Eculizumab Therapy for Dense Deposit Disease and C3 Nephropathy

• Status: Completed
• Trial end date: 2011-10-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Columbia University
• Collaborator: Alexion Pharmaceuticals
• Treatments: Eculizumab

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