EFFORT Further Extension Study

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

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.

Study Overview

• Status: Unknown
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Other: off-treatment follow-up; Drug: Telbivudine; Drug: Adefovir dipivoxil

• Study Type: Interventional
• Enrollment (Actual): 130
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • Beijing Ditan Hospital
    • Beijing, Beijing, China
      • 302 Military Hospital of China
    • Beijing, Beijing, China
      • BeiJing YouAn Hospital ,Capital Medical University
    • Beijing, Beijing, China
      • Department of infectious disease, First Hospital of Peking University
    • Beijing, Beijing, China
      • People's Hospital of Beijing University
  • Chongqing
    • Chongqing, Chongqing, China
      • The Second Affiliated of ChongQing University of Medical Science
  • Guangdong
    • Guangzhou, Guangdong, China
      • Department of Infectious Disease, Nanfang Hospital
    • Guangzhou, Guangdong, China
      • No. 8 People's Hospital In GuangZhou
    • Guangzhou, Guangdong, China
      • The Third Hospital of Sun Yat-Sen University
  • Hubei
    • Wuhan, Hubei, China
      • Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
  • Hunan
    • Changsha, Hunan, China
      • Xiangya Hospital Central-South Univrsity
  • Jiangsu
    • Nanjing, Jiangsu, China
      • No.81 Hospital of PLA
  • Jilin
    • Changchun, Jilin, China
      • First Hospital .Jilin Unniversity
  • Liaoning
    • Shengyang, Liaoning, China
      • Shengjing Hospital Of China Medical University
  • Shandong
    • Jinan, Shandong, China
      • JiNan Infectious Diseases Hospital
  • Shanghai
    • Shanghai, Shanghai, China
      • Changhai Hospital Affiliated to Second Military Medical University
    • Shanghai, Shanghai, China
      • Huashan Hospital,Fudan University
    • Shanghai, Shanghai, China
      • Shanghai Ruijin Hospital
  • Shanxi
    • XiAn, Shanxi, China
      • Tangdu Hospital
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital of College of Medicine, Zhejiang University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Off-treatment; 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
Other: On-treatment; 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; Telbivudine, 600mg, oral, daily; Drug: Adefovir dipivoxil; Adefovir dipivoxil 10mg, oral, daily

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Novartis; Major Science and Technology Special Project of China Twelfth-Five-Year Project
• Investigators: Principal Investigator: Jinlin Hou, Nanfang Hospital of Southern Medical University

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (Anticipated): October 1, 2016
• Study Completion (Anticipated): October 1, 2017

Study Registration Dates

• First Submitted: June 27, 2016
• First Submitted That Met QC Criteria: July 4, 2016
• First Posted (Estimate): July 7, 2016

Study Record Updates

• Last Update Posted (Estimate): July 7, 2016
• Last Update Submitted That Met QC Criteria: July 4, 2016
• Last Verified: June 1, 2016

More Information

Terms related to this study

• Keywords: Chronic Hepatitis B
• Additional Relevant MeSH Terms: Digestive System Diseases; RNA Virus Infections; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Telbivudine; Adefovir; Adefovir dipivoxil
• Other Study ID Numbers: MOH-09

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED