Effect of Teleprevir 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.

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Key information

Conditions

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

Age range

18 year–70 year

Sex eligibility

All sexes

Study type

Observational

Primary location

Reinier de Graaf Ziekenhuis, Delft, South Holland, Netherlands

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Primary outcomes

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

Time frame: 24 week follow-up

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.

Sponsors and collaborators

Lead sponsor

Foundation for Liver Research

Other

Collaborators

Janssen-Cilag B.V.

Registry information

Official study title

Effect of Telaprevir in Triple Therapy on Intrahepatic Immunological Mechanisms.

Acronym: ETIM

Important dates

Study start: 2012
Primary completion: 2014
Study completion: 2014
First posted: Jul 16, 2012
Registry last updated: Mar 11, 2015

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

Published trials that share one or more normalized conditions with this study.

Completed