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

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ClinicalTrials.gov Identifier: NCT00917761
Recruitment Status : Unknown
Verified December 2012 by National Taiwan University Hospital.
Recruitment status was:  Recruiting
First Posted : June 10, 2009
Last Update Posted : December 20, 2012
Sponsor:
Collaborator:
National Science Council, Taiwan
Information provided by (Responsible Party):
National Taiwan University Hospital

Study Description
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Brief Summary:
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 or disease Intervention/treatment Phase
Hepatitis B, Chronic Drug: Entecavir and peginterferon (Pegasys) (52 weeks) Drug: Peginterferon (Pegasys) (96 weeks) Drug: Peginterferon (Pegasys) (48 weeks) Phase 4

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.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 300 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (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
Study Start Date : February 2007
Estimated Primary Completion Date : December 2013
Estimated Study Completion Date : December 2013

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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


Outcome Measures
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Primary Outcome Measures :
  1. HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment [ Time Frame: 2.5 years ]

Secondary Outcome Measures :
  1. ALT normalization rate (ALT < 40 IU/L) 6 months after the cessation of treatment [ Time Frame: 2.5 years ]

Eligibility Criteria
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Information from the National Library of Medicine

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, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
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
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00917761


Contacts
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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
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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         
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         
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         
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         
Sponsors and Collaborators
National Taiwan University Hospital
National Science Council, Taiwan
Investigators
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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
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Layout table for additonal information
Responsible Party: National Taiwan University Hospital
ClinicalTrials.gov Identifier: NCT00917761    
Other Study ID Numbers: 950924
First Posted: June 10, 2009    Key Record Dates
Last Update Posted: December 20, 2012
Last Verified: December 2012
Keywords provided by National Taiwan University Hospital:
Hepatitis B, chronic
Peginterferon alfa-2a
Entecavir
Additional relevant MeSH terms:
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Hepatitis A
Hepatitis B
Hepatitis B, Chronic
Hepatitis
Liver Diseases
Digestive System Diseases
Hepatitis, Viral, Human
Virus Diseases
Infections
Enterovirus Infections
Picornaviridae Infections
RNA Virus Infections
Blood-Borne Infections
Communicable Diseases
 Hepadnaviridae Infections
DNA Virus Infections
Hepatitis, Chronic
Chronic Disease
Disease Attributes
Pathologic Processes
Peginterferon alfa-2a
Interferon-alpha
Entecavir
Antiviral Agents
Anti-Infective Agents
Immunologic Factors
Physiological Effects of Drugs