- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00299819
Safety and Tolerability of MEDI-545 in Patients Who Have Systemic Lupus Erythematosus (SLE)
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)
Study Overview
Status
Conditions
Intervention / Treatment
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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Ontario
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Toronto, Ontario, Canada, MST 258
- Toronto Western Hospital
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Quebec
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Montreal, Quebec, Canada, H3G 1A4
- Montreal General Hospital
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Alabama
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Anniston, Alabama, United States, 35207
- Pinnacle Research Group
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California
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Los Angeles, California, United States, 90048
- Wallace Rheumatic Study Center
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Florida
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Clearwater, Florida, United States, 33765
- Clinical Research of West Florida
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Ft. Lauderdale, Florida, United States, 03334
- Center for Rhematology, Immunology, and Arthritis
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Ocala, Florida, United States, 34474
- Ocala Rheumatology Research Center
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Tampa, Florida, United States, 33614
- Tampa Florida Medical Research Group
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Zephyrhills, Florida, United States, 33542
- Florida Medical Clinic, Clinical Research Division
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Louisiana
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Shreveport, Louisiana, United States, 71130
- Louisiana State University Health Sciences Center-Shreveport
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Maryland
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Baltimore, Maryland, United States, 21205
- Johns Hopkins University, School of Medicine
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Minnesota
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Duluth, Minnesota, United States, 55805
- St. Mary's Duluth Clinic
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New York
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New York, New York, United States, 10032
- Columbia University Medical Center
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New York, New York, United States, 10021
- Hospital for Special Surgery
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Oklahoma
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Oklahoma City, Oklahoma, United States, 73104
- Oklahoma Medical Research Foundation
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Oregon
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Portland, Oregon, United States, 97223
- Oregon Medical Research Center
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Pennsylvania
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Duncansville, Pennsylvania, United States, 16635
- Altoona Center for Clinical Research
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Texas
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Dallas, Texas, United States, 75390
- University of Texas Southwestern Medical Center
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Washington
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Seattle, Washington, United States, 98195
- University of Washington Div. of Rhematology
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Wisconsin
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Milwaukee, Wisconsin, United States, 53226
- Froedtert Hospital, Medical College of Wisconsin
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Milwaukee, Wisconsin, United States, 53226
- Center for Innovative Therapy, UCSD School of Medicine
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Single Group Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
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Active Comparator: 1
MEDI-545
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0.3 mg/kg IV (n=6) at Study Day 0
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Active Comparator: 2
MEDI-545
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0.3 mg/kg IV (n=6) at Study Day 0
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Active Comparator: 3
MEDI-545
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0.3 mg/kg IV (n=6) at Study Day 0
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Active Comparator: 4
MEDI-545
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0.3 mg/kg IV (n=6) at Study Day 0
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Active Comparator: 5
MEDI-545
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0.3 mg/kg IV (n=6) at Study Day 0
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
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Safety and tolerability of MEDI-545 will be assessed primarily by summarizing adverse events.
Time Frame: Day 84
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Day 84
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
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Evaluation of MEDI-545 pharmacokinetics and possible immunogenicity
Time Frame: Day 84
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Day 84
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Collaborators and Investigators
Sponsor
Investigators
- Study Director: Barbara White, M.D., MedImmune LLC
Publications and helpful links
General Publications
- Hannon CW, McCourt C, Lima HC, Chen S, Bennett C. Interventions for cutaneous disease in systemic lupus erythematosus. Cochrane Database Syst Rev. 2021 Mar 9;3(3):CD007478. doi: 10.1002/14651858.CD007478.pub2.
- Merrill JT, Wallace DJ, Petri M, Kirou KA, Yao Y, White WI, Robbie G, Levin R, Berney SM, Chindalore V, Olsen N, Richman L, Le C, Jallal B, White B; Lupus Interferon Skin Activity (LISA) Study Investigators. Safety profile and clinical activity of sifalimumab, a fully human anti-interferon alpha monoclonal antibody, in systemic lupus erythematosus: a phase I, multicentre, double-blind randomised study. Ann Rheum Dis. 2011 Nov;70(11):1905-13. doi: 10.1136/ard.2010.144485. Epub 2011 Jul 27.
- Yao Y, Richman L, Higgs BW, Morehouse CA, de los Reyes M, Brohawn P, Zhang J, White B, Coyle AJ, Kiener PA, Jallal B. Neutralization of interferon-alpha/beta-inducible genes and downstream effect in a phase I trial of an anti-interferon-alpha monoclonal antibody in systemic lupus erythematosus. Arthritis Rheum. 2009 Jun;60(6):1785-96. doi: 10.1002/art.24557.
Study record dates
Study Major Dates
Study Start
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- MI-CP126
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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