A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Subcutaneous Injection of ART101 Injection in Healthy Adult Subjects
A Phase I Clinical Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of a Single Subcutaneous Injection of ART101 Injection in Healthy Adult Subjects
This is a Phase I clinical study, which is a randomized, double-blind, placebo-controlled, single-dose, dose-escalation study. The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of a single subcutaneous injection of ART101 injection in healthy adult subjects.
This study is planned to include 5 dose groups, with an estimated maximum sample size of approximately 40 subjects. To reduce the safety risk to subjects, a sentinel method will be used in Dose Group 1, where 2 subjects (1 receiving the investigational drug and 1 receiving placebo) will be enrolled first, followed by 6 subjects (5 receiving the investigational drug and 1 receiving placebo). There will be at least a 7-day interval between the administration to the sentinel subjects and the other subjects in Dose Group 1. Subjects in each dose group will receive a single subcutaneous injection of ART101 injection or placebo on Day 1 after at least 8 hours of fasting.
Group 1 Single subcutaneous injection 25 mg (N=6) Placebo (N=2) Group 2 Single subcutaneous injection 75 mg (N=6) Placebo (N=2) Group 3 Single subcutaneous injection 150 mg (N=6) Placebo (N=2) Group 4 Single subcutaneous injection 300 mg (N=6) Placebo (N=2) Group 5 (Optional) Single subcutaneous injection ≤600 mg (N=6) Placebo (N=2) The study procedures include a screening period, a treatment period, a follow-up period, and an early termination/study completion follow-up.
The clinical trial was conducted by the Suzhou branch of Suzhou Arnatar Therapeutics Co., Ltd in China.
Inclusion Criteria:
1. Aged 18 to 60 years (inclusive) at the time of signing the informed consent form (ICF), male or female.
2. Generally good health, with no clinically significant abnormalities in vital signs, physical examination, laboratory tests, or 12-lead ECG results at screening.
3. Male subjects with body weight ≥50.0 kg, female subjects with body weight ≥45.0 kg, and Body Mass Index (BMI) between 18.0 and 28.0 kg/m² (inclusive).
4. Maintained a normal diet and salt intake for at least 4 weeks prior to the first dose, and has no plans to significantly change diet or body weight during the study.
5. Women of Childbearing Potential (WOCBP) or male subjects with partners who are WOCBP must agree to use highly effective contraceptive measures from the signing of the ICF until 6 months after dosing [for subjects not requiring extended follow-up (see Section 8.1.4)] or until the end of extended follow-up (for subjects requiring and accepting extended follow-up beyond 6 months), and must refrain from donating sperm or eggs. WOCBP subjects must confirm their menstrual period.
6. Voluntarily signed a written informed consent form, understands the study procedures and content, is able to communicate effectively with the investigator, and is willing to comply with study-related regulations.
Exclusion Criteria:
1. History or current presence of hypotension or orthostatic hypotension, or SBP <100 mmHg and/or DBP <60 mmHg at screening.
2. History of severe diseases of the musculoskeletal, neuropsychiatric, endocrine, circulatory, respiratory, digestive, urinary, or reproductive systems, or current presence of diseases in the aforementioned systems judged by the investigator to be clinically significant.
3. Comorbid type 1 diabetes at screening, or poorly controlled type 2 diabetes (Glycated Hemoglobin [HbA1c] >8.0%).
4. Known allergy to oligonucleotides, drugs containing GalNAc, the investigational product used in this study and its components, or drugs of the same class.
5. Presence of tattoos, scars, or birthmarks on the abdomen, upper arm, or thigh that may affect the assessment of injection site reactions.
6. Undergone major surgery within 3 months prior to the first dose, or undergone surgery that may significantly affect drug absorption, distribution, metabolism, or excretion, or planning to undergo elective surgery during the study period.
7. Donated blood or experienced significant blood loss (≥400 mL) within 3 months prior to the first dose (excluding menstrual bleeding in females), or received a blood transfusion within 12 months prior to the first dose.
8. Received a live vaccine within 4 weeks prior to the first dose, or planning to receive a live vaccine during the study period.
9. Use of any antisense oligonucleotide (ASO) or small interfering RNA (siRNA) drugs within 12 months prior to the first dose.
10. Participated in or is currently participating in other clinical trials and received investigational drugs/devices or placebos within 3 months prior to the first dose.
11. Use of any prescription drugs within 14 days prior to the first dose or within 5 half-lives of the washed-out drug (whichever is longer).
12. Use of any over-the-counter (OTC) drugs, vitamin supplements, or herbal medicines within 7 days prior to the first dose or within 5 half-lives of the washed-out drug (whichever is longer).
13. History of drug abuse/substance abuse within 5 years prior to the first dose, or positive urine drug screening (morphine, tetrahydrocannabinol, methamphetamine, methylenedioxymethamphetamine, ketamine) at screening.
14. Use of any tobacco products within 3 months prior to the first dose, or unwillingness to stop using any tobacco products during the study period.
15. Regular alcohol consumption within 3 months prior to the first dose, defined as consuming more than 14 units of alcohol per week (1 unit = 360 mL of beer or 45 mL of 40% spirits or 150 mL of wine), or unwillingness to abstain from alcohol during the study period, or alcohol breath test result >0 mg/100 mL.
16. Consumption of excessive amounts of tea, coffee, or caffeine-containing beverages (more than 8 cups per day, 1 cup = 250 mL) within 3 months prior to the first dose, or consumption of any such beverages within 48 hours prior to dosing, or unwillingness to abstain from such beverages during the study period.
17. Positive for Hepatitis B surface antigen (HBsAg), Hepatitis C antibody (HCV-Ab), Treponema pallidum antibody (TP-Ab), or Human Immunodeficiency Virus antibody (HIV-Ab) at screening.
18. Estimated Glomerular Filtration Rate (eGFR) <90 mL/min/1.73 m² (calculated using the Modification of Diet in Renal Disease [MDRD] formula) at screening.
19. WOCBP with a positive pregnancy test result at screening, women who are breastfeeding, or women planning to become pregnant during the study period.
20. Any other condition judged by the investigator to make the subject unsuitable for participation in this clinical trial.