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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT04629131




Registration number
NCT04629131
Ethics application status
Date submitted
5/11/2020
Date registered
16/11/2020

Titles & IDs
Public title
Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TNM002 in Healthy Adults
Scientific title
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
Secondary ID [1] 0 0
TNM002-P1-AU01
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Healthy Adult Subjects 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Other - TNM002 Dosage 1 (10 µg/kg)
Treatment: Other - Placebo
Treatment: Other - TNM002 Dosage 2 (35 µg/kg)
Treatment: Other - Placebo
Treatment: Other - TNM002 Dosage 3 (100 µg/kg)
Treatment: Other - Placebo
Treatment: Other - TNM002 Dosage 4 (250 µg/kg)
Treatment: Other - Placebo

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).

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).

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).

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).


Treatment: Other: TNM002 Dosage 1 (10 µg/kg)
TNM002 (human monoclonal antibody against tetanus toxin), 10 µg/kg, Intramuscular injection, given once.

Treatment: Other: Placebo
placebo to match TNM002 Dosage 1, given once

Treatment: Other: TNM002 Dosage 2 (35 µg/kg)
TNM002 (human monoclonal antibody against tetanus toxin), 35 µg/kg, Intramuscular injection, given once

Treatment: Other: Placebo
placebo to match TNM002 Dosage 2, given once

Treatment: Other: TNM002 Dosage 3 (100 µg/kg)
TNM002 (human monoclonal antibody against tetanus toxin), 100 µg/kg, Intramuscular injection, given once

Treatment: Other: Placebo
placebo to match TNM002 Dosage 3, given once

Treatment: Other: TNM002 Dosage 4 (250 µg/kg)
TNM002 (human monoclonal antibody against tetanus toxin), 250 µg/kg, Intramuscular injection, given once

Treatment: Other: Placebo
placebo to match TNM002 Dosage 4, given once
Intervention code [1] 0 0
Treatment: Other
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Incidence and severity of adverse events
Timepoint [1] 0 0
Up to 105 days post dosing
Primary outcome [2] 0 0
Clinically significant abnormality in physical examinations
Timepoint [2] 0 0
Up to 105 days post dosing
Primary outcome [3] 0 0
Change in RR intervals (msec)
Timepoint [3] 0 0
Up to 105 days post dosing
Primary outcome [4] 0 0
Change in PR intervals (msec)
Timepoint [4] 0 0
Up to 105 days post dosing
Primary outcome [5] 0 0
Change in QRS duration (msec)
Timepoint [5] 0 0
Up to 105 days post dosing
Primary outcome [6] 0 0
Change in QT intervals (msec)
Timepoint [6] 0 0
Up to 105 days post dosing
Primary outcome [7] 0 0
Change in QTcB intervals (msec)
Timepoint [7] 0 0
Up to 105 days post dosing
Primary outcome [8] 0 0
Change in QTcF intervals (msec)
Timepoint [8] 0 0
Up to 105 days post dosing
Primary outcome [9] 0 0
Change in Semi recumbent blood pressure (mmHg)
Timepoint [9] 0 0
Up to 105 days post dosing
Primary outcome [10] 0 0
Change in pulse rate (bpm)
Timepoint [10] 0 0
Up to 105 days post dosing
Primary outcome [11] 0 0
Change in body temperature (celsius)
Timepoint [11] 0 0
Up to 105 days post dosing
Primary outcome [12] 0 0
Change in Hematocrit (ratio)
Timepoint [12] 0 0
Up to 105 days post dosing
Primary outcome [13] 0 0
Change in Haemoglobin (g/L)
Timepoint [13] 0 0
Up to 105 days post dosing
Primary outcome [14] 0 0
Change in Mean corpuscular hemoglobin (pg)
Timepoint [14] 0 0
Up to 105 days post dosing
Primary outcome [15] 0 0
Change in Mean corpuscular hemoglobin concentration (g/L)
Timepoint [15] 0 0
Up to 105 days post dosing
Primary outcome [16] 0 0
Change in Mean corpuscular volume (fL)
Timepoint [16] 0 0
Up to 105 days post dosing
Primary outcome [17] 0 0
Change in Platelet count (cells x 10^9/L))
Timepoint [17] 0 0
Up to 105 days post dosing
Primary outcome [18] 0 0
Change in Red blood cell count (cells x 10^12/L)
Timepoint [18] 0 0
Up to 105 days post dosing
Primary outcome [19] 0 0
Change in White blood cell count (cells x 10^9/L)
Timepoint [19] 0 0
Up to 105 days post dosing
Primary outcome [20] 0 0
Change in differential leukocyte count (cells x 10^9/L)
Timepoint [20] 0 0
Up to 105 days post dosing
Primary outcome [21] 0 0
Change in Serum Alanine Aminotransferase (ALT) (U/L)
Timepoint [21] 0 0
Up to 105 days post dosing
Primary outcome [22] 0 0
Change in Serum Albumin (g/L)
Timepoint [22] 0 0
Up to 105 days post dosing
Primary outcome [23] 0 0
Change in Serum Alkaline Phosphatase (ALP) (U/L)
Timepoint [23] 0 0
Up to 105 days post dosing
Primary outcome [24] 0 0
Change in Serum Aspartate Aminotransferase (AST) (U/L)
Timepoint [24] 0 0
Up to 105 days post dosing
Primary outcome [25] 0 0
Change in Serum Total Bilirubin (umol/L)
Timepoint [25] 0 0
Up to 105 days post dosing
Primary outcome [26] 0 0
Change in Serum Blood urea nitrogen (BUN) (mmol/L)
Timepoint [26] 0 0
Up to 105 days post dosing
Primary outcome [27] 0 0
Change in Serum Calcium (mmol/L)
Timepoint [27] 0 0
Up to 105 days post dosing
Primary outcome [28] 0 0
Change in Serum Chloride (mmol/L)
Timepoint [28] 0 0
Up to 105 days post dosing
Primary outcome [29] 0 0
Change in Serum Cholesterol (mmol/L)
Timepoint [29] 0 0
Up to 105 days post dosing
Primary outcome [30] 0 0
Change in Serum Creatinine (umol/L)
Timepoint [30] 0 0
Up to 105 days post dosing
Primary outcome [31] 0 0
Change in Serum Creatine Kinase (U/L)
Timepoint [31] 0 0
Up to 105 days post dosing
Primary outcome [32] 0 0
Change in Serum Glucose (mmol/L)
Timepoint [32] 0 0
Up to 105 days post dosing
Primary outcome [33] 0 0
Change in Serum Lactate Dehydrogenase (U/L)
Timepoint [33] 0 0
Up to 105 days post dosing
Primary outcome [34] 0 0
Change in Serum Phosphorus (mmol/L)
Timepoint [34] 0 0
Up to 105 days post dosing
Primary outcome [35] 0 0
Change in Serum Potassium (mmol/L)
Timepoint [35] 0 0
Up to 105 days post dosing
Primary outcome [36] 0 0
Change in Serum Total protein (g/L)
Timepoint [36] 0 0
Up to 105 days post dosing
Primary outcome [37] 0 0
Change in Urine Bilirubin (U-BIL)
Timepoint [37] 0 0
Up to 105 days post dosing
Primary outcome [38] 0 0
Change in Urine Glucose (GLU) (mg/dL)
Timepoint [38] 0 0
Up to 105 days post dosing
Primary outcome [39] 0 0
Change in Urine erythrocytes (U-RBC)
Timepoint [39] 0 0
Up to 105 days post dosing
Primary outcome [40] 0 0
Change in Urinary leukocyte (U-LEU)
Timepoint [40] 0 0
Up to 105 days post dosing
Primary outcome [41] 0 0
Change in Urine nitrites (U-NIT)
Timepoint [41] 0 0
Up to 105 days post dosing
Primary outcome [42] 0 0
Change in Urine protein (U-PRO)
Timepoint [42] 0 0
Up to 105 days post dosing
Primary outcome [43] 0 0
Change in Urine specific gravity (U-SG)
Timepoint [43] 0 0
Up to 105 days post dosing
Primary outcome [44] 0 0
Change in Urine urobilinogen (URO)
Timepoint [44] 0 0
Up to 105 days post dosing
Primary outcome [45] 0 0
Change in Prothrombin time (sec)
Timepoint [45] 0 0
Up to 105 days post dosing
Primary outcome [46] 0 0
Change in Activated partial thromboplastin time (APTT)(sec)
Timepoint [46] 0 0
Up to 105 days post dosing
Primary outcome [47] 0 0
Change in fibrinogen (g/L)
Timepoint [47] 0 0
Up to 105 days post dosing
Primary outcome [48] 0 0
Change in international normalized ratio (INR)
Timepoint [48] 0 0
Up to 105 days post dosing
Secondary outcome [1] 0 0
Anti-TNM002 antibodies
Timepoint [1] 0 0
Up to 105 days post dosing
Secondary outcome [2] 0 0
Anti-TNM002 antibodies
Timepoint [2] 0 0
Up to 105 days post dosing
Secondary outcome [3] 0 0
Maximum observed plasma concentration (Cmax)
Timepoint [3] 0 0
Up to 105 days post dosing
Secondary outcome [4] 0 0
Time of maximum plasma concentration (Tmax)
Timepoint [4] 0 0
Up to 105 days post dosing
Secondary outcome [5] 0 0
Terminal half-life (T1/2)
Timepoint [5] 0 0
Up to 105 days post dosing
Secondary outcome [6] 0 0
Area under the plasma concentration-time curve from time-zero to the time of the last measurable concentration (AUC0-last)
Timepoint [6] 0 0
Up to 105 days post dosing
Secondary outcome [7] 0 0
Area under the plasma concentration-time curve from time-zero extrapolated to infinite time (AUC0-inf)
Timepoint [7] 0 0
Up to 105 days post dosing
Secondary outcome [8] 0 0
Apparent oral clearance (CL/F)
Timepoint [8] 0 0
Up to 105 days post dosing
Secondary outcome [9] 0 0
Apparent volume of distribution (Vz/F)
Timepoint [9] 0 0
Up to 105 days post dosing
Secondary outcome [10] 0 0
Mean retention time (MRT)
Timepoint [10] 0 0
Up to 105 days post dosing
Secondary outcome [11] 0 0
Lambda z - the reciprocal of elimination rate constant
Timepoint [11] 0 0
Up to 105 days post dosing
Secondary outcome [12] 0 0
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)
Timepoint [12] 0 0
Up to 105 days post dosing

Eligibility
Key inclusion criteria
Each subject must meet the following criteria to be enrolled in this study:

1. Healthy male or female, 18-55 years of age (both inclusive);
2. Able to give signed written informed consent form;
3. Able to well communicate with investigators as well as understand and adhere to the requirements of this study.
4. Body mass index (BMI, weight [kg]/height [m]2) within 18.0-32.0 kg/m2 (both inclusive);
5. Blood Pressure (BP) and 12-lead ECG showing no clinically significant abnormalities at the discretion of the Principal Investigator during screening;
6. Subjects having no clinically significant abnormality on physical examination, clinical laboratory tests, liver function or kidney function as determined by Principal Investigator (PI);
7. 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.)
Minimum age
18 Years
Maximum age
55 Years
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Subjects who meet any of the following criteria will be excluded from the study:

1. History or evidence of severe drug or excipient allergy, or hypersensitivity to other therapeutic mAbs;
2. History or evidence of autoimmune disease or possible immunodeficiency state, including positive screening test for HIV;
3. History or evidence of chronic hepatitis, including positive screening test for serum hepatitis B surface antigen (HBsAg), hepatitis C antibody;
4. History or evidence of tetanus infection, or exposure to tetanus vaccine within 6 months prior to the fist drug administration;
5. Exposure to any live attenuated vaccine within 4 weeks prior to the fist drug administration;
6. Exposure to any inactivated vaccine within 2 weeks prior to the fist drug administration;
7. 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
8. Subjects with surgery (except for minor outpatient surgery) within past 3 months prior to screening, or planned surgery during study;
9. Subjects with intolerance or insufficient venous access to permit regular venepuncture;
10. Known or suspected history of drug abuse within the past 5 years or with positive urine drug test at the screening;
11. 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;
12. 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;
13. 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);
14. Receipt of an Ig or blood product within 90 days prior to the first drug administration;
15. Receipt of immunosuppressive medications, other than inhaled or topical immunosuppressant drugs, within 45 days prior to the first drug administration;
16. 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;
17. 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.;
18. Malignancy within 5 years of screening visit (except basal cell skin carcinoma);
19. Subject who is considered unsuitable for participating in the study in the opinion of investigator;
20. Nursing mothers or pregnant women.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
25/11/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
13/08/2021
Sample size
Target
Accrual to date
Final
32
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Scientia Clinical Research - Sydney
Recruitment postcode(s) [1] 0 0
2031 - Sydney

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Zhuhai Trinomab Pharmaceutical Co., Ltd.
Address
Country
Other collaborator category [1] 0 0
Other
Name [1] 0 0
TIGERMED AUSTRALIA PTY LIMITED
Address [1] 0 0
Country [1] 0 0

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Charlotte Lemech, FRACP
Address 0 0
Scientia Clinical Research Ltd
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
Individual participant data that underlie the results reported in these articles, after deidentification (text, tables, figures, and appendices)

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Analytic code
When will data be available (start and end dates)?
Beginning 3 months and ending 5 years following article publication.
Available to whom?
Academics who provide a methodologically sound proposal.
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.


Results not provided in https://clinicaltrials.gov/study/NCT04629131