Clinical Trial: Pilot Study of Rituximab for Membranoproliferative Glomerulonephritis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Pilot Study of Rituximab for Membranoproliferative Glomerulonephritis

Brief Summary: Membranoproliferative glomerulonephritis (MPGN) is a relatively-rare, immune-mediated kidney disease. All current therapies are inadequate and MPGN frequently leads to kidney failure. This study is a 10 patient trial of the monoclonal antibody rituximab for adult patients with MPGN. Study patients will receive 2 doses of rituximab intravenously on days 1 and 15 and will then be followed for 1 year.

Detailed Summary: Membranoproliferative glomerulonephritis (MPGN) is a relatively-rare, immune-mediated glomerular disease. There is no accepted therapy and all current therapies are inadequate. Current therapeutic options include immunosuppression with corticosteroids alone or in combination with alkylating agents, antiplatelet therapy with aspirin and/or dipyridamole and/or warfarin, and angiotensin converting enzyme inhibitors and/or angiotensin receptor blockers. As with other glomerular diseases the amount of protein in the urine correlates well with the long-term prognosis. Thus, this parameter has been used in previous studies, and will be used in this study, as the primary indicator of therapeutic efficacy. We propose a pilot study to test the hypothesis that selective B lymphocyte depletion will result in disappearance of pathogenic antibodies and induce remission of proteinuria in patients with idiopathic membranoproliferative glomerulonephritis. Our population will be 10 adults with MPGN involving either the native kidneys or a renal transplant. We will enroll patients with a glomerular filtration rate (GFR) greater than or equal to 25 ml/min, as estimated by creatinine clearance, and with a 24 hour urinary ratio of protein to creatinine greater than or equal to 1, while receiving an angiotensin converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB). Patients will receive Rituximab 1g on Day 1 and 15. Patients will be followed for 1 year following completion of treatment. The primary outcome will be the change in urinary protein excretion at 6 months. Secondary outcomes will include changes in the GFR, changes in urinary protein excretion at 3, 9, and 12 months, the rate of change in urinary protein excretion, serum albumin concentration, serum cholesterol, the number of complete and partial remissions, time to remission, and the number of relapses.
Sponsor: Mayo Clinic

Current Primary Outcome: Proteinuria [ Time Frame: The primary endpoints are based on quantitative changes in urine protein measured at 6 months. Additional evaluations of urine protein will be done at 3, 9, and 12 months. ]

  1. Complete remission (CR) UP ≤ 0.3 g, without doubling of serum creatinine
  2. Partial remission (PR) Reduction in UP of > 50% plus final UP ≤ 3.5 g but >0.3 g, without doubling of serum creatinine
  3. Limited response (LR) Reduction in UP of > 50% with final UP > 3.5 g, without doubling of serum creatinine
  4. Non-response (NR) Reduction in UP of < 50%. (includes progression of UP), without doubling of serum creatinine
  5. Progression Proteinuria increases by > 50% or serum creatinine doubles
  6. Relapse New development of nephrotic range proteinuria, i.e. > 3.5 g/day


Original Primary Outcome: Proteinuria

Current Secondary Outcome:

  • Serum albumin [ Time Frame: 3, 6, 9 and 12 months ]
    Change in serum albumin concentration
  • Serum cholesterol [ Time Frame: 6 and 9 month timepoints ]
    Change in serum cholesterol levels


Original Secondary Outcome:

  • GFR
  • Serum albumin
  • Serum cholesterol
  • Complete and partial remissions


Information By: Mayo Clinic

Dates:
Date Received: January 10, 2006
Date Started: November 2005
Date Completion:
Last Updated: January 15, 2013
Last Verified: January 2013