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

This study is currently recruiting participants.
Verified July 2013 by Beijing 302 Hospital
Sponsor:
Information provided by (Responsible Party):
Beijing 302 Hospital
ClinicalTrials.gov Identifier:
NCT01906580
First received: May 30, 2013
Last updated: July 21, 2013
Last verified: July 2013
  Purpose

Currently, seven medications are approved for the treatment of hepatitis B: two formulations of interferon and five nucleos(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.


Condition Intervention Phase
Chronic Hepatitis B
Drug: Peg-IFNα-2a
Drug: Entecavir
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Combination or Sequential Therapy of Peginterferon Alfa-2a and Entecavir for Hepatitis B e Antigen-positive Patients With Chronic Hepatitis B

Resource links provided by NLM:


Further study details as provided by Beijing 302 Hospital:

Primary Outcome Measures:
  • the rates of HBeAg seroconversion [ Time Frame: at week 72 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • normalisation of ALT [ Time Frame: at week 2、4、12、24、36、48、60、72、84、96 ] [ Designated as safety issue: No ]
  • liver histological improvement [ Time Frame: at baseline and at week 72 ] [ Designated as safety issue: No ]
  • The rates of HBsAg negative [ Time Frame: at week12、24、36、48、60、72、84、96 ] [ Designated as safety issue: No ]
  • the rate of virological response [ Time Frame: at week 4、12、24、36、48、60、72、84、96 ] [ Designated as safety issue: No ]
  • the rate of HBeAg negative [ Time Frame: at week 12、24、36、48、60、72、84、96 ] [ Designated as safety issue: No ]

Estimated Enrollment: 105
Study Start Date: July 2011
Estimated Study Completion Date: July 2014
Estimated Primary Completion Date: July 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Peg-IFNα-2a monotherapy
Participants will receive 180ug peg-IFNα-2a therapy for 72 weeks, and then followed to 96 weeks.
Drug: Peg-IFNα-2a
180ug peg-IFNα-2a, subcutaneous injection per week
Other Name: peginterferon alfa-2a
Experimental: 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.
Drug: Peg-IFNα-2a
180ug peg-IFNα-2a, subcutaneous injection per week
Other Name: peginterferon alfa-2a
Drug: Entecavir
0.5mg,oral administration every day
Other Name: Baraclude
Experimental: Combination therapy
Participants will receive 180ug peg-IFNα-2a combined with entecavir therapy for 72 weeks, and then followed to 96 weeks.
Drug: Peg-IFNα-2a
180ug peg-IFNα-2a, subcutaneous injection per week
Other Name: peginterferon alfa-2a
Drug: Entecavir
0.5mg,oral administration every day
Other Name: Baraclude

  Eligibility

Ages Eligible for Study:   16 Years to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT01906580

Contacts
Contact: Sa Lv, MD 86-10-63879735 ext 2014.12 lvsa@sina.com

Locations
China
Research Center for Biological Therapy, The Institute of Translational Hepatology, Beijing 302 Hospital Recruiting
Beijing, China, 100039
Contact: Sa Lv, MD    86-10-63879735 ext 2015.12    lvsa@sina.com   
Sponsors and Collaborators
Beijing 302 Hospital
Investigators
Principal Investigator: Fu-Sheng Wang, Professor Beijing 302 Hospital
  More Information

Publications:
Responsible Party: Beijing 302 Hospital
ClinicalTrials.gov Identifier: NCT01906580     History of Changes
Other Study ID Numbers: 2011030D
Study First Received: May 30, 2013
Last Updated: July 21, 2013
Health Authority: China: Ministry of Health

Keywords provided by Beijing 302 Hospital:
HBV
entecavir
peginterferon

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Hepatitis, Viral, Human
Liver Diseases
Digestive System Diseases
Virus Diseases
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Hepadnaviridae Infections
DNA Virus Infections
Peginterferon alfa-2a
Interferon-alpha
Entecavir
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on April 22, 2014