A Multicenter, Randomized, Prospective, Open-Label Trial of Rituximab in the Treatment of Progressive IgA Nephropathy
Open for Enrollment
Why is this study being done?
Hypothesis: In patients with progressive IgA nephropathy an intravenous infusion of 1000 mg of rituximab on Day 1 and Day 15 and Days 168 and 182 is superior to conventional therapy in reducing 24 hour proteinuria, and slowing progression of chronic kidney disease. .
2.1 Primary Efficacy Endpoints:
Percentage of patients in each group achieving complete or partial response as defined below:
Complete Response: At 12 months
1. < 300 mg proteinuria/24 hours Pediatric Criteria: First morning void urine protein: creatinine ratio <0.3
2. No greater than a 10% reduction in baseline estimated GFR as determined by MDRD (4 point) formula Partial Response: At 12 months
1) > 50% reduction in 24 hour proteinuria 2) No greater than a 25% reduction in baseline estimated GFR as determined by MDRD formula No Response: At 12 months
1. A 50% reduction, unchanged or increasing proteinuria over baseline levels will be considered no response
2. A greater than a 30% reduction in baseline estimated GFR as determined by MDRD formula
2.2 Primary Safety Endpoints:
- Incidence of Infusion Related Reactions: Defined as the development of hypotension, generalized pruritus, chills/rigors, angioedema and/or bronchospasm.
- Pulmonary Complications: Defined as a hypoxia, pulmonary infiltrates and/or acute respiratory failure
- Incidence of Major Infections: Defined as the development of pneumonia, complicated UTI/Pyelonephritis, Sepsis, and Meningitis.
- Development of Progressive Multifocal Leukoencephalopathy (PML)
2.3 Secondary Exploratory Efficacy Endpoints:
A) For patients in Groups 1 & 2 consenting to a repeat kidney biopsy at 12 months, a secondary endpoint will include the percentage of patients in experiencing a 25% increase in cortical fibrosis. The response rate will be semi-quantified by the change in cortical fibrosis as measured by changes in Sirius Red staining of interstitial collagen. A patient will be considered a complete or partial response or no response according to the following criteria:
Complete: Less than 10% rise in cortical fibrosis as measured by Sirius Red staining and digital image analysis Partial: Rising cortical fibrosis > 10% but less than 25% No Response: Greater than 25% rise in cortical fibrosis over baseline levels-(if patient consents to repeat kidney biopsy)
Who can I contact for additional information about this study?
Rochester: Fernando C. Fervenza, M.D., Ph.D. 507-266-7961
Shirley A Jennison 507-255-0231