Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of TNM002 in Chinese 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

The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and pharmacodynamics properties of TNM002 following a single intramuscular dose in Chinese healthy adults.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: TNM002; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 28
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Guangdong
    • Zhuhai, Guangdong, China
      • The Fifth Affiliated Hospital Sun Yat-Sen University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

1. Healthy male or female, 18-55 years of age;
2. Body mass index (BMI) within 19.0-26.0 kg/m2;

Exclusion Criteria:

1. Any clinically significant chronic or acute medical condition that makes the volunteer unsuitable for participation;
2. Severe drug or excipient allergy, or history of hypersensitivity to other therapeutic mAbs;
3. History of alcohol or other substance abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Sequential Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Cohort 1: TNM002 35 μg/kg or placebo; Eight subjects will be randomly assigned to receive either TNM002 35 μg/kg or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo)	Drug: TNM002; TNM002, intramuscular injection; Drug: Placebo; Placebo, intramuscular injection
Experimental: Cohort 2: TNM002 100 μg/kg or placebo; Eight subjects will be randomly assigned to receive either TNM002 100 μg/kg or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo)	Drug: TNM002; TNM002, intramuscular injection; Drug: Placebo; Placebo, intramuscular injection
Experimental: Cohort 3：TNM002 250 μg/kg or placebo; Eight subjects will be randomly assigned to receive either TNM002 250 μg/kg or placebo at a 3:1 ratio (i.e. 6 subjects receive TNM002 and 2 with placebo)	Drug: TNM002; TNM002, intramuscular injection; Drug: Placebo; Placebo, intramuscular injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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 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 Red blood cell count (cells x 10^12/L)	Measured by hematology test	Up to 105 days post dosing
AEs	Incidence of AEs	Up to 105 days post dosing
Number of participants with 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 Platelet 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)	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 Aspartate Aminotransferase (AST) (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 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 Creatinine (umol/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 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
Change in QT intervals (msec)	Measured using a 12 Lead Electrocardiogram	Up to 105 days post dosing
Change in QTcB intervals (msec)	Measured using a 12 Lead Electrocardiogram	Up to 105 days post dosing
Change in QTcF intervals (msec)	Measured using a 12 Lead Electrocardiogram	Up to 105 days post dosing
Change in blood pressure (mmHg)		Up to 105 days post dosing

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Anti-TNM002 antibodies	The numbers of subjects who developed anti-TNM002 antibodies	Up to 105 days post dosing
Anti-TNM002 antibodies	The percentages of subjects who developed anti-TNM002 antibodies	Up to 105 days post dosing
Maximum observed plasma concentration (Cmax)	Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;	Up to 105 days post dosing
Time of maximum plasma concentration (Tmax)	Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;	Up to 105 days post dosing
Terminal half-life (T1/2)	Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;	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)	Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;	Up to 105 days post dosing
Area under the plasma concentration-time curve from time-zero extrapolated to infinite time (AUC0-inf)	Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;	Up to 105 days post dosing
Apparent total body clearance (CL/F)	Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;	Up to 105 days post dosing
Apparent volume of distribution (Vz/F)	Estimated by non-compartmental analysis (NCA) with WinNonlin Version 7. 0 or above CL/F, Vz/F, MRT, λz, and %AUCex;	Up to 105 days post dosing

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Tetanus-antibody titer	Geometric mean titers (GMTs) of tetanus-antibody titer in serum	Up to 105 days post dosing
Tetanus-antibody titer	The percentage of subjects with a change of titer > 10 IU/L from the baseline	Up to 105 days post dosing

Collaborators and Investigators

• Sponsor: Trinomab Biotech Co., Ltd.
• Investigators: Principal Investigator: Zhigang Liu, The Fifth Affiliated Hospital Sun Yat-Sen University

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2021
• Primary Completion (Actual): February 24, 2022
• Study Completion (Actual): February 24, 2022

Study Registration Dates

• First Submitted: April 10, 2023
• First Submitted That Met QC Criteria: April 24, 2023
• First Posted (Estimate): May 4, 2023

Study Record Updates

• Last Update Posted (Estimate): May 4, 2023
• Last Update Submitted That Met QC Criteria: April 24, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: TNM002-P1-CH01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data that underlie the results reported in these articles after deidentification
• IPD Sharing Time Frame: Beginning 3 months and ending 5 years following article publication.
• IPD Sharing Access Criteria: Academics who provide a methodologically sound proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No