A Study Describing the Efficacy and Safety of Belimumab Administered in Adult Participants With Early Systemic Lupus Erythematosus (SLE)

Inclusion Criteria:

• Documented clinical diagnosis of SLE within 2 years of signing the informed consentaccording to the American College of Rheumatology (ACR) SLE classification criteria 2019

• Have unequivocally positive autoantibody test results defined as an Anti-nuclearantibody (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 orequivalent dose ≥10 milligram per day (mg/day)

• The Systematic Lupus International Collaborating Clinics/American College ofRheumatology (SLICC/ACR) Damage Index (SDI) = 0 at Screening

• Male and/or female; a female participant is eligible to participate if she is notpregnant, 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 cellor squamous epithelial carcinomas of the skin that have been resected with noevidence of metastatic disease for 3 years.

• Have clinical evidence of significant unstable or uncontrolled acute or chronicdiseases not due to SLE (i.e., cardiovascular, pulmonary, hematologic,gastrointestinal (GI), hepatic, renal, neurological, psychiatric, malignancy, orinfectious diseases) and/or a planned surgical procedure, which, in the opinion ofthe principal investigator (PI), could confound the results of the clinical study orput 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 aspneumocystis, cytomegalovirus, herpes simplex virus, herpes zoster, or atypicalmycobacteria.

• A serious infection requiring treatment with intravenous or Intramuscular (IV/IM) antibiotics and/or hospitalization if the last dose of antibiotics orthe 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 andexamination, chest X-rays (posterior, anterior, and lateral), and TB testing: eithera positive tuberculin skin test (TST); defined as a skin induration ≥5millimeter (mm) at 48 to 72 hours, regardless of Bacillus Calmette-Guerin (BCG) or othervaccination history) or a positive (not indeterminate) interferon gamma releaseassay TB test.

• Confirmed Progressive multifocal leukoencephalopathy (PML) or unexplained new-onsetor deteriorating neurologic signs and symptoms.

• Have severe active central nervous system (CNS) lupus (including seizures,psychosis, organic brain syndrome, Cerebrovascular accident (CVA), cerebritis, orCNS vasculitis) requiring therapeutic intervention within 60 days of Screening.

• Lupus kidney disease defined by proteinuria >6 gram (g)/24 hour or equivalent usingspot urine protein to creatinine ratio, or serum creatinine >2.5 milligram perdecilitre (mg/dL) or have active LN requiring induction therapy within 35 days ofScreening.

• 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/orany 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 hypersensitivityreactions when treated with diagnostic or therapeutic monoclonal antibodies

• Live or live-attenuated vaccine(s) within 35 days prior to Screening or plans toreceive 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-1receptor 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 criteriafor 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 bilirubinis fractionated and direct bilirubin <35 percent [%])

• Have any other clinically significant abnormal laboratory value, that in the opinionof the investigator, is capable of significantly altering the absorption,metabolism, or elimination of the clinical study intervention; or constitutes a riskwhen taking the clinical study intervention or interferes with the interpretation ofthe 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 tostarting study intervention. NOTE: Participants with positive Hepatitis C antibodydue to prior resolved disease can be enrolled, only if a confirmatory negativeHepatitis C Ribonucleic acid (RNA) test is obtained.

• Positive Hepatitis C RNA test result at screening or within 3 months prior to firstdose of study intervention. NOTE: Test is optional and participants with negativeHepatitis C antibody test are not required to also undergo Hepatitis C RNA testing.

• Sensitivity to the clinical study intervention, or components thereof, or monoclonalantibodies 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 ordependence within 364 days prior to Day 1

• Current enrolment or past participation in any other clinical study involving aninvestigational study intervention (including investigational vaccines) within 3months or 5 half-lives of the investigational drug (whichever is longer) beforeenrolment

• Unable to administer clinical study intervention by subcutaneous (SC) auto-injectorand has no other reliable resource to administer the study intervention.