A Study of Outcomes in Chinese Patients Treated With Anifrolumab Who Have Active Mod-severe Systemic Lupus Erythematosus

Medical Conditions

1. History of, or current diagnosis of, a clinically significant non-SLE related vasculitis syndrome Vasculitis due to SLE is allowed in the study.

2. Non-SLE diseases that potentially require systemic glucocorticoids (e.g. IV or oral), as determined by medical judgment, e.g. asthma, chronic obstructive pulmonary disease (COPD).

3. 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, in the opinion of primary investigator or AstraZeneca, protocol-specified standard therapy is insufficient and utilisation of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated.

4. Active severe SLE-driven renal disease where, in the opinion of the primary investigator or AstraZeneca, protocol-specified standard therapy is insufficient and utilisation of a more aggressive therapeutic approach, such as adding IV cyclophosphamide and/or high dose IV pulse corticosteroid therapy or other treatments not permitted in the protocol, is indicated.

5. Subjects with SLE overlap syndromes such as scleroderma and mixed connective tissue disease are excluded. Subjects with an overlap syndrome of SLE with rheumatoid arthritis are not excluded as long as they meet the criteria for the classification of SLE.

6. Subjects with other autoimmune diseases (e.g., multiple sclerosis, psoriasis, IBD, etc.) are excluded. Subjects with type I autoimmune diabetes mellitus, thyroid autoimmune disease, Celiac disease, or secondary Sjögren's syndrome are not excluded.

7. History of, or current diagnosis of, catastrophic anti-phospholipid syndrome (APS) within one year prior to signing the ICF. 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 are excluded. Subjects with a history of 3 or more unexplained consecutive pregnancy losses would also be excluded. Participants with other degrees of APS adequately controlled by anticoagulants ((i.e., if on warfarin, an international normalized ratio \[INR\] target 2 to 3 or as appropriate for the clinical situation) or aspirin for at least 12 weeks can be recruited to the study.

8. Current or history of Hypothalamic-Pituitary-Adrenal (HPA) axis related disease, Addison disease, adrenal haemorrhage etc.

9. Current infections requiring hospitalisation.

10. History of recurrent infection requiring hospitalisation and IV antibiotics (e.g., 3 or more of the same type of infection over the previous 52 weeks).

11. 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 confirmed by central laboratory at Screening:

a) An HIV test must be performed during Screening, and the result should be available prior to Week 0 (Day 1). The participant is ineligible to participate in the study when positive for HIV antibody or infection (i.e., positive nucleic acid test) performed by the central laboratory. Participants refusing HIV testing during the Screening Period will not be eligible for study participation.

12. Severe herpes zoster or recurrent herpes zoster:

1. Any severe case, as defined by study guidelines, of herpes zoster infection at any time prior to Week 0 (Day 1), including, but not limited to, non-cutaneous herpes (ever), herpes encephalitis (ever), recurrent herpes zoster (defined as 2 episodes within 2 years) or ophthalmic herpes involving the retina (ever).

2. Any herpes zoster infection that has not completely resolved within 12 weeks prior to signing the ICF.

13. Confirmed positive test for hepatitis B serology for:

1. Hepatitis B surface antigen (HBsAg), OR

2. Hepatitis B core antibody (HBcAb) AND hepatitis B virus (HBV) DNA detected above the lower limit of quantitation (LLOQ) by reflex testing by the central laboratory at screening.

Note: Participants who are HBcAb positive at screening will be tested at least every 12 months for HBV DNA. To remain eligible for the study, the participant's HBV DNA levels must remain below the LLOQ as per the central laboratory.

14. Active hepatitis C infection (defined as positive hepatitis C virus \[HCV\] antibody and detectable HCV ribonucleic acid (RNA) as confirmed by central laboratory.

15. Any clinical cytomegalovirus (CMV) or Epstein-Barr virus (EBV) infection that has not completely resolved within 12 weeks prior to signing the ICF.

16. Active tuberculosis (TB):

1. Medical history or signs or symptoms of active TB prior to or during Screening.

2. A chest x-ray during the Screening Period or within 12 weeks prior to signing of the ICF with evidence of active or signs of prior TB infection

3. Recent contact with a person with active TB OR if there has been such contact, referral to a physician specializing in TB to undergo additional evaluation prior to Week 0 (Day 1) (documented comprehensively in source), and, if warranted, receipt of appropriate treatment for latent TB at or before the first administration of study intervention

17. Opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of Week 0 (Day 1).

18. Clinically significant chronic infection (e.g., osteomyelitis, bronchiectasis, etc.) within 8 weeks prior to signing the ICF (chronic nail infections are allowed).

19. Current or previous history of malignancies, apart from:

1. Squamous or basal cell carcinoma of the skin treated with documented success of curative therapy ≥3 months prior to Week 0 (Day 1).

2. Cervical cancer in situ treated with apparent success with curative therapy ≥1 year prior to Week 0 (Day 1).

20. Females with abnormal cervical cancer screening results Females who have been or are sexually active with an intact cervix must have documentation of a cervical cancer screening (Pap smear or human papilloma virus \[HPV\] tests as per local guidelines) with a normal test result within 2 years prior to Week 0 (Day 1). Any abnormal cervical cancer screening result documented within 2 years prior to Week 0 (Day 1) must be repeated to confirm participant eligibility.

Note: Females aged \< 25 years, who have never been sexually active or have well-documented HPV vaccination records may not, at the investigator's discretion, require a cervical cancer screening test.

21. Any history of an anaphylactic reaction to human proteins or monoclonal antibodies.

Prior/Concomitant Therapy

22. Prior receipt of anifrolumab.

23. Current receipt of other biologics or small molecule targeted treatments.

24. Currently participating in an interventional clinical trial with an IMP.

25. Participants with receipt of/use of any live or attenuated vaccine within 8 weeks prior to signing the ICF will be excluded from the study. Use of any live or attenuated vaccine is not allowed during the study up until study completion or at least 12 weeks after the last study dose.

26. Receipt of any prohibited medication listed in Appendix H.

27. Blood transfusion or receipt of blood products except albumin within 4 weeks prior to signing the ICF.

Diagnostic Assessments

28. At Screening (within 4 weeks before Week 0), any of the following (note: retesting of laboratory test results during Screening may be repeated once):

1. Serum creatinine \> 2.0 mg/dL (or \> 181 μmol/L)

2. Urine protein/creatinine ratio \> 2.0 mg/mg (or \> 226.30 mg/mmol)

3. Aspartate aminotransferase (AST) \> 2.0 × upper limit of normal (ULN)

4. Alanine aminotransferase (ALT) \> 2.0 × ULN

5. TBL \> ULN (unless due to Gilbert's syndrome)

6. Neutrophil count \< 1000/μL (or \< 1.0 × 109/L)

7. Hb \< 8 g/dL (or \< 80 g/L), or \< 7 g/dL (or \< 70 g/L) related to participant's SLE such as in active haemolytic anaemia

8. Glycosylated haemoglobin (HbA1c) \> 8% (or \> 0.08) at Screening (in diabetic participants only) Others

29. 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.

30. Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks prior to signing the ICF.

31. Major surgery within 8 weeks before signing the ICF or elective major surgery planned during the study period .

32. Any condition that, in the opinion of the investigator or AstraZeneca, would interfere with treatment outcomes of the study intervention or put participant at safety risk.

What this study is about