Clinical Investigation of Erlotinib as an HCV Entry Inhibitor

NCT ID: NCT01835938

Last Updated: 2014-06-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 12 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2013-05-31
• Study Completion Date: 2015-05-31

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.

Conditions

Chronic Hepatitis C Infection; HCV Genotype 1b

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: EXPERIMENTAL

1- Erlotinib

Intervention Type: DRUG

• 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

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

• 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,

Interventions

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,

Intervention Type: 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,

Intervention Type: DRUG

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

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Strasbourg, France

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dr Samira Fafi-Kremer, Pharma D, PhD

Role: STUDY_DIRECTOR

Laboratoire de Virologie PTM- Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg

Dr Catherine Mutter, MD

Role: STUDY_CHAIR

Centre d'investigation Clinique -P1002Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg

Dr François Habersetzer, MD, PhD

Role: STUDY_CHAIR

Service d'Hépato-Gastro-Entérologie - Nouvel Hôpital CivilHôpitaux Universitaires de Strasbourg

Dr. Thomas BAUMERT, MD, PhD

Role: STUDY_DIRECTOR

Service d'Hépatogastroentérologie, NHC1, place de l'hôpital - BP n°42667091 STRASBOURG CEDEX

Locations

Service d'Hépatogastroentérologie, NHC1, place de l'hôpital

Strasbourg, Alsace, France

Countries

France

Central Contacts

Pr. Michel Doffoel, MD, PhD

Role: CONTACT

michel.doffoel@chru-strasbourg.fr

03 69 55 04 82

Pr. Thomas BAUMERT, MD, PhD

Role: CONTACT

thomas.baumert@unistra.fr

03 68 85 37

Other Identifiers

5189

Identifier Type: -

Identifier Source: org_study_id