Continuing Lamivudine vs Switching to Entecavir in Patients With Detectable HBV DNA

Study Overview
=================
Brief Summary
-----------------
This is a randomized, open-labelled, prospective 96-week study comparing the antiviral efficacy and safety of switching to entecavir 1 mg QD from lamivudine versus maintaining lamivudine 100 mg QD treatment in HBV-infected subjects currently receiving lamivudine monotherapy.

Detailed Description
-----------------
Entecavir has a higher potent antiviral efficacy and a lower drug resistance rate than Lamivudine in nucleoside-naïve CHB patients. The prompt switch from Lamivudine to Entecavir in patients who have insufficient hepatitis B virus suppression (HBV DNA ≥ 60 IU/mL by PCR) may lead to full viral suppression to undetectable level by PCR method. The prompt switch from Lamivudine to Entecavir in patients who have insufficient hepatitis B virus suppression (HBV DNA ≥ 60 IU/mL) may preclude development of drug resistance. The results of this study will provide a rationale for switch treatment from one antiviral to another one, especially from LAM to ETV.

Official Title
-----------------
Randomized, Open-Labelled Study Evaluating the Antiviral Efficacy, Safety, and Tolerability of Continuing Lamivudine Therapy or Switching to Entecavir in Subjects With Chronic Hepatitis B With Detectable HBV DNA

Conditions
-----------------
Hepatitis B, Chronic

Intervention / Treatment
-----------------
* Drug: Entecavir
* Drug: Lamivudine


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Adult subjects (18-70 years of age) currently taking lamivudine monotherapy for chronic HBV infection for at least 6 months with ≥ HBV DNA 60 IU/mL level and HBeAg positive at baseline. Exclusion Criteria: All subjects will be tested for presence of M204V/I mutations in the YMDD motif at baseline. Subjects with M204V/I mutations in the YMDD motif at baseline are not eligible for the study. Subjects treated with other antiviral drugs (e.g. adefovir) in combination with lamivudine are not eligible for this study. Subjects should have ALT < 10 x ULN, and no evidence of hepatocellular carcinoma. Subjects should be without serological evidence of co-infection with HCV, HIV, or HDV. Subjects with decompensated liver disease, as well as pregnant or breast-feeding women, will not be eligible for the study.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: A<br>entecavir 1.0 mg QD | Drug: Entecavir<br>* entecavir 1.0 mg QD<br>* Other names: Baraclude 1.0mg;|
| Active Comparator: B<br>lamivudine 100 mg QD | Drug: Lamivudine<br>* lamivudine 100 mg QD<br>* Other names: Zeffix 100mg;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage number of patients with HBV DNA < 60 IU/mL (Undetectable serum HBV DNA by PCR method) while on randomized therapy |  | at Week 96 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage number of patients with HBV DNA < 60 IU/mL while on randomized therapy |  | at Week 48 | 
| Percentage number of patients who developed drug resistant mutations while on randomized therapy |  | at Week 48 and Week 96 | 
| Change from baseline in mean HBV DNA |  | at Week 48 and 96 | 
| Percentage number of patients who achieved ALT normalization, HBeAg loss, HBe seroconversion, HBsAg loss and HBs seroconversion |  | at Week 48 and 96 | 
| Cumulative discontinuation rates due to lamivudine or entecavir resistance mutations and clinical breakthrough Safety assessment |  | Follow up period | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Chronic hepatitis B, Lamivudine, Entecavir