Etanercept for the Treatment of Lupus Nephritis
Condition: Lupus Nephritis
MeSH terms: Nephritis; Lupus Nephritis
Intervention: Etanercept; Lupus Treatment- Standard of Care; Placebo
Intervention description: 1.) Immune suppressant. 2.) Tumor necrosis factor (TNF) inhibitor.; Individualized standard of care treatment for lupus with corticosteroids and with mycophenolate mofetil (MMF), mycophenolic acid, or azathioprine (AZA)
Intervention MeSH terms: Etanercept
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Care Provider)
Enrollment: 1.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility 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:

          -  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