Dose Finding and Early Efficacy Study of Erlotinib in Treatment of Chronic Hepatitis C Virus infection_proof of Concept Study
试验速览
- 阶段
- 1 期
- 发起方
- 入组人数
- 12
- 试验地点
- 1
- 主要终点
- Assessment of virologic response and short-term safety of Erlotinib in patients infected with HCV genotype 1b
研究概览
简要总结
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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)
排除标准
- •HIV or HBV infection
- •Cirrhosis or Liver decompensation
- •Chronic liver disease non related to HCV
研究组 & 干预措施
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.
干预措施: 1- Erlotinib (Drug)
placebo
干预措施: placebo (Drug)
结局指标
主要结局
Assessment of virologic response and short-term safety of Erlotinib in patients infected with HCV genotype 1b
时间窗: 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.
次要结局
- Assessment of pharmacokinetics of Erlotinib in HCV-infected patients(14-day assessment study)