Anifrolumab Asian PhIII Efficacy Study for Systemic Lupus Erythematosus (SLE)

Key inclusion criteria:

1. Aged 18 to 70 years.

2. Body weight ≥ 40 kg.

3. Confirmed diagnosis of SLE(1997 ACR revised criteria) for ≥ 24 weeks.

4. Must be receiving at least one of the following SOC regimens at screening:

5. oral prednisone monotherapy: ≥ 7.5 mg/day and ≤ 40 mg/day, stable for > 2weeks;

6. Immunosuppressant(s) with or without OCS and must be stable for ≥ 8 weeks;

7. Oral prednisone plus immunosuppressant: start date, stability and maximum doserequired.

8. At least one of these antibodies positive: ANA, anti-dsDNA and anti-Smith.

9. SLEDAI-2K score ≥ 6 points at screening and "Clinical" SLEDAI-2K score ≥4 points atboth screening and Day1(randomisation), and BILAG with at least 1 level A organsystem or 2 level B organ system, and PGA score ≥ 1.0 at screening.

10. Chest imaging shows no clinically significant abnormalities (unless due to SLE).

11. No evidence or medical history of active TB, indeterminate TB should be referred toa TB specialist.

12. All participants should use effective contraception methods as protocol requests.

13. Any negative SARS-CoV-2 RT-PCR test result at screening and no known or suspectedCOVID-19 infection or exposure within 2 weeks prior to screening and betweenscreening and randomisation visits.

Key exclusion criteria:

1. History or current diagnose of clinically significant non-SLE related vasculitis,severe or unstable neuropsychiatric SLE, active severe SLE-driven renal disease,catastrophic anti-phospholipid syndrome, inflammatory joint or skin disease otherthan SLE, non-SLE disease that has required treatment of certain dosage ofcorticosteroid.

2. History or evidence of suicidal ideation or suicidal behavior.

3. History or current diagnose of MTCD or overlap syndrome, unless overlap with RA orMTCD which has developed into SLE.

4. History of recurrent infection requiring hospitalization and IV antibiotics, oropportunistic infection requiring hospitalization or IV antimicrobial treatmentwithin 3 years of randomization, or clinically significant chronic infection within 3 months, or recent infection still under treatment.

5. History of immunodeficient condition, HIV positive included.

6. Confirmed HBsAg positive, or HBcAb positive and HBV DNA detectable, or hepatitis Cantibody positive.

7. History of severe case of herpes zoster.

8. Herpes zoster, CMV or EB infection which has not completely resolved within 12 weeksbefore screening.

9. Acute COVID-19 infection or history of severe COVID-19.

10. History of cancer, apart from cured squamous or basal cell carcinoma and cervicalcancer in situ.

11. Female participants with abnormal pap smear results.

12. Prior receipt of anifrolumab ,or any commercially available Janus kinase (JAK)inhibitor ≤ 12 weeks or Bruton's tyrosine kinase (BTK) inhibitor ≤ 24weeks prior tosigning the ICF; any investigational medicinal product(small molecule or biologicagent) within 4 weeks or 5 half-lives prior to signing of the ICF, whichever isgreater.

13. Known history of allergy to any component of the IP formulation or protein relatedproducts.

14. Receipt of any of the following:

15. Intramuscular or IV glucocorticosteroids within 6 weeks;

16. Any live or attenuated vaccine within 8 weeks;

17. Any restricted medication listed in protocol;

18. Blood transfusion within 4 weeks. 15 Regular use of > 1 NSAID within 2 weeks orreceipt of fluctuating doses of a NSAID within 2 weeks.

19. Certain laboratory test results requirements. 17. Concurrent enrolment in another clinical study. 18. History or current alcohol, drug or chemical abuse within 1 year. 19. Major surgery within 8 weeks or planned elective major surgery.