A Study to Evaluate Safety and Tolerability of IV or SC Dose of MEDI-545 in Patients With Systemic Lupus Erythematosus.

Study Overview
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Brief Summary
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The purpose of the study is to evaluate the safety and tolerability of MEDI-545 in Japanese adult SLE patients. This will be done by collecting the data from 3 cohorts of IV doses and 1 cohort of SC doses.

Official Title
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A Phase II, Multicenter, Open-Label, Dose-Escalation Study to Evaluate Safety and Tolerability of IV or SC Dose of MEDI-545, a Fully Human Monoclonal Antibody Directed Against Interferon Alpha Subtypes, in Japanese Patients Who Have Systemic Lupus Erythematosus (SLE)

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: MEDI-545
* Drug: MEDI-545
* Drug: MEDI-545
* Drug: MEDI-545
* Drug: MEDI-545
* Drug: MEDI-545 600


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have previously met ≥4 of the 11 revised ACR criteria Have positive antinuclear antibody test (ANA) at ≥1:80 serum dilute in the past or at screening Have at least 1 system with a score of A or 2 systems with a score of B on the BILAG index at screening, or have a SELENA-SLEDAI score ≥6 Exclusion Criteria: Have received prednisone >20 mg/day (or an equivalent dose of another oral corticosteroid) within 14 days before Visit 2 (Day 1) Have received the following medications within 28 days before Visit 2 (Day 1): Systemic cyclophosphamide at any dose Cyclosporine at any dose Tacrolimus at any dose Thalidomide at any dose Mycophenolate mofetil >2 g/day Methotrexate >15 mg/week Azathioprine >2 mg/kg/day Women who have a positive pregnancy test (serum hCG) at Visit 1

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 130 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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: MEDI-545 1.0 mg/kg<br>Cohort 1 | Drug: MEDI-545<br>* Stage I: MEDI-545 1.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 1.0 mg/kg IV once every 2 weeks for a total of 79 doses.<br>|
| Experimental: MEDI-545 3.0 mg/kg<br>Cohort 2 | Drug: MEDI-545<br>* Stage I: MEDI-545 3.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 3.0 mg/kg IV once every 2 weeks for a total of 79 doses<br>|
| Experimental: MEDI-545 10.0 mg/kg<br>Cohort 3 | Drug: MEDI-545<br>* Stage I: MEDI-545 10.0 mg/kg IV, on Day 1 and once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 10.0 mg/kg IV once every 2 weeks for a total of 79 doses.<br>|
| Experimental: MEDI-545 100 mg<br>Cohort 4 | Drug: MEDI-545<br>* Stage I: MEDI-545 100 mg SC, on Day 1 and weekly or once every 2 weeks from Day 29, for a total of 14 doses. Stage II: MEDI-545 100 mg SC once every 2 weeks for a total of 79 doses.<br>|
| Experimental: MEDI-545 600 mg<br>Cohort 5 | Drug: MEDI-545 600<br>* Stage I: MEDI-545 600 mg IV once every 4 weeks from Day 1 for a total of 8 doses. Stage II: MEDI-545 600 mg IV once every 4 weeks for a total of 40 doses.<br>|
| Experimental: MEDI-545 1,200 mg<br>Cohort 6 | Drug: MEDI-545<br>* Stage I: MEDI-545 1,200 mg IV once every 4 weeks from Day 1 for a total of 8 doses. Stage II: MEDI-545 1,200 mg IV once every 4 weeks for a total of 40 doses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Each Category of Adverse Events in Stage I |  | Stage I (up to 1 year) | 
| Number of Participants in Each Category of Adverse Events (AE) in Stage II |  | Stage II (1 year to 3.5 years after first dose) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Undre Curve (AUC) of MEDI-545 After First Dose in Stage I |  | After first dose in Stage I (0 upto 28 days) | 
| AUC0-14 of MEDI-545 After First Dose in Stage I | Summary of area under the concentration-time curve from zero to Day 14. | After first dose in Stage I | 
| Maximum Observed Concentration (Cmax) of MEDI-545 After First Dose in Stage I |  | After first dose in Stage I | 
| Change From Baseline in 21-gene Signature Fold Change in Stage I | 21-gene signature fold change is pharmacodynamics (PD) parameter measuring expression of type I IFN-inducible gene. | Stage I | 
| Number of Participants With Positive Anti-drug Antibody (ADA) During Stage I |  | Stage I | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus, Japanese, phase 2, safety, tolerability, MEDI-545, Autoimmune Disease, Immune System Diseases