Eculizumab Therapy for Dense Deposit Disease and C3 Nephropathy

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01221181
Recruitment Status : Unknown
Verified February 2014 by Gerald B. Appel, Columbia University.
Recruitment status was:  Active, not recruiting
First Posted : October 14, 2010
Last Update Posted : February 7, 2014
Alexion Pharmaceuticals
Information provided by (Responsible Party):
Gerald B. Appel, Columbia University

Brief Summary:

This is an 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. They 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.

All enrolled subjects will receive eculizumab treatment for one year. There will be 29 study visits over 53 weeks. The goal is to determine whether this treatment will improve kidney function, as evidenced by less protein in the urine and improved lab results.

An EXTENSION TREATMENT PHASE has been added. After completing the study, patients are followed with labs every four weeks as per standard of care. If labs suggest a relapse, they will be allowed to continue on therapy at the previous dosage until this drug receives FDA approval for this indication. Treatment intervals and dosage are identical to the original study.

Condition or disease Intervention/treatment Phase
Dense Deposit Disease Membranoproliferative Glomerulonephritis Drug: Eculizumab Phase 1

  Show Detailed Description

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 6 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Eculizumab Therapy for Dense Deposit Disease and C3 Nephropathy
Study Start Date : August 2010
Estimated Primary Completion Date : December 2015
Estimated Study Completion Date : December 2015

Arm Intervention/treatment
Experimental: Eculizumab
Eculizumab 900 mg IV one a week for 4 weeks, 1200 mg IV week 5, then 1200 mg IV every 2 weeks through week 53.
Drug: Eculizumab

900 mg IV once a week x 4 weeks, 1200 mg IV week 5, then 1200 mg IV every 2 weeks through week 53.

Patients will be observed for 60 minutes after the first 5 infusions, then 30 minutes after all subsequent infusions. Patients will not be allowed to take other immunomodulatory therapies during the study period but will continue on their other non-immunomodulatory therapies (e.g. ACE inhibitors, -statins, aspirin) without modifications unless clinically indicated. All patients, if unvaccinated, will be given N. meningitidis vaccine at least two weeks prior to first eculizumab exposure. All female patients of childbearing potential will be asked to use adequate contraception methods during treatment and up to 5 months following discontinuation of eculizumab treatment.

Other Name: Eculizumab (Soliris®)

Primary Outcome Measures :
  1. Number of subjects with complete remission of proteinuria [ Time Frame: Up to 1 year after therapy ]
    The primary end point is complete remission, defined as remission of proteinuria to <500 mg/day with normal renal function.

Secondary Outcome Measures :
  1. Change in proteinuria level [ Time Frame: Up to 1 year after therapy ]
    Partial remission, a secondary endpoint, will be defined as reduction in proteinuria by at least 50% and to <2 g/day with stable renal function (i.e. no more than a 20% increase in serum creatinine).

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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 against 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. meningitidis vaccine prior to therapy

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01221181

United States, New York
Columbia University Medical Center, Glomerular Center
New York, New York, United States, 10032
Columbia University Medical Center, Nephrology Clinical Research Center
New York, New York, United States, 10032
Sponsors and Collaborators
Columbia University
Alexion Pharmaceuticals
Principal Investigator: Gerald B Appel, MD Columbia University

Responsible Party: Gerald B. Appel, Professor of Clinical Medicine, Nephrology, Columbia University Identifier: NCT01221181     History of Changes
Other Study ID Numbers: AAAF2403
First Posted: October 14, 2010    Key Record Dates
Last Update Posted: February 7, 2014
Last Verified: February 2014

Keywords provided by Gerald B. Appel, Columbia University:
Dense deposit disease
C3 nephropathy

Additional relevant MeSH terms:
Kidney Diseases
Glomerulonephritis, Membranoproliferative
Urologic Diseases
Immune System Diseases