A Phase I Study of HLX109 in Healthy Participants

Inclusion Criteria:

1. Voluntarily participates in the clinical study, with a full understanding of the study procedures; provides written informed consent by signing and dating the informed consent form (ICF); and is willing and able to comply with all protocol-specified requirements and follow-up visits.
2. Adult male or female, aged 18 (inclusive) to 55 years (inclusive) at the time of ICF signing.
3. Body mass index (BMI) between 18.5 (inclusive) and 28.0 (exclusive) kg/m2 at screening.
4. No clinically significant abnormalities in medical history or clinical evaluations (including physical examination, clinical laboratory assessments, diagnostic imaging, vital signs, and 12-lead ECG) at screening. At the investigator's discretion, screening assessments may be repeated to confirm eligibility, provided that all assessments are completed within the defined screening window.
5. A female participant must be of no childbearing potential, postmenopausal, or premenopausal with one of the following records: hysterectomy, tubal ligation, or bilateral salpingectomy. The heterosexual partners of all participants and the participants must agree to take contraceptive measures during the treatment period and at least 3 months after the last dose of IMP. (Appendix 2.)
6. Prior to randomization, complete all age-appropriate vaccinations according to current immunization guidelines.

Exclusion Criteria:

1. Pregnant or lactating women.

2. With sunburn, scar tissue, tattoos (more than 25% of body area), open sores, or branding at screening that, in the opinion of the investigator, would interfere with the assessment of adverse skin reactions.

3. History of clinically significant hypersensitivity or allergic reactions to two or more medications, or known hypersensitivity to IMP or any of its excipients, or a history of anaphylaxis. Additionally, individuals with a history of multiple and/or severe allergic manifestations (including food allergies) are excluded. (Note: Prospective participants with seasonal allergic rhinitis/allergies are eligible for enrollment, provided they are currently asymptomatic or their symptoms are well-controlled).

4. History of venous thromboembolic events and/or has a first-degree relative with an idiopathic venous thromboembolic event.

5. History or evidence of substance or alcohol abuse, defined as follows:

   • A history of substance abuse within 1 year prior to screening, or a positive urine drug screen at the screening.
   • A history of alcohol abuse within 6 months prior to screening, or a positive breath alcohol test at the screening.

6. History of the following diseases with a clear diagnosis within 6 months prior to screening: cardiovascular diseases, hematological diseases, respiratory diseases, gastrointestinal diseases, hepatic impairment, renal impairment (e.g. glomerular filtration rate less than 75 mL/min/1.73m²), endocrine, metabolic, neurological, psychiatric, dermatological, musculoskeletal, or immunological disorders. Participants will also be excluded if they present with any other concurrent medical condition that, in the judgment of the investigator, may confound the interpretation of the study data or compromise participant safety.

7. History of hemorrhagic diathesis (including but not limited to non-traumatic bleeding) within 6 months before screening or diagnosed diseases that increase hemorrhagic diathesis.

8. Malignancy or increased risk of malignancy prior to screening: suspected and/or diagnosed with any malignancy (except for basal cell carcinoma, squamous cell carcinoma of skin in situ, or cervical carcinoma in situ occurring within 5 years prior to screening with no evidence of recurrence after treatment).

9. Major surgery (including procedures under general anesthesia) within 3 months prior to screening or organ transplantation prior to screening. Or still in the state of disease, trauma, or incomplete recovery after surgery at screening (significant changes in organ function, or significantly limited ability to live and work compared with that before disease, trauma, or surgery, or requiring continuous rehabilitation treatment), or planning to undergo surgery during the study.

10. Chronic or recurrent infection at screening, systemic or local severe infection requiring hospitalization or intravenous injection of antibiotics within 1 month before screening, or history of acute infection within 14 days before screening.

11. Any severe herpes infection at any time prior to before screening, but not limited to, disseminated herpes (ever), herpes encephalitis (ever), recurrent herpes zoster (defined as 2 episodes within 2 years prior to Screening), or ophthalmic herpes (ever).

12. Any condition requires medication and/or other treatments at screening.

13. Evidence of active or prior tuberculosis (TB) infection on lung imaging during the screening period.

14. Abnormalities in 12-lead ECG at screening or admission, such as corrected QT (QTc) interval > 450 ms in males and > 470 ms in females (Fridericia's method).

15. Abnormal results of the following Laboratory assessments at screening or admission:

    • Hemoglobin > 1.1 × upper limit of normal (ULN), or Hemoglobin < 0.9× lower limit of normal (LLN)
    • Platelet count > 1.1 ×ULN, or Platelet count < 0.9× LLN
    • Neutrophil count < 1.5 × 109/L.
    • Alkaline phosphatase (ALP) > 1.5 × ULN, or total bilirubin (TBIL) > 1.5 × ULN, or alanine aminotransferase (ALT) > 1.5 × ULN, or aspartate aminotransferase (AST) > 1.5 × ULN, or AST/ALT between 1-1.5 × ULN (inclusive) and considered clinically significant by the investigator, or blood amylase > 1 × ULN.
    • International normalized ratio (INR) > 1.5.
    • Blood thyroid-stimulating hormone (TSH) < 1×LLN, or TSH > 1 ×ULN.
    • Estimated glomerular filtration rate （eGFR） < 75mL/min/1.73 m2, or urine protein qualitative≥2+
    • Positive interferon-γ release assay.
    • Positive serology for Human Immunodeficiency Virus (HIV) antibody, Hepatitis B Virus surface antigen (HBsAg), or Hepatitis C Virus (HCV) antibody; or a positive treponemal test for syphilis.

16. Have participated in a clinical study of other investigational products before screening, with an interval between this study and the previous study being too short: within 1 month before the first dose of this study or within 5 half-lives of the previous investigational product (whichever is longer). Or plan to participate in clinical studies of other investigational products before completing all scheduled assessments in this clinical study. Participants who violate the restrictions on concomitant medications (Appendix 6) should be excluded.

17. Have participated in surgical or device clinical studies within 3 months prior to screening, or are currently participating in other surgical or device clinical studies, or plan to participate in other surgical or device clinical studies during this study.

18. Receipt of any vaccine within 14 days prior to randomization or planned receipt of any vaccine during the study.

19. Unable to follow the lifestyle restrictions (Appendix 3) during the study.

20. Prescription and over the counter (OTC) drugs, herbal medicines, vitamins, minerals, or oral iron supplements (Appendix 3) not approved by the investigator during the study.

21. Unable or unwilling to undergo repeated venipuncture due to poor tolerance or difficulty in finding a vein, or with a history of fear of blood or needles.

22. Donated whole blood or blood components (more than 400 mL) or lost a large amount of blood (more than 400 mL) within 2 months prior to IMP administration , or plan to donate whole blood or blood components during the study.

23. The participant has a hierarchical or dependent relationship with the investigator or the study site (including employees and their immediate family members), or has any other condition that, as determined by the investigator, renders the participants unsuitable for participation or places their rights and well-being at risk.