- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04629131
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TNM002 in Healthy Adults
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
Study Overview
Status
Conditions
Detailed Description
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
New South Wales
-
Sydney, New South Wales, Australia, 2031
- Scientia Clinical Research
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
- 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.)
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;
- 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Cohort 1 TNM002 10 μg/kg/Placebo
Sentinel dosing will be conducted for Cohort 1. Two participants will be dosed (1 with TNM002, 1 with placebo) at least 72 hours prior to subsequent dosing.
The remaining participants will only be dosed if no significant safety signals are identified in the sentinel participants.
In total, eight subjects will be randomly assigned to receive either TNM002 or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo).
|
TNM002 (human monoclonal antibody against tetanus toxin), 10 μg/kg, Intramuscular injection, given once.
placebo to match TNM002 Dosage 1, given once
placebo to match TNM002 Dosage 2, given once
placebo to match TNM002 Dosage 3, given once
placebo to match TNM002 Dosage 4, given once
|
Experimental: Cohort 2 TNM002 35 μg/kg/Placebo
Eight subjects will be randomly assigned to receive either TNM002 or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo).
|
placebo to match TNM002 Dosage 1, given once
placebo to match TNM002 Dosage 2, given once
placebo to match TNM002 Dosage 3, given once
placebo to match TNM002 Dosage 4, given once
TNM002 (human monoclonal antibody against tetanus toxin), 35 μg/kg, Intramuscular injection, given once
|
Experimental: Cohort 3 TNM002 100 μg/kg/Placebo
Eight subjects will be randomly assigned to receive either TNM002 or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo).
|
placebo to match TNM002 Dosage 1, given once
placebo to match TNM002 Dosage 2, given once
placebo to match TNM002 Dosage 3, given once
placebo to match TNM002 Dosage 4, given once
TNM002 (human monoclonal antibody against tetanus toxin), 100 μg/kg, Intramuscular injection, given once
|
Experimental: Cohort 4 TNM002 250 μg/kg/Placebo
Eight subjects will be randomly assigned to receive either TNM002 or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo).
|
placebo to match TNM002 Dosage 1, given once
placebo to match TNM002 Dosage 2, given once
placebo to match TNM002 Dosage 3, given once
placebo to match TNM002 Dosage 4, given once
TNM002 (human monoclonal antibody against tetanus toxin), 250 μg/kg, Intramuscular injection, given once
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
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.
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Up to 105 days post dosing
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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
|
Up to 105 days post dosing
|
Change in RR intervals (msec)
Time Frame: Up to 105 days post dosing
|
Measured using a 12 Lead Electrocardiogram
|
Up to 105 days post dosing
|
Change in PR intervals (msec)
Time Frame: Up to 105 days post dosing
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Measured using a 12 Lead Electrocardiogram
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Up to 105 days post dosing
|
Change in QRS duration (msec)
Time Frame: Up to 105 days post dosing
|
Measured using a 12 Lead Electrocardiogram
|
Up to 105 days post dosing
|
Change in QT intervals (msec)
Time Frame: Up to 105 days post dosing
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Calculated using measurements by a 12 Lead Electrocardiogram
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Up to 105 days post dosing
|
Change in QTcB intervals (msec)
Time Frame: Up to 105 days post dosing
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Calculated using measurements by a 12 Lead Electrocardiogram
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Up to 105 days post dosing
|
Change in QTcF intervals (msec)
Time Frame: Up to 105 days post dosing
|
Calculated using measurements by a 12 Lead Electrocardiogram
|
Up to 105 days post dosing
|
Change in Semi recumbent blood pressure (mmHg)
Time Frame: Up to 105 days post dosing
|
Up to 105 days post dosing
|
|
Change in pulse rate (bpm)
Time Frame: Up to 105 days post dosing
|
Up to 105 days post dosing
|
|
Change in body temperature (celsius)
Time Frame: Up to 105 days post dosing
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Up to 105 days post dosing
|
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Change in Hematocrit (ratio)
Time Frame: Up to 105 days post dosing
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Measured by hematology test
|
Up to 105 days post dosing
|
Change in Haemoglobin (g/L)
Time Frame: Up to 105 days post dosing
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Measured by hematology test
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Up to 105 days post dosing
|
Change in Mean corpuscular hemoglobin (pg)
Time Frame: Up to 105 days post dosing
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Measured by hematology test
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Up to 105 days post dosing
|
Change in Mean corpuscular hemoglobin concentration (g/L)
Time Frame: Up to 105 days post dosing
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Measured by hematology test
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Up to 105 days post dosing
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Change in Mean corpuscular volume (fL)
Time Frame: Up to 105 days post dosing
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Measured by hematology test
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Up to 105 days post dosing
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Change in Platelet count (cells x 10^9/L))
Time Frame: Up to 105 days post dosing
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Measured by hematology test
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Up to 105 days post dosing
|
Change in Red blood cell count (cells x 10^12/L)
Time Frame: Up to 105 days post dosing
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Measured by hematology test
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Up to 105 days post dosing
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Change in White blood cell count (cells x 10^9/L)
Time Frame: Up to 105 days post dosing
|
Measured by hematology test
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Up to 105 days post dosing
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Change in differential leukocyte count (cells x 10^9/L)
Time Frame: Up to 105 days post dosing
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Including eosinophils, monocytes, lymphocytes, basophils, and neutrophils, Measured by hematology test
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Up to 105 days post dosing
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Change in Serum Alanine Aminotransferase (ALT) (U/L)
Time Frame: Up to 105 days post dosing
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measured by serum chemistry
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Up to 105 days post dosing
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Change in Serum Albumin (g/L)
Time Frame: Up to 105 days post dosing
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measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Alkaline Phosphatase (ALP) (U/L)
Time Frame: Up to 105 days post dosing
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measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Aspartate Aminotransferase (AST) (U/L)
Time Frame: Up to 105 days post dosing
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measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Total Bilirubin (umol/L)
Time Frame: Up to 105 days post dosing
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measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Blood urea nitrogen (BUN) (mmol/L)
Time Frame: Up to 105 days post dosing
|
measured by serum chemistry
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Up to 105 days post dosing
|
Change in Serum Calcium (mmol/L)
Time Frame: Up to 105 days post dosing
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measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Chloride (mmol/L)
Time Frame: Up to 105 days post dosing
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measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Cholesterol (mmol/L)
Time Frame: Up to 105 days post dosing
|
measured by serum chemistry
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Up to 105 days post dosing
|
Change in Serum Creatinine (umol/L)
Time Frame: Up to 105 days post dosing
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measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Creatine Kinase (U/L)
Time Frame: Up to 105 days post dosing
|
measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Glucose (mmol/L)
Time Frame: Up to 105 days post dosing
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measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Lactate Dehydrogenase (U/L)
Time Frame: Up to 105 days post dosing
|
measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Phosphorus (mmol/L)
Time Frame: Up to 105 days post dosing
|
measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Potassium (mmol/L)
Time Frame: Up to 105 days post dosing
|
measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Serum Total protein (g/L)
Time Frame: Up to 105 days post dosing
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measured by serum chemistry
|
Up to 105 days post dosing
|
Change in Urine Bilirubin (U-BIL)
Time Frame: Up to 105 days post dosing
|
measured by Urinalysis
|
Up to 105 days post dosing
|
Change in Urine Glucose (GLU) (mg/dL)
Time Frame: Up to 105 days post dosing
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measured by Urinalysis
|
Up to 105 days post dosing
|
Change in Urine erythrocytes (U-RBC)
Time Frame: Up to 105 days post dosing
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measured by Urinalysis
|
Up to 105 days post dosing
|
Change in Urinary leukocyte (U-LEU)
Time Frame: Up to 105 days post dosing
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measured by Urinalysis
|
Up to 105 days post dosing
|
Change in Urine nitrites (U-NIT)
Time Frame: Up to 105 days post dosing
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measured by Urinalysis
|
Up to 105 days post dosing
|
Change in Urine protein (U-PRO)
Time Frame: Up to 105 days post dosing
|
measured by Urinalysis
|
Up to 105 days post dosing
|
Change in Urine specific gravity (U-SG)
Time Frame: Up to 105 days post dosing
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measured by Urinalysis
|
Up to 105 days post dosing
|
Change in Urine urobilinogen (URO)
Time Frame: Up to 105 days post dosing
|
measured by Urinalysis
|
Up to 105 days post dosing
|
Change in Prothrombin time (sec)
Time Frame: Up to 105 days post dosing
|
measured by Blood Coagulation test
|
Up to 105 days post dosing
|
Change in Activated partial thromboplastin time (APTT)(sec)
Time Frame: Up to 105 days post dosing
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measured by Blood Coagulation test
|
Up to 105 days post dosing
|
Change in fibrinogen (g/L)
Time Frame: Up to 105 days post dosing
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measured by Blood Coagulation test
|
Up to 105 days post dosing
|
Change in international normalized ratio (INR)
Time Frame: Up to 105 days post dosing
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measured by Blood Coagulation test
|
Up to 105 days post dosing
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Anti-TNM002 antibodies
Time Frame: Up to 105 days post dosing
|
The numbers of subjects who developed anti-TNM002 antibodies
|
Up to 105 days post dosing
|
Anti-TNM002 antibodies
Time Frame: Up to 105 days post dosing
|
The percentages of subjects who developed anti-TNM002 antibodies
|
Up to 105 days post dosing
|
Maximum observed plasma concentration (Cmax)
Time Frame: Up to 105 days post dosing
|
Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above
|
Up to 105 days post dosing
|
Time of maximum plasma concentration (Tmax)
Time Frame: Up to 105 days post dosing
|
Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above
|
Up to 105 days post dosing
|
Terminal half-life (T1/2)
Time Frame: Up to 105 days post dosing
|
Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above
|
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)
Time Frame: Up to 105 days post dosing
|
Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above
|
Up to 105 days post dosing
|
Area under the plasma concentration-time curve from time-zero extrapolated to infinite time (AUC0-inf)
Time Frame: Up to 105 days post dosing
|
Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above
|
Up to 105 days post dosing
|
Apparent oral clearance (CL/F)
Time Frame: Up to 105 days post dosing
|
Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above
|
Up to 105 days post dosing
|
Apparent volume of distribution (Vz/F)
Time Frame: Up to 105 days post dosing
|
Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above
|
Up to 105 days post dosing
|
Mean retention time (MRT)
Time Frame: Up to 105 days post dosing
|
Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above
|
Up to 105 days post dosing
|
Lambda z - the reciprocal of elimination rate constant
Time Frame: Up to 105 days post dosing
|
Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above
|
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)
Time Frame: Up to 105 days post dosing
|
Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above
|
Up to 105 days post dosing
|
Other Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Tetanus-antibody titer in serum
Time Frame: Up to 105 days post dosing
|
Up to 105 days post dosing
|
Time to achieve the maximum tetanus-antibody titer
Time Frame: Up to 105 days post dosing
|
Up to 105 days post dosing
|
The percentage of subjects with a change of titer ≥ 0.2 IU/mL from the baseline
Time Frame: Up to 105 days post dosing
|
Up to 105 days post dosing
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Charlotte Lemech, FRACP, Scientia Clinical Research Ltd
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Other Study ID Numbers
- TNM002-P1-AU01
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Statistical Analysis Plan (SAP)
- Analytic Code
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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