A Study of Ustekinumab in Participants With Active Systemic Lupus Erythematosus
Condition: Lupus Erythematosus, Systemic
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Placebo; Ustekinumab (approximately 6 mg/kg); Ustekinumab 90 mg
Intervention description: Participants will receive placebo matching to ustekinumab IV or SC.; Participants will receive ustekinumab approximately 6 mg/kg via IV route based on body weight-range.; Participants will receive 90 mg ustekinumab via SC route.
Intervention MeSH terms: Ustekinumab
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 516.0
Sex: All
Minimum age: 16 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      The purpose of this study is to evaluate the efficacy of ustekinumab in participants with
      active systemic lupus erythematosus (SLE) who have not adequately responded to one or more
      standard of care treatments.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Be male or female

          -  Has a documented medical history (that is, met at least 1 of the two criteria below)
             that participant met the Systemic Lupus International Collaborating Clinics (SLICC)
             classification criteria for systemic lupus erythematosus (SLE) at least 3 months prior
             to first dose of study agent:

               1. Met a total of at least 4 SLICC criteria, including at least 1 clinical and at
                  least 1 immunologic;

               2. Has a diagnosis of lupus nephritis, confirmed by renal biopsy and at least 1 of
                  the following autoantibodies: antinuclear antibodies (ANA) or
                  anti-double-stranded deoxyribonucleic acid (anti-dsDNA)

          -  Has a positive test in the medical history and confirmed at screening for at least 1
             of the following autoantibodies: antinuclear antibodies, anti-double-stranded
             deoxyribonucleic acid, and/or anti-Smith

          -  Has greater than or equal to (>=) 1 British Isles Lupus Assessment Group (BILAG) A
             and/or >= 2 BILAG B scores observed during screening

          -  Has a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity
             score >=4 (excluding diffuse non-inflammatory alopecia) or >= 4 joints with pain and
             signs of inflammation at screening, Week 0, or both

          -  Has a Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) score >=6
             at screening. Must also have SLEDAI-2K >= 4 for clinical features (excluding headache
             and laboratory abnormalities) at Week 0

          -  Cannot be pregnant, nursing, intending to become pregnant, or unwilling to follow
             contraception or egg/sperm donation guidelines

          -  Must be receiving stable doses of >=1 protocol-permitted standard of care SLE
             treatment: oral glucocorticoids, anti-malarials, immunomodulators (methotrexate,
             azathioprine, 6-mercaptopurine, mycophenolate mofetil, mycophenolic acid)

        Exclusion Criteria:

          -  Has any unstable or progressive SLE manifestation (example: central nervous system
             lupus, systemic vasculitis, end-stage renal disease, severe or rapidly progressive
             glomerulonephritis, pulmonary hemorrhage, myocarditis) that may warrant escalation in
             therapy beyond permitted background medications. Participants requiring renal
             hemodialysis or peritoneal dialysis are also excluded

          -  Has other co-existent inflammatory diseases (example: rheumatoid arthritis, psoriasis,
             psoriatic arthritis, Crohn's disease)

          -  Has a urinary protein to creatinine ratio of greater than (>)4 gram per gram (g/g) per
             day

          -  Has an acute or chronic infectious illness (example: human immunodeficiency virus,
             hepatitis B or C virus, tuberculosis, opportunistic infections)

          -  Has a history of cancer or lymphoproliferative disease within the last 5 years except
             for treated and non-recurrent cutaneous basal cell carcinoma, squamous cell carcinoma,
             or cervical carcinoma

          -  Has any condition requiring multiple courses of systemic glucocorticoids (example:
             uncontrolled asthma, chronic obstructive pulmonary disease)

          -  Has a history of major surgery within the last month

          -  Has received live virus or bacterial vaccines within 16 weeks prior to first dose of
             study agent or Bacille Calmette-Guerin (BCG) vaccination within 12 months of screening

          -  Has previously received ustekinumab

          -  Has received cyclophosphamide orally within 90 days or intravenously within 180 days
             of screening

          -  Has received a single B-cell targeted therapy (e.g. belimumab) within 3 months, >1
             previous B-cell targeted therapy within 6 months, or B-cell depleting therapy
             (example: rituximab) within 12 months of first dose of study agent

          -  Has received protocol-prohibited oral or biologic immunomodulatory therapy in the last
             3 months or less than (<)5 half-lives (whichever is longer) prior to first dose of
             study agent

          -  Has received adrenocorticotropic hormone (ACTH) within 1 month prior to first dose of
             study agent

          -  Has received epidural, intravenous, intramuscular, intraarticular, intrabursal,
             intralesional glucocorticoids within 6 weeks of first dose of study agent

          -  Locally-delivered therapies except for ophthalmic use of cyclosporine A or topical use
             of nonsteroidal anti inflammatory drugs (NSAIDs), analgesics, or high-potency
             glucocorticoids (World Health Organization criteria) are prohibited