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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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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

Conditions
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Chronic Hepatitis C

Intervention / Treatment
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* Drug: PEG-IFN-SA /RBV low dose
* Drug: PEG-IFN-SA /RBV middle dose
* Drug: PEG-IFN-SA /RBV high dose
* 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 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

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: A (PEG-IFN-SA /RBV low dose)<br>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） | Drug: PEG-IFN-SA /RBV low dose<br>* 24 weeks for genotype 2,3 and 48 weeks for non-genotype2,3<br>|
| Experimental: B (PEG-IFN-SA /RBV middle dose)<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） | Drug: PEG-IFN-SA /RBV middle dose<br>* 24 weeks for genotype 2,3 and 48 weeks for non-genotype2,3<br>|
| Experimental: C (PEG-IFN-SA /RBV high dose)<br>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） | Drug: PEG-IFN-SA /RBV high dose<br>* 24 weeks for genotype 2,3 and 48 weeks for non-genotype2,3<br>|
| Active Comparator: D (Pegasys /RBV)<br>Pegasys 180μg/week and RBV 1000mg-1200mg/d bid depending on body weight(BW),（BW<75kg，1000mg/d；BW≥75kg，1200mg/d） | Drug: Pegasys /RBV<br>* 24 weeks for genotype 2,3 and 48 weeks for non-genotype2,3<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| cEVR (complete early virologic response) | defined as the proportion of patients who had undetectable plasma HCV RNA at weeks 12 | weeks 12 of study therapy | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients who had undetectable plasma HCV RNA |  | weeks 4, 24, 48 of study therapy 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 | 
| eRVR ( extended rapid virologic response) | defined as the proportion of patients who had undetectable plasma HCV RNA at weeks 4 and 12 | weeks 4 and 12 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 24, 48 of study therapy | 
| Relapse | defined as the proportion of patients who had undetectable HCV RNA at the end of treatment, but reappearance of HCV RNA after then | 12 and 24 weeks after the end of treatment | 

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