Eculizumab Therapy for Dense Deposit Disease and C3 Nephropathy

The recruitment status of this study is unknown because the information has not been verified recently.

Verified February 2014 by Columbia University.
Recruitment status was Active, not recruiting

Sponsor:

Collaborator:

Alexion Pharmaceuticals

Information provided by (Responsible Party):

Gerald B. Appel, Columbia University

ClinicalTrials.gov Identifier:

NCT01221181

First received: October 13, 2010

Last updated: February 5, 2014

Last verified: February 2014

History of Changes

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 Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Eculizumab Therapy for Dense Deposit Disease and C3 Nephropathy

Resource links provided by NLM:

Genetics Home Reference related topics: C3 glomerulopathy

MedlinePlus related topics: Kidney Diseases

Drug Information available for: Eculizumab

Genetic and Rare Diseases Information Center resources: Glomerulonephritis Dense Deposit Disease Membranoproliferative Glomerulonephritis

U.S. FDA Resources

Further study details as provided by Columbia University:

Primary Outcome Measures:

Number of subjects with complete remission of proteinuria [ Time Frame: Up to 1 year after therapy ] [ Designated as safety issue: No ]
The primary end point is complete remission, defined as remission of proteinuria to <500 mg/day with normal renal function.

Secondary Outcome Measures:

Change in proteinuria level [ Time Frame: Up to 1 year after therapy ] [ Designated as safety issue: No ]
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.	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®)

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.

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®)

Show Detailed Description

Eligibility


Ages Eligible for Study:	18 Years and older (Adult, Senior)
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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 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

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01221181

Locations


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

Investigators


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
Study First Received:	October 13, 2010
Last Updated:	February 5, 2014
Health Authority:	United States: Institutional Review Board

Keywords provided by Columbia University:


Dense deposit disease C3 nephropathy Eculizumab

Additional relevant MeSH terms:


Kidney Diseases Glomerulonephritis Glomerulonephritis, Membranoproliferative	Urologic Diseases Nephritis Immune System Diseases

ClinicalTrials.gov processed this record on September 30, 2016

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