FSGS, Proteinuria
Conditions
Brief summary
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.
Detailed description
A total of 60 patients will be enrolled in the study.
Interventions
DRUGRituximab
Induction therapy
Sponsors
Genentech, Inc.
National Institutes of Health (NIH)
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
George W. Burke
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
7 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Days 3-30. | between post-transplant day 3 and day 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Months 3-12 | 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. |
| Renal Function as Measured by eGFR (Estimated Glomerular Filtration Rate) | 12 months post-transplant | Renal function as measured by eGFR (estimated glomerular filtration rate) using the MDRD formula |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Participants will receive Rituximab post within 24 of Kidney Transplant
Rituximab: Induction therapy | 15 |
| No Rituximab Participants will not receive Rituximab within 24 hours of Kidney Transplant | 15 |
| Total | 30 |
Baseline characteristics
| Characteristic | Rituximab | No Rituximab | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical >=65 years | 1 Participants | 0 Participants | 1 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 13 Participants | 26 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 5 Participants | 4 Participants | 9 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 11 Participants | 21 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 3 Participants | 7 Participants | 10 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) White | 11 Participants | 8 Participants | 19 Participants |
| Sex: Female, Male Female | 5 Participants | 5 Participants | 10 Participants |
| Sex: Female, Male Male | 10 Participants | 10 Participants | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 15 | 0 / 15 |
| other Total, other adverse events | 11 / 15 | 13 / 15 |
| serious Total, serious adverse events | 2 / 15 | 0 / 15 |
Outcome results
Primary
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.
Time frame: between post-transplant day 3 and day 30
Population: Intent-to-Treat Analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Days 3-30. | 1.44 ratio | Standard Error 1.33 |
| No Rituximab | Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Days 3-30. | 2.85 ratio | Standard Error 1.52 |
Comparison: T-test of the natural logarithmic transformed datap-value: 0.18t-test, 2 sided
Secondary
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.
Time frame: Post-Transplant Months 3-12
Population: Intent-to-Treat Analysis
| Arm | Measure | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Months 3-12 | 0.50 ratio | Standard Error 1.53 |
| No Rituximab | Maximum of the Urine Protein/Creatinine Ratio Observed Between Post-Transplant Months 3-12 | 0.35 ratio | Standard Error 1.34 |
Comparison: T-test of Natural Log Transformed Data.p-value: 0.49t-test, 2 sided
Secondary
Renal Function as Measured by eGFR (Estimated Glomerular Filtration Rate)
Renal function as measured by eGFR (estimated glomerular filtration rate) using the MDRD formula
Time frame: 12 months post-transplant
Population: Intent-to-Treat Analysis
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Renal Function as Measured by eGFR (Estimated Glomerular Filtration Rate) | 57.1 ml/min/1.73 m^2 | Standard Error 8.4 |
| No Rituximab | Renal Function as Measured by eGFR (Estimated Glomerular Filtration Rate) | 66.9 ml/min/1.73 m^2 | Standard Error 6.6 |
Comparison: T-testp-value: 0.37t-test, 2 sided