First-in-human Study of HSK56630 in Healthy Subjects

A Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of HSK56630 in Healthy Participants

This is a first-in-human, single ascending dose (SAD) study in healthy adult participants. This is a single-center, randomized, double-blind, placebo-controlled, SAD study to evaluate the safety, tolerability and PK of HSK56630 in healthy adult participants and preliminarily evaluate the PD of HSK56630.

Inclusion Criteria:

1. Must have given written informed consent before any study-related activities are carried out and must be able to understand the full nature and purpose of the study, including possible risks and adverse effects.
2. Adult males and females between ≥ 18 and ≤ 60 years (inclusive) at Screening.
3. Body mass index (BMI) ≥ 18.0 and ≤ 30.0 kg/m2 with a body weight ≥ 50 kg (males) or ≥45 kg (females) at Screening.
4. Participants with normal results or non-clinically significant (NCS) abnormal results in the opinion of the PI or delegate for a comprehensive examination, including physical examination, vital signs examination, laboratory tests (hematology, biochemistry, coagulation and urinalysis), chest X-ray and abdominal ultrasound.
5. Female participants are eligible to participate if they are not pregnant, not breastfeeding. Male participants must agree to practice true abstinence; be surgically sterilized (performed at least 6 months prior to screening and documented to no longer produce sperm - verbal confirmation through medical history review acceptable); or agree to use a condom plus effective contraception methods for their female partner.
6. Able and willing to attend the necessary visits to the study site.

Exclusion Criteria:

1. Participants with any clinically significant medical history that may affect the safety evaluation or in vivo process of IP as judged by the PI or delegate, including central nervous, cardiovascular, digestive, respiratory, urinary, blood, immune and endocrine diseases. Participants with childhood asthma (resolved) can be included at the discretion of the PI.
2. Underlying physical or psychological medical condition that, in the opinion of the PI or delegate, would make the participant unlikely to comply with the protocol or complete the study per protocol.
3. Participants having special dietary requirements that cannot be accommodated by the unit or that may interfere with study safety or data (e.g. exclusively vegan diet).
4. Participants who have taken any prescription drugs (excluding contraception) or herbal medicines within 14 days prior to dosing, or have taken any over-the-counter drugs or dietary supplements (including vitamin and calcium supplements) within 7 days prior to dosing; or participants still within 5 half-lives of a drug prior to dosing.
5. Alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) >1.5 × upper limit of normal (ULN) at Screening or Day -1. Repeat testing at Screening is acceptable for out-of-range values following approval by the PI or delegate.
6. Participants who have been vaccinated 4 weeks prior to first dose or plan to be vaccinated during the study.
7. Participants who have taken any other investigational product, participated in any other clinical trial, or participated in other medical research activities within 30 days or 5 half-lives whichever is longer prior to first dose and are unsuitable for participating in this study as judged by the PI or delegate.
8. Ascertained or presumptive hypersensitivity (including allergies) to any ingredient of the IP; history of other significant allergies or anaphylaxis, as determined by the PI or delegate.
9. Participants who have lost or donated more than 400 mL of blood (excluding menstrual blood loss in females) within 3 months prior to first dose, or plan to donate blood during the study or within 1 month after the end of the study.
10. Participants who drink excessive tea, coffee or caffeinated beverages (over 8 cups per day on average, 250 mL per cup) within 6 months prior to Screening, or those who cannot abstain from them on Day -1 and during confinement study in the CRU.
11. Current smoker who smoke more than 5 cigarettes (or equivalent for other nicotine-containing products) per day within 3 months prior to the first dose, or those who cannot abstain from smoking tobacco or the use of nicotine-containing products during the confinement period.
12. Participants who regularly drink more than 14 standard units of alcohol per week for females and more than 21 standard units of alcohol per week for males; 1 standard unit contains 10 g of alcohol, such as 285 mL of beer, 30 mL of 40% spirits or 100 mL of wine within 6 months prior to Screening or those who cannot abstain from alcohol on Day -1 and during the confinement study; or those with positive alcohol breath test.
13. Substance abuse-related disorder or a history of drug, and/or substance abuse deemed significant by the PI or delegate at Screening or a positive urine drug screen on Screening or Day -1 (including amphetamine, benzodiazepine, cocaine, methamphetamines, opiates, THC, MDMA, tricyclic antidepressants, barbiturates).
14. Participants with clinically significant abnormal 12-lead electrocardiogram (ECG) results as judged by the PI or delegate or with a corrected QTc (formula: QTcF = QT/RR1/3) interval ≤ 350 msec or greater than 450 msec in males and 470 msec in females.
15. Participants with positive test results for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab), treponema pallidum antibody (Syphilis TP Ab) or human immunodeficiency virus antibody (HIV Ab) at Screening.
16. Participants with positive result for quantiFERON gold at Screening.
17. Participants with estimated glomerular filtration rate (eGFR) < 90 mL/min/1.73m2 (using the CKD-EPI equation).
18. History or presence of a condition associated with significant immunosuppression.
19. Exposure to any drugs that cause significant immunosuppression (including experimental therapies as part of a clinical study) within 4 months or 5 half lives (whichever is longer), prior to Screening.
20. Participants who may not be able to complete the study for other reasons, cannot comply with the requirements of the study, or are unsuitable to participate in the study as judged by the PI or delegate.