Clinical trial NCT01903278: Efficacy and Safety Study of PEG-IFN-SA and Ribavirin to Treat Chronic Hepatitis C
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Chronic Hepatitis c
Keywords: interferon
ribavirin
sustained virological response
Lead sponsor: Beijing Kawin Technology Share-Holding Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2013-07-19
Enrollment: 719
Sex: ALL
Minimum age (years): 18
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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 .

Eligibility criteria: 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

Primary outcomes:
measure: SVR (sustained virologic response)
timeFrame: 24 weeks after 24 or 48 weeks of study therapy
Secondary outcomes:
measure: RVR(rapid virologic response)
timeFrame: weeks 4 of study therapy
measure: cEVR (complete early virologic response)
timeFrame: weeks 12 of study therapy
measure: ETVR( end of treatment virologic response)
timeFrame: weeks 24 of study therapy for genotype 2,3, and weeks 48 of study therapy for non-genotype 2,3
measure: eRVR ( extended rapid virologic response)
timeFrame: weeks 4 and 12 of study therapy
measure: No-responses
timeFrame: weeks 12 or weeks 24 of study therapy
measure: Breakthrough
timeFrame: weeks 12, 24 of study therapy for genotype 2,3, and weeks 12, 24 and 48 of study therapy for non-genotype 2,3
measure: Relapse
timeFrame: 12 and 24 weeks after 24 or 48 weeks of study therapy
Other outcomes:
Locations:
city: Lanzhou
country: China
facility: First Affiliated Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Guangzhou Eighth People's Hospital
state: Guangdong
city: Guangzhou
country: China
facility: Nanfang Hospital Southern Medical Unbiversity
state: Guangdong
city: Nanning
country: China
facility: The First Affiliated Hospital of Guangxi Medical University
state: Guangxi
city: Shijiazhuang
country: China
facility: Third Affiliated Hospital, Hebei Medical University
state: Hebei
city: Harbin
country: China
facility: The Second Affiliated Hospital of Harbin Medical University
state: Heilongjiang
city: Xinxiang
country: China
facility: The First Affiliated Hospital of Xinxiang Medical University
state: Henan
city: Zhengzhou
country: China
facility: Henan Provincial People's Hospital
state: Henan
city: Wuhan
country: China
facility: Tongji Hospital, Tongji Medical College Huazhong University of Science ＆ Technology
state: Hubei
city: Wuhan
country: China
facility: Union hospital, Tongji Medical College Huazhong University of Science ＆ Technology
state: Hubei
city: Wuhan
country: China
facility: Zhongnan Hospital of Wuhan University
state: Hubei
city: Changsha
country: China
facility: The Second Xiangya Hospital of Central South University
state: Hunan
city: Changsha
country: China
facility: Xiangya Hospital Central-South University
state: Hunan
city: Nanjing
country: China
facility: Jiangsu province hospital
state: Jiangsu
city: Nanjing
country: China
facility: The Second Hospital of Nanjing
state: Jiangsu
city: Nanchang
country: China
facility: First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Affiliated Hospital of Jilin University
state: Jilin
city: Yanji
country: China
facility: Yanbian University Hospital (Yanbian Hospital)
state: Jilin
city: Shenyang
country: China
facility: The Sixth People's Hospital of Shenyang
state: Liaoning
city: Xi'an
country: China
facility: First Affiliated Hospital Of Medical College of Xian Jiaotong University
state: Shaanxi
city: Xi'an
country: China
facility: Second Affiliated Hospital Of Medical College of Xian Jiaotong University
state: Shaanxi
city: Xi'an
country: China
facility: Tangdu Hospital，Fourth Military Medical University
state: Shaanxi
city: Jinan
country: China
facility: Jinan Infectious Disease Hospital
state: Shandong
city: Jinan
country: China
facility: Qilu Hospital of Shandong university
state: Shandong
city: Qingdao
country: China
facility: Qingdao Municipal Hospital
state: Shandong
city: Taiyuan
country: China
facility: The First Hospital of Shanxi Medical University
state: Shanxi
city: Chengdu
country: China
facility: Sichuan Academy of Medical Science ＆Sichuan Provincial People's Hospital
state: Sichuan
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Urumqi
country: China
facility: The First Teaching Hospital of Xinjiang Medical University
state: Xinjiang
city: Wenzhou
country: China
facility: The First Affiliated Hospital of Wenzhou Medical University
state: Zhejiang
city: Beijing
country: China
facility: 302 Military Hospital of China
city: Beijing
country: China
facility: Beijing Ditan Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Youan Hospital, Capital Medical University
city: Beijing
country: China
facility: Beijing Youyi Hospital, capital Medical University
city: Beijing
country: China
facility: General Hospital of Beijing Military Region
city: Beijing
country: China
facility: Peking University First Hospital
city: Beijing
country: China
facility: Peking University People's Hospital
city: Chongqing
country: China
facility: Chongqing Southwest Hospital
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
city: Shanghai
country: China
facility: Shanghai Public Health Clinical Center
city: Tianjin
country: China
facility: Tianjin Infectious Disease Hospital
Study officials:
affiliation: Beijing Ditan Hospital
name: Cheng jun, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: