Efficacy and Safety Study of PEG-IFN-SA and Ribavirin to Treat Chronic Hepatitis C

Study Overview
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Brief Summary
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This study is to confirm the potential effects and assess the safety 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.

Detailed Description
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Total 720 subjects are divided into two groups and treated separately according to the HCV genotype（genotype 2,3 and non-genotype 2,3). With 2:1 ratio between experimental group and positive-control group (Peginterferon alfa-2a (Pegasys) plus RBV), 216 subjects for genotype 2,3 and 504 subjects for non-genotype2,3 will be enrolled. Accordingly, PEG-IFN-SA once weekly and RBV twice a day (bid) are given for 24 weeks and 48 weeks respectively to the HCV genotype 2,3 and the HCV non-genotype 2,3 .

Official Title
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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

Conditions
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Chronic Hepatitis c

Intervention / Treatment
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* Drug: PEG-IFN-SA /RBV
* Drug: Pegasys /RBV


Participation Criteria
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Eligibility Criteria
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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 Hepatotoxic drugs was systematically used more than two weeks within past 6 months Systemic therapy with potent immunomodulatory agents such as adrenocorticotropic hormone, thymosin α1, etc more than two weeks within past 6 months, not including corticosteroid nasal sprays, inhaled steroids and / or topical steroids 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 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 above the ULN Serum creatine kinase> 3 ULN Diabetes mellitus or Poorly controlled Thyroid Diseases Poorly controlled hypertension (systolic blood pressure> 140mmHg, or diastolic blood pressure> 90 mmHg) with hypertension -related retinal lesions Immunodeficiency or autoimmune diseases including but not limited to inflammatory bowel disease, systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, scleroderma, Sjogren's syndrome, autoimmune thrombocytopenia, etc. Psychiatric and nervous system disorders, including history of Psychiatric illness or with family history (especially depression, depressive tendencies, epilepsy and hysteria, etc.) Severe cardiovascular diseases (New York Heart Association functional class (NYHA) Ⅲ level and above, myocardial infarction occurred within past 6 months or PTCA performed within past 6 months, unstable angina, uncontrolled arrhythmias) Serious blood disorders (all kinds of anemia, hemophilia, etc.) Severe kidney disease (chronic kidney disease, renal insufficiency, etc.) Serious digestive diseases (gastrointestinal ulcers, colitis, etc.) Severe respiratory disease (pneumonia, chronic obstructive pulmonary disease, interstitial lung disease, etc.) Retinal disease (retinal exfoliation, macular hole, retinal tumors, etc.) Malignancies Function organs transplant Allergies or severe allergies, especially allergic to study drugs or any ingredients of the study drugs 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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: PEG-IFN-SA /RBV T1(Genotype2,3)<br>PEG-IFN-SA/RBV, 1.5μg/kg/week im and RBV 1000mg-1200mg/d po bid（BW<75kg,1000mg/d; BW≥75kg, 1200mg/d）,24 weeks | Drug: PEG-IFN-SA /RBV<br> <br> |
| Active Comparator: Pegasys /RBV C1(Genotype 2,3)<br>Pegasys 180μg/week and RBV 1000mg-1200mg/d bid depending on body weight(BW),（BW<75kg，1000mg/d；BW≥75kg，1200mg/d）for 24 weeks | Drug: Pegasys /RBV<br> <br> |
| Experimental: PEG-IFN-SA /RBV T2(Non-genotype 2,3)<br>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）for 48 weeks | Drug: PEG-IFN-SA /RBV<br> <br> |
| Active Comparator: Pegasys /RBV C2(Non-genotype 2,3)<br>Pegasys 180μg/week and RBV 1000mg-1200mg/d bid depending on body weight(BW),（BW<75kg，1000mg/d；BW≥75kg，1200mg/d）for 48 weeks | Drug: Pegasys /RBV<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| SVR (sustained virologic response) | defined as the proportion of patients who had undetectable plasma HCV RNA (HCV RNA < 15 IU/mL) at 24 weeks after the end of SVR (sustained virologic response) defined as the proportion of patients who had undetectable plasma HCV RNA (HCV RNA < 15 IU/mL) at 24 weeks after the end of treatment | 24 weeks after 24 or 48 weeks of study therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| RVR(rapid virologic response) | defined as the proportion of patients who had undetectable plasma HCV RNA (HCV RNA < 15 IU/mL) at weeks 4 | weeks 4 of study therapy | 
| cEVR (complete early virologic response) | defined as the proportion of patients who had undetectable plasma HCV RNA (HCV RNA < 15 IU/mL) at weeks 12 | weeks 12 of study therapy | 
| ETVR( end of treatment virologic response) | defined as the proportion of patients who had undetectable plasma HCV RNA (HCV RNA < 15 IU/mL) at the end of treatment | weeks 24 of study therapy for genotype 2,3, and weeks 48 of study therapy for non-genotype 2,3 | 
| eRVR ( extended rapid virologic response) | defined as the proportion of patients who had undetectable plasma HCV RNA (HCV RNA < 15 IU/mL) at weeks 4 and 12 | weeks 4 and 12 of study therapy | 
| No-responses | defined as the proportion of patients who had less than a <2 log IU/ml plasma HCV RNA decline at weeks 12 or had detectable plasma HCV RNA at weeks 24 | weeks 12 or weeks 24 of study therapy | 
| Breakthrough | defined as the proportion of patients who had detectable plasma HCV RNA at any point during treatment after virological response( undetectable plasma HCV RNA) | weeks 12, 24 of study therapy for genotype 2,3, and weeks 12, 24 and 48 of study therapy for non-genotype 2,3 | 
| Relapse | defined as the proportion of patients who had undetectable HCV RNA at the end of treatment, but reappearance of HCV RNA after the then | 12 and 24 weeks after 24 or 48 weeks of study therapy | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ribavirin, interferon, sustained virological response