Clinical Investigation of Erlotinib as an HCV Entry Inhibitor

Sponsor
University Hospital, Strasbourg, France
Study ID
NCT01835938
Phase
PHASE1/PHASE2
Status
Unknown

Conditions

  • Chronic Hepatitis C Infection
  • HCV Genotype 1b

Eligibility Criteria

Sex
ALL
Age
18 Years - 65 Years
Healthy Volunteers
Not accepted

Interventions

  • 1- Erlotinib — 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 — 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,

Study Details

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.

Key Dates

First listed
Apr 19, 2013
Start date
May 31, 2013
Status verified
Jun 2014
Primary completion
May 31, 2015
Completion
May 31, 2015

Study Design

Enrollment
12 participants (estimated)
Allocation
RANDOMIZED
Intervention model
FACTORIAL
Primary purpose
TREATMENT

Arms

  • 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.
  • Placebo Comparator: placebo

Primary Outcome Measure

Assessment of virologic response and short-term safety of Erlotinib in patients infected with HCV genotype 1b [ Time Frame: 14-day assessment study ]

Central Contacts