- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01434212
Patterns of Early Hepatitis C Virus Decline Predict the Outcome of Interferon Therapy (sIFN-pred1)
Study of Parameters of Early Hepatitis C Virus Dynamics for Predicting the Outcome of Standard Interferon Therapy With Chinese Cohort
Study Overview
Detailed Description
Hepatitis C virus (HCV) infection rate in China is about 3%, which means about 30 million patients. Combination therapy of ribavirin and interferons (IFN) is the standard clinical treatment of HCV chronical infections. However, overall rate of sustained virological response (SVR) still do not exceed 60% even with ribavirin and peg-IFN. Due to several virus- and patient-related factors, treatment is even less successful in certain populations, especially in HCV genotype 1 infection. Thus the standard therapy duration is optimized according to the virus genotype in the clinical practice. Nowadays, two direct antiviral agents (DAAs) have been approved by Food and Drug Administration (FDA) of USA this year, which increases the SVR rate. However, high price, side effects and long duration render people to hesitate about the addition of the third drug in the traditional prescription.
Predicting the outcome of traditional therapy is the cornerstone of the personalized therapy for HCV infected patients. In order to obtain an accurate prediction, different methods have been tried. Several indicators have been suggested to predict the final treatment outcomes. Rapid Virus Response (RVR), which indicates the non-detectable virus at the forth week since therapy starts, has been used to predict the final treatment outcome.Other indicators, including virus genotype, host genotype of IL-28B, human race and interferon stimulated genes (ISG) expression have also been shown to relate to and be able to predict the treatment outcomes to some extent. Here the investigators propose that the HCV virus dynamics analysis will give a more precise prediction for the therapy outcome.
The general idea is that blood HCV titration data is obtained continuously in the early treatment period (first 6 weeks) of the patients who have strictly followed the therapy method. These titration data will be used to draw virus dynamics curve and calculate the corresponding parameters individually. The parameter(s) that can distinguish patients who reach the therapy evaluation standard from those who failed to reach the evaluation standard will be selected out, and such parameter(s) may be used to predict the therapy outcome of a new patient in the early stage of his/her treatment.
Study Type
Enrollment (Anticipated)
Contacts and Locations
Study Locations
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Jilin
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Changchun, Jilin, China, 130061
- First Hospital Jilin University
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
- Serologic evidence of chronic hepatitis C infection by an anti-HCV antibody test
- Serum HCV-RNA > 3 log IU/ml
- Has been infected by HCV for more than 6 months
- ALT,AST have been elevated continuously, inflammation and necrosis have been observed according to the histology diagnosis (G>=2),modest liver fibrosis (S>=2)
- For those patients whose ALT are normal,treatment accord to the liver biopsy. If obvious fibrosis has been detected (S2,S3),treatment should be done.For those S0,S1 stage patients, treatment could be delayed, but ALT/AST should be assayed every 3-6 months.
- Compensated liver disease
- Patients have never been treated with traditional interferon plus ribavirin or peginterferon plus ribavirin
Exclusion Criteria:
History:
- Has history of decompensated liver diseases
- Has been treated with other anti-virus drugs,or anti-tumor drugs,immuno-suppression drugs
- Has a history of autoimmune hepatitis
- History of a severe seizure disorder or current anticonvulsant use
- History or other evidence of a medical condition associated with chronic liver disease other than HCV which would make the patient, in the opinion of the investigator, unsuitable for the study (e.g., hemochromatosis, autoimmune hepatitis, metabolic liver disease, alcoholic liver disease, toxin exposures)
- Patients with documented or presumed coronary artery disease or cerebrovascular disease should not be enrolled if, in the judgment of the investigator, an acute decrease in hemoglobin by up to 4g/dL (as may be seen with ribavirin therapy) would not be well-tolerated
- History of thyroid disease poorly controlled on prescribed medications, elevated thyroid stimulating hormone (TSH) concentrations with elevation of antibodies to thyroid peroxidase and any clinical manifestations of thyroid disease
Current condition:
- Pregnant women or women during the lactation period
- Co-infected with hepatitis b virus or human immunodeficiency virus
- Liver cancer or alpha-fetoprotein > 100ng/ml
- Blood neutrophils count < 1500/mm3, or platelets count < 90000/mm3
- Female hemoglobin <11.5g/dL, male hemoglobin <12.5g/dL
- Blood creatinine > 1.5 ULN
- Have severe mental diseases,especially depression
- Severe pulmonary dysfunction
- Severe cardiovascular disease
- Uncontrolled diabetes
- Uncontrolled thalassemia
- Evidence of alcohol abuse (alcohol consumption>40 g/day)
- Unwillingness to provide informed consent or abide by the requirements of the study
- Local or System malignancy unstable status
Study Plan
How is the study designed?
Design Details
Cohorts and Interventions
Group / Cohort |
Intervention / Treatment |
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Interferon and ribavirin
All the patients followed the standard treatment protocol.
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Interferon:dosage,5 million units/person;frequency,every other day (qod);duration,48 weeks;Subcutaneous injection. Ribavirin: dosage,15mg/kg/day;frequency,three times a day (t.i.d);duration,48 weeks;take orally.
Other Names:
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Blood HCV RNA Copies
Time Frame: 0h,8h,10h,12h,18h,24h,37h,43h,3d,7d,2w,4w,6w,12w,24w,48w
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Blood HCV RNA copies were assayed with Roche - COBAS® AmpliPrep/COBAS® TaqMan® HCV Test.
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0h,8h,10h,12h,18h,24h,37h,43h,3d,7d,2w,4w,6w,12w,24w,48w
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
HCV genotype
Time Frame: Baseline
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HCV NS5A is cloned into T vector and sequenced for evolutionary analysis.
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Baseline
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Drug abuse history
Time Frame: Baseline
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Patients will be asked about their drug usage history.
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Baseline
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IL-28B polymorphism
Time Frame: Baseline
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IL28 gene polymorphism,rs8099917,rs12979860,etc
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Baseline
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Microarray Analysis of PBMC Gene Expression
Time Frame: Baseline,8h,18h,3d
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During the first 3 days, blood samples are collected for PBMC separation and microarray analysis.
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Baseline,8h,18h,3d
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Blood Anti-HCV,HBV Antibody
Time Frame: Baseline
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Co-infection status are analyzed.
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Baseline
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HCV genome sequencing
Time Frame: 0h,8h,10h,12h,18h,24h,37h,43h,3d
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Deep sequencing is used for blood serum HCV genome analysis.
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0h,8h,10h,12h,18h,24h,37h,43h,3d
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Alanine Aminotransferase (ALT) and Aspartate transaminase (AST)
Time Frame: Baseline,4w,6w,12w,24w,48w
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ALT AST are assayed to detect the hepatic function.
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Baseline,4w,6w,12w,24w,48w
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Fibrosis stage
Time Frame: Baseline,4w,12w,24w,48w
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Fibrosis is analyzed with Fibroscan.
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Baseline,4w,12w,24w,48w
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Regular blood test
Time Frame: Baseline,4w,12w,24w,48w
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The distribution and absolute count of the different types of blood cells are assayed.
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Baseline,4w,12w,24w,48w
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Electrocardiography
Time Frame: Baseline,4w,12w,24w,48w
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Electrocardiography is taken to avoid severe side effects.
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Baseline,4w,12w,24w,48w
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Alcohol ,smoking condition
Time Frame: Baseline,4w,12w,24w,48w
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Patients are asked whether they take alcohol or smoke cigarettes during the therapy period.
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Baseline,4w,12w,24w,48w
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Collaborators and Investigators
Collaborators
Investigators
- Study Chair: Junqi Niu, PhD/MD, First Hospital Jilin University
- Principal Investigator: Bing Sun, PhD/MD, Chinese Academy of Sciences
Publications and helpful links
General Publications
- Manns MP, McHutchison JG, Gordon SC, Rustgi VK, Shiffman M, Reindollar R, Goodman ZD, Koury K, Ling M, Albrecht JK. Peginterferon alfa-2b plus ribavirin compared with interferon alfa-2b plus ribavirin for initial treatment of chronic hepatitis C: a randomised trial. Lancet. 2001 Sep 22;358(9286):958-65. doi: 10.1016/s0140-6736(01)06102-5.
- Neumann AU, Lam NP, Dahari H, Gretch DR, Wiley TE, Layden TJ, Perelson AS. Hepatitis C viral dynamics in vivo and the antiviral efficacy of interferon-alpha therapy. Science. 1998 Oct 2;282(5386):103-7. doi: 10.1126/science.282.5386.103.
- Dahari H, Ribeiro RM, Perelson AS. Triphasic decline of hepatitis C virus RNA during antiviral therapy. Hepatology. 2007 Jul;46(1):16-21. doi: 10.1002/hep.21657.
- Snoeck E, Chanu P, Lavielle M, Jacqmin P, Jonsson EN, Jorga K, Goggin T, Grippo J, Jumbe NL, Frey N. A comprehensive hepatitis C viral kinetic model explaining cure. Clin Pharmacol Ther. 2010 Jun;87(6):706-13. doi: 10.1038/clpt.2010.35. Epub 2010 May 12.
- Dixit NM, Layden-Almer JE, Layden TJ, Perelson AS. Modelling how ribavirin improves interferon response rates in hepatitis C virus infection. Nature. 2004 Dec 16;432(7019):922-4. doi: 10.1038/nature03153.
- Dill MT, Duong FH, Vogt JE, Bibert S, Bochud PY, Terracciano L, Papassotiropoulos A, Roth V, Heim MH. Interferon-induced gene expression is a stronger predictor of treatment response than IL28B genotype in patients with hepatitis C. Gastroenterology. 2011 Mar;140(3):1021-31. doi: 10.1053/j.gastro.2010.11.039. Epub 2010 Nov 25.
- Araujo ES, Dahari H, Neumann AU, de Paula Cavalheiro N, Melo CE, de Melo ES, Layden TJ, Cotler SJ, Barone AA. Very early prediction of response to HCV treatment with PEG-IFN-alfa-2a and ribavirin in HIV/HCV-coinfected patients. J Viral Hepat. 2011 Apr;18(4):e52-60. doi: 10.1111/j.1365-2893.2010.01358.x.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- RNA Virus Infections
- Virus Diseases
- Infections
- Blood-Borne Infections
- Communicable Diseases
- Liver Diseases
- Flaviviridae Infections
- Hepatitis, Viral, Human
- Enterovirus Infections
- Picornaviridae Infections
- Hepatitis
- Hepatitis A
- Hepatitis C
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Antimetabolites
- Antineoplastic Agents
- Immunologic Factors
- Interferons
- Interferon-alpha
- Ribavirin
- Interferon alpha-2
Other Study ID Numbers
- 2008ZX10004-002-jida01
- 2008ZX10002-014-jida01 (Other Identifier: China: Ministry of Science and Technology)
- 2009ZX10004-105-jida01 (Other Identifier: China: Ministry of Science and Technology)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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