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

Hepatitis B, Chronic Clinical Trial

Official title:

Entecavir and Peginterferon Alfa-2a Sequential Therapy Versus Peginterferon Alfa-2a Monotherapy for HBeAg Negative Chronic Hepatitis B

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT00917761
• Other study ID #: 950924
• Status: Recruiting
• Phase: Phase 4
• First received: June 8, 2009
• Last updated: December 19, 2012
• Start date: February 2007
• Est. completion date: December 2013

Study information

• Verified date: December 2012
• Source: National Taiwan University Hospital
• Contact: Chen-Hua Liu, MD
• Phone: 886-2-23123456
• Email: jacque_liu[@]mail2000.com.tw
• Is FDA regulated: No
• Health authority: Taiwan: Department of Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 300
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Hepatitis
• Hepatitis A
• Hepatitis B
• Hepatitis B, Chronic
• Hepatitis, Chronic

Intervention

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
• Peginterferon (Pegasys) (96 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-96
• Peginterferon (Pegasys) (48 weeks)
Peginterferon alfa-2a 180 ug/week sc at week 1-48

Locations

Country	Name	City	State
Taiwan	National Taiwan University Hosptial, Yun-Lin Branch	Douliou
Taiwan	Taichung Veterans General Hospital	Taichung
Taiwan	Buddhist Tzu Chi General Hospital	Taipei
Taiwan	Far Eastern Memorial Hospital	Taipei
Taiwan	National Taiwan University Hospital	Taipei
Taiwan	Ren-Ai Branch, Taipei Municipal Hospital	Taipei

Sponsors (2)

Lead Sponsor	Collaborator
National Taiwan University Hospital	National Science Council, Taiwan

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HBV virologic response (HBV DNA < 2,000 IU/mL) 6 months after the cessation of treatment		2.5 years	No
Secondary	ALT normalization rate (ALT < 40 IU/L) 6 months after the cessation of treatment		2.5 years	No