Chronic Hepatitis B | Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Patients With Chronic Hepatitis B
Chronic Hepatitis B research study
What is the primary objective of this study?
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.
Who is eligible to participate?
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
Which medical condition, disease, disorder, syndrome, illness, or injury is researched?
Chronic Hepatitis B
Interventions can include giving participants drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available or noninvasive approaches such as surveys, education, and interviews.
Drug:Peg-IFNα-2a180ug peg-IFNα-2a, subcutaneous injection per week
Drug:Entecavir0.5mg,oral administration every day
Research studies and clinical trials typically have two or more research arms. An arm is a group of people who receive the same treatment in the study.
Peg-IFNα-2a monotherapyParticipants will receive 180ug peg-IFNα-2a therapy for 72 weeks, and then followed to 96 weeks.
Sequential therapyParticipants 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 therapyParticipants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks.
Start Date: July 2011
Completed Date: July 2016
Phase: Phase 4
Primary Outcome: the rates of HBeAg seroconversion
Secondary Outcome: normalisation of ALT
Study sponsors, principal investigator, and references
Principal Investigator: Fu-Sheng Wang, Professor
Lead Sponsor: Beijing 302 Hospital
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.