Safety and Tolerability of Intravenous Dose of MEDI-546 in Japanese Subjects With Systemic Lupus Erythematosus.

Study Overview
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Brief Summary
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The purpose of this study is to assess safety, tolerability, pharmacokinetics and pharmacodynamics of MEDI-546 in Japanese SLE patients.

Detailed Description
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A phase 2, multicenter, open-label, dose-escalation study to evaluate the safety and tolerability of intravenous dose of MEDI-546, a human monoclonal antibody directed against type I interferon receptor (IFNAR), in Japanese subjects with active systemic lupus erythematosus (SLE)

Official Title
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A Phase 2, Multicenter, Open-label, Dose-escalation Study to Evaluate the Safety and Tolerability of Intravenous Dose of MEDI-546, a Human Monoclonal Antibody Directed Against Type I Interferon Receptor (IFNAR), in Japanese Subjects With Active Systemic Lupus Erythematosus (SLE).

Conditions
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Systemic Lupus Erythematosus

Intervention / Treatment
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* Drug: MEDI-546
* Drug: MEDI-546
* Drug: MEDI-546


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fulfils at least 4 of the 11 American College of Rheumatology (ACR) classification criteria for SLE. Weight greater than or equal to 40.0 kg. Diagnosis of pediatric or adult SLE with chronic disease activity requiring ongoing treatment or observation for ≥ 24 weeks prior to screening. Currently receiving stable dose of oral prednisone and/or antimalarials/immunosuppressives. Active moderate to severe SLE disease based on SLE disease activity score. Exclusion Criteria: Active severe or unstable neuropsychiatric SLE. Active severe SLE-driven renal disease or unstable renal disease. Clinically significant active infection including ongoing and chronic infections. Known history of a primary immunodeficiency or an underlying condition such as human immunodeficiency virus infection or splenectomy that predisposes the subject to infection. Confirmed positive tests for hepatitis B or positive test for hepatitis C.

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: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>MEDI-546 100 mg IV | Drug: MEDI-546<br>* Stage I: 100 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks<br>|
| Experimental: 2<br>MEDI-546 300 mg IV | Drug: MEDI-546<br>* Stage I: 300 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 300 mg IV, multiple doses once every 4 wks for 156 wks<br>|
| Experimental: 3<br>MEDI-546 1000 mg IV | Drug: MEDI-546<br>* Stage I: 1000 mg IV, single dose and multiple doses once every 4 wks for 48 wks Stage II: 1000 mg IV, multiple doses once every 4 wks for 156 wks, the dose at Stage II was changed to 300 mg IV.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Summary of Adverse Events |  | Stage I (up to 48 weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic Parameters of MEDI-546 After Single Dose: Cmax |  | Pre-dose and within 30 minutes after end of infusion on Day 1, Days 2, 8, 15, and 22, and pre-dose on Day 29 | 
| Pharmacokinetic Parameters of MEDI-546 After Single Dose: AUClast |  | Pre-dose and within 30 minutes after end of infusion on Day 1, Days 2, 8, 15, and 22, and pre-dose on Day 29 | 
| Anti-drug Antibody (ADA) | MEDI-546 antibody detection measured by electrochemiluminescence (ECL). | Stage I (up to Week 48) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Japan, Phase2, Safety, Tolerability, Systemic Lupus Erythematosus, SLE, MEDI-546