Eculizumab Therapy for Dense Deposit Disease and C3 Nephropathy
Recruitment status was: Active, not recruiting
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Purpose
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 | Intervention | Phase |
|---|---|---|
| Dense Deposit Disease Membranoproliferative Glomerulonephritis | Drug: Eculizumab | Phase 1 |
| Study Type: | Interventional |
| Study Design: | 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 |
- 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.
- 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).
| Estimated Enrollment: | 6 |
| Study Start Date: | August 2010 |
| Estimated Study Completion Date: | December 2015 |
| Estimated Primary Completion Date: | December 2015 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
|
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.
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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®)
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Eligibility
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| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| 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
Contacts and Locations
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 ClinicalTrials.gov 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 | |
| Principal Investigator: | Gerald B Appel, MD | Columbia University |
More Information
| Responsible Party: | Gerald B. Appel, Professor of Clinical Medicine, Nephrology, Columbia University |
| ClinicalTrials.gov Identifier: | NCT01221181 History of Changes |
| Other Study ID Numbers: |
AAAF2403 |
| First Submitted: | October 13, 2010 |
| First Posted: | October 14, 2010 |
| Last Update Posted: | October 12, 2017 |
| Last Verified: | February 2014 |
Keywords provided by Gerald B. Appel, Columbia University:
|
Dense deposit disease C3 nephropathy Eculizumab |
Additional relevant MeSH terms:
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Kidney Diseases Glomerulonephritis Glomerulonephritis, Membranoproliferative |
Urologic Diseases Nephritis Immune System Diseases |