Efficacy and Safety of AMG 570 in Subjects With Active Systemic Lupus Erythematosus (SLE)

The purpose of the study is to evaluate safe and efficacious doses of AMG 570 for the treatment of active systemic lupus erythematosus (SLE) in patients who are not responding to the current standard of care. AMG 570 is a bispecific peptide immunoglobulin (Ig) G2 antibody conjugate. This study will help determine if AMG 570 could be a useful therapeutic agent in the current treatment landscape where subjects have ongoing disease activity despite treatment with standard of care therapies. If you meet the study requirements and are enrolled, you will be in this study for about 52 weeks.

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.