Evaluation of Clinical Efficacy and Immunologic Response After IL-2 Therapy in HCV-related Vasculitis Patients

Study Overview
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Brief Summary
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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
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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

Official Title
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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.

Conditions
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Cryoglobulinemia Vasculitis

Intervention / Treatment
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* Drug: Proleukin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: HCV+ patients with cryoglobulinemia Vasculitis resistant to conventional therapy (i.e. antiviral therapy and/or immunosuppressors). Vasculitis is defined according to international criteria: chronic HCV infection (HCV RNA+), serum cryoglobulin superior or equal to 0.05g/l in at least two determinations, presence of the triad purpura-arthralgia-asthenia and/or biopsy proven Vasculitis (kidney, nerve or skin).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: 1<br>it is a single arm study | Drug: Proleukin<br>* 3 millions IU/day from day 1 to 5 every 21 days will be carried out at W1, W3, W6, and W9)<br>* Other names: Novartis Pharma S.A.S;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immunologic follow-up of Treg and of HCV cellular immune response before, during and after IL-2 therapy |  | 9 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical tolerance: Absence of Vasculitis flare during and after IL-2 therapy |  | 9 months | 
| Clinical efficacy: follow-up of clinical manifestations of HCV-MC |  | 9 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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HCV+, cryoglobulinemia, Vasculitis, IL-2 treatment, safety and efficacy