Rituximab in Progressive IgA Nephropathy

Overview

About this study

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, we speculate that the reduction of circulating IgA may reduce proteinuria and injury in patients with IgA nephropathy. Moreover, the absence of prospective trials in the treatment of IgA disease and the lack of consensus for long-term treatment, the superior side-effect profile of this form of therapy may lead to significant advances in the treatment of this prevalent from of glomerulonephritis.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

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

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location Status

Rochester, Minn.

Mayo Clinic principal investigator

Fernando Fervenza, M.D., Ph.D.

Closed for enrollment

More information

Publications

Publications are currently not available

Study Results Summary

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Supplemental Study Information

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CLS-20128851

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