Rituximab in Progressive IgA Nephropathy

IgA Nephropathy Clinical Trial

Official title: A Multicenter, Randomized, Prospective, Open-Label Trial of Rituximab in the Treatment of Progressive IgA Nephropathy

Status Completed

Clinical Trial Summary

Recent clinical success in the use of Rituximab in the treatment of Lupus nephritis and other forms immune complex glomerulonephritis has led to its investigation in the treatment of IgA nephropathy. Because IgA class antibodies have comparatively short half-lives and that deposition of polymeric forms of IgA contributes to glomerular injury, we speculate that the reduction of circulating IgA may reduce proteinuria and injury in patients with IgA nephropathy. Moreover, the absence of prospective trials in the treatment of IgA disease and the lack of consensus for long-term treatment, the superior side-effect profile of this form of therapy may lead to significant advances in the treatment of this prevalent from of glomerulonephritis.

Clinical Trial Description

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) ;

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Glomerulonephritis, IGA
• IgA Nephropathy
• Kidney Diseases

• NCT number: NCT00498368
• Study type: Interventional
• Source: Mayo Clinic
• Status: Completed
• Phase: Phase 4
• Start date: February 2009
• Completion date: September 2015