Clinical Trials

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. . 2.0 OBJECTIVES 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)