A Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination With Rituximab to Adult Subjects With Systemic Lupus Erythematosus (SLE) - BLISS-BELIEVE
A Phase 3, Multi-Center, Randomized, Double-Blind, Placebo-Controlled, 104-Week Study to Evaluate the Efficacy and Safety of Belimumab Administered in Combination With Rituximab to Adult Subjects With Systemic Lupus Erythematosus (SLE)
2 other identifiers
interventional
292
11 countries
79
Brief Summary
The purpose of this study is to assess whether co-administration of belimumab and a single cycle of rituximab will optimize treatment with belimumab, which will result in improvements of clinical status with a favorable safety profile, by comparing subjects randomized to belimumab plus rituximab versus belimumab plus rituximab-placebo. Approximately 292 subjects will be randomized in a 1:2:1 ratio to 1 of 3 treatment arms; belimumab plus rituximab-placebo (Arm A, control), belimumab plus rituximab (Arm B, combination), or belimumab plus standard therapy (Arm C, reference). Belimumab will be administered as subcutaneous (SC) and rituximab-placebo or rituximab will be administered by intravenous (IV) infusions. The total duration of the study is for 104 weeks.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_3
Started Mar 2018
Typical duration for phase_3
79 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
October 13, 2017
CompletedFirst Posted
Study publicly available on registry
October 18, 2017
CompletedStudy Start
First participant enrolled
March 1, 2018
CompletedPrimary Completion
Last participant's last visit for primary outcome
May 29, 2020
CompletedStudy Completion
Last participant's last visit for all outcomes
July 7, 2021
CompletedResults Posted
Study results publicly available
April 25, 2022
CompletedFebruary 18, 2025
January 1, 2025
2.2 years
October 13, 2017
March 25, 2022
January 27, 2025
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Percentage of Participants With a State of Disease Control at Week 52
Percentage of participants with a state of disease control (Independent blinded assessor \[IBA\]) was defined as the percentage of participants with a Systemic Lupus Erythematosus Disease Activity Index 2000(SLEDAI-2K)score less than or equal to(\<=)2 achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of \<=5 mg/day at Week 52. SLEDAI-2K was a weighted, cumulative index for measuring systemic lupus erythematosus (SLE) disease activity in previous 10 days,consisting 24 individual items in which signs and symptoms, laboratory tests and physician's assessment for each item within each of 9 organ systems were given a weighted score(1 to 8 with higher score indicating increased activity)and summed if present at the time of visit or in preceding 10 days. The SLEDAI-2K score was sum of all 24 individual items from the SLEDAI-2K, ranges from 0(no symptoms) to 105(presence of all defined symptoms) with higher scores representing increased disease activity.
Week 52
Secondary Outcomes (27)
Percentage of Participants With a State of Clinical Remission at Week 64
Week 64
Percentage of Participants With a State of Disease Control at Week 104
Week 104
Percentage of Participants With a State of Disease Control by Visits
Weeks 12, 26, 40, 52, 64, 80 and 104
Percentage of Participants With a State of Clinical Remission by Visits
Weeks 64, 80 and 104
Percentage of Participants With a State of Complete Remission (CR) Sustained for at Least 24 Weeks During Week 52 to Week 104
Week 52 to Week 104
- +22 more secondary outcomes
Study Arms (3)
Belimumab + Placebo
PLACEBO COMPARATOREligible subjects will receive Belimumab 200 milligrams (mg) to be administered subcutaneously (SC) on Day 1 and then weekly (i.e., every 7 days) through Week 52. Subjects will also receive rituximab-placebo to be administered by intravenous (IV) infusions at Weeks 4 and 6 in double blind manner. Subjects will receive standard therapy excluding Immunosuppressants and including anti-malarials, non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids tapered down to prednisone equivalent of less than or equal to (\<=) 5 mg/day until Week 104. Subjects will not receive treatment after 52 weeks and will be in observation until Week 104.
Belimumab + Rituximab
EXPERIMENTALEligible subjects will receive Belimumab 200 mg to be administered SC on Day 1 and then weekly (i.e., every 7 days) through Week 52. Subjects will also receive rituximab 1000 mg to be administered by IV infusions at Weeks 4 and 6 in double blind manner. Subjects will receive standard therapy excluding Immunosuppressants and including anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of \<= 5 mg/day until Week 104. Subjects will not receive treatment after 52 weeks and will be in observation until Week 104.
Belimumab + Standard therapy
OTHEREligible subjects will receive open-label Belimumab 200 mg administered SC on Day 1 and then weekly (i.e., every 7 days) until Week 104. Subjects will also receive standard therapy including immunosuppressant, anti-malarials, NSAIDs, and/or corticosteroids tapered down to prednisone equivalent of \<= 5 mg/day until Week 104.
Interventions
Belimumab will be administered as SC injection once weekly via autoinjector in thigh or abdomen
Rituximab will be administered as IV infusion of 1000mg at Week 4 and Week 6
Saline will be administered as IV infusions at Week 4 and Week 6
Standard therapy will contain stable SLE medications including immunosuppressant to be administered from baseline through Week 104.
Standard therapy excluding Immunosuppressant will contain anti-malarials, NSAIDs, and/or corticosteroids with prednisone dose equivalent to \<= 5 mg/day will administered through Week 104.
Steroid taper will include prednisone doses equivalent to =\< 5 mg/day in all Arms through Week 104.
Eligibility Criteria
You may qualify if:
- Subjects must be \>=18 years of age at the time of signing the informed consent.
- Subjects who have clinical diagnosis of SLE based on 4 or more of the 11 American College of Rheumatology (ACR) criteria.
- Subjects who have a screening SLEDAI-2K score \>=6 (This refers to the total score. Serological activity, i.e., anti-double stranded deoxyribonucleic acid \[dsDNA\]) positivity and/or hypocomplementemia is not required to be present in SLEDAI-2K assessment, but are scored if present).
- Subjects who have unequivocally positive autoantibody test results defined as an anti-nuclear (ANA) titer \>=1:80 and/or a positive anti-dsDNA (\>=30 International Units per milliliter \[IU/mL\]) serum antibody test from 2 independent time points as follows: Positive test results from 2 independent time points within the study screening period. Screening results must be based on the study's central laboratory results. Or, one positive historical test result and 1 positive test result during the screening period.
- Subjects who are on a stable SLE treatment regimen consisting of any of these medications (alone or in combination) for a period of at least 30 days prior to Day 1 (i.e. day of first dose of study treatment) with the exception that switching one agent for another of the same class for tolerability or availability reasons, which will be allowed within 30 days of Day 1: Corticosteroids (prednisone or prednisone equivalent); For those subjects on alternating daily doses of steroids, use the average of 2 daily doses to calculate the average daily steroid dose; Any immunosuppressant or immunomodulatory agents including methotrexate, azathioprine, leflunomide, mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, and mycophenolate sodium), calcineurin inhibitors (example \[e.g.\] tacrolimus, cyclosporine), sirolimus, oral cyclophosphamide, 6-mercaptopurine, mizoribine, or thalidomide; Anti-malarials (e.g., hydroxychloroquine, chloroquine, quinacrine); Non steroidal anti-inflammatory drugs (NSAIDs).
- Male and/or female. A female subject is eligible to participate if she is not pregnant not breastfeeding, and at least one of the these conditions applies: Not a woman of childbearing potential (WOCBP) or A WOCBP who agrees to follow the contraceptive guidance during the treatment period and for at least 16 weeks after the last dose of belimumab, or at least 12 months after the last dose of rituximab or rituximab-placebo.
- Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the informed consent form (ICF) and in this protocol.
You may not qualify if:
- Symptomatic herpes zoster within 3 months prior to screening.
- Evidence of active or latent tuberculosis (TB). Documentation may include medical history and examination, chest X-rays (posterior, anterior, and lateral), and TB testing: either a positive tuberculin skin test (TST; defined as a skin induration ≥5 mm at 48 to 72 hours, regardless of Baccillus Calmette-Guerin (BCG) or other vaccination history) or a positive (not indeterminate) QuantiFERON-TB Gold Plus test.
- Significant allergies to humanized monoclonal antibodies.
- History of hypersensitivity to belimumab and/or rituximab or known to have titers of human anti-mouse antibody or history of hypersensitivity reactions when treated with other diagnostic or therapeutic monoclonal antibodies.
- Lymphoma, leukemia, or any malignancy within the past 5 years (yrs) except for basal cell or squamous epithelial carcinomas of the skin that have been resected with no evidence of metastatic disease for 3 yrs.
- Alanine transferase (ALT) greater than 2 times upper limit of normal (ULN).
- Bilirubin greater than 1.5 times ULN (isolated bilirubin greater than 1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin less than 35%).
- Immunoglobulin A (IgA) deficiency (IgA level less than 10 milligram per deciliter \[mg/dL\]).
- Immunoglobulin G (IgG) less than 250 mg/dL. For Germany only, IgG less than 400mg/dL.
- Neutrophils less than 1.5 times 10\^9.
- Current unstable liver or biliary disease per investigator assessment defined by the presence of ascites, encephalopathy, coagulopathy, hypoalbuminemia, esophageal or gastric varices, persistent jaundice, or cirrhosis.
- Severe heart failure (New York Heart Association Class IV) or other severe, uncontrolled cardiac disease.
- QT interval corrected (QTc) greater than 450 millisecond (msec) or QTc greater than 480 msec in subjects with bundle branch block.
- Subjects who have a history of a major organ transplant (e.g., heart, lung, kidney, liver) or hematopoietic stem cell/marrow transplant.
- Subjects who have clinical evidence of significant unstable or uncontrolled acute or chronic diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic, gastrointestinal, hepatic, renal, neurological, psychiatric, malignancy, or infectious diseases) which, in the opinion of the principal investigator, could confound the results of the study or put the subject at undue risk.
- +17 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- GlaxoSmithKlinelead
Study Sites (79)
GSK Investigational Site
Birmingham, Alabama, 35294, United States
GSK Investigational Site
La Mesa, California, 92020, United States
GSK Investigational Site
San Leandro, California, 94578, United States
GSK Investigational Site
Upland, California, 91786, United States
GSK Investigational Site
Denver, Colorado, 80230, United States
GSK Investigational Site
Aventura, Florida, 33180, United States
GSK Investigational Site
Miami, Florida, 33136, United States
GSK Investigational Site
Orlando, Florida, 32806-6264, United States
GSK Investigational Site
Tamarac, Florida, 33321, United States
GSK Investigational Site
Tampa, Florida, 33613, United States
GSK Investigational Site
Tampa, Florida, 33614, United States
GSK Investigational Site
Ann Arbor, Michigan, 48109-5542, United States
GSK Investigational Site
Brighton, Michigan, 48116, United States
GSK Investigational Site
Lansing, Michigan, 48910, United States
GSK Investigational Site
Lansing, Michigan, 48917, United States
GSK Investigational Site
Las Cruces, New Mexico, 88011, 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, 10032, United States
GSK Investigational Site
Charlotte, North Carolina, 28204, United States
GSK Investigational Site
Vandalia, Ohio, 45377, United States
GSK Investigational Site
Oklahoma City, Oklahoma, 73102, United States
GSK Investigational Site
Pittsburgh, Pennsylvania, 15224, United States
GSK Investigational Site
Summerville, South Carolina, 29486, United States
GSK Investigational Site
Austin, Texas, 78731, United States
GSK Investigational Site
League City, Texas, 77573, United States
GSK Investigational Site
Spokane, Washington, 99204, United States
GSK Investigational Site
Glendale, Wisconsin, 53217, United States
GSK Investigational Site
Ciudad Autonoma de Buenos Aires, Buenos Aires, C1046AAQ, Argentina
GSK Investigational Site
La Plata, Buenos Aires, B1904CFH,, Argentina
GSK Investigational Site
San Miguel de TucumĂ¡n, TucumĂ¡n Province, T4000AXL, Argentina
GSK Investigational Site
Salvador, Estado de Bahia, 40.150-150, Brazil
GSK Investigational Site
CuiabĂ¡, Mato Grosso, 78043-142, Brazil
GSK Investigational Site
Juiz de Fora, Minas Gerais, 36010-570, Brazil
GSK Investigational Site
SĂ£o JosĂ© do Rio Preto, SĂ£o Paulo, 15090-000, Brazil
GSK Investigational Site
Hamilton, Ontario, L8S 4K1, Canada
GSK Investigational Site
Toronto, Ontario, M5T 2S8, Canada
GSK Investigational Site
Trois-Rivières, Quebec, G8Z 1Y2, Canada
GSK Investigational Site
Saskatoon, Saskatchewan, S7K 0H6, Canada
GSK Investigational Site
Brest, 29609, France
GSK Investigational Site
Lille, 59037, France
GSK Investigational Site
Paris, 75013, France
GSK Investigational Site
Paris, 75571, France
GSK Investigational Site
Pessac, 33604, France
GSK Investigational Site
Strasbourg, 67091, France
GSK Investigational Site
Hanover, Lower Saxony, 30625, Germany
GSK Investigational Site
Kiel, Schleswig-Holstein, 24105, Germany
GSK Investigational Site
Frankfurt, 60590, Germany
GSK Investigational Site
Zapopan, Jalisco, 45070, Mexico
GSK Investigational Site
MĂ©rida, YucatĂ¡n, 97070, Mexico
GSK Investigational Site
Amersfoort, 3813 TZ, Netherlands
GSK Investigational Site
Groningen, 9713 GZ, Netherlands
GSK Investigational Site
Leiden, 2333 ZA, Netherlands
GSK Investigational Site
The Hague, 2545 AA, Netherlands
GSK Investigational Site
Utrecht, 3584 CX, Netherlands
GSK Investigational Site
Chelyabinsk, 454076, Russia
GSK Investigational Site
Kazan', 420097, Russia
GSK Investigational Site
Kemerovo, 650066, Russia
GSK Investigational Site
Moscow, 119435, Russia
GSK Investigational Site
Novosibirsk, 630117, Russia
GSK Investigational Site
Omsk, 644111, Russia
GSK Investigational Site
Petrozavodsk, 185019, Russia
GSK Investigational Site
Ryazan, 390026, Russia
GSK Investigational Site
Saint Petersburg, 190068, Russia
GSK Investigational Site
Ufa, 450005, Russia
GSK Investigational Site
Ulyanovsk, 432063, Russia
GSK Investigational Site
Yaroslavl, 150030, Russia
GSK Investigational Site
Daegu, 700-721, South Korea
GSK Investigational Site
Gwangju, 501-757, South Korea
GSK Investigational Site
Incheon, 400-711, South Korea
GSK Investigational Site
Seoul, 03080, South Korea
GSK Investigational Site
Seoul, 133-792, South Korea
GSK Investigational Site
Seoul, 137-701, South Korea
GSK Investigational Site
Suwon, 443-380, South Korea
GSK Investigational Site
Badalona, 08916, Spain
GSK Investigational Site
Barcelona, 08035, Spain
GSK Investigational Site
Valencia, 46017, Spain
GSK Investigational Site
Valladolid, 47010, Spain
GSK Investigational Site
Vigo (Pontevedra), 36214, Spain
Related Publications (5)
Aranow C, Allaart CF, Amoura Z, Bruce IN, Cagnoli PC, Chatham WW, Clark KL, Furie R, Groark J, Urowitz MB, van Vollenhoven R, Daniels M, Fox NL, Gregan YI, Henderson RB, van Maurik A, Ocran-Appiah JC, Oldham M, Roth DA, Shanahan D, Tak PP, Teng YO. Efficacy and safety of sequential therapy with subcutaneous belimumab and one cycle of rituximab in patients with systemic lupus erythematosus: the phase 3, randomised, placebo-controlled BLISS-BELIEVE study. Ann Rheum Dis. 2024 Oct 21;83(11):1502-1512. doi: 10.1136/ard-2024-225686.
PMID: 39159997BACKGROUNDArends 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: 38775637DERIVEDHannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
PMID: 33687069DERIVEDTeng YKO, Bruce IN, Diamond B, Furie RA, van Vollenhoven RF, Gordon D, Groark J, Henderson RB, Oldham M, Tak PP. Phase III, multicentre, randomised, double-blind, placebo-controlled, 104-week study of subcutaneous belimumab administered in combination with rituximab in adults with systemic lupus erythematosus (SLE): BLISS-BELIEVE study protocol. BMJ Open. 2019 Mar 20;9(3):e025687. doi: 10.1136/bmjopen-2018-025687.
PMID: 30898822DERIVEDParodis I, Lopez Benavides AH, Zickert A, Pettersson S, Moller S, Welin Henriksson E, Voss A, Gunnarsson I. The Impact of Belimumab and Rituximab on Health-Related Quality of Life in Patients With Systemic Lupus Erythematosus. Arthritis Care Res (Hoboken). 2019 Jun;71(6):811-821. doi: 10.1002/acr.23718.
PMID: 30055091DERIVED
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 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
- Expanded Access
- Yes
Study Record Dates
First Submitted
October 13, 2017
First Posted
October 18, 2017
Study Start
March 1, 2018
Primary Completion
May 29, 2020
Study Completion
July 7, 2021
Last Updated
February 18, 2025
Results First Posted
April 25, 2022
Record last verified: 2025-01
Data Sharing
- IPD Sharing
- Will share
- Shared Documents
- STUDY PROTOCOL, SAP, ICF, CSR
- Time Frame
- Anonymized IPD is made available within 6 months of publication of primary, key secondary and safety results for studies in product with approved indication(s) or terminated asset(s) across all indications.
- Access Criteria
- Anonymized IPD is shared with researchers whose proposals are approved by an 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 may be granted, when justified, for up to 6 months.
GSK will assess requests from qualified researchers for anonymized individual patient-level data (IPD) and related study documents. Data sharing is subject to certain criteria, conditions, and exceptions. For further information, refer to https://www.gsk-studyregister.com/About\_GSK\_Patient\_Level\_Data\_Sharing\_Final\_13July2023.pdf