Safety, Tolerability, Pharmacokinetics(PK), Pharmacodynamics(PD) and Food Effect of HRS9950 in Healthy and CHB Subjects

Inclusion criteria

• Healthy subjects

• Signed informed consent.
• Aged 18~55.
• Body weight ≥ 50 kg for male; ≥ 45 kg for female, body mass index (BMI) between 18 to 28 kg/m2.
• Vital signs, physical examination, laboratory results are within normal range or considered not clinically significant.
• Female subjects (including partner) of childbearing potential must be using a medically acceptable form of birth control.
• CHB subjects

• Signed informed consent.
• Aged 18~65.
• CHB subjects should meet the following two criteria:

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• IgM HBcAb negative and HBsAg positive.
• Two recorded HBsAg positive, and the time interval between the two tests was at least 6 months, one of which was the result of this screening 4. Treatment-experienced CHB subjects should also meet the following criteria:

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• Have received nucleoside analogue treatment for at least 6 months
• HBeAg positive or negative, and the HBV DNA concentration should be less than 20 IU/mL for at least 6 months before enrollment
• Confirm ALT <1.5 ULN (upper limit of normal value) by two measurements within 6 months before enrollment 5. Treatment-naïve CHB subjects should also meet the following criteria:

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• Have not received antiviral therapy (nucleosides or interferons) at screening
• HBeAg positive or negative, and the HBV DNA concentration should be greater than 2000 IU/mL for at least 6 months before enrollment
• Confirm ALT> 1 ULN by two measurements within 6 months before enrollment 6. Female subjects (including partner) of childbearing potential must be using a medically acceptable form of birth control.

Exclusion criteria

• Healthy subjects

• Currently suffering from cardiovascular, liver, kidney, digestive, nervous, blood, thyroid or mental diseases.
• Medical history of malignant tumor.
• Have a digestive system disease or a medical history of severe digestive system disease.
• Have severe infection, severe trauma or major surgical operations within 3 months.
• 12-ECG test have clinical significant abnormality or the QT interval (QTc) > 450 ms.
• Clinical laboratory examinations or chest radiographs have clinical significant abnormality.
• Have a medical history of immune-mediated diseases.
• Screening for infectious diseases is positive (Including HBsAg, Anti-HCV, TPPA, Anti-HIV).
• Suspected allergy to any ingredient in the study drug.
• Have any drug that inhibits or induces liver metabolism within 1 month.
• Take any prescription drugs, over-the-counter drugs and Chinese herbal medicines within 14 days before taking the study drug, or took any drugs within 5 half-lives at the time of screening; plan to take other drugs during the test period.
• Participated in clinical trials of any drug or medical device within 3 months before screening, or within 5 half-lives before screening.
• Had donated blood or blood transfusion in 8 weeks or ≥ 400 mL within 3 months prior to screening or ≥ 200 mL within 1 months.
• The average daily smoking ≥ 5 cigarettes within three months; the average daily alcohol intake in a month exceeds 15 g (15 g alcohol is equivalent to 450 mL beer or 150 mL wine or 50 mL low-alcohol);
• Keep smoking, drinking alcohol or consuming caffeinated foods or beverages (more than 8 cups, 1 cup = 250 mL) 2 days before taking the study drug and during the study; and those who have special dietary requirements and cannot follow the unified diet;
• Pregnant or lactating women;
• Drug screening or alcohol breath test is positive.
• Other conditions that the investigator believes the subject is not suitable.
• CHB subjects

• Currently suffering from serious cardiovascular, liver, kidney, digestive, nervous, blood, thyroid or mental diseases other than hepatitis B.
• People have acute or chronic liver disease by non-HBV infection.
• Liver stiffness (LSM)> 12.4 kPa by noninvasive transient liver elastography (eg Fibroscan®) or recorded liver biopsy suggesting cirrhosis or extensive fibrosis
• Primary liver cancer, high-risk groups of primary liver cancer or AFP> 50g/L;
• Have clinically demonstrated or history of liver function decompensation, including but not limited to: hepatic encephalopathy, hepatorenal syndrome, splenomegaly, ascites, etc.;
• Laboratory inspection:

• Platelet count <90×109/L;
• White blood cell count <3.0×109/L;
• Absolute value of neutrophils <1.5×109/L;
• Serum total bilirubin>2×ULN;
• Albumin <30 g/L;
• Creatinine clearance rate ≤60ml/min;
• INR>1.5;
• ALT exceeds 5 times the upper limit of normal value on screening/baseline visit
• HIV and/or syphilis antibody positive
• Subjects who have previously received organ/bone marrow transplantation;
• Have used immunosuppressants, immunomodulators or cytotoxic drugs within 6 months before the study medication;
• Suspected allergy to any ingredient in the study drug.
• The average daily smoking ≥ 5 cigarettes within three months; the average daily alcohol intake in a month exceeds 15 g (15 g alcohol is equivalent to 450 mL beer or 150 mL wine or 50 mL low-alcohol);
• Keep smoking, drinking alcohol or consuming caffeinated foods or beverages (more than 8 cups, 1 cup = 250 mL) 2 days before taking the study drug and during the study; and those who have special dietary requirements and cannot follow the unified diet;
• Pregnant or lactating women;
• Drug screening or alcohol breath test is positive.
• Other conditions that the investigator believes the subject is not suitable.