EFFORT Extension Study (EFFORT-Ex)

A 3-year, Open-label, Multi-center Extension Trial of Telbivudine Therapy for Patients Previously Treated in EFFORT Clinical Trial

• The purpose of this study is to to prove that the long-term efficacy of strategy of treatment adjustment at W24 according to virological response based on ROADMAP concept is better than standard of care strategy.
• To evaluate the off-treatment durability of HBeAg seroconversion in patients who discontinued treatment due to sustained HBeAg seroconversion and HBV DNA<300copies/ml with over 12 months consolidation treatment

Study Overview

• Status: Unknown
• Conditions: Hepatitis B, Chronic
• Intervention / Treatment: Drug: telbivudine (ROADMAP); Drug: Telbivudine (Standard of Care)

• Study Type: Interventional
• Enrollment (Anticipated): 576
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • Beijing, Beijing, China
      • 302 Military Hospital of China
    • Beijing, Beijing, China
      • Beijing Ditan Hospita
    • Beijing, Beijing, China
      • Beijing Friendship Hospital Attached to the Capital Medical University
    • 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 Under Beijnig 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
      • No.85 Hospital of PLA
    • Shanghai, Shanghai, China
      • Shanghai Ruijin Hospital
  • Shanxi
    • Xian, Shanxi, China
      • Tangdu Hospital
  • Sichuan
    • Chengdu, Sichuan, China
      • West China Hospital.SiChuan University
  • Zhejiang
    • Hangzhou, Zhejiang, China
      • The First Affiliated Hospital of College of Medicine, Zhejiang University
    • Hangzhou, Zhejiang, China
      • The Sixth People's Hospital of Hangzhou

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Treated with telbivudine or combined with adefovir in EFFORT study
• Patients are willing to participate in the extension study
• Patients provide information consent form

Exclusion Criteria:

• Adjustment of poor compliance by investigators

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: ROADMAP	Drug: telbivudine (ROADMAP); Patients will receive oral telbivudine 600mg, daily for 104 weeks, if HBV DNA breakthrough, add on oral adefovir 10mg daily Stopping rules: The participants who achieve HBeAg seroconversion and HBV DNA<300copies/ml with over 12 months consolidation treatment in EFFORT study will discontinue treatment. The participants who don't meet the rules above will continue their previous treatment and follow up at the interval of 12 weeks until they finish the 156 weeks therapy or achieve the stopping rules. Follow up： The participants who stopped treatment will follow up at the interval of 12 weeks for 52 weeks. Of these patients, if they have confirmed virologic relapse during follow-up period, they will be excluded from the trial.
Active Comparator: SOC (Standard of Care)	Drug: Telbivudine (Standard of Care); Patients will receive oral telbivudine 600mg, daily for 104 weeks, if HBV DNA breakthrough, add on oral adefovir 10mg daily Stopping rules: The participants who achieve HBeAg seroconversion and HBV DNA<300copies/ml with over 12 months consolidation treatment in EFFORT study will discontinue treatment. The participants who don't meet the rules above will continue their previous treatment and follow up at the interval of 12 weeks until they finish the 156 weeks therapy or achieve the stopping rules. Follow up： The participants who stopped treatment will follow up at the interval of 12 weeks for 52 weeks. Of these patients, if they have confirmed virologic relapse during follow-up period, they will be excluded from the trial.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
The difference of percentage of patients achieving HBV DNA< 300copies/mL at week 48 in Group I and Group II	Week 48

Secondary Outcome Measures

Outcome Measure	Time Frame
Percentage of patients achieving HBV DNA <300copies/mL at week 156	Week 156
The log10 reduction in HBV DNA from baseline of EFFORT study at week 156	Week 156
Percentage of patients with HBeAg loss or HBeAg seroconversion at week 156	Week 156
Percentage of patients with HBsAg loss or HBsAg seroconversion at week 156	Week 156
The percentage of patients with ALT normalization at week 156	Week 156
Percentage of patients with HBV DNA breakthrough at week 156	Week 156
Percentage of patients with genotypic resistance among the patients with HBV DNA breakthrough at week 156	Week 156
sustained response rate of durability of HBeAg seroconversion at week 52 of off-treatment duration	week 52 of off-treatment
percentage of hepatitis flare at week 52 of off-treatment duration	week 52 of off-treatment

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: Novartis; Major Science and Technology Special Project of China Eleventh Five-year

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Anticipated): August 1, 2015
• Study Completion (Anticipated): December 1, 2015

Study Registration Dates

• First Submitted: September 20, 2011
• First Submitted That Met QC Criteria: February 6, 2012
• First Posted (Estimate): February 8, 2012

Study Record Updates

• Last Update Posted (Estimate): June 19, 2014
• Last Update Submitted That Met QC Criteria: June 17, 2014
• Last Verified: June 1, 2014

More Information

Terms related to this study

• Keywords: Chronic Hepatitis B; Compensated Chronic hepatitis B
• Additional Relevant MeSH Terms: Digestive System Diseases; Virus Diseases; Infections; Blood-Borne Infections; Communicable Diseases; Liver Diseases; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Hepatitis, Chronic; Hepatitis B; Hepatitis; Hepatitis B, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Telbivudine
• Other Study ID Numbers: MOH-05