Safety Study of AMG 811 in Subjects With Systemic Lupus Erythematosus With and Without Glomerulonephritis

This is an interventional treatment trial for Nephritis focused on measuring Lupus, Nephritis Read More

Inclusion Criteria:

• Men and women, between the ages of 18 and 70 years of age;
• Body mass index from 18 to 40 kg/m2 [Body Weight (kg)/Height2 (m2)] at screening;
• Diagnosis of SLE at least 6 months before randomization, including a positive antinuclear antibodies (ANA) during screening; if screening ANA is negative, documented historical ANA with a titer of at least 1:80 will be acceptable;
• Any concurrent SLE pharmacologic regimen (including mycophenolate mofetil, azathioprine, leflunomide, methotrexate, and anti-malarials) must be stable for at least 30 days before randomization;
• Prednisone ≤ 20 mg/day (or equivalent) is permitted; one increase or one decrease of ≤ 5 mg/day prednisone equivalent will be allowed within 30 days before randomization;

Additional inclusion criteria for Part B:

- Active SLE with GN with no other apparent cause, defined by the following: Renal biopsy evidence (within 18 months) of nephritis using the WHO or International Society of Nephrology (ISN)/Renal Pathology Society (RPS) classification of SLE with GN (Class III or IV); Urine protein/creatinine ratio (UP/Cr) > 1 or 24 hour urine protein > 1g after at least 12 weeks of treatment with mycophenolate mofetil (at least 1.5 grams/day) or azathioprine (at least 100 mg orally per day); Superimposed membranous changes are allowed for those with Class III or Class IV SLE with GN;

- Prednisone ≤ 20 mg/day (or equivalent) at the time of randomization.

Exclusion Criteria:

• Any disorder (including psychiatric), condition or clinically significant disease (other than a diagnosis of SLE) that would, by its progressive nature and/or severity, interfere with the study evaluation, completion and/or procedures per the investigator's discretion;
• Creatinine clearance within the screening period of less than 50 mL/min as calculated by the Cockcroft-Gault method
• Signs or symptoms of a viral, bacterial or fungal infection within 30 days of study randomization, or recent history of repeated infections;
• Underlying condition other than SLE or being on allowed immunosuppressants that predisposes one to infections
• Prior use of the following agents:
• Administration of an investigational biologic agent that primarily targets the immune system
• Administration of cyclosporine, tacrolimus, sirolimus, IV immunoglobulin, and/or plasmapheresis within 3 months of randomization;
• Administration of oral or IV cyclophosphamide (or any other alkylating agent) within 12 months (Part A) or 3 months (Part B) of randomization;
• History of ethanol or drug abuse within the last one year prior to randomization;

Additional exclusion criteria for Part B:

• Rapidly progressive GN (defined as a doubling of serum creatinine within the past 3 months);
• Evidence of significant chronicity, defined as:

> 50% glomeruli with sclerosis or > 50% interstitial fibrosis on renal biopsy; or International Society of Nephrology (ISN)/Renal Pathology Society (RPS) 2003 Class III (C), IV-S (C) or IV-G (C).