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
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 28
- Locations
- 1
- Primary Endpoint
- Change in Urine protein (U-PRO)
Study Overview
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 Chinese healthy adults.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to 55 Years (Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
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.
Arms & Interventions
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)
Intervention: TNM002 (Drug)
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)
Intervention: Placebo (Drug)
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)
Intervention: TNM002 (Drug)
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)
Intervention: Placebo (Drug)
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)
Intervention: TNM002 (Drug)
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)
Intervention: Placebo (Drug)
Outcomes
Primary Outcomes
Change in Urine protein (U-PRO)
Time Frame: Up to 105 days post dosing
Measured by Urinalysis
Change in Urine specific gravity (U-SG)
Time Frame: Up to 105 days post dosing
Measured by Urinalysis
Change in Red blood cell count (cells x 10^12/L)
Time Frame: Up to 105 days post dosing
Measured by hematology test
Change in Urine urobilinogen (URO)
Time Frame: Up to 105 days post dosing
Measured by Urinalysis
Change in Prothrombin time (sec)
Time Frame: Up to 105 days post dosing
Measured by Blood Coagulation test
Change in Platelet count (cells x 10^9/L)
Time Frame: Up to 105 days post dosing
Measured by hematology test
AEs
Time Frame: Up to 105 days post dosing
Incidence of AEs
Number of participants with clinically significant abnormality in physical examinations
Time Frame: 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 Hematocrit (ratio)
Time Frame: Up to 105 days post dosing
Measured by hematology test
Change in Haemoglobin (g/L)
Time Frame: Up to 105 days post dosing
Measured by hematology test
Change in differential leukocyte count (cells x 10^9/L)
Time Frame: Up to 105 days post dosing
Measured by hematology test
Change in Serum Alanine Aminotransferase (ALT) (U/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Urine nitrites (U-NIT)
Time Frame: Up to 105 days post dosing
Measured by Urinalysis
Change in Serum Aspartate Aminotransferase (AST) (U/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Alkaline Phosphatase (ALP) (U/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Total Bilirubin (umol/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Blood urea nitrogen (BUN) (mmol/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Albumin (g/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Creatinine (umol/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Calcium (mmol/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Chloride (mmol/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Cholesterol (mmol/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Creatine Kinase (U/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Glucose (mmol/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Lactate Dehydrogenase (U/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Phosphorus (mmol/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Potassium (mmol/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Serum Total protein (g/L)
Time Frame: Up to 105 days post dosing
Measured by serum chemistry
Change in Urine Bilirubin (U-BIL)
Time Frame: Up to 105 days post dosing
Measured by Urinalysis
Change in Urine Glucose (GLU) (mg/dL)
Time Frame: Up to 105 days post dosing
Measured by Urinalysis
Change in Urine erythrocytes (U-RBC)
Time Frame: Up to 105 days post dosing
Measured by Urinalysis
Change in Urinary leukocyte (U-LEU)
Time Frame: Up to 105 days post dosing
Measured by Urinalysis
Change in Activated partial thromboplastin time (APTT)(sec)
Time Frame: Up to 105 days post dosing
Measured by Blood Coagulation test
Change in fibrinogen (g/L)
Time Frame: Up to 105 days post dosing
Measured by Blood Coagulation test
Change in international normalized ratio (INR
Time Frame: Up to 105 days post dosing
Measured by Blood Coagulation test
Change in RR intervals (msec)
Time Frame: Up to 105 days post dosing
Measured using a 12 Lead Electrocardiogram
Change in PR intervals (msec)
Time Frame: Up to 105 days post dosing
Measured using a 12 Lead Electrocardiogram
Change in QRS duration (msec)
Time Frame: Up to 105 days post dosing
Measured using a 12 Lead Electrocardiogram
Change in QT intervals (msec)
Time Frame: Up to 105 days post dosing
Measured using a 12 Lead Electrocardiogram
Change in QTcB intervals (msec)
Time Frame: Up to 105 days post dosing
Measured using a 12 Lead Electrocardiogram
Change in QTcF intervals (msec)
Time Frame: Up to 105 days post dosing
Measured using a 12 Lead Electrocardiogram
Change in blood pressure (mmHg)
Time Frame: Up to 105 days post dosing
Change in pulse rate (bpm)
Time Frame: Up to 105 days post dosing
Change in body temperature (celsius)
Time Frame: Up to 105 days post dosing
Secondary Outcomes
- Maximum observed plasma concentration (Cmax)(Up to 105 days post dosing)
- Time of maximum plasma concentration (Tmax)(Up to 105 days post dosing)
- Terminal half-life (T1/2)(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)(Up to 105 days post dosing)
- Area under the plasma concentration-time curve from time-zero extrapolated to infinite time (AUC0-inf)(Up to 105 days post dosing)
- Apparent total body clearance (CL/F)(Up to 105 days post dosing)
- Apparent volume of distribution (Vz/F)(Up to 105 days post dosing)
- Anti-TNM002 antibodies(Up to 105 days post dosing)