Study to Compare the Efficacy and Safety of Passive Immunization With TNM002 Injection and Human Tetanus Immunoglobulin as Prophylaxis Against Tetanus

A Multicenter, Randomized, Double-Blind, Parallel-Group, Active-Controlled Phase III Study to Compare the Efficacy and Safety of Passive Immunization With TNM002 Injection and Human Tetanus Immunoglobulin as Prophylaxis Against Tetanus

TNM002 Injection is a recombinant fully human native monoclonal antibody (mAb) against tetanus toxin and is currently under development for indication of prophylaxis against tetanus.

Study Overview

• Status: Completed
• Conditions: Tetanus
• Intervention / Treatment: Drug: TNM002; Drug: Human tetanus immunoglobulin (HTIG)

• Study Type: Interventional
• Enrollment (Actual): 675
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Jiayu Li; Phone Number: ++86 0756 726399; Email: Jiayu.li@trinomab.com

Study Locations

• China
  • Anhui
    • Hefei, Anhui, China, 230601
      • The Second Hospital of Anhui Medical University
    • Hefei, Anhui, China, 230061
      • Hefei First People's Hospital
      • Contact: Lei He, MD; Phone Number: +86 13013099602; Email: helei892259@qq.com
  • Beijing
    • Beijing, Beijing, China, 100034
      • Peking University First Hospital
      • Contact: Si Liu, MD; Phone Number: +86 13501220344; Email: DocLeo@vip.sina.com
    • Beijing, Beijing, China, 100044
      • Peking University People's Hospital
      • Contact: Chuanlin Wang, MD; Phone Number: +86 13911883012; Email: wangchuanlinvip@163.com
    • Beijing, Beijing, China, 100070
      • Beijing Tiantan Hospital Affiliated to Capital Medical University
      • Contact: Bin Xu, MD; Phone Number: +86 13683527280; Email: icexubin@aliyun.com
  • Guangdong
    • Guangzhou, Guangdong, China, 510180
      • Guangzhou First People's Hospital
      • Contact: Jianwei Wang, MD; Phone Number: +86 13316188653; Email: 13316188653@189.com
    • Guangzhou, Guangdong, China, 510515
      • Nanfang Hospital of Southern Medical University
      • Contact: Xu Li, MD; Phone Number: +86 18680248866; Email: mylx99@163.com
    • Guangzhou, Guangdong, China, 510120
      • Guangdong Provincial Hospital of Chinese Medicine
      • Contact: Banghan Ding, MD; Phone Number: +86 13682238225; Email: banghanding@139.com
    • Guangzhou, Guangdong, China, 510062
      • The First Affiliated Hospital, Sun Yat-sen University
      • Contact: Hong Zhan, MD; Phone Number: +86 13602796992; Email: zhanhong81@126.com
    • Guangzhou, Guangdong, China, 510150
      • The Third Affiliated Hospital of Guangzhou Medical University
      • Contact: Junyan Hu, MD; Phone Number: +86 18926197810; Email: hujunyan001@163.com
    • Guangzhou, Guangdong, China, 511407
      • The First Affiliated Hospital of Guangzhou Medical University
    • Shenzhen, Guangdong, China, 518025
      • Shenzhen Second People's Hospital
      • Contact: Zhe Deng, MD; Phone Number: +86 15815520928; Email: dengz163@163.com
  • Guangxi
    • Liuzhou, Guangxi, China, 545007
      • Liuzhou Worker's Hospital - Fourth Affiliated Hospital of Guangxi Medical University
  • Guizhou
    • Zunyi, Guizhou, China, 563000
      • Affiliated Hospital of Zunyi Medical College
      • Contact: Anyong Yu, MD; Phone Number: +86 13511897722; Email: 2360298076@qq.com
  • Hainan
    • Haikou, Hainan, China, 570311
      • Hainan General Hospital
      • Contact: Ouyang Yan-Hong, MD; Phone Number: +86 13907628077; Email: ouyang1893@126.com
  • Hangzhou
    • Hangzhou, Hangzhou, China, 310014
      • Zhejiang Provincial People's Hospital
      • Contact: Wenwei Cai, MD; Phone Number: +86 13588760325; Email: wweai@139.com
  • Hubei
    • Wuhan, Hubei, China, 430060
      • Renmin Hospital of Wuhan University
      • Contact: Wenqiang Li, MD; Phone Number: +86 15871358933; Email: 13971583624@139.com
    • Wuhan, Hubei, China, 430062
      • Zhongnan Hospital of Wuhan University
      • Contact: Yan Zhao, MD; Phone Number: +86 13995577963; Email: doctoryanzhao@whu.edu.cn
    • Wuhan, Hubei, China, 430030
      • Tongji Hospital, Tongji Medical College of Huazhong University of Science and Technology
    • Wuhan, Hubei, China, 430014
      • The Central Hospital of Wuhan, Tongji Medical College Huazhong University of Science&Technology
  • Hunan
    • Changsha, Hunan, China, 410011
      • The second Xiangya Hospital of Central South University
      • Contact: Dongshan Zhang, MD; Phone Number: +86 13875899625; Email: dongshanzhang@csu.edu.cn
    • Hengyang, Hunan, China, 421010
      • Affiliated Nanhua Hospital, University of South China
      • Contact: Wenkai Bin, MD; Phone Number: +86 15307340263; Email: syybwk@163.com
  • Jiangxi
    • Nanchang, Jiangxi, China, 330008
      • The Second Affiliated Hospital of Nanchang University
      • Contact: Lidong Wu, MD; Phone Number: +86 13807095219; Email: dongguawu89@163.com
  • Ningxia
    • Yinchuan, Ningxia, China, 750003
      • General Hospital of Ningxia Medical University
      • Contact: Lishan Yang, MD; Phone Number: +86 13995216188; Email: nyfyyls@126.com
  • Shandong
    • Zibo, Shandong, China, 255499
      • PKUCare Luzhong Hospital
      • Contact: Chunlei Wang, MD; Phone Number: +86 18553376986; Email: wcl800415@163.com
  • Shanxi
    • Jinzhong, Shanxi, China, 030602
      • The First People's Hospital of Jinzhong
      • Contact: Shugui Li, MD; Phone Number: +86 13903449239; Email: jzklsg@126.com
    • Taiyuan, Shanxi, China, 030032
      • Shanxi Academy of Medical Sciences - Shanxi Bethune Hospital (Shanxi Dayi Hospital)
      • Contact: Xinming Yan, MD; Phone Number: +86 13934572668; Email: 1943730288@qq.com
    • Yuncheng, Shanxi, China, 044099
      • Yuncheng Central Hospital - East Campus

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Chinese male or female adults aged ≥ 18 years;
2. Participants with dirty or contaminated wounds caused by various injury who require passive immunization as prophylaxis against tetanus;
3. Participants who provide signed written informed consent form.

Exclusion Criteria:

1. Known or suspected allergy to the investigational product or its excipients, or have a history of allergy to human immunoglobulin products or other therapeutic monoclonal immunoglobulins;
2. Suspect or diagnosed as tetanus;
3. Previously diagnosed as Immunoglobulin A (IgA) deficiency with anti-IgA antibodies
4. Prior vaccination history of ≥ 3 doses of tetanus toxoid or tetanus toxoid- containing vaccine;
5. Current alcohol abuse, drug abuse or drug addiction

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: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: TNM002; If randomized to TNM002, participant will receive a single IM gluteal injection of TNM002	Drug: TNM002; Dosage Form: Injection, solution Route of administration: IM gluteal injection
Active Comparator: Human tetanus immunoglobulin (HTIG); If randomized to HTIG, participant will receive a single IM gluteal injection of HTIG	Drug: Human tetanus immunoglobulin (HTIG); Dosage Form: Injection, solution Route of administration: IM gluteal injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Proportion of participants with an increase of anti-tetanus neutralizing antibody titers (∆ titers) over protective level.	Baseline up to 12 hours after receipt of study drug

Secondary Outcome Measures

Outcome Measure	Time Frame
Tetanus protection rate (1 - tetanus incidence)	Up to 28 days after receipt of study drug

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of adverse events (AEs)		Up to 105 days after receipt of study drug
Incidence of treatment related adverse events (AEs)		Up to 105 days after receipt of study drug
Incidence of serious adverse events (SAEs)		Up to 105 days after receipt of study drug
The number and percentage of subjects with abnormal hematology tests	The hemotology tests include red blood cell count, hemoglobin, platelet count, white blood cell count, absolute neutrophil count, neutrophil percentage, absolute lymphocyte count, lymphocytes percentage, absolute monocyte count, and hematocrit	Up to 90 days after receipt of study drug
The number and percentage of subjects with abnormal serum chemistry tests	The serum chemistry tests include total protein, albumin, sodium, potassium, chloride, calcium, glucose, aspartate aminotransferase, alanine aminotransferase, total bilirubin, direct bilirubin, urea (blood urea nitrogen) and creatinine	Up to 90 days after receipt of study drug
The number and percentage of subjects with abnormal urinalysis tests	The urinalysis tests include protein, glucose, urobilinogen, urine occult blood, red blood cell and white blood cell	Up to 90 days after receipt of study drug
The number and percentage of subjects with abnormal vital signs	The vital signs include blood pressure, pulse rate, respiratory rate, and body temperature	Up to 90 days after receipt of study drug
The number and percentage of subjects with abnormal physical examination	The physical examination includes skin, lymph nodes, eyes, head and neck, chest, abdomen, spine, extremities.	Up to 90 days after receipt of study drug
The number and percentage of subjects with abnormal 12-lead electrocardiogram (ECG)		Up to 90 days after receipt of study drug

Collaborators and Investigators

• Sponsor: Zhuhai Trinomab Pharmaceutical Co., Ltd.
• Investigators: Principal Investigator: Chuanlin Wang, MD, Peking University People's Hospital; Study Director: Shengyi Wang, Zhuhai Trinomab Pharmaceutical Co., Ltd.

Publications and helpful links

General Publications

• Wang CL, Liu S, Shao ZJ, Yin ZD, Chen QJ, Ma X, Ma C, Wang Q, Wang LH, Deng JK, Li YX, Zhao ZX, Wu D, Wu J, Zhang L, Yao KH, Gao Y, Xie X. [Guidelines for the use of post-traumatic tetanus vaccines and passive immune preparation]. Zhonghua Yu Fang Yi Xue Za Zhi. 2019 Dec 6;53(12):1212-1217. doi: 10.3760/cma.j.issn.0253-9624.2019.12.005. Chinese.
• Roper MH, Vandelaer JH, Gasse FL. Maternal and neonatal tetanus. Lancet. 2007 Dec 8;370(9603):1947-59. doi: 10.1016/S0140-6736(07)61261-6. Erratum In: Lancet. 2007 Dec 8;370(9603):1906.
• Tetanus vaccines: WHO position paper - February 2017. Wkly Epidemiol Rec. 2017 Feb 10;92(6):53-76. No abstract available. English, French.
• Yu Chao, Xu Yuming, Xu Jin, et al. Progress of clinical application and safety of tetanus antitoxin. Chinese Journal of Pharmacovigilance, 2016, 13 (1): 36-41.
• Perey BJ. Progress in tetanus prophylaxis: the advent of human antitoxin. Can Med Assoc J. 1966 Feb 26;94(9):437-41.
• Plotkin, S.A., W.A. Orenstein and P.A. Offit, Plotkin's vaccines. Seventh edition. ed. 2018. 1691.
• Ortiz JR, Hombach J. Announcing the publication of the WHO immunological basis for immunization series module on influenza vaccines. Vaccine. 2018 Sep 5;36(37):5504-5505. doi: 10.1016/j.vaccine.2017.09.010. Epub 2017 Oct 16.
• Forrat R, Dumas R, Seiberling M, Merz M, Lutsch C, Lang J. Evaluation of the safety and pharmacokinetic profile of a new, pasteurized, human tetanus immunoglobulin administered as sham, postexposure prophylaxis of tetanus. Antimicrob Agents Chemother. 1998 Feb;42(2):298-305. doi: 10.1128/AAC.42.2.298.

Helpful Links

• Srivastava P, B.K.C.J., Trends in tetanus epidemiology in the United States, 1972-2001. 39th National Immunization Conference Workshop 27, 2005. Available at: <http://cdc.confex.com/cdc/nic2005/techprogram/paper_7813.htm>. 2005.

Study record dates

Study Major Dates

• Study Start (Actual): December 22, 2022
• Primary Completion (Actual): March 24, 2023
• Study Completion (Actual): July 7, 2023

Study Registration Dates

• First Submitted: December 7, 2022
• First Submitted That Met QC Criteria: December 22, 2022
• First Posted (Actual): December 27, 2022

Study Record Updates

• Last Update Posted (Actual): March 8, 2024
• Last Update Submitted That Met QC Criteria: March 6, 2024
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Prophylaxis; Tetanus
• 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; Antibodies; Immunoglobulins; Immunoglobulins, Intravenous
• Other Study ID Numbers: TNM002-301

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

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