Overview
This is a prospective, open-label, single arm 3-year clinical study to describe the short-term and long-term efficacy and safety of belimumab in participants with autoantibody positive early SLE with ongoing disease activity despite stable initial SLE therapy.
Eligibility
Inclusion Criteria:
- Documented clinical diagnosis of SLE within 2 years of signing the informed consent according to the American College of Rheumatology (ACR) SLE classification criteria 2019
- Have unequivocally positive autoantibody test results defined as an Anti-nuclear antibody (ANA) titer ≥1:80 and/or a positive anti-
Double stranded deoxyribonucleic acid (dsDNA) serum antibody test from 2 independent time
points as follows:
- Active SLE defined as:
- Clinical SLEDAI-2K (excluding anti-dsDNA and C3/C4) score greater than (>) 4, OR
- Clinical SLEDAI-2K (excluding anti-dsDNA and C3/C4) ≤4 and prednisone or
equivalent dose ≥10 milligram per day (mg/day)
- The Systematic Lupus International Collaborating Clinics/American College of
Rheumatology (SLICC/ACR) Damage Index (SDI) = 0 at Screening
- Male and/or female; a female participant is eligible to participate if she is not
pregnant, not breastfeeding, and at least one of the following conditions applies:
- Not a Women of childbearing potential (WOCBP) OR
- Is a WOCBP and using a contraceptive method that is highly effective
- Capable of giving signed informed consent
Exclusion Criteria:
- Lymphoma, leukemia, or any malignancy within the past 5 years except for basal cell or
squamous epithelial carcinomas of the skin that have been resected with no evidence of
metastatic disease for 3 years.
- Have clinical evidence of significant unstable or uncontrolled acute or chronic
diseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic,
gastrointestinal (GI), hepatic, renal, neurological, psychiatric, malignancy, or
infectious diseases) and/or a planned surgical procedure, which, in the opinion of the
principal investigator (PI), could confound the results of the clinical study or put
the participant at undue risk.
- Have an acute or chronic infection including requiring management as follows:
- Currently on any suppressive therapy for a chronic infection such as
pneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypical
mycobacteria.
- A serious infection requiring treatment with intravenous or Intramuscular (IV/IM)
antibiotics and/or hospitalization if the last dose of antibiotics or the
hospital discharge date was within 60 days of the first day of dosing (Day 1).
Prophylactic anti-infective treatment is allowed.
- Evidence of active or latent tuberculosis (TB) as documented by 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 ≥5millimeter (mm) at
48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or other vaccination
history) or a positive (not indeterminate) interferon gamma release assay TB test.
- Confirmed Progressive multifocal leukoencephalopathy (PML) or unexplained new-onset or
deteriorating neurologic signs and symptoms.
- 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 Screening.
- Lupus kidney disease defined by proteinuria >6 gram (g)/24 hour or equivalent using
spot urine protein to creatinine ratio, or serum creatinine >2.5 milligram per
decilitre (mg/dL) or have active LN requiring induction therapy within 35 days of
Screening.
- Have evidence of serious suicide risk, defined as Patient Health Questionnaire (PHQ)-9
score ≥10, or any history of suicidal behavior in the last 6 months and/or any
suicidal ideation in the last 2 months or who, in the investigator's opinion, pose a
significant suicide risk.
- Known to have titers of human anti-mouse antibody or history of hypersensitivity
reactions when treated with diagnostic or therapeutic monoclonal antibodies
- Live or live-attenuated vaccine(s) within 35 days prior to Screening or plans to
receive such vaccines during the Screening period or during the clinical study
- Chronic oral steroid use for a non-SLE disorder at the Screening study visit (e.g.,
for asthma). Inhaled steroid use will be allowed.
- Treatment at or prior to Screening study visit:
• Treatment at Screening study visit with any of the following:
- Azathioprine (AZA) >200 mg/day
- Methotrexate (MTX) (any formulation) >25 mg/week
- Mycophenolate mofetil (MMF) (PO)/MMF hydrochloride (IV) >2 g/day
- Mycophenolate acid/sodium (PO) >1.44 g/day
- Oral cyclophosphamide >2.5 mg/kg/day
- Tacrolimus >0.2 mg/kg/day
- Cyclosporine (PO) >2.5 mg/kg/day
• Treatment at any time prior to Screening with any of the following:
- Second line use of conventional ISs or AMs
- Commercially available Belimumab (BEL)
- Anifrolumab
- Rituximab or other B cell depleting therapies
- Anti-TNF therapy (e.g., adalimumab, etanercept, infliximab)
- Other treatments with effects on the immune system (e.g., abatacept, interleukin-1
receptor antagonist [anakinra], Janus kinase (JAK) inhibitors)
- IV cyclophosphamide
- IV immunoglobulin
- Plasmapheresis
- Intra-articular, IM, or IV corticosteroids within 6 weeks of Day 1
- Daily use of >1 Nonsteroidal anti-inflammatory (NSAID) within 2 weeks prior to Day 1
- History of primary immunodeficiency, or hypogammaglobulinemia (Immunoglobulin G [IgG]
<400 mg/dL) or Immunoglobulin A (IgA) deficiency (IgA <10 mg/dL)
- Have a Grade 3 or greater neutropenia, defined as absolute neutrophil count
<1000/cubic millimetre (mm3) (<1.0 x109/L) based on the Common terminology criteria
for adverse events (CTCAE) v5.0 Alanine aminotransferase >2 x upper limit of normal
(ULN)
- Total bilirubin >1.5 x ULN (isolated bilirubin >1.5 x ULN is acceptable if bilirubin
is fractionated and direct bilirubin <35 percent [%])
- Have any other clinically significant abnormal laboratory value, that in the opinion
of the investigator, is capable of significantly altering the absorption, metabolism,
or elimination of the clinical study intervention; or constitutes a risk when taking
the clinical study intervention or interferes with the interpretation of the clinical
study data.
- Positive Human immunodeficiency virus (HIV) antibody test
- Presence of hepatitis B surface antigen (HBsAg) or Hepatitis B core antibody (HBcAb)
at screening or within 3 months prior to first dose of study intervention.
- Positive Hepatitis C antibody test result at screening or within 3 months prior to
starting study intervention. NOTE: Participants with positive Hepatitis C antibody due
to prior resolved disease can be enrolled, only if a confirmatory negative Hepatitis C
Ribonucleic acid (RNA) test is obtained.
- Positive Hepatitis C RNA test result at screening or within 3 months prior to first
dose of study intervention. NOTE: Test is optional and participants with negative
Hepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.
- Sensitivity to the clinical study intervention, or components thereof, or monoclonal
antibodies or drug or other allergy that, in the opinion of the investigator,
contraindicates participation in the clinical study
- Current drug or alcohol dependence, or a history of drug or alcohol abuse or
dependence within 364 days prior to Day 1
- Current enrolment or past participation in any other clinical study involving an
investigational study intervention (including investigational vaccines) within 3
months or 5 half-lives of the investigational drug (whichever is longer) before
enrolment
- Unable to administer clinical study intervention by subcutaneous (SC) auto-injector
and has no other reliable resource to administer the study intervention.