Effect of Teleprevir in Triple Therapy on Intrahepatic Immunological Mechanisms

NCT01641094 | Completed DMC

• 1 other identifier: ETIM
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 2

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.

Conditions

Chronic Hepatitis C

Keywords

Hepatitis C; Liver; Immunology; Genotype 1; Treatment; Chronic; RNA Virus Infections; Ribavirin; Peginterferon alfa-2a; Protease Inhibitors; Telaprevir

Outcome Measures

Primary Outcomes (1)

• 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

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with chronic hepatitis C, genotype 1

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Foundation for Liver Research: lead
• Janssen-Cilag B.V.: collaborator

Study Sites (2)

Reinier de Graaf Ziekenhuis

Delft, South Holland, Netherlands

Location

Erasmus Medical Center

Rotterdam, 3015 CE, Netherlands

Location

Related Links

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

Biospecimen

Retention: SAMPLES WITH DNA

Whole Blood

MeSH Terms

Conditions

Hepatitis C, Chronic; Hepatitis C; Bronchiolitis Obliterans Syndrome; RNA Virus Infections

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Hepatitis, Viral, Human; Virus Diseases; Flaviviridae Infections; Hepatitis, Chronic; Hepatitis; Liver Diseases; Digestive System Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Organizing Pneumonia; Bronchiolitis Obliterans; Bronchiolitis; Bronchitis; Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Graft vs Host Disease; Immune System Diseases

Study Officials

• A. Boonstra, PhD

  Erasmus Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 12, 2012
• First Posted: July 16, 2012
• Study Start: May 1, 2012
• Primary Completion: June 1, 2014
• Study Completion: December 1, 2014
• Last Updated: March 11, 2015

Record last verified: 2015-03

Locations

NL (2)