Pilot Study of Rituximab to Treat Fibrillary Glomerulonephritis

Study Overview
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Brief Summary
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This pilot study is being done to see if the study medication, Rituximab, preserves kidney function after 12 months of taking the drug.

Detailed Description
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This is a Phase II, open-label pilot study to determine if the use of Rituximab reduces proteinuria over a 12 month period and is there preservation of kidney function with the use of this study drug. Each patient will be treated with 2 intravenous infusions of rituximab 1000 mg, two weeks apart for a total of 2 doses. Each patient will be retreated with identical 2 intravenous infusions of rituximab, two weeks apart at 6 months after the first infusion, irrespective of cluster of differentiation (CD) 20+ cell counts. Thus, each participant will receive 4 infusions of rituximab.

Official Title
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A Single Center Pilot Trial of Rituximab in the Treatment of Fibrillary Glomerulonephritis

Conditions
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Fibrillary Glomerulonephritis

Intervention / Treatment
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* Drug: rituximab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fibrillary Glomerulonephritis with diagnostic biopsy performed within the last 2 years Proteinuria >1 gram Age > 18 years but < 80 years Adequately controlled blood pressure (BP<140/90 mmHg in >75% of the readings) for at least 3 months prior to enrollment with the use of (angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin-receptor blockers (ARB), if tolerated. Women must be post- menopausal, surgically sterile or practicing a medically approved method of contraception Able and willing to give written informed consent and comply with the requirements of the study protocol Adequate renal function as indicated by estimated glomerular filtration rate (GFR) > 25 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD/EPI) formula or a quantified creatinine clearance >25 mL/min, and/or serum creatinine <3.0 mg/dL in the presence of ACEi/ARB therapy Adequate bone marrow function, as indicated by hemoglobin >7.0 gm/dL, white count >3.0 x 10(9), platelet count >100 x 10(9) Negative chest x-ray within one year Negative serum pregnancy test (for women of child bearing age) Normal organ function. Subject agrees to use an acceptable method of birth control during treatment and for twelve months after completion of treatment Subject has provided written informed consent Subject agrees to discontinue routine use of non-steroidal anti-inflammatory drugs Absolute Neutrophil Count (ANC): > 1000/ mm3 Adequate liver function, as indicated by aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and total bilirubin < 2x upper limit or normal unless related to primary disease Negative HBsAg and anti-hepatitis B (HBc) lab values within 1 year of signing consent Exclusion Criteria: Pregnancy (determined by a serum pregnancy test for all women of childbearing potential within 7 days of treatment), or lactating. Inability to comply with study and/or follow-up procedures History of HIV (a documented positive lab value within one year of enrollment) Presence of active infection New York Heart Association Classification III or IV heart disease Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix History of psychiatric disorder At the Investigator's discretion, receipt of a live vaccine within 4 weeks prior to randomization At the Investigator's discretion, positive Hepatitis C serology Known history of diabetes mellitus or a Hemoglobin A1c result > 6.0% within 90 days prior to enrollment

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 79 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: rituximab<br>rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions. | Drug: rituximab<br>* 1000 mg infusion<br>* Other names: Rituxan;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in 24 Hour Creatinine Clearance | Change in 24 hour creatinine clearance with the use of rituximab at 12 months. Creatinine clearance results are reported as milliliters/minute/patient's body surface area (mL/min/SA). | Day 0, Day 365 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Proteinuria | Change in proteinuria in milligrams (mg) with the use of rituximab at 12 months. | Day 0, Day 365 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fibrillary glomerulonephritis, rituximab, Rituxan, MabThera, Zytux™