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

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics properties of TNM002 following a single intramuscular dose in Chinese healthy adults.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Dose-Escalation Phase I Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics Following Intramuscular Administration of a Single Dose of TNM002 in Healthy Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: TNM002
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male or female, 18-55 years of age; Body mass index (BMI) within 19.0-26.0 kg/m2; Exclusion Criteria: Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation; Severe drug or excipient allergy, or history of hypersensitivity to other therapeutic mAbs; History of alcohol or other substance abuse.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Sequential Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1: TNM002 35 μg/kg or placebo<br>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<br>* TNM002, intramuscular injection<br>Drug: Placebo<br>* Placebo, intramuscular injection<br>|
| Experimental: Cohort 2: TNM002 100 μg/kg or placebo<br>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<br>* TNM002, intramuscular injection<br>Drug: Placebo<br>* Placebo, intramuscular injection<br>|
| Experimental: Cohort 3：TNM002 250 μg/kg or placebo<br>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<br>* TNM002, intramuscular injection<br>Drug: Placebo<br>* Placebo, intramuscular injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AEs | Incidence of AEs | Up to 105 days post dosing | 
| 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 | Up to 105 days post dosing | 
| Change in Hematocrit (ratio) | Measured by hematology test | Up to 105 days post dosing | 
| Change in Haemoglobin (g/L) | Measured by hematology test | Up to 105 days post dosing | 
| Change in Platelet count (cells x 10^9/L) | Measured by hematology test | Up to 105 days post dosing | 
| Change in Red blood cell count (cells x 10^12/L) | Measured by hematology test | Up to 105 days post dosing | 
| Change in differential leukocyte count (cells x 10^9/L) | Measured by hematology test | Up to 105 days post dosing | 
| Change in Serum Alanine Aminotransferase (ALT) (U/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Aspartate Aminotransferase (AST) (U/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Albumin (g/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Alkaline Phosphatase (ALP) (U/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Total Bilirubin (umol/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Blood urea nitrogen (BUN) (mmol/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Creatinine (umol/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Calcium (mmol/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Chloride (mmol/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Cholesterol (mmol/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Creatine Kinase (U/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Glucose (mmol/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Lactate Dehydrogenase (U/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Phosphorus (mmol/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Potassium (mmol/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Serum Total protein (g/L) | Measured by serum chemistry | Up to 105 days post dosing | 
| Change in Urine Bilirubin (U-BIL) | Measured by Urinalysis | Up to 105 days post dosing | 
| Change in Urine Glucose (GLU) (mg/dL) | Measured by Urinalysis | Up to 105 days post dosing | 
| Change in Urine erythrocytes (U-RBC) | Measured by Urinalysis | Up to 105 days post dosing | 
| Change in Urinary leukocyte (U-LEU) | Measured by Urinalysis | Up to 105 days post dosing | 
| Change in Urine nitrites (U-NIT) | Measured by Urinalysis | Up to 105 days post dosing | 
| Change in Urine protein (U-PRO) | Measured by Urinalysis | Up to 105 days post dosing | 
| Change in Urine specific gravity (U-SG) | Measured by Urinalysis | Up to 105 days post dosing | 
| Change in Urine urobilinogen (URO) | Measured by Urinalysis | Up to 105 days post dosing | 
| Change in Prothrombin time (sec) | Measured by Blood Coagulation test | Up to 105 days post dosing | 
| Change in Activated partial thromboplastin time (APTT)(sec) | Measured by Blood Coagulation test | Up to 105 days post dosing | 
| Change in fibrinogen (g/L) | Measured by Blood Coagulation test | Up to 105 days post dosing | 
| Change in international normalized ratio (INR | Measured by Blood Coagulation test | Up to 105 days post dosing | 
| Change in RR intervals (msec) | Measured using a 12 Lead Electrocardiogram | Up to 105 days post dosing | 
| Change in PR intervals (msec) | Measured using a 12 Lead Electrocardiogram | Up to 105 days post dosing | 
| Change in QRS duration (msec) | Measured using a 12 Lead Electrocardiogram | Up to 105 days post dosing | 
| Change in QT intervals (msec) | Measured using a 12 Lead Electrocardiogram | Up to 105 days post dosing | 
| Change in QTcB intervals (msec) | Measured using a 12 Lead Electrocardiogram | Up to 105 days post dosing | 
| Change in QTcF intervals (msec) | Measured using a 12 Lead Electrocardiogram | Up to 105 days post dosing | 
| Change in 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 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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; | Up to 105 days post dosing | 
| 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; | Up to 105 days post dosing | 
| 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; | Up to 105 days post dosing | 
| 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; | Up to 105 days post dosing | 
| 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; | Up to 105 days post dosing | 
| 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; | Up to 105 days post dosing | 
| 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; | Up to 105 days post dosing | 
| Anti-TNM002 antibodies | The numbers of subjects who developed anti-TNM002 antibodies | Up to 105 days post dosing | 
| Anti-TNM002 antibodies | The percentages of subjects who developed anti-TNM002 antibodies | Up to 105 days post dosing |