Evaluation of Clinical Efficacy and Immunologic Response After IL-2 Therapy in HCV-related Vasculitis Patients
Primary Purpose
Cryoglobulinemia Vasculitis
Status
Completed
Phase
Phase 1
Locations
France
Study Type
Interventional
Intervention
Proleukin
Sponsored by
About this trial
This is an interventional treatment trial for Cryoglobulinemia Vasculitis focused on measuring HCV+, cryoglobulinemia, Vasculitis, IL-2 treatment, safety and efficacy
Eligibility Criteria
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).
Sites / Locations
- Hôpital de la Pitié
Arms of the Study
Arm 1
Arm Type
Other
Arm Label
1
Arm Description
it is a single arm study
Outcomes
Primary Outcome Measures
Immunologic follow-up of Treg and of HCV cellular immune response before, during and after IL-2 therapy
Secondary Outcome Measures
Clinical tolerance: Absence of Vasculitis flare during and after IL-2 therapy
Clinical efficacy: follow-up of clinical manifestations of HCV-MC
Full Information
NCT ID
NCT00574652
First Posted
December 14, 2007
Last Updated
January 23, 2013
Sponsor
French National Agency for Research on AIDS and Viral Hepatitis
1. Study Identification
Unique Protocol Identification Number
NCT00574652
Brief Title
Evaluation of Clinical Efficacy and Immunologic Response After IL-2 Therapy in HCV-related Vasculitis Patients
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 Type
Interventional
2. Study Status
Record Verification Date
January 2008
Overall Recruitment Status
Completed
Study Start Date
March 2008 (undefined)
Primary Completion Date
March 2010 (Actual)
Study Completion Date
September 2010 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
French National Agency for Research on AIDS and Viral Hepatitis
4. Oversight
Data Monitoring Committee
Yes
5. 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.
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 :
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Cryoglobulinemia Vasculitis
Keywords
HCV+, cryoglobulinemia, Vasculitis, IL-2 treatment, safety and efficacy
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
10 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Other
Arm Description
it is a single arm study
Intervention Type
Drug
Intervention Name(s)
Proleukin
Other Intervention Name(s)
Aldesleukin, Novartis Pharma S.A.S
Intervention Description
3 millions IU/day from day 1 to 5 every 21 days will be carried out at W1, W3, W6, and W9)
Primary Outcome Measure Information:
Title
Immunologic follow-up of Treg and of HCV cellular immune response before, during and after IL-2 therapy
Time Frame
9 months
Secondary Outcome Measure Information:
Title
Clinical tolerance: Absence of Vasculitis flare during and after IL-2 therapy
Time Frame
9 months
Title
Clinical efficacy: follow-up of clinical manifestations of HCV-MC
Time Frame
9 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Patrice Cacoub, MD, PHD
Organizational Affiliation
Hôpital de la Pitié, 83 Bd de l'Hôpital 75651 Paris cedex 13
Official's Role
Principal Investigator
Facility Information:
Facility Name
Hôpital de la Pitié
City
Paris
ZIP/Postal Code
75651
Country
France
12. IPD Sharing Statement
Citations:
PubMed Identifier
22129253
Citation
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.
Results Reference
derived
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Evaluation of Clinical Efficacy and Immunologic Response After IL-2 Therapy in HCV-related Vasculitis Patients
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