Rituximab in the Treatment of Idiopathic Membranous Nephropathy

NCT00405340 | Completed Early Phase 1

• 1 other identifier: 06-004833
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

Membranous glomerulopathy (MN) is still the most common glomerular disease associated with nephrotic proteinuria (NS). Up to 40% of patients reach end stage renal failure (ESRD), making MN the 2nd or 3rd most common cause of ESRD caused by a primary glomerulopathy. Current treatment options include corticosteroids, alkylating agents, and cyclosporin, but their use is controversial and the associated adverse effects and high cost temper their usage. Experimental data in MN suggests that B cell activation results in immunoglobulin deposition along the glomerular basement membrane causing injury to the membrane and subsequent proteinuria. Drugs that non-selectively inhibit B cells and, these pathogenic antibodies, are closely associated with improved outcomes. Based on the rationale that selective depletion of B cells in humans would prevent the production of ?nephrotoxic? immunoglobulins and subsequent renal injury we recently treated 15 patients with MN with rituximab 1g i.v. twice (day 1 and day 15). Baseline proteinuria of 13.0±5.5g/24h decreased to 9.1±7g, 9.7±8g and 6.5±6 g/24h at 3, 6, and 9 months, respectively (mean ± SD). Analysis of the pharmacokinetic data obtained from this study, however, suggests that in heavily nephrotic patients, rituximab dosed in this fashion results in patients being under-treated. The present study propose to test the hypothesis that rituximab, given in accordance to the standard lymphoma protocol (375mg/m2 x 4), will result in a more effective and profound depletion of B cells, a more complete suppression of pathogenic antibodies, and a higher remission rate of the NS while maintaining a favorable safety profile.

Conditions

Membranous Nephropathy

Outcome Measures

Primary Outcomes (1)

• Primary endpoint.

  12 months

Secondary Outcomes (5)

• Complete and partial remission rates at 6, 9, and 12 months

  6, 9, and 12 months

• Pharmacokinetics/bioavailability

  12 months

• Rate of decline in urinary protein

  12 months

• Frequency of relapse after CR

  12 months

• Toxicity

  12 months

Study Arms (1)

Drug

EXPERIMENTAL

Rituximab

Drug: Rituximab

Interventions

Rituximab DRUG

Patients will received rituximab 4 weekly doses of rituximab 375 mg/m2 at baseline. Patients will be retreated at 6 months.

Drug

Eligibility Criteria

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

* Idiopathic MN with diagnostic biopsy performed within the past 24 months. * Age \> 18 years * If female, must be post-menopausal, surgically sterile or practicing a medically approved method of contraception * Patients need to be treated with an ACEI and/or ARB, for at least 4 months prior to rituximab treatment and have adequately controlled blood pressure (BP \<130/75 mm Hg in \>75% of the readings). * Proteinuria as measured by urinary proteinuria / urinary creatinine \> 5.0 on a spot sample aliquot from a 24-hour urine collection. * Estimated GFR \&#8805; 30 ml/min/1.73m2 while taking ACEI/ARB therapy.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Mayo Clinic: lead
• Genentech, Inc.: collaborator

Study Sites (1)

Mayo Clinic

Rochester, Minnesota, 55905, United States

Location

MeSH Terms

Conditions

Glomerulonephritis, Membranous

Interventions

Rituximab

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Murine-Derived; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Fernando C. Fervenza, M.D., Ph.D.

  Mayo Clinic

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: M.D., Ph.D.

Study Record Dates

• First Submitted: November 29, 2006
• First Posted: November 30, 2006
• Study Start: October 1, 2006
• Primary Completion: July 1, 2010
• Study Completion: April 1, 2012
• Last Updated: October 27, 2015

Record last verified: 2015-10

Locations

US (1)