Entecavir and Pegasys Sequential Therapy Versus Pegasys for HBeAg Negative Chronic Hepatitis B
Information source: National Taiwan University Hospital
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Hepatitis B, Chronic
Intervention: Entecavir and peginterferon (Pegasys) (52 weeks) (Drug); Peginterferon (Pegasys) (96 weeks) (Drug); Peginterferon (Pegasys) (48 weeks) (Drug)
Phase: Phase 4
Status: Recruiting
Sponsored by: National Taiwan University Hospital Official(s) and/or principal investigator(s): Chen-Hua Liu, MD, Study Chair, Affiliation: National Taiwan University Hospital Jia-Horng Kao, MD, PhD, Principal Investigator, Affiliation: National Taiwan University Hospital Shih-Jer Hsu, MD, Principal Investigator, Affiliation: National Taiwan University Hosptial, Yun-Lin Branch Chih-Lin Lin, MD, Principal Investigator, Affiliation: Ren-Ai Branch, Taipei City Hospital Cheng-Chao Liang, MD, Principal Investigator, Affiliation: Far Eastern Memorial Hospital Ching-Sheng Hsu, MD, Principal Investigator, Affiliation: Buddhist Tzu Chi General Hospital Sheng-Shun Yang, MD, PhD, Principal Investigator, Affiliation: Taichung Veterans General Hospital
Overall contact: Chen-Hua Liu, MD, Phone: 886-2-23123456, Ext: 63572, Email: jacque_liu@mail2000.com.tw
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.
Clinical Details
Official title: Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Negative Chronic Hepatitis B
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment
Secondary outcome: ALT normalization rate (ALT < 40 IU/L) 6 months after the cessation of treatment
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Chen-Hua Liu, MD, Phone: 886-2-23123456, Ext: 63572, Email: jacque_liu@mail2000.com.tw
National Taiwan University Hosptial, Yun-Lin Branch, Douliou, Taiwan; Recruiting Shih-Jer Hsu, MD Shih-Jer Hsu, MD, Principal 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, Sub-Investigator
Taichung Veterans General Hospital, Taichung, Taiwan; Recruiting Sheng-Shun Yang, MD, PhD Sheng-Shun Yang, MD, PhD, Principal Investigator
Buddhist Tzu Chi General Hospital, Taipei, Taiwan; Recruiting Ching-Sheng Hsu, MD Ching-Sheng Hsu, MD, Principal Investigator Chia-Chi Wang, MD, Sub-Investigator Tai-Chung Tseng, MD, Sub-Investigator
Far Eastern Memorial Hospital, Taipei, Taiwan; Recruiting Cheng-Chao Liang, MD Cheng-Chao Liang, MD, Principal Investigator
National Taiwan University Hospital, Taipei 10002, Taiwan; Recruiting Chen-Hua Liu, MD Chen-Hua Liu, MD, Principal Investigator Jia-Horng Kao, MD, PhD, Principal 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, Sub-Investigator
Ren-Ai Branch, Taipei Municipal Hospital, Taipei, Taiwan; Recruiting Chih-Lin Lin, MD Chih-Lin Lin, MD, Principal Investigator Ping-Yeh Wu, MD, Sub-Investigator
Additional Information
Starting date: February 2007
Last updated: December 19, 2012
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