Rituximab in Membranous Nephropathy

NCT00425217 | Completed Phase 2

• 1 other identifier: IRB 627-04
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

Membranous glomerulopathy (MN) is a common immune-mediated glomerular disease and the leading cause of nephrotic syndrome in Caucasian adults. 1 Because of its frequency, it remains the second or third cause of end-stage renal disease caused by a primary glomerulonephritis. 2 At presentation, 70% to 80% of patients have the nephrotic syndrome. 1, 3, 4 Proteinuria greater than 2.0 grams per day is found in \> 80% of patients at presentation, with greater than 10 grams found in as many as 30%. 5 The disease affects patients of all ages, but it is most often diagnosed in middle age with the peak incidence during the fourth and fifth decades of life. There is close to a two-to-one predominance of males to females diagnosed with the disease. Idiopathic MN affects all races. Current therapeutic options include corticosteroids alone or in combination with alkylating agents, cyclosporin A, and mycophenolate mofetil. The most widely recognized, and best-validated regimen is combination therapy with corticosteroids and an alkylating agent, but its use is associated with significant adverse effects. Recent meta-analysis confirmed that present day treatments are far from ideal 6 Thus, it should not come as a surprise that the outcome of MN has not substantially improved over the past 30 years, and up to 40% of patients still progress to end-stage renal failure. 7 Like in other glomerular diseases the amount of protein in the urine correlates well with long term prognosis. Thus, this parameter has been used in previous studies, and will be used in this study, as the primary indicator of effectiveness of therapy. We proposed to do a pilot study to test the hypothesis that selective B lymphocyte depletion will result in disappearance of pathogenic antibodies and induction of remission of the nephrotic syndrome in patients with idiopathic membranous nephropathy. Our population will be 10 adults. The study will be conducted between our Nephrology Divisions at Mayo Clinic Rochester, Jacksonville, and Scottsdale. We will enroll patients with a GFR 25 ml/min as estimated by creatinine clearance and proteinuria \> 4g/24h, while receiving an ACEI or ARB and with BP controlled of \< 130/80 mmHg. Patients will receive Rituximab 1g on Day 1 and 15. Patients followed for 1 years following completion of treatment. The primary outcome will be change in urinary protein excretion at 6 months. Secondary outcomes will be changes in serum albumin, serum lipid?s profile, the number of partial remissions, time to remission, and incidence of relapses. We will also perform a pharmacokinetic study to evaluate the effect of proteinuria on the bio-availability and effects of the drug.

Conditions

Membranous Nephropathy

Outcome Measures

Primary Outcomes (3)

• 1. Change from baseline in proteinuria at six and twelve months following treatment

• Toxicity/Safety

• PK/bioavailability

Secondary Outcomes (4)

• Partial Remission at 6 months

• Complete and Partial Remission at 6 months

• Time to CR and time to CR or PR

• Rates of decline in GFR and UP

Interventions

Rituximab DRUG

Eligibility Criteria

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

You may qualify if:

• Membranous Nephropathy with diagnostic biopsy performed within the last 3 years. Renal biopsy slides and electron photomicrographs will be reviewed by study investigators, and must confirm a diagnosis of MN.
• Age \&#61619; 18 years.
• Proteinuria as measured via Uprot/UCr ratio \> 4.0 on a spot sample of a 24-hour urine collection, despite ACE inhibitor / ARB treatment. The choice of urine protein/creatinine ratios is in accord with recently developed National Kidney Foundation Chronic Kidney Disease (NKF-CKD) guidelines.107 The NKF-CKD guidelines advocate urine protein/creatinine ratios as the preferred method for evaluation of urinary protein excretion in both adults and children.
• Patients need to be treated with an ACEI and/or ARB, for at least 3 months prior to enrollment with adequately controlled blood pressure (BP \<140/80 mm Hg in \>75% of the readings).
• Women must be post-menopausal, surgically sterile or practicing a medically approved method of contraception.
• Patients with thromboembolic complications and/or clinical signs of NS that are not controlled with conventional medical treatment will enter the immunosuppressive portion of the protocol (Rituxan treatment) without the 3 months of ACE/ARB treatment (high risk patients).
• Able and willing to give written informed consent and comply with the requirements of the study protocol
• Adequate liver function, as indicated by bilirubin, AST, and alkaline phosphatase levels (up to \< 2.5 times the upper normal limit).
• Negative serum pregnancy test (for women of child bearing age)
• Men and women of reproductive potential must agree to use an acceptable method of birth control during treatment and for twelve months (1 year) after completion of treatment or a period of 21 months for those undergoing retreatment.

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: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: January 19, 2007
• First Posted: January 22, 2007
• Study Start: August 1, 2004
• Primary Completion: April 1, 2007
• Study Completion: April 1, 2007
• Last Updated: February 25, 2011

Record last verified: 2011-02

Locations

US (1)