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

Phase 4

• Conditions: Hepatitis B, Chronic
• Interventions: Drug: Entecavir and peginterferon alfa-2a; Drug: Placebo and peginterferon

• Registration Number: NCT00921180
• Lead Sponsor: National Taiwan University Hospital

Brief Summary

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.

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.

Study Timeline

• Study Start: 2007-02
• Study First Submitted: 2009-06-15
• Study First Submitted QC: 2009-06-15
• Study First Posted: 2009-06-16
• Status Verified: 2012-12
• Last Update Submitted: 2012-12-19
• Last Update Posted: 2012-12-20
• Primary Completion: 2013-12
• Study Completion: 2013-12

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 148

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

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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

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Entecavir and peginterferon	Entecavir and peginterferon alfa-2a	Entecavir 0.5 mg/day at week 1-4, followed by peginterferon alfa-2a 180 ug/week at week 5-52
Placebo and peginterferon	Placebo and peginterferon	Placebo 0.5 mg/day at week 1-4, followed by peginterferon alfa-2a 180 ug/week at week 5-52

Primary Outcome Measures

Name	Time	Method
HBeAg seroconversion rate 6 months after the cessation of therapy	76 weeks

Trial Locations

Locations (6)

National Taiwan University Hosptial, Yun-Lin Branch; 🇨🇳 Douliou, Taiwan

Taichung Veterans General Hospital; 🇨🇳 Taichung, Taiwan

Ren-Ai Branch, Taipei Municipal Hospital; 🇨🇳 Taipei, Taiwan

National Taiwan University Hospital; 🇨🇳 Taipei, Taiwan

Buddhist Tzu Chi General Hospital; 🇨🇳 Taipei, Taiwan

Far Eastern Memorial Hospital; 🇨🇳 Taipei, Taiwan