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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
ClinicalTrials.gov Identifier:
NCT00574652
First received: December 14, 2007
Last updated: January 23, 2013
Last verified: January 2008
  Purpose

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 Intervention Phase
Cryoglobulinemia Vasculitis
Drug: Proleukin
Phase 1
Phase 2

Study Type: Interventional
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.

Resource links provided by NLM:


Further study details as provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Enrollment: 10
Study Start Date: March 2008
Study Completion Date: September 2010
Primary Completion Date: March 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00574652

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

No publications provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS) ( French National Agency for Research on AIDS and Viral Hepatitis )
ClinicalTrials.gov Identifier: NCT00574652     History of Changes
Other Study ID Numbers: 2006-004039-31, ANRS HC 21 Vascu-IL2
Study First Received: December 14, 2007
Last Updated: January 23, 2013
Health Authority: France: Afssaps - Agence française de sécurité sanitaire des produits de santé (Saint-Denis)

Keywords provided by French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS):
HCV+
cryoglobulinemia
Vasculitis
IL-2 treatment
safety and efficacy

Additional relevant MeSH terms:
Cryoglobulinemia
Vasculitis
Hemostatic Disorders
Vascular Diseases
Cardiovascular Diseases
Paraproteinemias
Blood Protein Disorders
Hematologic Diseases
Hemorrhagic Disorders
Immunoproliferative Disorders
Immune System Diseases
Aldesleukin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents

ClinicalTrials.gov processed this record on April 17, 2014