Pilot Study of Rituximab for Membranoproliferative Glomerulonephritis

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT00275613
• Date of registration: 10/01/2006
• Prospective Registration: No
• Primary sponsor: Mayo Clinic
• Public title: Pilot Study of Rituximab for Membranoproliferative Glomerulonephritis
• Scientific title: Pilot Study of Rituximab for Membranoproliferative Glomerulonephritis
• Date of first enrolment: November 2005
• Target sample size: 10
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00275613
• Study type: Interventional
• Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 1

Countries of recruitment

United States

Contacts

• Name: John J. Dillon, M.D., M.S.
• Affiliation: Mayo Clinic

Key inclusion & exclusion criteria

Inclusion Criteria:

- MPGN either native/renal transplant kidneys with biopsy last 3 years

- Age > 18 years

- Urinary protein to creatinine ratio > 1.0 in a 24-hour urine collection, despite ACE
inhibitor/ARB treatment

- Patients need to be treated with an ACEI and/or ARB, for at least 3 months prior to
enrollment with the systolic blood pressure < 140 mm Hg for at least 75% of readings.
Goal systolic blood pressure will be < 130 mm Hg.)

- Women must be post-menopausal, surgically sterile or practicing a medically approved
method of contraception

- Patients intolerant of ACE inhibitors/ARBs may enter the study without being treated
with these agents

- Able/willing to give written informed consent/comply with the requirements of study
protocol

- Estimated GFR = 25 ml/min per 1.73m^2 in the presence of ACE inhibitor/ARB therapy.
The GFR will be estimated using the 4 variable Modification of Diet in Renal Disease
(MDRD) equation/National Kidney Foundation - Chronic Kidney Disease (NKF-CKD)
guidelines

- Adequate liver function, indicated by bilirubin, aspartate aminotransferase (AST),
and alkaline phosphatase levels not more than 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

Exclusion Criteria:

- Age <18 years.

- Estimated GFR < 25 ml/min per 1.73 m^2

- Concurrent use of immunosuppressive therapy with the exceptions of prednisone 10
mg/day or less or an equivalent amount of another glucocorticoid or, among transplant
patients, stable or decreasing transplant immunosuppression. Patient must be off
immunosuppressive medications for > 3 months prior to enrollment into the study

- Medical conditions causing MPGN (e.g. HIV, hepatitis B, hepatitis C, systemic lupus
erythematosus, monoclonal gammopathies). Patients with idiopathic cryoglobulinemia
will not be excluded

- Presence or suspicion of active infection

- Type 1 or type 2 diabetes mellitus

- Treatment with any investigational agent within 4 weeks of screening or 5 half-lives
of the investigational drug (whichever is longer)

- Receipt of a live vaccine within 4 weeks prior to randomization

- Previous Treatment with Rituximab (MabThera®/Rituxan®) or another B-cell depleting
antibody

- History of severe allergic or anaphylactic reactions to humanized or murine
monoclonal antibodies

- Human immunodeficiency virus (HIV)

- Hepatitis B or C

- History of recurrent significant or recurrent bacterial infections

- Known active bacterial, viral fungal mycobacterial, or other infection (including
tuberculosis or atypical mycobacterial disease, but excluding fungal infections of
nail beds) or any major episode of infection requiring hospitalization or treatment
with i.v. antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks
prior to screening

- Ongoing use of high dose steroids(> 10 mg/day)or unstable steroid dose past 4 weeks

- Lack of peripheral venous access

- Drug,alcohol or chemical abuse within 6 months prior to screening

- Pregnancy(negative serum pregnancy test performed all women of childbearing potential
within 7 days of treatment)

- Lactation

- Concomitant malignancies/previous malignancies within last 5 years, with the
exception of adequately treated basal/squamous cell carcinoma of skin or carcinoma of
cervix

- Major psychiatric disorder

- Significant cardiac or pulmonary disease

- Any other disease, metabolic dysfunction, physical examination finding, or clinical
laboratory suspicion of a disease/condition that contraindicates the use of an
investigational drug or that may affect the interpretation of the results or render
the patient at high risk from treatment complications

- Inability to comply with study and follow-up procedures

Laboratory Exclusion Criteria (Screening):

- Hemoglobin:< 8.5 gm/dL

- Platelets:< 100,000/mm

- Total bilirubin,AST/alkaline phosphatase > 2.5 x Upper Limit of Normal unless related
to primary disease

- Positive Hepatitis B or C serology

- Positive HIV



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

Health Condition(s) or Problem(s) studied

Glomerulonephritis, Membranoproliferative

Intervention(s)

Drug: Rituximab

Primary Outcome(s)

Proteinuria [Time Frame: The primary endpoints are based on quantitative changes in urine protein measured at 6 months. Additional evaluations of urine protein will be done at 3, 9, and 12 months.]

Secondary Outcome(s)

Serum cholesterol [Time Frame: 6 and 9 month timepoints]

Serum albumin [Time Frame: 3, 6, 9 and 12 months]

Secondary ID(s)

976-05

Source(s) of Monetary Support

Please refer to primary and secondary sponsors