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

Inclusion Criteria:

• Documented diagnosis of systemic lupus erythematosus (SLE) within 2 years of signingthe informed consent according to the European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) SLE classification criteria 2019

• Have unequivocally positive autoantibody test results defined as an Anti-nuclearantibody (ANA) titer greater than or equal to (≥) 1:80 and/or a positive anti-Doublestranded deoxyribonucleic acid (dsDNA) serum antibody test from 2 independent timepoints

• 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) less than or equal to (≤) 4 andprednisone or equivalent 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 Woman 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.

• Participants with history of major organ transplant or hematopoietic stemcell/marrow transplant or renal transplant.

• 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 hospitaldischarge date was within 60 days of the first day of dosing (Day 1). Prophylacticanti-infective treatment is allowed.

• Confirmed active or untreated latent tuberculosis (TB):

• Diagnosis of active TB confirmed by: 1) evidence of active TB disease from chestimaging (posterior anterior and lateral x-rays or chest computed tomography [CT]),

2. medical history and physical examination, and 3) either positive microscopysmear/culture for mycobacteria or positive TB polymerase chain reaction (PCR), i.e.,Xpert. A tuberculin skin test (TST) or an interferon gamma release assay (IGRA) willbe done for all participants. A positive TST or a positive (not indeterminate) IGRATB test such as QuantiFERON-TB Gold Plus test is indicative but not required fordiagnosis of active TB. A positive TST is defined as a skin induration ≥5 millimeter (mm) at 48 to 72 hours (regardless of Bacillus Calmette-Guerin or other vaccinationhistory).

• Untreated latent tuberculosis infection (LTBI) confirmed by: 1) no evidence ofactive TB based on chest imaging, medical history and physical examination andlaboratory evaluation of sputum; and 2) a positive TST, defined as a skin induration >5 mm at 48 to 72 hours, regardless of Bacillus Calmette-Guerin or other vaccinationhistory); or a positive (not indeterminate) IGRA TB test such as QuantiFERON-TB GoldPlus test. Those with IGRA positive tests or positive TST who can document ongoingLTBI treatment for at least 4 weeks may be enrolled. Those with IGRA positive testswith documentation of the following may also be enrolled:

• Successful completion of treatment for active TB.

• Completion of treatment for LTBI (with treatment as per local practice, for example: 3 months of isoniazid and rifampin or 4 months of rifampin or 3 months weeklyisoniazid and rifapentine, or 9 months of isoniazid).

• 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.

• Active Lupus Nephritis defined as active urinary sediment and/or proteinuria >500milligrams (mg) per 24 hours, or equivalent using spot urine protein to creatinineratio, requiring induction therapy not permitted by protocol.

• Participants with patient health questionnaire (PHQ)-9 score ≥10 that in the opinionof a mental healthcare professional pose a serious suicide risk, or any history ofsuicidal behavior in the last 6 months and/or any suicidal ideation in the last 2months, or who in the investigator's judgment, poses a significant suicide risk.NOTE: For participants with a PHQ-9 score ≥10, at the Screening visit or at the day 1 visit before the first administration of the study drug, it is required that theybe referred for an assessment by a mental healthcare professional (e.g., locallylicensed psychiatrist, psychologist, or master's level therapist) before theinvestigator makes a final decision regarding suitability for enrollment.

• 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) (oral [PO])/MMF hydrochloride (IV) >2 grams (g)/day

• Mycophenolate acid/sodium (PO) >1.44 g/day

• Oral cyclophosphamide >2.5 mg/kilograms (kg)/day

• Tacrolimus >0.2 mg/kg/day

• Cyclosporine (PO) >2.5 mg/kg/day

• Treatment within specified timeframe prior to Screening:

• 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

• Treatment at any time prior to Screening with any of the following:

• Second line use of conventional immunosuppressants (ISs) or anti-malarials (AMs)

• Commercially available Belimumab (BEL)

• Anifrolumab

• Rituximab or other B cell depleting therapies

• Anti-tumor necrosis factor (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

• History of primary immunodeficiency, or hypogammaglobulinemia (Immunoglobulin G [IgG] <400 mg/deciliter [dL]) or Immunoglobulin A (IgA) deficiency (IgA <10 mg/dL)at Screening

• Have a Grade 3 or greater neutropenia, defined as absolute neutrophil count <1000/cubic millimeter (mm3) (<1.0 x109/liter [L]) based on the Common terminologycriteria for adverse events (CTCAE) version (v) 5.0

• 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 [%]). Participants with Gilbert'ssyndrome can be included with total bilirubin >1.5xULN as long as direct bilirubinis ≤1.5xULN. Cirrhosis or current unstable liver or biliary disease per investigatorassessment defined by the presence of ascites, encephalopathy, coagulopathy,hypoalbuminemia, esophageal or gastric varices, persistent jaundice. NOTE: Stablenon-cirrhotic chronic liver disease (including Gilbert's syndrome), asymptomaticgallstones, and chronic stable hepatitis B (in whom Hepatitis D [HDV] has beenexcluded) or C are acceptable if participant otherwise meets entry criteria.

• 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

• Serologic evidence of Hepatitis B (HB) infection based on the results of testing forhepatitis B surface antigen (HBsAg), anti-hepatitis B core (HBc) and anti-HBs willbe excluded as follows:

• Participants positive for HBsAg.

• Participants negative for HBsAg but positive for Anti-HBc and detectable hepatitis Bvirus (HBV) DNA, regardless of Anti-HBs antibody status.

• 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-injectorat home and has no other reliable resource to administer the study intervention athome.