A Study to Investigate Pharmacokinetics, Pharmacodynamics, and Safety of Subcutaneous Anifrolumab in Pediatric Participants 5 to < 18 Years of Age With Systemic Lupus Erythematosus

This is an open-label, multicenter study.

The study includes -

• Screening Period of up to 35 days
• Period A (12-week, open-label treatment period)
• Period B (a possible 12-week dosing regimen adjustment period, if required)
• Treatment Extension Period (up-to-40-week, optional)
• Period C (a 12-week safety follow-up period)

The study intervention (anifrolumab) will be administered subcutaneously using an accessorized pre-filled syringe (APFS) in 2 cohorts.

Inclusion criteria

• Diagnosis of SLE.
• Must be receiving at least one of the following SoC regimens for ≥ 4 weeks: oral glucocorticoids (≤1.0 mg/kg/day or ≤ 40 mg/day prednisone equivalent), antimalarials (hydroxychloroquine, chloroquine, or quinacrine), or a single permitted immunosuppressant (azathioprine, mycophenolate mofetil/mycophenolic acid, methotrexate, mizoribine, or tacrolimus) within specified dose limits.
• Participant must have moderate to severe active SLE disease defined as Systemic lupus erythematosus disease activity index 2000 (SLEDAI-2K) ≥ 6 total points.
• Body weight ≥ 15 kg.
• Participants must agree to follow study specific contraception requirements as per local regulations.

Exclusion criteria

• Known diagnosis of an IFN mediated autoinflammatory interferonopathy.
• History of, or current diagnosis of, clinically significant non-SLE related vasculitides.
• Active, severe SLE-driven renal disease with significant proteinuria.
• Active severe or unstable neuropsychiatric SLE including but not limited to aseptic meningitis; cerebral vasculitis; myelopathy; demyelination syndromes (ascending, transverse, acute inflammatory demyelinating polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebellar ataxia; and mononeuritis multiplex.
• In participants ≥ 11 years of age, a history or evidence of suicidal ideation (severity of 4 [active: method and intent, but no plan] or 5 [active: method, intent, and plan]) within the past 6 months; or any suicidal behavior within the past 12 months or recurrent suicidal behavior in the lifetime of the participant based on an assessment with the Columbia suicide severity rating scale (C-SSRS).
• History of, or current diagnosis of, catastrophic antiphospholipid syndrome (APS).
• History of recurrent or opportunistic infection requiring hospitalization and intravenous (IV) antibiotics.
• Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for human immunodeficiency virus (HIV) infection.
• Active hepatitis B and C infection.
• Any active or recent herpes zoster (HZ) infection that has not completely resolved within 12 weeks prior to study entry or that emerges between screening and Day 1.
• Any history of severe or recurrent HZ, including non-cutaneous HZ, herpes encephalitis, ophthalmic herpes, or 2 or more prior HZ episodes.
• Any cytomegalovirus (CMV) or Epstein Barr virus (EBV) infection that has not completely resolved.
• History of cancer.
• Prior receipt of anifrolumab.
• Prior treatment with directly acting cytotoxic B-cell depleting therapeutics.
• A known history of allergy or reaction to any component of the study intervention formulation or history of anaphylaxis to any human gamma globulin therapy, human proteins, or monoclonal antibodies (mAbs).