Safety Study of AMG 557 in Subjects With Lupus Arthritis

Study Overview
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Brief Summary
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This is a multicenter, randomized, double-blind, parallel, placebo-controlled, multiple dose study that will enroll approximately 40 systemic lupus erythematosus subjects with active lupus arthritis.

Official Title
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A Randomized, Double-blind, Parallel, Placebo-controlled, Multiple Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Clinical Effect of AMG 557 in Systemic Lupus Erythematosus (SLE) Subjects With Active Lupus Arthritis

Conditions
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Lupus Arthritis, Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: AMG 557
* Drug: Matching Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of SLE for at least 6 months as defined by the most recent American College of Rheumatology criteria Presence of lupus related inflammatory arthritis with at least four tender and four swollen joints; and Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) ≥ 6 at screening; Other inclusion criteria may apply. Exclusion Criteria: Presence or history of vasculitis, and presence or history of active lupus nephritis requiring therapy within the last 3 years Any disorder (including psychiatric), condition, clinically significant disease, disease activity related to SLE Positive for HIV antibodies, hepatitis B surface antigen or anti-HBc, or hepatitis C antibodies Known residential exposure to an individual with tuberculosis or positive Quantiferon test or PPD test at screening Men and women of reproductive potential, unwilling to practice a highly effective method of birth control for the duration of the study Other exclusion criteria may apply

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: AMG 557<br>All will receive AMG 557 on Day 1, Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141 and Day 155. | Drug: AMG 557<br>* AMG 557 will be administered as subcutaneous injections in the anterior abdomen of the subjects.<br>|
| Placebo Comparator: AMG 557 Matching Placebo<br>All will receive AMG 557 on Day 1, Day 8, Day 15, Day 29, Day 43, Day 57, Day 71, Day 85, Day 99, Day 113, Day 127, Day 141 and Day 155. | Drug: Matching Placebo<br>* Placebo will be administered as subcutaneous injections in the anterior abdomen of the subjects.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Treatment-emergent adverse events, vital signs, physical examinations, clinical laboratory tests, ECGs, and the incidence of binding and neutralizing antibodies to AMG 557. |  | 330 days, including a 21-day screening period | 
| Lupus Arthritis Response Rate | Defined by: 1) achieving at least a 50% decrease in the combined tender and swollen joint count compared to baseline at Day 169; 2) achieving one letter improvement in the Musculoskeletal System BILAG at Day 169 compared to baseline; 3) reduction in and maintenance of prednisone (or its equivalent) dose to ≤ 50% of baseline corticosteroid dose (Day 1 predose) or ≤ 7.5 mg/day, whichever is lower, from Day 85 to Day 169 in subjects not treated with immunosuppressants at baseline, or reduction in and maintenance of prednisone (or its equivalent) dose to ≤ 7.5 mg/day from Day 85 to Day 169 and discontinuation of immunosuppressants by Day 29 in subjects treated with immunosuppressants at baseline | Day 169 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of subjects achieving a) one letter improvement; and b) 'C' or better score in the Musculoskeletal system from BILAG index at Day 169 compared to baseline, by treatment group. |  | Day 169 | 
| Percentage change in the tender and swollen joint counts at Day 169 relative to baseline. |  | Day 169 | 
| Proportion of subjects achieving reduction in and maintenance ≤ 7.5 mg/day of prednisone (or equivalent) from Day 85- Day 169 and discontinuation of immunosuppressants by Day 29 in subjects treated with immunosuppressants at baseline. |  | Days 85-169 | 
| Proportion of subjects achieving reduction in and maintenance of prednisone (or its |  | Days 85-169 | 
| Physician Global Assessment of Disease Activity (PGADA). |  | 330 days, including a 21-day screening period | 
| Subject Global Assessment of Disease Activity (SGADA). |  | 330 days, including a 21-day screening period | 
| Serum PK profile of AMG 557 after multiple dose administrations. |  | 330 days, including a 21-day screening period | 
| Proportion of subjects who discontinued immunosuppressants by Day 29 in subjects |  | Day 29 | 
| Cumulative dose of prednisone (or its equivalent) from Day 85 to Day 169. |  | Day 85 to Day 169 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Lupus Arthritis, Systemic Lupus Erythematosus, AMG 557, Lupus