Last updated: 01/27/2025 05:30:15
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
EudraCT ID
EU CT Number
Not applicable
Trial status
Study complete
Study complete
Trial overview
Official title: 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)
Trial description: 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.
Primary purpose:
Treatment
Trial design:
Parallel Assignment
Masking:
Triple (Participant, Investigator, Outcomes Assessor)
Allocation:
Randomized
Primary outcomes:
Proportion of subjects with a state of disease control at week 52
Timeframe: Week 52
Secondary outcomes:
Proportion of subjects with a state of clinical remission at Week 64 (Major)
Timeframe: Week 64
Proportion of subjects with a state of disease control at Week 104 (Major)
Timeframe: Week 104
Proportion of subjects with a state of disease control at each visit
Timeframe: Up to Week 104
Proportion of subjects with a state of clinical remission at each visit
Timeframe: Up to Week 104
Proportion of subjects with a state of complete remission sustained for at least 24 weeks
Timeframe: Up to Week 104
Proportion of subjects with a state of clinical remission at Week 104
Timeframe: Week 104
Proportion of subjects with a state of complete remission at each visit
Timeframe: Up to Week 104
Time to first severe flare (Measured by Modified SLE flare index)
Timeframe: Up to Week 104
Time to first flare (Measured by Modified SLE flare index)
Timeframe: Up to Week 104
Time to disease control sustained Week 104
Timeframe: Week 104
Time to clinical remission sustained at Week 104
Timeframe: Week 104
Duration of disease control at each visit
Timeframe: Up to Week 104
Duration of clinical remission
Timeframe: Up to Week 104
Change from baseline in SLEDAI-2K score by visit
Timeframe: Baseline and up to Week 104
Proportion of subjects with SLEDAI-2K organ improvement at each visit
Timeframe: Up to Week 104
Proportion of subjects with SLEDAI-2K organ worsening at each visit
Timeframe: Up to Week 104
Change from Baseline in Physician Global Assessment (PGA) at each visit
Timeframe: Baseline and up to Week 104
Proportion of subjects with Systemic Lupus International Collaborating Clinics (SLICC) damage index worsening compared with baseline at Week 52 and Week 104
Timeframe: Baseline, Week 52 and Week 104
Proportion of subjects that meet the Lupus Low Disease Activity State (LLDAS) response criteria by visit
Timeframe: Up to Week 104
Proportion of subjects with Adverse events (AE), serious AEs (SAE) and AEs of special interest (AESIs)
Timeframe: Up to Week 104
Change from Baseline in Patient Global Assessment (PtGA) at each visit
Timeframe: Baseline and up to Week 104
Change from Baseline in Lupus Quality of Life (LupusQoL) domain summary scores (8 domains) at each visit
Timeframe: Baseline and up to Week 104
Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at each visit
Timeframe: Baseline and up to Week 104
Proportion of subjects with improvement in FACIT-Fatigue score exceeding the Minimal Clinically Important Difference (MCID, >=4) at each visit
Timeframe: Up to Week 104
Proportion of participants with a state of disease control at each visit; using the Principal Investigators assessment of SLEDAI-2K
Timeframe: Up to Week 104
Proportion of participants with a state of clinical remission at each visit; using the Principal Investigators assessment of SLEDAI-2K
Timeframe: Up to Week 104
Interventions:
Enrollment:
292
Primary completion date:
2020-29-05
Observational study model:
Not applicable
Time perspective:
Not applicable
Clinical publications:
Cynthia Aranow, Cornelia F Allaart, Zahir Amoura, Ian N Bruce, Patricia C Cagnoli, Walter W Chatham, Kenneth L Clark, Richard Furie, James Groark, Murray B Urowitz, Ronald van Vollenhoven, Mark Daniels, Norma Lynn Fox, Yun Irene Gregan, Robert B Henderson, André van Maurik, Josephine C Ocran-Appiah, Mary Oldham, David A Roth, Don Shanahan, Paul P Tak, Yk Onno Teng. 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. Annals of the rheumatic diseases. 2024-Aug-19; doi:10.1136/ard-2024-225686 http://dx.doi.org/ard-2024-22568610.1136/ard-2024-225686
PMID: 39159997
DOI: 10.1136/ard-2024-225686
Medical condition
Systemic Lupus Erythematosus
Product
belimumab, rituximab
Collaborators
Not applicable
Study date(s)
March 2018 to July 2021
Type
Interventional
Phase
3
Participation criteria
Sex
Female & Male
Age
18+ years
Accepts healthy volunteers
No
- 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.
- 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.
Inclusion and exclusion criteria
Inclusion criteria:
- 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.
Exclusion criteria:
- 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.
- Subjects who have an acute or chronic infection requiring management as : Currently on any suppressive therapy for a chronic infection such as pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical mycobacteria); Hospitalization for treatment of infection within 60 days of Day 1; subjects who had infection requiring treatment with parenteral (IV or intramuscular [IM]) antibiotics (antibacterials, antivirals, anti-fungals, or anti-parasitic agents) within 60 days of Day 1. Prophylactic anti-infective treatment is allowed.
- Subjects who have severe lupus kidney disease (defined by proteinuria greater than 6 gram (g)/24 hours or equivalent using spot urine protein to creatinine ratio, or serum creatinine greater than 2.5 mg/dL), or have severe active nephritis requiring induction therapy not permitted by protocol (e.g., IV cyclophosphamide), or have required hemodialysis or high dose prednisone or equivalent (greater than 100 mg/day) within 90 days of Day 1.
- Subjects who 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 1.
- Subjects who have a planned surgical procedure, laboratory abnormality, or condition (e.g., poor venous access) that, in the opinion of the principal investigator, makes the subject unsuitable for the study.
- 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 Columbia-Suicide Severity Rating Scale (C-SSRS) in the last 2 months or who, in the investigator's opinion, pose a significant suicide risk.
- Subjects who have a history of an anaphylaxis reaction to parenteral administration of contrast agents, human or murine proteins, or monoclonal antibodies.
- Subjects who have received live vaccine(s) within 1 month prior to screening, or plans to receive such vaccines during the screening period or during the study.
- Subjects who have received any of the these prior/concomitant therapy within 364 days of Day 1: Belimumab; Rituximab; Abatacept; Any B cell targeted therapy (anti-cluster of differentiation-20 [CD] agents other than rituximab, anti CD22 [epratuzumab], anti-CD52 [alemtuzumab], BLyS-receptor fusion protein [BR3], Trans-membrane activator and calcium-modulator and cytophilin ligand interactor [TACI] Fc, anti B-cell activating factor [BAFF] (LY2127399), anti-Interferon alpha agents or anti-BLyS other than belimumab); A biologic investigational agent other than B cell targeted therapy (e.g., abetimus sodium, anti CD40L antibody [BG9588/ IDEC 1311]). (Investigational agent applies to any drug not approved for sale in the country in which it is being used).
- Subjects who have required 3 or more courses of systemic corticosteroids within 364 days of Day 1. (Topical or inhaled steroids are permitted).
- Subjects who have received any of these within 90 days of Day 1: Anti- Tumor Necrosis Factor (Anti-TNF) therapy (e.g., adalimumab, etanercept, infliximab); Interleukin-1 receptor antagonist (anakinra); Intravenous immunoglobulin (IVIG); High dose prednisone or equivalent (greater than 100 mg/day); Plasmapheresis.
- Subjects who have received any of the these within 60 days of Day 1: A non-biologic investigational agent (Investigational agent applies to any drug not approved for sale in the country in which it is being used); IV cyclophosphamide and, for Germany only, oral cyclophosphamide; Any steroid injection (e.g., intramuscular [IM], intraarticular, or IV).
- Positive immunodeficiency virus (HIV) antibody test.
- Positive serology for Hepatitis B (HB), defined as HB surface antigen positive (HBsAg+) OR HB core antibody positive (HBcAb+).
- Positive Hepatitis C (HCV) antibody test.
- Subjects who have current drug or alcohol dependence, or a history of drug or alcohol abuse or dependence within 364 days prior to Day 1.
- Sensitivity to any of the study treatments, or components thereof, or drug or other allergy that, in the opinion of the investigator, contraindicates participation in the study.
- Unable to administer study treatment (belimumab) by SC injection and has no other reliable resource to administer the injection.
Trial location(s)
Location
GSK Investigational Site
Ann Arbor, Michigan, United States, 48109-5542
Status
Study Complete
Location
GSK Investigational Site
Aventura, Florida, United States, 33180
Status
Study Complete
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Study documents
Study report synopsis
Available language(s): English
Protocol
Available language(s): English
Statistical analysis plan
Available language(s): English
If you wish to request for full study report, please contact - [email protected]
Results overview
Results posted on ClinicalTrials.gov
Recruitment status
Study complete
Actual primary completion date
2020-29-05
Actual study completion date
2021-07-07
Plain language summaries
Summary of results in plain language
Available language(s): English, Dutch, French (Canadian), French, German, Korean, Portuguese (Brazil), Russian, Spanish (Argentina), Spanish (Mexico), Spanish, Spanish (United States)
To view plain language summaries on trialsummaries.com click here.
Additional information about the trial
Additional information
Not applicable
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