Clinical trial NCT01906580: Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Patients With Chronic Hepatitis B
Official title: Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Hepatitis B e Antigen-positive Patients With Chronic Hepatitis B
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Hepatitis B
Keywords: HBV
entecavir
peginterferon
Lead sponsor: Beijing 302 Hospital
Sponsor class: OTHER
First posted: 2013-07-24
Enrollment: 105
Sex: ALL
Minimum age (years): 16
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: Inclusion Criteria:

1. Age≥16 years
2. HBsAg positive for more than 6 months, and HBeAg detection is positive for two times in 6 months before enrollment
3. Serum HBVDNA \>2×10\^4IU/ml
4. 80U/L \< serum ALT \< 400U/L, and TBIL \< 34 umol/L
5. Serum ALT \< 80U/L, but hepatic inflammation scores ≥ G2 or hepatic fibrosis stage ≥ S3

Exclusion Criteria:

1. Co-infected with HCV, HDV or HIV, or autoimmune liver diseases combined
2. Hepatic decompensation
3. received antiviral therapy or immunosuppressant drugs before 6 months prior to enrollment
4. Blood routine examination: WBC \<3×10\^9/L，neutrophile granulocyte \< 1.5×10\^9/L，PLT \<80×10\^9/L
5. Renal function: creatinine \>1.5 times of upper normal limit
6. Alcoholism or a history of addiction and abuse
7. Combined with hepatocarcinoma

Primary outcomes:
measure: the rates of HBeAg seroconversion
timeFrame: at week 72
Secondary outcomes:
measure: normalisation of ALT
timeFrame: at week 2、4、12、24、36、48、60、72、84、96
measure: liver histological improvement
timeFrame: at baseline and at week 72
measure: The rates of HBsAg negative
timeFrame: at week12、24、36、48、60、72、84、96
measure: the rate of virological response
timeFrame: at week 4、12、24、36、48、60、72、84、96
measure: the rate of HBeAg negative
timeFrame: at week 12、24、36、48、60、72、84、96
Other outcomes:
Locations:
city: Beijing
country: China
facility: Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital
Study officials:
affiliation: Beijing 302 Hospital
name: Fu-Sheng Wang, Professor
role: PRINCIPAL_INVESTIGATOR
References:
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citation: 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.
citation: Rehermann 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.