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Etanercept for the Treatment of Lupus Nephritis


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  • Purpose

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    Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease in which the body's immune system attacks its own normal tissues. This abnormal autoimmune response can result in damage to many parts of the body, including the skin, joints, lungs, heart, brain, intestines, and kidneys. Kidney problems occur in 60-75 % of lupus patients. The development of lupus-related kidney disease (called lupus nephritis) is associated with an overall worse prognosis.
    SLE is usually treated with drugs that try to block inflammation caused by the immune system. These treatments can create their own problems and they do not cure lupus. The drugs that are often used to treat lupus nephritis include prednisone (steroids), cyclophosphamide (Cytoxan), azathioprine (AZA or Imuran), and mycophenolate mofetil (MMF or Cellcept). The main purpose of this study is to evaluate the safety and tolerability of etanercept compared to placebo in combination with standard of care to treat individuals with active lupus nephritis.


    status: recruiting
    conditions: Lupus Nephritis
    interventions: Etanercept ; Lupus Treatment
    phase: Phase 2
    study type: Interventional
    study design: Treatment, Randomized, Double Blind (Subject, Caregiver), Placebo Control, Parallel Assignment, Safety Study
    official title: A Randomized, Double-Blind, Placebo-Controlled, Phase II, Multi-Center Study for Treatment of Lupus Nephritis by Inhibition of Tumor Necrosis Factor-Alpha Using Etanercept

  • Further study details (as provided by National Institute of Allergy and Infectious Diseases (NIAID))

    primary outcome measures:

    • Proportion of subjects in each study arm experiencing an adverse event of NCI CTCAE Grade 3 or greater [ Time Frame: At Week 24 ]

    secondary outcome measures:

    • Safety analysis [ Time Frame: Throughout study ]
    • Efficacy analysis [ Time Frame: Throughout study ]
    • Renal response [ Time Frame: Throughout study ]
    • Time to and duration of renal response [ Time Frame: Throughout study ]
    • Changes over time [ Time Frame: Throughout study ]

    enrollment: 28

    study start date: February 2008

    study completion date: February 2009


    Arms Assigned Interventions

    1: Experimental

    Participants in this group will self-administer 50 mg etanercept injections once a week for 24 weeks. They will continue receiving their usual treatment with corticosteroids and either MMF, Mycophenolic Acid, or AZA.

    Drug: Etanercept

    TNF inhibitor that increased the number of reactive B and T cells

    Drug: Lupus Treatment

    Individualized standard of care treatment for lupus with corticosteroids and with MMF, Mycophenolic Acid, or AZA

    2: Placebo Comparator

    Participants in this group will self-administer 50 mg placebo injections once a week for 24 weeks. They will continue receiving their usual treatment with corticosteroids and either MMF, Mycophenolic Acid, or AZA.

    Drug: Lupus Treatment

    Individualized standard of care treatment for lupus with corticosteroids and with MMF, Mycophenolic Acid, or AZA

    Detailed description

    Kidney problems associated with lupus nephritis range from asymptomatic protein in the urine to rapidly progressive glomerulonephritis, leading to end-stage renal disease. The goal of therapies is to control kidney manifestations in order to avoid kidney failure, the occurrence of other medical problems and death.
    The treatment of lupus nephritis remains problematic. Despite the use of currently available therapies, patients experience disease relapse. Over time, patients develop significant morbidity from the disease as well as from medications used for treatment.
    Etanercept, a TNF inhibitor, is proposed as a potential treatment for lupus nephritis. TNF increases the number of reactive B and T cells. TNF levels can be elevated in lupus.
    Etanercept is believed to work by blocking inflammation, and it is hoped that it will lessen the signs and symptoms of lupus-related kidney disease.
    The purpose of this study is to evaluate the safety and tolerability of etanercept compared to placebo in combination with standard therapy to treat individuals with mild or moderately active lupus nephritis.
    This study will last 1 year. Participants will be randomly assigned to receive either etanercept or placebo in addition to their regular medications. Participants will self-administer 50 mg etanercept or placebo injections once a week. They will continue receiving their usual treatment with corticosteroids and either MMF, Mycophenolic Acid, or AZA. Treatment with study medication will occur for 24 weeks.
    There will be a screening visit followed by a randomization visit, where subjects will receive and learn how to administer the study drug. Subjects will come to the clinic for 9 study visits. A physical exam and blood and urine collection will occur at most study visits. Participants will also be asked to complete a questionnaire on their health at most study visits. Subjects will be contacted by phone 5 times during the 24-week period to assess for adverse events and worsening disease status.

  • Eligibility

    ages eligible for study: 18 Years to 75 Years
    genders eligible for study: Both

    Criteria

    Inclusion Criteria:
    • Meets at least 4 of the 11 American College of Rheumatology (ACR) 1982 Revised Criteria for the Classification of SLE
    • Active lupus nephritis
    • Currently has antibodies to double-stranded DNA (dsDNA)
    • Currently receiving treatment consisting of at least 1.5 g/day of MMF OR at least 720 mg/day orally of Mycophenolic Acid OR at least 1.5 mg/kg once per day of AZA for lupus nephritis, for at least 28 days prior to study entry
    • Stable medication regimen for at least 4 weeks prior to study entry
    • Able and willing to self-administer study drug OR has a designated caregiver at home to administer study drug injections
    • Willing to use acceptable forms of contraception for the duration of the study

    Exclusion Criteria:
    Individuals with any of these conditions that are related to active SLE are not excluded.

  • Contacts and locations

    Please refer to this study by its ClinicalTrials.gov identifier: NCT00447265

    Locations

    United States , Alabama  - University of Alabama at Birmingham

    status: recruiting
    facility: Birmingham, Alabama, United States, 35294
    contact: Linda Cowden, RN   205-934-2991   Linda.Cowden@ccc.uab.edu
    Principal Investigator: Winn Chatham, MD

    United States , California  - University of California at San Francisco

    status: recruiting
    facility: San Francisco, California, United States, 94143
    contact: Steve Lund, NP   415-502-1886   Steve.lund@ucsf.edu
    Principal Investigator: Maria Dall'Era, MD

    United States , Colorado  - University of Colorado Health Sciences Center

    status: recruiting
    facility: Aurora, Colorado, United States, 80045
    contact: Janice Wagner, RN, CCRC   303-724-7516   Janice.Wagner@uchsc.edu
    Principal Investigator: Christopher Striebich, MD, PhD

    United States , New York  - Feinstein Institute for Medical Research NS-L1J Health System

    status: recruiting
    facility: Manhasset, New York, United States, 11030
    contact: Sanita Kandasami   516-562-2401   SKandasami@nshs.edu
    Principal Investigator: Cynthia Aranow, MD

    United States , New York  - University of Rochester

    status: recruiting
    facility: Rochester, New York, United States, 14642
    contact: Emily Cushing   585-275-7167   Emily_Cushing@urmc.rochester.edu
    Principal Investigator: John Looney, MD

    United States , North Carolina  - Duke University Medical Center

    status: recruiting
    facility: Durham, North Carolina, United States, 27709
    contact: Martin Tochacek   919-684-5586   martin.tochacek@duke.edu
    Principal Investigator: Lisa Criscione-Schreiber, MD

  • Sponsors and collaborators

    National Institute of Allergy and Infectious Diseases (NIAID)

    investigators: Maria Dall'Era, MD, Study Chair, Division of Rheumatology, University of California, San Francisco
    David Wofsy, MD, Study Chair, Department of Medicine, University of California, San Francisco

  • More information

    Other publications

    Aringer M, Graninger WB, Steiner G, Smolen JS. Safety and efficacy of tumor necrosis factor alpha blockade in systemic lupus erythematosus: an open-label study. Arthritis Rheum. 2004 Oct;50(10):3161-9.

    De Rycke L, Baeten D, Kruithof E, Van den Bosch F, Veys EM, De Keyser F. The effect of TNFalpha blockade on the antinuclear antibody profile in patients with chronic arthritis: biological and clinical implications. Lupus. 2005;14(12):931-7. Review.

    Mor A, Bingham C 3rd, Barisoni L, Lydon E, Belmont HM. Proliferative lupus nephritis and leukocytoclastic vasculitis during treatment with etanercept. J Rheumatol. 2005 Apr;32(4):740-3.

    Scheinfeld N. A comprehensive review and evaluation of the side effects of the tumor necrosis factor alpha blockers etanercept, infliximab and adalimumab. J Dermatolog Treat. 2004 Sep;15(5):280-94. Review.

    first received: March 12, 2007
    last updated: March 27, 2009
    ClinicalTrials.gov Identifier: NCT00447265
    health authority: United States: Food and Drug Administration

Information obtained from ClinicalTrials.gov on September 25, 2009   Link to the current ClinicalTrials.gov record.

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