Rituximab in Progressive Immunoglobulin A (IgA) Nephropathy
Condition: IgA Nephropathy
MeSH terms: Kidney Diseases; Glomerulonephritis, IGA
Intervention: Intravenous Rituximab; ACE/ARB; Omega-3 Fatty Acid Fish Oil Supplement
Intervention description: 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; 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; Omega-3 Fatty Acid Fish Oil Supplement 3.6 gm eicosapentaenoic acid (EPA)/day
Intervention MeSH terms: Rituximab; Angiotensin II
Phase: Phase 4
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 34.0
Sex: All
Minimum age: 18 Years
Maximum age: 70 Years
Healthy volunteers: No
Keywords: Estimated glomerular filtration rate (GFR); Proteinuria; Renal Fibrosis

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.
    

Eligibility criteria:

        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 Exclusion Criteria

          -  Patients with anaphylaxis and/or known allergic reactions to Rituximab

          -  Hemoglobin: <8.5 gm/dL

          -  Platelets: <100,000/mm

          -  Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) >2.5 x Upper Limit
             of Normal unless related to primary disease.

          -  Previous Treatment with Rituximab(MabThera®/Rituxan®)

          -  Previous treatment with Natalizumab(Tysabri®)

          -  History of severe allergic or anaphylactic reactions to humanized or murine monoclonal
             antibodies

          -  History of recurrent significant infection or recurrent bacterial infections

          -  Known active bacterial, viral fungal mycobacterial or atypical mycobacterial
             infections, but excluding fungal infections of nail beds

          -  Any major episode of infection requiring hospitalization or treatment with i.v.
             antibiotics within 4 weeks of screening or oral antibiotics within 2 weeks prior to
             screening

          -  Ongoing use of high dose steroids(>10 mg/day)or unstable steroid dose in the past 4
             weeks

          -  Lack of peripheral venous access

          -  History of drug, alcohol, or chemical abuse within 6 months prior to screening

          -  Pregnancy (a negative serum or urine pregnancy test will be performed for all women of
             childbearing potential no later than 7 days prior to treatment) or lactation

          -  Concomitant or previous malignancies, 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 that would interfere with normal participation in this
             protocol

          -  Significant cardiac or pulmonary disease (including obstructive pulmonary disease)

          -  Any other disease, metabolic dysfunction, physical examination finding, or clinical
             laboratory finding giving reasonable suspicion of a disease or condition that
             contraindicates the use of an investigational drug or that may affect the
             interpretation of the results or render the patient at high risk from treatment
             complication

          -  Inability to comply with study and follow-up procedures