Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TNM002 in Chinese Healthy Adults

Lead sponsor

Zhuhai Trinomab Pharmaceutical Co., Ltd. is the lead sponsor of 11 studies on the registry; 3 are open to participants now.

Of its 7 completed or terminated interventional studies of FDA-regulated products, 2 (29%) have results posted.

Study arms

• Experimental
  Cohort 1: TNM002 35 μg/kg or placebo

  Eight subjects will be randomly assigned to receive either TNM002 35 μg/kg or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo)

  Drug: TNM002 · Drug: Placebo

• Experimental
  Cohort 2: TNM002 100 μg/kg or placebo

  Eight subjects will be randomly assigned to receive either TNM002 100 μg/kg or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo)

  Drug: TNM002 · Drug: Placebo

• Experimental
  Cohort 3：TNM002 250 μg/kg or placebo

  Eight subjects will be randomly assigned to receive either TNM002 250 μg/kg or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo)

  Drug: TNM002 · Drug: Placebo

Interventions

• DrugTNM002

  TNM002, intramuscular injection

• DrugPlacebo

  Placebo, intramuscular injection

Primary outcomes

1. AEs

   Incidence of AEs

   Time frame: Up to 105 days post dosing

2. Number of participants with clinically significant abnormality in physical examinations

   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

   Time frame: Up to 105 days post dosing

3. Change in Hematocrit (ratio)

   Measured by hematology test

   Time frame: Up to 105 days post dosing

4. Change in Haemoglobin (g/L)

   Measured by hematology test

   Time frame: Up to 105 days post dosing

5. Change in Platelet count (cells x 10^9/L)

   Measured by hematology test

   Time frame: Up to 105 days post dosing

6. Change in Red blood cell count (cells x 10^12/L)

   Measured by hematology test

   Time frame: Up to 105 days post dosing

7. Change in differential leukocyte count (cells x 10^9/L)

   Measured by hematology test

   Time frame: Up to 105 days post dosing

8. Change in Serum Alanine Aminotransferase (ALT) (U/L)

   Measured by serum chemistry

   Time frame: Up to 105 days post dosing

9. Change in Serum Aspartate Aminotransferase (AST) (U/L)

   Measured by serum chemistry

   Time frame: Up to 105 days post dosing

10. Change in Serum Albumin (g/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

11. Change in Serum Alkaline Phosphatase (ALP) (U/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

12. Change in Serum Total Bilirubin (umol/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

13. Change in Serum Blood urea nitrogen (BUN) (mmol/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

14. Change in Serum Creatinine (umol/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

15. Change in Serum Calcium (mmol/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

16. Change in Serum Chloride (mmol/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

17. Change in Serum Cholesterol (mmol/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

18. Change in Serum Creatine Kinase (U/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

19. Change in Serum Glucose (mmol/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

20. Change in Serum Lactate Dehydrogenase (U/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

21. Change in Serum Phosphorus (mmol/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

22. Change in Serum Potassium (mmol/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

23. Change in Serum Total protein (g/L)

    Measured by serum chemistry

    Time frame: Up to 105 days post dosing

24. Change in Urine Bilirubin (U-BIL)

    Measured by Urinalysis

    Time frame: Up to 105 days post dosing

25. Change in Urine Glucose (GLU) (mg/dL)

    Measured by Urinalysis

    Time frame: Up to 105 days post dosing

26. Change in Urine erythrocytes (U-RBC)

    Measured by Urinalysis

    Time frame: Up to 105 days post dosing

27. Change in Urinary leukocyte (U-LEU)

    Measured by Urinalysis

    Time frame: Up to 105 days post dosing

28. Change in Urine nitrites (U-NIT)

    Measured by Urinalysis

    Time frame: Up to 105 days post dosing

29. Change in Urine protein (U-PRO)

    Measured by Urinalysis

    Time frame: Up to 105 days post dosing

30. Change in Urine specific gravity (U-SG)

    Measured by Urinalysis

    Time frame: Up to 105 days post dosing

31. Change in Urine urobilinogen (URO)

    Measured by Urinalysis

    Time frame: Up to 105 days post dosing

32. Change in Prothrombin time (sec)

    Measured by Blood Coagulation test

    Time frame: Up to 105 days post dosing

33. Change in Activated partial thromboplastin time (APTT)(sec)

    Measured by Blood Coagulation test

    Time frame: Up to 105 days post dosing

34. Change in fibrinogen (g/L)

    Measured by Blood Coagulation test

    Time frame: Up to 105 days post dosing

35. Change in international normalized ratio (INR

    Measured by Blood Coagulation test

    Time frame: Up to 105 days post dosing

36. Change in RR intervals (msec)

    Measured using a 12 Lead Electrocardiogram

    Time frame: Up to 105 days post dosing

37. Change in PR intervals (msec)

    Measured using a 12 Lead Electrocardiogram

    Time frame: Up to 105 days post dosing

38. Change in QRS duration (msec)

    Measured using a 12 Lead Electrocardiogram

    Time frame: Up to 105 days post dosing

39. Change in QT intervals (msec)

    Measured using a 12 Lead Electrocardiogram

    Time frame: Up to 105 days post dosing

40. Change in QTcB intervals (msec)

    Measured using a 12 Lead Electrocardiogram

    Time frame: Up to 105 days post dosing

41. Change in QTcF intervals (msec)

    Measured using a 12 Lead Electrocardiogram

    Time frame: Up to 105 days post dosing

42. Change in blood pressure (mmHg)

    Time frame: Up to 105 days post dosing

43. Change in pulse rate (bpm)

    Time frame: Up to 105 days post dosing

44. Change in body temperature (celsius)

    Time frame: Up to 105 days post dosing

Secondary outcomes

1. Maximum observed plasma concentration (Cmax)

   Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;

   Time frame: Up to 105 days post dosing

2. Time of maximum plasma concentration (Tmax)

   Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;

   Time frame: Up to 105 days post dosing

3. Terminal half-life (T1/2)

   Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;

   Time frame: Up to 105 days post dosing

4. Area under the plasma concentration-time curve from time-zero to the time of the last measurable concentration (AUC0-last)

   Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;

   Time frame: Up to 105 days post dosing

5. Area under the plasma concentration-time curve from time-zero extrapolated to infinite time (AUC0-inf)

   Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;

   Time frame: Up to 105 days post dosing

6. Apparent total body clearance (CL/F)

   Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;

   Time frame: Up to 105 days post dosing

7. Apparent volume of distribution (Vz/F)

   Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;

   Time frame: Up to 105 days post dosing

8. Anti-TNM002 antibodies

   The numbers of subjects who developed anti-TNM002 antibodies

   Time frame: Up to 105 days post dosing

9. Anti-TNM002 antibodies

   The percentages of subjects who developed anti-TNM002 antibodies

   Time frame: Up to 105 days post dosing

Other outcomes

1. Tetanus-antibody titer

   Geometric mean titers (GMTs) of tetanus-antibody titer in serum

   Time frame: Up to 105 days post dosing

2. Tetanus-antibody titer

   The percentage of subjects with a change of titer \> 10 IU/L from the baseline

   Time frame: Up to 105 days post dosing

Individual participant data

Plan to share: Yes — Individual participant data that underlie the results reported in these articles after deidentification

Supporting information: Study protocol, Sap