A Study to Evaluate the Treatment Outcomes of Subcutaneous Anifrolumab in Immunosuppressant-naïve and Biologic-naïve Systemic Lupus Erythematosus

Exclusion Criteria36

• Subjects with history of, or current diagnosis of, a clinically significant non-SLE related vasculitis syndrome.
• Subjects with antiphospholipid antibody syndrome on stable anticoagulant therapy at an effective dose (e.g., if on warfarin, an international normalized ratio \[INR\] target 2 to 3 or as appropriate for the clinical situation) are only allowed if this is not the sole or the predominant feature of their SLE.
• Subjects with a serious thrombotic event (e.g., pulmonary embolism stroke, deep vein thrombosis) or unexplained pregnancy loss within 1 year before the screening visit are excluded.
• Subjects with a history of catastrophic antiphospholipid syndrome or saddle embolism.
• Subjects with a history of 3 or more unexplained consecutive pregnancy losses.
• History or evidence of suicidal ideation 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) at Screening.
• 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, lupus headache and mononeuritis multiplex, where, protocol-specified standard therapy is insufficient.
• Active severe SLE-driven renal disease where, protocol-specified standard therapy is insufficient.
• Current diagnosis of, catastrophic antiphospholipid syndrome (APS).
• History of recurrent infection requiring hospitalization and IV antibiotics (e.g., 3 or more of the same type of infection over the previous 52 weeks).
• Known History of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the participant to infection, or a positive result for HIV at Screening.
• Confirmed positive test for hepatitis B.
• Any clinical cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection that has not completely resolved within 12 weeks prior to signing the ICF.
• Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of Week 0 (Day 1).
• Clinically significant chronic infection (e.g., osteomyelitis, bronchiectasis, etc.) within 8 weeks prior to signing the ICF (chronic nail infections are allowed).
• Severe HZ or recurrent HZ.
• Malignancy. History of cancer, apart from:
• (a) Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥ 3 months prior to Week 0 (Day 1).
• (a) Cervical cancer in situ treated with apparent success with curative therapy ≥ 1 year prior to Week 0 (Day 1).
• Received any SLE-related therapies other than antimalarials and GCs.
• History of allergy or reaction to any component of the study intervention formulation or history of anaphylaxis to any human gamma globulin therapy.
• History of an anaphylactic reaction to human proteins or mAbs.
• Received any live or attenuated vaccine within 8 weeks prior to signing the ICF.
• Blood transfusion or receipt of blood products except albumin.
• Received more than 2 investigational products for the SLE since time of diagnosis.
• Received any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to signing of the ICF, whichever is greater.
• Concurrent enrollment in another clinical study with a study intervention.
• Subjects with any abnormal lab result as specified in the protocol.
• Subjects with other autoimmune diseases (e.g., multiple sclerosis, psoriasis, IBD, etc.).
• Subjects with SLE overlap syndromes such as scleroderma and mixed connective tissue disease.
• Subject with non-SLE concomitant illness, as determined by medical judgment, who is likely to require additional systemic glucocorticosteroid therapy during the study (e.g., asthma).
• Any condition would interfere with treatment outcomes of the study intervention or put participant at safety risk.
• Lactating, breastfeeding, or pregnant females or females who intend to become pregnant or begin breastfeeding anytime from initiation of Screening until 16 weeks following last dose of study intervention.
• Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks prior to signing the ICF.
• Current alcohol, drug or chemical abuse, or a history of such abuse within 1 year before Week 0 (Day 1).
• Major surgery within 8 weeks before signing the ICF or elective major surgery planned during the study period.