Efficacy and Safety of Anifrolumab Compared to Placebo in Adult Subjects With Active Systemic Lupus Erythematosus

This is a Phase 3, multicentre, multinational, randomised, double-blind, placebo-controlled
study to evaluate the efficacy and safety of an intravenous treatment regimen of anifrolumab
versus placebo in subjects with moderately to severely active, autoantibody-positive systemic
lupus erythematosus (SLE) while receiving standard of care (SOC) treatment. The study will be
performed in adult subjects aged 18 to 70 years of age.

Approximately 360 subjects receiving SOC treatment will be randomised in a 1:1 ratio to
receive a fixed intravenous dose of anifrolumab or placebo every 4 weeks for a total of 13
doses (Week 0 to Week 48), with the primary endpoint evaluated at the Week 52 visit.
Investigational product will be administered as an intravenous (IV) infusion via an infusion
pump over a minimum of 30 minutes, every 4 weeks.

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 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:

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
indeterminate), 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 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:

1. Squamous or basal cell carcinoma of the skin that has been successfully treated

2. Cervical cancer in situ that has been successfully treated