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

Official title

A Single-Center, Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics, Preliminary Efficacy, Drug Concentration-QTc Relationship, and Immunogenicity Profiles of Single and Multiple Doses of ACT201 Injection in Healthy Participants and Participants With Chronic Hepatitis B

Overview

This is a single-center, randomized, double-blind, placebo-controlled Phase I clinical trial consisting of two parts. Part 1 includes single ascending dose (SAD) and multiple ascending dose (MAD) cohorts conducted in healthy participants. Part 2 is a multiple ascending dose (MAD) trial enrolling HBeAg-negative chronic hepatitis B (CHB) participants with suppressed HBV DNA under stable nucleos(t)ide analog (NA) therapy.

Interventions

• Drug ACT201 Injection
  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.
• Drug ACT201 Injection Placebo
  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 outcome measures

• Safety: number of participants with adverse event (AE), serious adverse events (SAE) and clinically significant examination results. [Time frame: throughout the full study period,an average of 4 months]

Secondary outcome measures (12)

• Plasma drug concentrations in healthy participants and participants withCHB [Time frame: 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） [Time frame: throughout the full study period,an average of 4 months]
• Area Under the Concentration-Time Curve from time zero to infinity（AUC₀-∞） [Time frame: throughout the full study period,an average of 4 months]
• Apparent Volume of Distribution（Vd/F） [Time frame: throughout the full study period,an average of 4 months]
• First-order Elimination Rate Constant(Kel) [Time frame: throughout the full study period,an average of 4 months]
• Elimination Half-life(t₁/₂) [Time frame: throughout the full study period,an average of 4 months]
• Mean Residence Time(MRT) [Time frame: throughout the full study period,an average of 4 months]
• Apparent Clearance(CL/F) [Time frame: throughout the full study period,an average of 4 months]
• Minimum Plasma Concentration at Steady State(Cₘᵢₙ,ₛₛ) [Time frame: throughout the full study period,an average of 4 months]
• Maximum Plasma Concentration at Steady State(Cₘₐₓ,ₛₛ) [Time frame: throughout the full study period,an average of 4 months]
• Average Plasma Concentration at Steady State(Cₐᵥ,ₛₛ) [Time frame: 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) [Time frame: throughout the full study period,an average of 4 months]

Eligibility criteria

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Sequential

Masking

Double blind

Primary purpose

Treatment

Study locations

China · 1 center

• Huashan Hospital, Fudan University — Shanghai

Identifiers

NCT: NCT07741461 · ACT201-4-1-001

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗