Clinical Investigation of Erlotinib as an HCV Entry Inhibitor

Chronic Hepatitis C Infection Clinical Trial

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT01835938
• Other study ID #: 5189
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• First received: April 9, 2013
• Last updated: June 14, 2014
• Start date: May 2013
• Est. completion date: May 2015

Study information

• Verified date: June 2014
• Source: University Hospital, Strasbourg, France
• Contact: Pr. Michel Doffoel, MD, PhD
• Phone: 03 69 55 04 82
• Email: michel.doffoel[@]chru-strasbourg.fr
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santé
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 12
• Est. completion date: May 2015
• Est. primary completion date: May 2015
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Factorial Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C Infection
• HCV Genotype 1b
• Hepatitis
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic
• Infection

Intervention

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
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,

Locations

Country	Name	City	State
France	Service d'Hépatogastroentérologie, NHC1, place de l'hôpital	Strasbourg Cedex	Alsace

Sponsors (1)

Lead Sponsor	Collaborator
University Hospital, Strasbourg, France

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Assessment of Erlotinib in HCV-infected patients and evaluation of drug resistance	Analyzing the variability of viral species during treatment and evaluate potential resistance to Erlotinib	14-day assessment study	Yes
Primary	Assessment of virologic response and short-term safety of Erlotinib in patients infected with HCV genotype 1b	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.	14-day assessment study	Yes
Secondary	Assessment of pharmacokinetics of Erlotinib in HCV-infected patients	- Evaluate the pharmacokinetics (AUC, Cmax) of Erlotinib.	14-day assessment study	Yes