Clinical Trial: Evaluation of Clinical Efficacy and Immunologic Response After IL-2 Therapy in HCV-related Vasculitis Patients
Study Status: Completed
Recruit Status: Completed
Study Type: Interventional
Official Title: ANRS HC 21 VASCU IL-2, Evaluation of the Cellular Immune Response, Clinical Efficacy and Tolerance After IL-2 Therapy in HCV-related Vasculitis Patients, Resistant to Conventional Therapy.
Brief 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 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 (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 :
- Clinical tolerance: Absence of Vasculitis flare during and after IL-2 therapy.
- Immunologic follow-up of Treg and of HCV cellular immune response before, during and after IL-2 therapy.
- Clinical
Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
Current Primary Outcome: Immunologic follow-up of Treg and of HCV cellular immune response before, during and after IL-2 therapy [ Time Frame: 9 months ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Clinical tolerance: Absence of Vasculitis flare during and after IL-2 therapy [ Time Frame: 9 months ]
- Clinical efficacy: follow-up of clinical manifestations of HCV-MC [ Time Frame: 9 months ]
Original Secondary Outcome: Same as current
Information By: French National Institute for Health and Medical Research-French National Agency for Research on AID
Dates:
Date Received: December 14, 2007
Date Started: March 2008
Date Completion:
Last Updated: January 23, 2013
Last Verified: January 2008
