Efficacy Optimizing Research of Lamivudine Therapy (EXPLORE)

A Prospective, Randomised, Open-label, Multi-centre Study to Compare Three Chronic Hepatitis B (CHB) Treatment Strategies Over a 2year Period in Chinese HBeAg Positive CHB Patients

The purpose of this study is to compare the adefovir early add-on to rescue therapy strategy, and also explore the efficacy of Lamivudine and adefovir de-novo combination therapy.

Study Overview

• Status: Completed
• Conditions: Compensated Chronic Hepatitis B
• Intervention / Treatment: Drug: lamivudine; Drug: lamivudine; Drug: lamivudine, adefovir

• Study Type: Interventional
• Enrollment (Actual): 366
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • BeiJing, Beijing, China
      • BeiJing YouAn Hospital ,Capital Medical University
    • BeiJing, Beijing, China
      • Department of infectious disease, First Hospital of Peking University
    • Beijing, Beijing, China
      • Beijing Ditan Hospita
    • Beijing, Beijing, China
      • Beijing Friendship Hospital Attached to the Capital Medical University
    • Beijing, Beijing, China
      • People'S Hospital Under Beijnig University
  • Chongqing
    • ChongQing, Chongqing, China
      • The Second Affiliated of ChongQing University of Medical Science
  • Fujian
    • FuZhou, Fujian, China
      • The First Affiliated Hospital of Fujian Medical University
  • Guangdong
    • FoShan, Guangdong, China
      • The First People's Hospital of Foshan
    • GuangZhou, Guangdong, China
      • Guangdong Provincial People's Hospital
    • GuangZhou, Guangdong, China
      • Department of Infectious Disease, Nanfang Hospital
  • Guangxi
    • NanNing, Guangxi, China
      • First Affiliated Hospital of Guangxi Medical 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
  • Jilin
    • ChangChun, Jilin, China
      • First Hospital .Jilin Unniversity
  • Liaoning
    • ShenYang, 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
      • HangZhou No.6 People Hospital

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:

• Male or female aged 18-65 years;
• Capable of understanding and signing the informed consent. Willing to comply with the study requirements;
• Serum HBsAg and HBeAg positive at study screening; Documented chronic hepatitis B infection determined by the presence of serum HBsAg for at least 6 months;

Exclusion Criteria:

• History of decompensated liver function, or current signs/symptoms of decompensation e.g. ascites, variceal bleeding, encephalopathy or spontaneous peritonitis;
• other protocol defined inclusion/exclusion criteria

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

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: early add-on	Drug: lamivudine; patients in this arm will receive oral lamivudine 100mg,daily for 24 weeks; if patients with HBV DNA higher than 1000 copies/ml at week 24, add on adefovir to week 104; otherwise, keep lamivudine monotherapy to week 104; Drug: lamivudine; Patients will receive oral lamivudine 100mg,daily for 104 weeks, if HBV DNA breakthrough, add on oral adefovir 10mg daily
Active Comparator: SOC; Patients will receive oral lamivudine 100mg,daily for 104 weeks, if HBV DNA breakthrough, add on oral adefovir 10mg daily	Drug: lamivudine; patients in this arm will receive oral lamivudine 100mg,daily for 24 weeks; if patients with HBV DNA higher than 1000 copies/ml at week 24, add on adefovir to week 104; otherwise, keep lamivudine monotherapy to week 104; Drug: lamivudine; Patients will receive oral lamivudine 100mg,daily for 104 weeks, if HBV DNA breakthrough, add on oral adefovir 10mg daily
Other: De-novo combination; patients in this arm will receive oral lamivudine 100mg and adefovir 10mg for 104 weeks	Drug: lamivudine, adefovir; patients in this arm will receive oral lamivudine 100mg daily and adefovir 10mg for 104 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
the proportion of virological breakthrough with confirmed Lamivudine resistant mutants	during 104 weeks study period

Secondary Outcome Measures

Outcome Measure	Time Frame
proportion of subjects with hepatitis B virus (HBV) DNA≤300 copies/mL	week 104
Reduction of serum HBV DNA level from baseline (log10 copies/mL) to week 104	baseline, week 104
The proportion of subjects with ALT normalization at week 104	week 104
The proportion of subjects with HBeAg loss and seroconversion at week 104	week 104
The proportion of subjects with HBsAg loss and seroconversion rates at week 104	week 104

Collaborators and Investigators

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

Publications and helpful links

General Publications

• Xiang KH, Michailidis E, Ding H, Peng YQ, Su MZ, Li Y, Liu XE, Dao Thi VL, Wu XF, Schneider WM, Rice CM, Zhuang H, Li T. Effects of amino acid substitutions in hepatitis B virus surface protein on virion secretion, antigenicity, HBsAg and viral DNA. J Hepatol. 2017 Feb;66(2):288-296. doi: 10.1016/j.jhep.2016.09.005. Epub 2016 Sep 17.

Study record dates

Study Major Dates

• Study Start: March 1, 2010
• Primary Completion (Actual): February 1, 2013
• Study Completion (Actual): May 1, 2013

Study Registration Dates

• First Submitted: March 15, 2010
• First Submitted That Met QC Criteria: March 15, 2010
• First Posted (Estimate): March 16, 2010

Study Record Updates

• Last Update Posted (Estimate): October 30, 2013
• Last Update Submitted That Met QC Criteria: October 28, 2013
• Last Verified: September 1, 2013

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 B; Hepatitis; Hepatitis A; Hepatitis B, Chronic; Hepatitis, Chronic; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Reverse Transcriptase Inhibitors; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Anti-HIV Agents; Anti-Retroviral Agents; Lamivudine; Adefovir
• Other Study ID Numbers: MOH-02