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Systemic Lupus ErythematosusPhase 4EMBRACENCT01632241

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

A Phase 4 study testing Belimumab 10 mg/kg plus standard therapy and Standard therapy in people with Systemic Lupus Erythematosus, run by Human Genome Sciences Inc., a GSK Company at 96 sites in 6 countries.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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). Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Systemic Lupus Erythematosus
What is being tested?
Belimumab 10 mg/kg plus standard therapy and Standard therapy
Type of treatment
Injection or infusion
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
503 participants
Where
96 sitesin 6 countries
Study dates
19 Feb 2013to 28 Jan 2019
Phase
Phase 4
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • One positive historical test result and 1 positive test result during the screening period.
  • Historical documentation of a positive ANA test (e.g., HEp-2 IFA or EIA) or anti-dsDNA (eg, anti-dsDNA by any validated commercial assay) must include the date and type of the test, the name of the testing laboratory, numerical reference range, and a key that explains values provided as positive versus negative OR negative, equivocal/borderline positive). Only unequivocally positive values as defined in the laboratory's reference range are acceptable; borderline values will not be accepted.
  • On a stable SLE treatment regimen consisting of any of the following medications (alone or in combination) for a period of at least 30 days prior to Day 0 (i.e., day of 1st dose of study agent):
  • Corticosteroids (prednisone or prednisone equivalent, up to 40 mg/day): For subjects on SLE combination therapy, their stable steroid dose must be fixed within the range of 0 to 40 mg/day (prednisone or prednisone equivalent). For subjects whose only SLE treatment is steroids, their stable steroid dose must be fixed within the range of 7.5 to 40 mg/day (prednisone or prednisone equivalent). For those subjects on alternating day doses of steroids, use the average of 2 daily doses to calculate the average daily steroid dose.
  • Other immunosuppressive or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin inhibitors (e.g., tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-mercaptopurine, mizoribine, or thalidomide.
  • Anti-malarials (e.g., hydroxychloroquine, chloroquine, quinacrine).
  • Non-steroidal anti-inflammatory drugs (NSAIDs).
  • Note:
  • Pre-existing SLE medications must be stable for at least 30 days prior to Day 0.
  • Corticosteroids may be added as new medication or their doses adjusted only up to 30 days prior to Day 0.
  • New SLE therapy other than corticosteroids must not be added within 60 days of Day 0.
  • A female subject is eligible to enter the study if she is:
  • Not pregnant or nursing;
  • Of non-childbearing potential defined as: pre-menopausal females with a documented tubal ligation, hysterectomy, documented hysteroscopic tubal occlusion procedure with follow-up confirmation of bilateral tubal occlusion, or documented bilateral oophorectomy, OR postmenopausal defined as 12 months of spontaneous amenorrhea with an appropriate clinical profile [e.g., > 45 years, in the absence of hormone replacement therapy or other cause for amenorrhea]; in questionable cases obtain a blood sample for follicle stimulating hormone (FSH) and estradiol simultaneously to confirm. Diagnostic levels for FSH and estradiol vary by specific laboratories/assays;
  • OR is of child-bearing potential with negative pregnancy test as determined by serum human chorionic gonadotrophin (hCG) test at screening and urine hCG test prior to dosing AND agrees to use one of the contraception methods for 2 weeks prior to the day of dosing to sufficiently minimize the risk of pregnancy at that point. Female subjects must agree to use contraception until 16 weeks following the last dose of study agent.
  • OR has only same-sex partners, when this is her preferred and usual lifestyle.
  • Have the ability to understand the requirements of the study, provide written informed consent (including consent for the use and disclosure of research-related health information), and comply with the study protocol procedures (including required study visits).

Who cannot join

  • 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.)
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  • Have received any of the following within 90 days of Day 0:
  • Anti-tumor necrosis factor (TNF) therapy (eg, adalimumab, certolizumab pegol, etanercept, golimumab, infliximab).
  • Intravenous (IV) cyclophosphamide
  • Interleukin-1 receptor antagonist (anakinra).
  • Intravenous immunoglobulin (IVIG).
  • High dose prednisone or equivalent (> 100 mg/day).
  • Plasmapheresis.
  • Have received any of the following within 60 days of Day 0:
  • A non-biologic investigational agent.
  • Any new immunosuppressive/immunomodulatory agent, anti-malarial, or NSAID Note: New inhaled and topical steroids and new topical immunosuppressive agents (e.g., eye drops, topical creams) are allowed. Any NSAID use for < 1 week is allowed.
  • Any steroid injection (e.g., intramuscular, intraarticular, or intravenous).
  • Have received any of the following within 30 days of Day 0:
  • A live vaccine.
  • A change in dose of a corticosteroid, other immunosuppressive/immunomodulatory agent, anti-malarial, or NSAID
  • Have severe lupus kidney disease (defined by proteinuria > 6 grams/24 hour or equivalent using spot urine protein to creatinine ratio, or serum creatinine > 2.5 mg/deciliter [dL]), or have severe active nephritis requiring acute therapy not permitted by protocol (e.g., IV cyclophosphamide within 90 days of Day 0), or have required hemodialysis or high-dose prednisone (> 100 mg/day) within 90 days of Day 0.
  • Have severe active central nervous system (CNS) lupus (including seizures, psychosis, organic brain syndrome, cerebrovascular accident [CVA], cerebritis, or CNS vasculitis) requiring therapeutic intervention within 60 days of Day 0.
  • Have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
  • Have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, malignancy, or infectious diseases) which, in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk.
  • Have a planned surgical procedure or a history of any other medical disease (e.g., cardiopulmonary), laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the principal investigator, makes the subject unsuitable for the study.
  • Have a history of malignant neoplasm within the last 5 years, except for adequately treated cancers of the skin (basal or squamous cell) or carcinoma in situ of the uterine cervix.
  • Have required management of acute or chronic infections, as follows:
  • Currently on any suppressive therapy for a chronic infection (such as tuberculosis, pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, and atypical mycobacteria).
  • Hospitalization for treatment of infection within 60 days of Day 0.
  • Use of parenteral (IV or intramuscular [IM]) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 60 days of Day 0.
  • Subjects who have evidence of serious suicide risk including any history of suicidal behavior in the last 6 months and/or any suicidal ideation of type 4 or 5 on the screening Columbia-Suicide Severity Rating Scale (C-SSRS) in the last 2 months or who, in the investigator's opinion, pose a significant suicide risk.
  • Have current drug or alcohol abuse or dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 0.
  • Have a historically positive test or test positive at screening for human immunodeficiency virus (HIV) antibody, hepatitis B surface antigen (HBsAg), hepatitis B core antibody, or hepatitis C antibody.
  • Have an immunoglobulin (Ig)A deficiency (IgA level < 10 mg/dL).
  • Have a grade 3 or greater laboratory abnormality based on the adverse event
  • Severity grading tables except for the following that are allowed:
  • Stable grade 3 prothrombin time (PT) secondary to anticoagulant, e.g., warfarin, treatment.
  • Stable grade 3 partial thromboplastin time (PTT) due to lupus anticoagulant and not related to liver disease or anti-coagulant therapy.
  • Stable grade 3/4 proteinuria (<=6 grams/24 hour equivalent by spot urine protein to creatinine ratio allowed).
  • Stable grade 3 hypoalbuminemia due to lupus nephritis, and not related to liver disease or malnutrition.
  • Stable grade 3 gamma glutamyl transferase (GGT) elevation due to lupus hepatitis, and not related to alcoholic liver disease, uncontrolled diabetes, or viral hepatitis. If present, any abnormalities in alanine transaminase (ALT) and/or aspartate transaminase (AST) must be <=grade 2.
  • Stable grade 3 hemoglobin reduction due to lupus.
  • Stable grade 3 neutropenia or stable grade 3 white blood cell count.
  • Have a history of an anaphylactic reaction to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies.

Trial locations and contacts

96 sites in 6 countries.

96 sites in 6 countries

United States64 sites

  • GSK Investigational Site

    Arlington, Virginia, 22205-3606

  • GSK Investigational Site

    Atlanta, Georgia, 30303

  • GSK Investigational Site

    Austin, Texas, 78705

  • GSK Investigational Site

    Austin, Texas, 78731

  • GSK Investigational Site

    Aventura, Florida, 33180

  • GSK Investigational Site

    Baton Rouge, Louisiana, 70809

  • GSK Investigational Site

    Birmingham, Alabama, 35216

  • GSK Investigational Site

    Boston, Massachusetts, 02115

  • GSK Investigational Site

    Bridgeport, Connecticut, 06606

  • GSK Investigational Site

    Brooklyn, New York, 11201

  • GSK Investigational Site

    Brooklyn, New York, 11203

  • GSK Investigational Site

    Brooklyn, New York, 11215

  • GSK Investigational Site

    Chapel Hill, North Carolina, 27599

  • GSK Investigational Site

    Charleston, South Carolina, 29425

  • GSK Investigational Site

    Charlotte, North Carolina, 28210

  • GSK Investigational Site

    Chicago, Illinois, 60612

  • GSK Investigational Site

    Cleveland, Ohio, 44195

  • GSK Investigational Site

    Clifton, New Jersey, 07012

  • GSK Investigational Site

    Columbia, South Carolina, 29204

  • GSK Investigational Site

    Columbia, South Carolina, 29229

  • GSK Investigational Site

    Columbus, Ohio, 43203

  • GSK Investigational Site

    Covina, California, 91723

  • GSK Investigational Site

    Dallas, Texas, 75246

  • GSK Investigational Site

    Dallas, Texas, 75390-8550

  • GSK Investigational Site

    DeBary, Florida, 32713

  • GSK Investigational Site

    Detroit, Michigan, 48202

  • GSK Investigational Site

    Duluth, Georgia, 30096

  • GSK Investigational Site

    Fort Lauderdale, Florida, 33334

  • GSK Investigational Site

    Great Neck, New York, 11021

  • GSK Investigational Site

    Greenville, North Carolina, 27834

  • GSK Investigational Site

    Houston, Texas, 77004

  • GSK Investigational Site

    Houston, Texas, 77034

  • GSK Investigational Site

    Jackson, Mississippi, 39216

  • GSK Investigational Site

    Jackson, Tennessee, 38305

  • GSK Investigational Site

    La Palma, California, 90623

  • GSK Investigational Site

    Lakewood, California, 90712

  • GSK Investigational Site

    Lansing, Michigan, 48917

  • GSK Investigational Site

    Las Vegas, Nevada, 89102

  • GSK Investigational Site

    Las Vegas, Nevada, 89128

  • GSK Investigational Site

    Longwood, Florida, 32750

  • GSK Investigational Site

    Los Alamitos, California, 90720

  • GSK Investigational Site

    Los Angeles, California, 90048

  • GSK Investigational Site

    Manhasset, New York, 11030

  • GSK Investigational Site

    Memphis, Tennessee, 38119

  • GSK Investigational Site

    Memphis, Tennessee, 38163

  • GSK Investigational Site

    Miami, Florida, 33136

  • GSK Investigational Site

    Miami, Florida, 33144

  • GSK Investigational Site

    Miami Lakes, Florida, 33014

  • GSK Investigational Site

    Murrieta, California, 92563

  • GSK Investigational Site

    New York, New York, 10016

  • GSK Investigational Site

    New York, New York, 10029

  • GSK Investigational Site

    New York, New York, 10032

  • GSK Investigational Site

    Orlando, Florida, 32804

  • GSK Investigational Site

    Orlando, Florida, 32806-6264

  • GSK Investigational Site

    Plantation, Florida, 33324

  • GSK Investigational Site

    Raleigh, North Carolina, 27617

  • GSK Investigational Site

    St Louis, Missouri, 63110

  • GSK Investigational Site

    Tamarac, Florida, 33321

  • GSK Investigational Site

    Tampa, Florida, 33603

  • GSK Investigational Site

    The Woodlands, Texas, 77382

  • GSK Investigational Site

    Upland, California, 91786

  • GSK Investigational Site

    Washington D.C., District of Columbia, 20060

  • GSK Investigational Site

    Wilmington, North Carolina, 28401

  • GSK Investigational Site

    Wyomissing, Pennsylvania, 19610

Other trials in United States

Brazil16 sites

  • GSK Investigational Site

    Belo Horizonte, Minas Gerais, 30150-221

  • GSK Investigational Site

    Campinas, São Paulo, 13015-001

  • GSK Investigational Site

    Campo Grande, 79080-190

  • GSK Investigational Site

    Cuiabá, Mato Grosso, 78048-902

  • GSK Investigational Site

    Curitba, Paraná, 80440-080

  • GSK Investigational Site

    Juiz de Fora, Minas Gerais, 36010-570

  • GSK Investigational Site

    Porto Alegre, Rio Grande do Sul, 90035-001

  • GSK Investigational Site

    Porto Alegre, Rio Grande do Sul, 90035-170

  • GSK Investigational Site

    Porto Alegre, Rio Grande do Sul, 90610000

  • GSK Investigational Site

    Rio de Janeiro, 22411-001

  • GSK Investigational Site

    Salvador, Estado de Bahia, 40.050-410

  • GSK Investigational Site

    Santo André, São Paulo, 09190-615

  • GSK Investigational Site

    São Paulo, 01323-020

  • GSK Investigational Site

    São Paulo, 04032-060

  • GSK Investigational Site

    São Paulo, 04039-901

  • GSK Investigational Site

    São Paulo, 05652-900

Other trials in Brazil

United Kingdom5 sites

  • GSK Investigational Site

    Basildon, Essex, SS165NL

  • GSK Investigational Site

    London, E1 1BB

  • GSK Investigational Site

    London, SE1 7RT

  • GSK Investigational Site

    London, WC1E 6JF

  • GSK Investigational Site

    Manchester, M13 9WL

Other trials in United Kingdom

Colombia4 sites

  • GSK Investigational Site

    Barranquilla, 080002

  • GSK Investigational Site

    Bucaramanga, 680005

  • GSK Investigational Site

    Cali, 760007

  • GSK Investigational Site

    Medellín, 574

Other trials in Colombia

South Africa4 sites

  • GSK Investigational Site

    Diepkloof, 2013

  • GSK Investigational Site

    Durban, KwaZulu-Natal, 4319

  • GSK Investigational Site

    Johannesburg, 2193

  • GSK Investigational Site

    Panorama / Cape Town, 7500

Other trials in South Africa

France3 sites

  • GSK Investigational Site

    Fort de France, 97261

  • GSK Investigational Site

    Paris, 75014

  • GSK Investigational Site

    Paris, 75018

Other trials in France

About this study

Official title: 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)

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).

Read the detailed description

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

Being tested
Placebo plus standard therapy, Belimumab 10 mg/kg plus standard therapy, Standard therapy
Keywords
Systemic Lupus Erythematosus, African Continental Ancestry Group, Autoimmune Disease, Antibodies, Minority Groups, Black Race, African Americans, SLE, Belimumab, Lupus
Medical subject headings
Lupus Erythematosus, Systemic, Autoimmune Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Placebo plus standard therapyBiological

    Placebo plus standard therapy

  • Belimumab 10 mg/kg plus standard therapyBiological

    Belimumab 10mg/kg plus standard therapy

  • Standard therapyDrug

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

Study groups in NCT01632241
Study groupRoleWhat they receive
Placebo plus standard therapyPlacebo 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.
Receives: Biological: Placebo plus standard therapy; Drug: Standard therapy
Belimumab 10 mg/kg plus standard therapyExperimentalBelimumab 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.
Receives: Biological: Belimumab 10 mg/kg plus standard therapy; Drug: Standard therapy

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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).

    Measured: Week 52

  2. 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.

    Measured: Week 24 of OL phase (Week 76)

  3. 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).

    Measured: Week 52 to Week 84

  4. 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).

    Measured: Week 52 to Week 84

  5. 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).

    Measured: Week 52 to Week 84

  6. 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).

    Measured: Week 52 to Week 84

  7. 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).

    Measured: Week 52 to Week 84

  8. 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).

    Measured: Week 52 to Week 84

  9. 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).

    Measured: Week 52 to Week 84

Secondary outcomes (12)

  1. 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).

    Measured: Week 52

  2. 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.

    Measured: Week 24 of OL phase (Week 76)

  3. 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.

    Measured: Up to 52 Weeks

  4. 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.

    Measured: Up to Week 24 of OL Phase (Week 76)

  5. 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).

    Measured: Baseline and Week 40 through Week 52

  6. 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.

    Measured: OL Baseline and Week 28 of OL Phase (Week 80)

  7. 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.

    Measured: Up to 52 Weeks

  8. 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.

    Measured: Up to 52 Weeks

  9. 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.

    Measured: Up to 52 Weeks

  10. 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.

    Measured: Up to 52 weeks

  11. 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.

    Measured: Up to 52 weeks

  12. 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.

    Measured: Up to 52 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Jul 2012 (estimated)
  2. Study start19 Feb 2013
  3. Primary completion18 Jun 2018
  4. Study completion28 Jan 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
503 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01632241
Sponsor's protocol ID
115471
Other IDs
HGS1006-C1112, 2011-005672-42, U1111-1139-9723
Acronym
EMBRACE
Status last verified
Aug 2021
First submitted
28 Jun 2012
Last updated
8 Sep 2021
Data monitoring committee
Yes
Individual data sharing
Yes: IPD for this study is available via the Clinical Study Data Request site

Publications

  • 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

  • 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.

    PubMed 39208825

  • 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.

    PubMed 39115551

  • 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.

    PubMed 38775637

  • 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.

    PubMed 38724182

  • 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.

    PubMed 34531304

  • 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.

    PubMed 34164944

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Belimumab 10 mg/kg plus standard therapy and Standard therapy in people with Systemic Lupus Erythematosus, run by Human Genome Sciences Inc., a GSK Company at 96 sites in 6 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 44 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Sep 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 96 sites in United States, Brazil, United Kingdom, Colombia, South Africa and 1 more country. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Jul 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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] (time frame: Week 52). The study lists 9 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01632241, which also lists 7 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2021.

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