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A Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination With Rituximab to Adult Subjects With Systemic Lupus Erythematosus (SLE) - BLISS-BELIEVE

Sponsor
GlaxoSmithKline (Industry)
Overall Status
Completed
CT.gov ID
NCT03312907
Collaborator
(none)
292
Enrollment
79
Locations
3
Arms
40.2
Actual Duration (Months)
3.7
Patients Per Site
0.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose of this study is to assess whether co-administration of belimumab and a single cycle of rituximab will optimize treatment with belimumab, which will result in improvements of clinical status with a favorable safety profile, by comparing subjects randomized to belimumab plus rituximab versus belimumab plus rituximab-placebo. Approximately 292 subjects will be randomized in a 1:2:1 ratio to 1 of 3 treatment arms; belimumab plus rituximab-placebo (Arm A, control), belimumab plus rituximab (Arm B, combination), or belimumab plus standard therapy (Arm C, reference). Belimumab will be administered as subcutaneous (SC) and rituximab-placebo or rituximab will be administered by intravenous (IV) infusions. The total duration of the study is for 104 weeks.

Condition or Disease Intervention/Treatment Phase
  • Drug: Belimumab
  • Drug: Rituximab
  • Drug: Rituximab-placebo
  • Drug: Standard therapy (Including Immunosuppressants)
  • Drug: Standard therapy (Excluding Immunosuppressants)
  • Drug: Steroid Taper
 Phase 3

Study Design

Study Type:
Interventional
Actual Enrollment :
292 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose:
Treatment
Official Title:
A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 104-Week Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination With Rituximab to Adult Subjects With Systemic Lupus Erythematosus (SLE)
Actual Study Start Date :
Mar 1, 2018
Actual Primary Completion Date :
May 29, 2020
Actual Study Completion Date :
Jul 7, 2021

Arms and Interventions

Arm Intervention/Treatment
Placebo Comparator: Belimumab + Placebo

Eligible subjects will receive Belimumab 200 milligrams (mg) to be administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Subjects will also receive rituximab-placebo to be administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Subjects will receive standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Subjects will not receive treatment after 52 weeks and will be in observation until Week 104.

Drug: Belimumab
Belimumab will be administered as SC injection once weekly via autoinjector in thigh or abdomen

Drug: Rituximab-placebo
Saline will be administered as IV infusions at Week 4 and Week 6

Drug: Standard therapy (Excluding Immunosuppressants)
Standard therapy excluding Immunosuppressant will contain anti-malarials, NSAIDs, and/or corticosteroids with prednisone dose equivalent to <= 5 mg/day will administered through Week 104.

Drug: Steroid Taper
Steroid taper will include prednisone doses equivalent to =< 5 mg/day in all Arms through Week 104.
Experimental: Belimumab + Rituximab

Eligible subjects will receive Belimumab 200 mg to be administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Subjects will also receive rituximab 1000 mg to be administered by IV infusions at Weeks 4 and 6 in double blind manner. Subjects will receive standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Subjects will not receive treatment after 52 weeks and will be in observation until Week 104.

Drug: Belimumab
Belimumab will be administered as SC injection once weekly via autoinjector in thigh or abdomen

Drug: Rituximab
Rituximab will be administered as IV infusion of 1000mg at Week 4 and Week 6

Drug: Standard therapy (Excluding Immunosuppressants)
Standard therapy excluding Immunosuppressant will contain anti-malarials, NSAIDs, and/or corticosteroids with prednisone dose equivalent to <= 5 mg/day will administered through Week 104.

Drug: Steroid Taper
Steroid taper will include prednisone doses equivalent to =< 5 mg/day in all Arms through Week 104.
Other: Belimumab + Standard therapy

Eligible subjects will receive open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Subjects will also receive standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.

Drug: Belimumab
Belimumab will be administered as SC injection once weekly via autoinjector in thigh or abdomen

Drug: Standard therapy (Including Immunosuppressants)
Standard therapy will contain stable SLE medications including immunosuppressant to be administered from baseline through Week 104.

Drug: Steroid Taper
Steroid taper will include prednisone doses equivalent to =< 5 mg/day in all Arms through Week 104.

Outcome Measures

Primary Outcome Measures

  1. Percentage of Participants With a State of Disease Control at Week 52 [Week 52]

    Percentage of participants with a state of disease control (Independent blinded assessor [IBA]) was defined as the percentage of participants with a Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K)score less than or equal to(<=)2 achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day at Week 52. SLEDAI-2K was a weighted, cumulative index for measuring systemic lupus erythematosus (SLE) disease activity in previous 10 days,consisting 24 individual items in which signs and symptoms, laboratory tests and physician's assessment for each item within each of 9 organ systems were given a weighted score(1 to 8 with higher score indicating increased activity)and summed if present at the time of visit or in preceding 10 days. The SLEDAI-2K score was sum of all 24 individual items from the SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms) with higher scores representing increased disease activity.

Secondary Outcome Measures

  1. Percentage of Participants With a State of Clinical Remission at Week 64 [Week 64]

    Percentage of participants with a state of clinical remission (IBA) was defined as percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-double stranded deoxyribonucleic [dsDNA] and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day at Week 64. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days, consisting 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.

  2. Percentage of Participants With a State of Disease Control at Week 104 [Week 104]

    Percentage of participants with a state of disease control (IBA) was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day at Week 104. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity.

  3. Percentage of Participants With a State of Disease Control by Visits [Weeks 12, 26, 40, 52, 64, 80 and 104]

    Percentage of participants with a state of disease control (IBA) was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity.

  4. Percentage of Participants With a State of Clinical Remission by Visits [Weeks 64, 80 and 104]

    Percentage of participants with a state of clinical remission (IBA) was defined as percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days, consisting 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity

  5. Percentage of Participants With a State of Complete Remission (CR) Sustained for at Least 24 Weeks During Week 52 to Week 104 [Week 52 to Week 104]

    Percentage of participants with a state of CR (Principal Investigator [PI] assessed) was defined as percentage of participants with a SLEDAI-2K=0 achieved without immunosuppressants and with corticosteroids at prednisone equivalent dose of 0 mg/day,sustained for at least 24 weeks. Sustained CR was longest period a participant maintains CR without break calculated as last consecutive CR date minus first consecutive CR date plus 1. SLEDAI-2K consisted of 24 individual items within each 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at time of visit or in preceding 10 days. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms),higher scores indicates increased disease activity. Percentage of participants with a state of CR sustained for at least 24 weeks at any visit during Week 52 to Week 104 were reported.

  6. Percentage of Participants With a State of Clinical Remission (CLR) Sustained for at Least 24 Weeks From Week 80 to Week 104 [From Week 80 to Week 104]

    Percentage of participants with a state of CLR (PI assessed) at Week 104 was defined as percentage of participants with a clinical SLEDAI-2K score=0 (does not include anti-dsDNA and complement activity scores) achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day, sustained for at least 24 weeks(from Week 80 to Week 104). Sustained CLR is longest period a participant maintains CLR without a break, calculated as last consecutive CLR date minus first consecutive CLR date plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score(1 to 8 with higher score indicating increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.

  7. Percentage of Participants With a State of Complete Remission by Visits [Weeks 60, 64, 72, 80, 88, 96 and 104]

    Percentage of participants with a state of complete remission (PI assessed) was defined as the percentage of participants with a SLEDAI-2K score =0, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. SLEDAI-2K was a weighted, cumulative index for measuring systemic lupus erythematosus (SLE) disease activity in the previous 10 days which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within for each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity.

  8. Time to First Severe Flare [Up to Week 104]

    Time to first severe SLE flare was the number of days from treatment start date until the participant met an event. Time to first severe flare was defined as event date minus treatment start date plus 1. Time to first severe flare was measured by Modified SLE flare index which identifies whether a participant had experienced a mild/moderate or severe flare. Analysis of first severe flare was performed on the modified SLE Flare index that excludes severe flares that were triggered only by an increase is SLEDAI-2K score to greater than 12.

  9. Time to First Flare [Up to Week 104]

    Time to first SLE flare was the number of days from treatment start date until the participant met an event. Time to first flare was defined as event date minus treatment start date plus 1. Time to first flare was measured by modified SLE flare index which identifies whether a participant had experienced a mild/moderate or severe flare.

  10. Time to Disease Control Sustained for at Least 24 Weeks and Maintained Through Week 104 [Up to Week 104]

    Disease control sustained for at least 24 weeks and maintained through Week 104 was defined as SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. Time to disease control (PI assessed) was defined as the first visit of sustained disease control until Week 104 on or before Week 80 minus treatment start date (Day 1) plus 1. Sustained disease control was longest period a participant maintained disease control without a break. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K , ranges from 0 (no symptoms) to 105 (presence of all defined symptoms),higher scores representing increased disease activity.

  11. Time to Clinical Remission Sustained for at Least 24 Weeks and Maintained Through Week 104 [Up to Week 104]

    Clinical remission sustained for at least 24 weeks and maintained through Week 104 was defined as clinical SLEDAI-2K score=0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. Time to CLR (PI assessed) was defined as first visit of sustained CLR until Week 104 on or before Week 80 minus treatment start date (Day 1) plus 1. Sustained CLR was longest period a participant maintained clinical remission without a break. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.

  12. Duration of Disease Control [Up to Week 104]

    Duration of disease control was defined as SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. The duration of disease control (PI assessed) was the longest period between 2 visits that the participant was a disease control responder at all visits and calculated as the first visit of disease control minus last visit of disease control plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105 (presence of all defined symptoms),higher scores representing increased disease activity

  13. Duration of Clinical Remission [Up to Week 104]

    Clinical remission was defined as clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. The duration of clinical remission (PI assessed) was the longest period between 2 visits that the participant was a clinical remission responder at all visits and was calculated as the first visit of clinical remission minus last visit of clinical remission plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.

  14. Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score by Visit (PI Assessed) [Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104]

    The SLEDAI-2K consisted of 24 individual items within 9 organ systems. Each item was given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of visit or in the preceding 10 days. Weighted scores for central nervous system (CNS) (7 items) was 8; for vascular (1 item) was 8; for Musculoskeletal (2 items) was 4; for Renal (4 items) was 4; for Mucocutaneous (3 items) was 2; for Cardiovascular and Respiratory (2 items) was 2; for Immunologic (2 items) was 2;for Constitutional (1 item) was 1 and for Hematologic (2 items) was 1. SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. Baseline value was latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

  15. Percentage of Participants With SLEDAI-2K Organ Improvement Compared to Baseline by Visits (PI Assessed) [Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104]

    SLEDAI-2K assessments consisted of 24 individual items with 9 organ systems. Each item was given a weighted score(1 to 8 with higher score indicating increased activity)and summed if present at the time of analysis. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K ranges from 0(no symptoms) to 105(presence of all defined symptoms). Higher scores indicates increased disease activity. An improvement was defined as a decrease(compared to Baseline) in SLEDAI-2K score within same organ system at a post-Baseline visit. Baseline value was latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for following organ systems was reported: CNS total, Vascular total, Musculoskeletal total, Renal total, Mucocutaneous total, Cardiovascular (Cardio) and Respiratory (Resp) total, Immunologic total and Hematologic total. Constitutional organ system was removed from analysis and its one item (fever)moved to hematologic organ system.

  16. Percentage of Participants With SLEDAI-2K Organ Worsening Compared to Baseline by Visits (PI Assessed) [Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104]

    SLEDAI-2K assessments consisted of 24 individual items with 9 organ systems. Each item was given a weighted score(1 to 8 with higher score indicating increased activity)and summed if present at time of analysis. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms). Higher scores indicates increased disease activity. A worsening was defined as an increase(compared to Baseline) in SLEDAI-2K score within same organ system at a post-Baseline visit. Baseline value was latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage of participants with SLEDAI-2K organ worsening for following organ systems were reported;CNS total,Vascular total,Musculoskeletal total,Renal total,Mucocutaneous total,Cardio and Resp total,Immunologic total and Hematologic total. Constitutional organ system was removed from analysis and its one item (fever)moved to hematologic organ system.

  17. Change From Baseline in Physician Global Assessment (PGA) by Visits [Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104]

    The Physician's Global Assessment (PGA) was a physician-reported visual analogue scale that provides an overall measure of the participant's current disease activity. Physician's Global Assessment was collected on a 10 centimeter (cm) visual analogue scale (VAS) by placing a mark on the scale between 0 (no disease activity) to 10 (maximum disease activity). The PGA score was then rescaled for reporting by multiplying the collected score by 3 divided by 10. Hence, the PGA score ranges from 0 to 3 with higher scores indicating greater disease activity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value.

  18. Percentage of Participants With Systemic Lupus International Collaborating Clinics (SLICC) -American College of Rheumatology (ACR) Damage Index Worsening Compared With Baseline at Week 52 and Week 104 [Baseline (Day 1), Week 52 and Week 104]

    The SLICC-ACR Damage Index measures irreversible (not related to active inflammation) changes occurring since the diagnosis of SLE ascertained by clinical assessment and present for at least 6 months. The questionnaire contains 39 items covering 12 different organ systems which were scored on a numerical scale between 0 (no damage) to 7 (increasing disease damage). Individual ranges for organ systems were; ocular: 0-2, neuropsychiatric: 0-6, renal: 0-3, pulmonary: 0-5, cardiovascular:0-6, peripheral vascular: 0-5, gastrointestinal:0-5, musculoskeletal: 0-6, skin: 0-3, endocrine (diabetes): 0-1, gonadal:0-1 and malignancies: 0-2. The SLICC-ACR score was calculated by taking sum of the individual scores for 12 organ systems which ranges from 0 (no damage) to 45 (increasing disease damage) where higher score indicates increasing disease damage severity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.

  19. Percentage of Participants That Met the Lupus Low Disease Activity State (LLDAS) Response Criteria by Visits (PI Assessed) [Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96 and 104]

    Lupus low disease activity state (LLDAS) was defined as a state which, if sustained, was associated with a low likelihood of adverse outcome, considering disease activity and medication safety. The LLDAS response criteria were: (1) SLEDAI-2K <=4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity; (2) no new features of lupus disease activity compared with the previous assessment; (3) PGA (scale 0-3), <=1; (4) current prednisolone (or equivalent) dose <=7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents, excluding investigational drugs. Percentage of participants that met the LLDAS response criteria were reported.

  20. Percentage of Participants With a State of Disease Control Using the PI Assessment of SLEDAI-2K by Visit [Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104]

    Percentage of participants with a state of disease control was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day, using the PI assessment of SLEDAI-2K. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K, ranges from 0 (no symptoms) to 105 (presence of all defined symptoms), higher scores representing increased disease activity. Percentage of participants with a state of disease control using the PI assessment of SLEDAI-2K were summarized.

  21. Percentage of Participants With a State of Clinical Remission Using the PI Assessment of SLEDAI-2K by Visit [Weeks 60, 64, 72, 80, 88, 96 and 104]

    Percentage of participants with a state of clinical remission was defined as the percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants (which was allowed in Belimumab+ Standard therapy arm only) and with corticosteroids at a prednisone equivalent dose of 0 mg/day using the PI assessment of SLEDAI-2K. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity. Percentage of participants with a state of clinical remission using the PI assessment of SLEDAI-2K were summarized.

  22. Number of Participants With Serious Adverse Events (SAE) and Non-serious AE (Non-SAE) [Up to Week 111 (including 8 weeks of safety follow-up)]

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situations as per medical or scientific judgment. Data for number of participants with SAE and non-SAE (>=5 %) has been summarized.

  23. Number of Participants With Adverse Events of Special Interest (AESIs) [Up to Week 104]

    An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. AESIs were Malignant Neoplasms, Post-Injection Systemic Reactions (PISR), All Infections of Special Interest (Opportunistic Infections (OI), Herpes Zoster (HZ), Tuberculosis (TB), and Sepsis), Depression (including mood disorders and anxiety)/suicide/self-injury and Deaths. Data for number of participants with AESIs has been summarized.

  24. Change From Baseline in Patient Global Assessment (PtGA) by Visits [Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104]

    The Patient's Global Assessment (PtGA) of Disease Activity is a single-item, participant reported scale developed for the assessment of the participant's overall rating of their disease activity due to SLE. The scale measures disease activity ranging from 0 (Very Well) to 10 (Very Poor) and the higher score indicates severe disease activity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value.

  25. Change From Baseline in Lupus Quality of Life (LupusQoL) Domain Scores by Visit [Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104]

    LupusQoL is a SLE-specific health related qualify of life (HRQOL) instrument with 34 questions across 8 domains:Physical health(8 items),Pain(3 items),Planning(3 items),Intimate relationship(2 items),Burden to others(3 items),Emotional health(6 items),Body image(5 items),Fatigue(4 items). Questions were related to participants experience in prior 4 weeks.A 5-point Likert response format was used, ranging from 0(all of the time) to 4(never) for each question. Individual domain scores were reported which were calculated by taking sum of responses to all items within each domain. Individual domain scores range:Physical health(0-32),Pain(0-12),Planning(0-12),Intimate relationship(0-8),Burden to others(0-12),Emotional health(0-24),Body image(0-20),Fatigue(0-16). Higher score indicates better HRQOL. Baseline value was latest pre-dose assessment with a non-missing value including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.

  26. Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score by Visit [Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104]

    The FACIT-Fatigue scale was a 13-item questionnaire completed by the participant, which provides a measure of fatigue/quality of life, with a 7-day recall period. The participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The higher score for the questions, the greater the fatigue. The total score was the sum of the responses from all questions (inverted for reversed items) multiplied by 13, then divided by the number of questions answered, ranging from 0 (worse fatigue) to 52 (no fatigue) where a higher score indicates an improvement in the participant's health status and decrease in the score indicates worse fatigue/quality of life. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value.

  27. Percentage of Participants With Improvement in FACIT-Fatigue Score Exceeding the Minimal Clinically Important Difference (MCID, Greater Than or Equal to [>=]4) [Weeks 8, 12, 26, 40, 52, 64, 72 and 104]

    The FACIT-Fatigue scale was a 13-item questionnaire completed by the participant, which provides a measure of fatigue/quality of life, with a 7-day recall period. The participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions, the greater the fatigue. The total score was the sum of the responses (inverted for reversed items) multiplied by 13, then divided by the number of questions answered, ranging from 0 (worse fatigue) to 52 (no fatigue) where a higher score indicates an improvement in the participant's health status and decrease in the score indicates worse fatigue/quality of life. A participant was considered to had an improvement exceeding the minimal clinically important difference if they had >=4 points improvement in their FACIT-Fatigue Scale score from Baseline. Percentage of participants with improvement in FACIT-Fatigue scale score exceeding the MCID (>=4 points) were summarized.

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:

  • Subjects must be >=18 years of age at the time of signing the informed consent.

  • Subjects who have clinical diagnosis of SLE based on 4 or more of the 11 American College of Rheumatology (ACR) criteria.

  • Subjects who have a screening SLEDAI-2K score >=6 (This refers to the total score. Serological activity, i.e., anti-double stranded deoxyribonucleic acid [dsDNA]) positivity and/or hypocomplementemia is not required to be present in SLEDAI-2K assessment, but are scored if present).

  • Subjects who have unequivocally positive autoantibody test results defined as an anti-nuclear (ANA) titer >=1:80 and/or a positive anti-dsDNA (>=30 International Units per milliliter [IU/mL]) serum antibody test from 2 independent time points as follows: Positive test results from 2 independent time points within the study screening period. Screening results must be based on the study's central laboratory results. Or, one positive historical test result and 1 positive test result during the screening period.

  • Subjects who are on a stable SLE treatment regimen consisting of any of these medications (alone or in combination) for a period of at least 30 days prior to Day 1 (i.e. day of first dose of study treatment) with the exception that switching one agent for another of the same class for tolerability or availability reasons, which will be allowed within 30 days of Day 1: Corticosteroids (prednisone or prednisone equivalent); For those subjects on alternating daily doses of steroids, use the average of 2 daily doses to calculate the average daily steroid dose; Any immunosuppressant or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin inhibitors (example [e.g.] tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-mercaptopurine, mizoribine, or thalidomide; Anti-malarials (e.g., hydroxychloroquine, chloroquine, quinacrine); Non steroidal anti-inflammatory drugs (NSAIDs).

  • Male and/or female. A female subject is eligible to participate if she is not pregnant not breastfeeding, and at least one of the these conditions applies: Not a woman of childbearing potential (WOCBP) or A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 16 weeks after the last dose of belimumab, or at least 12 months after the last dose of rituximab or rituximab-placebo.

  • Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.

Exclusion Criteria:

  • Symptomatic herpes zoster within 3 months prior to screening.

  • Evidence of active or latent tuberculosis (TB). Documentation may include medical history and examination, chest X-rays (posterior, anterior, and lateral), and TB testing: either a positive tuberculin skin test (TST; defined as a skin induration ≥5 mm at 48 to 72 hours, regardless of Baccillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold Plus test.

  • Significant allergies to humanized monoclonal antibodies.

  • History of hypersensitivity to belimumab and/or rituximab or known to have titers of human anti-mouse antibody or history of hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies.

  • Lymphoma, leukemia, or any malignancy within the past 5 years (yrs) except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 yrs.

  • Alanine transferase (ALT) greater than 2 times upper limit of normal (ULN).

  • Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).

  • Immunoglobulin A (IgA) deficiency (IgA level less than 10 milligram per deciliter [mg/dL]).

  • Immunoglobulin G (IgG) less than 250 mg/dL. For Germany only, IgG less than 400mg/dL.

  • Neutrophils less than 1.5 times 10^9.

  • Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.

  • Severe heart failure (New York Heart Association Class IV) or other severe, uncontrolled cardiac disease.

  • QT interval corrected (QTc) greater than 450 millisecond (msec) or QTc greater than 480 msec in subjects with bundle branch block.

  • Subjects who have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.

  • Subjects who have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, psychiatric, malignancy, or infectious diseases) which, in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk.

  • Subjects who have an acute or chronic infection requiring management as : Currently on any suppressive therapy for a chronic infection such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria); Hospitalization for treatment of infection within 60 days of Day 1; subjects who had infection requiring treatment with parenteral (IV or intramuscular [IM]) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 60 days of Day 1. Prophylactic anti-infective treatment is allowed.

  • Subjects who have severe lupus kidney disease (defined by proteinuria greater than 6 gram (g)/24 hours or equivalent using spot urine protein to creatinine ratio, or serum creatinine greater than 2.5 mg/dL), or have severe active nephritis requiring induction therapy not permitted by protocol (e.g., IV cyclophosphamide), or have required hemodialysis or high dose prednisone or equivalent (greater than 100 mg/day) within 90 days of Day 1.

  • Subjects who have severe active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis, or CNS vasculitis) requiring therapeutic intervention within 60 days of Day 1.

  • Subjects who have a planned surgical procedure, laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the principal investigator, makes the subject unsuitable for the study.

  • Subjects who have evidence of serious suicide risk, including any history of suicidal behavior in the last 6 months and/or any suicidal ideation of type 4 or 5 on the Columbia-Suicide Severity Rating Scale (C-SSRS) in the last 2 months or who, in the investigator's opinion, pose a significant suicide risk.

  • Subjects who have a history of an anaphylaxis reaction to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies.

  • Subjects who have received live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the screening period or during the study.

  • Subjects who have received any of the these prior/concomitant therapy within 364 days of Day 1: Belimumab; Rituximab; Abatacept; Any B cell targeted therapy (anti-cluster of differentiation-20 [CD] agents other than rituximab, anti CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS-receptor fusion protein [BR3], Trans-membrane activator and calcium-modulator and cytophilin ligand interactor [TACI] Fc, anti B-cell activating factor [BAFF] (LY2127399), anti-Interferon alpha agents or anti-BLyS other than belimumab); A biologic investigational agent other than B cell targeted therapy (e.g., abetimus sodium, anti CD40L antibody [BG9588/ IDEC 1311]). (Investigational agent applies to any drug not approved for sale in the country in which it is being used).

  • Subjects who have required 3 or more courses of systemic corticosteroids within 364 days of Day 1. (Topical or inhaled steroids are permitted).

  • Subjects who have received any of these within 90 days of Day 1: Anti- Tumor Necrosis Factor (Anti-TNF) therapy (e.g., adalimumab, etanercept, infliximab); Interleukin-1 receptor antagonist (anakinra); Intravenous immunoglobulin (IVIG); High dose prednisone or equivalent (greater than 100 mg/day); Plasmapheresis.

  • Subjects who have received any of the these within 60 days of Day 1: A non-biologic investigational agent (Investigational agent applies to any drug not approved for sale in the country in which it is being used); IV cyclophosphamide and, for Germany only, oral cyclophosphamide; Any steroid injection (e.g., intramuscular [IM], intraarticular, or IV).

  • Positive immunodeficiency virus (HIV) antibody test.

  • Positive serology for Hepatitis B (HB), defined as HB surface antigen positive (HBsAg+) OR HB core antibody positive (HBcAb+).

  • Positive Hepatitis C (HCV) antibody test.

  • Subjects who have current drug or alcohol dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 1.

  • Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.

  • Unable to administer study treatment (belimumab) by SC injection and has no other reliable resource to administer the injection.

Contacts and Locations

Locations

Site City State Country Postal Code
1 GSK Investigational Site Birmingham Alabama United States 35294
2 GSK Investigational Site La Mesa California United States 92020
3 GSK Investigational Site San Leandro California United States 94578
4 GSK Investigational Site Upland California United States 91786
5 GSK Investigational Site Denver Colorado United States 80230
6 GSK Investigational Site Aventura Florida United States 33180
7 GSK Investigational Site Miami Florida United States 33136
8 GSK Investigational Site Orlando Florida United States 32806-6264
9 GSK Investigational Site Tamarac Florida United States 33321
10 GSK Investigational Site Tampa Florida United States 33613
11 GSK Investigational Site Tampa Florida United States 33614
12 GSK Investigational Site Ann Arbor Michigan United States 48109-5542
13 GSK Investigational Site Brighton Michigan United States 48116
14 GSK Investigational Site Lansing Michigan United States 48910
15 GSK Investigational Site Lansing Michigan United States 48917
16 GSK Investigational Site Las Cruces New Mexico United States 88011
17 GSK Investigational Site Manhasset New York United States 11030
18 GSK Investigational Site New York New York United States 10016
19 GSK Investigational Site New York New York United States 10032
20 GSK Investigational Site Charlotte North Carolina United States 28204
21 GSK Investigational Site Vandalia Ohio United States 45377
22 GSK Investigational Site Oklahoma City Oklahoma United States 73102
23 GSK Investigational Site Pittsburgh Pennsylvania United States 15224
24 GSK Investigational Site Summerville South Carolina United States 29486
25 GSK Investigational Site Austin Texas United States 78731
26 GSK Investigational Site League City Texas United States 77573
27 GSK Investigational Site Spokane Washington United States 99204
28 GSK Investigational Site Glendale Wisconsin United States 53217
29 GSK Investigational Site Ciudad Autonoma de Buenos Aires Buenos Aires Argentina C1046AAQ
30 GSK Investigational Site La Plata Buenos Aires Argentina B1904CFH,
31 GSK Investigational Site San Miguel de Tucuman Tucumán Argentina T4000AXL
32 GSK Investigational Site Salvador Bahía Brazil 40.150-150
33 GSK Investigational Site Cuiabá Mato Grosso Brazil 78043-142
34 GSK Investigational Site Juiz de Fora Minas Gerais Brazil 36010-570
35 GSK Investigational Site Sao Jose do Rio Preto São Paulo Brazil 15090-000
36 GSK Investigational Site Hamilton Ontario Canada L8S 4K1
37 GSK Investigational Site Toronto Ontario Canada M5T 2S8
38 GSK Investigational Site Trois-Rivieres Quebec Canada G8Z 1Y2
39 GSK Investigational Site Saskatoon Saskatchewan Canada S7K 0H6
40 GSK Investigational Site Brest Cedex France 29609
41 GSK Investigational Site Lille Cedex France 59037
42 GSK Investigational Site Paris cedex 12 France 75571
43 GSK Investigational Site Paris France 75013
44 GSK Investigational Site Pessac cedex France 33604
45 GSK Investigational Site Strasbourg Cedex France 67091
46 GSK Investigational Site Hannover Niedersachsen Germany 30625
47 GSK Investigational Site Kiel Schleswig-Holstein Germany 24105
48 GSK Investigational Site Frankfurt Germany 60590
49 GSK Investigational Site Daegu Korea, Republic of 700-721
50 GSK Investigational Site Gwangju Korea, Republic of 501-757
51 GSK Investigational Site Incheon Korea, Republic of 400-711
52 GSK Investigational Site Seoul Korea, Republic of 03080
53 GSK Investigational Site Seoul Korea, Republic of 133-792
54 GSK Investigational Site Seoul Korea, Republic of 137-701
55 GSK Investigational Site Suwon-si Korea, Republic of 443-380
56 GSK Investigational Site Zapopan Jalisco Mexico 45070
57 GSK Investigational Site Merida Yucatán Mexico 97070
58 GSK Investigational Site Amersfoort Netherlands 3813 TZ
59 GSK Investigational Site Den Haag Netherlands 2545 AA
60 GSK Investigational Site Groningen Netherlands 9713 GZ
61 GSK Investigational Site Leiden Netherlands 2333 ZA
62 GSK Investigational Site Utrecht Netherlands 3584 CX
63 GSK Investigational Site Chelyabinsk Russian Federation 454076
64 GSK Investigational Site Kazan Russian Federation 420097
65 GSK Investigational Site Kemerovo Russian Federation 650066
66 GSK Investigational Site Moscow Russian Federation 119435
67 GSK Investigational Site Novosibirsk Russian Federation 630117
68 GSK Investigational Site Omsk Russian Federation 644111
69 GSK Investigational Site Petrozavodsk Russian Federation 185019
70 GSK Investigational Site Ryazan Russian Federation 390026
71 GSK Investigational Site Saint-Petersburg Russian Federation 190068
72 GSK Investigational Site Ufa Russian Federation 450005
73 GSK Investigational Site Ulyanovsk Russian Federation 432063
74 GSK Investigational Site Yaroslavl Russian Federation 150030
75 GSK Investigational Site Badalona Spain 08916
76 GSK Investigational Site Barcelona Spain 08035
77 GSK Investigational Site Valencia Spain 46017
78 GSK Investigational Site Valladolid Spain 47010
79 GSK Investigational Site Vigo (Pontevedra) Spain 36214

Sponsors and Collaborators

  • GlaxoSmithKline

Investigators

  • Study Director: GSK Clinical Trials, GlaxoSmithKline

Study Documents (Full-Text)

More Information

Publications

Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT03312907
Other Study ID Numbers:
  • 205646
  • 2016-003050-32
First Posted:
Oct 18, 2017
Last Update Posted:
Apr 25, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by GlaxoSmithKline
immunosuppressants
Systemic Lupus Erythematosus Disease Activity Index
Belimumab
Lupus Low Disease Activity State
Systemic Lupus Erythematosus
Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Rituximab
Belimumab
Immunosuppressive Agents

Study Results

Participant Flow

Recruitment Details This was a multicenter study conducted at 71 centers in 11 countries. This was a randomized, placebo-controlled, parallel study where participants received treatment in any one of the treatment arms.
Pre-assignment Detail A total of 396 participants were screened, of which 104 were screen failures. A total of 292 participants were enrolled in the study (Intent-to-Treat Population: It comprised of all randomized participants who received at least one dose of study treatment [Belimumab or Rituximab or Placebo]).
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Period Title: Overall Study
STARTED 72 144 76
COMPLETED 55 114 57
NOT COMPLETED 17 30 19

Baseline Characteristics

Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy Total
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Total of all reporting groups
Overall Participants 72 144 76 292
Age (Years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [Years]
40.6
(12.58)
40.1
(11.45)
41.0
(12.75)
40.5
(12.04)
Sex: Female, Male (Count of Participants)
Female
66
91.7%
129
89.6%
73
96.1%
268
91.8%
Male
6
8.3%
15
10.4%
3
3.9%
24
8.2%
Race/Ethnicity, Customized (Count of Participants)
White -Arabic/North African Heritage
0
0%
1
0.7%
1
1.3%
2
0.7%
White-White/Caucasian/European Heritage
39
54.2%
100
69.4%
47
61.8%
186
63.7%
Asian - Central/South Asian Heritage
0
0%
1
0.7%
1
1.3%
2
0.7%
Asian - East Asian Heritage
7
9.7%
14
9.7%
10
13.2%
31
10.6%
Asian - South East Asian Heritage
3
4.2%
2
1.4%
1
1.3%
6
2.1%
African American/African Heritage
21
29.2%
22
15.3%
13
17.1%
56
19.2%
American Indian or Alaskan Native
1
1.4%
3
2.1%
3
3.9%
7
2.4%
Native Hawaiian or Other Pacific Islander
1
1.4%
1
0.7%
0
0%
2
0.7%

Outcome Measures

1. Primary Outcome
Title Percentage of Participants With a State of Disease Control at Week 52
Description Percentage of participants with a state of disease control (Independent blinded assessor [IBA]) was defined as the percentage of participants with a Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K)score less than or equal to(<=)2 achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day at Week 52. SLEDAI-2K was a weighted, cumulative index for measuring systemic lupus erythematosus (SLE) disease activity in previous 10 days,consisting 24 individual items in which signs and symptoms, laboratory tests and physician's assessment for each item within each of 9 organ systems were given a weighted score(1 to 8 with higher score indicating increased activity)and summed if present at the time of visit or in preceding 10 days. The SLEDAI-2K score was sum of all 24 individual items from the SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms) with higher scores representing increased disease activity.
Time Frame Week 52

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population comprised of all randomized participants who received at least one dose of study treatment (Belimumab or Rituximab or Placebo) and excluding participants from Arm 3 (Belimumab + Standard therapy) who were randomized prior to 07-Sep-2018.
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Number (95% Confidence Interval) [Percentage of participants]
16.7
23.2%
19.4
13.5%
25.5
33.6%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Belimumab + Placebo, Belimumab + Rituximab
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.5342
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.27
Confidence Interval (2-Sided) 95%
0.60 to 2.71
Parameter Dispersion Type:
Value:
Estimation Comments Odds ratio was calculated using logistic regression model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose. Belimumab + Standard therapy arm was excluded from model.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Belimumab + Rituximab, Belimumab + Standard Therapy
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.71
Confidence Interval (2-Sided) 95%
0.32 to 1.54
Parameter Dispersion Type:
Value:
Estimation Comments Odds ratio was calculated using logistic regression model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, and Baseline prednisone equivalent dose. Belimumab + Placebo arm excluded from model.
2. Secondary Outcome
Title Percentage of Participants With a State of Clinical Remission at Week 64
Description Percentage of participants with a state of clinical remission (IBA) was defined as percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-double stranded deoxyribonucleic [dsDNA] and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day at Week 64. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days, consisting 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.
Time Frame Week 64

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Number (95% Confidence Interval) [Percentage of participants]
5.6
7.8%
6.3
4.4%
10.6
13.9%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Belimumab + Placebo, Belimumab + Rituximab
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.8582
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.12
Confidence Interval (2-Sided) 95%
0.33 to 3.78
Parameter Dispersion Type:
Value:
Estimation Comments Odds ratio was calculated using logistic regression model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Standard therapy arm was excluded from model.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Belimumab + Rituximab, Belimumab + Standard Therapy
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.53
Confidence Interval (2-Sided) 95%
0.17 to 1.70
Parameter Dispersion Type:
Value:
Estimation Comments Odds ratio was calculated using logistic regression model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Placebo arm was excluded from model.
3. Secondary Outcome
Title Percentage of Participants With a State of Disease Control at Week 104
Description Percentage of participants with a state of disease control (IBA) was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day at Week 104. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity.
Time Frame Week 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Number (95% Confidence Interval) [Percentage of participants]
6.9
9.6%
11.1
7.7%
21.3
28%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Belimumab + Placebo, Belimumab + Rituximab
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.3613
Comments
Method Regression, Logistic
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.64
Confidence Interval (2-Sided) 95%
0.57 to 4.72
Parameter Dispersion Type:
Value:
Estimation Comments Odds ratio was calculated using logistic regression model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Standard therapy arm was excluded from model.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Belimumab + Rituximab, Belimumab + Standard Therapy
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.45
Confidence Interval (2-Sided) 95%
0.19 to 1.09
Parameter Dispersion Type:
Value:
Estimation Comments Odds ratio was calculated using logistic regression model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Placebo arm excluded from model.
4. Secondary Outcome
Title Percentage of Participants With a State of Disease Control by Visits
Description Percentage of participants with a state of disease control (IBA) was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity.
Time Frame Weeks 12, 26, 40, 52, 64, 80 and 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 12
8.3
11.5%
12.5
8.7%
21.3
28%
Week 26
16.7
23.2%
21.5
14.9%
25.5
33.6%
Week 40
13.9
19.3%
20.8
14.4%
23.4
30.8%
Week 52
16.7
23.2%
19.4
13.5%
25.5
33.6%
Week 64
11.1
15.4%
18.1
12.6%
25.5
33.6%
Week 80
6.9
9.6%
13.2
9.2%
27.7
36.4%
Week 104
6.9
9.6%
11.1
7.7%
21.3
28%
5. Secondary Outcome
Title Percentage of Participants With a State of Clinical Remission by Visits
Description Percentage of participants with a state of clinical remission (IBA) was defined as percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. SLEDAI-2K was a weighted, cumulative index for measuring SLE disease activity in previous 10 days, consisting 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity
Time Frame Weeks 64, 80 and 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 64
5.6
7.8%
6.3
4.4%
10.6
13.9%
Week 80
4.2
5.8%
4.2
2.9%
12.8
16.8%
Week 104
1.4
1.9%
4.2
2.9%
6.4
8.4%
6. Secondary Outcome
Title Percentage of Participants With a State of Complete Remission (CR) Sustained for at Least 24 Weeks During Week 52 to Week 104
Description Percentage of participants with a state of CR (Principal Investigator [PI] assessed) was defined as percentage of participants with a SLEDAI-2K=0 achieved without immunosuppressants and with corticosteroids at prednisone equivalent dose of 0 mg/day,sustained for at least 24 weeks. Sustained CR was longest period a participant maintains CR without break calculated as last consecutive CR date minus first consecutive CR date plus 1. SLEDAI-2K consisted of 24 individual items within each 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at time of visit or in preceding 10 days. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms),higher scores indicates increased disease activity. Percentage of participants with a state of CR sustained for at least 24 weeks at any visit during Week 52 to Week 104 were reported.
Time Frame Week 52 to Week 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Number (95% Confidence Interval) [Percentage of participants]
2.8
3.9%
0
0%
6.4
8.4%
7. Secondary Outcome
Title Percentage of Participants With a State of Clinical Remission (CLR) Sustained for at Least 24 Weeks From Week 80 to Week 104
Description Percentage of participants with a state of CLR (PI assessed) at Week 104 was defined as percentage of participants with a clinical SLEDAI-2K score=0 (does not include anti-dsDNA and complement activity scores) achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day, sustained for at least 24 weeks(from Week 80 to Week 104). Sustained CLR is longest period a participant maintains CLR without a break, calculated as last consecutive CLR date minus first consecutive CLR date plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score(1 to 8 with higher score indicating increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.
Time Frame From Week 80 to Week 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Number (95% Confidence Interval) [Percentage of participants]
2.8
3.9%
2.1
1.5%
4.3
5.7%
8. Secondary Outcome
Title Percentage of Participants With a State of Complete Remission by Visits
Description Percentage of participants with a state of complete remission (PI assessed) was defined as the percentage of participants with a SLEDAI-2K score =0, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. SLEDAI-2K was a weighted, cumulative index for measuring systemic lupus erythematosus (SLE) disease activity in the previous 10 days which consisted of 24 individual items in which signs and symptoms, laboratory tests, and physician's assessment for each item within for each of 9 organ systems were given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of the visit or in the preceding 10 days. The SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity.
Time Frame Weeks 60, 64, 72, 80, 88, 96 and 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 60
5.6
7.8%
0.7
0.5%
6.4
8.4%
Week 64
5.6
7.8%
0.7
0.5%
6.4
8.4%
Week 72
4.2
5.8%
0.7
0.5%
6.4
8.4%
Week 80
2.8
3.9%
1.4
1%
8.5
11.2%
Week 88
2.8
3.9%
0
0%
4.3
5.7%
Week 96
1.4
1.9%
0.7
0.5%
6.4
8.4%
Week 104
1.4
1.9%
0.7
0.5%
4.3
5.7%
9. Secondary Outcome
Title Time to First Severe Flare
Description Time to first severe SLE flare was the number of days from treatment start date until the participant met an event. Time to first severe flare was defined as event date minus treatment start date plus 1. Time to first severe flare was measured by Modified SLE flare index which identifies whether a participant had experienced a mild/moderate or severe flare. Analysis of first severe flare was performed on the modified SLE Flare index that excludes severe flares that were triggered only by an increase is SLEDAI-2K score to greater than 12.
Time Frame Up to Week 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Median (Inter-Quartile Range) [Days]
372.0
379.0
730.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Belimumab + Placebo, Belimumab + Rituximab
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.2150
Comments
Method Cox proportional hazards model
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.81
Confidence Interval (2-Sided) 95%
0.57 to 1.13
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio was calculated using Cox proportional hazards model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Standard therapy arm was excluded from model.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Belimumab + Rituximab, Belimumab + Standard Therapy
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.64
Confidence Interval (2-Sided) 95%
1.03 to 2.63
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio was calculated using Cox proportional hazards model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Placebo arm excluded from model.
10. Secondary Outcome
Title Time to First Flare
Description Time to first SLE flare was the number of days from treatment start date until the participant met an event. Time to first flare was defined as event date minus treatment start date plus 1. Time to first flare was measured by modified SLE flare index which identifies whether a participant had experienced a mild/moderate or severe flare.
Time Frame Up to Week 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Median (Inter-Quartile Range) [Days]
168.0
170.0
168.0
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Belimumab + Placebo, Belimumab + Rituximab
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.3757
Comments
Method Cox proportional hazards model
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.87
Confidence Interval (2-Sided) 95%
0.64 to 1.19
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio was calculated using Cox proportional hazards model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Standard therapy arm was excluded from model.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Belimumab + Rituximab, Belimumab + Standard Therapy
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.03
Confidence Interval (2-Sided) 95%
0.71 to 1.49
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio was calculated using Cox proportional hazards model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Placebo arm excluded from model.
11. Secondary Outcome
Title Time to Disease Control Sustained for at Least 24 Weeks and Maintained Through Week 104
Description Disease control sustained for at least 24 weeks and maintained through Week 104 was defined as SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. Time to disease control (PI assessed) was defined as the first visit of sustained disease control until Week 104 on or before Week 80 minus treatment start date (Day 1) plus 1. Sustained disease control was longest period a participant maintained disease control without a break. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K , ranges from 0 (no symptoms) to 105 (presence of all defined symptoms),higher scores representing increased disease activity.
Time Frame Up to Week 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Median (Inter-Quartile Range) [Days]
NA
NA
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Belimumab + Placebo, Belimumab + Rituximab
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.5127
Comments
Method Cox proportional hazards model
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
0.42 to 5.78
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio was calculated using Cox proportional hazards model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Standard therapy arm was excluded from model.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Belimumab + Rituximab, Belimumab + Standard Therapy
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.70
Confidence Interval (2-Sided) 95%
0.23 to 2.10
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio was calculated using Cox proportional hazards model with covariates: Baseline SLEDAI-2K, Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Placebo arm excluded from model.
12. Secondary Outcome
Title Time to Clinical Remission Sustained for at Least 24 Weeks and Maintained Through Week 104
Description Clinical remission sustained for at least 24 weeks and maintained through Week 104 was defined as clinical SLEDAI-2K score=0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. Time to CLR (PI assessed) was defined as first visit of sustained CLR until Week 104 on or before Week 80 minus treatment start date (Day 1) plus 1. Sustained CLR was longest period a participant maintained clinical remission without a break. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.
Time Frame Up to Week 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Median (Inter-Quartile Range) [Days]
NA
NA
NA
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Belimumab + Placebo, Belimumab + Rituximab
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.8436
Comments
Method Cox proportional hazards model
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.83
Confidence Interval (2-Sided) 95%
0.14 to 5.05
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio was calculated using Cox proportional hazards model with covariates: Baseline SLEDAI-2K, Baseline prednisone equivalent dose and treatment group. Belimumab + Standard therapy arm was excluded from model.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Belimumab + Rituximab, Belimumab + Standard Therapy
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Hazard Ratio (HR)
Estimated Value 0.52
Confidence Interval (2-Sided) 95%
0.09 to 3.14
Parameter Dispersion Type:
Value:
Estimation Comments Hazard ratio was calculated using Cox proportional hazards model with covariates: Baseline SLEDAI-2K, Baseline prednisone equivalent dose and treatment group. Belimumab + Placebo arm excluded from model.
13. Secondary Outcome
Title Duration of Disease Control
Description Duration of disease control was defined as SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day. The duration of disease control (PI assessed) was the longest period between 2 visits that the participant was a disease control responder at all visits and calculated as the first visit of disease control minus last visit of disease control plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105 (presence of all defined symptoms),higher scores representing increased disease activity
Time Frame Up to Week 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population. Only those participants with at least one assessment where disease control was met were analyzed.
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 34 77 31
Median (Inter-Quartile Range) [Days]
49.5
116.0
116.0
14. Secondary Outcome
Title Duration of Clinical Remission
Description Clinical remission was defined as clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of 0 mg/day. The duration of clinical remission (PI assessed) was the longest period between 2 visits that the participant was a clinical remission responder at all visits and was calculated as the first visit of clinical remission minus last visit of clinical remission plus 1. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity.
Time Frame Up to Week 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population. Only those participants with at least one assessment where clinical remission was met were analyzed.
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 13 22 11
Median (Inter-Quartile Range) [Days]
31.0
73.0
176.0
15. Secondary Outcome
Title Change From Baseline in Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Score by Visit (PI Assessed)
Description The SLEDAI-2K consisted of 24 individual items within 9 organ systems. Each item was given a weighted score (1 to 8 with higher score indicating increased activity) and summed if present at the time of visit or in the preceding 10 days. Weighted scores for central nervous system (CNS) (7 items) was 8; for vascular (1 item) was 8; for Musculoskeletal (2 items) was 4; for Renal (4 items) was 4; for Mucocutaneous (3 items) was 2; for Cardiovascular and Respiratory (2 items) was 2; for Immunologic (2 items) was 2;for Constitutional (1 item) was 1 and for Hematologic (2 items) was 1. SLEDAI-2K score was the sum of all 24 individual items from the SLEDAI-2K which ranges from 0 (no symptoms) to 105 (presence of all defined symptoms) with higher scores representing increased disease activity. Baseline value was latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time Frame Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 4; n=69, 137, 43
-1.4
(2.75)
-0.8
(3.39)
-1.3
(3.15)
Week 8; n=63, 132, 43
-3.2
(3.59)
-2.9
(4.09)
-2.9
(3.43)
Week 12; n=63, 131, 43
-2.8
(3.50)
-3.6
(4.32)
-2.9
(3.68)
Week 16; n=65, 129, 43
-3.4
(4.12)
-4.4
(4.62)
-4.1
(3.29)
Week 20; n=63, 127, 44
-3.8
(4.06)
-5.0
(4.44)
-3.8
(3.98)
Week 24; n=61, 128, 43
-4.0
(3.71)
-5.0
(4.45)
-5.0
(4.00)
Week 26; n=61, 118, 40
-4.1
(3.61)
-5.4
(4.79)
-5.0
(3.18)
Week 28; n=62, 125, 43
-3.7
(3.79)
-5.1
(4.74)
-5.2
(4.31)
Week 32; n=61, 125, 43
-4.7
(3.87)
-5.7
(5.03)
-5.3
(3.90)
Week 36; n=61, 125, 43
-5.0
(4.43)
-5.6
(5.21)
-5.0
(3.68)
Week 40; n=62, 125, 43
-4.6
(4.14)
-5.8
(4.83)
-5.0
(3.78)
Week 44; n=62, 122, 43
-4.7
(4.71)
-6.1
(4.47)
-5.2
(4.06)
Week 48; n=59, 122, 40
-4.5
(4.16)
-6.2
(4.59)
-5.3
(4.08)
Week 52; n=62, 119, 39
-5.3
(4.62)
-6.1
(4.42)
-5.6
(4.02)
Week 60; n=57, 114, 37
-5.0
(4.15)
-5.8
(5.17)
-6.0
(3.94)
Week 64; n=60, 117, 36
-5.1
(4.16)
-6.2
(4.96)
-5.5
(4.40)
Week 72; n=49, 103, 30
-5.2
(4.32)
-6.6
(4.50)
-5.3
(4.63)
Week 80; n=46, 102, 36
-5.4
(4.58)
-6.5
(4.79)
-6.0
(4.08)
Week 88; n=49, 101, 34
-5.3
(4.61)
-6.5
(4.29)
-6.1
(3.80)
Week 96; n=49, 100, 34
-5.6
(4.35)
-7.0
(4.44)
-6.1
(3.80)
Week 104; n=50, 104, 34
-5.1
(3.69)
-7.2
(4.22)
-6.3
(3.76)
16. Secondary Outcome
Title Percentage of Participants With SLEDAI-2K Organ Improvement Compared to Baseline by Visits (PI Assessed)
Description SLEDAI-2K assessments consisted of 24 individual items with 9 organ systems. Each item was given a weighted score(1 to 8 with higher score indicating increased activity)and summed if present at the time of analysis. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K ranges from 0(no symptoms) to 105(presence of all defined symptoms). Higher scores indicates increased disease activity. An improvement was defined as a decrease(compared to Baseline) in SLEDAI-2K score within same organ system at a post-Baseline visit. Baseline value was latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Data for following organ systems was reported: CNS total, Vascular total, Musculoskeletal total, Renal total, Mucocutaneous total, Cardiovascular (Cardio) and Respiratory (Resp) total, Immunologic total and Hematologic total. Constitutional organ system was removed from analysis and its one item (fever)moved to hematologic organ system.
Time Frame Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). Only participants with organ system involvement at Baseline were included.
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
CNS Total; Week 4; n= 2,3,2
0
0%
33.3
23.1%
0
0%
CNS Total; Week 8; n= 2,3,2
50.0
69.4%
66.7
46.3%
0
0%
CNS Total; Week 12; n= 2,3,2
50.0
69.4%
66.7
46.3%
50.0
65.8%
CNS Total; Week 16; n= 2,3,2
50.0
69.4%
66.7
46.3%
0
0%
CNS Total; Week 20; n= 2,3,2
100
138.9%
66.7
46.3%
0
0%
CNS Total; Week 24; n= 2,3,2
100
138.9%
66.7
46.3%
100
131.6%
CNS Total; Week 26; n= 2,3,2
50.0
69.4%
66.7
46.3%
0
0%
CNS Total; Week 28; n= 2,3,2
100
138.9%
66.7
46.3%
100
131.6%
CNS Total; Week 32; n= 2,3,2
100
138.9%
66.7
46.3%
100
131.6%
CNS Total; Week 36; n= 2,3,2
100
138.9%
66.7
46.3%
50.0
65.8%
CNS Total; Week 40; n= 2,3,2
100
138.9%
66.7
46.3%
100
131.6%
CNS Total; Week 44; n= 2,3,2
100
138.9%
66.7
46.3%
100
131.6%
CNS Total; Week 48; n= 2,3,2
100
138.9%
66.7
46.3%
50.0
65.8%
CNS Total; Week 52; n= 2,3,2
100
138.9%
66.7
46.3%
100
131.6%
CNS Total; Week 60; n= 2,3,2
100
138.9%
66.7
46.3%
100
131.6%
CNS Total; Week 64; n= 2,3,2
100
138.9%
66.7
46.3%
100
131.6%
CNS Total; Week 72; n= 2,3,2
100
138.9%
33.3
23.1%
50.0
65.8%
CNS Total; Week 80; n= 2,3,2
100
138.9%
33.3
23.1%
50.0
65.8%
CNS Total; Week 88; n= 2,3,2
100
138.9%
33.3
23.1%
100
131.6%
CNS Total; Week 96; n= 2,3,2
100
138.9%
33.3
23.1%
100
131.6%
CNS Total; Week 104; n=2,3,2
100
138.9%
33.3
23.1%
100
131.6%
Vascular Total; Week 4; n= 6,11,0
50.0
69.4%
9.1
6.3%
Vascular Total; Week 8; n= 6,11,0
33.3
46.3%
36.4
25.3%
Vascular Total; Week 12; n= 6,11,0
50.0
69.4%
54.5
37.8%
Vascular Total; Week 16; n= 6,11,0
50.0
69.4%
54.5
37.8%
Vascular Total; Week 20; n=6,11,0
50.0
69.4%
72.7
50.5%
Vascular Total; Week 24; n= 6,11,0
50.0
69.4%
72.7
50.5%
Vascular Total; Week 26; n= 6, 11, 0
50.0
69.4%
63.6
44.2%
Vascular Total; Week 28; n= 6, 11,0
33.3
46.3%
72.7
50.5%
Vascular Total; Week 32; n= 6,11, 0
50.0
69.4%
72.7
50.5%
Vascular Total; Week 36; n= 6, 11,0
50.0
69.4%
63.6
44.2%
Vascular Total; Week 40; n= 6, 11,0
33.3
46.3%
72.7
50.5%
Vascular Total; Week 44; n= 6, 11, 0
33.3
46.3%
72.7
50.5%
Vascular Total; Week 48; n= 6, 11, 0
33.3
46.3%
63.6
44.2%
Vascular Total; Week 52; n= 6, 11, 0
66.7
92.6%
63.6
44.2%
Vascular Total; Week 60; n= 6, 11, 0
50.0
69.4%
63.6
44.2%
Vascular Total; Week 64; n= 6, 11, 0
50.0
69.4%
90.9
63.1%
Vascular Total; Week 72; n= 6, 11, 0
33.3
46.3%
81.8
56.8%
Vascular Total; Week 80; n= 6, 11, 0
50.0
69.4%
72.7
50.5%
Vascular Total; Week 88; n= 6, 11, 0
50.0
69.4%
45.5
31.6%
Vascular Total; Week 96; n= 6, 11, 0
50.0
69.4%
63.6
44.2%
Vascular Total; Week 104; n= 6, 11, 0
33.3
46.3%
72.7
50.5%
Musculoskeletal Total; Week 4; n= 57, 110, 34
22.8
31.7%
13.6
9.4%
23.5
30.9%
Musculoskeletal Total; Week 8; n=57,110, 34
40.4
56.1%
40.0
27.8%
50.0
65.8%
Musculoskeletal Total; Week 12; n= 57,110,34
36.8
51.1%
44.5
30.9%
47.1
62%
Musculoskeletal Total; Week 16; n= 57,110,34
42.1
58.5%
56.4
39.2%
67.6
88.9%
Musculoskeletal Total; Week 20; n= 57,110,34
47.4
65.8%
58.2
40.4%
64.7
85.1%
Musculoskeletal Total; Week 24; n= 57,110,34
42.1
58.5%
54.5
37.8%
70.6
92.9%
Musculoskeletal Total;; Week 26; n=57,110,34
43.9
61%
46.4
32.2%
73.5
96.7%
Musculoskeletal Total; Week 28; n= 57,110,34
49.1
68.2%
53.6
37.2%
76.5
100.7%
Musculoskeletal Total; Week 32; n= 57,110,34
54.4
75.6%
63.6
44.2%
76.5
100.7%
Musculoskeletal Total; Week 36; n= 57,110,34
61.4
85.3%
61.8
42.9%
76.5
100.7%
Musculoskeletal Total; Week 40; n= 57,110,34
54.4
75.6%
58.2
40.4%
73.5
96.7%
Musculoskeletal Total; Week 44; n= 57,110,34
50.9
70.7%
60.0
41.7%
76.5
100.7%
Musculoskeletal Total; Week 48; n= 57,110,34
57.9
80.4%
60.9
42.3%
73.5
96.7%
Musculoskeletal Total; Week 52; n= 57,110,34
59.6
82.8%
59.1
41%
73.5
96.7%
Musculoskeletal Total; Week 60; n= 57,110,34
54.4
75.6%
54.5
37.8%
67.6
88.9%
Musculoskeletal Total; Week 64; n= 57,110,34
56.1
77.9%
55.5
38.5%
67.6
88.9%
Musculoskeletal Total; Week 72; n= 57,110,34
47.4
65.8%
58.2
40.4%
58.8
77.4%
Musculoskeletal Total; Week 80; n= 57,110,34
47.4
65.8%
58.2
40.4%
76.5
100.7%
Musculoskeletal Total; Week 88; n= 57,110,34
57.9
80.4%
59.1
41%
67.6
88.9%
Musculoskeletal Total; Week 96; n= 57,110,34
50.9
70.7%
60.9
42.3%
70.6
92.9%
Musculoskeletal Total; Week 104; n= 57,110,34
47.4
65.8%
64.5
44.8%
67.6
88.9%
Renal Total; Week 4; n= 14,23,8
21.4
29.7%
30.4
21.1%
12.5
16.4%
Renal Total; Week 8; n= 14, 23, 8
50.0
69.4%
43.5
30.2%
12.5
16.4%
Renal Total; Week 12; n= 14, 23, 8
28.6
39.7%
52.2
36.3%
12.5
16.4%
Renal Total; Week 16; n= 14, 23, 8
35.7
49.6%
52.2
36.3%
12.5
16.4%
Renal Total; Week 20; n= 14, 23, 8
57.1
79.3%
60.9
42.3%
12.5
16.4%
Renal Total; Week 24; n= 14, 23, 8
35.7
49.6%
60.9
42.3%
12.5
16.4%
Renal Total; Week 26; n= 14, 23, 8
28.6
39.7%
65.2
45.3%
25.0
32.9%
Renal Total; Week 28; n= 14, 23, 8
21.4
29.7%
56.5
39.2%
37.5
49.3%
Renal Total; Week 32; n= 14, 23, 8
35.7
49.6%
65.2
45.3%
25.0
32.9%
Renal Total; Week 36; n= 14, 23, 8
42.9
59.6%
65.2
45.3%
50.0
65.8%
Renal Total; Week 40; n=14, 23, 8
42.9
59.6%
69.6
48.3%
25.0
32.9%
Renal Total; Week 44; n= 14, 23, 8
50.0
69.4%
69.6
48.3%
12.5
16.4%
Renal Total; Week 48; n=14, 23, 8
42.9
59.6%
69.6
48.3%
50.0
65.8%
Renal Total; Week 52; n= 14, 23, 8
64.3
89.3%
69.6
48.3%
25.0
32.9%
Renal Total; Week 60; n= 14, 23, 8
50.0
69.4%
65.2
45.3%
25.0
32.9%
Renal Total; Week 64; n= 14, 23, 8
50.0
69.4%
69.6
48.3%
12.5
16.4%
Renal Total; Week 72; n= 14, 23, 8
50.0
69.4%
65.2
45.3%
12.5
16.4%
Renal Total; Week 80; n= 14, 23, 8
42.9
59.6%
65.2
45.3%
50.0
65.8%
Renal Total; Week 88; n= 14, 23, 8
50.0
69.4%
73.9
51.3%
25.0
32.9%
Renal Total; Week 96; n= 14, 23, 8
35.7
49.6%
78.3
54.4%
37.5
49.3%
Renal Total; Week 104; n= 14, 23, 8
35.7
49.6%
69.6
48.3%
50.0
65.8%
Mucocutaneous Total; Week 4; n= 59, 126,43
30.5
42.4%
28.6
19.9%
32.6
42.9%
Mucocutaneous Total; Week 8; n= 59,126,43
54.2
75.3%
45.2
31.4%
51.2
67.4%
Mucocutaneous Total; Week 12; n= 59, 126, 43
55.9
77.6%
57.1
39.7%
55.8
73.4%
Mucocutaneous Total; Week 16; n= 59, 126, 43
57.6
80%
58.7
40.8%
67.4
88.7%
Mucocutaneous Total; Week 20; n= 59, 126, 43
50.8
70.6%
62.7
43.5%
69.8
91.8%
Mucocutaneous Total; Week 24; n= 59, 126, 43
59.3
82.4%
61.9
43%
69.8
91.8%
Mucocutaneous Total; Week 26; n=59, 126, 43
59.3
82.4%
60.3
41.9%
65.1
85.7%
Mucocutaneous Total; Week 28; n= 59, 126, 43
62.7
87.1%
62.7
43.5%
69.8
91.8%
Mucocutaneous Total; Week 32; n= 59, 126, 43
62.7
87.1%
65.1
45.2%
74.4
97.9%
Mucocutaneous Total; Week 36; n= 59, 126, 43
66.1
91.8%
65.9
45.8%
69.8
91.8%
Mucocutaneous Total; Week 40; n= 59, 126, 43
62.7
87.1%
66.7
46.3%
67.4
88.7%
Mucocutaneous Total; Week 44; n= 59, 126, 43
61.0
84.7%
61.1
42.4%
69.8
91.8%
Mucocutaneous Total; Week 48; n= 59, 126, 43
50.8
70.6%
66.7
46.3%
69.8
91.8%
Mucocutaneous Total; Week 52; n=59, 126, 43
64.4
89.4%
64.3
44.7%
69.8
91.8%
Mucocutaneous Total; Week 60; n=59, 126, 43
55.9
77.6%
65.1
45.2%
67.4
88.7%
Mucocutaneous Total; Week 64; n=59, 126, 43
64.4
89.4%
65.9
45.8%
62.8
82.6%
Mucocutaneous Total; Week 72; n=59, 126, 43
57.6
80%
60.3
41.9%
58.1
76.4%
Mucocutaneous Total; Week 80; n= 59, 126, 43
62.7
87.1%
61.9
43%
62.8
82.6%
Mucocutaneous Total; Week 88; n= 59, 126, 43
59.3
82.4%
62.7
43.5%
67.4
88.7%
Mucocutaneous Total; Week 96; n= 59, 126, 43
52.5
72.9%
62.7
43.5%
62.7
82.5%
Mucocutaneous Total; Week 104; n= 59, 126, 43
61.0
84.7%
69.0
47.9%
60.5
79.6%
Cardio and Resp Total; Week 4; n= 3, 7, 0
0
0%
42.9
29.8%
Cardio and Resp Total; Week 8; n= 3, 7, 0
0
0%
71.4
49.6%
Cardio and Resp Total; Week 12; n= 3, 7, 0
0
0%
71.4
49.6%
Cardio and Resp Total; Week 16; n= 3, 7, 0
0
0%
85.7
59.5%
Cardio and Resp Total; Week 20; n= 3,7, 0
33.3
46.3%
71.4
49.6%
Cardio and Resp Total; Week 24; n= 3, 7, 0
66.7
92.6%
100
69.4%
Cardio and Resp Total; Week 26; n=3, 7, 0
0
0%
85.7
59.5%
Cardio and Resp Total; Week 28; n= 3,7, 0
0
0%
85.7
59.5%
Cardio and Resp Total; Week 32; n= 3, 7, 0
33.3
46.3%
100
69.4%
Cardio and Resp Total; Week 36; n= 3, 7, 0
66.7
92.6%
85.7
59.5%
Cardio and Resp Total; Week 40; n=3,7, 0
33.3
46.3%
71.4
49.6%
Cardio and Resp Total; Week 44; n= 3,7, 0
66.7
92.6%
57.1
39.7%
Cardio and Resp Total; Week 48; n= 3, 7, 0
33.3
46.3%
85.7
59.5%
Cardio and Resp Total; Week 52; n= 3, 7, 0
66.7
92.6%
85.7
59.5%
Cardio and Resp Total; Week 60; n= 3,7,0
100
138.9%
71.4
49.6%
Cardio and Resp Total; Week 64; n=3,7,0
100
138.9%
85.7
59.5%
Cardio and Resp Total; Week 72; n= 3,7,0
66.7
92.6%
71.4
49.6%
Cardio and Resp Total; Week 80; n=3,7,0
66.7
92.6%
85.7
59.5%
Cardio and Resp Total; Week 88; n= 3,7,0
66.7
92.6%
71.4
49.6%
Cardio and Resp Total; Week 96; n= 3,7,0
66.7
92.6%
71.4
49.6%
Cardio and Resp Total; Week 104; n= 3,7,0
66.7
92.6%
71.4
49.6%
Immunologic Total; Week 4; n=48, 104, 34
12.5
17.4%
10.6
7.4%
17.6
23.2%
Immunologic Total; Week 8; n= 48, 104, 34
16.7
23.2%
17.3
12%
17.6
23.2%
Immunologic Total; Week 12; n= 48, 104, 34
22.9
31.8%
24.0
16.7%
17.6
23.2%
Immunologic Total; Week 16; n= 48, 104, 34
20.8
28.9%
30.8
21.4%
11.8
15.5%
Immunologic Total; Week 20; n= 48, 104, 34
20.8
28.9%
36.5
25.3%
23.5
30.9%
Immunologic Total; Week 24; n= 48, 104, 34
22.9
31.8%
34.6
24%
20.6
27.1%
Immunologic Total; Week 26; n= 48, 104, 34
18.8
26.1%
39.4
27.4%
11.8
15.5%
Immunologic Total; Week 28; n= 48, 104, 34
18.8
26.1%
34.6
24%
20.6
27.1%
Immunologic Total; Week 32; n= 48, 104, 34
25.0
34.7%
40.4
28.1%
23.5
30.9%
Immunologic Total; Week 36; n= 48, 104, 34
20.8
28.9%
41.3
28.7%
17.6
23.2%
Immunologic Total; Week 40; n= 48, 104, 34
14.6
20.3%
44.2
30.7%
23.5
30.9%
Immunologic Total; Week 44; n= 48, 104, 34
25.0
34.7%
39.4
27.4%
38.2
50.3%
Immunologic Total; Week 48; n= 48, 104, 34
20.8
28.9%
41.3
28.7%
29.4
38.7%
Immunologic Total; Week 52; n= 48, 104, 34
20.8
28.9%
37.5
26%
26.5
34.9%
Immunologic Total; Week 60; n= 48, 104, 34
25.0
34.7%
45.2
31.4%
20.6
27.1%
Immunologic Total; Week 64; n= 48, 104, 34
20.8
28.9%
43.3
30.1%
26.5
34.9%
Immunologic Total; Week 72; n=48, 104, 34
29.2
40.6%
36.5
25.3%
17.6
23.2%
Immunologic Total; Week 80; n=48, 104, 34
22.9
31.8%
31.7
22%
23.5
30.9%
Immunologic Total; Week 88; n=48, 104, 34
31.3
43.5%
29.8
20.7%
14.7
19.3%
Immunologic Total; Week 96; n=48, 104, 34
20.8
28.9%
33.7
23.4%
20.6
27.1%
Immunologic Total; Week 104; n=48, 104, 34
27.1
37.6%
40.4
28.1%
20.6
27.1%
Hematologic Total; Week 4; n= 8, 19, 3
50.0
69.4%
42.1
29.2%
0
0%
Hematologic Total; Week 8; n= 8, 19, 3
62.5
86.8%
63.2
43.9%
66.7
87.8%
Hematologic Total; Week 12; n= 8, 19, 3
62.5
86.8%
52.6
36.5%
33.3
43.8%
Hematologic Total; Week 16; n= 8, 19, 3
75.0
104.2%
63.2
43.9%
66.7
87.8%
Hematologic Total; Week 20; n= 8, 19, 3
87.5
121.5%
57.9
40.2%
100
131.6%
Hematologic Total; Week 24; n= 8, 19, 3
62.5
86.8%
52.6
36.5%
100
131.6%
Hematologic Total; Week 26; n= 8, 19, 3
75.0
104.2%
36.8
25.6%
100
131.6%
Hematologic Total; Week 28; n= 8, 19, 3
62.5
86.8%
57.9
40.2%
66.7
87.8%
Hematologic Total; Week 32; n= 8, 19, 3
62.5
86.8%
57.9
40.2%
66.7
87.8%
Hematologic Total; Week 36; n= 8, 19, 3
87.5
121.5%
63.2
43.9%
66.7
87.8%
Hematologic Total; Week 40; n= 8, 19, 3
62.5
86.8%
52.6
36.5%
66.7
87.8%
Hematologic Total; Week 44; n= 8, 19, 3
87.5
121.5%
57.9
40.2%
66.7
87.8%
Hematologic Total; Week 48; n= 8, 19, 3
37.5
52.1%
63.2
43.9%
66.7
87.8%
Hematologic Total; Week 52; n= 8, 19, 3
75.0
104.2%
52.6
36.5%
33.3
43.8%
Hematologic Total; Week 60; n= 8, 19, 3
50.0
69.4%
57.9
40.2%
33.3
43.8%
Hematologic Total; Week 64; n= 8, 19, 3
62.5
86.8%
68.4
47.5%
33.3
43.8%
Hematologic Total; Week 72; n= 8, 19, 3
62.5
86.8%
47.4
32.9%
0
0%
Hematologic Total; Week 80; n= 8, 19, 3
50.0
69.4%
52.6
36.5%
33.3
43.8%
Hematologic Total; Week 88; n= 8, 19, 3
37.5
52.1%
57.9
40.2%
33.3
43.8%
Hematologic Total; Week 96; n= 8, 19, 3
50.0
69.4%
52.6
36.5%
33.3
43.8%
Hematologic Total; Week 104; n= 8, 19, 3
50.0
69.4%
63.2
43.9%
33.3
43.8%
17. Secondary Outcome
Title Percentage of Participants With SLEDAI-2K Organ Worsening Compared to Baseline by Visits (PI Assessed)
Description SLEDAI-2K assessments consisted of 24 individual items with 9 organ systems. Each item was given a weighted score(1 to 8 with higher score indicating increased activity)and summed if present at time of analysis. SLEDAI-2K score was sum of all 24 individual items from SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms). Higher scores indicates increased disease activity. A worsening was defined as an increase(compared to Baseline) in SLEDAI-2K score within same organ system at a post-Baseline visit. Baseline value was latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Percentage of participants with SLEDAI-2K organ worsening for following organ systems were reported;CNS total,Vascular total,Musculoskeletal total,Renal total,Mucocutaneous total,Cardio and Resp total,Immunologic total and Hematologic total. Constitutional organ system was removed from analysis and its one item (fever)moved to hematologic organ system.
Time Frame Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles). Only participants with no organ system involvement at Baseline were included.
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
CNS Total; Week 4; n= 69, 136, 43
0
0%
0
0%
0
0%
CNS Total; Week 8; n= 64,132, 42
0
0%
0
0%
0
0%
CNS Total; Week 12; n= 65, 134, 42
0
0%
0
0%
0
0%
CNS Total; Week 16; n= 65, 130, 42
0
0%
0.8
0.6%
0
0%
CNS Total; Week 20; n= 63, 128, 42
0
0%
0
0%
0
0%
CNS Total; Week 24; n= 61, 127, 41
0
0%
0.8
0.6%
0
0%
CNS Total; Week 26; n=61, 116, 38
0
0%
0.9
0.6%
0
0%
CNS Total; Week 28; n=62, 124, 41
0
0%
0
0%
0
0%
CNS Total; Week 32; n= 61, 124, 41
0
0%
0.8
0.6%
0
0%
CNS Total; Week 36; n=61, 124, 41
0
0%
1.6
1.1%
0
0%
CNS Total; Week 40; n=61, 123, 41
0
0%
0
0%
0
0%
CNS Total; Week 44; n= 61, 121, 41
0
0%
0
0%
0
0%
CNS Total; Week 48; n= 58, 120,39
0
0%
0
0%
0
0%
CNS Total; Week 52; n= 62, 120, 38
0
0%
0
0%
0
0%
CNS Total; Week 60; n=59, 117, 35
0
0%
0
0%
0
0%
CNS Total; Week 64; n=60, 117, 34
0
0%
0
0%
0
0%
CNS Total; Week 72; n= 56, 109, 31
0
0%
0
0%
0
0%
CNS Total; Week 80; n=55, 111, 35
0
0%
0
0%
0
0%
CNS Total; Week 88; n= 57, 107, 34
0
0%
0
0%
0
0%
CNS Total; Week 96; n=52, 107, 33
0
0%
0
0%
0
0%
CNS Total; Week 104; n= 53, 112, 34
0
0%
0
0%
0
0%
Vascular Total;Week 4; n= 65, 128, 45
0
0%
3.9
2.7%
0
0%
Vascular Total;Week 8; n= 61, 124, 44
0
0%
2.4
1.7%
0
0%
Vascular Total; Week 12; n= 62, 126, 44
1.6
2.2%
1.6
1.1%
0
0%
Vascular Total; Week 16; n=62, 122, 44
0
0%
1.6
1.1%
0
0%
Vascular Total; Week 20; n=60, 120, 44
0
0%
0.8
0.6%
0
0%
Vascular Total; Week 24; n= 59, 119, 43
0
0%
0
0%
0
0%
Vascular Total; Week 26; n=58, 109, 40
0
0%
0.9
0.6%
0
0%
Vascular Total;Week 28; n= 61, 116, 43
0
0%
1.7
1.2%
0
0%
Vascular Total;Week 32; n=59, 116, 43
0
0%
2.6
1.8%
0
0%
Vascular Total;Week 36; n= 59, 116, 43
0
0%
1.7
1.2%
0
0%
Vascular Total;Week 40; n=59, 115, 43
0
0%
1.7
1.2%
0
0%
Vascular Total;Week 44; n= 59, 113, 43
0
0%
0
0%
0
0%
Vascular Total;Week 48; n= 57, 112, 40
0
0%
0
0%
0
0%
Vascular Total;Week 52; n=60, 112, 40
0
0%
0.9
0.6%
0
0%
Vascular Total;Week 60; n= 58, 109, 37
0
0%
0
0%
0
0%
Vascular Total;Week 64; n=59, 109, 36
0
0%
1.8
1.3%
0
0%
Vascular Total;Week 72; n=55, 101, 33
0
0%
0
0%
0
0%
Vascular Total;Week 80; n= 54, 104, 37
0
0%
1.0
0.7%
0
0%
Vascular Total;Week 88; n=56, 102, 36
0
0%
0
0%
0
0%
Vascular Total;Week 96; n=51, 101, 35
0
0%
0
0%
0
0%
Vascular Total;Week 104; n=53, 105, 36
0
0%
0
0%
0
0%
Musculoskeletal Total; Week 4; n=15, 33, 12
0
0%
12.1
8.4%
0
0%
Musculoskeletal Total; Week 8; n= 15, 33, 12
6.7
9.3%
6.1
4.2%
0
0%
Musculoskeletal Total; Week 12; n= 15, 33, 12
13.3
18.5%
6.1
4.2%
0
0%
Musculoskeletal Total; Week 16; n= 15, 32, 12
6.7
9.3%
3.1
2.2%
8.3
10.9%
Musculoskeletal Total; Week 20; n= 15, 32, 12
6.7
9.3%
6.3
4.4%
0
0%
Musculoskeletal Total; Week 24; n= 15, 31, 11
0
0%
6.5
4.5%
0
0%
Musculoskeletal Total; Week 26; n= 15, 31, 11
0
0%
3.2
2.2%
0
0%
Musculoskeletal Total; Week 28; n= 14, 31, 11
0
0%
3.2
2.2%
9.1
12%
Musculoskeletal Total; Week 32; n= 15, 30, 11
0
0%
6.7
4.7%
9.1
12%
Musculoskeletal Total; Week 36; n= 14, 30, 11
7.1
9.9%
3.3
2.3%
9.1
12%
Musculoskeletal Total; Week 40; n=15, 30, 11
0
0%
3.3
2.3%
9.1
12%
Musculoskeletal Total; Week 44; n=15, 29, 11
0
0%
6.9
4.8%
9.1
12%
Musculoskeletal Total; Week 48; n= 14, 30, 10
7.1
9.9%
3.3
2.3%
10.0
13.2%
Musculoskeletal Total; Week 52; n= 15, 30, 11
6.7
9.3%
6.7
4.7%
9.1
12%
Musculoskeletal Total; Week 60; n= 14, 28, 11
0
0%
0
0%
9.1
12%
Musculoskeletal Total; Week 64; n=14, 29, 10
0
0%
3.4
2.4%
10.0
13.2%
Musculoskeletal Total; Week 72; n= 14, 27, 10
0
0%
11.1
7.7%
10.0
13.2%
Musculoskeletal Total; Week 80; n= 13, 26, 9
0
0%
0
0%
11.1
14.6%
Musculoskeletal Total; Week 88; n= 13, 25, 9
15.4
21.4%
4.0
2.8%
0
0%
Musculoskeletal Total; Week 96; n= 12, 26, 9
0
0%
3.8
2.6%
0
0%
Musculoskeletal Total; Week 104; n= 13, 27, 9
0
0%
0
0%
0
0%
Renal Total; Week 4; n= 57, 117, 36
5.3
7.4%
6.0
4.2%
11.1
14.6%
Renal Total; Week 8; n=51, 110, 36
2.0
2.8%
3.6
2.5%
5.6
7.4%
Renal Total; Week 12; n=53, 115, 35
1.9
2.6%
3.5
2.4%
8.6
11.3%
Renal Total; Week 16; n=53, 112, 35
7.5
10.4%
4.5
3.1%
2.9
3.8%
Renal Total; Week 20; n= 49, 108, 36
8.2
11.4%
3.7
2.6%
8.3
10.9%
Renal Total; Week 24; n= 49, 111, 35
10.2
14.2%
3.6
2.5%
2.9
3.8%
Renal Total; Week 26; n= 49, 99, 33
6.1
8.5%
0
0%
0
0%
Renal Total; Week 28; n= 50, 106, 36
10.0
13.9%
1.9
1.3%
2.8
3.7%
Renal Total; Week 32; n= 50,107, 36
6.0
8.3%
2.8
1.9%
2.8
3.7%
Renal Total; Week 36; n= 50, 107, 36
8.0
11.1%
2.8
1.9%
5.6
7.4%
Renal Total; Week 40; n= 47, 106, 34
6.4
8.9%
4.7
3.3%
0
0%
Renal Total; Week 44; n= 49, 103, 35
6.1
8.5%
1.0
0.7%
2.9
3.8%
Renal Total; Week 48; n= 47, 101, 32
10.6
14.7%
5.9
4.1%
6.3
8.3%
Renal Total; Week 52; n= 49, 103, 32
8.2
11.4%
3.9
2.7%
3.1
4.1%
Renal Total; Week 60; n=47, 96, 30
6.4
8.9%
4.2
2.9%
0
0%
Renal Total; Week 64; n= 50, 99, 29
2.0
2.8%
2.0
1.4%
0
0%
Renal Total; Week 72; n= 40, 89, 26
5.0
6.9%
4.5
3.1%
0
0%
Renal Total; Week 80; n= 41, 90, 29
14.6
20.3%
3.3
2.3%
6.9
9.1%
Renal Total; Week 88; n= 44, 85, 29
13.6
18.9%
1.2
0.8%
0
0%
Renal Total; Week 96; n= 43, 85, 29
4.7
6.5%
1.2
0.8%
0
0%
Renal Total; Week 104; n= 44, 90, 30
6.8
9.4%
2.2
1.5%
0
0%
Mucocutaneous Total; Week 4; n= 13, 18, 4
15.4
21.4%
5.6
3.9%
0
0%
Mucocutaneous Total; Week 8; n= 12, 18, 4
8.3
11.5%
11.1
7.7%
0
0%
Mucocutaneous Total; Week 12; n= 12, 18, 4
8.3
11.5%
16.7
11.6%
0
0%
Mucocutaneous Total; Week 16; n= 12, 18, 4
0
0%
5.6
3.9%
0
0%
Mucocutaneous Total; Week 20; n= 12, 18, 4
25.0
34.7%
5.6
3.9%
0
0%
Mucocutaneous Total; Week 24; n= 11, 17, 4
18.2
25.3%
5.9
4.1%
0
0%
Mucocutaneous Total; Week 26; n= 10, 17, 4
20.0
27.8%
11.8
8.2%
0
0%
Mucocutaneous Total; Week 28; n= 10, 17, 4
0
0%
11.8
8.2%
0
0%
Mucocutaneous Total; Week 32; n= 10, 17, 4
10.0
13.9%
5.9
4.1%
0
0%
Mucocutaneous Total; Week 36; n= 10, 17, 4
0
0%
5.9
4.1%
0
0%
Mucocutaneous Total; Week 40; n= 10, 17, 4
20.0
27.8%
11.8
8.2%
0
0%
Mucocutaneous Total; Week 44; n= 10, 17, 4
10.0
13.9%
0
0%
0
0%
Mucocutaneous Total; Week 48; n=10, 16, 3
0
0%
6.3
4.4%
0
0%
Mucocutaneous Total; Week 52; n= 10, 17, 4
0
0%
5.9
4.1%
25.0
32.9%
Mucocutaneous Total; Week 60; n= 9, 17, 4
11.1
15.4%
11.8
8.2%
0
0%
Mucocutaneous Total; Week 64; n= 10, 16, 4
0
0%
6.3
4.4%
25.0
32.9%
Mucocutaneous Total; Week 72; n=10, 16, 4
20
27.8%
6.3
4.4%
25.0
32.9%
Mucocutaneous Total; Week 80; n= 9, 17, 4
0
0%
0
0%
25.0
32.9%
Mucocutaneous Total; Week 88; n= 9, 16, 4
0
0%
6.3
4.4%
25.0
32.9%
Mucocutaneous Total; Week 96; n= 9, 15, 4
11.1
15.4%
0
0%
25.0
32.9%
Mucocutaneous Total; Week 104; n= 9, 17, 4
11.1
15.4%
5.9
4.1%
0
0%
Cardio and Resp Total; Week 4; n= 68, 132, 45
2.9
4%
0.8
0.6%
0
0%
Cardio and Resp Total; Week 8; n= 63, 128, 44
0
0%
0.8
0.6%
0
0%
Cardio and Resp Total; Week 12; n= 64, 130, 44
0
0%
0.8
0.6%
0
0%
Cardio and Resp Total; Week 16; n= 64, 126, 44
3.1
4.3%
0
0%
0
0%
Cardio and Resp Total; Week 20; n= 63, 124, 44
1.6
2.2%
0.8
0.6%
0
0%
Cardio and Resp Total; Week 24; n= 60, 123, 43
0
0%
0
0%
0
0%
Cardio and Resp Total; Week 26; n=59, 112, 40
0
0%
0
0%
0
0%
Cardio and Resp Total; Week 28; n= 61, 120, 43
3.3
4.6%
0.8
0.6%
0
0%
Cardio and Resp Total; Week 32; n= 60, 120, 43
1.7
2.4%
0
0%
0
0%
Cardio and Resp Total; Week 36; n= 60, 120, 43
1.7
2.4%
0
0%
0
0%
Cardio and Resp Total; Week 40; n=60, 119, 43
0
0%
0
0%
0
0%
Cardio and Resp Total; Week 44; n= 60, 117, 43
1.7
2.4%
0
0%
0
0%
Cardio and Resp Total; Week 48; n= 57, 116, 40
0
0%
0
0%
2.5
3.3%
Cardio and Resp Total; Week 52; n=61, 116, 40
0
0%
0
0%
0
0%
Cardio and Resp Total; Week 60; n= 58, 114, 37
0
0%
0
0%
0
0%
Cardio and Resp Total; Week 64; n= 59, 114, 36
0
0%
0.9
0.6%
0
0%
Cardio and Resp Total; Week 72; n= 55, 106, 33
0
0%
0
0%
0
0%
Cardio and Resp Total; Week 80; n= 54, 107, 37
1.9
2.6%
0
0%
0
0%
Cardio and Resp Total; Week 88; n= 56, 104, 36
1.8
2.5%
0
0%
0
0%
Cardio and Resp Total; Week 96; n=51, 104, 35
0
0%
1.0
0.7%
0
0%
Cardio and Resp Total; Week 104; n= 52, 109, 36
0
0%
0
0%
0
0%
Immunologic Total; Week 4; n=23, 37, 13
17.4
24.2%
0
0%
7.7
10.1%
Immunologic Total; Week 8; n=20, 37, 12
20.0
27.8%
10.8
7.5%
0
0%
Immunologic Total; Week 12; n=21, 37,12
23.8
33.1%
8.1
5.6%
16.7
22%
Immunologic Total; Week 16; n= 21, 35, 12
9.5
13.2%
11.4
7.9%
0
0%
Immunologic Total; Week 20; n= 19, 35, 12
15.8
21.9%
11.4
7.9%
0
0%
Immunologic Total; Week 24; n= 18, 35, 12
5.6
7.8%
5.7
4%
0
0%
Immunologic Total; Week 26; n= 18, 30, 12
5.6
7.8%
6.7
4.7%
8.3
10.9%
Immunologic Total; Week 28; n= 19, 35, 12
15.8
21.9%
8.6
6%
16.7
22%
Immunologic Total; Week 32; n= 19, 33, 12
10.5
14.6%
12.1
8.4%
8.3
10.9%
Immunologic Total; Week 36; n= 19, 34, 12
15.8
21.9%
8.8
6.1%
16.7
22%
Immunologic Total; Week 40; n= 19, 33, 12
21.1
29.3%
6.1
4.2%
8.3
10.9%
Immunologic Total; Week 44; n= 18, 33, 12
22.2
30.8%
0
0%
0
0%
Immunologic Total; Week 48; n= 18, 33, 11
22.2
30.8%
3.0
2.1%
27.3
35.9%
Immunologic Total; Week 52; n= 19, 32, 12
21.1
29.3%
3.1
2.2%
8.3
10.9%
Immunologic Total; Week 60; n= 18, 32, 10
16.7
23.2%
6.3
4.4%
0
0%
Immunologic Total; Week 64; n= 19, 33, 10
21.1
29.3%
6.1
4.2%
20.0
26.3%
Immunologic Total; Week 72; n= 17, 28, 9
23.5
32.6%
7.1
4.9%
11.1
14.6%
Immunologic Total; Week 80; n= 18, 29, 11
5.6
7.8%
6.9
4.8%
18.2
23.9%
Immunologic Total; Week 88; n= 19, 29, 11
10.5
14.6%
6.9
4.8%
18.2
23.9%
Immunologic Total; Week 96; n= 16, 30, 11
12.5
17.4%
13.3
9.2%
18.2
23.9%
Immunologic Total; Week 104; n= 17, 28, 12
11.8
16.4%
17.9
12.4%
16.7
22%
Hematologic Total; Week 4; n= 59, 115, 40
5.1
7.1%
3.5
2.4%
5.0
6.6%
Hematologic Total; Week 8; n= 52, 109, 38
3.8
5.3%
5.5
3.8%
0
0%
Hematologic Total; Week 12; n= 55, 110, 38
1.8
2.5%
4.5
3.1%
10.5
13.8%
Hematologic Total; Week 16; n=54, 107, 34
1.9
2.6%
2.8
1.9%
2.9
3.8%
Hematologic Total; Week 20; n= 54, 108, 40
5.6
7.8%
5.6
3.9%
5.0
6.6%
Hematologic Total; Week 24; n= 53, 111, 37
3.8
5.3%
2.7
1.9%
2.7
3.6%
Hematologic Total; Week 26; n= 53, 101, 37
9.4
13.1%
5.0
3.5%
10.8
14.2%
Hematologic Total; Week 28; n= 52, 106, 39
7.7
10.7%
3.8
2.6%
5.1
6.7%
Hematologic Total; Week 32; n=52, 110, 38
0
0%
4.5
3.1%
7.9
10.4%
Hematologic Total; Week 36; n= 53, 109, 40
5.7
7.9%
6.4
4.4%
2.5
3.3%
Hematologic Total; Week 40; n= 51, 108, 37
0
0%
10.2
7.1%
5.4
7.1%
Hematologic Total; Week 44; n=53, 107, 38
7.5
10.4%
6.5
4.5%
5.3
7%
Hematologic Total; Week 48; n=51, 105, 35
5.9
8.2%
4.8
3.3%
0
0%
Hematologic Total; Week 52; n= 53, 103, 37
3.8
5.3%
3.9
2.7%
2.7
3.6%
Hematologic Total; Week 60; n=53, 101, 35
9.4
13.1%
5.0
3.5%
5.7
7.5%
Hematologic Total; Week 64; n=54, 98, 32
11.1
15.4%
5.1
3.5%
6.3
8.3%
Hematologic Total; Week 72; n= 47,96, 29
10.6
14.7%
5.2
3.6%
3.4
4.5%
Hematologic Total; Week 80; n= 45, 94, 35
0
0%
4.3
3%
5.7
7.5%
Hematologic Total; Week 88; n= 46, 88, 32
10.9
15.1%
9.1
6.3%
3.1
4.1%
Hematologic Total; Week 96; n= 45, 90, 32
4.4
6.1%
4.4
3.1%
3.1
4.1%
Hematologic Total; Week 104; n= 46, 94, 32
4.3
6%
6.4
4.4%
6.3
8.3%
18. Secondary Outcome
Title Change From Baseline in Physician Global Assessment (PGA) by Visits
Description The Physician's Global Assessment (PGA) was a physician-reported visual analogue scale that provides an overall measure of the participant's current disease activity. Physician's Global Assessment was collected on a 10 centimeter (cm) visual analogue scale (VAS) by placing a mark on the scale between 0 (no disease activity) to 10 (maximum disease activity). The PGA score was then rescaled for reporting by multiplying the collected score by 3 divided by 10. Hence, the PGA score ranges from 0 to 3 with higher scores indicating greater disease activity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value.
Time Frame Baseline (Day 1) and Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 4; n=72, 142, 45
-0.285
(0.4816)
-0.247
(0.4640)
-0.303
(0.5464)
Week 8; n=66, 135, 44
-0.535
(0.5134)
-0.520
(0.5243)
-0.585
(0.5793)
Week 12; n=66, 137, 44
-0.592
(0.5265)
-0.660
(0.5776)
-0.654
(0.5450)
Week 16; n=68, 132, 44
-0.619
(0.5475)
-0.717
(0.5802)
-0.759
(0.6072)
Week 20; n=66, 130, 44
-0.697
(0.6157)
-0.787
(0.5445)
-0.786
(0.6772)
Week 24; n=62, 130, 43
-0.770
(0.5888)
-0.766
(0.5059)
-0.965
(0.6413)
Week 26; n=62, 120, 40
-0.786
(0.5727)
-0.811
(0.5445)
-0.929
(0.6631)
Week 28; n=63, 127, 43
-0.781
(0.5395)
-0.817
(0.5360)
-0.980
(0.6286)
Week 32; n=62, 124, 43
-0.851
(0.5989)
-0.864
(0.5519)
-1.005
(0.6723)
Week 36; n=64, 126, 43
-0.916
(0.6141)
-0.927
(0.5400)
-0.917
(0.5504)
Week 40; n=63, 126, 43
-0.893
(0.6157)
-0.925
(0.5621)
-0.993
(0.6711)
Week 44; n=63, 124, 43
-0.800
(0.6764)
-0.905
(0.5289)
-0.970
(0.6065)
Week 48; n=59, 121, 40
-0.885
(0.6178)
-0.928
(0.5627)
-0.956
(0.5175)
Week 52; n=64, 122, 41
-0.947
(0.6918)
-0.938
(0.6125)
-1.004
(0.5527)
Week 60; n=61, 120, 37
-0.836
(0.6982)
-0.848
(0.6085)
-1.206
(0.5917)
Week 64; n=62, 120, 36
-0.876
(0.6971)
-0.943
(0.5711)
-1.095
(0.6365)
Week 72; n=58, 110, 33
-0.928
(0.6838)
-0.944
(0.5708)
-1.047
(0.6088)
Week 80; n=57, 112, 37
-0.949
(0.6909)
-0.954
(0.6221)
-1.138
(0.5574)
Week 88; n=59, 109, 36
-1.060
(0.6307)
-0.993
(0.5733)
-1.140
(0.5514)
Week 96; n=54, 109, 35
-1.016
(0.6093)
-0.994
(0.5669)
-1.214
(0.5580)
Week 104; n=55, 114, 36
-1.052
(0.5095)
-1.074
(0.5166)
-1.085
(0.5987)
19. Secondary Outcome
Title Percentage of Participants With Systemic Lupus International Collaborating Clinics (SLICC) -American College of Rheumatology (ACR) Damage Index Worsening Compared With Baseline at Week 52 and Week 104
Description The SLICC-ACR Damage Index measures irreversible (not related to active inflammation) changes occurring since the diagnosis of SLE ascertained by clinical assessment and present for at least 6 months. The questionnaire contains 39 items covering 12 different organ systems which were scored on a numerical scale between 0 (no damage) to 7 (increasing disease damage). Individual ranges for organ systems were; ocular: 0-2, neuropsychiatric: 0-6, renal: 0-3, pulmonary: 0-5, cardiovascular:0-6, peripheral vascular: 0-5, gastrointestinal:0-5, musculoskeletal: 0-6, skin: 0-3, endocrine (diabetes): 0-1, gonadal:0-1 and malignancies: 0-2. The SLICC-ACR score was calculated by taking sum of the individual scores for 12 organ systems which ranges from 0 (no damage) to 45 (increasing disease damage) where higher score indicates increasing disease damage severity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits.
Time Frame Baseline (Day 1), Week 52 and Week 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 52
1.4
1.9%
2.1
1.5%
2.1
2.8%
Week 104
5.6
7.8%
5.6
3.9%
6.4
8.4%
Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Belimumab + Placebo, Belimumab + Rituximab
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.7102
Comments
Method Regression, Logistic
Comments Week 52
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.55
Confidence Interval (2-Sided) 95%
0.15 to 15.70
Parameter Dispersion Type:
Value:
Estimation Comments Odds ratio at Week 52 was calculated using Logistic regression model with covariates:Baseline SLEDAI-2K,Baseline immunosuppressant,Baseline prednisone equivalent dose and treatment group. Belimumab+ Standard therapy arm was excluded from the model.
Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection Belimumab + Rituximab, Belimumab + Standard Therapy
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.06
Confidence Interval (2-Sided) 95%
0.10 to 10.71
Parameter Dispersion Type:
Value:
Estimation Comments Odds ratio at Week 52 was calculated using Logistic regression model with covariates:Baseline SLEDAI-2K,Baseline immunosuppressant, Baseline prednisone equivalent dose and treatment group. Belimumab + Placebo arm was excluded from the model.
Statistical Analysis 3
Statistical Analysis Overview Comparison Group Selection Belimumab + Placebo, Belimumab + Rituximab
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value 0.8641
Comments
Method Regression, Logistic
Comments Week 104
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 0.90
Confidence Interval (2-Sided) 95%
0.26 to 3.15
Parameter Dispersion Type:
Value:
Estimation Comments Odds ratio at Week 104 was calculated using Logistic regression model with covariates:Baseline SLEDAI-2K,Baseline immunosuppressant,Baseline prednisone equivalent dose and treatment group. Belimumab + Standard therapy arm was excluded from the model.
Statistical Analysis 4
Statistical Analysis Overview Comparison Group Selection Belimumab + Rituximab, Belimumab + Standard Therapy
Comments
Type of Statistical Test Other
Comments
Statistical Test of Hypothesis p-Value
Comments
Method
Comments
Method of Estimation Estimation Parameter Odds Ratio (OR)
Estimated Value 1.22
Confidence Interval (2-Sided) 95%
0.26 to 5.64
Parameter Dispersion Type:
Value:
Estimation Comments Odds ratio at Week 104 was calculated using Logistic regression model with covariates:Baseline SLEDAI-2K,Baseline immunosuppressant,Baseline prednisone equivalent dose and treatment group. Belimumab + Placebo arm was excluded from the model.
20. Secondary Outcome
Title Percentage of Participants That Met the Lupus Low Disease Activity State (LLDAS) Response Criteria by Visits (PI Assessed)
Description Lupus low disease activity state (LLDAS) was defined as a state which, if sustained, was associated with a low likelihood of adverse outcome, considering disease activity and medication safety. The LLDAS response criteria were: (1) SLEDAI-2K <=4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity; (2) no new features of lupus disease activity compared with the previous assessment; (3) PGA (scale 0-3), <=1; (4) current prednisolone (or equivalent) dose <=7.5 mg daily; and (5) well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents, excluding investigational drugs. Percentage of participants that met the LLDAS response criteria were reported.
Time Frame Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96 and 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 4
0
0%
2.1
1.5%
2.1
2.8%
Week 8
9.7
13.5%
1.4
1%
10.6
13.9%
Week 12
8.3
11.5%
9.7
6.7%
6.4
8.4%
Week 16
11.1
15.4%
16.7
11.6%
19.1
25.1%
Week 20
11.1
15.4%
25.7
17.8%
19.1
25.1%
Week 24
12.5
17.4%
22.2
15.4%
36.2
47.6%
Week 26
22.2
30.8%
25.7
17.8%
34.0
44.7%
Week 28
20.8
28.9%
25.0
17.4%
34.0
44.7%
Week 32
29.2
40.6%
31.9
22.2%
36.2
47.6%
Week 36
30.6
42.5%
34.0
23.6%
29.8
39.2%
Week 40
22.2
30.8%
33.3
23.1%
38.3
50.4%
Week 44
30.6
42.5%
37.5
26%
31.9
42%
Week 48
26.4
36.7%
37.5
26%
31.9
42%
Week 52
27.8
38.6%
34.0
23.6%
29.8
39.2%
Week 60
26.4
36.7%
23.6
16.4%
36.2
47.6%
Week 64
20.8
28.9%
30.6
21.3%
31.9
42%
Week 72
22.2
30.8%
31.3
21.7%
31.9
42%
Week 80
18.1
25.1%
26.4
18.3%
34.0
44.7%
Week 88
23.6
32.8%
24.3
16.9%
29.8
39.2%
Week 96
20.8
28.9%
30.6
21.3%
36.2
47.6%
Week 104
20.8
28.9%
32.6
22.6%
38.3
50.4%
21. Secondary Outcome
Title Percentage of Participants With a State of Disease Control Using the PI Assessment of SLEDAI-2K by Visit
Description Percentage of participants with a state of disease control was defined as the percentage of participants with a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day, using the PI assessment of SLEDAI-2K. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. SLEDAI-2K score was the sum of all 24 individual items from SLEDAI-2K, ranges from 0 (no symptoms) to 105 (presence of all defined symptoms), higher scores representing increased disease activity. Percentage of participants with a state of disease control using the PI assessment of SLEDAI-2K were summarized.
Time Frame Weeks 4, 8, 12, 16, 20, 24, 26, 28, 32, 36, 40, 44, 48, 52, 60, 64, 72, 80, 88, 96, 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 4
2.8
3.9%
3.5
2.4%
8.5
11.2%
Week 8
13.9
19.3%
9.0
6.3%
21.3
28%
Week 12
11.1
15.4%
12.5
8.7%
19.1
25.1%
Week 16
15.3
21.3%
22.2
15.4%
29.8
39.2%
Week 20
13.9
19.3%
24.3
16.9%
31.9
42%
Week 24
18.1
25.1%
25.0
17.4%
34.0
44.7%
Week 26
15.3
21.3%
25.7
17.8%
25.5
33.6%
Week 28
11.1
15.4%
25.7
17.8%
36.2
47.6%
Week 32
15.3
21.3%
28.5
19.8%
31.9
42%
Week 36
19.4
26.9%
27.8
19.3%
27.7
36.4%
Week 40
16.7
23.2%
24.3
16.9%
23.4
30.8%
Week 44
18.1
25.1%
26.4
18.3%
27.7
36.4%
Week 48
18.1
25.1%
26.4
18.3%
27.7
36.4%
Week 52
19.4
26.9%
20.1
14%
27.7
36.4%
Week 60
18.1
25.1%
20.8
14.4%
23.4
30.8%
Week 64
11.1
15.4%
18.1
12.6%
27.7
36.4%
Week 72
9.7
13.5%
12.5
8.7%
23.4
30.8%
Week 80
8.3
11.5%
13.2
9.2%
31.9
42%
Week 88
11.1
15.4%
9.7
6.7%
21.3
28%
Week 96
8.3
11.5%
12.5
8.7%
31.9
42%
Week 104
8.3
11.5%
11.8
8.2%
23.4
30.8%
22. Secondary Outcome
Title Percentage of Participants With a State of Clinical Remission Using the PI Assessment of SLEDAI-2K by Visit
Description Percentage of participants with a state of clinical remission was defined as the percentage of participants with a clinical SLEDAI-2K score =0 (does not include anti-dsDNA and complement activity scores), achieved without immunosuppressants (which was allowed in Belimumab+ Standard therapy arm only) and with corticosteroids at a prednisone equivalent dose of 0 mg/day using the PI assessment of SLEDAI-2K. SLEDAI-2K consisted of 24 individual items within each of 9 organ systems. Each item was given a weighted score (1 to 8, higher score indicates increased activity) and summed if present at the time of visit or in preceding 10 days. The clinical SLEDAI-2K score was sum of 22 out of all 24 individual items from the SLEDAI-2K and ranges from 0 (no symptoms) to 101 (presence of all defined symptoms) with higher scores representing increased disease activity. Percentage of participants with a state of clinical remission using the PI assessment of SLEDAI-2K were summarized.
Time Frame Weeks 60, 64, 72, 80, 88, 96 and 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 60
6.9
9.6%
3.5
2.4%
10.6
13.9%
Week 64
6.9
9.6%
5.6
3.9%
10.6
13.9%
Week 72
6.9
9.6%
3.5
2.4%
14.9
19.6%
Week 80
6.9
9.6%
4.2
2.9%
14.9
19.6%
Week 88
6.9
9.6%
2.1
1.5%
14.9
19.6%
Week 96
4.2
5.8%
4.2
2.9%
12.8
16.8%
Week 104
2.8
3.9%
3.5
2.4%
6.4
8.4%
23. Secondary Outcome
Title Number of Participants With Serious Adverse Events (SAE) and Non-serious AE (Non-SAE)
Description An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent disability/incapacity, is a congenital anomaly/birth defect or any other situations as per medical or scientific judgment. Data for number of participants with SAE and non-SAE (>=5 %) has been summarized.
Time Frame Up to Week 111 (including 8 weeks of safety follow-up)

Outcome Measure Data

Analysis Population Description
Intent-to-Treat Population comprised of all randomized participants who received at least one dose of study treatment (Belimumab or Rituximab or Placebo).
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 76
SAE
10
13.9%
32
22.2%
15
19.7%
non-SAE
48
66.7%
109
75.7%
53
69.7%
24. Secondary Outcome
Title Number of Participants With Adverse Events of Special Interest (AESIs)
Description An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. AESIs were Malignant Neoplasms, Post-Injection Systemic Reactions (PISR), All Infections of Special Interest (Opportunistic Infections (OI), Herpes Zoster (HZ), Tuberculosis (TB), and Sepsis), Depression (including mood disorders and anxiety)/suicide/self-injury and Deaths. Data for number of participants with AESIs has been summarized.
Time Frame Up to Week 104

Outcome Measure Data

Analysis Population Description
Intent-to-Treat Population
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 76
Malignant Neoplasms
1
1.4%
1
0.7%
1
1.3%
PISR
7
9.7%
19
13.2%
4
5.3%
All Infections of Special Interest
5
6.9%
12
8.3%
5
6.6%
Depression/suicide/self-injury
9
12.5%
16
11.1%
5
6.6%
Deaths
1
1.4%
2
1.4%
0
0%
25. Secondary Outcome
Title Change From Baseline in Patient Global Assessment (PtGA) by Visits
Description The Patient's Global Assessment (PtGA) of Disease Activity is a single-item, participant reported scale developed for the assessment of the participant's overall rating of their disease activity due to SLE. The scale measures disease activity ranging from 0 (Very Well) to 10 (Very Poor) and the higher score indicates severe disease activity. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value.
Time Frame Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 8; n=66, 132, 44
-0.96
(2.751)
-1.06
(2.141)
-0.91
(2.848)
Week 12; n=66, 133, 44
-0.69
(2.237)
-1.07
(2.290)
-1.57
(2.756)
Week 26; n=61, 115, 40
-0.95
(2.765)
-1.50
(2.596)
-1.57
(2.450)
Week 40; n=63, 123, 43
-1.77
(2.624)
-1.60
(2.809)
-1.67
(2.962)
Week 52; n=64, 120, 41
-1.74
(2.752)
-1.82
(2.631)
-1.84
(3.228)
Week 64; n=62, 117, 36
-1.41
(2.985)
-1.96
(2.595)
-1.96
(3.034)
Week 72; n=59, 107, 33
-1.46
(3.209)
-1.81
(2.609)
-1.43
(3.487)
Week 104; n=55, 111, 36
-1.61
(2.589)
-2.00
(2.739)
-1.98
(2.895)
26. Secondary Outcome
Title Change From Baseline in Lupus Quality of Life (LupusQoL) Domain Scores by Visit
Description LupusQoL is a SLE-specific health related qualify of life (HRQOL) instrument with 34 questions across 8 domains:Physical health(8 items),Pain(3 items),Planning(3 items),Intimate relationship(2 items),Burden to others(3 items),Emotional health(6 items),Body image(5 items),Fatigue(4 items). Questions were related to participants experience in prior 4 weeks.A 5-point Likert response format was used, ranging from 0(all of the time) to 4(never) for each question. Individual domain scores were reported which were calculated by taking sum of responses to all items within each domain. Individual domain scores range:Physical health(0-32),Pain(0-12),Planning(0-12),Intimate relationship(0-8),Burden to others(0-12),Emotional health(0-24),Body image(0-20),Fatigue(0-16). Higher score indicates better HRQOL. Baseline value was latest pre-dose assessment with a non-missing value including those from unscheduled visits. Change from Baseline was defined as post-dose visit value minus Baseline value.
Time Frame Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Physical health; Week 8; n=66, 132, 44
3.0
(15.20)
6.0
(15.08)
6.3
(18.79)
Physical health; Week 12; n=66, 133, 44
3.5
(16.60)
5.8
(17.15)
6.4
(20.06)
Physical health; Week 26; n=61, 115, 40
3.3
(18.74)
10.5
(17.27)
11.6
(19.19)
Physical health; Week 40; n=63, 122, 43
8.5
(19.53)
9.5
(19.29)
8.2
(19.46)
Physical health; Week 52; n=64, 120, 41
8.1
(19.90)
10.0
(20.16)
11.6
(19.53)
Physical health; Week 64; n=62, 117, 36
5.8
(18.66)
10.2
(18.60)
9.5
(21.74)
Physical health; Week 72; n=59, 107, 33
7.0
(21.13)
9.1
(18.84)
8.5
(22.59)
Physical health; Week 104; n=55, 111, 36
6.2
(20.19)
10.6
(19.96)
7.2
(23.33)
Pain; Week 8; n=66, 132, 44
5.8
(19.67)
11.4
(18.55)
10.4
(21.87)
Pain; Week 12; n=66, 133, 44
7.5
(19.78)
13.0
(20.81)
6.1
(28.44)
Pain; Week 26; n=61, 115, 40
7.0
(22.42)
17.2
(21.54)
13.1
(22.79)
Pain; Week 40; n=63, 122, 43
12.3
(23.18)
18.0
(22.70)
12.6
(29.17)
Pain; Week 52; n=64, 120, 41
13.9
(24.26)
17.6
(23.62)
15.7
(27.34)
Pain; Week 64; n=62, 117, 36
10.2
(21.89)
17.4
(23.59)
13.2
(26.90)
Pain; Week 72; n=59, 107, 33
13.1
(24.91)
17.0
(22.66)
11.9
(29.02)
Pain; Week 104; n=55, 111, 36
13.8
(25.82)
19.0
(22.59)
12.5
(27.92)
Planning; Week 8; n=66, 132, 44
3.4
(19.77)
8.0
(18.21)
10.0
(27.88)
Planning; Week 12; n=66, 133, 44
4.5
(23.03)
7.6
(20.15)
7.8
(27.81)
Planning; Week 26; n=61, 115, 40
3.4
(25.20)
9.9
(21.28)
12.1
(27.86)
Planning; Week 40; n=63, 122, 43
11.6
(29.08)
12.2
(22.30)
10.7
(26.62)
Planning; Week 52; n=64, 120, 41
11.6
(28.66)
12.6
(23.89)
14.0
(28.35)
Planning; Week 64; n=62, 117, 36
7.8
(24.42)
14.5
(23.65)
7.2
(30.55)
Planning; Week 72; n=59, 107, 33
9.2
(30.78)
11.4
(20.97)
6.6
(31.02)
Planning; Week 104; n=55, 111, 36
12.1
(30.76)
14.2
(20.77)
8.8
(34.96)
Intimate relationship; Week 8; n=51, 110, 36
-1.2
(21.83)
5.2
(20.63)
7.6
(19.66)
Intimate relationship; Week 12; n=52, 106, 36
-2.6
(25.16)
4.6
(23.42)
7.6
(27.10)
Intimate relationship; Week 26; n=48, 86, 30
-1.3
(29.20)
8.9
(24.32)
14.2
(28.38)
Intimate relationship; Week 40; n=50, 94, 30
4.3
(28.75)
7.7
(25.01)
15.8
(30.43)
Intimate relationship; Week 52; n=51, 91, 30
4.7
(29.36)
6.6
(22.54)
15.8
(30.78)
Intimate relationship; Week 64; n=47, 90, 25
-4.5
(28.00)
11.0
(25.41)
12.5
(29.76)
Intimate relationship; Week 72; n=42, 83, 21
0.0
(31.60)
8.6
(23.82)
5.4
(39.44)
Intimate relationship; Week 104; n=40, 85,27
-0.3
(23.93)
11.2
(25.59)
4.6
(35.21)
Burden to others; Week 8; n=66, 132, 44
7.3
(22.95)
6.8
(20.56)
10.6
(23.46)
Burden to others; Week 12; n=66, 133, 44
11.4
(27.91)
8.4
(23.65)
6.4
(29.90)
Burden to others; Week 26; n=61, 115, 40
8.7
(26.68)
10.5
(27.42)
7.5
(27.66)
Burden to others; Week 40; n=63, 122, 43
13.9
(27.23)
12.6
(26.94)
12.0
(27.66)
Burden to others; Week 52; n=64, 120, 41
16.5
(29.15)
14.9
(27.03)
15.0
(33.40)
Burden to others; Week 64; n=62, 117, 36
14.4
(28.83)
17.0
(26.67)
12.3
(28.21)
Burden to others; Week 72; n=59, 107, 33
17.1
(28.68)
14.4
(28.77)
11.1
(27.85)
Burden to others; Week 104; n=55, 111, 36
18.9
(25.93)
15.0
(29.25)
12.7
(33.42)
Emotional health; Week 8; n=66, 132, 44
5.2
(18.33)
6.4
(16.87)
11.6
(20.55)
Emotional health; Week 12; n=66, 133, 44
8.1
(17.32)
4.5
(19.67)
9.1
(23.87)
Emotional health; Week 26; n=61,115, 40
7.7
(19.84)
6.7
(17.35)
10.1
(18.12)
Emotional health; Week 40; n=63, 122, 43
9.7
(21.44)
6.7
(20.85)
9.4
(22.20)
Emotional health; Week 52; n=64, 120, 41
10.2
(21.48)
7.8
(20.63)
11.4
(21.99)
Emotional health; Week 64; n=62, 117, 36
8.1
(20.75)
9.3
(20.73)
8.1
(22.11)
Emotional health; Week 72; n=59, 107, 33
8.8
(21.39)
6.2
(19.05)
6.6
(21.80)
Emotional health; Week 104; n=55, 111, 36
6.8
(20.20)
9.3
(19.67)
10.5
(23.00)
Body image; Week 8; n=60, 114, 37
5.7
(19.57)
8.9
(19.26)
5.7
(25.05)
Body image; Week 12; n=58, 118, 39
1.9
(23.23)
10.1
(20.73)
5.9
(26.89)
Body image; Week 26; n=56, 96, 33
5.8
(20.62)
9.0
(25.03)
5.7
(23.07)
Body image; Week 40; n=54, 103, 35
8.9
(25.42)
8.2
(24.82)
5.1
(22.07)
Body image; Week 52; n=55, 101, 33
7.9
(25.77)
9.1
(24.07)
10.3
(25.24)
Body image; Week 64; n=52, 98, 27
6.0
(22.51)
11.3
(23.08)
7.7
(23.98)
Body image; Week 72; n=44, 93, 25
7.8
(26.74)
8.7
(24.91)
2.5
(29.28)
Body image; Week 104; n=48, 94, 28
4.4
(26.62)
11.4
(25.65)
3.5
(27.40)
Fatigue; Week 8; n=66,132, 44
9.8
(17.02)
9.2
(18.40)
8.5
(24.30)
Fatigue; Week 12; n=66, 133, 44
8.2
(18.48)
7.0
(17.96)
10.4
(28.11)
Fatigue; Week 26; n=61, 115, 40
8.6
(20.23)
11.4
(20.12)
11.9
(20.21)
Fatigue; Week 40; n=63, 122, 43
11.9
(22.33)
10.3
(22.41)
11.3
(24.75)
Fatigue; Week 52; n=64, 120, 41
14.2
(21.17)
12.0
(20.95)
16.6
(25.30)
Fatigue; Week 64; n=62, 117, 36
10.5
(21.94)
14.0
(20.35)
10.8
(25.21)
Fatigue; Week 72; n=59, 107, 33
12.1
(22.74)
13.1
(18.31)
11.6
(25.87)
Fatigue; Week 104; n=55, 111, 36
9.4
(20.41)
14.3
(20.18)
9.7
(24.25)
27. Secondary Outcome
Title Change From Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue Score by Visit
Description The FACIT-Fatigue scale was a 13-item questionnaire completed by the participant, which provides a measure of fatigue/quality of life, with a 7-day recall period. The participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The higher score for the questions, the greater the fatigue. The total score was the sum of the responses from all questions (inverted for reversed items) multiplied by 13, then divided by the number of questions answered, ranging from 0 (worse fatigue) to 52 (no fatigue) where a higher score indicates an improvement in the participant's health status and decrease in the score indicates worse fatigue/quality of life. Baseline value was the latest pre-dose assessment with a non-missing value, including those from unscheduled visits. Change from Baseline was defined as the post-dose visit value minus Baseline value.
Time Frame Baseline (Day 1) and Weeks 8, 12, 26, 40, 52, 64, 72 and 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 8; n=66, 132, 44
4.2
(9.84)
4.6
(8.84)
4.8
(8.25)
Week 12; n=66, 133, 44
4.7
(9.50)
4.0
(9.86)
3.8
(10.94)
Week 26; n=61, 115, 40
3.1
(10.08)
5.4
(9.17)
4.1
(8.54)
Week 40; n=63, 122, 43
6.0
(10.18)
5.2
(10.80)
5.2
(10.14)
Week 52; n=64, 120, 41
6.5
(10.12)
6.1
(10.84)
5.1
(10.51)
Week 64;n=62, 117, 36
4.9
(10.61)
6.2
(9.72)
4.6
(10.32)
Week 72; n=59, 107, 33
5.6
(10.21)
5.2
(10.31)
2.9
(12.75)
Week 104; n=55, 111, 36
5.7
(9.07)
7.1
(11.50)
3.1
(10.30)
28. Secondary Outcome
Title Percentage of Participants With Improvement in FACIT-Fatigue Score Exceeding the Minimal Clinically Important Difference (MCID, Greater Than or Equal to [>=]4)
Description The FACIT-Fatigue scale was a 13-item questionnaire completed by the participant, which provides a measure of fatigue/quality of life, with a 7-day recall period. The participant scored each item on a 5-point scale: 0 (Not at all) to 4 (Very much). The larger the participant's response to the questions, the greater the fatigue. The total score was the sum of the responses (inverted for reversed items) multiplied by 13, then divided by the number of questions answered, ranging from 0 (worse fatigue) to 52 (no fatigue) where a higher score indicates an improvement in the participant's health status and decrease in the score indicates worse fatigue/quality of life. A participant was considered to had an improvement exceeding the minimal clinically important difference if they had >=4 points improvement in their FACIT-Fatigue Scale score from Baseline. Percentage of participants with improvement in FACIT-Fatigue scale score exceeding the MCID (>=4 points) were summarized.
Time Frame Weeks 8, 12, 26, 40, 52, 64, 72 and 104

Outcome Measure Data

Analysis Population Description
Modified Intent-to-Treat (MITT) Population. Only those participants with data available at specified time points were analyzed (represented by n=X in category titles).
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
Measure Participants 72 144 47
Week 8; n=66, 132, 44
47.0
65.3%
51.5
35.8%
59.1
77.8%
Week 12; n=66, 133, 44
56.1
77.9%
50.4
35%
52.3
68.8%
Week 26; n=61, 115, 40
47.5
66%
56.5
39.2%
45.0
59.2%
Week 40; n=63, 122, 43
54.0
75%
54.1
37.6%
53.5
70.4%
Week 52; n=64, 120, 41
60.9
84.6%
58.3
40.5%
56.1
73.8%
Week 64; n=62, 117, 36
51.6
71.7%
59.8
41.5%
52.8
69.5%
Week 72; n=59, 107, 33
57.6
80%
57.0
39.6%
42.4
55.8%
Week 104; n=55, 111, 36
56.4
78.3%
62.2
43.2%
44.4
58.4%

Adverse Events

Time Frame All-cause mortality, serious adverse events (SAEs) and non-SAEs were collected up to Week 111 (including 8 weeks of safety follow-up).
Adverse Event Reporting Description Intent-To-Treat (ITT) Population was used to assess the all-cause mortality, SAEs and non-SAEs which comprised of all randomized participants who received at least one dose of study treatment (Belimumab or Rituximab or placebo) .
Arm/Group Title Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Arm/Group Description Participants received Belimumab 200 milligrams (mg) administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab-placebo administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (<=) 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Participants also received rituximab 1000 mg administered by IV infusions at Weeks 4 and 6 in double blind manner. Participants received standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104. Participants did not receive treatment after 52 weeks and were in observation until Week 104. Participants received open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Participants also received standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of <= 5 mg/day until Week 104.
All Cause Mortality
Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 1/72 (1.4%) 2/144 (1.4%) 0/76 (0%)
Serious Adverse Events
Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 10/72 (13.9%) 32/144 (22.2%) 15/76 (19.7%)
Blood and lymphatic system disorders
Agranulocytosis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Anaemia 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Hyperplasia of thymic epithelium 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Leukocytosis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Lymphadenopathy 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Neutropenia 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Thrombocytopenic purpura 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Cardiac disorders
Atrial fibrillation 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Cardiac failure congestive 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Myocarditis 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Pericarditis 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Pleuropericarditis 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Ear and labyrinth disorders
Tinnitus 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Eye disorders
Ocular myasthenia 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Gastrointestinal disorders
Abdominal pain lower 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Diarrhoea 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Gastritis 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Hiatus hernia 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Volvulus 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
General disorders
Chest pain 1/72 (1.4%) 1 1/144 (0.7%) 1 0/76 (0%) 0
Pyrexia 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Sudden death 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Hepatobiliary disorders
Autoimmune hepatitis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Immune system disorders
Allergy to vaccine 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Anaphylactic reaction 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Infections and infestations
Pneumonia 0/72 (0%) 0 1/144 (0.7%) 1 1/76 (1.3%) 1
Urinary tract infection 0/72 (0%) 0 2/144 (1.4%) 2 0/76 (0%) 0
Acute sinusitis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Appendicitis 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Arthritis bacterial 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Bartholinitis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
COVID-19 pneumonia 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Cellulitis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Gangrene 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Gastritis viral 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Gastroenteritis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Hepatitis A 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Influenza 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Latent tuberculosis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Orchitis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Pyelonephritis 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Respiratory tract infection viral 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Sepsis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Septic shock 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Sinusitis 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Spinal cord abscess 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Injury, poisoning and procedural complications
Overdose 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Poisoning deliberate 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Post lumbar puncture syndrome 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Wrist fracture 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Metabolism and nutrition disorders
Hypoglycaemia 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Musculoskeletal and connective tissue disorders
Musculoskeletal pain 1/72 (1.4%) 1 1/144 (0.7%) 1 0/76 (0%) 0
Systemic lupus erythematosus 0/72 (0%) 0 1/144 (0.7%) 1 1/76 (1.3%) 1
Arthritis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Haematoma muscle 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Cervix carcinoma stage 0 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Cholangiocarcinoma 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Nervous system disorders
Hemiparesis 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Nervous system disorder 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Neuropsychiatric lupus 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Pregnancy, puerperium and perinatal conditions
Abortion spontaneous 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Psychiatric disorders
Suicidal behaviour 0/72 (0%) 0 1/144 (0.7%) 1 1/76 (1.3%) 1
Adjustment disorder 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Suicidal ideation 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Suicide attempt 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Renal and urinary disorders
Nephrolithiasis 0/72 (0%) 0 1/144 (0.7%) 1 1/76 (1.3%) 1
Neurogenic bladder 0/72 (0%) 0 0/144 (0%) 0 1/76 (1.3%) 1
Reproductive system and breast disorders
Uterine haemorrhage 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Uterine polyp 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Respiratory, thoracic and mediastinal disorders
Pneumonitis 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Pulmonary hypertension 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Shrinking lung syndrome 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Skin and subcutaneous tissue disorders
Angioedema 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Pemphigoid 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Surgical and medical procedures
Abortion induced 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Vascular disorders
Vasculitis 0/72 (0%) 0 2/144 (1.4%) 3 0/76 (0%) 0
Jugular vein thrombosis 1/72 (1.4%) 1 0/144 (0%) 0 0/76 (0%) 0
Thrombophlebitis superficial 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Vasculitis necrotising 0/72 (0%) 0 1/144 (0.7%) 1 0/76 (0%) 0
Other (Not Including Serious) Adverse Events
Belimumab + Placebo Belimumab + Rituximab Belimumab + Standard Therapy
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total 48/72 (66.7%) 109/144 (75.7%) 53/76 (69.7%)
Blood and lymphatic system disorders
Neutropenia 2/72 (2.8%) 2 7/144 (4.9%) 9 4/76 (5.3%) 4
Gastrointestinal disorders
Nausea 2/72 (2.8%) 3 18/144 (12.5%) 22 2/76 (2.6%) 5
Diarrhoea 6/72 (8.3%) 6 6/144 (4.2%) 6 5/76 (6.6%) 9
Vomiting 2/72 (2.8%) 2 11/144 (7.6%) 12 2/76 (2.6%) 4
Abdominal pain upper 5/72 (6.9%) 7 7/144 (4.9%) 7 1/76 (1.3%) 1
Abdominal pain 2/72 (2.8%) 2 9/144 (6.3%) 9 1/76 (1.3%) 1
Dyspepsia 0/72 (0%) 0 4/144 (2.8%) 4 4/76 (5.3%) 4
General disorders
Pyrexia 1/72 (1.4%) 1 10/144 (6.9%) 11 3/76 (3.9%) 9
Chest pain 1/72 (1.4%) 1 6/144 (4.2%) 8 4/76 (5.3%) 5
Fatigue 5/72 (6.9%) 7 5/144 (3.5%) 7 1/76 (1.3%) 2
Infections and infestations
Urinary tract infection 12/72 (16.7%) 16 23/144 (16%) 27 10/76 (13.2%) 27
Nasopharyngitis 9/72 (12.5%) 13 23/144 (16%) 32 11/76 (14.5%) 18
Upper respiratory tract infection 5/72 (6.9%) 6 22/144 (15.3%) 31 9/76 (11.8%) 12
Bronchitis 6/72 (8.3%) 6 10/144 (6.9%) 10 7/76 (9.2%) 7
Influenza 9/72 (12.5%) 12 4/144 (2.8%) 4 4/76 (5.3%) 4
Oral herpes 3/72 (4.2%) 6 9/144 (6.3%) 13 3/76 (3.9%) 7
Sinusitis 4/72 (5.6%) 4 7/144 (4.9%) 8 2/76 (2.6%) 2
Pharyngitis 1/72 (1.4%) 1 4/144 (2.8%) 7 4/76 (5.3%) 4
Musculoskeletal and connective tissue disorders
Arthralgia 5/72 (6.9%) 5 12/144 (8.3%) 13 10/76 (13.2%) 13
Back pain 4/72 (5.6%) 5 8/144 (5.6%) 8 4/76 (5.3%) 7
Systemic lupus erythematosus 6/72 (8.3%) 9 3/144 (2.1%) 3 2/76 (2.6%) 2
Musculoskeletal chest pain 1/72 (1.4%) 1 2/144 (1.4%) 3 4/76 (5.3%) 4
Nervous system disorders
Headache 13/72 (18.1%) 13 30/144 (20.8%) 44 8/76 (10.5%) 14
Psychiatric disorders
Depression 2/72 (2.8%) 2 6/144 (4.2%) 6 4/76 (5.3%) 4
Respiratory, thoracic and mediastinal disorders
Cough 4/72 (5.6%) 4 9/144 (6.3%) 9 4/76 (5.3%) 4
Vascular disorders
Hypertension 1/72 (1.4%) 1 7/144 (4.9%) 8 4/76 (5.3%) 5

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

GSK agreements may vary with individual investigators, but will not prohibit any investigator from publishing. GSK supports the publication of results from all centers of a multi-center trial but requests that reports based on single-site data not precede the primary publication of the entire clinical trial

Results Point of Contact

Name/Title GSK Response Center
Organization GlaxoSmithKline
Phone 866-435-7343
Email GSKClinicalSupportHD@gsk.com
Responsible Party:
GlaxoSmithKline
ClinicalTrials.gov Identifier:
NCT03312907
Other Study ID Numbers:
  • 205646
  • 2016-003050-32
First Posted:
Oct 18, 2017
Last Update Posted:
Apr 25, 2022
Last Verified:
Feb 1, 2022