Efficacy and Safety of Belimumab in Black Race Patients With Systemic Lupus Erythematosus (SLE)
EMBRACE
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)
4 other identifiers
interventional
503
6 countries
96
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).
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P75+ for phase_4
Started Feb 2013
Longer than P75 for phase_4
96 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
First Submitted
Initial submission to the registry
June 28, 2012
CompletedFirst Posted
Study publicly available on registry
July 2, 2012
CompletedStudy Start
First participant enrolled
February 19, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 18, 2018
CompletedStudy Completion
Last participant's last visit for all outcomes
January 28, 2019
CompletedResults Posted
Study results publicly available
July 5, 2019
CompletedSeptember 8, 2021
August 1, 2021
5.3 years
June 28, 2012
June 12, 2019
August 15, 2021
Conditions
Keywords
Outcome Measures
Primary Outcomes (9)
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).
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
Secondary Outcomes (12)
Percentage of Participants Achieving SRI-SS Response Rate at Week 52 [DB Phase]
Week 52
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)
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 Flare (as Measured by the Modified SLE Flare Index) [OL Phase]
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]
Baseline and Week 40 through Week 52
- +7 more secondary outcomes
Study Arms (2)
Placebo plus standard therapy
PLACEBO COMPARATORPlacebo 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
EXPERIMENTALBelimumab 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.
Interventions
Belimumab 10mg/kg plus standard 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.
Eligibility Criteria
You may qualify if:
- 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.
- +8 more criteria
You may not qualify if:
- 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.
- +29 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Human Genome Sciences Inc., a GSK Companylead
- GlaxoSmithKlinecollaborator
Study Sites (96)
GSK Investigational Site
Birmingham, Alabama, 35216, United States
GSK Investigational Site
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
Medellín, 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
Related Publications (4)
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.
PMID: 34164944BACKGROUNDNikolopoulos 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.
PMID: 39115551DERIVEDArends 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.
PMID: 38775637DERIVEDBrunner 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.
PMID: 34531304DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- GSK Response Center
- Organization
- GlaxoSmithKline
Study Officials
- STUDY DIRECTOR
GSK Clinical Trials
GlaxoSmithKline
Publication Agreements
- PI is Sponsor Employee
- No
- Restriction Type
- OTHER
- Restrictive Agreement
- Yes
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
June 28, 2012
First Posted
July 2, 2012
Study Start
February 19, 2013
Primary Completion
June 18, 2018
Study Completion
January 28, 2019
Last Updated
September 8, 2021
Results First Posted
July 5, 2019
Record last verified: 2021-08
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- IPD is available via the Clinical Study Data Request site (copy the URL below to your browser)
- Access Criteria
- 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.
IPD for this study is available via the Clinical Study Data Request site