Pilot Study of Velcade® in IgA Nephropathy

Velcade Therapy for Severe IgA Nephropathy

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.

Study Overview

• Status: Completed
• Conditions: Chronic Kidney Disease; IgA Nephropathy
• Intervention / Treatment: Drug: Bortezomib (Velcade®)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 11
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • New York
    • New York, New York, United States, 10021
      • The Rogosin Institute

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, 18 years of age or older.
2. Must have IgA nephropathy documented by kidney biopsy.
3. Must have greater than 1gm of proteinuria a day.
4. 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:

1. Low platelet count and neutrophil count within certain limits defined for enrollment.
2. Underlying peripheral neuropathy.
3. 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.
4. Allergic to VELCADE®, boron or mannitol.
5. Female subjects who are pregnant or breast-feeding.
6. Recent use of investigational drug within 14 days before enrollment.
7. Having serious medical conditions and infections (including HIV,or hepatitis B or C) or psychiatric illness likely to interfere with participation in the study.
8. 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Velcade® therapy; Patients with greater than 1gm of proteinuria per day will receive Velcade®.	Drug: Bortezomib (Velcade®); Velcade® at 1.3 mg/m2, on days 1, 4, 8 and 11 (=1 cycle).; Other Names: Bortezomib; Velcade®

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: The Rogosin Institute
• Collaborators: Weill Medical College of Cornell University
• Investigators: Principal Investigator: Choli Hartono, MD, The Rogosin Institute

Publications and helpful links

General Publications

• Yeo SC, Liew A, Barratt J. Emerging therapies in immunoglobulin A nephropathy. Nephrology (Carlton). 2015 Nov;20(11):788-800. doi: 10.1111/nep.12527.
• Hartono C, Chung M, Perlman AS, Chevalier JM, Serur D, Seshan SV, Muthukumar T. Bortezomib for Reduction of Proteinuria in IgA Nephropathy. Kidney Int Rep. 2018 Mar 11;3(4):861-866. doi: 10.1016/j.ekir.2018.03.001. eCollection 2018 Jul.
• Hartono C, Muthukumar T. Treating IgA nephropathy: quid novi? Discov Med. 2014 Mar;17(93):131-8.

Helpful Links

• The Rogosin Institute

Study record dates

Study Major Dates

• Study Start: July 1, 2010
• Primary Completion (Actual): April 17, 2017
• Study Completion (Actual): April 17, 2017

Study Registration Dates

• First Submitted: April 13, 2010
• First Submitted That Met QC Criteria: April 14, 2010
• First Posted (Estimate): April 15, 2010

Study Record Updates

• Last Update Posted (Actual): November 16, 2018
• Last Update Submitted That Met QC Criteria: October 16, 2018
• Last Verified: October 1, 2018

More Information

Terms related to this study

• Keywords: Chronic kidney disease; Proteinuria; Bortezomib; IgA nephropathy; Proteasome inhibitor; Velcade®
• Additional Relevant MeSH Terms: Immune System Diseases; Autoimmune Diseases; Urologic Diseases; Renal Insufficiency; Nephritis; Glomerulonephritis; Kidney Diseases; Renal Insufficiency, Chronic; Glomerulonephritis, IGA; Antineoplastic Agents; Bortezomib
• Other Study ID Numbers: X05320; 1001010854 (Other Identifier: Weill Cornell Medical College IRB)