Eculizumab Therapy for Dense Deposit Disease and C3 Nephropathy
Condition: Dense Deposit Disease; Membranoproliferative Glomerulonephritis
MeSH terms: Kidney Diseases; Glomerulonephritis; Glomerulonephritis, Membranoproliferative
Intervention: Eculizumab
Intervention description: Dosage/Frequency: 900 mg IV once a week for 4 weeks, 1200 mg IV week 5, then 1200 mg IV every 2 weeks through week 53.
Intervention MeSH terms: Eculizumab
Phase: Phase 1
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 6.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Dense deposit disease; C3 nephropathy; Eculizumab

Summary:

      This open label, non-blinded, proof of concept efficacy and safety study of eculizumab in
      patients with biopsy proven DDD or C3 nephropathy. The trial will consist of adult patients
      with these diseases who have > 1 gram of proteinuria or a decreased glomerular filtration
      rate (GFR), both predictors of a poor long-term outcome in many glomerular diseases. The
      patients will be treated with eculizumab for one year.

      The goals will be to determine whether treatment leads to an improvement in kidney function,
      defined by remissions of proteinuria and improvements in estimated GFR (measured by serum
      creatinine), and to improvement in histologic parameters, including percentage of
      non-affected glomeruli, interstitial fibrosis, intensity of C3 staining of
      immunofluorescence, and amount of electron dense deposits by electron microscopy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Adult patients with biopsy proven DDD or C3 nephropathy, at least 18 years of age

          -  24-hour urine protein > 1000 mg/day, urine protein:creatinine ratio > 1.0, or acute
             renal failure (defined as > 50% increase in serum creatinine from baseline)

          -  Willing and able to sign informed consent

          -  Patients of childbearing age must agree to use birth control

          -  Patients must be willing to be vaccinated against meningococcal disease or have
             documentation of previous vaccination against meningococcal disease

        Exclusion Criteria:

          -  Patients under 18 years of age

          -  Patients unable to sign informed consent

          -  Patients having received rituximab or another monoclonal antibody within 6 months of
             the trial

          -  Patients currently taking and unable to discontinue other immunomodulatory therapies
             (e.g. cyclosporine, high-dose steroids, mycophenolate mofetil) unless these other
             therapies are indicated for prophylaxis of transplant rejection (e.g. stable doses of
             mycophenolate mofetil and/or calcineurin inhibitor). Patients on chronic steroid
             therapy who are unable to taper down to <10 mg/day will be excluded.

          -  Patients of childbearing age who refuse to use birth control

          -  Patients with a baseline estimated GFR less than 30 ml/min/1.73m2

          -  Patients with other renal diseases (e.g. diabetic nephropathy, renal vascular disease)
             that would interfere with interpretation of the study.

          -  Patients with comorbid conditions that would interfere with completion of the trial
             (malignancies, congestive heart failure (CHF), recent myocardial infarction).

          -  Patients with known contraindications to the use of eculizumab, including refusal to
             receive N. meningitides vaccine prior to therapy