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

This study has been completed.
Sponsor:
Information provided by:
MedImmune LLC
ClinicalTrials.gov Identifier:
NCT00299819
First received: March 6, 2006
Last updated: December 17, 2007
Last verified: December 2007
  Purpose

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.


Condition Intervention Phase
Lupus
Biological: MEDI-545
Biological: MEDI 545
Phase 1

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

Resource links provided by NLM:


Further study details as provided by MedImmune LLC:

Primary Outcome Measures:
  • Safety and tolerability of MEDI-545 will be assessed primarily by summarizing adverse events. [ Time Frame: Day 84 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Evaluation of MEDI-545 pharmacokinetics and possible immunogenicity [ Time Frame: Day 84 ] [ Designated as safety issue: No ]

Enrollment: 45
Study Start Date: March 2006
Study Completion Date: October 2007
Arms Assigned Interventions
Active Comparator: 1
MEDI-545
Biological: MEDI 545
0.3 mg/kg IV (n=6) at Study Day 0
Active Comparator: 2
MEDI-545
Biological: MEDI-545
0.3 mg/kg IV (n=6) at Study Day 0
Active Comparator: 3
MEDI-545
Biological: MEDI-545
0.3 mg/kg IV (n=6) at Study Day 0
Active Comparator: 4
MEDI-545
Biological: MEDI-545
0.3 mg/kg IV (n=6) at Study Day 0
Active Comparator: 5
MEDI-545
Biological: MEDI-545
0.3 mg/kg IV (n=6) at Study Day 0

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00299819

  Show 21 Study Locations
Sponsors and Collaborators
MedImmune LLC
Investigators
Study Director: Barbara White, M.D. MedImmune LLC
  More Information

No publications provided by MedImmune LLC

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Greg Dennis, M.D., MedImmune Inc.
ClinicalTrials.gov Identifier: NCT00299819     History of Changes
Obsolete Identifiers: NCT00394719
Other Study ID Numbers: MI-CP126
Study First Received: March 6, 2006
Last Updated: December 17, 2007
Health Authority: United States: Food and Drug Administration

Keywords provided by MedImmune LLC:
Lupus

Additional relevant MeSH terms:
Lupus Erythematosus, Systemic
Connective Tissue Diseases
Autoimmune Diseases
Immune System Diseases

ClinicalTrials.gov processed this record on September 16, 2014