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

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 first-line SLE therapy.

Inclusion Criteria: * Documented diagnosis of systemic lupus erythematosus (SLE) within 2 years of signing the 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-nuclear antibody (ANA) titer greater than or equal to (\>=) 1:80 and/or a positive anti-Double stranded deoxyribonucleic acid (dsDNA) serum antibody test from 2 independent time points * 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) score 1 to 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 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 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. * Participants with history of major organ transplant or hematopoietic stem cell/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 hospital discharge date was within 60 days of the first day of dosing (Day 1). Prophylactic anti-infective treatment is allowed. * Confirmed active or untreated latent tuberculosis (TB): * Diagnosis of active TB confirmed by: 1) evidence of active TB disease from chest imaging (posterior anterior and lateral x-rays or chest computed tomography \[CT\]), 2) medical history and physical examination, and 3) either positive microscopy smear/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) will be done for all participants. A positive TST or a positive (not indeterminate) IGRA TB test such as QuantiFERON-TB Gold Plus test is indicative but not required for diagnosis 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 vaccination history). * Untreated latent tuberculosis infection (LTBI) confirmed by: 1) no evidence of active TB based on chest imaging, medical history and physical examination and laboratory 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 vaccination history); or a positive (not indeterminate) IGRA TB test such as QuantiFERON-TB Gold Plus test. Those with IGRA positive tests or positive TST who can document ongoing LTBI treatment for at least 4 weeks may be enrolled. Those with IGRA positive tests with 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 weekly isoniazid and rifapentine, or 9 months of isoniazid). * 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. * Active Lupus Nephritis defined as active urinary sediment and/or proteinuria \>500 milligrams (mg) per 24 hours, or equivalent using spot urine protein to creatinine ratio, requiring induction therapy not permitted by protocol. * Participants with patient health questionnaire (PHQ)-9 score \>=10 that in the opinion of a mental healthcare professional pose a serious suicide risk, 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 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 they be referred for an assessment by a mental healthcare professional (e.g., locally licensed psychiatrist, psychologist, or master's level therapist) before the investigator makes a final decision regarding suitability for enrollment. * 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) (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-1 receptor antagonist \[anakinra\], Janus kinase (JAK) inhibitors) * IV cyclophosphamide * IV immunoglobulin * Plasmapheresis Any addition of a new IS or AM, or IS or AM switch, performed more than 3 months after initiating first line therapy in response to inadequate disease control is considered second-line therapy and is therefore exclusionary. Therapy changes made due to intolerance or toxicity are not considered second-line, provided that the intolerance/toxicity is clearly documented. Any therapy changes after initiating first line therapy considered to be due to intolerance/toxicity must be reviewed and confirmed by the EAC prior to determining eligibility. * History of primary immunodeficiency, or hypogammaglobulinemia (Immunoglobulin G \[IgG\] \