To evaluate in detail the functionality of immune cells in the liver and blood in chronic HCV patients before, during and after treatment with telaprevir, pegylated-IFN-alfa and ribavirin.
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Viral infectious disorders
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Difference in immunological parameters between patients with a high and a low
viral load. (indirect to compare the patients who respond to the therapy and
patients who stay infected)
Secondary outcome
Not applicable
Background summary
Chronic hepatitis C infection (HCV) is a disease that affects worldwide about
170 million people. The current standard of care therapy of chronic HCV
patients consists of pegylated-IFN-α combined with ribavirin, and results in
sustained clearance of HCV-RNA in only about 50% of the HCV genotype 1 infected
patients. Telaprevir, a NS3A-4A inhibitor, has previously proven to offer
therapeutic options to previous non-responders to the standard of care.
Although, not all chronic HCV patients benefit from telaprevir and it is still
not known why certain patients are also non-responsive to this triple therapy.
In this study we try to understand why certain patients are also non-responsive
to telaprevir, how triple therapy modulates the responsiveness to IFN-α and
what the immunological consequences are of treatment with telaprevir, either
directly or as a result of telaprevir-induced reduction of HCV-RNA levels.
Study objective
To evaluate in detail the functionality of immune cells in the liver and blood
in chronic HCV patients before, during and after treatment with telaprevir,
pegylated-IFN-alfa and ribavirin.
Study design
In this study, 25 chronic hepatitis C patients will be treated with telaprevir,
peginterferon-alfa and ribavirin in triple therapy. During this therapy, extra
blood and fine needle aspiration biopsies (FNAB) will be taken.
Study burden and risks
For each patient, extra blood and four fine-needle aspiration biopsies (FNAB)
will be collected for the assessment of intrahepatic immune responses and
analyzed by either micro-array or flowcytometry.
Using this minimally-invasive technique of fine-needle aspiration biopsy
(FNAB), it is now possible to obtain safe and frequent liver samples to monitor
local antiviral immune responses in chronic HCV patients during antiviral
therapy. The procedure is well tolerated by patients. A large series, in which
thousands of FNABs were evaluated, describes an excellent safety profile with
little discomfort reported by the patients. Furthermore, in our clinic, we are
experienced with the collection of over hundreds of FNABs without any serious
complications to the patient. Results from laboratory tests on these FNABs have
been published in several papers. Finally, the FNAB can be performed on any
patient without anaesthesia or other preparations.
's Gravendijkwal 230
Rotterdam 3015CE
NL
's Gravendijkwal 230
Rotterdam 3015CE
NL
Listed location countries
Age
Inclusion criteria
• Patients between 18 and 70 years of age, with a chronic hepatitis C - genotype 1 infection.
• Patients are naive, non-responders or relapsers to previous treatment with peginterferon or conventional interferon plus ribavirin combination therapy.
• High viral load (>400,000 IU/ml)
• Indication for antiviral therapy of hepatitis C according to current clinical guidelines.
• Written informed consent.
Exclusion criteria
• Signs of progressive liver disease, beyond generally accepted criteria for HCV antiviral therapy
• History or other evidence of severe illness, malignancy or any other condition which would make the patient, in the opinion of the investigators, unsuitable for the study
• Co-infections with human immunodeficiency virus (HIV) or Hepatitis B virus (HBV).
• Presence of contra-indications for antiviral therapy with telaprevir, peginterferon or ribavirin.
• Interfering substance abuse, such as alcohol (indicator: 28 drinks/ week).
• Earlier treatment with a protease/polymerase inhibitor or treatment with peginterferon/ ribavirin within 6 months before start of therapy
•Any other condition which in the opinion of the investigator would make the patient unsuitable for enrollment, or could interfere with the patient participating and completing in the study.
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2011-005636-26-NL |
| CCMO | NL38193.078.12 |