A Multicenter, Randomized, Double-Blind, Parallel-Controlled, Dose-Finding Phase II Study to Compare the Anti-tetanus Neutralizing Antibody Titers and Safety of TNM002 Injection With Human Tetanus Immunoglobulin or Placebo Following a Single Intramuscular Injection in Chinese Adult Volunteers
Phase: PHASE2
Conditions: Tetanus
Sponsor: Zhuhai Trinomab Pharmaceutical Co., Ltd.

Trinomab 
TNM002-P2-CH01 
 
Page | 1  
 
A Multicenter, Randomized, Double-Blind, Parallel-Controlled, Dose-Finding Phase 2 
Study to Compare the Anti-tetanus Neutralizing Antibody Titers and Safety of TNM002 
Injection with Human Tetanus Immunoglobulin or Placebo Following a Single 
Intramuscular Injection in Chinese Adult Volunteers  
  
Version No.: V2.2 Version Date: 20-June-2022 
NCT No.: 
NCT05625477 
Protocol No.: 
TNM002-P2-CH01 
Investigational Product: 
TNM002 Injection 
Study Phase: 
2 
Study Site: 
PKUCare Luzhong Hospital 
Sponsor: 
Trinomab Biotech Co., Ltd. 
Compliance Statement: 
This study will be conducted in strict compliance with Good 
Clinical Practice 
 
 

Trinomab 
TNM002-P2-CH01 
 
Page | 2  
 
Study Protocol 
Title 
A Multicenter, Randomized, Double-Blind, Parallel-Controlled, Dose-Finding Phase II Study 
to Compare the Anti-tetanus Neutralizing Antibody Titers and Safety of TNM002 Injection 
with Human Tetanus Immunoglobulin or Placebo Following a Single Intramuscular Injection 
in Chinese Adult Volunteers 
Protocol 
No. 
TNM002-P2-CH01 
Study 
Phase 
II 
Objectives 
Primary: 
• 
To compare the anti-tetanus neutralizing antibody titers of TNM002 with human tetanus 
immunoglobulin (HTIG) following a single intramuscular (IM) injection in Chinese 
adult volunteers. 
Secondary: 
• 
To compare the safety and tolerability of TNM002 with HTIG and placebo following a 
single IM injection in Chinese adult volunteers. 
• 
To assess the pharmacokinetic (PK) properties of TNM002 in Chinese adult volunteers. 
• 
To assess the immunogenicity of TNM002 in Chinese adult volunteers. 
Exploratory: 
• 
To explore the population pharmacokinetic/pharmacodynamic (PopPK-PD) properties 
of TNM002 in Chinese adult volunteers. 
Endpoints 
Primary: 
• 
Proportion of volunteers with an increase of anti-tetanus neutralizing antibody titers 
from baseline (ΔTiters) ≥ 0.01 IU/mL at 24 hours post-dose 
In this study, serum anti-tetanus neutralizing antibody titers is a pharmacodynamic (PD) 
parameter. 
Secondary: 
• 
Safety endpoints, including type and incidence of adverse events (AEs) and serious 
adverse events (SAEs), physical examinations, vital signs, 12-lead ECGs, and laboratory 
tests (hematology, blood chemistry, and urinalysis); 
• 
The anti-tetanus neutralizing antibody ΔTiters at 24 hours, 48 hours (Day 3), and on Days 
7, 21, 30, and 90 post-dose; 
• 
Proportion of volunteers with anti-tetanus neutralizing antibody ΔTiters ≥0.01 IU/mL at 
48 hours (Day 3) and on Days 7, 21, 30, and 90 post-dose; 
• 
Proportion of volunteers with anti-tetanus neutralizing antibody ΔTiters ≥0.01 IU/mL at 
both 24 hours and Day 30 post-dose; 
• 
Proportion of volunteers with anti-tetanus neutralizing antibody ΔTiters ≥0.1 IU/mL at 
24 hours, 48 hours (Day 3) and on Days 7, 21, 30, and 90 post-dose; 
• 
Duration of anti-tetanus neutralizing antibody ΔTiters ≥0.01 IU/mL post-dose; 
• 
Duration of anti-tetanus neutralizing antibody ΔTiters ≥0.1 IU/mL post-dose; 
• 
The anti-tetanus neutralizing antibody titers at 24 hours, 48 hours (Day 3), and on Days 
7, 21, 30, and 90 post-dose; 
• 
Proportion of volunteers with anti-tetanus neutralizing antibody titers ≥0.01 IU/mL at 24 
hours, 48 hours (Day 3), and on Days 7, 21, 30, and 90 post-dose; 
• 
Proportion of volunteers with anti-tetanus neutralizing antibody titers ≥0.1 IU/mL at 24 
hours, 48 hours (Day 3), and on Days 7, 21, 30, and 90 post-dose; 
• 
PK parameters of TNM002 including maximum concentration (Cmax), time to maximum 
concentration (Tmax), elimination half-life (t1/2), area under the plasma concentration-time 
curve from time 0 to t (AUC0-t), and area under the plasma concentration-time curve from 
time 0 to ∞ (AUC0-∞); and apparent clearance (CL/F) and apparent volume of distribution 

Trinomab 
TNM002-P2-CH01 
 
Page | 3  
 
(Vd/F) if data permitted; 
• 
Positive rate of anti-drug antibody (ADA) in the TNM002 group. 
Study 
Design 
This study is designed as a multicenter, randomized, double-blind, active- and placebo-
controlled study to compare the anti-tetanus neutralizing antibody titers and safety of 
TNM002 Injection with HTIG or placebo following a single IM injection, and determine the 
dose of TNM002 Injection for tetanus prophylaxis in phase III clinical study. The study will 
be conducted at approximately 5-10 study centers, and approximately 240 Chinese male or 
female adult volunteers are planned to be enrolled. Eligible volunteers will be randomized 
in a ratio of 2: 2: 1: 2: 1 to TNM002 Injection 5 mg, TNM002 Injection 10 mg, TNM002 
Injection 15 mg, HTIG 250 IU, and placebo groups. At randomization, the volunteers will 
be stratified by the rapid test results of tetanus antibody IgG (negative and positive), and the 
proportion of volunteers with negative test results is at least 50%. The study drug and number 
of volunteers in each treatment group are shown in the table below. 
Group 
Number of 
Volunteers 
Drug for Injection 
Dose 
Dose Volume 
1 
60 
TNM002 Injection 
5 mg 
0.25 mL 
2 
60 
TNM002 Injection 
10 mg 
0.5 mL 
3 
30 
TNM002 Injection 
15 mg 
0.75 mL 
4 
60 
HTIG Injection 
250 IU 
2.5 mL  
5 
30 
Placebo 
NA 
0.5 mL 
This study will consist of a screening period (D-28 to D-2), an in-patient period (D-1 to D4), 
and a follow-up period (D5 to D106). Eligible volunteers will be admitted to the study site 
on D-1. After completing the relevant tests required by the protocol and randomization, all 
volunteers will receive the study drug on D1. Dispensing and administration of the study 
drug will be performed by unblinded study personnel, and the injection time of all study 
drugs should be controlled within 30 (± 3) seconds. After dosing, volunteers will undergo 
the safety assessment at the study site, including physical examination, vital signs, 12-lead 
ECGs, and laboratory tests (hematology, blood chemistry, and urinalysis). At the same time, 
the investigator will also collect serum samples at specified time points for anti-tetanus 
neutralizing antibody titers, PK, and immunogenicity analysis. Safety results on D-1 are 
defined as the baseline of safety assessment, and anti-tetanus neutralizing antibody titers, 
PK, and immunogenicity analysis results of serum samples collected prior to dosing on D1 
are defined as the baseline of the relevant assessment. Volunteers will be discharged from 
the hospital after completing safety assessment and serum sample collection on D4. After 
completing the blood collection at 48 hours post-dose and safety assessment during the in-
patient period, the subject can be discharged early at the comprehensive judgment of the 
investigator. 
Volunteers will return to the study site on Days 7, 14, 21, 30, 60, 90, and 106 for safety 
assessment and/or serum sample collection for anti-tetanus neutralizing antibody titers, PK, 
and immunogenicity analysis. The visit on D106 is considered as the end of study (EOS) 
visit, during which the volunteers will undergo a comprehensive safety assessment. 
 
 

Trinomab 
TNM002-P2-CH01 
 
Page | 4  
 
Study 
Population Chinese adult volunteers 
Inclusion 
Criteria 
Each subject must meet the following criteria to be enrolled in this study: 
1) 
Chinese male or female adults aged ≥ 18 years; 
2) 
 Healthy volunteers with normal or abnormal but not clinical significant results on 
physical examination, vital signs and clinical laboratory tests at screening or volunteers 
with stable chronic diseases and who are not expected to be at significant risk for 
participating in the clinical study as judged by the investigator; 
The chronic diseases include hypertension, diabetes mellitus, hyperlipidemia, 
hyperuricemia, etc.  
A volunteer with stable chronic disease is defined as follows: 
• 
A volunteer without hospitalization or emergency visits due to worsening 
chronic disease/state within 12 months prior to screening; 
• 
A volunteer who maintains a stable regimen for chronic diseases within 3 months 
prior to screening; 
• 
A volunteer with no acute change in chronic disease/status within 1 month prior 
to screening and who is not expected to worsen or have significant change in 
treatment during the study as judged by the investigator. 
3) 
Women of childbearing potential and at risk of pregnancy and men of childbearing 
potential must agree to use at least one of the following highly effective contraceptive 
methods throughout the study and for 150 days after dosing, including: 
• 
Intrauterine device (IUD); 
• 
Oral, injectable, or implantable hormonal contraceptives; 
• 
Barrier contraception + spermicide; 
• 
Surgical contraceptive methods (e.g., vasectomy, salpingectomy, hysterectomy, 
etc.); 
Women of no childbearing potential will be authorized to participate in this study if 
at least one of the following criteria are met: 
• 
Documented hysterectomy and/or bilateral oophorectomy; 
• 
Medically confirmed ovarian function failure; 
• 
Postmenopausal, defined as follows: cessation of regular menses for at least 12 
consecutive months with no alternative pathological or physiological cause; and 
have a serum follicle stimulating hormone (FSH) level confirming the post-
menopausal status. 
4) 
Volunteers who are able to well communicate with investigator as well as understand 
and adhere to the requirements and procedures of this study; 
5) 
Volunteers who voluntarily provide signed written informed consent form. 
 
 

Trinomab 
TNM002-P2-CH01 
 
Page | 5  
 
Exclusion 
Criteria 
Volunteers who meet any of the following criteria will be excluded from the study: 
1) 
History of allergy to the investigational product, human immunoglobulin preparation 
or any component of other therapeutic monoclonal immunoglobulins; 
2) 
History of chronic eczema or urticaria or multiple drug allergies; 
3) 
History of blood phobia or needle sickness; 
4) 
History of acute infection within 1 week prior to screening; 
5) 
Previously diagnosed or suspected immunodeficiency or autoimmune disease; 
6) 
Exposure to tetanus vaccine within the 10 years; 
7) 
Receipt of an immunoglobulin or blood products within 6 months prior to dosing; 
8) 
Exposure to any live attenuated or inactivated vaccines (including COVID-19 vaccine) 
within 4 weeks prior to dosing or plan to receive such vaccines within 3 months after 
dosing; 
9) 
Use of any new drug therapy within 2 weeks or 5 drug half-lives (whichever is longer) 
prior to screening; 
10) Known or suspected history of drug abuse within the past 5 years or a previous history 
of drug addiction or with positive urine drug test; 
11) History of significant alcohol abuse within 6 months prior to 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); 
12) Participation in any clinical studies with drugs or device within 3 months prior to 
screening, or ≤ 5 elimination half-lives (whichever is longer) from the last dose of the 
investigational drug, except for participation in clinical studies that do not use the 
investigational drug or device after screening or the observational, non-interventional 
studies; 
13) History of clinically significant bleeding disorders (e.g., coagulation factor deficiency, 
coagulation defects, or platelet disorder); 
14) Scars, tattoos, rash at the injection site that affect the administration or assessment; 
15) Positive for human immunodeficiency virus (HIV) or hepatitis C virus (HCV) 
antibodies, or treponema pallidum-specific antibody or hepatitis B surface antigen 
(HBsAg) at screening; 
16) Ear temperature ˃ 37.5 °C, pulse rate ˃ 100 beats/min or ˂ 50 beats/min at screening; 
17) For volunteers with no prior chronic disease or age ˂ 60 years, systolic blood pressure 
(SBP) ≥ 140 mmHg or ˂ 90 mmHg, and/or diastolic blood pressure (DBP) ≥ 90 mmHg 
or ˂ 50 mmHg or ECG QTcF (heart rate-corrected) ˃ 450 ms and/or other clinically 
significant abnormalities expected to be at significant risk for participating in the 
clinical study; 
18) Laboratory tests: alanine aminotransferase (ALT) or aspartate aminotransferase (AST) 
˃ 2 ULN, total bilirubin ˃ 1.5 ULN, decreases in haemoglobin (˂ 120 g/L in males and 
˂ 100 g/L in females), platelet count ˂ 120 × 109/L, white blood cell  count ˂ 3 × 109/L, 
neutrophil count ˂ 1.8 × 109/L or abnormal and clinically significant test results as 
judged by the investigator (except for the abnormal and clinically significant test results 
that can be explained by chronic disease); 
19) Pregnant or lactating women; 
20) Study personnel involved in the design and/or conduct of this study; 
21) Other conditions that are considered to be not suitable for the study by the investigator. 
 
 

Trinomab 
TNM002-P2-CH01 
 
Page | 6  
 
Study 
Drugs 
 
Drug 
Name 
TNM002 Injection 
Human Tetanus 
Immunoglobulin 
Placebo 
Dosage 
Form 
Injection, solution 
Injection, solution 
Injection, solution 
Strength 
20.0 mg/1.0 mL/vial 
250 IU/2.5 mL/vial 
1 mL/vial 
Route of 
Administr
ation 
IM gluteal injection 
IM gluteal injection 
IM gluteal injection 
Sample 
Size 
Estimation 
Approximately 240 Chinese adult volunteers are planned to be enrolled in this study. Since 
this study is a phase II dose-finding study, the sample size is not estimated based on formal 
statistical assumptions. 

Trinomab 
TNM002-P2-CH01 
 
Page | 7  
 
Study Flow Chart 
Period 
Screening 
Period 
In-Patient Perioda 
Follow-up Period 
Premature 
Withdraw
al 
Study Day 
D-28~D-2 
D-1 
D1 
D2 
D3 
D4 
D7 
D14 
D21 
D30 
D60 
D90 
D106 
Time window 
/ 
/ 
/ 
/ 
/ 
/ 
±1d 
±2d 
±2d 
±2d 
±3d 
±5d 
±7d 
±7d 
Informed consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical/treatment history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Weight/height 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vital sign1 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 
X 
 
 
 
 
X 
 
X 
 
 
X 
 
X 
X 
12-lead ECG 
X 
 
X2 
 
 
X 
 
X 
 
 
X 
 
X 
X 
Rapid test of tetanus antibody 
IgG 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Serum pregnancy test3 
X 
X 
 
 
 
 
 
 
 
X 
X 
X 
X 
X 
Serum FSH test4 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Viral serology test5 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Laboratory tests (including 
hematology, blood chemistry, 
and urinalysis) 
X 
X6 
 
 
 
X 
 
X 
 
 
X 
 
X 
X 
Urine drug test 
X 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Admission 
 
X 
X 
X 
X 
X 
 
 
 
 
 
 
 
 
Study drug administration 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Injection site assessment7 
 
 
X 
 
 
 
 
 
 
 
 
 
 
 
Serum sample collection for  
anti-tetanus neutralizing 
antibody titers test8 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum sample collection for 
PK analysis8 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Serum sample collection for 
immunogenicity analysis8 
 
 
X 
 
 
 
X 
X 
X 
X 
X 
 
X 
X 
 
 

Trinomab 
TNM002-P2-CH01 
 
Page | 8  
 
Recording of concomitant 
medications 
X 
Recording of AEs 
X 
Notes: 
a. 
After completing the blood collection at 48 hours post-dose and safety assessment during the in-patient period, the subject can be discharged early at the comprehensive 
judgment of the investigator. 
1. 
A vital sign test will be performed within 2 hours prior to dosing on Study Day D1. For other visits, a vital sign test should be performed on the same day. 
2. 
A 12-lead ECG will be performed within 2 hours prior to dosing on D1. Before 12-lead ECG measurements, the volunteers should have a rest for at least 5 minutes and 
smoking, alcohol consumption, strenuous exercise, and mood fluctuation will be not allowed. 
3. 
A serum (beta human chorionic gonadotropin [β-HCG]) pregnancy test will be performed for women of childbearing potential only. 
4. 
Female volunteers who have not undergone hysterectomy or bilateral oophorectomy and have been menopausal for at least 1 year without other pathological or 
physiological reasons will undergo the serum FSH test to determine their post-menopausal status. The serum FSH test is not required for female volunteers of childbearing 
potential. Female volunteers with amenorrhea for less than 1 year should be considered fertile and do not require FSH test. 
5. 
Viral serology tests include HBsAg, HCV antibody, HIV and treponema pallidum-specific antibodies. 
6. 
If laboratory tests have been performed within 7 days prior to admission (D-8 to D-1), then the tests do not need to be repeated on D-1. 
7. 
On D1 of the in-patient period, an injection reaction assessment will be performed 30 minutes (± 5 minutes) after IM injection of the study drug, and the local reactions 
at the injection site will be closely monitored and recorded. 
8. 
The collection time of serum samples for anti-tetanus neutralizing antibody titers, PK and immunogenicity analysis are detailed in Section 8.2-8.4 of the text. 

Trinomab 
TNM002-P2-CH01 
 
Page | 9  
 
Statistical Analysis Plan 
 
All statistical analysis will be performed using SAS version 9.4 or above. 
The statistical analysis is mainly descriptive analysis. The continuous variables will be 
statistically described using the number of volunteers, mean, median, standard deviation (SD), 
minimum and maximum. The categorical and grade variables will be statistically described 
using frequencies and percentages for each category or grade, and missing values will not be 
included in the calculation of percentages unless otherwise stated. 
No formal hypothesis testing will be performed on the data, but two-sided 95% confidence 
interval (CI) will be calculated based on α = 0.05. 
Statistical Analysis Population 
• 
Full Analysis Set (FAS): all randomized volunteers who receive at least one dose of the 
study drug will be included in the FAS, which will be used for the analysis of volunteer 
disposition, demographics and baseline characteristics. 
• 
Anti-tetanus Neutralizing Antibody Titers Analysis Set: all randomized volunteers 
who receive at least one dose of the study drug with at least one valid post-dose serum 
anti-tetanus neutralizing antibody titers test data will be included in the anti-tetanus 
neutralizing antibody titers analysis set. If an event occurred that could affect the anti-
tetanus neutralizing antibody titer or the detection (e.g., major violation of protocol 
inclusion criteria, use of prohibited drugs during the study, etc.), all or partial test data of 
corresponding volunteers will not be included in the anti-tetanus neutralizing antibody 
titers analysis. 
• 
Safety Set (SS): all randomized volunteers who receive at least one dose of the study 
drug with at least one post-dose safety evaluation will be included in the SS. SS is the 
safety evaluation population for this study. 
• 
PK Concentration Set (PKCS): all randomized volunteers who receive at least one 
dose of the study drug with at least one analyzable PK concentration point during the 
study will be included in the PKCS. If an event occurred that could affect the PK 
concentration or the detection (e.g., major violation of protocol inclusion criteria, use of 
prohibited drugs during the study, etc.), all or partial PK data of corresponding 
volunteers will not be included in the PKCS. The PKCS will be used for the PK 
concentration analysis. 
PK Parameter Set (PKPS): all randomized volunteers who receive at least one dose of the 
study drug with at least one analyzable PK parameter during the study will be included in the 
PKPS. If an event occurred that could affect the PK parameters (e.g., major violation of 
protocol inclusion criteria, use of prohibited drugs during the study, etc.), all or partial PK 
data of corresponding volunteers will not be included in the PKPS. The PKPS will be used for 
the PK parameter analysis. 
• 
Immunogenicity Analysis Set: all randomized volunteers who receive TNM002 with at 
least one post-dose immunogenicity data will be included in the immunogenicity 

Trinomab 
TNM002-P2-CH01 
 
Page | 10  
 
analysis set. 
The anti-tetanus neutralizing antibody titers, PK, immunogenicity, and safety analysis will be 
based on the actual treatment group, and the remaining analysis will be based on the 
randomized treatment group unless otherwise specified. 
Demographic Data and Other Baseline Characteristics 
Demographic data and other baseline characteristics will be analyzed descriptively by 
treatment group using descriptive statistics, and data will be tabulated and summarized. 
Anti-tetanus neutralizing antibody titers Analysis 
The number, percentage, 90% CI and 95% CI (based on the Clopper-Pearson method) of 
volunteers with an increase of anti-tetanus neutralizing antibody titers (∆ titers) ≥ 0.01 IU/mL 
from baseline at 24 hours post-dose will be calculated. The difference in the percentage of 
volunteers with ∆ titers ≥ 0.01 IU/mL as well as 90% CI and 95% CI (based on the stratified 
Miettinen-Nurminen method, stratified by the rapid tetanus antibody IgG test results of at 
randomization stratification) of the difference between groups will be provided. Volunteers 
who withdraw from the study prematurely without detectable anti-tetanus neutralizing 
antibody titers at the respective time points will not be included in the analysis. 
The anti-tetanus neutralizing antibody titers will be summarized by treatment group at each 
scheduled time point using the descriptive statistics, including number, median, minimum, 
maximum, geometric mean titer (GMT), geometric SD, 90% CI and 95% CI of GMT. In 
addition, the anti-tetanus neutralizing antibody titers at each scheduled time point after dosing 
will be compared and analyzed between treatment groups based on the mixed-effect model 
for repeated measures (MMRM). The MMRM model uses the log-transformed anti-tetanus 
neutralizing antibody titers (referred to as "log antibody titer") at each scheduled time point as 
the dependent variable, the treatment group, the rapid tetanus antibody IgG test results at 
randomization stratification, time point, and treatment group-time point interaction as the 
independent variables, and the intra-subject variance-covariance structure as the nonstructured 
variance structure (UN). The difference in log antibody titer and the 90% CI and 95% CI of 
the difference between different treatment groups will be calculated. The difference and 
corresponding CI of the difference will be antilog-transformed to obtain the ratio of GMT and 
CI of ratio between different treatment groups. If the model does not converge when the 
covariance structure is UN, other possible covariance structures, such as Toelitz, 
autoregression (1) (AR (1)), etc., can be selected, and the covariance structure with the 
smallest final AIC value will be used for the final model. 
The change from baseline in anti-tetanus neutralizing antibody titers at different time points 
post-dose and the proportion of volunteers with anti-tetanus neutralizing antibody titers ≥ 0.01 
IU/mL and ≥ 0.1 IU/mL, ≥ 0.01 IU/mL and ≥ 0.1 IU/mL increase from baseline in anti-
tetanus neutralizing antibody titers, ≥0.01 IU/mL increase from baseline in anti-tetanus 
neutralizing antibody titers at 24 hours and on Day 30 post-dose in different treatment groups 
will be summarized and compared using a similar statistical analysis method. 
The duration of ∆ titers≥ 0.01 IU/mL post-dose from baseline is defined as the time interval 
from the first to the last observed increase of ∆titers ≥ 0.01 IU/mL from baseline. Subjects 
whose ∆ titers remain ≥ 0.01 IU/mL at the last test time point of the study will be considered 

Trinomab 
TNM002-P2-CH01 
 
Page | 11  
 
censored in duration calculation. The median duration, corresponding two-sided 90% CI, 95% 
CI, minimum and maximum will be estimated using the Kaplan-Meier method. The duration 
between different treatment groups will be compared using the Cox proportional hazards 
model, which will include the treatment groups and the rapid tetanus antibody IgG test results 
at randomization stratification. If the censoring proportion is low, a descriptive summary of 
duration will be considered and the duration between different treatment groups will be 
analyzed based on an analysis of covariance (ANCOVA) model, which will include the 
treatment groups and the rapid tetanus antibody IgG test results at randomization 
stratification. The duration of ∆Titers≥ 0.1 IU/mL post-dose from baseline will be analyzed 
using the same analytical method. 
If data are applicable, the subjects will be divided into two subgroups (＜0.01 IU/mL and ≥ 
0.01 IU/mL) based on the test results of anti-tetanus antibody in serum samples collected 
prior to dosing to repeat the above analysis. 
The anti-tetanus neutralizing antibody titers at baseline, the post-baseline anti-tetanus 
neutralizing antibody titers at each time point and the change from baseline in  anti-tetanus 
neutralizing antibody titers will be tabulated by treatment group. 
Safety Analysis 
AEs will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) version 
24.0 or higher. The analysis of AE will be based on treatment-emergent adverse events 
(TEAEs), while AEs before treatment will be tabulated. All TEAEs, TEAEs related to the 
study drug, and SAEs will be summarized and analyzed by system organ class (SOC) and 
preferred term (PT), and the number and incidence will be calculated. 
The quantitative safety variables such as laboratory tests, vital signs, 12-lead ECGs, and their 
changes from baseline will be summarized using descriptive statistics. The changes from 
baseline in clinical significance of safety variables such as laboratory tests, 12-lead ECGs, 
and physical examinations will be described using the shift tables. 
Pharmacokinetics Analysis 
The plasma concentration of the study drug at each scheduled sampling time point for each 
treatment group will be summarized descriptively, and the mean plasma concentration-time 
curves (both linear and semi-log scales) will be plotted. The PK concentration data at 
different time points will be tabulated separately by treatment group. 
The PK parameters will be summarized by treatment group using appropriate descriptive 
statistics including number of volunteers, mean, geometric mean, SD, minimum, median, 
maximum, and coefficient of variation (CV), and the PK parameters will be tabulated. 
Immunogenicity Analysis 
The positive rate of ADA in TNM002 group at baseline and at different post-baseline time 
points will be summarized. For ADA-positive volunteers, the number and percentage of Nab 
positive volunteers will also be further calculated if data permit. The impact of ADA and/or 
Nab production on the efficacy, PK profile, and safety of TNM002 will be assessed, as 
applicable. 

Trinomab 
TNM002-P2-CH01 
 
Page | 12  
 
PopPK-PD Analysis 
PK/PD analysis will be performed using NONMEM (version 7.3 or higher) and/or R software 
(version 4.0.5 or higher).