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
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 32
- 试验地点
- 2
- 主要终点
- Change in Semi recumbent blood pressure (mmHg)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 55 Years（Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
- •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.)
排除标准
- •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;
- •Known or suspected history of drug abuse within the past 5 years or with positive urine drug test at the screening;
- •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;
- •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;
- •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);
- •Receipt of an Ig or blood product within 90 days prior to the first drug administration;
- •Receipt of immunosuppressive medications, other than inhaled or topical immunosuppressant drugs, within 45 days prior to the first drug administration;
- •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;
- •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.;
- •Malignancy within 5 years of screening visit (except basal cell skin carcinoma);
- •Subject who is considered unsuitable for participating in the study in the opinion of investigator;
- •Nursing mothers or pregnant women.
结局指标
主要结局
Change in Semi recumbent blood pressure (mmHg)
时间窗: Up to 105 days post dosing
Change in pulse rate (bpm)
时间窗: Up to 105 days post dosing
Change in PR intervals (msec)
时间窗: Up to 105 days post dosing
Measured using a 12 Lead Electrocardiogram
Incidence and severity of adverse events
时间窗: 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)
时间窗: Up to 105 days post dosing
Measured using a 12 Lead Electrocardiogram
Change in Hematocrit (ratio)
时间窗: Up to 105 days post dosing
Measured by hematology test
Change in Platelet count (cells x 10^9/L))
时间窗: Up to 105 days post dosing
Measured by hematology test
Change in QRS duration (msec)
时间窗: Up to 105 days post dosing
Measured using a 12 Lead Electrocardiogram
Change in QT intervals (msec)
时间窗: Up to 105 days post dosing
Calculated using measurements by a 12 Lead Electrocardiogram
Change in Mean corpuscular hemoglobin (pg)
时间窗: Up to 105 days post dosing
Measured by hematology test
Change in Mean corpuscular hemoglobin concentration (g/L)
时间窗: Up to 105 days post dosing
Measured by hematology test
Change in Serum Alanine Aminotransferase (ALT) (U/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Serum Total Bilirubin (umol/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Serum Cholesterol (mmol/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Serum Glucose (mmol/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Prothrombin time (sec)
时间窗: Up to 105 days post dosing
measured by Blood Coagulation test
Clinically significant abnormality in physical examinations
时间窗: 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)
时间窗: Up to 105 days post dosing
Calculated using measurements by a 12 Lead Electrocardiogram
Change in QTcF intervals (msec)
时间窗: Up to 105 days post dosing
Calculated using measurements by a 12 Lead Electrocardiogram
Change in body temperature (celsius)
时间窗: Up to 105 days post dosing
Change in Haemoglobin (g/L)
时间窗: Up to 105 days post dosing
Measured by hematology test
Change in differential leukocyte count (cells x 10^9/L)
时间窗: Up to 105 days post dosing
Including eosinophils, monocytes, lymphocytes, basophils, and neutrophils, Measured by hematology test
Change in Mean corpuscular volume (fL)
时间窗: Up to 105 days post dosing
Measured by hematology test
Change in Red blood cell count (cells x 10^12/L)
时间窗: Up to 105 days post dosing
Measured by hematology test
Change in Serum Chloride (mmol/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Serum Lactate Dehydrogenase (U/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Serum Phosphorus (mmol/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Urine Bilirubin (U-BIL)
时间窗: Up to 105 days post dosing
measured by Urinalysis
Change in Urine nitrites (U-NIT)
时间窗: Up to 105 days post dosing
measured by Urinalysis
Change in Activated partial thromboplastin time (APTT)(sec)
时间窗: Up to 105 days post dosing
measured by Blood Coagulation test
Change in fibrinogen (g/L)
时间窗: Up to 105 days post dosing
measured by Blood Coagulation test
Change in White blood cell count (cells x 10^9/L)
时间窗: Up to 105 days post dosing
Measured by hematology test
Change in Serum Aspartate Aminotransferase (AST) (U/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Serum Total protein (g/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Urine protein (U-PRO)
时间窗: Up to 105 days post dosing
measured by Urinalysis
Change in Urine specific gravity (U-SG)
时间窗: Up to 105 days post dosing
measured by Urinalysis
Change in international normalized ratio (INR)
时间窗: Up to 105 days post dosing
measured by Blood Coagulation test
Change in Serum Albumin (g/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Serum Alkaline Phosphatase (ALP) (U/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Serum Blood urea nitrogen (BUN) (mmol/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Serum Calcium (mmol/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Serum Potassium (mmol/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Urine Glucose (GLU) (mg/dL)
时间窗: Up to 105 days post dosing
measured by Urinalysis
Change in Urine erythrocytes (U-RBC)
时间窗: Up to 105 days post dosing
measured by Urinalysis
Change in Urine urobilinogen (URO)
时间窗: Up to 105 days post dosing
measured by Urinalysis
Change in Serum Creatinine (umol/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Serum Creatine Kinase (U/L)
时间窗: Up to 105 days post dosing
measured by serum chemistry
Change in Urinary leukocyte (U-LEU)
时间窗: Up to 105 days post dosing
measured by Urinalysis
次要结局
- 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)
- 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)
- Anti-TNM002 antibodies(Up to 105 days post dosing)