A Phase 1, Randomized, Double-blind, Placebo-controlled, Single and Multiple Dose Escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics (PK) and Food Effect of Orally Administered IPG11406 in Healthy Adult Participants
Phase: PHASE1
Conditions: Inflammatory Bowel Diseases
Sponsor: Nanjing Immunophage Biotech Co., Ltd

IPG11406-Phase I Clinical Trial in Healthy Subjects
Study ID: IPG11406-C001
A randomized, double-blind, placebo-controlled, single-dose and multiple-
dose escalation Phase I clinical first-in-human trial evaluating the safety,
tolerability, and pharmacokinetics of IPG11406 in healthy adult subjects
Clinical Trial Protocol
Plan ID:
IPG11406-C001
Solution version:
V1.0
Version date:
07 April 2023
Sponsoring organization:
Nanjing Immunophage Biotech Co., Ltd.
declaration of secrecy
This protocol is provided solely for review by the investigators, the ethics committee, and relevant drug
regulatory authorities. All rights related to the investigational drug mentioned herein belong to the
sponsor, Nanjing Immunophage Biotech Co., Ltd. Without the written consent of the sponsor, no
information related to the investigational drug shall be disclosed or communicated in any manner to
third parties unrelated to this clinical trial, except for necessary explanations to potential
participants in this clinical trial.
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Sponsor's protocol signature page for the first-phase human trial ofIPG11406,
a
randomized,
double-blind,
placebo-controlled,
single-dose
and
multiple-dose escalation
study evaluating
safety, tolerability,
and
pharmacokinetics in healthy adult subjects
I will conscientiously fulfill the sponsor's responsibilities in accordance with Good Clinical
Practice (GCP) and all applicable regulatory requirements, including the initiation, application,
organization, and funding of this clinical trial. I shall assume legal liability for the medical expenses
and provide appropriate economic compensation for any trial-related harm or death of subjects
during the clinical trial, and provide legal guarantees to the investigators. I hereby agree to conduct
this clinical trial in accordance with the design and provisions of this protocol (Version No.: V1.0,
Version Date: April 7, 2023).
personal name：
________________________________
Signature:
________________________________
date：
________________________________
Sponsoring Organization: Nanjing Immunophage Biotech Co., Ltd.

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Study ID: IPG11406-C001
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A first-phase, randomized, double-blind, placebo-controlled, single-dose and
multiple-dose escalation clinical trial evaluating the safety, tolerability,
and pharmacokinetics ofIPG11406 in healthy adult subjects
Principal Investigator's Protocol Signature Page
I have read and understood this trial protocol (Version: V1.0, Date: April 7, 2023) and agree to
conduct this trial in accordance with the protocol and related annexes. I will provide a copy of the
protocol to my research team and engage in discussions with them to ensure their full understanding
of the trial. I am aware that the trial may be terminated or enrollment may be halted at any time due
to certain predefined reasons, and the trial may also be discontinued to protect the rights and
interests of the participants. I consent to conduct this trial in strict compliance with Good Clinical
Practice (GCP).
Meanwhile, as the principal investigator of this trial, I will coordinate all participating
researchers in accordance with Good Clinical Practice (GCP) requirements.
personal name：________________________________
signature：________________________________
date：
________________________________
Test Center Name: ________________________________

IPG11406-Phase I Clinical Trial in Healthy Subjects
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Catalogue
catalogue............................................................................................................................................. 4
abbreviation..........................................................................................................................................5
Summary of Trial Protocol.................................................................................................................. 7
1 Background.................................................................................................................................... 22
2 purpose of research......................................................................................................................... 23
2. 1 purpose ofresearch.............................................................................................................. 23
3 study end point............................................................................................................................... 24
4 experiment design.......................................................................................................................... 24
4.1 basis of scheme design......................................................................................................... 24
4.2 system design...................................................................................................................... 24
4.3 sample capacity.................................................................................................................... 25
4.4 dose design.......................................................................................................................... 25
4.5 dose escalation rule.............................................................................................................. 26
4.6 Discontinuation Rules.......................................................................................................... 26
5 study population............................................................................................................................. 26
5.1 Selection criteria.................................................................................................................. 26
5.2 exclusion criteria.................................................................................................................. 27
6 Termination criteria........................................................................................................................ 28
7 exit trial criteria.............................................................................................................................. 29
8 randomization and blinding............................................................................................................ 29
8.1 randomize............................................................................................................................ 29
8.2 blind method........................................................................................................................ 29
9 Study administration....................................................................................................................... 30
9.1 test drug............................................................................................................................... 30
9.2 placebo................................................................................................................................ 31
9.3 Administration Methods and Precautions........................................................................... 31
9.4 Drug packaging.................................................................................................................... 31
9.5 Drug Dispensing and Management...................................................................................... 31
10 stages ofresearch......................................................................................................................... 31
10.1 Part A study (single dose escalation)................................................................................ 31
10.2 Part B study (multiple dose escalation)............................................................................ 35
11 evaluating indicator...................................................................................................................... 37
11.1 pharmacokinetics............................................................................................................... 37
11.1.1 Setting ofblood collection time points for PK....................................................... 37

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11.1.2 PK evaluating indicator.......................................................................................... 37
11.2 Specimen Collection and Processing................................................................................. 38
11.3 Safety and Tolerance Indicators........................................................................................ 38
11.3.1 adverse event.......................................................................................................... 38
11.3.2 Serious adverse events........................................................................................... 40
11.3.3 Safety Assessment in Clinical Laboratories........................................................... 41
11.3.4 Other safety assessments........................................................................................ 42
12 Detection ofbiological samples................................................................................................... 43
13 Data Management and Statistical Analysis.................................................................................. 43
13.1 data management............................................................................................................... 43
13.2 Requirements for data completion by researchers............................................................ 44
13.3 Ombudsman's requirement for data monitoring................................................................ 44
13.4 data cleaning..................................................................................................................... 45
13.5 Blind audit and database locking...................................................................................... 45
13.6 Recording and preservation oftest data............................................................................ 45
14 Analysis Plan............................................................................................................................... 45
14.1 Statistical Analysis Data Set............................................................................................. 45
14.2 statistical analysis technique............................................................................................. 46
15 risk/benefit ratio of this trial......................................................................................................... 47
16 Research Management................................................................................................................. 48
16.1 quality control and quality assurance................................................................................ 48
16.2 Clinical Monitoring........................................................................................................... 49
16.3 data management............................................................................................................... 50
17 ethical requirements..................................................................................................................... 50
17.1 ethical principle................................................................................................................. 50
17.2 Approval ofresearch protocols and protocol modifications............................................. 50
17.3 informed consent............................................................................................................... 51
17.4 Confidentiality of trial data............................................................................................... 51
18 Responsibilities of all parties....................................................................................................... 51
18.1 Responsibilities ofthe Sponsor......................................................................................... 51
18.2 Assume responsibilities of a clinical research medical institution.................................... 52
18.3 Responsibilities of Contract Research Organization (CRO)............................................ 52
19 publication ofresearch findings................................................................................................... 53
20 research summary......................................................................................................................... 53
21 References..................................................................................................................................... 53
Abbreviation

IPG11406-Phase I Clinical Trial in Healthy Subjects
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Phrases and specialized terms
Explain
AE
Adverse event
ALB
Albumin
ALT
Alanine aminotransferase/Aspartate aminotransferase
ALP
Alkaline phosphatase
AST
Aspartate aminotransferase/Aspartate aminotransferase
AUC0~t
Area under the concentration-time curve from zero to the final measu-
rable concentration
AUC0~∞
Area under the concentration-time curve from zero to infinity
BMI
Baric index
BP
Blood pressure
BUN
Usea nitrogen
Cmax
The highest observed plasma concentration
Css，max
Steady-state peak concentration
Css,min
Steady-state valley concentration
Css,av
Mean steady-state plasma concentration
CK
Serum creatine kinase
CL/F
Apparent clearance rate/F
CRE/Cr
Creatinine
ECG
Electrocardiogram
ECHO
Echocardiogram
GCP
Good Clinical Practice (GCP)
γ-GT/GGT
γ-glutamyl transferase
HBsAg
Hepatitis B surface antigen
HB
Hemoglobin
HCT
Hematocrit
HCV
HCV
HIV
Human immunodeficiency virus
MRSD
Maximum recommended starting dose
NOAEL
Non-toxic dose
PLT
Blood cells
RBC
RBC
SD
Standard deviation
SAE
Serious adverse events
SOP
Standard practice
TBA
TBA
T-bili/TBIL
Total bilirubin
Urea
Urea
ULN
Upper limit of normal value

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Summary of Trial Protocol
Study
title
A randomized, double-blind, placebo-controlled, single-dose and multiple-dose
escalation Phase I clinical first-in-human trial evaluating the safety, tolerability, and
pharmacokinetics of IPG11406 in healthy adult subjects
Protocol
number
IPG11406-C001
Version/
Date
1.0 Version, April 7, 2023
Sponsor
Nanjing Immunophage Biotech Co., Ltd.
Study drug IPG11406 tablets, 0.5 mg/tablet, 10 mg/tablet, 40 mg/tablet
Studyphase I
Indication
Inflammatory bowel disease (IBD), multiple sclerosis (MS), systemic lupus
erythematosus (SLE), rheumatoid arthritis (RA)
Purpose of
research
A. Partial Single-Dose Increment (SAD)
fundamental purpose：
1. Evaluation of the safety and tolerability of a single oral dose ofIPG11406
secondary objectives:
1. Evaluation of the pharmacokinetic (PK) characteristics of single-dose oral
IPG11406
2. Evaluation of Food Effects on the Pharmacokinetics of Single-Dose Oral
IPG11406
A. Partial Single-Dose Increment (SAD)
exploratory purpose
Evaluation of the pharmacokinetic (PK) characteristics of single-dose oral IPG11406
Part B – Multiple Dose Increment (MAD)
fundamental purpose：
1. Evaluation of the safety and tolerability of high-dose oral IPG11406
secondary objectives:
1. Evaluation of the pharmacokinetic (PK) characteristics of the oral IPG
11406 in multiple-dose administration
Study end
point
Part A (single dose escalation)
Primary study endpoint:
1. Safety indicators: adverse events, vital signs, and clinical laboratory parameters;
secondary end points:
1. Pharmacokinetic parameters:Cmax，Tmax，t1/2,AUC0-t,AUC0-inf, CL/F;
exploratory end point
1. Measurement of IPG11406 parameters in urine: Renal clearance (CLR0-t),
cumulative fraction excreted in urine from time 0 to t (Ae0-t), fraction of
excreted dose in urine from time 0 to t (Fe0-t)
Part B (Multiple Dose Increases)
Primary study endpoint:
1. Safety indicators: adverse events, vital signs, and clinical laboratory parameters;
secondary end points:
1. Pharmacokinetic parameters:Css,max,t 1/2,Tss,max,AUC0-τ,CLss/F, accumulat-
ion index Rac(AUC), Rac(Cmax).
Trial popul-
ation
Health volunteer
Sample ca-
pacity
Approximately 66 healthy subjects: 42 in part A and 24 in part B.

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IPG11406-Phase I Clinical Trial in Healthy Subjects
Study ID: IPG11406-C001
Trial period
PART A (excluding the food effect cohort): up to 36 days (screening period: 28
days; single-dose administration period: 1 day; safety evaluation + follow-up: 7
days)
Part A (food effect cohort): ≥41 days (screening period: ≤28 days; single-dose
administration period (fasting): 1 day; washout period ≥4 days; single-dose
administration period (postprandial): 1 day; safety evaluation + follow-up: 7 days)
Part B: Maximum 45 days (screening period: 28 days; multiple-dose administration
period: 10 days; safety evaluation + follow-up)
Visit period: 7 days
Research
design
Randomized, double-blind, placebo-controlled, single-dose and multiple-dose
escalation
Experiment
design
Overview
This study is the first Phase I clinical trial conducted in humans, randomized,
double-blind, placebo-controlled, with single-dose and multiple-dose escalation,
aimed at evaluating the safety, tolerability, and pharmacokinetic characteristics of
IPG11406 in healthy adult subjects administered with single-dose escalation and
multiple-dose escalation.
This study was divided into two consecutive phases: Phase A, a single-dose
escalation (SAD), and Phase B, a multiple-dose escalation (MAD). Both phases
included a 28-day screening period and a 7-day safety evaluation and follow-up
after the completion of the dosing period.
The design pattern of single-dose escalation in part A and multi-dose escalation
in part B is shown in the figure below.
Overview ofpart A ofthe study:
In this study, six dose groups will be administered: 0.5 mg (Cohort 1),2 mg
(Cohort 2),6 mg (Cohort 3),20 mg (Cohort 4),40 mg (Cohort 5), and 80 mg (Cohort
6). In Cohorts 1 to 3, each cohort will consist of 6 participants, with 2 receiving
placebo and 4 receiving IPG11406. In Cohorts 4 to 6, each cohort will consist of 8
participants, with 2 receiving placebo and 6 receiving IPG11406. All participants
will undergo screening 28 days prior to administration. Eligible participants will
enter the research center 1 day before the 5-day administration and observation
period (with a 6-day hospital stay). This part of the study plans to enroll
approximately 42 healthy adult participants.

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In each dose group, 2 sentinel subjects will be randomly selected and
administered the drug 48 hours prior to the scheduled dose. One of these subjects
will receive IPG11406, while the other will receive a placebo. If neither of the two
sentinel subjects exhibits any significant safety issues within 48 hours, the
remaining subjects will continue to receive the drug.
After completing all safety assessments and PK sampling analyses, the subjects
will be discharged on day 5 and undergo follow-up on day 8.
One cohort (provisional cohort 5, subject to adjustment based on decisions
from the SMC meeting) will be selected to evaluate the effects of food on
pharmacokinetic parameters. Subjects in this cohort will receive a second dose of
IPG11406 or placebo postprandially on day 5 after completing the first dose,
following a standard high-fat meal (total caloric intake approximately 800-1000
kcal, with approximately 50% of total calories derived from fat).
After each cohort completes 5 days of administration and evaluation (with the
food-influence cohort evaluated on day 10), the Safety Monitoring Committee
(SMC) will assess the safety and tolerability of IPG11406 based on all accumulated
safety data (including follow-up data) and available pharmacokinetic (PK) data
from the blinded study. Based on the evaluation results of safety and tolerability, the
SMC will determine whether to proceed with administration of the next dose group.
B Summary ofthe study
After the safety and tolerability evaluation of IPG11406 in Part A (SAD) is
completed, the Part B study with multiple dose escalation will commence. The
Safety Monitoring Committee will determine the appropriate dose levels for Part B
based on the safety and tolerability data from Part A. In Part B, three dose
escalation levels will be administered to evaluate the safety and tolerability of IPG
11406.
The study plans to enroll approximately 24 healthy adult subjects, divided into
three dose groups, with 8 subjects in each cohort. Subjects will sequentially receive
doses of 10 mg (cohort M1),20 mg (cohort M2), and 40 mg (cohort M3). Among
the 8 subjects in each cohort, two will receive the placebo control, while the
remaining 6 subjects will receive IPG11406.
All subjects will undergo screening 28 days prior to administration. Eligible
subjects will enter the research center one day in advance and subsequently undergo
a 14-day dosing and observation period. The first dose will be administered on the
morning of day 1, with daily dosing continuing for 10 consecutive days. During the
dosing period, blood samples will be collected as planned to evaluate the
pharmacokinetic (PK) parameters ofIPG11406.
After completing all safety assessments and PK sampling analyses, the subjects
were discharged on day 14, with follow-up conducted on day 3 post-discharge.
After completing all safety assessments and PK sample analyses, subjects will
be discharged on day 14 and followed up on day 3 post-discharge. Following the
completion of 14 days of dosing and evaluation in each cohort, the Safety
Monitoring Committee (SMC) will evaluate all accumulated safety data (including
follow-up data) based on the blinded protocol and available

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PK data were collected to evaluate the safety and tolerability of IPG11406, and the
decision on whether to proceed with the next dose cohort was based on the
evaluation results.
Rationality
of initial
dose
select-
ion
According to the "Guidelines for Estimating the Maximum Recommended Starting
Dose of a Drug in the First Clinical Trial of Healthy Adult Volunteers," IPG11406
is a novel mechanism compound. To calculate the Minimum Recommended Safe
Dose (MRSD) of IPG11406, we selected 1/10 of the dose at which no toxic effects
were observed (NOAEL) in nonclinical safety evaluations in beagle dogs or SD rats
after 28 days of repeated administration, and considered the pharmacologically
active dose (PAD) in mouse models. Based on the pharmacologically active dose,
we chose 2 as the safety factor, resulting in a calculated MRSD of 0.5 mg for IPG
11406. Considering that rats are a sensitive species, the starting human dose was
calculated as 1/10 of the NOAEL in rats after 28 days of repeated administration,
yielding 24 mg. Therefore, 0.5 mg was selected as the starting ramp-up dose for
humans, and this dose was deemed to have good safety and tolerability in humans.
Calculation ofthe Maximum Recommended Starting Dose (MRSD)
Computational method
Genera
Dosage /
mg/kg
Equivalent human
dose/mg/kg
Safety facto MRSD*/mg
PAD
Mouse
0.1，BID
0.018
2
0.5
NOAEL
Rat
20
4.04
10
24
Dog
15
8.73
10
52
* Assume the body weight is 60 kg; BID: twice daily.
Selection cr-
iteria
1.
Healthy volunteers aged between 18 and 50 years old, both male and female,
are required. Participants must undergo medical history investigation, physical
examination, vital signs examination, electrocardiogram, chest X-ray examina-
tion, and laboratory tests during the screening period to ensure good health.
2.
The body mass index (BMI) is between 18 and 32, calculated as: BMI= weight
(kg)/ height 2(m 2);
3.
Participants were required to be in a non-menstrual, non-pregnant, and non-
lactating period during the trial and to agree to have no childcare plans for the
next 6 months.
4.
Physical health, defined as: detailed and clear medical history, comprehensive
physical examination (including blood pressure and pulse rate, laboratory tests,
and 12-lead electrocardiogram) with no clinical abnormalities detected;
5.
After 10 minutes of supine position testing, vital signs should be within the
following range:
95 mmHg <systolic blood pressure (SBP) <140 mmHg
45 mmHg <Diastolic Blood Pressure (DBP) <90 mmHg
45 bpm <Heart Rate (HR) <90 bpm
6.
After 10 minutes of resting supine position, 12-lead ECG readings: PR interval
<120 ms <220 ms, QRS complex <120 ms, QTc (Fridericia recommended
algorithm) ≤450 ms, normal ECG; or abnormal ECG results deemed clinically
insignificant by the investigator.
7.
Laboratory test results must fall within the normal range (or within the
established screening threshold) or show no clinically significant abnormalities;
however, serum creatinine, alkaline phosphatase, and liver enzymes (aspartate
aminotransferase,

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Alanine aminotransferase (ALT) should not exceed the upper limit of the laboratory
normal range. Total bilirubin should not exceed 1.5 times the upper limit of the
normal range for conjugated bilirubin (unless the subject has a history of Gilbert
syndrome).
8.
Willing and able to comply with all medical visitation, medication administra-
tion, and laboratory testing protocols, agree to take the oral test medication, and
meet other study requirements
9.
Contraceptive requirements for female subjects:
a.
Fertile female participants: Must undergo a urine pregnancy test during the
screening period with a negative result, and agree to use effective
contraception for 3 months after signing the informed consent until the last
dose of the investigational drug. Contraception must always be strictly
followed according to the instructions of the contraceptive product and the
investigator. Effective contraception includes: complete abstinence, intra-
uterine device (IUD) or intrauterine contraceptive system (IUS), double-
barrier method (e.g., spermicide plus male condom, female condom,
diaphragm, cervical cap, or intrauterine device), or a partner who has
undergone vasectomy and whose semen cannot be detected for sperm.
b.
Fertile women: This includes postmenopausal women (with complete
cessation of menstruation for ≥1 year) or women with surgical records of
hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (as
opposed to tubal ligation). Fertile women do not need to adhere to the
listed contraceptive measures.
10. Contraceptive requirements for male subjects:
Male subjects must agree to use the listed effective contraceptive methods or have
undergone vasectomy within 3 months after signing the informed consent and
receiving the last dose of the investigational drug.
11. Participants must provide informed consent for this study prior to enrollment
and voluntarily sign a written informed consent form.
Exclusion
criteria
1.
History of severe cardiovascular, pulmonary, hepatic, renal, hematologic,
gastrointestinal, endocrine, immune, dermatological, neurological, or psychiat-
ric disorders.
2.
Abnormal chest X-ray findings.
3.
Recurrent headache and/or migraine,
recurrent nausea
and/or vomiting
(vomiting only: more than twice a month).
4.
Blood donation within 2 months prior to inclusion is permitted, with no volume
restrictions.
5.
Symptomatic or asymptomatic orthostatic hypotension: defined as a drop in
systolic blood pressure of ≥30 mmHg within 3 minutes when changing from
supine to standing position.
6.
History of drug allergy or confirmed allergic disease.
7.
Known to be allergic to any component of the pharmaceutical preparation.
8.
History of drug or alcohol abuse (regular daily alcohol intake exceeding 40
mL).
9.
Heavy smokers (smoking 5 or more cigarettes per day). For light smokers
(smoking fewer than 5 cigarettes per day), smoking should be discontinued
during the trial period.
10. Individuals who consume excessive amounts of tea or coffee (more than 8 cups
per day).
11. Take any medication within 14 days before inclusion or within 5 times the half-
life or pharmacodynamic half-life of the medication;
12. Eat any citrus fruit (e.g. grapefruit, orange) or juice in the 5 days before
selection.

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13. Any vaccination within 28 days prior to inclusion and any injection of
a biological agent (antibody or its derivative) within 4 months.
14. According to the investigators' assessment, the subjects may have poor
compliance during the study or may not be able to cooperate due to
language issues or intellectual developmental delays.
15. Participants were registered or had previously participated in any other
clinical study involving a drug clinical trial or any other type of
medical research within 3 months prior to enrollment or within the 5
half-life period (whichever is shorter).
16. Participants who could not be contacted in an emergency.
17. Researchers or associate researchers, research assistants, pharmacists,
study coordinators, or other staff members who are directly or
indirectly involved in the study, or anyone associated with the study
site (including employees or immediate family members), investigato-
rs, or the sponsor.
18. Any of the following tests are positive: hepatitis B surface antigen
(HBsAg), hepatitis B core antigen (anti-HBcAg), anti-HCV antibody,
anti-human immunodeficiency virus 1 and 2 antibody (anti-HIV1 and
anti-HIV2 Ab), or Treponema pallidum antibody.
19. Positive urine
drug
screening
(amphetamines/methamphetamine,
barbiturates, benzodiazepines, cannabinoids, cocaine, opioids).
20. Alcohol test positive.
21. Subjects with difficulty in venous blood collection.
Medication
Administer orally on an empty stomach (defined as fasting for 10 hours
overnight). Swallow the test drug with a specified volume of warm water,
and the investigator must inspect each subject's mouth to ensure the drug is
swallowed.
Dose escalation and
discontinuation rules
Dose escalation rule
In both Part A and Part B, the decision to increase the drug dose will be
based on a review of all available safety information, including adverse
events, electrocardiograms (ECGs), vital signs, clinical laboratory test
results, and available pharmacokinetic data. The dose may be adjusted
based on safety and pharmacokinetic data observed during the study. The
dose escalation from Cohort 1 to Cohort 2 will be entirely based on safety
and tolerability data. The food effect cohort will be based on all safety and
tolerability data as well as the pharmacokinetic data of the first dose at that
level. The decision to escalate the dose will be made by the Safety
Monitoring Committee (SMC), and all dose escalation meetings and
decisions will be formally documented.
Discontinuation Rules
1.
Adverse events of grade 3 or higher that cannot be ruled out as related
to IPG11406 were evaluated according to the National Cancer Institute
Common Terminology Criteria for Adverse Events (NCI-CTCAE).
2.
Alanine aminotransferase (ALT) or aspartate aminotransferase (AST)
≥3×upper limit of normal (ULN), total bilirubin ≥2×ULN
3.
QTcF≥500 ms

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4.
If a subject meets any of the above criteria, the subject will
discontinue administration; additionally:
For each cohort: If two or more subjects at each dose level meet any of the
above criteria, the sponsor will unblind the relevant subjects.
If two or more subjects received IPG11406 rather than placebo, after
review of all data, the sponsor and investigators may choose the approach
they consider safe: 1) all subjects in the dose group will discontinue
administration; 2) Part A or Part B of the study will be discontinued.
if a placebo subject is among two or more subjects, the sponsor and
investigator may choose the approach they consider safe after review of
all data: 1: continue with the original protocol; 2: reduce the dose or
frequency of administration; or 3: stop part A or part B of the study.
Pharmacokinetic bl-
ood sampling
The pharmacokinetic evaluation method for IPG11406 involves parameter
comparison between dose groups. Due to the lack of clear clinical
prediction for this novel drug, adjustments to blood collection time points
may be required based on actual data obtained. The following time points
are provisionally designated for blood sample collection:
A Partial blood collection time points (excluding the food-influence
cohort):
Day 1:before administration (within 1 h); 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9,
12,24,36,48,72, and 96h after administration.
A Partial blood collection time points (food-influenced cohort):
Days 1 and 6:before administration (within 1 h); 0.5, 1, 1.5, 2, 2.5, 3, 4, 5,
6, 9, 12,24,36,48,72, and 96h after administration.
B Partial blood collection time points:
Day 1:before administration (within 1 h), 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9,
12, and 24h after administration.
Day 4, Day 6, Day 8:before administration (within 1h before administrat-
ion).
Day 10:before administration (within 1h before administration), 0.5, 1,
1.5, 2, 2.5, 3, 4, 5, 6, 9, 12,24,36,48,72, and 96h after administration.
Pharmacokinetic
eva-
luation
The following pharmacokinetic parameters of IPG11406 in human were
calculated by WinNonlin non-ventricular model.
1.
Terminal half-life (t1/2);
2.
area under the curve (AUC) of the drug;
3.
apparent volume of distribution (Vss);
4.
Systemic clearance (CL/F):
5.
Peak blood concentration Cmax and time to peak Tmax

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6.
the valley concentration, steady-state distribution volume, and accumulation
index (AI);
7.
Other analyzable PK parameters, etc.
Tolerability
and safety
evaluation
Adverse events occurring during the entire study period were evaluated
according to the National Cancer Institute Common Terminology Criteria for
Adverse Events (NCI-CTCAE) version 5.0. The assessment included vital signs,
physical examination, 12-lead electrocardiogram (ECG), 24-hour electrocardiogr-
aphic monitoring, clinical laboratory tests (complete blood count, blood biochemis-
try, urinalysis, coagulation function tests, etc.), adverse events, and serious adverse
events.
Statistical
method
Upon finalization of the trial protocol, statistical specialists shall collaborate
with principal investigators to develop the statistical analysis plan. Statistical
analysis will be performed using SAS9.4 (or later versions) statistical software,
while non-ventricular pharmacokinetic models in WinNonlin pharmacokinetic
software will be employed to calculate key pharmacokinetic parameters for each
subject. Measurement data will be described statistically using case numbers, mean,
standard deviation, median, maximum value, and minimum value. Categorical or
ordinal data will be described using frequency and frequency distributions.
Safety evaluation
Safety evaluation will be performed on the safety dataset.
For physical examination, 12-lead electrocardiogram (ECG), 24-hour ECG
monitoring, and clinical laboratory tests (including complete blood count, bioche-
mical blood tests, urinalysis with sediment, coagulation function, etc.) were
conducted. All completed tests and descriptive statistics were listed in a cross-
tabulation format before and after medication administration (based on clinical
judgment). Abnormal findings from ECG, physical examination, and laboratory
tests at each time point were documented in a checklist. Vital signs (blood pressure,
body temperature, pulse, respiration) were described, including values at each time
point and their relative changes from baseline. For example, the relationship
between ECG intervals and baseline changes in drug concentrations was analyzed to
evaluate the exposure-response relationship.
Summarize all adverse events and the incidence of study drug-related adverse
events according to the CTCAE 5.0 standard levels, and summarize the incidence of
adverse events with toxicity grade greater than level 3 and study drug-related
adverse events. The types of adverse events and their relationship to the study drug
will be described in a list. List all adverse events, study drug-related adverse events,
events leading to discontinuation, and serious adverse events.
Pharmacokinetic evaluation
The pharmacokinetic parameters of the non-ventricular model were estimated
and analyzed using WinNonlin (version 6.4 or later). Key pharmacokinetic
parameters were calculated to comprehensively reflect the drug's absorption,
distribution, metabolism, and excretion characteristics in humans. These parameters
include but are not limited to:t 1/2, AUC, Vss, CL/F,Cmax, and Tmax. Descriptive
statistical analyses were performed on pharmacokinetic parameters across different
dose groups, including arithmetic mean, standard deviation, coefficient of variation,
median, maximum value, minimum value, and geometric mean. In multi-dose
escalation studies, the primary pharmacokinetic parameters for different dose
groups were evaluated.

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IPG11406-Phase I Clinical Trial in Healthy Subjects
Study ID: IPG11406-C001
The pharmacokinetic parameters were analyzed for linear pharmacokinetics, and the
drug accumulation was studied based on the peak and trough concentrations over
multiple cycles.
Duration
of
study
Annum

WPIPG11406-Phase I Clinical Trial in Healthy Subjects
Study ID: IPG11406-C001
Table 1 A Flowchart ofthe Study (excluding the Food Effect Cohort)
Study period
Filter period Enter the test ce-
nter
Administration
period
Safety evaluation
Fl.up
Time window
D-28~-2
D-1
D1
D2
D3
D4
D51
D8 (±1 day)
Sign the informed consent
form
X
Height/Weight/Body Mass
Index
X
Demographic data
X
Medical history and treat-
ment history
X
X
Selection criteria
X
X
Check-up
X
Xa
X
Breath alcohol test
X
Urine drug screening 2
X
Urine nicotine test
X
Chest X-ray (anteroposterior
and lateral views)
X
12 lead ECG
X
Xb
X
X
X
X
24 24-hour ECG monitoring
<…… >c
Laboratory tests 3
X
Xa
X
X
Pregnancy test 4
X
X
X
Virological testing 5
X
Randomization
X
Enter the test center
X
Administration 6
X
Leave hospital
X
Life signs 7
X
X
Xb
X
X
X
X
X
Pharmacokinetics
(PK)
bl-
ood sampling 8
X
Adverse event (AE) record
X
X
X
X
X
X
X
X
Concomitant medication
records
X
X
X
X
X
X
X
X
a.
If examinations were performed within 7 days prior to hospital admission, no repeat testing is required post-admission.
b.
Time of inspection: before administration (within 2 hours), after administration (2 hours ± 30 minutes, 6 hours ± 1 hour, and 24 hours ± 2 hours).
c.
Duration of 24-hour ECG monitoring: 2 hours prior to administration; 24 hours from the first day of administration to the second day.
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.

IPG11406-Phase I Clinical Trial in Healthy Subjects
Study ID: IPG11406-C001
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1.
Handling of subject withdrawal: a. If a subject withdraws after administration, the withdrawal should be completed after the blood collection and examination on
day 5; b. If a subject withdraws before administration, the investigator will decide whether to conduct early examinations for certain items based on the specific
reasons for withdrawal.
2.
The screening of urine drugs includes: acetaminophen, amphetamine, methamphetamine, barbiturates, benzodiazepines, cocaine, methadone, opioids,
benzociclidine, tetrahydrocannabinol, tricyclic antidepressants, etc.
3.
Laboratory tests include: complete blood count (CBC), blood biochemistry, coagulation function, urinalysis, etc.
4.
Pregnancy testing is only applicable to women of childbearing age, with urine samples used for screening; blood samples are used for testing one day prior to
medication administration.
5.
Virological testing includes: HBsAg, HCV Ab, HIV Ab, and antiretroviral therapy (ART) - tested within 28 days prior to the first dose, with the investigator's
discretion on whether to repeat testing.
6.
Administration ofIPG11406 (or placebo): Fasting, administered with a specified volume ofwater.
7.
The vital signs include: blood pressure, pulse, respiratory rate, and body temperature.
8.
Pharmacokinetic evaluation blood collection time: On day 1, before administration (within 1 hour); after administration, at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9,
12,24,36,48,72, and 96 hours (the blood collection time window is ±10% of the normal time, e.g., the time window for the 1-hour collection point is 1 hour ± 6
minutes).

IPG11406-Phase I Clinical Trial in Healthy Subjects
Study ID: IPG11406-C001
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Table 2A Flowchart ofthe Study (food Influence Cohort)
Study period
Filter pe-
riod
Enter
the
test center
Administration pe-
riod
Safety evaluation (elution per-
iod ≥4 days)
Administration
period
Safety evaluation
Fl.up
Time window
D-
28~-2
D-1
D1
D2
D3
D4
D5
D6
D7
D8
D9
D101
D13
(±1
day)
Sign the informed co-
nsent form
X
Height/Weight/Body
Mass Index
X
Demographic data
X
Medical
history
and
treatment history
X
X
Selection criteria
X
X
Check-up
X
Xa
X
Breath alcohol test
X
Urine drug screening 2
X
Urine nicotine test
X
Chest X-ray (anterop-
osterior and lateral
views)
X
12 lead ECG
X
Xb
X
X
X
Xb
X
X
X
X
24 24-hour ECG
monitoring
<…… >c
<…… >c
Laboratory tests 3
X
Xa
X
X
X
Pregnancy test 4
X
X
X
Virological testing 5
X
Randomization
X
Enter the test center
X
Administration 6
X
X
Leave hospital
X
Life signs 7
X
X
Xb
X
X
X
X
Xb
X
X
X
X
X
Pharmacokinetic
(PK)
blood sampling 8
X
.
.

IPG11406-Phase I Clinical Trial in Healthy Subjects
Study ID: IPG11406-C001
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Adverse Event
(AE) Record
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant me-
dication records
X
X
X
X
X
X
X
X
X
X
X
X
X
a.
If examinations were performed within 7 days prior to hospital admission, no repeat testing is required post-admission.
b.
Time of inspection: before administration (within 2 hours), after administration (2 hours ± 30 minutes, 6 hours ± 1 hour, and 24 hours ± 2 hours).
c.
Duration of 24-hour ECG monitoring: 2 hours prior to administration; 24 hours from the first and sixth day after administration to the following day.
1.
Handling of subject withdrawal: a. If a subject withdraws after administration, the withdrawal should be completed after blood collection and testing on day 5 or
day 10; b. If a subject withdraws before administration, the investigator will decide whether to conduct early testing for certain items based on the specific reason
for withdrawal.
2.
The screening for narcotic drugs includes: acetaminophen, amphetamine, methamphetamine, barbiturates, benzodiazepines, cocaine, methadone, opioids,
benzociclidine, tetrahydrocannabinol, tricyclic antidepressants, etc.
3.
Laboratory tests include: complete blood count (CBC), blood biochemistry, coagulation function, urinalysis, etc.;
4.
Pregnancy testing is only applicable to women of childbearing age, with urine samples used for screening; blood samples are used for testing one day prior to
medication administration.
5.
Virological testing includes: HBsAg, HCV Ab, HIV Ab, and antiretroviral therapy (ART) - tested within 28 days prior to the first dose, with the investigator's
discretion on whether to repeat testing.
6.
Study drug administration: Subjects will receive a single oral dose of the specified study drug (IPG11406 or placebo) with 240 mL of water on day 1 in a fasting
state, and a single oral dose of the specified study drug (IPG11406 or placebo) with 240 mL ofwater on day 6 in a fed state.
Fasting conditions:Subjects were required to fast overnight for at least 10 hours before taking IPG11406 or placebo orally with 240 ml of water. They were
allowed to drink water freely but not eat within 1 hour before and 1 hour after taking the medication.
Fasting Protocol:Participants must fast overnight for at least 10 hours before consuming a high-fat breakfast, which must be finished within 30 minutes. Thirty
minutes after breakfast, participants will take either IPG11406 or a placebo orally with 240 mL of water. No food or beverages may be consumed for at least 4
hours after administration. Except for breakfast on the first day of each study cycle, participants will receive standardized meals at scheduled intervals during their
stay at the research center.
The preparation of a high-fat breakfast will adhere to FDA recommendations (a breakfast comprising high-fat foods (approximately 50% of total meal calories) and
high-calorie foods (approximately 800 to 1000 calories), with protein, carbohydrates, and fat contents of approximately 150,250, and 500 to 600 calories,
respectively. Examples include 2 fried eggs (fried in butter), 2 strips of bacon, 2 slices of toast (buttered), 4 ounces of potato pancakes, and 8 ounces of whole
milk).
7.
Biological signs include: blood pressure, pulse, respiratory rate, and body temperature;
8.
Pharmacokinetic evaluation blood collection time: On day 1, before administration on day 6 (within 1 hour); after administration, at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6,
9, 12,24,36,48,72, and 96 hours (the blood collection time window is ±10% of the normal time, e.g., the time window for the 1-hour collection point is 1 hour ± 6
minutes).

IPG11406-Phase I Clinical Trial in Healthy Subjects
Study ID: IPG11406-C001
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Table 3B Flowchart ofthe Study
Study period
Filter per-
iod
Get into
Trial
Centrality
Administration Period and Safety Evaluation
Safety evalua-
tion
Fl.up
Time window
D-28~-
2
D-1
D1~10
D11~17
D1
D2
D3
D4
D5
D6
D7
D8
D9
D10
D141
D17 ± 2
days
Sign the informed consent
form
X
Height/Weight/Body Mass
Index
X
Demographic data
X
Medical history and treatment
history
X
Selection criteria
X
X
Check-up
X
Xa
X
X
Breath alcohol test
X
Urine drug screening 2
X
Urine nicotine test
X
Chest X-ray (anteroposterior
and lateral views)
X
12 lead ECG
X
Xb
X
X
X
X
Laboratory tests 3
X
Xa
X
X
X
X
Pregnancy test 4
X
X
Virological testing 5
X
Randomization
X
Enter the test center
X
Administration 6
X
X
X
X
X
X
X
X
X
X
Leave hospital
X
Life signs 7
X
X
Xb
X
X
X
X
X
X
X
X
X
X
X
Pharmacokinetics (PK) blood
sampling 8
X
Adverse event (AE) record
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medication rec-
ords
X
X
X
X
X
X
X
X
X
X
X
X
X
X
a.
If examinations were performed within 7 days prior to hospital admission, no repeat testing is required post-admission.
b.
Time of inspection: before administration (within 2 hours), after administration (2 hours ± 30 minutes, 6 hours ± 1 hour, and 24 hours ± 2 hours).

IPG11406-Phase I Clinical Trial in Healthy Subjects
Study ID: IPG11406-C001
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1.
Handling of subject withdrawal: a. If a subject withdraws after administration, the withdrawal should be completed after the blood collection and examination on
day 14; b. If a subject withdraws before administration, the investigator will decide whether to conduct early examinations for certain items based on the specific
reasons for withdrawal.
2.
The screening of urine drugs includes: acetaminophen, amphetamine, methamphetamine, barbiturates, benzodiazepines, cocaine, methadone, opioids,
benzociclidine, tetrahydrocannabinol, tricyclic antidepressants, etc.
3.
Laboratory tests include: complete blood count (CBC), blood biochemistry, coagulation function, urinalysis, etc.
4.
Pregnancy testing is only applicable to women of childbearing age, with urine samples used for screening; blood samples are used for testing one day prior to
medication administration.
5.
Virological testing includes: HBsAg, HCV Ab, HIV Ab, and antiretroviral therapy (ART) - tested within 28 days prior to the first dose, with the investigator's
discretion on whether to repeat testing.
6.
Administration ofIPG11406 (or placebo): Fasting, administered with a specified volume ofwater.
7.
The vital signs include: blood pressure, pulse, respiratory rate, and body temperature.
8.
Pharmacokinetic evaluation blood sampling time:
Day 1: before administration (within 1 hour), and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12, and 24 hours after administration.
Day 4, Day 6, Day 8: Before administration (within 1 hour prior to administration).
Day 10: Before administration (within 1 hour prior to administration), and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 9, 12,24,36,48,72, and 96 hours post-
administration (the blood collection time window is ±10% of the normal time, e.g., the time window for the 1-hour collection point is 1 hour ±6
minutes).