A Randomized, Open-Label, Parallel-Design Pharmacokinetic and Pharmacodynamic Interaction Study of TNM002 and Adsorbed Tetanus Vaccine

A Randomized, Open-Label, Parallel-Design Pharmacokinetic and Pharmacodynamic Interaction Study of TNM002 and Adsorbed Tetanus Vaccine Administered Alone and Simultaneously Administered in Chinese Healthy Subjects

This study is designed as a randomized, open-label, parallel-design study to evaluate the effect of TNM002 simultaneously administered with adsorbed tetanus vaccine on the PK, PD and immunogenicity properties of TNM002 and on the PD properties of the adsorbed tetanus vaccine, and to evaluate the safety and tolerability of TNM002 administered alone and simultaneously administered with adsorbed tetanus vaccine.

Study Overview

• Status: Completed
• Conditions: Tetanus
• Intervention / Treatment: Biological: TNM002; Biological: Adsorbed tetanus vaccine; Biological: TNM002 + adsorbed tetanus vaccine

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 1

Contacts and Locations

Study Locations

• China
  • Shandong
    • Zibo, Shandong, China, 255000
      • PKUcare Luzhong Hospital

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 (inclusive) at enrollment;
2. Subjects who voluntarily provide signed written ICF;
3. Subjects who are able to well communicate with investigator as well as understand and adhere to the requirements of this study;

Exclusion Criteria:

1. Previous history of gastrointestinal, renal, hepatic, neurological, hematological, endocrine, oncologic, respiratory, immunological, cardiovascular and cerebrovascular diseases, which, as judged by the investigator, may affect the safety of the patient or may affect the PK, PD or immunogenicity assessment of this study;
2. Exposure to tetanus vaccines or vaccines containing antigenic components of tetanus toxoid within the past 10 years;
3. Exposure to tetanus immunoglobulin, receipt of blood transfusion or use of blood products within the past 6 months prior to screening;
4. History or family history of neurologic symptoms such as convulsions, epilepsy, encephalopathy and psychosis;
5. Subjects with thrombopenia or other coagulation disorders, or bleeding constitution or bleeding time prolongation, which may cause contraindications to IM injection;
6. Subjects with any acute illness requiring systemic antibiotics or antiviral therapy within 7 days prior to screening. Subjects with fever within 3 days prior to screening;
7. Receipt of immunosuppressants or immunopotentiators, other than inhaled or topical immunosuppressants within 3 months prior to dosing;
8. Allergy to the investigational product or its excipients, or have a history of allergy to vaccines or human immunoglobulin products or other therapeutic monoclonal antibodies (mAbs);
9. History of surgery within 3 months prior to screening, or planned surgery during the study;
10. Known or suspected history of drug abuse within 5 years prior to screening, or with positive urine drug abuse screening result; or a previous history of drug addiction;
11. Participation in other clinical studies with the investigational drugs or devices within 3 months or within 5 times the half-life of the specific drugs/biological products prior to dosing, except for observational, non-interventional clinical studies;
12. Use of any other drug, including over-the-counter medications and Chinese herbal medicines within 14 days prior to dosing ;
13. Exposure to other vaccines within 1 month prior to dosing, or plan to receive live vaccines within 3 months after dosing;
14. Pregnant or lactating women;

Other protocol defined Inclusion/Exclusion criteria may apply.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Group 1; TNM002	Biological: TNM002; A single intramuscular (IM) gluteal injection
Active Comparator: Group 2; Adsorbed tetanus vaccine	Biological: Adsorbed tetanus vaccine; A single IM deltoid injection
Experimental: Group 3; TNM002 + adsorbed tetanus vaccine	Biological: TNM002 + adsorbed tetanus vaccine; A single IM gluteal injection+ a single IM deltoid injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Maximum concentration (Cmax) of TNM002, area under the plasma concentration-time curve from time 0 to the last quantifiable time point post-dose (AUC0-last)	Up to Day 106
Percentage of subjects with an increase of serum TNM002-specific anti-tetanus neutralizing antibody titers (ΔTiters) ≥ 0.01 IU/mL from baseline at 24 hours after immunization	Up to 24 hours after administration
Percentage of subjects with serum anti-tetanus antibody titers ≥ 0.1 IU/mL on 28 days after immunization	Up to 28 days after administration

Secondary Outcome Measures

Outcome Measure	Time Frame
Time to maximum serum TNM002 concentration (Tmax), elimination half-life (t1/2), and if data permit, apparent clearance (CL/F) and apparent volume of distribution (Vz/F) after immunization	Up to Day 106
Percentage of subjects with anti-tetanus neutralizing antibody ΔTiters ≥ 0.01 IU/mL at post-dose time points other than 24 hours after immunization	Up to Day 106
Serum TNM002-specific anti-tetanus neutralizing antibody titer and ΔTiters at each post-dose time point after immunization	Up to Day 106
Percentage of subjects with anti-tetanus antibody titer ≥ 0.1 IU/mL at post-dose time points other than 28 days after immunization	Up to Day 106
Percentage of subjects with serum anti-tetanus antibody titer ≥ 1.0 IU/mL at each post-dose time point after immunization	Up to Day 106
Serum anti-tetanus antibody titers, and fold increases from baseline at each post-dose time point	Up to Day 106
Adverse events (AEs), safety laboratory test, 12-lead electrocardiogram (ECG), physical examination, and vital signs	Up to Day 106
Percentage of subjects with positive anti-TNM002 antibody (ADA) in serum.	Up to Day 106

Collaborators and Investigators

• Sponsor: Zhuhai Trinomab Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Jie Hou, Doctor, Peking University Care Luzhong Hospital

Study record dates

Study Major Dates

• Study Start (Actual): August 13, 2022
• Primary Completion (Actual): April 10, 2023
• Study Completion (Actual): April 17, 2023

Study Registration Dates

• First Submitted: September 12, 2024
• First Submitted That Met QC Criteria: September 19, 2024
• First Posted (Actual): September 23, 2024

Study Record Updates

• Last Update Posted (Actual): September 23, 2024
• Last Update Submitted That Met QC Criteria: September 19, 2024
• Last Verified: September 1, 2024

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Metabolic Diseases; Nervous System Diseases; Infections; Neurologic Manifestations; Bacterial Infections; Bacterial Infections and Mycoses; Gram-Positive Bacterial Infections; Neuromuscular Manifestations; Clostridium Infections; Hypocalcemia; Calcium Metabolism Disorders; Tetanus; Tetany; Physiological Effects of Drugs; Immunologic Factors; Vaccines
• Other Study ID Numbers: TNM002-P1-CH02

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 the article, after deidentification.
• IPD Sharing Time Frame: Starting 6 months and ending 5 years following article publication.
• IPD Sharing Access Criteria: Academics who provide a methodologically sound proposal. The leading clinical site and sponsor will review the request.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL

Drug and device information, study documents

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