Eculizumab Therapy for Dense Deposit Disease and C3 Nephropathy

NCT01221181 | Completed Phase 1 Results DMC FDA Drug

• 1 other identifier: AAAF2403
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Dense Deposit Disease; Membranoproliferative Glomerulonephritis

Keywords

Dense deposit disease; C3 nephropathy; Eculizumab

Outcome Measures

Primary Outcomes (1)

• Number of Patients With Change in Proteinuria or Serum Creatinine Over Treatment Period

  This is designed to measure response to eculizumab through clinical and histological data, including a reduction in serum creatinine or in proteinuria, or histopathologic improvement. Any reduction in serum creatinine and/or proteinuria was included in our descriptive analysis.

  One year

Study Arms (1)

Eculizumab

EXPERIMENTAL

Patients will receive Eculizumab and 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. meningitides 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.

Drug: Eculizumab

Interventions

Eculizumab DRUG

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.

Also known as: Eculizumab (Soliris®)

Eculizumab

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients with biopsy proven DDD or C3 nephropathy, at least 18 years of age
• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Columbia University: lead
• Alexion Pharmaceuticals, Inc.: collaborator

Study Sites (2)

Columbia University Medical Center, Glomerular Center

New York, New York, 10032, United States

Location

Columbia University Medical Center, Nephrology Clinical Research Center

New York, New York, 10032, United States

Location

Related Publications (1)

• Bomback AS, Smith RJ, Barile GR, Zhang Y, Heher EC, Herlitz L, Stokes MB, Markowitz GS, D'Agati VD, Canetta PA, Radhakrishnan J, Appel GB. Eculizumab for dense deposit disease and C3 glomerulonephritis. Clin J Am Soc Nephrol. 2012 May;7(5):748-56. doi: 10.2215/CJN.12901211. Epub 2012 Mar 8.

  PMID: 22403278 RESULT

Related Links

• Eculizumab for dense deposit disease and C3 glomerulonephritis
• Pathology after eculizumab in dense deposit disease and C3 glomerulonephritis

MeSH Terms

Conditions

Glomerulonephritis, Membranoproliferative

Interventions

eculizumab

Condition Hierarchy (Ancestors)

Glomerulonephritis; Nephritis; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Immune System Diseases

Results Point of Contact

• Title: Andrew Bomback, MD, MPH
• Organization: Columbia University Medical Center

asb68@cumc.columbia.edu

212-305-0320

Study Officials

• Gerald B Appel, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Clinical Medicine, Nephrology

Study Record Dates

• First Submitted: October 13, 2010
• First Posted: October 14, 2010
• Study Start: July 1, 2010
• Primary Completion: October 1, 2011
• Study Completion: October 1, 2011
• Last Updated: February 19, 2019
• Results First Posted: February 19, 2019

Record last verified: 2019-02

Locations

US (2)