Medically stable on the basis of physical examination, medical history, vital signs and 12-lead electrocardiogram (ECG) performed at screening
Clinical diagnosis of systemic lupus erythematosus (SLE) for more than or equal to (\>=) 24 weeks prior to screening and meeting european league against rheumatism/american college of rheumatology (EULAR/ACR) classification criteria
Must have a systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) score \>= 6 and a clinical SLEDAI-2K \>= 4 at screening, AND a clinical SLEDAI-2K score \>= 4 points at Week 0. For eligibility, points attributed to "lupus headache," "alopecia," and "organic brain syndrome" are excluded
Participants of childbearing potential must have a negative serum beta human chorionic gonadotropin (β-hCG) test at screening and a negative urine (β- hCG) test at Week 0 prior to randomization
Has at least 1 BILAG-2004 A score or 2 BILAG-2004 B scores observed at screening
You may not be if
History of severe, progressive and/or uncontrolled hepatic, gastrointestinal, renal, pulmonary, cardiovascular, psychiatric, neurological or musculoskeletal disorder, hypertension, and/or any other medical or uncontrolled autoimmune disorder (s) or clinically significant abnormalities in screening laboratory
Any unstable or progressive manifestation of SLE that is likely to warrant escalation in therapy beyond permitted background medications
Confirmed or suspected clinical immunodeficiency syndrome not related to treatment of SLE or has a family history of congenital or hereditary immunodeficiency unless confirmed absent in the participant
Has shown a previous severe immediate hypersensitivity reaction, such as anaphylaxis, to therapeutic proteins
Suspected or known allergies, hypersensitivity, or intolerance to nipocalimab or its excipients, or excipients used in the placebo formulation
