This study is divided into two parts. Part A is a multicenter, randomized, double-blind, placebo controlled phase Ill clinical trial, designed to evaluate the efficacy and safety of ZM-H1505R in combination with NAs versus NAs monotherapy with HBV DNA ≥ 50 IU/mL and are HBeAg positive who have received NAs monotherapy for at least 12months.Part B is an open-label extension and follow-up period designed to evaluate the long-term safety and efficacy of ZM-H1505R in combination with NAs.

This study is divided into two parts. Part A is a multicenter, randomized, double-blind, placebo controlled phase Ill clinical trial, designed to evaluate the efficacy and safety of ZM-H1505R in combination with NAs versus NAs monotherapy with HBV DNA ≥ 50 IU/mL and are HBeAg positive who have received NAs monotherapy for at least 12months.Part B is an open-label extension and follow-up period designed to evaluate the long-term safety and efficacy of ZM-H1505R in combination with NAs.

- Part A (Double-Blind Treatment Period): Eligible subjects will be randomized in a 1:1 ratio into 2 groups. Group A:ZM-H1505R 100mg +NAs Group B:ZM-H1505R placebo +NAs Two randomization stratification factors were set: NAs type of ETV, TDF,TAF, or TMF (no less than 15% of ETV, TDF, and TAF); HBV DNA <2000 IU/mL and HBV DNA >2000 IU/mL . All subjects completed a 48-week efficacy and safety evaluation followed by an interim analysis, the results of which were used to submit an NDA application.

- Part B (Open-Label Extension Period): At the end of the 48-week randomized double-blind treatment period, all eligible subjects will transfer to the open-label extension period and were treated with ZM-H1505R 100 mg +NAs while the study drug was evaluated for efficacy and safety until the end of the 144 weeks.

- Follow-up Period: At the end of the 144-week open-label extension period, all subjects will continue to take NAs, as a monotherapy for a 4-week follow-up period for observation of efficacy and safety of after discontinuation of study drug in ZM-H1505R .

Inclusion Criteria:

• 1.Able to understand and sign the written informed consent form;
• 2.Adult males and females aged 18-65 years(inclusive) at screening;
• 3.Have been used NAs monotherapy with ETV(0.5 mg or 1.0mg, QD),TDF (300 mg, QD),TAF (25 mg, QD),or TMF (25 mg, OD)for at least 12 months at the time of enrollment; Have been on stable and continuous use of one of these medications for at least 6months, and do not plan to switch to any other NAs class of medications after entering this clinical trial;
• 4.Evidence of prior HBV infection (e.g., HBsAg and/or HBV DNA positive), or HBsAg positive at screening;
• 5.HBV DNA ≥50 IU/mL as measured by a local healthcare facility within 30 days prior to screening and HBV DNA ≥50 IU/mL as confirmed by central laboratory testing at the time of screening;
• 6.HBeAg positivity confirmed by central laboratory testing at screening;
• 7.Women of childbearing potential or males with female partners of childbearing potential must agree to voluntarily use the contraceptive methods specified in the protocol from screening to 28 days after the last dose of the study.

Exclusion Criteria:

• 1.Progressive fibrosis or cirrhosis detected at screening, or progressive fibrosis or cirrhosis defined as follows: Metavir ≥ 3 or Ishak fibrosis score ≥ 4 by liver biopsy within 1 year prior to screening; or in the absence of an appropriate liver biopsy, liver stiffness test (FibroScan) ≥ 9 kPa within 3 months prior to screening, or liver stiffness test (FibroTouch) ≥ 9.6 kPa(FibroScan preferred) ;

• 2.History of hepatocellular carcinoma (HCC); or serum alpha-fetoprotein (AFP) ≥ 50 ng/mL at screening, or imaging examination such as abdominal ultrasound, CT (computed tomography) or MRI (magnetic resonance imaging) suggesting possible HCC;

• 3.Subjects meeting any of the following clinical laboratory parameters at screening:

  1. Hemoglobin < 110 g/L (for males) or < 100 g/L (for females);
  2. Platelet count < 90 × 109/L;
  3. Neutrophil count < 1.5 × 109/L;
  4. Alanine aminotransferase (ALT) or Aspartate aminotransferase(AST)> 3 × upper limit of normal (×ULN);
  5. International normalized ratio (INR) of prothrombin time > 1.3;
  6. Albumin < 35 g/L;
  7. Total bilirubin > 2 × ULN, and direct bilirubin > 1.5 × ULN;
  8. Estimated glomerular filtration rate < 60 mL/min/1.73 m2(calculated using the CKD-MDRD formula).

• 4.Abnormal result of electrocardiogram (ECG) at screening and inappropriate for the study participation judged by the investigator; or QTcF (QT corrected using the Fridericia formula): > 450 ms for males, > 470 ms for females at screening;

• 5.Co-infection with human immunodeficiency virus (HIV), hepatitis A virus (HAV), hepatitis C virus (HCV), hepatitis D virus (HDV) or hepatitis E virus (HEV); Note: Subjects with positive HCV antibody (Ab) but negative HCV RNA and subjects with positive HEV immunoglobulin M (IgM) but negative HEV RNA will NOT be excluded.

• 6.Other malignancy unless the subject's malignancy has been cured by surgical resection (e.g., basal cell skin cancer); Note: Subjects who are suspected of having malignancy must be excluded regardless of evidence of local recurrence or metastasis.

• 7.History of chronic liver disease with a non-HBV etiology, such as alcoholic liver disease, autoimmune liver disease, hereditary liver disease, non-alcoholic fatty liver disease, except for simple fatty liver disease;

• 8.Other concurrent severe systemic diseases or clinical manifestations, for which the investigator considers not suitable to participate in this study;

• 9.Use of any investigational product or drug not approved by regulatory authorities within 3 months prior to screening;

• 10.History of persistent alcohol consumption (alcohol consumption exceeding 40 g ethanol for males or 20g ethanol for females per day on average) within 6 months prior to screening;

• 11.History of drug dependence or drug abuse;

• 12.Pregnant or breastfeeding women;

• 13.Known hypersensitivity to the active ingredient or formulation excipients of the investigational drug;

• 14.Inappropriate for the study participation for any reason not otherwise listed as judged by the investigator.