Safety Study of Recombinant Interferon Variant(PEG-IFN-SA) to Treat HCV Disease
Safety Study of Recombinant Interferon Variant(PEG-IFN-SA) to Treat HCV Disease
The purpose of this study is to determine whether PEG-IFN-SA is safe, tolerant and effective
 in the treatment of HCV patients.
Chronic infection with the hepatitis C virus (HCV) is a significant public health problem in
 china. Progressive liver disease, as a result of chronic HCV infection, usually develops
 slowly over 20-50 years and may lead to cirrhosis, hepatocellular carcinoma, liver failure
 and eventual death. Symptoms are typically mild and non-specific but nevertheless can cause a
 decrease in quality of life. Peginterferon alfa and ribavirin combination therapy is
 currently used in the china for treatment of chronic HCV. Successful treatment is considered
 to be attainment of a sustained virological response (SVR), defined as undetectable serum HCV
 ribonucleic acid (RNA) 6 months after cessation of treatment.

 PEG-IFN-SA is a new recombinant interferon variant. Its N-terminus is modified by 20KD
 molecular weight single-methoxy polyethylene glycol (PEG). It consists of 171 amino acids
 before modification. PEG-IFN-SA is reorganization, unnatural existence and a new type of
 interferon (171Arg126Asp171IFN) after modification. The safety, tolerance and antiviral
 activity of PEG-IFN-SA was tested in adults with HCV infection.

 PEG-IFN-SA was injected subcutaneously one times per week for 12 times. Peginterferon alfa-2a
 (Pegasys) is the positive control drug. 80 patients were randomly assigned to eight groups
 (PEG-IFN-SA 1.0μg/kg, Peginterferon alfa-2a 180 μg, PEG-IFN-SA 1.5 μg/kg，PEG-IFN-SA 2 μg/kg，
 PEG-IFN-SA 3 μg/kg，PEG-IFN-SA 1.5μg/kg + ribavirin 0.45g/bid group，Intergen 15μg/48hours for
 7 times and ribavirin 0.45g/bid for 10 times).

 Clinical and biological adverse effects were recorded every week such as headache, nausea and
 vomiting. HCV RNA level was tested by COBAS Taqman HCV Test system of Roche. Blood cell
 counts were tested using an automatic cell counter such as WBC, neutrophil, PLT and HGB.
 Biochemical indicators were tested by automatic biochemical analysis instrument.
Inclusion Criteria:

 1. enrolled voluntarily, can understand and sign informed consent;

 2. More than 18 years and less than 65 years;

 3. body mass index (BMI) is at 18 - 26;

 4. anti-HCV antibodies and / or HCV RNA positive, and / or other evidence of chronic
 hepatitis C;

 5. HCV RNA level ≥ 2000IU/ml (or equal to this viral load);

 6. Women's urine pregnancy test was negative, and the subjects (male subjects) is willing
 to have no pregnancy plans at next 18 months. (7) ALT is within 6 times of the upper
 limit of normal

 Exclusion Criteria:

 1. pregnant women, lactating women or plan to pregnant the next 18 months.

 2. mental disorder, including history of mental illness (especially the history of
 depression or depressive tendencies, epilepsy, etc.);

 3. The patient who received interferon therapy within the past six months or had no
 response at previous interferon therapy.

 4. The patient who used a strong immune regulator over two weeks with three months before
 screening, such as adrenocorticotropic hormone, thymosin of α1, thymus 5 peptide.

 5. The patient who used hepatotoxic drugs with 6 months before screening, such as
 dapsone, erythromycin, fluconazole, ketoconazole, rifampin.

 6. co-infection with other viruses (HAV, HBV, HEV, the HIV, EBV, CMV) .

 7. patients with a history of hepatocellular carcinoma (HCC), or may had hepatocellular
 carcinoma evidence, such as imaging of suspicious nodules, or AFP abnormal (AFP>
 200ng/mL). FibroScan value greater than or equal to F3 at Screening

 8. other causes of liver disease: a chronic alcoholic hepatitis, drug-induced hepatitis,
 autoimmune liver disease, nonalcoholic steatohepatitis.

 9. autoimmune diseases, including psoriasis, systemic lupus erythematosus,
 thrombocytopenic purpura, and so on.

 10. heart and vascular system diseases, a history of myocarditis, hypertension, coronary
 heart disease, pathological arrhythmia, stroke.

 11. endocrine system diseases, including thyroid disease, diabetes, etc.

 12. pulmonary diseases, including invasive pulmonary disease, pneumonia, shortness of
 breath.

 13. Eye diseases, including retinopathy, retinopathy.

 14. chronic infectious disease history (history of tuberculosis).

 15. chronic kidney disease, serum creatinine level> 1.5 times upper limit of normal at
 screening, renal insufficiency, renal anemia history.

 16. anemia (including thalassemia, sickle hemoglobin, anemia), and hemophilia.

 17. peptic ulcer not controlled, colitis, pancreatitis and others.

 18. malignancies.

 19. peripheral blood checking: white blood cell count <3 × 109 / L; neutrophil count <1.5
 x 109 / L; platelet count <90 × 109 / L; hemoglobin was less than the normal reference
 limit.

 20. serum total bilirubin> 2 times normal maximum reference value (ULN); serum albumin
 <35g / L; a history of decompensated cirrhosis evidence.

 21. evidence of drug addiction (including excessive alcohol intake, average alcohol
 consumption: men> 40g / day; women> 20g / day, equivalent to 50 degrees white wine
 100ml / day and 50ml / day) within one year before screening.

 22. a serious history of drug and food allergy, especially towards the test drug
 (interferon, ribavirin).

 23. plans to accept an organ transplant or have organ transplant.

 24. participated other clinical trials before 3 months at screening

 25. The researchers judged the patients have other factors which may influence the
 experiment.

 ribavirin exclusion criteria:

 1. women Hgb <12g/dl or men Hgb <13gdl at screening.

 2. anemia patients (eg, thalassemia, spherocytosis hyperlipidemia, gastrointestinal
 bleeding history) or suspected anemia patients.

 3. patients have a history of coronary artery disease or patients with cerebrovascular
 disease should not join this study, hemoglobin decline up to 4g/dl (it may be observed
 in the ribavirin treatment).