An Open-label Study to Evaluate the Long-term Safety of MEDI-546, for the Treatment of SLE, in Adults

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the long-term safety of anifrolumab (MEDI-546) in adults with moderate to severe active systemic lupus erythematosus (SLE).

Detailed Description
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This is an open-label extension study to evaluate long-term safety and tolerability of intravenous (IV) anifrolumab in adult participants with moderately-to-severely active SLE. Participants must have completed the qualifying Phase 2 study and meet this study criteria in order to be eligible.

Official Title
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A Phase 2, Open-label Extension Study to Evaluate Long-term Safety of MEDI-546 in Adults With Systemic Lupus Erythematosus

Conditions
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Lupus Erythematosus, Systemic

Intervention / Treatment
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* Biological: Anifrolumab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be willing to use 2 methods of effective contraception Must have venous access Must be willing to forego participation in other clinical trials for SLE. Exclusion Criteria: Any concurrent condition that in the opinion of the investigator would interfere with the evaluation of the investigational product Major surgery within 8 weeks before signing informed consent form (ICF) Elective major surgery planned during the study period Concomitant Medications within the last 12 weeks: Azathioprine > 200 mg/day, Mycophenolate mofetil/mycophenolic acid > 2.0 g/day, oral, subcutaneous, or intramuscular methotrexate > 25 mg/week A live or attenuated vaccine within 4 weeks of signing the ICF Bacillus of Calmette and Guérin (BCG) vaccine within 1 year of ICF

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 68 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
Intervention Model: Single Group Assignment
Interventional Model Description: This is an Open Label Extension study.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anifrolumab<br>Participants will receive IV infusion of anifrolumab 1000 milligrams (mg) every 4 weeks (Q4W) from Day 1 (Week 0) until 12-Feb-2015 (approval of protocol amendment 4); and thereafter will receive 300 mg Q4W for up to 3 years or until the sponsor discontinued development of anifrolumab, whichever came first. | Biological: Anifrolumab<br>* Intravenous infusion of anifrolumab will be administered as 1000 mg Q4W from Day 1 (Week 0) until 12-Feb-2015 (approval of protocol amendment 4); and thereafter 300 mg Q4W up to 3 years or until the sponsor discontinued development of anifrolumab, whichever came first.<br>* Other names: MEDI-546;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Particpants With Treatment-emergent Adverse Events (TEAEs) and Treatment-emergent Serious Adverse Events (TESAEs) | An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. Serious adverse event is any AE that resulted in death, life threatening, inpatient hospitalization or prolongation of existing hospitalization, persistent or significant disability or incapacity, is a congenital anomaly/birth defect in offspring of a study participant, is an important medical event that may jeopardize the participant or may require medical intervention. TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. | From first dose of study drug (Day 1) through 168 weeks | 
| Number of Participants With Adverse Events Resulting in Discontinuation (DAEs) of Anifrolumab | Number of participants with DAEs are reported. | From first dose of study drug (Day 1) through 168 weeks | 
| Number of Participants With Adverse Events of Special Interest (AESIs) | An AESI is scientific and medical concern specific to understanding of the study drug. An AESI may be serious or non-serious. Number of participants with AESIs are reported. | From first dose of study drug (Day 1) through 168 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants With Positive Anti-Drug Antibodies (ADA) Titer to Anifrolumab | The number of participants with positive serum antibodies to anifrolumab at anytime (including baseline) are reported. | Baseline (Pre-dose on Day 1) up to Week 168 | 
| Anti-Drug Antibodies (ADA) Titer to Anifrolumab | Median ADA titer in participants with ADA-positive assessments and reportable ADA titer results are reported. | Baseline (Pre-dose on Day 1) up to Week 168 | 
| Number of ADA-positive Participants With Decreased Serum Concentration of Anifrolumab | Number of participants with decreased serum concentration of anifrolumab due to ADA-positive results are reported. | Baseline (Pre-dose on Day 1) up to Week 168 | 
| Number of ADA-positive Participants With Decreased Pharmacodynamics Response of Anifrolumab | Number of participants with decreased pharmacodynamic response of anifrolumab due to ADA-positive results are reported. | Baseline (Pre-dose on Day 1) up to Week 168 | 
| Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K) Global Score for ADA Positive Participants | The SLEDAI-2K is an activity index that measures disease activity and records feature of active lupus as present or not present. SLEDAI-2K uses a weighted checklist to assign a numerical score based on the presence or absence of 24 symptoms. Each symptom present is assigned between 1 and 8 points based on its usual clinical importance, yielding a total score that ranges from 0 points (no symptoms) to 105 points (presence of all defined symptoms). | Baseline (Pre-dose on Day 1); and Weeks 12, 24, 36, 48, 60, 72, 84, 96, 108, 120, 132, 144, 156, 160, and 168 | 
| Number of ADA-positive Participants With TEAEs and TESAEs | The number of ADA-positive participants with TEAEs and TESAEs are reported. | Baseline (Pre-dose on Day 1) up to Week 168 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Systemic Lupus Erythematosus