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
Overview
- Phase
- Phase 1
- Intervention
- Not specified
- Conditions
- Healthy Adult Subjects
- Sponsor
- Zhuhai Trinomab Pharmaceutical Co., Ltd.
- Enrollment
- 32
- Locations
- 1
- Primary Endpoint
- Change in Semi recumbent blood pressure (mmHg)
- Status
- Completed
- Last Updated
- 3 years ago
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 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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Each subject must meet the following criteria to be enrolled in this study:
- •Healthy male or female, 18-55 years of age (both inclusive);
- •Able to give signed written informed consent form;
- •Able to well communicate with investigators as well as understand and adhere to the requirements of this study.
- •Body mass index (BMI, weight \[kg\]/height \[m\]2) within 18.0-32.0 kg/m2 (both inclusive);
- •Blood Pressure (BP) and 12-lead ECG showing no clinically significant abnormalities at the discretion of the Principal Investigator during screening;
- •Subjects having no clinically significant abnormality on physical examination, clinical laboratory tests, liver function or kidney function as determined by Principal Investigator (PI);
- •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
Exclusion Criteria
- •Subjects who meet any of the following criteria will be excluded from the study:
- •History or evidence of severe drug or excipient allergy, or hypersensitivity to other therapeutic mAbs;
- •History or evidence of autoimmune disease or possible immunodeficiency state, including positive screening test for HIV;
- •History or evidence of chronic hepatitis, including positive screening test for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody;
- •History or evidence of tetanus infection, or exposure to tetanus vaccine within 6 months prior to the fist drug administration;
- •Exposure to any live attenuated vaccine within 4 weeks prior to the fist drug administration;
- •Exposure to any inactivated vaccine within 2 weeks prior to the fist drug administration;
- •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
- •Subjects with surgery (except for minor outpatient surgery) within past 3 months prior to screening, or planned surgery during study;
- •Subjects with intolerance or insufficient venous access to permit regular venepuncture;
Outcomes
Primary Outcomes
Change in Semi recumbent 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 PR intervals (msec)
Time Frame: Up to 105 days post dosing
Measured using a 12 Lead Electrocardiogram
Incidence and severity of adverse events
Time Frame: 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.
Change in RR intervals (msec)
Time Frame: Up to 105 days post dosing
Measured using a 12 Lead Electrocardiogram
Change in Hematocrit (ratio)
Time Frame: Up to 105 days post dosing
Measured by hematology test
Change in Platelet count (cells x 10^9/L))
Time Frame: Up to 105 days post dosing
Measured by hematology test
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
Calculated using measurements by a 12 Lead Electrocardiogram
Change in Mean corpuscular hemoglobin (pg)
Time Frame: Up to 105 days post dosing
Measured by hematology test
Change in Mean corpuscular hemoglobin concentration (g/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 Serum Total Bilirubin (umol/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 Glucose (mmol/L)
Time Frame: Up to 105 days post dosing
measured by serum chemistry
Change in Prothrombin time (sec)
Time Frame: Up to 105 days post dosing
measured by Blood Coagulation test
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 QTcB intervals (msec)
Time Frame: Up to 105 days post dosing
Calculated using measurements by a 12 Lead Electrocardiogram
Change in QTcF intervals (msec)
Time Frame: Up to 105 days post dosing
Calculated using measurements by a 12 Lead Electrocardiogram
Change in body temperature (celsius)
Time Frame: Up to 105 days post dosing
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
Including eosinophils, monocytes, lymphocytes, basophils, and neutrophils, Measured by hematology test
Change in Mean corpuscular volume (fL)
Time Frame: Up to 105 days post dosing
Measured by hematology test
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 Serum Chloride (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 Urine Bilirubin (U-BIL)
Time Frame: Up to 105 days post dosing
measured by Urinalysis
Change in Urine nitrites (U-NIT)
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 White blood cell count (cells x 10^9/L)
Time Frame: Up to 105 days post dosing
Measured by hematology test
Change in Serum Aspartate Aminotransferase (AST) (U/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 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 international normalized ratio (INR)
Time Frame: Up to 105 days post dosing
measured by Blood Coagulation test
Change in Serum Albumin (g/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 Blood urea nitrogen (BUN) (mmol/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 Potassium (mmol/L)
Time Frame: Up to 105 days post dosing
measured by serum chemistry
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 Urine urobilinogen (URO)
Time Frame: Up to 105 days post dosing
measured by Urinalysis
Change in Serum Creatinine (umol/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 Urinary leukocyte (U-LEU)
Time Frame: Up to 105 days post dosing
measured by Urinalysis
Secondary Outcomes
- Terminal half-life (T1/2)(Up to 105 days post dosing)
- Maximum observed plasma concentration (Cmax)(Up to 105 days post dosing)
- Time of maximum plasma concentration (Tmax)(Up to 105 days post dosing)
- Mean retention time (MRT)(Up to 105 days post dosing)
- Anti-TNM002 antibodies(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 oral clearance (CL/F)(Up to 105 days post dosing)
- Apparent volume of distribution (Vz/F)(Up to 105 days post dosing)
- Lambda z - the reciprocal of elimination rate constant(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)
- 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)