Phase Ⅱ, Multi-center, Randomized, Open-label, Parallel-group, Active Controlled Study for the Efficacy and Safety of Pegylated Recombinant Consensus Interferon Variant Solution for Injection in the Treatment of Chronic Hepatitis C
试验速览
- 阶段
- 2 期
- 状态
- 已完成
- 发起方
- 入组人数
- 212
- 试验地点
- 52
- 主要终点
- cEVR (complete early virologic response)
研究概览
简要总结
This dose-escalating study is to evaluate the efficacy and the safety of different doses of a new bio-product Pegylated Recombinant Consensus Interferon Variant Solution for Injection (PEG-IFN-SA) and Ribavirin（RBV） in the treatment of Chronic hepatitis C who have not been previously treated with Interferon(IFN) by exploring the dose-effect relationship, while identity the optimal dose for phase Ⅲ study. In addition, population pharmacokinetic method is adopted to assess the pharmacokinetic behavior, individuals / intra-individual variability, and the possible factors for further study.
详细描述
Total 200 subjects will be randomized and enrolled into four groups proportionally receiving experimental drug of high dose, middle dose, low dose and positive-control drug. Treatment duration will be 24 or 48 weeks corresponding to different HCV genotype, genotype 2,3 and non-genotype2,3.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
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
- •Age 18- 65 years
- •Body Mass Index (BMI) 18-30
- •Chronic hepatitis C , diagnosed according to Chinese guideline of Hepatitis C (year 2004)
- •Detectable serum HCV-RNA by quantitative polymerase chain reaction assay and positive anti-HCV antibody
- •Female subjects of childbearing age with no history of menopause and negative pregnancy test, both female and male( including their partners ) subjects were required to conduct adequate contraception since screening until the 6 months after treatment
- •Volunteered to participate in this study, understood and signed an informed consent
排除标准
- •Previous IFN treated patients
- •Co-infection with HAV, HBV, HEV, EBV, CMV and HIV
- •Evidences of hepatic decompensation, including but not limited to serum total bilirubin> 2 times the upper limit of normal (ULN); serum albumin <35g/L; prothrombin activity (PTA) <60%; ascites, upper gastrointestinal bleeding and hepatic encephalopathy; Child-Pugh score B/C grade
- •Hepatotoxic drugs was used for a long time within past 6 months
- •Diagnosed with primary hepatocellular carcinoma or supported by evidences including but not limited to AFP> l00ng/ml, suspicious liver nodules by imaging examinations
- •Liver diseases from causes other than HCV infection, including alcoholic liver disease, non-alcoholic steatohepatitis, drug-induced hepatitis, autoimmune hepatitis (antinuclear antibody titer higher than 1:100), hepatolenticular degeneration (Wilson's disease) and hemochromatosis, etc.
- •White blood cell count <3×109/L; Neutrophil count<1.5×109/L; platelet count<90×109/L; hemoglobin below the lower limit of normal
- •Serum creatinine not within the normal range
- •Serum creatine kinase> 3 ULN
- •Positive thyroid antibodies (A-TPO, A-TG)
- •Therapy with potent immunomodulatory agents such as adrenocorticotropic hormone, thymosin α1 etc. within past 6 months or an anticipated usage during the period of study
- •Allergies or severe allergies, especially allergic to study drugs or any ingredients of the study drugs
- •Severe autoimmune diseases; psychiatric and nervous system disorders, including history of Psychiatric illness or with family history (especially depression, depressive tendencies, epilepsy and hysteria, etc.); Serious blood disorders (all kinds of anemia, hemophilia, etc.); Severe kidney disease (chronic kidney disease, renal insufficiency, etc.); poorly controlled digestive diseases; endocrine disorders such as thyroid disease and diabetes; severe respiratory disease (pneumonia, chronic obstructive pulmonary disease, interstitial lung disease, etc.); cardiovascular diseases (hypertension, uncontrolled coronary atherosclerotic heart disease, heart failure, etc.); retinal disease; malignancies; or unsuitable for study considered by clinician
- •Function organs transplant
- •Evidence of alcohol or drug abuse (average alcohol consumption male> 40g / day, female> 20g / day)
- •Pregnant or lactating women
- •Usage of prohibition drugs in this study
- •Participated in other clinical trials 3 months prior to the screening
- •Unwilling to sign the informed consent and adhere to treatment requirements
- •Other conditions not suitable for study judged by investigators
研究组 & 干预措施
A (PEG-IFN-SA /RBV low dose)
PEG-IFN-SA 0.75μg/kg/week and RBV 1000mg-1200mg/d bid depending on body weight(BW),（BW<75kg，1000mg/d；BW≥75kg，1200mg/d）
干预措施: PEG-IFN-SA /RBV low dose (Drug)
B (PEG-IFN-SA /RBV middle dose)
PEG-IFN-SA 1.5μg/kg/week and RBV 1000mg-1200mg/d bid depending on body weight(BW),（BW<75kg，1000mg/d；BW≥75kg，1200mg/d）
干预措施: PEG-IFN-SA /RBV middle dose (Drug)
C (PEG-IFN-SA /RBV high dose)
PEG-IFN-SA 2.0μg/kg/week and RBV 1000mg-1200mg/d bid depending on body weight(BW),（BW<75kg，1000mg/d；BW≥75kg，1200mg/d）
干预措施: PEG-IFN-SA /RBV high dose (Drug)
D (Pegasys /RBV)
Pegasys 180μg/week and RBV 1000mg-1200mg/d bid depending on body weight(BW),（BW<75kg，1000mg/d；BW≥75kg，1200mg/d）
干预措施: Pegasys /RBV (Drug)
结局指标
主要结局
cEVR (complete early virologic response)
时间窗: weeks 12 of study therapy
defined as the proportion of patients who had undetectable plasma HCV RNA at weeks 12
次要结局
- Proportion of patients who had undetectable plasma HCV RNA(weeks 4, 24, 48 of study therapy and 24 weeks after the end of treatment)
- eRVR ( extended rapid virologic response)(weeks 4 and 12 of study therapy)
- Breakthrough(weeks 24, 48 of study therapy)
- Relapse(12 and 24 weeks after the end of treatment)
- HCV RNA load reduction(weeks 4, 12, 24, 48 of study therapy and 24 weeks after the end of treatment)
研究者
Cheng jun
vice president
Beijing Kawin Technology Share-Holding Co., Ltd.