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

NCT ID: NCT01906580

Last Updated: 2015-08-17

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-07-31
• Study Completion Date: 2016-07-31

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.

Conditions

Chronic Hepatitis B

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Peg-IFNα-2a monotherapy

Participants will receive 180ug peg-IFNα-2a therapy for 72 weeks, and then followed to 96 weeks.

Group Type: EXPERIMENTAL

Peg-IFNα-2a

Intervention Type: DRUG

180ug peg-IFNα-2a, subcutaneous injection per week

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.

Group Type: EXPERIMENTAL

Peg-IFNα-2a

Intervention Type: DRUG

180ug peg-IFNα-2a, subcutaneous injection per week

Entecavir

Intervention Type: DRUG

0.5mg,oral administration every day

Combination therapy

Participants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks.

Group Type: EXPERIMENTAL

Peg-IFNα-2a

Intervention Type: DRUG

180ug peg-IFNα-2a, subcutaneous injection per week

Entecavir

Intervention Type: DRUG

0.5mg,oral administration every day

Interventions

Peg-IFNα-2a

180ug peg-IFNα-2a, subcutaneous injection per week

Intervention Type: DRUG

Entecavir

0.5mg,oral administration every day

Intervention Type: DRUG

Other Intervention Names

peginterferon alfa-2a; Baraclude

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

• Minimum Eligible Age: 16 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Beijing 302 Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Fu-Sheng Wang, Professor

Role: PRINCIPAL_INVESTIGATOR

Beijing 302 Hospital

Locations

Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital

Beijing, , China

Site Status: RECRUITING

Countries

China

Central Contacts

Sa Lv, MD

Role: CONTACT

lvsa@sina.com

86-10-63879735 ext. 2014.12

Facility Contacts

Sa Lv, MD

Role: primary

lvsa@sina.com

86-10-63879735 ext. 2015.12

References

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.

Reference Type: BACKGROUND

PMID: 21423260 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 21978243 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22541703 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15738952 (View on PubMed)

Other Identifiers

2011030D

Identifier Type: -

Identifier Source: org_study_id