Clinical Trial: Evaluate Rituximab Treatment for Idiopathic Membranous Nephropathy

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Prospective Randomized Multicentric Open Label Study to Evaluate Rituximab Treatment for Idiopathic Membranous Nephropathy (IMN)

Brief Summary:

The Membranous Nephropathy is one of the most common cause of Nephrotic Syndrome of adults. In 2/3 of patients the cause of the disease is idiopathic. This can also be referred to as idiopathic membranous nephropathy (IMN).The most of these patients are treated by non immunosuppressive symptomatic treatment (NIST): antiproteinuric and antihypertensive blocking the rennin-angiotensine system. However, the patients resistant to antiproteinuric treatment risk to develop an end stage renal disease (ESRD).

Rituximab has been recently used in patients suffering of nephrotic syndrome related to IMN in four international studies. Rituximab appears effective and safe in reducing proteinuria in nearly 60% of patients.

The primary outcome of the investigators prospective randomized study is to determine whether or not the Rituximab associated with NIST is more effective than non immunologic symptomatic treatment alone in inducing long term remission of proteinuria.


Detailed Summary:

The IMN exposes patients to severe complications which engage the vital prognosis or Nephrotic Syndrome.

The development of well tolerated and effective pathogenesis linked therapies is needed to treat patients with idiopathic Membranous Nephropathy Rituximab, a monoclonal antibody (mAb) against the CD20 present on B cells, has been recently used in patients suffering of nephrotic syndrome related to IMN in four international studies. Rituximab appears effective and safe in reducing proteinuria in nearly 60% of patients.

However, no randomized controlled study has been published to date.

In a previous study, outcome of 28 patients treated with rituximab for idiopathic MN is analysed. Anti-PLA2R antibodies in serum and PLA2R antigen in kidney biopsy were assessed in 10 and 9 patients.

Proteinuria was significantly decreased by 56%, 62% and 87% at 3 months, 6 months and 12 months. At 6 months, 2 patients achieved full remission and 12 partial remission (overall renal response, 50%). At 12 months (n=23), complete remission was achieved in 6 patients and partial remission in 13 patients (overall renal response, 82,6%). Three patients suffered a relapse of nephrotic proteinuria 27 to 50 months after treatment. Univariate analysis suggested that the degree of renal failure (MDRD < 45/ml/min/1.73 m²) is an independent factor that predicts lack of response to rituximab. Anti-PLA2R antibodies were detected in serum in 10 patients, and PLA2R antigen in immune deposits in 8 of 9 patients. Antibodies became negative in all 5 responsive patients with available follow-up. In this retrospective study, a high rate of remission was achieved at 12 months after treatment.

Our trial is a
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Evaluation of efficacy of Rituximab associated with Non Immunosuppressive Symptomatic Treatment (NIST) in (IMN) in reducing the rate of proteinuria (patients with persistent urinary protein excretion rate ≥3,5g/24 h and albuminemia < 30g/l ) [ Time Frame: 6 months ]

Evaluation of efficacy of Rituximab associated with Non Immunosuppressive Symptomatic Treatment (NIST) in (IMN) in reducing the rate of proteniuria


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Effect of Rituximab on the progression of chronic renal disease [ Time Frame: 6 months ]

    Effect of Rituximab on the progression of chronic renal disease by measuring :

    • Percentage of proteinuria variation at 6 months
    • Percentage of nephrotic syndrome complication: measuring serum creatinine and glomerular filtration rate (GFR) at 6 months, infections, hydrops, vein thrombosis, arterial thrombosis.
  • Evaluation of Rituximab tolerance in IMN [ Time Frame: 6 months ]

    Evaluation of Rituximab tolerance in IMN :

    -Percentage of serious allergic reaction after Rituximab infusion "drop in blood pressure and/or bronchospasm"

  • serologic diagnosis with identification of anti-NEP and anti-PLA2R antibodies in IMN before and after treatment with Rituximab [ Time Frame: 6 months ]
    serologic diagnosis with identification of anti-NEP and anti-PLA2R antibodies in IMN before and after treatment with Rituximab
  • genetic analysis [ Time Frame: 6 months ]
    genetic analysis Study of the alleles "HLA-DQA1 and PLA2R1" situated respectively on chromosomes 6p21 and 2q24.
  • Lymphocyte CD19 dosing at month 3 and month 6. [ Time Frame: 6 months ]
    Lymphocyte CD19 dosing at month 3 and month 6.


Original Secondary Outcome: Same as current

Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: December 9, 2011
Date Started: January 2012
Date Completion: September 2016
Last Updated: August 23, 2016
Last Verified: August 2016