Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Patients With Chronic Hepatitis B
1 other identifier
interventional
105
1 country
1
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_4
Started Jul 2011
Longer than P75 for phase_4
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2011
CompletedFirst Submitted
Initial submission to the registry
May 30, 2013
CompletedFirst Posted
Study publicly available on registry
July 24, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
July 1, 2016
CompletedStudy Completion
Last participant's last visit for all outcomes
July 1, 2016
CompletedAugust 17, 2015
August 1, 2015
5 years
May 30, 2013
August 14, 2015
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
the rates of HBeAg seroconversion
at week 72
Secondary Outcomes (5)
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
Study Arms (3)
Peg-IFNα-2a monotherapy
EXPERIMENTALParticipants will receive 180ug peg-IFNα-2a therapy for 72 weeks, and then followed to 96 weeks.
Sequential therapy
EXPERIMENTALParticipants 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.
Combination therapy
EXPERIMENTALParticipants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks.
Interventions
180ug peg-IFNα-2a, subcutaneous injection per week
0.5mg,oral administration every day
Eligibility Criteria
You may qualify if:
- 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
- U/L \< serum ALT \< 400U/L, and TBIL \< 34 umol/L
- Serum ALT \< 80U/L, but hepatic inflammation scores ≥ G2 or hepatic fibrosis stage ≥ S3
You may not qualify if:
- Co-infected with HCV, HDV or HIV, or autoimmune liver diseases combined
- Hepatic decompensation
- received antiviral therapy or immunosuppressant drugs before 6 months prior to enrollment
- Blood routine examination: WBC \<3×10\^9/L，neutrophile granulocyte \< 1.5×10\^9/L，PLT \<80×10\^9/L
- Renal function: creatinine \>1.5 times of upper normal limit
- Alcoholism or a history of addiction and abuse
- Combined with hepatocarcinoma
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital
Beijing, 100039, China
Related Publications (4)
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.
PMID: 21423260BACKGROUNDAyoub 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.
PMID: 21978243BACKGROUNDKuo A, Gish R. Chronic hepatitis B infection. Clin Liver Dis. 2012 May;16(2):347-69. doi: 10.1016/j.cld.2012.03.003.
PMID: 22541703BACKGROUNDRehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005 Mar;5(3):215-29. doi: 10.1038/nri1573.
PMID: 15738952BACKGROUND
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Fu-Sheng Wang, Professor
Beijing 302 Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- phase 4
- Allocation
- RANDOMIZED
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 30, 2013
First Posted
July 24, 2013
Study Start
July 1, 2011
Primary Completion
July 1, 2016
Study Completion
July 1, 2016
Last Updated
August 17, 2015
Record last verified: 2015-08