Efficacy Optimizing Research of Chronic Hepatitis B Patients With Inadequate Response to NUC Therapy

A Multi-center, Randomized, Controlled Study to Evaluate the Efficacy and Safety of Generic Entecavir Monotherapy or in Combination With Adefovir for Chronic Hepatitis B Patients With Inadequate Response to NUC Therapy

The purpose of this study is to evaluate the efficacy and safety of generic entecavir monotherapy or in combination with adefovir for chronic hepatitis B patients with inadequate response to NUC therapy

Study Overview

• Status: Unknown
• Conditions: Hepatitis B
• Intervention / Treatment: Drug: Entecavir; Drug: Entecavir, Adefovir; Drug: Entecavir, Adefovir

• Study Type: Interventional
• Enrollment (Anticipated): 360
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing
    • 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
  • 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
  • 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

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 positive and ALT<10ULN at study screening;
• Patients have been treated with one nucleoside/nucleotide analogue for more than 6 months and are still on treatment;

Exclusion Criteria:

• History of viral breakthrough or genotypic resistance on previous therapy;
• History of decompensated liver function, or current signs/symptoms of decompensation e.g. ascites, variceal bleeding, encephalopathy or spontaneous peritonitis;
• Patient has a history of hepatocellular carcinoma(HCC) or findings suggestive of possible HCC;
• Other protocol defined 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
Active Comparator: A; oral entecavir 1mg daily for 104 weeks	Drug: Entecavir; patients will receive oral entecavir 1mg, daily for 104 weeks.
Active Comparator: B; oral entecavir 1mg daily and adefovir 10mg daily for 104 weeks	Drug: Entecavir, Adefovir; patients in this arm will receive oral entecavir 1mg daily and adefovir 10mg daily for 104 weeks; Drug: Entecavir, Adefovir; patients in this arm will receive oral entecavir 0.5mg daily and adefovir 10mg daily for 104 weeks
Active Comparator: C; oral entecavir 0.5mg daily and adefovir 10mg daily for 104 weeks	Drug: Entecavir, Adefovir; patients in this arm will receive oral entecavir 1mg daily and adefovir 10mg daily for 104 weeks; Drug: Entecavir, Adefovir; patients in this arm will receive oral entecavir 0.5mg daily and adefovir 10mg daily for 104 weeks

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
proportion of subjects with hepatitis B virus (HBV)DNA<300copies/ml at week 104	week 104

Secondary Outcome Measures

Outcome Measure	Time Frame
serum HBV DNA reduction from baseline at week 104	week 104
The proportion of subjects with ALT normalization at week 104	week104
The proportion of subjects with HBeAg loss and seroconversion at week 104	week104
The proportion of subject with HBsAg loss and seroconversion at week 104	week104
The proportion of subjects with mutations of rtN236T/A181V, rtL180M/rtM204V/rtT184/rtS202 and/or rtM250 at week 104	week104

Collaborators and Investigators

• Sponsor: Nanfang Hospital of Southern Medical University
• Collaborators: JiangSu Chia-Tai Tianqin Pharmacy Co.Ltd

Study record dates

Study Major Dates

• Study Start: December 1, 2010
• Primary Completion (Anticipated): June 1, 2014
• Study Completion (Anticipated): December 1, 2014

Study Registration Dates

• First Submitted: February 16, 2011
• First Submitted That Met QC Criteria: April 25, 2011
• First Posted (Estimate): April 26, 2011

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; inadequate response; NUC therapy
• 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; Entecavir; Adefovir; Adefovir dipivoxil
• Other Study ID Numbers: MOH-04