- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00275613
Pilot Study of Rituximab for Membranoproliferative Glomerulonephritis
January 15, 2013 updated by: John Dillon, Mayo Clinic
Membranoproliferative glomerulonephritis (MPGN) is a relatively-rare, immune-mediated kidney disease.
All current therapies are inadequate and MPGN frequently leads to kidney failure.
This study is a 10 patient trial of the monoclonal antibody rituximab for adult patients with MPGN.
Study patients will receive 2 doses of rituximab intravenously on days 1 and 15 and will then be followed for 1 year.
Study Overview
Status
Completed
Conditions
Intervention / Treatment
Detailed Description
Membranoproliferative glomerulonephritis (MPGN) is a relatively-rare, immune-mediated glomerular disease.
There is no accepted therapy and all current therapies are inadequate.
Current therapeutic options include immunosuppression with corticosteroids alone or in combination with alkylating agents, antiplatelet therapy with aspirin and/or dipyridamole and/or warfarin, and angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers.
As with other glomerular diseases the amount of protein in the urine correlates well with the long-term prognosis.
Thus, this parameter has been used in previous studies, and will be used in this study, as the primary indicator of therapeutic efficacy.
We propose a pilot study to test the hypothesis that selective B lymphocyte depletion will result in disappearance of pathogenic antibodies and induce remission of proteinuria in patients with idiopathic membranoproliferative glomerulonephritis.
Our population will be 10 adults with MPGN involving either the native kidneys or a renal transplant.
We will enroll patients with a glomerular filtration rate (GFR) greater than or equal to 25 ml/min, as estimated by creatinine clearance, and with a 24 hour urinary ratio of protein to creatinine greater than or equal to 1, while receiving an angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB).
Patients will receive Rituximab 1g on Day 1 and 15.
Patients will be followed for 1 year following completion of treatment.
The primary outcome will be the change in urinary protein excretion at 6 months.
Secondary outcomes will include changes in the GFR, changes in urinary protein excretion at 3, 9, and 12 months, the rate of change in urinary protein excretion, serum albumin concentration, serum cholesterol, the number of complete and partial remissions, time to remission, and the number of relapses.
Study Type
Interventional
Enrollment (Actual)
10
Phase
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Minnesota
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Rochester, Minnesota, United States, 55905
- Mayo Clinic
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
16 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Rituximab, IV infusion
The Rituximab dose is 1000 mg (1 gm) given as an IV infusion every two weeks for 2 doses (days 1 and 15)
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The Rituximab dose is 1000 mg (1 gm) given as an IV infusion every two weeks for 2 doses (days 1 and 15)
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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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.
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Serum albumin
Time Frame: 3, 6, 9 and 12 months
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Change in serum albumin concentration
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3, 6, 9 and 12 months
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Serum cholesterol
Time Frame: 6 and 9 month timepoints
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Change in serum cholesterol levels
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6 and 9 month timepoints
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: John J. Dillon, M.D., M.S., Mayo Clinic
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
Helpful Links
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
November 1, 2005
Primary Completion (Actual)
March 1, 2009
Study Completion (Actual)
March 1, 2009
Study Registration Dates
First Submitted
January 10, 2006
First Submitted That Met QC Criteria
January 10, 2006
First Posted (Estimate)
January 12, 2006
Study Record Updates
Last Update Posted (Estimate)
January 16, 2013
Last Update Submitted That Met QC Criteria
January 15, 2013
Last Verified
January 1, 2013
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 976-05
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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