Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TNM002 in Healthy Adults

NCT04629131 | Completed Phase 1

• 1 other identifier: TNM002-P1-AU01
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Healthy Adult Subjects

Outcome Measures

Primary Outcomes (48)

• Incidence and severity of adverse events

  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.

  Up to 105 days post dosing

• Clinically significant abnormality in physical examinations

  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)

  Measured using a 12 Lead Electrocardiogram

  Up to 105 days post dosing

• Change in PR intervals (msec)

  Measured using a 12 Lead Electrocardiogram

  Up to 105 days post dosing

• Change in QRS duration (msec)

  Measured using a 12 Lead Electrocardiogram

  Up to 105 days post dosing

• Change in QT intervals (msec)

  Calculated using measurements by a 12 Lead Electrocardiogram

  Up to 105 days post dosing

• Change in QTcB intervals (msec)

  Calculated using measurements by a 12 Lead Electrocardiogram

  Up to 105 days post dosing

• Change in QTcF intervals (msec)

  Calculated using measurements by a 12 Lead Electrocardiogram

  Up to 105 days post dosing

• Change in Semi recumbent blood pressure (mmHg)

  Up to 105 days post dosing

• Change in pulse rate (bpm)

  Up to 105 days post dosing

• Change in body temperature (celsius)

  Up to 105 days post dosing

• Change in Hematocrit (ratio)

  Measured by hematology test

  Up to 105 days post dosing

• Change in Haemoglobin (g/L)

  Measured by hematology test

  Up to 105 days post dosing

• Change in Mean corpuscular hemoglobin (pg)

  Measured by hematology test

  Up to 105 days post dosing

• Change in Mean corpuscular hemoglobin concentration (g/L)

  Measured by hematology test

  Up to 105 days post dosing

• Change in Mean corpuscular volume (fL)

  Measured by hematology test

  Up to 105 days post dosing

• Change in Platelet count (cells x 10^9/L))

  Measured by hematology test

  Up to 105 days post dosing

• Change in Red blood cell count (cells x 10^12/L)

  Measured by hematology test

  Up to 105 days post dosing

• Change in White blood cell count (cells x 10^9/L)

  Measured by hematology test

  Up to 105 days post dosing

• Change in differential leukocyte count (cells x 10^9/L)

  Including eosinophils, monocytes, lymphocytes, basophils, and neutrophils, Measured by hematology test

  Up to 105 days post dosing

• Change in Serum Alanine Aminotransferase (ALT) (U/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Albumin (g/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Alkaline Phosphatase (ALP) (U/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Aspartate Aminotransferase (AST) (U/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Total Bilirubin (umol/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Blood urea nitrogen (BUN) (mmol/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Calcium (mmol/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Chloride (mmol/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Cholesterol (mmol/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Creatinine (umol/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Creatine Kinase (U/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Glucose (mmol/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Lactate Dehydrogenase (U/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Phosphorus (mmol/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Potassium (mmol/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Serum Total protein (g/L)

  measured by serum chemistry

  Up to 105 days post dosing

• Change in Urine Bilirubin (U-BIL)

  measured by Urinalysis

  Up to 105 days post dosing

• Change in Urine Glucose (GLU) (mg/dL)

  measured by Urinalysis

  Up to 105 days post dosing

• Change in Urine erythrocytes (U-RBC)

  measured by Urinalysis

  Up to 105 days post dosing

• Change in Urinary leukocyte (U-LEU)

  measured by Urinalysis

  Up to 105 days post dosing

• Change in Urine nitrites (U-NIT)

  measured by Urinalysis

  Up to 105 days post dosing

• Change in Urine protein (U-PRO)

  measured by Urinalysis

  Up to 105 days post dosing

• Change in Urine specific gravity (U-SG)

  measured by Urinalysis

  Up to 105 days post dosing

• Change in Urine urobilinogen (URO)

  measured by Urinalysis

  Up to 105 days post dosing

• Change in Prothrombin time (sec)

  measured by Blood Coagulation test

  Up to 105 days post dosing

• Change in Activated partial thromboplastin time (APTT)(sec)

  measured by Blood Coagulation test

  Up to 105 days post dosing

• Change in fibrinogen (g/L)

  measured by Blood Coagulation test

  Up to 105 days post dosing

• Change in international normalized ratio (INR)

  measured by Blood Coagulation test

  Up to 105 days post dosing

Secondary Outcomes (12)

• Anti-TNM002 antibodies

  Up to 105 days post dosing

• Anti-TNM002 antibodies

  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

• Terminal half-life (T1/2)

  Up to 105 days post dosing

Other Outcomes (3)

• Tetanus-antibody titer in serum

  Up to 105 days post dosing

• Time to achieve the maximum tetanus-antibody titer

  Up to 105 days post dosing

• The percentage of subjects with a change of titer ≥ 0.2 IU/mL from the baseline

  Up to 105 days post dosing

Study Arms (4)

Cohort 1 TNM002 10 μg/kg/Placebo

EXPERIMENTAL

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).

Biological: TNM002 Dosage 1 (10 μg/kg); Biological: Placebo

Cohort 2 TNM002 35 μg/kg/Placebo

EXPERIMENTAL

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).

Biological: TNM002 Dosage 2 (35 μg/kg); Biological: Placebo

Cohort 3 TNM002 100 μg/kg/Placebo

EXPERIMENTAL

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).

Biological: TNM002 Dosage 3 (100 μg/kg); Biological: Placebo

Cohort 4 TNM002 250 μg/kg/Placebo

EXPERIMENTAL

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).

Biological: TNM002 Dosage 4 (250 μg/kg); Biological: Placebo

Interventions

TNM002 Dosage 1 (10 μg/kg) BIOLOGICAL

TNM002 (human monoclonal antibody against tetanus toxin), 10 μg/kg, Intramuscular injection, given once.

Cohort 1 TNM002 10 μg/kg/Placebo

Placebo BIOLOGICAL

placebo to match TNM002 Dosage 1, given once

Cohort 1 TNM002 10 μg/kg/Placebo

TNM002 Dosage 2 (35 μg/kg) BIOLOGICAL

TNM002 (human monoclonal antibody against tetanus toxin), 35 μg/kg, Intramuscular injection, given once

Cohort 2 TNM002 35 μg/kg/Placebo

TNM002 Dosage 3 (100 μg/kg) BIOLOGICAL

TNM002 (human monoclonal antibody against tetanus toxin), 100 μg/kg, Intramuscular injection, given once

Cohort 3 TNM002 100 μg/kg/Placebo

TNM002 Dosage 4 (250 μg/kg) BIOLOGICAL

TNM002 (human monoclonal antibody against tetanus toxin), 250 μg/kg, Intramuscular injection, given once

Cohort 4 TNM002 250 μg/kg/Placebo

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.)

You may not qualify if:

• 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;

Sponsors & Collaborators

• Zhuhai Trinomab Pharmaceutical Co., Ltd.: lead
• TIGERMED AUSTRALIA PTY LIMITED: collaborator

Study Sites (1)

Scientia Clinical Research

Sydney, New South Wales, 2031, Australia

Location

Study Officials

• Charlotte Lemech, FRACP

  Scientia Clinical Research Ltd

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 5, 2020
• First Posted: November 16, 2020
• Study Start: November 25, 2020
• Primary Completion: August 13, 2021
• Study Completion: August 13, 2021
• Last Updated: November 7, 2022

Record last verified: 2022-11

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ANALYTIC CODE
• Time Frame: Beginning 3 months and ending 5 years following article publication.
• Access Criteria: Academics who provide a methodologically sound proposal.

Locations

AU (1)