Tetanus
Conditions
Keywords
Tetanus Antitoxin
Brief summary
A Randomized, Double-blind, Controlled, Dose-escalation Phase I Clinical Trial to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Intramuscular Injection of Recombinant Human Anti-tetanus toxin Monoclonal Antibody Injection in Healthy Participants.
Detailed description
The primary objective of the study ： evaluate the safety and tolerability of a single intramuscular injection of recombinant human anti-tetanus toxin monoclonal antibody injection in healthy adult participants. The secondary objectives are: 1. to evaluate the pharmacokinetic (PK) characteristics of a single intramuscular injection of recombinant human anti-tetanus toxin monoclonal antibody injection in healthy adult participants; 2. to evaluate the pharmacodynamic (PD) characteristics of a single intramuscular injection of recombinant human anti-tetanus toxin monoclonal antibody injection in healthy adult participants; 3. to evaluate the immunogenicity of a single intramuscular injection of recombinant human anti-tetanus toxin monoclonal antibody injection in healthy adult participants.
Interventions
DRUGRecombinant Human Anti-Tetanus Toxin Monoclonal Antibody Injection
intramuscular injection
intramuscular injection
DRUGPlacebo
intramuscular injection
Sponsors
Lanzhou Institute of Biological Products Co., Ltd
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Participants voluntarily agree to participate in the study and sign the informed consent form (ICF); 2. Aged 18-60 years (inclusive) at the time of ICF signing, regardless of gender, with valid legal identification; 3. Body weight ≥45.0 kg for female participants and ≥50.0 kg for male participants, with a body mass index (BMI) between 18.0 and 28.0 kg/m² (inclusive) (BMI = weight \[kg\]/height \[m²\]); 4. Female participants of childbearing potential must have no plans for pregnancy or egg donation during the trial and for 6 months after investigational product administration and must voluntarily use at least one effective contraceptive method. Male participants must have no plans for pregnancy or sperm donation during the trial and for 6 months after investigational product administration, and either the male participant or his female partner of childbearing potential must voluntarily use at least one effective contraceptive method.
Exclusion criteria
1. Known allergy to the investigational product (including excipients or similar drugs), or documented hypersensitivity to essential materials used in the trial (e.g., skin disinfectants); or history of severe allergic diseases, hypersensitivity to monoclonal antibodies, or allergic constitution deemed by investigators to compromise participant safety; 2. Acute/chronic medical conditions that may significantly affect drug metabolism or safety assessments per investigator judgment; 3. History of autoimmune diseases or immunodeficiency disorders (including HIV-positive screening); 4. Chronic hepatitis B/C (HBsAg or HCV antibody-positive during screening); 5. History/family history of seizures, epilepsy, or neuropsychiatric disorders; 6. Major surgery within 3 months (90 days) prior to dosing, or planned surgery during the trial; 7. Prior tetanus infection or use of passive tetanus immunoglobulins within 6 months (180 days) before dosing; 8. Tetanus-toxoid-containing vaccination (e.g., DTaP, Td, meningococcal conjugate vaccines) within 10 years; 9. Positive tetanus IgG rapid test during screening; 10. Receipt of live/inactivated vaccines within 1 month (30 days) before dosing or planned vaccination during the trial; 11. Systemic corticosteroids/immunosuppressants within 3 months (90 days) (excluding inhaled/topical use); 12. Prescription/OTC/herbal medications within 14 days or \<5 half-lives (whichever is longer) prior to dosing, particularly those interfering with the investigational monoclonal antibody's PK/safety (per criterion #11 for exceptions); 13. Participation in other clinical trials involving investigational drugs/devices within 3 months (90 days) or planned concurrent enrollment; 14. Excessive alcohol intake (\>14 units/week; 1 unit = 360 mL beer/45 mL 40% liquor/150 mL wine), alcohol use within 48 hours pre-dose, or positive breathalyzer test; 15. Heavy smoking (\>10 cigarettes/day or equivalent) within 1 month (30 days); 16. Blood loss/donation \>400 mL within 3 months (90 days) or planned donation/transfusion during the trial; 17. Inability to avoid strenuous exercise within 14 days post-dosing; 18. Substance abuse history or positive drug screening; 19. Positive syphilis antibody test during screening; 20. Clinically significant abnormalities in screening assessments (e.g., ALT \>1.5×ULN, creatinine \>ULN, neutrophils \<1.5×10⁹/L, platelets \<100×10⁹/L, hemoglobin \<100 g/L); 21. Pregnant/lactating women or positive pregnancy test; 22. Needle phobia, poor venous access, or intolerance to venipuncture; 23. Any other condition deemed by investigators to preclude compliance or safe participation.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The occurrence of adverse events (AEs)/serious adverse events (SAEs) (including injection site reactions) from administration to the last visit | 105 days | Types of Adverse Events / Serious Adverse Reactions |
| The clinical significance of changes in observation indicators at different time points after drug injection compared to pre-administration. | 105Days | 12-lead electrocardiogram examination：P Wave |
| Clinically significant changes in laboratory parameters from baseline at specified timepoints post-dosing | 105Days | Complete Blood Count (CBC) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Endpoints | 105Days | Cmax: Maximum plasma concentration |
| Pharmacodynamic Endpoints | 0 to 12 hours | Change in tetanus-neutralizing antibody titer from baseline within 12 hours post-dose across treatment groups |
| Exposure-Response Analysis, E-R Analysis | 105Days | Exposure-response (E-R) analysis of serum drug concentrations versus anti-tetanus toxin neutralizing antibody titers at each post-dose timepoint across treatment groups |
| Immunogenicity Endpoints | 105Days | Anti-drug antibody (ADA) titers against the investigational drug (recombinant human anti-tetanus toxin monoclonal antibody) in serum at each post-dose timepoint across treatment groups |
Countries
China
Contacts
PRINCIPAL_INVESTIGATORJianchang He
Yunnan Provincial Hospital of Traditional Chinese Medicine
Outcome results
None listed