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

This study is currently recruiting participants. (see Contacts and Locations)
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

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

ClinicalTrials.gov processed this record on October 23, 2014