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

• ClinicalTrials.gov Identifier: NCT00574652
• Recruitment Status: Completed
• First Posted: December 17, 2007
• Last Update Posted: January 24, 2013
• Sponsor: French National Agency for Research on AIDS and Viral Hepatitis
• Information provided by (Responsible Party): ANRS, Emerging Infectious Diseases ( French National Agency for Research on AIDS and Viral Hepatitis )

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Cryoglobulinemia Vasculitis	Drug: Proleukin	Phase 1; Phase 2

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

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 10 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (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.
• Study Start Date: March 2008
• Actual Primary Completion Date: March 2010
• Actual Study Completion Date: September 2010

Arms and Interventions

Arm	Intervention/treatment
1; it is a single arm study	Drug: Proleukin; 3 millions IU/day from day 1 to 5 every 21 days will be carried out at W1, W3, W6, and W9); Other Names: Aldesleukin; Novartis Pharma S.A.S

Outcome Measures

Primary Outcome Measures :

1. Immunologic follow-up of Treg and of HCV cellular immune response before, during and after IL-2 therapy [ Time Frame: 9 months ]

Secondary Outcome Measures :

1. Clinical tolerance: Absence of Vasculitis flare during and after IL-2 therapy [ Time Frame: 9 months ]
2. Clinical efficacy: follow-up of clinical manifestations of HCV-MC [ Time Frame: 9 months ]

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 75 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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).

Contacts and Locations

Locations

France

Hôpital de la Pitié

Paris, France, 75651

Sponsors and Collaborators

French National Agency for Research on AIDS and Viral Hepatitis

Investigators

• Principal Investigator: Patrice Cacoub, MD, PHD; Hôpital de la Pitié, 83 Bd de l'Hôpital 75651 Paris cedex 13

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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. Erratum In: N Engl J Med. 2014 Feb 20;370(8):786.

• Responsible Party: French National Agency for Research on AIDS and Viral Hepatitis
• ClinicalTrials.gov Identifier: NCT00574652
• Other Study ID Numbers: 2006-004039-31; ANRS HC 21 Vascu-IL2
• First Posted: December 17, 2007
• Last Update Posted: January 24, 2013
• Last Verified: January 2008

Keywords provided by ANRS, Emerging Infectious Diseases ( French National Agency for Research on AIDS and Viral Hepatitis ):

HCV+; cryoglobulinemia; Vasculitis; IL-2 treatment; safety and efficacy

Additional relevant MeSH terms:

Vasculitis; Cryoglobulinemia; Vascular Diseases; Cardiovascular Diseases; Hemostatic Disorders; Paraproteinemias; Blood Protein Disorders; Hematologic Diseases; Hemorrhagic Disorders; Skin Diseases, Vascular; Skin Diseases; Immunoproliferative Disorders; Immune System Diseases; Aldesleukin; Antineoplastic Agents; Anti-HIV Agents; Anti-Retroviral Agents; Antiviral Agents; Anti-Infective Agents