Effect of Teleprevir in Triple Therapy on Intrahepatic Immunological Mechanisms (ETIM)

Effect of Telaprevir in Triple Therapy on Intrahepatic Immunological Mechanisms.

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.

Study Overview

• Status: Completed
• Conditions: Chronic Hepatitis C

• Study Type: Observational
• Enrollment (Actual): 20

Contacts and Locations

Study Locations

• Netherlands
  • Rotterdam, Netherlands, 3015 CE
    • Erasmus Medical Center
  • Zuid-Holland
    • Delft, Zuid-Holland, Netherlands
      • Reinier de Graaf Ziekenhuis

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with chronic hepatitis C, genotype 1

Description

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 Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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

Collaborators and Investigators

• Sponsor: Foundation for Liver Research
• Collaborators: Janssen-Cilag B.V.
• Investigators: Principal Investigator: A. Boonstra, PhD, Erasmus Medical Center

Publications and helpful links

Helpful Links

• website of the Erasmus Medical Center Rotterdam

Study record dates

Study Major Dates

• Study Start: May 1, 2012
• Primary Completion (Actual): June 1, 2014
• Study Completion (Actual): December 1, 2014

Study Registration Dates

• First Submitted: July 12, 2012
• First Submitted That Met QC Criteria: July 12, 2012
• First Posted (Estimate): July 16, 2012

Study Record Updates

• Last Update Posted (Estimate): March 11, 2015
• Last Update Submitted That Met QC Criteria: March 10, 2015
• Last Verified: March 1, 2015

More Information

Terms related to this study

• Keywords: Treatment; Immunology; Hepatitis C; Protease Inhibitors; Ribavirin; Chronic; Genotype 1; Liver; RNA Virus Infections; Peginterferon alfa-2a; Telaprevir
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepatitis, Chronic; Hepatitis; Hepatitis C; Hepatitis C, Chronic
• Other Study ID Numbers: ETIM