Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)
Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)
The purpose of this study is to determine if AMG 570 could be a useful therapeutic agent in
 the current treatment landscape where subjects with systemic lupus erythematosus (SLE) have
 ongoing disease activity despite treatment with standard of care therapies.
This is a Bayesian adaptive phase 2b, multi-center, double-blind, randomized,
 placebo-controlled, 52-week, dose-ranging study in subjects with active SLE and inadequate
 response to SOC therapies including oral corticosteroids (OCS), immunosuppressants and
 immunomodulators. Previous biologic use is allowed with an adequate washout period.
Inclusion Criteria Screening Visit:

 -  Subject has provided informed consent prior to initiation of any study-specific
 activities/procedures.

 -  Age ≥ 18 years to ≤ 75 years at screening visit.

 -  Fulfills classification criteria for SLE according to the 2019 European League Against
 Rheumatism (EULAR)/American College of Rheumatology (ACR) classification criteria for
 SLE (Aringer et al, 2019), with antinuclear antibody ≥ 1:80 by immunofluorescence on
 Hep-2 cells being present at screening.

 -  Hybrid SLEDAI score ≥ 6 points with a "Clinical" hSLEDAI score ≥ 4 points. The
 "Clinical" hSLEDAI is the hSLEDAI assessment score without the inclusion of points
 attributable to laboratory results, including urine or immunologic parameters.

 Additional protocol-specific rules are applied at screening and throughout the study, as
 follows:

 -  Arthritis: Arthritis (at least 3 tender and swollen joints) must involve joints in the
 hands or wrists for the hSLEDAI scoring.

 -  Alopecia: Subjects should have hair loss without scarring; should neither have
 alopecia areata nor androgenic alopecia; and should have a CLASI activity score for
 alopecia ≥ 2.

 -  Oral ulcers: Ulcers location and appearance must be documented by the investigator.

 -  Scleritis and Episcleritis: the presence of stable SLE-related scleritis and
 episcleritis must be documented by an ophthalmologist and other causes excluded.

 -  Renal: subjects with urine protein/creatinine ratio < 3000 mg/g (or equivalent method)
 in a clear catch spot urine sample can enroll and be scored in the hSLEDAI, provided
 the subject has a clinical hSLEDAI ≥ 4 and did not receive induction treatment for
 nephritis within the last year.

 -  Pleurisy and Pericarditis: symptoms of pleurisy and pericarditis must be accompanied
 by objective findings to be scored in the hSLEDAI.

 -  Must be taking at least 1 but not more than 2 of the following SLE treatments
 unless there is a documented intolerance to the following treatments:
 anti-malarial (hydroxychloroquine, chloroquine, or quinacrine), azathioprine,
 methotrexate, mycophenolate mofetil/acid mycophenolic, or dapsone. Treatment
 should be taken for ≥12 weeks prior to screening and must be a stable dose for ≥
 8 weeks prior to screening. If subject is taking 2 of the above mentioned SLE
 treatments, 1 of these must be either hydroxychloroquine, quinacrine, or
 chloroquine.

 -  For subjects taking OCS, dose must be ≤ 20 mg/day of prednisone or OCS
 equivalent, and the dose must be stable at baseline visit for ≥ 2 weeks prior to
 screening visit.

 Exclusion Criteria Screening Visit

 Subjects are excluded from the study if any of the following criteria apply:

 Disease Related

 -  Urine protein creatinine ratio ≥ 3000 mg/g (or equivalent) at screening or induction
 therapy for lupus nephritis within 1 year prior to screening visit.

 -  Active CNS lupus within 1 year prior to screening including, but not limited to,
 aseptic meningitis, ataxia, CNS vasculitis, cranial neuropathy, demyelinating
 syndrome, optic neuritis, psychosis, seizures, or transverse myelitis.