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

Chronic Hepatitis B Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT01906580
• Other study ID #: 2011030D
• Status: Recruiting
• Phase: Phase 4
• First received: May 30, 2013
• Last updated: August 14, 2015
• Start date: July 2011
• Est. completion date: July 2016

Study information

• Verified date: August 2015
• Source: Beijing 302 Hospital
• Contact: Sa Lv, MD
• Phone: 86-10-63879735
• Email: lvsa[@]sina.com
• Is FDA regulated: No
• Health authority: China: Ministry of Health
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 105
• Est. completion date: July 2016
• Est. primary completion date: July 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 16 Years to 60 Years

Eligibility

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

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Chronic Hepatitis B
• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

Drug:
• Peg-IFNa-2a
180ug peg-IFNa-2a, subcutaneous injection per week
• Entecavir
0.5mg,oral administration every day

Locations

Country	Name	City	State
China	Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital	Beijing

Sponsors (1)

Lead Sponsor	Collaborator
Beijing 302 Hospital

Country where clinical trial is conducted

China, 

References & Publications (4)

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. Review. — View 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. Review. — View Citation

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. — View Citation

Rehermann B, Nascimbeni M. Immunology of hepatitis B virus and hepatitis C virus infection. Nat Rev Immunol. 2005 Mar;5(3):215-29. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	the rates of HBeAg seroconversion		at week 72	No
Secondary	normalisation of ALT		at week 2?4?12?24?36?48?60?72?84?96	No
Secondary	liver histological improvement		at baseline and at week 72	No
Secondary	The rates of HBsAg negative		at week12?24?36?48?60?72?84?96	No
Secondary	the rate of virological response		at week 4?12?24?36?48?60?72?84?96	No
Secondary	the rate of HBeAg negative		at week 12?24?36?48?60?72?84?96	No