Rituximab Versus Steroids and Cyclophosphamide in the Treatment of Idiopathic Membranous Nephropathy

Conditions

• Glomerulonephritis, Membranous

Eligibility Criteria

Sex

ALL

Age

18 Years - N/A

Healthy Volunteers

Not accepted

Interventions

• Rituximab — DRUG
  Rituximab,1 g IV, day 1 and day 15
• Methylprednisolone — DRUG
  Methylprednisolone 1 g IV daily for 3 doses, then oral methylprednisolone (0.4 mg/kg/day) or oral prednisone (0.5mg/kg/day) for 27 days during Month 1, 3, 5.
• Cyclophosphamide — DRUG
  Month 2, 4 and 6: Oral Cyclophosphamide (2.0 mg/kg/day) for 30 days

Study Details

Idiopathic Membranous nephropathy (IMN) is an auto-immune glomerular disease. Recent studies suggest that circulating auto-antibodies against the podocyte surface antigens phospholipase A2 receptor1 (PLA2R1) and thrombospondin type 1 domain-containing 7A (THSD7A) cause the disease in the majority of the patients. Additional autoantibodies, directed to podocyte neo-expressed cytoplasm proteins have been described, including aldose reductase (AR), Mn-superoxide dismutase (SOD2) and alpha-enolase (alpha-ENO). The commonest presentation of IMN is nephrotic syndrome. Data from placebo arms of interventional studies show that 30-40% of the untreated patients with persistent nephrotic syndrome (NS) progress to end-stage renal disease (ESRD). The best-validated treatment regimen of IMN is combination therapy with steroids and cyclophosphamide, capable to induce remission of protenuria in two-third of the patients. Despite this evidence of efficacy, there are concerns about the use of cyclophosphamide, since it may be associated with adverse events, including bone marrow suppression, gonadal toxicity, infections and oncogenic effects. Thus, the availability of alternative therapies highly effective but with a greater safety profile is desirable. Given the key role of IgG antibodies in IMN, B cell depletion may favourably impact the glomerular disease. The anti-CD20 monoclonal antibody Rituximab is a selective B cell depleting agent. There is evidence that Rituximab is effective in the treatment of other diseases in which B cells play a key role, such as ANCA-related vasculitis. Observational studies in IMN provided encouraging data; in addition, the drug seems well tolerated. Head-to-head comparisons between Rituximab and steroid plus ciclophosphamide in randomized clinical trials are missing. The investigators propose this study in order to test, in a randomized controlled trial, the hypothesis that Rituximab is more effective than cyclical steroid/alkylating-agent therapy in inducing remission in patients with IMN and NS undergoing the initial treatment. In addition, the levels of the above-mentioned pathogenetic autoantibodies will be measured at baseline and during treatment. Finally, the study will compare the safety profile of steroid plus cyclophosphamide and Rituximab by evaluating the rate and severity of adverse events

Key Dates

Start date

Jan 31, 2012

Status verified

May 2019

Primary completion

Dec 31, 2019

Completion

Dec 31, 2019

Study Design

Enrollment

76 participants (actual)

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Arms

• Experimental: RITUXIMAB
  1 g. IV of Rituximab on days 1 and 15
• Active Comparator: Corticosteroids and Cyclophosphamide
  Month 1, 3 and 5: 1g IV methylprednisolone daily for 3 doses; oral methylprednisolone (0.4mg/kg/day) or prednisone (0.5/mg/kg/day); Month 2, 4 and 6: Oral Cyclophosphamide (2.0 mg/kg/day)

Primary Outcome Measure

change in probability of complete remission (proteinuria < 0.3 g/day) Primary Outcome Measures The primary outcome measure is the change in probability of complete remission (proteinuria < 0.3 g/day) at one year (see Design and power considerations). [ Time Frame: 1 year ]