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

Key inclusion criteria

• Aged 18 to 70 years.
• Body weight ≥ 40 kg.
• Confirmed diagnosis of SLE(1997 ACR revised criteria) for ≥ 24 weeks.
• Must be receiving at least one of the following SOC regimens at screening:
• oral prednisone monotherapy: ≥ 7.5 mg/day and ≤ 40 mg/day, stable for > 2 weeks;
• Immunosuppressant(s) with or without OCS and must be stable for ≥ 8 weeks;
• Oral prednisone plus immunosuppressant: start date, stability and maximum dose required.
• At least one of these antibodies positive: ANA, anti-dsDNA and anti-Smith.
• SLEDAI-2K score ≥ 6 points at screening and "Clinical" SLEDAI-2K score ≥4 points at both screening and Day1(randomisation), and BILAG with at least 1 level A organ system or 2 level B organ system, and PGA score ≥ 1.0 at screening.
• Chest imaging shows no clinically significant abnormalities (unless due to SLE).
• No evidence or medical history of active TB, indeterminate TB should be referred to a TB specialist.
• All participants should use effective contraception methods as protocol requests.
• Any negative SARS-CoV-2 RT-PCR test result at screening and no known or suspected COVID-19 infection or exposure within 2 weeks prior to screening and between screening and randomisation visits.

Key exclusion criteria

• 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 other than SLE, non-SLE disease that has required treatment of certain dosage of corticosteroid.
• History or evidence of suicidal ideation or suicidal behavior.
• History or current diagnose of MTCD or overlap syndrome, unless overlap with RA or MTCD which has developed into SLE.
• History of recurrent infection requiring hospitalization and IV antibiotics, or opportunistic infection requiring hospitalization or IV antimicrobial treatment within 3 years of randomization, or clinically significant chronic infection within 3 months, or recent infection still under treatment.
• History of immunodeficient condition, HIV positive included.
• Confirmed HBsAg positive, or HBcAb positive and HBV DNA detectable, or hepatitis C antibody positive.
• History of severe case of herpes zoster.
• Herpes zoster, CMV or EB infection which has not completely resolved within 12 weeks before screening.
• Acute COVID-19 infection or history of severe COVID-19.
• History of cancer, apart from cured squamous or basal cell carcinoma and cervical cancer in situ.
• Female participants with abnormal pap smear results.
• Prior receipt of anifrolumab , or any commercially available Janus kinase (JAK) inhibitor ≤ 12 weeks or Bruton's tyrosine kinase (BTK) inhibitor ≤ 24weeks prior to signing the ICF; any investigational medicinal product(small molecule or biologic agent) within 4 weeks or 5 half-lives prior to signing of the ICF, whichever is greater.
• Known history of allergy to any component of the IP formulation or protein related products.
• Receipt of any of the following:
• Intramuscular or IV glucocorticosteroids within 6 weeks;
• Any live or attenuated vaccine within 8 weeks;
• Any restricted medication listed in protocol;
• Blood transfusion within 4 weeks. 15 Regular use of > 1 NSAID within 2 weeks or receipt of fluctuating doses of a NSAID within 2 weeks.
• 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.