Evaluation of Clinical Efficacy and Immunologic Response After IL-2 Therapy in HCV-related Vasculitis Patients
Condition: Cryoglobulinemia Vasculitis
MeSH terms: Vasculitis; Cryoglobulinemia
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      A systemic Vasculitis is found in 5 to 10% of HCV infected patients with mixed
      cryoglobulinemia (MC). It mainly involves the skin, peripheral nerve and the kidney and may
      be life threatening. Twenty to 30% of HCV-MC Vasculitis patients are resistant to
      conventional therapy (i.e. antiviral therapy and/or immunosuppressors) and still have an
      active disease. Thus, new therapeutic approaches are necessary in such patients. We recently
      described a regulatory T cell (Treg) deficiency in HCV-related Vasculitis patients.
      Immunomodulatory effects of interleukin-2 (IL-2) are well established, notably the
      preferential expansion of Treg able to suppress inflammatory responses mediated by CD4+ and
      CD8+ T cells.
    

Detailed description: 
      A systemic Vasculitis is found in 5 to 10% of HCV infected patients with mixed
      cryoglobulinemia (MC). It mainly involves the skin, peripheral nerve and the kidney and may
      be life threatening (15% of death). Twenty to 30% of HCV-MC Vasculitis patients are resistant
      to conventional therapy (i.e. antiviral therapy and/or immunosuppressors) and still have an
      active disease. An antiviral therapy with Peg-interféron is generally prescribed to control
      Vasculitis lesions and to slow down the hepatic fibrosis progression. Thus, new therapeutic
      approaches are necessary in such patients. We recently described a CD4+ CD25+ regulatory T
      cell (Treg) deficiency in HCV-related Vasculitis patients. Immunomodulatory effects of
      interleukin-2 (IL-2) are well established, notably the preferential expansion of Treg able to
      suppress inflammatory responses mediated by CD4+ and CD8+ T cells.

      Objective : To evaluate the cellular immune response after IL-2 therapy in HCV-MC Vasculitis
      patients, resistant to conventional therapy.

      Methods : This is an open prospective phase I/II trial. Four cycle of subcutaneous IL-2
      therapy (3 millions IU/day from day 1 to 5 every 21 days will be carried out at W1, W3, W6,
      and W9). The first cure will be carried out with half-dose of IL-2 (1.5 millions IU/day) in
      the hospital. If the tolerance is satisfactory, the later cures will be done ambulatory. All
      patients will be followed after IL-2 therapy (S11 to S37).

      End points :

        1. Clinical tolerance: Absence of Vasculitis flare during and after IL-2 therapy.

        2. Immunologic follow-up of Treg and of HCV cellular immune response before, during and
           after IL-2 therapy.

        3. Clinical efficacy: follow-up of clinical manifestations of HCV-MC Vasculitis during and
           after IL-2 therapy.

      Schedule : Duration of patients' inclusion period is estimated 18 months. Duration of therapy
      and follow-up is estimated 9 months. Analysis of data will last 7 months. Overall duration:
      34 months
    

Intervention name(s): Proleukin
Intervention type(s): Drug
Intervention description(s): 3 millions IU/day from day 1 to 5 every 21 days will be carried out at W1, W3, W6, and W9)
Other intervention name(s): Aldesleukin; Novartis Pharma S.A.S
Intervention MeSH terms: Aldesleukin
Allocation: Non-Randomized
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: HCV+; cryoglobulinemia; Vasculitis; IL-2 treatment; safety and efficacy