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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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03312907
Recruitment Status : Active, not recruiting
First Posted : October 18, 2017
Last Update Posted : July 8, 2020
Sponsor:
Information provided by (Responsible Party):
GlaxoSmithKline

Tracking Information
First Submitted Date  ICMJE October 13, 2017
First Posted Date  ICMJE October 18, 2017
Last Update Posted Date July 8, 2020
Actual Study Start Date  ICMJE March 1, 2018
Actual Primary Completion Date May 29, 2020   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 7, 2020)
Proportion of subjects with a state of disease control at week 52 [ Time Frame: Week 52 ]
State of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 milligram per day (mg/day). The SLEDAI-2K is a clinical index for measuring SLE disease activity.
Original Primary Outcome Measures  ICMJE
 (submitted: October 13, 2017)
Proportion of subjects with a state of disease control at week 52 [ Time Frame: Week 52 ]
State of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 milligram per day (mg/day). The SLEDAI-2K is a clinical index for measuring SLE disease activity
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 7, 2020)
  • Proportion of subjects with a state of clinical remission at Week 64 (Major) [ Time Frame: Week 64 ]
    State of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day. Serological activity score, i.e., anti-dsDNA positivity, and/or hypocomplementemia, is excluded from the Clinical SLEDAI-2K endpoint.
  • Proportion of subjects with a state of disease control at Week 104 (Major) [ Time Frame: Week 104 ]
    State of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day.
  • Proportion of subjects with a state of disease control at each visit [ Time Frame: Up to Week 104 ]
    State of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day.
  • Proportion of subjects with a state of clinical remission at each visit [ Time Frame: Up to Week 104 ]
    State of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Proportion of subjects with a state of complete remission sustained for at least 24 weeks [ Time Frame: Up to Week 104 ]
    State of complete remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day that should at least sustain for 24 weeks.
  • Proportion of subjects with a state of clinical remission at Week 104 [ Time Frame: Week 104 ]
    State of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Proportion of subjects with a state of complete remission at each visit [ Time Frame: Up to Week 104 ]
    State of complete remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Time to first severe flare (Measured by Modified SLE flare index) [ Time Frame: Up to Week 104 ]
    The SLE flare index is categorized as "mild/moderate" or "severe" flare.
  • Time to first flare (Measured by Modified SLE flare index) [ Time Frame: Up to Week 104 ]
    SLE flare indicates an increase in SLE disease activity. SLE flare index identifies whether a subject has experienced mild/moderate or severe flare.
  • Time to disease control sustained Week 104 [ Time Frame: Week 104 ]
    Time to disease control sustained defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day.
  • Time to clinical remission sustained at Week 104 [ Time Frame: Week 104 ]
    Time to clinical remission sustained defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Duration of disease control at each visit [ Time Frame: Up to Week 104 ]
    Duration of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day.
  • Duration of clinical remission [ Time Frame: Up to Week 104 ]
    Duration of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Change from baseline in SLEDAI-2K score by visit [ Time Frame: Baseline and up to Week 104 ]
    The SLEDAI-2K is a clinical index for measuring SLE disease activity.
  • Proportion of subjects with SLEDAI-2K organ improvement at each visit [ Time Frame: Up to Week 104 ]
    The SLEDAI-2K is a clinical index for measuring SLE disease activity.
  • Proportion of subjects with SLEDAI-2K organ worsening at each visit [ Time Frame: Up to Week 104 ]
    The SLEDAI-2K is a clinical index for measuring SLE disease activity.
  • Change from Baseline in Physician Global Assessment (PGA) at each visit [ Time Frame: Baseline and up to Week 104 ]
    PGA is a physician-reported visual analogue scale that provides an overall measure of the subject's current disease activity.
  • Proportion of subjects with Systemic Lupus International Collaborating Clinics (SLICC) damage index worsening compared with baseline at Week 52 and Week 104 [ Time Frame: Baseline, Week 52 and Week 104 ]
    The SLICC-American College of Rheumatology (ACR) Damage Index measures irreversible changes occurring since the diagnosis of SLE.
  • Proportion of subjects that meet the Lupus Low Disease Activity State (LLDAS) response criteria by visit [ Time Frame: Up to Week 104 ]
    The LLDAS incorporates multiple measures of disease activity, such as :SLEDAI-2K <=4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity; no new features of lupus disease activity compared with the previous assessment; PGA (scale 0-3), <=1; current prednisolone (or equivalent) dose <=7.5 mg daily; well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents.
  • Proportion of subjects with Adverse events (AE), serious AEs (SAE) and AEs of special interest (AESIs) [ Time Frame: Up to Week 104 ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose may result in death, life-threatening, requires in-subject hospitalization or prolongation of hospitalization, results in persistent disability or incapacity, or causes to congenital anomaly or birth defect. AESIs included changes in laboratory parameters and immunogenicity (both anti-belimumab and anti-rituximab antibodies will be assessed).
  • Change from Baseline in Patient Global Assessment (PtGA) at each visit [ Time Frame: Baseline and up to Week 104 ]
    In PtGA subjects will be asked to rate the severity of their SLE between 0 (Very Well) and 10 (Very Poor) that best represents their current level of disease activity.
  • Change from Baseline in LupusQoL domain summary scores (8 domains) at each visit [ Time Frame: Baseline and up to Week 104 ]
    The LupusQoL is a valid SLE specific health related qualify of life (HRQOL) instrument with 34 questions across 8 domains. Questions are related to the subject experience in the prior 4 weeks, and a 5-point Likert response format is used, ranging from 0 (all of the time) to 4 (never). A LupusQoL summary score for each domain is reported on a 0 to 100 scale, with greater values indicating better HRQOL.
  • Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at each visit [ Time Frame: Baseline and up to Week 104 ]
    FACIT-Fatigue scale includes 13-fatigue related questions for subject rates fatigue during the previous 7 days, yielding an overall score 0 to 52, with lowest score representing worst fatigue.
  • Proportion of subjects with improvement in FACIT-Fatigue score exceeding the Minimal Clinically Important Difference (MCID, >=4) at each visit [ Time Frame: Up to Week 104 ]
    FACIT-Fatigue scale includes 13-fatigue related questions for subject rates fatigue during the previous 7 days, yielding an overall score 0 to 52, with lowest score representing worst fatigue.
  • Proportion of participants with a state of disease control at each visit; using the Principal Investigators assessment of SLEDAI-2K [ Time Frame: Up to Week 104 ]
    State of disease control is defined as a SLEDAI-2K score <=2, achieved without immunosuppressants and with corticosteroids at a prednisone equivalent dose of <=5 mg/day, by visit; using the Principal Investigators assessment of SLEDAI-2K. The SLEDAI-2K is a clinical index for measuring SLE disease activity.
  • Proportion of participants with a state of clinical remission at each visit; using the Principal Investigators assessment of SLEDAI-2K [ Time Frame: Up to Week 104 ]
    State of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day by visit; using the Principal Investigators assessment of SLEDAI-2K. Serological activity score, i.e. anti-dsDNA positivity and/or hypocomplementemia, is excluded from the Clinical SLEDAI-2K endpoint.
Original Secondary Outcome Measures  ICMJE
 (submitted: October 13, 2017)
  • Proportion of subjects with a state of clinical remission at Week 64 (Major) [ Time Frame: Week 64 ]
    State of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day. Serological activity score, i.e., anti-dsDNA positivity, and/or hypocomplementemia, is excluded from the Clinical SLEDAI-2K endpoint
  • Proportion of subjects with a state of disease control at Week 104 (Major) [ Time Frame: Week 104 ]
    State of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day.
  • Proportion of subjects with a state of disease control at each visit [ Time Frame: Up to Week 104 ]
    State of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day.
  • Proportion of subjects with a state of clinical remission at each visit [ Time Frame: Up to Week 104 ]
    State of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Proportion of subjects with a state of complete remission sustained for at least 24 weeks [ Time Frame: Up to Week 104 ]
    State of complete remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day that should at least sustain for 24 weeks
  • Proportion of subjects with a state of clinical remission at Week 104 [ Time Frame: Week 104 ]
    State of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Proportion of subjects with a state of complete remission at each visit [ Time Frame: Up to Week 104 ]
    State of complete remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day
  • Time to first severe flare (Measured by Modified SLE flare index) [ Time Frame: Up to Week 104 ]
    The SLE flare index is categorized as "mild/moderate" or "severe" flare.
  • Time to first flare (Measured by Modified SLE flare index) [ Time Frame: Up to Week 104 ]
    SLE flare indicates an increase in SLE disease activity. SLE flare index identifies whether a subject has experienced mild/moderate or severe flare
  • Time to disease control sustained Week 104 [ Time Frame: Week 104 ]
    Time to disease control sustained defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day
  • Time to clinical remission sustained at Week 64 [ Time Frame: Week 64 ]
    Time to clinical remission sustained defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Duration of disease control at each visit [ Time Frame: Up to Week 104 ]
    Duration of disease control defined as SLEDAI-2K score <=2, achieved without the use of immunosuppressant and with corticosteroids at a prednisone equivalent dose of <=5 mg/day
  • Duration of clinical remission [ Time Frame: Up to Week 104 ]
    Duration of clinical remission defined as Clinical SLEDAI-2K score =0 achieved without immunosuppressant and with corticosteroids at a prednisone equivalent dose of 0 mg/day.
  • Change from baseline in SLEDAI-2K score by visit [ Time Frame: Baseline and up to Week 104 ]
    The SLEDAI-2K is a clinical index for measuring SLE disease activity.
  • Proportion of subjects with SLEDAI-2K organ improvement at each visit [ Time Frame: Up to Week 104 ]
    The SLEDAI-2K is a clinical index for measuring SLE disease activity
  • Proportion of subjects with SLEDAI-2K organ worsening at each visit [ Time Frame: Up to Week 104 ]
    The SLEDAI-2K is a clinical index for measuring SLE disease activity
  • Change from Baseline in Physician Global Assessment (PGA) at each visit [ Time Frame: Baseline and up to Week 104 ]
    PGA is a physician-reported visual analogue scale that provides an overall measure of the subject's current disease activity.
  • Proportion of subjects with Systemic Lupus International Collaborating Clinics (SLICC) damage index worsening compared with baseline at Week 52 and Week 104 [ Time Frame: Baseline and up to Week 104 ]
    The SLICC-American College of Rheumatology (ACR) Damage Index measures irreversible changes occurring since the diagnosis of SLE.
  • Proportion of subjects that meet the Lupus Low Disease Activity State (LLDAS) response criteria by visit [ Time Frame: Up to Week 104 ]
    The LLDAS incorporates multiple measures of disease activity, such as :SLEDAI-2K <=4, with no activity in major organ systems (renal, CNS, cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal activity; no new features of lupus disease activity compared with the previous assessment; PGA (scale 0-3), <=1; current prednisolone (or equivalent) dose <=7.5 mg daily; well tolerated standard maintenance doses of immunosuppressive drugs and approved biological agents.
  • Proportion of subjects with Adverse events (AE), serious AEs (SAE) and AEs of special interest (AESIs) [ Time Frame: Up to Week 104 ]
    An AE is any untoward medical occurrence in a clinical study subject, temporally associated with the use of a study treatment, whether or not considered related to the study treatment. A SAE is defined as any untoward medical occurrence that, at any dose may result in death, life-threatening, requires in-subject hospitalization or prolongation of hospitalization, results in persistent disability or incapacity, or causes to congenital anomaly or birth defect. AESIs included changes in laboratory parameters and immunogenicity (both anti-belimumab and anti-rituximab antibodies will be assessed).
  • Change from Baseline in Patient Global Assessment (PtGA) at each visit [ Time Frame: Baseline and up to Week 104 ]
    In PtGA subjects will be asked to rate the severity of their SLE between 0 (Very Well) and 10 (Very Poor) that best represents their current level of disease activity.
  • Change from Baseline in LupusQoL domain summary scores (8 domains) at each visit [ Time Frame: Baseline and up to Week 104 ]
    The LupusQoL is a valid SLE specific health related qualify of life (HRQOL) instrument with 34 questions across 8 domains. Questions are related to the subject experience in the prior 4 weeks, and a 5-point Likert response format is used, ranging from 0 (all of the time) to 4 (never). A LupusQoL summary score for each domain is reported on a 0 to 100 scale, with greater values indicating better HRQOL
  • Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at each visit [ Time Frame: Baseline and up to Week 104 ]
    FACIT-Fatigue scale includes 13-fatigue related questions for subject rates fatigue during the previous 7 days, yielding an overall score 0 to 52, with lowest score representing worst fatigue.
  • Proportion of subjects with improvement in FACIT-Fatigue score exceeding the Minimal Clinically Important Difference (MCID, >=4) at each visit [ Time Frame: Up to Week 104 ]
    FACIT-Fatigue scale includes 13-fatigue related questions for subject rates fatigue during the previous 7 days, yielding an overall score 0 to 52, with lowest score representing worst fatigue.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE 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
Official Title  ICMJE 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)
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 280 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). Arm A and Arm B will be double-blinded and Arm C will be open-labeled. The open-label arm will provide a qualitative reference to standard therapy. 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. Double-blinded phase will be for 52-weeks with subjects from Arm A and B who cannot tolerate discontinuation of immunosuppressant or taper of corticosteroids. Subjects in Arm C will continue to receive belimumab SC and their stable immunosuppressant during Weeks 53 through 104.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Condition  ICMJE Systemic Lupus Erythematosus
Intervention  ICMJE
  • Drug: Belimumab
    Belimumab will be administered as SC injection once weekly via autoinjector in thigh or abdomen
  • Drug: Rituximab
    Rituximab will be administered as IV infusion of 1000mg at Week 4 and Week 6
  • Drug: Rituximab-placebo
    Saline will be administered as IV infusions at Week 4 and Week 6
  • Drug: Standard therapy (Including Immunosuppressants)
    Standard therapy will contain stable SLE medications including immunosuppressant to be administered from baseline through Week 104.
  • Drug: Standard therapy (Excluding Immunosuppressants)
    Standard therapy excluding Immunosuppressant will contain anti-malarials, NSAIDs, and/or corticosteroids with presdnisone dose equivalent to <= 5 mg/day will administered by subjects in Arm A and B through Week 104.
  • Drug: Steroid Taper
    Steroid taper will include prednisone doses equivalent to =< 5 mg/day in all Arms through Week 104.
Study Arms  ICMJE
  • Placebo Comparator: Arm A (Control) 0-52 Weeks
    Eligible subjects will receive belimumab plus rituximab-placebo. No immunosuppressant medications are allowed after week 4. Subjects may receive standard of care therapy which may include anti-malarials, Non-steroidal anti-inflammatory drugs (NSAIDs), and/or corticosteroids with presdnisone dose equivalent to <= 5 mg/day through Week 52. Doses of corticosteroids taper shall be reduced at Week 12 and reach a prednisone equivalent dose of =< 5 mg/day by Week 26 which may be maintained throughout the study. Subjects will stop receiving Belimumab injections after week 52.
    Interventions:
    • Drug: Belimumab
    • Drug: Rituximab-placebo
    • Drug: Standard therapy (Excluding Immunosuppressants)
    • Drug: Steroid Taper
  • Placebo Comparator: Arm A (Control) 53-104 Weeks
    Eligible subjects may receive standard of care therapy which may include anti-malarials, NSAIDs, and/or corticosteroids with presdnisone dose equivalent to <= 5 mg/day in Week 53 through 104. Doses of corticosteroids taper shall be reduced at Week 12 and reach a prednisone equivalent dose of =< 5 mg/day by Week 26 which may be maintained throughout the study.
    Interventions:
    • Drug: Standard therapy (Excluding Immunosuppressants)
    • Drug: Steroid Taper
  • Experimental: Arm B (Combination) 0-52 Weeks
    Eligible subjects will receive belimumab plus rituximab. No immunosuppressant medications are allowed after week 4 (Other than Rituximab at Week 6). Subjects may receive standard of care therapy which may include anti-malarials, NSAIDs, and/or corticosteroids with presdnisone dose equivalent to <= 5 mg/day through Week 52. Doses of corticosteroids taper shall be reduced at Week 12 and reach a prednisone equivalent dose of =< 5 mg/day by Week 26 which may be maintained throughout the study. Subjects will stop receiving Belimumab injections after week 52.
    Interventions:
    • Drug: Belimumab
    • Drug: Rituximab
    • Drug: Standard therapy (Excluding Immunosuppressants)
    • Drug: Steroid Taper
  • Experimental: Arm B (Combination) 53-104 Weeks
    Eligible subjects may receive standard of care therapy which may include anti-malarials, NSAIDs, and/or corticosteroids with presdnisone dose equivalent to <= 5 mg/day in Week 53 through 104. Doses of corticosteroids taper shall be reduced at Week 12 and reach a prednisone equivalent dose of =< 5 mg/day by Week 26 which may be maintained throughout the study.
    Interventions:
    • Drug: Standard therapy (Excluding Immunosuppressants)
    • Drug: Steroid Taper
  • Experimental: Arm C (Reference) 0-52 Weeks
    Eligible subjects will receive belimumab plus standard therapy including immunosuppressant which may be continued throughout the study. Doses of corticosteroids taper shall be reduced at Week 12 and reach a prednisone equivalent dose of =< 5 mg/day by Week 26 which may be maintained throughout the study.
    Interventions:
    • Drug: Belimumab
    • Drug: Standard therapy (Including Immunosuppressants)
    • Drug: Steroid Taper
  • Experimental: Arm C (Reference) 53-104 Weeks
    Eligible subjects will receive belimumab plus standard therapy which may be continued throughout the study. Doses of corticosteroids taper shall be reduced at Week 12 and reach a prednisone equivalent dose of =< 5 mg/day by Week 26 which may be maintained throughout the study.
    Interventions:
    • Drug: Belimumab
    • Drug: Standard therapy (Including Immunosuppressants)
    • Drug: Steroid Taper
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: July 7, 2020)
292
Original Estimated Enrollment  ICMJE
 (submitted: October 13, 2017)
200
Estimated Study Completion Date  ICMJE July 9, 2021
Actual Primary Completion Date May 29, 2020   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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 decilitre [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 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 hr 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-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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Argentina,   Brazil,   Canada,   France,   Germany,   Korea, Republic of,   Mexico,   Netherlands,   Russian Federation,   Spain,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03312907
Other Study ID Numbers  ICMJE 205646
2016-003050-32 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: IPD for this study will be made available via the Clinical Study Data Request site.
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints of the study.
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.
URL: http://clinicalstudydatarequest.com
Responsible Party GlaxoSmithKline
Study Sponsor  ICMJE GlaxoSmithKline
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: GSK Clinical Trials GlaxoSmithKline
PRS Account GlaxoSmithKline
Verification Date June 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP