Efficacy and Safety of Two Doses of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus
Condition: Active Systemic Lupus Erythematosus
MeSH terms: Lupus Erythematosus, Systemic
Intervention: Anifrolumab; Placebo
Intervention description: Anifrolumab IV administration every 4 weeks from Week 0 to Week 48 for a total of 13 doses; Placebo IV administration every 4 weeks from Week 0 to Week 48
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 460.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Active Systemic Lupus Erythematosus

Summary:

      The purpose of this study is to evaluate the efficacy and safety of an intravenous treatment
      regimen of two doses of anifrolumab versus placebo in adult subjects with moderately to
      severely active, autoantibody-positive systemic lupus erythematosus (SLE).
    

Eligibility 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:

               1. 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.

               2. 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.

               3. 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 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:

               1. Positive antinuclear antibody (ANA) test at screening by immunofluorescent assay
                  (IFA) at the central laboratory with titre ≥1:80; OR

               2. Anti-dsDNA antibodies at screening elevated to above normal (including
                  indeterminante), as per the central laboratory; OR

               3. 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 and negative
             urine pregnancy test at randomisation (Day 1) 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. 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:

               1. Squamous or basal cell carcinoma of the skin that has been successfully treated

               2. Cervical cancer in situ that has been successfully treated