Chronic Hepaititis B
Conditions
Keywords
Chronic Hepaititis B, ACT201 Injection
Brief summary
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
DRUGACT201 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.
DRUGACT201 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.
Sponsors
Xiamen Amoytop Biotech Co., Ltd.
Huashan Hospital
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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 |
Countries
China
Contacts
CONTACTJing Zhang, Ph.D.
CONTACTWenhong Zhang, Ph.D.
PRINCIPAL_INVESTIGATORJing Zhang, Ph.D.
Huashan Hospital
PRINCIPAL_INVESTIGATORWenhong Zhang, Ph.D.
Huashan Hospital
Outcome results
None listed