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

Официальное название

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

Обзор

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.

Вмешательства

• Препарат 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.
• Препарат 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.

Первичные конечные точки

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

Вторичные конечные точки (12)

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

Критерии участия

Критерии включения

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.

Критерии исключения

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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Да

Дизайн исследования

Распределение

Рандомизированное

Модель

Последовательный дизайн

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

Китай · 1 центр

• Huashan Hospital, Fudan University — Шанхай

Идентификаторы

NCT: NCT07741461 · ACT201-4-1-001

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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