Conditions: Moderate-to-severe Atopic Dermatitis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 330
Healthy volunteers: no

Brief summary:
This study will evaluate the efficacy and safety of CBP-201 in Chinese subjects with moderate to severe atopic dermatitis.

Detailed description:
This study is a randomized, double-blind, multi-center, controlled study designed to assess the efficacy, safety and PK characteristics of CBP-201 in eligible subjects with moderate to severe AD.

The study includes a screening period, a treatment period and a follow-up period. The treatment period is divided into two stages.

Arms:
arm 1: CBP-201 Dose subcutaneous (SC) injection arm 2: subcutaneous (SC) injection

Interventions: intervention 1: CBP-201 intervention 2: Placebo
Intervention descriptions: intervention 1: CBP-201 subcutaneous(SC) injection. intervention 2: subcutaneous(SC) injection

Protocol document:
Prot_000.pdf: 
Clinical Trial Protocol 
A double-blind, multi-center, randomized controlled clinical 
study to evaluate the efficacy and safety of CBP-201 in 
Chinese subjects with moderate to severe atopic dermatitis 
Investigational product: CBP-201 
Protocol number: 
CBP-201-CN002 
Version number: 
4.0 
Date: 
August 1, 2022 
Sponsor: 
Suzhou Connect Biopharmaceuticals, Ltd. 
Confidential Information 
All information contained in this protocol is owned by the sponsor. Therefore, it is only 
provided to investigators, co-investigators, ethics committees, supervision and management 
departments and other relevant medical institutions for review. Without the written approval 
of the sponsor, it is strictly forbidden to disclose any information to a third party unrelated to 
the study, except for necessary explanations made for signing the informed consent form with 
subjects who may participate in the study. 
NCT Number:                         NCT05017480


Protocol Number: CBP-201-CN002 
V4.0/August 1, 2022 
Confidential Information 
 
Page 2 of 129  
Protocol Signature Page—Principal Investigator 
Study title: A double-blind, multi-center, randomized controlled clinical study to evaluate the 
efficacy and safety of CBP-201 in Chinese subjects with moderate to severe atopic dermatitis 
Protocol number: CBP-201-CN002 
The signature below indicates that the principal investigator has read and understood the 
clinical study protocol and its amendments, and agrees to conduct this study in 
accordance with the content of the study protocol, the Declaration of Helsinki, the Good 
Clinical Practice for Pharmaceuticals, and all applicable regulatory requirements. I will 
provide all the study staff participating in this study with a copy of this protocol and 
discuss the protocol and related files with them to ensure that they fully understand the 
study drug and how to conduct this study. 
 
 
Signature 
Name of principal 
investigator:  
Zhang Jianzhong 
 
 
 
 
 
 
 
 
Signature: 
 
Date:   
 
 
 
 
 
 
Name of study facility: 
Peking University People’s Hospital 
 
 
 
 
 
Address of study facility: 
No. 11, Xizhimen South Street, Xicheng District, Beijing 
 
 
 
 
 
 
 


Protocol Number: CBP-201-CN002 
V4.0/August 1, 2022 
Confidential Information 
 
Page 3 of 129  
Protocol Signature Page—Sponsor 
Protocol title: A double-blind, multi-center, randomized controlled clinical study to evaluate 
the efficacy and safety of CBP-201 in Chinese subjects with moderate to severe atopic 
dermatitis 
Protocol number: CBP-201-CN002 
The signature below indicates that the sponsor has read and understood the clinical study 
protocol and its amendments, and agrees to conduct this study in accordance with the 
content of the study protocol, the Declaration of Helsinki, the Good Clinical Practice for 
Pharmaceuticals, and all applicable regulatory requirements. 
 
 
Signature  
Name of the sponsor’s 
person in charge: 
Guo Jiawang 
 
 
 
 
Clinical Operation 
Director 
 
 
 
Signature: 
 
Date:  
 
 
 
 
 
 
 
Name of the sponsor 
Suzhou Connect Biopharmaceuticals, Ltd. 
 
 
 
 
 
 
 
 


Protocol Number: CBP-201-CN002 
V4.0/August 1, 2022 
Confidential Information 
 
Page 4 of 129  
Protocol Signature Page—Statistical Analysis Unit  
Study title: A double-blind, multi-center, randomized controlled clinical study to evaluate the 
efficacy and safety of CBP-201 in Chinese subjects with moderate to severe atopic dermatitis 
Protocol number: CBP-201-CN002 
The signature below indicates that the statistical analysis unit has read and understood 
the clinical study protocol and its amendments, and agrees to conduct this study in 
accordance with the content of the study protocol, the Declaration of Helsinki, the Good 
Clinical Practice for Pharmaceuticals, and all applicable regulatory requirements. 
 
 
Signature 
Name of the statistical analysis 
unit’s person in charge: 
Xu Jinmei 
 
 
 
 
 
 
 
 
Signature: 
 
Date:  
 
 
 
 
 
 
 
Name of statistical unit: 
Hangzhou Tigermed Consulting Co., Ltd.  
 
 
 
 
 
 


Protocol Number: CBP-201-CN002 
V4.0/August 1, 2022 
Confidential Information 
 
Page 5 of 129  
Protocol Signature Page—Statistical Analysis Unit (Pharmacokinetics) 
Study title: A double-blind, multi-center, randomized controlled clinical study to evaluate the 
efficacy and safety of CBP-201 in Chinese subjects with moderate to severe atopic dermatitis 
Protocol number: CBP-201-CN002 
The signature below indicates that the statistical analysis unit has read and understood 
the clinical study protocol and its amendments, and agrees to conduct this study in 
accordance with the content of the study protocol, the Declaration of Helsinki, the Good 
Clinical Practice for Pharmaceuticals, and all applicable regulatory requirements. 
 
 
Signature 
Name of the statistical analysis 
unit’s person in charge: 
Sun Xiaoyan 
 
 
 
 
 
 
 
 
Signature: 
 
Date:  
 
 
 
 
 
 
 
Name of statistical unit: 
Hangzhou Tigermed Consulting Co., Ltd. 
 
 
 
 
 
 


Protocol Number: CBP-201-CN002 
V4.0/August 1, 2022 
Confidential Information 
 
Page 6 of 129  
Protocol Signature Page—Other Study Centers 
Study title: A double-blind, multi-center, randomized controlled clinical study to evaluate the 
efficacy and safety of CBP-201 in Chinese subjects with moderate to severe atopic dermatitis 
Protocol number: CBP-201-CN002 
The signature below indicates that the investigator has read and understood the clinical 
study protocol and its amendments, and agrees to conduct this study in accordance with 
the content of the study protocol, the Declaration of Helsinki, the Good Clinical Practice 
for Pharmaceuticals, and all applicable regulatory requirements. 
 
 
Signature 
Name of investigator: 
 
 
 
 
 
 
 
Signature: 
 
Date:  
 
 
 
 
 
Name of study facility:  
 
 
 
 
 
 
 
 


Protocol Number: CBP-201-CN002 
V4.0/August 1, 2022 
Confidential Information 
 
Page 7 of 129  
Sponsor  
Company name 
Suzhou Connect Biopharmaceuticals, Ltd. 
Project leader 
Meng Yuhui 
Contact address 
3/F, R&D East Building, Science and 
Technology Park, No. 6, Beijing West Road, 
Taicang City, Jiangsu Province 
Postal code 
215400 
Tel 
0512-53577866 
Mobile 
18521400021 
Fax 
0512-53577866-8018 
E-mail 
yhmeng@connectpharm.com 
Contract Research Organization 
Company name 
Hangzhou Tigermed Consulting Co., Ltd.  
Project leader 
Zheng Kefei 
Contact address 
18/F, Block A, Shengda Science Park, No. 19, 
Jugong Road, Binjiang District, Hangzhou 
Postal code 
310051 
Tel 
025-86627521-8078 
Mobile 
13611109817 
Fax 
/ 
E-mail 
kefei.zheng@tigermedgrp.com 
Data Management 
Company name 
Hangzhou Tigermed Consulting Co., Ltd.  
Project leader 
Zhang Ying 
Contact address 
18/F, Block A, Shengda Science Park, No. 19, 
Jugong Road, Binjiang District, Hangzhou 
Postal code 
310051 
Tel 
/ 
Mobile 
15757302966 
Fax 
/ 
E-mail 
ying.zhang@tigermedgrp.com 
Statistical Analysis 
Company name 
Hangzhou Tigermed Consulting Co., Ltd.  
Project leader 
Xu Jinmei 
Contact address 
9/F, Block C, No. 232, Liangjing Road, Pudong 
New Area, Shanghai 
Postal code 
201203 
Tel 
025-50276030-5279 
Mobile 
13917944197 
Fax 
/ 
E-mail 
Jenny.xu@tigermedgrp.com 
Statistical Analysis (Pharmacokinetics) 
Company name 
Hangzhou Tigermed Consulting Co., Ltd.  
Project leader 
Sun Xiaoyan 
Contact address 
18/F, Block A, Shengda Science Park, No. 19, 
Jugong Road, Binjiang District, Hangzhou 
Postal code 
310051 
Tel 
021-50831672 
Mobile 
18317062768 
Fax 
/ 
E-mail 
xiaoyan.sun@mosim.com 


Protocol Number: CBP-201-CN002 
V4.0/August 1, 2022 
Confidential Information 
 
Page 8 of 129  
Central Laboratory 
Company name 
Teddy Clinical Research Laboratory (Shanghai) Limited 
Project leader 
Jin Lin 
Contact address 
Room 101-110, Block C, 3/F, Building 12, No. 
128, 
Xiangyin 
Road, 
Yangpu 
District, 
Shanghai 
Postal code 
200433 
Tel 
+ 86 021 61230400 
Mobile 
13817681191 
Fax 
+ 86 021 60952736 
E-mail 
lin.jin@teddylaboratory.com 
Bioanalysis Laboratory 
Company 
name 
Frontage Laboratories (Shanghai), Inc. 
Project leader 
Zhou Xuanyi 
Contact 
address 
No. 13, Lane 67, Libing Road, Pudong 
New Area, Shanghai 
Postal code 
201203 
Tel 
+ 86 021 50796566 
Mobile 
18217009357 
Fax 
+ 86 021 5079 6603 
E-mail 
xuanyizhou@frontagelab.com.cn 
 
 
 


Protocol Number: CBP-201-CN002 
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Confidential Information 
 
Page 9 of 129  
1. 
Protocol Synopsis 
Sponsor 
Suzhou Connect Biopharmaceuticals, Ltd. 
Protocol number 
CBP-201-CN002 
Study title 
A double-blind, multi-center, randomized controlled clinical study to evaluate 
the efficacy and safety of CBP-201 in Chinese subjects with moderate to severe 
atopic dermatitis 
Version/date 
V4.0/August 1, 2022 
Phase  
Phase II 
Indication 
Moderate to severe atopic dermatitis (AD) 
Study objectives 
Primary objective: 
• 
To assess the efficacy of CBP-201 in subjects with moderate to 
severe AD 
Secondary objectives: 
• 
To assess the safety and tolerability of CBP-201 in subjects with 
moderate to severe AD 
• 
To assess the pharmacokinetic (PK) characteristics of CBP-201 in 
subjects with moderate to severe AD 
• 
To assess the pharmacodynamic (PD) characteristics of CBP-201 
• 
To assess the immunogenicity of CBP-201 
Study design 
This study is a randomized, double-blind, multi-center, controlled study 
designed to assess the efficacy, safety and PK characteristics of CBP-201 in 
eligible subjects with moderate to severe AD. 
The study includes a screening period, a treatment period and a follow-up 
period. The treatment period is divided into two stages: 
Stage 1 study: It is a placebo-controlled study, in which subjects who meet the 
inclusion criteria and do not meet the exclusion criteria will be stratified 
according to the severity of their baseline disease (moderate [IGA=3] and 
severe [IGA=4]) and  randomized into one of the following 2 groups to receive 
investigational product or placebo treatment by the ratio of 2:1: 
• 
Group A (CBP-201): the subjects will receive a subcutaneous injection of 
CBP-201 600 mg (4 ml in total, 2 injections of 2 ml each in different sites) 
on Day 1, begin to receive a subcutaneous injection of CBP-201 300 mg 
(2 ml) from Week 2 (W2), and receive treatment at the same dose every 2 
weeks thereafter until W14; 
• 
Group B (placebo): the subjects will receive a subcutaneous injection of 
placebo 4 ml (2 injections of 2 ml each in different sites), begin to receive 
a subcutaneous injection of placebo 2 ml from W2, and receive placebo 2 
ml every 2 weeks thereafter until W14. 
The grouped dosing regimen in Stage 1 is shown in the table below:  
Group 
W0 
W2 
W4 
W6 
W8 
W10 
W12 
W14 
Group A 
4XC 
2XC 
2XC 
2XC 
2XC 
2XC 
2XC 
2XC 
Group B 
4XP 
2XP 
2XP 
2XP 
2XP 
2XP 
2XP 
2XP 
Note: C=CBP-201; P=placebo; #X=number of ampoules 
Before the administration of study drug at W16 visit, all subjects will be 
assessed for efficacy, and the treatment assignment for Stage 2 maintenance 
treatment is based on whether a subject achieves a 50% or greater reduction in 


Pr ot oc ol N u m ber: C B P- 2 0 1- C N 0 0 2  
V 4. 0/ A u g ust 1, 2 0 2 2 
C o nfi de ntial I nf or mati o n 
Pa ge 1 0 of 1 2 9  
Ecze ma Area a n d Se verit y I n de x ( E A SI) sc ore (ie E A SI- 5 0).
St a ge 2 st u dy: T he gr o u pi n g f or Sta ge 2 mai nte na n ce treat me nt is as f oll o ws:
S u bjects w h o ha ve ac hie ve d E A SI- 5 0 i n t he W 1 6 pre-a d mi nistrati o n 
treat me nt assess me nt  will be 1: 1 ra nd o mize d t o o ne of t he f oll o wi n g 
t w o gr o u ps t o recei ve st u d y treat me nt starti n g fr o m W 1 6:
Gr o u p C: T he s u bjects will recei ve a s u bc uta ne o us i njecti o n of 
C B P- 2 0 1 3 0 0 m g e ver y 2 wee ks u ntil W 5 0; 
Gr o u p D: T he s u bjects will recei ve a s u bc uta ne o us i njecti o n of 
C B P- 2 0 1  3 0 0  m g e ver y  4  wee ks.  
I n  or der  t o  mai ntai n  t he  
i njecti o n e ver y 2 wee ks bli n d, w he n n ot recei vi n g C B P- 2 0 1, t he 
s u bjects will recei ve a n i njecti o n of place b o 2 ml o nce e ver y 4 
wee ks u ntil W 5 0. 
S u bjects  w h o  ha ve  n ot  ac hie ve d  E A SI- 5 0  i n  t he  W 1 6  pre-
a d mi nistrati o n  treat me nt  assess me nt will  recei ve  t he  f oll o wi n g  
treat me nt starti n g fr o m W 1 6:
Gr o u p E: T he s u bjects will recei ve a s u bc uta ne o us i njecti o n of 
C B P- 2 0 1 3 0 0 m g e ver y 2 wee ks u ntil W 5 0.
If s u bjects i n gr o u p C a n d gr o u p D ha ve n ot ac hie ve d E A SI- 5 0 i n 
t w o c o nti n u o us pre-a d mi nistrati o n treat me nt assess me nts, t he y will 
be assi g ne d t o gr o u p E t o be trea te d wit h s u bc uta ne o us i njecti o n of 
C B P- 2 0 1 3 0 0 m g e ver y 2 wee ks fr o m t he visit w he n E A SI- 5 0 is n ot 
ac hie ve d f or t he sec o n d ti me t o  W 5 0.  
T he d osi n g re gi me n i n Sta ge 2 is s h o w n i n t he ta ble bel o w:
Gr o u p
W 1 6 
W 1 8 
W 2 0 
W 2 2 
W 2 4 
… … 
W 5 0 
Gr o u p C
2 X C 
2 X C 
2 X C 
2 X C 
2 X C  
… … 
2 X C
Gr o u p D
2 X C 
2 X P
 2 X C 
2 X P 
2 X C  
… …
  
2 X P
 
Gr o u p E
2 X C 
2 X C 
2 X C 
2 X C 
2 X C  
… …
 2 X C
N ote: C = C B P- 2 0 1; P = place b o; # X = n u m b er of a m p o ules
All s u bjects (i ncl u di n g t he s u bjects w h o are earl y ter mi nate d of t he treat me nt)
will be f oll o we d u p f or 8 wee ks after t he last d ose. 
I n t his st u d y, a n i n de pe n de nt Data a n d Safet y M o nit ori n g B oar d ( D S M B) will 
be esta blis he d t o re g ularl y re vie w a n d e val uate t he c u m ulati ve st u d y data, t o 
g uara ntee t he safet y of s u bjects, i m ple m e ntati o n a n d pr o gress of t he st u d y, a n d 
t o gi ve t he s p o ns or a s u g gesti o n o n w het her t o c o nti n ue t he st u d y.  
T he o verall st u d y desi g n is s h o w n i n t he dia gra m bel o w:
N ote:  1.  T he  s u bjects  will  recei ve  a  l oa di n g  d ose  of  t he  st u d y  dr u g  
(i n vesti gati o nal pr o d uct/ place b o) o n D 1 at a d ose of 6 0 0 m g ( 4 ml); 2. Res p o nse 
is defi ne d as a 5 0 % or m ore decrease i n t he E A SI sc ore; 3. I n or der t o mai ntai n 
( n = 8 5)
( n = 1 7 0)


Protocol Number: CBP-201-CN002 
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Confidential Information 
 
Page 11 of 129  
the injection every 2 weeks blind, when not receiving CBP-201, the subjects 
will receive an injection of placebo 2 ml once every 4 weeks until W52; 4: If 
subjects in group C and group D have not achieved EASI-50 in two continuous 
pre-administration treatment assessments, they will be assigned to group E to 
be treated with subcutaneous injection of CBP-201 300 mg every 2 weeks from 
the visit when EASI-50 is not achieved for the second time to W50. 
Planned number of 
study sites 
Approximately 55 
Planned number of 
subjects to be enrolled 
Expected to enroll about 255 cases (due to protocol changes, the actual number 
of subjects enrolled is expected to be approximately 336) 
Study cycle 
The study consists of a screening period, a treatment period (2 stages) and a 
follow-up period: 
• 
Screening period: D-28~D-1 
• 
Treatment period: 
o 
Stage 1 treatment: 16 weeks (D1~W16) 
o 
Stage 2 maintenance treatment: 36 weeks (W16~W52) 
• 
Follow-up period: 8 weeks (W53~W60) 
Study duration 
The longest duration of each subject’s participation in the study is 64 weeks 
(including a screening period of 4 weeks, Stage 1 treatment period of 16 weeks, 
Stage 2 maintenance treatment period of 36 weeks, and a follow-up period of 8 
weeks). 
The study duration is expected to be about 2 years.  
Eligibility criteria 
Inclusion criteria 
Patients must meet all of the following criteria to be enrolled into this study: 
1) 
12≤ age ≤75 years at the screening visit, male or female; note: the 
adolescent subjects aged <18 years should have body weight ≥40 kg. 
2) 
Diagnosed with atopic dermatitis (according to the American Academy of 
Dermatology’s Guidelines of care for the management of atopic dermatitis, 
2014[1]) at the screening, visit and: 
a) The subject has been suffering from the disease for more than 1 year 
at the time of screening, and according to the judgment of the 
investigator, the subject has had poor response to topical drugs such 
as corticosteroids, phosphodiesterase-4 (PDE-4) inhibitors or 
calcineurin inhibitors (TCI), or it is not medically suitable for the 
subject to receive topical drug treatment (e.g., there are important side 
effects or safety risks); 
Note: Poor response is defined as any of the following conditions: 
i. The patient has not achieved and maintained response or reached a low 
disease activity state (equivalent to IGA 0=asymptomatic to 2=mild) 
despite regular use of topical therapy during the 1 year before baseline; 
ii. The patient has received systemic treatment for AD despite regular use 
of topical therapy during the 1 year before baseline. 
b) At the screening and baseline visit, Investigator's Global Assessment 
(IGA) score ≥3 (according to the validated Investigator Global 
Assessment for Atopic Dermatitis [vIGA-AD™] scale, see Section 
17.4 Appendix D), Eczema Area and Severity Index (EASI) score≥16 
(see Section 17.5, Appendix E), and≥10% body surface area (BSA) of 


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Page 12 of 129  
AD involvement(see Section 17.6, Appendix F); 
c) The average score of the maximum pruritus intensity in the Peak 
Pruritus Numerical Rating Scale (PP-NRS) ≥4 (see Section 17.1, 
Appendix A). 
Note: The baseline average maximum pruritus PP-NRS intensity 
score will be calculated based on the average value of the maximum 
pruritus intensity PP-NRS score [daily score range 0-10] every day 
within 7 days before randomization. In these 7 days, the scores of at 
least 4 days are required for the calculation of the baseline average 
score. If the patient’s reporting days are less than 4 days in the 7 days 
before the planned date of randomization, randomization should be 
postponed until the requirements are met, but it is not allowed to 
exceed the maximum screening period of 28 days. 
3) 
Able and willing to use a stable dose of a mild emollient at the AD 
involvement area at least twice a day starting from at least 7 days before 
baseline and continue to use it during the study period (see Section 8.1.1.2 
Emollients). 
4) 
Female subjects of childbearing potential (FCBP) and male subjects who 
have not undergone vasectomy must take highly effective contraceptive 
measures during the entire study period, including the 8-week follow-up 
period after discontinuation of study drug. Postmenopausal women 
(determined by testing follicle stimulating hormone [FSH]) and women 
with a record of surgical sterilization (i.e., tubal ligation or hysterectomy 
or bilateral oophorectomy) before the screening visit can be considered 
infertile. 
Highly effective contraceptive measures include: 
i. Abstinence (acceptable only if it is part of the subject's routine lifestyle); 
ii. Hormones (oral, patch, ring, injection, implant) combined with male 
condoms. This measure must be used at least 30 days before the first 
study drug administration. Otherwise, another acceptable method of 
contraception must be used; 
iii. Intrauterine device (IUD) combined with male condoms; 
iv. Exceptions are: a) women who have had amenorrhea for at least 12 
consecutive months without using drugs known to cause amenorrhea, 
and have a recorded FSH level greater than 40 mIU/mL or in the 
postmenopausal range; or b) surgical sterilization (e.g., hysterectomy, 
bilateral oophorectomy). 
5) 
Subjects and/or their guardians have the ability to learn the study 
requirements and process, and voluntarily take part in the clinical trial and 
sign an informed consent form (ICF); note: for subjects ≥18 years: subjects 
voluntarily agree to take part in the study by themselves and sign ICF; for 
subjects aged 12-17 years: subjects and their guardians voluntarily agree 
to take part in the study, the guardians sign the ICF, and the subjects sign 
the informed assent form for minors by themselves. 
6) 
Subjects and/or their guardians are willing and able to comply with study 
visits and related procedures. 
Exclusion criteria 
Patients who meet any of the following criteria cannot participate in this study: 


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Page 13 of 129  
1) 
Patients who have received any of the following treatments:  
a) 
Treatment with dupilumab or any anti-IL-4Rα or IL-13 antibodies; 
b) Topical drugs for treatment of AD or have the potential to affect the 
assessment of AD, including but not limited to corticosteroids, PDE-
4 inhibitors, Janus kinase (JAK) inhibitors, aromatic hydrocarbon 
receptor agonists, tacrolimus or pimecrolimus, or traditional Chinese 
medicine (TCM) or herbal medicine, etc. within 2 weeks before 
baseline; 
c) 
Have undergone bleaching baths ≥ twice within 2 weeks before 
baseline; 
d) Have begun to use prescription emollients or emollients containing 
additives (e.g., ceramide, hyaluronic acid, urea, or filaggrin 
breakdown products) to treat AD from the screening period (if the 
subject has started using this kind of emollient before the screening 
visit, they can continue to use it at a stable dose; if the subject is 
intolerable to the emollients provided uniformly by the sponsor 
during the screening period, he/she can change to emollient of this 
kind used previously, but it must be used at a stable dose for at least 
7 days before baseline and during the study period); 
e) 
Treatment 
with 
systemic 
corticosteroids 
or 
other 
immunosuppressive/immunomodulating 
substances 
(e.g., 
cyclosporine, mycophenolate mofetil, azathioprine, methotrexate, or 
oral JAK inhibitors) due to AD or other diseases within 4 weeks 
before baseline (except for corticosteroid inhalers and nasal sprays); 
f) 
Treatment with systemic TCM or herbal treatment within 4 weeks 
before baseline (note: except for those for the treatment of diseases 
other than AD, which are necessary and will neither increase the risks 
of the subjects nor affect the assessment of the study in accordance 
with the medical judgements of the investigator and/or specialist 
physician); 
g) Treatment with phototherapy (narrow band ultraviolet B [NBUVB], 
ultraviolet B [UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A 
[PUVA]), sunbed or any other light emitting device (LED) therapy 
within 4 weeks before baseline; 
h) Have used any investigational drug/treatment within 4 weeks before 
baseline or 5 drug half-lives, whichever is longer; 
i) 
Treatment with other biological agents (e.g., omalizumab) within 3 
months before baseline or 5 drug half-lives (if known), whichever is 
longer; 
j) 
Have been vaccinated with live (attenuated) vaccine within 8 weeks 
before baseline; 
k) Treatment with cell depletion agents (e.g., rituximab) within 6 months 
before baseline; 
l) 
Treatment with allergen specific immunotherapy (SIT) within 6 
months before baseline (except those who were already on stable-
dose therapy before baseline). 
2) 
Patients who meet any of the following: 
a) 
History of hypersensitivity to L-histidine, trehalose or Tween 80; 


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Page 14 of 129  
b) 
Other skin complications in addition to AD that may interfere with 
the study assessments; 
c) 
Any history of vernal keratoconjunctivitis (VKC) and atopic 
keratoconjunctivitis (AKC); 
d) 
History of malignant tumor within 5 years before screening, except 
for cervical carcinoma in situ or non-metastatic cutaneous squamous 
cell carcinoma or basal cell carcinoma; 
e) 
Active tuberculosis (TB) at the screening visit, latent tuberculosis or 
a history of non-tuberculous Mycobacterium infection; 
Note:  
- 
Unless there is a clear specialist record proving that the patient has 
received adequate treatment and is currently able to start receiving 
biological treatment (based on the medical judgment of the 
investigator and/or infectious disease specialist); 
- 
If necessary, T-spot test may be used for auxiliary diagnosis of 
suspected tuberculosis patients; 
f) 
Positive for hepatitis B surface antigen (HBsAg), or positive for 
hepatitis B core antibody (HBcAb) and HBV-DNA, or positive for 
hepatitis C antibody and HCV RNA polymerase chain reaction; or 
serologically positive for human immunodeficiency virus (HIV) at 
the screening visit; 
g) 
Any of the following laboratory test abnormalities at the screening 
visit: 
i. Aspartate aminotransferase or alanine aminotransferase > 2 times 
the upper limit of normal (ULN), or total bilirubin > 1.5×ULN; 
ii. Serum creatinine > 1.2×ULN; 
iii. Hemoglobin < 8.5 g/dl (85.0 g/L) in male patients and < 8.0 g/dl 
(80.0 g/L) in female patients; 
iv. White blood cell count <3.0×109/L or ≥14×109/L; 
v. Platelet count <100×109/L. 
Note: if the subjects have the above laboratory test abnormalities at screening, 
after being assessed as necessary by the investigator, they are allowed to receive 
a retest at another day within 28 days of the screening period, and those 
qualified for the retest are permitted to be enrolled (it is forbidden to conduct 
drug intervention for those laboratory test abnormalities before retest). 
h) 
Planning to undergo major surgical operations during the study 
period; 
i) 
Used systemic treatment with antibiotics, antiviral drugs, 
antiparasitic drugs, antigenic drugs, or antifungal drugs due to 
infection within 4 weeks before the baseline visit, or suffered from 
superficial skin infection (e.g., impetigo) within 2 weeks before 
baseline (after the infection subsides, the subjects can be rescreened); 
j) 
History of parasite infection (e.g., helminth) within 6 months before 
baseline; 
k) 
According to the investigator's judgment, there is a known or 
suspected history of immunosuppression within 6 months before 
baseline, including a history of invasive opportunistic infections, 
such as aspergillosis, coccidiosis, histoplasmosis, HIV, listeriosis, 
Pneumocystis or tuberculosis, even if the infection has subsided; or 


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there is an abnormally frequently recurrent or persistent infection; 
l) 
History of alcohol or drug abuse within 2 years before the screening 
visit; 
m) 
Any other medical or psychological condition (including clinically 
significant laboratory test abnormalities, electrocardiogram (ECG) 
parameters, etc.) at the screening visit, which, as judged by the 
investigator, may indicate new and/or insufficiently understood 
diseases, may put the patient at an unreasonable risk due to his/her 
participation in the clinical trial, may lead to unreliable results of the 
patient's participation, or may interfere with the study assessments. 
The specific reasons for patients excluded due to this criterion will 
be indicated in the study documents (medical records, electronic case 
report form [eCRF], etc.). 
3) 
Pregnant or lactating women, or subjects with pregnancy or lactation plans 
during the study period. 
Study drug 
 
Investigational drug/placebo 
Study drug 
Investigational drug 
Placebo 
Drug name 
CBP-201 
/ 
Dosage form 
Injection  
Composition  
CBP-201 is prepared from a 
solution 
containing 
inactive 
excipients 
(including 
NaCl, 
trehalose, 
Tween 
80 
and 
L-
histidine) at a concentration of 150 
mg/ml. 
Contains the same 
excipients, 
but 
does not contain 
CBP-201 API. 
Storage  
CBP-201 preparation and the corresponding placebo 
solution should be stored at 2-8 ℃. 
Method 
of 
administration 
Subcutaneous injection (SC) 
Dosing 
regimen 
Detailed in Section 6.1. 
 
Emollients 
From at least 7 days before baseline to the end of the study, subjects will be 
required to apply a mild emollient to the AD involvement area at least twice a 
day as background treatment, but should avoid using emollients within 4 hours 
before AD assessment at each visit. If the subject is intolerable to the emollients 
provided uniformly by the sponsor during the screening period, he/she can 
change to the emollient of this kind used previously, but it must be used at a 
stable dose for at least 7 days before baseline and during the study period. 
Study cycle/steps 
Screening period (D-28~D-1) 
After the subjects and/or their guardians signing the ICF, the subjects will be 
assessed for study eligibility at the screening visit within 28 days prior to the 
baseline visit. 
Baseline (D1) 
Before D1 administration of study drug, subjects who were eligible at the 
screening visit will be confirmed again for their eligibility. After baseline 
assessment, the subjects who are confirmed to meet the inclusion criteria will 


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Page 16 of 129  
be randomized to Group A (CBP-201) or Group B (placebo) in a 2:1 ratio. 
Stage 1 treatment period (D1~W16) 
Randomized subjects will receive CBP-201 or placebo SC administration 
(CBP-201 600 mg or placebo at D1, and CBP-201 300 mg or placebo, Q2W 
starting from W2). Vital signs monitoring will be conducted at the study site 
before D1, W2 and W4 administration and 2 hours after administration, and 
before and 30 minutes after each administration from W6 to W14. 
Before W16 administration, all subjects will be assessed for efficacy, and 
treatment assignment for Stage 2 maintenance treatment is based on whether a 
subject achieves a 50% or greater reduction in EASI score (ie EASI-50). 
Stage 2 treatment period (W16~W52) 
Subjects who are assessed to have achieved EASI-50 before W16 
administration will be 1:1 randomized to Group C or Group D and start 
receiving SC administration of CBP-201 300 mg Q2W or once every 4 weeks 
(Q4W) until W50 (If subjects in group C and group D have not achieved EASI-
50 in two continuous pre-administration treatment assessments, they will be 
assigned to group E to be treated with subcutaneous injection of CBP-201 300 
mg every 2 weeks from the visit when EASI-50 is not achieved for the second 
time to W50.); subjects who are assessed to have not achieved EASI-50 before 
W16 administration will be assigned to Group E to start receiving SC injection 
of CBP-201 300 mg Q2W until W50. 
All subjects should undergo vital signs monitoring before administration and 2 
h after administration at W16, W18 and W20 at the study site, and before and 
30 min after each administration from W22 to W50. 
All subjects will return to the study site for examinations and assessments 
according to the time specified in the Study Flow Chart. Throughout the study 
period, AE assessment will be continued and concomitant medication/treatment 
information will be collected. 
Follow-up period (W53~W60) 
After the end of Stage 2 (W52), subjects will be followed up for safety and 
efficacy for 8 weeks to further explore the PK and PD characteristics of CBP-
201, and return to the study site for examinations and assessments according to 
the time specified in the Study Flow Chart. 
If a subject early terminates (ET) the study for any reason, the subject should 
complete the ET visit within 7 days after ET, and complete the 8-week follow-
up visit as much as possible after the ET visit. 
Blood samples from all subjects will be collected during the whole study period 
to evaluate the steady-state PK characteristics of CBP-201 and its PD effects on 
serum thymus activation regulated chemokine (TARC) level, total 
immunoglobulin E (IGE) level, peripheral blood eosinophil count and serum 
IL-4 and IL-13 levels, and to detect anti-drug antibodies (ADA) (all ADA 
positive samples will be further tested for the presence of anti-CBP-201 
neutralizing antibody [NAb]). 
The detailed study procedures are shown in the Study Flow Chart. 
Concomitant 
medications/treatmen
ts 
Prohibited drugs/treatments 
The following drugs/treatments are prohibited during the study period. If any 
of the following treatment is started after the first dose of study drug on D1, the 
study treatment must be early terminated:  


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Page 17 of 129  
• 
Dupilumab or any anti-il-4r α or IL-13 antibodies; 
• 
Topical PDE-4 inhibitors or JAK inhibitors; 
• 
Systemic treatment with corticosteroids or other immunosuppressive 
and/or 
immunomodulatory 
agents 
such 
as 
cyclosporine, 
mycophenolate mofetil, azathioprine, methotrexate or oral JAK 
inhibitors; 
• 
Cell depletion agents (e.g., rituximab) or other biological agents; 
• 
Other investigational drugs (non CBP-201) or treatments. 
The following treatments are also prohibited during the study period:  
• 
Initiation of SIT or dose up-regulation; 
• 
(Attenuated) live vaccine; 
• 
Topical corticosteroids (TCS) or TCI; 
• 
Phototherapy (NBUVB, UVB, UVA1, PUVA), sunbed or any other 
LED therapies; 
• 
Bleaching baths more than 2 times a week; 
• 
Any drug (except mild emollients) that may interfere with the 
evaluation of efficacy results or affect the evaluation of AD severity. 
Permitted drugs/treatments  
AD is a chronic recurrent skin disease characterized by periodic aggravation or 
gradual deterioration of symptoms. If medically necessary (i.e. in order to 
control intolerable AD symptoms), the investigator can provide patients with 
rescue therapy for AD by using drugs or treatment regimens that were originally 
prohibited at their own discretion. According to the investigator's judgment, AD 
aggravation or deterioration of symptoms which requires drugs or treatments 
originally prohibited by the protocol for rescue therapy will be defined as “AD 
recurrence” event, and the onset and duration of these events will be recorded 
as AE according to the site of attack.  
Note: The investigator should limit the first-step rescue therapy to topical drugs 
(TCS or TCI) as far as possible. Only patients who do not respond adequately 
after at least 7 days of topical medication can be upgraded to systemic 
medication or other treatments. If a subject receives systemic corticosteroid or 
non-steroid systemic immunosuppressive/immunomodulatory rescue therapy, 
the study drug administration will be stopped immediately. (refer to Section 8.2 
for details) 
Other drugs that are permitted may include: 
• 
Emollients (as the background treatment of this study, at least 7 days before 
baseline, all subjects need to use mild emollients at least twice a day, and 
continue to use them throughout the study period. During the screening 
period or the study period, subjects cannot start using prescription 
emollients or emollients containing additives. However, if a subject has 
already started using these emollients before the screening visit, he/she 
needs to continue using them at a stable dose throughout the study period. 
If the subject is intolerable to the emollients provided uniformly by the 
sponsor during the screening period, he/she can change to the emollient of 
this kind used previously, but it must be used at a stable dose for at least 7 
days before baseline and during the study period.); 
• 
Basic skin care (cleansing and bathing); 


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• 
Oral antihistamines (maintain a stable dose within 7 days before baseline 
and during the study period); 
• 
Drugs for the treatment of chronic diseases (e.g., hypertension, diabetes, 
etc.); 
• 
Local or systemic anti-infective drugs (as required by the condition). 
Before any rescue therapy, the investigator should make every effort to assess 
the efficacy and safety (e.g., disease severity score, safety laboratory tests). If 
necessary, unscheduled visits can be conducted. 
Efficacy endpoints 
Primary endpoint: 
The proportion of subjects whose IGA score is 0-1 and decreased by ≥2 points 
from baseline at W16. 
Key secondary endpoints: 
• 
The proportion of subjects achieving EASI-75 at W16; 
• 
The proportion of subjects whose weekly average PP-NRS is decreased 
by ≥ 4 points from baseline at W16; 
• 
The proportion of subjects whose weekly average PP-NRS is decreased 
by ≥ 3 points from baseline at W16; 
• 
Change and percentage change in the weekly average PP-NRS from 
baseline at W16; 
• 
The proportion of subjects achieving EASI-90 at W16; 
Other secondary endpoints: 
• 
Change and percentage change in the EASI score from baseline at 
W16; 
• 
The proportion of subjects achieving EASI-50 at W16; 
• 
Percentage change in the BSA of AD involvement from baseline at 
W16; 
• 
Percentage change in the SCORAD score from baseline at W16; 
• 
Change in DLQI from baseline at W16; 
• 
Change in POEM from baseline at W16; 
• 
Percentage change in the weekly average PP-NRS from baseline at W2. 
Other efficacy endpoints: 
• 
The proportion of subjects whose IGA score is decreased by ≥ 2 points 
from baseline at W16; 
• 
The proportion of subjects achieving EASI-100 at W16; 
• 
The number of AD recurrences and number of days from baseline to 
W16;  
• 
Change in efficacy parameters (e.g., IGA, EASI, BSA, SCORAD, 
POEM and DLQI) from baseline to W16; 
• 
Change in weekly average PP-NRS from baseline at W16; 
• 
The proportion of subjects whose IGA score is 0-1 and decreased by 
≥2 points from baseline at W52; 
• 
The percentage decrease in the overall EASI score between W16 and 
W52; 
• 
The proportion of subjects achieving EASI-50 at W52; 
• 
The proportion of subjects achieving EASI-75 at W52; 


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• 
The proportion of subjects achieving EASI-90 at W52; 
• 
The proportion of subjects achieving EASI-100 at W52; 
• 
Change in weekly average PP-NRS compared with baseline from W16 
to W52; 
• 
Change in POEM compared with baseline from W16 to W52; 
• 
The proportion of subjects whose IGA score is decreased by ≥2 points 
from baseline at W52;  
• 
Percentage change in the AD-affected BSA compared with baseline 
from W16 to W52; 
• 
Change in SCORAD compared with baseline from W16 to W52; 
• 
The proportion of subjects whose weekly average PP-NRS is decreased 
by ≥3 points from baseline at W52; 
• 
The proportion of subjects whose weekly average PP-NRS is decreased 
by ≥4 points from baseline at W52; 
• 
Change in PDLQI compared with baseline from W16 to W52; 
• 
The number of subjects with AD recurrence from baseline to W8; 
• 
The number of subjects with AD recurrence from W8 to W16; 
• 
The number of subjects with AD recurrence from W16 to W52; 
• 
The number of AD recurrences and number of days from W16 to W52. 
Note: EASI 50: EASI score is decreased by ≥50% from baseline; EASI 75: 
EASI score is decreased by ≥75% from baseline; EASI 90: EASI score is 
decreased by ≥90% from baseline; EASI-100: EASI score is decreased by 100% 
from baseline; PP-NRS: Peak Pruritus Numerical Rating Scale; AD recurrence: 
According to the investigator's judgment, AD aggravation or deterioration of 
symptoms which requires drugs or treatments originally prohibited by the 
protocol for rescue therapy will be defined as “AD recurrence” event; POEM: 
Patient Oriented Eczema Measure; SCORAD: Scoring Atopic Dermatitis 
Index; DLQI: Dermatology Life Quality Index.  
Safety  endpoints 
• 
Incidence and severity of AE, AE of special interest (AESI) and serious 
adverse event (SAE); 
• 
Abnormal changes in vital signs, physical examination, and the 
injection site; 
• 
Abnormal changes in laboratory tests, ECG parameters, etc.; 
• 
Percentage of subjects positive for ADA. 
PK  endpoints 
To analyze the blood concentration of CBP-201, and calculate the PK 
characteristics of steady-state trough concentrations of individuals and each 
group of subjects at each treatment time point. 
PD endpoints  
Change in serum IL-4, IL-13, IgE, TARC levels and peripheral blood 
eosinophil count from baseline. 
Statistical 
analysis 
methods 
Determination of sample size 
The sample size of 255 cases (in a 2:1 ratio, 170 cases in the CBP-201 300 mg 
Q2W group, and 85 cases in the placebo group. Assume that the dropout rate in 
the treatment group is 15%, then about 144 cases in the CBP-201 300 mg Q2W 
group and 72 cases in the placebo group will be able to complete the study) can 
provide a power of 90% to detect the therapeutic effect on the primary endpoint 
in the CBP-201 300 mg Q2W group and the placebo group. This power is 


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Page 20 of 129  
calculated based on the following assumption: the proportion of subjects 
reaching the primary efficacy endpoint is 27% in the CBP-201 300 mg Q2W 
group and 9% in the placebo group, and the significance level for two-sided 
tests is 0.05. 
The primary analysis of this study will still be based on the 255 subjects 
enrolled in accordance with V2.1 and its earlier versions of the protocol. 
Subjects newly enrolled (approximately 81 cases) based on the protocol after 
V2.1 will not be included in the primary analysis, and only supplementary 
analysis will be performed. 
Statistical analysis populations 
In this study, it is planned to perform statistical analyses in two stages: 
First of all, after the 255 subjects enrolled based on the V2.1 and prior versions 
of the protocol complete the administration and treatment, related evaluations 
and follow-up of Stage 1 (W16 pre-dose visit), the primary analysis will be 
performed based on the data of the 255 subjects, and the following 6 analysis 
populations are defined as:  
• 
Screening set 1 will include all subjects who have signed the ICF. 
• 
Randomization set 1 will include all subjects randomized at baseline 
(D1), regardless of whether they have received the treatment of 
study drug.  
• 
Full analysis set 1 (FAS1) will include all subjects in randomization 
set 1 who have received at least one dose of the study drug. FAS1 
will determine the treatment groups based on the planned treatment.  
• 
Per protocol set 1 (PPS1) will include all subjects in FAS1 without 
any major protocol deviation.  
• 
Safety set 1 (SS1) will include all subjects who have received at least 
one dose of study drug. SS1 will determine the treatment groups 
based on the actually received treatment.  
• 
PK set 1 (PKS1) will include subjects in randomization set 1 who 
have received at least one dose of CBP-201 active drug and had at 
least 1 collected and analyzable PK sample.  
After all subjects (including approximately 81 additional subjects enrolled) 
entering Stage 2 have completed the treatment, evaluations and follow-up of 
Stage 2, a Stage 2 analysis will be performed.  
The Stage 2 analysis is defined as the following 6 analysis populations:  
• 
Randomization set 2 will include all subjects entering Stage 2, 
including all subjects who are randomized into Group C or Group 
D, and subjects entering Group E. 
• 
Full analysis set 2 (FAS2) will include all subjects in randomization 
set 2 who have received at least one dose of study drug in Stage 2. 
FAS2 will determine the treatment groups based on the planned 
treatment.  
• 
Per protocol set 2 (PPS2) will include all subjects in FAS2 without 
any major protocol deviation. 
• 
Safety set 2 (SS2) will include all subjects in randomization set 2 
who have received the at least one dose of study drug in Stage 2. 
SS2 will determine the treatment groups based on the actually 


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Page 21 of 129  
received treatment. 
• 
Safety set 3 (SS3) will include all subjects in SS1 and SS2 who have 
received at least one dose of the study drug. 
• 
PK set 2 (PKS2) will include subjects who have received at least one 
dose of CBP-201 active drug in Stage 2 and had at least 1 collected 
and analyzable PK sample.  
Statistical analysis methods 
Statistical analyses will be performed using SAS 9.4 or higher version. 
Descriptive statistics will be used to summarize the safety, PK, and PD data. 
Descriptive statistics will include the number of observed subjects, the number 
of subjects with missing observations, mean, standard deviation (SD), standard 
error, minimum, median and maximum, frequency, and percentage. For 
lognormally distributed data, the geometric mean, geometric standard deviation 
and geometric coefficient of variation will be calculated. Demographic 
characteristics and baseline characteristics will be listed and summarized.  
After the 255 subjects enrolled based on the V2.1 and prior versions of the 
protocol complete the administration and treatment, related evaluations, and 
follow-up of Stage 1 (W16 pre-dose visit), the primary analysis will be 
performed, in which the W16 data will be unblinded and statistically analyzed. 
The primary efficacy endpoint—the proportion of subjects whose IGA score is 
0-1 and decreased by ≥2 points from baseline at W16 will be analyzed by 
stratified CMH Chi-square test, and the estimation of 95% confidence interval 
for inter-group difference will be provided. The statistically significant type I 
error level of the primary efficacy endpoint analysis is set at 0.05 (two-sided 
test). In order to control the probability of multiple comparison type I errors, a 
fixed-sequence method will be used. First of all, the treatment group and the 
placebo group will be compared for the primary efficacy endpoint; when the 
efficacy at the primary efficacy endpoint reaches statistical significance, the 
treatment group and the placebo group will be compared for the key secondary 
efficacy endpoints according to the set sequence in the protocol. Statistical 
inference will not be performed during the Stage 2 analysis. 
Efficacy analysis: The primary efficacy endpoint will be analyzed by stratified 
CMH Chi-square test, and the estimation of 95% interval for inter-group 
difference will be provided. Continuous efficacy endpoints will be summarized 
by treatment group using descriptive statistics, and comparisons between 
groups will be performed using Mixed-Effect Model for Repeated Measure 
(MMRM). The secondary efficacy endpoint analysis will be performed using 
the same method as the primary efficacy endpoint analysis. 
Safety analysis: Safety data will be summarized using frequency tables (counts 
and percentages) and presented by treatment and scheduled time if applicable. 
AEs will be classified with the Medical Dictionary for Regulatory Activities 
(MedDRA) terms. If applicable, descriptive statistics will be used to summarize 
safety data by treatment and scheduled time. 
The data will be compared with the reference range provided to check for 
abnormalities and/or clinically relevant changes from baseline (where 
applicable). 
PK analysis: If applicable, descriptive statistics will be used to summarize 
individual blood drug concentrations by treatment and scheduled time, or plot 


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Page 22 of 129  
a curve of means over time.  
PD analysis: Descriptive statistics will be used to summarize changes in serum 
IL-4, IL-13, IgE, TARC levels and peripheral blood eosinophil counts by 
treatment and scheduled time, and where applicable, plot the mean and SD 
change curves in each treatment group. 
The complete details of statistical analysis and methods (including data 
specifications) will be introduced in a separate Statistical Analysis Plan (SAP), 
in which PK and PD analyses will be described separately in PK/PD SAP. 
Interim analysis 
No interim analysis is planned for this study. 
 


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1.1. Study Design Diagram 
 
Figure 1: Study Design Diagram  
Note: 
1. The subjects will receive a loading dose of the study drug (investigational product/placebo) on D1 at a dose of 600 mg (4 ml);  
2. Response is defined as a 50% or more decrease in the EASI score;  
3. In order to maintain the injection every 2 weeks blind, when not receiving CBP-201, the subjects will receive an injection of placebo 2 ml once every 4 weeks until 
W52. 
4. If subjects in group C and group D have not achieved EASI-50 in two continuous pre-administration treatment assessments, they will be assigned to group E to be 
treated with subcutaneous injection of CBP-201 300 mg every 2 weeks from the visit when EASI-50 is not achieved for the second time to W50. 
 
 
(n=170) 
n=(85) 


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1.2. Study Flow Chart 
Table 1.1 Screening Period + Stage 1 Treatment Period Flow 
Assessment 
Screening period 
D-28~D-1 
Stage 1 treatment period 
D1 
Pre-dose 
D1 
Post-dose 
D15 
W2 
(±3d) 
D29 
W4 
(±3d) 
D43 
W6 
(±3d) 
D57 
W8 
(±3d) 
D71 
W10 
(±3d) 
D85 
W12 
(±3d) 
D99 
W14 
(±3d) 
D113 
W16 pre-dose 
(±3d) 
Informed consent1 
√ 
 
 
 
 
 
 
 
 
 
 
Demographic characteristics 
√ 
 
 
 
 
 
 
 
 
 
 
Medical history1 
√ 
 
 
 
 
 
 
 
 
 
 
Inclusion 
and 
exclusion 
criteria1 
√ 
√ 
 
 
 
 
 
 
 
 
 
Height  
√ 
 
 
 
 
 
 
 
 
 
 
Weight  
√ 
√ 
 
 
√ 
 
√ 
 
√ 
 
√ 
Physical examination2 
√ 
 
 
 
 
 
 
 
 
 
√ 
Vital signs 3 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
12-lead ECG 
√ 
√ 
 
 
 
 
 
 
 
 
√ 
Chest X-ray 
√ 
 
 
 
 
 
 
 
 
 
 
Eye examination4 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Hepatitis and HIV screening5 
√ 
 
 
 
 
 
 
 
 
 
 
Safety laboratory tests6 
√ 
√ 
 
√ 
√ 
 
√ 
 
 
 
√ 
Pregnancy test7 
√ 
√ 
 
 
√ 
 
√ 
 
√ 
 
√ 
FSH test8 
√ 
 
 
 
 
 
 
 
 
 
 
PK blood sample9 
 
√ 
 
√ 
√ 
 
√ 
 
√ 
 
√ 
PD blood sample9 
 
√ 
 
√ 
√ 
 
√ 
 
√ 
 
√ 
ADA10 
 
√ 
 
√ 
√ 
 
√ 
 
√ 
 
√ 
Investigator’s 
efficacy 
assessment11 
√ 
√ 
 
√ 
√ 
 
√ 
 
√ 
 
√ 
Patient reported outcomes12 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
PP-NRS13 
√ 
√ 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Randomization14 
 
√ 
 
 
 
 
 
 
 
 
√ 
SC administration of study 
drug15 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
Injection site assessment16 
 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
AE17 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
Prior 
and 
concomitant 
medication/treatment 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 


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Table 1.2 Stage 2 Maintenance Treatment Period + Follow-up Period Flow (Including Unscheduled Visit + Early Termination) 
Assessment  
Stage 2 maintenance treatment period 
Follow-up 
visit 
Unsc
hedul
ed 
visit17 
ET1
8 
+7d 
D113 
W16 
post-
dose 
(±3d) 
D12
7 
W1
8 
±3d 
D14
1 
W2
0 
±3d 
D15
5 
W2
2 
±3d 
D16
9 
W24 
±3d 
D18
3 
W26 
±3d 
D19
7 
W28 
±3d 
D21
1 
W30 
±3d 
D22
5 
W32 
±3d 
D23
9 
W34 
±3d 
D25
3 
W36 
±3d 
D26
7 
W38 
±3d 
D28
1 
W40 
±3d 
D29
5 
W42 
±3d 
D30
9 
W44 
±3d 
D32
3 
W46 
±3d 
D33
7 
W48 
±3d 
D35
1 
W50 
±3d 
D36
5 
EO
T 
W52 
±3d 
D393 
W56 
±3d 
EOS 
D421 
W60 
±3d 
Weight  
 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
√ 
√ 
 
√ 
Physical 
examination2 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
 
√ 
√ 
√ 
Vital signs3 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
12-lead ECG 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
√ 
 
√ 
 
√ 
Eye 
examination4 
 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
√ 
 
√ 
Safety 
laboratory tests6 
 
 
 
 
√ 
 
 
 
√ 
 
 
 
√ 
 
 
 
√ 
 
 
 
√ 
 
√ 
Pregnancy test7 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
√ 
√ 
 
√ 
PK blood 
sample9 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
√ 
√ 
 
√ 
PD blood 
sample9 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
√ 
√ 
 
√ 
ADA10 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
√ 
√ 
 
√ 
Investigator’s 
efficacy 
assessment11 
 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
 
√ 
√ 
√ 
 
√ 
Patient reported 
outcomes12 
 
√ 
√ 
√ 
√ 
√ 
√ 
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PP-NRS13 
 
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administration 
of study drug15 
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Injection site 
assessment16 
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medication/trea
tment 
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Abbreviations: AD=atopic dermatitis; ADA=anti-drug antibody; AE=adverse event; DLQI=Dermatology Life Quality Index; EASI=eczema Area and Severity Index; 
ECG=electrocardiogram; EOS=end of study; EOT=end of treatment; ET: early termination; FCBP=female of childbearing potential; HIV=human immunodeficiency 
virus; HR=heart rate; ICF=informed consent form; IGA=validated investigator global assessment; PD=pharmacodynamics; PK=pharmacokinetics; PP-NRS=Peak 
Pruritus Numerical Rating Scale; POEM=Patient Oriented Eczema Measure; SAE=serious adverse event; SC=subcutaneous injection; SCORAD=Scoring Atopic 
Dermatitis Index; VS=vital signs. 
Footnotes 
1. 
Before D1 administration of study drug, it must be reconfirmed that the subject has signed the ICF and is eligible for selection. The medical history should also 
be reviewed before D1 administration. 
2. 
A complete physical examination (PE) is required at screening, W16, W52, EOS/ET and unscheduled visits. The items included are as follows: general appearance, 
skin, eyes/ears/nose/throat, head and neck, cardiovascular system, respiratory system, abdomen, limbs, lymph nodes, musculoskeletal and nervous systems. 
Unless it is necessary to assess the status of AD involvement, there is no need to perform rectal or genital examinations. Priority physical examinations can be 
performed at visits where PE are not scheduled. Attention should be paid to the AD involvement areas and assessment of any AE. 
3. 
Vital signs (VS) include body temperature, respiratory rate, blood pressure, and heart rate. In the Stage 1 treatment period, on D1 and at W2 and W4, VS should 
be monitored every hour (±10 min) pre-dose and during the 2-hour monitoring period post-dose; from W6 to W14, VS should be monitored pre-dose and 30 min 
(±10 min) post-dose. In the Stage 2 maintenance treatment period, VS should be monitored every hour (±10 min) pre-dose and during the 2-hour monitoring 
period post-dose at W16, W18, and W20; from W22 to W50, VS should be monitored pre-dose and 30 (±10 min) min post-dose. During the follow-up period, 
VS should be monitored at each visit. 
4. 
Eye examination: At each visit, the investigator must assess whether the subject has any eye discomfort, such as redness, itching, photophobia and abnormal 
discharge, as well as related signs/symptoms, such as conjunctival hyperemia and exudate. If these discomforts are considered to be related to conjunctivitis or 
keratitis or any uncertain diagnosis, an ophthalmologist should conduct further assessment and give appropriate treatment. 
5. 
Hepatitis screening: Hepatitis B surface antigen, core antibody, HBV-DNA and hepatitis C antibody, HCV-RNA. 
6. 
Safety laboratory tests: Including hematology, blood biochemistry and urinalysis. See Table 9.1 for safety laboratory tests; the test results within 7 days before 
baseline can be accepted for D1, and there is no need to repeat the test. If the test is performed on the treatment day, samples need to be collected for laboratory 
tests before administration. 
7. 
For all female subjects of childbearing potential (FCBP), a blood pregnancy test should be performed during the screening period and a urine pregnancy test 
should be performed on D1 and every 4 weeks thereafter. The test results within 7 days before baseline  can be accepted for D1, and there is no need to repeat 
the test. 
8. 
FSH test: Only for menopausal female subjects; subjects who can provide FSH test results before the screening visit do not need to repeat the test. 
9. 
The trough-concentration (pre-dose) PK/PD samples should be collected (D1, W2, W4 and every 4 weeks thereafter, until W16; once every 8 weeks at W20 and 
thereafter, until W52); PK/PD samples should also be collected at the early termination visit and follow-up period (W60); among them, blood samples will not 


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be collected for PD parameter—peripheral blood eosinophils at W12, W20, W28, W36, W44, W52; the collection date and time of each sample will be recorded. 
10. 
If ADA is positive, NAb analysis is also required. 
11. 
Investigator assessments before administration include EASI, IGA, BSA, and SCORAD. If possible, the investigator assessment of the individual subject should 
be performed by the same person. 
12. 
Patient reported outcomes includes DLQI and POEM, which are assessed once a week. The investigator will dispense the subject diary at each visit and collect 
DLQI and POEM data of that day, and the data among two visits will be assessed by the subjects themselves and recorded in the subject diary. Old diaries 
dispensed last time will be collected at the next visit and the new ones will be dispensed. DLQI score will only be assessed among subjects ≥16 years. 
13. 
The PP-NRS (Daily Pruritus Diary) will be distributed at the beginning of the screening and will be reviewed by the study staff at baseline (D1). Baseline PP-
NRS must be completed during the screening period, and subjects should complete the daily records within 7 days before the baseline visit (in these 7 days, the 
scores of at least 4 days are required for the calculation of the baseline average score. If the patient’s reporting days are less than 4 days in the 7 days before 
the planned date of randomization, randomization should be postponed until the requirements are met, but it is not allowed to exceed the maximum screening 
period of 28 days) to determine the baseline severity of pruritus before treatment. During the study period, subjects should record the PP-NRS score of the 
maximum pruritus intensity in the past 24 hours in the subject’s daily diary. 
14. 
Randomization: Two randomizations will be conducted during this study: 
• 
First time: After subjects complete the screening period and meet the inclusion criteria after D1 pre-dose assessment, they can be randomized to Group A (CBP-
201 300 mg Q2W) or Group B (placebo Q2W) in a 2:1 ratio before D1 administration; 
• 
Second time: Subjects who are assessed to have achieved EASI-50 before W16 administration will be randomized to Group C (CBP-201 300 mg Q2W) or Group 
D (CBP-201 300 mg Q4W) in a ratio of 1:1. 
15. 
Unless otherwise stated, all study assessments and examinations should be completed before administration of study drug at each visit. The injection site should 
be rotated: the abdomen (avoid the area near the umbilicus), the outer thigh, and the upper arm (outer or posterior lateral). 
16. 
The assessment of the injection site will be performed using the injection site response evaluation criteria (Appendix H) provided to each study site. A clinically 
significant response judged by the investigator will be reported as an AE. At the visit of dosing day, the previous injection site should be assessed before 
administration (except D1), and the new injection site should be assessed before the subject leaves the study site; only the previous injection site is assessed at 
the visits when no drug is administered.  
17. 
AEs (the AEs collected before the signing of the ICF to D1 are recorded as pre-treatment adverse events [PTAE]) and SAEs will be collected from the signing 
of the ICF. AEs and AEs of special interest (AESI) will be collected at each study visit. 
18. Unscheduled visits (UV) or the ET visit can be conducted at any time. UV can be conducted for reasons such as AE or disease progression assessment. The 
investigator can decide which assessments are suitable for an UV, but at least VS and PE (including injection site assessment) should be performed, and the 
subject should be asked whether any AE has occurred and whether there are new concomitant medications or treatments. If a subject has ET for any reason, an 


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ET visit should be completed within 7 days after ET to determine the cause of ET, and such assessments should be conducted under the assumption that subject 
is willing to return to the study site to undergo the end-of-study assessment procedures. It should be noted that ET subjects should also try their best to complete 
the 8-week follow-up visit after the last dose of study drug. 


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2. 
Table of Contents 
Protocol Signature Page—Principal Investigator ..................................................... 2 
Protocol Signature Page—Sponsor............................................................................. 3 
Protocol Signature Page—Statistical Analysis Unit .................................................. 4 
Protocol Signature Page—Statistical Analysis Unit (Pharmacokinetics) ............... 5 
Protocol Signature Page—Other Study Centers ....................................................... 6 
1. 
Protocol Synopsis .......................................................................................................... 9 
1.1. 
Study Design Diagram .................................................................................... 23 
1.2. 
Study Flow Chart ............................................................................................ 24 
2. 
Table of Contents ........................................................................................................ 29 
2.1. 
List of Tables ................................................................................................... 32 
3. 
List of Abbreviations and Definitions of Terms ...................................................... 33 
4. 
Introduction ................................................................................................................ 36 
4.1. 
Background ...................................................................................................... 36 
4.2. 
Physical, Chemical and Pharmacological Properties .................................. 37 
4.3. 
Preclinical Studies ........................................................................................... 37 
4.4. 
Clinical Studies ................................................................................................ 38 
4.5. 
Other Safety Considerations .......................................................................... 43 
4.6. 
Study Rationale ............................................................................................... 44 
5. 
Study Objectives ......................................................................................................... 47 
5.1. 
Primary Objective ........................................................................................... 47 
5.2. 
Secondary Objectives ...................................................................................... 47 
6. 
Study Plan ................................................................................................................... 48 
6.1. 
Overall Study Design and Plan ...................................................................... 48 
6.2. 
Study Steps ....................................................................................................... 49 
6.3. 
Randomization and Blinding ......................................................................... 59 
7. 
Subject Selection and Withdrawal ............................................................................ 61 
7.1. 
Inclusion Criteria ............................................................................................ 61 
7.2. 
Exclusion Criteria ........................................................................................... 62 
7.3. 
Early Withdrawal ........................................................................................... 65 
7.4. 
Study Termination .......................................................................................... 66 
8. 
Study Treatment ......................................................................................................... 68 
8.1. 
Study Treatment Drugs .................................................................................. 68 
8.2. 
Concomitant Medications/Treatments .......................................................... 69 
8.3. 
Treatment Compliance ................................................................................... 71 
9. 
Study Procedures and Endpoints .............................................................................. 71 
9.1. 
Informed Consent ........................................................................................... 71 


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9.2. 
Demographics and Other Baseline Characteristics ..................................... 71 
9.3. 
AD Assessments ............................................................................................... 72 
9.4. 
Other Safety Assessments ............................................................................... 73 
9.5. 
Study Endpoints .............................................................................................. 74 
10. 
Adverse Events ............................................................................................................ 76 
10.1. Definition of Adverse Events .......................................................................... 76 
10.2. Determination of Severity of AEs .................................................................. 78 
10.3. Determination of Relationship between AEs and Study Drugs .................. 78 
10.4. Investigator’s Responsibility for Safety Reports .......................................... 80 
10.5. Sponsor’s Responsibility for Safety Reports ................................................ 84 
11. 
Data Management ...................................................................................................... 86 
11.1. Data Management Process ............................................................................. 86 
11.2. Data Collection ................................................................................................ 86 
11.3. Database Design .............................................................................................. 86 
11.4. Data Entry and Modification ......................................................................... 87 
11.5. Data Verification ............................................................................................. 87 
11.6. Medical Coding ............................................................................................... 88 
11.7. Data Locking ................................................................................................... 88 
12. 
Statistical Analysis ...................................................................................................... 88 
12.1. Statistical Analysis Plan .................................................................................. 88 
12.2. Statistical Hypothesis ...................................................................................... 89 
12.3. Basis of Sample Size ........................................................................................ 89 
12.4. Analysis Populations ....................................................................................... 89 
12.5. Analysis Plan ................................................................................................... 91 
12.6. Study Subjects and Demographics ................................................................ 92 
12.7. Efficacy Endpoint Analysis ............................................................................ 92 
12.8. Safety Analysis ............................................................................................... 102 
12.9. PK Analysis .................................................................................................... 103 
12.10. PD Analysis .................................................................................................... 103 
12.11. Data Convention ............................................................................................ 103 
12.12. Interim Analysis ............................................................................................ 103 
13. 
Clinical Trial Management ...................................................................................... 104 
13.1. Statement ....................................................................................................... 104 
13.2. Ethics .............................................................................................................. 104 
13.3. Verification of Original Records ................................................................. 105 
13.4. Quality Assurance and Review .................................................................... 105 
13.5. Electronic Case Report Form ...................................................................... 106 
13.6. Drug Counting ............................................................................................... 106 
13.7. Study Monitoring .......................................................................................... 106 


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13.8. Protocol Deviations ....................................................................................... 109 
13.9. Study Completion .......................................................................................... 109 
13.10. Intellectual Property Rights ......................................................................... 110 
13.11. Subject Privacy .............................................................................................. 110 
14. 
Paper Publication ..................................................................................................... 111 
15. 
Data Archiving .......................................................................................................... 112 
15.1. Source Data and Source Files ...................................................................... 112 
15.2. Materials Preservation of Study Facilities .................................................. 112 
15.3. Sponsor’s Materials Preservation ................................................................ 112 
16. 
References ................................................................................................................. 114 
17. 
Appendices ................................................................................................................ 117 
17.1. Appendix A (Peak Pruritus NRS) ................................................................ 117 
17.2. Appendix B (DLQI) ...................................................................................... 118 
17.3. Appendix C (POEM) .................................................................................... 120 
17.4. Appendix D (IGA) ......................................................................................... 122 
17.5. Appendix E (EASI) ....................................................................................... 123 
17.6. Appendix F (BSA) ......................................................................................... 127 
17.7. Appendix G (SCORAD) ............................................................................... 128 
17.8. Appendix H (Injection Site Assessment) ..................................................... 129 
 
 


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2.1. List of Tables 
Table 1.1 Screening Period + Stage 1 Treatment Period Flow ................................................ 24 
Table 1.2 Stage 2 Maintenance Treatment Period + Follow-up Period Flow (Including 
Unscheduled Visit + Early Termination) ................................................................................. 25 
Table 6.1 Grouped Dosing Regimen in Stage 1 ...................................................................... 48 
Table 6.2 Grouped Dosing Regimen in Stage 2 ...................................................................... 49 
Table 8.1 Detailed Information of Investigational Drug/Placebo ............................................ 68 
Table 9.1 Safety Laboratory Tests ........................................................................................... 73 
Table 12.1 Intercurrent Events ................................................................................................. 93 
Table 12.2 Definition of Estimand for the Primary Endpoint and Strategies for Managing 
Intercurrent Events ................................................................................................................... 94 
Table 12.3 Definition of Estimand for Key Secondary Endpoints and Strategies for Managing 
Intercurrent Events ................................................................................................................... 96 
Table 12.4 Summary of Statistical Methods and Sensitivity Analysis for the Primary Endpoint 
and Key Secondary Endpoints ................................................................................................. 99 
 
 
 


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3. 
List of Abbreviations and Definitions of Terms 
Abbreviations 
Terms 
AD 
Atopic Dermatitis 
ADA 
Anti-Drug Antibody 
ADL 
Activities of Daily Living 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
AKC 
Atopic Keratoconjunctivitis 
ANCOVA 
Analysis of Covariance 
AUC 
Area Under the Concentration-Time Curve 
AUClast 
The Area Under the Concentration-Time Curve from the Zero Time Point to the 
Last Time Point 
BP 
Blood Pressure 
BSA 
Body Surface Area 
CDISC 
Clinical Data Interchange Standards Consortium 
CFR 
Code of Federal Regulations 
Cmax 
Maximum Blood Concentration 
CRO 
Contract Research Organization 
CS 
Clinically Significant 
CSR 
Clinical Study Report 
D# or D-# 
Day # (the date in the study), Day -# (before the start of treatment) 
DLQI 
Dermatology Life Quality Index 
EASI 
Eczema Area and Severity Index 
DSMB 
Data Safety Monitoring Board 
EC 
Ethics Committee 
ECG 
Electrocardiogram 
eCRF 
Electronic Case Report Form 
EDC 
Electronic Data Collection 
EMA 
European Medicines Agency 
EOS 
End of Study 
EOT 
End of Treatment 
ET 
Early Termination 
FAS 
Full Analysis Set 
FCBP 
Female of Childbearing Potential 
FDA 
U.S. Food and Drug Administration 
FSH 
Follicle Stimulating Hormone 
GCP 
Good Clinical Practice 
H/h 
Hour 
HBsAg 
Hepatitis B Surface Antigen 
HCV 
Hepatitis C Virus 
HIV 
Human Immunodeficiency Virus 
ICF 
Informed Consent Form 
ICH 
International Conference on Harmonization of Technical Requirements for 


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Abbreviations 
Terms 
Registration of Pharmaceuticals for Human Use 
IGA 
Validated Investigator Global Assessment 
IgE 
Immunoglobulin E 
IL 
Interleukin 
IL-13 
Interleukin-13 
IL-4Rα 
Interleukin-4 Receptor Alpha 
IUD 
Intrauterine Contraceptive Device 
JAK 
Janus Kinase 
LDH 
Lactate Dehydrogenase 
LOCF 
Last Observation Carried Forward 
MAD 
Multiple Ascending Dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
mg 
Milligram 
min 
Minute 
mL 
Milliliter 
MMRM 
Mixed Model Repeated Measures 
NAb 
Neutralizing Antibody 
NCS 
Not Clinically Significant 
PD 
Pharmacodynamics 
PDE-4 
Phosphodiesterase-4 
PE 
Physical Examination 
PEF 
Peak Expiratory Flow 
PK 
Pharmacokinetics 
P-NRS 
Pruritus Numerical Rating Scale 
POEM 
Patient Oriented Eczema Measure 
PTAE 
Pre-treatment adverse event 
PP-NRS 
Peak Pruritus Numerical Rating Scale in the past 24 hours (0-10) 
PPS 
Per Protocol Set 
PRO 
Patient Reported Outcome 
Q2W 
Once Every 2 Weeks 
Q4W 
Once Every 4 Weeks 
QA 
Quality Assurance 
QOL 
Quality Of Life 
SAD 
Single Ascending Dose 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SC 
Subcutaneous Injection 
SCORAD 
Scoring Atopic Dermatitis Index 
SD 
Standard Deviation 
SIT 
Allergen-specific Immunotherapy 
SOC 
System Organ Class 
SS 
Safety Set 


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Abbreviations 
Terms 
SUSAR 
Suspected Unexpected Serious Adverse Reaction 
t½ 
Elimination half-life 
TARC 
Thymus Activation Regulatory Chemokine 
TB 
Tuberculosis 
TCI 
Calcineurin Inhibitor 
TCM 
Traditional Chinese Medicine 
TCS 
Topical Corticosteroids 
TEAE 
Treatment-Emergent Adverse Event 
vIGA-AD™ 
Validated Investigator Global Assessment for Atopic Dermatitis 
VKC 
Vernal Keratoconjunctivitis 
W# 
Visit in Week # after the start of treatment 
WHO 
World Health Organization 
WHODD 
World Health Organization Drug Dictionary 
 
 


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4. 
Introduction 
4.1. Background 
Atopic dermatitis (AD) is a chronic inflammatory skin disease that affects millions of patients 
worldwide. AD usually develops in childhood, most commonly in infancy. Two-thirds of 
patients have the onset before the age of 2, but AD may also develop in subsequent stages [2]. 
However, a recent study carried out in a Chinese hospital reported that 77.5% of the 2662 
patients had the onset after 12 years of age [3]. AD afflicts 15%-20% of children [2], and is less 
common in adults than children (the point prevalence rate is 1.6%-11.5%, but there are great 
differences between different countries or regions) [1, 4]. In addition to other annoying symptoms, 
the main features of AD are intense pruritus and recurring eczematous skin lesions [5]. The 
resultant sleep disturbance, persistent pruritus and social distress can cause depression and 
other psychological disorders [6, 7, 8, 9, 10]. 
The pathophysiology of AD is very complex, involving the interactions of skin barrier function, 
genetics, environmental factors, and immune response. The skin barrier function of AD patients 
will decrease, and the loss of water through the skin will increase. Local inflammation and 
scratching trauma can lead to further destruction of barrier function and further deterioration 
of infection [11, 12, 13, 14]. Atopic family history is closely related to the onset of AD, and so is 
the loss of filaggrin gene mutation [15]. Regarding immune disorders, the excessive activation 
of T cells accompanied by skin infiltration caused by T cells and dendritic cells is a sign of AD 
[14]. Interleukin (IL)-4, IL-5, IL-13 and IL-31 and other T helper cell cytokines are related to 
the pathophysiology of AD [16]. Therapies targeting cytokines are an active area of research and 
drug development [17]. 
The diagnosis of AD is based on clinical manifestations and diagnostic guidelines. Diagnostic 
guidelines such as Hanafin and Rajka criteria have been used in clinical practice and research 
[1]. The Hanafin and Rajka criteria require a comprehensive consideration of primary criteria 
(e.g., pruritus, chronic dermatitis, and history of respiratory/skin allergies) and secondary 
criteria (e.g., facial paleness, periorbital dark areas, environmental or food triggers) to diagnose 
AD. No specific laboratory or histopathological findings related to AD have yet been found, 
but AD is sometimes associated with increased levels of immunoglobulin E and eosinophil 
counts [18, 19, 20]. 
Topical drugs, such as emollients and corticosteroids, are often used in the treatment of AD [21]. 
Other topical medications include calcineurin inhibitors, such as tacrolimus, antibiotics and 
phosphodiesterase inhibitors [22]. There are limitations in the use of topical drugs, such as 
limited efficacy, various reactions at the site of administration, limited sites of administration, 
and possibility of complications caused by long-term use (corticosteroids, calcineurin 
inhibitors) [23]. Systemic therapy drugs include antibiotics, corticosteroids, cyclosporine, and 
methotrexate, but the existing systemic therapy drugs have great limitations, such as 
insufficient efficacy, and safety issues such as adrenal suppression, Cushing’s syndrome, and 


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organ toxicity and cancer risks [24, 25, 26]. Dupilumab is a monoclonal antibody against IL-4 
receptor α. It has been approved in the United States for the treatment of moderate to severe 
AD in adult (2017) and adolescent (2019) patients when topical therapeutic drugs cannot 
adequately control the disease; it has been approved in China for the treatment of moderate to 
severe AD in adults whose disease is not well controlled with topical prescription drugs or for 
whom the use of topical prescription drugs is not recommended; similar indications have also 
been approved in other countries or regions [27, 28, 29]. 
CBP-201 is a human IgG4κ monoclonal antibody against IL-4 receptor α. Like dupilumab, 
CBP-201 can block the signaling pathways of IL-4 and IL-13 which play an important role in 
the pathogenesis of AD. Preclinical studies have proven that CBP-201 has ideal 
pharmacological characteristics, higher affinity and specificity for the target, higher potency 
and longer half-life compared with dupilumab. CBP-201 is currently being developed for the 
treatment of AD, and is planned to be developed for other indications, such as asthma and other 
inflammatory diseases. 
4.2. Physical, Chemical and Pharmacological Properties 
CBP-201 is a recombinant fully human monoclonal antibody that can bind to human 
interleukin-4 receptor α (IL-4Rα), that is, the common subunit of interleukin 4 (IL-4) and 
interleukin 13 (IL-13) receptor dimers. It is a human IgG4 containing κ light chain, and the 
protein molecular weight is about 146.45 kDa. The amino acid Ser223 in the Fc region of the 
heavy chain has been mutated to Pro223 to promote the stability of the molecule. 
CBP-201 injection is a clear to slightly opalescent, colorless to pale yellow  liquid. The 
container is a vial whose strength is 150 mg (1 ml)/vial, which can be directly used for 
administration. The CBP-201 injection preparation contains a variety of excipients, including 
L-histidine, NaCl, trehalose and Tween 80. The placebo control solution contains the same 
excipients as the CBP-201 injection, but does not contain the CBP-201 active drug. 
4.3. Preclinical Studies 
Preclinical data [31] has proven that CBP-201 has ideal pharmacological characteristics, and has 
high affinity and specificity for antigens. Therefore, compared with dupilumab, the potency is 
higher, with a longer half-life. At present, a large number of in vitro studies have been carried 
out to characterize the pharmacological properties of CBP-201. CBP-201 has a high affinity 
for soluble recombinant human IL-4Rα and can inhibit the proliferation of erythroleukemia 
(TF-1) cells. In addition, CBP-201 can also inhibit the activation of IL 4 and IL 13 mediated 
signal transducer and activator of transcription 6 (STAT6) in human embryonic kidney (HEK) 
BlueTMIL-4/IL-13 SEAP cells. In vitro test results show that CBP-201 can inhibit the 
production of IL-4 and IL-13-induced thymus activation regulatory chemokine (TARC, also 
known as CCL17) and MDC (chemokine derived from human macrophages [CCL22]) in 
human peripheral blood mononuclear cells. These studies indicate that CBP-201 is an antibody 
with high affinity for IL 4Rα. The PK characteristics of CBP-201 have been studied in mice 


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and monkeys, and excellent dose proportionality has been observed at three dose levels, 
indicating that it has good bioavailability.  
Similar to other similar drugs (e.g., dupilumab), CBP-201 does not cross-react with IL-4Rα in 
preclinical species (mouse, rat, monkey). Therefore, the toxicity of CBP-201 in inhibiting IL-
4Rα cannot be directly assessed in these animals. Connect conducted a 4-week monkey 
toxicology study to assess the potential off-target toxicity of CBP-201 to support the first-in-
human single-dose study in healthy volunteers. In this study, cynomolgus monkeys were 
injected SC with CBP-201 at doses of 6 mg/kg, 40 mg/kg and 200 mg/kg, once a week, with a 
total of 4 injections. The results showed that the tolerability was good. The no observed adverse 
effect level (NOAEL) of CBP-201 was 200mg/kg, the corresponding maximum blood 
concentration (Cmax) was about 6279μg/mL, and the area under the concentration-time curve 
(AUClast) from zero time point to the last measurable concentration after the last dose was about 
837.4 h*mg/mL. In this study, there were no clinically significant changes in clinical 
observation results, gross observation results, coagulation, clinical biochemistry, hematology, 
lymphocyte count, plasma complement, or cytokine levels. 
4.4. Clinical Studies 
4.4.1. Phase I Single Ascending Dose Study  
A single ascending dose (SAD) study of CBP-201 has been completed in 40 healthy adult 
subjects (Connect study CBP-201AU001) [30]. The subjects in 4 dose groups (75 mg, 150 mg, 
300 mg and 600 mg) received a subcutaneous injection of CBP-201 or placebo, and the subjects 
in another dose group received an intravenous injection of CBP-201 or placebo 300 mg. After 
the administration was completed, subjects in all dose groups were followed up for 12 weeks 
to assess the safety, tolerability, PK and PD characteristics of the drug. In all treatment groups, 
31 out of a total of 40 subjects had at least 1 TEAE. Among all subjects who received CBP-
201 administration, 80.0% had at least 1 TEAE; among all subjects who received placebo 
administration, 70.0% had at least 1 TEAE. The frequency of TEAE did not increase with the 
increase of CBP-201 dose. In all treatment groups, the most common TEAEs were various 
neurological symptoms and infectious diseases. The most common AEs were headache 
(subjects in all CBP-201 groups, 53.3%; subjects in all placebo groups, 30.0%) and upper 
respiratory tract infection (combined CBP-201 group subjects, 33.3%; placebo group subjects, 
40.0%). Injection site reactions were uncommon, with single episodes of injection site pain 
(CBP-201 75 mg SC), injection site paresthesia (CBP-201 300 mg SC), and injection site 
bruises. In general, CBP-201 had good safety and tolerability. All AEs in the study were mild 
to moderate, no SAEs, no AEs related to abnormal laboratory tests or ECG abnormalities 
occurred, and no AEs resulted in early withdrawal from the study. The most common 
treatment-emergent adverse events (TEAE) and TEAEs related to the study drug were 
headache and upper respiratory tract infection. AEs at the injection site were uncommon.  
The increase ratio of CBP-201 exposure was greater than the increase ratio of dose, indicating 


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that the drug is cleared in a non-linear manner, consistent with the clearance of targeted-
mediated drugs. Its absolute bioavailability was 58%, and the median time from the zero time 
point to the last detectable drug ranged from 338 hours (14 days, 75 mg) to 1345 hours (56 
days, 600 mg). A single subcutaneous injection of 75 mg to 600 mg of CBP-201 significantly 
reduced the serum level of thymus activation regulatory chemokine (TARC; also known as 
CCL-17). The level of CCL-17 in serum can be adjusted by blocking IL-4Rα, so it can be used 
as a biomarker for judging AD or other related inflammatory diseases. 
4.4.2. Phase I Multiple Ascending Dose Study 
CBP201 was evaluated in a multiple ascending dose (MAD) study in adult patients with AD 
[30] (Connect study CBP-201AU002). In this randomized, double-blind, placebo-controlled, 
multiple ascending dose study, 31 moderate to severe AD patients aged 20 to 65 were enrolled 
at 13 study sites in Australia and New Zealand. The patients received CBP-201 (SC, 75 mg, 
150 mg or 300mg) or matching placebo once a week for 4 consecutive weeks. About 10 patients 
were randomly enrolled in each dose group and received CBP-201 or placebo treatment in a 
ratio of 4:1. 
In general, CBP-201 had good safety and tolerability when the dose of subcutaneous injection 
was up to 300mg. No SAE, life-threatening TEAEs, or deaths were reported in the study, and 
no TEAEs that led to discontinuation of the study were reported. No clinically significant 
injection site reactions were reported as AEs. The most common AEs during the study period 
were deterioration of AD (26.1% in the combined CBP-201 treatment group and 37.5% in the 
placebo group), headache, and upper respiratory tract infection. Most TEAEs were mild. 
The number and severity of TEAEs and treatment-related TEAEs did not increase with the 
increase of CBP-201 dose levels. There were no clinically significant (CS) or study treatment-
related changes in vital signs, ECG parameters, or physical examination results. 
At the doses of 150 mg and 300 mg, CBP-201 administration for 4 weeks could quickly 
improve EASI, IGA and PP-NRS. On Day 29, 87.5% (7/8 cases) of the patients in the 150 mg 
group had a 50% reduction in EASI score (EASI-50), and 100% (7/7 cases) of the patients in 
the 300 mg group achieved EASI-50, while only 37.5% (3/8 cases) of the patients in the placebo 
group achieved EASI-50. For IGA, 50.0% (4/8 cases) of the patients in the 150mg group, 42.9% 
(3/7 cases) in the 300 mg group, and only 12.5% (1/8 cases) in the placebo group had an IGA 
score of 0-1 (clearance, basic clearance). The average weekly PP-NRS severity was decreased 
by 41.0% and 52.8% in the CBP-201 150 mg group and 300 mg group, respectively, and by 
22.8% in the placebo group. On Day 29, the P-NRS response rates (decreased by >3 points) in 
the 150 mg (50%, 4/8) and 300 mg groups (57%, 4/7) were higher than that in the placebo 
group (25%, 2/8). 
The results of PK analysis showed that about one week (Day 29) after the 4th administration of 
CBP-201 on Day 22, the peak concentration of CBP-201 was observed. The dose proportionity 
assessed based on AUC0-t and Cmax showed that when the dose was increased from 75 mg to 


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150 mg, the increase in exposure was greater than the increase in dose; when the dose was 
increased from 150 mg to 300 mg, the increase in exposure was proportional to the increase in 
dose. 
Serum TARC was decreased steadily after CBP-201 was administered at 150 mg and 300 mg. 
The decrease in TARC was always related to the improvement of AD. 
4.4.3. China Phase Ia Single Dose Escalation Study  
A “randomized double-blind, placebo-controlled, single-dose, dose-escalation Phase I clinical 
study to evaluate the safety, tolerability, PK and PD of CBP-201 in Chinese healthy adult 
subjects” is being carried out in China to explore the safety, tolerability and PK/PD 
characteristics of CBP-201 in Chinese healthy adult subjects. 
This study sets 3 dose groups, namely 150 mg, 300 mg and 600 mg. It is planned to enroll 36 
healthy subjects, both male and female, who will be divided into 3 groups, with 12 cases in 
each group (among them, 10 cases will receive the study drug CBP-201 and 2 cases placebo). 
All subjects will continue to be observed at the clinical site for 72 hours after receiving the 
investigational drug, and PK, PD and ADA samples will be collected to assess AEs and 
injection site reactions. After more than 8 subjects have completed the observation period of at 
least 15 days after the single-dose administration, the PI, study doctor, and sponsor’s medical 
monitor will first blindly assess the safety data of this dose group, and then decide whether to 
administer the drug in the next dose group. 
Up to now, the study has successfully completed the enrollment and follow-up of 36 healthy 
subjects planned for the 3 dose groups, and sample testing and data collection are in progress. 
In this study, at three blinded safety review committee meetings conducted 15 days after the 
administration in each dose group, the investigators all agreed that CBP-201 was safe and well 
tolerated. 
4.4.4. Phase II International Multicenter Clinical Study in Patients with Moderate to 
Severe AD 
CBP-201 was evaluated in a Phase 2b, randomized, double-blind, placebo-controlled efficacy 
and safety study in adult patients (n = 226) with moderate-to-severe AD in Australia, New 
Zealand, US, and China. Baseline disease characteristics (including duration of AD history, 
baseline IGA score, total EASI score, and BSA involvement) were generally balanced between 
the All CBP-201 group and the placebo group. The median age of the overall population was 
38.5 years (range18-73 years). Patients were randomized (1:1:1:1) to receive CBP-201 (600 
mg loading dose followed by 150 mg Q2W), CBP-201 (600 mg loading dose followed by 300 
mg Q4W), CBP-201 (600 mg loading dose followed by 300 mg Q2W), or matching placebo 
administered SC for 16 weeks and followed with an 8-week post-treatment follow-up. 
The safety profile of CBP-201 in this study was generally comparable to that of placebo, with 
no clinically relevant differences observed between treatment groups. CBP-201 treatment 


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groups and placebo had a similar incidence of TEAEs, SAEs, and TEAEs leading to 
discontinuation. The most common TEAEs in the CBP-201 dose groups were atopic dermatitis 
(15%) and headache (5%); all other TEAEs were reported for ≤ 2% of CBP-201-treated 
subjects. Most reported TEAEs were mild to moderate in severity. The proportion of subjects 
with Grade ≥ 3 TEAEs was higher in the 300 mg Q4W group than the 150 mg Q2W group, 
300 mg Q2W group, or placebo group. One subject in the 300 mg Q4W CBP-201 group 
experienced a fatal (Grade 5) TEAE of cardiac arrest 57 days after last dose of study drug. 
There were no clinically relevant trends in clinical safety laboratory (hematology, blood 
chemistry, and urinalysis) values, vital sign values, ECG findings, or physical examination 
findings across doses or over time for up to 16 weeks of treatment.  
Administration of CBP-201 resulted in rapid improvements in EASI, IGA, and PP-NRS at 16 
weeks. All doses of CBP-201 met the primary endpoint (LS mean percent change from baseline 
in EASI at Week 16 versus placebo), with greater reductions observed in EASI in the 300 mg 
Q2W and Q4W groups. Significant improvements with CBP-201 were also seen for a range of 
secondary efficacy endpoints, including proportions of EASI and IGA 0/1 responders and 
change in PP-NRS. The efficacy responses of 300 mg CBP-201 Q2W and Q4W were more 
consistently greater than 150 mg Q2W when compared to placebo across most outcomes. 
ADA/NAb results 
In the 150 mg Q2W dose group, 8 subjects tested positive for ADA. Five of these subjects 
tested positive at a single timepoint only, either in the middle of the time course (transient, n = 
2) or at only the final timepoint (indeterminate, n = 3). Three subjects had persistent ADA, 
testing positive at two or more consecutive timepoints. Titers were low, with all titers <1000. 
Six subjects were positive for Nab.  
In the 300 mg Q4W dose group, 7 subjects tested positive for ADA. Four of these subjects 
tested positive at a single timepoint only (transient n = 3; indeterminate n = 1). Three subjects 
had persistent ADA, testing positive at more than one timepoint. Titers were low, with all but 
one titer reported as <1000. One subject had a Day 169 (last timepoint collected) titer at 32,000. 
Five subjects were positive for Nab.  
In the 300mg Q2W dose group, 2 subjects tested positive for ADA. One subject (0304-0020) 
was positive for pre-existing ADA only, with no detection of a treatment boosted ADA (titer 
did not exceed the initial titer of 160). This subject was positive for NAb. The second subject 
positive for ADA in this dose group was transiently positive on Day 113, had a titer of <10, 
and was NAb negative. 
In the Placebo dose group, 10 subjects tested positive for ADA. Seven of these subjects were 
positive at a single timepoint only (transient n = 6; indeterminate n = 1), with titer <10, and 
NAb negative. As such, they may represent false positives. One subject (0340-0003) had a pre-
existing ADA positive/NAb positive response, and subsequent timepoints were also ADA/NAb 
positive. Titers did not exceed 80. Two subjects showed persistent, treatment-emergent ADA. 


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One of these subjects, 0304-0014, was ADA/NAb positive at the last 3 timepoints collected, 
with titers <40. The second subject, 0401-0015, was ADA/NAb positive beginning at Day 29 
with all subsequent timepoints also ADA/NAb positive. In this subject, titers were all >1000 
(range 1034 to 4825). The treatment-emergent ADA/NAb responses are unusual and 
unexpected for subjects in a Placebo arm, particularly the subject with high titers. No anomalies 
in the bioanalysis or other aspects of the study were identified to account for these results.  
Overall, there was a low incidence of ADA/NAb and most responses were not persistent. All 
ADA responses were low titer (<1000) except for 2 subjects (one placebo outlier, one subject 
in 300 mg Q4W group). The PK analysis indicated that in the allometric model, subjects for 
whom anti-drug antibodies were present had 15% higher non-saturable clearance than those 
for whom they were absent. 
PK results 
The pharmacokinetic analysis demonstrated the need for two elimination pathways, one of 
which was concentration dependent saturable, consistent with a previous analysis of CBP-201 
in healthy subjects and subjects with atopic dermatitis. The concentration at which the saturable 
pathway was 50% inhibited was 164 – 184 ng/mL, a value lower than typical trough 
concentrations seen with multiple dosing in the present study. As a result, saturable clearance 
is unlikely to influence the concentration profile of CBP-201 in clinical practice. . 
Body size was incorporated into the model using two approaches: allometric scaling and weight 
normalized scaling. After incorporation of other covariates, these scaling approaches yielded 
similar fits. However, the model with allometric scaling showed the least amount of bias in the 
relationship between post hoc etas for non-saturable clearance and weight. 
Chinese subjects had up to 23% lower bioavailability than non-Chinese subjects. 
Distinguishing whether these differences in exposure between Chinese and non-Chinese 
subjects results from bioavailability or clearance differences between these two populations is 
difficult in the presence of sparse sampling. Regardless, both approaches suggest that systemic 
exposure is lower in Chinese subjects. It should be noted that bioanalysis for samples from 
China was performed in a different laboratory (Frontage) compared to ex-China samples 
(Syneos). Although assay comparability between the two laboratories was established, these 
data should be reviewed, and conclusions made, with that in mind. 
Both clearance pathways increased with increasing baseline neutrophil or white blood cell 
counts. Simulation showed that over the range of neutrophil counts observed in the study, 
exposure ranged approximately 2-fold. 
Finally, in the allometric model, subjects for whom anti-drug antibodies were present had 15% 
higher non-saturable clearance than those for whom they were absent. ADA was not 
incorporated into the models using the other scaling approach. 
Simulations of fixed dose and weight-proportional dose regimens suggested that there would 


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be no advantage in terms of exposure variability in switching from a fixed to a weight-based 
dose. 
Simulations based on region (China or ex-China) suggested approximately 25% lower 
exposure in Chinese subjects compared to non-Chinese subjects. 
Simulations based on post hoc parameter estimates and actual dosing history suggest that 300 
mg Q2W maintained the highest Ctrough, Cmax, and Cmean. Of the remaining two regimens, 300 
mg Q4W maintained the higher Cmax and the lower Ctrough. Cmean was similar for 150 mg Q2W 
and 300 mg Q4W. 
Exposure-response 
Investigator ratings consistently showed that increasing exposure, best assessed by mean 
concentration during the first or final dosing interval, was associated with a larger response. In 
most instances, there were no differences between treatment groups. Lighter subjects had larger 
values for some exposure metrics (e.g., mean concentration during the first dosing interval); 
for some response metrics, this resulted in these subjects having a larger response compared to 
heavier subjects. For EASI, the response in Chinese subjects was larger compared to ex-China. 
Of the patient ratings, POEM yielded the best relationship between increasing exposure and 
response. The relationship for DLQI was inconsistent between exposure metrics. For PP-NRS, 
there was no evidence of an association between exposure and response. 
The five biomarkers failed to yield a consistent exposure-response relationship. For each of 
these biomarkers, the presence of outlier values at baseline and later timepoints may have 
limited the ability to detect an exposure-response relationship.. 
The primary efficacy endpoint for this study was EASI, for which a strong exposure-response 
relationship was apparent. 
4.5. Other Safety Considerations 
The current clinical experience of CBP-201 is limited. Given that dupilumab is a similar 
product that has been marketed and binds to the same target (IL-4Rα), examples of existing 
safety observations include but are not limited to the following: 
• 
Hypersensitivity reactions (e.g., urticaria, rash, erythema nodosa, immediate severe 
allergic reactions, serum sickness); 
• 
Eosinophilic disease (e.g., systemic eosinophilia, sometimes manifested as 
eosinophilic pneumonia or clinical features of vasculitis consistent with eosinophilic 
granulomatous polyangiitis, worsening of pulmonary symptoms, cardiac 
complications and/or neuropathy in patients with eosinophilia); 
• 
Reactions caused by reduced doses of glucocorticoids (abrupt discontinuation of 
systemic, local or inhaled glucocorticoids may be related to systemic withdrawal 
symptoms and/or the appearance of symptoms previously suppressed by systemic 


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glucocorticoid therapy); 
• 
Injection site reactions; 
• 
Oropharyngeal pain; 
• 
Eosinophilia; 
• 
Conjunctivitis, including allergic conjunctivitis, bacterial conjunctivitis, viral 
conjunctivitis, giant papillary conjunctivitis, eye irritation and eye inflammation; 
• 
Blepharitis; 
• 
Oral herpes; 
• 
Keratitis, including ulcerative keratitis, allergic keratitis, atopic keratoconjunctivitis 
and ocular herpes simplex; 
• 
Itchy eyes; 
• 
Other herpes simplex virus infections, including genital herpes, herpes simplex otitis 
externa and herpes virus infections; 
• 
Dry eye; 
• 
Joint pain; 
• 
Gastritis; 
• 
Insomnia; 
• 
Toothache. 
4.6. Study Rationale 
As mentioned above, it can be seen from the results of Phase Ia and Ib clinical studies 
completed in Australia and New Zealand that in healthy subjects, a single subcutaneous 
injection of CBP-201 75 mg, 150 mg, 300 mg and 600 mg and intravenous injection of 300 mg 
or subcutaneous injections of 75 mg, 150 mg and 300 mg once a week for 4 times in patients 
with moderate to severe AD have good safety and tolerability. At the same time, in patients 
with moderate to severe AD, CBP-201 150 mg and 300 mg injected subcutaneously every week 
demonstrated preliminary clinical efficacy, and the changes in TARC, a biomarker related to 
AD severity, showed a consistent trend with the improvement of the disease. At the same time, 
there was no significant difference in TEAEs between each dose group and the placebo group. 
These study results support further research on the therapeutic effects of CBP-201 on AD. At 
the same time, the ongoing Phase I study of a single subcutaneous injection of CBP-201 150 
mg, 300 mg and 600 mg in healthy Chinese subjects has completed enrollment and follow-up, 
and at three blinded safety review committee meetings conducted 15 days after the 
administration in each dose group, the investigators all believed that CBP-201 was safe and 
well tolerated, supporting the continued clinical development of CBP-201 in China. Therefore, 


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this study is planned to further assess the efficacy, safety and PK characteristics of CBP-201 
in patients with moderate to severe AD in China. 
Compared with adults, the prevalence of AD is significantly higher in children and adolescents 
[1,2,4], and the treatment options available for children and adolescents aged 12 years and above 
are more limited. For children with moderate to severe AD, in particular, there is still a huge 
unmet clinical need. CBP-201 has demonstrated good safety, tolerability and efficacy in 
previously completed clinical studies, and the marketed same-target (IL-4Rα) product 
dupilumab has been approved by the U.S. Food and Drug Administration (FDA) and the 
European Medicines Agency (EMA) for the treatment of moderate to severe AD in children 
aged 6-11 years and adolescents aged 12 years and above, and also been approved in China for 
the treatment of moderate to severe AD in adolescents aged 12 years and above. The safety and 
efficacy data of dupilumab in pediatric AD patients have provided strong support for the 
rationality and feasibility of clinical studies of CBP-201 in the pediatric population, that is, no 
unique pediatric safety issues have been observed with the marketed medicinal product of the 
same class sharing the same target as CBP-201 (IL-4Rα), and the efficacy in the pediatric 
population is definite. In order to encourage and facilitate the research and development of 
medicinal products for the pediatric population, the International Council for Harmonization 
of Technical Requirements for Pharmaceuticals for Human Use (ICH) has formulated ICH E11 
(R1), a specific guideline for the clinical studies of medicinal products for the pediatric 
population (including adolescents aged 12 years and above). With regard to the timing of the 
initiation of pediatric studies during the research and development of a medicinal product, ICH 
E11 (R1) recommends that factors such as the medicinal product, the type of disease being 
treated, safety considerations, and the efficacy and safety of alternative treatments should be 
comprehensively considered. In cases where the medicinal product will be used in pediatric 
patients but the disease to be treated is not urgent, ICH E11 (R1) recommends that testing of 
these medicinal products in pediatric populations can usually begin at clinical phase 2 or 3 
(Section 2.3.3). For medicinal products intended to treat serious or life-threatening diseases, 
occurring in both adults and pediatric patients, for which there are currently no or limited 
therapeutic options, ICH E11 (R1) recommends that medicinal product development should 
begin early in pediatric population, following assessment of initial safety data and reasonable 
evidence of potential benefit (Section 2.3.2). In conclusion, this study plans to enroll certain 
number of adolescents with moderate to severe AD aged 12 years and above under the premise 
of meeting the requirements of the ICH E11 (R1) guideline. The safety and efficacy data of 
adolescent AD patients obtained in this study will provide an important reference for further 
design and conduct of clinical studies in younger pediatric populations in the future. 
The treatment in this study is divided into two stages. Stage 1 is a placebo-controlled design 
(subjects will receive CBP-201 600 mg or placebo SC administration on D1, and start to receive 
CBP-201 300 mg or placebo administration Q2W starting from Week 2); Stage 2 is the 
maintenance treatment period with different dosing regimens of CBP-201 (CBP-201 300 mg, 


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Q2W or Q4W). 
 
 


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5. 
Study Objectives 
5.1. Primary Objective 
• 
To assess the efficacy of CBP-201 in subjects with moderate to severe AD 
5.2. Secondary Objectives 
• 
To assess the safety and tolerability of CBP-201 in subjects with moderate to severe 
AD 
• 
To assess the PK characteristics of CBP-201 in subjects with moderate to severe AD 
• 
To assess the PD characteristics of CBP-201 
• 
To assess the immunogenicity of CBP-201 
 
 


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6. 
Study Plan 
6.1. Overall Study Design and Plan 
This study is a randomized, double-blind, multi-center, controlled study designed to assess the 
efficacy, safety and PK characteristics of CBP-201 in eligible subjects with moderate to severe 
AD. 
The study includes a screening period, a treatment period and a follow-up period. The treatment 
period is divided into two stages: 
Stage 1 study: It is a placebo-controlled study, in which subjects who meet the inclusion criteria 
and do not meet the exclusion criteria will be stratified according to the severity of their 
baseline disease (moderate [IGA=3] and severe [IGA=4]) and  randomized into one of the 
following 2 groups to receive investigational product or placebo treatmentby the ratio of 2:1: 
• 
Group A (CBP-201): the subjects will receive a subcutaneous injection of CBP-201 
600 mg (4 ml in total, 2 injections of 2ml each in different sites) on Day 1, begin to 
receive a subcutaneous injection of CBP-201 300 mg (2 ml) from Week 2 (W2), and 
receive treatment at the same dose every 2 weeks thereafter until W14; 
• 
Group B (placebo): the subjects will receive a subcutaneous injection of placebo 4 
ml (2 injections of 2ml each in different sites), begin to receive a subcutaneous 
injection of placebo 2 ml from W2, and receive placebo 2 ml every 2 weeks 
thereafter until W14. 
The grouped dosing regimen in Stage 1 is shown in the table below:  
Table 6.1 Grouped Dosing Regimen in Stage 1 
Group 
W0 
W2 
W4 
W6 
W8 
W10 
W12 
W14 
Group A 
4XC 
2XC 
2XC 
2XC 
2XC 
2XC 
2XC 
2XC 
Group B 
4XP 
2XP 
2XP 
2XP 
2XP 
2XP 
2XP 
2XP 
Note: C=CBP-201; P=placebo; #X=number of ampoules 
Before the administration of study drug at W16 visit, all subjects will be assessed for efficacy, 
and treatment assignment for Stage 2 maintenance treatment is based on whether a subject 
achieves a 50% or greater reduction in EASI score (ie EASI-50). 
Stage 2 study: The grouping for Stage 2 maintenance treatment is as follows: 
• 
Subjects who have achieved EASI-50 in the W16 pre-administration treatment 
assessment will be 1:1 randomized to one of the following two groups to receive 
study treatment starting from W16: 
• 
Group C: The subjects will receive a subcutaneous injection of CBP-201 300 mg 
every 2 weeks until W50;  
• 
Group D: The subjects will receive a subcutaneous injection of CBP-201 300 mg 
every 4 weeks. In order to maintain the injection every 2 weeks blind, when not 


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receiving CBP-201, the subjects will receive an injection of placebo 2 ml once 
every 4 weeks until W50.  
• 
Subjects who have not achieved EASI-50 in the W16 pre-administration treatment 
assessment will receive the following treatment starting from W16: 
• 
Group E: The subjects will receive a subcutaneous injection of CBP-201 300 mg 
every 2 weeks until W50. 
• 
If subjects in group C and group D have not achieved EASI-50 in two continuous 
pre-administration treatment assessments, they will be assigned to group E to be 
treated with subcutaneous injection of CBP-201 300 mg every 2 weeks from the visit 
when EASI-50 is not achieved for the second time to W50. 
The grouped dosing regimen in Stage 2 is shown in the table below: 
Table 6.2 Grouped Dosing Regimen in Stage 2 
Group 
W16 
W18 
W20 
W22 
W24 
…… 
W50 
Group C 
2XC 
2XC 
2XC 
2XC 
2XC 
…… 
2XC 
Group D 
2XC 
2XP 
2XC 
2XP 
2XC 
…… 
2XP 
Group E 
2XC 
2XC 
2XC 
2XC 
2XC 
…… 
2XC 
Note: C=CBP-201; P=placebo; #X=number of ampoules 
During the study period, subjects must apply a mild emollient to the AD-affected area at least 
twice a day as background treatment (but should avoid using emollients within 4 hours before 
AD assessment at each visit. 
All subjects (including the subjects who are early terminated of the treatment) will be followed 
up for 8 weeks after the last dose.  
In this study, an independent DSMB will be established to regularly review and evaluate the 
cumulative study data, to guarantee the safety of subjects, implementation and progress of the 
study, and to give the sponsor a suggestion on whether to continue the study. 
The overall study design is shown in Figure 1. 
6.2. Study Steps 
The study consists of a screening period, a treatment period (including Stage 1 treatment [16 
weeks] and Stage 2 maintenance treatment [36 weeks] and a follow-up period (8 weeks). 
After signing the ICF, subjects will be assessed for study eligibility at the screening visit within 
28 days prior to the baseline visit. Before D1 administration of study drug, subjects who were 
eligible at the screening visit will be confirmed again for their eligibility. After baseline 
assessment, the subjects who are confirmed to meet the inclusion criteria will be randomized 
to Group A (CBP-201) or Group B (placebo) in a 2:1 ratio to receive CBP-201 or placebo SC 
administration. Vital signs monitoring will be conducted at the study site before D1, W2 and 
W4 administration and 2 hours after administration, and before and 30 minutes after each 


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administration from W6 to W14. 
Before W16 administration, the therapeutic results of all subjects will be assessed, and 
treatment assignment for Stage 2 maintenance treatment is based on whether a subject achieves 
a 50% or greater reduction in EASI score (ie EASI-50). Subjects who are assessed to have 
achieved EASI-50 before W16 administration will be 1:1 randomized to Group C or Group D 
and start receiving SC administration of CBP-201 300 mg Q2W or Q4W until W50 (If subjects 
in group C and group D have not achieved EASI-50 in two continuous pre-administration 
treatment assessments, they will be assigned to group E to be treated with subcutaneous 
injection of CBP-201 300 mg every 2 weeks from the visit when EASI-50 is not achieved for 
the second time to W50.); subjects who are assessed to have not achieved EASI-50 before W16 
administration will be assigned to Group E to start receiving SC administration of CBP-201 
300 mg Q2W until W50. All subjects should undergo vital signs monitoring before 
administration and 2 h after administration at W16, W18 and W20 at the study site, and before 
and 30 min after each administration from W22 to W50. After the end of Stage 2 (W52), 
subjects will be followed up for safety and efficacy for 8 weeks to further explore the PK and 
PD characteristics of CBP-201. 
Subjects will return to the study site for examinations and assessments according to the time 
specified in the Study Flow Chart. Various study assessments and examinations should be 
completed before administration at each visit (unless otherwise specified). 
Blood samples from all subjects will be collected during the whole study period to evaluate the 
steady-state PK characteristics of CBP-201 and its PD effects on serum thymus activation 
regulated chemokine (TARC) level, total immunoglobulin E (IGE) level, peripheral blood 
eosinophil count and serum IL-4 and IL-13 levels, and to detect ADA (all ADA positive samples 
will be further tested for the presence of anti-CBP-201 NAb). 
During the study period, subjects are also required to apply mild emollients to the AD-affected 
area at least twice a day (in order to facilitate the assessment of dryness and scales, the use of 
emollients should be avoided within 4 hours before the assessment) and fill in a daily pruritus 
diary every day. If an intolerable AD recurrence or worsening of the condition occurs, the 
subject should notify the study site to assess the condition and confirm whether it is necessary 
to use rescue drugs for treatment.  
Throughout the study period, AE assessment will be continued and concomitant 
medication/treatment information will be collected. 
If a subject has ET for any reason, the subject should complete the ET visit within 7 days after 
ET, and complete the 8-week follow-up visit as much as possible after the ET visit. 
The assessment of the severity and impact of AD will be divided into two parts: the 
investigator’s efficacy assessments and the patient reported outcomes:  
1) 
Patient reported outcomes (completed by the subject):  


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• 
PP-NRS: It is a single self-reported item designed to measure the peak pruritus or 
“worst” pruritus in the past 24 hours based on the following questions: “The scores 
are 0-10, in which 0 represents ‘no pruritus’ and 10 “worst imaginable pruritus’. 
How do you rate your most severe puritus in the past 24 hours?” [31]. Refer to 
Section 17.1, Appendix A. The PP-NRS (Daily Pruritus Diary) will be distributed 
at the beginning of the screening visit. Subjects will be instructed to complete the 
PP-NRS (Daily Pruritus Diary) within 7 days before the baseline visit (D1) to 
calculate the baseline average score of subjects, which will be reviewed by the 
study staff at the baseline visit (D1). Thereafter (from D1), the daily PP-NRS will 
be collected every day (in the past 24 hours). 
• 
DLQI: It is a questionnaire containing 10 items to assess the impact of AD on 
quality of life (QOL) in the past week, and the scores range from 0 (no disease) to 
30 (severe disease); the higher the score, the worse the quality of life. Refer to 
Section 17.2, Appendix B. DLQI score will only be assessed among subjects ≥16 
years, and it  will be assessed once a week during the study period. 
• 
POEM: It is a questionnaire composed of 7 items to assess disease symptoms on 
a scale of 0-4 (dryness, itching, flaking off, cracking, sleeplessness, bleeding and 
weeping or oozing); the scores range from 0 (no disease) to 28 (severe disease); 
the higher the score, the worse the quality of life. Refer to Section 17.3, Appendix 
C. It will be assessed once a week during the study period. 
2) 
Investigator’s efficacy assessments (completed by the investigator): 
• 
IGA: The Validated Investigator Global Assessment for AD (vIGA-AD™) Scale 
is a 5-point classification scale based on the overall appearance of the skin lesions 
at a specific time point (0=clear; 1=almost clear; 2=mild; 3=moderate; 4=severe). 
It should be noted that in order to be eligible for selection, the IGA score must be 
≥3. See Section 17.4, Appendix D. Please also note that IGA-1 should not contain 
scales. 
• 
EASI: The EASI scale quantifies the severity and extent of AD, as well as the 
severity of erythema, infiltration, excoriation and lichenification of the four 
anatomical regions—head and neck, trunk, upper extremities and lower 
extremities. The total EASI score ranges from 0 (lowest) to 72 (highest); the higher 
the score, the higher the severity of AD (more severe). It should be noted that in 
order to be eligible for selection, the EAS score must be ≥16. See Section 17.5, 
Appendix E. 
• 
The “Rule of Nines” is used to estimate the maximum percentage of AD-affected 
BSA in each area: head and neck [9%], anterior trunk [18%], back [18%], upper 
limbs [18%], lower limbs [36%] and genitals [1%]. The number of palms of AD-
affected skin in a body part can be used to determine the extent (%) of AD 
involvement in that body part. Regardless of the age of the subject, the area of the 
subject's entire palm (five fingers adducted together) is about 1% of the subject's 


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BSA. The number of palms in different body parts is assessed to calculate the 
percentage of BSA affected by AD. It should be noted that in order to be eligible 
for selection, the percentage of AD-affected BSA must be ≥10. See Section 17.6, 
Appendix F. 
• 
AD score (SCORAD): It is a clinical tool used to assess the severity of AD 
(extent/severity) and subjective signs/symptoms (e.g., itch/sleeplessness). The 
degree of lesions is scored using the “rule of nines” method. The severity is 
determined by grading the severity of the 6 signs (erythema, edema, 
oozing/crusting, excoriation, lichenification, and skin dryness) on a 0-3 subscale. 
The assessment of each sign is scored on the most representative skin lesions. See 
Section 17.7, Appendix G. 
Note: in order to facilitate the assessment of dryness and scales, the use of emollients should 
be avoided within 4 hours before the assessment of AD. 
6.2.1. Screening Period (D-28~D-1) 
After the patient signs the ICF, the patient’s eligibility for study enrollment will be assessed at 
the first screening visit within 28 days before the baseline visit. During this period, patient 
information to be collected or assessment to be performed is as follows: 
• 
Demographic characteristics; 
• 
Medical history; 
• 
Review of inclusion and exclusion criteria; 
• 
Height and weight; 
• 
Hepatitis and HIV screening: Hepatitis screening includes HBsAg, HBcAb, HBV-
DNA and hepatitis C antibodies, HCV-RNA; 
• 
Physical examination: A complete physical examination is required, including 
general appearance, skin, eyes/ears/nose/throat, head and neck, cardiovascular 
system, respiratory system, abdomen, limbs, lymph nodes, musculoskeletal and 
nervous systems. Unless it is necessary to assess the status of AD involvement, there 
is no need to perform rectal or genital examinations; 
• 
Vital signs (VS): Including body temperature, respiratory rate, blood pressure (BP), 
and heart rate (HR). The subject should sit and rest for at least 3 minutes before VS 
assessment; 
• 
12-lead ECG; 
• 
Chest X-ray examination; 
• 
Eye examination: At each visit, the investigator must assess whether the subject has 
any eye discomfort, such as redness, itching, photophobia and abnormal discharge, 
as well as related signs/symptoms, such as conjunctival hyperemia and exudate. If 
these discomforts are considered to be related to conjunctivitis or keratitis or any 
uncertain diagnosis, an ophthalmologist should conduct further assessment and give 


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appropriate treatment. 
• 
Safety laboratory tests: Including hematology, blood biochemistry and urinalysis. 
See Table 9.1 for details; 
• 
Blood pregnancy test: Only for FCBP; 
• 
FSH test: Only for menopausal female subjects; subjects who can provide FSH test 
results before screening do not need to repeat the test; 
• 
Investigator’s efficacy assessments;  
• 
Patient reported outcomes (including DLQI and POEM): To be assessed once a 
week during study period. The investigator will dispense the subject diary at each 
visit and collect DLQI and POEM data of that day, and the data among two visits 
will be assessed by the subjects themselves and recorded in the subject diary. Old 
diaries dispensed last time will be collected at the next visit and the new ones will 
be dispensed; 
• 
PP-NRS score: The subject should record the PP-NRS score of the maximum 
pruritus intensity in the past 24 hours every day within 7 days before the baseline 
visit (in these 7 days, the scores of at least 4 days are required for the calculation 
of the baseline average score. If the patient’s reporting days are less than 4 days in 
the 7 days before the planned date of randomization, randomization should be 
postponed until the requirements are met, but it is not allowed to exceed the 
maximum screening period of 28 days); 
• 
Use of mild emollients: Emollients should be used at least 7 days before the baseline 
visit, at least twice a day; if the subject is intolerable to the emollients provided 
uniformly by the sponsor during the screening period, he/she can change to  
emollient of this kind used previously, but it must be used at a stable dose for at least 
7 days before baseline and during the study period; 
• 
Pre-treatment adverse event (PTAE); 
• 
Prior and concomitant medication/treatment. 
6.2.2. Stage 1 Treatment Period 
6.2.2.1. 
D1: Baseline and Study Drug Administration   
The study staff must review all screening laboratory test results before baseline (D1) to confirm 
that the subjects are eligible for selection. 
D1 pre-dose visit  
Subjects who are qualified during the screening visit must return to the study site within 28 
days after the screening. 
Before D1 administration, the subject’s information to be collected or assessment to be 
performed is as follows: 
• 
Confirmation of ICF signing; 


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• 
Review of inclusion and exclusion criteria; 
• 
Weight; 
• 
VS; 
• 
12-lead ECG; 
• 
Eye examination; 
• 
Safety laboratory tests: Test results within 7 days before baseline are acceptable, 
and there is no need to repeat the test; 
• 
Urine pregnancy test: Only for FCBP; 
• 
PK blood sample collection; 
• 
PD/ADA blood sample collection; 
• 
Investigator’s efficacy assessments; 
• 
Patient reported outcomes; 
• 
PP-NRS score: The PP-NRS score of the maximum pruritus intensity in the past 24 
hours is recorded every day; 
• 
Randomization: Subjects who are eligible for enrollment after D1 pre-
administration screening will be randomized in a 2:1 ratio to the CBP-201 group or 
placebo group for treatment; 
• 
PTAEs; 
• 
Concomitant medication/treatment. 
D1 post-dose visit 
After D1 administration, the subject’s information to be collected or assessment/procedure to 
be performed is as follows: 
• 
SC administration of study drug; 
• 
VS: VS will be recorded q1h × 2h (±10 min) after administration (T0). Subjects 
should rest in a sitting position for at least 3 min before VS assessment;  
• 
Use of mild emollients: At least twice a day; 
• 
Assessment of injection site reactions; 
• 
AEs; 
• 
Concomitant medication/treatment. 
6.2.2.2. 
D15/W2 Visit 
Subjects will return to the study site at W2±3d to receive study drug injections and the 
following assessments: 
• 
VS: VS will be recorded before and q1h × 2h (±10 min) after administration. 
Subjects should rest in a sitting position for at least 3 min before VS assessment; 
• 
Eye examination; 
• 
Safety laboratory tests; 
• 
PK blood sample collection; 


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• 
PD/ADA blood sample collection; 
• 
Investigator’s efficacy assessments; 
• 
Patient reported outcomes; 
• 
PP-NRS score: The PP-NRS score of the maximum pruritus intensity in the past 24 
hours is recorded every day; 
• 
SC administration of study drug; 
• 
Use of mild emollients: At least twice a day; 
• 
Assessment of injection site reactions: The previous injection site should be 
assessed before administration, and the new injection site should be assessed before 
the subject leaves the study site; 
• 
AEs; 
• 
Concomitant medication/treatment. 
6.2.2.3. 
Q2W Visits During D29/W4~D99/W14 
Subjects will return to the study site at W4±3d and every 2 weeks during the treatment period 
thereafter until W14±3d to receive study drug injections and complete the corresponding study 
procedures according to the Study Flow Chart. 
The subject’s information to be collected or assessment/procedure to be performed during 
W4~W14 is as follows: 
• 
Weight: Measured at W4, W8 and W12; 
• 
VS: VS will be recorded before and q1h × 2h (±10 min) after administration at W4, 
and before and 30 min (±10 min) after administration from W6 to W14. Subjects 
should rest in a sitting position for at least 3 min before VS assessment; 
• 
Eye examination: This must be performed at each visit during W4~W14; 
• 
Safety laboratory tests: Performed at W4 and W8; 
• 
Urine pregnancy test: Only for FCBP, performed at W4, W8 and W12; 
• 
PK blood sample collection: Performed at W4, W8 and W12; 
• 
PD/ADA blood sample collection: Performed at W4, W8 and W12; note: blood 
samples will not be collected for PD parameter—peripheral blood eosinophils at 
W12; 
• 
Investigator’s efficacy assessments: Performed at W4, W8 and W12; 
• 
Patient reported outcomes: Performed at each visit; 
• 
PP-NRS score: The PP-NRS score of the maximum pruritus intensity in the past 24 
hours is recorded every day; 
• 
SC administration of study drug: During W4~W14, Q2W; 
• 
Use of mild emollients: At least twice a day; 
• 
Assessment of injection site reactions: The previous injection site should be assessed 
before administration, and the new injection site should be assessed before the 
subject leaves the study site; 


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• 
AEs; 
• 
Concomitant medication/treatment. 
6.2.2.4. 
D113/W16 Pre-Dose Visit 
Subjects will return to the study site at W16±3d to receive the following assessments:  
• 
Weight; 
• 
Physical examination; 
• 
VS: VS will be recorded before administration. Subjects should rest in a sitting 
position for at least 3 min before VS assessment. 
• 
12-lead ECG; 
• 
Eye examination; 
• 
Safety laboratory tests; 
• 
Urine pregnancy test; 
• 
PK blood sample collection; 
• 
PD/ADA blood sample collection; 
• 
Investigator’s efficacy assessments; 
• 
Patient reported outcomes; 
• 
PP-NRS score: The PP-NRS score of the maximum pruritus intensity in the past 24 
hours is recorded every day; 
• 
Randomization: Only subjects whose W16 pre-dose treatment assessment meets the 
response criteria will be randomized; 
• 
Use of mild emollients: At least twice a day; 
• 
Assessment of injection site reactions: The previous injection site should be assessed 
before administration; 
• 
AE; 
• 
Concomitant medication/treatment. 
6.2.3. Stage 2 Maintenance Treatment Period (W16~W52) 
Before W16 administration, all subjects will be assessed for efficacy, and treatment assignment 
for Stage 2 maintenance treatment is based on whether a subject achieves a 50% or greater 
reduction in EASI score (ie EASI-50). The first dose of Stage 2 will be administrated at W16. 
After that, subjects will return to the study site every 2 weeks to receive the study drug 
injections and complete the corresponding study procedures according to the Study Flow Chart. 
6.2.3.1. 
D113/W16 Post-Dose Visit 
Subjects will return to the study site at W16±3d to receive the study drug injections and the 
following assessments:  
• 
VS: VS will be recorded q1h × 2h (±10 min) after administration; 
• 
SC administration of study drug; 


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• 
Use of mild emollients: At least twice a day; 
• 
Assessment of injection site reactions: The new injection site should be assessed 
before the subject leaves the study site; 
• 
AEs; 
• 
Concomitant medication/treatment. 
6.2.3.2. 
Q2W Visits During D127/W18~D365/W52 
Subjects will return to the study site at W18±3d and every 2 weeks during the treatment period 
thereafter until W52±3d to receive study drug injections and complete the corresponding study 
procedures according to the Study Flow Chart. 
The subject’s information to be collected or assessment/procedure to be performed during 
W18~W52 is as follows 
• 
Weight: During W20~W52, Q4W; 
• 
Physical examination: Performed at W52; 
• 
VS:  
• At W18 and W20, VS will be recorded before and q1h × 2h (±10 min) after 
administration; 
• From W22 to W50, VS will be recorded before and 30 min (±10 min) after 
administration; 
• Subjects should rest in a sitting position for at least 3 min before VS assessment; 
• 
12-lead ECG: Performed at W52; 
• 
Eye examination: During W18~W52, this must be performed at each visit; 
• 
Safety laboratory tests: Performed at W24, W32, W40 and W48; 
• 
Urine pregnancy test: Only for FCBP, from W20 to W52, Q4W; 
• 
PK blood sample collection: During W20~W52, Q8W; 
• 
PD/ADA blood sample collection: During W20~W52, Q8W; note: blood samples 
will not be collected for PD parameter—peripheral blood eosinophils at W20, W28, 
W36, W44 or W52; 
• 
Investigator’s efficacy assessments: During W20~W52, Q4W; 
• 
Patient reported outcomes: Performed at each visit during W20~W52; 
• 
PP-NRS score: The PP-NRS score of the maximum pruritus intensity in the past 24 
hours is recorded every day; 
• 
SC administration of study drug: During W18~W50, Q2W; 
• 
Use of mild emollients: At least twice a day; 
• 
Assessment of injection site reactions: The previous injection site should be assessed 
before administration, and the new injection site should be assessed before the 
subject leaves the study site (only previous injection site is assessed at W52); 
• 
AEs; 
• 
Concomitant medication/treatment. 


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6.2.4. Follow-up Period (D393/W56, D421/W60) 
After W52, subjects will not receive any study drug SC treatment, but return to the study site 
within the next 8 weeks to receive a follow-up visit and other study procedures.  
At the follow-up visit, the subject’s information to be collected or the assessment/procedure to 
be performed is as follows:  
• 
Weight: Measured at W56 and W60; 
• 
Physical examination: Performed at W60; 
• 
VS: Monitored at W56 and W60; 
• 
12-lead ECG: Performed at W60; 
• 
Eye examination: Performed at W56 and W60; 
• 
Safety laboratory tests: Performed at W60; 
• 
Urine pregnancy test: Only for FCBP, performed at W56 and W60; 
• 
PK blood sample collection: Performed at W60; 
• 
PD/ADA blood sample collection: Performed at W60;  
• 
Investigator’s efficacy assessments: Performed at W56 and W60; 
• 
Patient reported outcomes: Performed at W56 and W60; 
• 
PP-NRS score: The PP-NRS score of the maximum pruritus intensity in the past 24 
hours is recorded every day; 
• 
Use of mild emollients: At least twice a day; 
• 
Assessment of injection site reactions: The previous injection site should be 
assessed at W56 and W60; 
• 
AEs; 
• 
Concomitant medication/treatment. 
6.2.5. Early Termination (ET) 
If the subject early terminates (ET) the study for any reason, the ET visit should be completed 
within 7 days after ET. If the treatment is early terminated, the 8-week follow-up visit is 
required.  
At the ET visit, the subject’s information to be collected or the assessment/procedure to be 
performed is as follows:  
• 
Weight; 
• 
Physical examination; 
• 
VS; 
• 
12-lead ECG; 
• 
Eye examination; 
• 
Safety laboratory tests; 
• 
Urine pregnancy test: Only for FCBP; 
• 
PK blood sample collection; 


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• 
PD/ADA blood sample collection; 
• 
Investigator’s efficacy assessments; 
• 
Patient reported outcomes; 
• 
PP-NRS score: The PP-NRS score of the maximum pruritus intensity in the past 24 
hours is recorded every day; 
• 
Use of mild emollients: At least twice a day; 
• 
Assessment of injection site reactions: The previous injection site should be 
assessed; 
• 
AEs; 
• 
Concomitant medication/treatment. 
6.2.6. Unscheduled Visits 
During the study period, the investigator can decide whether to increase unscheduled visits 
based on clinical needs (e.g., AD deterioration, clinically significant laboratory test 
abnormalities, AEs, etc.). During the unscheduled visits, the corresponding examinations and 
AEs should be truthfully recorded. 
At unscheduled visits, the subject’s information to be collected or the assessment/procedure to 
be performed is as follows: 
• 
Physical examination; 
• 
VS; 
• 
PP-NRS score: The PP-NRS score of the maximum pruritus intensity in the past 24 
hours is recorded every day; 
• 
Assessment of injection site reactions: The previous injection site should be 
assessed; 
• 
AEs; 
• 
Concomitant medication/treatment. 
6.3. Randomization and Blinding 
6.3.1. Randomization 
In the course of this study, subjects will be randomized twice: 
1) 
After subjects complete the screening period and meet the inclusion criteria after D1 
pre-dose assessment, they can be randomized to Group A (CBP-201 300 mg Q2W) 
or Group B (placebo Q2W) in a 2:1 ratio before D1 administration; 
2) 
Subjects who are assessed to have met the response criteria before W16 
administration will be randomized to Group C (CBP-201 300 mg Q2W) or Group D 
(CBP-201 300 mg Q4W) in a ratio of 1:1. 
Subjects will be stratified and randomized according to their baseline disease severity 
(moderate [IGA=3] and severe [IGA=4]) to avoid bias and increase the likelihood of keeping 


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known and unknown subject attributes (e.g., demographics and other baseline characteristics) 
or other variables balanced between treatment groups and increase the validity of statistical 
comparisons between treatment groups. 
The placebo control will be used to determine the frequency and magnitude of changes in 
clinical endpoints that may occur in the absence of active drug treatment, and to minimize the 
bias of subjects and investigators. 
6.3.2. Blinding 
Double-blind treatment will be used to reduce the potential bias of subjects and investigators 
during data collection and assessment of clinical endpoints. 
During the study period, double-blind treatment group assignment will be adopted. Subjects, 
study site staff, the sponsor, and personnel designated by the sponsor directly involved in the 
conduct and/or monitoring of this study shall not be aware of the status of treatment group 
assignment. In the PK part of the study, blood will be collected from all subjects participating 
in the study (regardless of receiving CBP-201 or placebo treatment) at a designated time point 
and sent to the bioanalysis laboratory for subsequent processing. Since the treatment group 
assigned to any subject is not unblinded to any of the study site staff, the blindness can be 
maintained during PK sampling. 
At each stage of the study, unblinding of subject grouping information of corresponding stages 
shall not be performed until all subjects have completed scheduled visits of corresponding 
stages and the data cleaning, blind data reviewing and locking is completed. During the study 
period, unblinding can only be performed when the investigator believes that it is necessary to 
unblind in order to treat the AE or other emergency medical events that have occurred in the 
subject. If possible, the investigator should contact the sponsor before unblinding and after 
taking any measures. Whenever the treatment sequence is unblinded early, the reason for 
unblinding, the date, time and implementer of unblinding must be recorded.  
After the 255 subjects enrolled based on the V2.1 and prior versions of the protocol complete 
the stage 1 study, the study data of the 255 subjects at stage 1 will be unblinded and analyzed, 
but the investigator and other staff related to the study site will still be blinded to the subject 
grouping information. See unblinding limitations and blinding maintenance charter of this 
project for details. 
 
 


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7. 
Subject Selection and Withdrawal 
7.1. Inclusion Criteria 
Patients must meet all of the following criteria to be enrolled into this study: 
1) 
12≤ age ≤75 years at the screening visit, male or female; note: the adolescent subjects 
aged <18 years should have body weight ≥40 kg. 
2) 
Diagnosed with atopic dermatitis (according to the American Academy of Dermatology’s 
Guidelines of care for the management of atopic dermatitis, 2014[1]) at the time of 
screening, and:  
a) 
The subject has been suffering from the disease for more than 1 year at the time of 
screening, and according to the judgment of the investigator, the subject has had poor 
response to topical drugs such as corticosteroids, phosphodiesterase-4 (PDE-4) 
inhibitors or calcineurin inhibitors (TCI), or it is not medically suitable for the subject 
to receive topical drug treatment (e.g., there are important side effects or safety risks);  
Note: Poor response is defined as any of the following conditions: 
i. The patient has not achieved and maintained response or reached a low disease 
activity state (equivalent to IGA 0=asymptomatic to 2=mild) despite regular use 
of topical therapy during the 1 year before baseline; 
ii. The patient has received systemic treatment for AD despite regular use of topical 
therapy during the 1 year before baseline. 
b) At the screening and baseline visit, Investigator's Global Assessment (IGA) score≥3 
(according to the validated Investigator Global Assessment for Atopic Dermatitis 
[vIGA-AD™] scale, see Section 17.4 Appendix D), Eczema Area and Severity Index 
(EASI) score ≥16 (see Section 17.5, Appendix E), and ≥10% body surface area (BSA) 
of AD involvement (see Section 17.6, Appendix F); 
c) 
The average score of the maximum pruritus intensity in the Peak Pruritus Numerical 
Rating Scale (PP-NRS)≥4(see Section 17.1, Appendix A). 
Note: The baseline average maximum pruritus PP-NRS intensity score will be calculated based 
on the average value of the maximum pruritus intensity PP-NRS score [daily score range 0-10] 
every day within 7 days before randomization. In these 7 days, the scores of at least 4 days are 
required for the calculation of the baseline average score. If the patient’s reporting days are less 
than 4 days in the 7 days before the planned date of randomization, randomization should be 
postponed until the requirements are met, but it is not allowed to exceed the maximum 
screening period of 28 days. 
3) 
Be able to and willing to use a stable dose of a mild emollient at the AD involvement area 
at least twice a day starting from at least 7 days before baseline and continue to use it 
during the study period (see Section 8.1.1.2 Emollients). 


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4) 
Female subjects of childbearing potential (FCBP) and male subjects who have not 
undergone vasectomy must take highly effective contraceptive measures during the entire 
study period, including the 8-week follow-up period after discontinuation of study drug. 
Postmenopausal women (determined by testing follicle stimulating hormone [FSH]) and 
women with a record of surgical sterilization (i.e., tubal ligation or hysterectomy or 
bilateral oophorectomy) before the screening visit can be considered infertile. 
Highly effective contraceptive measures include: 
i. Abstinence (acceptable only if it is part of the subject's routine lifestyle); 
ii. Hormones (oral, patch, ring, injection, implant) combined with male condoms. 
This measure must be used at least 30 days before the first study drug 
administration. Otherwise, another acceptable method of contraception must be 
used; 
iii. Intrauterine device (IUD) combined with male condoms; 
iv. Exceptions are: a) women who have had amenorrhea for at least 12 consecutive 
months without using drugs known to cause amenorrhea, and have a recorded 
FSH level greater than 40 mIU/mL or in the postmenopausal range; or b) surgical 
sterilization (e.g., hysterectomy, bilateral oophorectomy). 
5) 
Subjects and/or their guardians have the ability to learn the study requirements and 
process, and voluntarily take part in the clinical trial and sign an informed consent form 
(ICF); note: for subjects ≥18 years: subjects voluntarily agree to take part in the study by 
themselves and sign ICF; for subjects aged 12-17 years, subjects and their guardians 
voluntarily agree to take part in the study, the guardians sign the ICF, and the subjects 
sign the informed assent form for minors by themselves. 
6) 
Subjects and/or their guardians are willing and able to comply with study visits and 
related procedures. 
7.2. Exclusion Criteria 
Patients who meet any of the following criteria cannot participate in this study: 
1) 
Patients who have received any of the following treatments: 
a) 
Treatment with dupilumab or any anti-IL-4Rα or IL-13 antibody treatment; 
b) 
Topical drugs for treatment of AD or have the potential to affect the assessment of 
AD, including but not limited to corticosteroids, PDE-4 inhibitors, Janus kinase 
(JAK) inhibitors, aromatic hydrocarbon receptor agonists, tacrolimus or 
pimecrolimus, or traditional Chinese medicine (TCM) or herbal medicine, etc. 
within 2 weeks before baseline;  
c) 
Have undergone bleaching baths ≥ twice within 2 weeks before baseline; 
d) 
Have begun to use prescription emollients or emollients containing additives (e.g., 
ceramide, hyaluronic acid, urea, or filaggrin breakdown products) to treat AD from 


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the screening period (if the subject has started using this kind of emollient before 
the screening visit, they can continue to use it at a stable dose; if the subject is 
intolerable to the emollients provided uniformly by the sponsor during the screening 
period, he/she can change to emollient of this kind used previously, but it must be 
used at a stable dose for at least 7 days before baseline and during the study period); 
e) 
Treatment 
with 
systemic 
corticosteroids 
or 
other 
immunosuppressive/immunomodulating 
substances 
(e.g., 
cyclosporine, 
mycophenolate mofetil, azathioprine, methotrexate, or oral JAK inhibitors) due to 
AD or other diseases within 4 weeks before baseline (except for corticosteroid 
inhalers and nasal sprays); 
f) 
Treatment with systemic TCM or herbal treatment within 4 weeks before baseline 
(note: except for those for the treatment of diseases other than AD, which are 
necessary and will neither increase the risks of the subjects nor affect the assessment 
of the study in accordance with the medical judgements of the investigator and/or 
specialist physician); 
g) 
Treatment with phototherapy (narrow band ultraviolet B [NBUVB], ultraviolet B 
[UVB], ultraviolet A1 [UVA1], psoralen + ultraviolet A [PUVA]), sunbed or any 
other light emitting device (LED) therapy within 4 weeks before baseline; 
h) 
Have used any investigational drug/treatment within 4 weeks before baseline or 5 
drug half-lives, whichever is longer; 
i) 
Treatment with other biological agents (e.g., omalizumab) within 3 months before 
baseline or 5 drug half-lives (if known), whichever is longer; 
j) 
Have been vaccinated with live (attenuated) vaccine within 8 weeks before baseline; 
k) 
Treatment with cell depletion agents (e.g., rituximab) within 6 months before 
baseline; 
l) 
Treatment with allergen specific immunotherapy (SIT) within 6 months before 
baseline (except those who were already on stable-dose therapy before baseline). 
2) 
Patients who meet any of the following: 
a) 
History of hypersensitivity to L-histidine, trehalose or Tween 80; 
b) 
Other skin complications in addition to AD that may interfere with the study 
assessments; 
c) 
Any history of vernal keratoconjunctivitis (VKC) and atopic keratoconjunctivitis 
(AKC); 
d) 
History of malignant tumor within 5 years before screening, except for cervical 
carcinoma in situ or non-metastatic cutaneous squamous cell carcinoma or basal 
cell carcinoma; 
e) 
Active tuberculosis (TB) at the screening visit, latent tuberculosis or a history of 
non-tuberculous Mycobacterium infection; 
Note:  


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- 
Unless there is a clear specialist record proving that the patient has received adequate 
treatment and is currently able to start receiving biological treatment (based on the 
medical judgment of the investigator and/or infectious disease specialist); 
- 
If necessary, T-spot test may be used for auxiliary diagnosis of suspected tuberculosis 
patients; 
f) 
Positive for hepatitis B surface antigen (HBsAg), or positive for hepatitis B core 
antibody (HBcAb) and HBV-DNA, or positive for hepatitis C antibody and HCV 
RNA polymerase chain reaction, or serologically positive for human 
immunodeficiency virus (HIV) at the screening visit; 
g) 
Any of the following laboratory test abnormalities at the screening visit: 
i. Aspartate aminotransferase or alanine aminotransferase > 2 times the upper 
limit of normal (ULN), or total bilirubin > 1.5×ULN; 
ii. Serum creatinine > 1.2×ULN; 
iii. Hemoglobin < 8.5 g/dl (85.0 g/L) in male patients and < 8.0 g/dl (80.0 g/L) in 
female patients; 
iv. White blood cell count <3.0×109/L or ≥14×109/L; 
v. Platelet count <100×109/L. 
Note: if the subjects have the above laboratory test abnormalities at screening, after being 
assessed as necessary by the investigator, they are allowed to receive a retest at another day 
within 28 days of the screening period, and those qualified for the retest are permitted to be 
enrolled (it is forbidden to conduct drug intervention for those laboratory test abnormalities 
before retest). 
h) 
Planning to undergo major surgical operations during the study period; 
i) 
Used systemic treatment with antibiotics, antiviral drugs, antiparasitic drugs, 
antigenic drugs, or antifungal drugs due to infection within 4 weeks before the 
baseline visit, or suffered from superficial skin infection (e.g., impetigo) within 2 
weeks before baseline (after the infection subsides, the subjects can be rescreened); 
j) 
History of parasite infection (e.g., helminth) within 6 months before baseline; 
k) 
According to the investigator's judgment, there is a known or suspected history of 
immunosuppression within 6 months before baseline, including a history of 
invasive opportunistic infections, such as aspergillosis, coccidiosis, histoplasmosis, 
HIV, listeriosis, Pneumocystis or tuberculosis, even if the infection has subsided, 
or there is an abnormally frequently recurrent or persistent infection; 
l) 
History of alcohol or drug abuse within 2 years before the screening visit; 
m) 
Any other medical or psychological condition (including clinically significant 
laboratory test abnormalities, ECG parameters, etc.) at the screening visit, which, 
as judged by the investigator, may indicate new and/or insufficiently understood 
diseases, may put the patient at an unreasonable risk due to his/her participation in 
the clinical trial, may lead to unreliable results of the patient's participation, or may 


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interfere with the study assessments. The specific reasons for patients excluded due 
to this criterion will be indicated in the study documents (medical records, CRF, 
etc.). 
3) 
Pregnant or lactating women, or subjects with pregnancy or lactation plans during the 
study period. 
7.3. Early Withdrawal 
During the trial, subjects have the right to withdraw from the study at any time for any reason. 
The investigator can also require subjects to withdraw from the study for safety, subject 
compliance and other reasons. Subjects who withdraw from this study will not be discriminated 
or retaliated upon, and their medical treatment and rights will not be affected.  
For subjects who early withdraw from the study, while respecting the personal wishes of the 
subjects, the investigator should make every effort to determine the reason why the subjects 
early withdraw from the study and make corresponding records. 
The reasons for the subject's withdrawal from the study may include but not be limited to the 
following: 
1) 
The subject withdraws the informed consent.  
2) 
The subject is lost to follow-up.  
3) 
Complications and medical conditions that require termination of the study 
treatment, based on the judgment of the investigator and the sponsor. 
4) 
Protocol deviations, based on the judgment of the investigator and the sponsor. 
5) 
The investigator believes that the subject has an intolerable AE or SAE, is not 
suitable for continuing the study treatment, and needs to withdraw from the study. 
6) 
The investigator judges that withdrawing from the study is to protect the interests 
of the subject.  
7) 
Pregnancy. 
8) 
The investigator believes that the subject has poor compliance, which may make 
the subject’s study results unevaluable.  
9) 
The treatment is unblinded. 
10) 
The sponsor requires so. 
11) 
Other situations where the investigator believes that the subject has to withdraw 
from the trial. 
12) 
The study is terminated. 
Subjects who early withdraw from the study during the study treatment period (including Stage 
1 treatment period and Stage 2 maintenance treatment period) should complete the early 


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termination visit as far as possible within 7 days of ET according to the protocol, and complete 
the 8-week safety follow-up as far as possible. The investigator or study-related personnel with 
corresponding qualifications should contact the subjects as much as possible, try their best to 
collect the assessment content that needs to be completed at the corresponding visits, and make 
records, including the date of the last study drug administration, the date of withdrawal from 
the study, and the reason for withdrawal. 
For subjects who withdraw from the study, regardless of the reason, their eCRF should be 
retained. The biological samples that have been obtained should be retained, processed and 
tested. 
7.4. Study Termination 
The sponsor has the right to terminate this study at any time, and the sponsor and the 
investigator have the right to close the study site at any time. Of course, this can only be 
implemented after mutual negotiation. When terminating the study early, the investigator 
should promptly notify the subject and complete the follow-up visit as planned in the protocol. 
If there is an AE, the subject should be followed up until the AE disappears or stabilizes. 
When the sponsor early terminates the study, the sponsor should immediately inform the 
investigator, clinical trial institution, and drug regulatory authority, and explain the reason for 
the termination of the study. 
If the investigator early terminates the study without consulting the sponsor, the investigator 
should immediately report to the clinical trial institution, the sponsor and the EC, and provide 
a detailed written explanation; if the sponsor early terminates the study, the investigator should 
immediately report to the clinical trial institution and the EC, and provide a detailed written 
explanation. 
When the EC terminates the study, the investigator should immediately report to the clinical 
trial institution and the sponsor, and provide a detailed written explanation. 
The reasons for early termination of the study or closure of a study site may include but not be 
limited to the following: 
• 
The sponsor requests termination under the premise of fully protecting the rights and 
interests and safety of subjects (e.g., funding reasons, management reasons, etc.). 
• 
A significant deviation or human error is found during the implementation of the 
trial, which seriously affects the quality of the trial and makes it difficult to achieve 
the objectives of the trial. 
• 
New information leads to unfavorable risk/benefit judgments of the study drug, such 
as: 
− 
The study drug lacks efficacy, whether in this study or other studies; or 
− 
Significant, previously unknown adverse drug reactions or unexpected, high-
severity/incidence known adverse drug reactions occur; or 


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− 
Other adverse safety findings, including clinical examination and non-clinical 
manifestations. 
• 
Due to the difficulty in patient enrollment, making it unlikely to complete the study 
within an acceptable time frame.  
• 
The study is discontinued or terminated as required by the EC.  
• 
The study is discontinued or terminated as required by the competent health or 
regulatory authority. 
 
 


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8. 
Study Treatment 
8.1. Study Treatment Drugs 
8.1.1. Basic Information of Study Treatment Drugs 
8.1.1.1. 
Investigational Drug/Placebo 
Table 8.1 Detailed Information of Investigational Drug/Placebo 
Study drug 
Investigational drug 
Placebo 
Drug name 
CBP-201 
/ 
Dosage form 
Injection  
Composition  
CBP-201 is prepared from a solution containing inactive 
excipients (including NaCl, trehalose, Tween 80 and L-
histidine) at a concentration of 150 mg/ml. 
Contains 
the 
same 
excipients, but does not 
contain CBP-201 API. 
Storage  
CBP-201 preparation and the corresponding placebo solution should be stored at 2-8 ° 
C. 
Method of 
administration 
Subcutaneous injection (SC) 
Dosing 
regimen 
Detailed in Section 6.1. 
All study treatment drug bottles are blinded and can only be identified by the drug bottle 
number on the bottle label. 
8.1.1.2. 
Emollients (Background Treatment) 
From at least 7 days before baseline to the end of the study, subjects will be required to apply 
a mild emollient to the AD-affected area at least twice a day as background treatment, but 
should avoid using emollients within 4 hours before AD assessment at each visit. During the 
screening period or the study period, subjects cannot start using prescription emollients or 
emollients containing additives. However, if subjects have already started using these 
emollients before the screening visit, they can use them at a stable dose throughout the study 
period. If the subject is intolerable to the emollients provided uniformly by the sponsor during 
the screening period, he/she can change to the emollient of this kind used previously, but it 
must be used at a stable dose for at least 7 days before baseline and during the study period. 
8.1.2. Dose Selection 
The preliminary safety of CBP-201 has been established in a Phase I SAD study in healthy 
subjects (subjects receiving doses ranging from 75 mg to 600 mg) and a MAD study in AD 
subjects (subjects receiving 75 mg, 150 mg, or 300 mg QW for 4 times), and it was seen that 
300 mg QW showed more significant efficacy. Based on the above studies, the dosage regimen 
(CBP-201 300 mg Q2W or Q4W) selected in this study may be well tolerated. 
8.1.3. Drug Package and Label 
The sponsor and the contract research organization (CRO) will design labels for all study drugs 
and perform drug packaging and labeling in accordance with the Good Clinical Practice (GCP) 


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and applicable national regulations. The label content includes information such as protocol 
number, drug number, drug name, dosage form, strength, batch number, production date, 
expiration date, instructions for use, package, storage, appropriate warnings and name of the 
sponsor, and “for clinical research use only” should be indicated. 
From the perspective of the blinding method of the clinical trial, the inner and outer packaging 
of the study drug will be kept consistent with that of the placebo. 
8.1.4. Drug Distribution, Recording and Recovery 
The study drugs used in this trial (investigational drug CBP-201 and placebo) will be provided 
by the sponsor free of charge and distributed to each study site as planned. Each clinical study 
site will appoint a person to be responsible for the reception, custody, distribution, recovery 
and corresponding recording of study drugs. 
The study drug management of each clinical study site should meet the following requirements: 
1) 
A designated person (e.g., a pharmacist) will receive the study drugs and materials 
provided by the sponsor and keep a record; 
2) 
A designated person is responsible for the reasonable and safe storage of study drugs, 
and should ensure that the storage conditions of study drugs meet the requirements; 
3) 
The distribution and use of study drugs and materials need to be fully recorded; 
4) 
Study drugs can only be prescribed by the investigator or a study doctor authorized 
by the investigator; 
5) 
Study drugs can only be distributed to qualified subjects in accordance with the trial 
protocol, and non-study subjects are not allowed to use study drugs; 
6) 
The investigator should keep unused medicines and packaging, and outer packaging 
of used medicines for inspection by the clinical research associate (CRA); 
7) 
After the drugs are counted during the visit, detailed records should be kept on 
medication errors, overdose, drug loss and other situations; 
8) 
After being counted by the CRA, the remaining unused drugs and the outer 
packaging of used drugs will be recovered by the sponsor. 
The investigator or his designated personnel must agree not to provide study drugs to any 
subjects who have not been enrolled into this study, or any physician or scientist who is not 
authorized for this study. 
At the end of the trial, the study drug delivery records must be consistent with the used and 
destroyed/returned quantities. Any discrepancies need to be recorded and the reasons for the 
discrepancies should be specified. 
8.2. Concomitant Medications/Treatments 
8.2.1. Prohibited Drugs/Treatments 


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The following drugs/treatments are prohibited during the study period. If any of the following 
treatment is started after the first dose of study drug on D1, the study treatment must be early 
terminated: 
• 
Dupilumab or any anti-IL-4Rα or IL-13 antibodies; 
• 
Topical PDE-4 inhibitors or JAK inhibitors; 
• 
Systemic treatment with corticosteroids or other immunosuppressive and/or 
immunomodulatory agents such as cyclosporine, mycophenolate mofetil, 
azathioprine, methotrexate or oral JAK inhibitors; 
• 
Cell depletion agents (e.g., Rituximab) or other biological agents; 
• 
Other investigational drugs (non CBP-201) or treatments. 
The following treatments are also prohibited during the study period: 
• 
Initiation of SIT or dose up-regulation; 
• 
(Attenuated) live vaccine; 
• 
TCS or TCI; 
• 
Phototherapy (NBUVB, UVB, UVA1, PUVA), sunbed or any other LED therapies; 
• 
Bleaching baths more than 2 times a week; 
• 
Any drug (except mild emollients) that may interfere with the evaluation of efficacy 
results or affect the evaluation of AD severity. 
8.2.2. Permitted Drugs/Treatments 
a. 
AD recurrence and rescue therapy  
AD is a chronic recurrent skin disease characterized by periodic aggravation or gradual 
deterioration of symptoms. If medically necessary (i.e. in order to control intolerable AD 
symptoms), the investigator can provide patients with rescue therapy for AD by using drugs or 
treatment regimens that were originally prohibited at their own discretion. According to the 
investigator's judgment, AD aggravation or deterioration of symptoms which requires drugs or 
treatments originally prohibited by the protocol for rescue therapy will be defined as “AD 
recurrence” event, and the onset and duration of these events will be recorded as AE according 
to the site of attack. 
Note: The investigator should limit the first-step rescue therapy to topical drugs (TCS or TCI)
 as far as possible. Only patients who do not respond adequately after at least 7 days of topica
l medication can be upgraded to systemic medication or other treatments. If a subject receives
 systemic corticosteroid or non-steroid systemic immunosuppressive/immunomodulatory resc
ue therapy, the study drug administration will be stopped immediately. 
b. 
Other drugs that are permitted may include: 


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• 
Emollients (as the background treatment of this study, at least 7 days before baseline, 
all subjects need to use mild emollients at least twice a day, and continue to use 
them throughout the study period. During the screening period or the study period, 
subjects cannot start using prescription emollients or emollients containing additives. 
However, if a subject has already started using these emollients before the screening 
visit, he/she can continue using them at a stable dose throughout the study period. If 
the subject is intolerable to the emollients provided uniformly by the sponsor during 
the screening period, he/she can change to the emollient of this kind used previously, 
but it must be used at a stable dose for at least 7 days before baseline and during the 
study period.); 
• 
Basic skin care (cleansing and bathing); 
• 
Oral antihistamines (maintain a stable dose within 7 days before baseline and during 
the study period); 
• 
Drugs for the treatment of chronic diseases (e.g., hypertension, diabetes, etc.); 
• 
Local or systemic anti-infective drugs (as required by the condition). 
Before any rescue therapy, the investigator should make every effort to assess the efficacy and 
safety (e.g., disease severity score, safety laboratory tests). If necessary, unscheduled visits can 
be conducted. 
8.3. Treatment Compliance 
As all study treatment drugs (CBP-201 and placebo) are administered by study personnel, the 
subjects therefore are not required to follow procedures. 
9. 
Study Procedures and Endpoints 
9.1. Informed Consent 
The investigator or designated study staff will explain to the subjects and/or their guardians the 
nature of the study and its risks and benefits. Before performing any study-related procedures, 
subjects and/or their guardians must voluntarily sign an ethically approved ICF to provide 
written informed consent. 
9.2. Demographics and Other Baseline Characteristics 
9.2.1. Demographics/Baseline Characteristics 
Demographic data of subjects will be recorded, including age and gender. 
9.2.2. Medical History and History of Surgery 
The complete medical history and surgical history will specifically include the history of AD 
and acute, chronic or infectious diseases within 1 year before screening, the history of surgery 
or tumor, and any reported diseases that affect major body systems. The investigator will assess 
the clinical significance of the subject's medical history. The medical history should be 


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reviewed and updated at the baseline visit (D1 pre-dose). 
9.2.3. Medication/Treatment History 
All drugs (prescription drugs and over-the-counter drugs, herbal/natural health products or 
study drugs) taken by the subjects within 30 days before the screening visit will be recorded in 
the source file as a medication history and recorded in the database of the prior and concomitant 
medications. Similarly, any treatment received by the subject will also be recorded in the source 
file as a treatment history. 
Any new medications/treatments during the study period will be recorded in the source file and 
recorded in the appropriate CRF. 
9.2.4. Height and Weight 
Height: Measured during the screening period only. 
Weight: Measured once each during the screening period and on D1, and measured once every 
4 weeks during W4~W60. If the subject early terminates the study, it is also necessary to 
measure the weight at the ET visit. 
9.2.5. Vital Signs 
VS should be monitored at each visit. After the subject has a sitting rest for at least 3 minutes, 
the following vital signs will be measured: blood pressure (mmHg), heart rate (beats/min), 
respiratory rate (breaths/min), and body temperature. On D1 and at W2, W4, W16, W18, and 
W20, VS should be monitored every hour (±10 min) pre-dose and during the 2-hour monitoring 
period post-dose; from W6 to W14 and from W22 to W50, VS must be monitored pre-dose 
and 30 min (±10 min) post-dose. 
If the investigator believes that the fluctuation of vital signs is clinically significant, it will be 
considered an AE. 
9.2.6. Physical Examination 
A complete physical examination (PE) is required at screening, W16, W52, EOS/ET and 
unscheduled visits. The items included are as follows: general appearance, skin, 
eyes/ears/nose/throat, head and neck, cardiovascular system, respiratory system, abdomen, 
limbs, lymph nodes, musculoskeletal and nervous systems. Unless it is necessary to assess the 
status of AD involvement, there is no need to perform rectal or genital examinations. Priority 
PE can be performed at visits where PE are not scheduled. Attention should be paid to the 
assessment of AD involvement areas. 
9.3. AD Assessments 
The assessment of the severity and impact of AD will be divided into two parts: the 
investigator’s efficacy assessments and the patient reported outcomes. See Section 6.2 for 
details. 


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9.4. Other Safety Assessments 
9.4.1. Safety Laboratory Tests 
The hematology stipulated in the protocol will be performed in the central laboratory, and blood 
biochemistry and urinalysis performed in the local laboratory (if they can not be performed in 
the local laboratory, the samples will be sent out to the central laboratory for detection). Blood 
samples will be collected, processed and transported in accordance with the instructions of the 
central laboratory. If the laboratory results are abnormal or clinical symptoms appear, the 
investigator can collect additional samples for retesting as appropriate to ensure safety. The 
required laboratory assessments are listed in the table below. 
Table 9.1 Safety Laboratory Tests 
Hematology 
Blood biochemistry 
Urinalysis 
White blood cell count 
Hemoglobin 
Hematocrit 
Red blood cell count 
Platelet count 
Neutrophil percentage 
Lymphocyte percentage 
Monocyte percentage 
Basophil percentage 
Eosinophil percentage 
Absolute neutrophil count 
Absolute lymphocyte count 
Absolute monocyte count 
Absolute eosinophil count 
Absolute basophil count 
Sodium 
Potassium 
Calcium 
Chlorine 
Serum urea/urea nitrogen 
Creatinine 
Glucose 
Total protein 
Albumin 
Total bilirubin 
Alanine aminotransferase 
Aspartate aminotransferase 
γ-glutamyltransferase 
Alkaline phosphatase 
Lactate dehydrogenase 
Creatine phosphokinase 
Total cholesterol 
Low-density lipoprotein 
High-density lipoprotein 
Bilirubin 
Red blood cells 
White blood cells 
Glucose 
Ketone 
Nitrite 
pH 
Protein 
Urine specific gravity 
Urobilinogen 
Microscopic examination (if 
necessary) 
The investigator is responsible for reviewing and signing all laboratory tests reports, and for 
recording the appropriate safety monitoring of the study subjects. The investigator should sign 
and date each laboratory report while reviewing it, and should indicate the clinical significance 
of each abnormality/marked value by indicating “NCS” (not clinically significant) or “CS” 
(clinically significant). Annotations indicating that a value has clinical significance should also 
include a short description of the underlying disease or condition associated with the value, 
such as “CS/mild anemia”. Generally, abnormal laboratory values which are clinically 
significant judged by the investigator are expected to be associated with items recorded in the 
medical history or AEs. The investigator can use the Common Terminology Criteria for 
Adverse Events (CTCAE) V5.0 [32] to assist in judging the severity and clinical significance. 


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9.4.2. 12-lead ECG (ECG) 
The 12-lead ECG should be performed after the subject rests for at least 5 minutes in the 
lying/supine position. ECG variables include ventricular heart rate and PR, QRS, QT and QTcF 
intervals (formula: QTcF=QT/RR 0.33). The ECG will be signed and dated by a medically 
qualified person to confirm that the ECG has been reviewed and to confirm whether an ECG 
abnormality (if any) is clinically significant. 
9.4.3. PK and PD Sampling 
PK sampling will be implemented according to the Study Flow Chart. About 4 ml of whole 
blood will be collected each time, and plasma will be separated to analyze the blood 
concentration of CBP-201. The PK characteristics of steady-state trough concentrations of 
individuals and each group of subjects at each treatment time point will be calculated. 
PD sampling will be implemented according to the Study Flow Chart. About 5 ml of whole 
blood will be collected each time to summarize the changes in serum IL-4, IL-13, IgE and 
TARC and peripheral blood eosinophil count from baseline.  
9.4.4. ADA Sampling 
ADA sampling will be implemented according to the Study Flow Chart. About 5 ml of whole 
blood will be collected each time for ADA testing. All ADA-positive samples will be further 
tested to determine the presence of anti-CBP-201 NAb. 
9.4.5. Sample Processing 
Please refer to the CBP-201-CN002 laboratory manual for a detailed description of the 
processing and labeling requirements after the collection of PK/PD/ADA samples. 
9.5. Study Endpoints 
9.5.1. Efficacy Endpoints 
 
Primary endpoint 
The proportion of subjects whose IGA score is 0-1 and decreased by ≥2 points from 
baseline at W16. 
 
Key secondary endpoints 
• 
The proportion of subjects achieving EASI-75 at W16; 
• 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥ 4 
points from baseline at W16; 
• 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥ 3 
points from baseline at W16; 
• 
Change and percentage change in the weekly average PP-NRS from baseline at W16; 
• 
The proportion of subjects achieving EASI-90 at W16; 


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 
Other secondary endpoints 
• 
Change and percentage change in the EASI score from baseline at W16; 
• 
The proportion of subjects achieving EASI-50 at W16; 
• 
Percentage change in the BSA of AD involvement from baseline at W16; 
• 
Percentage change in the SCORAD score from baseline at W16; 
• 
Change in DLQI from baseline at W16; 
• 
Change in POEM from baseline at W16; 
• 
Percentage change in the weekly average PP-NRS from baseline at W2. 
 
Other efficacy endpoints 
• 
The proportion of subjects whose IGA score is decreased by ≥ 2 points from baseline 
at W16; 
• 
The proportion of subjects achieving EASI-100 at W16; 
• 
The number of AD recurrences and number of days from baseline to W16;  
• 
Change in efficacy parameters (e.g., IGA, EASI, BSA, SCORAD, POEM and DLQI) 
from baseline to W16; 
• 
Change in weekly average PP-NRS from baseline at W16; 
• 
The proportion of subjects whose IGA score is 0-1 and decreased by ≥2 points from 
baseline at W52; 
• 
The percentage decrease in the overall EASI score between W16 and W52; 
• 
The proportion of subjects achieving EASI-50 at W52; 
• 
The proportion of subjects achieving EASI-75 at W52; 
• 
The proportion of subjects achieving EASI-90 at W52; 
• 
The proportion of subjects achieving EASI-100 at W52; 
• 
Change in weekly average PP-NRS compared with baseline from W16 to W52; 
• 
Change in POEM compared with baseline from W16 to W52; 
• 
The proportion of subjects whose IGA score is decreased by ≥2 points from baseline 
at W52;  
• 
Percentage change in the AD-affected BSA compared with baseline from W16 to 
W52; 
• 
Change in SCORAD compared with baseline from W16 to W52; 


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• 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥3 points 
from baseline at W52; 
• 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥4 points 
from baseline at W52; 
• 
Change in PDLQI compared with baseline from W16 to W52; 
• 
The number of subjects with AD recurrence from baseline to W8; 
• 
The number of subjects with AD recurrence from W8 to W16; 
• 
The number of subjects with AD recurrence from W16 to W52; 
• 
The number of AD recurrences and number of days from W16 to W52. 
Note: EASI 50: EASI score is decreased by ≥50% from baseline; EASI 75: EASI score is 
decreased by ≥75% from baseline; EASI 90: EASI score is decreased by ≥90% from baseline; 
EASI-100: EASI score is decreased by 100% from baseline; PP-NRS: Peak Pruritus Numerical 
Rating Scale; AD recurrence: According to the investigator's judgment, AD aggravation or 
deterioration of symptoms which requires drugs or treatments originally prohibited by the 
protocol for rescue therapy will be defined as “AD recurrence” event; POEM: Patient Oriented 
Eczema Measure; SCORAD: Scoring Atopic Dermatitis Index; DLQI: Dermatology Life 
Quality Index. 
9.5.2. Safety Endpoints 
Safety assessments are based on the following indicators:  
• 
Incidence and severity of AE, AESI and SAE; 
• 
Abnormal changes in vital signs, physical examination, and the injection site; 
• 
Abnormal changes in laboratory tests, ECG parameters, etc.; 
• 
Percentage of subjects positive for ADA. 
9.5.3. PK Endpoints 
To analyze the blood concentration of CBP-201, and calculate the PK characteristics of steady-
state trough concentrations of individuals and each group of subjects at each treatment time 
point. 
9.5.4. PD Endpoints 
Change in serum IL-4, IL-13, IgE, TARC levels and peripheral blood eosinophil count from 
baseline. 
10. 
Adverse Events 
10.1. Definition of Adverse Events 
10.1.1. Adverse Event 


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Adverse events refer to all adverse medical events that occur after subjects receive the 
investigational medicinal product, which can be manifested as symptoms, signs, diseases or 
laboratory test abnormalities, but are not necessarily related to the investigational medicinal 
product. 
10.1.2. Serious Adverse Event 
An event will be considered a SAE if the following situations occur: 
• 
Leading to death; 
• 
Life-threatening: The investigator determines that the patient is at immediate risk of 
death when the event occurs. This definition does not include events that may lead 
to death if it is assumed to be more serious; 
• 
Requiring hospitalization or prolongation of the original hospital stay; 
• 
Leading to permanent or major disability or incapacitation (ie, significant 
impairment of the subject's activities of daily living); 
• 
Including congenital abnormalities or birth defects in the offspring of the patient; 
• 
Significant medical events: According to the medical judgment of the investigator, 
other significant medical events that may endanger the patient and may require 
medical or surgical intervention to prevent one of the above outcomes. 
Hospitalization is defined as any first admission (even less than 24 h) to a hospital or equivalent 
medical institution. Emergency room visits do not necessarily constitute hospitalization, but 
the medical importance of the events leading up to emergency room visits should be assessed. 
In the absence of emergency clinical AEs, hospitalization itself cannot be considered as SAE, 
including optional admissions for elective surgery, managed admissions for treatment (annual 
physical examination or routine diagnostic procedures not related to AEs), or admissions to a 
hospital for pre-existing diseases unrelated to new AEs or the deterioration of pre-existing 
diseases. 
Other significant medical events refer to other situations where medical and scientific 
judgments must be used to determine whether to expedite the reporting. When a significant 
medical event may not immediately threaten life or lead to death or hospitalization, but if 
medical measures are needed to prevent one of the above situations from occurring, it is usually 
considered serious, such as allergic bronchospasm requiring intensive care, blood cachexia, 
convulsions without leading to hospitalization, progression to drug dependence or abuse. The 
above significant medical events should also be regarded as SAEs.  
10.1.3. Acquisition of Adverse Event Information 
At each study visit, the investigator will ask the patient to obtain any medically relevant 
changes in their health, and whether they were hospitalized, used any new drugs, or changed 
the concomitant medication regimens (prescription and over-the-counter drugs). 
In addition to patient observations, AEs will be recorded in the eCRF based on any data 


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collected from the source files and the eCRF (e.g., laboratory tests, physical examination results, 
medical history, ECG changes) or other documents related to patient safety (e.g., patient 
diaries). An adverse medical condition that has been assessed to preexist from the screening 
period to before the administration of the study drug and worsens after the exposure of the 
study drug should be regarded as an AE. Abnormalities in laboratory tests that have occurred 
or worsened since the last laboratory assessment and are considered by the investigator to be 
clinically significant should be regarded as AEs. 
10.2. Determination of Severity of AEs 
The severity of AEs will be assessed based on the following criteria:  
The investigator can use CTCAE V5.0 to assist in determining the severity and clinical 
significance. Below is the CTCAE classification of AE severity:  
• 
Grade 1/mild: Asymptomatic or mild symptoms; clinical or diagnostic observations 
only; intervention not indicated. 
• 
Grade 2/moderate: Minimal, local or noninvasive intervention indicated; limiting 
age-appropriate instrumental ADL. Instrumental ADL refer to preparing meals, 
shopping for groceries or clothes, using the telephone, managing money, etc. 
• 
Grade 3/severe or medically significant but not immediately life-threatening: 
Hospitalization or prolongation of hospitalization indicated; disabling; limiting self 
care ADL. Self care ADL refer to bathing, dressing and undressing, feeding self, 
using the toilet, taking medications, and not bedridden. 
• 
Grade 4/life-threatening consequences: Urgent intervention indicated 
• 
Grade 5/death related to AE. 
Note: CTCAE terms present grades of specific laboratory test abnormalities. Grade 4 
laboratory test abnormalities do not automatically indicate life-threatening event. Abnormal 
laboratory test result should be assessed whether it is regarded as an AE.  
AEs not listed in the CTCAE will be graded according to the following methods:  
• 
Grade 1/mild: Discomfort is observed but does not interfere with normal daily 
activities. 
• 
Grade 2/moderate: Discomfort sufficient to reduce or affect daily activities. 
• 
Grade 3/severe: Inability to work or to perform normal daily activities. 
• 
Grade 4/life-threatening: Will be life-threatening immediately. 
• 
Grade 5/death. 
10.3. Determination of Relationship between AEs and Study Drugs 
For all AEs (serious and non-serious), the investigator's causality assessment results must be 
provided. The investigator must record this causality on the eCRF. The investigator's causality 
evaluation is to determine whether there is a reasonable possibility that the study drug has 
caused the AE. In general, facts (evidence) or arguments suggesting the causality should be 


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provided. 
The relationship between AE/SAE and study drug is determined according to the five-category 
classification, as shown in the table below: 
Correlation  
Criteria for determination 
Related 
• 
There is a reasonable temporal sequence between the occurrence of AE and the 
medication; 
• 
The study drug explains the AE more reasonably than other reasons (e.g., the 
patient's existing disease, environmental or toxic factors, or other treatments 
the patient received, etc.); 
• 
The AE disappears or lessens after the drug is stopped or the dose is reduced; 
• 
The AE meets the known AE types of the suspect drug or its similar drugs; 
• 
The AE recurs after re-administration. 
Possibly related 
• 
There is a reasonable temporal sequence between the occurrence of AE and the 
medication; 
• 
The study drug explains the AE as reasonably as other reasons (e.g., the 
patient's existing disease, environmental or toxic factors, or other treatments 
the patient received, etc.); 
• 
The AE disappears or lessens after the drug is stopped or the dose is reduced 
(if applicable). 
Unlikely related 
• 
Other reasons (e.g., the patient's existing disease, environmental or toxic 
factors, or other treatments the patient received, etc.) explain the AE more 
reasonably than the study drug; 
• 
The AE does not disappear or lessen after the drug is stopped or the dose is 
reduced (if applicable), or the situation is unclear. 
• 
The AE does not recur after re-administration, or the situation is unclear. 
Not related 
• 
There is no reasonable temporal sequence between the occurrence of AE and 
the medication, or; 
• 
The AE has other evidence reasons (e.g., the patient's existing disease, 
environmental or toxic factors, or other treatments the patient received, etc.).  
Indeterminable 
• 
The above information is unclear, and the investigator believes that it cannot 
be judged based on the existing information, and the investigator cannot obtain 
further follow-up information. 
It may happen that although an AE has occurred, very little information is available in theinitial 
report. However, before transmitting AE data to the sponsor for the first time, it is still very 
important for the investigator to assess the correlation of the event. The investigator can change 
his/her view of the correlation based on the follow-up information, and at the same time modify 
the AE report page and SAE report form (if applicable) in the eCRF accordingly. 
The investigator can refer to the Investigator's Brochure for CBP-201 provided by the sponsor, 
safety findings of similar drugs (e.g., the safety data of dupilumab, a marketed product with 
the same target), and support correlation judgment based on the study drug’s pharmacological 
properties and the nature of the disease. For some information, please refer to Section 4 of this 
protocol. 
In this study, AEs whose causality is judged as “related”, “possibly related” and 


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“indeterminable” will be regarded as adverse drug reactions. 
10.4. Investigator’s Responsibility for Safety Reports 
10.4.1. Principle of AE Reporting 
All AEs that occur from the signing of the ICF to the end of the patient’s study as specified in 
the protocol (to the completion of the follow-up visit for early withdrawals). During the entire 
study period, all AEs must be fully recorded in the source file and transcribed in the eCRF, 
regardless of whether they are considered drug-related or not. 
PTAE is defined as any adverse medical event that occurs after the subject signs the ICF to 
before receiving the study drug administration, and it is not necessarily causally related to study 
participation. TEAE is defined as an AE that occurs or worsens during treatment. The treatment 
period refers to the period from the first study drug administration to the end of the protocol-
specified follow-up period. 
Laboratory test abnormalities that are not clinically significant will not be recorded as AEs. 
Abnormal laboratory tests, vital signs, electrocardiogram, and injection site reactions that are 
clinically significant (ie, “clinically significant abnormalities”) should be reported as AEs. If a 
laboratory test abnormality is part of a syndrome, the AE should be recorded as a syndrome or 
diagnostic result (e.g., anemia) rather than a laboratory test result (e.g., hemoglobin reduction). 
Unless related to the study procedure, any medical condition that was present at the time of 
patient screening but does not deteriorate will not be reported as an AE. However, if it worsens 
at any time during the study, it should be recorded as an AE. 
The investigator should assess and record all AEs, and report diagnostic results or syndromes 
as much as possible, rather than symptoms. AE-related information should be clearly recorded 
on the eCRF AE report page, including but not limited to the following: 
• 
AE term 
• 
Start date 
• 
Stop date 
• 
Severity 
• 
Relationship with the study drug 
• 
Action taken with the study drug in response to the AE 
• 
AE outcome 
Any adverse event should be followed up until the event resolved/recovered and/or stabilizes, 
regardless of whether the event is considered to be related to the study drug. If the patient 
rejects further follow-up, is lost to follow-up, or under other circumstances where the outcome 
of the event cannot be obtained, relevant information needs to be recorded in the patient's 
medical record. The MedDRA will be used to code AEs and medical history. In addition, the 
World Health Organization Drug Dictionary (WHODrug) will be used to code drug usage. 
10.4.2. Guidance for the Reporting of Serious Adverse Events 


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Any SAE that occurs from the signing of the ICF to the end of the patient’s study as stipulated 
in the protocol (to the completion of the follow-up visit for early withdrawals) should be 
reported, regardless of whether it is related to the study drug. 
The SAE must be reported to the sponsor or its designated personnel within 24 hours of receipt. 
If the SAE is fatal or life-threatening, the sponsor/CRO must be notified immediately, 
regardless of the extent of information available on the event. 
All SAEs must be immediately (within 24 h of being learned) reported to the CRO by 
email: 
Email for SAE reports: PV@tigermedgrp.com 
Tigermed’s fax for SAE safety reports: 021-33275864 
The initial report should include all the information known at the time of the report (additional 
information can be reported after it is obtained). Do not delay the initial report in order to obtain 
the outcome or follow-up information. 
The investigator reports SAEs by filling in the SAE report form provided by the sponsor/CRO. 
Usually, it will include a sufficiently detailed description of the AE to allow a complete medical 
assessment of the case and independent determination of possible causality. Any information 
related to the event must be provided, such as concomitant drugs and diseases. The SAE report 
form will include the following information: 
• 
Patient number 
• 
Country where the event occurs 
• 
Event information 
• 
Related test results and laboratory data 
• 
Any other related history 
• 
Action taken with the study drug 
• 
Investigator’s assessment of relationship 
• 
Other measures (treatments, etc.)  
The medical monitor of the CRO or the designated personnel of the CRO/sponsor can contact 
the investigator to request additional information of the event or to confirm information. All 
SAEs will be entered in the AE case report form. The same term should be used in the sponsor's 
SAE report form and AE case report form. The investigator is responsible for reporting all 
SAEs to the sponsor (or designated personnel) in a complete and timely manner, reporting 
follow-up information about SAEs (the SAE follow-up report method is the same as the initial 
report), and notifying the EC of the occurrence and related details of the event in accordance 
with local regulations; for reports involving deaths, the investigator should provide the sponsor 
and the EC with other required information, such as autopsy reports and final medical reports. 
If there is a problem with whether it is an SAE, the event should be reported. 
Any SAE should be followed up until the event has resolved/recovered or stabilized, so follow-


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up may continue beyond the last visit planned by the protocol, and the sponsor's monitoring 
team may require additional inspections. At any time after the end of the study, any serious 
adverse event noticed by the investigator should be reported to the monitoring team or the 
sponsor/designated personnel within 24 h if he/she believes that there is a reasonable possibility 
that it has been caused by the study drug. 
10.4.3. AE of Special Interest 
AESIs refer to the sponsor's product or project-specific AEs (serious or non-serious) that 
require scientific and medical attention and require continuous monitoring, which should be 
notified by the investigator to the sponsor by email. Further research may be required to 
characterize and understand these events, and these events should be marked as “AESI” in the 
eCRF. During the study period, AESI can be added or removed through protocol clarification 
or revision. 
Conjunctivitis and keratitis were events of interest in the research experience of dupilumab. 
Akinlade 2019 [33] reported that in the combined experience of dupilumab in the treatment of 
patients with AD (n=1047), a total of 90 patients (8.6%) reported at least one “conjunctivitis” 
AE, while among patients in the placebo group (n=517), 11 cases (2.1%) of such events were 
reported. The severity of conjunctivitis AEs was mostly mild to moderate, and severe events 
were reported by ≤0.5% of patients in the dupilumab combined group and ≤0.3% of patients in 
the placebo group. In the dupilumab group, 2 patients permanently discontinued study drug 
due to conjunctivitis. Conjunctivitis usually occurred between Week 4 and Week 8, and events 
became less common after long-term treatment. Conjunctivitis was more common in patients 
with severe AD at baseline, patients with a previous history of conjunctivitis, and patients with 
high baseline TARC and IgE levels. The combined dupilumab data indicate that the incidence 
of conjunctivitis may decrease as the trough concentration of dupilumab increases.  
This pattern has not been observed in studies of other indications for dupilumab, including 
asthma and chronic sinusitis with nasal polyps. 
Based on lessons from the experience of dupilumab in the treatment of AD, the ophthalmology 
adverse events “conjunctivitis” and “keratitis” will be regarded as AESIs, which should be 
evaluated by an ophthalmologist if the investigators or sponsor consider necessary and 
appropriate treatment should be given until it is resolved. 
In addition to conjunctivitis and keratitis, the following AEs are also classified as AESIs, 
including serious immediate hypersensitivity, all reactions at injection site which persist over 
24 h, AST/ALT increased>5× ULN, parasitic and opportunistic infection, pregnancy and 
symptomatic overdoses.  
The immediate hypersensitivity will be defined according to the symptoms described in 
Sampson et al. 2006 [34], as follows: 
Should any one of the following 3 criteria be met, the immediate hypersensitivity is likely to 


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occur: 
1. Acute onset (minutes to several hours) of certain illness with involvement of the skin 
or mucosal tissue, or both (eg, generalized hives, pruritus or Hushing, swollen lips-
tongue-uvula) and associated with at least one of the following: 
a. 
Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, PEF 
decreased, hypoxemia) 
b. 
Reduced blood pressure (BP) or associated symptoms of end-organ dysfunction 
(e.g., , hypotonia (collapse), syncope, incontinence) 
2. Two or more of the following that occur after exposure to a likely allergen for that 
patient (minutes to several hours): 
a. 
Involvement of the skin-mucosal tissue (e.g., , generalized hives, itching-
flushing, swollen lips-tongue-uvula) 
b. 
Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, PEF 
decreased, hypoxemia) 
c. 
Reduced BP or associated symptoms (e.g., hypotonia (collapse), syncope, 
incontinence) 
d. 
Persistent gastrointestinal symptoms (e.g., cramping abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several 
hours); systolic blood pressure (SBP) lower than 90 mmHg or reduction from baseline 
greater than 30%; 
Whether the infection is classified as opportunistic infection will be determined after discussion 
with medical monitors. When reporting opportunistic infection, the investigators will take 
Winthrop et al. 2015 [35] as reference. 
10.4.4. Pregnancy Report 
For all pregnancies of the female subjects participating in the study and the female partners of 
the male subjects determined from the subject’s first drug administration to 8 weeks after the 
last dose of study drug, the investigator must report to the medical monitor and the sponsor 
within 24h by using the pregnancy report form provided by the sponsor/CRO. The patient 
will be asked to provide information about the outcome of the pregnancy, including early 
termination (selective abortion). Abnormal pregnancy outcomes such as spontaneous abortion 
and congenital abnormalities will be reported as SAEs, and an SAE form should be submitted. 
Pregnancy itself is not an SAE. Female patients who become pregnant during the study period 
and after randomization must immediately withdraw from the study drug treatment and be 
followed up to the pregnancy outcome, including delivery or termination of pregnancy. Every 
effort should be made to follow up the pregnancy until the end of the pregnancy. If possible, 
the investigator will follow the delivery for 4 weeks to observe possible congenital 


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abnormalities. The pregnancy of a male patient’s partner is not considered an AE, and the male 
patient should not withdraw from the study. If the partner of a male patient becomes pregnant 
during this period (from the first dose to 8 weeks after the last dose), the investigator will notify 
the sponsor and the EC, and provide appropriate medical follow-up with the consent of the 
partner.  
10.5. Sponsor’s Responsibility for Safety Reports 
The sponsor will monitor and assess the safety of the study drug during the study period, 
manage and report all AE in accordance with all applicable regulations, and include them in 
the final clinical study report. All suspected unexpected SAEs (SUSAR) that are reasonably 
related to the study drug should be reported to the investigator, clinical trial institution/EC, 
drug regulatory authority, and competent health authority. 
10.5.1. Suspected Unexpected Serious Adverse Reactions  
Before an SAE is determined as a suspected unexpected serious adverse reaction (SUSAR), 
the SAEs and SUSAR should be handled in the same way. The investigator should report all 
SAEs within the agreed time limit to the sponsor.  
If the nature and severity of the AE is inconsistent with the existing information provided by 
the sponsor, such as the Investigator's Brochure for the study drug, the package insert of the 
marketed drug, or the summary of product characteristics, it is an “unexpected” AE. Since 
CBP-201 has not yet been approved for marketing, information related to the study drug can 
be found in the Investigator's Brochure. For unexpected events where the investigator or 
sponsor judges that there is a reasonable possibility that the SAEs have been caused by the 
study drug, the sponsor will expedite the report in accordance with the relevant requirements 
of the Good Clinical Practice for Pharmaceuticals (2020 Edition): 
• 
After receiving the safety-related information from any source, the sponsor shall 
immediately analyse and assess it, including the severity, correlation with the study 
drug, and whether it is an expected event. The sponsor shall promptly report SUSAR 
to all investigators and clinical trial institutions participating in the clinical trial and 
the Ethics Committee; the sponsor shall report SUSAR to the drug regulatory 
authority and the competent health authority. 
• 
After receiving the relevant safety information of the clinical trial provided by the 
sponsor, the investigator should sign and read it in time, and consider the treatment 
of the subject and whether to make corresponding adjustments, communicate with 
the subject as soon as possible if necessary, and report the SUSAR provided by the 
sponsor to the EC. 
• 
According to the Standards and Procedures for Rapid Reporting of Safety Data 
during Drug Clinical Trials, for fatal or life-threatening SUSARs, the sponsor should 
report as soon as possible after being first notified, but no more than 7 days, and 
report and improve follow-up information within the following 8 days. For non-fatal 


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or life-threatening SUSAR, the sponsor should report it as soon as possible after first 
being notified, but no more than 15 days. 
The sponsor will conduct regular and annual reports in accordance with the requirements of 
laws and regulations. 
 
 


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11. 
Data Management 
11.1. Data Management Process 
The data management of this study is in the charge of the CRO’s Data Department to ensure 
the authenticity, completeness, privacy and traceability of clinical research data. The detailed 
data management procedures will be described in a separate data management plan. 
11.2. Data Collection 
Data will be collected through an electronic data collection system (EDC). The investigator or 
the site staff authorized by the investigator will enter the subject data into the eCRF. The 
investigator or the staff authorized by the investigator will receive appropriate training and take 
appropriate information security measures before the initiation of the study site or data entry. 
The investigator should supervise the data collection at the study site. The investigator should 
ensure that all clinical trial data are obtained from clinical trial source files and trial records, 
and are accurate, complete, readable and timely. The source data should be attributable, legible, 
contemporaneous, original, accurate, complete, consistent, and enduring. The modification of 
the source data should leave trails, the original data should not be concealed, and the reason for 
the modification should be recorded. 
Unless otherwise specified, eCRF will only be used as a form for collecting data and cannot be 
used as original materials. Source documents refer to the original records, documents and data 
generated in this study, such as hospital medical records, medical images, laboratory records, 
memos, subject diaries or assessment forms, drug distribution records, data automatically 
recorded by instruments, X-rays, subject files, clinical trial-related documents and records kept 
by pharmacies, laboratories, and medical technology departments, including certified copies. 
The source file includes the source data, which can exist in paper or electronic forms. In order 
to avoid differences in assessments between different assessors, it is necessary to ensure that 
the baseline and all subsequent efficacy and safety evaluations of the same subject are 
completed by the same assessor. 
The investigator is responsible for maintaining all original documents and ensuring that they 
are monitored by the CRA at each visit. In addition, the investigator is required to submit a 
complete eCRF for each subject participating in the study, regardless of the length of time the 
subject has participated in the study, carefully verify the study number and subject number of 
all supporting documents (such as laboratory records or study site records) submitted with the 
eCRF, and delete all personal private information (including the subject’s name) or make it 
illegible to protect the privacy of subjects. 
11.3. Database Design 
The eCRF is constructed in the EDC system by the CRO’s Data Department, and the process 
should meet the requirements of the FDA 21 CFR Part 11. The database should manage the 
system login, data entry, modification, deletion and other data traces, and the establishment of 


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the database should adopt the standards of the Clinical Data Interchange Standards Consortium 
(CDISC). 
The sponsor should have written procedures to ensure that their changes to eCRF are necessary, 
recorded, and approved by the investigator. The investigator should keep records of revisions 
and corrections. 
11.4. Data Entry and Modification 
The investigator or the site staff authorized by the investigator should fill in and modify the 
eCRF in accordance with the instructions provided by the CRO’s Data Department. The CRA 
does not have this authority. The investigator should ensure that the data in various eCRF and 
other reports is accurate, complete, clear and timely. All data should be entered into the EDC 
during the visit or as soon as possible after the visit, and data entry should be carried out in 
strict accordance with the principle of “what you see is what you record”. The EDC must be 
kept up-to-date to ensure that it reflects the latest dynamics of the subjects. If certain 
assessments are not carried out during the study, or certain information is unavailable, 
inapplicable or unknown, the investigator or the authorized site staff should record it in the 
eCRF. 
The data in eCRF will be delivered to the data server. The investigator must review the data to 
ensure the accuracy and correctness of all entered data, and electronically sign the verified data. 
The signed information (including the date of signing) will be stored in the audit trail and shall 
not be changed. 
The data in the eCRF should be consistent with the source file. If there is any inconsistency, a 
reasonable explanation should be made. Any correction or modification of eCRF made by the 
investigator or the authorized site staff should make the initial record clear and identifiable, 
keep the modification trails, explain the reason if necessary, and sign and date the modification. 
Change to the data that have been approved require the investigator to electronically sign again. 
11.5. Data Verification 
According to the finalized data verification plan, data manager will set up a data logic check 
program in the EDC system. 
After the data is entered into the EDC system, the data will be verified through computer logic 
check and manual verification to ensure the logic, consistency and accuracy of the data. 
After the data is entered into the EDC system, if there is any data that does not conform to logic, 
the system logic check will start operation and trigger a query. These queries need to be 
reviewed and answered by the investigator or personnel authorized by the investigator. When 
the updated data makes the logic check no longer valid, the data query will be immediately 
closed; when the study site confirms the data and provides a response, data manager needs to 
review and respond to the information. If the reason provided by the study site is reasonable, 
the data query will be closed; if the data problem is not resolved, data manager can continue to 


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communicate with the study site by continuing to add data queries until the data problem is 
finally resolved. 
The subject data list/report is generated by programming to support manual data verification 
throughout the research process. When any data needs to be clarified/verified/confirmed by the 
investigator, manual queries can be added to the EDC system. These queries will be manually 
closed after the data is corrected or confirmed. The query will be recorded in the audit trail of 
the EDC system, including the operator's name, time and date. 
The data manager should ensure that all queries are resolved before the database is locked, and 
the investigator should complete all electronic signatures in the EDC system to ensure the 
completeness and accuracy of the subject data in the EDC system. 
11.6. Medical Coding 
The data manager of the CRO’s Data Department is responsible for the medical coding work 
of this study. The coding content includes medical history, AE, prior/concomitant medication, 
and prior/concomitant non-drug treatment. 
Medical history and AEs will be coded according to the MedDRA (Version 22.1 or above) and 
submitted in the form of System Organ Class (SOC) and preferred terms. Prior medications 
and concomitant/concurrent medications will be coded using the World Health Organization 
Drug Dictionary (WHODD) (September 2018 version or above), and only the versions 
confirmed by the sponsor will be used for all dictionaries. 
During the coding process, if there is a problem that any data cannot be coded due to improper, 
inaccurate, or vague medical terms, data manager will ask the investigator to verify and confirm 
by way of data queries. 
Before the database is locked, data manager should send a medical coding report to the sponsor, 
which must be reviewed by the sponsor. 
11.7. Data Locking 
After reviewing and confirming that the established database is correct, the principal 
investigator, the sponsor, and the statistician will jointly decide to lock the database, and data 
manager will lock the database in the EDC system. In principle, the locked database is not 
allowed to be changed. If any data that needs to be modified is discovered after the data is 
locked, the main principal investigator, the sponsor, the statistician and data manager must 
agree to unlock the database before modifying it, and save written records and signatures of all 
parties. 
12. 
Statistical Analysis 
12.1. Statistical Analysis Plan 
This section explains the statistical methods used for safety and efficacy analysis. The final 
analysis methods and specific details will be recorded in the official Statistical Analysis Plan 


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(SAP), where PK and PD analyses will be described separately in a PK/PD SAP. The SAP will 
be completed before the database is locked, and include detailed information on how to 
generate variables, how to handle missing data, and how to present the data, as well as detailed 
information on statistical methods used for safety and efficacy analysis. The final clinical study 
report will discuss deviations from the SAP (if any). 
12.2. Statistical Hypothesis 
Primary hypothesis: 
H0: There is no efficacy difference between the CBP-201 300 mg Q2W group and the 
placebo group at W16 of treatment;  
H1: There is an efficacy difference between the CBP-201 300 mg Q2W group and the 
placebo group at W16 of treatment. 
12.3. Basis of Sample Size 
The sample size of 255 cases (in a 2:1 ratio, 170 cases in the CBP-201 300 mg Q2W group, 
and 85 cases in the placebo group. Assuming that the dropout rate in the treatment group is 
15%, then about 144 cases in the CBP-201 300 mg Q2W group and 72 cases in the placebo 
group will be able to complete the study) can provide a power of 90% to detect the therapeutic 
effect on the primary endpoint in the CBP-201 300 mg Q2W group and the placebo group. This 
power is calculated based on the following assumption: the proportion of subjects reaching the 
primary efficacy endpoint is 27% in the CBP-201 300 mg Q2W group and 9% in the placebo 
group, and the significance level for two-sided tests is 0.05. 
Based on the results of another conducted phase II international multicenter clinical study of 
CBP-201 in patients with moderate-to-severe atopic dermatitis, the proportion of subjects 
reaching the primary efficacy endpoint was 28.1% in the CBP-201 300mg Q2W group and 
10.7% in the placebo group, at a two-sided test significance level of 0.05, and if the results of 
this trial are similar to that of the WW001 trial, the above sample size would provide a power 
of more than 85% to detect the therapeutic effect on the primary endpoint between the CBP-
201 300 mg Q2W group and the placebo group. Therefore, no adjustment is made to the sample 
size. 
The primary analysis of this study will still be based on the 255 subjects enrolled in accordance 
with V2.1 and its earlier versions of the protocol. Subjects newly enrolled (approximately 81 
cases) based on the protocol after V2.1 will not be included in the primary analysis, and only 
supplementary analysis will be performed.  
12.4. Analysis Populations 
In this study, it is planned to perform statistical analyses in two stages: 
First of all, after the 255 subjects enrolled based on the V2.1 and prior versions of the protocol 
complete the administration and treatment, related evaluations and follow-up of Stage 1 (W16 


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pre-dose visit), the primary analysis will be performed based on the data of the 255 subjects, 
and the following 6 analysis populations are defined as: 
• 
Screening set 1 will include all subjects who have signed the ICF. 
• 
Randomization set 1 will include all subjects randomized at baseline (D1), regardless 
of whether they have received the treatment of study drug.  
• 
Full analysis set 1 (FAS1) will include all subjects in randomization set 1 who have 
received at least one dose of the study drug. FAS1 will determine the treatment 
groups based on the planned treatment.  
• 
Per protocol set 1 (PPS1) will include all subjects in FAS1 without any major 
protocol deviation.  
• 
Safety set 1 (SS1) will include all subjects who have received at least one dose of 
the study drug. SS1 will determine the treatment groups based on the actually 
received treatment.  
• 
PK set 1 (PKS1) will include subjects in randomization set 1 who have received at 
least one dose of CBP-201 active drug and had at least 1 collected and analyzable 
PK sample. 
After all subjects (including approximately 81 additional subjects enrolled) entering Stage 2 
have completed the treatment, evaluations and follow-up of Stage 2, a Stage 2 analysis will be 
performed. The Stage 2 analysis will be defined as the following 6 analysis populations: 
• 
Randomization set 2 will include all subjects entering Stage 2, including all subjects 
who are randomized into Group C or Group D, and subjects entering Group E. 
• 
Full analysis set 2 (FAS2) will include all subjects in randomization set 2 who have 
received at least one dose of study drug in Stage 2. FAS2 will determine the treatment 
groups based on the planned treatment.  
• 
Per protocol set 2 (PPS2) will include all subjects in FAS2 without any major 
protocol deviation. 
• 
Safety set 2 (SS2) will include all subjects in randomization set 2 who have received 
at least one dose of study drug in Stage 2. SS2 will determine the treatment groups 
based on the actually received treatment. 
• 
Safety set 3 (SS3) will include all subjects in SS1 and SS2 who have received at least 
one dose of the study drug. 
• 
PK set 2 (PKS2) will include subjects who have received at least one dose of CBP-
201 active drug in Stage 2 and had at least 1 collected and analyzable PK sample.  
At stage 2, for subjects in group C or group D who have not achieved EASI-50 and are therefore 
assigned to group E to receive subcutaneous injection of CBP-201 300 mg every 2 weeks, their 


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efficacy variables and safety variables will be analyzed by assigned treatment groups or actual 
treatment groups and by stages.   
The detailed definition of the statistical analysis data sets will be supplemented or adjusted in 
the SAP. 
12.5. Analysis Plan 
Statistical analyses will be performed using SAS 9.4 or higher version. 
Descriptive statistics will be used to summarize demographics, baseline characteristics, 
exposure, safety data, PK and PD data. For continuous variables, descriptive statistics will 
include the number of observed subjects, the number of subjects with missing observations, 
mean, SD, standard error, minimum, median, maximum, frequency, and percentage. For 
lognormally distributed data, the geometric mean, geometric standard deviation and geometric 
coefficient of variation will be calculated. For categorical variables or ordinal data, the 
frequency and percentage of each category will be listed. 
For changes in continuous variables from baseline, the results will be presented according to 
their corresponding post-baseline visits. All research data and other clinically significant data 
used to generate tables and figures will be listed by treatment group, subject, and time point. 
Definition of baseline: 
Primary analysis: The baseline of efficacy analysis is defined as the last available value before 
randomization in Stage 1, and the baseline of safety analysis is defined as the last available 
value before the first dose in Stage 1. 
Stage 2 analysis: Two sets of baselines are defined. 
• 
The first set of baselines: the baseline of efficacy analysis is defined as the last 
available value before randomization in Stage 1, and the baseline of safety analysis 
is defined as the last available value before the first dose. 
• 
The second set of baselines: The baseline of efficacy analysis is defined as the last 
available value before randomization in Stage 2 or before entering Group E, and the 
baseline for safety analysis is defined as the last available value before the first dose 
in Stage 2. 
After the 255 subjects enrolled based on the V2.1 and prior versions of the protocol complete 
the administration and treatment, related evaluations and follow-up of Stage 1 (W16 pre-dose 
visit), the primary analysis will be performed.  
For subjects entering stage 2 study, analyses will be performed based on the baseline of the 
two groups. 
During the primary analysis, the W16 data will be unblinded and statistically analyzed. The 
statistically significant type I error level of the primary efficacy endpoint analysis is set at 0.05 
(two-sided test).  


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After all subjects (including approximately 81 additional subjects enrolled) entering Stage 2 
have completed the treatment, evaluations and follow-up of Stage 2, a Stage 2 analysis will be 
performed. Statistical inference will not be performed during the Stage 2 analysis. 
12.6. Study Subjects and Demographics 
12.6.1.  Disposition and Withdrawal 
The number of subjects who have failed screening (along with the reason), been randomized, 
completed the study, and early terminated the study (along with the reason for ET) will be 
summarized in the table and classified by treatment group. The number of subjects in each 
analysis population will be reported. 
12.6.2. Protocol Deviations 
Before the database is locked, all protocol deviations will be classified and recorded, and 
discussed in the CSR. All protocol deviations (including minor deviations and major deviations) 
will be listed in the data listings. 
12.6.3. Demographics and Other Baseline Characteristics 
Demographic data and baseline characteristics (including age, gender, weight, and height) will 
be summarized for each treatment group and the overall population using descriptive statistics. 
Demographic characteristics and baseline characteristics will be listed and summarized. The 
medical history and clinical laboratory test results at the time of screening will be listed. 
Prior medications and concomitant medications will be summarized by treatment group and 
the number and percentage of subjects who have used each drug, and classified by using the 
World Health Organization Drug Dictionary’s Anatomical, Therapeutic, and Chemical 
Classification (WHO ATC) and preferred terms.  
12.6.4. Exposure 
This study is a 2-stage repeated dosing study, and the study treatment dosing will be 
summarized according to the study stage and treatment regimen group. 
12.7. Efficacy Endpoint Analysis 
12.7.1. Test Strategies 
In order to control the probability of type I error in multiple comparison, a fixed-sequence 
method (based on the sequence for key secondary endpoints listed in this protocol) will be used. 
First of all, comparison of primary efficacy endpoint will be made between the treatment group 
and the placebo group. If the efficacy of primary efficacy endpoint is statistically significant, 
the comparison of key secondary efficacy endpoints between treatment group and the placebo 
group will be made based on the sequence specified in the protocol.  
12.7.2. Estimand and Intercurrent Events 


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Table 12.1 Intercurrent Events 
Label 
Intercurrent event 
Strategy 
Remarks 
Intercurrent 
event 1 (use of 
prohibited 
drugs/treatments 
specified in the 
protocol for 
which the study 
treatment must 
be early 
terminated due to 
poor treatment 
effect) 
 
Dupilumab or any anti-IL-4Rα or IL-13 
antibodies; 
 
Topical PDE-4 inhibitors or JAK inhibitors; 
 
Systemic treatment with corticosteroids or 
other immunosuppressive and/or 
immunomodulatory agents, such as 
cyclosporine, mycophenolate mofetil, 
azathioprine, methotrexate, or oral JAK 
inhibitors; 
 
Cell depletion agents (e.g., Rituximab) or 
other biological agents; 
 
Other investigational drugs (non CBP-201) 
or treatments. 
Due to the poor treatment effect, the above 
prohibited drugs/treatments have been used 
before the W16 visit.  
Composite 
strategy 
This type of 
intercurrent 
event occurs 
because of 
poor treatment 
effect, and 
should be 
treated as non-
response. 
 
If it is a 
continuous 
variable, the 
data after the 
occurrence of 
the 
intercurrent 
event should 
be imputed 
with WOCF. 
Intercurrent 
event 2 (use of 
other prohibited 
drugs/treatments 
specified in the 
protocol other 
than those in 
Intercurrent 
Event 1, with a 
negligible impact 
on the 
assessment of the 
primary 
endpoint) 
 
Initiation of SIT or dose up-regulation; 
 
TCS or TCI; 
 
Phototherapy (NBUVB, UVB, UVA1, 
PUVA), sunbed or any other LED therapies; 
 
Bleaching baths more than 2 times a week; 
 
Any drug (except mild emollients) that may 
interfere with the evaluation of efficacy 
results or affect the evaluation of AD 
severity. 
The cumulative duration of use of the above 
prohibited drugs/treatments before the W16 visit 
is no more than 7 days, and the end date is at least 
4 weeks away from the W16 visit. 
Treatment 
policy 
strategy 
The impact on 
the assessment 
of efficacy 
endpoints can 
be ignored, 
and the actual 
observed value 
is used. If the 
actual 
observed value 
is missing, it 
will be 
processed 
according to 
the principle 
for processing 
missing 
values. 
Intercurrent 
event 3 (use of 
other prohibited 
drugs/treatments 
specified in the 
protocol other 
than those in 
Intercurrent 
 
Initiation of SIT, or dose up-regulation; 
 
TCS or TCI; 
 
Phototherapy (NBUVB, UVB, UVA1, 
PUVA), sunbed or any other LED therapies; 
 
Bleaching baths more than 2 times a week; 
 
Any drug (except mild emollients) that may 
interfere with the evaluation of efficacy 
results or affect the evaluation of AD 
Composite 
strategy 
This type of 
intercurrent 
event occurs 
because of 
poor treatment 
effect, and 
should be 
treated as non-


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Label 
Intercurrent event 
Strategy 
Remarks 
Event 1 due to 
poor treatment 
effect, with a 
major impact on 
the assessment of 
the primary 
endpoint)  
severity. 
The cumulative duration of use of the above 
prohibited drugs/treatments before the W16 visit 
is more than 7 days, or the end date is less than 4 
weeks away from the W16 visit. 
response. 
 
If it is a 
continuous 
variable, the 
data after the 
occurrence of 
the 
intercurrent 
event should 
be imputed 
with WOCF. 
Intercurrent 
event 4 (early 
termination of 
treatment/EOT 
due to adverse 
events)  
The subject experiences an AE or SAE that is 
considered by the investigator to be intolerable 
before the W16 visit, and is unsuitable for 
continuing the study treatment, resulting in early 
termination of treatment/EOT. 
Composite 
strategy 
This type of 
intercurrent 
event occurs 
because of 
poor safety of 
treatment, and 
should be 
treated as non-
response. 
 
If it is a 
continuous 
variable, the 
data after the 
occurrence of 
the 
intercurrent 
event should 
be imputed 
with WOCF. 
Intercurrent 
event 5 (the 
subject’s 
administration is 
missing due to 
the COVID-19 
epidemic)   
The administration at two consecutive visits 
immediately before the W16 visit is missing or 
the administration in the Stage 1 treatment period 
is missing for ≥3 times. 
Hypothetical 
strategy 
The actual 
observed 
values are not 
used, and the 
J2R (jump to 
reference) 
method is used 
for imputation. 
Table 12.2 Definition of Estimand for the Primary Endpoint and Strategies for 
Managing Intercurrent Events 
Primary objective 
To assess the efficacy of CBP-201 in subjects with moderate to severe 
AD 
Label of estimand 
Estimand of primary endpoint 


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Description of Estimand 
A patient is considered as treatment success if: 
The patient has an IGA score of 0-1 which is decreased by ≥ 2 points 
from baseline at W16. 
A patient should be regarded as treatment failure if he/she uses 
prohibited drugs/treatments specified in the protocol for which the 
study treatment must be early terminated or other rescue therapy that 
has a major impact on the assessment of the primary endpoint due to 
poor treatment effect, or has early termination of treatment/EOT due 
to adverse events.  
Target population 
Patients aged 12 years and older with moderate to severe AD and 
weighing ≥40 kg 
Primary endpoint 
1) IGA score is 0 or 1 at W16, and improved by at least 2 grades from 
baseline at W16;  
2) A patient should be regarded as treatment failure if he/she uses 
prohibited drugs/treatments specified in the protocol for which the 
study treatment must be early terminated or other rescue therapy that 
has a major impact on the assessment of the primary endpoint due to 
poor treatment effect, or has early termination of treatment/EOT due 
to adverse events.  
Study treatment 
 
The subjects will receive a subcutaneous injection of CBP-201 
600 mg (4 ml) on Day 1, begin to receive a subcutaneous 
injection of CBP-201 300 mg (2 ml) from Week 2 (W2), and 
receive treatment at the same dose every 2 weeks thereafter until 
W14; 
 
The subjects will receive a subcutaneous injection of placebo 4 
ml on Day 1, begin to receive a subcutaneous injection of 
placebo 2 ml from W2, and receive placebo 2 ml every 2 weeks 
thereafter until W14. 
Population-level summary 
The difference in the proportion of subjects whose IGA score is 0-1 
and decreased by ≥2 points from baseline at W16 between the CBP-
201 group and the placebo group. 
Strategies for Managing 
Intercurrent Events 
  
Intercurrent event 1 (use of 
prohibited 
drugs/treatments 
specified in the protocol for 
which the study treatment must 
be early terminated due to poor 
treatment effect) 
Composite strategy 
Intercurrent event 2 (use of other 
prohibited 
drugs/treatments 
specified in the protocol other 
than those in Intercurrent Event 
1, with a negligible impact on the 
assessment 
of 
the 
primary 
endpoint) 
Treatment policy strategy 
Intercurrent event 3 (use of other 
prohibited 
drugs/treatments 
Composite strategy 


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specified in the protocol other 
than those in Intercurrent Event 1 
due to poor treatment effect, with 
a major impact on the assessment 
of the primary endpoint) 
Intercurrent 
event 
4 
(early 
termination of treatment/EOT 
due to adverse events) 
Composite strategy 
Intercurrent event 5 (the subject’s 
administration is missing due to 
the COVID-19 epidemic)   
Hypothetical strategy 
Rationale for the strategies 
The primary objective of the trial is to prove the clinical efficacy of 
CBP-201 compared with placebo in patients aged 12 years and older 
with moderate to severe AD and weighing ≥40 kg. A patient should 
be regarded as treatment failure if he/she uses prohibited 
drugs/treatments specified in the protocol for which the study 
treatment must be early terminated or other rescue therapy that has a 
major impact on the assessment of the primary endpoint due to poor 
treatment effect, or has early termination of treatment/EOT due to 
adverse events. For cases in which subjects are affected by the 
COVID-19 epidemic to result in missing administrations that will 
affect the assessment of efficacy (ie, intercurrent event 5), subsequent 
data will no longer be used. 
Table 12.3 Definition of Estimand for Key Secondary Endpoints and Strategies for 
Managing Intercurrent Events 
Label of estimand 
Estimand of key secondary endpoints 
Description of estimand 
• 
Achieving EASI-75 at W16; 
• 
Weekly average PP-NRS decreased by ≥ 4 points from baseline 
at W16; 
• 
Weekly average PP-NRS decreased by ≥ 3 points from baseline 
at W16; 
• 
Change and percentage change in the weekly average PP-NRS 
from baseline at W16; 
• 
Achieving EASI-90 at W16. 
A patient should be regarded as treatment failure if he/she uses 
prohibited drugs/treatments specified in the protocol for which the 
study treatment must be early terminated or other rescue therapy that 
has a major impact on the assessment of the key secondary endpoints 
due to poor treatment effect, or has early termination of 
treatment/EOT due to adverse events. In this case, continuous 
variables should be imputed with WOCF. 
Target population 
Patients aged 12 years and older with moderate to severe AD and 
weighing ≥40 kg 
Key secondary endpoints 
• 
The proportion of subjects achieving EASI-75 at W16; 
• 
The proportion of subjects whose weekly average PP-NRS is 
decreased by ≥ 4 points from baseline at W16; 


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• 
The proportion of subjects whose weekly average PP-NRS is 
decreased by ≥ 3 points from baseline at W16; 
• 
Change and percentage change in the weekly average PP-NRS 
from baseline at W16; 
• 
The proportion of subjects achieving EASI-90 at W16. 
Study treatment 
The subjects will receive a subcutaneous injection of CBP-201 600 
mg (4 ml) on Day 1, begin to receive a subcutaneous injection of 
CBP-201 300 mg (2 ml) from Week 2 (W2), and receive treatment at 
the same dose every 2 weeks thereafter until W14; 
The subjects will receive a subcutaneous injection of placebo 4 ml on 
Day 1, begin to receive a subcutaneous injection of placebo 2 ml from 
W2, and receive placebo 2 ml every 2 weeks thereafter until W14. 
Population-level summary 
The differences in the following endpoint measures between the CBP-
201 group and the placebo group: 
• 
The proportion of subjects achieving EASI-75 at W16; 
• 
The proportion of subjects whose weekly average PP-NRS is 
decreased by ≥ 4 points from baseline at W16; 
• 
The proportion of subjects whose weekly average PP-NRS is 
decreased by ≥ 3 points from baseline at W16; 
• 
Change and percentage change in the weekly average PP-NRS 
from baseline at W16; 
• 
The proportion of subjects achieving EASI-90 at W16. 
Strategies for Managing 
Intercurrent Events 
  
Intercurrent event 1 (use of 
prohibited 
drugs/treatments 
specified in the protocol for 
which the study treatment must 
be early terminated due to poor 
treatment effect) 
Composite strategy 
Intercurrent event 2 (use of other 
prohibited 
drugs/treatments 
specified in the protocol other 
than those in Intercurrent Event 
1, with a negligible impact on the 
assessment 
of 
the 
primary 
endpoint) 
Treatment policy strategy 
Intercurrent event 3 (use of other 
prohibited 
drugs/treatments 
specified in the protocol other 
than those in Intercurrent Event 1 
due to poor treatment effect, with 
a major impact on the assessment 
of the primary endpoint) 
Composite strategy 
Intercurrent 
event 
4 
(early 
termination of treatment/EOT 
due to adverse events) 
Composite strategy 
Intercurrent event 5 (the subject’s Hypothetical strategy 


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administration is missing due to 
the COVID-19 epidemic)   
Rationale for the strategies 
The primary objective of the trial is to prove the clinical efficacy of 
CBP-201 compared with placebo in patients aged 12 years and older 
with moderate to severe AD and weighing ≥40 kg. A patient should 
be regarded as treatment failure if he/she uses prohibited 
drugs/treatments specified in the protocol for which the study 
treatment must be early terminated or other rescue therapy that has a 
major impact on the assessment of the key secondary endpoints due 
to poor treatment effect, or has early termination of treatment/EOT 
due to adverse events. Continuous variables should be imputed with 
WOCF. For cases in which subjects are affected by the COVID-19 
epidemic to result in missing administrations that will affect the 
assessment of efficacy (ie, intercurrent event 5), subsequent data will 
no longer be used. 
12.7.3.  Overview of Statistical Methods: Estimation of Estimand and Sensitivity Analysis 


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Table 12.4 Summary of Statistical Methods and Sensitivity Analysis for the Primary Endpoint and Key Secondary Endpoints 
Label 
of 
estimand  
Description of estimand 
Main estimator 
Sensitivity/ Supplementary 
analysis 
Analysis sets 
Rules for imputation 
Model/method for the 
main analytical methods 
Estimand 
of 
the 
primary 
endpoint  
The difference in efficacy in 
patients aged 12 years and older 
with moderate to severe atopic 
dermatitis and weighing > 40 kg 
between the CBP-201 300 mg 
Q2W group and placebo group. 
 
A 
patient 
is 
considered 
as 
treatment success if the patient has 
an IGA score of 0-1 which is 
decreased by ≥ 2 points from 
baseline at W16. 
A patient should be regarded as 
treatment failure if he/she uses 
prohibited 
drugs/treatments 
specified in the protocol for which 
the study treatment must be early 
terminated or other rescue therapy 
that has a major impact on the 
assessment 
of 
the 
primary 
endpoint due to poor treatment 
effect, or has early termination of 
treatment/EOT due to adverse 
events.  
FAS (will include 
all 
subjects 
in 
Randomization Set 
1 
who 
have 
received the study 
drug at least once.) 
For 
subjects 
who 
experience intercurrent 
events, their visits after 
the intercurrent events 
will 
be 
handled 
in 
accordance 
with 
the 
strategies for managing 
intercurrent events listed 
in Table 12.1 and Table 
12.2. 
If the target variable is 
still 
missing 
after 
application 
of 
the 
strategies for managing 
intercurrent events, the 
multiple imputation (MI) 
method will be used to 
impute the missing data 
in the placebo group, and 
the 
J2R 
(jump 
to 
reference) method will 
be used to impute the 
missing data in the CBP-
201 group. The detailed 
methods 
will 
be 
specified in the SAP. 
Differences 
in 
response 
rates between the treatment 
group and placebo group 
and their 95% confidence 
intervals will be analyzed 
using the Cochran-Mantel-
Haenszel test stratified by 
baseline disease severity 
(IGA 3 or 4). The Type I 
error level for statistical 
significance 
of 
the 
difference in response rates 
between 
CBP-201 
and 
placebo is set at 0.05 (two-
sided test). 
Sensitivity 
analysis 
1: 
When the target variable is 
still missing after application 
of the strategy for managing 
intercurrent events, it will be 
classified 
as 
treatment 
failure. 
 
Sensitivity 
analysis 
2: 
When the target variable is 
still missing after application 
of the strategy for managing 
intercurrent events, tipping 
point analysis will be used 
for analysis. 
 
Supplementary Analysis 1: 
Primary analysis will be 
performed using the PPS. 
Supplementary analysis 2: 
The 
treatment 
policy 
strategy will be used for all 
intercurrent events; the FAS 
will be used, and the missing 
data will be subject to the 


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imputation rules of the main 
estimator, 
that 
is, 
the 
multiple imputation method 
(MI) will be used to impute 
the missing data in the 
placebo group, and the J2R 
(jump to reference) method 
will be used to impute the 
missing data in the CBP-201 
group. 
Estimand 
of 
key secondary 
endpoints 
The differences in the following 
measures in patients aged 12 years 
and older with moderate to severe 
AD and weighing ≥40 kg between 
the CBP-201 300mg Q2W group 
and the placebo group: 
• 
The 
proportion 
of 
subjects achieving EASI-
75 at W16; 
• 
The 
proportion 
of 
subjects whose weekly 
average 
PP-NRS 
is 
decreased by ≥ 4 points 
from baseline at W16; 
• 
The 
proportion 
of 
subjects whose weekly 
average 
PP-NRS 
is 
decreased by ≥ 3 points 
from baseline at W16; 
• 
Change and percentage 
change in the weekly 
FAS (will include 
all 
subjects 
in 
Randomization Set 
1 
who 
have 
received the study 
drug at least once.) 
For 
subjects 
who 
experience intercurrent 
events, their visits after 
the intercurrent events 
will 
be 
handled 
in 
accordance 
with 
the 
strategies for managing 
intercurrent events listed 
in Table 12.1 and Table 
12.3. 
If the target variable is 
still 
missing 
after 
application 
of 
the 
strategies for managing 
intercurrent events, the 
multiple imputation (MI) 
method will be used to 
impute the missing data 
in the placebo group, and 
the 
J2R 
(jump 
to 
reference) method will 
be used to impute the 
For categorical variables, 
differences 
in 
response 
rates between the treatment 
group and placebo group 
and their 95% confidence 
intervals will be analyzed 
using the Cochran-Mantel-
Haenszel test stratified by 
baseline disease severity 
(IGA 3 or 4). 
For continuous variables, 
analysis will be performed 
using an MMRM model 
that will include treatment 
group, 
baseline 
disease 
severity (IGA 3 or 4), 
baseline 
value 
of 
the 
corresponding 
endpoint, 
visit, interaction of visit and 
treatment group, and the 
LSMEAN estimate values 
and their 95% confidence 
Sensitivity 
analysis 
1: 
When the target variable is 
still missing after application 
of the strategy for managing 
intercurrent 
events, 
categorical variables will be 
classified 
as 
treatment 
failure. Continuous variables 
should be imputed with 
WOCF. 
  
Supplementary Analysis 1: 
Primary analysis will be 
performed using the PPS. 
Supplementary analysis 2: 
The 
treatment 
policy 
strategy will be used for all 
intercurrent events; the FAS 
will be used, and the missing 
data will be subject to the 
imputation rules of the main 


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average PP-NRS from 
baseline at W16; 
• 
The 
proportion 
of 
subjects achieving EASI-
90 at W16. 
A patient should be regarded as 
treatment failure if he/she uses 
prohibited 
drugs/treatments 
specified in the protocol for which 
the study treatment must be early 
terminated or other rescue therapy 
that has a major impact on the 
assessment of the key secondary 
endpoints due to poor treatment 
effect, or has early termination of 
treatment/EOT due to adverse 
events. 
Continuous 
variables 
should be imputed with WOCF. 
missing data in the CBP-
201 group. The detailed 
methods 
will 
be 
specified in the SAP. 
intervals 
will 
be 
summarized. 
estimator, 
that 
is, 
the 
multiple imputation method 
(MI) will be used to impute 
the missing data in the 
placebo group, and the J2R 
(jump to reference) method 
will be used to impute the 
missing data in the test 
group. 
 
  


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12.7.4. Subgroup Analysis 
For the primary endpoints and key secondary endpoints, subgroup analysis will be performed 
by baseline characteristics of subjects (e.g., age, severity of disease at baseline, etc.) using the 
same methodology as the main estimator. 
12.8. Safety Analysis 
Safety results will be summarized by treatment group. All safety analyses will be performed 
on SS1 or SS2. AEs will also be analyzed in all subjects who have received at least one dose 
of study drug in SS3. Safety analyses include TEAEs, AESIs, SAEs, TEAEs at the injection 
site, eye examination results, laboratory tests, VS, PE, 12-lead ECG results, and ADA test 
results. Safety data will be summarized by Frequency Tables (counts and percentages) and, 
where applicable, presented by treatment and scheduled time. The data will be compared with 
the reference range provided to check for abnormalities and/or clinically relevant changes from 
baseline (where applicable). In addition, subgroup analysis of part of safety endpoints will be 
analyzed by age groups(≥18 years and <18 years). 
Treatment-emergent adverse event (TEAE) 
AEs will be classified in accordance with the terms of Medical Dictionary for Regulatory 
Activities (MedDRA). The incidence table and the number (n) and the percentage (%) of 
patients with TEAEs in each treatment group will be provided according to the system organ 
class (SOC) (sorted according to the internationally agreed order) and preferred term (PT) (in 
alphabetical order). Multiple occurrences of the same event in the same patient are counted 
only once in the table during the treatment period. The denominator of the percentage 
calculation is the safety population in each treatment group. 
According to SOC and PT, the severity of TEAE in each treatment group and the correlation 
with study drug will be summarized. 
TEAEs at the injection site will be summarized in the same way. 
The number (%) of patients with at least one treatment-emergent SAE will be summarized by 
treatment group, and displayed by major SOC and PT (in alphabetical order). SAEs will be 
listed by treatment group and patient. 
The number (%) of patients with at least one TEAE that leads to permanent discontinuation of 
treatment will be summarized by treatment group (%), and displayed by major SOC and PT (in 
alphabetical order). The TEAEs that lead to permanent discontinuation of treatment will be 
listed by treatment group and patient. 
According to AESI category and PT, the total number of patients (%) who have experienced 
AESI during treatment will be displayed in a descending order of the incidence of PT in each 
AESI category. 
Safety laboratory tests 


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Descriptive statistics will be used to summarize the baseline value of laboratory test results and 
the changes from baseline to each visit. 
- 
According to laboratory-wide specifications, clinical laboratory parameters will be 
classified into low, normal, or high, and the number and percentage of subjects in 
each category will be summarized. 
- 
Shift tables based on normal/abnormal baseline values and other tabular and 
graphical methods may be used to display the results of laboratory tests of interest. 
- 
Lists with flags that indicate values outside the laboratory's range will be provided. 
Vital signs 
Descriptive statistics will be used to summarize the baseline values of vital signs (body 
temperature, pulse, blood pressure, and respiratory rate) and the changes from baseline to each 
visit. 
Other safety data, including eye examination results, PE, 12-lead ECG results, and ADA test 
results will be classified and summarized, and the frequency and percentage of each category 
will be listed. 
12.9. PK Analysis 
If applicable, descriptive statistics will be used to summarize individual blood drug 
concentrations by treatment and scheduled time, or plot a curve of means over time. 
12.10. PD Analysis 
Descriptive statistics will be used to summarize changes in serum IL-4, IL-13, IgE, TARC 
levels and peripheral blood eosinophil counts by treatment and scheduled time, and where 
applicable, plot the mean and SD change curves in each treatment group. 
12.11. Data Convention 
If the start date of an AE or concomitant medication is incomplete or missing, it is assumed 
that the AE has occurred during or after the use of the study drug, unless the incomplete date 
(e.g., month and year) clearly shows that the event began before treatment. If part of the date 
indicates the same month or year as the study drug use date, the start date of the AE is imputed 
according to the study drug use date. Otherwise, the missing day or month is imputed according 
to the first day or month. 
Missing laboratory data, ECG data, vital signs data, physical examination and other safety data 
will not be imputed. 
12.12. Interim Analysis 
No interim analysis is planned for this study. 
 
 


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13. 
Clinical Trial Management 
13.1. Statement 
This clinical trial will be conducted in accordance with the standard operating procedures of 
the sponsor and the CRO. These SOPs are designed to ensure that the trial complies with the 
Declaration of Helsinki (2017 Edition), the Guidelines for Good Clinical Practice promulgated 
by ICH, the Good Clinical Practice for Pharmaceuticals promulgated by the NMPA, and the 
requirements of drug clinical trial regulations. 
When signing the protocol, the investigator will agree to conduct the study in strict accordance 
with the protocol, clinical trial specifications, and relevant laws and regulations, and keep all 
the information provided by the sponsor in accordance with confidentiality requirements. 
13.2. Ethics 
13.2.1. Ethical Implementation/Approval of the Study 
The clinical study protocol must be reviewed and approved by the EC of each study site before 
implementation. The sponsor and the investigator should provide relevant documents to the EC 
during the review period. The clinical study must follow the Declaration of Helsinki (2013 
Edition), the GCP guidelines promulgated by the NMPA and applicable regulatory 
requirements. 
Any modification of the clinical study protocol during the research process must be approved 
by the EC. The investigator is responsible for regularly submitting study progress reports in 
accordance with the relevant requirements of the EC. After the study ends, a clinical study 
report should be submitted to the EC for review. 
13.2.2. Subjects’ Informed Consent 
Subjects and/or their guardians must give their informed consent before the subjects 
undergoing any operations related to the study in order to protect their legitimate rights and 
interests. The investigator is responsible for fully and completely introducing the study 
objectives, methods, effects of the study drug, reasonable expected benefits, possible adverse 
reactions, and possible study risks to the subjects and/or their guardians. Subjects and/or their 
guardians should be informed of rights, risks, and benefits of the subjects, and any new 
information about the study drug should be notified thereto in a timely manner. Subjects and/or 
their guardians should be informed that the clinical study is completely based on the principle 
of voluntary participation. Subjects can unconditionally withdraw from the study at any time 
during the trial and will not be punished for withdrawing from the study. Subjects and/or their 
guardians should be informed that the investigator and the sponsor have the right to read, store, 
and statistically analyze the data of subjects in the study in accordance with relevant regulations. 
The version of the ICF and the date of writing or revision should be indicated. Only subjects 
who fully understand the risks and benefits of the clinical study, as well as potential AEs, and 
sign and date on the ICF can participate in the clinical study. If the clinical study protocol is 


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modified to a certain extent during the research process, the ICF may be modified according to 
the revised content. After the revised ICF is approved by the EC, an updated ICF re-signed by 
the subjects and/or their guardians must be obtained.  
13.2.3. Clinical Study Protocol Changes and Protocol Modifications 
The modifications of the study protocol must be communicated with the study site in written 
form. The investigator is responsible for obtaining the EC approval for all protocol 
modifications and forwarding a copy of the approval to the sponsor. The investigator shall not 
implement this study in accordance with the study protocol amendment before it is approved 
by the EC. 
13.3. Verification of Original Records 
The investigator must properly handle all data obtained in the course of the clinical study to 
ensure the rights and privacy of subjects participating in the clinical study. The investigator 
must agree that the monitor/auditor/inspector can access and review the required clinical 
research data in order to verify the accuracy of the original materials and understand the 
progress of the study. If the original record cannot be verified, the investigator should agree to 
assist the monitor/auditor/inspector to further confirm the quality control of the data. 
13.4. Quality Assurance and Review 
All drugs and materials used in the clinical study must be based on quality control. The sponsor 
and its authorized personnel or related medical management agencies have the right to review 
the clinical study, the purpose of which is to ensure the authenticity of the clinical study record 
data and to comply with the provisions of the clinical study protocol. 
This study will be organized, carried out and reported in accordance with the protocol and the 
standard operating procedures of the sponsor and CRO. In ICH E6, quality assurance (QA) is 
defined as “all those planned and systematic actions that are established to ensure that the trial 
is performed and the data are generated, documented (recorded), and reported in compliance 
with Good Clinical Practice (GCP) and the applicable regulatory requirement(s)”. The 
sponsor's QA work will be carried out in accordance with the regulations of the study audit 
plan. Section 5.19.3 (b) of ICH E6 stipulates that the audit plan and procedures for a trial audit 
should be guided by the importance of the trial to submission to regulatory authorities, the 
number of subjects in the trial, the type and complexity of the trial, the level of risks to the trial 
subjects, and any identified problem(s). The QA work can be outsourced to a CRO or an 
independent consulting agency. The investigator is required to support the audit work, attend 
the audit action as required by the auditor, and allow the auditor to directly access the original 
data/documents, including all medical records, study-related documents and letters, and the 
informed consent documents of the clinical trial. Clinical study subjects will be informed of 
the inspection or audit process of the clinical study, but the privacy and data of subjects will be 
strictly protected.  


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13.5. Electronic Case Report Form 
CRO database programmers will establish eCRF in the EDC system. The eCRF only uses 
appropriate identification codes (e.g., study site number and subject number) to identify 
different subjects. eCRF is used to record the clinical research data of subjects and is an integral 
part of the study and related study reports, so the entry must be accurate and complete. The 
investigator or the site staff authorized by the investigator is responsible for entering, correcting 
or modifying the subject data in the EDC system. It must be ensured that all data is entered and 
stored. The investigator must declare that all the information in the eCRF is true through an 
electronic signature. 
All data should be entered into the EDC during the visit or as soon as possible after the visit in 
order to record the subject's condition. The eCRF must be kept up-to-date to ensure that it 
reflects the latest dynamics of the subjects. 
The sponsor or the CRA designated by the CRO will regularly monitor the eCRF of the study 
site, and check the data recorded in the eCRF with the source files and source data to ensure 
the completeness and accuracy of the data. Manual queries will be proposed in the EDC system 
for questions about data omissions, modifications or clarifications. 
13.6. Drug Counting 
The sponsor is responsible for the supply of study drugs. After receiving the study drug, the 
investigator or authorized personnel must sign for receipt after verifying that it is correct, and 
store it in accordance with the specified storage conditions. 
The investigator or authorized relevant personnel is responsible for accurately recording and 
keeping records of the distribution or use of study drugs by subjects. The study site must keep 
all used and unused study drugs in the original packaging for the sponsor or CRO company 
personnel to monitor. At the end of the study, all used and unused drugs and packaging boxes 
should be returned to the sponsor. 
13.7. Study Monitoring 
The sponsor will entrust the CRO to conduct research and monitoring work. The CRA 
appointed by the CRO should be familiar with the relevant knowledge of the investigational 
medicinal product, familiar with the trial protocol, informed consent form and other written 
materials provided to the subjects, and familiar with the clinical trial standard operating 
procedures, GCP and other related regulations. Monitors should earnestly perform their 
monitoring duties in accordance with the requirements of the sponsor to ensure that the clinical 
trial is correctly implemented and recorded in accordance with the trial protocol. 
Before the start of the study, the sponsor or the CRA appointed by the CRO should inspect the 
clinical study site to confirm that the investigator has sufficient qualifications and resources to 
complete the trial, that the clinical trial institution has the appropriate conditions to complete 
the trial, including staffing and training, and that the laboratory is well-equipped and well-


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functioning, and has various inspection conditions related to the trial. 
The CRA appointed by the CRO will regularly conduct on-site monitoring of the study site, 
and the visit date of each monitoring needs to be recorded on the site visit record of the study 
site. 
The CRA’s study monitoring activities include: 
• 
Verify that the investigational medicinal product is within the validity period, the 
storage conditions are acceptable, and the supply is sufficient during the clinical trial; 
the investigational medicinal product is only provided to appropriate subjects in 
accordance with the dose specified in the trial protocol; the subject receives the 
instructions for correct use, handling, storage and return of the investigational 
medicinal product; the clinical trial institution has proper control and records for 
receiving, using, and returning the investigational medicinal product; the clinical trial 
institution’s disposal of unused investigational medicinal products meets relevant 
laws and regulations and the requirements of the sponsor. 
• 
Verify the investigator's implementation of the trial protocol during the 
implementation of the clinical trial; confirm that all subjects or their guardians have 
signed the informed consent form before the trial; ensure that the investigator receives 
the latest version of the Investigator's Brochure, all trial-related documents and 
required supplies for the trial, and implement in accordance with the requirements of 
relevant laws and regulations; ensure that the study staff has a full understanding of 
the clinical trial. 
• 
Verify that the study staff performs the duties stipulated in the trial protocol and 
contract, and whether these duties are delegated to unauthorized personnel; confirm 
that the selected subjects are qualified and report the enrollment rate and the progress 
of the clinical trial; confirm that the record and the report are correct and complete, 
the trial records and files are updated in real time and kept intact; verify that all 
medical reports, records and files provided by the investigator are traceable, clear, 
synchronized, original, accurate and complete, with the date and trial number 
specified. 
• 
Verify the accuracy and completeness of the eCRF entry and compare it with the 
source files. The monitor should pay attention and verify that the data specified in the 
trial protocol is accurately recorded in the eCRF and consistent with the source files; 
confirm the subject's dose changes, treatment changes, adverse events, concomitant 
medications, complications, loss to follow-up, and omissions in examinations are all 
recorded in the eCRF; confirm that the follow-up not performed, tests not 
implemented and examinations not performed by the investigator, and whether 
mistakes and omissions have been corrected are all recorded in the eCRF; verify that 
the withdrawal and loss to follow-up of selected subjects have been recorded and 
explained in the eCRF. 


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• 
The investigator should be notified of errors, omissions or unclear writing of eCRF; 
the monitor should confirm that the corrections, additions, or deletions made are 
operated by the investigator or authorized personnel, and have been signed and dated 
by the modifier. If necessary, the reason for the modification should be explained. 
• 
Confirm that AEs have been reported within the specified time limit in accordance 
with relevant laws and regulations, the trial protocol, and the requirements of the EC 
and the sponsor. 
• 
Confirm whether the investigator has saved the necessary documents in accordance 
with the  
• 
In the event of deviations from the trial protocol, standard operating procedures, and 
relevant laws and regulations, it is necessary to communicate with the investigator in 
a timely manner, and appropriate measures should be taken to prevent recurrence. 
• 
The sponsor authorizes the monitor to have the right to verify; all observations and 
discoveries during the audit must be able to be verified. If the electronic records are 
kept in the research base, the method of verification must be discussed with the study 
members. 
The source files must at least be used to verify: 
− 
The identity of the subject and whether he/she is qualified; 
− 
Appropriate informed consent procedures; 
− 
Visit date; 
− 
Records of safety and efficacy parameters; 
− 
Adequate AE reports and visits; 
− 
Treatment with concomitant medication; 
− 
Receipt/distribution/return records of drugs; 
− 
Study drug administration information; 
− 
The subject’s completion of the treatment, termination of the treatment or 
withdrawal from the study, and the appropriate reason; 
− 
The data is true, accurate and complete; 
− 
The safety and rights of subjects are protected; 
− 
The investigator's implementation complies with the currently approved 
protocol, GCP and all relevant regulatory requirements. 
The objectives that need to be achieved during the monitoring include: 
• 
Check and evaluate the study progress 
• 
Review the collected research data 
• 
Implement source file verification process 
• 
Identify any problems and develop solutions 
After each monitoring, the monitor should promptly report in writing to the sponsor and/or the 
CRO entrusted by the sponsor; the report should include the date and location of the monitoring, 


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the name of the monitor, and the name of the investigator and other personnel contacted by the 
monitor; the report should also include the summary of the monitoring work, a description of 
the problems and facts found in the clinical trial, deviations and defects from the trial protocol, 
and the monitoring conclusion; the report should state corrective actions that have been adopted 
or are to be adopted in response to the problems found in the monitoring, and recommendations 
to ensure that the trial is implemented in compliance with the trial protocol; the report should 
provide sufficient details to verify compliance with the monitoring plan. The centralized 
monitoring report can be submitted separately from the on-site monitoring report. The sponsor 
should review and follow up on the problems in the monitoring report, and keep them in the 
form of a document. 
During the study period, the CRA needs to directly consult the source data and source files 
related to the clinical trial with the consent of the investigator and the clinical trial institution. 
The investigator must ensure that he/she and related study staff regularly meet with the monitor 
to discuss the findings during the visit and any related issues. In addition, the investigator and 
the clinical trial institution will allow auditors, EC reviewers and inspectors of the drug 
regulatory authority to directly access source data and source files related to the clinical trial. 
The investigator will also allow sponsor representatives, NMPA and/or relevant health 
authorities to inspect the facilities and records related to the study. 
The medical information of the subjects obtained during the research process is confidential, 
and disclosure to third parties other than the above is prohibited.  
13.8. Protocol Deviations 
The investigator should perform this clinical trial in accordance with the clinical trial protocol 
approved by the EC and follow the GCP regulations. The protocol is designed to enable the 
investigator to follow the provisions of Section 4 of ICH E6. During the trial, the investigator 
shall not deviate from the protocol unless emergency measures are required to eliminate the 
direct harm to the subjects. When there are other unexpected situations that require deviation 
from the procedures specified in the protocol, the investigator should consult with the medical 
monitor (and the EC, if necessary) to determine appropriate measures. 
The study site should record all protocol deviations, including but not limited to the time when 
the protocol deviation occurs, the time of discovery, the description of the event and the 
measures taken. In the event of serious protocol deviations, the study site should promptly 
notify the medical monitor, CRA, and EC. 
13.9. Study Completion 
After the study is completed and/or terminated, the sponsor or the CRO requires the provision 
of the following data and materials:  
• 
All case report forms correctly completed by the study staff and signed by the 
investigator;  


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• 
All laboratory results, clinical data and specific test results obtained from the study 
screening to the end of the follow-up period;  
• 
Printed results of pathological diagnosis and assessment of original materials during 
the study period; 
• 
Completed drug inventory records and study materials return records. 
13.10. Intellectual Property Rights 
All information obtained from the sponsor falls into the intellectual property rights of the 
sponsor. Therefore, the clinical trial investigator and all other relevant personnel must strictly 
keep it confidential, and shall not disclose it to any third party without the prior consent of the 
trial sponsor. 
13.11. Subject Privacy 
The investigator must ensure the privacy of clinical study subjects. In all documents submitted 
to the sponsor, only the subjects’ number and initials are used to identify the clinical study 
subjects, and the subjects’ full names cannot be displayed. The investigator must properly keep 
the subjects’ names, addresses and corresponding registration forms. These registration forms 
are to be kept strictly confidential by the investigator and cannot be submitted to the sponsor. 
 
 


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14. 
Paper Publication 
The sponsor has exclusive rights to this study. Because there are many study sites participating 
in this study, unless approved by the sponsor, individual sites or investigators are not allowed 
to write and publish personal articles until the final report of the multi-center study is completed. 
Regarding the manuscript and publication, the sponsor has the right of final decision. 
 
 


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15. 
Data Archiving 
15.1. Source Data and Source Files 
In this trial, the source data includes clinical findings, observations, and records of other related 
activities required to reconstruct and evaluate the clinical trial. The original data is contained 
in the source files. 
The source files involved in the clinical study are original records, documents and data (such 
as hospital medical records, medical images, laboratory records, memos, subject diaries or 
assessment forms, drug distribution records, data automatically recorded by instruments, 
microfilms, photographic plates, magnetic media, X-rays, subject files, clinical trial-related 
documents and records kept by pharmacies, laboratories, and medical technology departments, 
including certified copies, etc.). Source files must be preserved to support the information 
provided in the eCRF. 
15.2. Materials Preservation of Study Facilities 
15.2.1. Materials Related to the Ethics Committee 
The personnel in charge of materials preservation in the study facility must keep the EC 
meeting minutes and abstracts until 5 years after the trial is suspended or completed. If the 
sponsor wishes to keep them for a longer period of time, both parties will discuss and decide 
on the retention time and method. If the study facility makes any changes to the file 
preservation, the personnel in charge of materials preservation or the investigator should 
contact the sponsor. 
15.2.2. Materials Related to the Trial Implementation 
The personnel in charge of materials preservation in the study facility must keep the following 
files until 5 years after the investigational drug is approved for marketing. If the sponsor wishes 
to keep them for a longer period of time, both parties will discuss and decide on the retention 
time and method. If the study facility makes any changes to the file preservation, the personnel 
in charge of materials preservation or the investigator should contact the sponsor. 
 
Original files; 
 
The original or copy of the trial contract and informed consent form, and other GCP-
related materials provided by the staff of the study facility; 
 
Trial protocol, GCP-related data obtained from the EC, or other GCP-related 
materials obtained; 
 
Records of investigational medicinal product management and other records related 
to trial implementation. 
15.3. Sponsor’s Materials Preservation  
The sponsor will keep the following materials (including files and data) until 5 years after the 


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investigational drug is approved for marketing. According to relevant regulations, a longer term 
of preservation may be required. It is the responsibility of the sponsor to inform the 
investigator/study facility when it is no longer necessary to preserve such materials. 
 
The original or copy of the trial protocol, trial contract and study report, and GCP-
related materials provided by the sponsor; 
 
Case report forms, GCP-related notices, or GCP-related materials obtained from the 
investigator; 
 
Monitoring and audit-related records, or other related operation records; 
 
Data obtained in the trial; 
 
Relevant records required by the GCP. 
 
 


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16. 
References 
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27. Blauvelt A, de Bruin-Weller M, Gooderham M et al. Long-term management of 
moderate-to-severe atopic dermatitis with Dupilumab and concomitant topical 
corticosteroids (LIBERTY AD CHRONOS): a 1-year, randomized, double-blinded, 
placebo-controlled, phase 3 trial. Lancet 2017 Jun 10;389(10086):2287-2303. doi: 
10.1016/S0140-6736(17)31191-1. Epub 2017 May 4. 
28. Simpson EL, Paller AS, Siegfried EC et al. Efficacy and safety of Dupilumab in 
adolescents with uncontrolled moderate to severe atopic dermatitis: a Phase 3 randomized 
clinical trial. JAMA Dermatol 2019 Nov 6. doi: 10.1001/jamadermatol.2019.3336. 
29. Thaci D, Simpson EL, Deleuran M et al. Efficacy and safety of dupilumab monotherapy 
in adults with moderate-to-severe atopic dermatitis: a pooled analysis of two phase 3 
randomized trials (LIBERTY AD SOLO 1 and LIBERTY AD SOLO 2). J Dermatol Sci 
2019 May; 94(2):266-75. 
30. CBP-201 IB V5_24Aug2020_CN_Final. 
31. Yosipovitch G, Reaney M, Mastey V et al. Peak Pruritus Numerical Rating Scale: 
psychometric validation and responder definition for assessing itch in moderate-to-severe 
atopic dermatitis. Br J Dermatol. 2019 Oct;181(4):761-769. 
32. https://ctep.cancer.gov/protocolDevelopment/electronic_applications/ctc.htm. 
33. Akinlade B, Guttman-Yassky E, de Bruin-Weller M, et al. Conjunctivitis in dupilumab 
clinical trials. Br J Dermatol. 2019 Sep;181(3): 459-473. doi: 10.1111/bjd.17869. Epub 
2019 May 7. PMID: 30851191; PMCID: PMC6850316. 
34. Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the 
definition and management of anaphylaxis: Summary Report-Second National Institute 
of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network Symposium. J 
Allergy Clin Immunol 2006;117(2):391-97) 
35. Winthrop KL, Novosad SA, Baddley JW, Calabrese L, Chiller T, Polgreen P, Bartalesi F, 
Lipman M, Mariette X, Lortholary O, Weinblatt ME, Saag M, and Smolen J.  
Opportunistic infections and biologic therapies in immune-mediated inflammatory 
diseases:  consensus recommendations for infection reporting during clinical trials and 
postmarketing surveillance.  Ann Rheum Dis 2015 74:2107-2116. 
 
 


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17. 
Appendices 
17.1. Appendix A (Peak Pruritus NRS) 
Peak Pruritus Numerical Rating Scale (PP-NRS) 
Site No.: 
Date: 
Subject initials:  
Subject No.: 
Visit: 
Score: 
The score ranges from 0 to 10, in which 0 represents “no pruritus” and 10 “worst imaginable 
pruritus”. How do you rate your most severe puritus in the past 24 hours?  
 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
□ 
0 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
No 
pruritus 
 
 
 
 
 
 
 
 
 
Worst 
imaginable 
pruritus 
 
 
 


Pr ot oc ol N u m ber: C B P- 2 0 1- C N 0 0 2  
V 4. 0/ A u g ust 1, 2 0 2 2 
C o nfi de ntial I nf or mati o n  
  
Pa ge 1 1 8 of 1 2 9  
1 7. 2.  A p pe n di x B ( D L QI) 
Der m at ol o g y Life Q u alit y I n de x ( D L QI) 
Site N o.:  
Date:  
S u bject i nitials:   
S u bject N o.: 
Visit:
 Sc ore:
 
T he ai m of t his q uesti o n n aire is t o me as ure h o w m uc h y o ur s ki n pr o ble m h as affecte d 
y o ur life O V E R T H E L A S T W E E K. Ple ase  c hec k o ne b o x f or e ac h q uesti o n. 
 
1.  O ver t he last wee k, h o w itc h y, s ore, p ai nf ul  
or sti n gi n g has y o ur s ki n bee n? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
2.  O ver t he last wee k, h o w e m b arr asse d or self 
c o nsci o us  ha ve y o u bee n beca use of y o ur 
s ki n? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
3.  O ver t he last wee k, h o w m uc h has y o ur s ki n 
i nterfere d  wit h  y o u  g oi n g  s h o p pi n g or  
l o o ki n g after y o ur h o me  or y ar d ?  
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
4.  O ver t he last wee k, h o w m uc h has y o ur s ki n 
i nfl ue nce d t he cl ot hes y o u wear? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
5.  O ver t he last wee k, h o w m uc h has y o ur s ki n 
affecte d a n y s oci al or leis ure acti vities? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
6.  O ver t he last wee k, h o w m uc h has y o ur s ki n 
ma de it diffi c ult f or y o u t o d o a n y s p ort ? 
Ver y m uc h 
 
A l ot 
 
A little 
 


Pr ot oc ol N u m ber: C B P- 2 0 1- C N 0 0 2  
V 4. 0/ A u g ust 1, 2 0 2 2 
C o nfi de ntial I nf or mati o n  
  
Pa ge 1 1 9 of 1 2 9  
N ot at all 
 
N ot rele va nt 
 
7.  O ver t he last wee k, has y o ur s ki n pre ve nte d 
y o u fr o m w or ki n g  or st u d yi n g ? 
Yes 
 
N o 
 
N ot rele va nt 
 
If “ N o”, o ver t he last wee k h o w m uc h has y o ur 
s ki n bee n a pr o ble m at w or k  or st u d yi n g? 
A l ot 
 
A little 
 
N ot at all 
 
8.  O ver t he last wee k, h o w m uc h has y o ur s ki n 
create d pr o ble ms wit h y o ur p art ner  or a n y 
of y o ur cl ose frie n ds or rel ati ves? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
9.  O ver t he last wee k, h o w m uc h has y o ur s ki n 
ca use d a n y se x u al diffic ulties? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
1 0.  O ver t he last wee k, h o w m uc h of a pr o ble m 
has t he tre at me nt f or y o ur s ki n bee n, f or 
e xa m ple b y ma ki n g y o ur h o me mess y, or b y 
ta ki n g u p ti me? 
Ver y m uc h 
 
A l ot 
 
A little 
 
N ot at all 
 
N ot rele va nt 
 
Ple ase c hec k y o u h a ve a n s were d E V E R Y q uesti o n.  
T h a n k y o u. 
 
D L QI - I nstr ucti o ns f or use 
T he Der mat ol o g y Life Q ualit y I n de x q uesti o n naire is desi g ne d f or use i n a d ults ( patie nts o ver 
t he a ge of 1 6). It is self e x pla nat or y a n d ca n be si m pl y ha n de d t o t he patie nt w h o is as ke d t o 
fill it i n wit h o ut t he nee d f or detaile d e x pla nati o n. It is us uall y c o m plete d i n o ne t o t w o mi n utes. 
T he sc ori n g of eac h q uesti o n is as f oll o ws: 
 
Ver y m uc h  
sc ore d 3  
 
A l ot  
sc ore d 2  


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• 
A little 
scored 1  
• 
Not at all 
scored 0  
• 
Not relevant 
scored 0  
• 
Question 7: “prevented work or studying”  scored 3  
The DLQI is calculated by summing the score of each question resulting in a maximum of 30 
and a minimum of 0. The higher the score, the more quality of life is impaired.  
Meaning of DLQI Scores 
• 
0-1  
no effect at all on patient's life 
• 
2-5  
small effect on patient's life 
• 
6-10  
moderate effect on patient's life 
• 
11-20  
very large effect on patient's life 
• 
21-30  
extremely large effect on patient's life 
17.3. Appendix C (POEM) 
Patient Oriented Eczema Measure (POEM) 
Site No.: 
Date:  
Subject initials:  
Subject No.: 
Visit: 
Score: 
Please circle one response for each of the seven questions below about your/your child’s 
eczema. If your child is old enough to understand the questions then please fill in the 
questionnaire together. Please leave blank any questions you feel unable to answer. 
1. 
Over the last week, on how many days has your/your child’s skin been itchy because 
of the eczema? 
0 days 
1-2 days 
3-4 days 
5-6 days 
Every day 
2. 
Over the last week, on how many nights has your/your child’s sleep been disturbed 
because of the eczema? 
0 days 
1-2 days 
3-4 days 
5-6 days 
Every day 
3. 
Over the last week, on how many days has your/your child’s skin been bleeding 
because of the eczema? 
0 days 
1-2 days 
3-4 days 
5-6 days 
Every day 
4. 
Over the last week, on how many days has your/your child’s skin been weeping or 
oozing clear fluid because of the eczema? 


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0 days 
1-2 days 
3-4 days 
5-6 days 
Every day 
5. 
Over the last week, on how many days has your/your child’s skin been cracked 
because of the eczema? 
0 days 
1-2 days 
3-4 days 
5-6 days 
Every day 
6. 
Over the last week, on how many days has your /your child’s skin been flaking off 
because of the eczema? 
0 days 
1-2 days 
3-4 days 
5-6 days 
Every day 
7. 
Over the last week, on how many days has your/your child’s skin felt dry or rough 
because of the eczema? 
0 days 
1-2 days 
3-4 days 
5-6 days 
Every day 
Total (maximum 28)______ 
Scores are as follows: 
• 
0 days=0 
• 
1-2 days=1 
• 
3-4 days=2 
• 
5-6 days=3 
• 
Every day=4 


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17.4. Appendix D (IGA) 
Validated Investigator Global Assessment Scale for Atopic Dermatitis  
vIGA-AD™ 
Instruction: 
The IGA score is selected using the descriptors below that best describe the overall appearance 
of the lesions at a given time point. It is not necessary that all characteristics under 
Morphological Description be present. 
Score  
Morphological Description 
0-Clear 
No inflammatory signs of atopic dermatitis (no erythema, no induration/papulation, no 
lichenification, no oozing/crusting). Post-inflammatory hyperpigmentation and/or 
hypopigmentation may be present. 
1-Almost clear 
Barely perceptible erythema, barely perceptible induration/papulation, and/or minimal 
lichenification. No oozing or crusting. 
2-Mild 
Slight but definite erythema (pink), slight but definite induration/papulation, and/or 
slight but definite lichenification. No oozing or crusting. 
3-Moderate 
Clearly perceptible erythema (dull red), clearly perceptible induration/papulation, 
and/or clearly perceptible lichenification. Oozing and crusting may be present. 
4-Severe 
Marked erythema (deep or bright red), marked induration/papulation, and/or marked 
lichenification. Disease is widespread in extent. Oozing or crusting may be present. 
Notes: 
1. 
In indeterminate cases, please use extent to differentiate between scores. 
For example: 
• Patient with marked erythema (deep or bright red), marked papulation and/or marked 
lichenification that is limited in extent, will be considered “3 – Moderate” 
2. 
Excoriations should not be considered when assessing disease severity 
Copyright ©2017 Eli Lilly and Company – Used with the permission of Eli Lilly and Company 
under a Creative Commons Attribution-NoDerivatives 4.0 International License–
https://creotivecommons.org/licenses/bv-nd/4.0/ 


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17.5. Appendix E (EASI) 
Eczema Area and Severity Index (EASI) 
The EASI score quantifies the severity and extent of AD, as well as the severity of erythema, 
infiltration, excoriation and lichenification of the four anatomical regions—head and neck, 
trunk, upper extremities and lower extremities. 
The total EASI score ranges from 0 (lowest) to 72 (highest); the higher the score, the higher 
the severity of AD (more severe). 
How to Use EASI 
The EASI scoring system uses a defined process to grade the severity of the signs of eczema 
and the extent affected: 
 


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How to record your scores 
The assessed parameters are inserted into a table (example shown below for age≥8 years). The 
final EASI score ranges from 0-72. 
Body 
region 
Erythema 
Edema/papula
tion 
Excoriatio
n 
Lichenificat
ion 
Area 
score  
Multipl
ier 
Score  
Head/neck 
 ( 
+ 
+ 
+ 
) 
× 
× 0.1 
 
Trunk  
 ( 
+ 
+ 
+ 
) 
× 
× 0.3 
 
Upper 
extremities 
 ( 
+ 
+ 
+ 
) 
× 
× 0.2 
 
Lower 
extremities 
 ( 
+ 
+ 
+ 
) 
× 
× 0.4 
 
The final EASI score is the sum of the 4 region scores 
______ 
 (0-72) 
Two forms of the EASI scoring system are available depending on the age of the patients. The 
multipliers for the region score are different in the under 8’s version to reflect the relative 
proportion of body regions in young children. 
 


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What is the difference between edema/papulation and lichenification? 
Consider edema/papulation as corresponding to the acute signs of atopic dermatitis 
that reflect histological spongiosis. Lichenification are more firm thickened plaques 
with accentuation of the skin markings that develop as a result of prolonged 
scratching or rubbing in chronic disease. In darker skin types, follicular 
lichenification may present as firm flat-topped discrete papules. Grade these 
chronic lesions as lichenification. 
How do I grade prurigo nodules? 
Prurigo nodules are larger, deeper lesions as a result of chronic scratching and are 
graded as areas of lichenification. 
How do I grade erythema in darker skin? 
To avoid underestimating inflammation in patients with darker skin tones, take into 
account the underlying skin pigment when grading erythema. Often this means 
increasing your erythema grade by one level. 
What if most areas in a region are a severity grade of 1, but there are some 
areas that are a grade 3? 
Attempt to average the severity across the involved areas in that region. If these 
areas are close to equal in size, a score of 2 would be most appropriate. If the 
majority of involved areas are a grade 1, a score of 1 or 1.5 is more appropriate. Be 
careful not to score the highest severity in a region but the average one. 
How do I grade xerosis (dryness), ichthyosis and hyperlinear palms? 
Unless there is active acute or chronic eczema overlying these findings, they are 
not included in the EASI assessment. 
How precise should my assessment of eczema extent be? 
The region scores, which reflect the extent of eczema, were designed and 
validated as rough estimates of the percentage of involved skin. Each region is 
given a score ranging from 0 to 6, based on a “ballpark” estimation of extent 
(see region score table in page 1). If you find it difficult to provide a rough 
estimate of disease extent, you can use the schematics in Appendix 1 to guide 
you. More time-consuming methods for evaluating disease extent such as the 
rule of nines or the ‘palm’ method are generally unnecessary, as the EASI was 
designed to be easy. 
My patient has responded well to treatment and significantly improved 
since the last visit. Should I adjust the grading based on the patient’s 
relative improvement? 
No. The EASI is a static score, meaning that it is done independently at each 
time point to reflect current severity. You should grade the EASI per visit 
regardless of the previous status. Studies have shown that the EASI score has 
good responsiveness, meaning that overall it is sensitive to change and the 
improvement will be reflected in the total score. 
What do the terms erythema, edema/papulation, excoriation and 
lichenification mean? 
These are key signs of atopic dermatitis. Recognizing and grading them 
properly requires training on the visual and physical exam consistent with these 
signs. Generally speaking, erythema is skin redness; edema/papulation refers 
to an elevation or swelling of the skin (that should be differed from 
lichenification below); excoriations are scratch marks that have broken the skin 
surface; and lichenification is a leathery thickening of the skin with exaggerated 
skin markings. 


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17.6. Appendix F (BSA) 
Percentage of body surface area (BSA) affected by AD 
The “Rule of Nines” is used to estimate the maximum percentage in each area: 
• 
Head and neck [9%] 
• 
Anterior trunk [18%] 
• 
Back [18%]  
• 
Upper limbs [18%] 
• 
Lower limbs [36%] 
• 
Genitals [1%]) 
The number of palms of AD-affected skin in a body part can be used to determine the extent 
(%) of AD involvement in that body part. Regardless of the age of the subject, the area of the 
subject's entire palm (five fingers adducted together) is about 1% of the subject's BSA. As part 
of the EASI assessment, the number of palms in different body parts is assessed to calculate 
the percentage of BSA affected by AD. 
 
 


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17.7. Appendix G (SCORAD) 
Scoring Atopic Dermatitis Index (SCORAD) 
SCORAD is a clinical tool used to assess the severity of AD (extent/severity) and subjective 
signs/symptoms (e.g., itch/sleeplessness). The degree of lesions is scored using the “rule of 
nines” method. The severity is determined by grading the severity of the 6 signs (erythema, 
edema, oozing/crusting, excoriation, lichenification, and skin dryness) on a 0-3 subscale. The 
assessment of each sign is scored on the most representative skin lesions. A visual analog scale 
(VAS) is used to score subjective symptoms, with 0=no itch (or sleeplessness) and 10=most 
severe itch (or sleeplessness). The total score is the sum of extensiveness/5+7 x 
severity/2+VAS (symptoms). SCORAD results range from 0 and 103. The higher the score, 
the more severe the AD. 
 
 


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17.8. Appendix H (Injection Site Assessment) 
Injection Site Assessment 
Parameter 
Grade  
Description  
Erythema  
0 
No 
1 
Very slight (hardly visible) 
2 
Slight (clear boundary) 
3 
Moderate 
4 
Severe (beet red) to slight eschar formation (deep damage) 
Oozing 
0 
No 
1 
Serous 
2 
Bloody serous 
3 
Bloody 
4 
Suppuration 
Edema  
0 
No 
1 
Very slight (hardly visible) 
2 
Slight (clear boundary) 
3 
Moderate (elevated by approximately 1mm) 
4 
Severe (elevated by > 1mm and beyond the exposed area) 
Induration  
0 
No 
1 
Very mild 
2 
Mild (sponge tissue) 
3 
Moderate (hard, warm) 
4 
Severe (hard, red, hot, crepitus) 
Hematoma 
0 
No 
1 
Very mild 
2 
Mild 
3 
Moderate 
4 
Severe 
 

SAP_001.pdf: 
Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
1 
Suzhou Connect Biopharmaceuticals, Ltd. 
A double-blind, multi-center, randomized controlled clinical study to 
evaluate the efficacy and safety of CBP-201 in Chinese subjects with 
moderate to severe atopic dermatitis 
CBP-201-CN002 
Statistical Analysis Plan 
Version: 2.0 
Date: October 23, 2023 
NCT Number：NCT05017480


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
2 
Approval Page of Sponsor 
A double-blind, multi-center, randomized controlled clinical study to evaluate 
the efficacy and safety of CBP-201 in Chinese subjects with moderate to severe 
atopic dermatitis 
 
CBP-201-CN002 
 
Statistical Analysis Plan 
 
Version: 2.0 
 
Author: 
Chen Danping 
Company: 
Hangzhou Tigermed Consulting Co., Ltd. 
Signature: 
<signed> 
Date: 23Oct2023 | 18:59:57 
CST 
Reviewer: 
Xu Jinmei 
Company: 
Hangzhou Tigermed Consulting Co., Ltd. 
Signature: 
<signed> 
Date: 23Oct2023 | 19:02:35 
CST 
Sponsor reviewer: 
Han Jinming 
Company: 
Suzhou Connect Biopharmaceuticals, 
Ltd. 
Signature: 
<signed> 
Date: 23Oct2023 | 19:20:56 
CST 
Sponsor approval: 
Meng Yuhui 
Company: 
Suzhou Connect Biopharmaceuticals, 
Ltd. 
Signature: 
<signed> 
Date: 23Oct2023 | 19:35:13 
CST 
 
 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
3 
Record of revisions 
Version 
Version date 
Author 
Description 
1.0 
September 20, 2022 
Chen Jingyun 
Final version 1.0 
2.0 
October 23, 2023 
Chen Danping 
Final version 2.0 
 
 
 
 
 
 
 
 
 
 
 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
4 
Table of Contents 
1. 
Introduction ................................................................................................................ 7 
2. 
Study Objectives ........................................................................................................ 7 
2.1. 
Primary Objective ...................................................................................................... 7 
2.2. 
Secondary Objectives................................................................................................. 7 
3. 
Study Design .............................................................................................................. 7 
3.1. 
Overall Design ........................................................................................................... 7 
3.2. 
Sample Size ................................................................................................................ 9 
4. 
Study Endpoints ....................................................................................................... 10 
4.1. 
Efficacy Endpoints ................................................................................................... 10 
4.1.1. 
Primary endpoint ...................................................................................................... 10 
4.1.2. 
Secondary endpoints ................................................................................................ 10 
4.1.3. 
Other efficacy endpoints .......................................................................................... 10 
4.2. 
Safety Endpoints ...................................................................................................... 12 
4.2.1. 
Drug exposure and compliance ................................................................................ 12 
4.2.2. 
Adverse events (AEs) .............................................................................................. 13 
4.2.3. 
Laboratory tests ........................................................................................................ 14 
4.2.4. 
Electrocardiogram (ECG) ........................................................................................ 15 
4.2.5. 
Others ....................................................................................................................... 15 
4.3. 
PK/PD Endpoints ..................................................................................................... 15 
5. 
Statistical Hypothesis ............................................................................................... 16 
6. 
Analysis Datasets ..................................................................................................... 16 
7. 
Statistical Methods ................................................................................................... 19 
7.1. 
Overall Statistical Consideration ............................................................................. 19 
7.2. 
Methods for Data Processing ................................................................................... 20 
7.2.1. 
Convention of data processing and processing of missing data .............................. 20 
7.2.2. 
Derived and transformed data .................................................................................. 20 
7.3. 
Study Subjects .......................................................................................................... 21 
7.3.1. 
Subject disposition ................................................................................................... 21 
7.3.2. 
Protocol deviations................................................................................................... 21 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
5 
7.3.3. 
Analysis datasets ...................................................................................................... 21 
7.3.4. 
Demographics and baseline characteristics ............................................................. 21 
7.3.5. 
Medical history of subjects ...................................................................................... 21 
7.3.6. 
Prior medication, concomitant medication, and prior and concomitant non-drug 
therapies ................................................................................................................... 22 
7.4. 
Efficacy Analysis ..................................................................................................... 23 
7.4.1. 
Visit window of efficacy analysis ............................................................................ 23 
7.4.2. 
Intercurrent events and handling strategies.............................................................. 23 
7.4.3. 
Analysis of the primary efficacy endpoint and key secondary efficacy endpoints
.................................................................................................................................. 26 
7.4.4. 
Other efficacy endpoint analysis .............................................................................. 30 
7.4.5. 
Efficacy analysis in stage 2 ...................................................................................... 30 
7.5. 
Safety Analysis ........................................................................................................ 31 
7.5.1. 
Drug exposure and compliance ................................................................................ 31 
7.5.2. 
AEs ........................................................................................................................... 32 
7.5.3. 
Laboratory test results .............................................................................................. 33 
7.5.4. 
ECG.......................................................................................................................... 33 
7.5.5. 
Other safety evaluation ............................................................................................ 34 
7.6. 
Pharmacokinetics (PK) analysis .............................................................................. 34 
7.7. 
Pharmacodynamics (PD) and Biomarker Analysis.................................................. 34 
7.8. 
Changes to Planned Analysis in the Protocol .......................................................... 34 
8. 
References ................................................................................................................ 36 
 
 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
6 
Abbreviation 
Abbreviation 
Explanation 
AD 
Atopic Dermatitis 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
ANCOVA 
Analysis of Covariance 
CTCAE 
Common Terminology Criteria for Adverse Event 
DSMB 
Data Safety Monitoring Board 
EASI 
Eczema Area and Severity Index 
EOT 
End of Treatment 
FAS 
Full Analysis Set 
IGA 
Validated Investigator Global Assessment 
MedDRA 
Medical Dictionary for Regulatory Activities 
MI 
Multiple Imputation 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
PT 
Preferred Term 
Q1 
25% Quartile 
Q2W 
Once Every 2 Weeks 
Q3 
75% Quartile 
Q4W 
Once Every 4 Weeks 
RS 
Randomization Set 
SAE 
Serious Adverse Event 
SE 
Standard Error 
SOC 
System Organ Class 
SS 
Safety Set 
TEAE 
Treatment-Emergent Adverse Event 
WHO 
World Health Organization 
WOCF 
Worst Observation Carried Forward 
 
 
 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
7 
1. Introduction 
This statistical analysis plan (SAP) describes the detailed statistical analysis methods planned 
for the protocol entitled “a double-blind, multi-center, randomized controlled clinical study to 
evaluate the efficacy and safety of CBP-201 in Chinese subjects with moderate to severe atopic 
dermatitis” 
(protocol 
number: 
CBP-201-CN002) 
sponsored 
by 
Suzhou 
Connect 
Biopharmaceuticals, Ltd. 
This plan is prepared based on the Study Protocol Version 4.0 dated 01Aug2022 and the Case 
Report Form (CRF) Version 3.0 dated 27Apr2022.  
2. Study Objectives 
2.1. Primary Objective 
 
To assess the efficacy of CBP-201 in subjects with moderate to severe AD. 
2.2. Secondary Objectives 
● 
To assess the safety and tolerability of CBP-201 in subjects with moderate to severe AD; 
● 
To assess the pharmacokinetic (PK) characteristics of CBP-201 in subjects with moderate 
to severe AD; 
● 
To assess the pharmacodynamic (PD) characteristics of CBP-201; 
● 
To assess the immunogenicity of CBP-201. 
3. Study Design 
3.1. Overall Design 
This study is a randomized, double-blind, multi-center, controlled study designed to assess the 
efficacy, safety, and PK characteristics of CBP-201 in eligible subjects with moderate to severe 
AD. 255 subjects will be randomized in a 2:1 ratio to receive either CBP-201 300 mg Q2W or 
placebo. 
The study includes a screening period, a treatment period and a follow-up period. The treatment 
period is divided into two stages: 
Stage 1 study: It is a placebo-controlled study, in which subjects who meet the inclusion 
criteria and do not meet the exclusion criteria will be stratified according to the severity of their 
baseline disease (moderate [IGA=3] and severe [IGA=4]) and randomized into one of the 
following 2 groups to receive investigational product or placebo treatment by the ratio of 2:1: 
● 
Group A (CBP-201): the subjects will receive a subcutaneous injection of CBP-201 600 
mg (4 ml in total, 2 injections of 2 ml each in different sites) on Day 1, begin to receive a 
subcutaneous injection of CBP-201 300 mg (2 ml) from Week 2 (W2), and receive 
treatment at the same dose every 2 weeks thereafter until W14; 
● 
Group B (placebo): the subjects will receive a subcutaneous injection of placebo 4 ml (2 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
8 
injections of 2 ml each in different sites) on Day 1, begin to receive a subcutaneous 
injection of placebo 2 ml from W2, and receive placebo 2 ml every 2 weeks thereafter until 
W14. 
Table 1: Dosing Regimen by Group in Stage 1 
Group 
W0 
W2 
W4 
W6 
W8 
W10 
W12 
W14 
Group A 
4XC 
2XC 
2XC 
2XC 
2XC 
2XC 
2XC 
2XC 
Group B 
4XP 
2XP 
2XP 
2XP 
2XP 
2XP 
2XP 
2XP 
Note: C=CBP-201; P=placebo; #X=number of ampoules. 
Before the administration of study drug at W16 visit, all subjects will be assessed for efficacy, 
and the treatment assignment for Stage 2 maintenance treatment is based on whether a subject 
achieves a 50% or greater reduction in Eczema Area and Severity Index (EASI) score (ie EASI-
50). 
Stage 2 study: The grouping for Stage 2 maintenance treatment is as follows: 
● 
Subjects who have achieved EASI-50 in the W16 pre-administration efficacy assessment 
will be randomized in a 1:1 ratio into one of the following two groups to receive study 
treatment starting from W16: 
● Group C: The subjects will receive a subcutaneous injection of CBP-201 300 mg 
every 2 weeks until W50; 
● Group D: The subjects will receive a subcutaneous injection of CBP-201 300 mg 
every 4 weeks. In order to maintain the injection every 2 weeks blind, when not 
receiving CBP-201, the subjects will receive an injection of placebo 2 ml once every 
4 weeks until W50. 
● 
Subjects who have not achieved EASI-50 in the W16 pre-administration treatment 
assessment will receive the following treatment starting from W16: 
● Group E: The subjects will receive a subcutaneous injection of CBP-201 300 mg 
every 2 weeks until W50. 
● 
If subjects in group C and group D have not achieved EASI-50 in two continuous pre-
administration treatment assessments, they will be assigned to group E to be treated with 
subcutaneous injection of CBP-201 300 mg every 2 weeks from the visit when EASI-50 
is not achieved for the second time to W50. 
Table 2: Dosing Regimen by Group in Stage 2 
Group 
W16 
W18 
W20 
W22 
W24 
…… 
W50 
Group C 
2XC 
2XC 
2XC 
2XC 
2XC 
…… 
2XC 
Group D 
2XC 
2XP 
2XC 
2XP 
2XC 
…… 
2XP 
Group E 
2XC 
2XC 
2XC 
2XC 
2XC 
…… 
2XC 
Note: C=CBP-201; P=placebo; #X=number of ampoules. 
 
 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
9 
All subjects (including the subjects who prematurely discontinue treatment) will be followed 
up for 8 weeks after the last dose. 
The overall study design is shown in the diagram below: 
 
Figure 1: Study Design Diagram 
Note: 
1： The subjects will receive a loading dose of the study drug (investigational product/placebo) on D1 at a 
dose of 600 mg (4 ml); 
2： Response is defined as a 50% or greater decrease in the EASI score; 
3： In order to maintain the injection every 2 weeks blind, when not receiving CBP-201, the subjects will 
receive an injection of placebo 2 ml once every 4 weeks until W50. 
4： If subjects in group C and group D have not achieved EASI-50 in two continuous pre-administration 
treatment assessments, they will be assigned to group E to be treated with subcutaneous injection of 
CBP-201 300 mg every 2 weeks from the visit when EASI-50 is not achieved for the second time to 
W50. 
3.2. Sample Size 
It is planned to enroll 255 subjects (in a 2:1 ratio, 170 subjects in the CBP-201 300 mg Q2W 
group, and 85 subjects in the placebo group) who will randomly receive either CBP-201 300 
mg Q2W or placebo. 
This sample size provides a power of approximately more than 90% to detect the difference 
between groups at a two-sided significance level of 5% under the assumption that 27% and 9% 
of subjects in the CBP-201 Q2W group and the placebo group can achieve an IGA score of 0-
1 at W16 for the primary endpoint, respectively, accounting for a dropout rate of 15%. 
Based on the results of another completed phase II international multicenter clinical study of 
CBP-201 in patients with moderate-to-severe atopic dermatitis, the proportion of subjects 
achieving the primary efficacy endpoint was 28.1% in the CBP-201 300 mg Q2W group and 
10.7% in the placebo group, at a two-sided significance level of 0.05. If the results of this trial 
are similar to that of the WW001 trial, the above sample size would provide a power of more 
than 85% to detect the difference of the therapeutic effect on the primary endpoint between the 
CBP- 201 300 mg Q2W group and the placebo group. Therefore, no adjustment is made to the 
sample size. 
Screening 
period 
(D-28~D-1) 
Stage 1 treatment 
period 
(D1~W16) 
Stage 2 treatment 
period 
(W16~W52) 
Follow-up 
period 
(W53~W60) 
Primary analysis 
Primary endpoint 
assessment 
2:1 
Rando
mize
W52/end of 
treatment or 
premature 
termination of 
treatment 
W60 End 
of study 
Not meeting the criteria for response 
Meeting the criteria for 
response2, 1:1 randomize 
Group E: 
Group D: 
Group C: 
Group A: CBP-201 300 mg q2w (n=170) 
Group B: Placebo q2w (n=85) 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
10 
The primary analysis and Stage 2 analysis of this study will still be based on the 255 subjects 
enrolled in accordance with V2.1 and its earlier versions of the protocol. Subjects newly 
enrolled (a total of 75 cases) based on the protocol after V2.1 will not be included in the primary 
analysis and Stage 2 analysis, and only supplementary analysis will be performed. 
4. Study Endpoints 
4.1. Efficacy Endpoints 
4.1.1. Primary endpoint 
The primary efficacy endpoint is the proportion of subjects whose IGA score is 0-1 and 
decreased by ≥2 points from baseline at W16. 
4.1.2. Secondary endpoints 
Key secondary endpoints 
● 
The proportion of subjects achieving EASI-75 at W16; 
● 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥ 4 points from 
baseline at W16; 
● 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥ 3 points from 
baseline at W16; 
● 
Change and percentage change in the weekly average PP-NRS from baseline at W16; 
● 
The proportion of subjects achieving EASI-90 at W16. 
Other secondary endpoints 
● 
Change and percentage change in the EASI score from baseline at W16; 
● 
The proportion of subjects achieving EASI-50 at W16; 
● 
Percentage change in the BSA of AD involvement from baseline at W16; 
● 
Percentage change in the SCORAD score from baseline at W16; 
● 
Change in DLQI from baseline at W16; 
● 
Change in POEM from baseline at W16; 
● 
Percentage change in the weekly average PP-NRS from baseline at W2; 
4.1.3. Other efficacy endpoints 
● 
The proportion of subjects whose IGA score is decreased by ≥2 points from baseline at 
W16; 
● 
The proportion of subjects achieving EASI-100 at W16; 
● 
The number of AD recurrences and number of days from baseline to W16; 
● 
Change in efficacy parameters (e.g., IGA, EASI, BSA, SCORAD, POEM and DLQI) from 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
11 
baseline to W16; 
● 
Change in weekly average PP-NRS from baseline at W16; 
● 
The proportion of subjects whose IGA score is 0-1 and decreased by ≥2 points from 
baseline at W52; 
● 
Change and percentage change in the EASI score from baseline at each visit time point 
from the start of Stage 2 maintenance treatment to the end of study (W60); 
● 
The proportion of subjects achieving EASI-50 at W52; 
● 
The proportion of subjects achieving EASI-75 at W52; 
● 
The proportion of subjects achieving EASI-90 at W52; 
● 
The proportion of subjects achieving EASI-100 at W52; 
● 
Change and percentage change in the weekly average PP-NRS from baseline at each visit 
time point from the start of Stage 2 maintenance treatment to the end of study (W60); 
● 
Change and percentage change in POEM from baseline at each visit time point from the 
start of Stage 2 maintenance treatment to the end of study (W60); 
● 
The proportion of subjects whose IGA score is decreased by ≥2 points from baseline at 
W52; 
● 
Change and percentage change in the percentage of BSA of AD involvement from 
baseline at each visit time point from the start of Stage 2 maintenance treatment to the 
end of study (W60); 
● 
Change and percentage change in SCORAD from baseline at each visit time point from 
the start of Stage 2 maintenance treatment to the end of study (W60); 
● 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥ 3 points 
from baseline at W52; 
● 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥ 4 points 
from baseline at W52; 
● 
Change and percentage change in DLQI from baseline at each visit time point from the 
start of Stage 2 maintenance treatment to the end of study (W60); 
● 
The number of subjects with AD recurrence from baseline to W8; 
● 
The number of subjects with AD recurrence from W8 to W16; 
● 
The number of subjects with AD recurrence from W16 to W52; 
● 
The number of AD recurrences and number of days from W16 to W52; 
● 
The proportion of subjects who maintain EASI-75 response at W52 to the subjects who 
achieve EASI-75 at W16; 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
12 
● 
The proportion of subjects whose IGA score remains 0-1 at W52 to the subjects whose 
IGA score is 0-1 at W16; 
● 
The proportion of subjects who achieve EASI-75 at each visit time point of Stage 2 
maintenance treatment to the subjects who achieve EASI-50 but not EASI-75 at W16; 
● 
The proportion of subjects achieving EASI-50 at each of the other visit time points from 
the start of Stage 2 maintenance treatment to the end of study (W60); 
● 
The proportion of subjects achieving EASI-75 at each of the other visit time points from 
the start of Stage 2 maintenance treatment to the end of study (W60); 
● 
The proportion of subjects achieving EASI-90 at each of the other visit time points from 
the start of Stage 2 maintenance treatment to the end of study (W60); 
● 
The proportion of subjects achieving EASI-100 at each of the other visit time points from 
the start of Stage 2 maintenance treatment to the end of study (W60); 
● 
The proportion of subjects whose IGA score is 0-1 and decreased by ≥ 2 points from 
baseline at each of the other visit time points from the start of Stage 2 maintenance 
treatment to the end of study (W60); 
● 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥ 4 points 
from baseline at each of the other visit time points from the start of Stage 2 maintenance 
treatment to the end of study (W60); 
● 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥ 3 points 
from baseline at each of the other visit time points from the start of Stage 2 maintenance 
treatment to the end of study (W60); 
4.2. Safety Endpoints 
4.2.1. Drug exposure and compliance 
Study drug exposure duration will be summarized by study stage. The duration will be 
calculated with the following formula: 
Exposure duration = date of the last dose - date of the first dose + 14 
For analysis of study drug exposure dose, total drug exposure dose of subjects will be 
summarized. 
The compliance with the study drug and emollients (background treatment) will be calculated 
respectively. If the compliance is lower than 70% or higher than 130%, it will be determined 
as poor compliance. 
Calculation formula of compliance with study drug: Compliance% = actual dose/planned dose 
* 100%. 
Where the actual dose is the total dose of the drug actually used in Stage 1 or 2, and the planned 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
13 
dose is the total dose of the drug that should be used in Stage 1 or 2. 
Calculation formula of compliance with emollients: Compliance% = number of days of using 
emollients as required by protocol/total number of days for which emollients should be used * 
100% 
4.2.2. Adverse events (AEs) 
AEs 
An adverse event refers to any untoward medical occurrence after subjects receive the 
investigational medicinal product, which can be manifested as symptoms, signs, diseases or 
laboratory test abnormalities, but are not necessarily related to the investigational medicinal 
product. See Section 10.1 of the protocol for details. 
Treatment-emergent adverse event (TEAE) 
TEAE is defined as an AE that occurs or worsens during treatment. The treatment period refers 
to the period from the first study drug administration to the end of the protocol-specified 
follow-up period. The cut-off date of TEAEs in Stage 1 is immediately before the first dose for 
Stage 2 or 10 weeks (70 days) after end of dosing in Stage 1, whichever occurs first; for the 
subjects who discontinue administration in Stage 1, the cut-off date of TEAEs is the end of 
follow-up period. TEAEs in Stage 2 is from the end of the first dose for Stage 2 to the end of 
the follow-up period. 
Drug-related AEs 
A drug-related AE refers to an AE whose relationship with the drug is related, possibly related 
or indeterminable. 
The criteria for determination of the correlation of AEs with treatment are as follows: 
Correlation 
Criteria for determination 
Related 
● 
There is a reasonable temporal sequence between the occurrence of AE and the 
medication; 
● 
The study drug explains the AE more reasonably than other reasons (e.g., the 
patient's preexisting disease, environmental or toxic factors, or other treatments 
the patient received, etc.); 
● 
The AE disappears or lessens after the drug is stopped or the dose is reduced; 
● 
The AE meets the known AE types of the suspect drug or its similar drugs; 
● 
The AE recurs after re-administration. 
Possibly related 
● 
There is a reasonable temporal sequence between the occurrence of AE and the 
medication; 
● 
The study drug explains the AE as reasonably as other reasons (e.g., the 
patient's preexisting disease, environmental or toxic factors, or other treatments 
the patient received, etc.); 
● 
The AE disappears or lessens after the drug is stopped or the dose is reduced 
(if applicable). 
Unlikely related 
● 
Other reasons (e.g., the patient's preexisting disease, environmental or toxic 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
14 
factors, or other treatments the patient received, etc.) explain the AE more 
reasonably than the study drug; 
● 
The AE does not disappear or lessen after the drug is stopped or the dose is 
reduced (if applicable), or the situation is unclear; 
● 
The AE does not recur after re-administration, or the situation is unclear. 
Not related 
● 
There is no reasonable temporal sequence between the occurrence of AE and 
the medication, or; 
● 
The AE has other evidence reasons (e.g., the patient's preexisting disease, 
environmental or toxic factors, or other treatments the patient received, etc.). 
Indeterminable 
● 
The above information is unclear, and the investigator believes that it cannot 
be judged based on the existing information, and the investigator cannot obtain 
further follow-up information. 
Serious Adverse Event (SAE) 
An event will be considered an SAE if the following situations occur. See Section 10.1.2 of the 
protocol for definition of SAE. SAEs will be judged by investigators on CRF. 
● 
Leading to death; 
● 
Life-threatening: The investigator determines that the patient is at immediate risk of death 
when the event occurs. This definition does not include events that may lead to death if it 
is assumed to be more serious; 
● 
Requiring hospitalization or prolongation of the original hospital stay; 
● 
Leading to permanent or major disability or incapacitation (i.e., significant impairment of 
the subject's activities of daily living); 
● 
Including congenital abnormalities or birth defects in the offspring of the patient; 
● 
Significant medical events: According to the medical judgment of the investigator, other 
significant medical events that may endanger the patient and may require medical or 
surgical intervention to prevent one of the above outcomes. 
Adverse Event of Special Interest (AESI) 
AESIs in the study include: Conjunctivitis, keratitis, anaphylactic reaction, injection site 
reactions which persist over 24 h, AST/ALT increased > 5 × ULN, parasitic and opportunistic 
infection, pregnancy and symptomatic overdoses. 
AEs leading to treatment discontinuation 
In the study, action taken with study drug is drug discontinued or the subject will be withdrawn 
from treatment in response to these AEs. 
4.2.3. Laboratory tests 
Laboratory tests: Including hematology, blood biochemistry and urinalysis. The specific 
assessments are shown in Table as follows: 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
15 
Table 3: Laboratory tests 
Hematology 
Blood biochemistry 
Urinalysis 
White blood cell count 
Hemoglobin 
Hematocrit 
Red blood cell count 
Platelet count 
Neutrophil percentage 
Lymphocyte percentage 
Monocyte percentage 
Basophil percentage 
Eosinophil percentage 
Absolute neutrophil count 
Absolute lymphocyte count 
Absolute monocyte count 
Absolute eosinophil count 
Absolute basophil count 
Sodium 
Potassium 
Calcium 
Chlorine 
Serum urea/urea nitrogen 
Creatinine 
Glucose 
Total protein 
Albumin 
Total bilirubin 
Alanine aminotransferase 
Aspartate aminotransferase 
γ-glutamyltransferase 
Alkaline phosphatase 
Lactate dehydrogenase 
Creatine phosphokinase 
Total cholesterol 
Low-density lipoprotein 
High-density lipoprotein 
Bilirubin 
Red blood cells 
White blood cells 
Glucose 
Ketone 
Nitrite 
pH 
Protein 
Urine specific gravity 
Urobilinogen 
Microscopic examination (if 
necessary) 
4.2.4. Electrocardiogram (ECG) 
12-lead ECG will be performed to collect ventricular rhythm, PR, QRS, QT, and QTcF. 
4.2.5. Others 
Vital signs 
Vital signs include systolic and diastolic blood pressure, heart rate, body temperature, and 
respiratory rate. 
Physical examination 
Physical examination includes general appearance, skin, eyes/ears/nose/throat, head and neck, 
cardiovascular system, respiratory system, abdomen, limbs, lymph nodes, musculoskeletal and 
nervous systems. Unless it is necessary to assess the status of AD involvement, there is no need 
to perform rectal or genital examinations. 
Other tests 
ADA test. 
4.3. PK/PD Endpoints 
PK endpoints: To analyze the blood concentration of CBP-201, and calculate the PK 
characteristics at steady-state trough concentrations of individuals and each group of subjects 
at each treatment time point. 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
16 
PD endpoints: Change in serum IL-4, IL-13, IgE, TARC levels and peripheral blood eosinophil 
count from baseline. 
5. Statistical Hypothesis 
The primary efficacy endpoint of the study is the proportion of subjects whose IGA score is 0-
1 and decreased by ≥ 2 points from baseline at W16. The following null and alternative 
hypotheses will be evaluated by statistical tests based on the efficacy endpoint. A two-sided 
significance level of 5% (α = 0.05) will be adopted. If p value is ≤ 0.05, the null hypothesis 
will be rejected and it is considered that there is a statistically significant difference in IGA 
parameter between the CBP-201 300 mg Q2W group and the placebo group. 
Null hypothesis (H0):  Efficacy in the CBP-201 300 mg Q2W group = efficacy in the placebo 
group 
Alternative hypothesis (H1):  Efficacy in the CBP-201 300 mg Q2W group ≠ efficacy in the 
placebo group 
6. Analysis Datasets 
The primary analysis of the study will be performed based on the data of Stage 1, that is, 
placebo-controlled stage. The data of primary analysis will include all Stage 1 data from the 
255 subjects who are enrolled in accordance with V2.1 and its earlier versions of the protocol. 
After the 255 subjects enrolled based on the V2.1 and its earlier versions of the protocol 
complete the treatment, related evaluations and follow-up of Stage 1 (W16 pre-dose visit), the 
primary analysis will be performed based on the data of the 255 subjects. 
The analyses for Stage 2 will still be based on the data from 255 subjects who are enrolled in 
accordance with V2.1 and its earlier versions of the protocol. The data analyzed for Stage 2 
will include all data from the 255 subjects who are enrolled in accordance with V2.1 and its 
earlier versions of the protocol that are collected from the start of Stage 2 to the end of study. 
After all subjects who enter Stage 2 (including the 75 subjects newly enrolled) have completed 
treatment, evaluation and follow-up, the analyses for Stage 2 will be performed based on the 
data from 255 subjects who are enrolled in accordance with V2.1 and its earlier versions of the 
protocol. 
Supplementary analysis will include all subjects (including the 75 subjects newly enrolled). 
The same analysis method as that for the primary analysis and Stage 2 analysis will be used. 
The following 6 analysis datasets will be included in the primary analysis. 
Screening set 1 
It will include all subjects who have signed the informed consent form.  
Randomization set 1 (RS1) 
RS1 will include all subjects who have been randomized at baseline (D1), regardless of whether 
they have received the study drug. 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 2.0 
 
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Full analysis set 1 (FAS1) 
FAS1 will include all subjects who have been randomized and received at least one dose of the 
study drug.  Subjects are analyzed within FAS1 according to treatment assigned. 
Per protocol set 1 (PPS1) 
PPS1 will include all subjects in FAS1 without any major protocol deviation that affects 
efficacy analysis. Major protocol deviations that affect efficacy analysis have been discussed 
and determined at the blinded data review meeting for the primary analysis of the study on 
September 19, 2022, and have been discussed and determined again at the blinded data review 
meeting for the final analysis of the study on October 18, 2023. Minutes of the data review 
meeting will be presented in an annex. 
By far, protocol deviations that affect efficacy analysis of the 255 subjects in Stage 1 are due 
to the following causes: 
1. Missing doses (I. Missing W12 and W14 doses; II. Missing 3 doses in Stage 1, equivalent 
to a compliance with study drug lower than 70%); 
2. Missing key efficacy results at W16 (both IGA and EASI missing); 
3. Key efficacy results at W16 out of window (both IGA and EASI out of window >10 days); 
4. Incorrect stratified randomization (only Stage 1); 
5. Violation of inclusion or exclusion criteria (topical corticosteroids are used before baseline; 
baseline disease severity fails to meet the requirements); 
6. Prohibited drugs (non-rescue treatment) that may affect efficacy 
Safety set 1 (SS1) 
SS1 will include all randomized subjects who have received at least one dose of study drug. 
Subjects are analyzed within SS1 according to the treatment they actually received. 
PK set 1 (PKS1) 
PKS1 will include subjects who have received at least one dose of CBP-201 active drug and 
had at least 1 collected and analyzable PK sample. 
The Stage 2 analysis will be defined as the following analysis populations. 
Randomization set 2 (RS2) 
RS2 will include all subjects who have been randomized to Group C or D and all subjects 
assigned to Group E. 
RS2_R: RS2_R will include all subjects who have been randomized to Group C or D. 
RS2_NR: RS2_NR will include all subjects who have been assigned to Group E. 
Full analysis set 2 (FAS2) 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
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18 
FAS2 will include all subjects who have been randomized to Group C or D and all subjects 
who have been assigned to Group E and received at least one dose of the study drug in Stage 
2. Subjects are analyzed within FAS2 according to treatment assigned. 
FAS2_R: FAS2_R will include all subjects who have been randomized to Group C or D and 
received at least one dose of the study drug for Stage 2. 
FAS2_NR: FAS2_NR will include all subjects who have been assigned to Group E and 
received at least one dose of the study drug for Stage 2. 
Safety set 2 (SS2) 
SS2 will include all subjects in RS2 who have received at least one dose of the study drug for 
Stage 2. Subjects are analyzed within SS2 according to the treatment they actually received. 
Safety set 3 (SS3) 
SS3 will include all subjects in SS1 and SS2 who have received at least one dose of the study 
drug. 
PK set 2 (PKS2) 
PKS2 will include all subjects who have received at least one dose of CBP-201 active drug for 
Stage 2 and have at least 1 collected and analyzable PK sample for Stage 2. 
For the supplementary analysis based on all subjects (including the 75 subjects newly enrolled), 
the definitions of analysis sets are the same as above. 
Table 4: Analysis Population, Treatment Group and Analysis Stage 
Analysis Populations 
Treatment Groups 
Analysis Stage 
RS1/ FAS1/ PPS1/ SS1 
1) 
Placebo 
2) 
CBP-201 300 mg Q2W 
Stage 1 treatment period. 
RS2_R/ FAS2_R 
1) 
Placebo/CBP-201 300 mg Q2W 
2) 
Placebo/CBP-201 300 mg Q4W 
3) 
CBP-201 300 mg Q2W/CBP-201 300 
mg Q2W 
4) 
CBP-201 300 mg Q2W/CBP-201 300 
mg Q4W 
5) 
Q2W Total 
6) 
Q4W Total 
7) 
Total 
From the completion of 
Stage 2 randomization to the 
end of study for subjects who 
have completed Stage 1 and 
been randomized to Group C 
or D. 
RS2_NR/ FAS2_NR 
1) 
Placebo/CBP-201 300 mg Q2W 
2) 
CBP-201 300 mg Q2W/CBP-201 300 
mg Q2W 
3) 
Open-Label Q2W Total 
From the start of Stage 2 to 
the end of study for subjects 
who have completed Stage 1 
and been assigned to Group 
E. 
SS2 
1) 
CBP-201 300 mg Q2W（Group C） 
2) 
CBP-201 300 mg Q4W（Group D） 
From the first dose for Stage 
2 to the end of Stage 2. 


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Protocol number: CBP-201-CN002 
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3) 
CBP-201 300 mg Q2W（Group E） 
4) 
Total 
SS3 
1) 
CBP-201 300 mg Q2W 
2) 
CBP-201 300 mg Q2W/CBP-201 300 
mg Q4W 
3) 
CBP-201 300 mg Q2W/CBP-201 300 
mg Q4W/CBP-201 300 mg Q2W 
4) 
CBP-201 300 mg Q4W 
5) 
CBP-201 300 mg Q4W/CBP-201 300 
mg Q2W 
6) 
Total 
It includes all subjects who 
have received at least one 
dose of CBP-201 from Stage 
1 to Stage 2. From the first 
dose of CBP-201 to the end 
of study. 
7. Statistical Methods 
7.1. Overall Statistical Consideration 
In the statistical tabulations, screening number of subjects is the universal unique identifier of 
subjects in the study. 
General rules of descriptive statistics: Quantitative variables are described by mean, standard 
deviation, median, minimum, maximum, Q1 and Q3. In terms of rounding, the numbers of 
decimal places of the minimum and maximum are consistent with that of original value, while 
those of mean, medium, Q1, and Q3 are 1 more than that of the original value, and that of 
standard deviation is 2 more than that of the original value. Categorical variables are described 
by number and percentage of each category. The number of subjects is rounded to integer and 
percentage is rounded to one decimal place. It is unnecessary to present a percentage when the 
count is 0. 
General rules of inferential statistics: Two-sided test is adopted for all statistical tests (unless 
otherwise specified). P<0.05 will be considered statistically significant (unless otherwise 
specified). P value is rounded to 4 decimal places. If P < 0.0001, it is presented as ‘< .0001’; if 
P > 0.9999, it is presented as ‘> .9999’. 
For primary analysis, the baseline of efficacy analysis is defined as the last available value 
before randomization in Stage 1, and the baseline of safety analysis is defined as the last 
available value before the first dose in Stage 1. 
For the analysis in Stage 2, one group of baselines is defined for efficacy analysis and two 
groups of baselines are defined for safety analysis. The baseline of efficacy analysis is defined 
as the last available value before randomization in Stage 1. The baseline of safety analysis in 
Group 1 is defined as the last available value before the first dose. The baseline of safety 
analysis in Group 2 is defined as the last available value before the first dose in Stage 2. 
Efficacy analysis will be performed using the baseline of Group 1. Safety analysis will be 
performed to analyze the changes from baseline in laboratory test, ECG and vital signs at each 
visit using the baseline of Group 1 and the baseline of Group 2, respectively. 


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Statistical analyses will be performed using SAS 9.4. 
7.2. Methods for Data Processing 
7.2.1. Convention of data processing and processing of missing data 
The missing dates of AEs or concomitant medications/treatments will be imputed as follows. 
The imputation of missing dates will be used for classification only. When tabulations of 
relevant data are generated, unimputed dates will be still presented. 
Missing of start date: 
1) If the year and month are known and both are earlier than those of the first dose of the 
investigational product, the last day of the known month will be used for imputation. 
2) If the year and month are known and same as those of the first dose of the investigational 
product, the start date is the date of the first dose of the investigational product (date refers 
to “month, day”). 
3) If the year and month are known and later than those of the first dose of the investigational 
product, it will be imputed with the first day of the known month. 
4) If only the year is known and earlier than that of the first dose of the investigational product, 
“December 31” will be used for imputation. 
5) If only the year is known and same as that of the first dose of the investigational product, 
the start date is the date of the first dose of the investigational product (date refers to 
“month, day”). 
6) If only the year is known and later than that of the first dose of the investigational product, 
it will be imputed with “January 1”. 
7) In other situations, the date of the first dose of the investigational product will be taken as 
corresponding start date. 
Missing of end date: 
1) If the year and month are known, it will be imputed with the last day of the known month. 
2) If only the year is known, it will be imputed with “December 31”. 
3) If the end date imputed is earlier than the start date, the end date will be taken as 
corresponding start date. 
4) Other conditions are regarded as missing. 
Missing laboratory data, ECG data, vital signs data, physical examination and other safety data 
will not be imputed. 
7.2.2. Derived and transformed data 
When the units of data from laboratories of different sites are inconsistent, the data will be 
converted according to international standard units. 


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For laboratory data, if the same parameter is measured multiple times on the same day, the 
average value of multiple measurements will be used as the measurement this day for analysis. 
Duration of exposure to drug (day) = date of the last dose - date of the first dose + 14. 
7.3. Study Subjects 
7.3.1. Subject disposition 
Screening and randomization of subjects will be summarized based on Screening Set 1. The 
number and percentage of subjects will be calculated, and the reasons for screening failure will 
be presented; in addition, study drug discontinuation and study termination in both stages will 
be summarized based on RS1 and RS2, respectively, and the number and percentage of subjects 
will be calculated. Subject disposition will be tabulated. 
7.3.2. Protocol deviations 
All subjects who have protocol deviations in Stage 1 will be summarized based on RS1, the 
number and percentage of subjects will be calculated and tabulated. In addition, all subjects 
with protocol deviations that have occurred from Stage 2 to end of study will be summarized 
based on RS2, the number and percentage of subjects will be calculated and tabulated. 
7.3.3. Analysis datasets 
The subjects who are included to SS1, FAS1, and PPS1 will be summarized based on RS1, and 
the number and percentage of subjects will be calculated. 
The subjects who are included into SS2, FAS2, and PPS2 will be summarized based on RS2, 
and the number and percentage of subjects will be calculated. 
SS3 will include all subjects who have received at least one dose of the study drug. The total 
number of subjects included into SS3 as well as the specific number of subjects in each 
treatment group (See Table 4. Analysis Population, Treatment Group and Analysis Stage) will 
be listed. 
7.3.4. Demographics and baseline characteristics 
The primary analysis will be performed based on RS1, and Stage 2 analysis will be performed 
based on RS2. 
Demographics such as age, gender, body height, body weight, and BMI will be summarized 
by descriptive statistics. The severity (moderate [IGA = 3] and severe [IGA = 4]) of atopic 
dermatitis (AD) at baseline will be summarized, and the number of percentage of subjects will 
be calculated. The baseline EASI/PP-NRS/BSA/SCORAD/POEM/DLQI will be summarized 
by descriptive statistics. Demographics and baseline characteristics will be tabulated. 
7.3.5. Medical history of subjects 
The primary analysis will be performed based on RS1, and Stage 2 analysis will be performed 
based on RS2. 


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Medical history will be coded based on Medical Dictionary for Regulatory Activities 
(MedDRA), and the number and percentage of subjects will be summarized by System Organ 
Class (SOC) and Preferred Term (PT). Medical history of allergic diseases and allergy history 
will be summarized separately, and the number and percentage of subjects will be calculated. 
Medical history will be ranked in descending order of total number of subjects by SOC and PT. 
All medical histories will be tabulated, and medical history of allergic diseases and allergy 
history will be tabulated separately. 
7.3.6. Prior medication, concomitant medication, and prior and concomitant non-drug 
therapies 
The primary analysis will be performed based on RS1. Stage 2 analysis will be performed 
based on RS2 (only concomitant medications and treatments in Stage 2). 
Prior and Concomitant Medications 
Prior medication refers to a non-study drug that is started and ended before the first dose of 
study drug. Concomitant medication refers to a drug that is started at the time of or after the 
first dose of study drug, or a drug that is started before the first dose of the study drug and 
continued after the first dose of the study drug. 
Prior and concomitant medications will be coded based on World Health Organization Drug 
Dictionary (WHODrug), and summarized based on ATC Level 2, ATC Level 4 (if the code is 
missing, it will be analyzed with the code of previous level) and PT. The number and 
percentage of subjects will be calculated. Prior and concomitant medications will be ranked in 
descending order of total number of subjects by ATC Level 2, ATC Level 4 and PT. In addition, 
they will be tabulated. 
Prior and Concomitant Non-drug Therapies 
Prior non-drug therapy refers to a therapy that is started and ended before the first dose of study 
drug. Concomitant non-drug therapy refers to a therapy that is started at the time of or after the 
first dose of study drug, or a therapy that is started before the first dose of the study drug and 
continued after the first dose of the study drug. 
Prior and concomitant non-drug therapies will be coded by MedDRA. Concomitant non-drug 
therapies will be summarized by PT. The number and percentage of subjects will be calculated. 
Prior and concomitant non-drug therapies will be ranked in descending order of total number 
of subjects. They will be tabulated. 
Rescue Treatment 
Rescue treatments during treatment period of Stages 1 and 2 will be summarized based on ATC 
Level 2, ATC Level 4 (if the code is missing, it will be analyzed with the code of previous 
level) and PT. The number and percentage of subjects will be calculated. These rescue 
treatments will be ranked in descending order of total number of subjects by ATC Level 2, 
ATC Level 4 and PT. They will be tabulated. 


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7.4. Efficacy Analysis 
Efficacy analysis in Stage 1 will be performed based on FAS1 and PPS1, mainly the FAS1. 
In order to control the type I error rate for multiplicity, a fixed-sequence method will be used. 
First of all, the active treatment group and the placebo group will be compared for the primary 
efficacy endpoint; when the primary efficacy endpoint reaches statistical significance, the 
active treatment group and the placebo group will be compared for the key secondary efficacy 
endpoints according to the sequence specified in the protocol. 
Efficacy analysis in Stage 2 will be performed based on FAS2. 
7.4.1. Visit window of efficacy analysis 
For scheduled visits, the visit window for efficacy analysis will be based on the visit where the 
original data are collected. For unscheduled visits and premature withdrawal visit, the visit 
window for efficacy analysis will be based on the visit closest to the reference date (the 
previous visit when the distance is the same). 
7.4.2. Intercurrent events and handling strategies 
See table below for intercurrent events and handling strategies of the primary analysis: 
Label 
Intercurrent event 
Strategy 
Remarks 
Intercurrent 
event 1 (use of 
prohibited 
drugs/treatments 
specified in the 
protocol for 
which the study 
treatment must 
be early 
terminated due 
to poor 
response) 
 
Dupilumab or any anti-IL-4Rα or IL-13 
antibodies; 
 
Topical PDE-4 inhibitors or JAK 
inhibitors; 
 
Systemic treatment with corticosteroids 
or other immunosuppressive and/or 
immunomodulatory agents, such as 
cyclosporine, mycophenolate mofetil, 
azathioprine, methotrexate, or oral JAK 
inhibitors; 
 
Cell depletion agents (e.g., rituximab) or 
other biological agents; 
 
Other investigational drugs (non CBP-
201) or treatments. 
Due to the poor response, the above prohibited 
drugs/treatments have been used before the 
W16 visit. 
Composite 
strategy 
This type of 
intercurrent event 
occurs because of 
poor response, 
should be treated as 
non-response. 
 
If it is a continuous 
variable, the data 
after the occurrence 
of the intercurrent 
event should be 
imputed with 
WOCF. 
Intercurrent 
event 2 (use of 
other prohibited 
drugs/treatments 
specified in the 
protocol other 
than those in 
Intercurrent 
Event 1, with a 
 
Initiation of SIT, or dose up-regulation; 
 
TCS or TCI; 
 
Phototherapy (NBUVB, UVB, UVA1, 
PUVA), sunbed or any other LED 
therapies; 
 
Bleaching baths more than 2 times a 
week; 
 
Any drug for the treatment of AD (except 
Treatment 
policy 
strategy 
The impact on the 
assessment of 
efficacy endpoints 
can be ignored, and 
the actual observed 
value is used. If the 
actual observed 
value is missing, it 
will be processed 


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Label 
Intercurrent event 
Strategy 
Remarks 
negligible 
impact on the 
assessment of 
the primary 
endpoint) 
mild emollients) that may interfere with 
the evaluation of efficacy results or affect 
the evaluation of AD severity. 
The cumulative duration of use of the above 
prohibited drugs/treatments before the W16 
visit is no more than 7 days, and the end date 
is at least 4 weeks away from the W16 visit. 
according to the 
principle for 
processing missing 
values. 
Intercurrent 
event 3 (use of 
other prohibited 
drugs/treatments 
specified in the 
protocol 
other 
than those in 
Intercurrent 
Event 1 due to 
poor 
response, 
with 
a 
major 
impact on the 
assessment 
of 
the 
primary 
endpoint) 
 
Initiation of SIT, or dose up-regulation; 
 
TCS or TCI; 
 
Phototherapy (NBUVB, UVB, UVA1, 
PUVA), sunbed or any other LED 
therapies; 
 
Bleaching baths more than 2 times a 
week; 
 
Any drug for the treatment of AD (except 
mild emollients) that may interfere with 
the evaluation of efficacy results or affect 
the evaluation of AD severity. 
The cumulative duration of use of the above 
prohibited drugs/treatments due to poor 
response before the W16 visit is more than 7 
days, or the end date is less than 4 weeks away 
from the W16 visit. 
Composite 
strategy 
This type of 
intercurrent event 
occurs because of 
poor response, 
should be treated as 
non-response. 
 
 
If it is a continuous 
variable, the data 
after the occurrence 
of the intercurrent 
event should be 
imputed with 
WOCF. 
Intercurrent 
event 
4 
(premature 
discontinuation 
of 
treatment/EOT 
due to AEs) 
The subject experiences an AE or SAE that is 
considered 
by 
the 
investigator 
to 
be 
intolerable before the W16 visit, and is 
unsuitable for continuing the study treatment, 
resulting in premature discontinuation of 
treatment/EOT. 
Composite 
strategy 
This type of 
intercurrent event 
occurs because of 
poor safety of 
treatment, should be 
treated as non-
response. 
 
If it is a continuous 
variable, 
the 
data 
after the occurrence 
of the intercurrent 
event 
should 
be 
imputed with WOCF. 
Intercurrent 
event 
5 
(the 
subject’s 
administration is 
missing due to 
the COVID-19 
epidemic) 
The administration at two consecutive visits 
(W12 and W14) immediately before the W16 
visit is missing or the administration in the 
Stage 1 treatment period is missing for ≥3 
times. 
Hypothetical 
strategy 
The observed values 
are not used, and the 
J2R 
(jump 
to 
reference) method is 
used for imputation. 
Intercurrent 
event 6 (use of 
prohibited 
The following prohibited drugs/treatments 
have been used before the W16 visit not 
because of the poor response: 
Hypothetical 
strategy 
The observed values 
are not used, and the 
J2R 
(jump 
to 


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Label 
Intercurrent event 
Strategy 
Remarks 
drugs/treatments 
specified in the 
protocol not for 
poor 
response, 
with 
a 
major 
impact on the 
assessment 
of 
the 
primary 
endpoint) 
 
Dupilumab or any anti-IL-4Rα or IL-13 
antibodies; 
 
Topical PDE-4 inhibitors or JAK 
inhibitors; 
 
Systemic treatment with corticosteroids 
or other immunosuppressive and/or 
immunomodulatory agents, such as 
cyclosporine, mycophenolate mofetil, 
azathioprine, methotrexate, or oral JAK 
inhibitors; 
 
Cell depletion agents (e.g., rituximab) or 
other biological agents; 
 
Other investigational drugs (non CBP-
201) or treatments. 
Or 
The cumulative duration of use of the 
following prohibited drugs/treatments not due 
to the poor response before the W16 visit is 
more than 7 days, or the end date is less than 
4 weeks away from the W16 visit: 
 
Initiation of SIT, or dose up-regulation; 
 
TCS or TCI (topical drugs can be used 
for AD lesion areas only); 
 
Phototherapy (NBUVB, UVB, UVA1, 
PUVA), sunbed or any other LED 
therapies; 
 
Bleaching baths more than 2 times a 
week; 
 
Any drug for the treatment of AD 
(topical drugs can be used for AD lesion 
areas only) that may interfere with the 
evaluation of efficacy results or affect the 
evaluation of AD severity. 
reference) method is 
used for imputation. 


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7.4.3. Analysis of the primary efficacy endpoint and key secondary efficacy endpoints 
Label of 
estimand 
Description of estimand 
Main estimator 
Sensitivity/ Supplementary analysis 
Analysis sets 
Rules for imputation 
Model/method for the 
main analytical 
methods 
Estimand of 
primary 
endpoint 
The difference in efficacy in 
patients aged 12 years and older 
with moderate to severe AD and 
weighing > 40 kg between the 
CBP-201 300 mg Q2W group 
and placebo group. 
 
A patient is considered as 
treatment success if the patient 
has an IGA score of 0-1 which is 
decreased by ≥ 2 points from 
baseline at W16. 
 
A patient should be regarded as 
treatment failure if he/she uses 
prohibited 
drugs/treatments 
specified in the protocol for 
which the study treatment must 
be early terminated or other 
rescue therapy that has a major 
impact on the assessment of the 
primary endpoint due to poor 
response, 
or 
has 
premature 
discontinuation 
of 
treatment/EOT due to AEs. 
FAS1 (will include 
all subjects in RS1 
who have received 
the study drug at 
least once). 
For 
subjects 
who 
experience intercurrent 
events, their visits after 
the intercurrent events 
will be handled in 
accordance with the 
strategies for managing 
intercurrent 
events 
listed in Table 7.4.2. 
If the target variable is 
still 
missing 
after 
application 
of 
the 
strategies for managing 
intercurrent events, the 
multiple 
imputation 
(MI) method will be 
used to impute the 
missing data in the 
placebo group, and the 
J2R (jump to reference) 
method will be used to 
impute the missing data 
in the CBP- 201 group. 
Differences in response 
rates 
between 
the 
treatment 
group 
and 
placebo group and their 
95% confidence intervals 
will be analyzed using 
the 
Cochran-Mantel- 
Haenszel test stratified 
by 
baseline 
disease 
severity (IGA 3 or 4). 
The Type I error level for 
statistical significance of 
the 
difference 
in 
response rates between 
CBP-201 and placebo is 
set at 0.05 (two-sided 
test). 
Sensitivity analysis 1: When the target 
variable is still missing after application of 
the strategy for managing intercurrent 
events, it will be classified as treatment 
failure. 
 
Sensitivity analysis 2: When the target 
variable is still missing after application of 
the strategy for managing intercurrent 
events, tipping point analysis will be used 
for analysis. 
 
Sensitivity analysis 3: For the subjects who 
are incorrectly stratified and randomized, 
the analysis will be performed using the 
stratification during randomization and the 
same method as the main estimand; 
 
Supplementary analysis 1: The analysis 
will be performed using the same method as 
the main estimand based on the PPS1. 
 
Supplementary analysis 2: The treatment 
policy strategy will be used for all 
intercurrent events; the FAS1 will be used, 


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Label of 
estimand 
Description of estimand 
Main estimator 
Sensitivity/ Supplementary analysis 
Analysis sets 
Rules for imputation 
Model/method for the 
main analytical 
methods 
and the missing data will be subject to the 
imputation rules of the main estimator, that 
is, the multiple imputation method (MI) will 
be used to impute the missing data in the 
placebo group, and the J2R (jump to 
reference) method will be used to impute the 
missing data in the test group. 
Estimand of 
key 
secondary 
endpoints 
The differences in the following 
measures in patients aged 12 
years and older with moderate to 
severe AD and weighing ≥40 kg 
between the CBP-201 300mg 
Q2W group and the placebo 
group: 
 
 
The proportion of subjects 
achieving EASI-75 at W16 
 
The proportion of subjects 
whose weekly average PP-
NRS is decreased by ≥ 4 
points from baseline at 
W16; 
 
The proportion of subjects 
whose weekly average PP-
NRS is decreased by ≥ 3 
points from baseline at 
W16; 
FAS1 (will include 
all subjects in RS1 
who have received 
the study drug at 
least once). 
For 
subjects 
who 
experience intercurrent 
events, their visits after 
the intercurrent events 
will be handled in 
accordance with the 
strategies for managing 
intercurrent 
events 
listed in Table 7.4.2. 
If the target variable is 
still 
missing 
after 
application 
of 
the 
strategies for managing 
intercurrent events, the 
multiple 
imputation 
(MI) method will be 
used to impute the 
missing data in the 
placebo group, and the 
J2R (jump to reference) 
For categorical variables, 
differences in response 
rates 
between 
the 
treatment 
group 
and 
placebo group and their 
95% confidence intervals 
will be analyzed using 
the 
Cochran-Mantel- 
Haenszel test stratified 
by 
baseline 
disease 
severity (IGA 3 or 4). 
 
For continuous 
variables, analysis will 
be performed using an 
MMRM model that will 
include treatment group, 
baseline disease severity 
(IGA 3 or 4), baseline 
value of the 
Sensitivity analysis 1: When the target 
variable is still missing after application of 
the strategy for managing intercurrent 
events, 
categorical 
variables 
will 
be 
classified as treatment failure. Continuous 
variables should be imputed with WOCF. 
 
Sensitivity analysis 2:  For the subjects who 
are incorrectly stratified and randomized, 
the analysis will be performed using the 
stratification during randomization and the 
method the same as the main estimator; 
 
Supplementary analysis 1: The analysis 
will be performed using the same method as 
the main estimand based on the PPS1. 
 
Supplementary analysis 2: The treatment 
policy strategy will be used for all 
intercurrent events; the FAS1 will be used, 


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Label of 
estimand 
Description of estimand 
Main estimator 
Sensitivity/ Supplementary analysis 
Analysis sets 
Rules for imputation 
Model/method for the 
main analytical 
methods 
 
Change 
and 
percentage 
change 
in 
the 
weekly 
average 
PP-NRS 
from 
baseline at W16; 
 
The proportion of subjects 
achieving EASI-90 at W16 
 
A patient should be regarded as 
treatment failure if he/she uses 
prohibited 
drugs/treatments 
specified in the protocol for 
which the study treatment must 
be early terminated or other 
rescue therapy that has a major 
impact on the assessment of the 
key secondary endpoints due to 
poor response, or has premature 
discontinuation 
of 
treatment/EOT due to AEs. In 
this case, continuous variables 
should be imputed with WOCF. 
method will be used to 
impute the missing data 
in the CBP- 201 group. 
corresponding endpoint, 
visit, interaction of visit 
and treatment group, and 
the LSMEAN estimate 
values and their 95% 
confidence intervals will 
be summarized. 
and the missing data will be subject to the 
imputation rules of the main estimator, that 
is, the multiple imputation method (MI) will 
be used to impute the missing data in the 
placebo group, and the J2R (jump to 
reference) method will be used to impute the 
missing data in the test group. 


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In the J2R (jump to reference) method, when the data of subjects of the active treatment group 
are missing, it is assumed that their statistical results are the same as those of the placebo group, 
that is, it is considered that the pharmacological action of the drug for the active treatment 
group is the same as that of the placebo group. PROC MI will be used for J2R imputation, and 
the missing data of the active treatment group will be imputed with the results obtained by 
posterior predictive distribution of the placebo group. Markov Chain Monte Carlo (MCMC) 
will be used to extend the data, and a regression method will be used to generate M datasets 
(M is set as 30 for the primary analysis and as 1000 for other cases in this study). The imputed 
variables should include: treatment group, stratification factor (severity of baseline disease), 
baseline value of corresponding endpoint and measurement at each visit. Random seed is the 
earliest date of the first dose to all subjects. 
Table 5 Random Seeds of Multiple Imputation 
Endpoints 
Random Seeds 
IGA 
Minimum date of the first dose 
EASI 
Minimum date of the first dose + 1 
PP-NRS 
Minimum date of the first dose + 2 
BSA 
Minimum date of the first dose + 3 
SCORAD 
Minimum date of the first dose + 4 
DLQI 
Minimum date of the first dose + 5 
POEM 
Minimum date of the first dose + 6 
Tipping point analysis: To evaluate the robustness of the primary efficacy endpoint analysis, 
tipping point analysis should be performed on the primary efficacy endpoint at W16. The 
tipping point method is binary, that is, the assumptions of missing values of the active treatment 
group and the placebo group are mutually independent. Assuming that the response rate of 
missing values of the two groups increases by 10% from 0 to 100%, the subjects with a missing 
response in the two groups at a certain percentage will be randomly assigned as responders and 
non-responders in a specified number of imputed datasets randomly generated by the binomial 
distribution. Then the same analysis method as that for the primary study endpoint will be used 
to obtain the comparison results between the two groups in each imputed dataset. Finally, 
Rubin’s Rule will be used to pool these results. If there is a pair of assumed response rate that 
overturns the study conclusion, that is, p value is more than 0.05, the two assumed response 
rates will be the cut-off points. 
Subgroup analysis will be performed on the primary efficacy endpoint (the proportion of 
subjects whose IGA score is 0-1 and decreased by ≥ 2 points from baseline at W16) and the 
key secondary efficacy endpoint (the proportion of subjects achieving EASI-75 at W16) by 
gender (male/female), severity of baseline disease (moderate [IGA = 3]/severe [IGA = 4]), 
history of allergic diseases or allergy history (yes/no), baseline EASI (< baseline median 
EASI/≥ baseline median EASI), baseline PP-NRS (< baseline median PP-NRS/≥ baseline 
median PP-NRS). The analytical method is the same as the primary analysis method for the 


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primary efficacy endpoint and the key secondary efficacy endpoint. The subjects with missing 
subgroup variables will not be included. 
Sensitivity analysis will be performed on the primary efficacy endpoint (the proportion of 
subjects whose IGA score is 0-1 and decreased by ≥ 2 points from baseline at W16) and the 
key secondary efficacy endpoint (the proportion of subjects achieving EASI-75 at W16) using 
the stratification during randomization and the method the same as the main estimator. 
7.4.4. Other efficacy endpoint analysis 
The categorical efficacy endpoint analysis in Stage 1 will be performed using the same method 
as the primary efficacy endpoint analysis. 
The continuous efficacy endpoint analysis in Stage 1 will be performed using the same method 
as the secondary efficacy endpoint analysis. 
According to the investigator's judgment, AD aggravation or deterioration of symptoms which 
requires drugs or treatments originally prohibited by the protocol for rescue therapy will be 
defined as “AD recurrence” event. 
The number of AD recurrence, the number of subjects with AD recurrence, and the number of 
days of AD recurrence in Stage 1, from baseline to W8, from W9 to W16 will be analyzed. 
The total number of AD recurrence in each stage will be summarized. AD recurrence will be 
summarized by the number of recurrences, that is, 0, 1, 2 and ≥ 3. The number and percentage 
of subjects will be calculated. Chi-squared test will be adopted to compare whether the 
differences between the two groups are statistically significant. The total number of subjects 
with AD recurrence in each stage will be summarized, and the number and percentage of 
subjects will be calculated. Chi-squared test will be performed to compare whether the 
differences between the two groups are statistically significant. The number of days of AD 
recurrence in each stage will be summarized by descriptive statistics. 
7.4.5. Efficacy analysis in stage 2 
During efficacy analysis in Stage 2, the percentage of subjects achieving efficacy endpoint and 
its confidence interval will be calculated for categorical efficacy endpoints. For continuous 
efficacy endpoints, ANCOVA model will be used to calculate the mean, the Least Square Mean, 
95% confidence interval and SE of the change from baseline and percentage change from 
baseline of each efficacy endpoint. The model will include treatment group, severity of baseline 
disease (IGA 3 or 4), and baseline value of corresponding endpoint. Inferential statistics will 
not be performed during the Stage 2 analysis. The following two analyses will be performed. 
Analysis method 1: Categorical efficacy endpoints after the occurrence of events will be 
regarded as no response for subjects who have the following conditions; continuous efficacy 
endpoints after the occurrence of events will be imputed using WOCF in Stage 2; other missing 
data except for the conditions above will be imputed using multiple imputation (MI). 
• Group adjustment 


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• Premature discontinuation of treatment/EOT due to AEs 
• Use of prohibited drugs/treatments specified in the protocol as a rescue treatment for AD 
due to poor response, which has a major impact on the assessment of the efficacy endpoints, 
including: 
The following prohibited drugs/treatments are used during Stage 2 (W16 to W52): 
 Dupilumab or any anti-IL-4Rα or IL-13 antibodies; 
 Topical PDE-4 inhibitors or JAK inhibitors; 
 Systemic treatment with corticosteroids or other immunosuppressive and/or 
immunomodulatory agents, such as cyclosporine, mycophenolate mofetil, azathioprine, 
methotrexate, or oral JAK inhibitors; 
 Cell depletion agents (e.g., rituximab) or other biological agents; 
 Other investigational drugs (non CBP-201) or treatments. 
Or the following prohibited drugs/treatments are used for a cumulative period of more than 7 
days during Stage 2 (W16 to W52): 
 Initiation of SIT, or dose up-regulation; 
 TCS or TCI (topical drugs can be used for AD lesion areas only); 
 Phototherapy (NBUVB, UVB, UVA1, PUVA), sunbed or any other LED therapies; 
 Bleaching baths more than 2 times a week; 
 Any drug for the treatment of AD (If topical drugs, only those used for AD lesion areas 
will be counted) that may interfere with the evaluation of efficacy results or affect the 
evaluation of AD severity. 
Analysis method 2: The analysis will be performed using the actual observed values. If the 
actual observed value is missing, it will be imputed by MI. 
During MI in Stage 2, M data sets will be generated by regression method (M is set as 1000 
during Stage 2 analysis). 
7.5. Safety Analysis 
7.5.1. Drug exposure and compliance 
Study drug exposure will be analyzed based on SS1, SS2 and SS3. Study drug exposure 
duration and exposure dose during treatment period of Stages 1 and 2 will be summarized by 
descriptive statistics. 
The compliance with the study drug and emollients (background treatment) in Stages 1 and 2 
will be summarized by descriptive statistics. The subjects with a compliance < 70%, ≥ 70% 
and ≤ 130%, and > 130% will be summarized, and the number and percentage of subjects will 


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32 
be calculated. Subjects’ compliance with the study drug and emollients (background treatment) 
will be tabulated. 
7.5.2. AEs 
AEs will be analyzed based on the SS1 and SS2. Subjects who have received at least one dose 
of the study drug will be analyzed based on SS3. 
AEs will be coded using MedDRA. 
The occurrence of overall AEs will be summarized to generate summary tabulations of TEAEs. 
TEAEs of special interest and drug-related AESIs will be summarized. The numbers of subjects 
with various AEs, numbers and incidences of events will be calculated. The number of subjects 
with various AEs, the number of events, the incidence and annual incidence of events will be 
calculated based on SS3. 
AEs, drug-related AEs, SAEs, AESIs, AEs leading to death, AEs leading to treatment 
discontinuation, injection site AEs, CTCAE grade 3-5 AEs, AEs with an incidence of > 5%, 
and AD recurrence-related AEs will be tabulated. 
The incidences of the following TEAEs will be summarized by SOC and PT, the numbers of 
subjects with various AEs, and the numbers and incidences of events will be calculated. They 
will be ranked in descending order of total number of subjects by SOC and PT. In addition, 
annual incidences of TEAEs, treatment-emergent SAEs, treatment-emergent AESIs, drug-
related AEs, drug-related SAEs will be calculated by SOC and PT based on SS3. 
1) TEAEs; 
2) Drug-related AEs; 
3) SAEs; 
4) Drug-related SAEs; 
5) AEs leading to death; 
6) AEs leading to treatment discontinuation; 
7) AEs leading to treatment interruption; 
8) AESIs; 
9) Drug-related AESIs; 
10) Injection site AEs; 
11) CTCAE grade 3-5 AEs; 
12) AEs with an incidence of > 5%; 
In addition, the incidences of TEAEs, AESIs, and injection site AEs will be summarized by 
CTCAE Grade, correlation with study drug, SOC and PT, and the number and percentage of 
subjects will be calculated. 


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33 
A subject with an AE of the same SOC and PT more than once will have that event counted 
only once within each SOC and PT. 
7.5.3. Laboratory test results 
Analysis will be performed based on SS1, SS2 and SS3. Analysis will not be performed using 
SS3 by visit.  
The hematology, blood biochemistry and urinalysis parameters at baseline and each visit and 
their changes from baseline at each visit will be summarized by descriptive statistics. 
The number and percentage of subjects whose hematology, blood biochemistry and urinalysis 
parameters at baseline and each visit are below, within and above the normal range will be 
summarized. 
Pre-treatment and post-treatment laboratory test results are classified into abnormal with 
clinical significance, abnormal without clinical significance, normal, and not tested in an order 
of abnormal with clinical significance > abnormal without clinical significance > normal > not 
tested. Then shift tables are generated. The shift tables are generated based on CTCAE 5.0. 
All laboratory test results and abnormal laboratory test results for hematology, blood 
biochemistry, urinalysis and urine pregnancy will be tabulated. 
Qualitative laboratory test results will be summarized by visit. The number and percentage of 
subjects for each category will be calculated and tabulated. 
7.5.4. ECG 
Analysis will be performed based on SS1, SS2 and SS3. Analysis will not be performed using 
SS3 by visit. 
Ventricular rhythm, PR, QRS, QT and QTcF results at each post-baseline visit and their 
changes from baseline at each visit will be summarized by descriptive statistics. The analysis 
of variance will be used to detect possible difference between groups. 
Special attention will be paid to QTcF interval prolongation: 
 
QTcF interval > 450 ms 
 
QTcF interval > 480 ms 
 
QTcF interval > 500 ms 
 
Increase in QTcF interval from baseline > 30 ms 
 
Increase in QTcF interval from baseline > 60 ms 
Pre-treatment and post-treatment ECG results are classified into abnormal with clinical 
significance, abnormal without clinical significance, normal, and not tested in an order of 
abnormal with clinical significance > abnormal without clinical significance > normal > not 
tested. Then shift tables are generated. 


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ECG results of QTcF interval prolongation will be tabulated. All ECG results and clinically 
significant abnormal ECG results will be tabulated. 
7.5.5. Other safety evaluation 
The following analyses will be performed based on SS1, SS2 and SS3. Analysis will not be 
performed using SS3 by visit. 
Physical examination 
Physical examination results at each visit in Stages 1 and 2 will be classified into abnormal 
with clinical significance, abnormal without clinical significance, normal and not tested. The 
frequency and percentage of each category will be summarized. 
All physical examination results and abnormal physical examination results with clinical 
significance will be tabulated. 
Vital signs 
The vital signs at baseline and their changes from baseline at each visit of Stages 1 and 2 will 
be summarized by descriptive statistics. The analysis of variance will be used to detect possible 
difference between groups. 
Vital sign results at each visit of Stages 1 and 2 will be classified into abnormal with clinical 
significance, abnormal without clinical significance, normal and not tested. The frequency and 
percentage of each category will be summarized. 
All vital sign results and abnormal vital sign results with clinical significance will be tabulated. 
Eye examination 
Eye examination results at each visit of Stages 1 and 2 will be classified into abnormal with 
clinical significance, abnormal without clinical significance, normal and not tested. The 
frequency and percentage of each category will be summarized. 
All eye examination results and abnormal eye examination results with clinical significance 
will be tabulated. 
ADA test 
See PK/PD statistical analysis plan for details. 
7.6. Pharmacokinetics (PK) analysis 
See PK/PD statistical analysis plan for details. 
7.7. Pharmacodynamics (PD) and Biomarker Analysis 
See PK/PD statistical analysis plan for details. 
7.8. Changes to Planned Analysis in the Protocol 
For the other efficacy endpoints, the following updates will be made: 


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Description in protocol 
Updated description in SAP 
The percentage decrease in the overall EASI score 
between W16 and W52 
Change and percentage change in the EASI score 
from baseline at each visit time point from the start 
of Stage 2 maintenance treatment to the end of 
study (W60) 
Change in weekly average PP-NRS from baseline 
between W16 and W52 
Change and percentage change in the weekly 
average PP-NRS from baseline at each visit time 
point from the start of Stage 2 maintenance 
treatment to the end of study (W60) 
Change in POEM from baseline between W16 and 
W52 
Change and percentage change in POEM from 
baseline at each visit time point from the start of 
Stage 2 maintenance treatment to the end of study 
(W60) 
Percentage change in the BSA of AD involvement 
from baseline between W16 and W52 
Change and percentage change in the percentage 
of BSA of AD involvement from baseline at each 
visit time point from the start of Stage 2 
maintenance treatment to the end of study (W60) 
Change in SCORAD from baseline between W16 
and W52 
Change and percentage change in SCORAD from 
baseline at each visit time point from the start of 
Stage 2 maintenance treatment to the end of study 
(W60) 
Change in DLQI from baseline between W16 and 
W52 
Change and percentage change in DLQI from 
baseline at each visit time point from the start of 
Stage 2 maintenance treatment to the end of study 
(W60) 
None 
Other new efficacy endpoints: 
• 
The proportion of subjects who maintain 
EASI-75 response at W52 to the subjects 
who achieve EASI-75 at W16 
• 
The proportion of subjects whose IGA score 
remains 0-1 at W52 to the subjects whose 
IGA score is 0-1 at W16 
• 
The proportion of subjects who achieve 
EASI-75 at each visit time point of Stage 2 
maintenance treatment to the subjects who 
achieve EASI-50 but not EASI-75 at W16 
• 
The proportion of subjects achieving EASI-
50 at each of the other visit time points 
from the start of Stage 2 maintenance 
treatment to the end of study (W60) 
• 
The proportion of subjects achieving EASI-
75 at each of the other visit time points 
from the start of Stage 2 maintenance 
treatment to the end of study (W60) 
• 
The proportion of subjects achieving EASI-
90 at each of the other visit time points 
from the start of Stage 2 maintenance 


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treatment to the end of study (W60) 
• 
The proportion of subjects achieving EASI-
100 at each of the other visit time points 
from the start of Stage 2 maintenance 
treatment to the end of study (W60) 
• 
The proportion of subjects whose IGA score 
is 0-1 and decreased by ≥ 2 points from 
baseline at each of the other visit time 
points from the start of Stage 2 maintenance 
treatment to the end of study (W60) 
• 
The proportion of subjects whose weekly 
average PP-NRS is decreased by ≥ 4 
points from baseline at each of the other 
visit time points from the start of Stage 2 
maintenance treatment to the end of study 
(W60) 
• 
The proportion of subjects whose weekly 
average PP-NRS is decreased by ≥ 3 
points from baseline at each of the other 
visit time points from the start of Stage 2 
maintenance treatment to the end of study 
(W60) 
 
8. References 
Guidelines for Management and Statistical Analysis Plan of Drug Clinical Trial Data 2021. 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 1.0 
1 
Suzhou Connect Biopharmaceuticals, Ltd. 
A double-blind, multi-center, randomized controlled clinical study to 
evaluate the efficacy and safety of CBP-201 in Chinese subjects with 
moderate to severe atopic dermatitis 
CBP-201-CN002 
Statistical Analysis Plan 
Version: 1.0 
Date: September 20, 2022 
NCT Number：NCT05017480


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 1.0 
 
2 
Approval Page of Sponsor 
A double-blind, multi-center, randomized controlled clinical study to evaluate 
the efficacy and safety of CBP-201 in Chinese subjects with moderate to severe 
atopic dermatitis 
 
CBP-201-CN002 
 
Statistical Analysis Plan 
 
Version: 1.0 
 
Author: 
Chen Jingyun 
Company: 
Hangzhou Tigermed Consulting Co., Ltd. 
Signature: 
<signed> 
Date: September 21, 2022 
Reviewer: 
Xu Jinmei 
Company: 
Hangzhou Tigermed Consulting Co., Ltd. 
Signature: 
<signed> 
Date: September 21, 2022 
Sponsor approval: 
Meng Yuhui 
Company: 
Suzhou Connect Biopharmaceuticals, 
Ltd. 
Signature: 
<signed> 
Date: September 21, 2022 
 
 
 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 1.0 
 
3 
Record of revisions 
Version 
Version date 
Author 
Description 
1.0 
September 20, 2022 
Chen Jingyun 
Initial version 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 1.0 
 
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Table of Contents 
1. 
Introduction ......................................................................................................................... 7 
2. 
Study objectives .................................................................................................................. 7 
2.1. 
Primary Objective ........................................................................................................ 7 
2.2. 
Secondary Objectives .................................................................................................. 7 
3. 
Study design ........................................................................................................................ 7 
3.1. 
Overall design .............................................................................................................. 7 
3.2. 
Sample size .................................................................................................................. 9 
4. 
Study Endpoints ................................................................................................................ 10 
4.1. 
Efficacy endpoints ..................................................................................................... 10 
4.1.1. Primary endpoint ................................................................................................... 10 
4.1.2. Secondary endpoints .............................................................................................. 10 
4.1.3. Other efficacy endpoints ....................................................................................... 10 
4.2. 
Safety endpoints ......................................................................................................... 11 
4.2.1. Drug Exposure and Compliance ............................................................................ 11 
4.2.2. Adverse events (AEs) ............................................................................................ 11 
4.2.3. Laboratory tests ..................................................................................................... 13 
4.2.4. Electrocardiogram (ECG) ...................................................................................... 14 
4.2.5. Others .................................................................................................................... 14 
4.3. 
PK/PD Endpoints ....................................................................................................... 14 
5. 
Statistical Hypothesis ........................................................................................................ 14 
6. 
Analysis datasets ............................................................................................................... 14 
7. 
Statistical methods ............................................................................................................ 16 
7.1. 
Overall statistical consideration ................................................................................. 16 
7.2. 
Methods for Data Processing ..................................................................................... 16 
7.2.1. Convention of data processing and processing of missing data ............................ 16 
7.2.2. Derived and Transformed Data ............................................................................. 17 
7.3. 
Study Subjects ........................................................................................................... 17 
7.3.1. Subject disposition ................................................................................................ 17 
7.3.2. Protocol Deviations ............................................................................................... 17 


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7.3.3. Analysis datasets ................................................................................................... 18 
7.3.4. Demographics and Baseline Characteristics ......................................................... 18 
7.3.5. Medical history of subjects .................................................................................... 18 
7.3.6. Prior Medication, Concomitant Medication, and Prior and Concomitant Non-
drug Therapies ....................................................................................................... 18 
7.4. 
Efficacy analysis ........................................................................................................ 19 
7.4.1. Visit window of efficacy analysis ......................................................................... 19 
7.4.2. Intercurrent events and handling strategies ........................................................... 19 
7.4.3. Analysis of the primary efficacy endpoint and key secondary efficacy 
endpoints ............................................................................................................... 23 
7.4.4. Other efficacy endpoint analysis ........................................................................... 27 
7.5. 
Safety Analysis .......................................................................................................... 27 
7.5.1. Drug exposure and compliance ............................................................................. 27 
7.5.2. AEs ........................................................................................................................ 27 
7.5.3. Laboratory test results ........................................................................................... 28 
7.5.4. ECG ....................................................................................................................... 29 
7.5.5. Other safety evaluation .......................................................................................... 29 
7.6. 
Pharmacokinetics (PK) analysis ................................................................................ 30 
7.7. 
Pharmacodynamics (PD) and Biomarker Analysis ................................................... 30 
7.8. 
Changes to Planned Analysis in the Protocol ............................................................ 30 
8. 
References ......................................................................................................................... 30 
 
 


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Abbreviation 
Abbreviation 
Explanation 
AD 
Atopic Dermatitis 
AE 
Adverse Event 
AESI 
Adverse Event of Special Interest 
CTCAE 
Common Terminology Criteria for Adverse Event 
DSMB 
Data Safety Monitoring Board 
EASI 
Eczema Area and Severity Index 
FAS 
Full Analysis Set 
IGA 
Validated Investigator Global Assessment 
MedDRA 
Medical Dictionary for Regulatory Activities 
PD 
Pharmacodynamics 
PK 
Pharmacokinetics 
PT 
Preferred Term 
Q1 
25% Quartile 
Q2W 
Once Every 2 Weeks 
Q3 
75% Quartile 
Q4W 
Once Every 4 Weeks 
RS 
Randomization Set 
SAE 
Serious Adverse Event 
SOC 
System Organ Class 
SS 
Safety Set 
TEAE 
Treatment-Emergent Adverse Event 
WHO 
World Health Organization 
 
 
 


Suzhou Connect Biopharmaceuticals, Ltd. 
Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 1.0 
 
7 
1. Introduction 
This statistical analysis plan (SAP) describes the detailed statistical analysis methods planned 
for the protocol entitled “a double-blind, multi-center, randomized controlled clinical study to 
evaluate the efficacy and safety of CBP-201 in Chinese subjects with moderate to severe atopic 
dermatitis” 
(protocol 
number: 
CBP-201-CN002) 
sponsored 
by 
Suzhou 
Connect 
Biopharmaceuticals, Ltd. 
This plan is prepared based on the Study Protocol Version 4.0 dated 01Aug2022 and the Case 
Report Form (CRF) Version 3.0 dated 27Apr2022. The planned analyses are mainly prepared 
for Stage 1. The analyses planned for Stage 2 will be described in subsequent update. 
2. Study objectives 
2.1. Primary Objective 
 
To assess the efficacy of CBP-201 in subjects with moderate to severe AD. 
2.2. Secondary Objectives 
● 
To assess the safety and tolerability of CBP-201 in subjects with moderate to severe AD; 
● 
To assess the pharmacokinetic (PK) profile of CBP-201 in subjects with moderate to 
severe AD; 
● 
To assess the pharmacodynamic (PD) profile of CBP-201; 
● 
To assess the immunogenicity of CBP-201. 
3. Study design 
3.1. Overall design 
This study is a randomized, double-blind, multi-center, controlled study designed to assess the 
efficacy, safety, and PK profiles of CBP-201 in eligible subjects with moderate to severe AD. 
255 subjects will be randomized in a 2:1 ratio to receive either CBP-201 300 mg Q2W or 
placebo. 
The study includes a screening period, a treatment period and a follow-up period. The treatment 
period is divided into two stages: 
Stage 1: This is a placebo-controlled part. Subjects who meet all the inclusion criteria and do 
not meet any of the exclusion criteria will be randomized in a 2:1 ratio into one of the following 
2 groups to receive either investigational product or placebo treatment. The randomization will 
be stratified by the severity of their baseline disease (moderate [IGA=3] and severe [IGA=4]). 
● 
Group A (CBP-201): the subjects will receive 600 mg of CBP-201 subcutaneously (4 ml 
in total, 2 injections of 2 ml each in different sites) on Day 1, followed by 300 mg of CBP-
201 (2 ml) at Week 2 (W2) and every 2 weeks thereafter until W14; 
● 
Group B (placebo): the subjects will receive 4 ml of placebo subcutaneously (2 injections of 2 ml 


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Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
Version: 1.0 
 
8 
each in different sites) on Day 1, followed by 2 ml of placebo at W2 and every 2 weeks thereafter 
until W14. 
Table 1: Dosing Regimen by Group in Stage 1 
Group 
W0 
W2 
W4 
W6 
W8 
W10 
W12 
W14 
Group A 
4XC 
2XC 
2XC 
2XC 
2XC 
2XC 
2XC 
2XC 
Group B 
4XP 
2XP 
2XP 
2XP 
2XP 
2XP 
2XP 
2XP 
Note: C=CBP-201; P=placebo; #X=number of ampoules. 
Before the administration of study drug at W16 visit, all subjects will be assessed for efficacy. 
Treatment assignment for Stage 2 maintenance treatment will be performed based on whether 
a 50% or greater reduction in EASI score (i.e. EASI-50) is achieved. 
Stage 2: The grouping for Stage 2 maintenance treatment is as follows: 
● 
Subjects who have achieved EASI-50 in the W16 pre-administration efficacy assessment 
will be  randomized in a 1:1 ratio into one of the following two groups to receive study 
treatment starting from W16: 
● Group C: The subjects will receive 300 mg of CBP-201 subcutaneously every 2 
weeks until W50; 
● Group D: The subjects will receive 300 mg of CBP-201 300 mg subcutaneously 
every 4 weeks. In order to maintain the study drugs administered every 2 weeks blind, 
at the middle of the 4-week dose interval, the subjects will receive 2 ml of placebo 
subcutaneously every 4 weeks until W50. 
● 
Subjects who have not achieved EASI-50 in the W16 pre-administration efficacy 
assessment will receive the following treatment starting from W16: 
● Group E: The subjects will receive 300 mg of CBP-201 subcutaneously every 2 
weeks until W50. 
● 
If subjects in group C and group D have not achieved EASI-50 in two continuous pre-
administration efficacy assessments, they will be assigned to group E to be treated with 
300 mg of CBP-201 subcutaneously every 2 weeks from the visit when EASI-50 is not 
achieved for the second time until W50. 
Table 2: Dosing Regimen by Group in Stage 2 
Group 
W16 
W18 
W20 
W22 
W24 
…… 
W50 
Group C 
2XC 
2XC 
2XC 
2XC 
2XC 
…… 
2XC 
Group D 
2XC 
2XP 
2XC 
2XP 
2XC 
…… 
2XP 
Group E 
2XC 
2XC 
2XC 
2XC 
2XC 
…… 
2XC 
Note: C=CBP-201; P=placebo; #X=number of ampoules. 
 
 


Suzhou Connect Biopharmaceuticals, Ltd. 
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Version: 1.0 
 
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All subjects (including the subjects who prematurely discontinue treatment) will be followed 
up for 8 weeks after the last dose. 
The overall study design is shown in the diagram below: 
 
Figure 1: Study Design Diagram 
Note: 
1： The subjects will receive a loading dose of the study drug (investigational product/placebo) on D1 at a 
dose of 600 mg (4 ml); 
2： Response is defined as a 50% or greater reduction in the EASI score; 
3： In order to maintain the study drugs administered every 2 weeks blind, at the middle of the 4-week dose 
interval, the subjects will receive 2 ml of placebo subcutaneously every 4 weeks until W50. 
4： If subjects in group C and group D have not achieved EASI-50 in two continuous pre-administration 
efficacy assessments, they will be assigned to group E to be treated with 300 mg of CBP-201 
subcutaneously every 2 weeks from the visit when EASI-50 is not achieved for the second time until 
W50. 
3.2. Sample size 
It is planned to enroll 255 subjects (in a 2:1 ratio, 170 subjects in the CBP-201 300 mg Q2W 
group, and 85 subjects in the placebo group) who will randomly receive either CBP-201 300 
mg Q2W or placebo. 
This sample size provides a power of approximately more than 90% to detect the difference 
between groups at a two-sided significance level of 5% under the assumption that 27% and 9% 
of subjects in the CBP-201 Q2W group and the placebo group can achieve an IGA score of 0-
1 at W16 for the primary endpoint, respectively, accounting for a dropout rate of 15%. 
Based on the results of another completed phase II international multicenter clinical study of 
CBP-201 in patients with moderate-to-severe atopic dermatitis, the proportion of subjects 
achieving the primary efficacy endpoint was 28.1% in the CBP-201 300 mg Q2W group and 
10.7% in the placebo group, at a two-sided significance level of 0.05. If the results of this trial 
are similar to that of the WW001 trial, the above sample size would provide a power of more 
than 85% to detect the difference of the therapeutic effect on the primary endpoint between the 
CBP- 201 300 mg Q2W group and the placebo group. Therefore, no adjustment is made to the 
sample size. 
Screening 
period 
(D-28~D-1) 
Stage 1 treatment 
period 
(D1~W16) 
Stage 2 treatment 
period 
(W16~W52) 
Follow-up 
period 
(W53~W60) 
Primary analysis 
Primary endpoint 
assessment 
2:1 
R
d
W52/end of 
treatment or 
premature 
termination of 
treatment 
W60 End 
of study 
Not meeting the criteria for response 
Meeting the criteria for 
response2, 1:1 randomize 
Group E: 
Group D: 
Group C: 
Group A: CBP-201 300 mg q2w (n=170) 
Group B: Placebo q2w (n=85) 


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Version: 1.0 
 
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The primary analysis of this study will still be based on the 255 subjects enrolled in accordance 
with V2.1 and its earlier versions of the protocol. Subjects newly enrolled (approximately 81 
cases) based on the protocol after V2.1 will not be included in the primary analysis, and only 
supplementary analysis will be performed. 
4. Study Endpoints 
4.1. Efficacy endpoints 
4.1.1. Primary endpoint 
The primary efficacy endpoint is the proportion of subjects whose IGA score is 0-1 and 
decreased by ≥2 points from baseline at W16. 
4.1.2. Secondary endpoints 
Key secondary endpoints 
● 
The proportion of subjects achieving EASI-75 at W16; 
● 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥ 4 points from 
baseline at W16; 
● 
The proportion of subjects whose weekly average PP-NRS is decreased by ≥ 3 points from 
baseline at W16; 
● 
Change and percentage change in the weekly average PP-NRS from baseline at W16; 
● 
The proportion of subjects achieving EASI-90 at W16. 
Other secondary endpoints 
● 
Change and percentage change in the EASI score from baseline at W16; 
● 
The proportion of subjects achieving EASI-50 at W16; 
● 
Percentage change in the BSA of AD involvement from baseline at W16; 
● 
Percentage change in the SCORAD score from baseline at W16; 
● 
Change in DLQI from baseline at W16; 
● 
Change in POEM from baseline at W16; 
● 
Percentage change in the weekly average PP-NRS from baseline at W2; 
4.1.3. Other efficacy endpoints 
● 
The proportion of subjects whose IGA score is decreased by ≥2 points from baseline at 
W16; 
● 
The proportion of subjects achieving EASI-100 at W16; 
● 
The number of AD recurrences and number of days with recurrences from baseline to W16; 
● 
Change in efficacy parameters (e.g., IGA, EASI, BSA, SCORAD, POEM and DLQI) from 


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Statistical Analysis Plan 
Protocol number: CBP-201-CN002 
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11 
baseline to W16; 
● 
Change in weekly average PP-NRS from baseline at W16; 
● 
The number of subjects with AD recurrence from baseline to W8; 
● 
The number of subjects with AD recurrence from W8 to W16; 
4.2. Safety endpoints 
4.2.1. Drug Exposure and Compliance 
Study drug exposure duration will be summarized by study stage. The duration will be 
calculated with the following formula: 
Exposure duration = date of the last dose - date of the first dose + 14 
For analysis of study drug exposure dose, total drug exposure dose of subjects will be 
summarized. 
The compliance with the study drug and emollients (background treatment) will be calculated 
respectively. If the compliance is lower than 70% or higher than 130%, it will be determined 
as poor compliance. 
Calculation formula of compliance with study drug: Compliance% = actual dose/planned dose 
* 100%. 
Where the actual dose is the total dose of the drug actually used in Stage 1, and the planned 
dose is the total dose of the drug that should be used in Stage 1. 
Calculation formula of compliance with emollients: Compliance% = number of days of using 
emollients as required by protocol/total number of days for which emollients should be used * 
100% 
4.2.2. Adverse events (AEs) 
AEs 
An adverse event refer to any untoward medical occurrence after subjects receive the 
investigational medicinal product, which can be manifested as symptoms, signs, diseases or 
laboratory test abnormalities, but are not necessarily related to the investigational medicinal 
product. See Section 10.1 of the protocol for details. 
Treatment-emergent adverse event (TEAE) 
TEAE is defined as an AE that occurs or worsens during treatment. The treatment period refers 
to the period from the first study drug administration to the end of the protocol-specified 
follow-up period. The cut-off date of TEAEs in Stage 1 is immediately before the first dose for 
Stage 2 or 10 weeks (70 days) after end of dosing in Stage 1, whichever occurs first; for the 
subjects who discontinue administration in Stage 1, the cut-off date of TEAEs is the end of 
follow-up period. 
 


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Drug-related AEs 
A drug-related AE refers to an AE whose relationship with the drug is related, possibly related 
or indeterminable. 
The criteria for determination of the correlation of AEs with treatment are as follows: 
Correlation 
Criteria for determination 
Related 
● 
There is a reasonable temporal sequence between the occurrence of AE and the 
medication; 
● 
The study drug explains the AE more reasonably than other reasons (e.g., the 
patient's preexisting disease, environmental or toxic factors, or other treatments 
the patient received, etc.); 
● 
The AE disappears or lessens after the drug is stopped or the dose is reduced; 
● 
The AE meets the known AE types of the suspect drug or its similar drugs; 
● 
The AE recurs after re-administration. 
Possibly related 
● 
There is a reasonable temporal sequence between the occurrence of AE and the 
medication; 
● 
The study drug explains the AE as reasonably as other reasons (e.g., the 
patient's preexisting disease, environmental or toxic factors, or other treatments 
the patient received, etc.); 
● 
The AE disappears or lessens after the drug is stopped or the dose is reduced 
(if applicable). 
Unlikely related 
● 
Other reasons (e.g., the patient's preexisting disease, environmental or toxic 
factors, or other treatments the patient received, etc.) explain the AE more 
reasonably than the study drug; 
● 
The AE does not disappear or lessen after the drug is stopped or the dose is 
reduced (if applicable), or the situation is unclear; 
● 
The AE does not recur after re-administration, or the situation is unclear. 
Not related 
● 
There is no reasonable temporal sequence between the occurrence of AE and 
the medication, or; 
● 
The AE has other evidence reasons (e.g., the patient's preexisting disease, 
environmental or toxic factors, or other treatments the patient received, etc.). 
Indeterminable 
● 
The above information is unclear, and the investigator believes that it cannot 
be judged based on the existing information, and the investigator cannot obtain 
further follow-up information. 
Serious Adverse Event (SAE) 
An event will be considered an SAE if the following situations occur. See Section 10.1.2 of the 
protocol for definition of SAE. SAEs will be judged by investigators on CRF. 
● 
Leading to death; 
● 
Life-threatening: The investigator determines that the patient is at immediate risk of death 
when the event occurs. This definition does not include events that may lead to death if it 
is assumed to be more serious; 
● 
Requiring hospitalization or prolongation of the original hospital stay; 


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● 
Leading to permanent or major disability or incapacitation (i.e., significant impairment of 
the subject's activities of daily living); 
● 
Including congenital abnormalities or birth defects in the offspring of the patient; 
● 
Significant medical events: According to the medical judgment of the investigator, other 
significant medical events that may endanger the patient and may require medical or 
surgical intervention to prevent one of the above outcomes. 
Adverse Event of Special Interest (AESI) 
AESIs in the study include: Conjunctivitis, keratitis, anaphylactic reaction, injection site 
reactions which persist over 24 h, AST/ALT increased > 5 × ULN,  parasitic and opportunistic 
infection, pregnancy and symptomatic overdoses. 
AEs leading to treatment discontinuation 
In the study, action taken with study drug is drug discontinued or the subject will be withdrawn 
from treatment in response to these AEs. 
4.2.3. Laboratory tests 
Laboratory tests: Including hematology, blood biochemistry and urinalysis. The specific 
assessments are shown in Table as follows: 
Table 3: Laboratory tests 
Hematology 
Blood biochemistry 
Urinalysis 
White blood cell count 
Hemoglobin 
Hematocrit 
Red blood cell count 
Platelet count 
Neutrophil percentage 
Lymphocyte percentage 
Monocyte percentage 
Basophil percentage 
Eosinophil percentage 
Absolute neutrophil count 
Absolute lymphocyte count 
Absolute monocyte count 
Absolute eosinophil count 
Absolute basophil count 
Sodium 
Potassium 
Calcium 
Chlorine 
Serum urea/urea nitrogen 
Creatinine 
Glucose 
Total protein 
Albumin 
Total bilirubin 
Alanine aminotransferase 
Aspartate aminotransferase 
γ-glutamyltransferase 
Alkaline phosphatase 
Lactate dehydrogenase 
Creatine phosphokinase 
Total cholesterol 
Low-density lipoprotein 
High-density lipoprotein 
Bilirubin 
Red blood cells 
White blood cells 
Glucose 
Ketone 
Nitrite 
pH 
Protein 
Urine specific gravity 
Urobilinogen 
Microscopic examination (if 
necessary) 


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4.2.4. Electrocardiogram (ECG) 
12-lead ECG will be performed to collect ventricular rhythm, PR, QRS, QT, and QTcF. 
4.2.5. Others 
Vital signs 
Vital signs include systolic and diastolic blood pressure, heart rate, body temperature, and 
respiratory rate. 
Physical examination 
Physical examination includes general appearance, skin, eyes/ears/nose/throat, head and neck, 
cardiovascular system, respiratory system, abdomen, limbs, lymph nodes, musculoskeletal and 
nervous systems. Unless it is necessary to assess the status of AD involvement, there is no need 
to perform rectal or genital examinations. 
Other tests 
ADA test. 
4.3. PK/PD Endpoints 
PK endpoints: To analyze the blood concentration of CBP-201, and calculate the PK profile at 
steady-state trough concentrations of individuals and each group of subjects at each treatment 
time point. 
PD endpoints: Change in serum IL-4, IL-13, IgE, TARC levels and peripheral blood eosinophil 
count from baseline. 
5. Statistical Hypothesis 
The primary efficacy endpoint of the study is the proportion of subjects whose IGA score is 0-
1 and decreased by ≥ 2 points from baseline at W16. The following null and alternative 
hypotheses will be evaluated by statistical tests based on the efficacy endpoint. A two-sided 
significance level of 5% (α = 0.05) will be adopted. If p value is ≤ 0.05, the null hypothesis 
will be rejected and it is considered that there is a statistically significant difference in IGA 
parameter between the CBP-201 300 mg Q2W group and the placebo group. 
Null hypothesis (H0):  Efficacy in the CBP-201 300 mg Q2W group = efficacy in the placebo 
group 
Alternative hypothesis (H1):  Efficacy in the CBP-201 300 mg Q2W group ≠ efficacy in the 
placebo group 
6. Analysis datasets 
After the 255 subjects enrolled based on the V2.1 and prior versions of the protocol complete 
the administration and treatment, related evaluations and follow-up of Stage 1 (W16 pre-dose 
visit), the primary analysis will be performed based on the data of the 255 subjects, and the 


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following 6 analysis datasets are included. 
Screening set 1 
It will include all subjects who have signed the informed consent form.  
Randomization set 1 (RS1) 
RS1 will include all subjects randomized at baseline (D1), regardless of whether they have 
received the study drug. 
Full analysis set 1 (FAS 1) 
FAS 1 will include all subjects who have been randomized and received at least one dose of 
the study drug.  Subjects are analyzed within FAS 1 according to treatment assigned. 
Per protocol set (PPS 1) 
PPS 1 will include all subjects in FAS1 without any major protocol deviation that affects 
efficacy analysis.  Major protocol deviations that affect efficacy analysis have been discussed 
and determined at the blinded data review meeting of the study on September 19, 2022. Minutes 
of the data review meeting will be presented in an annex. 
By far, protocol deviations that affect efficacy analysis of the 255 subjects in Stage 1 are due 
to the following causes: 
1. Missing dose (I. Missing W12 and W14 doses; II. Missing 3 doses in Stage 1, equivalent 
to a compliance with study drug lower than 70%); 
2. Missing key efficacy results at W16 (both IGA and EASI missing); 
3. Key efficacy results at W16 out of window (both IGA and EASI out of window >10 days); 
4. Incorrect stratified randomization (only Stage 1); 
5. Violation of inclusion and exclusion criteria (topical corticosteroids are used before 
baseline; baseline disease severity fails to meet the requirements); 
6. Prohibited drugs (non-rescue treatment) that may affect efficacy 
Safety set 1 (SS 1) 
SS 1 will include all randomized subjects who have received at least one dose of study drug. 
Subjects are analyzed within SS 1 according to the treatment they actually received. 
PK set 1 (PKS1) 
PKS1 will include subjects who have received at least one dose of CBP-201 active drug and 
had at least 1 collected and analyzable PK sample. 
Table 4: Analysis Population and Treatment Group in Stage 1 
Analysis Populations 
Treatment Groups 
Analysis Stage 
RS1/ FAS1/ PPS1/ SS1 
1) 
Placebo 
Stage 1 treatment period. 


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2) 
CBP-201 300 mg Q2W 
7. Statistical methods 
7.1. Overall statistical consideration 
In the statistical tabulations, screening number of subjects is the universal unique identifier of 
subjects in the study. 
General rules of descriptive statistics: Quantitative variables are described by mean, standard 
deviation, median, minimum, maximum, Q1 and Q3. In terms of rounding, the numbers of 
decimal places of the minimum and maximum are consistent with that of original value, while 
those of mean, medium, Q1, and Q3 are 1 more than that of the original value, and that of 
standard deviation is 2 more than that of the original value. Categorical variables are  described 
by number and percentage of each category. The number of subjects is rounded to integer and 
percentage is rounded to one decimal place. It is unnecessary to present a percentage when the 
count is 0. 
General rules of inferential statistics: Two-sided test is adopted for all statistical tests (unless 
otherwise specified). P<0.05 will be considered statistically significant (unless otherwise 
specified). P value is rounded to 4 decimal places. If P < 0.0001, it is presented as ‘< .0001’; if 
P > 0.9999, it is presented as ‘> .9999’. 
The primary analysis of the study will be performed based on the data of Stage 1, that is, the 
placebo-controlled stage. The data analyzed will include all Stage 1 data from subjects who 
have completed Stage 1 or those who withdraw from Stage 1. 
For primary analysis, the baseline of efficacy analysis is defined as the last available value 
before randomization in Stage 1, and the baseline of safety analysis is defined as the last 
available value before the first dose in Stage 1. 
Statistical analyses will be performed using SAS 9.4. 
7.2. Methods for Data Processing 
7.2.1. Convention of data processing and processing of missing data 
The missing dates of AEs or concomitant medications/treatments will be imputed as follows. 
The imputation of missing dates will be used for classification only. When tabulations of 
relevant data are generated, unimputed dates will be still presented. 
Missing of start date: 
1) If the year and month are known and both are earlier than those of the first dose of the 
investigational product, the last day of the known month will be used for imputation. 
2) If the year and month are known and same as those of the first dose of the investigational 
product, the start date is the date of the first dose of the investigational product (date refers 
to “month, day”). 


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3) If the year and month are known and later than those of the first dose of the investigational 
product, it will be imputed with the first day of the known month. 
4) If only the year is known and earlier than that of the first dose of the investigational product, 
“December 31” will be used for imputation. 
5) If only the year is known and same as that of the first dose of the investigational product, 
the start date is the date of the first dose of the investigational product (date refers to 
“month, day”). 
6) If only the year is known and later than that of the first dose of the investigational product, 
it will be imputed with “January 1”. 
7) In other situations, the date of the first dose of the investigational product will be taken as 
corresponding start date. 
Missing of end date: 
1) If the year and month are known, it will be imputed with the last day of the known month. 
2) If only the year is known, it will be imputed with “December 31”. 
3) If the end date imputed is earlier than the start date, the end date will be taken as 
corresponding start date. 
4) Other conditions are regarded as missing. 
Missing laboratory data, ECG data, vital signs data, physical examination and other safety data 
will not be imputed. 
7.2.2. Derived and Transformed Data 
When the units of data from laboratories of different sites are inconsistent, the data will be 
converted according to international standard units. 
Apart from the calculation of study endpoints based on the data collected from CRF, other data 
will not be derived or transformed. 
Duration of exposure to drug (day) = date of the last dose - date of the first dose + 14. 
7.3. Study Subjects 
7.3.1. Subject disposition 
Screening and randomization of subjects will be summarized based on Screening Set 1. The 
number and percentage of subjects will be calculated, and the reasons for screening failure will 
be presented; in addition, study drug discontinuation and study termination in both stages will 
be summarized based on RS1, and the number and percentage of subjects will be calculated. 
Subject disposition will be tabulated. 
7.3.2. Protocol Deviations 
All subjects who have protocol deviations in Stage 1 will be summarized based on RS1, the 


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number and percentage of subjects will be calculated and tabulated. In addition, all subjects 
with major protocol deviations that affect efficacy analysis will be summarized, the number 
and percentage of subjects will be calculated and tabulated. 
7.3.3. Analysis datasets 
The subjects who are included to SS1, FAS1, and PPS1 will be summarized based on RS1, and 
the number and percentage of subjects will be calculated. 
7.3.4. Demographics and Baseline Characteristics 
Analysis will be performed based on RS1. 
Demographics such as age, gender, body height, body weight, and BMI will be summarized 
by descriptive statistics. The severity (moderate [IGA = 3] and severe [IGA = 4]) of atopic 
dermatitis (AD) at baseline will be summarized, and the number of percentage of subjects will 
be calculated. The baseline EASI/PP-NRS/BSA/SCORAD/POEM/DLQI will be summarized 
by descriptive statistics. Demographics and baseline characteristics will be tabulated. 
7.3.5. Medical history of subjects 
Analysis will be performed based on RS1. 
Medical history will be coded based on Medical Dictionary for Regulatory Activities 
(MedDRA), and the number and percentage of subjects will be summarized by System Organ 
Class (SOC) and Preferred Term (PT). Medical history of allergic diseases and allergy history 
will be summarized separately, and the number and percentage of subjects will be calculated. 
Medical history will be ranked in descending order of total number of subjects by SOC and PT. 
All medical histories will be tabulated, and medical history of allergic diseases and allergy 
history will be tabulated separately. 
7.3.6. Prior Medication, Concomitant Medication, and Prior and Concomitant Non-
drug Therapies 
Analysis will be performed based on RS1. 
Prior and Concomitant Medications 
Prior medication refers to a non-study drug that is started and ended before the first dose of 
study drug. Concomitant medication refers to a drug that is started at the time of or after the 
first dose of study drug, or a drug that is started before the first dose of the study drug and 
continued after the first dose of the study drug. 
Prior and concomitant medications will be coded based on World Health Organization Drug 
Dictionary (WHODrug), and summarized based on ATC Level 2, ATC Level 4 (if the code is 
missing, it will be analyzed with the code of previous level) and PT. The number and 
percentage of subjects will be calculated. Prior and concomitant medications will be ranked in 
descending order of total number of subjects by ATC Level 2, ATC Level 4 and PT. In addition, 
they will be tabulated. 


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Prior and Concomitant Non-drug Therapies 
Prior non-drug therapy refers to a therapy that is started and ended before the first dose of study 
drug. Concomitant non-drug therapy refer to a therapy that is started at the time of or after the 
first dose of study drug, or a therapy that is started before the first dose of the study drug and 
continued after the first dose of the study drug. 
Prior and concomitant non-drug therapies will be coded by MedDRA. Concomitant non-drug 
therapies will be summarized by PT. The number and percentage of subjects will be calculated. 
Prior and concomitant non-drug therapies will be ranked in descending order of total number 
of subjects. They will be tabulated. 
Rescue treatment 
Rescue treatments during treatment period of Stage 1 will be summarized based on ATC Level 
2, ATC Level 4 (if the code is missing, it will be analyzed with the code of previous level) and 
PT. The number and percentage of subjects will be calculated. These rescue treatments will be 
ranked in descending order of total number of subjects by ATC Level 2, ATC Level 4 and PT. 
They will be tabulated. 
7.4. Efficacy analysis 
Efficacy analysis in Stage 1 will be performed based on FAS1 and PPS1, mainly the FAS1. 
In order to control the type I error rate for multiplicity, a fixed-sequence method will be used. 
First of all, the active treatment group and the placebo group will be compared for the primary 
efficacy endpoint; when the primary efficacy endpoint reaches statistical significance, the 
active treatment group and the placebo group will be compared for the key secondary efficacy 
endpoints according to the sequence specified in the protocol. 
7.4.1. Visit window of efficacy analysis 
For scheduled visits, the visit window for efficacy analysis will be based on the visit where the 
original data are collected. For unscheduled visits and premature withdrawal visit, the visit 
window for efficacy analysis will be based on the visit closest to the reference date (the 
previous visit when the distance is the same). 
7.4.2. Intercurrent events and handling strategies 
See table below for intercurrent events and handling strategies: 
Label 
Intercurrent event 
Strategy 
Remarks 
Intercurrent 
event 1 (use of 
prohibited 
drugs/treatments 
specified in the 
protocol for 
which the study 
treatment must 
 
Dupilumab or any anti-IL-4Rα or IL-13 
antibodies; 
 
Topical PDE-4 inhibitors or JAK 
inhibitors; 
 
Systemic treatment with corticosteroids 
or other immunosuppressive and/or 
immunomodulatory agents, such as 
Composite 
strategy 
This type of 
intercurrent event 
occurs because of 
poor treatment effect, 
and should be treated 
as non-response. 
 


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Label 
Intercurrent event 
Strategy 
Remarks 
be early 
terminated due 
to poor 
treatment effect) 
cyclosporine, mycophenolate mofetil, 
azathioprine, methotrexate, or oral JAK 
inhibitors; 
 
Cell depletion agents (e.g., rituximab) or 
other biological agents; 
 
Other investigational drugs (non CBP-
201) or treatments. 
Due to the poor treatment effect, the above 
prohibited drugs/treatments have been used 
before the W16 visit. 
If it is a continuous 
variable, the data 
after the occurrence 
of the intercurrent 
event should be 
imputed with 
WOCF. 
Intercurrent 
event 2 (use of 
other prohibited 
drugs/treatments 
specified in the 
protocol other 
than those in 
Intercurrent 
Event 1, with a 
negligible 
impact on the 
assessment of 
the primary 
endpoint) 
 
Initiation of SIT, or dose up-regulation; 
 
TCS or TCI; 
 
Phototherapy (NBUVB, UVB, UVA1, 
PUVA), sunbed or any other LED 
therapies; 
 
Bleaching baths more than 2 times a 
week; 
 
Any drug for the treatment of AD (except 
mild emollients) that may interfere with 
the evaluation of efficacy results or affect 
the evaluation of AD severity. 
The cumulative duration of use of the above 
prohibited drugs/treatments before the W16 
visit is no more than 7 days, and the end date 
is at least 4 weeks away from the W16 visit. 
Treatment 
policy 
strategy 
The impact on the 
assessment of 
efficacy endpoints 
can be ignored, and 
the actual observed 
value is used. If the 
actual observed 
value is missing, it 
will be processed 
according to the 
principle for 
processing missing 
values. 
Intercurrent 
event 3 (use of 
other prohibited 
drugs/treatments 
specified in the 
protocol 
other 
than those in 
Intercurrent 
Event 1 due to 
poor 
treatment 
effect, with a 
major impact on 
the assessment 
of the primary 
endpoint) 
 
Initiation of SIT, or dose up-regulation; 
 
TCS or TCI; 
 
Phototherapy (NBUVB, UVB, UVA1, 
PUVA), sunbed or any other LED 
therapies; 
 
Bleaching baths more than 2 times a 
week; 
 
Any drug for the treatment of AD (except 
mild emollients) that may interfere with 
the evaluation of efficacy results or affect 
the evaluation of AD severity. 
The cumulative duration of use of the above 
prohibited drugs/treatments due to poor 
treatment effect before the W16 visit is more 
than 7 days, or the end date is less than 4 
weeks away from the W16 visit. 
Composite 
strategy 
This type of 
intercurrent event 
occurs because of 
poor treatment effect, 
and should be treated 
as non-response. 
 
 
If it is a continuous 
variable, the data 
after the occurrence 
of the intercurrent 
event should be 
imputed with 
WOCF. 
Intercurrent 
event 4 (early 
termination 
of 
treatment/EOT 
due to adverse 
The subject experiences an AE or SAE that is 
considered 
by 
the 
investigator 
to 
be 
intolerable before the W16 visit, and is 
unsuitable for continuing the study treatment, 
resulting 
in 
early 
termination 
of 
Composite 
strategy 
This type of 
intercurrent event 
occurs because of 
poor safety of 
treatment, and should 


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Label 
Intercurrent event 
Strategy 
Remarks 
events) 
treatment/EOT. 
be treated as non-
response. 
 
If it is a continuous 
variable, 
the 
data 
after the occurrence 
of the intercurrent 
event 
should 
be 
imputed with WOCF. 
Intercurrent 
event 
5 
(the 
subject’s 
administration is 
missing due to 
the COVID-19 
epidemic) 
The administration at two consecutive visits 
(W12 and W14) immediately before the W16 
visit is missing or the administration in the 
Stage 1 treatment period is missing for ≥3 
times. 
Hypothetical 
strategy 
The observed values 
are not used, and the 
J2R 
(jump 
to 
reference) method is 
used for imputation. 
Intercurrent 
event 6 (use of 
prohibited 
drugs/treatments 
specified in the 
protocol not for 
poor 
treatment 
effect, with a 
major impact on 
the assessment 
of the primary 
endpoint) 
The following prohibited drugs/treatments 
have been used before the W16 visit not 
because of the poor treatment effect: 
 
Dupilumab or any anti-IL-4Rα or IL-13 
antibodies; 
 
Topical PDE-4 inhibitors or JAK 
inhibitors; 
 
Systemic treatment with corticosteroids 
or other immunosuppressive and/or 
immunomodulatory agents, such as 
cyclosporine, mycophenolate mofetil, 
azathioprine, methotrexate, or oral JAK 
inhibitors; 
 
Cell depletion agents (e.g., rituximab) or 
other biological agents; 
 
Other investigational drugs (non CBP-
201) or treatments. 
Or 
The cumulative duration of use of the 
following prohibited drugs/treatments not due 
to the poor treatment effect before the W16 
visit is more than 7 days, or the end date is less 
than 4 weeks away from the W16 visit: 
 
Initiation of SIT, or dose up-regulation; 
 
TCS or TCI (topical drugs can be used 
for AD lesion areas only); 
 
Phototherapy (NBUVB, UVB, UVA1, 
PUVA), sunbed or any other LED 
therapies; 
 
Bleaching baths more than 2 times a 
Hypothetical 
strategy 
The observed values 
are not used, and the 
J2R 
(jump 
to 
reference) method is 
used for imputation. 


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Label 
Intercurrent event 
Strategy 
Remarks 
week; 
 
Any drug for the treatment of AD 
(topical drugs can be used for AD lesion 
areas only) that may interfere with the 
evaluation of efficacy results or affect the 
evaluation of AD severity. 


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7.4.3. Analysis of the primary efficacy endpoint and key secondary efficacy endpoints 
Label of 
estimand 
Description of estimand 
Main estimator 
Sensitivity/ Supplementary analysis 
Analysis sets 
Rules for imputation 
Model/method for the 
main analytical 
methods 
Estimand of 
primary 
endpoint 
The difference in efficacy in 
patients aged 12 years and older 
with moderate to severe AD and 
weighing > 40 kg between the 
CBP-201 300 mg Q2W group 
and placebo group. 
 
A patient is considered as 
treatment success if the patient 
has an IGA score of 0-1 which is 
decreased by ≥ 2 points from 
baseline at W16. 
 
A patient should be regarded as 
treatment failure if he/she uses 
prohibited 
drugs/treatments 
specified in the protocol for 
which the study treatment must 
be early terminated or other 
rescue therapy that has a major 
impact on the assessment of the 
primary endpoint due to poor 
treatment effect, or has early 
termination of treatment/EOT 
due to adverse events. 
FAS (will include 
all subjects in RS1 
who have received 
the study drug at 
least once). 
For 
subjects 
who 
experience intercurrent 
events, their visits after 
the intercurrent events 
will be handled in 
accordance with the 
strategies for managing 
intercurrent 
events 
listed in Table 7.4.2. 
If the target variable is 
still 
missing 
after 
application 
of 
the 
strategies for managing 
intercurrent events, the 
multiple 
imputation 
(MI) method will be 
used to impute the 
missing data in the 
placebo group, and the 
J2R (jump to reference) 
method will be used to 
impute the missing data 
in the CBP- 201 group. 
Differences in response 
rates 
between 
the 
treatment 
group 
and 
placebo group and their 
95% confidence intervals 
will be analyzed using 
the 
Cochran-Mantel- 
Haenszel test stratified 
by 
baseline 
disease 
severity (IGA 3 or 4). 
The Type I error level for 
statistical significance of 
the 
difference 
in 
response rates between 
CBP-201 and placebo is 
set at 0.05 (two-sided 
test). 
Sensitivity analysis 1: When the target 
variable is still missing after application of 
the strategy for managing intercurrent 
events, it will be classified as treatment 
failure. 
Sensitivity analysis 2: When the target 
variable is still missing after application of 
the strategy for managing intercurrent 
events, tipping point analysis will be used 
for analysis. 
Sensitivity analysis 3: For the subjects who 
are incorrectly stratified and randomized, 
the analysis will be performed using correct 
stratification factors and the same method as 
the main estimand; 
Supplementary 
analysis 
1: 
Primary 
analysis will be performed using the PPS. 
Supplementary analysis 2: The treatment 
policy strategy will be used for all 
intercurrent events; the FAS will be used, 
and the missing data will be subject to the 
imputation rules of the main estimator, that 
is, the multiple imputation method (MI) will 
be used to impute the missing data in the 
placebo group, and the J2R (jump to 


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Label of 
estimand 
Description of estimand 
Main estimator 
Sensitivity/ Supplementary analysis 
Analysis sets 
Rules for imputation 
Model/method for the 
main analytical 
methods 
reference) method will be used to impute the 
missing data in the test group. 
Estimand of 
key 
secondary 
endpoints 
The differences in the following 
measures in patients aged 12 
years and older with moderate to 
severe AD and weighing ≥40 kg 
between the CBP-201 300mg 
Q2W group and the placebo 
group: 
 
 
The proportion of subjects 
achieving EASI-75 at W16 
 
The proportion of subjects 
whose weekly average PP-
NRS is decreased by ≥ 4 
points from baseline at 
W16; 
 
The proportion of subjects 
whose weekly average PP-
NRS is decreased by ≥ 3 
points from baseline at 
W16; 
 
Change 
and 
percentage 
change 
in 
the 
weekly 
average 
PP-NRS 
from 
baseline at W16; 
 
The proportion of subjects 
FAS (will include 
all subjects in RS1 
who have received 
the study drug at 
least once). 
For 
subjects 
who 
experience intercurrent 
events, their visits after 
the intercurrent events 
will be handled in 
accordance with the 
strategies for managing 
intercurrent 
events 
listed in Table 7.4.2. 
If the target variable is 
still 
missing 
after 
application 
of 
the 
strategies for managing 
intercurrent events, the 
multiple 
imputation 
(MI) method will be 
used to impute the 
missing data in the 
placebo group, and the 
J2R (jump to reference) 
method will be used to 
impute the missing data 
in the CBP- 201 group. 
For categorical variables, 
differences in response 
rates 
between 
the 
treatment 
group 
and 
placebo group and their 
95% confidence intervals 
will be analyzed using 
the 
Cochran-Mantel- 
Haenszel test stratified 
by 
baseline 
disease 
severity (IGA 3 or 4). 
 
For continuous 
variables, analysis will 
be performed using an 
MMRM model that will 
include treatment group, 
baseline disease severity 
(IGA 3 or 4), baseline 
value of the 
corresponding endpoint, 
visit, interaction of visit 
and treatment group, and 
the LSMEAN estimate 
values and their 95% 
Sensitivity analysis 1: When the target 
variable is still missing after application of 
the strategy for managing intercurrent 
events, 
categorical 
variables 
will 
be 
classified as treatment failure. Continuous 
variables should be imputed with WOCF. 
 
Sensitivity analysis 2:  For the subjects who 
are incorrectly stratified and randomized, 
the analysis will be performed using a 
correct stratification factor and the method 
the same as the main estimator; 
 
Supplementary 
analysis 
1: 
Primary 
analysis will be performed using the PPS. 
 
Supplementary analysis 2: The treatment 
policy strategy will be used for all 
intercurrent events; the FAS will be used, 
and the missing data will be subject to the 
imputation rules of the main estimator, that 
is, the multiple imputation method (MI) will 
be used to impute the missing data in the 
placebo group, and the J2R (jump to 
reference) method will be used to impute the 


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Version: 1.0 
 
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Label of 
estimand 
Description of estimand 
Main estimator 
Sensitivity/ Supplementary analysis 
Analysis sets 
Rules for imputation 
Model/method for the 
main analytical 
methods 
achieving EASI-90 at W16 
 
A patient should be regarded as 
treatment failure if he/she uses 
prohibited 
drugs/treatments 
specified in the protocol for 
which the study treatment must 
be early terminated or other 
rescue therapy that has a major 
impact on the assessment of the 
key secondary endpoints due to 
poor treatment effect, or has early 
termination of treatment/EOT 
due to adverse events. In this 
case, continuous variables should 
be imputed with WOCF. 
confidence intervals will 
be summarized. 
missing data in the test group. 


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In the J2R (jump to reference) method, when the data of subjects of the active treatment group 
are missing, it is assumed that their statistical results are the same as those of the placebo group, 
that is, it is considered that the pharmacological action of the drug for the active treatment 
group is the same as that of the placebo group. PROC MI will be used for J2R imputation, and 
the missing data of the active treatment group will be imputed with the results obtained by 
posterior predictive distribution of the placebo group. Markov Chain Monte Carlo (MCMC) 
will be used to extend the data, and a regression method will be used to generate M datasets 
(M is set as 30 in this study). The imputed variables should include: treatment group, 
stratification factor (severity of baseline disease), baseline value of corresponding endpoint and 
measurement at each visit. Random seed is the earliest date of the first dose to all subjects. 
Table 5 Random Seeds of Multiple Imputation 
Endpoints 
Random Seeds 
IGA 
Minimum date of the first dose 
EASI 
Minimum date of the first dose + 1 
PP-NRS 
Minimum date of the first dose + 2 
BSA 
Minimum date of the first dose + 3 
SCORAD 
Minimum date of the first dose + 4 
DLQI 
Minimum date of the first dose + 5 
POEM 
Minimum date of the first dose + 6 
Tipping point analysis: To evaluate the robustness of the primary efficacy endpoint analysis, 
tipping point analysis should be performed on the primary efficacy endpoint at W16. The 
tipping point method is binary, that is, the assumptions of missing values of the active treatment 
group and the placebo group are mutually independent. Assuming that the response rate of 
missing values of the two groups increases by 10% from 0 to 100%, the subjects with a missing 
response in the two groups at a certain percentage will be randomly assigned as responders and 
non-responders in 30 imputed datasets randomly generated by the binomial distribution. Then 
the same analysis method as that for the primary study endpoint will be used to obtain the 
comparison results between the two groups in each imputed dataset. Finally, Rubin’s Rule will 
be used to pool these results. If there is a pair of assumed response rate that overturns the study 
conclusion, that is, p value is more than 0.05, the two assumed response rates will be the cut-
off points. 
Subgroup analysis will be performed on the primary efficacy endpoint (the proportion of 
subjects whose IGA score is 0-1 and decreased by ≥ 2 points from baseline at W16) and the 
key secondary efficacy endpoint (the proportion of subjects achieving EASI-75 at W16) by 
gender (male/female), severity of baseline disease (moderate [IGA = 3]/severe [IGA = 4]), 
history of allergic diseases or allergy history (yes/no), baseline EASI (< baseline median 
EASI/≥ baseline median EASI), baseline PP-NRS (< baseline median PP-NRS/≥ baseline 
median PP-NRS). The analytical method is the same as the primary analysis method for the 
primary efficacy endpoint and the key secondary efficacy endpoint. The subjects with missing 


Suzhou Connect Biopharmaceuticals, Ltd. 
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subgroup variables will not be included to analysis. 
Sensitivity analysis will be performed on the primary efficacy endpoint (the proportion of 
subjects whose IGA score is 0-1 and decreased by ≥ 2 points from baseline at W16) and the 
key secondary efficacy endpoint (the proportion of subjects achieving EASI-75 at W16) using 
the correct stratification factor and the method the same as the main estimator. 
7.4.4. Other efficacy endpoint analysis 
The categorical efficacy endpoint analysis will be performed using the same method as the 
primary efficacy endpoint analysis. 
The continuous efficacy endpoint analysis will be performed using the same method as the 
secondary efficacy endpoint analysis. 
According to the investigator's judgment, AD aggravation or deterioration of symptoms which 
requires drugs or treatments originally prohibited by the protocol for rescue therapy will be 
defined as “AD recurrence” event. 
The number of AD recurrence, the number of subjects with AD recurrence, and the number of 
days of AD recurrence in Stage 1, from baseline to W8, from W8 to W16 will be analyzed. 
The total number of AD recurrence in each stage will be summarized. AD recurrence will be 
summarized by the number of recurrences, that is, 0, 1, 2 and ≥ 3. The number and percentage 
of subjects will be calculated. Chi-squared test will be adopted to compare whether the 
differences between the two groups are statistically significant. The total number of subjects 
with AD recurrence in each stage will be summarized, and the number and percentage of 
subjects will be calculated. Chi-squared test will be performed to compare whether the 
differences between the two groups are statistically significant. The number of days of AD 
recurrence in each stage will be summarized by descriptive statistics. 
7.5. Safety Analysis 
7.5.1. Drug exposure and compliance 
Study drug exposure will be analyzed based on SS1. Study drug exposure duration and 
exposure dose during treatment period of Stage 1 will be summarized by descriptive statistics. 
The compliance with the study drug and emollients (background treatment) in Stage 1 will be 
summarized by descriptive statistics. The subjects with a compliance < 70%, ≥ 70% and ≤ 
130%, and > 130% will be summarized, and the number and percentage of subjects will be 
calculated. Subjects’ compliance with the study drug and emollients (background treatment) 
will be tabulated. 
7.5.2. AEs 
AEs will be analyzed based on the SS1 
AEs will be coded using MedDRA. 


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The occurrence of overall AEs will be summarized to generate summary tabulations of TEAEs. 
TEAEs of special interest and drug-related AESIs will be summarized. The numbers of subjects 
with various AEs, numbers and incidences of events  will be calculated. 
AEs, drug-related AEs, SAEs, AESIs, AEs leading to death, AEs leading to treatment 
discontinuation, injection site AEs, CTCAE grade 3-5 AEs, AEs with an incidence of > 5%, 
and AD recurrence-related AEs will be tabulated. 
The incidences of the following TEAEs will be summarized by SOC and PT, the numbers of 
subjects with various AEs, and the numbers and incidences of events will be calculated. They 
will be ranked in descending order of total number of subjects by SOC and PT. 
1) TEAEs; 
2) Drug-related AEs; 
3) SAEs; 
4) Drug-related SAEs; 
5) AEs leading to death; 
6) AEs leading to treatment discontinuation; 
7) AEs leading to treatment interruption; 
8) AESIs; 
9) Drug-related AESIs; 
10) Injection site AEs; 
11) CTCAE grade 3-5 AEs; 
12) AEs with an incidence of > 5%; 
In addition, the incidences of TEAEs, AESIs, and injection site AEs will be summarized by 
CTCAE Grade, correlation with study drug, SOC and PT, and the number and percentage of 
subjects will be calculated. 
A subject with an AE of the same SOC and PT more than once will have that event counted 
only once within each SOC and PT. 
7.5.3. Laboratory test results 
Laboratory test results will be analyzed based on the SS1. 
The hematology, blood biochemistry and urinalysis parameters at baseline and each visit and 
their changes from baseline at each visit will be summarized by descriptive statistics. 
The number and percentage of subjects whose hematology, blood biochemistry and urinalysis 
parameters at baseline and each visit are below, within and above the normal range will be 
summarized. 


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Pre-treatment and post-treatment laboratory test results are classified into abnormal with 
clinical significance, abnormal without clinical significance, normal, and not tested in an order 
of abnormal with clinical significance > abnormal without clinical significance > normal > not 
tested. Then shift tables are generated. The shift tables are generated based on CTCAE 5.0. 
All laboratory test results and abnormal laboratory test results for hematology, blood 
biochemistry, urinalysis and urine pregnancy will be tabulated. 
Qualitative laboratory test results will be summarized by visit. The number and percentage of 
subjects for each category will be calculated and tabulated. 
7.5.4. ECG 
ECG findings will be analyzed based on the SS1. 
Ventricular rhythm, PR, QRS, QT and QTcF results at each post-baseline visit and their 
changes from baseline at each visit will be summarized by descriptive statistics. The analysis 
of variance will be used to detect possible difference between groups. 
Special attention will be paid to QTcF interval prolongation: 
 
QTcF interval > 450 ms 
 
QTcF interval > 480 ms 
 
QTcF interval > 500 ms 
 
Increase in QTcF interval from baseline > 30 ms 
 
Increase in QTcF interval from baseline > 60 ms 
Pre-treatment and post-treatment ECG results are classified into abnormal with clinical 
significance, abnormal without clinical significance, normal, and not tested in an order of 
abnormal with clinical significance > abnormal without clinical significance > normal > not 
tested. Then shift tables are generated. 
ECG results of QTcF interval prolongation will be tabulated. All ECG results and clinically 
significant abnormal ECG results will be tabulated. 
7.5.5. Other safety evaluation 
The following analyses are based on SS1. 
Physical examination 
Physical examination results at each visit in Stage 1 will be classified into abnormal with 
clinical significance, abnormal without clinical significance, normal and not tested. The 
frequency and percentage of each category will be summarized. 
All physical examination results and abnormal physical examination results with clinical 
significance will be tabulated. 
Vital signs 


Suzhou Connect Biopharmaceuticals, Ltd. 
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The vital signs at baseline and their changes from baseline at each visit of Stage 1 will be 
summarized by descriptive statistics. The analysis of variance will be used to detect possible 
difference between groups. 
Vital sign results at each visit of Stage 1 will be classified into abnormal with clinical 
significance, abnormal without clinical significance, normal and not tested. The frequency and 
percentage of each category will be summarized. 
All vital sign results and abnormal vital sign results with clinical significance will be tabulated. 
Eye examination 
Eye examination results at each visit of Stage 1 will be classified into abnormal with clinical 
significance, abnormal without clinical significance, normal and not tested. The frequency and 
percentage of each category will be summarized. 
All eye examination results and abnormal eye examination results with clinical significance 
will be tabulated. 
ADA test 
See PK/PD statistical analysis plan for details. 
7.6. Pharmacokinetics (PK) analysis 
See PK/PD statistical analysis plan for details. 
7.7. Pharmacodynamics (PD) and Biomarker Analysis 
See PK/PD statistical analysis plan for details. 
7.8. Changes to Planned Analysis in the Protocol 
Description of intercurrent event 6 and strategies for managing intercurrent event 6 is added. 
8. References 
Guidelines for Management and Statistical Analysis Plan of Drug Clinical Trial Data 2021.