Not provided
| ID | Type | Description | Link |
|---|---|---|---|
| HGS1006-C1112 | Other Identifier | Human Genome Sciences Inc. | |
| 2011-005672-42 | EudraCT Number | ||
| U1111-1139-9723 | Other Identifier | Universal Trial Number |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Class |
|---|---|
| GlaxoSmithKline | INDUSTRY |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
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).
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.
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo plus standard therapy | Placebo Comparator | Placebo IV plus standard therapy; placebo administered on Days 0, 14, 28, and every 28 days thereafter through Week 48, with a final evaluation at Week 52 in the double-blind period. In the open-label extension period, placebo patients who opt to participate will receive belimumab 10 mg/kilogram (kg) IV every 28 days for an additional 6 months. |
|
| Belimumab 10 mg/kg plus standard therapy | Experimental | Belimumab 10 mg/kg IV plus standard therapy; belimumab administered on Days 0, 14, 28, and then every 28 days thereafter through Week 48, with a final evaluation at Week 52 in the double-blind period. In the open-label extension period, patients who opt to participate will continue to receive belimumab 10 mg/kg IV every 28 days for an additional 6 months. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Placebo plus standard therapy | Biological | Placebo plus standard therapy |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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] | 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). | Week 52 |
| Percentage of Participants Achieving a SRI Response Rate With the Modified SLEDAI-2K Scoring for Proteinuria at Week 24 of OL Phase | 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. | Week 24 of OL phase (Week 76) |
| Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Event (SAEs) [OL Phase] | 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). |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Participants Achieving SRI-SS Response Rate at Week 52 [DB Phase] | 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). |
Not provided
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:
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):
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:
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:
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:
Have received any of the following within 60 days of Day 0:
Have received any of the following within 30 days of Day 0:
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:
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:
Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies.
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
| Name | Affiliation | Role |
|---|---|---|
| GSK Clinical Trials | GlaxoSmithKline | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| GSK Investigational Site | Birmingham | Alabama | 35216 | United States | ||
| GSK Investigational Site |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| Background | Ellen Ginzler, Luiz Barbosa, David D'Cruz, Richard Furie, Kathleen Maksimowicz-McKinnon, James Oates, Mittermayer Barreto Santiago, Amit Saxena, Saira Sheikh, Damon Bass, Susan Burriss, Jennifer Gilbride, James Groark, Michelle Miller, Amy Pierce, David Roth, Beulah Ji. EMBRACE: Phase 3/4, Randomized, 52-Week Study of Belimumab Efficacy and Safety in Patients of Black African Ancestry With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2021; DOI: 10.1002/art.41900 PMID: 34164944 | ||
| 39208825 | Derived | Parodis I, Lindblom J, Levy RA, Zen M, Cetrez N, Gomez A, Oon S, Henning C, Khamashta M, Quasny HA, Chauhan D, Askanase A, van Vollenhoven R, Nikpour M. Attainment of remission and low disease activity after treatment with belimumab in patients with systemic lupus erythematosus: a post-hoc analysis of pooled data from five randomised clinical trials. Lancet Rheumatol. 2024 Nov;6(11):e751-e761. doi: 10.1016/S2665-9913(24)00162-0. Epub 2024 Aug 26. | |
| 39115551 |
Not provided
Not provided
IPD for this study is available via the Clinical Study Data Request site
IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months but an extension can be granted, when justified, for up to another 12 months.
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.
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).
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Double-blinded (Up to Week 52) |
|
Not provided
Not provided
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Feb 9, 2017 | Apr 1, 2019 |
Not provided
Not provided
Not provided
Not provided
Not provided
| Belimumab 10 mg/kg plus standard therapy | Biological | Belimumab 10mg/kg plus standard therapy |
|
| Standard therapy | Drug | 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. |
|
| Week 52 to Week 84 |
| Number of Participants With Severe AEs [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 severe AEs have been presented. For Safety, participants that completed DB and OL phase, an additional 8 weeks follow-up was conducted (Week 84). | Week 52 to Week 84 |
| 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). | Week 52 to Week 84 |
| Number of Participants With Worst Toxicity Grade 3 or 4 for Hematology Parameters [OL Phase] | 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). | Week 52 to Week 84 |
| Number of Participants With Worst Toxicity Grade of 3 or 4 for Clinical Chemistry Parameters [OL Phase] | 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). | Week 52 to Week 84 |
| Number of Participants With Worst Toxicity Grade of 3 or 4 for Urinalysis Parameters [OL Phase] | 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). | Week 52 to Week 84 |
| Number of Participants With Worst Toxicity Grade of 3 or 4 of Immunoglobulins [OL Phase] | 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). | Week 52 to Week 84 |
| Week 52 |
| Percentage of Participants Achieving SRI-SS Response Rate With the SELENA SLEDAI for Scoring of Proteinuria at Week 24 of OL Phase | 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. | Week 24 of OL phase (Week 76) |
| Time to First Severe Flare (as Measured by the Modified SLE Flare Index) up to 52 Weeks [DB Phase] | 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. | Up to 52 Weeks |
| Time to First Severe Flare (as Measured by the Modified SLE Flare Index) [OL Phase] | 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. | Up to Week 24 of OL Phase (Week 76) |
| 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] | 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). | Baseline and Week 40 through Week 52 |
| 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) | 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. | OL Baseline and Week 28 of OL Phase (Week 80) |
| Number of Participants With nSAEs and SAEs [DB 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. 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. | Up to 52 Weeks |
| Number of Participants With Severe AEs [DB 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 severe AEs have been presented. | Up to 52 Weeks |
| Number of Participants With AEs Leading to Treatment Discontinuation [DB 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. | Up to 52 Weeks |
| Number of Participants With Worst Toxicity Grade 3 or 4 for Hematology Parameters [DB Phase] | 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. | Up to 52 weeks |
| Number of Participants With Worst Toxicity Grade of 3 or 4 for Clinical Chemistry Parameters [DB Phase] | 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. | Up to 52 weeks |
| Number of Participants With Worst Toxicity Grade of 3 or 4 for Urinalysis Parameters [DB Phase] | 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. | Up to 52 weeks |
| Covina |
| California |
| 91723 |
| United States |
| GSK Investigational Site | La Palma | California | 90623 | United States |
| GSK Investigational Site | Lakewood | California | 90712 | United States |
| GSK Investigational Site | Los Alamitos | California | 90720 | United States |
| GSK Investigational Site | Los Angeles | California | 90048 | United States |
| GSK Investigational Site | Murrieta | California | 92563 | United States |
| GSK Investigational Site | Upland | California | 91786 | United States |
| GSK Investigational Site | Bridgeport | Connecticut | 06606 | United States |
| GSK Investigational Site | Washington D.C. | District of Columbia | 20060 | United States |
| GSK Investigational Site | Aventura | Florida | 33180 | United States |
| GSK Investigational Site | DeBary | Florida | 32713 | United States |
| GSK Investigational Site | Fort Lauderdale | Florida | 33334 | United States |
| GSK Investigational Site | Longwood | Florida | 32750 | United States |
| GSK Investigational Site | Miami | Florida | 33136 | United States |
| GSK Investigational Site | Miami | Florida | 33144 | United States |
| GSK Investigational Site | Miami Lakes | Florida | 33014 | United States |
| GSK Investigational Site | Orlando | Florida | 32804 | United States |
| GSK Investigational Site | Orlando | Florida | 32806-6264 | United States |
| GSK Investigational Site | Plantation | Florida | 33324 | United States |
| GSK Investigational Site | Tamarac | Florida | 33321 | United States |
| GSK Investigational Site | Tampa | Florida | 33603 | United States |
| GSK Investigational Site | Atlanta | Georgia | 30303 | United States |
| GSK Investigational Site | Duluth | Georgia | 30096 | United States |
| GSK Investigational Site | Chicago | Illinois | 60612 | United States |
| GSK Investigational Site | Baton Rouge | Louisiana | 70809 | United States |
| GSK Investigational Site | Boston | Massachusetts | 02115 | United States |
| GSK Investigational Site | Detroit | Michigan | 48202 | United States |
| GSK Investigational Site | Lansing | Michigan | 48917 | United States |
| GSK Investigational Site | Jackson | Mississippi | 39216 | United States |
| GSK Investigational Site | St Louis | Missouri | 63110 | United States |
| GSK Investigational Site | Las Vegas | Nevada | 89102 | United States |
| GSK Investigational Site | Las Vegas | Nevada | 89128 | United States |
| GSK Investigational Site | Clifton | New Jersey | 07012 | United States |
| GSK Investigational Site | Brooklyn | New York | 11201 | United States |
| GSK Investigational Site | Brooklyn | New York | 11203 | United States |
| GSK Investigational Site | Brooklyn | New York | 11215 | United States |
| GSK Investigational Site | Great Neck | New York | 11021 | United States |
| GSK Investigational Site | Manhasset | New York | 11030 | United States |
| GSK Investigational Site | New York | New York | 10016 | United States |
| GSK Investigational Site | New York | New York | 10029 | United States |
| GSK Investigational Site | New York | New York | 10032 | United States |
| GSK Investigational Site | Chapel Hill | North Carolina | 27599 | United States |
| GSK Investigational Site | Charlotte | North Carolina | 28210 | United States |
| GSK Investigational Site | Greenville | North Carolina | 27834 | United States |
| GSK Investigational Site | Raleigh | North Carolina | 27617 | United States |
| GSK Investigational Site | Wilmington | North Carolina | 28401 | United States |
| GSK Investigational Site | Cleveland | Ohio | 44195 | United States |
| GSK Investigational Site | Columbus | Ohio | 43203 | United States |
| GSK Investigational Site | Wyomissing | Pennsylvania | 19610 | United States |
| GSK Investigational Site | Charleston | South Carolina | 29425 | United States |
| GSK Investigational Site | Columbia | South Carolina | 29204 | United States |
| GSK Investigational Site | Columbia | South Carolina | 29229 | United States |
| GSK Investigational Site | Jackson | Tennessee | 38305 | United States |
| GSK Investigational Site | Memphis | Tennessee | 38119 | United States |
| GSK Investigational Site | Memphis | Tennessee | 38163 | United States |
| GSK Investigational Site | Austin | Texas | 78705 | United States |
| GSK Investigational Site | Austin | Texas | 78731 | United States |
| GSK Investigational Site | Dallas | Texas | 75246 | United States |
| GSK Investigational Site | Dallas | Texas | 75390-8550 | United States |
| GSK Investigational Site | Houston | Texas | 77004 | United States |
| GSK Investigational Site | Houston | Texas | 77034 | United States |
| GSK Investigational Site | The Woodlands | Texas | 77382 | United States |
| GSK Investigational Site | Arlington | Virginia | 22205-3606 | United States |
| GSK Investigational Site | Salvador | Estado de Bahia | 40.050-410 | Brazil |
| GSK Investigational Site | Cuiabá | Mato Grosso | 78048-902 | Brazil |
| GSK Investigational Site | Juiz de Fora | Minas Gerais | 36010-570 | Brazil |
| GSK Investigational Site | Curitba | Paraná | 80440-080 | Brazil |
| GSK Investigational Site | Porto Alegre | Rio Grande do Sul | 90035-001 | Brazil |
| GSK Investigational Site | Porto Alegre | Rio Grande do Sul | 90035-170 | Brazil |
| GSK Investigational Site | Porto Alegre | Rio Grande do Sul | 90610000 | Brazil |
| GSK Investigational Site | Campinas | São Paulo | 13015-001 | Brazil |
| GSK Investigational Site | Santo André | São Paulo | 09190-615 | Brazil |
| GSK Investigational Site | Belo Horizonte, Minas Gerais | 30150-221 | Brazil |
| GSK Investigational Site | Campo Grande | 79080-190 | Brazil |
| GSK Investigational Site | Rio de Janeiro | 22411-001 | Brazil |
| GSK Investigational Site | São Paulo | 01323-020 | Brazil |
| GSK Investigational Site | São Paulo | 04032-060 | Brazil |
| GSK Investigational Site | São Paulo | 04039-901 | Brazil |
| GSK Investigational Site | São Paulo | 05652-900 | Brazil |
| GSK Investigational Site | Barranquilla | 080002 | Colombia |
| GSK Investigational Site | Bucaramanga | 680005 | Colombia |
| GSK Investigational Site | Cali | 760007 | Colombia |
| GSK Investigational Site | MedellÃn | 574 | Colombia |
| GSK Investigational Site | Fort de France | 97261 | France |
| GSK Investigational Site | Paris | 75014 | France |
| GSK Investigational Site | Paris | 75018 | France |
| GSK Investigational Site | Durban | KwaZulu-Natal | 4319 | South Africa |
| GSK Investigational Site | Diepkloof | 2013 | South Africa |
| GSK Investigational Site | Johannesburg | 2193 | South Africa |
| GSK Investigational Site | Panorama / Cape Town | 7500 | South Africa |
| GSK Investigational Site | Basildon | Essex | SS165NL | United Kingdom |
| GSK Investigational Site | London | E1 1BB | United Kingdom |
| GSK Investigational Site | London | SE1 7RT | United Kingdom |
| GSK Investigational Site | London | WC1E 6JF | United Kingdom |
| GSK Investigational Site | Manchester | M13 9WL | United Kingdom |
| Derived |
| Nikolopoulos D, Cetrez N, Lindblom J, Parodis I. Neuropsychiatric involvement in systemic lupus erythematosus contributes to organ damage beyond the nervous system: a post-hoc analysis of 5 phase III randomized clinical trials. Rheumatol Int. 2024 Sep;44(9):1679-1689. doi: 10.1007/s00296-024-05667-5. Epub 2024 Aug 8. |
| 38775637 | Derived | Arends EJ, Zlei M, Tipton CM, Cotic J, Osmani Z, de Bie FJ, Kamerling SWA, van Maurik A, Dimelow R, Gregan YI, Fox NL, Rabelink TJ, Roth DA, Sanz I, van Dongen JJM, van Kooten C, Teng YKO. Disruption of memory B-cell trafficking by belimumab in patients with systemic lupus erythematosus. Rheumatology (Oxford). 2024 Sep 1;63(9):2387-2398. doi: 10.1093/rheumatology/keae286. |
| 38724182 | Derived | Rendas-Baum R, Chen WH, Gairy K, Anderson S, Henning C, Hammer A, Kosinski M. SF-36v2 and FACIT-Fatigue quality of life improvements with organ-specific SELENA-SLEDAI response and belimumab treatment in patients with systemic lupus erythematosus. Lupus Sci Med. 2024 May 8;11(1):e001118. doi: 10.1136/lupus-2023-001118. |
| 34531304 | Derived | Brunner HI, Abud-Mendoza C, Mori M, Pilkington CA, Syed R, Takei S, Viola DO, Furie RA, Navarra S, Zhang F, Bass DL, Eriksson G, Hammer AE, Ji BN, Okily M, Roth DA, Quasny H, Ruperto N. Efficacy and safety of belimumab in paediatric and adult patients with systemic lupus erythematosus: an across-study comparison. RMD Open. 2021 Sep;7(3):e001747. doi: 10.1136/rmdopen-2021-001747. |
| 34164944 | Derived | Ginzler E, Guedes Barbosa LS, D'Cruz D, Furie R, Maksimowicz-McKinnon K, Oates J, Santiago MB, Saxena A, Sheikh S, Bass DL, Burriss SW, Gilbride JA, Groark JG, Miller M, Pierce A, Roth DA, Ji B. Phase III/IV, Randomized, Fifty-Two-Week Study of the Efficacy and Safety of Belimumab in Patients of Black African Ancestry With Systemic Lupus Erythematosus. Arthritis Rheumatol. 2022 Jan;74(1):112-123. doi: 10.1002/art.41900. Epub 2021 Dec 9. |
| FG001 |
| 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. |
| COMPLETED |
|
| NOT COMPLETED |
|
|
| Open-label (Week 52 to Week 76) |
|
|
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | 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. |
| BG001 | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||
| Race/Ethnicity, Customized | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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] | 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). | mITT Population. One participant in the mITT population Belimumab 10 mg/kg arm did not have a screening or Baseline PGA assessment; therefore, this participant did not contribute to the SRI/component analysis. | Posted | Number | Percentage of participants | Week 52 |
|
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Percentage of Participants Achieving a SRI Response Rate With the Modified SLEDAI-2K Scoring for Proteinuria at Week 24 of OL Phase | 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. | mITT OL population comprised of Intent-to-Treat (ITT) OL population (all randomized participants who received at least one dose of OL treatment) excluding participants who had any assessment at 3 sites (202196, 202513 or 107286). Only those participants with data available at the specified data points were analyzed. | Posted | Number | Percentage of participants | Week 24 of OL phase (Week 76) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Non-serious Adverse Events (nSAEs) and Serious Adverse Event (SAEs) [OL Phase] | 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). | Intent-to-Treat (ITT) OL Population comprised of all randomized participants who received atleast one dose of open label treatment. | Posted | Count of Participants | Participants | Week 52 to Week 84 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Severe AEs [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 severe AEs have been presented. For Safety, participants that completed DB and OL phase, an additional 8 weeks follow-up was conducted (Week 84). | ITT OL Population | Posted | Count of Participants | Participants | Week 52 to Week 84 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| 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). | ITT OL Population | Posted | Count of Participants | Participants | Week 52 to Week 84 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Worst Toxicity Grade 3 or 4 for Hematology Parameters [OL Phase] | 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). | ITT OL Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Count of Participants | Participants | Week 52 to Week 84 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Worst Toxicity Grade of 3 or 4 for Clinical Chemistry Parameters [OL Phase] | 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). | ITT OL Population. Only those participants with data available at the specified data points were analyzed. | Posted | Count of Participants | Participants | Week 52 to Week 84 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Worst Toxicity Grade of 3 or 4 for Urinalysis Parameters [OL Phase] | 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). | ITT OL Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Count of Participants | Participants | Week 52 to Week 84 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Primary | Number of Participants With Worst Toxicity Grade of 3 or 4 of Immunoglobulins [OL Phase] | 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). | ITT OL Population. Only those participants with data available at the specified data points were analyzed. | Posted | Count of Participants | Participants | Week 52 to Week 84 |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Achieving SRI-SS Response Rate at Week 52 [DB Phase] | 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). | mITT Population. One participant in the mITT population Belimumab 10 mg/kg arm did not have a screening or Baseline PGA assessment; therefore, this participant did not contribute to the SRI/component analysis. | Posted | Number | Percentage of participants | Week 52 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Percentage of Participants Achieving SRI-SS Response Rate With the SELENA SLEDAI for Scoring of Proteinuria at Week 24 of OL Phase | 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. | mITT OL Population. Only those participants with data available at the specified data points were analyzed. | Posted | Number | Percentage of participants | Week 24 of OL phase (Week 76) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to First Severe Flare (as Measured by the Modified SLE Flare Index) up to 52 Weeks [DB Phase] | 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. | mITT Population | Posted | Median | Inter-Quartile Range | Days | Up to 52 Weeks |
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Time to First Severe Flare (as Measured by the Modified SLE Flare Index) [OL Phase] | 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. | mITT OL Population | Posted | Median | Inter-Quartile Range | Days | Up to Week 24 of OL Phase (Week 76) |
|
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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] | 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). | mITT Population. Only participants with Baseline prednisone dose >7.5 mg/day were included. | Posted | Number | Percentage of participants | Baseline and Week 40 through Week 52 |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | 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) | 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. | mITT OL Population. Only those participants with data available at the specified data points were analyzed. | Posted | Number | Percentage of participants | OL Baseline and Week 28 of OL Phase (Week 80) |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With nSAEs and SAEs [DB 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. 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. | Safety Population | Posted | Count of Participants | Participants | Up to 52 Weeks |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Severe AEs [DB 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 severe AEs have been presented. | Safety Population | Posted | Count of Participants | Participants | Up to 52 Weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With AEs Leading to Treatment Discontinuation [DB 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. | Safety Population | Posted | Count of Participants | Participants | Up to 52 Weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Worst Toxicity Grade 3 or 4 for Hematology Parameters [DB Phase] | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Count of Participants | Participants | Up to 52 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Worst Toxicity Grade of 3 or 4 for Clinical Chemistry Parameters [DB Phase] | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed. | Posted | Count of Participants | Participants | Up to 52 weeks |
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Secondary | Number of Participants With Worst Toxicity Grade of 3 or 4 for Urinalysis Parameters [DB Phase] | 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. | Safety Population. Only those participants with data available at the specified data points were analyzed (represented by n=X in the category titles). | Posted | Count of Participants | Participants | Up to 52 weeks |
|
|
nSAEs and SAEs were collected from the start of study treatment up to Week 52 for Double Blind phase and from Week 52 to Week 84 for the Open Label phase. Participants that completed DB and OL phase, an additional 8 weeks follow-up was conducted (Week 84).
nSAEs and SAEs were reported for the Safety Population which comprised of all randomized participants who received at least 1 dose of study treatment for Double Blind phase and ITT OL Population which comprised of all randomized participants who received at least 1 dose of OL treatment for OL phase.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Placebo (DB Phase) | In DB phase, participants received matching placebo to belimumab administered as IV infusion plus standard of care through 52 weeks. | 0 | 165 | 31 | 165 | 77 | 165 |
| EG001 | Belimumab 10 mg/kg (DB Phase) | In DB phase, participants received belimumab 10 mg/kg administered as IV infusion plus standard of care through 52 weeks. | 2 | 331 | 36 | 331 | 196 | 331 |
| EG002 | Placebo to Belimumab 10 mg/kg (OL Phase) | In OL phase, participants received belimumab 10 mg/kg administered as IV infusion plus standard of care every 28 days from Week 52 through Week 76 | 0 | 117 | 6 | 117 | 23 | 117 |
| EG003 | Belimumab 10 mg/kg to Belimumab 10 mg/kg (OL Phase) | In OL phase, participants received belimumab 10 mg/kg administered as IV infusion plus standard of care every 28 days from Week 52 through Week 76 | 0 | 242 | 13 | 242 | 49 | 242 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Pneumonia | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Systemic lupus erythematosus | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Lupus nephritis | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pericarditis | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
| |
| SLE arthritis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 21.1 | Systematic Assessment |
| |
| Asthma | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Cellulitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Costochondritis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dyspnoea | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Lupus pneumonitis | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Muscular weakness | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Non-cardiac chest pain | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pyrexia | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Abdominal pain | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Accidental overdose | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Acute kidney injury | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Acute myocardial infarction | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Amoebic colitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Anaemia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Appendicitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Arthritis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Arthritis gonococcal | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Atrial fibrillation | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Atypical pneumonia | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Azotaemia | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Butterfly rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Cardiomyopathy | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Cerebrovascular accident | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Chest pain | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Cholecystitis | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Cholecystitis acute | Hepatobiliary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Clostridium difficile infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Colitis | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Coma | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dehydration | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Dengue fever | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Depression suicidal | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Diverticulitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Dystonia | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Ectopic pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 21.1 | Systematic Assessment |
| |
| Enteritis | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Fatigue | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Fibromyalgia | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Glomerulonephritis | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Haematoma | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hypoalbuminaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Idiopathic intracranial hypertension | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Idiopathic orbital inflammation | Eye disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Intestinal obstruction | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Joint injury | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Leukopenia | Blood and lymphatic system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Lung consolidation | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Lung infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Lupus pleurisy | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Lupus vasculitis | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Malignant hypertension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Meningitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Musculoskeletal chest pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Myocardial infarction | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Myositis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Nephrotic syndrome | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Orthostatic hypotension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Osteoarthritis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pancreatitis acute | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Paronychia | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Pelvic fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Proteinuria | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Pulmonary contusion | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Radiculopathy | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Raynaud's phenomenon | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Renal failure | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Rhabdomyolysis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Sepsis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Serositis | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Small intestinal perforation | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Soft tissue inflammation | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Squamous cell carcinoma of the cervix | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | MedDRA 21.1 | Systematic Assessment |
| |
| Staphylococcal sepsis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Suicidal ideation | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Systemic lupus erythematosus rash | Skin and subcutaneous tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Tachycardia | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Transient ischaemic attack | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Upper respiratory tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Urinary retention | Renal and urinary disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Vasculitis | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Ventricular tachycardia | Cardiac disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Viral tonsillitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Syncope | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Chorea | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hemiparesis | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Bacteraemia | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Oesophageal candidiasis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Soft tissue infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Tendonitis | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Vertigo | Ear and labyrinth disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Oedema | General disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Wrist fracture | Injury, poisoning and procedural complications | MedDRA 21.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Upper respiratory tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Urinary tract infection | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Headache | Nervous system disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Influenza | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Diarrhoea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Sinusitis | Infections and infestations | MedDRA 21.1 | Systematic Assessment |
| |
| Nausea | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Insomnia | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Vomiting | Gastrointestinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Cough | Respiratory, thoracic and mediastinal disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Depression | Psychiatric disorders | MedDRA 21.1 | Systematic Assessment |
| |
| Hypertension | Vascular disorders | MedDRA 21.1 | Systematic Assessment |
|
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.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| GSK Response Center | GlaxoSmithKline | 866-435-7343 | GSKClinicalSupportHD@gsk.com |
| Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Feb 14, 2019 | Jan 21, 2020 | SAP_002.pdf |
| ID | Term |
|---|---|
| D008180 | Lupus Erythematosus, Systemic |
| D001327 | Autoimmune Diseases |
| ID | Term |
|---|---|
| D003240 | Connective Tissue Diseases |
| D017437 | Skin and Connective Tissue Diseases |
| D007154 | Immune System Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| D059039 | Standard of Care |
| C511911 | belimumab |
| ID | Term |
|---|---|
| D019984 | Quality Indicators, Health Care |
| D011787 | Quality of Health Care |
| D006298 | Health Services Administration |
| D017530 | Health Care Quality, Access, and Evaluation |
Not provided
Not provided
| Lost to Follow-up |
|
| Site Closed |
|
| Protocol Violation |
|
| Lack of Efficacy |
|
| Adverse Event |
|
| Male |
|
In OL phase, participants received belimumab 10 mg/kg administered as IV infusion plus standard of care every 28 days from Week 52 through Week 76
|
|
|
|
|
|
|
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
| Participants |
|
|
| Units | Counts |
|---|
| Participants |
|
|
|
| Units | Counts |
|---|---|
| Participants |
|
|
|
|
|
| Participants |
|
|
In DB phase, participants received belimumab 10 mg/kg administered as IV infusion plus standard of care through 52 weeks. |
|
|
|
|
|
| Units |
|---|
| Counts |
|---|
| Participants |
|
|
|
|
|
|
|
|
|
|