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EFFORT Further Extension Study

Primary Purpose

Hepatitis B, Chronic

Status
Unknown status
Phase
Phase 4
Locations
China
Study Type
Interventional
Intervention
Telbivudine
Adefovir dipivoxil
off-treatment follow-up
Sponsored by
Nanfang Hospital, Southern Medical University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hepatitis B, Chronic focused on measuring Chronic Hepatitis B

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • 302 Military Hospital Of China
  • Beijing Ditan Hospital
  • BeiJing YouAn Hospital ,Capital Medical University
  • Department of infectious disease, First Hospital of Peking University
  • People's Hospital of Beijing University
  • The Second Affiliated of ChongQing University of Medical Science
  • Department of Infectious Disease, Nanfang Hospital
  • No. 8 People's Hospital In GuangZhou
  • The Third Hospital of Sun Yat-Sen University
  • Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
  • Xiangya Hospital Central-South Univrsity
  • No.81 Hospital of PLA
  • First Hospital .Jilin Unniversity
  • ShengJing Hospital of China Medical University
  • JiNan Infectious Diseases Hospital
  • Changhai Hospital affiliated to Second Military Medical University
  • Huashan Hospital，Fudan University
  • Shanghai Ruijin Hospital
  • Tangdu Hospital
  • The First Affiliated Hospital of College of Medicine, Zhejiang University

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

Other

Arm Label

Off-treatment

On-treatment

Arm Description

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.

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.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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

Full Information

First Posted
June 27, 2016
Last Updated
July 4, 2016
Sponsor
Nanfang Hospital, Southern Medical University
Collaborators
Major Science and Technology Special Project of China Twelfth-Five-Year Project, Novartis
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1. Study Identification

Unique Protocol Identification Number
NCT02826070
Brief Title
EFFORT Further Extension Study
Official Title
Efficacy of Long-term Telbivudine Treatment on Histological Improvements in Patients With Chronic Hepatitis B (EFFORT Further Extension Study)
Study Type
Interventional

2. Study Status

Record Verification Date
June 2016
Overall Recruitment Status
Unknown status
Study Start Date
April 2015 (undefined)
Primary Completion Date
October 2016 (Anticipated)
Study Completion Date
October 2017 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Nanfang Hospital, Southern Medical University
Collaborators
Major Science and Technology Special Project of China Twelfth-Five-Year Project, Novartis

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hepatitis B, Chronic
Keywords
Chronic Hepatitis B

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
130 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Off-treatment
Arm Type
Other
Arm Description
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.
Arm Title
On-treatment
Arm Type
Other
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Telbivudine
Intervention Description
Telbivudine, 600mg, oral, daily
Intervention Type
Drug
Intervention Name(s)
Adefovir dipivoxil
Intervention Description
Adefovir dipivoxil 10mg, oral, daily
Intervention Type
Other
Intervention Name(s)
off-treatment follow-up
Primary Outcome Measure Information:
Title
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 Outcome Measure Information:
Title
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
Title
Percentage of patients with HBeAg loss or HBeAg seroconversion at week 48 and 96 in on-treatment group
Time Frame
week 48, week 96
Title
Percentage of patients with HBsAg loss or HBsAg seroconversion at week 48 and 96 in on-treatment group
Time Frame
week 48, week 96
Title
The percentage of patients with alanine aminotransferase (ALT) normalization at week 48 and 96 in on-treatment group
Time Frame
week 48, week 96
Title
Percentage of patients with HBV DNA breakthrough at week 48 and 96 in on-treatment group
Time Frame
week 48, week 96
Title
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
Title
Incidence of adverse effect at week 48 and 96 in on-treatment group
Time Frame
week 48, week 96
Title
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
Title
Sustained response rate of durability of HBeAg seroconversion at week 48 and 96 in off-treatment group
Time Frame
week 48, week 96
Title
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
Title
Incidence of abnormal laboratory examination at week 48 and 96 in on-treatment group
Time Frame
week 48, week 96
Title
Percentage of hepatitis flare at week 48 and 96 in off-treatment group
Time Frame
week 48, week 96

10. Eligibility

Sex
All
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients who completed EFFORT extension study. Patients who had baseline (that is the week 0 of EFFORT study) HBV DNA <9 Log copies/mL and ALT ≥2×ULN. Patients who are willing to participate in the further extension study. Patient is willing and able to comply with the study drug regimen and all other study requirements. Patients must give written informed consent before any assessment is performed. Exclusion Criteria: 1. Poor compliance judged by investigators
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Jinlin Hou
Organizational Affiliation
Nanfang Hospital, Southern Medical University
Official's Role
Principal Investigator
Facility Information:
Facility Name
302 Military Hospital Of China
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Beijing Ditan Hospital
City
Beijing
State/Province
Beijing
Country
China
Facility Name
BeiJing YouAn Hospital ,Capital Medical University
City
Beijing
State/Province
Beijing
Country
China
Facility Name
Department of infectious disease, First Hospital of Peking University
City
Beijing
State/Province
Beijing
Country
China
Facility Name
People's Hospital of Beijing University
City
Beijing
State/Province
Beijing
Country
China
Facility Name
The Second Affiliated of ChongQing University of Medical Science
City
Chongqing
State/Province
Chongqing
Country
China
Facility Name
Department of Infectious Disease, Nanfang Hospital
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
No. 8 People's Hospital In GuangZhou
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
The Third Hospital of Sun Yat-Sen University
City
Guangzhou
State/Province
Guangdong
Country
China
Facility Name
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology
City
Wuhan
State/Province
Hubei
Country
China
Facility Name
Xiangya Hospital Central-South Univrsity
City
Changsha
State/Province
Hunan
Country
China
Facility Name
No.81 Hospital of PLA
City
Nanjing
State/Province
Jiangsu
Country
China
Facility Name
First Hospital .Jilin Unniversity
City
Changchun
State/Province
Jilin
Country
China
Facility Name
ShengJing Hospital of China Medical University
City
Shengyang
State/Province
Liaoning
Country
China
Facility Name
JiNan Infectious Diseases Hospital
City
Jinan
State/Province
Shandong
Country
China
Facility Name
Changhai Hospital affiliated to Second Military Medical University
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Huashan Hospital，Fudan University
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Shanghai Ruijin Hospital
City
Shanghai
State/Province
Shanghai
Country
China
Facility Name
Tangdu Hospital
City
XiAn
State/Province
Shanxi
Country
China
Facility Name
The First Affiliated Hospital of College of Medicine, Zhejiang University
City
Hangzhou
State/Province
Zhejiang
Country
China

12. IPD Sharing Statement

Plan to Share IPD
Undecided

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