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Entecavir and Pegasys Sequential Therapy Versus Pegasys for HBeAg Negative Chronic Hepatitis B

This study is currently recruiting participants.
Verified December 2012 by National Taiwan University Hospital
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by (Responsible Party):
National Taiwan University Hospital
ClinicalTrials.gov Identifier:
NCT00917761
First received: June 8, 2009
Last updated: December 19, 2012
Last verified: December 2012
History of Changes
  Purpose

Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg negative CHB, with the overall ALT normalization and HBV viral suppression far from satisfactory. Therefore, efforts on the various combinations with the currently available drugs are needed to improve the overall response rates. The simultaneous combination therapy with oral nucleoside and peginterferon alfa-2a from large-scaled randomized trials did not show a superior response rate over peginterferon alfa-2a monotherapy. Recently, sequential monotherapy with lamivudine for the first 4 weeks, followed by weekly peginterferon alfa-2a has shown favorable HBeAg seroconversion rate over peginterferon alfa-2a monotherapy, based on the assumption that early viral suppression by lamivudine can restore the immune function to facilitate the later immunomodulatory response by peginterferon alfa-2a. Furthermore, prior studies using 24 months of standard interferon alfa showed better ALT normalization and HBV suppression rates to 12 months of therapy. With the recent introduction of entecavir, the more potent oral nucleoside with few drug resistance, sequential monotherapy with entecavir can potently suppress HBV DNA with 4 weeks of treatment, which may facilitate the response of peginterferon alfa-2a to achieve HBV viral suppression. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate if adding entecavir early in the course of therapy or extending the treatment duration of peginterferon alfa-2a can improve the treatment response.


Condition Intervention Phase
Hepatitis B, Chronic
 Drug: Entecavir and peginterferon (Pegasys) (52 weeks)
Drug: Peginterferon (Pegasys) (96 weeks)
Drug: Peginterferon (Pegasys) (48 weeks)
 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: Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Negative Chronic Hepatitis B

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by National Taiwan University Hospital:

Primary Outcome Measures:
  • HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • ALT normalization rate (ALT < 40 IU/L) 6 months after the cessation of treatment [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]

Estimated Enrollment: 300
Study Start Date: February 2007
Estimated Study Completion Date: December 2013
Estimated Primary Completion Date: December 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Entecavir and peginterferon (52 weeks)
Entecavir 0.5 mg/day po at week 1-4 Peginterferon alfa-2a 180 ug/week sc at week 5-52
 Drug: Entecavir and peginterferon (Pegasys) (52 weeks)
Entecavir 0.5 mg/day po at week 1-4 Peginterferon alfa-2a 180 ug/week sc at week 5-52
Other Names:
  • Entecavir (Baraclude)0.5 mg/day po at week 1-4
  • Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 5-52
Experimental: Peginterferon (96 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-96
 Drug: Peginterferon (Pegasys) (96 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-96
Other Name: Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 1-96
Active Comparator: Peginterferon (48 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-48
 Drug: Peginterferon (Pegasys) (48 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-48
Other Name: Peginterferon alfa-2a (Pegasys) 180 ug/week sc at week 1-48

Detailed Description:

Chronic hepatitis B (CHB) is prevalent in the world, with estimated chronic carriers of 350 millions worldwide. Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg negative CHB, with the overall ALT normalization and HBV viral suppression far from satisfactory. Therefore, efforts on the various combinations with the currently available drugs are needed to improve the overall response rates. The simultaneous combination therapy with oral nucleoside and peginterferon alfa-2a from large-scaled randomized trials did not show a superior response rate over peginterferon alfa-2a monotherapy. Recently, sequential monotherapy with lamivudine for the first 4 weeks, followed by weekly peginterferon alfa-2a has shown favorable HBeAg seroconversion rate over peginterferon alfa-2a monotherapy, based on the assumption that early viral suppression by lamivudine can restore the immune function to facilitate the later immunomodulatory response by peginterferon alfa-2a. Furthermore, prior studies using 24 months of standard interferon alfa showed better ALT normalization and HBV suppression rates to 12 months of therapy. With the recent introduction of entecavir, the more potent oral nucleoside with few drug resistance, sequential monotherapy with entecavir can potently suppress HBV DNA with 4 weeks of treatment, which may facilitate the response of peginterferon alfa-2a to achieve HBV viral suppression. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate if adding entecavir early in the course of therapy or extending the treatment duration of peginterferon alfa-2a can improve the treatment response.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Chronic hepatitis B (presence of HBsAg > 6 months) with anti-HBe persistence and abscence of HBeAg for more than 3 months
  • Age older than 18 years
  • HBV DNA > 2,000 IU/mL for more than 2 occasions
  • Serum ALT levels between 2 to 10 folds the upper limit of normal (ULN)
  • A liver biopsy compatible with chronic hepatitis B

Exclusion Criteria:

  • Anemia (hemoglobin < 13 gram per deciliter for men and < 12 gram per deciliter for women)
  • Neutropenia (neutrophil count <1,500 per cubic milliliter)
  • Thrombocytopenia (platelet <90,000 per cubic milliliter)
  • Co-infection with hepatitis B virus (HBV), hepatitis D virus (HDV) or human immunodeficiency virus (HIV)
  • Chronic alcohol abuse (daily consumption > 20 gram per day)
  • Decompensated liver disease (Child-Pugh class B or C)
  • Serum creatinine level more than 1.5 times the upper limit of normal
  • Autoimmune liver disease
  • Neoplastic disease
  • An organ transplant
  • Immunosuppressive therapy
  • Poorly controlled autoimmune diseases, pulmonary diseases, cardiac diseases, psychiatric diseases, neurological diseases, diabetes mellitus
  • Evidence of drug abuse
  • Unwilling to have contraception
  • Known allergic reaction to entecavir or peginterferon alfa-2a
  • Unwilling to sign inform consent
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00917761

Contacts
Contact: Chen-Hua Liu, MD 886-2-23123456 ext 63572 jacque_liu@mail2000.com.tw
Contact: Jia-Horng Kao, MD, PhD 886-2-23123456 ext 67307 kaojh@ntu.edu.tw

Locations
Taiwan
National Taiwan University Hosptial, Yun-Lin Branch Recruiting
Douliou, Taiwan
Contact: Shih-Jer Hsu, MD            
Principal Investigator: Shih-Jer Hsu, MD            
Sub-Investigator: Ping-Huei Tseng, MD            
Sub-Investigator: Chieh-Chang Chen, MD            
Sub-Investigator: Ming-Lun Han, MD            
Sub-Investigator: Jou-Wei Lin, MD, PhD            
Sub-Investigator: Jun-Herng Chen, MD            
Taichung Veterans General Hospital Recruiting
Taichung, Taiwan
Contact: Sheng-Shun Yang, MD, PhD            
Principal Investigator: Sheng-Shun Yang, MD, PhD            
Far Eastern Memorial Hospital Recruiting
Taipei, Taiwan
Contact: Cheng-Chao Liang, MD            
Principal Investigator: Cheng-Chao Liang, MD            
Ren-Ai Branch, Taipei Municipal Hospital Recruiting
Taipei, Taiwan
Contact: Chih-Lin Lin, MD            
Principal Investigator: Chih-Lin Lin, MD            
Sub-Investigator: Ping-Yeh Wu, MD            
Buddhist Tzu Chi General Hospital Recruiting
Taipei, Taiwan
Contact: Ching-Sheng Hsu, MD            
Principal Investigator: Ching-Sheng Hsu, MD            
Sub-Investigator: Chia-Chi Wang, MD            
Sub-Investigator: Tai-Chung Tseng, MD            
National Taiwan University Hospital Recruiting
Taipei, Taiwan, 10002
Contact: Chen-Hua Liu, MD            
Principal Investigator: Chen-Hua Liu, MD            
Principal Investigator: Jia-Horng Kao, MD, PhD            
Sub-Investigator: Chun-Jen Liu, MD, PhD            
Sub-Investigator: Ming-Yang Lai, MD, PhD            
Sub-Investigator: Pei-Jer Chen, MD, PhD            
Sub-Investigator: Ding-Shinn Chen, MD            
Sponsors and Collaborators
National Taiwan University Hospital
National Science Council, Taiwan
Investigators
Study Chair: Chen-Hua Liu, MD National Taiwan University Hospital
Principal Investigator: Jia-Horng Kao, MD, PhD National Taiwan University Hospital
Principal Investigator: Shih-Jer Hsu, MD National Taiwan University Hosptial, Yun-Lin Branch
Principal Investigator: Chih-Lin Lin, MD Ren-Ai Branch, Taipei City Hospital
Principal Investigator: Cheng-Chao Liang, MD Far Eastern Memorial Hospital
Principal Investigator: Ching-Sheng Hsu, MD Buddhist Tzu Chi General Hospital
Principal Investigator: Sheng-Shun Yang, MD, PhD Taichung Veterans General Hospital
  More Information

No publications provided

Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00917761     History of Changes
Other Study ID Numbers: 950924
Study First Received: June 8, 2009
Last Updated: December 19, 2012
Health Authority: Taiwan: Department of Health

Keywords provided by National Taiwan University Hospital:
Hepatitis B, chronic
Peginterferon alfa-2a
Entecavir

Additional relevant MeSH terms:
Hepatitis
Hepatitis A
Hepatitis B
Hepatitis, Chronic
Hepatitis B, Chronic
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
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 May 19, 2013