Clinical trial NCT01835938: Clinical Investigation of Erlotinib as an HCV Entry Inhibitor
Official title: Dose Finding and Early Efficacy Study of Erlotinib in Treatment of Chronic Hepatitis C Virus infection_proof of Concept Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE1
PHASE2
Conditions: Chronic Hepatitis C Infection
HCV Genotype 1b
Keywords: Hepatitis C Virus infection
entry inhibitor
kinase inhibitor
Lead sponsor: University Hospital, Strasbourg, France
Sponsor class: OTHER
First posted: 2013-04-19
Enrollment: 12
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: Chronic Hepatitis C Virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma world-wide. Current combination therapy of pegylated interferon-alfa, ribavirin and protease inhibitors is limited by resistance and substantial side effects.

The investigators identified epidermal growth factor receptor (EGFR) as host factor for HCV infection. Inhibition of kinase function of EGFR by approved inhibitor Erlotinib (TarcevaTM) broadly inhibits HCV infection of all major genotypes including viral escape variants resistant to host immune responses.

Completed preclinical proof-of-concept studies in HCV cell culture and animal model systems demonstrate that inhibition of EGFR function by Erlotinib constitutes a novel antiviral approach for prevention and treatment of HCV infection (European patent application EP 08 305 604.4, Filing date: September 26, 2008; Inserm, Paris, France and Lupberger et al. Nature Medicine 2011).

Since Erlotinib (TarcevaTM) is an established approved drug for cancer treatment and has a well characterized safety profile in humans, the aim of the study is to investigate the safety, efficacy and pharmacokinetics of Erlotinib, a first-in-class entry inhibitor, for treatment of HCV infection in a randomized placebo-controlled double blind clinical trial in patients chronically infected with HCV. Following completion, this trial will set the stage for a further investigation of entry inhibitors as antivirals in combination with standard of care or direct antivirals such as HCV protease inhibitors. Thus, this randomized clinical trial will be an important step in the development of novel urgently needed antiviral therapies overcoming resistance.


Eligibility criteria: Inclusion Criteria:

* Chronic genotype 1b hepatitis C infection with detectable HCV RNA (\> 1x104 UI/mL)
* Naïve, relapser or non-responder to interferon with or without ribavirin
* Weight \> 45kg, BMI between 18 and 25 Kg/m2 who had a liver biopsy or liver FibroScan eliminating the presence of cirrhosis in the year before enrollment,
* Non-smoker or occasional smoker ( ie \< 3 cig/day)

Exclusion Criteria:

* HIV or HBV infection
* Cirrhosis or Liver decompensation
* Chronic liver disease non related to HCV

Primary outcomes:
measure: Assessment of virologic response and short-term safety of Erlotinib in patients infected with HCV genotype 1b
timeFrame: 14-day assessment study
Secondary outcomes:
measure: Assessment of pharmacokinetics of Erlotinib in HCV-infected patients
timeFrame: 14-day assessment study
Other outcomes:
measure: Assessment of Erlotinib in HCV-infected patients and evaluation of drug resistance
timeFrame: 14-day assessment study
Locations:
city: Strasbourg Cedex
country: France
facility: Service d'Hépatogastroentérologie, NHC1, place de l'hôpital
state: Alsace
Study officials:
affiliation: Laboratoire de Virologie PTM- Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg
name: Dr Samira Fafi-Kremer, Pharma D, PhD
role: STUDY_DIRECTOR
affiliation: Centre d'investigation Clinique -P1002Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg
name: Dr Catherine Mutter, MD
role: STUDY_CHAIR
affiliation: Service d'Hépato-Gastro-Entérologie - Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg
name: Dr François Habersetzer, MD, PhD
role: STUDY_CHAIR
affiliation: Service d'Hépatogastroentérologie, NHC1, place de l'hôpital - BP n°42667091 STRASBOURG CEDEX
name: Dr. Thomas BAUMERT, MD, PhD
role: STUDY_DIRECTOR
References: