This is an open label, randomized, multi-center, comparative study. Subjects will be screened prior to study entry to establish eligibility. 60 Subjects who meet all the selection criteria will be randomly assigned to (A) QL007 200mg BID+ Tenofovir dipirofurate fumarate （TDF）300 mg QD, (B) QL007 200 mg BID+ Entecavir 0.5 mg QD, (C)TDF 300 mg QD, (D) Entecavir 0.5 mg QD.

The purpose of this study was to evaluate the efficacy and safety of QL-007 tables in combination with TDF or Entecavir in patients with chronic hepatitis b who have received nucleoside (acid) therapy, and to recommend a reasonable regimen for phase III study.

The subjects received the drug treatment for a maximum of 96 weeks: divided into two stages: the first stage: 0-24 weeks as the core treatment period, 25-48 weeks as the extended treatment period. The second stage: 49-96 weeks is the extended treatment period. Stage 2: subjects in stage 1 group A and C were grouped into group E(QL-007 200 mg BID或XX mg +TDF 300 mg QD), and subjects in group B and D were grouped into group F(QL-007 200 mg BID或XX mg + Entecavir 0.5 mg QD). Subjects in group E and F entered the second stage of treatment according to 200 mg BID. After the efficacy data of the original treatment clinical trial (protocol 201) determine the optimal dose of 007, all subjects entering the second phase will receive the optimal dose of 007 and continue treatment withTDF or Entecavir tablets (007 XXmg+TDF or ETV) into the second phase 49-96 weeks of extended treatment.

Inclusion Criteria:

1. Patients aged 18-70 years (inclusive) with chronic HBV infection prior to baseline;
2. Subjects who have received a entecavir or tenofovir ester treatment for more than 1 year before screening ;
3. HBsAg > 250 IU/mL and HBV DNA < 60 IU/mL at screening period;
4. ALT≤ 2×ULN;
5. Participants must have understood and signed the ICF.

Exclusion Criteria:

1. Confirmed co-infection with human immunodeficiency virus (HIV), hepatitis C virus (HCV) or hepatitis D virus (HDV);

2. History of liver disease other than chronic hepatitis B;

3. History of Gilbert's Disease;

4. History of decompensated liver disease or any sign of decompensated liver disease at the screening period;

5. Evidence of moderate or severe fibrosis or cirrhosis;

6. Evidence of HCC or AFP > 50 ng/ml at the screening period.

7. Any Clinical laboratory values meet the certain standards at the screening period;

8. Subjects have clinically significant, uncontrolled heart disease and/or recent cardiac event;

9. Risks of serious kidney and respiratory diseases;

10. Impaired gastrointestinal (GI) function or GI disease that may alter absorption of QL-007 as determined by the Investigator;

11. Receiving medications that meet one of the following criteria and that cannot be discontinued ≥1 week prior to the start of treatment QL-007:

    • Medication with a known risk of prolonging the QT interval or inducing Torsades de Pointes;
    • Moderate or strong inhibitors or strong inducers of CYP3A4

12. Intake of any drugs that can reduce enzyme activity;

13. History of bleeding diathesis;

14. Risks of mental and nervous system diseases during screening;

15. Pregnant or lactating female subjects; Female subjects of childbearing age who were not willing to use effective contraception throughout the study period or male subjects whose partners were fertile but were not willing to use effective contraception;

16. Volunteers who took an Investigational Product within 3 months or who have been within 5 half-lives of other trial drugs before the randomization;

17. Any other condition , which in the opinion of investigator would make a patient unfit for participation in a clinical study.