Safety and Tolerability of MEDI-545 in Patients Who Have Systemic Lupus Erythematosus (SLE)

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to evaluate the safety and tolerability of intravenously administered MEDI-545 compared with placebo, over a dose escalation range of 0.3-30 mg/kg, in adult patients with SLE and who are receiving 20 mg/day or less of prednisone orally or an equivalent dose of another oral corticosteroid.

Detailed Description
-----------------
The primary objective of this study is to evaluate the safety and tolerability of intravenously administered MEDI-545 compared with placebo, over a dose escalation range of 0.3-30 mg/kg, in adult patients who have SLE and who are receiving 20 mg/day or less of prednisone orally or an equivalent dose of another oral corticosteroid. The secondary objective of this study is to describe the pharmacokinetics and potential immunogenicity of MEDI-545.

Official Title
-----------------
A Phase I, Randomized, Double-Blind, Placebo Controlled, Dose-Escalation Study to Evaluate Safety and Tolerability of a Single IV Dose of MEDI-545, a Fully Human Monoclonal Antibody Directed Against Interferon Alpha Subtypes, in Patients With Systemic Lupus Erythematosus (SLE)

Conditions
-----------------
Lupus

Intervention / Treatment
-----------------
* Biological: MEDI-545
* Biological: MEDI 545
* Biological: MEDI-545
* Biological: MEDI-545
* Biological: MEDI-545


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients must meet all of the following criteria: Adult males and females ≥ 18 years at the time of the first dose of study drug. Written informed consent obtained from the patient/patient's legal guardian Diagnosis of SLE: Patients must have previously met ≥ 4 of the 11 revised ACR criteria Current background treatments may include the following medications prior to randomization: acetaminophen, non-steroidal anti-inflammatory drugs (NSAIDs), and antimalarials, such as hydroxychloroquine ≤ 600 mg/day, and prednisone ≤ 20 mg daily (or an equivalent dose of another oral corticosteroid) for at least 28 days Sexually active females, unless surgically sterile or at least two years post-menopausal, must use an effective method of avoiding pregnancy (including oral, injectable, transdermal, or implanted contraceptives, IUD, female condom, diaphragm with spermicide, cervical cap, abstinence, use of a condom by the sexual partner or sterile sexual partner) for 28 days before the first dose of study drug, and must agree to continue using such precautions through the study period of 84 days. Cessation of birth control after this point should be discussed with a responsible physician. Sexually active males, unless surgically sterile, must likewise use an effective method of birth control (condom or abstinence) and must agree to continue using such precautions through Study Day 84. Ability to complete follow-up period of 84 days as required by the protocol. Exclusion Criteria: Weight ≥ 120 kg Use of cyclophosphamide, azathioprine, methotrexate, mycophenolate mofetil or cyclosporine within 28 days before study entry Use of doses of corticosteroids higher than the equivalent of prednisone 20 mg/day (or an equivalent dose of another corticosteroid) within 28 days before study entry In the opinion of the investigator, a likelihood of requiring initiation of immunosuppressant therapy (e.g., prednisone >20 mg daily (or an equivalent dose of another oral corticosteroid), azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, or dapsone) within the 28 days after study entry. Antimalarial dosing must be held constant during the study, but analgesics and NSAIDs may be varied. Current treatment with coumadin Treatment with immunoglobulin or blood products within 28 days before entry into the study Treatment with any investigational drug therapy within 28 days before entry into the study; in the case of cell-depleting therapies, such as B or T cell depletion, cell counts that remain below acceptable or baseline levels (use of licensed agents for indications not listed in the package insert is permitted) History of primary immunodeficiency History of allergic reactions likely to be exacerbated by any component of the study drug Previous medical history, or evidence, of an intercurrent illness, other than SLE, that may compromise the safety of the patient in the study Clinically significant cardiac disease, including: unstable angina; myocardial infarction within 6 months; congestive heart failure; arrhythmia requiring active therapy, with the exception of clinically insignificant extra systoles, or minor conduction abnormalities; and history of clinically significant abnormality on electrocardiogram Evidence of significant active infection, or vaccination with live attenuated viruses, currently or in the 2 weeks before randomization Evidence of infection with hepatitis B or C virus, or HIV-1 or HIV-2, or active infection with hepatitis A, as determined by results of testing at screening A history of severe infection with viruses of the herpes family including Epstein-Barr virus requiring hospitalization, disseminated herpes, herpes encephalitis, ophthalmic herpes, or cytomegalovirus Herpes zoster ≤ 3 months prior to screening Current suppressive antiviral therapy for herpes or other viral infections Ongoing, chronic infectious disease such as chronic renal infection or chronic chest infection with bronchiectasis or sinusitis Pregnancy (females, unless surgically sterile or at least two years post-menopausal must have a negative serum pregnancy test within 14 days before receiving the study drug and a negative urine pregnancy test on Study Day 0 before receiving the study drug) Nursing mother History of alcohol or drug abuse within the past 2 years Presence of end-stage renal disease, or rapidly progressive glomerulonephritis Active central nervous system lupus History of stroke, or any cerebrovascular disease requiring medication/treatment. History of cancer, apart from basal cell carcinoma or in situ carcinoma of the cervix treated with apparent success with curative therapy >1 year prior to enrollment At screening (must be within14 days before entry into the study) any of the following: AST > 1.5x upper limit of normal range (ULN) ALT > 1.5x ULN creatinine > 1.5x ULN for patient's age, sex and weight serum K above or below the normal range hemoglobin < 8 g/dL white blood cell count < 1,800/mm3 (Superscript) neutrophils < 1,500/mm3 (Superscript) platelet count < 50,000/mm3 (Superscript) other abnormal laboratory values in the screening panel that in the opinion of the principal investigator are judged to potentially confound analysis of study results

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>MEDI-545 | Biological: MEDI 545<br>* 0.3 mg/kg IV (n=6) at Study Day 0<br>|
| Active Comparator: 2<br>MEDI-545 | Biological: MEDI-545<br>* 0.3 mg/kg IV (n=6) at Study Day 0<br>|
| Active Comparator: 3<br>MEDI-545 | Biological: MEDI-545<br>* 0.3 mg/kg IV (n=6) at Study Day 0<br>|
| Active Comparator: 4<br>MEDI-545 | Biological: MEDI-545<br>* 0.3 mg/kg IV (n=6) at Study Day 0<br>|
| Active Comparator: 5<br>MEDI-545 | Biological: MEDI-545<br>* 0.3 mg/kg IV (n=6) at Study Day 0<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and tolerability of MEDI-545 will be assessed primarily by summarizing adverse events. |  | Day 84 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of MEDI-545 pharmacokinetics and possible immunogenicity |  | Day 84 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Lupus