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

Condition(s) targeted: Hepatitis B, Chronic

Intervention: Entecavir and peginterferon alfa-2a (Drug); Placebo and peginterferon (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

Currently, peginterferon alfa-2a or oral nucleos(t)ides are approved for the treatment with HBeAg positive CHB, with the overall HBeAg seroconversion 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. 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 HBeAg seroconversion. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate of adding entecavir early in the course of therapy can improve the treatment response.

Official title: Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Positive Chronic Hepatitis B

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Primary outcome: HBeAg seroconversion rate 6 months after the cessation of therapy

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 positive CHB, with the overall HBeAg seroconversion 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. 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 HBeAg seroconversion. Therefore, we aimed to conduct a placebo controlled randomized control trial to evaluate of adding entecavir early in the course of therapy can improve the treatment response.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Chronic hepatitis B (presence of HBsAg > 6 months) with HBeAg persistence for more

than 3 months

- Age older than 18 years

- HBV DNA > 20,000 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

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

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, Phone: +886-2-23123456, Ext: 63572, Email: jacque_liu@mail2000.com.tw
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

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

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

Starting date: February 2007
Last updated: December 19, 2012