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

NCT ID: NCT00299819

Last Updated: 2007-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

45 participants

Study Classification

INTERVENTIONAL

Study Start Date

2006-03-31

Study Completion Date

2007-10-31

Brief Summary

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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

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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.

Conditions

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Lupus

Keywords

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Lupus

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

DOUBLE

Participants Investigators

Study Groups

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1

MEDI-545

Group Type ACTIVE_COMPARATOR

MEDI 545

Intervention Type BIOLOGICAL

0.3 mg/kg IV (n=6) at Study Day 0

2

MEDI-545

Group Type ACTIVE_COMPARATOR

MEDI-545

Intervention Type BIOLOGICAL

0.3 mg/kg IV (n=6) at Study Day 0

3

MEDI-545

Group Type ACTIVE_COMPARATOR

MEDI-545

Intervention Type BIOLOGICAL

0.3 mg/kg IV (n=6) at Study Day 0

4

MEDI-545

Group Type ACTIVE_COMPARATOR

MEDI-545

Intervention Type BIOLOGICAL

0.3 mg/kg IV (n=6) at Study Day 0

5

MEDI-545

Group Type ACTIVE_COMPARATOR

MEDI-545

Intervention Type BIOLOGICAL

0.3 mg/kg IV (n=6) at Study Day 0

Interventions

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MEDI-545

0.3 mg/kg IV (n=6) at Study Day 0

Intervention Type BIOLOGICAL

MEDI 545

0.3 mg/kg IV (n=6) at Study Day 0

Intervention Type BIOLOGICAL

MEDI-545

0.3 mg/kg IV (n=6) at Study Day 0

Intervention Type BIOLOGICAL

MEDI-545

0.3 mg/kg IV (n=6) at Study Day 0

Intervention Type BIOLOGICAL

MEDI-545

0.3 mg/kg IV (n=6) at Study Day 0

Intervention Type BIOLOGICAL

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

80 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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MedImmune LLC

INDUSTRY

Sponsor Role lead

Responsible Party

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MedImmune Inc.

Principal Investigators

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Barbara White, M.D.

Role: STUDY_DIRECTOR

MedImmune LLC

Locations

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Pinnacle Research Group

Anniston, Alabama, United States

Site Status

Wallace Rheumatic Study Center

Los Angeles, California, United States

Site Status

Clinical Research of West Florida

Clearwater, Florida, United States

Site Status

Center for Rhematology, Immunology, and Arthritis

Fort Lauderdale, Florida, United States

Site Status

Ocala Rheumatology Research Center

Ocala, Florida, United States

Site Status

Tampa Florida Medical Research Group

Tampa, Florida, United States

Site Status

Florida Medical Clinic, Clinical Research Division

Zephyrhills, Florida, United States

Site Status

Louisiana State University Health Sciences Center-Shreveport

Shreveport, Louisiana, United States

Site Status

Johns Hopkins University, School of Medicine

Baltimore, Maryland, United States

Site Status

St. Mary's Duluth Clinic

Duluth, Minnesota, United States

Site Status

Hospital for Special Surgery

New York, New York, United States

Site Status

Columbia University Medical Center

New York, New York, United States

Site Status

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, United States

Site Status

Oregon Medical Research Center

Portland, Oregon, United States

Site Status

Altoona Center for Clinical Research

Duncansville, Pennsylvania, United States

Site Status

University of Texas Southwestern Medical Center

Dallas, Texas, United States

Site Status

University of Washington Div. of Rhematology

Seattle, Washington, United States

Site Status

Center for Innovative Therapy, UCSD School of Medicine

Milwaukee, Wisconsin, United States

Site Status

Froedtert Hospital, Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status

Toronto Western Hospital

Toronto, Ontario, Canada

Site Status

Montreal General Hospital

Montreal, Quebec, Canada

Site Status

Countries

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United States Canada

References

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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.

Reference Type DERIVED
PMID: 33687069 (View on PubMed)

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.

Reference Type DERIVED
PMID: 21798883 (View on PubMed)

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.

Reference Type DERIVED
PMID: 19479852 (View on PubMed)

Other Identifiers

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MI-CP126

Identifier Type: -

Identifier Source: org_study_id

NCT00394719

Identifier Type: -

Identifier Source: nct_alias