IgA Nephropathy
Conditions
Keywords
Estimated glomerular filtration rate (GFR), Proteinuria, Renal Fibrosis
Brief summary
This study was about IgA nephropathy, a form of kidney disease characterized by the presence of blood and protein in the urine. This study was done to determine if the medication rituximab could reduce protein in the patient's urine. Hypothesis: In patients with progressive IgA nephropathy an intravenous infusion of 1000 mg of rituximab on Day 1 and Day 15 and Days 168 and 182 is superior to conventional therapy in reducing 24 hour proteinuria, and slowing progression of chronic kidney disease.
Detailed description
Recent clinical success in the use of Rituximab in the treatment of Lupus nephritis and other forms immune complex glomerulonephritis has led to its investigation in the treatment of IgA nephropathy. Because IgA class antibodies have comparatively short half-lives and that deposition of polymeric forms of IgA contributes to glomerular injury, the researchers speculated that the reduction of circulating IgA could reduce proteinuria and injury in patients with IgA nephropathy. Treatment and Follow-up: Subjects were randomly assigned to receive rituximab or to continue standard care. Both arms received a Omega-3 Fatty Acid Fish Oil Supplement and angiotensin converting enzyme (ACE) inhibitors and/or Angiotensin II receptor blockers (ARBs). ACE inhibitors and/or ARBs were used to achieve a blood pressure goal of \<130/80 mmHg. The study was an open-label trial; those assigned to rituximab received a 1 g infusion of rituximab followed by an identical dose 2 weeks later. Premedication with corticosteroids (10 mg dexamethasone intravenously) was also given 30 min prior to the first infusion of each series of rituximab. They received an identical 2 g course of rituximab 6 months later. Subjects were assessed at least every 3 months or as needed for clinical events. This assessment included physical examination, a questionnaire for adverse events, and measurement of routine hematology, serum chemistry, timed urine protein excretion, and for those assigned to rituximab, B-cell subsets. Follow-up was considered complete at 12 months.
Interventions
Rituximab Therapy \[27 Patients\] * Rituximab 1 gm IV on Treatment Day 1 * Rituximab 1 gm IV on Treatment Day 15 * Rituximab 1 gm IV on Treatment Day 168 * Rituximab 1 gm IV on Treatment Day 182
DRUGACE/ARB
ACE inhibitors and /or ARBs will be used to achieve a blood pressure goal of \<130/80 millimeters of mercury (mmHg). Patients not attaining the target blood pressure with an ACE inhibitor or ARB alone should be treated with the combination of ACE inhibitor (ACEi) + ARB
DIETARY_SUPPLEMENTOmega-3 Fatty Acid Fish Oil Supplement
Omega-3 Fatty Acid Fish Oil Supplement 3.6 gm eicosapentaenoic acid (EPA)/day
Sponsors
Ohio State University
Stanford University
University of North Carolina, Chapel Hill
Columbia University
Genentech, Inc.
Biogen
Mayo Clinic
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
* Any patient between the age of 18 and 70 years of age and able to give informed consent * GFR by Cockcroft-Gault or MDRD equations \<90 mls/min and \>30 mls/min * Greater than or equal to 1000 mg of proteinuria/24 hours while on stable ACEi, ARB or renin inhibitor therapy for 2 months. Patients receiving combination ACE or ARB or ACEi and a renin inhibitor for 2 months will only require 500mg/24 hours * Blood pressure \<130/80 mmHg. The presence of hypertension is not required for study entry, but any patient requiring long term hypertensive medications must have blood pressure controlled \<130-80 mmHg, to be considered eligible for the study * Female patients with IgA will be considered eligible for study entry if they have a negative urine or serum pregnancy test at the time of screening are agreeable to 2 years of contraception * Biopsy proven IgA nephropathy and clinical features consistent with Henoch Schonlein Purpura will be considered eligible for the study * Able to swallow the oral medications
Exclusion criteria
* Clinical and histologic evidence of IgA predominant Lupus nephritis * Clinical and histologic evidence of idiopathic IgA forms of membranoproliferative glomerulonephritis * Clinical evidence of cirrhosis, chronic active liver disease or known infection with hepatitis B, C or HIV * Estimated GFR \<30 ml/min/1.73m² at the time of screening * Greater than 50% glomerular senescence or cortical scarring on renal biopsy * Active systemic infection or history of serious infection within one month of entry * History of Crohn's disease or Celiac Sprue * Positive pregnancy test or breast feeding at time of study entry or unwilling to comply with contraceptive measures * Current or recent (within 30 days) exposure to any investigational drug * Serum Cr \>3.5 mg/dl or Modification of Diet in Renal Disease (MDRD) calculated GFR \<30 mls/min * Patients receiving \>6 months therapy with oral prednisone or glucocorticoid equivalent * Live vaccine within 28 days of study enrollment. General Safety & Laboratory
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Change in Proteinuria at 12 Months | 1 year |
Secondary
| Measure | Time frame |
|---|---|
| Biochemical Marker IgA at 12 Months | 12 months |
| Biochemical Marker Gd-Immunoglobulin A Subclass 1 (IgA1) at 12 Months | 12 months |
| Biochemical Marker Immunoglobulin G (IgG) AutoAb at 12 Months | 12 months |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Rituximab Plus ACE/ARB Intravenous Rituximab therapy, ACE/ARB combination therapy, and Omega-3 Fatty Acid Fish Oil Supplement
Intravenous Rituximab: Rituximab Therapy \[27 Patients\]
* Rituximab 1 gm IV on Treatment Day 1
* Rituximab 1 gm IV on Treatment Day 15
* Rituximab 1 gm IV on Treatment Day 168
* Rituximab 1 gm IV on Treatment Day 182
* An ACE inhibitors and /or ARBs will be used to achieve a blood pressure goal of \<130/80 millimeters of mercury (mmHg)
Omega-3 Fatty Acid Fish Oil Supplement: Omega-3 Fatty Acid Fish Oil Supplement 3.6 gm eicosapentaenoic acid (EPA)/day | 17 |
| ACE/ARB ACE/ARB therapy and Omega-3 Fatty Acid Fish Oil Supplement
ACE/ARB: ACE inhibitors and /or ARBs will be used to achieve a blood pressure goal of \<130/80 millimeters of mercury (mmHg)
Omega-3 Fatty Acid Fish Oil Supplement: Omega-3 Fatty Acid Fish Oil Supplement 3.6 gm eicosapentaenoic acid (EPA)/day | 17 |
| Total | 34 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 3 | 2 |
Baseline characteristics
| Characteristic | Rituximab Plus ACE/ARB | ACE/ARB | Total |
|---|---|---|---|
| Age, Continuous | 43 years | 33 years | 40 years |
| Gender Female | 7 Participants | 2 Participants | 9 Participants |
| Gender Male | 10 Participants | 15 Participants | 25 Participants |
| Region of Enrollment United States | 17 participants | 17 participants | 34 participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 17 | 0 / 17 |
| serious Total, serious adverse events | 0 / 17 | 0 / 17 |
Outcome results
Primary
Change in Proteinuria at 12 Months
Time frame: 1 year
Population: The number of participants differs from the participant flow because not all participants had the laboratory test done.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Rituximab Plus ACE/ARB | Change in Proteinuria at 12 Months | Number of participants with > 50% reduction | 3 participants |
| Rituximab Plus ACE/ARB | Change in Proteinuria at 12 Months | Number of participants with >50% increase | 1 participants |
| Rituximab Plus ACE/ARB | Change in Proteinuria at 12 Months | Number of participants with <500 mg of protein | 2 participants |
| ACE/ARB | Change in Proteinuria at 12 Months | Number of participants with > 50% reduction | 3 participants |
| ACE/ARB | Change in Proteinuria at 12 Months | Number of participants with >50% increase | 2 participants |
| ACE/ARB | Change in Proteinuria at 12 Months | Number of participants with <500 mg of protein | 2 participants |
Secondary
Biochemical Marker Gd-Immunoglobulin A Subclass 1 (IgA1) at 12 Months
Time frame: 12 months
Population: The number of participants differs from the participant flow because not all participants had the laboratory test done.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab Plus ACE/ARB | Biochemical Marker Gd-Immunoglobulin A Subclass 1 (IgA1) at 12 Months | 60.5 U/100ng IgA | Standard Deviation 13 |
| ACE/ARB | Biochemical Marker Gd-Immunoglobulin A Subclass 1 (IgA1) at 12 Months | 58.9 U/100ng IgA | Standard Deviation 5.6 |
Secondary
Biochemical Marker IgA at 12 Months
Time frame: 12 months
Population: The number of participants differs from the participant flow because not all participants had the laboratory test done.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab Plus ACE/ARB | Biochemical Marker IgA at 12 Months | 4.4 mg/ml | Standard Deviation 1.4 |
| ACE/ARB | Biochemical Marker IgA at 12 Months | 4.6 mg/ml | Standard Deviation 1.9 |
Secondary
Biochemical Marker Immunoglobulin G (IgG) AutoAb at 12 Months
Time frame: 12 months
Population: The number of participants differs from the participant flow because not all participants had the laboratory test done.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Rituximab Plus ACE/ARB | Biochemical Marker Immunoglobulin G (IgG) AutoAb at 12 Months | 1751.3 U/ml | Standard Deviation 2469.4 |
| ACE/ARB | Biochemical Marker Immunoglobulin G (IgG) AutoAb at 12 Months | 1075 U/ml | Standard Deviation 908.7 |