A Clinical Trial of TQF6422 Injection in Overweight or Obese Healthy Subjects.

A Phase 1 Clinical Trial of TQF6422 Injection to Evaluate Safety, Tolerability, Pharmacokinetic and Pharmacodynamic Profiles Following Single and Multiple Ascending Doses in Healthy Overweight or Obese Subjects.

This is a placebo-controlled, double-blind trial to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single and multiple ascending doses of TQF6422 Injection in overweight or obese healthy participants.

Inclusion Criteria:

1. Chinese male or female trial participants aged ≥18 years (inclusive) and ≤55 years (inclusive).

2. Participant body weight ≥50 kg, with body-mass index (BMI) of 24-40 kg/m² (end-points included).

3. At screening, the following findings shall be within normal limits, or deemed clinically insignificant by the Investigator despite being abnormal and not meeting exclusion criteria: vital signs, physical examination, 12-lead electrocardiogram (ECG), chest X-ray, abdominal ultrasound, and clinical laboratory tests (including but not limited to hematology, urinalysis, serum biochemistry, coagulation function, serological virology, and thyroid function).

4. Negative human immunodeficiency virus antibody (HIV-Ab) test.

5. For female participants:

   1. Non-childbearing potential: including surgical sterilization performed at least 6 weeks prior to screening visit (documented tubal ligation, hysterectomy, or bilateral oophorectomy), or post-menopausal status for ≥12 months prior to screening visit (confirmed by follicle-stimulating hormone (FSH) level ≥40 IU/L); OR
   2. Child-bearing potential: must be non-pregnant and non-lactating, and must agree to use effective (at least one highly-effective) non-pharmacological contraceptive measures from 14 days before screening, throughout the study period, and for 6 months after study drug administration. Serum pregnancy test shall be negative with human chorionic gonadotropin (hCG) <5 mIU/mL at screening and baseline (D-1). Participants shall not donate ova during this period.

6. Male participants with female partners of child-bearing potential must agree to use effective (at least one highly-effective) non-pharmacological contraceptive measures from 14 days before screening, throughout the study period, and for 6 months after study drug administration. Male participants shall not donate sperm during this period.

7. Voluntarily provide written informed consent prior to trial participation, with full understanding of trial content, procedures and potential adverse reactions; able to communicate adequately with the Investigator, and understand and comply with all study-related requirements.

Exclusion Criteria:

Participants meeting any of the following criteria will be excluded from enrollment:

1. Presence of clinically-significant ongoing disease, or history of chronic/severe disease, including but not limited to circulatory, lymphatic, respiratory, endocrine, urinary, digestive, nervous, psychiatric, or infectious diseases, malignant neoplasms, severe trauma; or other conditions judged by the Investigator to be exclusionary or likely to confound interpretation of trial results.

2. History of second-degree or higher cardiac conduction block, or PR interval >220 ms; risk factors or history of torsades de pointes ventricular tachycardia, including but not limited to unexplained syncope, long-QT syndrome, heart failure; OR any abnormal 12-lead ECG at screening judged by the Investigator to increase risks associated with study participation.

3. History of gastrointestinal surgery causing malabsorption (except for endoscopic resections such as gastric polypectomy), or long-term use of medications directly affecting gastrointestinal motility.

4. Use within 3 months prior to screening, or ongoing use of medications known to significantly affect body weight (regardless of therapeutic indication), including: GLP-1R agonists, GLP-1R/GIPR agonists, GLP-1R/GCGR agonists, systemic corticosteroids (intravenous, oral or intra-articular), metformin, sodium-glucose cotransporter-2 (SGLT-2) inhibitors, thiazolidinediones (TZDs), tricyclic antidepressants, psychotropic or sedative agents (e.g., imipramine, amitriptyline, mirtazapine, paroxetine, phenelzine, chlorpromazine, thioridazine, clozapine, olanzapine, valproic acid and its derivatives, lithium salts).

5. Known comorbid diseases affecting the skeletal-muscle system (e.g., myasthenia gravis, muscular dystrophy); or use of any medications or supplements known to affect muscle anabolism/catabolism within 3 months prior to screening.

6. Sunburn, scar tissue, tattoos covering >25 % of total body surface area, open ulcers or branding at screening, judged by the Investigator to interfere with interpretation of cutaneous adverse reactions.

7. Clinically-significant infection at screening, including but not limited to upper respiratory tract infection, lower respiratory tract infection, herpes simplex, herpes zoster, requiring antibiotic or antiviral therapy.

8. Receipt of live-virus vaccine within 4 weeks prior to randomization, or planned live-virus vaccination during the study.

9. Surgical procedure performed within 4 weeks prior to randomization, or planned surgery during the study.

10. Blood transfusion, blood loss or blood donation exceeding 400 mL within 3 months prior to screening (excluding physiological menstrual blood loss in female subjects), and/or platelet donation within 2 weeks prior to study drug administration.

11. Use of any prescription, over-the-counter, or herbal medicines within 4 weeks prior to randomization (if 5-half-lives of the relevant drug exceed 14 days, the 5-half-life period shall apply).

12. History of needle-phobia or venipuncture-related vasovagal syncope, difficult-to-access venipuncture, or intolerance to venous puncture.

13. Known hypersensitivity to any component of TQF6422 injection, or prior history of severe allergic reactions (including any food or drug allergy).

14. History of substance abuse within 3 months prior to screening, or positive urine drug screen.

15. Cigarette smoking >10 cigarettes per day, or equivalent nicotine-containing product use within 3 months prior to screening; or inability to abstain from all tobacco-containing products during the study.

16. Chronic alcohol abuse, or alcohol intake exceeding 14 units per week within 3 months prior to screening (1 unit = 360 mL beer, or 45 mL 40 %-proof spirit, or 150 mL wine); or inability to refrain from alcohol during the study; or positive alcohol breath test.

17. Habitual excessive intake of caffeine-containing beverages or food within 4 weeks prior to randomization (e.g., coffee, tea, milk-tea, chocolate, cola, energy drinks). Daily caffeine intake shall not exceed 6 units. 1 caffeine-unit = 1 cup coffee (177.4 mL) = 2 cans cola (354.9 mL) = 1 cup tea (354.9 mL) = ½ can energy drink = 85 g chocolate.

18. Consumption of grapefruit, Seville-orange or their juices within 7 days prior to first-dose, or inability to discontinue consumption of grapefruit, Seville-orange or their juices during the study.

19. Special-dietary requirements that prevent adherence to standard-diet instructions.

20. Participation in any investigational drug or medical-device clinical trial within 3 months prior to screening, or planned participation in another clinical trial during this study.

21. Body-weight change >5 % within 3 months prior to screening.

22. Positive hepatitis B surface antigen (HBsAg), hepatitis C antibody (HCV-Ab), or treponema pallidum antibody (TP-Ab).

23. Meeting any of the following clinical laboratory criteria at screening:

    1. Alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) >1.0×ULN, and/or total bilirubin (TBIL) >1.2×ULN;
    2. Estimated glomerular filtration rate (eGFR) calculated by CKD-EPI formula <90 mL/min/1.73 m²;
    3. Serum creatine kinase (CK) >1.2×ULN;
    4. Serum amylase or lipase >1.0×ULN.

24. Any other condition or factor judged by the Investigator rendering the subject unsuitable for study participation.