A Phase Ⅱ Dose-escalating Study of PEG-IFN-SA and Ribavirin in IFN Naive Patients With Chronic Hepatitis C
A Phase Ⅱ Dose-escalating Study of PEG-IFN-SA and Ribavirin in IFN Naive Patients With Chronic Hepatitis C
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.
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.
Inclusion Criteria:

 -  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

 Exclusion Criteria:

 -  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