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

Chronic Hepatitis C Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01908335
• Other study ID #: KAWIN-002-1
• Status: Completed
• Phase: Phase 2
• First received: July 23, 2013
• Last updated: October 16, 2014
• Start date: October 2012
• Est. completion date: July 2014

Study information

• Verified date: October 2014
• Source: Beijing Kawin Technology Share-Holding Co., Ltd.
• Contact: n/a
• Is FDA regulated: No
• Health authority: China: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 212
• Est. completion date: July 2014
• Est. primary completion date: August 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 65 Years

Eligibility

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 a1 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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis C
• Hepatitis
• Hepatitis A
• Hepatitis C
• Hepatitis C, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• PEG-IFN-SA /RBV low dose
24 weeks for genotype 2,3 and 48 weeks for non-genotype2,3
• PEG-IFN-SA /RBV middle dose
24 weeks for genotype 2,3 and 48 weeks for non-genotype2,3
• PEG-IFN-SA /RBV high dose
24 weeks for genotype 2,3 and 48 weeks for non-genotype2,3
• Pegasys /RBV
24 weeks for genotype 2,3 and 48 weeks for non-genotype2,3

Locations

Country	Name	City	State
China	302 Military Hospital of China	Beijing
China	Beijing Ditan Hospital, Capital Medical University	Beijing
China	Beijing Youan Hospital, Capital Medical University	Beijing
China	Beijing Youyi Hospital, capital Medical University	Beijing
China	General Hospital of Beijing Military Region	Beijing
China	Peking Union Medical College Hospital	Beijing
China	Peking University First Hospital	Beijing
China	Peking University People's Hospital	Beijing
China	The First Affiliated Hospital of Jilin University	Changchun	Jilin
China	The Second Xiangya Hospital of Central South University	Changsha	Hunan
China	Xiangya Hospital Central-South University	Changsha	Hunan
China	Sichuan Academy of Medical Science &Sichuan Provincial People's Hospital	Chengdu	Sichuan
China	West China Hospital, Sichuan University	Chengdu	Sichuan
China	Chongqing Southwest Hospital	Chongqing
China	Daping Hospital, Research Institute of Surgery Third Military Medical University	Chongqing
China	The Second Affiliated Hospital of Chongqing Medical University	Chongqing
China	The First Affiliated Hospital of Fujian Medical University	Fuzhou	Fujian
China	Guangdong General Hospital	Guangzhou	Guangdong
China	Guangzhou Eighth People's Hospital	Guangzhou	Guangdong
China	Nanfang Hospital Southern Medical Unbiversity	Guangzhou	Guangdong
China	Xixi Hospital of Hangzhou	Hangzhou	Zhejiang
China	The First Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	The Second Affiliated Hospital of Harbin Medical University	Harbin	Heilongjiang
China	Jinan Infectious Disease Hospital	Jinan	Shandong
China	Qilu Hospital of Shandong university	Jinan	Shandong
China	Shandong Provincial Hospital	Jinan	Shandong
China	First Affiliated Hospital of Lanzhou University	Lanzhou	Gansu
China	First Affiliated Hospital of Nanchang University	Nanchang	Jiangxi
China	Jiangsu province hospital	Nanjing	Jiangsu
China	The Second Hospital of Nanjing	Nanjing	Jiangsu
China	The First Affiliated Hospital of Guangxi Medical University	Nanning	Guangxi
China	Qingdao Municipal Hospital	Qingdao	Shandong
China	Ruijing Hospital, Shanghai Jiaotong University School of Medicine	Shanghai
China	Shanghai Public Health Clinical Center	Shanghai
China	The Sixth People's Hospital of Shenyang	Shenyang	Liaoning
China	The third people's hospital of Shenzhen	Shenzhen	Guangdong
China	Third Affiliated Hospital, Hebei Medical University	Shijiazhuang	Hebei
China	The first affiliated hospital of suzhou university	Suzhou	Jiangsu
China	The First Hospital of Shanxi Medical University	Taiyuan	Shanxi
China	Tianjin Infectious Disease Hospital	Tianjin
China	The First Teaching Hospital of Xinjiang Medical University	Urumqi	Xinjiang
China	The First Affiliated Hospital of Wenzhou Medical University	Wenzhou	Zhejiang
China	Tongji Hospital, Tongji Medical College Huazhong University of Science & Technology	Wuhan	Hubei
China	Union hospital, Tongji Medical College Huazhong University of Science & Technology	Wuhan	Hubei
China	Zhongnan Hospital of Wuhan University	Wuhan	Hubei
China	First Affiliated Hospital Of Medical College of Xian Jiaotong University	Xi'an	Shaanxi
China	Second Affiliated Hospital Of Medical College of Xian Jiaotong University	Xi'an	Shaanxi
China	Tangdu Hospital , , Fourth Military Medical University	Xi'an	Shaanxi
China	The First Affiliated Hospital of Xinxiang Medical University	Xinxiang	Henan
China	Yanbian University Hospital (Yanbian Hospital)	Yanji	Jilin
China	First Affiliated Hospital of Zhengzhou University	Zhengzhou	Henan
China	Henan Provincial People's Hospital	Zhengzhou	Henan

Sponsors (1)

Lead Sponsor	Collaborator
Beijing Kawin Technology Share-Holding Co., Ltd.

Country where clinical trial is conducted

China, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	Proportion of patients who had undetectable plasma HCV RNA		weeks 4, 24, 48 of study therapy and 24 weeks after the end of treatment	No
Secondary	HCV RNA load reduction		weeks 4, 12, 24, 48 of study therapy and 24 weeks after the end of treatment	No
Secondary	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	No
Secondary	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	No
Secondary	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	No