Clinical Trial: Comparison Study of Two Rituximab Regimens in the Remission of ANCA Associated Vasculitis

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

Official Title: MAINtenance of Remission Using RITuximab in Systemic ANCA-associated Vasculitis II

Brief Summary: The aim of this study is to assess the efficacy of a rituximab regimen based on rate of ANCA and CD19 lymphocytes for maintenance treatment in systemic ANCA-associated vasculitis: prospective, multicenter, controlled, randomized comparative study of two rituximab regimens: one based on ANCA and CD19 lymphocytes versus systematic infusions.

Detailed Summary: Randomized, controlled, national, multicenter, prospective study to compare systematic rituximab infusions (conventional therapy) to rituximab infusion based on rate of ANCA and CD19 lymphocytes in patients with systemic ANCA-associated vasculitis, in remission (achieved with an induction treatment combining corticosteroids and an immunosuppressant after the first flare of the disease (new diagnosis) or after a relapse. Patients will be stratified by first flare (66% of the patients) or relapse (33% of the patients). Patients complying with the inclusion criteria may be included when they are in remission from their vasculitis. Patients will be included at the time of remission and then randomized. They will receive maintenance treatment by 1)2 rituximab infusions mg at D1, D15 then every 6 months until month 18 (i.e. a total of 5 infusions), at the dose of 500 mg. 2) 1 rituximab infusion at the dose of 500 mg at D0 then ANCA status and CD19+ lymphocyte count will be monitored every 3 months, and patients will receive new 500 mg rituximab infusions either if CD19 are > to 0/mm3, or if ANCA are positive again or if ANCA titer significantly raises. After the 18 month length of maintenance phase, i.e. after stopping immunosuppressive maintenance therapy, patients will be followed for an additional 10 month period. Patients with granulomatosis with polyangiitis will be prescribed cotrimoxazole 160/800 tid (for 2 additional years).
Sponsor: Assistance Publique - Hôpitaux de Paris

Current Primary Outcome: Number of relapses [ Time Frame: at 28 months ]

Number of relapses (BVAS>0) majors and minors in each group at the end of the maintenance treatment (18 months treatment + 10 months follow-up)


Original Primary Outcome: Number of relapses [ Time Frame: at 34 months ]

Number of relapses (BVAS>0) majors and minors in each group at the end of the maintenance treatment (18 months treatment + 16 months follow-up)


Current Secondary Outcome:

  • Number of patients with ANCA (Anti-Neutrophil Cytoplasmatic Antibodies) [ Time Frame: at 28 months ]
    Number of patients with ANCA in each group
  • Number of adverse events [ Time Frame: at 28 months ]
    To assess the number of adverse events and their severity in each group
  • Mortality rate [ Time Frame: at 28 months ]
    To assess mortality rate in each group
  • Number of minor relapse [ Time Frame: at 28 months ]
    number of minor relapse in each group
  • Cumulated dose of corticosteroid treatment [ Time Frame: at 28 months ]
    Cumulated dose of corticosteroid treatment in each group at 28 months
  • Number and severity of damages [ Time Frame: at 28 months ]
    Number and severity of damages in each group
  • Evolution of ANCA and the link of the clinical events [ Time Frame: at 28 months ]
    Evolution of ANCA in each group and the link of the clinical events
  • Distribution of events by severity [ Time Frame: at 28 months ]
    Distribution of events by severity and it will be assigned to the drug and its mode of administration and/or the severity of the disease (in each group).
  • Length of corticosteroid treatment [ Time Frame: at 28 months ]
    The length of corticosteroid treatment in each group at 28 months
  • Rate of B-Lymphocytes CD-19 and the link of the clinical events [ Time Frame: at 28 months ]
    The rate of B-Lymphocytes CD-19 and the link of the clinical events
  • Evolution of gammaglobulins [ Time Frame: at 28 months ]
  • Quality of life : SF36 (The Short Form (36) Health Survey) [ Time Frame: at 28 months ]
  • Functional capacities : HAQ (Health Assessment Questionnaire) [ Time Frame: at 28 months ]


Original Secondary Outcome:

  • Number of patients with ANCA (Anti-Neutrophil Cytoplasmatic Antibodies) [ Time Frame: at 34 months ]
    Number of patients with ANCA in each group
  • Number of adverse events [ Time Frame: at 34 months ]
    To assess the number of adverse events and their severity in each group
  • Mortality rate [ Time Frame: at 34 months ]
    To assess mortality rate in each group
  • Number of minor relapse [ Time Frame: at 34 months ]
    number of minor relapse in each group
  • Cumulated dose of corticosteroid treatment [ Time Frame: at 34 months ]
    Cumulated dose of corticosteroid treatment in each group at 34 months
  • Number and severity of damages [ Time Frame: at 34 months ]
    Number and severity of damages in each group
  • Evolution of ANCA and the link of the clinical events [ Time Frame: at 34 months ]
    Evolution of ANCA in each group and the link of the clinical events
  • Distribution of events by severity [ Time Frame: at 34 months ]
    Distribution of events by severity and it will be assigned to the drug and its mode of administration and/or the severity of the disease (in each group).
  • Length of corticosteroid treatment [ Time Frame: at 34 months ]
    The length of corticosteroid treatment in each group at 34 months
  • Rate of B-Lymphocytes CD-19 and the link of the clinical events [ Time Frame: at 34 months ]
    The rate of B-Lymphocytes CD-19 and the link of the clinical events


Information By: Assistance Publique - Hôpitaux de Paris

Dates:
Date Received: October 12, 2012
Date Started: November 2012
Date Completion: December 2016
Last Updated: November 18, 2016
Last Verified: November 2016