EFFORT Further Extension Study

Sponsor

Nanfang Hospital of Southern Medical University (Other)

Overall Status

Unknown status

CT.gov ID

NCT02826070

Collaborator

Major Science and Technology Special Project of China Twelfth-Five-Year Project (Other), Novartis (Industry)

130

Enrollment

Locations

Arms

Duration (Months)

6.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B, Chronic	Drug: Telbivudine Drug: Adefovir dipivoxil Other: off-treatment follow-up	Phase 4

Study Design

Study Type:

Interventional

Actual Enrollment :

130 participants

Allocation:

Non-Randomized

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Apr 1, 2015

Anticipated Primary Completion Date :

Oct 1, 2016

Anticipated Study Completion Date :

Oct 1, 2017

Arms and Interventions

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

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

Outcome Measures

Primary Outcome Measures

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

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]

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

Poor compliance judged by investigators

Contacts and Locations

Locations

	Site	City	State	Country
1	302 Military Hospital Of China	Beijing	Beijing	China
2	Beijing Ditan Hospital	Beijing	Beijing	China
3	BeiJing YouAn Hospital ,Capital Medical University	Beijing	Beijing	China
4	Department of infectious disease, First Hospital of Peking University	Beijing	Beijing	China
5	People's Hospital of Beijing University	Beijing	Beijing	China
6	The Second Affiliated of ChongQing University of Medical Science	Chongqing	Chongqing	China
7	Department of Infectious Disease, Nanfang Hospital	Guangzhou	Guangdong	China
8	No. 8 People's Hospital In GuangZhou	Guangzhou	Guangdong	China
9	The Third Hospital of Sun Yat-Sen University	Guangzhou	Guangdong	China
10	Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology	Wuhan	Hubei	China
11	Xiangya Hospital Central-South Univrsity	Changsha	Hunan	China
12	No.81 Hospital of PLA	Nanjing	Jiangsu	China
13	First Hospital .Jilin Unniversity	Changchun	Jilin	China
14	ShengJing Hospital of China Medical University	Shengyang	Liaoning	China
15	JiNan Infectious Diseases Hospital	Jinan	Shandong	China
16	Changhai Hospital affiliated to Second Military Medical University	Shanghai	Shanghai	China
17	Huashan Hospital，Fudan University	Shanghai	Shanghai	China
18	Shanghai Ruijin Hospital	Shanghai	Shanghai	China
19	Tangdu Hospital	XiAn	Shanxi	China
20	The First Affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou	Zhejiang	China