Phase 1 Study of HS-20152 in Healthy Participants

A Randomized, Double-blind, Placebo-Controlled, Single Ascending Dose, Phase 1 Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of HS-20152 in Healthy Participants

This first-in-human, randomized, double-blind, placebo-controlled, single ascending dose study will evaluate the safety and tolerability of HS-20152, an investigational therapy targeting the complement pathway, in healthy adults. Secondary objectives include characterization of pharmacokinetics and pharmacodynamic effects on complement-related biomarkers.

HS-20152 is an investigational therapeutic designed to target a component of the complement pathway and modulate complement activity. This is a randomized, double-blinded, placebo-controlled, single ascending dose, first-in-human study of HS-20152 in healthy adult participants. Participants will be enrolled sequentially into dose cohorts and randomized within each cohort to receive a single administration of HS-20152 or placebo. Dose escalation to subsequent cohorts will proceed after protocol-defined review of safety and tolerability.

The primary objective is to evaluate the safety and the tolerability of HS-20152 following single-dose administration. Secondary objectives include characterization of pharmacokinetics and assessment of pharmacodynamics effects on complement-related biomarkers. Safety assessments include adverse events, clinical laboratory tests, vital signs, physical examinations, and electrocardiograms, with follow-up through the protocol-specified observation period.

Inclusion Criteria:

1. Males or females aged 18 to 64 years (inclusive) when signing the ICF.
2. Body Mass Index (BMI = weight/height²) ≥ 19 kg/m² and ≤ 28 kg/m² at screening, and males must weigh ≥50 kg, and females must weigh ≥ 45 kg.
3. Female participants must agree to practice highly effective contraception from 2 weeks prior to screening until 6 months after dosing.
4. Male participants with childbearing potential must agree to practice highly effective contraception from the date of signing the ICF until 6 months after dosing; male participants without childbearing potential (e.g, having undergone effective sterilization) must agree to use additional highly effective contraception if there is any uncertainty about the presence of sperm.
5. Participants should be able to complete vaccinations against Neisseria meningitidis (types A, C, Y, and W-135) and streptococcus pneumoniae at least 2 weeks prior to the first dose.
6. The participants are able to communicate clearly with the investigator, understand and comply with the requirements of this study, have a comprehensive understanding of the study content, process and possible adverse reactions, and sign the ICF voluntarily.

Exclusion Criteria:

1. Consumption of any caffeine, tea, alcohol, xanthine-rich foods or beverages within 24 hours before dosing.
2. Consumption of red wine, citrus fruits (such as grapefruit, oranges, tangerines, etc.), grapes, mangoes, or star fruits, or juices containing these fruits, within 72 hours prior to dosing.
3. Abnormal and clinically significant results in vital signs, physical examination, laboratory tests, 12-lead ECG, chest X-ray (anteroposterior and lateral)/CT, or abdominal ultrasound at screening, which, in the investigator's judgement, may increase the participant's risk in the study or affect the interpretation of the study results.
4. Positive for hepatitis B surface antigen (HBsAg), hepatitis B core antibody (HBcAb), HCV Ab, HIV antibody, or syphilis-specific antibodies at screening.
5. Presence of non-active, active, or latent tuberculosis infection at screening (indicated by chest X-ray or CT showing tuberculosis lesions, or positive T-SPOT.TB results).
6. Positive pregnancy test at screening, or pregnant or breastfeeding at screening, or planning to become pregnant during the study.
7. Use of any medications, including prescription drugs, over-the-counter (OTC) drugs, herbal medicines, or dietary supplements, within 2 weeks prior to screening, or within 5 half-lives after the last dose of such medications, whichever is longer.
8. Receipt of any live attenuated vaccine within 30 days prior to dosing; receipt of any vaccine not specified in the protocol within 5 days prior to dosing; or planned receipt of any vaccine not specified in the protocol during the study.
9. Participation in other drug or medical device intervention clinical trials within 1 month prior to screening, and receipt of investigational drugs or use of medical devices, or being within 5 half-lives of the last dose of other investigational drugs, whichever is longer; or adverse events (AEs) from other trials that have not resolved to CTCAE Grade 1 or normal at screening.
10. Receipt of siRNA or antisense oligonucleotide therapy within 18 months prior to dosing.
11. Blood donation or blood loss of ≥ 450 mL (excluding menstruation) within 3 months prior to screening, or planned blood donation during the study.
12. Average smoking of > 5 cigarettes per day within 3 months prior to screening.
13. Known history of drug abuse or drug use within 6 months prior to screening, or test positive for drug abuse at screening.
14. Known history of alcohol dependence (average consumption of ≥14 units per week, with each unit equivalent to 285 mL of beer, 125 mL of wine, or 25 mL of spirits) within 6 months prior to screening, or positive alcohol breath test at screening.
15. Undergone ≥ Grade 2 surgery within 6 months prior to screening, or plan to have surgery or hospitalization during the study.
16. History of severe allergies to medications, foods, or environmental factors, or known allergies to the active substances or excipients of the investigational product (including HS-20152 and placebo).
17. History of infection with encapsulated organisms (such as Neisseria meningitidis or Streptococcus pneumoniae), or close contact with individuals infected with Neisseria meningitidis.
18. Difficulty with blood draws, inability to tolerate multiple venous blood draws, or any contraindications to blood draws; or severe skin conditions that, in the investigator's judgement, make subcutaneous injection unsuitable.
19. Special dietary requirements or inability to comply with the dietary requirements of the study site.
20. As judged by the investigator, any prior or current disease or condition that may increase the risk to the participant from participating in the study, interfere with the participant's compliance with the protocol, or affect the participant's ability to complete the study.