A Study to Learn About the Safety of Litifilimab (BIIB059) Injections and Whether They Can Improve Symptoms of Adult Participants Who Have Systemic Lupus Erythematosus

Other illness

• History of or positive test result for human immunodeficiency virus (HIV).
• Current hepatitis C infection (defined as positive hepatitis C virus (HCV) antibody and detectable HCV ribonucleic acid \[RNA\]).
• Current hepatitis B infection (defined as positive for antibody to hepatitis B surface antigen (HBsAg) and/or positive for total hepatitis antibody to B core antigen \[anti-HBc\] with positive reflex HBV DNA).
• History of severe herpes infection.
• Presence of uncontrolled or New York Heart Association class III or IV congestive heart failure.
• Any active skin conditions other than cutaneous lupus erythematosus (CLE) that may interfere with the study assessment of CLE such as but not limited to psoriasis, dermatomyositis, systemic sclerosis, non-LE skin lupus manifestation or drug-induced lupus.
• History or current diagnosis of a clinically significant non-SLE-related vasculitis syndrome.

Lab values

• Active severe lupus nephritis where, in the opinion of the Investigator, protocol-specified SOC is insufficient and use of a more aggressive therapeutic approach is indicated, such as adding IV cyclophosphamide and/or high-dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol is indicated; or urine protein-creatinine ratio \> 2.0 or severe chronic kidney disease (estimated glomerular filtration rate \< 30 milliliters per minute per 1.73 meter square \[mL/min/1.73 m\^2\]) calculated using the abbreviated modification of diet in renal disease equation.

Other

• Active neuropsychiatric SLE.
• Use of oral prednisone (or equivalent) above 20 mg/day.
  • Note: Other protocol defined Inclusion/Exclusion criteria may apply.

• Participant must be diagnosed with systemic lupus erythematosus (SLE) at least 24 weeks prior to screening and must meet the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) classification criteria for SLE at screening by a qualified physician.
• Participant has a modified Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score ≥ 6 (excluding alopecia, fever, lupus-related headache, and organic brain syndrome) at screening (adjudicated).
• Participant has a modified clinical SLEDAI-2K score ≥ 4 (excluding anti-dsDNA, low complement component 3 (C3) and/or complement component 4 (C4), alopecia, fever, lupus-related headache, and organic brain syndrome) at Screening (adjudicated) and randomization.
• Participant has BILAG-2004 grade A in ≥ 1 organ system or BILAG-2004 grade B in ≥ 2 organ systems at Screening (adjudicated) and randomization.
• Participant must be treated with one of the following background nonbiologic lupus SOC therapies, initiated ≥ 12 weeks prior to Screening and at stable dose ≥ 4 weeks prior to randomization:
  • Antimalarials as stand-alone treatment
  • Antimalarial treatment in combination with OCS and/or a single immunosuppressant
  • Treatment with OCS and/or a single immunosuppressant