Clinical Investigation of Erlotinib as an HCV Entry Inhibitor

Sponsor

University Hospital, Strasbourg, France (Other)

Overall Status

Unknown status

CT.gov ID

NCT01835938

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Chronic Hepatitis C Infection HCV Genotype 1b	Drug: 1- Erlotinib Drug: placebo	Phase 1/Phase 2

Study Design

Study Type:

Interventional

Anticipated Enrollment :

12 participants

Allocation:

Randomized

Intervention Model:

Factorial Assignment

Masking:

Triple (Participant, Care Provider, Investigator)

Primary Purpose:

Treatment

Official Title:

Dose Finding and Early Efficacy Study of Erlotinib in Treatment of Chronic Hepatitis C Virus infection_proof of Concept Study

Study Start Date :

May 1, 2013

Anticipated Primary Completion Date :

May 1, 2015

Anticipated Study Completion Date :

May 1, 2015

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1- Erlotinib Erlotinib is a first class HCV entry inhibitor. In this study, Erlotinib will be administered in escalating doses in sequential patient cohorts for 14 days as follows: Dose level (DL) 1 = 50 mg / day, Dose level (DL) 2 = 100 mg / day, and Dose level (DL) 3 = 150 mg / day . Each Dose Level (DL) includes 4 patients (3 patients treated with Erlotinib and one patient treated with the Placebo). Dose escalation will proceed to the subsequent DL in the absence of DLT (dose-limiting toxicity) in 2 patients receiving Erlotinib.	Drug: 1- Erlotinib Erlotinib 50 mg tablet by mouth every day for 14 days, Erlotinib 100 mg tablet by mouth every day for 14 days, Erlotinib 150 mg tablet by mouth every day for 14 days,
Placebo Comparator: placebo	Drug: placebo Placebo 50 mg tablet by mouth every day for 14 days, Placebo 100 mg tablet by mouth every day for 14 days, Placebo 150 mg tablet by mouth every day for 14 days,

Arm

Intervention/Treatment

Experimental: 1- Erlotinib

Erlotinib is a first class HCV entry inhibitor. In this study, Erlotinib will be administered in escalating doses in sequential patient cohorts for 14 days as follows: Dose level (DL) 1 = 50 mg / day, Dose level (DL) 2 = 100 mg / day, and Dose level (DL) 3 = 150 mg / day . Each Dose Level (DL) includes 4 patients (3 patients treated with Erlotinib and one patient treated with the Placebo). Dose escalation will proceed to the subsequent DL in the absence of DLT (dose-limiting toxicity) in 2 patients receiving Erlotinib.

Drug: 1- Erlotinib

Erlotinib 50 mg tablet by mouth every day for 14 days, Erlotinib 100 mg tablet by mouth every day for 14 days, Erlotinib 150 mg tablet by mouth every day for 14 days,

Placebo Comparator: placebo

Drug: placebo

Placebo 50 mg tablet by mouth every day for 14 days, Placebo 100 mg tablet by mouth every day for 14 days, Placebo 150 mg tablet by mouth every day for 14 days,

Outcome Measures

Primary Outcome Measures

Assessment of virologic response and short-term safety of Erlotinib in patients infected with HCV genotype 1b [14-day assessment study]
Determination of the recommended dose on the end point of dise-limiting toxicity (DLT), establishment of the maximum-tolerated dose (MTD), and response rate defined as a reduction of at least 1 log10 HCV RNA Levels after the last dose of study drug.

Secondary Outcome Measures

Assessment of pharmacokinetics of Erlotinib in HCV-infected patients [14-day assessment study]
- Evaluate the pharmacokinetics (AUC, Cmax) of Erlotinib.

Other Outcome Measures

Assessment of Erlotinib in HCV-infected patients and evaluation of drug resistance [14-day assessment study]
Analyzing the variability of viral species during treatment and evaluate potential resistance to Erlotinib

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 65 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Service d'Hépatogastroentérologie, NHC1, place de l'hôpital	Strasbourg Cedex	Alsace	France	BP n°426

Sponsors and Collaborators

University Hospital, Strasbourg, France

Investigators

Study Director: Dr Samira Fafi-Kremer, Pharma D, PhD, Laboratoire de Virologie PTM- Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg
Study Chair: Dr Catherine Mutter, MD, Centre d'investigation Clinique -P1002Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg
Study Chair: Dr François Habersetzer, MD, PhD, Service d'Hépato-Gastro-Entérologie - Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg
Study Director: Dr. Thomas BAUMERT, MD, PhD, Service d'Hépatogastroentérologie, NHC1, place de l'hôpital - BP n°42667091 STRASBOURG CEDEX