Healthy Adult Subjects
Conditions
Brief summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics properties of TNM002 following a single intramuscular dose in healthy adult subjects.
Detailed description
The study a randomized, double-blinded, placebo-controlled, dose-escalation phase I trial. A total of 32 healthy adult subjects will be enrolled into 4 cohorts sequentially. Each participant will receive a single IM dose of TNM002 or placebo according to the cohort in which they were enrolled. After injection (Day 1), participants remain in the study site for observation up to 5 days. Following completion of the safety assessments and sampling for PK/PD analyses on Day 4, participants will be discharged from the study site. On Day 8, 15, 29, 43, 64 and 85, participants will return for safety assessments.
Interventions
BIOLOGICALTNM002 Dosage 1 (10 μg/kg)
TNM002 (human monoclonal antibody against tetanus toxin), 10 μg/kg, Intramuscular injection, given once.
BIOLOGICALPlacebo
placebo to match TNM002 Dosage 1, given once
BIOLOGICALTNM002 Dosage 2 (35 μg/kg)
TNM002 (human monoclonal antibody against tetanus toxin), 35 μg/kg, Intramuscular injection, given once
BIOLOGICALTNM002 Dosage 3 (100 μg/kg)
TNM002 (human monoclonal antibody against tetanus toxin), 100 μg/kg, Intramuscular injection, given once
BIOLOGICALTNM002 Dosage 4 (250 μg/kg)
TNM002 (human monoclonal antibody against tetanus toxin), 250 μg/kg, Intramuscular injection, given once
Sponsors
TIGERMED AUSTRALIA PTY LIMITED
Zhuhai Trinomab Pharmaceutical Co., Ltd.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
Each subject must meet the following criteria to be enrolled in this study: 1. Healthy male or female, 18-55 years of age (both inclusive); 2. Able to give signed written informed consent form; 3. Able to well communicate with investigators as well as understand and adhere to the requirements of this study. 4. Body mass index (BMI, weight \[kg\]/height \[m\]2) within 18.0-32.0 kg/m2 (both inclusive); 5. Blood Pressure (BP) and 12-lead ECG showing no clinically significant abnormalities at the discretion of the Principal Investigator during screening; 6. Subjects having no clinically significant abnormality on physical examination, clinical laboratory tests, liver function or kidney function as determined by Principal Investigator (PI); 7. Females must be either under surgical sterile (i.e. had a bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months before the first dose of study drug) or under postmenopausal for at least 1 year before the first dose of study drug or agree to use an acceptable method of contraception from screening until 90 days after last study drug administration. Males who are sexually active and who are partners of women of childbearing potential must agree to use effective contraception from screening until 90 days after last drug administration. * acceptable method of contraception * Use of intrauterine device * Use of oral, injected or implanted hormonal methods of contraception * Concomitant use of barrier contraception method * Surgical contraception methods (e.g., vasectomy, salpingectomy, hysterectomy, etc.)
Exclusion criteria
Subjects who meet any of the following criteria will be excluded from the study: 1. History or evidence of severe drug or excipient allergy, or hypersensitivity to other therapeutic mAbs; 2. History or evidence of autoimmune disease or possible immunodeficiency state, including positive screening test for HIV; 3. History or evidence of chronic hepatitis, including positive screening test for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody; 4. History or evidence of tetanus infection, or exposure to tetanus vaccine within 6 months prior to the fist drug administration; 5. Exposure to any live attenuated vaccine within 4 weeks prior to the fist drug administration; 6. Exposure to any inactivated vaccine within 2 weeks prior to the fist drug administration; 7. History or evidence of any other acute or chronic disease that, in the opinion of the investigator, may have interfered with the evaluation of the safety or immunogenicity of the drug or compromised the safety of the subject; for example, a clinically relevant history of respiratory, thyroid, gastrointestinal, renal, hepatic, hematological, lymphatic, oncologic, cardiovascular, psychiatric, neurological, musculoskeletal, genitourinary, infective, inflammatory, immunological, dermatological, or connective tissue disease 8. Subjects with surgery (except for minor outpatient surgery) within past 3 months prior to screening, or planned surgery during study; 9. Subjects with intolerance or insufficient venous access to permit regular venepuncture; 10. Known or suspected history of drug abuse within the past 5 years or with positive urine drug test at the screening; 11. Donated blood \>400 mL or significant blood loss equivalent to 400 mL or received blood transfusion within 3months of screening; or donated blood \>200 mL or significant blood loss equivalent to 200 mL within 1 month prior to the screening; 12. Participation in any other clinical studies with chemical or biological drugs or device within 4 weeks or 5 times the half-life of the specific drug/biologics (whichever is longer), prior to the first drug administration; 13. Use of any other drug, including over-the-counter medications, herb medicines within 14 days prior to the first drug administration (except for contraceptive medication in WOCBP, or concomitant medications that are considered necessary for the subject's welfare and unlikely to interfere with the study); 14. Receipt of an Ig or blood product within 90 days prior to the first drug administration; 15. Receipt of immunosuppressive medications, other than inhaled or topical immunosuppressant drugs, within 45 days prior to the first drug administration; 16. Habitual use of nicotine products or smoking within 3 months (more than 5 cigarettes per day) prior to screening or unwilling to refrain from nicotine products during study participation; 17. History of significant alcohol abuse within 6 months of screening or any indication of regular use of more than 14 units of alcohol per week (1 Unit=360 mL of beer or 45 mL of alcohol 40% or 150 mL of wine) or taking a product containing alcohol 2 days prior to dosing, or having a positive alcohol breath test during the screen period.; 18. Malignancy within 5 years of screening visit (except basal cell skin carcinoma); 19. Subject who is considered unsuitable for participating in the study in the opinion of investigator; 20. Nursing mothers or pregnant women.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in international normalized ratio (INR) | Up to 105 days post dosing | measured by Blood Coagulation test |
| Change in Serum Phosphorus (mmol/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Potassium (mmol/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Total protein (g/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Urine Bilirubin (U-BIL) | Up to 105 days post dosing | measured by Urinalysis |
| Change in Urine Glucose (GLU) (mg/dL) | Up to 105 days post dosing | measured by Urinalysis |
| Change in Urine erythrocytes (U-RBC) | Up to 105 days post dosing | measured by Urinalysis |
| Change in Urinary leukocyte (U-LEU) | Up to 105 days post dosing | measured by Urinalysis |
| Change in Urine nitrites (U-NIT) | Up to 105 days post dosing | measured by Urinalysis |
| Change in Urine protein (U-PRO) | Up to 105 days post dosing | measured by Urinalysis |
| Change in Urine specific gravity (U-SG) | Up to 105 days post dosing | measured by Urinalysis |
| Change in Urine urobilinogen (URO) | Up to 105 days post dosing | measured by Urinalysis |
| Change in Prothrombin time (sec) | Up to 105 days post dosing | measured by Blood Coagulation test |
| Change in Activated partial thromboplastin time (APTT)(sec) | Up to 105 days post dosing | measured by Blood Coagulation test |
| Change in fibrinogen (g/L) | Up to 105 days post dosing | measured by Blood Coagulation test |
| Incidence and severity of adverse events | Up to 105 days post dosing | The investigator will assess the intensity for each AE reported during the study based on the investigator's clinical judgment. Adverse events will be recorded according to CTCAE V5.0. |
| Clinically significant abnormality in physical examinations | Up to 105 days post dosing | clinically significant abnormality in general condition, skin, eyes/ears/nose/mouth/throat, neck/thyroid, chest/lungs, heart, vascular system, lymph nodes, abdomen, extremities, nervous systems/reflexes, musculoskeletal, spine |
| Change in RR intervals (msec) | Up to 105 days post dosing | Measured using a 12 Lead Electrocardiogram |
| Change in PR intervals (msec) | Up to 105 days post dosing | Measured using a 12 Lead Electrocardiogram |
| Change in QRS duration (msec) | Up to 105 days post dosing | Measured using a 12 Lead Electrocardiogram |
| Change in QT intervals (msec) | Up to 105 days post dosing | Calculated using measurements by a 12 Lead Electrocardiogram |
| Change in QTcB intervals (msec) | Up to 105 days post dosing | Calculated using measurements by a 12 Lead Electrocardiogram |
| Change in QTcF intervals (msec) | Up to 105 days post dosing | Calculated using measurements by a 12 Lead Electrocardiogram |
| Change in Semi recumbent blood pressure (mmHg) | Up to 105 days post dosing | — |
| Change in pulse rate (bpm) | Up to 105 days post dosing | — |
| Change in body temperature (celsius) | Up to 105 days post dosing | — |
| Change in Hematocrit (ratio) | Up to 105 days post dosing | Measured by hematology test |
| Change in Haemoglobin (g/L) | Up to 105 days post dosing | Measured by hematology test |
| Change in Mean corpuscular hemoglobin (pg) | Up to 105 days post dosing | Measured by hematology test |
| Change in Mean corpuscular hemoglobin concentration (g/L) | Up to 105 days post dosing | Measured by hematology test |
| Change in Mean corpuscular volume (fL) | Up to 105 days post dosing | Measured by hematology test |
| Change in Platelet count (cells x 10^9/L)) | Up to 105 days post dosing | Measured by hematology test |
| Change in Red blood cell count (cells x 10^12/L) | Up to 105 days post dosing | Measured by hematology test |
| Change in White blood cell count (cells x 10^9/L) | Up to 105 days post dosing | Measured by hematology test |
| Change in differential leukocyte count (cells x 10^9/L) | Up to 105 days post dosing | Including eosinophils, monocytes, lymphocytes, basophils, and neutrophils, Measured by hematology test |
| Change in Serum Alanine Aminotransferase (ALT) (U/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Albumin (g/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Alkaline Phosphatase (ALP) (U/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Aspartate Aminotransferase (AST) (U/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Total Bilirubin (umol/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Blood urea nitrogen (BUN) (mmol/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Calcium (mmol/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Chloride (mmol/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Cholesterol (mmol/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Creatinine (umol/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Creatine Kinase (U/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Glucose (mmol/L) | Up to 105 days post dosing | measured by serum chemistry |
| Change in Serum Lactate Dehydrogenase (U/L) | Up to 105 days post dosing | measured by serum chemistry |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Lambda z - the reciprocal of elimination rate constant | Up to 105 days post dosing | Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above |
| The ratio of area under the plasma concentration-time curve from time-zero to the time of the last measurable concentration (AUC0-last) extrapolated to AUC0-inf over AUC0-inf (% AUCex) | Up to 105 days post dosing | Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above |
| Anti-TNM002 antibodies | Up to 105 days post dosing | The numbers of subjects who developed anti-TNM002 antibodies |
| Maximum observed plasma concentration (Cmax) | Up to 105 days post dosing | Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above |
| Time of maximum plasma concentration (Tmax) | Up to 105 days post dosing | Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above |
| Terminal half-life (T1/2) | Up to 105 days post dosing | Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above |
| Area under the plasma concentration-time curve from time-zero to the time of the last measurable concentration (AUC0-last) | Up to 105 days post dosing | Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above |
| Area under the plasma concentration-time curve from time-zero extrapolated to infinite time (AUC0-inf) | Up to 105 days post dosing | Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above |
| Apparent oral clearance (CL/F) | Up to 105 days post dosing | Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above |
| Apparent volume of distribution (Vz/F) | Up to 105 days post dosing | Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above |
| Mean retention time (MRT) | Up to 105 days post dosing | Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above |
Other
| Measure | Time frame |
|---|---|
| Tetanus-antibody titer in serum | Up to 105 days post dosing |
| The percentage of subjects with a change of titer ≥ 0.2 IU/mL from the baseline | Up to 105 days post dosing |
| Time to achieve the maximum tetanus-antibody titer | Up to 105 days post dosing |
Countries
Australia
Outcome results
None listed