Rituximab to Prevent Recurrence of Proteinuria

The Use of Rituximab to Prevent Recurrence of Proteinuria in Patients Receiving Kidney Transplant for FSGS

The investigators propose to study novel targets of rituximab in podocytes, with a particular focus on recurrent focal segmental glomerulosclerosis (FSGS). The proposed study has strong clinical implications, since it may extend the approved indications for rituximab treatment to recurrent FSGS as well as to other proteinuric diseases. Furthermore, it will offer new insights into the role of sphyngomyelin related enzymes in podocyte function in health and disease, thus allowing the identification of novel targets for antiproteinuric drug development. Finally, the proposed study offers the opportunity to identify a correlation between the patient's specific clinical outcome and the experimental results obtained after exposing podocytes to patient sera in the presence or absence of rituximab. Therefore, it may lead to the development of an assay for the pre-transplant identification of patients at high-risk for recurrent disease and, among them, may allow the identification of those patients that will respond to rituximab.

Study Overview

• Status: Terminated
• Conditions: Proteinuria; FSGS
• Intervention / Treatment: Drug: Rituximab

Detailed Description

A total of 60 patients will be enrolled in the study.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 3

Contacts and Locations

Study Locations

• United States
  • Florida
    • Miami, Florida, United States, 33136
      • University of Miami

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 65 years (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion:

1. Patient has been fully informed and has signed a dated IRB-approval informed consent form.
2. Age 7-65 years.
3. Male and Females diagnosed of FSGS by kidney biopsy. Kidney biopsy report is not required once the physician confirms the diagnosis. Transcribed reports from referring physicians are also valid.

Exclusion:

1. Recipient or donor is seropositive for human immunodeficiency virus (HIV), Hepatitis C viruses, or Hepatitis B virus antigenemia.
2. Patient has a current malignancy or a history of malignancy (within the past 5 years), except non-metastatic basal or squamous cell carcinoma of the skin that has been treated successfully or carcinoma in situ of the cervix that has been treated successfully.
3. Patient has uncontrolled concomitant infections and/or severe diarrhea, vomiting, active upper gastro-intestinal tract malabsorption or an active peptic ulcer or any other unstable medical condition that could interfere with study objectives.
4. Patient is pregnant or lactating.
5. Patient has any form of substance abuse, psychiatric disorder or a condition that, in opinion of the investigator, may invalidate communication with the investigator.
6. Patients with a defined genetic cause of FSGS.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Rituximab; Participants will receive Rituximab post within 24 of Kidney Transplant	Drug: Rituximab; Induction therapy; Other Names: Rituxan
No Intervention: No rituximab; Participants will not receive Rituximab within 24 hours of Kidney Transplant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Days 3-30.	Primary Outcome - Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Days 3-30 will be compared between the two treatment arms using an intent-to-treat approach.	between post-transplant day 3 and day 30

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Months 3-12	Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Months 3-12 will be compared between the two treatment arms using an intent-to-treat approach.	Post-Transplant Months 3-12
Renal Function as Measured by eGFR (Estimated Glomerular Filtration Rate)	Renal function as measured by eGFR (estimated glomerular filtration rate) using the MDRD formula	12 months post-transplant

Collaborators and Investigators

• Sponsor: George W. Burke
• Collaborators: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); Genentech, Inc.; National Institutes of Health (NIH)
• Investigators: Principal Investigator: Alessia Fornoni, M.D., University of Miami; Study Director: George W. Burke, M.D., University of Miami

Study record dates

Study Major Dates

• Study Start: February 1, 2012
• Primary Completion (Actual): October 1, 2016
• Study Completion (Actual): October 1, 2016

Study Registration Dates

• First Submitted: July 15, 2010
• First Submitted That Met QC Criteria: July 15, 2010
• First Posted (Estimate): July 16, 2010

Study Record Updates

• Last Update Posted (Actual): September 20, 2018
• Last Update Submitted That Met QC Criteria: September 18, 2018
• Last Verified: September 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Urologic Diseases; Urological Manifestations; Disease Attributes; Urination Disorders; Recurrence; Proteinuria; Physiological Effects of Drugs; Antirheumatic Agents; Antineoplastic Agents; Immunologic Factors; Antineoplastic Agents, Immunological; Rituximab
• Other Study ID Numbers: 20100498; 1R01DK090316-01A1 (U.S. NIH Grant/Contract)