A Clinical Study of APG-1387 in Combination With Entecavir in Patients With Chronic Hepatitis B

Inclusion Criteria:

• Body mass index (BMI) within the range of 18 - 27.9
• Documented chronic HBV infection (e.g., HBsAg positive for at least 6 months).
• HBeAg-positive or HBeAg-negative
• Treatment-naïve and treatment-experienced subjects are required to:

1. Treatment-naïve subjects:

• No antiviral therapies including nucleos(t)ide analogues or immunomodulatorssuch as interferon within 180 days prior to screening
• HBV DNA ≥ 2x10˄3 IU/mL for HBeAg negative subjects and ≥ 2x10˄4 IU/mL forHBeAg positive subjects (PCR)
• Alanine transaminase (ALT) ≥ upper limit of normal (ULN) and < 10 × ULN (andexcluding ALT elevation caused by non-HBV reasons such as drug or alcoholconsumption)

2. Treatment-experienced subjects:

• Using entecavir > 180 days prior to screening, and should continue thetreatment regimen until enrolled into the study
• HBV DNA less than the lower limit of quantification (LLOQ) or < 20 IU/mL (PCR)
• ALT < 1.5 × ULN
• Adequate hematological function:
• White blood cell count (WBC) ≥ 3.5 × 10˄9/L
• Hemoglobin ≥ 120 g/L for males and ≥ 110 g/L for females
• Platelet count ≥ 100 × 10˄9/L
• Adequate renal and liver function:
• Serum creatinine ≤ 1×ULN
• Serum albumin ≥ 35.0g/L
• Urine protein is negative or 1 + (re-examination is required when 1 + or 24-hoururine protein quantification is added when necessary. If it turns negative or iswithin the normal range, it can be included)
• Estimated creatinine clearance (CLCr) ≥ 50 mL/min based on serum creatininemeasured at the screening assessment and actual body weight (calculatedcreatinine clearance by the Cockcroft-Gault formula)
• Total bilirubin ≤1.5×ULN
• International normalized ratio (INR) ≤ 1.5×ULN
• Alkaline phosphatase ≤ 2.5×ULN
• Female subjects of childbearing potential should have a negative serum pregnancy testwithin 7 days prior to the first dose
• Subjects and theirs partners are willing to use effective contraception as defined inthe protocol during the treatment and for at least 6 months after the last dose ofstudy drug
• Ability to understand and willingness to sign a written informed consent form (theconsent form must be signed by the subject prior to any study-specific procedures)
• Willingness and ability to comply with study procedures and follow-up examination

Exclusion Criteria:

• Co-infection with HIV, hepatitis C virus (HCV), or hepatitis delta virus (HDV); orother active and severe infections
• Syphilis with positive antibody for treponema pallidum
• Subjects with liver disease other than hepatitis B, including but not limited tochronic alcoholic hepatitis, drug-induced liver injury, autoimmune liver disease,hereditary liver disease (such as Wilson's disease), and active hepatitis due to othercauses
• History or manifestation of hepatic decompensation (e.g., Child-Pugh Class B or C, orhistory of ascites, gastrointestinal bleeding, hepatic encephalopathy, or spontaneousbacterial peritonitis)
• Progressive fibrosis/cirrhosis, defined by liver fibrosis scan ≥ 12 kilopascal (kPa)at screening, or cirrhosis diagnosed by imaging examinations, or Metavir score F3, F4fibrosis on liver biopsy at any time
• Clinically diagnosed hepatocellular carcinoma, or diagnosis of hepatocellularcarcinoma cannot be excluded, or serum alpha-fetoprotein greater than 50 μg/L
• History of malignancy (except cured and no evidence of recurrence of basal cellcarcinoma of the skin or situ cervical cancer) or lymphoproliferative disease
• History of neurological or mental disorders, such as epilepsy, dementia, and poorcompliance
• Uncontrolled primary diseases of other important organs, such as clear medical historyof nervous system, cardiovascular system, urinary system (including chronic orintermittent urinary system diseases), digestive system, respiratory system,endocrine/metabolic and musculoskeletal system, such as poorly controlled diabetes,hypertension, etc., making the investigator consider the subject unsuitable
• QTcB [QTcB = QT/(RR^ 0.5); RR is the normalized heart rate value, obtained by dividing 60 by heart rate in seconds; other parameters in milliseconds] > 450 milliseconds formen and > 470 milliseconds for women; any clinically important abnormality in therhythm, conduction, or morphology of the resting electrocardiogram (ECG) (e.g.,complete left bundle branch block, third degree heart block, second degree heartblock); congenital long QT syndrome or family history of long QT syndrome
• History of alcoholism (mean daily intake of ethanol ≥ 30 g (male) or ≥ 20 g (female)within 1 year), and drug abuse
• Subjects planning to become pregnant within 1 year, who are pregnant or breastfeeding
• Received or may receive continuous treatment with immunomodulators (e.g., steroids) orbiological agents (e.g., monoclonal antibodies, interferons) within 3 months beforescreening
• Participated in clinical trials within 3 months before screening
• Trauma or major surgical operation within 4 weeks before screening
• Previous treatment with inhibitors of apoptosis proteins
• Any subject considered unsuitable for the trial by the investigator