Clinical Trial: Sequential Therapy With Tacrolimus and Rituximab in Primary Membranous Nephropathy

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: European Multicenter and Open-Label Controlled Randomized Trial to Evaluate the Efficacy of Sequential Treatment With Tacrolimus-Rituximab Versus Steroids Plus Cyclophosphamide in Patients With Primar

Brief Summary:

In this study, investigators will evaluated the long-term efficacy and safety (two years) of Tacrolimus-Rituximab (RTX) therapy compared to Methylprednisolone-Cyclophosphamide (CYC) therapy in patients with primary Membranous Nephropathy (MN).

PRINCIPAL OBJECTIVE To evaluate whether sequential therapy with tacrolimus leads to a greater increase in the proportion of primary MN patients with Complete or Partial Remission when compared with patients receiving standard treatment. It will be assessed 24 months after the beginning of treatment.

Phase of the trial: and design: Phase III study, open label, randomized, and active controlled trial.

This study will have 3 stages: screening and recruitment of patients for 18 months, treatment period for six months in corticosteroids plus CYC group and 9 months in Tacrolimus-RTX group, and finally post-treatment follow-up period until to complete 24 months of follow-up since initial treatment.

This study will compare the standard therapy for primary MN patients with nephrotic range proteinuria (active control of steroids plus CYC) with a novel sequential therapy of tacrolimus and RTX, an approach of potential high efficacy, low toxicity and more acceptable safety profile.


Detailed Summary:

PRIMARY AND SECONDARY ENDPOINTS/OUTCOME MEASURES

Primary end-point:

The proportion of patients reaching CR defined as a reduction of proteinuria since baseline level to a value equal or lower than 0.5 g/24 h proteinuria plus stable renal function (eGFR ≥ 45 ml/min/1.73m2) or PR defined as a reduction of proteinuria since baseline level to a value less than 3.5 g/24 h and 50% lower than baseline proteinuria plus stable renal function (eGFR ≥ 45ml/min/1.73m2) at 24 months of study treatment.

Secondary end-points

  • The proportion of patients with Limited response (LR) defined as a reduction of proteinuria since baseline level > 50% but to a value > 3.5g/24 h. at 12, 18 and 24 months of study treatment..
  • The number of patients with an increase ≥ 50% of serum creatinine (SCr) from baseline at 12, 18 and 24 months (end of the follow-up).
  • The time of renal survival (status free of increase ≥ 50% of baseline SCr) in both arms overall after the study.
  • The proportion of patients with preserved renal function (estimated GFR ≥ 60 ml/min) in both treatment arms after the treatment period.
  • The proportion of patients with relapse (defines as the reappearance of proteinuria > 3.5 gr/24h and at least 50% increase over the lowest baseline value in at least three consecutive visits in those patients who previously presented a PR or CR) and the time to relapse after the treatment period.
  • Serum levels of anti-phospholipase A2 receptor antibodies (anti-PLA2R), before of treatment and at 3, 6, 9, 12, 18 and
    Sponsor: Hospital Universitario 12 de Octubre

    Current Primary Outcome: Proportion of patients with complete and/or partial remission. [ Time Frame: 24 months ]

    The proportion of patients reaching complete remission, defined as a reduction of proteinuria since baseline level to a value equal or lower than 0.5 g/24 h proteinuria plus stable renal function (eGFR ≥ 45 ml/min/1.73m2) or partial remission, defined as a reduction of proteinuria since baseline level to a value less than 3.5 g/24 h and 50% lower than baseline proteinuria plus stable renal function (eGFR ≥ 45 ml/min/1.73m2) at 24 months of study treatment.


    Original Primary Outcome: Proportion of patients with complete and/or partial remission. [ Time Frame: 24 months ]

    The proportion of patients reaching complete remission, defined as a reduction of proteinuria since baseline level to a value equal or lower than 0.5 g/24 h proteinuria plus stable renal function (eGFR ≥ 60 ml/min/1.73m2) or partial remission, defined as a reduction of proteinuria since baseline level to a value less than 3.5 g/24 h and 50% lower than baseline proteinuria plus stable renal function (eGFR ≥ 60 ml/min/1.73m2) at 24 months of study treatment.


    Current Secondary Outcome:

    • Proportion of patients with limited response [ Time Frame: 12, 18, and 24 months ]
      The proportion of patients with limited response, defined as a reduction of proteinuria since baseline level > 50% but to a value > 3.5g/24 h. at 12, 18 and 24 months of study treatment.
    • Proportion of patients with increase of baseline serum creatinine ≥ 50% [ Time Frame: 12, 18, and 24 months ]
      The number of patients with an increase ≥ 50% of serum creatinine (SCr) from baseline at 12, 18 and 24 months (end of the follow-up).
    • Proportions of patients with relapses [ Time Frame: 9, 12, 18, and 24 months ]
      The proportion of patients with relapses (defines as the reappearance of proteinuria > 3.5 gr/24h and at least 50% increase over the lowest baseline value in at least three consecutive visits in those patients who previously presented a PR or CR) and the time to relapse after the treatment period.
    • Proportion of patients with drug-related adverse events [ Time Frame: During all therapy period and until 24 months post-beginning of therapy ]
      The proportion of patient with drug-related adverse events and serious adverse events.


    Original Secondary Outcome: Same as current

    Information By: Hospital Universitario 12 de Octubre

    Dates:
    Date Received: September 19, 2013
    Date Started: January 2014
    Date Completion: April 2019
    Last Updated: August 18, 2016
    Last Verified: August 2016