Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Patients With Chronic Hepatitis B

Phase 4

• Conditions: Chronic Hepatitis B
• Interventions: Drug: Peg-IFNα-2a; Drug: Entecavir

• Registration Number: NCT01906580
• Lead Sponsor: Beijing 302 Hospital

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2011-07
• Study First Submitted: 2013-05-30
• Study First Submitted QC: 2013-07-21
• Study First Posted: 2013-07-24
• Status Verified: 2015-08
• Last Update Submitted: 2015-08-14
• Last Update Posted: 2015-08-17
• Primary Completion: 2016-07
• Study Completion: 2016-07

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 105

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Peg-IFNα-2a monotherapy	Peg-IFNα-2a	Participants will receive 180ug peg-IFNα-2a therapy for 72 weeks, and then followed to 96 weeks.
Sequential therapy	Peg-IFNα-2a	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.
Sequential therapy	Entecavir	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.
Combination therapy	Peg-IFNα-2a	Participants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks.
Combination therapy	Entecavir	Participants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks.

Primary Outcome Measures

Name	Time	Method
the rates of HBeAg seroconversion	at week 72

Secondary Outcome Measures

Name	Time	Method
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

Trial Locations

Locations (1)

Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital; 🇨🇳 Beijing, China