Week 24, Week 48, Week 72 and Week 96

Population: mITT analysis set was used. For this outcome measure, baseline was measured as reference timepoint for response in the screening visit from core study. Here "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified categories.

SRI-4 response was defined as greater than or equal to 4-point reduction in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) total score, no new British Isles Lupus Assessment Group (BILAG) A and no more than 1 new BILAG B domain score and no worsening (less than 10 percent increase) from baseline Physician's Global Assessment of Disease Activity (PGA). SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms).

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Number of Participants Who Achieved SLE Responder Index (SRI-4) Response (a Disease Activity Composite Index) LTE Day 1	42 Participants	52 Participants	57 Participants
Number of Participants Who Achieved SLE Responder Index (SRI-4) Response (a Disease Activity Composite Index) LTE Week 24	43 Participants	57 Participants	60 Participants
Number of Participants Who Achieved SLE Responder Index (SRI-4) Response (a Disease Activity Composite Index) LTE Week 48	44 Participants	46 Participants	51 Participants
Number of Participants Who Achieved SLE Responder Index (SRI-4) Response (a Disease Activity Composite Index) LTE Week 72	21 Participants	23 Participants	23 Participants
Number of Participants Who Achieved SLE Responder Index (SRI-4) Response (a Disease Activity Composite Index) LTE Week 96	6 Participants	9 Participants	12 Participants

SECONDARY outcome

Timeframe: Baseline: Core study Screening; LTE Day 1, Week 24, Week 48, Week 72 and Week 96

Population: mITT BILAG analysis set included mITT population with at least one BILAG A and/or B at screening visit. Here "Number Analyzed" signifies those participants who were evaluable for this outcome measure at specified categories.

The BICLA response was defined as BILAG-2004 improvement (all screening visit BILAG A improving to B/C/D, all screening visit BILAG B to C/D, and less than or equal to (\<=1) new BILAG B and no new BILAG A); no deterioration in SLEDAI total score; PGA increase by less than (\<) 0 percentage (%) (defined as less then (\<)0.3 point increase for the statistical analyses) and no non-permitted medication/treatment. Baseline was defined as core study screening visit.

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=76 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=70 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=86 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Number of Participants Who Achieved BILAG-based Combined Lupus Assessment (BICLA) Response (a Disease Activity Composite Index) LTE Day 1	43 Participants	43 Participants	50 Participants
Number of Participants Who Achieved BILAG-based Combined Lupus Assessment (BICLA) Response (a Disease Activity Composite Index) LTE Week 24	40 Participants	45 Participants	53 Participants
Number of Participants Who Achieved BILAG-based Combined Lupus Assessment (BICLA) Response (a Disease Activity Composite Index) LTE Week 48	35 Participants	34 Participants	43 Participants
Number of Participants Who Achieved BILAG-based Combined Lupus Assessment (BICLA) Response (a Disease Activity Composite Index) LTE Week 72	16 Participants	17 Participants	21 Participants
Number of Participants Who Achieved BILAG-based Combined Lupus Assessment (BICLA) Response (a Disease Activity Composite Index) LTE Week 96	4 Participants	7 Participants	9 Participants

SECONDARY outcome

Timeframe: Baseline: Screening Visit (Core Study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Percent Change From Baseline in Prednisone-equivalent Corticosteroid Dose Percent Change at LTE Day 1	-11.04 Percent change Standard Deviation 31.139	-5.25 Percent change Standard Deviation 55.697	-11.54 Percent change Standard Deviation 26.117
Percent Change From Baseline in Prednisone-equivalent Corticosteroid Dose Percent Change at LTE Week 24	-11.89 Percent change Standard Deviation 41.411	-4.79 Percent change Standard Deviation 59.371	-1.21 Percent change Standard Deviation 94.677
Percent Change From Baseline in Prednisone-equivalent Corticosteroid Dose Percent Change at LTE Week 48	-9.19 Percent change Standard Deviation 54.364	-6.01 Percent change Standard Deviation 45.605	-17.97 Percent change Standard Deviation 37.040
Percent Change From Baseline in Prednisone-equivalent Corticosteroid Dose Percent Change at LTE Week 72	-19.32 Percent change Standard Deviation 38.157	-8.69 Percent change Standard Deviation 28.112	-22.34 Percent change Standard Deviation 36.058
Percent Change From Baseline in Prednisone-equivalent Corticosteroid Dose Percent Change at LTE Week 96	-36.67 Percent change Standard Deviation 58.146	-12.40 Percent change Standard Deviation 73.793	-28.57 Percent change Standard Deviation 43.080

SECONDARY outcome

Timeframe: Baseline (Core Study Day 1); LTE Day 1, Week 24, Week 48, Week 72 and Week 96

The 36-Item Short-Form Health Survey (SF-36) is a standardized survey evaluating 8 aspects of functional health and well-being. These eight subscales were summarized as relating to either physical health or mental health. Physical component summary (PCS) is based primarily on physical functioning, role-physical, bodily pain, and general health scales and mental component summary (MCS) encompasses vitality, social functioning, role-emotional, and mental health scales. Score from mental health, role emotional, social functioning, and vitality domains were averaged to calculate MCS. Total score range for MCS was 0-100 (100=highest level of mental functioning). Score from physical function, role physical, bodily pain, and general health domains were averaged to calculate PCS. Total score range for PCS was 0-100 (100=highest level of physical functioning).

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score PCS: Baseline (Core Study Day 1)	37.7 Units on a scale Standard Deviation 9.20	37.8 Units on a scale Standard Deviation 10.56	38.8 Units on a scale Standard Deviation 9.27
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score PCS: Change at LTE Day 1	4.8 Units on a scale Standard Deviation 10.00	4.8 Units on a scale Standard Deviation 8.30	4.0 Units on a scale Standard Deviation 7.46
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score PCS: Change at LTE Week 24	5.3 Units on a scale Standard Deviation 8.62	5.1 Units on a scale Standard Deviation 8.78	5.9 Units on a scale Standard Deviation 7.74
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score PCS: Change at LTE Week 48	6.4 Units on a scale Standard Deviation 9.56	6.2 Units on a scale Standard Deviation 9.67	4.6 Units on a scale Standard Deviation 8.23
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score PCS: Change at LTE Week 72	5.8 Units on a scale Standard Deviation 8.61	3.4 Units on a scale Standard Deviation 7.37	6.7 Units on a scale Standard Deviation 5.33
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score PCS: Change at LTE Week 96	13.0 Units on a scale Standard Deviation 9.51	3.1 Units on a scale Standard Deviation 9.29	8.9 Units on a scale Standard Deviation 6.08
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score MCS: Baseline (Core Study Day 1)	41.3 Units on a scale Standard Deviation 10.70	43.3 Units on a scale Standard Deviation 12.09	43.2 Units on a scale Standard Deviation 10.81
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score MCS: Change at LTE Day 1	2.1 Units on a scale Standard Deviation 11.38	2.2 Units on a scale Standard Deviation 12.62	1.9 Units on a scale Standard Deviation 9.30
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score MCS: Change at LTE Week 24	4.4 Units on a scale Standard Deviation 10.43	3.0 Units on a scale Standard Deviation 11.75	2.0 Units on a scale Standard Deviation 10.26
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score MCS: Change at LTE Week 48	3.3 Units on a scale Standard Deviation 11.72	2.8 Units on a scale Standard Deviation 13.19	3.5 Units on a scale Standard Deviation 11.39
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score MCS Change at LTE Week 72	3.8 Units on a scale Standard Deviation 10.96	1.1 Units on a scale Standard Deviation 11.74	1.5 Units on a scale Standard Deviation 13.64
Change From Baseline in the Short-Form (SF-36) Health Survey Physical Component Score and Mental Component Score MCS: Change at LTE Week 96	10.3 Units on a scale Standard Deviation 15.86	0.6 Units on a scale Standard Deviation 9.03	3.2 Units on a scale Standard Deviation 12.20

SECONDARY outcome

Timeframe: Baseline (Core Study Day 1); LTE Day 1, Week 24, Week 48, Week 72, and Week 96

The LupusQoL was a lupus-specific health related QoL (HRQoL) questionnaire consisting of 34 items grouped in 8 domains: physical health, pain, planning, intimate relationships, burden to others, emotional health, body image, and fatigue. Participants indicate their responses on a 5-point Likert response format, where 4 = never, 3 = occasionally, 2 = a good bit of the time, 1 = most of the time, and 0 = all of the time. Summary scores can be calculated for all 8 domains. A LupusQoL score for each domain was reported on a 0 to 100 scale, with greater values indicating better HRQoL. Baseline was defined as Day 1 of core study.

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Physical Health: Change at LTE Week 96	25.0 Units on a scale Standard Deviation 21.46	12.9 Units on a scale Standard Deviation 17.97	14.4 Units on a scale Standard Deviation 10.33
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Pain: Change at LTE Week 72	16.7 Units on a scale Standard Deviation 26.73	10.3 Units on a scale Standard Deviation 18.91	17.2 Units on a scale Standard Deviation 26.63
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Planning: Change at LTE Week 72	10.3 Units on a scale Standard Deviation 22.23	0.0 Units on a scale Standard Deviation 28.37	15.5 Units on a scale Standard Deviation 30.52
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Intimate Relationship: Change at LTE Week 24	3.6 Units on a scale Standard Deviation 26.29	7.1 Units on a scale Standard Deviation 24.50	6.3 Units on a scale Standard Deviation 25.67
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Body Image: Baseline (Core study Day 1)	63.8 Units on a scale Standard Deviation 27.82	61.9 Units on a scale Standard Deviation 31.45	64.4 Units on a scale Standard Deviation 30.51
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Planning: Change at LTE Week 24	11.2 Units on a scale Standard Deviation 27.34	7.0 Units on a scale Standard Deviation 24.16	8.4 Units on a scale Standard Deviation 25.29
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Planning: Change at LTE Week 48	14.5 Units on a scale Standard Deviation 29.27	6.5 Units on a scale Standard Deviation 26.88	10.9 Units on a scale Standard Deviation 26.16
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Planning: Change at LTE Week 96	19.8 Units on a scale Standard Deviation 36.98	3.0 Units on a scale Standard Deviation 24.59	21.8 Units on a scale Standard Deviation 26.03
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Intimate Relationship: Baseline (Core study Day 1)	67.2 Units on a scale Standard Deviation 30.99	60.6 Units on a scale Standard Deviation 34.17	62.1 Units on a scale Standard Deviation 31.62
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Intimate Relationship: Change at LTE Day 1	3.9 Units on a scale Standard Deviation 26.95	0.2 Units on a scale Standard Deviation 27.77	-1.6 Units on a scale Standard Deviation 23.94
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Intimate Relationship: Change at LTE Week 48	2.3 Units on a scale Standard Deviation 29.19	5.7 Units on a scale Standard Deviation 33.02	8.4 Units on a scale Standard Deviation 30.58
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Intimate Relationship: Change at LTE Week 72	-6.3 Units on a scale Standard Deviation 20.67	-2.8 Units on a scale Standard Deviation 29.89	5.2 Units on a scale Standard Deviation 32.95
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Intimate Relationship: Change at LTE Week 96	12.5 Units on a scale Standard Deviation 15.31	2.9 Units on a scale Standard Deviation 16.26	-14.3 Units on a scale Standard Deviation 39.81
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Burden to Others: Baseline (Core study Day 1)	49.0 Units on a scale Standard Deviation 31.22	48.5 Units on a scale Standard Deviation 32.34	47.3 Units on a scale Standard Deviation 32.97
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Burden to Others: Change at LTE Day 1	13.4 Units on a scale Standard Deviation 26.31	14.7 Units on a scale Standard Deviation 25.83	12.5 Units on a scale Standard Deviation 25.36
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Burden to Others: Change at LTE Week 24	13.1 Units on a scale Standard Deviation 26.08	16.8 Units on a scale Standard Deviation 27.35	15.7 Units on a scale Standard Deviation 27.73
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Burden to Others: Change at LTE Week 48	13.4 Units on a scale Standard Deviation 25.69	18.3 Units on a scale Standard Deviation 30.36	17.9 Units on a scale Standard Deviation 28.73
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Burden to Others: Change at Week 72	12.1 Units on a scale Standard Deviation 21.89	14.4 Units on a scale Standard Deviation 32.23	22.1 Units on a scale Standard Deviation 31.68
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Burden to Others: Change at LTE Week 96	17.7 Units on a scale Standard Deviation 32.56	20.2 Units on a scale Standard Deviation 33.29	30.1 Units on a scale Standard Deviation 37.51
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Emotional Health: Baseline (Core study Day 1)	64.1 Units on a scale Standard Deviation 23.43	68.3 Units on a scale Standard Deviation 25.86	67.6 Units on a scale Standard Deviation 27.10
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Emotional Health: Change at LTE Day 1	7.9 Units on a scale Standard Deviation 19.73	6.0 Units on a scale Standard Deviation 20.08	7.0 Units on a scale Standard Deviation 21.21
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Emotional Health: Change at LTE Week 24	11.2 Units on a scale Standard Deviation 20.67	6.7 Units on a scale Standard Deviation 21.87	7.9 Units on a scale Standard Deviation 20.68
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Emotional Health: Change at LTE Week 48	14.2 Units on a scale Standard Deviation 21.91	9.3 Units on a scale Standard Deviation 25.66	8.0 Units on a scale Standard Deviation 21.73
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Emotional Health: Change at LTE Week 72	10.1 Units on a scale Standard Deviation 20.49	3.2 Units on a scale Standard Deviation 17.50	11.5 Units on a scale Standard Deviation 26.30
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Emotional Health: Change at LTE Week 96	22.4 Units on a scale Standard Deviation 26.16	6.8 Units on a scale Standard Deviation 12.40	16.3 Units on a scale Standard Deviation 22.08
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Body Image: Change at LTE Day 1	12.9 Units on a scale Standard Deviation 24.47	6.2 Units on a scale Standard Deviation 20.69	4.7 Units on a scale Standard Deviation 25.29
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Body Image: Change at LTE Week 24	13.2 Units on a scale Standard Deviation 25.94	9.1 Units on a scale Standard Deviation 22.33	4.5 Units on a scale Standard Deviation 29.34
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Body Image: Change at LTE Week 48	11.6 Units on a scale Standard Deviation 25.39	14.9 Units on a scale Standard Deviation 25.10	7.5 Units on a scale Standard Deviation 28.45
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Body Image: Change at Week 72	11.0 Units on a scale Standard Deviation 19.15	8.5 Units on a scale Standard Deviation 16.34	13.8 Units on a scale Standard Deviation 29.79
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Body Image: Change at LTE Week 96	27.1 Units on a scale Standard Deviation 32.79	13.4 Units on a scale Standard Deviation 21.87	10.5 Units on a scale Standard Deviation 38.19
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Fatigue: Baseline (Core study Day 1)	53.4 Units on a scale Standard Deviation 26.83	55.6 Units on a scale Standard Deviation 27.82	56.8 Units on a scale Standard Deviation 29.00
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Fatigue: Change at LTE Day 1	9.3 Units on a scale Standard Deviation 21.47	5.9 Units on a scale Standard Deviation 21.05	7.0 Units on a scale Standard Deviation 20.93
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Fatigue: Change at LTE Week 24	10.6 Units on a scale Standard Deviation 23.77	7.1 Units on a scale Standard Deviation 20.89	8.2 Units on a scale Standard Deviation 21.96
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Fatigue: Change at LTE Week 48	7.1 Units on a scale Standard Deviation 23.28	11.9 Units on a scale Standard Deviation 22.05	10.8 Units on a scale Standard Deviation 20.05
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Fatigue: Change at LTE Week 72	6.7 Units on a scale Standard Deviation 25.98	2.7 Units on a scale Standard Deviation 20.55	14.7 Units on a scale Standard Deviation 30.63
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Fatigue: Change at LTE Week 96	21.1 Units on a scale Standard Deviation 33.73	2.7 Units on a scale Standard Deviation 23.09	20.2 Units on a scale Standard Deviation 21.06
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Physical Health: Baseline (Core study Day 1)	60.2 Units on a scale Standard Deviation 23.08	62.0 Units on a scale Standard Deviation 27.17	61.3 Units on a scale Standard Deviation 27.87
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Physical Health: Change at LTE Day 1	8.8 Units on a scale Standard Deviation 21.86	7.5 Units on a scale Standard Deviation 17.37	8.2 Units on a scale Standard Deviation 16.40
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Physical Health: Change at LTE Week 24	10.4 Units on a scale Standard Deviation 21.27	10.8 Units on a scale Standard Deviation 18.86	10.9 Units on a scale Standard Deviation 18.46
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Physical Health: Change at LTE Week 48	9.3 Units on a scale Standard Deviation 22.23	11.2 Units on a scale Standard Deviation 24.80	12.8 Units on a scale Standard Deviation 20.30
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Physical Health: Change at LTE Week 72	8.0 Units on a scale Standard Deviation 19.42	5.9 Units on a scale Standard Deviation 17.61	11.9 Units on a scale Standard Deviation 20.02
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Pain: Baseline (Core study Day 1)	58.7 Units on a scale Standard Deviation 26.77	61.2 Units on a scale Standard Deviation 30.27	57.7 Units on a scale Standard Deviation 31.52
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Pain: Change at LTE Day 1	11.8 Units on a scale Standard Deviation 24.86	11.0 Units on a scale Standard Deviation 23.93	13.4 Units on a scale Standard Deviation 21.78
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Pain: Change at LTE Week 24	14.4 Units on a scale Standard Deviation 26.21	11.9 Units on a scale Standard Deviation 23.38	16.4 Units on a scale Standard Deviation 24.10
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Pain: Change at LTE Week 48	12.8 Units on a scale Standard Deviation 27.76	14.0 Units on a scale Standard Deviation 29.64	17.3 Units on a scale Standard Deviation 24.67
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Pain: Change at LTE Week 96	41.7 Units on a scale Standard Deviation 30.21	11.9 Units on a scale Standard Deviation 23.73	17.9 Units on a scale Standard Deviation 23.78
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Planning: Baseline (Core study Day 1)	65.6 Units on a scale Standard Deviation 27.52	68.3 Units on a scale Standard Deviation 30.81	64.6 Units on a scale Standard Deviation 33.26
Change From Baseline in Lupus Quality of Life (LupusQoL) Questionnaire Score Planning: Change at LTE Day 1	8.4 Units on a scale Standard Deviation 25.60	1.5 Units on a scale Standard Deviation 22.79	7.5 Units on a scale Standard Deviation 23.08

SECONDARY outcome

Timeframe: Baseline (Core Study Day 1); LTE Day 1, Week 24, Week 48, Week 72 and Week 96

The PGIC is self-rated scale that asks the participant to describe the change in activity limitations, symptoms, emotions, and overall Quality of life (QoL) related to the participant'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). Number of participants in the PGIC categories of very much improved (1) and much improved (2) are reported.

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Number of Participants With Patient Global Impression of Change (PGIC) LTE Week 96: Much improved	4 Participants	7 Participants	5 Participants
Number of Participants With Patient Global Impression of Change (PGIC) LTE Day 1: Very much improved	13 Participants	19 Participants	25 Participants
Number of Participants With Patient Global Impression of Change (PGIC) LTE Day 1: Much improved	29 Participants	33 Participants	27 Participants
Number of Participants With Patient Global Impression of Change (PGIC) LTE Week 24: Very much improved	18 Participants	22 Participants	22 Participants
Number of Participants With Patient Global Impression of Change (PGIC) LTE Week 24: Much improved	35 Participants	29 Participants	40 Participants
Number of Participants With Patient Global Impression of Change (PGIC) LTE Week 48: Very much improved	16 Participants	20 Participants	24 Participants
Number of Participants With Patient Global Impression of Change (PGIC) LTE Week 48: Much improved	26 Participants	24 Participants	30 Participants
Number of Participants With Patient Global Impression of Change (PGIC) LTE Week 72: Very much improved	7 Participants	10 Participants	10 Participants
Number of Participants With Patient Global Impression of Change (PGIC) LTE Week 72: Much improved	13 Participants	13 Participants	13 Participants
Number of Participants With Patient Global Impression of Change (PGIC) LTE Week 96: Very much improved	4 Participants	2 Participants	7 Participants

SECONDARY outcome

Timeframe: Baseline: Day 1 (Core Study), LTE Day 1, Week 24, Week 48, Week 72 and Week 96

EQ-5D questionnaire comprised of 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression measured on 3 levels; 1=no problem, 2=moderate problems, 3=extreme problems. This part, called the EQ-5D descriptive system, provides a 5-dimensional description of health status. 5 dimensional 3-level system was converted into single index utility score. Possible values for single index utility score ranged from -0.594 (severe problems in all dimensions) to 1.0 (no problem in all dimensions) on scale where 1 represented best possible health state. Baseline was defined as Day 1 of Core study.

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Change From Baseline in EuroQoL 5 Dimension Instrument (EQ-5D) Score Baseline (Core Study Day 1)	0.736 Units on a scale Standard Deviation 0.1707	0.775 Units on a scale Standard Deviation 0.1754	0.751 Units on a scale Standard Deviation 0.2388
Change From Baseline in EuroQoL 5 Dimension Instrument (EQ-5D) Score Change at LTE Day 1	0.038 Units on a scale Standard Deviation 0.1764	0.042 Units on a scale Standard Deviation 0.1759	0.070 Units on a scale Standard Deviation 0.1912
Change From Baseline in EuroQoL 5 Dimension Instrument (EQ-5D) Score Change at LTE Week 24	0.078 Units on a scale Standard Deviation 0.1651	0.024 Units on a scale Standard Deviation 0.2207	0.072 Units on a scale Standard Deviation 0.1933
Change From Baseline in EuroQoL 5 Dimension Instrument (EQ-5D) Score Change at LTE Week 48	0.065 Units on a scale Standard Deviation 0.2050	0.045 Units on a scale Standard Deviation 0.2393	0.076 Units on a scale Standard Deviation 0.2414
Change From Baseline in EuroQoL 5 Dimension Instrument (EQ-5D) Score Change at LTE Week 72	0.045 Units on a scale Standard Deviation 0.1531	0.000 Units on a scale Standard Deviation 0.2126	0.087 Units on a scale Standard Deviation 0.2609
Change From Baseline in EuroQoL 5 Dimension Instrument (EQ-5D) Score Change at LTE Week 96	0.138 Units on a scale Standard Deviation 0.1257	-0.015 Units on a scale Standard Deviation 0.1767	0.132 Units on a scale Standard Deviation 0.1927

SECONDARY outcome

Timeframe: Baseline: Day 1 (Core Study), LTE Day 1, Week 24, Week 48, Week 72 and Week 96

EQ-5D is a participant rated questionnaire to assess health-related QoL in terms of a single index value. The VAS component rates current health state on a scale from 0 millimeters (mm) (worst imaginable health state) to 100 mm (best imaginable health state); higher scores indicate a better health state. Baseline defined as Day 1 of core study.

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores Change at LTE Week 96	19 mm Standard Deviation 17.6	12 mm Standard Deviation 20.9	10 mm Standard Deviation 21.6
Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores Baseline (Core Study Day 1)	61 mm Standard Deviation 18.8	65 mm Standard Deviation 21.4	65 mm Standard Deviation 22.2
Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores Change at LTE Day 1	9 mm Standard Deviation 16.0	11 mm Standard Deviation 21.5	8 mm Standard Deviation 18.1
Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores Change at LTE Week 24	13 mm Standard Deviation 19.7	12 mm Standard Deviation 21.4	11 mm Standard Deviation 18.4
Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores Change at LTE Week 48	15 mm Standard Deviation 18.4	14 mm Standard Deviation 23.9	9 mm Standard Deviation 19.6
Change From Baseline in EQ-5D Visual Analogue Scale (VAS) Scores Change at LTE Week 72	12 mm Standard Deviation 18.9	12 mm Standard Deviation 19.6	10 mm Standard Deviation 18.1

SECONDARY outcome

Timeframe: Baseline: Day 1 (Core study); LTE Day 1, Week 24, Week 48, Week 72 and Week 96

The FACIT-Fatigue score was calculated according to a 13-item questionnaire that assesses self-reported fatigue and its impact upon daily activities and function. It uses a 5-point Likert-type scale (0 = not at all; 1 = a little bit; 2 = somewhat; 3 = quite a bit; 4 = very much). The sum of all responses resulted in the FACIT-Fatigue score for a total possible score of 0 (worse possible score) to 52 (best score). A higher score reflected an improvement in the participant's health status.

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score Baseline; Day 1 (Core Study)	29 Units on a scale Standard Deviation 10.1	32 Units on a scale Standard Deviation 13.1	31 Units on a scale Standard Deviation 13.1
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score Change at LTE Week 72	4 Units on a scale Standard Deviation 11.3	2 Units on a scale Standard Deviation 10.2	6 Units on a scale Standard Deviation 10.2
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score Change at LTE Week 96	13 Units on a scale Standard Deviation 15.5	3 Units on a scale Standard Deviation 8.4	9 Units on a scale Standard Deviation 9.2
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score Change at LTE Day 1	4 Units on a scale Standard Deviation 9.5	4 Units on a scale Standard Deviation 10.2	4 Units on a scale Standard Deviation 9.8
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score Change at LTE Week 24	5 Units on a scale Standard Deviation 10.1	3 Units on a scale Standard Deviation 10.9	4 Units on a scale Standard Deviation 9.9
Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score Change at LTE Week 48	5 Units on a scale Standard Deviation 11.2	4 Units on a scale Standard Deviation 12.3	5 Units on a scale Standard Deviation 9.9

SECONDARY outcome

Timeframe: Baseline (Day 1 of Core study) up to maximum duration of 167.7 weeks

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Number of Participants With at Least One Adverse Event	68 Participants	67 Participants	76 Participants

SECONDARY outcome

Timeframe: LTE Day 1, Week 24, Week 48, Week 72 and Week 98

The C-SSRS assesses the suicidal behavior and suicidal ideation in participants. Occurrence of suicidal behavior after study entry is defined as having answered "yes" to a least 1 of the 4 suicidal behavior subcategories (actual attempt, interrupted attempt, aborted attempt, and preparatory acts or behavior). Occurrence of suicidal ideation is defined as having answered "yes" to at least 1 of the suicidal ideation sub-categories (1) wish to be dead, (2) nonspecific active suicidal thoughts, (3) active suicidal ideation with any methods (no plan) without intent to act, (4) active suicidal ideation with some intent to act (without specific plan), and (5) active suicidal ideation with specific plan and intent).

Outcome measures

Outcome measures
Measure	Placebo/Atacicept 150 mg n=83 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 Participants Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 Participants Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score Occurrence of Suicidal Behavior at LTE Day 1	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score Occurrence of Suicidal Behavior at LTE Week 24	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score Occurrence of Suicidal Behavior at LTE Week 48	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score Occurrence of Suicidal Behavior at LTE Week 72	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score Occurrence of Suicidal Behavior at LTE Week 96	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score Occurrence of Suicidal Ideation at LTE Day 1	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score Occurrence of Suicidal Ideation at LTE Week 24	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score Occurrence of Suicidal Ideation at LTE Week 48	0 Participants	0 Participants	0 Participants
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score Occurrence of Suicidal Ideation at LTE Week 72	1 Participants	0 Participants	1 Participants
Number of Participants With Columbia-Suicide Severity Rating Scale (C-SSRS) Score Occurrence of Suicidal Ideation at LTE Week 96	0 Participants	1 Participants	0 Participants

Adverse Events

Placebo/Atacicept 150 mg

Serious events: 19 serious events

Other events: 65 other events

Deaths: 0 deaths

Atacicept 75 mg

Serious events: 13 serious events

Other events: 65 other events

Deaths: 0 deaths

Atacicept 150 mg

Serious events: 11 serious events

Other events: 75 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	Placebo/Atacicept 150 mg n=83 participants at risk Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.7 weeks.	Atacicept 75 mg n=82 participants at risk Participants received atacicept 75 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 143.7 weeks.	Atacicept 150 mg n=88 participants at risk Participants received atacicept 150 mg as once-weekly subcutaneous injection during this LTE study up to a maximum of 97.9 weeks.
Infections and infestations Urinary tract infection	21.7% 18/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	17.1% 14/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	19.3% 17/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
Infections and infestations Upper respiratory tract infection	8.4% 7/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	13.4% 11/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	17.0% 15/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
Infections and infestations Nasopharyngitis	9.6% 8/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	9.8% 8/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	5.7% 5/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
Infections and infestations Bronchitis	8.4% 7/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	12.2% 10/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	2.3% 2/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
Infections and infestations Sinusitis	3.6% 3/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	8.5% 7/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	5.7% 5/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
Infections and infestations Pharyngitis	3.6% 3/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	7.3% 6/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	6.8% 6/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
General disorders Injection site reaction	27.7% 23/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	17.1% 14/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	25.0% 22/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
General disorders Injection site pain	13.3% 11/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	4.9% 4/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	15.9% 14/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
General disorders Injection site erythema	6.0% 5/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	3.7% 3/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	1.1% 1/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
Gastrointestinal disorders Gastritis	6.0% 5/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	2.4% 2/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	4.5% 4/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
Nervous system disorders Headache	13.3% 11/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	3.7% 3/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	11.4% 10/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
Musculoskeletal and connective tissue disorders Back pain	3.6% 3/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	8.5% 7/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	4.5% 4/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.
Vascular disorders Hypertension	1.2% 1/83 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	4.9% 4/82 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.	6.8% 6/88 • Baseline up to maximum duration of 167.7 weeks The safety analyses set included all participants enrolled into the LTE study and who received at least 1 dose of planned study treatment. Participants were analyzed according to the actual treatment they received.

Additional Information

Communication Center

Merck KGaA Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place