EFFORT Further Extension Study

NCT02826070 — Phase 4, Unknown, 130 participants, Nanfang Hospital, Southern Medical University

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

Registry	NCT02826070
Status	Unknown
Phase	Phase 4
Study type	Interventional; non randomized, single group, masking: none, treatment
Enrollment	130 (Actual)
Sponsor	Nanfang Hospital, Southern Medical University (Other); collaborators: Major Science and Technology Special Project of China Twelfth-Five-Year Project, Novartis
Conditions	Hepatitis B, Chronic
Interventions	Telbivudine, Adefovir dipivoxil, off-treatment follow-up (Drug, other)
Dates	start 2015-04-01, primary completion 2016-10-01 (estimated), completion 2017-10-01 (estimated), first posted 2016-07-07, last updated 2016-07-07
Locations	20 sites in China

-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.

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+Arms and interventions

Arm	Type	Interventions	Description
Off-treatment	Other	Other: off-treatment follow-up	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.
On-treatment	Other	Drug: Telbivudine; Drug: Adefovir dipivoxil	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.

Telbivudine (Drug): Telbivudine, 600mg, oral, daily
Adefovir dipivoxil (Drug): Adefovir dipivoxil 10mg, oral, daily
off-treatment follow-up (Other)

+Outcome measures

Primary outcomes

Percentage of patients with histological improvement (≥2-point decrease in the Knodell necroinflammatory score and no worsening in Ishak fibrosis score). [Week 48]

Secondary outcomes

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

Sex: All

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

+Locations (20)

Facility	City	Country
302 Military Hospital Of China	Beijing, Beijing Municipality	China
Beijing Ditan Hospital	Beijing, Beijing Municipality	China
BeiJing YouAn Hospital ,Capital Medical University	Beijing, Beijing Municipality	China
Department of infectious disease, First Hospital of Peking University	Beijing, Beijing Municipality	China
People's Hospital of Beijing University	Beijing, Beijing Municipality	China
The Second Affiliated of ChongQing University of Medical Science	Chongqing, Chongqing Municipality	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	Guangzhou, Guangdong	China
Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology	Wuhan, Hubei	China
Xiangya Hospital Central-South Univrsity	Changsha, Hunan	China
No.81 Hospital of PLA	Nanjing, Jiangsu	China
First Hospital .Jilin Unniversity	Changchun, Jilin	China
ShengJing Hospital of China Medical University	Shengyang, Liaoning	China
JiNan Infectious Diseases Hospital	Jinan, Shandong	China
Changhai Hospital affiliated to Second Military Medical University	Shanghai, Shanghai Municipality	China
Huashan Hospital，Fudan University	Shanghai, Shanghai Municipality	China
Shanghai Ruijin Hospital	Shanghai, Shanghai Municipality	China
Tangdu Hospital	XiAn, Shanxi	China
The First Affiliated Hospital of College of Medicine, Zhejiang University	Hangzhou, Zhejiang	China

+Investigators

Jinlin Hou, Principal investigator, Nanfang Hospital, Southern Medical University