Ensayos clínicos

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 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
• AST or 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