Clinical trial NCT01641094: Effect of Teleprevir in Triple Therapy on Intrahepatic Immunological Mechanisms
Official title: Effect of Telaprevir in Triple Therapy on Intrahepatic Immunological Mechanisms.
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Chronic Hepatitis C
Keywords: Hepatitis C
Liver
Immunology
Genotype 1
Treatment
Chronic
RNA Virus Infections
Ribavirin
Peginterferon alfa-2a
Protease Inhibitors
Telaprevir
Lead sponsor: Foundation for Liver Research
Sponsor class: OTHER
Collaborators: name: Janssen-Cilag B.V.
First posted: 2012-07-16
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Patients with chronic hepatitis C, genotype 1

Brief summary: Chronic hepatitis C infection (HCV) is a disease that affects worldwide about 170 million people. The previous 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.


Eligibility criteria: 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

Exclusion Criteria:

* Decompensated cirrhosis (Child-Pugh Grade B or C)
* Hepatic imaging (ultrasound, CT or MRI) with the evidence of hepatocellular carcinoma.
* Females who are pregnant or breast-feeding
* 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:
* Telaprevir is contraindicated when combined with drugs that are highly dependent on CYP3A for clearance and for which elevated plasma concentrations are associated with serious and/or life-threatening events. Telaprevir in contraindicated when combined with drugs that strongly induce CYP3A and thus may lead to lower exposure and loss of efficacy of Telaprevir. The contraindicated medications include the following:
* Alfuzosin
* Rifampicin
* Dihydroergotamine, ergonovine, ergotamine, methylergonovine
* Cisapride
* St John's wort
* Atorvastatin, lovastatin, simvastatin
* Pimozide
* Sildenafil or tadalafil
* Triazolam
* Presence of contra-indications for antiviral therapy with peginterferon or ribavirin
* Severe psychiatric disorder, such as major psychoses, suicidal ideation, suicidal attempt and/or manifest depression.
* Visual symptoms related to retinal abnormalities
* Pregnancy, breast-feeding or inadequate contraception
* Thalassemia, spherocytosis
* Interfering substance abuse, such as high alcohol intake (indicator: 28 drinks/ week)

Primary outcomes:
measure: Determine functionality of immune cells in the liver and blood in chronic HCV patients before, during and after treatment with telaprevir, pegylated-IFN-a and ribavirin
timeFrame: 24 week follow-up
Secondary outcomes:
Other outcomes:
Locations:
city: Delft
country: Netherlands
facility: Reinier de Graaf Ziekenhuis
state: Zuid-Holland
city: Rotterdam
country: Netherlands
facility: Erasmus Medical Center
Study officials:
affiliation: Erasmus Medical Center
name: A. Boonstra, PhD
role: PRINCIPAL_INVESTIGATOR
References: