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

June 8, 2009
December 19, 2012
February 2007
December 2013   (final data collection date for primary outcome measure)
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 ]
Same as current
Complete list of historical versions of study NCT00917761 on ClinicalTrials.gov Archive Site
ALT normalization rate (ALT < 40 IU/L) 6 months after the cessation of treatment [ Time Frame: 2.5 years ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Entecavir and Pegasys Sequential Therapy Versus Pegasys for HBeAg Negative Chronic Hepatitis B
Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Negative Chronic Hepatitis B

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.

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.

Interventional
Phase 4
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Hepatitis B, Chronic
  • 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
  • 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
  • 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
  • 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
    Intervention: Drug: Entecavir and peginterferon (Pegasys) (52 weeks)
  • Experimental: Peginterferon (96 weeks)
    Peginterferon alfa-2a 180 ug/week sc at week 1-96
    Intervention: Drug: Peginterferon (Pegasys) (96 weeks)
  • Active Comparator: Peginterferon (48 weeks)
    Peginterferon alfa-2a 180 ug/week sc at week 1-48
    Intervention: Drug: Peginterferon (Pegasys) (48 weeks)
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
300
December 2013
December 2013   (final data collection date for primary outcome measure)

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
Both
18 Years and older
No
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
Taiwan
 
NCT00917761
950924
Yes
National Taiwan University Hospital
National Taiwan University Hospital
National Science Council, Taiwan
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
National Taiwan University Hospital
December 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP