Rituximab in Membranous Nephropathy

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00425217
• Date of registration: 19/01/2007
• Prospective Registration: No
• Primary sponsor: Mayo Clinic
• Public title: Rituximab in Membranous Nephropathy
• Scientific title: The Use of Rituximab in the Treatment of Idiopathic Membranous Nephropathy
• Date of first enrolment: August 2004
• Target sample size: 15
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00425217
• Study type: Interventional
• Study design: Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2/Phase 3

Countries of recruitment

United States

Contacts

• Name: Fernando C. Fervenza, M.D., Ph.D.
• Affiliation: Mayo Clinic

Key inclusion & exclusion criteria

Patients must meet the following inclusion criteria to be eligible for study entry:

- 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  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 renal function as indicated by estimated GFR ≥ 25 ml/min per 1.73m2
and/or or serum creatinine <4.0 mg/dL in the presence of ACE inhibitor/ARB therapy.
The GFR will be estimated using the 4 variable MDRD equation as published in the
NKF-CKD guidelines. The same NKF-CKD guidelines also promote the use of estimated GFR
(GFRest) values rather than serum creatinine levels or creatinine clearance
measurements as the preferred non-invasive method of determining glomerular
filtration rates.107 We have opted to use this approach rather than the much more
expensive and more invasive techniques that employ clearance measurements of
exogenous substances (such as inulin or iothalamate) since the likelihood of
detecting significant changes in GFR in this short term study is remote - no matter
which method is chosen. The inclusion of and/or serum creatinine <4.0 mg/dL is to
cover possibility of incomplete 24-hour collection at time baseline creatinine
clearance.)

- 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Membranous Nephropathy

Intervention(s)

Drug: Rituximab

Primary Outcome(s)

PK/bioavailability

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

Toxicity/Safety

Secondary Outcome(s)

Complete and Partial Remission at 6 months

Time to CR and time to CR or PR

Partial Remission at 6 months

Rates of decline in GFR and UP

Secondary ID(s)

IRB 627-04

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Genentech, Inc.