EFFORT Further Extension Study

Study Overview
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Brief Summary
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The purpose of this study is to demonstrate that long-term treatment (up to six years) with telbivudine or telbivudine plus adefovir results in the regression in liver inflammation and fibrosis/cirrhosis.

Official Title
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Efficacy of Long-term Telbivudine Treatment on Histological Improvements in Patients With Chronic Hepatitis B (EFFORT Further Extension Study)

Conditions
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Hepatitis B, Chronic

Intervention / Treatment
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* Drug: Telbivudine
* Drug: Adefovir dipivoxil
* Other: off-treatment follow-up


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients who completed EFFORT extension study. Patients who had baseline (that is the week 0 of EFFORT study) HBV DNA <9 Log copies/mL and ALT ≥2×ULN. Patients who are willing to participate in the further extension study. Patient is willing and able to comply with the study drug regimen and all other study requirements. Patients must give written informed consent before any assessment is performed. Exclusion Criteria: 1. Poor compliance judged by investigators
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Off-treatment<br>Patients who had stopped treatment during EFFORT extension study could receive 2-year off-treatment follow-up. All the patients in Part I will be followed up at the interval of 12 weeks. For these patients, if they have hepatitis flare during follow-up, they will be re-treated with telbivudine combined with adefovir for the left study period ( the total study period is 2 years) and followed up at the interval of 12 weeks. Hepatitis flare is defined as HBV DNA>4 Log10 copies/mL with either ALT≥5 times upper limit of normal (ULN) or TBIL≥2×ULN，or 2 ≤ALT ≤5 ×ULN (at two consecutive visits at least 2 weeks apart) and total bilirubin (TBIL) <2×ULN. | Other: off-treatment follow-up<br> <br> |
| Other: On-treatment<br>Patients with continuous treatment during EFFORT extension study will continue treatment, without off-treatment rule in the further extension study. The treatment strategy is depended on the HBV DNA level of each individual, that is, for patients with negative HBV DNA level (defined as HBV DNA <20 IU/mL) will continue their previous treatment strategy; and for patients with positive HBV DNA level (defined as HBV DNA>=20 IU/mL) will receive the combination therapy of telbivudine and adefovir, irrespective of their previous treatment strategy. All the patients in Part II will be followed up at the interval of 24 weeks until they complete the 2-year on-treatment follow-up. Patients will be conducted liver biopsy at the sixth year of treatment. All the patients with telbivudine monotherapy will be switched to telbivudine plus adefovir once confirmed HBV DNA breakthrough developed. | Drug: Telbivudine<br>* Telbivudine, 600mg, oral, daily<br>Drug: Adefovir dipivoxil<br>* Adefovir dipivoxil 10mg, oral, daily<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with histological improvement (≥2-point decrease in the Knodell necroinflammatory score and no worsening in Ishak fibrosis score). |  | Week 48 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients achieving hepatitis B virus (HBV) DNA <300copies/mL at week 48 and 96 in on-treatment group |  | week 48, week 96 | 
| Percentage of patients with HBeAg loss or HBeAg seroconversion at week 48 and 96 in on-treatment group |  | week 48, week 96 | 
| Percentage of patients with HBsAg loss or HBsAg seroconversion at week 48 and 96 in on-treatment group |  | week 48, week 96 | 
| The percentage of patients with alanine aminotransferase (ALT) normalization at week 48 and 96 in on-treatment group |  | week 48, week 96 | 
| Percentage of patients with HBV DNA breakthrough at week 48 and 96 in on-treatment group |  | week 48, week 96 | 
| Percentage of patients with genotypic resistance among the patients with HBV DNA breakthrough at week 48 and 96 in on-treatment group |  | week 48, week 96 | 
| Incidence of adverse effect at week 48 and 96 in on-treatment group |  | week 48, week 96 | 
| Percentage of patients with glomerular filtration rate (GFR) shifting to >90 mL/min/1.73 m2 for patients with GFR <90 mL/min/1.73 m2 at baseline of EFFORT study at week 48 and 96 in on-treatment group |  | week 48, week 96 | 
| Sustained response rate of durability of HBeAg seroconversion at week 48 and 96 in off-treatment group |  | week 48, week 96 | 
| Percentage of patients who re-achieved ALT normalization and HBV DNA <300 copies/mL in the patients retreated who developed hepatitis flare after stopping treatment in off-treatment group |  | week 96 | 
| Incidence of abnormal laboratory examination at week 48 and 96 in on-treatment group |  | week 48, week 96 | 
| Percentage of hepatitis flare at week 48 and 96 in off-treatment group |  | week 48, week 96 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Chronic Hepatitis B