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

Lupus Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00299819
• Other study ID #: MI-CP126
• Status: Completed
• Phase: Phase 1
• First received: March 6, 2006
• Last updated: December 17, 2007
• Start date: March 2006
• Est. completion date: October 2007

Study information

• Verified date: December 2007
• Source: MedImmune LLC
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Other known NCT identifiers

• NCT00394719

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: October 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Lupus
• Lupus Erythematosus, Systemic

Intervention

Biological:
• MEDI-545
0.3 mg/kg IV (n=6) at Study Day 0
• MEDI 545
0.3 mg/kg IV (n=6) at Study Day 0
• MEDI-545
0.3 mg/kg IV (n=6) at Study Day 0
• MEDI-545
0.3 mg/kg IV (n=6) at Study Day 0
• MEDI-545
0.3 mg/kg IV (n=6) at Study Day 0

Locations

Country	Name	City	State
Canada	Montreal General Hospital	Montreal	Quebec
Canada	Toronto Western Hospital	Toronto	Ontario
United States	Pinnacle Research Group	Anniston	Alabama
United States	Johns Hopkins University, School of Medicine	Baltimore	Maryland
United States	Clinical Research of West Florida	Clearwater	Florida
United States	University of Texas Southwestern Medical Center	Dallas	Texas
United States	St. Mary's Duluth Clinic	Duluth	Minnesota
United States	Altoona Center for Clinical Research	Duncansville	Pennsylvania
United States	Center for Rhematology, Immunology, and Arthritis	Ft. Lauderdale	Florida
United States	Wallace Rheumatic Study Center	Los Angeles	California
United States	Center for Innovative Therapy, UCSD School of Medicine	Milwaukee	Wisconsin
United States	Froedtert Hospital, Medical College of Wisconsin	Milwaukee	Wisconsin
United States	Columbia University Medical Center	New York	New York
United States	Hospital for Special Surgery	New York	New York
United States	Ocala Rheumatology Research Center	Ocala	Florida
United States	Oklahoma Medical Research Foundation	Oklahoma City	Oklahoma
United States	Oregon Medical Research Center	Portland	Oregon
United States	University of Washington Div. of Rhematology	Seattle	Washington
United States	Louisiana State University Health Sciences Center-Shreveport	Shreveport	Louisiana
United States	Tampa Florida Medical Research Group	Tampa	Florida
United States	Florida Medical Clinic, Clinical Research Division	Zephyrhills	Florida

Sponsors (1)

Lead Sponsor	Collaborator
MedImmune LLC

Countries where clinical trial is conducted

United States,  Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability of MEDI-545 will be assessed primarily by summarizing adverse events.		Day 84	Yes
Secondary	Evaluation of MEDI-545 pharmacokinetics and possible immunogenicity		Day 84	No