Efficacy and Safety of Anifrolumab compared to placebo in adult subjects with Active Systemic Lupus Erythematosus

Inclusion Criteria

• Inclusion Criteria:
• 1. Aged 18 through 70 years at the time of screening
• 2. Diagnosis of paediatric or adult SLE with a diagnosis of SLE according to the ACR 1982 revised criteria ≥24 weeks prior to signing the Informed Consent form (ICF)
• 3. Currently receiving at least 1 of the following:
• (a) Where prednisone is the single standard of care medication (ie, the subject is not concurrently receiving any medication listed in inclusion criterion 3(c)), a dose of oral prednisone ≥7.5 mg/day but ≤40 mg/day (or prednisone equivalent) for a minimum of 8 weeks prior to Day 1. In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation
• (b) Where prednisone is not the single standard of care medication (ie, the subject is concurrently receiving at least one medication listed in inclusion criterion 3(c), a dose of oral prednisone (≤40 mg/day) (or prednisone equivalent) for a minimum of 2 weeks prior to signing of the ICF. In addition, the dose of oral prednisone or prednisone equivalent the subject is taking must be stable for a minimum of 2 weeks prior to randomisation.
• (c) Any of the following medications administered for a minimum of 12 weeks prior to signing the informed consent, and at a stable dose for a minimum of 8 weeks prior to signing the informed consent and through Day 1:
• (i) Azathioprine ≤200 mg/day
• (ii) Antimalarial (eg, chloroquine, hydroxychloroquine, quinacrine)
• (iii) Mycophenolate mofetil ≤2 g/day or mycophenolic acid ≤1.44 g/day
• (iv) Oral, subcutaneous (SC), or intramuscular methotrexate ≤25 mg/week
• (v) Mizoribine ≤150 mg/day
• 4. Fulfils at least 4 of the 11 ACR modified 1982 classification criteria for SLE, at least 1 of which must be:
• (a) Positive antinuclear antibody (ANA) test at screening by immunofluorescent assay (IFA) at the central laboratory with titre ≥1:80; OR
• (b) Anti-dsDNA antibodies at screening elevated to above normal (including indeterminate), as per the central laboratory; OR
• (c) Anti-Smith (anti-Sm) antibody at screening elevated to above normal as per the central laboratory
• 5. At Screening, Disease Activity Adjudication Group confirmation of:
• SLEDAI-2K Criteria: SLEDAI-2K score ≥6 points and “Clinical” SLEDAI-2K score ≥4 points. The “Clinical” SLEDAI-2K is the SLEDAI-2K assessment score without the inclusion of points attributable to any urine or laboratory results including immunologic measures.
• 6. Must not have active or latent TB on either chest radiograph or by quantiferon gold test
• 7. Day 1 “Clinical” SLEDAI-2K score ≥4 points
• 8. OCS dose stable for at least 2 weeks prior to randomisation
• 9. Stable SLE SOC treatment at the time of randomisation
• 10. Women of child-bearing potential must have a negative serum β-hCG test at and negative urine pregnancy test at randomisation prior to administration of investigational product
• Exclusion Criteria:
• 1. Receipt of any investigational product (small molecule or biologic agent) within 4 weeks or 5 half-lives prior to signing of the ICF, whichever is greater
• 2. Receipt of any of the following:
• (a) Intra-articular, intramuscular or IV glucocorticosteroids within 6 weeks prior to Day 1
• 3. History of, or current diagnosis of, a clinically significant non SLE-related vasculitis syndrome.
• 4. Active severe or unstable neuropsychiatric SLE
• 5. Active severe SLE-driven renal disease
• 6. Diagnosis (within 1 year of signing the ICF) of mixed connective tissue disease or any history of overlap syndromes of SLE or SSc.
• 7. History of, or current, inflammatory joint or skin disease other than SLE
• 8. History of any non-SLE disease that has required treatment with oral or parenteral corticosteroids for more than 2 weeks within the last 24 weeks prior to signing the ICF
• 9. 26.27. Known history of a primary immunodeficiency, splenectomy, or any underlying condition that predisposes the subject to infection, or a positive result for human immunodeficiency virus (HIV) infection confirmed by central laboratory at screening. Subjects refusing HIV testing during the screening period will not be eligible for study participation
• 10. Confirmed positive test for hepatitis B or hepatitis C
• 11. Any severe herpes infection at any time prior to Week 0 (Day 1)
• 12. Opportunistic infection requiring hospitalisation or intravenous antimicrobial treatment within 3 years prior to randomization
• 13. History of cancer, apart from:
• (a) Squamous or basal cell carcinoma of the skin that has been successfully treated
• (b) Cervical cancer in situ that has been successfully treated