Safety, Tolerability, and PK of AH-008 Following Single Ascending Dose in Healthy Subjects

Inclusion criteria

• Age range: 18 to 65 years.
• Body Mass Index (BMI) between 19 and 32 kg/m² (inclusive). Males: Body weight ≥ 50 kg; Females: Body weight ≥ 40 kg
• Subjects understand and agree to comply with planned study procedures, can communicate well with the Investigator, understand the requirements of the study, and have provided written informed consent.
• Subject is considered healthy, in the opinion of the Investigator, based on a detailed medical history, complete physical examination, vital signs, 12-lead ECG, and safety laboratory tests evaluation.
• Female of non-childbearing potential (FONCBP) are considered inclusionary provided they meet one of the following criteria regarding non-childbearing potential: (A) Permanently sterile: Permanent and irreversible infertility via documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy. (B) Postmenopausal: Defined as 12 months of spontaneous amenorrhea. In questionable cases, a blood test with Follicle Stimulating Hormone (FSH) levels \>40 mIU/mL at Screening will be used to confirm postmenopausal status.
• Male subjects are considered inclusionary provided they meet one of the following criteria regarding reproductive potential and partner status: (A) Partners of Non-Childbearing Potential: Male subjects with female partners of non-childbearing potential (defined as surgically sterile via hysterectomy, bilateral salpingectomy, or bilateral oophorectomy; or confirmed postmenopausal for at least 12 months) are eligible and are not required to use additional contraception. (B) Partners Using Effective Contraception: Male subjects with female partners of childbearing potential who are already utilizing a highly effective contraceptive method (failure rate of \<1% per year) are eligible and are not required to use condoms or other barriers, unless the partner is currently pregnant. (C) Vasectomized Males: Males who have undergone a successful vasectomy (at least 3 months prior to dosing) are eligible without further contraceptive requirements.

Exclusion criteria

• A history of any clinically serious illness, such as circulatory system, endocrine system, nervous system, digestive system, respiratory system, hematology, renal, immunology, psychiatry, and metabolic abnormalities, or any other disease or physiological condition that, in the investigator's judgment may interfere with test results or pose an undue safety risk.
• A history of autoimmune disease, spinal trauma, and various demyelinating diseases, including acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome).
• In the opinion of the investigator, A history of multiple episodes or severe allergies (e.g., food, drug allergy), or has had anaphylactic reaction or significant intolerance to prescription drugs, over-the-counter drugs or foods.
• Human Immunodeficiency Virus-Antibody (HIV-Ab), Hepatitis B Surface Antigen (HBsAg) or Hepatitis C Virus-Antibody (HCV-Ab) serologically positive at Screening.
• Surgery within 4 weeks prior to Screening or planned to have surgery during the trial period.
• Use of any prescription medicine, over-the-counter drug, herbal medicine, including herbal remedies such as St. John's wort, homeopathic and traditional medicines within 14 days or approximately 5 half-lives (whichever is longer) before the first dosing during the trial period, except for paracetamol/acetaminophen, ibuprofen, and hormonal contraceptives.
• Participation in any clinical trial and taking any investigational drug 30 days or approximately 5 half-lives (whichever is longer) before the first dosing.
• Subjects who have donated or experienced loss of \>500 mL of whole blood within 90 days prior to Screening, or donated plasma within 14 days prior to Screening, or received a transfusion of blood or blood products within 90 days prior to Screening.
• Special dietary requirements or cannot follow a uniform diet during the trial period.
• Consumption of excessive amounts of tea, coffee, and/or caffeinated beverages per day (more than 8 cups, 1 cup = 250 mL) within 6 months prior to the first dosing and during the trial period.
• Positive breath test for alcohol at Screening or at admission, heavy drinkers or regular drinkers within 90 days prior to Screening, i.e., drinking more than 14 units of alcohol per week (1 unit = 360 mL beer or 45 mL 40% spirits or 150 mL wine), or unable to stop using any alcoholic products during the trial period.
• Subjects who have smoked more than 5 cigarettes per day, used e-cigarettes or vaping products, or were unable to abstain from any tobacco or nicotine-containing products (including non-tobacco products such as nicotine patches, gum, or lozenges) in the 90 days prior to Screening and throughout the study.
• Drug abusers or those who had used soft drugs (e.g., marijuana) within 90 days prior to Screening or hard drugs (e.g., cocaine, phencyclidine, etc.) within 1 year prior to Screening, or who test positive for drugs at Screening or Baseline, will be excluded.
• Subjects with resting vital signs outside the following reference ranges at Screening or Baseline, unless deemed not clinically significant by the Investigator: \<90 mmHg or \>140 mmHg, diastolic pressure \<50 mmHg or \>90 mmHg; Pulse beat \<50 BPM or \>100 BPM, respiration \<12 times/minute or \>20 times/minute.
• Subjects with any clinically significant abnormality on 12-lead ECG or a QT interval corrected with the Fridericia formula (QTcF) \>450 milliseconds for females and \>430 milliseconds for males at Screening or Baseline.
• Subjects with conditions that can potentially reduce drug clearance (eg, renal or hepatic insufficiency) at Screening or Baseline. A. Alanine Aminotransferase (ALT) \> 1.5 x ULN B. Aspartate Aminotransferase (AST) \> 1.5 x ULN C. Alkaline phosphatase (ALP) \> ULN D. Glomerular filtration rate (GFR) \< 80 mL/min/1.73 m² as calculated by the CKD-EPI equation. E.Total Protein (TP) \> ULN F. Total Bilirubin (TBIL) \> 1.2 x ULN G. Gamma-Glutamyl Transferase \> ULN H. Lactate Dehydrogenase (LDH) \> ULN I. International Normalized Ratio (INR) \> 1.5 x ULN
• Subjects with significant bleeding or clotting diathesis, as judged by the investigator, that may interfere with venous blood collection or intravenous infusion.
• For females of childbearing potential (FOCBP): unwillingness to use a highly effective contraceptive method (method of birth control which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as implants, injectables, combined oral contraceptives, non-hormonal or hormonal intrauterine devices (IUDs), sexual abstinence or vasectomized partner) during sexual intercourse with a partner of childbearing potential throughout the trial and for 30 days after last dose.
• For male subjects who are not surgically sterile (vasectomy) for at least 3 months prior to dosing and who are sexually active with a female partner of childbearing potential (childbearing potential females are defined as women that are neither post-menopausal nor surgically sterile): unwillingness to simultaneously use a condom and a highly effective contraceptive method, as mentioned above, for the female partner throughout the trial and for 30 days after the last dose.
• Subjects may not be able to complete the study for other reasons or should not be included in the study as determined by the investigator.