Clinical trial NCT01908335: A Phase Ⅱ Dose-escalating Study of PEG-IFN-SA and Ribavirin in IFN Naive Patients With Chronic Hepatitis C
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Chronic Hepatitis C
Keywords: interferon
ribavirin
virological response
Lead sponsor: Beijing Kawin Technology Share-Holding Co., Ltd.
Sponsor class: INDUSTRY
First posted: 2013-07-25
Enrollment: 212
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 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.

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
* 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

Primary outcomes:
measure: cEVR (complete early virologic response)
timeFrame: weeks 12 of study therapy
Secondary outcomes:
measure: Proportion of patients who had undetectable plasma HCV RNA
timeFrame: weeks 4, 24, 48 of study therapy and 24 weeks after the end of treatment
measure: HCV RNA load reduction
timeFrame: weeks 4, 12, 24, 48 of study therapy and 24 weeks after the end of treatment
measure: eRVR ( extended rapid virologic response)
timeFrame: weeks 4 and 12 of study therapy
measure: Breakthrough
timeFrame: weeks 24, 48 of study therapy
measure: Relapse
timeFrame: 12 and 24 weeks after the end of treatment
Other outcomes:
Locations:
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Lanzhou
country: China
facility: First Affiliated Hospital of Lanzhou University
state: Gansu
city: Guangzhou
country: China
facility: Guangdong General Hospital
state: Guangdong
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: Shenzhen
country: China
facility: The third people's hospital of Shenzhen
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 First Affiliated Hospital of Harbin Medical University
state: Heilongjiang
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: First Affiliated Hospital of Zhengzhou 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: Suzhou
country: China
facility: The first affiliated hospital of suzhou university
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: Jinan
country: China
facility: Shandong Provincial Hospital
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: Hangzhou
country: China
facility: Xixi Hospital of Hangzhou
state: Zhejiang
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 Union Medical College Hospital
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: Daping Hospital, Research Institute of Surgery Third Military Medical University
city: Chongqing
country: China
facility: The Second Affiliated Hospital of Chongqing Medical University
city: Shanghai
country: China
facility: Ruijing Hospital, Shanghai Jiaotong University School of Medicine
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: