Overview

This trial is active, not recruiting.

Condition hepatitis b, chronic
Treatments telbivudine, adefovir dipivoxil, off-treatment follow-up
Phase phase 4
Sponsor Nanfang Hospital of Southern Medical University
Collaborator Major Science and Technology Special Project of China Twelfth-Five-Year Project
Start date April 2015
End date October 2016
Trial size 130 participants
Trial identifier NCT02826070, MOH-09

Summary

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.

United States No locations recruiting
Other Countries No locations recruiting

Study Design

Allocation non-randomized
Endpoint classification safety/efficacy study
Intervention model single group assignment
Masking open label
Primary purpose treatment
Arm
(Other)
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.
off-treatment follow-up
(Other)
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.
telbivudine
Telbivudine, 600mg, oral, daily
adefovir dipivoxil
Adefovir dipivoxil 10mg, oral, daily

Primary Outcomes

Measure
Percentage of patients with histological improvement (≥2-point decrease in the Knodell necroinflammatory score and no worsening in Ishak fibrosis score).
time frame: Week 48

Secondary Outcomes

Measure
Percentage of patients achieving hepatitis B virus (HBV) DNA <300copies/mL at week 48 and 96 in on-treatment group
time frame: week 48, week 96
Percentage of patients with HBeAg loss or HBeAg seroconversion at week 48 and 96 in on-treatment group
time frame: week 48, week 96
Percentage of patients with HBsAg loss or HBsAg seroconversion at week 48 and 96 in on-treatment group
time frame: week 48, week 96
The percentage of patients with alanine aminotransferase (ALT) normalization at week 48 and 96 in on-treatment group
time frame: week 48, week 96
Percentage of patients with HBV DNA breakthrough at week 48 and 96 in on-treatment group
time frame: 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
time frame: week 48, week 96
Incidence of adverse effect at week 48 and 96 in on-treatment group
time frame: 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
time frame: week 48, week 96
Sustained response rate of durability of HBeAg seroconversion at week 48 and 96 in off-treatment group
time frame: 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
time frame: week 96
Incidence of abnormal laboratory examination at week 48 and 96 in on-treatment group
time frame: week 48, week 96
Percentage of hepatitis flare at week 48 and 96 in off-treatment group
time frame: week 48, week 96

Eligibility Criteria

Male or female participants of any age.

Inclusion Criteria: 1. Patients who completed EFFORT extension study. 2. Patients who had baseline (that is the week 0 of EFFORT study) HBV DNA <9 Log copies/mL and ALT ≥2×ULN. 3. Patients who are willing to participate in the further extension study. 4. Patient is willing and able to comply with the study drug regimen and all other study requirements. 5. Patients must give written informed consent before any assessment is performed. Exclusion Criteria: 1. Poor compliance judged by investigators

Additional Information

Official title Efficacy of Long-term Telbivudine Treatment on Histological Improvements in Patients With Chronic Hepatitis B (EFFORT Further Extension Study)
Principal investigator Jinlin Hou
Trial information was received from ClinicalTrials.gov and was last updated in July 2016.
Information provided to ClinicalTrials.gov by Nanfang Hospital of Southern Medical University.