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

• Register: ClinicalTrials.gov
• Last refreshed on: 4 January 2022
• Main ID: NCT03312907
• Date of registration: 13/10/2017
• Prospective Registration: Yes
• Primary sponsor: GlaxoSmithKline
• Public title: 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
• Scientific 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)
• Date of first enrolment: March 1, 2018
• Target sample size: 292
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT03312907
• Study type: Interventional
• Study design: Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Triple (Participant, Investigator, Outcomes Assessor).
• Phase: Phase 3

Countries of recruitment

Argentina, Brazil, Canada, France, Germany, Korea, Republic of, Mexico, Netherlands, Russian Federation, Spain, United States

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & 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 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


Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Systemic Lupus Erythematosus

Intervention(s)

Drug: Rituximab

Drug: Steroid Taper

Drug: Rituximab-placebo

Drug: Standard therapy (Including Immunosuppressants)

Drug: Belimumab

Drug: Standard therapy (Excluding Immunosuppressants)

Primary Outcome(s)

Proportion of subjects with a state of disease control at week 52 [Time Frame: Week 52]

Secondary Outcome(s)

Change from Baseline in Patient Global Assessment (PtGA) at each visit [Time Frame: Baseline and up to Week 104]

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]

Proportion of subjects with a state of clinical remission at Week 64 (Major) [Time Frame: Week 64]

Proportion of subjects with a state of complete remission sustained for at least 24 weeks [Time Frame: Up to Week 104]

Duration of disease control at each visit [Time Frame: Up to Week 104]

Proportion of subjects with a state of complete remission at each visit [Time Frame: Up to Week 104]

Change from Baseline in Physician Global Assessment (PGA) at each visit [Time Frame: Baseline and up to Week 104]

Proportion of subjects with a state of disease control at each visit [Time Frame: Up to Week 104]

Proportion of subjects with a state of disease control at Week 104 (Major) [Time Frame: Week 104]

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]

Duration of clinical remission [Time Frame: Up to Week 104]

Proportion of subjects with Adverse events (AE), serious AEs (SAE) and AEs of special interest (AESIs) [Time Frame: Up to Week 104]

Proportion of subjects with SLEDAI-2K organ improvement at each visit [Time Frame: Up to Week 104]

Time to first flare (Measured by Modified SLE flare index) [Time Frame: Up to Week 104]

Proportion of subjects with SLEDAI-2K organ worsening at each visit [Time Frame: Up to Week 104]

Change from Baseline in LupusQoL domain summary scores (8 domains) at each visit [Time Frame: Baseline and up to Week 104]

Time to clinical remission sustained at Week 104 [Time Frame: Week 104]

Change from baseline in SLEDAI-2K score by visit [Time Frame: Baseline and up to Week 104]

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]

Proportion of subjects that meet the Lupus Low Disease Activity State (LLDAS) response criteria by visit [Time Frame: Up to Week 104]

Change from Baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue score at each visit [Time Frame: Baseline and up to Week 104]

Proportion of subjects with a state of clinical remission at each visit [Time Frame: 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 [Time Frame: Baseline, Week 52 and Week 104]

Time to first severe flare (Measured by Modified SLE flare index) [Time Frame: Up to Week 104]

Proportion of subjects with a state of clinical remission at Week 104 [Time Frame: Week 104]

Time to disease control sustained Week 104 [Time Frame: Week 104]

Secondary ID(s)

205646

2016-003050-32

Source(s) of Monetary Support

Please refer to primary and secondary sponsors