Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Patients With Chronic Hepatitis B
Study Details
Study Description
Brief Summary
Currently, seven medications are approved for the treatment of hepatitis B: two formulations of interferon and five nucleons(t)ide analogues. The current treatment strategy of chronic hepatitis B is now standard: initial selection of entecavir, tenofovir, or peginterferon alfa-2a (peg-IFNα-2a). Interferon is administered for a finite duration while nucleotide analogues are usually administered for many years. But among hepatitis B e antigen （HBeAg） positive patients with high serum hepatitis B virus DNA levels, the rates of virological response are poor. And antiviral drug resistance is a major limiting factor to the success of nucleotide analogue treatment. Therefore, combination therapy using peginterferon with an oral agent with a high genetic barrier to resistance might be superior to standard current monotherapy. However, the addition of lamivudine to peg-IFNα-2a therapy led to a greater decrease in serum HBV DNA levels during treatment but did not increase the rate of HBeAg sero¬conversion. Entecavir is a nucleoside analogue superior to lamivudine and adefovir in achieving higher virological response, histological improvement and normalisation of ALT. Moreover, Entecavir has a high genetic barrier with a very low incidence of drug resistance. This study is aimed to investigate the efficacy of combination or sequential therapy using peg-IFNα-2a and entecavir in HBeAg-positive chronic hepatitis B(CHB) patients.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 4 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Peg-IFNα-2a monotherapy Participants will receive 180ug peg-IFNα-2a therapy for 72 weeks, and then followed to 96 weeks. |
Drug: Peg-IFNα-2a
180ug peg-IFNα-2a, subcutaneous injection per week
Other Names:
|
| Experimental: Sequential therapy Participants will receive entecavir monotherapy for 12 weeks, and 180ug peg-IFNα-2a therapy is added for the following 12 weeks. After that, entecavir will be stopped and 180ug peg-IFNα-2a monotherapy for the following 48 weeks. All participants will followed to 96 weeks. |
Drug: Peg-IFNα-2a
180ug peg-IFNα-2a, subcutaneous injection per week
Other Names:
Drug: Entecavir
0.5mg,oral administration every day
Other Names:
|
| Experimental: Combination therapy Participants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks. |
Drug: Peg-IFNα-2a
180ug peg-IFNα-2a, subcutaneous injection per week
Other Names:
Drug: Entecavir
0.5mg,oral administration every day
Other Names:
|
Outcome Measures
Primary Outcome Measures
- the rates of HBeAg seroconversion [at week 72]
Secondary Outcome Measures
- normalisation of ALT [at week 2、4、12、24、36、48、60、72、84、96]
- liver histological improvement [at baseline and at week 72]
- The rates of HBsAg negative [at week12、24、36、48、60、72、84、96]
- the rate of virological response [at week 4、12、24、36、48、60、72、84、96]
- the rate of HBeAg negative [at week 12、24、36、48、60、72、84、96]
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Age≥16 years
-
HBsAg positive for more than 6 months, and HBeAg detection is positive for two times in 6 months before enrollment
-
Serum HBVDNA >2×10^4IU/ml
-
80U/L < serum ALT < 400U/L, and TBIL < 34 umol/L
-
Serum ALT < 80U/L, but hepatic inflammation scores ≥ G2 or hepatic fibrosis stage ≥ S3
Exclusion Criteria:
-
Co-infected with HCV, HDV or HIV, or autoimmune liver diseases combined
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Hepatic decompensation
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received antiviral therapy or immunosuppressant drugs before 6 months prior to enrollment
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Blood routine examination: WBC <3×109/L，neutrophile granulocyte < 1.5×109/L，PLT <80×10^9/L
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Renal function: creatinine >1.5 times of upper normal limit
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Alcoholism or a history of addiction and abuse
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Combined with hepatocarcinoma
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital | Beijing | China | 100039 |
Sponsors and Collaborators
- Beijing 302 Hospital
Investigators
- Principal Investigator: Fu-Sheng Wang, Professor, Beijing 302 Hospital
Study Documents (Full-Text)
None provided.More Information
Publications
- Ayoub WS, Keeffe EB. Review article: current antiviral therapy of chronic hepatitis B. Aliment Pharmacol Ther. 2011 Nov;34(10):1145-58. doi: 10.1111/j.1365-2036.2011.04869.x. Epub 2011 Oct 7. Review.
- Kuo A, Gish R. Chronic hepatitis B infection. Clin Liver Dis. 2012 May;16(2):347-69. doi: 10.1016/j.cld.2012.03.003. Review.
- Kwon H, Lok AS. Hepatitis B therapy. Nat Rev Gastroenterol Hepatol. 2011 May;8(5):275-84. doi: 10.1038/nrgastro.2011.33. Epub 2011 Mar 22. Review.
- Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005 Mar;5(3):215-29. Review.
- 2011030D