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

NCT00299819 | Completed Phase 1

• 1 other identifier: MI-CP126
• Study Type: interventional
• Target: 45
• Locations: 2 countries
• Sites: 21

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.

Conditions

Lupus

Keywords

Lupus

Outcome Measures

Primary Outcomes (1)

• Safety and tolerability of MEDI-545 will be assessed primarily by summarizing adverse events.

  Day 84

Secondary Outcomes (1)

• Evaluation of MEDI-545 pharmacokinetics and possible immunogenicity

  Day 84

Study Arms (5)

1

ACTIVE COMPARATOR

MEDI-545

Biological: MEDI 545

2

ACTIVE COMPARATOR

MEDI-545

Biological: MEDI-545

3

ACTIVE COMPARATOR

MEDI-545

Biological: MEDI-545

4

ACTIVE COMPARATOR

MEDI-545

Biological: MEDI-545

5

ACTIVE COMPARATOR

MEDI-545

Biological: MEDI-545

Interventions

MEDI-545 BIOLOGICAL

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

2

MEDI 545 BIOLOGICAL

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

1

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• MedImmune LLC: lead

Study Sites (21)

Pinnacle Research Group

Anniston, Alabama, 35207, United States

Location

Wallace Rheumatic Study Center

Los Angeles, California, 90048, United States

Location

Clinical Research of West Florida

Clearwater, Florida, 33765, United States

Location

Center for Rhematology, Immunology, and Arthritis

Fort Lauderdale, Florida, 03334, United States

Location

Ocala Rheumatology Research Center

Ocala, Florida, 34474, United States

Location

Tampa Florida Medical Research Group

Tampa, Florida, 33614, United States

Location

Florida Medical Clinic, Clinical Research Division

Zephyrhills, Florida, 33542, United States

Location

Louisiana State University Health Sciences Center-Shreveport

Shreveport, Louisiana, 71130, United States

Location

Johns Hopkins University, School of Medicine

Baltimore, Maryland, 21205, United States

Location

St. Mary's Duluth Clinic

Duluth, Minnesota, 55805, United States

Location

Hospital for Special Surgery

New York, New York, 10021, United States

Location

Columbia University Medical Center

New York, New York, 10032, United States

Location

Oklahoma Medical Research Foundation

Oklahoma City, Oklahoma, 73104, United States

Location

Oregon Medical Research Center

Portland, Oregon, 97223, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

University of Texas Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

University of Washington Div. of Rhematology

Seattle, Washington, 98195, United States

Location

Center for Innovative Therapy, UCSD School of Medicine

Milwaukee, Wisconsin, 53226, United States

Location

Froedtert Hospital, Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

Location

Toronto Western Hospital

Toronto, Ontario, MST 258, Canada

Location

Montreal General Hospital

Montreal, Quebec, H3G 1A4, Canada

Location

Related Publications (3)

• 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.

  PMID: 33687069 DERIVED

• 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.

  PMID: 21798883 DERIVED

• 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.

  PMID: 19479852 DERIVED

MeSH Terms

Interventions

sifalimumab

Study Officials

• Barbara White, M.D.

  MedImmune LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: March 6, 2006
• First Posted: March 7, 2006
• Study Start: March 1, 2006
• Study Completion: October 1, 2007
• Last Updated: December 18, 2007

Record last verified: 2007-12

Locations

US (19); CA (2)