Effect of Teleprevir in Triple Therapy on Intrahepatic Immunological Mechanisms

Chronic Hepatitis C Clinical Trial

— ETIM  

Official title:

Effect of Telaprevir in Triple Therapy on Intrahepatic Immunological Mechanisms.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01641094
• Other study ID #: ETIM
• Status: Completed
• Phase: N/A
• First received: July 12, 2012
• Last updated: March 10, 2015
• Start date: May 2012
• Est. completion date: December 2014

Study information

• Verified date: March 2015
• Source: Foundation for Liver Research
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)
• Study type: Observational

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: December 2014
• Est. primary completion date: June 2014
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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)

Study Design

Observational Model: Cohort, Time Perspective: Prospective

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Locations

Country	Name	City	State
Netherlands	Reinier de Graaf Ziekenhuis	Delft	Zuid-Holland
Netherlands	Erasmus Medical Center	Rotterdam

Sponsors (2)

Lead Sponsor	Collaborator
Foundation for Liver Research	Janssen-Cilag B.V.

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	By looking at T cells, NK cells and monocytes during triple therapy, as well intrahepatic as in peripheral blood, we try to better understand why some patients respond and others do not respond to therapy.	24 week follow-up	No

External Links

•   Website of the Department of Gastroenterology & Hepatology - Erasmus Medical Center
•   Website of the Erasmus Medical Center Rotterdam