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

NCT ID: NCT00574652

Last Updated: 2013-01-24

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-03-31
• Study Completion Date: 2010-09-30

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 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

Conditions

Cryoglobulinemia Vasculitis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

it is a single arm study

Group Type: OTHER

Proleukin

Intervention Type: DRUG

3 millions IU/day from day 1 to 5 every 21 days will be carried out at W1, W3, W6, and W9)

Interventions

Proleukin

3 millions IU/day from day 1 to 5 every 21 days will be carried out at W1, W3, W6, and W9)

Intervention Type: DRUG

Other Intervention Names

Aldesleukin; Novartis Pharma S.A.S

Eligibility Criteria

Inclusion Criteria

1. HCV+ patients with cryoglobulinemia Vasculitis

2. resistant to conventional therapy (i.e. antiviral therapy and/or immunosuppressors).

3. Vasculitis is defined according to international criteria: chronic HCV infection (HCV RNA+),

4. serum cryoglobulin superior or equal to 0.05g/l in at least two determinations,

5. presence of the triad purpura-arthralgia-asthenia and/or biopsy proven Vasculitis (kidney, nerve or skin).

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

French National Agency for Research on AIDS and Viral Hepatitis

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Patrice Cacoub, MD, PHD

Role: PRINCIPAL_INVESTIGATOR

Hôpital de la Pitié, 83 Bd de l'Hôpital 75651 Paris cedex 13

Locations

Hôpital de la Pitié

Paris, , France

Countries

France

References

Saadoun D, Rosenzwajg M, Joly F, Six A, Carrat F, Thibault V, Sene D, Cacoub P, Klatzmann D. Regulatory T-cell responses to low-dose interleukin-2 in HCV-induced vasculitis. N Engl J Med. 2011 Dec 1;365(22):2067-77. doi: 10.1056/NEJMoa1105143.

Reference Type: DERIVED

PMID: 22129253 (View on PubMed)

Other Identifiers

ANRS HC 21 Vascu-IL2

Identifier Type: -

Identifier Source: secondary_id

2006-004039-31

Identifier Type: -

Identifier Source: org_study_id