A Phase Ⅱ Dose-escalating Study of PEG-IFN-SA and Ribavirin in IFN Naive Patients With Chronic Hepatitis C
- Conditions
- Chronic Hepatitis C
- Interventions
- Drug: PEG-IFN-SA /RBV low doseDrug: PEG-IFN-SA /RBV high doseDrug: PEG-IFN-SA /RBV middle dose
- Registration Number
- NCT01908335
- Lead Sponsor
- Beijing Kawin Technology Share-Holding Co., Ltd.
- Brief Summary
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
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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 212
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description A (PEG-IFN-SA /RBV low dose) 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） C (PEG-IFN-SA /RBV high dose) 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） D (Pegasys /RBV) Pegasys /RBV Pegasys 180μg/week and RBV 1000mg-1200mg/d bid depending on body weight(BW),（BW\<75kg，1000mg/d；BW≥75kg，1200mg/d） B (PEG-IFN-SA /RBV middle dose) 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）
- Primary Outcome Measures
Name Time Method cEVR (complete early virologic response) weeks 12 of study therapy defined as the proportion of patients who had undetectable plasma HCV RNA at weeks 12
- Secondary Outcome Measures
Name Time Method 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 defined as the proportion of patients who had undetectable plasma HCV RNA at weeks 4 and 12
Breakthrough weeks 24, 48 of study therapy defined as the proportion of patients who had detectable plasma HCV RNA at any point during treatment after virological response( undetectable plasma HCV RNA)
Relapse 12 and 24 weeks after the end of treatment defined as the proportion of patients who had undetectable HCV RNA at the end of treatment, but reappearance of HCV RNA after then
HCV RNA load reduction weeks 4, 12, 24, 48 of study therapy and 24 weeks after the end of treatment
Trial Locations
- Locations (52)
The First Affiliated Hospital of Fujian Medical University
🇨🇳Fuzhou, Fujian, China
First Affiliated Hospital of Lanzhou University
🇨🇳Lanzhou, Gansu, China
Guangdong General Hospital
🇨🇳Guangzhou, Guangdong, China
Guangzhou Eighth People's Hospital
🇨🇳Guangzhou, Guangdong, China
Nanfang Hospital Southern Medical Unbiversity
🇨🇳Guangzhou, Guangdong, China
The third people's hospital of Shenzhen
🇨🇳Shenzhen, Guangdong, China
The First Affiliated Hospital of Guangxi Medical University
🇨🇳Nanning, Guangxi, China
Third Affiliated Hospital, Hebei Medical University
🇨🇳Shijiazhuang, Hebei, China
The First Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
The Second Affiliated Hospital of Harbin Medical University
🇨🇳Harbin, Heilongjiang, China
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