Evaluation of Clinical Efficacy and Immunologic Response After IL-2 Therapy in HCV-related Vasculitis Patients
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|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.|
- Immunologic follow-up of Treg and of HCV cellular immune response before, during and after IL-2 therapy [ Time Frame: 9 months ] [ Designated as safety issue: Yes ]
- Clinical tolerance: Absence of Vasculitis flare during and after IL-2 therapy [ Time Frame: 9 months ] [ Designated as safety issue: No ]
- Clinical efficacy: follow-up of clinical manifestations of HCV-MC [ Time Frame: 9 months ] [ Designated as safety issue: No ]
|Study Start Date:||March 2008|
|Study Completion Date:||September 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
it is a single arm study
3 millions IU/day from day 1 to 5 every 21 days will be carried out at W1, W3, W6, and W9)
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 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00574652
|Hôpital de la Pitié|
|Paris, France, 75651|
|Principal Investigator:||Patrice Cacoub, MD, PHD||Hôpital de la Pitié, 83 Bd de l'Hôpital 75651 Paris cedex 13|