Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)

A Phase 3/4, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 52-Week Study to Evaluate the Efficacy and Safety of Belimumab (HGS1006) in Adult Subjects of Black Race With Systemic Lupus Erythematosus (SLE)

Status

Completed

Phases

Phase 4

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01632241

Acronym

EMBRACE

Enrollment

503

Registered

2012-07-02

Start date

2013-02-19

Completion date

2019-01-28

Last updated

2021-09-08

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Systemic Lupus Erythematosus

Keywords

Systemic Lupus Erythematosus, African Continental Ancestry Group, Autoimmune Disease, Antibodies, Minority Groups, Black Race, African Americans, SLE, Belimumab, Lupus

Brief summary

The purpose of this study is to evaluate the efficacy, safety, and tolerability of belimumab in adult patients of black race with systemic lupus erythematosus (SLE; lupus).

Detailed description

Study participants receive stable standard therapy for lupus in addition to receiving either placebo (no active medicine) or belimumab. The controlled period of the study is 52 weeks. The random assignment in this study is 2 to 1 which means that for every 3 participants, 2 will receive belimumab and 1 will receive placebo. Participants who successfully complete the 52-week study may enter into a 6-month open-label extension. All participants in the open-label extension receive belimumab plus standard therapy.

Interventions

BIOLOGICALPlacebo plus standard therapy

Placebo plus standard therapy

BIOLOGICALBelimumab 10 mg/kg plus standard therapy

Belimumab 10mg/kg plus standard therapy

DRUGStandard therapy

Standard therapy comprises any of the following (alone or in combination): corticosteroids, antimalarials, non-steroidal anti-inflammatory drugs (NSAIDs), and immunosuppressives; biologics and intravenous cyclophosphamide are not permitted.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

* At least 18 years of age. * Self-identified black race. * Have a clinical diagnosis of SLE according to the American College of Rheumatology (ACR) criteria * Have active SLE disease defined as a SELENA SLEDAI score \>= 8 at screening * Have 2 unequivocally positive autoantibody test results defined as a positive antinuclear antibody (ANA) test \[i.e., titer \>= 1:80 by human epithelial cell line 2 (HEp-2) immunofluorescence assay (IFA) and/or positive enzyme immunoassay (EIA)\] and/or a positive anti- double stranded deoxyribonucleic acid (dsDNA) (\>= 30 international units \[IU\]/milliliter \[mL\]) serum antibody test as follows: * 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. Historical documentation of a positive ANA test (e.g., HEp-2 IFA or EIA) or anti-dsDNA (eg, anti-dsDNA by any validated commercial assay) must include the date and type of the test, the name of the testing laboratory, numerical reference range, and a key that explains values provided as positive versus negative OR negative, equivocal/borderline positive). Only unequivocally positive values as defined in the laboratory's reference range are acceptable; borderline values will not be accepted. * On a stable SLE treatment regimen consisting of any of the following medications (alone or in combination) for a period of at least 30 days prior to Day 0 (i.e., day of 1st dose of study agent): * Corticosteroids (prednisone or prednisone equivalent, up to 40 mg/day): For subjects on SLE combination therapy, their stable steroid dose must be fixed within the range of 0 to 40 mg/day (prednisone or prednisone equivalent). For subjects whose only SLE treatment is steroids, their stable steroid dose must be fixed within the range of 7.5 to 40 mg/day (prednisone or prednisone equivalent). For those subjects on alternating day doses of steroids, use the average of 2 daily doses to calculate the average daily steroid dose. * Other immunosuppressive or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin inhibitors (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). Note: * Pre-existing SLE medications must be stable for at least 30 days prior to Day 0. * Corticosteroids may be added as new medication or their doses adjusted only up to 30 days prior to Day 0. * New SLE therapy other than corticosteroids must not be added within 60 days of Day 0. * A female subject is eligible to enter the study if she is: * Not pregnant or nursing; * Of non-childbearing potential defined as: pre-menopausal females with a documented tubal ligation, hysterectomy, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, or documented bilateral oophorectomy, OR postmenopausal defined as 12 months of spontaneous amenorrhea with an appropriate clinical profile \[e.g., \> 45 years, in the absence of hormone replacement therapy or other cause for amenorrhea\]; in questionable cases obtain a blood sample for follicle stimulating hormone (FSH) and estradiol simultaneously to confirm. Diagnostic levels for FSH and estradiol vary by specific laboratories/assays; * OR is of child-bearing potential with negative pregnancy test as determined by serum human chorionic gonadotrophin (hCG) test at screening and urine hCG test prior to dosing AND agrees to use one of the contraception methods for 2 weeks prior to the day of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 16 weeks following the last dose of study agent. * OR has only same-sex partners, when this is her preferred and usual lifestyle. * Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study protocol procedures (including required study visits).

Exclusion criteria

* Have received treatment with anti-B lymphocyte stimulator (BLyS) \[belimumab\] at any time. * Have received any of the following within 364 days of Day 0: * Abatacept * Other B cell targeted therapy (e.g., rituximab, other anti-cluster of differentiation \[CD\] 20 agents, anti-CD22 \[epratuzumab\], anti-CD52 \[alemtuzumab\], BLyS-receptor fusion protein \[BR3\], TACI-Fc, or anti-B-cell activating factor \[BAFF\] (LY2127399). * A biologic investigational agent other than B cell targeted therapy (e.g., abetimus sodium, anti-CD40L antibody \[BG9588/IDEC-131\]). * Have required 3 or more courses of systemic corticosteroids for concomitant conditions (e.g., asthma, atopic dermatitis) within 364 days of Day 0. (Topical or inhaled steroids are permitted.) * Have received any of the following within 90 days of Day 0: * Anti-tumor necrosis factor (TNF) therapy (eg, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab). * Intravenous (IV) cyclophosphamide * Interleukin-1 receptor antagonist (anakinra). * Intravenous immunoglobulin (IVIG). * High dose prednisone or equivalent (\> 100 mg/day). * Plasmapheresis. * Have received any of the following within 60 days of Day 0: * A non-biologic investigational agent. * Any new immunosuppressive/immunomodulatory agent, anti-malarial, or NSAID Note: New inhaled and topical steroids and new topical immunosuppressive agents (e.g., eye drops, topical creams) are allowed. Any NSAID use for \< 1 week is allowed. * Any steroid injection (e.g., intramuscular, intraarticular, or intravenous). * Have received any of the following within 30 days of Day 0: * A live vaccine. * A change in dose of a corticosteroid, other immunosuppressive/immunomodulatory agent, anti-malarial, or NSAID * Have severe lupus kidney disease (defined by proteinuria \> 6 grams/24 hour or equivalent using spot urine protein to creatinine ratio, or serum creatinine \> 2.5 mg/deciliter \[dL\]), or have severe active nephritis requiring acute therapy not permitted by protocol (e.g., IV cyclophosphamide within 90 days of Day 0), or have required hemodialysis or high-dose prednisone (\> 100 mg/day) within 90 days of Day 0. * 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 0. * Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant. * 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, 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. * Have a planned surgical procedure or a history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the principal investigator, makes the subject unsuitable for the study. * Have a history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix. * Have required management of acute or chronic infections, as follows: * Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, and atypical mycobacteria). * Hospitalization for treatment of infection within 60 days of Day 0. * Use of parenteral (IV or intramuscular \[IM\]) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 60 days of Day 0. * 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 screening Columbia-Suicide Severity Rating Scale (C-SSRS) in the last 2 months or who, in the investigator's opinion, pose a significant suicide risk. * Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 0. * Have a historically positive test or test positive at screening for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis B core antibody, or hepatitis C antibody. * Have an immunoglobulin (Ig)A deficiency (IgA level \< 10 mg/dL). * Have a grade 3 or greater laboratory abnormality based on the adverse event * Severity grading tables except for the following that are allowed: * Stable grade 3 prothrombin time (PT) secondary to anticoagulant, e.g., warfarin, treatment. * Stable grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy. * Stable grade 3/4 proteinuria (\<=6 grams/24 hour equivalent by spot urine protein to creatinine ratio allowed). * Stable grade 3 hypoalbuminemia due to lupus nephritis, and not related to liver disease or malnutrition. * Stable grade 3 gamma glutamyl transferase (GGT) elevation due to lupus hepatitis, and not related to alcoholic liver disease, uncontrolled diabetes, or viral hepatitis. If present, any abnormalities in alanine transaminase (ALT) and/or aspartate transaminase (AST) must be \<=grade 2. * Stable grade 3 hemoglobin reduction due to lupus. * Stable grade 3 neutropenia or stable grade 3 white blood cell count. * Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies.

Design outcomes

Primary

Measure	Time frame	Description
Percentage of Participants Achieving a Systemic Lupus Erythematosus Responder Index (SRI) Response Rate With the Modified Systemic Lupus Erythematosus Disease Activity Index- 2K (SLEDAI-2K) Scoring for Proteinuria at Week 52 [DB Phase]	Week 52	SRI response is defined as \>=4 point reduction, from Baseline in safety of estrogen in Lupus National Assessment(SELENA)SLEDAI\[SS\] score (with modified SLEDAI-2K scoring for proteinuria \[PU\]), no worsening (increase of \<0.30 points from Baseline) in Physician's Global Assessment (PGA) and no new British Isles Lupus Assessment Group of SLE clinics(BILAG)A organ domain score \[ODS\] or 2 new BILAG B ODS compared with Baseline. Drop-outs and treatment failures were set to non-responders. Analysis performed using a logistic regression model for comparison between belimumab and placebo with covariates treatment group, Baseline SS score (with modified SLEDAI-2K scoring for PU) (\<=9 versus \[vs.\] \>=10), Baseline complement levels (low C3 and/or C4 vs. no low C3 or C4) and region (United States \[US\]/Canada vs. Rest of World). The Modified Intention-To-Treat (mITT) population comprised of safety population excluding participants who had any assessment at 3 sites (202196, 202513 or 107286).
Percentage of Participants Achieving a SRI Response Rate With the Modified SLEDAI-2K Scoring for Proteinuria at Week 24 of OL Phase	Week 24 of OL phase (Week 76)	SRI response is defined as \>=4 point reduction, from OL Baseline in SS score (with the modified SLEDAI-2K scoring for PU), no worsening (increase of \<0.30 points from OL Baseline) in PGA and no new BILAG A ODS or 2 new BILAG B ODS compared with OL Baseline. For participants switching from placebo to belimumab 10 mg/kg IV in the OL phase, Baseline was defined as the last assessment at the end of the double-blind phase (i.e. Week 52) pre-OL treatment. For participants that received belimumab 10 mg/kg IV during the double-blind phase and continued to receive belimumab 10 mg/kg IV during the OL phase, Baseline was defined as Day 1 of the double-blind phase.
Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Event (SAEs) [OL Phase]	Week 52 to Week 84	An adverse event (AE) is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Number of participants who had common nSAEs (\>=5%) and any SAEs are presented. For Safety, participants that completed DB and OL phase, an additional 8 weeks follow-up was conducted (Week 84).
Number of Participants With Severe AEs [OL Phase]	Week 52 to Week 84	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with severe AEs have been presented. For Safety, participants that completed DB and OL phase, an additional 8 weeks follow-up was conducted (Week 84).
Number of Participants With AEs Leading to Treatment Discontinuation [OL Phase]	Week 52 to Week 84	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with AEs leading to treatment discontinuation have been presented. For Safety, participants that completed DB and OL phase, an additional 8 weeks follow-up was conducted (Week 84).
Number of Participants With Worst Toxicity Grade 3 or 4 for Hematology Parameters [OL Phase]	Week 52 to Week 84	Blood samples were collected for the assessment of hematology parameters. The parameters assessed were activated partial thromboplastin time (APTT), hemoglobin, leukocytes, neutrophils, platelets and prothrombin time. Grading was assigned as mild (Grade 1), moderate (grade 2), severe (Grade 3) and potentially life-threatening (Grade 4) according to Division of Microbiology and Infectious Diseases (DMID \[Modified from DMID Adult Toxicity Tables, 2001\]) AE Severity Grading. Number of participants with worst toxicity Grade 3 or 4 for hematology parameters have been presented. For Safety, participants that completed DB and OL phase, an additional 8 weeks follow-up was conducted (Week 84).
Number of Participants With Worst Toxicity Grade of 3 or 4 for Clinical Chemistry Parameters [OL Phase]	Week 52 to Week 84	Blood samples were collected for the assessment of liver function and other chemistry parameters. The parameters assessed were alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), bilirubin, albumin, creatinine, hyperglycemia, hypoglycemia and urate. Grading was assigned as mild (Grade 1), moderate (grade 2), severe (Grade 3) and potentially life-threatening (Grade 4) according to DMID AE Severity Grading. Number of participants with worst toxicity Grade of 3 or 4 for liver function and other chemistry parameters have been presented. For Safety, participants that completed DB and OL phase, an additional 8 weeks follow-up was conducted (Week 84).
Number of Participants With Worst Toxicity Grade of 3 or 4 for Urinalysis Parameters [OL Phase]	Week 52 to Week 84	Urinalysis parameters assessed were urine protein and protein/creatinine. Urine samples were collected for the measurement of urinalysis parameters by dipstick method. Grading was assigned as mild (Grade 1), moderate (grade 2), severe (Grade 3) and potentially life-threatening (Grade 4) according to DMID AE Severity Grading. Number of participants with worst toxicity grade of 3 or 4 for urinalysis parameters have been presented. For Safety, participants that completed DB and OL phase, an additional 8 weeks follow-up was conducted (Week 84).
Number of Participants With Worst Toxicity Grade of 3 or 4 of Immunoglobulins [OL Phase]	Week 52 to Week 84	Serum samples were obtained for the measurement of immunoglobulin G. Grading was assigned as mild (Grade 1), moderate (grade 2), severe (Grade 3) and potentially life threatening (Grade 4) according to DMID AE Severity Grading. Number of participants with worst toxicity grade of 3 or 4 of immunoglobulin G have been presented. For Safety, participants that completed DB and OL phase, an additional 8 weeks follow-up was conducted (Week 84).

Secondary

Measure	Time frame	Description
Number of Participants With Worst Toxicity Grade 3 or 4 for Hematology Parameters [DB Phase]	Up to 52 weeks	Blood samples were collected for the assessment of hematology parameters up to 52 Weeks. The parameters assessed were APTT, hemoglobin, leukocytes, neutrophils, platelets and prothrombin time. Grading was assigned as mild (Grade 1), moderate (grade 2), severe (Grade 3) and potentially life threatening according to DMID AE Severity Grading. Number of participants with worst toxicity Grade of 3 or 4 for hematology parameters have been presented.
Percentage of Participants Achieving SRI-SS Response Rate at Week 52 [DB Phase]	Week 52	SRI is defined as \>=4 point reduction, from Baseline in SS score, no worsening (increase of \<0.30 points from Baseline) in PGA and no new BILAG A organ domain score or 2 new BILAG B organ domain scores compared with Baseline. Drop-outs and Treatment failures were set to non-responders. Analysis was performed using a logistic regression model for the comparison between belimumab and placebo with covariates treatment group, Baseline SS score (\<=9 vs. \>=10), Baseline complement levels (low C3 and/or C4 vs. no low C3 or C4) and region (US/Canada vs. Rest of World).
Number of Participants With Worst Toxicity Grade of 3 or 4 for Urinalysis Parameters [DB Phase]	Up to 52 weeks	Urinalysis parameters assessed were urine protein and protein/creatinine. Urine samples were collected for the measurement of urinalysis parameters by dipstick method up to 52 Weeks. Grading was assigned as mild (Grade 1), moderate (grade 2), severe (Grade 3) and potentially life threatening according to DMID AE Severity Grading. Only those participants with worst toxicity grade of 3 or 4 for urinalysis parameters have been presented.
Number of Participants With Worst Toxicity Grade of 3 or 4 for Clinical Chemistry Parameters [DB Phase]	Up to 52 weeks	Blood samples were collected for the assessment of liver function and other chemistry parameters up to 52 Weeks. The parameters assessed were ALT, AST, GGT, albumin, hyperglycemia and hypoglycemia. Grading was assigned as mild (Grade 1), moderate (grade 2), severe (Grade 3) and potentially life threatening according to DMID AE Severity Grading. Only those participants with worst toxicity Grade of 3 or 4 for other chemistry parameters have been presented.
Percentage of Participants Achieving SRI-SS Response Rate With the SELENA SLEDAI for Scoring of Proteinuria at Week 24 of OL Phase	Week 24 of OL phase (Week 76)	SRI response is defined as \>=4 point reduction, from OL Baseline in SS scoring for PU, no worsening (increase of \<0.30 points from OL Baseline) in PGA and no new BILAG A ODS or 2 new BILAG B ODS compared with OL Baseline. For participants switching from placebo to belimumab 10 mg/kg IV in the open-label phase, Baseline was defined as the last assessment at the end of the double-blind phase (i.e. Week 52) pre-OL treatment. For participants that received belimumab 10 mg/kg IV during the double-blind phase and continued to receive belimumab 10 mg/kg IV during the open-label phase, Baseline was defined as Day 1 of the double-blind phase.
Time to First Severe Flare (as Measured by the Modified SLE Flare Index) up to 52 Weeks [DB Phase]	Up to 52 Weeks	Time to first severe SLE flare is defined as the number of days from treatment start date until the participant met an event (event date - treatment start date +1). Analyses of severe SLE flare was performed on modified SS SLE flare index that excludes severe flares (SF) that were triggered only by an increase in SS score to \>12 (this may only represent a modest increase in disease activity). Treatment failures were imputed as SF. For participants who died, data were censored at date of death if no SF occurred before death. Only post-Baseline SF were considered. Analysis was performed using Cox proportional hazards model for the comparison between belimumab and placebo adjusting for Baseline SS-S2K score (\<=9 vs. \>=10), baseline complement levels (at least 1 C3/C4 low vs. no C3/C4 low), and region (US/Canada vs. Rest of World). Median and inter-Quartile range (1st and 3rd Quartiles) have been presented.
Time to First Severe Flare (as Measured by the Modified SLE Flare Index) [OL Phase]	Up to Week 24 of OL Phase (Week 76)	Time to first severe SLE flare is defined as the number of days from OL treatment start date until the participant met an event (event date - OL treatment start date +1). Analyses of severe SLE flare was performed on modified SS SLE flare index that excludes SF that were triggered only by an increase in SS score to \>12. For participants who died, data were censored at date of death if no SF occurred before death. Only post first OL treatment SF were considered. Median and inter-Quartile range (25th and 75th percentile) have been presented.
Percent of Participants Whose Average Prednisone Dose Had Been Reduced by >=25% From Baseline to <=7.5 mg/Day During Week 40 Through 52, in Participants Receiving Greater Than 7.5 mg/Day at Baseline [DB Phase]	Baseline and Week 40 through Week 52	Average (avg.) daily prednisone (PRED.) dose was calculated taking into account all steroids taken intravenously, intramuscularly, subcutaneously, intradermally and orally for both Systemic Lupus Erythema (SLE) and non-SLE reasons. A responder was defined as having a PRED. reduction \[REDN.\] by \>=25% from Baseline to \<=7.5 mg/day during Weeks 40 through 52. Drop-outs and Treatment failures were imputed as having no REDN. in PRED. (if Baseline PRED. \>7.5 mg/day). At Baseline, the avg. daily prednisone dose \[PD\] was the sum of all PDs over 7 consecutive days \[excluding Day 0\], divided (DIV.) by 7. For analysis, the avg. PD was the total PD during Weeks 40 through 52 DIV. by the number of days during Weeks 40 through 52. Analysis was performed using a logistic regression model with covariates treatment group, Baseline PD, Baseline SS-S2K score, (\<=9 vs \>=10), Baseline complement levels (low C3 and/or C4 vs. no low C3 or C4) and region (US/Canada vs. Rest of World).
Percent of Participants Whose Average Prednisone Dose Had Been Reduced to <=7.5 mg/Day in Participants Receiving Greater Than 7.5 mg/Day at Pre-belimumab Baseline (at Week 28 of OL Phase)	OL Baseline and Week 28 of OL Phase (Week 80)	Average daily prednisone dose was calculated taking into account all steroids taken intravenously, intramuscularly, subcutaneously, intradermally and orally for both SLE and non-SLE reasons. A responder was defined as a participant who decreased their daily prednisone dose to \<=7.5 mg/day from an OL Baseline dose \>7.5 mg/day. The OL Baseline was defined as the last available value prior to the initiation of treatment with belimumab. The average daily prednisone dose was the sum of all PDs over 7 consecutive days including OL Week 28 divided by 7. Only those participants with data available at the specified data points were analyzed.
Number of Participants With nSAEs and SAEs [DB Phase]	Up to 52 Weeks	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. A SAE is defined as any untoward medical occurrence that; results in death, is life-threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, is a congenital anomaly/birth defect, other situations judged by physician, is associated with liver injury and impaired liver function. Safety population was defined as all participants who were randomized and treated with at least one dose of study treatment. Number of participants who had common nSAEs (\>=5%) and any SAEs are presented.
Number of Participants With Severe AEs [DB Phase]	Up to 52 Weeks	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with severe AEs have been presented.
Number of Participants With AEs Leading to Treatment Discontinuation [DB Phase]	Up to 52 Weeks	An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with AEs leading to treatment discontinuation have been presented.

Countries

Brazil, Colombia, France, South Africa, United Kingdom, United States

Participant flow

Recruitment details

This study evaluated the efficacy and safety of belimumab compared with placebo in adult participants with Systemic Lupus Erythematosus (SLE). This was a multicenter study conducted at United States (88 centers), United Kingdom (6), South Africa (5), France (4), Columbia (6) and Brazil (18).

Pre-assignment details

A total of 503 participants were randomized of which 496 received at-least one dose of study medication during double-blinded phase (7 participants were randomized but not treated as they were randomized in error). A total of 359 out of 373 participants who completed double-blinded phase opted to continue optional open-label (OL) extension phase.

Participants by arm

Arm	Count
Placebo to Belimumab 10 mg/kg In double-blinded phase, participants received matching placebo to belimumab administered as intravenous (IV) infusion plus standard of care through 52 weeks. In open-label phase, participants received belimumab 10 milligram per kilogram (mg/kg) administered as IV infusion plus standard of care every 28 days from Week 52 through Week 76.	165
Belimumab 10 mg/kg to Belimumab 10 mg/kg In double-blinded phase, participants received belimumab 10 mg/kg administered as IV infusion plus standard of care through 52 weeks. In open-label phase, participants received belimumab 10 mg/kg administered as IV infusion plus standard of care every 28 days from Week 52 through Week 76.	331
Total	496

Withdrawals & dropouts

Period	Reason	FG000	FG001
Double-blinded (Up to Week 52)	Adverse Event	10	19
Double-blinded (Up to Week 52)	Lack of Efficacy	9	15
Double-blinded (Up to Week 52)	Lost to Follow-up	1	8
Double-blinded (Up to Week 52)	Physician Decision	9	12
Double-blinded (Up to Week 52)	Protocol Violation	2	6
Double-blinded (Up to Week 52)	Site Closed	3	5
Double-blinded (Up to Week 52)	Withdrawal by Subject	10	14
Open-label (Week 52 to Week 76)	Adverse Event	1	0
Open-label (Week 52 to Week 76)	Lack of Efficacy	0	2
Open-label (Week 52 to Week 76)	Lost to Follow-up	1	4
Open-label (Week 52 to Week 76)	Physician Decision	1	4
Open-label (Week 52 to Week 76)	Protocol Violation	0	2
Open-label (Week 52 to Week 76)	Site Closed	2	8
Open-label (Week 52 to Week 76)	Withdrawal by Subject	5	2

Baseline characteristics

Characteristic	Placebo to Belimumab 10 mg/kg	Belimumab 10 mg/kg to Belimumab 10 mg/kg	Total
Age, Continuous	39.5 Years STANDARD_DEVIATION 12.06	38.7 Years STANDARD_DEVIATION 11	38.9 Years STANDARD_DEVIATION 11.36
Race/Ethnicity, Customized Race Black or African American	165 Participants	331 Participants	496 Participants
Sex: Female, Male Female	158 Participants	322 Participants	480 Participants
Sex: Female, Male Male	7 Participants	9 Participants	16 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk	EG003 affected / at risk
deaths Total, all-cause mortality	0 / 165	2 / 331	0 / 117	0 / 242
other Total, other adverse events	77 / 165	196 / 331	23 / 117	49 / 242
serious Total, serious adverse events	31 / 165	36 / 331	6 / 117	13 / 242

Outcome results

Primary

Number of Participants With AEs Leading to Treatment Discontinuation [OL Phase]

An AE is any untoward medical occurrence in a clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. Number of participants with AEs leading to treatment discontinuation have been presented. For Safety, participants that completed DB and OL phase, an additional 8 weeks follow-up was conducted (Week 84).