ACT201 Injection in Healthy Participants and Participants With Chronic Hepatitis B (CHB)

• ACT201 Injection (Drug): Part 1 SAD (Single Ascending Dose): Single-dose subcutaneous injection per assigned dose group. Part 1 MAD (Multiple Ascending Dose) and Part 2: Subcutaneous injection per assigned dose group; treatment duration shall follow the study protocol.
• ACT201 Injection Placebo (Drug): Part 1 SAD (Single Ascending Dose): Single-dose subcutaneous injection administered per assigned dose group. Part 1 MAD (Multiple Ascending Dose) and Part 2: Subcutaneous injection administered per assigned dose group; the treatment duration shall comply with the study protocol.

Primary outcomes

• Safety: number of participants with adverse event (AE), serious adverse events (SAE) and clinically significant examination results. [throughout the full study period,an average of 4 months]: Assessments include vital signs, physical examinations, laboratory tests, and 12-lead electrocardiograms (ECGs).

Secondary outcomes

• Plasma drug concentrations in healthy participants and participants withCHB [throughout the full study period,an average of 4 months]
• Area Under the Concentration-Time Curve from time zero to the last measurable concentration（AUC₀-ₜ） [throughout the full study period,an average of 4 months]
• Area Under the Concentration-Time Curve from time zero to infinity（AUC₀-∞） [throughout the full study period,an average of 4 months]
• Apparent Volume of Distribution（Vd/F） [throughout the full study period,an average of 4 months]
• First-order Elimination Rate Constant(Kel) [throughout the full study period,an average of 4 months]
• Elimination Half-life(t₁/₂) [throughout the full study period,an average of 4 months]
• Mean Residence Time(MRT) [throughout the full study period,an average of 4 months]
• Apparent Clearance(CL/F) [throughout the full study period,an average of 4 months]
• Minimum Plasma Concentration at Steady State(Cₘᵢₙ,ₛₛ) [throughout the full study period,an average of 4 months]
• Maximum Plasma Concentration at Steady State(Cₘₐₓ,ₛₛ) [throughout the full study period,an average of 4 months]
• Average Plasma Concentration at Steady State(Cₐᵥ,ₛₛ) [throughout the full study period,an average of 4 months]
• Area Under the Concentration-Time Curve over one dosing interval at steady state(AUC₀-τ) [throughout the full study period,an average of 4 months]
• Degree of Fluctuation (DF) [throughout the full study period,an average of 4 months]
• Accumulation Factor (Rac) [throughout the full study period,an average of 4 months]
• Urinary Concentration [throughout the full study period,an average of 4 months]
• Cumulative Amount Excreted in Urine [throughout the full study period,an average of 4 months]
• Cumulative Percentage of Dose Excreted in Urine [throughout the full study period,an average of 4 months]
• Renal Clearance(CL) [throughout the full study period,an average of 4 months]
• HBsAg and HBsAb levels and changes from baseline among participants with CHB [throughout the full study period,an average of 4 months]
• HBsAg seroclearance rate among participants with CHB [throughout the full study period,an average of 4 months]
• HBsAg seroconversion rate among participants with CHB [throughout the full study period,an average of 4 months]
• Placebo-corrected baseline-adjusted ΔQTc (ΔΔQTc) among healthy participants [throughout the full study period,an average of 4 months]
• Anti-drug antibody (ADA) positive rate among healthy participants and participants with CHB [throughout the full study period,an average of 4 months]
• Antibody titers among healthy participants and participants with CHB [throughout the full study period,an average of 4 months]

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

Part 1:

* Participants fully understand the purpose, nature and methods of the trial as well as potential adverse events, voluntarily participate in this trial and provide written informed consent;
* Aged between 18 and 55 years old (inclusive) at the time of informed consent, male or female;
* Body mass index meets specified criteria;
* Physical examination, vital signs, laboratory tests, electrocardiogram and imaging examinations at screening are normal or abnormalities are considered clinically insignificant;
* Participants (including their partners) are willing to use effective contraceptive measures from screening through 6 months after the last administration of investigational product, with no plans for pregnancy, sperm donation or oocyte donation.

Part 2:

* Participants fully understand the purpose, nature and methods of the trial as well as potential adverse events, voluntarily participate in this trial and provide written informed consent;
* Aged between 18 and 65 years old (inclusive) at the time of informed consent, male or female;
* Body mass index meets specified criteria;
* HBsAg-positive or HBV DNA-positive for at least 6 months, or previous liver biopsy confirming chronic HBV infection;
* Receiving stable nucleos(t)ide analogue (NA) therapy at screening, with no planned changes to NA regimen during the trial;
* Serum ALT ≤ 2 × ULN at screening; HBeAg, HBV DNA and HBsAg levels meet protocol-specified criteria;
* Participants (including their partners) are willing to use effective contraceptive measures from screening through 6 months after the last administration of investigational product, with no plans for pregnancy, sperm donation or oocyte donation.

Exclusion Criteria:

Part 1:

* Known or suspected hypersensitivity to ACT201 or its excipients; or participants with allergic diathesis (multiple drug and food allergies judged clinically significant by the Investigator).
* History of clinically significant diseases involving cardiovascular, hematologic and lymphatic, urinary, endocrine, immune, psychiatric, or nervous systems (e.g., epilepsy).
* Vital signs or laboratory examinations at screening meet the exclusion cut-off values specified in the protocol.
* Use of any prescription drugs, over-the-counter medications, vitamin products or herbal medicines within 2 weeks prior to the first dose (topical medications with local effects are excluded).
* Positive HBsAg, hepatitis B core antibody, hepatitis C antibody, human immunodeficiency virus antibody, or Treponema pallidum antibody at screening.
* QTcF interval (QT corrected by Fridericia's formula) > 450 ms at screening.
* Daily cigarette consumption exceeding 5 cigarettes within 3 months before screening.
* History of drug abuse or illicit drug use within 1 year before screening, or positive urine drug screen at screening.
* History of alcohol abuse within 6 months before screening (14 alcohol units per week: 1 unit = 285 mL beer with \~3.5% alcohol, or 25 mL spirits with \~40% alcohol, or 100 mL wine with \~10% alcohol), or positive breath alcohol test at screening.
* Vaccination administered within 1 month before screening, or planned vaccination during the trial period.
* Blood loss or blood donation ≥ 400 mL within 3 months before screening (menstrual bleeding in female participants excluded), or planned blood donation during the trial period.
* Female participants who are breastfeeding or have a positive serum pregnancy test at screening.
* Participation in any clinical trial with an investigational medicinal product/investigational device within 3 months before screening or within 5 half-lives (whichever is longer).
* Any other condition deemed unsuitable for trial participation by the Investigator.

Part 2：

* Major trauma or major surgery within 3 months before screening; or planned surgery during the trial period that may impair trial compliance or safety assessment as assessed by the Investigator.
* Uncontrolled and clinically significant abnormalities other than chronic HBV infection, such as acute cerebrovascular disease, severe or unstable cardiac disease, uncontrolled diabetes, uncontrolled hypertension, uncontrolled dyslipidemia, etc.
* History of other clinically significant liver diseases.
* History of liver cirrhosis or progressive liver fibrosis; or liver stiffness measurement (LSM) ≥ 8.5 kPa at screening.
* Alpha-fetoprotein > 50 ng/mL, or imaging suggestive of possible malignant hepatic lesions.
* Past or current manifestations of hepatic decompensation.
* History of extrahepatic diseases potentially related to HBV immune status.
* History of vasculitis; or signs/symptoms suggestive of underlying vasculitis; or past/current other diseases potentially associated with vasculitic disorders.
* Active infection requiring systemic antiviral or antibacterial treatment at screening, excluding HBV infection.
* History of malignant tumors within 5 years before screening, except for specific curable cancers resected surgically.
* Prior solid organ or bone marrow transplantation.
* Use of systemic immunosuppressants within 3 months before the first dose of investigational product \[short-term (≤7 days) glucocorticoids for prophylaxis or treatment of non-autoimmune diseases excluded\]; use of immunomodulators or cytotoxic agents within 6 months before the first dose of investigational product.
* Receipt of any oligonucleotide or small interfering RNA (siRNA) therapy within 12 months before the first dose of investigational product.
* Coexisting indication for anticoagulant therapy or anticipated requirement for anticoagulation during the trial.
* Any of the following laboratory results at screening, or other clinically significant abnormalities rendering the participant unsuitable for trial participation:

Platelet count < 125 × 10\^9/L Absolute neutrophil count < 1.5 × 10\^9/L Hemoglobin < 100 g/L Total bilirubin > 1.25 × ULN Serum albumin < 35 g/L Estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m\^2 (calculated using the CKD-EPI formula) Prothrombin time international normalized ratio (INR) > 1.25 Positive hepatitis C antibody, human immunodeficiency virus antibody, or Treponema pallidum antibody

* QTcF interval (QT corrected by Fridericia's formula) > 450 ms at screening, or other clinically significant electrocardiogram abnormalities identified at screening.
* Known or suspected hypersensitivity to ACT201 or its excipients; or participants with allergic diathesis (multiple drug and food allergies judged clinically significant by the Investigator).
* Daily cigarette consumption exceeding 5 cigarettes within 3 months before screening.
* History of drug abuse or illicit drug use within 1 year before screening, or positive urine drug screen at screening.
* History of alcohol abuse within 6 months before screening, or positive breath alcohol test at screening.
* Vaccination administered within 1 month before screening, or planned vaccination during the trial period.
* Blood loss or blood donation ≥ 400 mL within 3 months before screening (menstrual bleeding in female participants excluded), or planned blood donation during the trial period.
* Female participants who are breastfeeding or have a positive serum pregnancy test at screening.
* Participation in any clinical trial with an investigational medicinal product/investigational device within 3 months before screening or within 5 half-lives (whichever is longer).
* Any other condition deemed unsuitable for trial participation by the Investigator.

• Jing Zhang, Ph.D., Principal investigator, Huashan Hospital
• Wenhong Zhang, Ph.D., Principal investigator, Huashan Hospital