Clinical Investigation of Erlotinib as an HCV Entry Inhibitor

University Hospital, Strasbourg, France

Status and phase: Unknown; Phase 2; Phase 1

Conditions: HCV Genotype 1b; Chronic Hepatitis C Infection

Treatments: Drug: placebo; Drug: 1- Erlotinib

Study type: Interventional

Funder types: Other

Identifiers

NCT01835938

5189

Details and patient eligibility

About

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.

Enrollment: 12 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Triple Blind

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12 participants in 2 patient groups, including a placebo group

1- Erlotinib

Experimental group

Description:

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.

Treatment:

Drug: 1- Erlotinib

placebo

Placebo Comparator group

Treatment:

Drug: placebo