Fibrillary Glomerulonephritis
Conditions
Keywords
fibrillary glomerulonephritis, rituximab, Rituxan, MabThera, Zytux™
Brief summary
This pilot study is being done to see if the study medication, Rituximab, preserves kidney function after 12 months of taking the drug.
Detailed description
This is a Phase II, open-label pilot study to determine if the use of Rituximab reduces proteinuria over a 12 month period and is there preservation of kidney function with the use of this study drug. Each patient will be treated with 2 intravenous infusions of rituximab 1000 mg, two weeks apart for a total of 2 doses. Each patient will be retreated with identical 2 intravenous infusions of rituximab, two weeks apart at 6 months after the first infusion, irrespective of cluster of differentiation (CD) 20+ cell counts. Thus, each participant will receive 4 infusions of rituximab.
Interventions
DRUGrituximab
1000 mg infusion
Sponsors
Genentech, Inc.
Mayo Clinic
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 79 Years
Healthy volunteers
No
Inclusion criteria
* Fibrillary Glomerulonephritis with diagnostic biopsy performed within the last 2 years * Proteinuria \>1 gram * Age \> 18 years but \< 80 years * Adequately controlled blood pressure (BP\<140/90 mmHg in \>75% of the readings) for at least 3 months prior to enrollment with the use of (angiotensin converting enzyme inhibitors (ACEi) and/or angiotensin-receptor blockers (ARB), if tolerated. * Women must be post- menopausal, surgically sterile or practicing a medically approved method of contraception * Able and willing to give written informed consent and comply with the requirements of the study protocol * Adequate renal function as indicated by estimated glomerular filtration rate (GFR) \> 25 mL/min using the Chronic Kidney Disease Epidemiology Collaboration (CKD/EPI) formula or a quantified creatinine clearance \>25 mL/min, and/or serum creatinine \<3.0 mg/dL in the presence of ACEi/ARB therapy * Adequate bone marrow function, as indicated by hemoglobin \>7.0 gm/dL, white count \>3.0 x 10(9), platelet count \>100 x 10(9) * Negative chest x-ray within one year * Negative serum pregnancy test (for women of child bearing age) * Normal organ function. * Subject agrees to use an acceptable method of birth control during treatment and for twelve months after completion of treatment * Subject has provided written informed consent * Subject agrees to discontinue routine use of non-steroidal anti-inflammatory drugs * Absolute Neutrophil Count (ANC): \> 1000/ mm3 * Adequate liver function, as indicated by aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase and total bilirubin \< 2x upper limit or normal unless related to primary disease * Negative HBsAg and anti-hepatitis B (HBc) lab values within 1 year of signing consent
Exclusion criteria
* Pregnancy (determined by a serum pregnancy test for all women of childbearing potential within 7 days of treatment), or lactating. * Inability to comply with study and/or follow-up procedures * History of HIV (a documented positive lab value within one year of enrollment) * Presence of active infection * New York Heart Association Classification III or IV heart disease * Concomitant malignancies or previous malignancies within the last five years, with the exception of adequately treated basal or squamous cell carcinoma of the skin or carcinoma in situ of the cervix * History of psychiatric disorder * At the Investigator's discretion, receipt of a live vaccine within 4 weeks prior to randomization * At the Investigator's discretion, positive Hepatitis C serology * Known history of diabetes mellitus or a Hemoglobin A1c result \> 6.0% within 90 days prior to enrollment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in 24 Hour Creatinine Clearance | Day 0, Day 365 | Change in 24 hour creatinine clearance with the use of rituximab at 12 months. Creatinine clearance results are reported as milliliters/minute/patient's body surface area (mL/min/SA). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Proteinuria | Day 0, Day 365 | Change in proteinuria in milligrams (mg) with the use of rituximab at 12 months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab rituximab 1000 mg infusion two weeks apart for a total of two infusions. Retreated with identical rituximab 1000 mg infusion two weeks apart at six months after the first infusion for a grand total of four infusions.
rituximab: 1000 mg infusion | 11 |
| Total | 11 |
Baseline characteristics
| Characteristic | Rituximab | — |
|---|---|---|
| Age, Continuous | 58.5 years STANDARD_DEVIATION 2.03 | — |
| Race and Ethnicity Not Collected | — | — Participants |
| Region of Enrollment United States | 11 participants | — |
| Sex: Female, Male Female | 8 Participants | — |
| Sex: Female, Male Male | 3 Participants | — |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 11 |
| other Total, other adverse events | 0 / 11 |
| serious Total, serious adverse events | 0 / 11 |
Outcome results
Primary
Change in 24 Hour Creatinine Clearance
Change in 24 hour creatinine clearance with the use of rituximab at 12 months. Creatinine clearance results are reported as milliliters/minute/patient's body surface area (mL/min/SA).
Time frame: Day 0, Day 365
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Change in 24 Hour Creatinine Clearance | 41.0 mL/min/SA | Standard Deviation 15.52 |
p-value: 0.072t-test, 2 sided
Secondary
Change in Proteinuria
Change in proteinuria in milligrams (mg) with the use of rituximab at 12 months.
Time frame: Day 0, Day 365
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab | Change in Proteinuria | 2589.8 mg | Standard Deviation 1741.5 |
p-value: 0.068t-test, 2 sided