Pilot Study of Velcade® in IgA Nephropathy

Study Overview
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Brief Summary
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The primary objective of this study is to investigate the ability of Velcade® (bortezomib) to induce complete or partial remission in patients with severe IgA nephropathy. The secondary objectives are to assess clinical outcomes relating to safety and efficacy, such as infection, malignancy, preservation of renal function, partial responders, relapse rate, and to study mechanistic assays to predict remission.

Detailed Description
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This exploratory single center, open-label, single treatment group assignment, safety and efficacy study will enroll 15 patients with severe IgA nephropathy. Subjects will receive 1 cycle of Velcade® to induce clinical remission. Follow-up visits will occur monthly for a year. For this pilot study, the proportion of patients with clinical remission or partial response will be analyzed.

Official Title
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Velcade Therapy for Severe IgA Nephropathy

Conditions
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Chronic Kidney Disease, IgA Nephropathy

Intervention / Treatment
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* Drug: Bortezomib (Velcade®)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, 18 years of age or older. Must have IgA nephropathy documented by kidney biopsy. Must have greater than 1gm of proteinuria a day. Must be on a stable dose of Angiotensin Converting Enzyme Inhibitor (ACEI) and/or Angiotensin Receptor Blocking agent (ARB) for at least 4 weeks prior to screening. Exclusion Criteria: Low platelet count and neutrophil count within certain limits defined for enrollment. Underlying peripheral neuropathy. Having cardiac problems, such as myocardial infarction, heart failure, uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Allergic to VELCADE®, boron or mannitol. Female subjects who are pregnant or breast-feeding. Recent use of investigational drug within 14 days before enrollment. Having serious medical conditions and infections (including HIV,or hepatitis B or C) or psychiatric illness likely to interfere with participation in the study. Diagnosed or treated for cancer within 3 years of participation in the study, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, and in situ malignancy, or low-risk prostate cancer after curative therapy.

Ages Eligible for Study
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Minimum Age: 18 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: Velcade® therapy<br>Patients with greater than 1gm of proteinuria per day will receive Velcade®. | Drug: Bortezomib (Velcade®)<br>* Velcade® at 1.3 mg/m2, on days 1, 4, 8 and 11 (=1 cycle).<br>* Other names: Bortezomib;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proteinuria | Quantification of urinary protein will be made after treatment by measuring 24 hr urine protein. | Baseline and 1 year | 
| Number of Participants With Complete Remission, Partial Response, or no Response. | Complete remission was defined as daily proteinuria of less than 300mg measured by 24 hr urine collection. Partial response was defined as any reduction in daily proteinuria from baseline as measure by 24 hr urine collection. | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Creatinine | Preservation of renal function will be assessed. | Baseline and 1 year | 
| Number of Participants With Abnormal Lab Values or Infections Related to Exposure to Study Medication. | Complete blood count will be checked at regular intervals to monitor for anemia; liver panel; serum immunoglobulin profile will also be followed. | 1 year | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic kidney disease, IgA nephropathy, Velcade®, Proteinuria, Bortezomib, Proteasome inhibitor