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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

Phase 2
18 Years
75 Years
Not Enrolling
Lupus Nephritis

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Trial Information

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

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.

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:

- Moderately severe anemia

- Neutropenia

- Thrombocytopenia

- Blood creatinine levels greater than 3.0 mg/dl

- Positive PPD without ongoing treatment for at least 30 days prior to study entry

- Pulmonary fibrotic changes

- Active infections (e.g., HIV, hepatitis B virus [HBV], hepatitis C virus [HCV])
and/or serologic evidence of prior exposure to hepatitis B

- Received a live vaccine within 3 months prior to study entry

- Doubled serum creatinine levels within the 3 months prior to study entry OR end-stage
kidney disease

- Dialysis-dependent end-stage kidney disease or membranous nephritis

- History of cancer. Individuals with a history of cervical carcinoma in situ and
resected basal and squamous cell carcinomas of the skin are not excluded.

- Receiving prednisone greater than 20 mg/day or equivalent corticosteroid treatment

- Pulse intravenous methylprednisolone within 30 days prior to study entry

- Receiving immunosuppressive agents other than prednisone, MMF, Mycophenolic Acid,
AZA, or hydroxychloroquine

- Oral or intravenous cyclosporine, leflunomide IVIG, or plasmapheresis within 3 months
prior to study entry

- Current or previous cyclophosphamide treatment

- Use of other experimental agent within 90 days prior to study entry

- Severe, progressive, or uncontrolled kidney, liver, blood, stomach, lung, heart, or
brain disease. Individuals with any of these conditions that are related to active
SLE are not excluded.

- Previous use of rituximab within 12 months prior to study entry

- Previous or current exposure to any of the following: etanercept (Enbrel), adalimumab
(Humira), infliximab (Remicade), or anakinra (Kineret)

- Meets New York Heart Association classification of congestive heart failure (CHF)
Class III or greater

- History of myocardial infarction or ischemia

- Current or history of substance abuse

- Known hypersensitivity to any component of the study drug

- Poorly controlled or advanced diabetes mellitus

- History of multiple sclerosis, transverse myelitis, optic neuritis, or epilepsy

- History of noncompliance with other therapies

- Pregnancy or breastfeeding

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver), Primary Purpose: Treatment

Outcome Measure:

Number of Adverse Events (AEs)Grade 3 or Higher Experienced by Participant During Treatment Phase of Study

Outcome Description:

Number of adverse events (AEs) or serious adverse events (SAEs) Grade 3 or higher experienced by participant over the duration of the treatment period. [1] [1] This study graded the severity of AEs experienced by the study participant according to the criteria set forth in the National Cancer Institute's Common Terminology Criteria for Adverse Events Version 3.0.

Outcome Time Frame:

24 Weeks

Safety Issue:


Principal Investigator

Maria Dall'Era, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Division of Rheumatology, University of California, San Francisco


United States: Food and Drug Administration

Study ID:




Start Date:

February 2008

Completion Date:

March 2009

Related Keywords:

  • Lupus Nephritis
  • Lupus Nephritis
  • Nephritis



University of Alabama at BirminghamBirmingham, Alabama  35294-3300
Duke University Medical CenterDurham, North Carolina  27710
University of Colorado Health Sciences CenterDenver, Colorado  80262
University of RochesterRochester, New York  14642
University of California at San FranciscoSan Francisco, California  94115
Feinstein Institute for Medical Research NS-L1J Health SystemManhasset, New York  11030