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

Key Inclusion Criteria:

• Participant must be diagnosed with systemic lupus erythematosus (SLE) at least 24weeks prior to screening and must meet the 2019 European League Against Rheumatism (EULAR) / American College of Rheumatology (ACR) classification criteria for SLE atscreening 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, andorganic brain syndrome) at screening (adjudicated).

• Participant has a modified clinical SLEDAI-2K score ≥ 4 (excluding anti-dsDNA, lowcomplement component 3 (C3) and/or complement component 4 (C4), alopecia, fever,lupus-related headache, and organic brain syndrome) at Screening (adjudicated) andrandomization.

• Participant has BILAG-2004 grade A in ≥ 1 organ system or BILAG-2004 grade B in ≥ 2organ systems at Screening (adjudicated) and randomization.

• Participant must be treated with one of the following background nonbiologic lupusSOC therapies, initiated ≥ 12 weeks prior to Screening and at stable dose ≥ 4 weeksprior to randomization:

1. Antimalarials as stand-alone treatment

2. Antimalarial treatment in combination with OCS and/or a singleimmunosuppressant

3. Treatment with OCS and/or a single immunosuppressant

Key Exclusion Criteria:

• History of or positive test result for human immunodeficiency virus (HIV).

• Current hepatitis C infection (defined as positive hepatitis C virus (HCV) antibodyand detectable HCV ribonucleic acid [RNA]).

• Current hepatitis B infection (defined as positive for antibody to hepatitis Bsurface antigen (HBsAg) and/or positive for total hepatitis antibody to B coreantigen [anti-HBc] with positive reflex HBV DNA).

• History of severe herpes infection.

• Presence of uncontrolled or New York Heart Association class III or IV congestiveheart failure.

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

• Any active skin conditions other than cutaneous lupus erythematosus (CLE) that mayinterfere with the study assessment of CLE such as but not limited to psoriasis,dermatomyositis, systemic sclerosis, non-LE skin lupus manifestation or drug-inducedlupus.

• History or current diagnosis of a clinically significant non-SLE-related vasculitissyndrome.

• Active neuropsychiatric SLE.

• Use of oral prednisone (or equivalent) above 20 mg/day.

Note: Other protocol defined Inclusion/Exclusion criteria may apply.