Conditions: Moderate to Severe Ulcerative Colitis
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 145
Healthy volunteers: no

Brief summary:
This study will evaluate the efficacy and safety of CBP-307 in subjects with moderate to severe ulcerative colitis (UC).

Detailed description:
This is a multicenter, multicountry, randomized, double-blind, placebo-controlled phase II clinical trial to evaluate the efficacy and safety of CBP-307 in subjects with moderate to severe ulcerative colitis (UC). CBP-307 capsules are administered orally. This study includes stage 1 and stage 2.

Study Stage 1 After screening, subjects entered the randomized, double-blind, placebo-controlled induction therapy for 12 weeks.

Subjects were screened at 1 to 21 days prior to the baseline visit. The eligible subjects were enrolled and randomized at the baseline visit. As per study protocol (version 5.0 or earlier), subjects received CBP 307 0.1 mg, CBP-307 0.2 mg, and placebo at a ratio of 1:1:1. The subjects enrolled under protocol (version 6.0) were randomized to CBP-307 0.2 mg and placebo at a ratio of 1:1 into the 2 groups (approximately 52 subjects in each group) and stratified according to whether the subject failed a previous tumor necrosis factor (TNF)-α antagonist therapy. Subjects assigned were blinded to their treatment assignment (CBP-307 or placebo) in the 12-week double-blinded placebo-controlled treatment period.

Subjects randomized to CBP-307 group underwent dose titration for 1 week, while those in placebo group underwent simulated titration. Both CBP-307 and placebo were administered through the oral route. For subjects in the CBP-307 0.1 mg QD group, a daily dose of 0.05 mg CBP-307 was given from Day 1 to Day 4; then a daily dose of 0.1 mg CBP-307 was given for 3 days from Day 5 to Day 7; from Day 8, a daily target dose of 0.1 mg was administered. For subjects in the group of CBP-307 0.2 mg QD, a daily dose of 0.05 mg CBP-307 was given from Day 1 to Day 4; then, a dose of 0.1 mg CBP-307 was given daily for 3 days from Day 5 to Day 7; from Day 8, a daily target dose of 0.2 mg was administered.

For the subjects already enrolled as per study protocol version 5.0 or earlier, they continued the treatment in the Stage 1 according to the previous planned schedule.

Eligible subjects completing 12 weeks of induction therapy in Stage 1 were permitted to enter Stage 2 to be evaluated for the long-term maintenance administration of CBP-307. Subjects who withdrew early from the study or completed the Stage 1, but did not enter Stage 2, entered a 4-week safety follow-up period.

Study stage 2 All subjects who completed 12 weeks of induction therapy in the study Stage 1 and completed all examinations (including colonoscopy) at Week 12 (visit 11) could choose to enter the study Stage 2 of a total length of 40 weeks, including 36 weeks of continuous treatment and 4 weeks of safety follow up after the last dose. Subjects who chose to enter the Stage 2 signed an updated informed consent form (ICF) and screened for eligibility.

The study Stage 2 contained sub-study 1 and sub-study 2. Subjects entered 1 of sub-studies based on their results of efficacy evaluation in the study Stage 1.

Sub-study 1 (subjects who achieved clinical response by adapted Mayo score): Subjects who achieved clinical response at Week 12 in the study Stage 1 and met the eligibility criteria for Stage 2 entered sub study 1 of the study Stage 2 to receive double-blind maintenance treatment for 36 weeks (Week 13 to 48), i.e., the therapeutic regimen for them in Stage 1 was continually maintained. Safety follow-up was completed at 4 weeks after the last dose. Subjects who presented with recurrent UC during maintenance treatment were terminated from the treatment and withdrew from the study.

For the subjects already enrolled as per study protocol version 5.0 or earlier, they followed the previous planned treatment in the sub-study 1 of Stage 2 study.

Sub-study 2 (subjects who did not achieve clinical response by adapted Mayo score): Subjects who did not achieve clinical response at Week 12 in study Stage 1 and met the eligibility criteria for Stage 2 entered open-label treatment with CBP-307 0.2 mg. Subjects received CBP-307 QD at an oral dose of 0.2 mg in sub study 2 regardless of whether they received CBP-307 or placebo in the study Stage 1.

For subjects who entered sub-study 2 of study Stage 2, 1-week dose titration was performed at Week 13. Dose titration involved administration of CBP 0.05 mg for 4 consecutive days from Titration Day 1 to Day 4, followed by administration of CBP-307 0.1 mg for 3 days from Titration Day 5 to Day 7, and administration of CBP-307 at a target dose of 0.2 mg initiated on Titration Day 8. After dose titration was completed, subjects received oral treatment with CBP-307 0.2 mg QD, for 36 weeks. Safety follow-up was completed at 4 weeks after the last dose. If the subjects did not achieve clinical response by the efficacy evaluation including colonoscopy at Week 24, the treatment was to be discontinued and the subjects were to withdraw from the study.

Arms:
arm 1: 0.2 mg CBP-307 capsules oral administration. arm 2: Placebo capsules oral administration. arm 3: 0.2 mg CBP-307 capsules oral administration. arm 4: 0.1 mg CBP-307 capsules oral administration.

Interventions: intervention 1: Double-Blind 0.2mg CBP-307 intervention 2: Double-Blind Placebo intervention 3: Open-label CBP-307 intervention 4: Double-Blind 0.1mg CBP-307
Intervention descriptions: intervention 1: 0.2 mg capsule oral administration intervention 2: Placebo capsule oral administration intervention 3: 0.2 mg capsule oral administration intervention 4: 0.1 mg capsule oral administration

Protocol document:
Prot_000.pdf: 
Protocol No.: CBP-307CN002 
Confidential 
VERSION 6.0/DECEMBER 25, 2020 
PAGE 1 OF 129 
Clinical Study Protocol 
A multicenter, randomized, double-blind, placebo-controlled phase II 
clinical trial to evaluate the efficacy and safety of CBP-307 in subjects with 
moderate to severe ulcerative colitis (UC) 
Investigational product: 
CBP-307 
Protocol No.: 
CBP-307CN002 
Version date: 
December 25, 2020/ Final Version 6.0 
Substituted version: 
December 17, 2019/ Final Version 5.0 
Regulatory agency 
identifying number(s): 
To be determined 
Sponsor: Suzhou Connect Biopharmaceuticals, Ltd. 
Medical expert of sponsor: Wei Zheng, PhD 
Address: F3, R&D East Building, Science and Technology Venture Park, No.6, Beijing West 
Road, Taicang City, Jiangsu Province, China 215400 
Tel.: 0512 -53577866 
Cellphone: 18962401588 
Fax: 0512-53577866 
E-mail: zhengwei@connectpharm.com 
Coordinating investigator: Jiaming Qian 
Affiliation (study leading site): Peking Union Medical College Hospital 
Address: No.1, Shuaifuyuan, Dongcheng District, Beijing, China 100730 
Statement of Confidentiality 
This document is confidential to Suzhou Connect Biopharmaceuticals, Ltd. It is only available to relevant 
investigators, the contract research organization (CRO) providing consulting services, or designated persons 
and regulatory authority reviewers, experts and/or members of the ethical review committee for their 
investigation and/or evaluation of the project. The fact that you are receiving/reading this document indicates 
that you have agreed that all information contained in this document will not be disclosed to any other person 
without the approval from Connect or its affiliates, except the purpose of obtaining the approval of the 
Independent Ethics Committee/Institutional Review Board. 
NCT04700449


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Table of Contents 
CLINICAL STUDY PROTOCOL .............................................................................................................. 1 
TABLE OF CONTENTS ............................................................................................................................. 2 
ABBREVIATIONS ....................................................................................................................................... 7 
1 
STUDY SYNOPSIS ........................................................................................................................... 12 
2 
ETHICAL CONSIDERATIONS ..................................................................................................... 43 
2.1. 
REGULATORY AND ETHICAL CONSIDERATIONS ........................................................................ 43 
2.2. 
SUBJECT INFORMATION AND THE INFORMED CONSENT FORM .................................................. 44 
3 
STUDY BACKGROUND ................................................................................................................. 44 
3.1. 
OVERVIEW OF ULCERATIVE COLITIS.......................................................................................... 44 
3.2. 
DRUG OVERVIEW, STRUCTURE AND PHYSICOCHEMICAL PROPERTIES ....................................... 45 
3.3. 
NONCLINICAL PHARMACOLOGY, PHARMACOKINETICS AND TOXICOLOGY ............................... 46 
3.3.1. 
Nonclinical pharmacology ......................................................................................... 46 
3.3.2. Pharmacokinetics and metabolism ................................................................................. 47 
3.3.3. Toxicology ....................................................................................................................... 48 
3.4. 
CLINICAL STUDY DATA.............................................................................................................. 49 
3.4.1 Overview of the clinical study .......................................................................................... 50 
3.4.2. Pharmacodynamics ......................................................................................................... 50 
3.4.3. Pharmacokinetics ............................................................................................................ 51 
3.4.4. Safety ............................................................................................................................... 51 
3.5. 
STUDY RATIONALE AND BENEFIT/RISK ASSESSMENT ................................................................ 52 
4 
STUDY OBJECTIVES AND ENDPOINTS ................................................................................... 54 
5 
STUDY PLAN .................................................................................................................................... 57 
5.1. 
STUDY DESIGN AND STUDY PROCEDURES.................................................................................. 57 
5.2. 
RATIONALE FOR STUDY DESIGN AND DOSE SELECTION ............................................................. 60 
5.2.1. Rationale for study design............................................................................................... 60 
5.2.2. Rationale for dose selection ............................................................................................ 60 
5.3. 
STUDY DURATION ...................................................................................................................... 61 
5.4. 
STUDY POPULATION .................................................................................................................. 62 
5.4.1. Inclusion criteria and Exclusion criteria for study stage 1 ............................................. 62 
5.4.2. Inclusion and exclusion criteria for subjects' entry into the study stage 2 from the 
stage 1: 68 
5.4.3. Re-screening after the failure of screening ..................................................................... 70 
5.4.4. Criteria for termination of treatment or early withdrawal of subjects ........................... 71 
5.4.5. Criteria for termination of the clinical study. ................................................................. 73 
5.4.6. Procedure for termination of or withdrawal from the study ........................................... 73 
6 
TREATMENT REGIMEN ............................................................................................................... 73 
6.1. 
RANDOMIZATION AND BLINDING METHOD ................................................................................ 74 
6.1.1. Randomization method .................................................................................................... 74 
6.1.2. Allocation of subjects ...................................................................................................... 74 
6.1.3. Blinding and blinding process ........................................................................................ 74 
6.2. 
TREATMENT REGIMEN ............................................................................................................... 75 
6.2.1. Cardiac monitoring during titration ............................................................................... 76 
6.2.2. Missing dose.................................................................................................................... 79 
6.3. 
LABELING AND PACKAGING OF THE INVESTIGATIONAL PRODUCT ............................................ 79 


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6.4. 
DISTRIBUTION OF INVESTIGATIONAL PRODUCT......................................................................... 80 
6.5. 
ACCOUNTABILITY OF INVESTIGATIONAL PRODUCT AND TREATMENT COMPLIANCE ................. 80 
6.5.1. Accountability of investigational product ....................................................................... 80 
6.5.2. Study treatment compliance ............................................................................................ 81 
6.6. 
CONCOMITANT MEDICATION AND TREATMENTS ....................................................................... 81 
6.6.1. Medications and treatments allowed to be used ............................................................. 81 
6.6.2. Prohibited medications and treatments .......................................................................... 83 
6.7. 
PLAN FOR TRIAL TERMINATION ................................................................................................. 84 
7 
STUDY ASSESSMENTS .................................................................................................................. 85 
7.1. 
GENERAL INFORMATION ........................................................................................................... 85 
7.2. 
EFFICACY ASSESSMENTS ........................................................................................................... 85 
7.2.1. Subject diary ................................................................................................................... 85 
7.2.2. Colonoscopy .................................................................................................................... 86 
7.2.3. Mayo score ...................................................................................................................... 86 
7.2.3.1 Complete Mayo scores .................................................................................................. 87 
7.2.3.2 Adapted Mayo score ..................................................................................................... 88 
7.2.3.3 Partial Mayo scores ...................................................................................................... 88 
7.2.4 Inflammatory bowel disease questionnaire ...................................................................... 88 
7.3. 
SAFETY ASSESSMENTS ............................................................................................................... 88 
7.3.1. Chest X-ray examination ................................................................................................. 89 
7.3.2. Vital signs ....................................................................................................................... 89 
7.3.3. Physical examination ...................................................................................................... 90 
7.3.4. Pulmonary function test .................................................................................................. 90 
7.3.5. Dermatology examination ............................................................................................... 90 
7.3.6. Ophthalmologic examination .......................................................................................... 91 
7.3.7. 12-lead ECG ................................................................................................................... 91 
7.3.8. Holter monitoring ........................................................................................................... 91 
7.3.9. Monitoring of concomitant treatment ............................................................................. 91 
7.3.10. Monitoring of AEs and SAEs ........................................................................................ 91 
7.3.11. Safety laboratory parameters ........................................................................................ 92 
7.4. 
PHARMACOKINETICS/PHARMACODYNAMICS ASSESSMENT (APPLICABLE ONLY FOR STUDY 
STAGE 1) .............................................................................................................................................. 93 
7.4.1. Pharmacokinetics ............................................................................................................ 93 
7.4.2. Pharmacodynamics and biomarker evaluation............................................................... 94 
7.5. 
MONITORING OF ADVERSE EVENTS OF SPECIAL INTEREST ........................................................ 96 
8 
DEFINITION, MONITORING AND REPORTING OF A SAFETY EVENT ........................... 98 
8.1. 
ADVERSE EVENT ........................................................................................................................ 99 
8.1.1. Definition and recording of adverse events .................................................................... 99 
8.1.2. Grading of adverse events............................................................................................. 100 
8.1.3. Determination of causality between adverse events and investigational product ........ 100 
8.2. 
SERIOUS ADVERSE EVENT ....................................................................................................... 101 
8.2.1. Definitions of serious adverse events ............................................................................ 101 
8.2.2. Reporting and follow-up of serious adverse events ...................................................... 102 
8.3. 
REPORTING OF ADVERSE EVENTS OF SPECIAL INTEREST ......................................................... 103 
8.4. 
FOLLOW UP OF SUBJECTS WITH ADVERSE EVENTS/SERIOUS ADVERSE EVENTS ....................... 104 
8.5. 
HANDLING OF ABNORMAL LABORATORY TEST RESULTS ......................................................... 104 
8.6. 
CLINICAL LABORATORY PARAMETERS AND ABNORMAL LABORATORY TEST RESULTS ........... 104 
8.7. 
TREATMENT OF OVERDOSE ..................................................................................................... 106 
8.8. 
PREGNANCY REPORT ............................................................................................................... 106 


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9 
DATA MANAGEMENT AND STATISTICAL ANALYSIS ...................................................... 106 
9.1. 
DATA MANAGEMENT ............................................................................................................... 106 
9.2. 
DETERMINATION OF SAMPLE SIZE ........................................................................................... 106 
9.3. 
STATISTICAL ANALYSIS PLAN .................................................................................................. 107 
9.4. 
RANDOMIZATION .................................................................................................................... 107 
9.5. 
ANALYSIS POPULATION ........................................................................................................... 107 
9.6. 
DEMOGRAPHIC AND BASELINE DATA ...................................................................................... 109 
9.7. 
SUBJECTS TREATMENT ............................................................................................................ 109 
9.8. 
EFFICACY ANALYSIS ................................................................................................................ 109 
9.8.1. Study endpoints ............................................................................................................. 109 
9.8.2. Efficacy analysis ........................................................................................................... 110 
9.9. 
PHARMACOKINETIC ANALYSIS ................................................................................................ 111 
9.10. PHARMACODYNAMICS AND BIOMARKER ANALYSIS ................................................................ 112 
9.11. SAFETY ANALYSIS ................................................................................................................... 112 
9.12. MISSING DATA ......................................................................................................................... 112 
9.13. INTERIM ANALYSIS .................................................................................................................. 113 
9.14. INDEPENDENT DATA MONITORING COMMITTEE ..................................................................... 113 
10 
DATA QUALITY ASSURANCE ................................................................................................... 113 
10.1. ELECTRONIC CASE REPORT FORM ............................................................................................ 114 
10.2. DATA COLLECTION .................................................................................................................. 114 
10.3. MONITORING AND SOURCE DATA REVIEW............................................................................... 114 
10.4. AUDIT AND INSPECTION .......................................................................................................... 115 
10.5. STORAGE OF ORIGINAL DOCUMENTS AND RECORDS ............................................................... 115 
11 
TRIAL MANAGEMENT ............................................................................................................... 115 
11.1. PROTOCOL COMPLIANCE OR DEVIATIONS ................................................................................ 116 
11.2. PUBLICATION POLICY .............................................................................................................. 116 
11.3. CLINICAL STUDY REPORT ........................................................................................................ 116 
11.4. CONTRACT AND FINANCIAL DETAILS ...................................................................................... 116 
11.5. INSURANCE, COMPENSATION AND REMUNERATION ................................................................ 116 
11.6. CLINICAL TRIAL TERMINATION ............................................................................................... 117 
11.7. MANAGEMENT OF STUDY SITE DOCUMENTS............................................................................ 117 
12 
REFERENCES ................................................................................................................................ 117 
13 
ANNEXES ........................................................................................................................................ 119 
ANNEX 1 INFLAMMATORY BOWEL DISEASE QUESTIONNAIRE (IBDQ) ............................. 119 
ANNEX 2: AMENDMENTS TO THE STUDY PROTOCOL ............................................................. 129 
  
 
 


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Table List 
Table 1 
Stage 1 Titration dosing regimen ....................................................................................... 15 
Table 2 
Study Flow Chart of Study Stage 1 .................................................................................... 29 
Table 3.  
Sub-study 1 of the Study Stage 2: Study Flow Chart for the Entry of Subjects into Double-
Blind Maintenance Treatment After Achieving Clinical Response at Week 12 ................................... 35 
Table 4. 
Sub-study 2 of the Study Stage 2: Study Flow Chart for The Entry of Subjects into 
Open-Label Treatment After No Clinical Response Is Achieved at Week 12 ...................................... 39 
Table 5. 
Titration dosing regimen .................................................................................................... 75 
Table 6. 
Administration regimen dose titration in study stage 2 ..................................................... 76 
Table 7. 
Stage 1 Cardiac monitoring ............................................................................................... 77 
Table 8. 
Sub-study 2 of Study Stage 2 Cardiac Monitoring ............................................................ 78 
Table 9. 
Examples of Prohibited Cardiac Medications .................................................................... 84 
Table 10. 
Safety Laboratory Parameters ......................................................................................... 92 
 
 
 


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Figure List 
Figure 1 
Schematic Diagram of Study Stage 1 Design .................................................................... 16 
Figure 2 
Schematic Diagram of Transition from Stage 1 to Stage 2 Substudies ............................. 18 
Figure 3. 
Chemical structure of CBP-307 ......................................................................................... 46 
Figure 4. 
Study design of the stage 1 ................................................................................................ 58 
Figure 5. 
Study design of stages 1 and 2 ........................................................................................... 60 
 


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Abbreviations 
Abbreviation 
Meaning 
5-ASA 
5-aminosalicylic acid 
ACLS 
Advanced cardiac life support 
AE 
Adverse event 
AESI 
Adverse event of special interest 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area under the concentration-time curve 
ALK 
Alkaline phosphatase 
γ-GT 
γ-glutamyltransferase 
BP 
Blood pressure 
cAMP 
Cyclic adenosine monophosphate 
CD 
Crohn’s disease 
C. difficile 
Clostridioides difficile 
CIOMS 
Council for International Organizations of Medical Sciences 
Cmax 
Drug maximum concentration 
CMH 
Cochran-Mantel-Haenszel 
CRO 
Contract research organization 
CRP 
C-reactive protein 
CTCAE 
Common terminology criteria for adverse events 
DLCO 
Diffusing capacity of the lung for carbon monoxide 
EC50 
Half maximum effect concentration 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
FAS 
Full analysis set 
FEV1 
Forced expiratory volume in 1 second 
FVC 
Forced vital capacity 
GCP 
Good Clinical Practice 
GD 
Gestation day 
GLP 
Good Laboratory Practice 
HBV 
Hepatitis B virus 
HBcAb 
Hepatitis B core antibody 
HBsAb 
Hepatitis B surface antibody 
HBsAg 
Hepatitis B surface antigen 
HCV 
Hepatitis C virus 
Hgb 
Hemoglobin 
HIPAA 
Health Insurance Portability and Accountability Act 
HIV 
Human immunodeficiency virus 


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HR 
Heart rate 
IBD 
Inflammatory bowel disease 
IBDQ 
Inflammatory bowel disease questionnaire 
ICF 
Informed Consent Form 
ICH 
International Council for Harmonisation 
IDMC 
Independent Data Monitoring Committee 
IFX 
Infliximab 
Ig 
Immunoglobulin 
IRB 
Institutional Review Board 
ISF 
Investigator Site File 
IWRS 
Interactive web response system 
LFT 
Liver function test 
LQTS 
Long QT syndrome 
MTD 
Maximum tolerated dose 
NOAEL 
No observed adverse effect level 
OCT 
Optical coherence tomography 
PK 
Pharmacokinetics 
PD 
Pharmacodynamics 
PPS 
Per-protocol set 
QTcF 
QT interval corrected using Fridericia’s formula 
RAVE 
Electronic data capture system 
RBC 
Red blood cell 
RTSM 
Randomization and Trial Supply Management 
S1P1 
Sphingol-1-phosphate receptor isoform 1 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SS 
Safety set 
SUSAR 
Suspected unexpected serious adverse reaction 
TB 
Tuberculosis 
TEAE 
Treatment-emergent adverse event 
Tmax 
Time to maximum concentration 
TNF 
Tumor necrosis factor 
TPE 
Therapeutic plasma exchange 
UC 
Ulcerative colitis 
ULN 
Upper limit of normal 
WBC 
White blood cell 


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Sponsor Signature Page of Protocol 
Sponsor (Suzhou Connect Biopharmaceuticals, Ltd.) will, in accordance with the requirements 
of the clinical study protocol, strictly follow the guidelines below throughout the study, giving 
the greatest respect for subjects: 
● 
the Declaration of Helsinki: ethical principles for medical research involving human 
subjects; 
● 
the International Council for Harmonisation (ICH) Good Clinical Practice (GCP) (E6); 
● 
the local Good Clinical Practice; 
● 
all applicable laws and regulations, including but not limited to Privacy Protection Act as 
well as laws and regulations governing clinical trial disclosure. 
I have read the full text of the protocol and agree to all the contents. 
 
 
Name of Sponsor’s Representative: Ping Li 
                          
Signature of Sponsor’s Representative:  
Signing Date:        
 
` 
Title of Sponsor’s Representative: Vice President, Clinical Development 
 
Name of Sponsor: Suzhou Connect Biopharmaceuticals, Ltd.     
 
 


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Investigator Signature Page of Protocol 
I agree: 
I will, in accordance with the requirements of the clinical study protocol, strictly follow the 
guidelines below throughout the study, giving the greatest respect for subjects: 
● 
the Declaration of Helsinki: ethical principles for medical research involving human 
subjects; 
● 
the ICH-GCP (E6); 
● 
the local GCP; 
● 
all applicable laws and regulations, including but not limited to Privacy Protection Act as 
well as laws and regulations governing clinical trial disclosure. 
I have read the full text of the protocol and agree to all the contents. 
 
 
Name of Investigator: 
 
Signature of Investigator: 
                        
Signing Date: 
 
Title of Investigator: 
 
Name of Study Site: 


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Statistician Signature Page of Protocol 
I agree: 
● 
To strictly follow the protocol, GCP and applicable regulations and laws when carrying 
out the study. 
● 
To keep all materials supplied by Suzhou Connect Biopharmaceuticals, Ltd. confidential 
according to confidentiality requirements, and must specify these materials are 
confidential when submitting to the Independent Ethics Committee (IEC)/Institutional 
Review Board (IRB). 
I have read the full text of the protocol and agree to all the contents. 
 
 
Name of Statistician: Boran Zheng 
 
Signature of Statistician: 
 
Signing Date:   
 
Title of Statistician: Senior Biostatistician 
 
Name of Statistical Agency: IQVIA 
 
 


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1 STUDY SYNOPSIS 
Protocol Title: A multicenter, randomized, double-blind, placebo-controlled phase II clinical 
trial to evaluate the efficacy and safety of CBP-307 in subjects with moderate to severe 
ulcerative colitis (UC) 
Protocol No.: CBP-307CN002 
Phase of Clinical Trial: II 
Investigators and Study Sites: The clinical trial is planned to be carried out in approximately 
77 sites globally in China, Pakistan, Ukraine and the United States. 
Planned Duration of Study: March 2018 to September 2022 
Study Objectives and Endpoints: 
 
Study objectives 
Study endpoints 
Primary 
endpoint 
● To compare clinical efficacy 
of CBP-307 vs placebo by 
evaluating the change of 
adapted Mayo score after 12 
consecutive weeks treatment 
in subjects with moderate to 
severe UC 
● Change in adapted Mayo score from baseline at 
week 12 compared between CBP-307 0.2 mg and 
placebo 
Secondary 
endpoint 
● To compare clinical efficacy 
of CBP-307 vs placebo by 
evaluating 
the 
clinical 
response 
rate, 
clinical 
remission rate and mucosal 
healing 
rate 
after 
12 
consecutive weeks treatment 
in subjects with moderate to 
severe UC 
● Change in adapted Mayo score from baseline at 
week 12 after treatment compared between CBP-
307 0.1 mg and placebo 
● Change in complete Mayo score from baseline at 
week 12 after treatment 
● Comparison of clinical response rate at week 12 
by adapted Mayo score (defined as a decrease of 
≥ 2 points and at least 30% from baseline, 
accompanied with a decrease of ≥ 1 point from 
baseline in the rectal bleeding subscore or an 
absolute rectal bleeding subscore of ≤ 1 point) 
● Comparison of clinical response rate at week 12 
by complete Mayo score (defined as a decrease of 
≥ 3 points and at least 30% from baseline, 
accompanied with a decrease of ≥ 1 point from 
baseline in the rectal bleeding subscore or an 
absolute rectal bleeding subscore of ≤ 1 point) 
● Comparison of clinical remission rate at week 12 
by adapted Mayo score (defined as a rectal 
bleeding subscore = 0 and a stool frequency 
subscore ≤ 1, with an Endoscopy subscore ≤ 1 
[excluding friability]) 


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● Comparison of clinical remission rate at week 12 
by complete Mayo score (defined as a total Mayo 
score of ≤ 2 points with no individual subscore > 
1 point) 
● Mucosal healing rate at week 12 after treatment 
(mucosal healing is defined as Mayo endoscopic 
subscore ≤ 1) 
● To compare the clinical 
safety and tolerability of 
CBP-307 with those of 
placebo administered for 
12 weeks in subjects with 
moderate to severe UC 
● 
Incidence, type and severity of TEAEs and SAEs 
as well as their relations with the investigational 
product, 
AEs 
and 
SAEs 
that 
lead 
to 
discontinuation of study, and AEs of special 
interest (cardiac events as well as pulmonary 
function tests, ophthalmologic examinations skin 
examinations, and nervous system physical 
examinations); AEs will be graded according to 
CTCAE version 5.0 in the study stage 1 
● 12-lead 
ECG 
findings, 
abnormal 
clinical 
laboratory tests (the hematology test, blood 
chemistry test, urinalysis and coagulation test), 
vital signs and results of physical examination 
Exploratory 
● 
To evaluate the PK/PD of 
CBP-307 
orally 
administered 
in 
subjects 
with moderate to severe UC 
in study stage 1 
● 
To evaluate IBDQ in study 
stage 1 and stage 2 
● 
To evaluate the safety and 
tolerability of CBP-307 
after medium or long-term 
administration (in study 
stage 2) in subjects with 
moderate to severe UC 
● 
To evaluate clinical 
remission, clinical response 
and mucosal healing in 
subjects with moderately to 
severely active UC who 
respond after 12 weeks of 
induction therapy in the 
stage 1 study, thereby to 
evaluate the efficacy of 
CBP-307 orally 
administered for 
maintenance treatment 
compared with placebo in 
sub-study 1 of the study 
stage 2 
● 
To 
evaluate 
clinical 
remission, clinical response 
and mucosal healing in 
● Plasma concentration of CBP-307 in subjects with 
moderate to severe UC 
● Absolute lymphocyte count 
● Total Igs (IgA, IgG and IgM) 
● C-reactive protein (CRP) as a biomarker of plasma 
protein 
● Fecal calprotectin as a fecal biomarker to be 
analyzed 
● Change from baseline in IBDQ total score and 
subscore at week 12 after treatment (in the study 
stage 1), at week 24, and week 48 (in the study 
stage 2) 
● Incidence, type and severity of TEAEs and SAEs 
as well as their relations with the investigational 
product, 
AEs 
and 
SAEs 
that 
lead 
to 
discontinuation of study, and AEs of special 
interest (cardiac events as well as pulmonary 
function tests, ophthalmologic examinations, skin 
examinations, and nervous system physical 
examinations); AEs will be graded according to 
CTCAE version 5.0 in study stage 2 
● Change in 12-lead ECG findings, abnormal 
clinical laboratory tests (the hematology test, 
blood chemistry test, urinalysis and coagulation 
test), vital signs and results of physical 
examination in the study stage 2 
● To explore the following efficacy endpoints in 
subjects with moderately to severely active UC 


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subjects with moderately to 
severely active UC who do 
not 
achieve 
clinical 
response after 12 weeks of 
induction therapy in the 
study stage 1, thereby to 
evaluate the efficacy of 
CBP-307 
when 
orally 
administered for treatment 
in the sub-study 2 of the 
study stage 2. 
who achieved clinical response after 12 weeks of 
induction therapy in study stage 1: 
o 
Percentage of subjects who maintain 
clinical response at week 48  
o 
Percentage of subjects who achieve 
clinical remission at week 48 
o 
Percentage of subjects who achieve 
mucosal healing under endoscope at 
week 48 
o 
Percentage of subjects who take oral 
corticosteroids at baseline but has 
discontinued treatment of 
corticosteroids at week 48 and achieved 
clinical remission 
o 
Change in the complete Mayo score at 
week 48 from baseline 
o 
Change in the adapted Mayo score at 
week 48 from baseline 
● To explore the following efficacy endpoints in 
subjects with moderately to severely active UC 
who do not achieve response after 12 weeks of 
induction therapy in study stage 1: 
o 
Percentage of subjects who achieve 
clinical response at week 24 (after 12 
weeks of treatment in sub-study 2)  
o 
Percentage of subjects who achieve 
clinical remission at week 24 (after 12 
weeks of treatment in sub-study 2)  
o 
Percentage of subjects who achieve 
mucosal healing under endoscope at 
week 24 (after 12 weeks of treatment in 
sub-study 2) 
o 
Change in the complete Mayo score at 
week 24 (after 12 weeks of treatment in 
sub-study 2) from week 12 
o 
Change in the adapted Mayo score at 
week 24 (after 12 weeks of treatment in 
sub-study 2) from week 12 
o 
Percentage of subjects who maintain 
clinical response at week 48 (after 36 
weeks of treatment in sub-study 2) (i.e., 
have clinical response at both week 24 
and week 48) 
o 
Percentage of subjects who achieve 
clinical remission at week 48 (after 36 
weeks of treatment in sub-study 2) 
o 
Percentage of subjects who achieve 
mucosal healing under endoscope at 
week 48 (after 36 weeks of treatment in 
sub-study 2) 
o 
Change in the complete Mayo score at 
week 48 (after 36 weeks of treatment in 
sub-study 2) from week 12 


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o 
Change in the adapted Mayo score at 
week 48 (after 36 weeks of treatment in 
sub-study 2) from week 12 
AE=adverse events; CRP=C-reactive protein; CTCAE=common terminology criteria for adverse events; 
IBDQ=inflammatory bowel disease questionnaire; Ig=immunoglobulin; PD=pharmacodynamics; 
PK=pharmacokinetics; SAE: serious adverse event; TEAE: treatment-emergent adverse event; 
UC=ulcerative colitis. 
Study design: 
This is a multicenter, multicountry, phase II clinical trial to evaluate the efficacy and safety of 
CBP-307 in subjects with moderate to severe ulcerative colitis (UC). This study includes stage 
1 and stage 2. 
Study stage 1  
After screening, subjects will enter the randomized, double-blind, placebo-controlled induction 
therapy for 12 weeks, i.e., the study stage 1. Subjects will be given CBP-307 capsules 0.2 mg 
(or placebo) orally once daily for 12 consecutive weeks. The eligible subjects are planned to 
be enrolled and randomized at a ratio of 1:1 into the 2 groups (approximately 52 subjects in 
each group) and stratified according to whether the subject failed in a previous tumor necrosis 
factor (TNF)-α antagonist therapy. Subjects will be screened at 1-21 days prior to the baseline 
visit. Subjects with moderate to severe UC (adapted Mayo score ≥ 4) who meet all inclusion 
criteria and do not meet any exclusion criteria will be randomized into one of the following 2 
groups at the baseline visit: a group treated with CBP-307 0.2 mg once daily (2 capsules of 
CBP-307 0.1 mg), and a placebo group (treated with 2 capsules of placebo). Placebo capsules 
are completely identical with the CBP-307 capsules in appearance and weight. 
Subjects randomized to CBP-307 group will undergo dose titration for 1 week, while those in 
placebo group will undergo simulated titration. Both CBP-307 and placebo will be 
administered through the oral route. For subjects in the group of CBP-307 0.2 mg once daily, 
a dose of 0.05 mg CBP-307 will be given from day 1 to day 4; then, a dose of 0.1 mg CBP-307 
will be given for later 3 days; from day 8, a target dose (0.2 mg) will be administered. See 
Table 1 for details on the Stage 1 dose titration. 
Table 1 
Stage 1 Titration dosing regimen 
Target dose 
Day 1 to day 4 
Day 5 to day 7 
From day 8 
CBP-307 0.2 mg 
0.05 mg 
0.1 mg 
0.2 mg 
Placebo 
Placebo capsules 
Placebo capsules 
Placebo capsules 
Note: During the titration period, CBP-307 0.05 mg will be orally administered at doses of 
0.05 mg (1 capsule) and 0.1 mg will be orally administered at 0.05 mg (2 capsules); in the 
placebo group, placebo capsules at the corresponding quantity (completely identical with 


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CBP-307 in appearance and weight) are orally administered. From day 8, in the 0.2 mg group, 
2 capsules of 0.1 mg will be orally administered; and in the placebo group, 2 capsules of 
placebo (completely identical with CBP-307 in appearance and weight) will be orally 
administered. The drugs taken daily are sub-packaged in bottles in a GMP-compliant workshop, 
the investigational product is independently packaged in boxes based on visit intervals. 
For the subjects already enrolled as per the previous approved protocols (version 5.0 or earlier), 
they will continue the treatment in the stage 1 according to the previous planned schedule. 
Administration will be continued for 12 weeks. If subjects who complete 12 weeks of induction 
therapy of the stage 1 meet the criteria for the study stage 2, they can choose to enter it to 
further evaluate the safety and efficacy of CBP-307 in medium or long-term administration in 
subjects with moderate to severe UC. Subjects who early withdraw from the study or complete 
the study stage 1 but do not enter the stage 2 will enter a 4-week safety follow-up period. 
Schematic diagram of design of study stage 1 entering to the stage 2 is shown in Figure 1. 
Figure 1 
Schematic Diagram of Study Stage 1 Design 
 
Study stage 2 
All subjects who complete 12 weeks of induction therapy (with CBP-307 or placebo) in the 
study stage 1 and complete all examinations (including colonoscopy) at the week 12 visit can 
choose to enter the study stage 2 of a total of 40 weeks, including 36 weeks of continuous 
administration and 4 weeks of safety follow-up after the last dose. Subjects who choose to enter 
the stage 2 will be required to sign an updated informed consent form and will be screened for 
0.2 mg CBP-307 QD, 52 subjects 
Placebo QD, 52 subjects 


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eligibility. 
The study stage 2 contains two sub-studies: sub-study 1 and sub-study 2. Subjects entering the 
study stage 2 will enter one of sub-studies based on their results of efficacy evaluation in the 
study stage 1 (Figure 2). 
Sub-study 1 (subjects who have achieved clinical response by adapted Mayo score): Subjects 
who have achieved clinical response shown by efficacy evaluation at week 12 in the study 
stage 1 and meet the eligibility criteria for stage 2 will enter sub-study 1 of the study stage 2 to 
receive double-blind maintenance treatment for 36 weeks (weeks 13 to 48), i.e., the therapeutic 
regimen for them in study stage 1 will be continually maintained (Figure 2). Safety follow-up 
will be completed at 4 weeks after the last dose. Subjects who present with recurrent UC during 
maintenance treatment are required to terminate treatment and withdraw from the study. 
For the subjects already enrolled as per the previous approved protocols (version 5.0 or earlier), 
they will follow the previous planned treatment in the sub-study 1 of stage 2 study. 
UC disease recurrence i.e., an increased activity of UC, is defined as a repeated (occurring at 
2 consecutive visits) partial Mayo score that is at least 5 points and is also ≥3 points higher 
than the score at week 12 (the end of induction therapy), and where the possibility of increased 
disease activity being due to other potential factors unrelated to UC can be excluded (e.g., 
infection, medication changes).  
Sub-study 2 (subjects who have not achieved clinical response by adapted Mayo score): 
Subjects who have not achieved clinical response shown by efficacy evaluation at week 12 
in the study stage 1 and meet the eligibility criteria for study stage 2 will enter open-label 
treatment with CBP-307 0.2 mg (Figure 2). Subjects will receive CBP-307 once daily at an oral 
dose of 0.2 mg in sub-study 2 regardless of whether they receive CBP-307 0.2 mg or placebo 
in the study stage 1. 
For subjects who enter sub-study 2 of study stage 2, 1-week dose titration will be performed at 
the first week (week 13). Dose titration will involve administration of CBP 0.05 mg initiated 
on day 1 and used for 4 consecutive days, followed by administration of CBP-307 0.1 mg for 
3 days, and administration of CBP-307 at a target dose of 0.2 mg initiated on day 8. After dose 
titration is completed, subjects will receive oral treatment with CBP-307 0.2 mg once daily, for 
36 weeks. Safety follow-up will be completed at 4 weeks after the last dose. 
At week 24, subjects will undergo efficacy evaluation including colonoscopy. If any subject 
still has not achieved clinical response, the treatment will be discontinued and the subject will 
be withdrawn from the study. 


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Figure 2 
Schematic Diagram of Transition from Stage 1 to Stage 2 Substudies 
 
Inclusion and exclusion criteria: 
The following criteria are used to select eligible subjects for this study. A subject is eligible to 
be included in the study only if all of the inclusion criteria apply and none of the exclusion 
criteria apply. 
Inclusion criteria: 
Subjects are eligible to be included in the study only if all of the following criteria apply: 
1. Male or female subjects aged 18-75 years (inclusive). 
2. In the opinion of the investigator, the subject is capable of understanding and complying 
with protocol requirements. The subject signs and dates a written informed consent form 
prior to the initiation of any study procedures. 
3. Female subjects of childbearing potential and male subjects who have not undergone 
vasectomy should use at least one highly effective method of contraception during the 
entire study and 4 weeks after the last dose of investigational products after signing the 
informed consent form. The highly effective methods of contraception in this study 
include: 
a. 
Abstinence is acceptable only if it is part of the participant’s regularly practiced 
lifestyle; 
b. Hormone (oral, patch, ring, injection, implant) in combination with a male condom. 
This must be used for at least 30 days before the first dose of investigational products 
or an alternative acceptable method must be used; 
c. 
Intrauterine device (IUD) in combination with a male condom; 


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d. Exceptions are: a) women with at least 12 consecutive months amenorrhea in the 
absence of medications known to induce amenorrhea and have a documented follicle 
stimulating hormone (FSH) level of greater than 40 mIU/mL or in the postmenopausal 
range; or b) surgical sterilization (e.g., hysterectomy, bilateral oophorectomy). 
4. The subject has a diagnosis of UC established at least 3 months prior to screening by 
clinical and endoscopic evidence corroborated by a histopathology report. Subjects are 
confirmed to have moderate to severe active UC within 14 days prior to the first dose of 
the investigational product, which is based on an adapted Mayo score of 4-9, and an 
endoscopic subscore of ≥ 2. Endoscopy must be performed during the screening period 
(day -14 to day -3, allowing centralized reading and evaluation before the first dose at 
week 0). 
5. The subject has evidence of UC extending to the rectum with ≥15 cm involvement on 
endoscopy.  
6. Subjects must be UC patients who are receiving treatment. They can be enrolled if they 
meet any items below. 
a. 
Prior to the randomization visit, subjects have received oral 5-ASA (e.g., mesalazine, 
sulfasalazine, olsalazine, balsalazide) for at least 4 weeks with the dose stable for at 
least 2 weeks. 
b. Prior to the randomization visit, subjects have received oral or IV corticosteroids e.g. 
prednisone (daily doses ≤ 30 mg), budesonide (daily doses ≤ 9 mg), 
methylprednisolone (daily doses ≤ 24 mg), or equivalent dose of corticosteroids for at 
least 4 weeks, with the dose stable for at least 2 weeks. 
7. If oral 5-ASA or corticosteroid for treatment of UC have been recently discontinued, they 
must have been stopped for at least 2 weeks prior to the screening endoscopy examination 
which is used for Mayo score assessment. 
8. If subjects use non-prohibited concomitant medications, a stable dosing regimen must be 
used, that is, within 7 days prior to first dose of investigational product or within 
5 half-lives of the drug (whichever is longer), there's no new concomitant medications 
started or changes in the dose of existing non-prohibited concomitant medications.   
9. The subject who has extensive colitis or pancolitis of >8 years duration or limited colitis 
of >12 years duration must have documented evidence that a surveillance colonoscopy 
was performed within 12 months prior to initial screening visit (can be performed during 
Screening if not performed in previous 12 months).  
10. For subject who has a family history of colorectal cancer, personal history of increased 
colorectal cancer risk, age >50 years, or other known risk factor, the data of colorectal 
cancer surveillance within 12 months prior to screening visit must be available (colorectal 
cancer surveillance can be performed during screening if not in previous 12 months). 


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Exclusion criteria: 
Exclusion criteria are classified into indication-specific exclusion criteria, exclusion criteria for 
general condition and exclusion criteria for infectious diseases. Patients who meet any of the 
following criteria will be excluded: 
UC-related exclusion criteria: 
1. 
At the screening visit, subjects have evidence of toxic megacolon. 
2. 
The subject has had subtotal or total colectomy. 
3. 
The subject has an existing ileostomy, colostomy (a history of ileostomy or colostomy 
that has been reversed may be acceptable), or known symptomatic stenosis of the intestine. 
4. 
Investigator judges the subject currently requires or is anticipated to require surgical 
intervention for UC during the study. 
5. 
The subject has a history or evidence of adenomatous colonic polyps that have not been 
removed. 
6. 
The subject has a history or evidence of colonic mucosal dysplasia including low or high-
grade dysplasia, as well as indeterminate for dysplasia. 
7. 
Subjects have a suspected or confirmed diagnosis of Crohn's enterocolitis, undiagnosed 
types of colitis, ischemic colitis, or radiation colitis. 
8. 
Subjects were previously exposure to the following treatments: 
• Lymphocyte-depleting therapies (e.g., alemtuzumab, anti-CD4 antibody, 
cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total body 
irradiation, bone marrow transplantation and daclizumab). 
• Previous treatment with D-penicillamine, leflunomide. 
9. 
The subject has had prior exposure to approved or investigational products that inhibit the 
lymphocyte trafficking (e.g., natalizumab, fingolimod, ozanimod or etrasimod, etc.) 
Subjects who were previously exposed to vedolizumab and did not respond to its 
treatment. 
10. Within 60 days prior to the screening visit, the subject has received any of the following 
for the treatment of UC: 
a. 
Intravenous immunoglobulin; 
b. 
Therapeutic plasma exchange (TPE). 
11. Within 30 days prior to randomization visit, the subject has received any of the following 
for the treatment of UC: 
a. 
Immunosuppressants (such as cyclosporine, tacrolimus, sirolimus or mycophenolate 
mofetil), thalidomide or traditional Chinese medicine; 
b. 
Approved non-biologic agents or traditional Chinese medicine treatment. 
12. Patients who plan to concurrently use an immunosuppressant (such as azathioprine, 


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6-mercaptopurine or methotrexate) after randomization. Patients treated with azathioprine, 
6-mercaptopurine or methotrexate at screening are required to discontinue it prior to the 
first dose of the study drug. 
13. The subject has received any investigational biologic or non-biologic agent, or approved 
biologic agent or biosimilars within 60 days or 5 half-lives prior to screening (whichever 
is longer). 
14. The subject has used topical (rectal) treatment with aminosalicylic acid, corticosteroid or 
traditional Chinese medicine enemas/suppositories or for UC treatment within 2 weeks of 
the administration of the first dose of study drug. 
Exclusion criteria for general conditions: 
15. The subject has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, 
gastrointestinal, 
genitourinary, 
hematological, 
coagulation, 
immunological, 
endocrine/metabolic, or other medical disorders that, in the opinion of the investigator, 
would confound the study results or compromise subject safety. 
16. History of uveitis or macular oedema. 
17. Clinically relevant cardiovascular conditions, including history or presence of any one of 
below: 
a. 
Ischemic heart disease or myocardial infarction; Unstable angina; History of angina 
pectoris caused by coronary artery spasm, or raynaud's phenomenon (Raynauds); 
b. 
Congestive heart failure (NYHA class III-IV), cardiac arrest; 
c. 
Stroke, transient ischemic attack; 
d. 
History of recurrent syncope or positive result of vasovagal syncope tilt test; 
e. 
Symptomatic bradycardia, sick sinus syndrome, sinoatrial block, second degree 
atrioventricular block (e.g., Mobitz type 2 atrioventricular block) or third degree 
atrioventricular block; 
f. 
Congenital long QT syndrome (LQTS), or prolonged QT interval corrected using 
Fridericia’s formula (QTcF) in screening ECG (QTcF >450 ms in men, 
QTcF > 470 ms in women); 
g. 
Subjects at increased risk for QT prolongation due to hypokalemia or 
hypomagnesemia; or subjects who are currently taking medications to prolong QT 
interval 
(e.g., 
citalopram, 
chlorpromazine, 
haloperidol, 
methadone, 
and 
erythromycin) which result in risk for torsades de pointes; 
h. 
Under treatment or expected to taking treatment during the study with medications 
with a known impact on the cardiac conduction system (e.g., beta blockers, calcium 
channel blockers, Class Ia or Class III anti-arrhythmic drugs. [amiodarone, 
bromobenzylamine, sotalol, ibutilide, azimilide, dofetilide]); 
i. 
Hypertension (except well-controlled hypertension after pharmacotherapy); systolic 


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blood pressure < 95 mm Hg or >140 mm Hg and diastolic blood pressure ≤ 50 mm 
Hg or ≥ 95 mm Hg at the screening visit; 
j. 
Resting heart rate < 55 times/min or ventricular rate < 55 times/min in 12-lead ECG 
at screening visit; 
k. 
Investigator deems that the 12-lead ECG at screening visit is clinically significant 
abnormal, such as, myocardial ischemia, any significant cardiac conduction 
abnormalities (such as the left bundle branch block), that would put the subject at 
risk or interfere with the study results; 
l. 
Any other significant heart disease that the investigator judges would put the subject 
at risk or interfere with the study results. 
m. Subjects have a family history of premature coronary heart disease. 
18. History of type 1 diabetes, uncontrolled type 2 diabetes (HbA1c > 7%) judged by 
investigator, patients with diabetes accompanied with significant complications, e.g., 
retinopathy or kidney disease. 
19. The subject has a history of malignancies, including malignant solid tumors and 
hematological malignancies (Except basal cell carcinomas and in situ squamous 
carcinomas of the skin that have been excised or cured). 
20. The subject has had any surgical procedure requiring general anesthesia within 30 days 
prior to screening or is planning to undergo major surgery during the study period. 
21. The subject has chronic obstructive pulmonary disease, asthma, pulmonary fibrosis or 
other any significant history of pulmonary diseases, except for mild intermittent asthma 
that does not require regular maintenance treatment. 
22. Pulmonary function test (including examinations of lung ventilation function and 
pulmonary gas exchange) at the screening visit shows one of the following abnormalities: 
forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 70% of 
normal expected value. 
23. During screening period, any of the following laboratory abnormalities: 
a. 
Hgb < 8 g/dL; 
b. 
WBC count < 3.5 × 10 9/L; 
c. 
Neutrophils count < 1.5 × 10 9/L; 
d. 
Lymphocyte count < 0.8 × 10 9/L; 
e. 
Platelet count < 100 × 10 9/L or >1200 × 10 9/L; 
f. 
Serum creatinine > 124 μmol/L for female or > 141 μmol/L for male;  
If the WBC count, neutrophil count or lymphocyte count meets the above criteria 
during the screening period, a retest can be scheduled during the screening period. It 
is required that the results of the retest should not meet the above criteria, otherwise 
subjects do not meet the enrollment criteria. 
24. Abnormal liver function test during the screening period, such as abonormalities in 


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alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase 
(γ-GT), alkaline phosphatase (ALK) or serum total bilirubin, which suggests liver diseases 
or liver function impairment. The investigator should make a determination according to 
the following criteria: 
a. 
Subjects with serum total bilirubin > 1.2 times the upper limit of normal (ULN) 
shown by initial and repeat tests should be excluded from the study; 
b. 
Subjects with any of the other liver function parameters listed above, such as AST, 
ALT, γ-GT or ALK > 1.5 times the ULN shown by initial and repeat tests, should be 
excluded from the study; 
c. 
Subjects with increased level of more than 1 parameter in liver function test should 
be excluded from the study; 
d. 
During the screening period, if a single transaminase level (AST, ALT, γ-GT or ALK) 
is elevated by more than 1.5 times the ULN, or serum total bilirubin is elevated by 
more than 1.2 times the ULN, a repeat test can be scheduled as soon as possible 
before enrollment/randomization to exclude laboratory errors. Only if the results of 
the repeat test meet the requirements, subjects could be enrolled. 
25. Allergic to any component of the study drug (and its excipients). 
26. The subject has a history of drug abuse (defined as any illicit drug use) or a history of 
alcohol abuse within 1 year prior to Screening. 
27. The subject has an active mental disorder that, in the opinion of investigator, may interfere 
with compliance with study procedures. 
28. The subject is unable to participate in all study visits or comply with study procedures. 
29. The subject is in a health condition that requires to take prohibited medications listed in 
Section 6.6. 
30. If female, the subject is intending to become pregnant before, during, or within 4 weeks 
after participating in the study or intending to donate ova during such period. 
31. If male, the subject intends to donate sperm during the study or for 4 weeks thereafter. 
32. The subject is an immediate family member, study site employee, or is in a dependent 
relationship with a study site employee who is involved in the conduct of this study (e.g., 
spouse, parent, child, sibling) or may consent under duress. 
33. Female subjects who are lactating or have a positive serum pregnancy test during the 
Screening Period or a positive urine pregnancy test at week 0, prior to study drug 
administration. 
Exclusion criteria for infectious diseases: 
34. The subject has evidence of known active infection during the screening period. 
35. The subject has evidence of treatment for Clostridioides difficile (C. difficile) infection 
or other intestinal pathogen with 28 days prior to first dose of study drug. 


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36. Patients with the histories of following infectious diseases: 
● 
Treatment with oral anti-infection medication due to acute infection within 2 weeks 
prior to screening visit or intravenous anti-infection treatment due to acute infection 
within 4 weeks prior to screening visit; 
● 
Clinically significant infection (e.g., pneumonia, nephropyelitis and herpes zoster) 
within 4 weeks prior to screening visit, or ongoing chronic infection; 
37. Active or latent tuberculosis (TB) evidenced by the followings: 
● 
A positive diagnostic TB test within 30 days before screening or during the screening 
period is defined as: 
- 
Quantiferon or Quantiferon Plus test positive, or 
- 
Two consecutive indeterminate Quantiferon tests or Quantiferon Plus tests, or 
- 
Chest X-ray within 3 months prior to week 0 for which the results are suspicious 
for pulmonary TB. 
Note: Subjects with documented evidence of previously successfully treated TB, or with a negative 
Quantiferon or Quantiferon Plus test result, can be enrolled in the study. If Quantiferon or Quantiferon 
Plus test result is indeterminate at screening, it could be retested during screening period. If Quantiferon 
or Quantiferon Plus retest result is indeterminate, the subject should not participate in the study. If 
Quantiferon or Quantiferon Plus retest result is negative, the subject can be enrolled in the study.  
38.  Chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV) 
infection**. 
*Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) and hepatitis B core 
antibody (HBcAb) must be evaluated for all the patients at screening. Patients with positive hepatitis 
B surface antigen (HBsAg) will be excluded. HBV-DNA test should be carried out at screening if the 
subject is negative for Hepatitis B surface antigen, negative or positive for hepatitis B surface antibody, 
and positive for hepatitis B core antibody. The subject should be excluded from the study if HBV-DNA 
test result is positive, or he/her can be enrolled in the study in case of negative result of HBV-DNA 
test. 
**An HCV viral load test should be carried out if HCV antibody (HCVAb) is positive. The subject 
should be excluded from the study in case of positive HCV viral load test result. If the HCV viral load 
test result is negative, the subject can be enrolled in the study. 
39. The subject has any identified congenital or acquired immunodeficiency (e.g., common 
variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ 
transplantation). 
40. The subject has received any live vaccine within 30 days prior to screening, or subjects 
are scheduled for immunization with any live vaccine during the study or within 1 month 
after the last dose of the investigational product. 
41. Positive syphilis antibody at screening. 


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42. Subjects with a history of more than one episode of herpes zoster, or a history of 
disseminated herpes zoster or disseminated herpes simplex. 
Inclusion and exclusion criteria for subjects' entry into the study stage 2 from the stage 1: 
Inclusion criteria: 
Subjects cannot enter the study stage 2 if any of the following criteria is not satisfied: 
1. 
Subjects must be those with UC who participate in the study of CBP-307CN002 and have 
completed 12 weeks of treatment with CBP-307 or placebo in the stage 1 and have 
completed all the assessments (including colonoscopy) at study visit of week 12 in study 
stage 1. 
2. 
Subjects have good compliance in stage 1, can understand all information about the study 
stage 2, and are able and willing to comply with the requirements specified in the study 
protocol. 
3. 
Subjects or their legal representatives voluntarily sign informed consent forms for study 
stage 2. 
4. 
Female subjects of childbearing potential and male subjects who have not undergone 
vasectomy should use at least one highly effective method of contraception during the 
entire study and 4 weeks after the last dose of investigational products after signing the 
informed consent form. The highly effective methods of contraception in this study 
include: 
a 
Abstinence is acceptable only if it is part of the participant’s regularly practiced 
lifestyle; 
b 
Hormone (oral, patch, ring, injection, implant) in combination with a male condom. 
This must be used for at least 30 days before the first dose of investigational products 
or an alternative acceptable method must be used; 
c 
Intrauterine device (IUD) in combination with a male condom; 
d 
Exceptions are: a) women with at least 12 consecutive months amenorrhea in the 
absence of medications known to induce amenorrhea and have a documented FSH 
level of greater than 40 mIU/mL or in the postmenopausal range; or b) surgical 
sterilization (e.g., hysterectomy, bilateral oophorectomy). 
Exclusion criteria: 
Subjects who meet any of the following criteria will not be included in study stage 2: 
1. 
The subject has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, 
GI, genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or 
other medical disorder that, in the opinion of the investigator, would confound the study 
results or compromise subject safety. 
2. 
Subjects who are known to be allergic to CBP-307 or its excipients, or subjects experience 
significant adverse events related to the study drug during the stage 1 of the 


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CBP-307CN002 study, and the investigator deems that subjects are not appropriate to 
participate in the stage 2. 
3. 
Subjects currently have evidence of active or untreated latent tuberculosis. 
4. 
Subjects currently have active or chronic recurrent infections, and in the opinion of the 
investigator subjects are not appropriate to participate in the stage 2 of the study. 
5. 
History of uveitis or macular oedema. 
6. 
Subjects had received any of the following treatments after administration of the first dose 
in the stage 1 of the study: 
• 
Biological product; 
• 
Prednisone>30 mg/day, budesonide>9 mg/day, methylprednisolone>24 mg/day or 
equivalent dose of steroid treatment; 
• 
Immunosuppressant (such as azathioprine and 6-mercaptopurine or methotrexate). 
7. 
Investigator deems that the 12-lead ECG results at the study visit of week 12 during study 
stage 1 is clinically significant abnormal, such as myocardial ischemia, any significant 
cardiac conduction abnormalities (such as the left bundle branch block), any abnormality 
that would put the subject at risk or interfere with the study results. 
8. 
Pulmonary function test (including examinations of lung ventilation function and 
pulmonary gas exchange) of subjects at the study visit of week 12 during the study stage 1 
shows 1 of the following abnormalities: forced expiratory volume in 1 second (FEV1) or 
forced vital capacity (FVC) < 50% of normal predicted value. 
9. 
Subjects’ laboratory measurements at week 12 visit during the study stage 1 meet any of 
the following criteria:  
• 
AST or ALT> 3 ULN; 
• 
Absolute lymphocyte count < 0.2×10 9/L; 
• 
Serum creatinine > 124 μmol/L (in females) or > 141 μmol/L (in males) 
10. Any other reason that in the opinion of the investigator may interfere with subject 
compliance or evaluation of the results of the study. 
Study drug, dose and route of administration: 
Study drugs in this study include CBP-307 and placebo (both in capsule form). The route of 
administration will be oral administration. In the study stage 1, subjects with moderate to severe 
UC will be randomized into one of the following two groups: a group treated with CBP-307 
0.2 mg once daily (2 capsules of CBP-307 0.1 mg), and a placebo group (treated with 2 capsules 
of placebo). Placebo capsules are completely identical with the CBP-307 capsules in 
appearance and weight. 
In the study stage 2, subjects entering sub-study 1 will continue receiving double-blind 
maintenance treatment according to their treatment regimen in the stage 1; all subjects entering 


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sub-study 2 will receive CBP-307 0.2 mg (2 CBP-307 capsules 0.1 mg) once daily. 
Study duration: 
Study stage 1: The duration for treatment is 12 weeks. Subjects who complete the 12-week 
treatment of stage 1 but do not enter the stage 2 or early withdraw from the study will undergo 
safety follow-up for 4 weeks after the last dose. 
Study stage 2: All subjects who complete the 12-week study stage 1 treatment (induction 
therapy with CBP-307 or placebo) and complete all assessments (including colonoscopy) at 
week 12 visit can choose to enter the study stage 2 for a total of 40 weeks. In the stage 2, 
subjects will continuously be administered for 36 weeks (week 13-48 of the study), and they 
will undergo safety follow-up for 4 weeks after the last dose (week 49-52 of the study). Subjects 
who early withdraw from the study will undergo safety follow-up for 4 weeks after the last 
dose. 
For subjects who complete both stages (stage 1 + stage 2), the study will last for a total of 
52 weeks: 48 weeks of administration, and 4 weeks of follow-up. 
Study procedures: 
The study procedures in the stage 1 are shown in Table 2 Study Flow Chart. 
Study procedures in the stage 2 are shown in Table 3 Study Flow Chart (sub-study 1) and Table 
4 (sub-study 2). 
Sample size: 
Approximately 134 subjects with moderate to severe UC will be randomized in the study. 
Among them, approximately 30 subjects who have already enrolled in CBP-307 0.1 mg group 
based on protocol version 5.0 or earlier will be analyzed for exploratory purpose. No further 
subjects will be enrolled in CBP-307 0.1 mg group from protocol version 6.0. 
Approximately 104 eligible subjects will be randomized at 1:1 into one of the following 2 
groups to undergo induction therapy in the study stage 1: CBP-307 0.2 mg once daily, or 
placebo (52 subjects in each group) based on protocol amendment and sample size 
recalculation。 
All subjects who complete the 12-week study stage 1 and all tests (including colonoscopy) at 
visit at week 12 can be selected to enter the study stage 2. 
Statistical method: 
The primary efficacy endpoint of the study is the change in adapted Mayo score from baseline 
at week 12 after treatment compared between CBP-307 0.2 mg and placebo at the study stage 


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1. 
The sample size was calculated based on the estimation on primary efficacy endpoint. 
Assuming that the difference between the 0.2 mg group and the placebo group of the change 
from baseline at week 12 after treatment in adapted Mayo score is 1.2, and the common 
standard deviation is 2.0, a significance level of α=0.05 (two-sided), and a dropout rate is 15%, 
then each group needs to enroll at least 52 subjects to provide a power of 80% to detect the 
difference between the 0.2 mg group and the placebo group on the primary efficacy endpoint. 
The covariance (ANCOVA) model with baseline as covariate will be used to analyze the 
changes in adapted Mayo score from baseline at week 12 between the CBP-307 0.2 mg group 
and the placebo group. Descriptive statistics will be applied to continuous variables (the 
number of subjects, mean, standard deviation, minimum, median, and maximum) and 
categorical variables (the frequency and percentage). 
Statistical analysis will be conducted using SAS® 9.4 or higher (SAS Institute Inc., Cary, NC, 
USA). 
Independent Data Monitoring Committee: 
The Independent Data Monitoring Committee (IDMC) will be responsible for monitoring data 
of this study, including the main aspects of the study implementation process. 


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Table 2 
Study Flow Chart of Study Stage 1 
Study plan 
Screening Baseline 
Titration 
Treatment Period 
Last dose/early 
Termination 
Follow-up26 
 
First 3 
weeks 
Day 0 
Week 1 
Week 
2 
Week 3 
Week 4 
Week 6 
Week 8 
Week 10 
Week 12 
Week 16 
Visit No. 1 
1 
2 
31 
4 
5 
6 
7 
8 
9 
10 
111 
12 
Day 
Day -21 
to -1 
Day 0 
Day 1 
Day 5 
Day 8 
Day 
15±2  
Day 
28±3  
Day 42±3  
Day 56±3  
Day 70±3  
Day 84±5 
Day 112±7  
Informed Consent  
X 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria 
X 
X 
 
 
 
 
 
 
 
 
 
 
Demographic data 
X 
 
 
 
 
 
 
 
 
 
 
 
Medical history, family 
history 2 
X 
X 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
Quantiferon 
or 
Quantiferon Plus test 3 
X 
 
 
 
 
 
 
 
 
 
 
 
Chest 
imaging 
examination 4 
X 
 
 
 
 
 
 
 
 
 
X4 
 
12-lead ECG 5 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
Holter monitoring 6 
 
X 
X 
X 
X 
 
 
 
 
 
 
 
Vital signs 7 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 8 
X 
X 
X 
X 
X 
 
X 
 
X 
 
X 
X 
Nervous system physical 
examination 9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pulmonary function test 10 
X 
 
 
 
 
 
X 
 
X 
 
X 
 
Dermatology examination 
11 
X 
 
 
 
 
 
X 
 
X 
 
X 
X 


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Study plan 
Screening Baseline 
Titration 
Treatment Period 
Last dose/early 
Termination 
Follow-up26 
 
First 3 
weeks 
Day 0 
Week 1 
Week 
2 
Week 3 
Week 4 
Week 6 
Week 8 
Week 10 
Week 12 
Week 16 
Visit No. 1 
1 
2 
31 
4 
5 
6 
7 
8 
9 
10 
111 
12 
Day 
Day -21 
to -1 
Day 0 
Day 1 
Day 5 
Day 8 
Day 
15±2  
Day 
28±3  
Day 42±3  
Day 56±3  
Day 70±3  
Day 84±5 
Day 112±7  
Ophthalmologic 
examination 12 
X 
 
 
 
 
 
X 
 
X 
 
X 
X 
OCT13 
X 
 
 
 
 
 
 
 
 
 
X 
 
Laboratory tests 
 
Hematology 14 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Blood chemistry 
X 
X 
 
X 
X 
X15 
X 
X15 
X 
X15 
X 
X 
Lipids (fasting) 
X 
X 
 
 
 
 
X 
 
X 
 
X 
 
Blood β-HCG and 
urine pregnancy test 
(WOCBP) 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
X 
FSH (only for 
postmenopausal 
women) 
X 
 
 
 
 
 
 
 
 
 
 
 
Coagulation  
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
Serum 
virological 
markers and syphilis 
antibody 16 
X 
 
 
 
 
 
 
 
 
 
 
 
Urinalysis /microscopy 
17 
X 
X 
 
 
X 
 
X 
 
X 
 
X 
 
Fecal 
culture/microscopy 18 
X 
 
 
 
 
 
 
 
 
 
 
 
Colonoscopy 19 
X 
 
 
 
 
 
 
 
 
 
X 
 


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Study plan 
Screening Baseline 
Titration 
Treatment Period 
Last dose/early 
Termination 
Follow-up26 
 
First 3 
weeks 
Day 0 
Week 1 
Week 
2 
Week 3 
Week 4 
Week 6 
Week 8 
Week 10 
Week 12 
Week 16 
Visit No. 1 
1 
2 
31 
4 
5 
6 
7 
8 
9 
10 
111 
12 
Day 
Day -21 
to -1 
Day 0 
Day 1 
Day 5 
Day 8 
Day 
15±2  
Day 
28±3  
Day 42±3  
Day 56±3  
Day 70±3  
Day 84±5 
Day 112±7  
Concomitant medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigational product 
dispensing/return 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
Recording the time of IP 
administration on the day 
of visit 20 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
Assessment of treatment 
compliance 
 
 
 
X 
X 
 
X 
 
X 
 
X 
 
Adverse event 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PK blood sampling 21 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
PD 22 
 
 
X 
X 
X 
 
X 
 
X 
 
X 
 
Total Igs (IgA, IgG, IgM) 
X 
 
 
 
 
 
 
 
 
 
X 
 
Score 
 
 
 
 
 
 
 
 
 
 
 
 
Complete Mayo scores 
23 
X 
 
 
 
 
 
 
 
 
 
X 
 
Adapted Mayo scores23 
X 
 
 
 
 
 
 
 
 
 
X 
 
Partial Mayo scores 23 
 
 
 
 
X 
 
X 
 
X 
 
X 
 
Diary dispensing24 
X 
 
 
 
 
 
 
 
 
 
 
 
Diary Review 24 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
IBDQ25 
 
X 
 
 
 
 
 
 
 
 
X 
 
Biomarker analysis 
 
CRP 
X 
X 
 
 
 
 
X 
 
X 
 
X 
 


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Study plan 
Screening Baseline 
Titration 
Treatment Period 
Last dose/early 
Termination 
Follow-up26 
 
First 3 
weeks 
Day 0 
Week 1 
Week 
2 
Week 3 
Week 4 
Week 6 
Week 8 
Week 10 
Week 12 
Week 16 
Visit No. 1 
1 
2 
31 
4 
5 
6 
7 
8 
9 
10 
111 
12 
Day 
Day -21 
to -1 
Day 0 
Day 1 
Day 5 
Day 8 
Day 
15±2  
Day 
28±3  
Day 42±3  
Day 56±3  
Day 70±3  
Day 84±5 
Day 112±7  
Fecal calprotectin 
X 
 
 
 
 
 
 
 
 
 
X 
 
Abbreviations: β-HCG=β-human chorionic gonadotropin; CRP=C-reactive protein;  ECG=electrocardiogram; FEV1= Forced Expiratory Volume in 1 second; FSH=follicle stimulating 
hormone; FVC=forced vital capacity; HBcAb=hepatitis B core antibody; HBsAb=hepatitis B surface antibody; HBsAg =hepatitis B surface antigen; HBV=hepatitis B virus; 
HCV=hepatitis c virus; HIV=human immunodeficiency virus; IBDQ=inflammatory bowel disease questionnaire; Ig=immunoglobulin; OCT=optical coherence tomography; 
PD=pharmacodynamics; PK=pharmacokinetics; SAE=serious adverse event; TB=tuberculosis. 
1. 
It is recommended that the subjects are admitted to the study center 1 day prior to baseline and stay at the study center until examinations including ECG are completed on day 2 if 
no further monitoring is required. It is recommended that the scheduled visits should be in the morning. On visit days, subjects are required to take investigational product at site. If 
time permits, the evaluation time point for subjects should be approximately the same. 
For subjects who cannot continue participating in the study for any reason, the investigator should try to complete evaluation for them during last dose/early termination visit. 
2. 
Medical history survey includes a history of smoking and alcohol drinking and drug abuse. Family history should include a family history of colon cancer and a family history of 
premature coronary heart disease. The medical history within 3 years before screening is necessarily recorded (the records of history of major diseases and history of surgery are not 
subject to this limitation.) 
3. 
Patients can be enrolled in the study if it is evidenced that previous TB was treated successfully and Quantiferon or Quantiferon Plus test result at screening is negative. If Quantiferon 
or Quantiferon Plus test result is indeterminate at screening, it could be retested during screening period. If Quantiferon or Quantiferon Plus retest result is indeterminate, the subject 
should not participate in the study. If Quantiferon or Quantiferon Plus retest result is negative, the subject can be enrolled in the study. 
4. 
Chest X-ray taken within 3 months prior to screening will be accepted. If no chest X-ray are taken within 3 months before screening, a chest X-ray will be performed at the screening 
visit. Subjects who prematurely terminated from the study need to undergo chest radiography at the last dose/early termination visit. 
5. 
On Day 1, 2, 5 and 8, 12-lead ECG will be performed within 2 hours before dosing and at 4, 6 hours after dosing. At other follow-up time points, 12-lead ECG tests will be performed 
at 4 hours after dosing. Time window for 12-lead ECG tests is ± 0.5 hours.  
6. 
On Day 0, 1, 5 and 8, 24 ± 0.5 hour continuous Holter monitoring will be performed from 30 min± 10  min before dosing (the same time point as day 0).  
7. 
Vital signs include the heart rate, blood pressure, body temperature and respiratory rate. On Day 1, 2, 5 and 8, vital signs are measured before dosing and at 1, 2, 3, 4, 5 and 6 hours 
(±10 minutes) after dosing. At other scheduled visits, vital signs will be measured before dosing. 


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8. 
Physical examination includes height and weight, evaluation of the neck/thyroid, chest/lung, heart, lymph nodes, abdomen, nervous system, etc. Body height is measured only at the 
screening visit. A complete physical examination (except height measurement) is performed at screening and on Day 1, 28 ± 3, 84 ± 5, and 112 ± 7. At other visits, only the body 
weight needs to be measured. 
9. 
Nervous system physical examination is required for each visit, and the investigators should actively query about nervous system symptoms such as cephalgia, convulsions, confusion, 
vision loss, speech disturbances, facial drooping, weakness, problems with coordination, gait and sensory loss, and mental impairment. If any of the above symptoms appear, a 
neurology consult would be ordered for further assessment, and extra examinations including CT scanning, MRI examination and other related tests will be conducted by neurologists’ 
judgment. 
10. 
At screening visit, if pulmonary function tests show FEV1 or FVC < 70% of normal predicted value, the subject needs to be excluded. 
11. 
Dermatology examination includes an overall examination of the skin for lesions and examinations of the extremities. It is mainly aimed at excluding suspected lesions of basal cell 
carcinoma. Dermatology examinations at screening and on day 84 ± 5 (12 weeks) visits need to be performed in the department of dermatology. Dermatology examinations at other 
visits can be performed by the investigator. 
12. 
Ophthalmologic examination includes checking of visual abnormalities (for example, blurred vision or decreased visual acuity) in subjects and needs to be performed in the 
department of ophthalmology. 
13. 
In case optical coherence tomography (OCT) shows suspected macular edema, it is required to perform a complete retinal examination including collecting history of eye diseases, 
visual acuity check, and dilated fundus examination. During the study, if an ophthalmologic examination identifies visual abnormalities (e.g., blurred vision or decreased visual 
acuity), then, additional OCT can be performed. All subjects diagnosed with macular edema must discontinue the investigational product. 
14. 
On Day 1, 5 and 8, hematology tests need to be performed before administration and at 4-6 hours after administration respectively. At other visits during treatment, only hematology 
tests prior to administration need to be performed. 
15. 
Blood chemistry tests on Day 15 (visit 6), 42 (visit 8) and 70 (visit 10) only include liver function tests. 
16. 
At screening, serological tests are performed for all subjects to determine the subjects' immune status against the viruses: HIV antibody, HBsAg, HBsAb and HBcAb and anti-HCV.  
*Subjects with positive HBsAg will be excluded. HBV-DNA test should be carried out at screening if the subject is negative for HBsAg, negative or positive for HBsAb, and positive 
for HBcAb. The subject should be excluded from the study if HBV-DNA test result is positive, or he/her can be enrolled in the study in case of negative result of HBV-DNA test. 
**An HCV viral load test should be carried out if HCV antibody is positive in the subject. The subject should be excluded from the study in case of positive HCV viral load test 
result. If the HCV viral load test result is negative, the subject can be enrolled in the study. 
17. 
If urinalysis show occult blood or abnormal urine protein in subjects' urine samples, a microscopy examination needs to be performed. A microscopy examination mainly focuses 
on the presence of white blood cells and red blood cells. All other parameters will be tested with test strips. 
18. 
Fecal culture/microscopy (involving fecal culture, C. difficile, parasite ovas and parasites) is required to be performed at screening. During the screening period and at any time 
point during the study, if the subject has symptoms including aggravation of the disease condition or recurrence of previous disease activity, stool samples can be collected for fecal 
culture/microscopy and C. difficile analysis. 
19. 
Within 14 days prior to randomization at screening, colonoscopy will be performed to obtain a Mayo endoscopic subscore and a complete Mayo score and then determine subject 


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eligibility. Colonoscopy will also be performed at week 12 (or early termination from the study visit). 
20. 
On the days of visits during the study treatment period, the investigational product will be taken at the study sites and the time of administration will be recorded according to the 
study flow chart. 
21. 
Collection of PK blood samples only applies to subjects in the PK subgroup. Time points for the collection of PK blood samples: 15-30 min before administration and 4-6 hours 
after administration at week 1 (day 1 and day 5), week 2 (day 8), week 4 (day 28), week 8 (day 56), and week 12 (day 84); 1-2h after administration at week 1 (day 1 and day 5) and 
week 4 (day 28). 
22. 
The subjects in the PK subgroup are required to undergo measurement of lymphocyte counts (used for investigating the PD) at all time points for the collection of PK blood samples. 
According to the study flow chart, if there are corresponding hematology tests at the time points for the collection of PK blood samples, such as time points before administration 
and at 4-6 hours after administration on day 1, it is not necessary to collect additional PD blood samples, otherwise it is required to collect PD blood samples simultaneously. For 
the subjects in the non-PK subgroup, lymphocyte counts used for the PD study are obtained from hematology tests, so it is not necessary to collect additional PD blood samples. 
23. 
Mayo score: The complete Mayo score is calculated from the stool frequency, rectal bleeding, endoscopic findings, and physician overall evaluation. See section 7.2.3. The adapted 
Mayo score is calculated from stool frequency, rectal bleeding, and endoscopic findings, See Section 7.2. Partial Mayo scores will be calculated based on the data of item 1, 2 and 
4 in Section 7.2. (stool frequency, rectal bleeding, endoscopic findings,).  
24. 
Subject diaries are dispensed at screening visits and reviewed at all visits from baseline to last dose/early termination from the study. 
25. 
IBDQ will be completed by subjects at baseline and week 12 visits. 
26. 
Subjects who complete the 12 weeks of study stage 1 but do not enter the study stage 2 or early withdraw from the study will undergo safety follow-up for 4 weeks after the last 
dose. 
 
 


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Table 3.  
Sub-study 1 of the Study Stage 2: Study Flow Chart for the Entry of Subjects into Double-Blind Maintenance 
Treatment After Achieving Clinical Response at Week 12 
Study Plan 
Stage 2 
Screening1 
Sub-study 1 of the Study Stage 2 Treatment Period 
Last dose/early 
Termination 
Follow-up 
Week 13 
Week 18 
Week 24 
Week 32 
Week 40 
Week 48 
Week 52 
Visit No. 2 
12 
13 
14 
15 
16 
17 
18 
Day 
Day 90 ± 5 1 
Day 126 ± 5  
Day 168 ± 5  
Day 224 ± 5  
Day 280 ± 5  
Day 336 ± 5  
Day364 ± 5  
Informed Consent 3 
X 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
Quantiferon or Quantiferon Plus Test 4 
X 
 
 
 
 
 
 
Chest imaging examination 5 
 
 
 
 
 
X 
 
12-lead ECG 6 
X 
X 
X 
X 
X 
X 
X 
Vital signs 7 
 
X 
X 
X 
X 
X 
X 
Physical examination 8 
 
X 
X 
X 
X 
X 
X 
Nervous system physical examination 9 
X 
X 
X 
X 
X 
X 
X 
Pulmonary function test 10 
 
 
X 
X 
 
X 
 
Dermatology examination 11 
 
 
X 
 
X 
X 
X 
Ophthalmologic examination12 
 
 
X 
X 
 
X 
X 
OCT 13 
 
 
X 
 
 
X 
 
Laboratory tests 
 
 
 
 
 
 
 
Hematology 14 
 
X 
X 
X 
X 
X 
X 
Blood chemistry 15 
 
X 
X 
X 
X 
X 
X 
Lipids (fasting) 
 
 
X 
 
 
X 
 
Blood β-HCG and urine pregnancy 
test (WOCBP) 
 
X 
X 
X 
X 
X 
X 
Coagulation 
 
 
X 
 
 
X 
 
Urinalysis /microscopy 16 
 
X 
X 
X 
X 
X 
 
Fecal culture/microscopy 17 
X 
 
 
 
 
 
 


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Study Plan 
Stage 2 
Screening1 
Sub-study 1 of the Study Stage 2 Treatment Period 
Last dose/early 
Termination 
Follow-up 
Week 13 
Week 18 
Week 24 
Week 32 
Week 40 
Week 48 
Week 52 
Visit No. 2 
12 
13 
14 
15 
16 
17 
18 
Day 
Day 90 ± 5 1 
Day 126 ± 5  
Day 168 ± 5  
Day 224 ± 5  
Day 280 ± 5  
Day 336 ± 5  
Day364 ± 5  
Colonoscopy 18 
 
 
 
 
 
X 
 
Concomitant medication 
X 
X 
X 
X 
X 
X 
X 
Investigational product dispensing/return 
X 
X 
X 
X 
X 
X 
 
Recording the time of IP administration on the 
day of visit 19 
X 
X 
X 
X 
X 
X 
 
Assessment of treatment compliance 
 
X 
X 
X 
X 
X 
 
Adverse event 
X 
X 
X 
X 
X 
X 
X 
Score 
 
 
 
 
 
 
 
Complete Mayo scores 20 
 
 
 
 
 
X 
 
Adapted Mayo scores 20 
 
 
 
 
 
X 
 
Partial Mayo scores 20 
 
X 
X 
X 
X 
 
 
Diary Review 21 
X 
X 
X 
X 
X 
X 
 
IBDQ22 
 
 
X 
 
 
X 
 
Biomarker analysis 
 
 
 
 
 
 
 
CRP 
 
 
X 
 
 
X 
 
Fecal calprotectin 
 
 
 
 
 
X 
 
Total immunoglobulin (IgA, IgG, IgM） 
 
 
 
 
 
X 
 
Abbreviation: beta-hcg = beta - human chorionic gonadotropin; CRP= c-reactive protein;  ECG = electrocardiogram; FEV1= maximum forced respiration of 1 second; FVC= forced vital 
capacity; IBDQ= qol questionnaire for ibd; Ig= immunoglobulin; OCT = optical coherence tomography; SAE= severe adverse events; TB= tuberculosis 
Notes: 
1. 
Subjects who have completed the 12-week induction therapy in study stage 1 and have completed the evaluation of study visit 11 (see Table 1) and reached the clinical response at 
visit 11, can choose to enter the maintenance period of sub-study 1 of study stage 2. If the subject is eligible, the study process will follow this flow chart. visit 12 will be the screening 
visit in study stage 2, and the qualification assessment of visit 12 will be based on the results of the 11th visit in the study. Subjects who meet the study stage 2 eligibility criteria and 


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have achieved clinical response will enter study stage 2 sub-study 1 (maintenance treatment period) and continue their treatment in study stage 1. The interval between the first 
administration of sub-study 2 and the last administration of study stage 1 will be less than 1 week. 
2. 
Subjects are recommended to be followed up in the morning. At the indicated visits, subjects will be given medication at the site. If time permits, subjects in the study should be 
evaluated at roughly the same time. For subjects who cannot continue to participate in the study for any reason, the investigator should make every effort to complete the evaluation 
during the end of the study/early termination of the follow-up visit. 
3. 
The signing of informed consent can also be done at visit 11 of study stage 1 (week 12). 
4. 
The Quantiferon or Quantiferon Plus of the screening of stage 1 can be used as the basis. However, if the subjects had a history of exposure to TB patients during study stage 1, or 
suspected TB infection, the Quantiferon or Quantiferon Plus assay should be performed again. If possible, the blood samples of the Quantiferon or Quantiferon Plus assay could be 
collected at visit 11 (week 12). If the Quantiferon or Quantiferon Plus results are negative, the subject could be included in the study. If the Quantiferon or Quantiferon Plus results 
are indeterminate, they can be tested again. If the Quantiferon or Quantiferon Plus results are still indeterminate, the patient should not be included. If the Quantiferon or Quantiferon 
Plus repeat test results are negative, the subject could be enrolled. 
5. 
Only patients who do not have abnormal chest radiographs at visit 11 of study stage 1 are allowed to be included; during the study period, the investigator may review the chest X-
ray or chest CT according to the clinical situation. 
6. 
The 12-lead ECG will be examined at 4 hours after administration and 6 hours after administration at visit 12, and will be examined at 4 hours after administration at the remaining 
visits (except the follow-up visit after treatment ends). The time window for 12-lead ECG is + / - 0.5 hours. 
7. 
Vital signs include heart rate, blood pressure, body temperature and respiratory rate. Vital signs will be checked before administration. 
8. 
Physical examination in sub-study 1 of study stage 2 included measurement of body weight, assessment of neck/thyroid, chest/lung, heart, lymph nodes, abdomen, nervous system, 
etc. Complete physical examination was required at each visit. 
9. 
Nervous system physical examination is required for each visit, and the investigators should actively query about nervous system symptoms such as cephalgia, convulsions, confusion, 
vision loss, speech disturbances, facial drooping, weakness, problems with coordination, gait and sensory loss, and mental impairment. If any of the above symptoms appear, a 
neurology consult would be ordered for further assessment, and extra examinations including CT scanning, MRI examination and other related tests will be conducted by neurologists’ 
judgment. 
10. 
According to the pulmonary function test results of visit 11, subjects with FEV1 or FVC < 50% of the predicted normal value cannot be enrolled. Pulmonary function test will be 
performed at weeks 24, 32, and 48, and additional pulmonary function tests will be performed during the study, depending on the subject's clinical status. 
11. 
The dermatology examination includes an overall examination of the skin for lesions and examinations of extremities. Dermatology examinations at visits of weeks 24 and 48 need 
to be performed in the department of dermatology. Dermatology examinations at other visits can be performed by the investigator. 
12. 
Ophthalmologic examination that includes checking of visual abnormalities (for example, blurred vision or decreased visual acuity) are required at weeks 24, 32, 48, and 52 to be 
examined by an ophthalmologist. 
13. 
In case OCT shows suspected macular edema, it is required to perform a complete retinal examination including collecting history of eye diseases, visual acuity check, and dilated 
fundus examination. During the study, if an ophthalmologic examination identifies visual abnormalities (e.g., blurred vision or decreased visual acuity), then, additional OCT can 


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be performed. All subjects diagnosed with macular edema must discontinue the investigational product. 
14. 
Hematology tests will be performed before dosing at weeks 18, 24, 32, 40, and 48. Hematology tests are also required at week 52. 
15. 
Blood chemistry tests will be performed before dosing at weeks 18, 24, 32, 40 and 48. Blood chemistry tests are also required at week 52. 
16. 
If urinalysis show occult blood or abnormal urine protein in subjects' urine samples, a microscopy examination needs to be performed. A microscopy examination mainly focuses 
on the presence of white blood cells and red blood cells. All other parameters will be tested with test strips. 
17. 
During the study period, fecal culture/microscopic examination (including fecal culture, c. difficile toxin, parasite ovas and parasites) may also be performed if the subject's status 
requires it. 
18. 
Colonoscopy will be performed at visit 11 in study stage 1 to obtain the individual Mayo endoscopic subscore and complete Mayo score of the subjects and to determine their 
eligibility. Colonoscopy will also be performed at week 48 (end of the study visits or early termination visit). 
19. 
On the days of visits during the study treatment period, the investigational product will be taken in the study sites and the time of administration will be recorded according to the 
study flow chart. 
20. 
Mayo score: the complete Mayo score is calculated from the stool frequency, rectal bleeding, endoscopic findings, and physician overall evaluation; The adapted Mayo score is 
calculated from stool frequency, rectal bleeding and endoscopic findings. Partial Mayo score is calculated from stool frequency, rectal bleeding, and physician overall evaluation. 
21. 
Review of subject diaries: subject diary review is required for all visits from visit 12 to the end of the study/early termination visit.  
22. 
The IBDQ is to be completed by the subjects at week 24 and 48 or early termination visit.


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Table 4. 
Sub-study 2 of the Study Stage 2: Study Flow Chart for The Entry of Subjects into Open-Label Treatment After No 
Clinical Response Is Achieved at Week 12 
Study plan 
Stage2 
Screening 1 
Titration 2 
Sub-study 2 of Study Stage 2 
Treatment Period 
Last dose/early 
Termination 
Follow-up 
Week 13 
Week 13 
Week 14 
Week 16 
Week 24 
Week 32 
Week 40 
Week 48 
Week 52 
Visit No. 3 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
Day 
Day 90 ± 5  
Titration 
Day1 2,# 
Titration 
Day5 2 
Titration Day 
8 
Day 112 ± 5  Day 168 ± 5  Day 224 ± 5  Day 280 ± 5  
Day 336 ± 5 
Day 364 ± 5  
Informed Consent 4 
X 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion criteria 
X 
 
 
 
 
 
 
 
 
 
Quantiferon or 
Quantiferon Plus Test 5 
X 
 
 
 
 
 
 
 
 
 
Chest imaging examination 6 
 
 
 
 
 
 
 
 
X 
 
12-lead ECG 7 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Holter monitoring 8 
 
X 
X 
X 
 
 
 
 
 
 
Vital signs 9 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination 10 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Nervous system physical 
examination 11 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pulmonary function test 12 
 
 
 
 
X 
 
X 
 
X 
 
Dermatology examination 13 
 
 
 
 
X 
 
X 
 
X 
X 
Ophthalmologic examination 14 
 
 
 
 
X 
 
X 
 
X 
X 
OCT15 
 
 
 
 
 
X 
 
 
X 
 
Laboratory tests 
 
 
 
 
 
 
 
 
 
 
Hematology 16 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Blood chemistry 17 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Lipids (fasting) 
 
 
 
 
 
X 
 
 
X 
 
Blood β-HCG and urine 
pregnancy test (WOCBP) 
 
 
 
X 
X 
X 
X 
X 
X 
X 
Coagulation 
 
 
 
 
 
X 
 
 
X 
 
Urinalysis /microscopy 18 
 
 
 
X 
X 
X 
X 
X 
X 
 
Fecal culture/microscopy 19 
X 
 
 
 
 
 
 
 
 
 


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Study plan 
Stage2 
Screening 1 
Titration 2 
Sub-study 2 of Study Stage 2 
Treatment Period 
Last dose/early 
Termination 
Follow-up 
Week 13 
Week 13 
Week 14 
Week 16 
Week 24 
Week 32 
Week 40 
Week 48 
Week 52 
Visit No. 3 
12 
13 
14 
15 
16 
17 
18 
19 
20 
21 
Day 
Day 90 ± 5  
Titration 
Day1 2,# 
Titration 
Day5 2 
Titration Day 
8 
Day 112 ± 5  Day 168 ± 5  Day 224 ± 5  Day 280 ± 5  
Day 336 ± 5 
Day 364 ± 5  
Colonoscopy 20 
 
 
 
 
 
X 
 
 
X 
 
Concomitant medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Investigational product 
dispensing/return 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Recording the time of IP 
administration on the day of 
visit 21 
 
X 
X 
X 
X 
X 
X 
X 
X 
 
Assessment of treatment 
compliance 
 
 
X 
X 
X 
X 
X 
X 
X 
 
Adverse event 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Score 
 
 
 
 
 
 
 
 
 
 
Complete Mayo scores 22 
 
 
 
 
 
X 
 
 
X 
 
Adapted Mayo scores22 
 
 
 
 
 
X 
 
 
X 
 
Partial Mayo scores 22 
 
 
 
 
X 
 
X 
X 
 
 
Diary Review 23 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
IBDQ24 
 
 
 
 
 
X 
 
 
X 
 
Biomarker analysis 
 
 
 
 
 
 
 
 
 
 
CRP 
 
 
 
 
 
X 
 
 
X 
 
Fecal calprotectin 
 
 
 
 
 
X 
 
 
X 
 
Total immunoglobulin 
(IgA, IgG, IgM) 
 
 
 
 
 
 
 
 
X 
 
Abbreviation: beta-hcg = beta - human chorionic gonadotropin; CRP= c-reactive protein; ECG = electrocardiogram; FEV1= maximum forced respiration of 1 second; FVC= forced vital 
capacity; IBDQ= qol questionnaire for ibd; Ig= immunoglobulin; OCT = optical coherence tomography; SAE= severe adverse events; TB= tuberculosis. 
 
Notes: 


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#.     It is recommended that the subjects are admitted to this study center prior to Day1-dosing of titration and stay at the study center until examinations including ECG are completed on 
day 2 if no further monitoring is required. It is recommended that the scheduled visits should be in the morning. On visit days, subjects are required to take investigational product 
at site. If time permits, the evaluation time point for subjects should be approximately the same. 
1. 
Subjects who have completed the 12-week induction therapy of study stage 1 and have completed the evaluation of study visit 11 (see Table 1) while not achieved clinical response 
at visit 11, can choose the sub-study 2 of study stage 2 to receive open-label treatment of 0.2 mg CBP-307 daily. If the subject is eligible, the study process will follow this flow chart. 
Visit 12 is the screening visit in study stage 2, and the qualification assessment will be based on the results of visit 11. Subjects who meet the eligibility criteria for stage 2 and have 
not achieved clinical response will be enrolled in sub-study 2 of stage 2 and treated with 0.2mg CBP-307. The interval between the first administration of sub-study 2 and the last 
administration of study stage 1 will be less than 1 week. 
2. 
Subjects eligible for inclusion in sub-study 2 of study stage 2 at visit 12 will receive dose titration for one week from visit 13. If the assessment at visit 12 meets the requirements 
and time permits, the dose titration can be started and the required procedures of visit 13 can be completed on the same day. The dose titration includes 0.05 mg CBP-307 for four 
consecutive days from the first day, 0.1 mg CBP-307 for the subsequent three days, and target dose of 0.2 mg CBP-307 will be started on the 8th day. Upon completion of the dose 
titration, subjects will receive oral treatment of 0.2 mg CBP-307 once a day. 
3. 
Subjects are recommended to be followed up in the morning. At the indicated visits, subjects will be given medication at the site. If time permits, subjects in the study should be 
evaluated at roughly the same time. For subjects who cannot continue to participate in the study for any reason, the investigator should make every effort to complete the evaluation 
during the end of the study/early termination visit. 
4. 
The signing of informed consent can also be done at visit 11 (week 12). 
5. 
The Quantiferon or Quantiferon Plus of the screening of study stage 1 can be used as the basis. However, if the subjects had a history of exposure to TB patients during study stage 
1, or if TB infection was suspected, the Quantiferon or Quantiferon Plus assay should be performed again. If possible, the Quantiferon or Quantiferon Plus blood samples could be 
collected at visit 11 (week 12). If the Quantiferon or Quantiferon Plus results are negative, the subject could be included in the study. If the Quantiferon or Quantiferon Plus results 
are indeterminate, they can be tested again. If the results of the Quantiferon or Quantiferon Plus results are still indeterminate, the subject could not be included. If the Quantiferon 
or Quantiferon Plus repeat test results are negative, the subject could be enrolled. 
6. 
Only patients who do not have abnormal chest radiographs at visit 11 of study stage 1 are allowed to be included; During the study period, the investigator may review chest X-ray 
or chest CT according to the clinical situation. 
7. 
12-lead ECG examination will be performed within 2 hours before administration, 4 hours after administration and 6 hours after administration on Day 1, 2, 5 and 8 of treatment 
titration, and 12-lead ECG were performed at 4 hours after administration for other visits. The ECG time window will be ± 0.5 h. 
8. 
On Titration Day 1, 5 and 8, 24-hour ± 0.5 hour continuous Holter monitoring will be performed from 30min ± 10 min before dosing . 
9. 
Vital signs include heart rate, blood pressure, body temperature and respiratory rate. Vital signs will be measured before dosing and at 1, 2, 3, 4, 5 and 6 hours (± 10 minutes) after 
dosing on Day 1, 2, 5 and 8 of treatment titration. At other visits, vital signs will be measured before dosing. 
10. 
Physical examination of stage 2 sub-study 2 will includes measurement of body weight, assessment of neck/thyroid, chest/lung, heart, lymph nodes, abdomen, nervous system, etc. 
At titration day 1, week 16, week 24, week 32, week 40, week 48, and week 52, complete physical examination will be conducted; at the rest visits, only the body weight will be 


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measured. 
11. 
Nervous system physical examination is required for each visit, and the investigators should actively query about nervous system symptoms such as cephalgia, convulsions, confusion, 
vision loss, speech disturbances, facial drooping, weakness, problems with coordination, gait and sensory loss, and mental impairment. If any of the above symptoms appear, a 
neurology consult would be ordered for further assessment, and extra examinations including CT scanning, MRI examination and other related tests will be conducted by neurologists’ 
judgment. 
12. 
Based on the pulmonary function test results of visit 11, subjects with FEV1 or FVC < 50% of the predicted normal value cannot be enrolled. Pulmonary function test will be 
performed at weeks 16, 32, and 48, and additional pulmonary function tests can be performed during the study, depending on the subject's clinical status. 
13. 
The dermatology examination includes an overall examination of the skin for lesions and examination of extremities. Dermatology examinations at visits of weeks 32 and 48 need 
to be performed in the department of dermatology. Dermatology examinations at other visits can be performed by the investigator. 
14. 
Ophthalmologic examination that includes checking of visual abnormalities (for example, blurred vision or decreased visual acuity) are required at weeks 16, 32, 48, and 52 to be 
examined by an ophthalmologist. 
15. 
In case OCT shows suspected macular edema, it is required to perform a complete retinal examination including collecting history of eye diseases, visual acuity check, and dilated 
fundus examination. During the study, if an ophthalmologic examination identifies visual abnormalities (e.g., blurred vision or decreased visual acuity), then, additional OCT can 
be performed. All subjects diagnosed with macular edema must discontinue the investigational product. 
16. 
Hematology tests will be performed before dosing at weeks 14, 16, 24, 32, 40, and 48. Hematology tests are also required at week 52. 
17. 
Blood chemistry tests will be performed before dosing at weeks 14, 16, 24, 32, 40 and 48. Blood chemistry tests are also required at week 52. 
18. 
If urinalysis shows occult blood or abnormal urine protein in subjects' urine samples, a microscopy examination needs to be performed. A microscopy examination mainly focuses 
on the presence of white blood cells and red blood cells. All other parameters are to be tested with test strips. 
19. 
During sub-study 2 of study stage 2, fecal culture/microscopy (including fecal culture, clostridium difficile toxin, parasites ovas and parasites) may also be performed if the subject's 
status requires it. 
20. 
Colonoscopy will be performed at visit 11 in study stage 1 to obtain the Mayo endoscopic subscore and complete Mayo score of the subjects and to determine their eligibility. 
Colonoscopies will also be performed at week 24 and week 48 (end of the study visit or early termination visit). 
21. 
On the days of visits during the study treatment period, the investigational product will be taken at the study sites and the time of administration will be recorded according to the 
study flow chart. 
22. 
Mayo score: the complete Mayo score is calculated from the stool frequency, rectal bleeding, endoscopic findings, and physician overall evaluation; The adapted Mayo score is 
calculated from stool frequency, rectal bleeding and endoscopic findings. Partial Mayo score is calculated from stool frequency, rectal bleeding, and physician overall evaluation. 
23. 
Review of subject diaries: subject diary review is required for all visits from visit 12 to the end of the study/early termination visit. 
24. 
The IBDQ is to be completed by the subjects at week 24 and 48 or early termination visit. 


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2 ETHICAL CONSIDERATIONS 
2.1. 
Regulatory and Ethical considerations 
This study will be conducted in accordance with the protocol and with the following: 
• Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences (CIOMS) International Ethical Guidelines. 
• Applicable ICH Good Clinical Practice (GCP) Guidelines. 
• Applicable laws and regulations. 
Before the study starts, the investigator is required to submit the Protocol, Protocol Amendment, 
Investigator's Brochure, Informed Consent Form (ICF) and other relevant documents such as 
recruitment advertisements (if applicable) to the Independent Ethics Committee 
(IEC)/Institutional Review Board (IRB) for approval. All correspondence with the IEC/IRB 
needs to be kept in the Investigator Site File (ISF). A copy of the approval letter issued by the 
IEC/IRB approval needs to be submitted to sponsor. The study can only be started after 
approved by the IEC/IRB. 
If the protocol needs to be amended during the study, the revised protocol should be submitted 
to the IEC/IRB for approval before the implementation of the protocol amendment. If new 
important information involving investigational product is obtained, ICF must be revised and 
then submitted to the IEC/IRB in written form for review and approval. The subjects must be 
informed of the update and re-consented to the most current, approved ICF version. 
The Investigator will be responsible for the following: 
• Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by 
the IRB/IEC. 
• Notifying the IRB/IEC of SAEs or other significant safety findings as required by 
IRB/IEC procedures. 
• Providing oversight of the conduct of the study at the study center and adherence to 
requirements of 21 CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 
for clinical studies (if applicable), and all other applicable local regulations. 
After reading the protocol, each investigator will sign the protocol signature page and send a 


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copy of the signed page to the sponsor or representative. The study will not start at any study 
center at which the investigator has not signed the protocol. 
2.2. 
Subject information and the Informed Consent Form 
Sponsor will not obtain the name of the subjects. The subject's number will be recorded in the 
electronic case report form (eCRF). If the subject's name appears in any document (such as a 
laboratory test report), the name must be erased from the copy of the document to be submitted 
to sponsor. The study data must be stored in computers in accordance with local regulations 
for data protection. It is required that subjects be informed that clinical quality assurance 
auditors, the IEC/IRB, the regulatory authority, or other authorized personnel appointed by the 
sponsor may review their medical records to verify the collected data and that all personal 
information for review will be kept strictly confidential in accordance with local regulations 
for data protection. 
The investigator will keep a subject identification code list (containing the subject’s number 
and corresponding name), so that subject records can be identified. 
Informed consent must be obtained from a subject before the start of any study procedures. 
Subjects must be informed that their participation is voluntary. Subjects or their legally 
authorized representative will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, Health Insurance Portability 
and Accountability Act (HIPAA) requirements, where applicable, and the IRB/IEC or study 
center. The medical record must include a statement that written informed consent was 
obtained before the subject was entered in the study and the date the written consent was 
obtained. The authorized person obtaining the informed consent must also sign the ICF. 
Subjects must be re-consented to the most current version of the ICF(s) during their 
participation in the study. A copy of the ICF(s) must be provided to the subject or the subject’s 
legally authorized representative. 
Subjects are required to sign an updated ICF before entering the study stage 2. 
3 
STUDY BACKGROUND 
3.1. Overview of ulcerative colitis 
Inflammatory bowel disease (IBD) is a type of intestinal inflammatory disease that includes 
ulcerative colitis (UC) and Crohn's disease (CD). The cause of IBD is unknown. UC is a 
chronic non-specific inflammatory disease of the rectum and colon. The lesion is characterized 
by diffuse and superficial inflammation of the colonic mucosa. It is located mostly in the 
rectosigmoid colon, but can extend to the entire colon. 
The clinical manifestations of UC include diarrhea, bloody purulent stool, and abdominal pain. 


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Systemic features of UC, such as fever, weight loss, weakness, and hypoproteinemia, mostly 
appear in patients with moderate to severe UC. Extra-intestinal manifestations such as uveitis, 
arthritis, ankylosing spondylitis, or primary sclerosing cholangitis may also be seen in 
association with UC. Most of the patients show a chronic course of recurrent episodes, 
alternating with remission, and the symptoms of some patients are persistent and gradually 
worsening. Patients with IBD are at a higher risk of colorectal cancer.  
In recent decades, the incidence of UC in Asia and the world has tended to increase persistently. 
The prevalence of UC in the United States, Western Europe, and Japan is approximately 
200/100,000, 150/100,000 and 63.6/100,000, respectively. It is estimated that the prevalence 
of UC in China has reached 11.6 cases per 100,000 person-years. Although the prevalence in 
China is lower than in Western countries, it increases rapidly: an analysis of 10218 UC cases 
in China suggests that the prevalence of UC increased by 3.08 times from 2506 cases in 1980s 
to 7512 cases in 1990s. 
3.2. Drug overview, structure and physicochemical properties 
CBP-307 is a novel sphingosine-1-phosphate receptor subtype 1 (S1P1) modulator. It works 
by blocking the egress of T cells out from lymph nodes and thereby reducing their entry into 
intestinal tissues to exacerbate inflammation.  
The active pharmaceutical ingredient (API) of CBP-307 is a white or off-white crystalline 
powder. 
Name of the compound: CBP-307 
Chemical formula: C23H24FN3O3•1/2 H2O 
Molecular weight: 418.46 
Chemical name: 1-(2-fuoro-4-(5-(4-isobutylphenyl)-1, 2, 4-oxadiazol-3-yl) benzyl) azetidine-
3-carboxylic acid 1/2 hydrate 
Chemical structure:  
 
 
 


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Figure 3. 
Chemical structure of CBP-307 
 
3.3. Nonclinical pharmacology, pharmacokinetics and toxicology 
3.3.1. 
Nonclinical pharmacology 
In vitro and in vivo pharmacology 
CBP-307 is a highly potent and specific second-generation S1P1 agonist. The sponsor has 
conducted a series of in vitro cell-based assays (i.e., compound-induced changes in the levels 
of intracellular cyclic adenosine monophosphate (cAMP) and β-arrestin, and S1P receptor 
internalization) to verify the activity and selectivity of CBP-307. The test results showed that 
CBP-307 increased the levels of cAMP and β-arrestin in S1P1-expressing cells with half 
maximal effective concentrations (EC50) of 0.09 nM and 0.67 nM, respectively, whereas it had 
no effect on S1P3, a S1P receptor subtype known to induce fibrosis in human and animal tissues. 
The sponsor also evaluated the effect of CBP-307 in the induction of internalization of S1P 
receptors expressed in Chinese hamster ovary (CHO). Data show that CBP-307 effectively 
induced the internalization of S1P1 with an EC50 of 7.05 nM and S1P5 with an EC50 of 
22.21 nM. 
CBP-307 activates and induces S1P1 internalization, thereby inhibiting the migration of 
lymphocytes from lymph nodes in animals and humans and thus reducing the number of 
lymphocytes in the peripheral blood. When CBP-307 0.1 mg/kg, 0.1 mg/kg and 0.3 mg/kg was 
orally administered to rats, mice and beagle dogs, respectively, it reduced the number of 
lymphocytes in the peripheral blood of these animals by more than 50%. This effect was 
dose-dependent and reversible. The numbers of lymphocytes in the peripheral blood of animals 
typically returned to the pre-dose level 12-48 hours after a single dose.  
Safety pharmacology 
The results of safety pharmacology studies that meet the requirements of Good Laboratory 
Practice (GLP) for Nonclinical Laboratory Studies showed that oral administration of CBP-307 
50 mg/kg has no effect on the respiratory function of beagle dogs, and CBP-307 100 mg/kg 
has no effect on central nervous system (CNS) functions in SD rats. Cardiovascular safety 
studies showed that CBP-307 50 mg/kg caused a slight increase in diastolic blood pressure in 
O
N
N
N
COOH
F
.1/2H2O


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female beagle dogs within 1 to 3 hours after administration, and it had no effect on ECG 
parameters, including heart rate, RR interval, PR interval, QRS duration, QRS voltage, QT 
interval, QTcF interval, Tp-e interval, ST voltage and systolic blood pressure. 
CBP-307 30 μM does not inhibit the activity of any major human cytochrome P450 enzymes 
including 1A2, 2C9, 2C19, 2D6, 3A4, 2B6 and 2C8, thus CBP-307 is unlikely to interact with 
other drugs metabolized by the P450 enzymes. Besides, it was found that CBP-307 10 μM had 
only 12% inhibitory effect on astemizole, which was able to bind to the hERG potassium 
channel (expressed on the surface of HEK cells). Such finding indicates that the potential of 
CBP-307 to cause QT prolongation in human is very low. 
3.3.2. Pharmacokinetics and metabolism 
Preclinical pharmacokinetics studies showed that the bioavailability of CBP-307 1 mg/kg in 
rats and beagle dogs were 62% and 37%, respectively. Therefore, the apparent clearance of 
CBP-307 was relatively low in rats (approximately 11% of hepatic blood flow), while slightly 
higher in beagle dogs (approximately equal to hepatic blood flow); and the half-lives of 
CBP-307 in rats and beagle dogs after a single oral dose were 5.3 and 2.7 hours, respectively. 
The half-life of CBP-307 in Cynomolgus monkeys ranged from 1.91 hours to 2.34 hours (mean: 
2.13 hours) after a single oral dose; the maximum concentration (Cmax) ranged from 112.25 
ng/mL to 183.25 ng/mL (mean: 146.62 ng/mL); AUClast ranged from 405.22 ng*h/mL to 
639.96 ng*h/mL (mean: 523.18 ng*h/mL). The bioavailability of CBP-307 was between 
15.75%-30.99% with an average of 21.64%. 
Toxicokinetic analysis showed that, with CBP-307 administered orally in rats and dogs, 
exposure increased with increasing doses. Exposure increases in rats were dose proportional at 
1 to 10 mg/kg and less than dose-proportional at 100 mg/kg. Exposure in dogs was dose 
proportional at 1 to 80 mg/kg. No sex-associated differences were seen in exposure in rats or 
beagle dogs. Exposure accumulation was observed after 28 days of repeat dosing in rats, but 
no accumulation after repeat dosing was seen in dogs. 
After 13 weeks of repeat dosing in Cynomolgus monkeys, no significant accumulation of 
CBP-307 was observed. 
A recent open-label study to evaluate the absorption, distribution, metabolism and elimination 
of a single oral dose of [14C]-labeled CBP-307 in SD rats showed that the overall mean recovery 
of radiation was 97.94% within 0-168 h after a single dose of 3 mg/100 Ci/kg in male and 
female SD rats. CBP-307 was mainly excreted through the feces, and its excreted amount 
accounted for 78.24% of its dose. It was partly excreted through the urine, and its excreted 
amount accounted for 13.48% of its dose. Excretion mainly occurred within 72 hours after 


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administration, and the total excreted amount accounted for 86.90% of the dose. 
Preliminary in vitro metabolism studies in liver microsomes identified 5 main metabolites of 
CBP-307. No metabolite was present in amount > 10% of the parent compound. Metabolite 
profiles were similar between mice, rats, dogs, monkeys, and humans. 
Preliminary studies of protein binding showed that CBP-307 had high plasma protein binding 
rates: >99% in humans and approximately 98-99% in animals. 
Studies of the permeability and transport properties in the Caco-2 cell model showed that 
CBP-307 exhibited high permeability in the Caco-2 cell model: no significantly inhibited efflux 
of CBP-307 (1-20 μM) by P-gp, suggesting that CBP-307 is not a potential substrate of P-gp. 
3.3.3. Toxicology 
A series of GLP toxicological studies in preclinical species including SD rats and Cynomolgus 
monkeys were carried out to determine the side effects, target organs, maximum tolerated dose 
(MTD) and no-observed-adverse-effect level (NOAEL). 
No death occurred in rats treated with a single dose of ≤ 1000 mg/kg CBP-307, or 4-week 
repeat doses of ≤ 100 mg/kg; similarly, no deaths were seen in dogs treated with a single dose 
of ≤ 500 mg/kg, or 4-week repeat doses of 80 mg/kg. A 4-week multiple-dose study showed 
that the MTD for rats was >100 mg/kg, whereas the MTD for beagle dogs was ≥80 mg/kg/day. 
AUC0-24 corresponding to the MTD for rats was 154584.94 h ng/mL (in males) and 
224954.18 h ng/mL (in females); while AUC0-24 corresponding to the MTD for beagle dogs 
was 28547.40 h ng/mL. The NOAEL for rats was 1 mg/kg with corresponding AUC0-24 of 
1472.37 h·ng/mL in males and 1507.79 h·ng/mL in fe
males. The NOAEL for beagle dogs was 
1 mg/kg with corresponding AUC0-24 of 479.90 h ng/mL. 
A 13-week repeated dose toxicity study showed that in all groups of SD rats that were given 
oral doses of 0.1, 1, and 10 mg/kg once daily for 13 consecutive weeks, there were visible 
decreases in the white blood cell (WBC) count and the number of lymphocytes. These changes 
were considered to be related to the expected pharmacology action of CBP-307. Under the test 
conditions above, the NOAEL of CBP-307 was 10 mg/kg. The mean Cmax and AUC0-24 under 
this dose for 13 weeks are 3416.57 ng/mL and 30913.66 h·ng/m L, respectively. In Cynomolgus 
monkeys that were intragastrically given repeated doses of 0.1, 1, and 10 mg/kg, respectively, 
once daily for 13 consecutive weeks, there were visible increases in the number of neutrophils 
and decreases in the numbers of WBCs and lymphocytes. All these changes were related to the 
expected pharmacological action (immunosuppressive effect) of CBP-307. During the study, 
2 animals in the 1 mg/kg dose group presented with moribund condition and were then 
euthanized. The cause of moribund condition was related to the aggravation of infection after 


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drug administration. Excluding these 2 animals, other animals had a mean Cmax of 477.08 
ng/mL and a mean AUC0-24 of 2005.64 h·ng/mL, respectively, at NOAEL of 10 mg/kg for 
13 weeks. 
In a phase I reproductive toxicity test, rats were intragastrically given CBP-307 with repeated 
doses of 1, 10, 80 mg/kg/day, respectively, once daily. At doses of 1, 10, and 80 mg/kg/day, 
there were decreases in body weight, slowdown of weight gain, and decreases in food 
consumption in female and male rats. At a dose of 80 mg/kg/day, there was a decrease in the 
fertility of female and male rats, and the NOAEL for the fertility of female and male rats was 
10 mg/kg/day. At a dose of 80 mg/kg/day, there were increases in the number of stillbirths and 
fetal loss after implantation, and the NOAEL for early embryo development was 10 mg/kg/day. 
At a dose of 10 mg/kg/day, the exposure (AUC0-t) after administration on day 29 in male rats 
was 28812.62 h·ng/mL, and the exposure (AUC0-t) on embryo implantation (Gestation day 6, 
GD6) in female rats was 21966.31 h·ng/mL. 
In a phase II reproductive toxicity test, rats were intragastrically given repeated doses of 
CBP-307 0.03, 0.3 and 3 mg/kg/day, respectively, once daily for 10 consecutive days from 
GD6 to hard palate closure (GD15). The test results showed that at doses of 0.3 and 
3 mg/kg/day, CBP-307 caused a decrease in food consumption in pregnant female rats. At a 
dose of 3 mg/kg/day, CBP-307 caused decreases in the live birth rate and the body weight and 
decreases in the body length and tail length in fetal rats. At doses of 0.3 and 3 mg/kg/day, 
CBP-307 caused increases in incidence rates of visceral and skeletal abnormalities and 
variations in fetal rats. The NOAEL for embryo-fetal development was 0.03 mg/kg/day. At a 
dose of 0.03 mg/kg/day, the maternal exposure (AUC0-24) after last administration was 
32.31 h•ng/mL. 
In a phase II reproductive toxicity test, New Zealand rabbits were orally administered once 
daily doses of 0.1, 0.5, or 2.5 mg/kg/day for 13 consecutive days from GD6 to hard palate 
closure (GD18). The test showed that at a dose of 2.5 mg/kg/day, CBP-307 caused an increase 
in the fetal loss rate after implantation, a decrease in the live birth rate and increases in the 
number and percentage of absorbed fetuses in early fetal period. The NOAEL for embryo-fetal 
development was 0.5 mg/kg/day. At all doses of 0.1, 0.5 and 2.5 mg/kg/day, no fetal 
teratogenicity was observed. At a dose of 0.5 mg/kg/day, the maternal exposure (AUC0-24) to 
CBP-307 after last administration was 210.89 h•ng/mL. 
GLP-compliant genetic toxicology studies have shown that CBP-307 may not induce mutations. 
The preclinical study data of CBP-307 are detailed in the Investigator's Brochure[14]. 
3.4. Clinical study data 


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3.4.1 Overview of the clinical study 
Between November 2014 and September 2015, sponsor conducted and completed a phase I 
clinical study on CBP-307 in Australia (Study Protocol No.: CBP-307AU001). This study was 
a randomized, double-blind, placebo-controlled, parallel-group clinical trial in healthy subjects, 
which included a single-dose escalation part and a multiple-dose escalation part. The primary 
objective of the trial was to evaluate the safety and tolerability of CBP-307 following oral 
single- and multiple-dose administration. The secondary objectives were to characterize the 
pharmacokinetics and pharmacodynamics of CBP 307 following oral single- and multiple-dose 
administration and to determine the effect of foods on the pharmacokinetics and 
pharmacodynamics of the drug. 
In the single-dose escalation part, 8 subjects in each cohort were randomized to investigational 
product (administered in 6 subjects) or placebo (administered in 2 subjects). Four CBP 307 
doses were evaluated: 0.1, 0.25, 0.5, and 2.5 mg. A total of 28 subjects took the drug, and 8 of 
them participated in a test on the effect of foods. 
CBP-307 was also studied in subjects at doses of 0.15 or 0.25 mg in the 28 days multiple-dose 
regimen. In each dose cohort, 6 study participants were given CBP 307 and 2 were given 
placebo.  
The clinical trial showed that at a single dose of 0.1, 0.25 and 0.5 mg, CBP-307 had a good 
safety profile, good tolerability, good pharmacokinetic characteristics and a half-life of 
approximately 25 hours which allows once daily oral administration. Results of the 4-week 
repeat dose part showed that a dose of 0.1 mg and 0.25 mg once daily was able to effectively 
reduce the number of peripheral blood lymphocytes and had good tolerability. After continuous 
administration for 4 weeks, at 7 days after the dosing ended, peripheral blood lymphocyte 
counts in subjects receiving the multiple-dose regimen had returned to predose levels for the 
0.15 and 0.25 mg cohorts.  
3.4.2. Pharmacodynamics 
CBP-307 can effectively reduce the number of human peripheral lymphocytes. The effect of 
the reduction in the number of lymphocytes was dose-dependent at the doses studied. The 
maximal peripheral blood lymphocyte count reduction for subjects receiving the single-dose 
regimen was observed at approximately 6 hours postdosing. The mean counts of peripheral 
lymphocytes in the 0.1 mg, 0.25 mg, 0.5 mg and 2.5 mg cohorts decreased by approximately 
11%, 40%, 71% and 77% from baseline, respectively, which indicates that CBP-307 has potent 
effect on regulating the number of peripheral lymphocytes. The 4-week daily multiple-dose 
part showed that both 0.15 mg and 0.25 mg could significantly reduce the number of peripheral 


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lymphocytes in human. After the continuous administration of 0.25 mg once daily, the 
lymphocyte count decreased by more than 75% from baseline. 
3.4.3. Pharmacokinetics 
At 1-2 hours after a single oral dose of CBP-307, it was detectable in the blood; and the time 
to maximum concentration (Tmax) was 4-6 hours after administration. Subjects taking CBP-307 
while eating a standard high-fat breakfast had higher blood concentrations than those who took 
CBP-307 under fasting conditions. The drug exposure (AUClast and Cmax) was positively 
correlated with the dose within the range of 0.1 mg to 2.5 mg. 
After a single oral dose of 0.25 mg, 0.5 mg and 2.5 mg, the elimination of CBP-307 followed 
the single exponential decay, and CBP-307 was still detectable in plasma at 72 hours after 
administration. The 4-week multiple-dose part showed that in both the 0.15 mg group and the 
0.25 mg group, the plasma concentrations gradually increased in the first 10 days and then 
reached a steady state. The plasma concentrations at 0-24 hours after administration on day 28 
was higher than that at 0-24 hours after administration on day 1, which indicated that the drug 
was accumulated after repeated administration. After a daily dose of 0.15 mg for 28 consecutive 
days, the accumulation ratios of AUC0-24 and Cmax were 2.8 and 3.3, respectively. 
3.4.4. Safety 
The side effects of S1P1 agonists include bradycardia, sinus arrest and second-degree 
atrioventricular block. Currently the commonly accepted mechanism of these side effects is 
due to the activation of S1P1 in atrial myocytes causing bradycardia. Most of these side effects 
have no clinical manifestations/symptoms, and they appear mainly within a few hours after 
oral administration on day 1. Fingolimod and all second-generation S1P1 regulators (including 
ozanimod [Celgene], Siponimod [Novartis] and Ponesimod [Actelion]) were reported to have 
the same side effects, whose severity was positively correlated with the dose.  
Observations showed that CBP-307 had side effects consistent with the reported ones above: a 
moderate decrease of the heart rate within 2-4 hours after administration and its severity was 
dose-dependent. At doses of 0.1 mg, 0.25 mg and 0.5 mg, no cardiac adverse events (AEs) 
occurred after a single dose; and at these doses, the most common AEs caused by CBP-307 
and placebo were headache and dizziness, and no serious adverse events (SAEs) occurred. At 
an ultra-high dose (i.e., 2.5 mg, approximately 10 times of the target clinical dose), one subject 
experienced bradycardia and transient cardiac arrest for 9 seconds after administration, which 
resolved spontaneously on the same day without specific treatment. This subject had a 
relatively low baseline heart rate (55 beats/minute) and a lower heart rate of 33 beats/minute 
after dosing, which was the only SAE in the phase I clinical trial. As a comparison, it was also 
reported that the first dose of fingolimod 0.5 mg caused transient cardiac arrest in a subject, 


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which resolved within 24 hours. 
The 4-week multiple-dose part showed that at doses of 0.15 mg and 0.25 mg once daily, 
CBP-307 had a good safety profile. The most common AEs were headache, dizziness and 
lymphopenia. In individual subjects, the alanine aminotransferase (ALT) levels slightly 
increased but were all lower than 3 times the upper limit of normal and were not accompanied 
by changes in levels of other liver enzymes or total bilirubin and returned to normal after the 
last dose of CBP-307. Elevated ALT has also been reported associated with both fingolimod 
and second-generation drugs. 
No apparent effect of CBP-307 on pulmonary function, blood pressure, ophthalmic parameters 
or blood chemistry parameters were observed. 
The clinical study data of CBP-307 are detailed in the Investigator's Brochure. 
3.5. Study rationale and benefit/risk assessment 
In clinical practice, treatment protocol for UC are mainly developed according to the severity 
of UC and the extent of its involvement. Although the incidence of UC is increasing rapidly 
globally, for patients with moderate to severe UC, there are still many limitations to current 
available treatment options. 
5-aminosalicylic acid (5-ASA) is the main drug for induction and maintenance of remission in 
patients with mild to moderate UC, but it is less effective in patients with severe UC. It is still 
controversial whether patients with moderately to severely active UC can benefit from the 
administration of 5-ASA. For UC patients who fail the treatment with 5-ASA, especially those 
with extensive lesions, systemic glucocorticoid therapy is generally required. Although 
systemic glucocorticoid can induce UC remission quickly and effectively, they are not 
recommended for maintenance treatment due to its significant side effects, including 
osteoporosis, impaired glucose tolerance, and increased risk of infection.  
Immunomodulators (including 6-mercaptopurine, azathioprine) can maintain the remission of 
patients with moderate to severe UC. Due to their relatively slow onset of action (azathioprine 
does not achieve the maximum efficacy before 12-16 weeks following administration), they 
cannot be used for rapid induction of remission during flares of UC. Adverse reactions related 
to the use of immunomodulators include myelosuppression, leukopenia, liver function 
impairment and infection etc. In addition, aminosalicylic acid preparations are often combined 
with thiopurine drugs for clinical treatment of UC, but 5-ASA preparations may increase the 
risk of myelosuppression. It was reported that these immunomodulators might increase the 
potential risk for lymphoma in patients with inflammatory bowel disease.  
Monoclonal antibodies targeting TNF-α have been approved for the treatment of UC in several 


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countries around the world. They include infliximab (IFX), a chimeric murine-human 
monoclonal IgG 1 antibody, adalimumab (ADA), a fully human monoclonal antibody, and 
certolizumab pegol (CZP), a pegylated (polyethylene glycol) antigen-binding fragment (Fab). 
Monoclonal antibodies targeting TNF-α can induce and maintain remission, and are indicated 
for patients with severely active UC that is resistant to corticosteroid administered 
intravenously, 
and 
patients 
with 
corticosteroid-dependent 
active 
UC 
who 
fail 
immunomodulators treatment or are intolerant to them (due to the presence of contraindications 
or serious adverse reactions). Although TNF-α antagonists represent an important addition to 
the UC therapeutic medications, they are effective in only a subset of UC patients. IFX can 
only induce remission in 31%-39% of UC patients and maintain long-term (1-year observation 
period) clinical remission in 26% of UC patients. In addition, secondary failure associated with 
the immunogenicity of monoclonal antibodies to TNF-α is also common. Although patients 
have initial responses, it will gradually lose response over time. The TNF-α antagonists are 
also associated with a number of serious safety concerns based on their suppression of systemic 
immunity, including reactivation of tuberculosis (TB); bacterial, viral, fungal and opportunistic 
infections, and malignancies. Infusion reactions to TNF-α antagonists are not rare, e.g., the 
incidence of infusion reactions to IFX can reach to 3%-10%. 
In summary, although pharmacotherapy for UC has made great progress in recent years, the 
current treatment options, especially oral medications, still cannot meet the medical needs of 
patients with moderate to severe UC. CBP-307 currently being developed is a novel, potent 
S1P1 modulator in oral form, and has shown to induce rapid and reversible lymphopenia in 
rodents and dogs. It is predicted that CBP307 may be effective and well-tolerated for UC 
treatment as shown by the completed preclinical pharmacology and toxicology studies on 
CBP-307, the phase I clinical study in healthy subjects, and the published results of a clinical 
study on the treatment of ozanimod (also known as RPC1036), a S1P1 modulator, for patients 
with moderate to severe UC. Similar to other S1P1 class members, its proposed mechanism for 
the treatment of UC is to inhibit the transfer of inflammatory T cells from lymph nodes and 
reduce their entry into intestinal tissues, thereby relieving intestinal inflammation. However, 
given its reduced effect on S1P3, it may confer a safety advantage over other S1P1 products. 
A good safety profile of CBP-307 was demonstrated in available clinical data. Headache, 
dizziness and lymphopenia were the most common AEs observed. CBP-307 showed no impact 
on pulmonary function, blood pressure, ophthalmic parameters or blood chemistry parameters. 
Similar to other S1P1 regulators, CBP-307 showed side effect of dose-dependent moderate 
heart rate slowdown within 2-4 hours after administration; however, at single doses of 0.1 mg, 
0.25 mg and 0.5 mg, no adverse cardiac events were reported.  
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of CBP-307 when orally administered in patients with moderate to severe UC, thereby 
providing a basis for a further clinical study and determining the dose to be administered in the 
phase III clinical study. The study includes two stages. In stage 1, subjects will be randomized 
at a ratio of 1:1 to receive double-blind therapy with CBP-307 0.2 mg or placebo for 12 weeks. 
Study stage 1 is aimed at evaluating the efficacy, safety and pharmacokinetic characteristics of 
different doses of CBP-307 when orally administered. Stage 2 of the study will further evaluate 
the safety and efficacy of CBP-307 in medium and long-term oral administration (for 36 weeks). 
In this study, to protect patients from potential cardiac risk, dose titration will be performed 
before the patient is administered with the target dose. During the period of titration, 12-lead 
electrocardiogram (ECG) and 24-hour Holter will be applied for cardiac monitoring. 
Bradycardia and cardiac conduction abnormalities are defined as adverse events of special 
interest (AESI) of this study which will be given special attention and prompt reporting. Other 
potential safety risks including pulmonary toxicity, hepatotoxicity, macular edema, severe and 
opportunistic infections, skin tumors, posterior reversible encephalopathy syndrome, and 
progressive multifocal leukoencephalopathy, though not observed with CBP-307 in prior 
clinical trials, have been reported with other S1P1 agonist; therefore, these AEs are also defined 
as AESI of this study. Based on these benefit/risk assessments above, the conduct of this study 
is considered justifiable.  
4 
STUDY OBJECTIVES AND ENDPOINTS 
 
Study objectives 
Study endpoints 
Primary 
● 
To 
compare 
clinical 
efficacy of CBP-307 vs 
placebo by evaluating the 
change of adapted Mayo 
score after 12 consecutive 
weeks 
treatment 
in 
subjects with moderate to 
severe UC 
● 
Change in adapted Mayo score from baseline at 
week 12 compared between CBP-307 0.2 mg and 
placebo 
Secondary 
● 
To 
compare 
clinical 
efficacy of CBP-307 vs 
placebo by evaluating the 
clinical 
response 
rate, 
clinical remission rate and 
mucosal healing rate after 
12 
consecutive 
weeks 
treatment in subjects with 
moderate to severe UC 
● 
Change in adapted Mayo score from baseline at 
week 12 compared between CBP-307 0.1 mg and 
placebo 
● 
Change in complete Mayo score from baseline at 
week 12 after treatment 
● 
Comparison of clinical response rate at week 12 
by adapted Mayo score (defined as a decrease of 
≥ 2 points and at least 30% from baseline, 
accompanied with a decrease of ≥ 1 point from 
baseline in the rectal bleeding subscore or an 
absolute rectal bleeding subscore of ≤ 1 point) 
● 
Comparison of clinical response rate at week 12 
by complete Mayo score (defined as a decrease of 
≥ 3 points and at least 30% from baseline, 


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accompanied with a decrease of ≥ 1 point from 
baseline in the rectal bleeding subscore or an 
absolute rectal bleeding subscore of ≤ 1 point) 
● 
Comparison of clinical remission rate at week 12 
by adapted Mayo score (defined as a rectal 
bleeding subscore = 0 and stool frequency 
subscore ≤ 1, with an Endoscopy subscore ≤ 1 
[excluding friability]) 
● 
Comparison of clinical remission rate at week 12 
by complete Mayo score (defined as a total Mayo 
score of ≤ 2 points with no individual 
subscore > 1 point) 
● 
Mucosal healing rate at week 12 after treatment 
(mucosal healing is defined as Mayo endoscopic 
subscore ≤ 1) 
● 
To compare the clinical 
safety and tolerability of 
CBP-307 with those of 
placebo administered for 
12 weeks in subjects with 
moderate to severe UC 
● 
Incidence, type and severity of TEAEs and SAEs 
as well as their relations with the investigational 
product, 
AEs 
and 
SAEs 
that 
lead 
to 
discontinuation of study, and AEs of special 
interest (cardiac events as well as abnormal 
pulmonary 
function 
tests, 
ophthalmologic 
examinations, skin examinations, and nervous 
system physical examinations); AEs will be 
graded according to CTCAE version 5.0 in study 
stage 1 
● 
12-lead 
ECG 
findings, 
abnormal 
clinical 
laboratory tests (the hematology test, blood 
chemistry test, urinalysis and Coagulation test), 
vital signs and results of physical examination 
Exploratory • 
To evaluate the PK/PD of 
CBP-307 
orally 
administered in subjects 
with moderate to severe 
UC in the study stage 1 
• 
To evaluate IBDQ in 
study stage 1 and stage 2 
• 
To evaluate the safety and 
tolerability of CBP-307 
after medium or long-
term administration (in 
study stage 2) in subjects 
with moderate to severe 
UC 
• 
To evaluate clinical 
remission, clinical 
response and mucosal 
healing in subjects with 
moderately to severely 
active UC who respond 
after 12 weeks of 
induction therapy in the 
● 
Plasma concentrations of CBP 307 in subjects 
with moderate to severe UC 
● 
Absolute lymphocyte count 
● 
Total Igs (IgA, IgG and IgM) 
● 
C-reactive protein (CRP) as a biomarker of 
plasma protein 
● 
Fecal calprotectin as a fecal biomarker to be 
analyzed 
● 
Change in the total IBDQ score and subscore 
from baseline at week 12 after treatment (in study 
stage 1), at week 24, and week 48 (in study stage 
2) 
● 
Incidence, type and severity of TEAEs and SAEs 
as well as their relations with the investigational 
product, 
AEs 
and 
SAEs 
that 
lead 
to 
discontinuation of study, and AEs of special 
interest (cardiac events as well as pulmonary 
function tests, ophthalmologic examinations, 
skin examinations, and nervous system physical 


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stage 1 study, thereby to 
evaluate the efficacy of 
CBP-307 orally 
administered for 
maintenance treatment 
compared with placebo in 
sub-study 1 of the study 
stage 2 
• 
To 
evaluate 
clinical 
remission, 
clinical 
response 
and 
mucosal 
healing in subjects with 
moderately to severely 
active UC who do not 
achieve clinical response 
after 
12 
weeks 
of 
induction therapy in the 
study stage 1, thereby to 
evaluate the efficacy of 
CBP-307 
when 
orally 
administered for treatment 
in sub-study 2 of the study 
stage 2. 
examinations); AEs will be graded according to 
CTCAE version 5.0 in study stage 2 
● 
Change in 12-lead ECG findings, abnormal 
clinical laboratory tests (the hematology test, 
blood chemistry test, urinalysis and coagulation 
test), vital signs and results of physical 
examination in the study stage 2 
● 
To explore the following efficacy endpoints in 
subjects with moderately to severely active UC 
who achieved clinical response after 12 weeks of 
induction therapy in study stage 1: 
o 
Percentage of subjects who maintain 
clinical response at week 48  
o 
Percentage of subjects who achieve 
clinical remission at week 48 
o 
Percentage of subjects who achieve 
mucosal healing under endoscope at 
week 48 
o 
Percentage of subjects who take oral 
corticosteroids at baseline but has 
discontinued treatment of 
corticosteroids at week 48 and achieved 
clinical remission 
o 
Change in the complete Mayo score at 
week 48 from baseline 
o 
Change in the adapted Mayo score at 
week 48 from baseline 
● 
To explore the following efficacy endpoints in 
subjects with moderately to severely active UC 
who do not achieve response after 12 weeks of 
induction therapy in study stage 1: 
o 
Percentage of subjects who achieve 
clinical response at week 24 (after 
12 weeks of treatment in sub-study 2)  
o 
Percentage of subjects who achieve 
clinical remission at week 24 (after 
12 weeks of treatment in sub-study 2)  
o 
Percentage of subjects who achieve 
mucosal healing under endoscope at 
week 24 (after 12 weeks of treatment in 
sub-study 2) 
o 
Change in the complete Mayo score at 
week 24 (after 12 weeks of treatment in 
sub-study 2) from week 12 
o 
Change in the adapted Mayo score at 
week 24 (after week 12 of treatment in 
sub-study 2) from week 12 
o 
Percentage of subjects who maintain 
clinical response at week 48 (after 
36 weeks of treatment in sub-study 2) 
(i.e., achieve clinical response at both 
week 24 and week 48) 


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o 
Percentage of subjects who achieve 
clinical remission at week 48 (after 
36 weeks of treatment in sub-study 2) 
o 
Percentage of subjects who achieve 
mucosal healing under endoscope at 
week 48 (after 36 weeks of treatment in 
sub-study 2) 
o 
Change in the complete Mayo score at 
week 48 (after 36 weeks of treatment in 
sub-study 2) from week 12 
o 
Change in the adapted Mayo score at 
week 48 (after 36 weeks of treatment in 
sub-study 2) from week 12 
AE=adverse events; CRP=C-reactive protein; CTCAE=common terminology criteria for adverse 
events; 
IBDQ=inflammatory 
bowel 
disease 
questionnaire; 
Ig=immunoglobulin; 
PD=pharmacodynamics; 
PK=pharmacokinetics; 
SAE: 
serious 
adverse 
event; 
TEAE: 
treatment-emergent adverse event; UC=ulcerative colitis. 
5 
STUDY PLAN 
5.1. Study design and study procedures 
This study is a multicenter, multicountry, phase II clinical trial to evaluate the efficacy and 
safety of CBP-307 in subjects with moderate to severe ulcerative colitis (UC). This study is 
scheduled to be carried out approximately between March 2018 and September 2022 in 
approximately 77 sites globally in China, Pakistan, Ukraine and the United States. 
This study includes stage 1 and stage 2. 
Study stage 1 
After screening, subjects will enter the randomized, double-blind, placebo-controlled induction 
therapy for 12 weeks, i.e., the study stage 1. Subjects will be given CBP-307 capsules 0.2 mg 
(or placebo) orally once daily for 12 consecutive weeks. The eligible patients are planned to be 
enrolled and randomized at a ratio of 1:1 into the 2 groups (approximately 52 subjects per each 
group) and stratified according to whether the subject failed in a previous tumor necrosis factor 
(TNF)-α antagonist therapy. Subjects will be screened at 1-21 days prior to the baseline visit. 
Subjects with moderate to severe UC (adapted Mayo score ≥ 4) who meet all inclusion criteria 
and do not meet any exclusion criteria will be randomized into one of the following 2 groups 
at the baseline visit: a group treated with CBP-307 0.2 mg once daily (2 capsules of CBP-307 
0.1 mg), and a placebo group (treated with 2 capsules of placebo). Placebo capsules are 
completely identical with the CBP-307 capsules in appearance and weight. 
In study stage 1, subjects randomized to the CBP-307 group will undergo dose titration for 
1 week while those in placebo group will undergo simulated titration (Figure 4). Both CBP-
307 and placebo will be administered through the oral route. For subjects in the group of dose 
titration of CBP-307 0.2 mg once daily, a dose of 0.05 mg CBP-307 will be given from day 1 


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to day 4; then, a dose of 0.1 mg CBP-307 will be given for later 3 days; from day 8, a target 
dose (0.2 mg) will be administered. The titration dosing regimen is detailed in Section 6.2. 
For the subjects already enrolled as per the previous approved protocols (version 5.0 or earlier), 
they will continue the treatment in the stage 1 according to the previous planned schedule. 
Administration will be continued for 12 weeks. If subjects who complete 12 weeks of induction 
therapy of the stage 1 meet the criteria for the study stage 2, they can choose to enter it to 
further evaluate the safety and efficacy of CBP-307 in medium or long-term administration in 
subjects with moderate to severe UC. Subjects who early withdraw from the study or complete 
the study stage 1 but do not enter the stage 2 will enter a 4-week safety follow-up period. 
Figure 4. 
Study design of the stage 1 
 
Study stage 2 
All subjects who complete 12 weeks of induction therapy (with CBP-307 or placebo) in the 
study stage 1 and complete all examinations (including colonoscopy) at the week 12 visit can 
choose to enter the study stage 2 of a total length of 40 weeks, including 36 weeks of continuous 
treatment and 4 weeks of safety follow-up after the last dose. Subjects who choose to enter the 
stage 2 will be required to sign an updated informed consent form and will be screened for 
eligibility. 
The study stage 2 contains two sub-studies: sub-study 1 and sub-study 2. Subjects entering the 
study stage 2 will enter one of sub-studies based on their results of efficacy evaluation in the 
study stage 1 (Figure 5). 
0.2 mg CBP-307 QD, 52 subjects 
Placebo QD, 52 subjects 


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Sub-study 1 (subjects who have achieved clinical response by adapted Mayo score): Subjects 
who have clinical response shown by efficacy evaluation at week 12 in the study stage 1 and 
meet the eligibility criteria for stage 2 will enter sub-study 1 of the study stage 2 to receive 
double-blind maintenance treatment for 36 weeks (weeks 13 to 48), i.e., the therapeutic 
regimen for them in stage 1 will be continually maintained. Safety follow-up will be completed 
at 4 weeks after the last dose. Subjects who present with recurrent UC during maintenance 
treatment are required to terminate treatment and withdraw from the study. 
For the subjects already enrolled as per the previous approved protocols (version 5.0 or earlier), 
they will follow the previous planned treatment in the sub-study 1 of stage 2 study. 
UC disease recurrence i.e., an increased activity of UC, is defined as a repeated (occurring at 
2 consecutive visits) partial Mayo score that is at least 5 points and is also ≥3 points higher 
than the score at week 12 (the end of induction therapy), and where the possibility of increased 
disease activity being due to other potential factors unrelated to UC can be excluded (e.g., 
infection, medication changes).  
Sub-study 2 (subjects who have not achieved clinical response by adapted Mayo score): 
Subjects who have not achieved clinical response shown by efficacy evaluation at week 12 
in the study stage 1 and meet the eligibility criteria for stage 2 will enter open-label treatment 
with CBP-307 0.2 mg. Subjects will receive CBP-307 once daily at an oral dose of 0.2 mg in 
sub-study 2 regardless of whether they receive CBP-307 0.2 mg or placebo in the study stage 1. 
For subjects who enter sub-study 2 of study stage 2, 1-week dose titration will be performed at 
the first week (week 13). Dose titration will involve administration of CBP 0.05 mg initiated 
on day 1 and used for 4 consecutive days, followed by administration of CBP-307 0.1 mg for 
3 days, and administration of CBP-307 at a target dose of 0.2 mg initiated on day 8. After dose 
titration is completed, subjects will receive oral treatment with CBP-307 0.2 mg once daily, for 
36 weeks. Safety follow-up will be completed at 4 weeks after the last dose. 
At week 24, subjects will undergo efficacy evaluation including colonoscopy. If the subjects 
have not achieved clinical response, the treatment will be discontinued and the subjects will be 
withdrawn from the study. 


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Figure 5. 
Study design of stages 1 and 2 
 
5.2. Rationale for study design and dose selection 
5.2.1. Rationale for study design 
The design of the study stage 1 allows for a double-blind, placebo-controlled comparison of 
efficacy and safety parameters of CBP-307 vs. placebo during the induction period of 12 weeks 
in subjects with moderately to severely active UC. 
The study stage 2 is designed to evaluate the efficacy and safety of CBP-307 in its medium and 
long-term treatment. Sub-study 1 of the study stage 2 will include subjects who have achieved 
clinical response during the induction period and will continue the blinded maintenance 
treatment for 36 weeks with the regimen used during the induction period. Such study design 
could avoid the re-assignment of responded subjects, and blinding maintenance could reduce 
bias in efficacy and safety evaluation. Sub-study 2 of the study stage 2 is an open-label 
treatment with CBP-307 at dose of 0.2 mg/day to evaluate the clinical response of subjects 
(who do not respond during the induction period) at a daily dose of 0.2 mg, as well as its 
efficacy and safety in medium and long-term maintenance treatment. 
5.2.2. Rationale for dose selection 
The dose selection for this study has taken into account the results of previous non-clinical 
pharmacological & toxicological studies and clinical studies. The doses of CBP-307 for 
humans have been screened based on fingolimod and other similar S1P1 agonists administered 
in non-clinical and clinical studies. 
The decrease in the number of lymphocytes in peripheral blood is a typical PD response to (or 


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a PD marker for) S1P1 agonists. fingolimod (FTY720), a first-generation S1P1 agonist, 
second-generation S1P1 agonists under development, such as ozanimod and etrasimod, and 
CBP-307 belong to the same class of drugs. In all clinical studies of S1P1 agonists including 
fingolimod, ozanimod and etrasimod, the decrease in the number of lymphocytes in peripheral 
blood was used as a PD marker for S1P1 agonists, the doses administered in phase II clinical 
studies were selected based on a decrease by 50%-70% in the lymphocyte count in peripheral 
blood from the baseline. A lot of clinical data on fingolimod have demonstrated that after a 
decrease by approximately 70% in the lymphocyte count, an increased dose may fail to further 
improve the therapeutic effect on multiple sclerosis. Among these studies in different 
compounds, more therapeutically potential was observed in patients treated with higher doses 
when safety risks were comparable in different dosages. Thus, in this phase II UC study, the 
clinical data on similar S1P1 agonists are fully referred to, and the doses are determined based 
on the PD data of CBP-307 derived from the phase I clinical studies and the efficacy data from 
the phase II Crohn’s disease study. 
An Australian study of the safety, pharmacokinetics and efficacy of repeated doses of CBP-307 
administered once daily for 28 days showed that the pre-dose lymphocyte counts in the 0.15-mg 
and 0.25 mg groups decreased by 48.5% and 75%, respectively, after the pharmacokinetics 
(PK) reached steady state. The phase I clinical study of CBP-307 (administered once daily for 
14 days) in Chinese healthy subjects, found that the pre-dose lymphocyte counts in the 0.1-mg 
and 0.2 mg groups decreased by approximately 50% and 70%, respectively, after steady state 
was reached. This observation is consistent to pharmacodynamic (PD) requirement for the 
selection of a low dose and a high dose to be administered in a phase II clinical study. From 
the experience in a CBP-307 phase II Crohn’s disease study, 0.1 mg or 0.2mg orally 
administered once daily is selected. Obvious therapeutic effects could be observed only in 
patients treated by 0.2 mg once daily, including the clinical improvement as well as the 
biomarker changes in parallel. Additionally, safety data from all these different CBP-307 
phase I and II studies showed that both 0.1 mg and 0.2 mg once daily administration had 
comparably overall safety profile. 
Thus, in order to achieve the PD requirement (the reduction in lymphocyte), and meanwhile to 
reduce the exposure to the less effective / ineffective dose, 0.2 mg orally administered once 
daily is selected as an appropriate dose in this study. 
5.3. Study duration 
Study stage 1: The duration for treatment is 12 weeks. Subjects who complete the 12-week 
treatment of stage 1 but do not enter the stage 2 or early withdraw from the study will undergo 
safety follow-up for 4 weeks after the last dose.  


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Study stage 2: All subjects who complete the 12-week study stage 1 treatment (induction 
therapy with CBP-307 or placebo) and complete all assessments (including colonoscopy) at 
week 12 visit can choose to enter the study stage 2 for a total of 40 weeks. In the stage 2, 
subjects will continuously be administered for 36 weeks (week 13-48 of the study), and they 
will undergo safety follow-up for 4 weeks after the last dose (week 49-52 of the study). Subjects 
who early withdraw from the study will undergo safety follow-up for 4 weeks after the last 
dose. 
For subjects who complete both stages (stage 1 + stage 2), the study will last for a total of 
52 weeks: 48 weeks of administration, and 4 weeks of follow-up.  
5.4. Study population 
Subjects aged 18-75 years (inclusive), regardless of sex, who are diagnosed with moderate to 
severe UC (adapted Mayo score ≥ 4). 
5.4.1. Inclusion criteria and Exclusion criteria for study stage 1 
Inclusion criteria: 
Subjects are eligible to be included in the study only if all of the following criteria apply: 
1. Male or female subjects aged 18-75 years (inclusive). 
2. In the opinion of the investigator, the subject is capable of understanding and complying 
with protocol requirements. The subject signs and dates a written informed consent form 
prior to the initiation of any study procedures. 
3. Female subjects of childbearing potential and male subjects who have not undergone 
vasectomy should use at least one highly effective method of contraception during the 
entire study and 4 weeks after the last dose of investigational products after signing the 
informed consent form. The highly effective methods of contraception in this study 
include: 
a. 
Abstinence is acceptable only if it is part of the participant’s regularly practiced 
lifestyle; 
b. Hormone (oral, patch, ring, injection, implant) in combination with a male condom. 
This must be used for at least 30 days before the first dose of investigational products 
or an alternative acceptable method must be used; 
c. 
Intrauterine device (IUD) in combination with a male condom; 
d. Exceptions are: a) women with at least 12 consecutive months amenorrhea in the 
absence of medications known to induce amenorrhea and have a documented follicle 
stimulating hormone (FSH) level of greater than 40 mIU/mL or in the postmenopausal 
range; or b) surgical sterilization (e.g., hysterectomy, bilateral oophorectomy). 
4. The subject has a diagnosis of UC established at least 3 months prior to screening by 


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clinical and endoscopic evidence corroborated by a histopathology report. Subjects are 
confirmed to have moderate to severe active UC within 14 days prior to the first dose of 
the investigational product, which is based on an adapted Mayo score of 4-9, and an 
endoscopic subscore of ≥ 2. Endoscopy must be performed during the screening period 
(day -14 to day -3, allowing centralized reading and evaluation before the first dose at 
week 0). 
5. The subject has evidence of UC extending to the rectum with ≥15 cm involvement on 
endoscopy. 
6. Subjects must be UC patients who are receiving treatment. They can be enrolled if they 
meet any items below. 
a. 
Prior to the randomization visit, subjects have received oral 5-ASA (e.g., mesalazine, 
sulfasalazine, olsalazine, balsalazide) for at least 4 weeks with the dose stable for at 
least 2 weeks  
b. Prior to the randomization visit, subjects have received oral or IV corticosteroids e.g. 
prednisone (daily doses ≤ 30 mg), budesonide (daily doses ≤ 9 mg), 
methylprednisolone (daily doses ≤ 24 mg), or equivalent dose of corticosteroids for at 
least 4 weeks, with the dose stable for at least 2 weeks. 
7. If oral 5-ASA or corticosteroid for treatment of UC have been recently discontinued, they 
must have been stopped for at least 2 weeks prior to the screening endoscopy examination 
which is used for Mayo score assessment. 
8. If subjects use non-prohibited concomitant medications, a stable dosing regimen must be 
used, that is, within 7 days prior to first dose of investigational product or within 
5 half-lives of the drug (whichever is longer), there's no new concomitant medications 
started or changes in the dose of existing non-prohibited concomitant medications.   
9. The subject who has extensive colitis or pancolitis of >8 years duration or limited colitis 
of >12 years duration must have documented evidence that a surveillance colonoscopy 
was performed within 12 months prior to initial screening (can be performed during 
Screening if not performed in previous 12 months). 
10. For subject who has a family history of colorectal cancer, personal history of increased 
colorectal cancer risk, age >50 years, or other known risk factor, the data of colorectal 
cancer surveillance within 12 months prior to screening visit must be available (colorectal 
cancer surveillance can be performed during screening if not in previous 12 months). 
Exclusion criteria 
Exclusion criteria are classified into indication-specific exclusion criteria, exclusion criteria for 
general condition and exclusion criteria for infectious diseases. Patients who meet any of the 
following criteria will be excluded: 
UC-related exclusion criteria: 


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1. At the screening visit, subjects have evidence of toxic megacolon. 
2. The subject has had subtotal or total colectomy. 
3. The subject has an existing ileostomy, colostomy (a history of ileostomy or colostomy that 
has been reversed may be acceptable), or known symptomatic stenosis of the intestine. 
4. Investigator judges the subject currently requires or is anticipated to require surgical 
intervention for UC during the study. 
5. The subject has a history or evidence of adenomatous colonic polyps that have not been 
removed. 
6. The subject has a history or evidence of colonic mucosal dysplasia including low or 
high-grade dysplasia, as well as indeterminate for dysplasia. 
7. Subjects have a suspected or confirmed diagnosis of Crohn's enterocolitis, undiagnosed 
types of colitis, ischemic colitis, or radiation colitis. 
8. Previous exposure to the following treatments: 
• Lymphocyte-depleting therapies (e.g., alemtuzumab, anti-CD4 antibody, 
cladribine, rituximab, ocrelizumab, cyclophosphamide, mitoxantrone, total 
body irradiation, bone marrow transplantation and daclizumab). 
• Previous treatment with D-penicillamine, leflunomide. 
9. The subject has had prior exposure to approved or investigational products that inhibit the 
lymphocyte trafficking (e.g., natalizumab, fingolimod, ozanimod or etrasimod, etc.) 
Subjects who were previously exposed to vedolizumab and did not respond to its treatment. 
10. Within 60 days prior to the screening visit, the subject has received any of the following 
for the treatment of UC: 
a. 
Intravenous immunoglobulin (IVIG); 
b. Therapeutic plasma exchange (TPE). 
11. Within 30 days prior to randomization visit, the subject has received any of the following 
for the treatment of UC: 
a. 
Immunosuppressants (such as cyclosporine, tacrolimus, sirolimus or mycophenolate 
mofetil), thalidomide or traditional Chinese medicine; 
b. Approved non-biologic agents or traditional Chinese medicine treatment. 
12. Patients who plan to concurrently use an immunosuppressant (such as azathioprine, 
6-mercaptopurine or methotrexate) after randomization. Patients treated with azathioprine, 
6-mercaptopurine or methotrexate at screening are required to discontinue it prior to the 
first dose of the study drug. 
13. The subject has received any investigational biologic or non-biologic agent, or approved 
biologic agent or biosimilars within 60 days or 5 half-lives prior to screening (whichever 
is longer). 
14. The subject has used topical (rectal) treatment with aminosalicylic acid, corticosteroid or 
traditional Chinese medicine enemas/suppositories or for UC treatment within 2 weeks of 


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the administration of the first dose of study drug. 
Exclusion criteria for general conditions: 
15. The subject has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, 
gastrointestinal, 
genitourinary, 
hematological, 
coagulation, 
immunological, 
endocrine/metabolic, or other medical disorders that, in the opinion of the investigator, 
would confound the study results or compromise subject safety. 
16. History of uveitis or macular oedema. 
17. Clinically relevant cardiovascular conditions, including history or presence of any one of 
below: 
a. 
Ischemic heart disease or myocardial infarction; Unstable angina; History of angina 
pectoris caused by coronary artery spasm or raynaud's phenomenon (Raynauds); 
b. Congestive heart failure (NYHA class III-IV), cardiac arrest; 
c. 
Stroke, transient ischemic attack; 
d. History of recurrent syncope or positive result of vasovagal syncope tilt test; 
e. 
Symptomatic bradycardia, sick sinus syndrome, sinoatrial block, second degree 
atrioventricular block (e.g., Mobitz type 2 atrioventricular block) or third degree 
atrioventricular block; 
f. 
Congenital long QT syndrome (LQTS) or prolonged QT interval corrected using 
Fridericia’s formula (QTcF) in screening ECG (QTcF >450 ms in men, QTcF > 
470 ms in women) ; 
g. Subjects at increased risk for QT prolongation due to hypokalemia or 
hypomagnesemia; or subjects who are currently taking medications to prolong QT 
interval (e.g., citalopram, chlorpromazine, haloperidol, methadone, and erythromycin) 
which result in risk for torsades de pointes; 
h. Under treatment or expected to taking treatment during the study with medications 
with a known impact on the cardiac conduction system (e.g., beta blockers, calcium 
channel blockers, Class Ia or Class III anti-arrhythmic drugs [amiodarone, 
bromobenzylamine, sotalol, ibutilide, azimilide, dofetilide]); 
i. 
Hypertension (except well-controlled hypertension after pharmacotherapy); systolic 
blood pressure < 95 mm Hg or >140 mm Hg and diastolic blood pressure ≤ 50 mm 
Hg or ≥ 95 mm Hg at the screening visit; 
j. 
Resting heart rate < 55 times/min or ventricular rate < 55 times/min in 12-lead ECG 
at screening visit; 
k. Investigator deems that the 12-lead ECG at screening visit is clinically significant 
abnormal, such as myocardial ischemia, any significant cardiac conduction 
abnormalities (such as the left bundle branch block), that would put the subject at risk 
or interfere with the study results; 


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l. 
Any other significant heart disease that the investigator judges would put the subject 
at risk or interfere with the study results. 
m. Subjects have a family history of premature coronary heart disease. 
18. History of type 1 diabetes, uncontrolled type 2 diabetes judged (HbA1c > 7%) by 
investigator, patients with diabetes accompanied with significant complications, e.g., 
retinopathy or kidney disease. 
19. The subject has a history of malignancies, including malignant solid tumors and 
hematological malignancies (Except basal cell carcinomas and in situ squamous 
carcinomas of the skin that have been resected or cured). 
20. The subject has had any surgical procedure requiring general anesthesia within 30 days 
prior to screening or is planning to undergo major surgery during the study period. 
21. The subject has chronic obstructive pulmonary disease, asthma, pulmonary fibrosis or any 
other significant history of pulmonary diseases except for mild intermittent asthma that 
does not require regular maintenance treatment. 
22. Pulmonary function test (including examinations of lung ventilation function and 
pulmonary gas exchange) at the screening visit shows one of the following abnormalities: 
forced expiratory volume in 1 second (FEV1) or forced vital capacity (FVC) < 70% of 
normal expected value. 
23. During screening period, any of the following laboratory abnormalities: 
a. 
Hgb < 8 g/dL; 
b. WBC count < 3.5 × 10 9/L; 
c. 
Neutrophils count < 1.5 × 10 9/L; 
d. Lymphocyte count < 0.8 × 10 9/L; 
e. 
Platelet count < 100 × 10 9/L or >1200 × 10 9/L; 
f. 
Serum creatinine > 124 μmol/L for female or > 141 μmol/L for male; 
If the WBC count, neutrophil count or lymphocyte count meets the above criteria during 
the screening period, a retest can be scheduled during the screening period. It is required 
that the results of the retest should not meet the above criteria, otherwise subjects do not 
meet the enrollment criteria. 
24. Abnormal liver function test during the screening period, such as abnormalities in alanine 
aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyltransferase (γ-GT), 
alkaline phosphatase (ALK) or serum total bilirubin, which suggest liver disease or liver 
function impairment. The investigator should make a determination according to the 
following criteria: 
a. 
Subjects with serum total bilirubin > 1.2 times the upper limit of normal (ULN) shown 
by initial and repeat tests should be excluded from the study; 
b. Subjects with any of the other liver function parameters listed above, such as AST, 


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ALT, γ-GT or ALK > 1.5 times the ULN shown by initial and repeat tests, should be 
excluded from the study; 
c. 
Subjects with increased level of more than 1 parameter in liver function test should be 
excluded from the study; 
d. During the screening period, if a single transaminase level (AST, ALT, γ-GT or ALK) 
is elevated by more than 1.5 times the ULN, or serum total bilirubin is elevated by 
more than 1.2 times the ULN, a repeat test can be scheduled as soon as possible before 
enrollment/randomization to exclude laboratory errors. Only if the results of the repeat 
test meet the requirements, subjects could be enrolled. 
25. Allergic to any component of the study drug (and its excipients). 
26. The subject has a history of drug abuse (defined as any illicit drug use) or a history of 
alcohol abuse within 1 year prior to Screening. 
27. The subject has an active mental disorder that, in the opinion of investigator’s opinion, 
may interfere with compliance with study procedures. 
28. The subject is unable to participate in all study visits or comply with study procedures. 
29. The subject is in a health condition that requires to take prohibited medications listed in 
Section 6.6. 
30. If female, the subject is intending to become pregnant before, during, or within 4 weeks 
after participating in the study or intending to donate ova during such period. 
31. If male, the subject intends to donate sperm during the study or for 4 weeks thereafter. 
32. The subject is an immediate family member, study site employee, or is in a dependent 
relationship with a study site employee who is involved in the conduct of this study (e.g., 
spouse, parent, child, sibling) or may consent under duress. 
33. Female subjects who are lactating or have a positive serum pregnancy test during the 
Screening Period or a positive urine pregnancy test at week 0, prior to study drug 
administration. 
Exclusion criteria for infectious diseases: 
34. The subject has evidence of known active infection during the screening period. 
35. The subject has evidence of treatment for Clostridioides difficile (C. difficile) infection or 
other intestinal pathogen with 28 days prior to first dose of study drug. 
36. Patients with the histories of following infectious diseases: 
● Treatment with oral anti-infection medication due to acute infection within 2 weeks 
prior to screening visit or intravenous anti-infection treatment due to acute infection 
within 4 weeks prior to screening visit; 
● Clinically significant infection (e.g., pneumonia, nephropyelitis and herpes zoster) 
within 4 weeks prior to screening visit, or ongoing chronic infection; 


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37. Active or latent tuberculosis (TB) evidenced by the followings: 
● A positive diagnostic TB test within 30 days before screening or during the screening 
period is defined as: 
- 
Quantiferon or Quantiferon Plus test positive, or 
- 
Two consecutive indeterminate Quantiferon tests or Quantiferon Plus tests, or 
- 
Chest X-ray within 3 months prior to week 0 for which the results are suspicious 
for pulmonary TB. 
Note: Subjects with documented evidence of previously successfully treated TB, or with a 
negative Quantiferon or Quantiferon Plus test result, can be enrolled in the study. If 
Quantiferon or Quantiferon Plus test result is indeterminate at screening, it could be retested 
during screening period. If Quantiferon or Quantiferon Plus retest result is indeterminate, the 
subject should not participate in the study. If Quantiferon or Quantiferon Plus retest result is 
negative, the subject can be enrolled in the study.  
38.  Chronic hepatitis B virus (HBV) infection* or chronic hepatitis C virus (HCV) infection**. 
*Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (HBsAb) and hepatitis B core antibody 
(HBcAb) must be evaluated for all the patients at screening. Patients with positive hepatitis B surface antigen 
(HBsAg) will be excluded. HBV-DNA test should be carried out at screening if the subject is negative for 
Hepatitis B surface antigen, negative or positive for hepatitis B surface antibody, and positive for hepatitis 
B core antibody. The subject should be excluded from the study if HBV-DNA test result is positive, or he/her 
can be enrolled in the study in case of negative result of HBV-DNA test. 
**An HCV viral load test should be carried out if HCV antibody (HCVAb) is positive. The subject should 
be excluded from the study in case of positive HCV viral load test result. If the HCV viral load test result is 
negative, the subject can be enrolled in the study. 
39. The subject has any identified congenital or acquired immunodeficiency (e.g., common 
variable immunodeficiency, human immunodeficiency virus [HIV] infection, organ 
transplantation). 
40. The subject has received any live vaccine within 30 days prior to screening. Or subjects 
are scheduled for immunization with any live vaccine during the study or within 1 month 
after the last dose of the investigational product. 
41. Positive syphilis antibody at screening. 
42. Subjects with a history of more than one episode of herpes zoster, or a history of 
disseminated herpes zoster or disseminated herpes simplex. 
5.4.2. Inclusion and exclusion criteria for subjects' entry into the study stage 2 from the 
stage 1: 
Inclusion criteria: 
Subjects cannot enter the study stage 2 if any of the following criteria is not satisfied: 


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1. Subjects must be those with UC who participate in the study of CBP-307CN002 and have 
completed 12 weeks of treatment with CBP-307 or placebo in the stage 1 and have 
completed all the assessments (including colonoscopy) at study visit of week 12 in study 
stage 1. 
2. Subjects have good compliance in stage 1, can understand all information about the study 
stage 2, and are able and willing to comply with the requirements specified in the study 
protocol. 
3. Subjects or their legal representatives voluntarily sign informed consent forms for study 
stage 2. 
4. Female subjects of childbearing potential and male subjects who have not undergone 
vasectomy should use at least one highly effective method of contraception during the 
entire study and 4 weeks after the last dose of investigational products after signing the 
informed consent form. The highly effective methods of contraception in this study 
include: 
a. Abstinence is acceptable only if it is part of the participant’s regularly practiced lifestyle; 
b. Hormone (oral, patch, ring, injection, implant) in combination with a male condom. 
This must be used for at least 30 days before the first dose of investigational products 
or an alternative acceptable method must be used; 
c. Intrauterine device (IUD) in combination with a male condom; 
d. Exceptions are: a) women with at least 12 consecutive months amenorrhea in the 
absence of medications known to induce amenorrhea and have a documented FSH level 
of greater than 40 mIU/mL or in the postmenopausal range; or b) surgical sterilization 
(e.g., hysterectomy, bilateral oophorectomy). 
Exclusion criteria: 
Subjects who meet any of the following criteria will not be included in study stage 2: 
1. The subject has any unstable or uncontrolled cardiovascular, pulmonary, hepatic, renal, GI, 
genitourinary, hematological, coagulation, immunological, endocrine/metabolic, or other 
medical disorder that, in the opinion of the investigator, would confound the study results 
or compromise subject safety. 
2. Subjects who are known to be allergic to CBP-307 or its excipients, or subjects experience 
significant adverse events related to the study drug during the stage 1 of the 
CBP-307CN002 study, and the investigator deems that subjects are not appropriate to 
participate in the stage 2. 
3. Subjects currently have evidence of active or untreated latent tuberculosis. 


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4. Subjects currently have active or chronic recurrent infections, and in the opinion of the 
investigator subjects are not appropriate to participate in stage 2 of the study. 
5. History of uveitis or macular oedema. 
6. Subjects had received any of the following treatments after administration of the first dose 
in stage 1 of the study: 
a) 
Biological product; 
b) 
Prednisone>30 mg/day, budesonide>9 mg/day, methylprednisolone>24 mg/day or 
equivalent dose of steroid treatment; 
c) 
Immunosuppressant (such as azathioprine and 6-mercaptopurine or methotrexate). 
7. Investigator deems that the 12-lead ECG results at the study visit of week 12 during study 
stage 1 is clinically significant abnormal, such as myocardial ischemia, any significant 
cardiac conduction abnormalities (such as the left bundle branch block), any abnormality 
that would put the subject at risk or interfere with the study results. 
8. Pulmonary function test (including examinations of lung ventilation function and 
pulmonary gas exchange) of subjects at the study visit of week 12 during the study stage 
1 shows 1 of the following abnormalities: forced expiratory volume in 1 second (FEV1) or 
forced vital capacity (FVC) < 50% of normal predicted value. 
9. Subjects’ laboratory measurements at week 12 visit during the study stage 1 meet any of 
the following criteria:  
• 
AST or ALT> 3 ULN; 
• 
Absolute lymphocyte count < 0.2×10 9/L; 
• 
Serum creatinine > 124 μmol/L (in females) or > 141 μmol/L (in males). 
10. Any other reason that in the opinion of the investigator may interfere with subject 
compliance or evaluation of the results of the study. 
5.4.3. Re-screening after the failure of screening 
The numbers of all subjects who fail the screening will not be used again. Whether a subject 
who fails the screening is allowed to undergo re-screening will be evaluated by the sponsor's 
medical monitor based on individual case. Subjects receiving re-screening will be required to 
complete all laboratory tests and procedures during the screening period, including 
colonoscopy (except that recent colonoscopy videos are available for the centralized reading at 
the site and the ilecolonoscopy is performed within 30 days prior to the first dose). In case the 
results of the pulmonary function test, ophthalmologic examination (including OCT) or 
dermatology examination during initial screening period at the study site are within 30 days 


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prior to the first dose, the results could be re-used after the investigators’ evaluation based on 
individual case. Subject is allowed to be re-screened only once. 
5.4.4. Criteria for termination of treatment or early withdrawal of subjects 
Subjects should be encouraged to complete the study, but they are allowed to voluntarily 
withdraw from the study at any time during its conduct. The investigator should provide written 
statements of the withdrawal of subjects from the study. Primary reasons why subjects 
terminate or withdraw from the study or discontinue the investigational product should be 
recorded in the eCRF according to the following classifications.   
1) Adverse events (AEs) 
The Subject has experienced an AE that requires early termination because continued 
participation imposes an unacceptable risk to the subject’s health or the subject is unwilling 
to continue because of the AE.   
● 
Liver function test (LFT) abnormalities   
The investigational product should be discontinued immediately, and appropriate clinical 
follow-up should be performed (including repeated laboratory tests until the subject's 
laboratory measurements returns to normal or baseline, please refer to Section 7.5), if the 
following circumstances occur at any time during study medication treatment:  
- 
ALT or AST > 8 × ULN, or  
- 
ALT or AST > 5 × ULN and a re test > 5 × ULN, or  
- 
ALT or AST > 3 × ULN and elevated total bilirubin > 2 × ULN, or international 
normalized ratio (INR) > 1.5, or 
- 
ALT or AST > 3 × ULN with fatigue, nausea, vomiting, right upper quadrant pain or 
tenderness, fever and rashes.   
● 
Decrease in pulmonary function 
If the subject's pulmonary function test results (FEV1 and/or FVC) fall below 50% of the 
predicted values, treatment should be discontinued immediately, and appropriate clinical 
follow-up should be performed (please refer to Section 7.5).  
● 
Macular edema 
All subjects diagnosed with macular edema must discontinue the investigational product (see 
Section 7.5). 
2) Significant protocol deviation at the time of enrollment or during the study 


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The discovery post randomization that the subject fails to meet protocol entry criteria or does 
not adhere to protocol requirements, and continued participation in the study may poses 
unacceptable risk to the subject's health.   
3) Lost to follow-up 
The subject does not return to the study site, and the investigator makes multiple attempts to 
contact the subject but fails. If a subject is lost to follow-up, the investigator should make every 
effort to contact the subject and record each attempt to contact the subject (where possible, 
3 telephone calls and, if necessary, a certified letter to the subject’s last known mailing address 
or local equivalent methods). 
4) Subject non-compliance with the protocol 
If a subject is in significant non-compliance with the protocol, the subject could be early 
terminated after discussion/consultation by the investigator, the medical monitor of the contract 
research organization (CRO), and sponsor. 
5) Withdrawal of informed consent by the subject 
The subject voluntary withdraws from the study. The subject (or their legal representatives) 
wishes to withdraw from the study. The reason for withdrawal, if provided should be recorded 
in the eCRF.   
6) Termination of study 
Sponsor, Ethics Committee or regulatory body terminates the study.   
7) Pregnancy 
Subject pregnancy. 
Note: If a subject is found to be pregnant, the subject must withdraw from the study 
immediately. The procedure for withdrawal from the study is detailed in Section 8.8. 
8) Treatment failure or disease progression 
Study stage 1: The investigator considers that subject is not benefiting from investigational 
treatment, and present with disease progression during the study: e.g., in the opinion of the 
investigator, continued participation would pose an unacceptable risk to the subject or need for 
surgical intervention for treatment of UC. 
Study stage 2: In sub-study 1, if the subject present with UC recurrence during maintenance 
treatment, the subject is required to terminate the treatment and withdraw from the study. 
UC disease recurrence i.e., an increased activity of UC, is defined as a repeated (occurring at 
2 consecutive visits) partial Mayo score that is at least 5 points and is also ≥3 points higher 
than the score at week 12 (the end of induction therapy), and where the possibility of increased 


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disease activity being due to other potential factors unrelated to UC can be excluded (e.g., 
infection, medication changes).  
In sub-study 2, if subjects have not achieved clinical response yet at week 24, they will be 
required to terminate treatment and withdraw from the study. In addition, for all subjects who 
enter the study stage 2, if the investigator judges that they are not benefiting from the study 
treatment, or present with disease progression during the study period, or need for surgical 
intervention for UC treatment, the investigational treatment should also be terminated. 
9) Others  
Note: Specific reasons should be recorded in the eCRF. The investigator should do their utmost 
to determine the primary reason of withdrawal, and if possible, document it (e.g., withdrawal 
due to AEs or treatment failure).  
5.4.5. Criteria for termination of the clinical study. 
The study may be terminated prematurely in case of the following: 
● 
The principal investigator and sponsor believe that the number and severity of AEs indicate 
that the study must be terminated. 
● 
Newly obtained data raise concerns about the safety of the investigational product: 
continuation of the study may pose a risk to subjects. 
● 
The principal investigator and sponsor believe that a flawed study design or unplanned 
unblinding has impaired the integrity of the study, thereby making it impossible to evaluate 
the efficacy and safety of the investigational product. 
The premature termination of the study must be determined and recorded by the principal 
investigator in consultation with sponsor. Study results must be reported as far as possible 
according to the protocol requirements. 
5.4.6. Procedure for termination of or withdrawal from the study 
If possible, perform a complete follow-up visit for subject who withdraws from the study, 
including a physical examination, vital signs, an ECG test and a laboratory test (Refer to Study 
Flow Chart Table 1, 2 and 3). To evaluate AEs or laboratory abnormalities and ensure that they 
are reversible or stable, follow-up visits will be conducted at an appropriate time for all subjects 
who withdraw after the last dose of the investigational product. Results will be recorded in the 
original medical record and eCRF. The reasons for withdrawal will also be recorded in the 
original medical record and eCRF. 
6 TREATMENT REGIMEN 


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6.1. Randomization and blinding method 
6.1.1. Randomization method 
Subjects meeting all eligibility criteria of study stage 1 will be randomized into the study and 
stratified according to whether the subject had previous failure of a tumor necrosis factor 
(TNF)-α antagonist therapy. 
Sub-study 1 of the study stage 2 will include subjects who have achieved clinical response by 
adapted Mayo score in the 12-week induction therapy in study stage 1 as shown by efficacy 
evaluation and who meet eligibility criteria for entering study stage 2: they will receive blinded 
maintenance treatment with the regimen used during study stage 1. Sub-study 2 of the study 
stage 2 will include subjects who have not achieved clinical response by adapted Mayo score 
in the induction therapy in study stage 1 and who meet eligibility criteria for stage 2: they will 
receive open-label treatment with CBP-307 0.2 mg/day. 
6.1.2. Allocation of subjects 
In study stage 1, subjects will be randomly assigned to one of the following 2 groups in a 1:1 
ratio: 
● 
CBP-307 0.2 mg, once daily 
● 
Placebo, once daily  
In study stage 2, subjects included in sub-study 1 will continue treatment with the regimen used 
during stage 1. Subjects included in sub-study 2 will receive oral treatment with CBP-307 
0.2 mg once daily after dose titration. 
6.1.3. Blinding and blinding process 
The study stage 1 is a randomized, double-blind, placebo-controlled clinical study, and sub-
study 1 of the study stage 2 will aim at investigating the long-term safety and efficacy in 
subjects who have achieved clinical response in study stage 1 by continuing with the 
double-blind treatment. Sponsor, the clinical team entrusted by the CRO, the investigator, the 
clinical center’s personnel involved in the study and the subjects do not know to which group 
subjects are randomly assigned throughout the study. 
In case of an emergency, the investigator has the responsibility for determining if unblinding 
of a subject’s treatment assignment is warranted. Subject safety must always be the first 
consideration in making such a determination. Generally, sponsor must be informed of 
unblinding in advance, unless in urgent cases where unblinding is necessary for the medical 
treatment of the subject, sponsor must be notified within 48 hours after unblinding. The date 
and reason for unblinding must be entered into the clinical trial management database. 


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The investigator should not perform unblinding recklessly. If unblinding occurs, the subject’s 
participation in the trial will be discontinued, but they should remain in the study for 4-week 
safety follow-up. 
Sub-study 2 of the study stage 2 will be open-label treatment with a dose of 0.2 mg/day of 
CBP-307, so blinding process is not applicable. 
6.2. Treatment regimen 
Oral administration within half an hour after meal at 7:00~10:00 am every day. If possible, 
subjects should try to keep taking the drug at a similar time point every day. 
Dose regimen of the dose titration period in the study stage 1 
Subjects in CBP-307 group will undergo dose titration for 1 week while those in placebo group 
will undergo simulated titration. Both CBP-307 and placebo will be administered through the 
oral route. For subjects in the group of CBP-307 0.2 mg once daily, a dose of 0.05 mg CBP-
307 will be given from day 1 to day 4; then, a dose of 0.1 mg CBP-307 will be given for later 
3 days; from day 8, a target dose (0.2 mg) will be administered. 
Detailed steps for dose titration are in Table 5. 
Table 5. 
Titration dosing regimen 
Target dose 
Day 1 to day 4 
Day 5 to day 7 
From day 8 
CBP-307 0.2 mg 
0.05 mg 
0.1 mg 
0.2 mg 
Placebo 
Placebo capsules 
Placebo capsules 
Placebo capsules 
Note: During the titration period, CBP-307 0.05 mg will be orally administered at doses of 0.05 mg 
(1 capsule) and 0.1 mg will be orally administered at 0.05mg (2 capsules); in the placebo group, placebo 
capsules at the corresponding quantity (completely identical with CBP-307 in appearance and weight) will 
also be orally taken. From day 8, in the 0.2 mg group, 2 capsules of 0.1 mg will be orally administered; and 
in the placebo group, 2 capsules of placebo (completely identical with CBP-307 in appearance and weight) 
will also be orally taken. The drugs taken daily will be sub-packaged in bottles in a GMP-compliant 
workshop, the investigational product will be independently packaged in boxes based on visit intervals. 
Dose regimen of the dose titration in study stage 2 
Subjects included in sub-study 1 of study stage 2 are no longer required to undergo dose 
titration. Subjects included in sub-study 2 (open-label treatment) of stage 2 will undergo 
1-week dose titration. Dose titration involves administration of CBP-307 0.05 mg initiated on 
day 1 for 4 consecutive days, followed by administration of CBP-307 0.1 mg for 3 days, and 
administration of CBP-307 at a target dose of 0.2 mg initiated on day 8. 
Dose titration in the sub-study 2 of stage 2 are in Table 6. 


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Table 6. 
Administration regimen dose titration in study stage 2 
Target dose 
Day 1 to day 4 
Day 5 to day 7 
From day 8 
CBP-307 0.2 mg/day 
0.05 mg/day 
0.1 mg/day 
0.2 mg/day 
Note: During the titration period, CBP-307 0.05 mg will be achieved with 1 capsule of 0.05 mg strength and 
0.1 mg will be achieved with 2 capsules of 0.05mg strength; From day 8, 2 capsules of 0.1 mg will be 
administered. The drugs taken daily will be sub-packaged in bottles in a GMP-compliant workshop, the 
investigational product will be independently packaged in boxes based on visit intervals. 
 
6.2.1. Cardiac monitoring during titration 
In study stage 1, detailed schedule for cardiac monitoring during titration is provided in Table 
7. 
In the stage 2 sub-study 2, detailed schedule for cardiac monitoring during titration is provided 
in Table 8. 


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Table 7. 
Stage 1 Cardiac monitoring 
 
Cardiac monitoring 
Titration day 1 
Titration day 2 
Titration day 5 and day 8 
Monitoring 
method 
Before 
administration 
Every hour 
within the 6 h 
after 
administration 
The 4th 
hour and 
6th hour 
Continuous 
monitoring 
for 24 
hours 
Before 
administration 
Every hour 
within the  
6 h after 
administration 
The 4th 
hour 
and 6th 
hour 
Continuous 
monitoring 
for 24 
hours 
 
Before 
administration 
Every hour 
within the  
6 h after 
administration 
The 4th 
hour and 
6th hour 
Continuous 
monitoring 
for 24 
hours 
Vital signs 
X 
X 
X3 
X 
X 
X3 
 
X 
X 
X3 
 
12-lead 
ECG 
X 
X3 
X 
 
X3 
 
X 
 
X3 
 
Holter 
monitoring 
X1 
X2 
 
 
 
 
X2 
 
 
X2 
Notes: 
1. 24-hour Holter monitoring before day 1 will be initiated 1 day before drug administration (baseline day 0). 
2. 24-hour Holter monitoring will be initiated from 30min ± 10min before drug administration until 24 ho urs after drug administration. 
3. Subjects still need further monitoring in the following cases: 
● at 6 hours after drug administration, the subject’s heart rate is still < 45 times/min; 
● at 6 hours after drug administration, the subject’s heart rate is still at the lowest level after drug administration; 
● at 6 hours after drug administration, 12-lead ECG shows newly-occurring second degree or higher degree atrioventricular block; 
● at 6 hours after drug administration, the QTcF interval is prolonged (> 450 ms in males; > 470 ms in females); 
● at 6 hours after drug administration, if the subject has symptomatic bradycardia, they will be monitored until it has resolved. 


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Table 8. 
Sub-study 2 of Study Stage 2 Cardiac Monitoring 
 
Cardiac monitoring 
Titration day 1 
Titration day 2 
Titration day 5 and day 8 
Monitoring 
method 
Before 
administration 
Every hour 
within the 6 h 
after 
administration 
The 4th 
hour and 
6th hour 
Continuous 
monitoring 
for 24 
hours 
Before 
administration 
Every hour 
within the  
6 h after 
administration 
The 4th 
hour 
and 6th 
hour 
Continuous 
monitoring 
for 24 
hours 
 
Before 
administration 
Every hour 
within the  
6 h after 
administration 
The 4th 
hour and 
6th hour 
Continuous 
monitoring 
for 24 
hours 
Vital signs 
X 
X 
X3 
X 
X 
X3 
 
X 
X 
X3 
 
12-lead 
ECG 
X 
X3 
X 
 
X3 
 
X 
 
X3 
 
Holter 
monitoring 
X1 
X2 
 
 
 
 
X2 
 
 
X2 
Notes: 
1. 
24-hour Holter monitoring before day 1 will be initiated 1 day before drug administration. 
2. 24-hour Holter monitoring will be initiated from 30min ± 10min before drug administration until 24 hours after drug administration. 
3. Subjects still need further monitoring in the following cases: 
● at 6 hours after drug administration, the subject’s heart rate is still < 45 times/min; 
● at 6 hours after drug administration, the subject’s heart rate is still at the lowest level after drug administration; 
● at 6 hours after drug administration, 12-lead ECG shows newly-occurring second degree or higher degree atrioventricular block; 
● at 6 hours after drug administration, the QTcF interval is prolonged (> 450 ms in males; > 470 ms in females). 
● at 6 hours after drug administration, if the subject has symptomatic bradycardia, they will be monitored until it has resolved. 


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6.2.2. Missing dose 
Subjects should be informed that they can take a missed dose within 4 hours after the normal 
time for oral administration; otherwise they will need to take the drug of original dose at the 
normal time on the following day. If subjects experience vomiting after taking the capsules, 
they do not need to re-take the drug on the same day but need to take the drug at the original 
dose at the normal time on the following day. If subjects cannot take the drug due to other 
medical conditions, which leads to dose discontinuation, they are required to contact the 
investigator in time. 
On occasions of missed doses: 
• Within the first 2 weeks of treatment, if dose is missed for more than 1 day (2 to7 days 
interruption), the drug dosing needs to be restarted at the site and the first-dose 
monitoring procedures need to be repeated for subjects.  
• After 2 weeks of treatment, if the dosing is missed no more than 2 days, subjects can 
take the original dose at the normal time on the following day; if the dosing is 
interrupted for 3 to 7 consecutive days, the drug will need to be restarted at the site with 
proper oversight. ECG will be performed before dose administration and at 4 and 6 
hours after dose; vital signs will be monitored hourly. However, there will be no 
24-hour Holter monitoring. 
Subjects, except those who experience dose discontinuation due to a significant decrease in the 
peripheral lymphocyte count, will be required to withdraw from the study if the dose is 
discontinued for more than 7 days (see Section 8.6 for details). 
6.3. Labeling and packaging of the investigational product 
The investigational product will be provided by sponsor: Suzhou Connect Biopharmaceuticals 
Ltd. 
The label of the investigational product will contain the following information: 
● 
Statement that it is used for clinical study only 
● 
Warning “Please keep out of reach of children” 
● 
Sponsor's name and production address 
● 
Drug name (a statement: “CBP-307 or Placebo”) 


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● 
Drug number 
● 
Protocol No. 
● 
Dosing instructions 
● 
Storage condition 
● 
Shelf life 
● 
Batch No. 
6.4. Distribution of investigational product 
In study stage 1, the investigator or his/her designee will register subjects in an electronic data 
capture system (Medidata RAVE) at screening, complete randomization using the RAVE 
Randomization and Trial Supply Management (RTSM) system, and obtain random numbers in 
RAVE and dispense drugs accordingly. Before drug dispensing, a drug identifying number will 
be provided by the RAVE RTSM system and displayed in real time in RAVE, so that the study 
site's investigator or his/her designee is accessible to the identifying number. If the drug 
provided by sponsor is lost or damaged, the study site's investigator or his/her designee will 
complete drug replacement procedures on RAVE's interface. At visits for drug dispensing, the 
investigator or his/her designee will access the RAVE as the above to keep a record of drug 
dispensing and return. 
Subjects who complete the study stage 1 and enter sub-study 1 of study stage 2 will receive 
double-blind maintenance treatment for 36 weeks (weeks 13-48) with the same regimen used 
in the stage 1. The approach to drug dispensing is the same as that in the stage 1. Subjects 
who complete study stage 1 and enter sub-study 2 of study stage 2 will enter open-label 
treatment with CBP-307 0.2 mg/day. Subjects, regardless of whether they receive CBP-307 
0.2 mg or placebo in stage 1, will receive CBP-307 at an oral dose of 0.2 mg once daily in 
sub-study 2 of the study stage 2. Drugs for open-label treatment will be directly distributed by 
the investigator, and their ID numbers are entered into the RAVE. 
Note: For the subjects already enrolled as per the previous approved protocols (version 5.0 
or earlier), they will follow the previous planned treatment until they finish the study. 
6.5. Accountability of investigational product and treatment compliance 
6.5.1. Accountability of investigational product 
CBP-307 capsules and placebo should be stored at controlled 2-8°C. The investigational 
product must be stored in a cabinet according to the storage conditions on the label. The cabinet 


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will be locked and managed by a specially designated person. 
The study site's investigator or his/her authorized representative (such as a pharmacist) will 
ensure that the investigational product is stored in a safe area in accordance with the 
recommended storage conditions and regulations. 
The investigator must keep a detailed accountability record containing the information on the 
receipt, use, loss, or other disposal of the investigational product. To maintain a complete 
record, all drugs will be described in detail in the drug quantity and inventory record, and at 
each visit, the drugs that are not used yet and returned by the subject will be counted. 
After the end of the trial, sponsor will instruct how to dispose of the unused investigational 
product. If sponsor authorizes the study site to dispose of the drug, the investigator must ensure 
that the materials are disposed of in accordance with relevant regulatory requirements and the 
hospital’s procedures, and then, disposal will be recorded well. At the end of the study, the 
subject cannot take the investigational product anymore. 
6.5.2. Study treatment compliance 
Study stage 1: At each visit (exclusive of visit 6, 8 and 10) from visit 4 (day 5) to the end of 
treatment (week 12), the study site will evaluate treatment compliance.  
Study stage 2: The study site will evaluate treatment compliance at each visit from visit 13 
(week 18) to the end of maintenance treatment (week 48) in sub-study 1. At each visit from 
visit 14 (day 5 of titration) to the end of treatment (week 48) during the study stage 2, the study 
site will evaluate treatment compliance. 
Poor compliance is defined as when actual oral dose is less than 80% of the oral dose specified 
in the package insert or more than 120% of the specified oral dose. The investigator will decide 
whether the subject with poor treatment compliance should withdraw from the study. The 
investigator needs to record the condition of the subject with poor treatment compliance in the 
original medical record and the corresponding eCRF. 
Throughout the study, the study site must strictly manage the investigational product until all 
drugs are returned to sponsor. Any discrepancies between the drug record and the drug 
inventory must be reported to sponsor. 
6.6. Concomitant medication and treatments 
6.6.1. Medications and treatments allowed to be used 
Subjects can use the following medications at therapeutic doses: 


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● 
Oral 5-ASAs compounds (e.g., mesalazine, sulfasalazine, olsalazine, balsalazide) provided 
that these medications have been used for at least 6 weeks and with the dose stable for at 
least 2 weeks prior to randomization visit. 
● 
Oral or IV corticosteroid therapy e.g. prednisone at a stable dose ≤ 30 mg/day, budesonide 
dose ≤ 9 mg, methylprednisolone dose ≤ 24 mg) or equivalent dose of steroid provided the 
corticosteroid treatment has been used for at least 4 weeks, with a stable dose for at least 
2 weeks prior to randomization visit. The dose of corticosteroid should remain stable 
throughout the treatment period unless the subject experiences medical conditions causing 
failure to tolerate the original dose of corticosteroids or continued use of the original dose 
of steroids will pose significant risk to the subject in the opinion of investigators. After 
discussing with the medical monitor, the corticosteroid could be tapered according to the 
subject's condition and the reason should be recorded in detail in the medical document. 
All subjects included in study stage 2 who meet the criteria of tapering should start 
corticosteroids tapering. The detailed plan for tapering is shown in below section. 
● 
If the dose of probiotics (such as Bifidobacterium and Saccharomyces boulardii) has been 
stable for 2 weeks prior to the first dose of the investigational product, then, probiotics can 
be used. 
● 
Antibiotics used for UC treatment (i.e., ciprofloxacin and metronidazole), provided that 
their dose has remained stable for 2 weeks prior to the first dose of the investigational 
product. 
Note: The dose of all medications above should be kept stable throughout the study. 
Corticosteroids tapering 
Sub-study 1 of the study stage 2: After subjects are included in sub-study 1 of the study 
stage 2, corticosteroids tapering should be initiated. The dose of oral 5-ASA must still be kept 
stable. The recommended schedule for corticosteroid tapering in the study is as follows: 
• 
If the dose of prednisone is >20 mg/day (or equivalent), it is recommended to reduce the 
dose at a rate of 5 mg/week until the dose reaches 20 mg/day. 
• 
If the dose of prednisone is ≤20 mg/day (or equivalent) or reduced to 20 mg/day (or 
equivalent), it is recommended to reduce the dose at a rate of 2.5 mg/week until drug 
withdrawal. 
• 
The dose of budesonide should be reduced at a rate of 3 mg every 3 weeks 
For subjects who cannot tolerate the corticosteroid taper without recurrence of clinical 
symptoms, corticosteroids may be increased up to the original dose at the beginning of 


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induction therapy (should not exceed baseline dose). In such cases, the tapering regimen above 
must be reinitiated within 2 weeks. 
Sub-study 2 of the study stage 2: After subjects are included in sub-study 2 of the study stage 2 
and complete dose titration, the investigator can decide whether to maintain the original dose 
or gradually reduce the dose of corticosteroids according to the subjects' treatment course and 
dose of corticosteroid. If subjects have achieved clinical response at week 24, corticosteroids 
tapering must be initiated. The recommended plan for such reduction is the same as above. 
6.6.2. Prohibited medications and treatments 
Precautions to be taken into account throughout the study: 
● 
Subjects should not receive major surgery after participating in the study. 
● 
Subjects should not donate blood, semen or oocyte samples during the study or within 
4 weeks after the last dose of the investigational product. 
The following drugs are prohibited during the study: 
● 
Any other medications used to treat UC, including those that have been approved or are 
being developed (5-ASA drugs or glucocorticoids are allowed to be used, but their dose 
should maintain stable). 
● 
Live vaccines, except the flu vaccine (during the treatment period and within 1 month after 
the last dose of the investigational product). 
● 
Chronic nonsteroidal anti-inflammatory drug (NSAID) (note: occasional use of NSAID or 
acetaminophen for headache, arthritis, myalgias, menstrual cramps, etc., or low-dose 
aspirin [81-162.5 mg] for cardiovascular prophylaxis are permitted). 
● 
The following drugs cannot be used in the study: 
- 
Treatment with medications with known impact on the cardiac conduction system and 
QT interval prolongation, and the second degree or higher degree atrioventricular 
block. A list of examples of prohibited cardiac medications is provided in Table 9. 
- 
Marketed biologic therapies such as abatacept, infliximab, etanercept, adalimumab, 
anakinra, rituximab and golimumab. 
- 
Immunosuppressants (e.g., azathioprine, 6-mercaptopurine or cyclosporine, 
methotrexate, tacrolimus, sirolimus or mycophenolate mofetil). 
- 
Any medication administered through the rectum for UC treatment, including enemas 


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(e.g., 5-ASA and corticosteroids), other than required for endoscopy preparation. 
- 
Treatment with immunoadsorption column. 
- 
Any investigational drug other than the study treatment. 
- 
Intravenous immunoglobulin or therapeutic plasma exchange (TPE). 
- 
D-penicillamine, leflunomide or thalidomide. 
- 
Treatment with lymphocyte inhibitors (natalizumab, vedolizumab, fingolimod, 
ozanimod or etrasimod). 
- 
Immunosuppressants that deplete lymphocyte (such as alemtuzumab, anti-CD4, 
cladribine, 
rituximab, 
ocrelizumab, 
cyclophosphamide, 
mitoxantrone 
and 
daclizumab). 
Table 9. 
Examples of Prohibited Cardiac Medications  
Drug classification 
Example of medication 
β-blockers 
Acebutolol, atenolol, betaxolol, bisoprolol, carteolol, metoprolol, nadolol, 
propranolol, sotalol and timolol 
Calcium 
channel 
blockers 
Diltiazem and verapamil 
Antiarrhythmic 
drugs 
Amiodarone, bepridil hydrochloride, disopyramide, dofetilide, dronedarone, 
flecainide, ibutilide, lidocaine, procainamide, propafenone, quinidine and 
tocainide 
Drugs that prolong 
the QT interval 
Citalopram (>20 mg/day), chlorpromazine, haloperidol, methadone and 
erythromycin 
The investigator should record any use of concomitant medications in the original medical 
record and the corresponding eCRF, including the dose, specification, the route of 
administration, the date of administration, and the cause of administration. All information of 
prior medication related to UC treatment must be recorded, and the information of prior 
medication related to non-UC treatment within 60 days before screening must be recorded. For 
drugs containing a single active ingredient, their generic names should be recorded as far as 
possible. For drugs containing multiple ingredients, their brand names should be recorded. In 
addition, the daily dose should be recorded as far as possible. 
6.7. Plan for trial termination 
Sponsor has the right to terminate the study prematurely for safety reasons. In addition, sponsor 
has the right to terminate the study prematurely for management reasons. In any case, safety 


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follow-up should be ensured for all subjects who have entered the study. Any premature 
termination of the trial should be notified in writing to the Ethics Committee and relevant 
regulatory authorities. 
7 STUDY ASSESSMENTS 
For visit plan details refer to the Study Flow Chart (Study stage 1, sub-study 1 of the study 
stage 2, and sub-study 2 of the study stage 2 referring to flow chart Table 2, Table 3, Table 4 
respectively). 
7.1. General information 
General information to collect will include demographics, family history, medical history, 
concomitant disease and treatments, a history of current medication use, and symptoms and 
signs related to the disease. 
7.2. Efficacy assessments 
7.2.1. Subject diary 
Subject diary information will be collected using an electronic validation system for China and 
US sites only. For sites in other countries, subject diary information will be collected by paper 
subject diary instead. The investigator will dispense subject diaries at the screening visit and 
instruct subjects how to record information appropriately. Subject diaries need to be reviewed 
at all visits from baseline to last dose/early termination. The investigator should continually 
give sufficient instructions to subjects for them to properly complete the subject diary. 
Subject diary will contain the following information: 
• 
Frequency of "normal" bowel movements (during the improvement of ulcerative colitis or 
within 24 hours prior to the initial appearance of signs and symptoms of ulcerative colitis) 
• 
Bowel movement frequency/day 
• 
Blood in the stool 
• 
Degree of abdominal discomfort 
• 
General health 
• 
Other discomforts 
• 
Daily medication log 
In each study stage, from study start to last dose/early termination, the study site will review 
the information recorded in the subject diary at each study visit. The most recent 3 consecutive 
days within the week before the visit should be used to calculate stool frequency and rectal 


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bleeding subscores for Mayo score calculation; and then, evaluation will be performed by the 
study site. 
Because the colonoscopy preparation can interfere with the assessment, diary entries used to 
calculate the stool frequency and rectal bleeding subscores should not be taken from the day 
before (the preparation day), the day of, and the day after the colonoscopy is performed. 
7.2.2. Colonoscopy 
In study stage 1, colonoscopy will be performed to obtain a Mayo endoscopic subscore and a 
complete Mayo score and then determine subject eligibility within 14 days prior to 
randomization during screening period. Colonoscopy will also be performed at week 12 (or 
early termination). Besides, subjects who enter study stage 2 will undergo colonoscopy at 
week 24 (only for sub-study 2) and week 48 (or early termination visit). 
To ensure data quality and standardization, each study site should examine with the same 
colonoscope throughout the clinical study wherever possible, and all the colonoscopic results 
will be centrally read and evaluated. All the colonoscopy examinations should be performed 
by a properly trained endoscopist to complete colonoscopy at each site, and the same 
endoscopist should be used for a certain subject throughout the study wherever possible. If 
impossible, it is required to record the exact name of the endoscopist responsible for each 
colonoscopy. 
For the information on requirements for colonoscopy and evaluation by the central reader, see 
the relevant operating document. 
7.2.3. Mayo score 
The Mayo score is a standard, widely accepted, quantitative assessment of UC severity in 
subjects. The Mayo scores range from 0 to 12 and consist of 4 subscores, each ranging from 0 
to 3 (shown below). The higher the score is, the more severe the disease is: 
1. 
Stool frequency a 
0 = Normal numbers of stools for this patient 
1 = 1-2 stools more than normal  
2 = 3-4 stools more than normal  
3 = 5 or more stools than normal  


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2. 
Rectal bleeding b 
0 = No blood seen 
1 = Streaks of blood with stool less than half the time 
2 = Obvious blood with stool most of the time 
3 = Blood alone passes 
 3. 
Findings on Endoscopy 
0 = Normal or inactive disease  
1 = Mild disease (erythema, decreased vascular pattern) 
2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions)  
3 = Severe disease (spontaneous bleeding, ulceration) 
4. 
Physician’s global assessment c 
0 = Normal 
1 = Mild disease 
2 = Moderate disease 
3 = Severe disease 
Notes: 
a. 
Each subject serves as his or her own control to establish the degree of abnormality of the 
stool frequency. 
b. The daily bleeding score represents the most severe bleeding of the day.  
c. The physician’s global assessment will serve to acknowledge the 3 other criteria, and the 
physician will record the subject’s daily abdominal discomfort and general sense of 
well-being and other observations, such as physical examination findings and the 
patient’s performance status. 
7.2.3.1 Complete Mayo scores 
Complete Mayo scores will be calculated based on data in the above items 1, 2, 3, and 4 (stool 
frequency, rectal bleeding, endoscopic findings, and physician’s global assessment). 
Evaluation of the complete Mayo score will be performed at the visit at screening and week 12 


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(or early termination visit) during study stage 1 as well as at week 24 (only for sub-study 2) 
and week 48 (or premature withdrawal from study visits) during the study stage 2. 
7.2.3.2 Adapted Mayo score 
Adapted Mayo score will be calculated based on the above items1, 2 and 3 (stool frequency, 
rectal bleeding, endoscopic findings). The adapted Mayo score will be calculated at the visit 
at screening and week 12 (or early termination visit) during study stage 1 as well as at 
week 24 (only sub-study 2) and week 48 (or early termination visit) during study stage 2. 
7.2.3.3 Partial Mayo scores 
Partial Mayo scores will be calculated at weeks 2, 4, 8 and 12 (i.e., Mayo score without 
colonoscopy findings) in study stage 1. In sub-study 1 of study stage 2, partial Mayo scores 
will be calculated at weeks 18, 24, 32 and 40. In sub-study 2 of study stage 2, partial Mayo 
scores will be calculated at weeks 16, 32 and 40. 
Partial Mayo scores will be calculated based on data in the items 1, 2, and 4 of section 7.2.3 
(stool frequency, rectal bleeding, and physician’s global assessment). 
7.2.4 Inflammatory bowel disease questionnaire 
The Inflammatory Bowel Disease Questionnaire (IBDQ) (see Annex 1) is a psychometrically 
validated patient self-assessment scale used to measure the disease-specific quality of life in 
patients with inflammatory bowel diseases including UC. IBDQ contains 32 items related to 
four aspects: Bowel Systems (10 items), Emotion Health (12 items), Systemic Systems 
(5 items) and Social Function (5 items). The 4 aspects are scored as follows: 
• 
Bowel Systems (10-70) 
• 
Emotion Health (12-84) 
• 
Systemic Systems (5-35) 
• 
Social Function (5-35) 
Subjects will be asked to recall symptoms and quality of life from the last 2 weeks and rate 
each item on a 7-point Likert scale (higher scores equate to higher quality of life). A total IBDQ 
score will be calculated by summing the scores from each domain. IBDQ is used as an endpoint 
of the study and will be completed by the subjects themselves.  
7.3. Safety assessments 
Safety assessments involves vital signs, physical examination, pulmonary function tests, 
ophthalmologic examination, OCT, Holter monitor, 12-lead ECG, laboratory tests (hematology 
test, blood chemistry test, urinalysis, and coagulation test), as well as monitoring of AEs in all 


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subjects after drug administration. 
To ensure the health of subjects, the investigator will review the data from each subject 
throughout the study. 
7.3.1. Chest X-ray examination 
Chest X-ray taken within 3 months prior to screening could be accepted. If no chest X-ray has 
been taken within 3 months before screening, a chest X-ray examination will be performed at 
the screening visit. 
7.3.2. Vital signs 
Vital signs include the heart rate (HR), blood pressure (BP, including systolic blood pressure 
and diastolic blood pressure), body temperature and respiratory rate. Evaluation of vital signs 
are scheduled to be performed according to Table 2, Table 3 and Table 4 (the study flow chart). 
At screening and baseline, HR and BP need to be measured after at least 5 minutes rest in 
supine position. 
During study stage 1 and sub-study 2 of the study stage 2, when obtaining the predose HR 
and BP on titration day 1, the subject should rest in the supine position for at least 5 minutes 
before measurement to ensure the accuracy of the baseline measurement. In case the cuff 
sizes available does not match the subject's upper arm circumference, a sphygmomanometer 
with an appropriately sized cuff can be used instead. The repeat HR and BP measurements 
will be made at 2-minute intervals. The lowest predose value of supine HR and BP (based on 
the systolic BP) should be taken as the baseline measure and used for comparison to postdose 
values. Orthostatic blood pressure will then be measured once with the subject in the upright 
position (after standing for 2 minutes). A sudden, significant fall in BP (> 20 mmHg) at 
2-5 minutes after standing from the supine position will be considered as orthostatic 
hypotension and will be documented in the subject chart and eCRF. 
Post-baseline HR and BP need to be measured after the subject has been supine for at least 
5 minutes. Any clinically significant changes from baseline values should be confirmed by 
repeated measurement. Post-baseline blood pressure in the upright position will be measured 
in the same way (at 2 minutes after standing). If there is a significant decrease in blood 
pressure (> 20 mmHg) at 2-5 minutes after standing from the supine position to the upright 
position, it is considered as orthostatic hypotension and is to be recorded in the subject's 
medical record and eCRF. 


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7.3.3. Physical examination 
All abnormal findings during screening must be documented in the original medical record and 
the eCRF to report the relevant medical history/current condition of disease. Important findings 
after randomization that meet the definitions of AEs must be documented in the original 
medical record and the AE of eCRF. 
A complete physical examination should involve the evaluation of the neck/thyroid, chest/lung, 
heart, lymph nodes, abdomen, nervous system, etc., the overall examination of the skin and 
extremities, and the detection of possible visual abnormalities (e.g., blurred vision or decreased 
visual acuity) in subjects. 
The height and body weight should be measured when the subjects take off its heavy clothes 
and shoes, the height should be in centimeter and rounded off, and the body weight is in 
kilogram (kg) and accurate to one decimal place. 
Nervous system physical examination 
Nervous system physical examination will be performed by the investigators by actively query 
about nervous system symptoms such as cephalgia, convulsions, confusion, vision loss, speech 
disturbances, facial drooping, weakness, problems with coordination, gait and sensory loss, 
and mental impairment. If any of the above symptoms appear, a neurology consult would be 
ordered for further assessment, and extra examinations including CT scanning, MRI 
examination and other related tests will be conducted by neurologists’ judgment. 
7.3.4. Pulmonary function test 
Pulmonary function tests include FEV1, FVC, and diffusing capacity of the lung for carbon 
monoxide (DLCO). Specialized equipment is required to measure DLCO; therefore, this test 
will only be conducted at sites that have, or have access to, the right facilities. The pulmonary 
function tests will be conducted in a qualified pulmonary function laboratory or respiratory 
department. 
7.3.5. Dermatology examination 
Dermatology examination includes a thorough examination of skin injuries and limbs. It is 
mainly aimed at excluding suspected lesions of basal cell carcinoma. Dermatology 
examinations should be completed in the department of dermatology for following visits: 
screening visit and day 84 ± 3 (12 weeks) visit in study stage 1; weeks 24  and 48 during sub-
study 1 of the study stage 2; weeks32 and 48 during sub-study 2 of the study stage 2. 
Dermatology examinations at other visits can be performed by the investigator: weeks 4, 8 and 


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16 during study stage 1; weeks 40 and 52 during sub-study 1 of the study stage 2; weeks 16 
and 52 during sub-study 2 of the study stage 2. 
7.3.6. Ophthalmologic examination 
Ophthalmologic examination will check for visual abnormalities (for example, blurred vision 
or decreased visual acuity) in subjects and needs to be performed in the department of 
ophthalmology. 
When optical coherence tomography (OCT) shows suspected macular edema, it is required to 
perform a complete retinal examination including collecting history of eye diseases, visual 
acuity check, and dilated fundus examination. During the study, if an ophthalmologic 
examination finds visual abnormalities (e.g., blurred vision or decreased visual acuity), then, 
additional OCT can be performed. All subjects diagnosed with macular edema must 
discontinue the drug and withdraw from the study. 
7.3.7. 12-lead ECG 
Subjects cannot undergo 12-lead ECG measurement before having rested in the supine position 
for at least 10-15 minutes. 
7.3.8. Holter monitoring 
Holter monitoring will start at least 30 min prior to drug administration and last until at least 
24 hours after drug administration. Subjects will remain in a supine position prior to Holter 
monitoring. Holter analysis parameters will be described in detail in the operating document. 
7.3.9. Monitoring of concomitant treatment 
The use of concomitant medications and procedures will be monitored throughout the study. 
Except the investigational product, any other medications used will be regarded as concomitant 
medication. These medications could be prescription drugs prescribed by doctors or over-the-
counter drugs purchased by subjects. At each visit during the period from the subject signs the 
informed consent form to the end of the study, the investigator will ask the subject whether 
he/she has used any other medication besides the investigational product. All medications 
(including vitamin preparations, over-the-counter medicines, and Traditional Chinese 
Medicine preparations) need to be recorded in the original medical record and the e-CRF. 
Concomitant treatment prohibited in the protocol is shown in Section 6.6. 
7.3.10. Monitoring of AEs and SAEs 
Throughout the study, the investigator will do his/her best to closely monitor the occurrence of 


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AEs and SAEs. See Section 8.1 for the definition of an AE/SAE and relevant follow-up and 
reporting. For AEs of special interest, please refer to Section 7.5. 
7.3.11. Safety laboratory parameters 
In the study, all samples except the PK blood sample will be analyzed in the central laboratory 
(Q Squared Solutions). 
It is required to collect blood samples according to the Table 10 below. Details involving 
sample collection, transportation, results reporting, as well as laboratory reference ranges and 
abnormalities warning will be specified in the laboratory manual and provided to each study 
site prior to the initiation of the study. 
This protocol clearly specifies the time points for collecting blood, urine and fecal samples 
(Table 2, Table 3, Table 4). To evaluate safety, the investigator can decide to conduct 
unscheduled laboratory tests at any time during the study. 
Table 10. 
Safety Laboratory Parameters 
Laboratory test item 
Parameter 
Hematology 
Red blood cell (RBC) count, HGB, hematocrit (HCT), white blood cell 
count, blood platelet count, leukocyte differential count (lymphocyte count, 
neutrophil count, monocyte count, eosinophil count, basophil count) 
Blood chemistry 
(fasting) 
 
Liver function test 
Total bilirubin, conjugated bilirubin, ALT, AST, γ-GT, alkaline 
phosphatase, albumin, total protein, lactate dehydrogenase 
Kidney function test 
Urea, creatinine, uric acid, Na, K, Cl, Ca, P, amylase 1 
Blood glucose 
examination 
Fasting blood glucose (FBG) 
Fasting blood fat 2 
Total cholesterol, low-density lipoprotein cholesterol, high-density 
lipoprotein cholesterol and triglycerides 
Coagulation 
Prothrombin time, activated partial thromboplastin time, and international 
normalized ratio 
Urinalysis/microscopy 3 
Specific gravity, pH, nitrite, protein, glucose, ketone bodies, urobilinogen, 
bilirubin, occult blood, esterase leukocyte/erythrocyte, and white blood cells 
Fecal 
culture/microscopy 4 
Fecal culture, C. difficile, parasite ovas and parasites, and fecal calprotectin 
Others 
 
Virological and 
serological tests 
HIV antibody, HBsAg, HBsAb, HBcAb and HCVAb 
Syphilis antibody 
HBV-DNA, HCV viral loads 
Detection of 
immunoglobulin 
Immunoglobulin A, G, M 


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Detection of C-reactive 
protein 
C-reactive protein 
Pregnancy test 5 
Blood β-human chorionic gonadotropin and urine pregnancy test 
Quantiferon or 
Quantiferon Plus test 6 
TB 
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; γ-GT=γ-
glutamyltransferase; HBcAb=hepatitis B core antibody; HBsAb=hepatitis B surface antibody; 
HBsAg=hepatitis B surface antigen; HCVAb=hepatitis C antibody; HIV=human immunodeficiency 
virus; IgG=immunoglobulin G; TB=tuberculosis. 
1. Abnormal laboratory parameters or potential medical condition inconsistent with the clinical 
manifestations of UC should be repeatedly measured. At any visit after drug administration, if the 
amylase level is significantly higher than the clinical reference range (≥300 U/L), the lipase level 
should be measured to determine the source of elevated amylase (outside the pancreas). 
2. Subjects must be fasting for 9 hours before a laboratory test. 
3. If urinalysis shows occult blood or abnormal urine protein in subjects' urine samples, a microscopy 
examination needs to be performed. A microscopy examination will mainly focus on the presence of 
white blood cells and red blood cells. All other parameters will be tested with test strips. 
4. Fecal culture/microscopy (including fecal culture, C. difficile, parasite ovas and parasites) is 
required to be performed at screening. During the screening period and at any time point during the 
study, if the subject has symptoms including aggravation of the disease condition or recurrence of 
previous disease activity, stool samples can be collected for fecal culture/microscopy and C. 
difficile analysis. 
5. Women of childbearing potential are required to take a pregnancy test (including blood β-human 
chorionic gonadotropin and urine pregnancy test). At screening, postmenopausal women with 
amenorrhea for <5 years are required to undergo measurement of follicle stimulating hormone to 
confirm postmenopausal condition. 
6. Subjects with documented evidence of previously successfully treated TB accompanied with 
negative Quantiferon or Quantiferon Plus test result at screening can be enrolled in the study. If 
Quantiferon or Quantiferon Plus test result is indeterminate at screening, it could be retested during 
screening period. If Quantiferon or Quantiferon Plus retest result is indeterminate, the subject 
should not participate in the study. If Quantiferon or Quantiferon Plus retest result is negative, the 
subject can be enrolled in the study.  
The investigator must assess clinical significance for all abnormal laboratory test results, 
including the clinical significance of each abnormal value in the source document of the subject. 
The laboratory test results will be submitted with the subject's source document. Any diagnosis 
related to abnormal findings (or presenting symptoms or signs in case a diagnosis cannot be 
made) should be recorded in the medical record and the AE page of eCRF. 
7.4. Pharmacokinetics/pharmacodynamics assessment (Applicable only for study 
stage 1) 
7.4.1. Pharmacokinetics 
To measure the concentration of CBP-307 in plasma and its metabolic characteristics in plasma, 


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the investigator will ask subjects whether they are willing to participate in a PK study. 
Subsequently, blood will be collected from the PK subgroup. Approximately 90 subjects will 
be scheduled to enter the PK subgroup for sparse sampling, and plasma samples will be 
collected at the following time points: 
● 
15-30 minutes before administration and 4-6 hours after administration at week 1 (day 1 
and day 5), week 2 (day 8), week 4 (day 28), week 8 (day 56) and week 12 (day 84). 
● 
1-2 hours after administration at week 1 (day 1 and day 5) and week 4 (day 28). 
Three mL venous blood will be collected from upper limb at each time point of blood sampling. 
During the study, approximately 45 mL blood will be collected from each subject who 
participates into PK analysis subgroup for PK evaluation. See separate laboratory manual for 
specific procedures of blood collection, storage conditions and transport instructions. 
The plasma concentration of CBP-307 will be measured by Frontage Laboratories (Shanghai) 
Co. Ltd. Results will be presented in biological analysis report. 
Actual collection time of each blood sample and all information relevant to blood collection 
and handling have to be recorded on eCRF. 
Blood sample handling and transport 
The following information should be clearly indicated for plasma samples: 
● 
Protocol No. 
● 
Subject No. 
● 
Theoretical sampling time point 
● 
No. 1 or 2 blood sample 
Contents on sample label cannot be erased. Samples 1 and 2 collected from each sampling time 
point (to be separately sent by post) should be sent to the designated central laboratory under 
dry ice conditions. Before completion of the clinical study report, all remaining samples will 
be stored at ≤ -70℃, and can only be destroyed after sponsor acknowledges the final clinical 
study report. 
7.4.2. Pharmacodynamics and biomarker evaluation 
Biomarkers of UC activity include various substances detected in the blood, urine or feces that 
are associated with intestinal inflammation, clinical symptoms, and disease status. Biomarkers 
in this study include CRP and fecal calprotectin. Pharmacodynamic indicators include absolute 


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number of lymphocytes and total Igs. 
The blood collection points for biomarker evaluation are shown in Table 1, 2 and 3. Details 
involving sample collection, transportation, results reporting, as well as laboratory reference 
ranges and abnormalities warning will be specified in the laboratory manual and provided to 
each study site prior to the initiation of the study. 
7.4.2.1 Peripheral blood lymphocyte count 
The lymphocyte count as a maker of the pharmacodynamic effect will be derived from 
hematology test results. The PK subgroup is required to undergo measurement of lymphocyte 
counts (used for the PD study) at all time points for the collection of PK blood samples. 
According to Table 1, if there are corresponding hematology tests at the time points for the 
collection of PK blood samples, such as before and 4-6 hours after dose on day 1, it is not 
necessary to collect additional PD blood samples, otherwise it is required to collect PD blood 
samples simultaneously. In the non-PK subgroup, lymphocyte counts used for the PD study 
will be obtained from hematology tests, so it is not necessary to collect additional PD blood 
samples. Samples will be tested by the central laboratory. See Table 1 and the laboratory 
manual for details. 
7.4.2.2 Total immunoglobulins 
Measurements of total immunoglobulins in blood samples (including IgA, IgG and IgM) will 
be completed by the central laboratory at screening, week 12 and week 48. 
7.4.2.3 C-reactive protein 
C-reactive protein is induced by interleukin-6, tumor necrosis factor, and other 
pro-inflammatory cytokines produced in the intrinsic membrane of the intestine. It is an 
acute-phase protein that can be used as an objective indicator for the evaluation of 
inflammatory activity. The half-life of CRP is short (19 hours), so CRP level rises in the early 
stage of the onset of inflammation and then drops rapidly after inflammation resolves. 
In this study, a CRP test will be completed by the central laboratory according to the study flow 
chart, Table 1, 2 and 3. 
7.4.2.4 Fecal calprotectin 
Fecal calprotectin is a calcium and zinc binding protein with a molecular weight of 36,000 
Daltons. It is derived from neutrophils and accounts for 60% of the cytoplasmic proteins in 
granulocytes. Fecal calprotectin is confirmed to be a measure of the migration of neutrophils 
into the gastrointestinal tract. Fecal calprotectin is a very stable marker (stable for 1 week at 


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room temperature). 
Fecal calprotectin testing will be completed by the central laboratory at screening, week 12, 
week 24 (only for sub-study 2 of the study stage 2) and week 48. 
7.5. Monitoring of adverse events of special interest 
During the study on CBP-307, AEs caused by S1P1 receptor stimulation that were found in 
previous clinical studies on other similar drugs will be closely monitored. These AEs include: 
a. Bradycardia and cardiac conduction abnormalities: It was reported that the adverse 
reactions caused by the first dose of similar drugs mainly included reversible bradycardia, 
first grade atrioventricular block and sinus arrest. Reduced heart rate is an expected 
adverse reaction to S1P1 agonists. These negative chronotropic effects of S1P1R agonists 
appear to attenuate over time after S1PR desensitization and internalization into cardiac 
myocytes. This effect appears to occur with increasing exposure to study drug; thus, 
gradual titration of the dose of CBP-307 within 1 week may mitigate against larger 
reductions in heart rate. 
b. Pulmonary toxicity: An initial sharp decrease followed by slow progressive decline over 
time in FEV1 was observed in clinical studies of the same category of drugs. In this study, 
FEV1 and FVC in all subjects will be measured; DLCO will be measured in sites that are 
equipped with the right facilities. Each subject with abnormal pulmonary function test 
results will be followed up. If the subject's pulmonary function test results (FEV1 and/or 
FVC) fall below 50% of the predicted values, treatment should be discontinued 
immediately, and appropriate clinical follow-up (for at least 3 months) should be performed 
until the resolution is confirmed or no further aggravation is expected by investigator. 
c. Hepatotoxicity: fingolimod caused frequent, reversible liver enzyme elevations greater 
than 3-fold above the ULN in up to 12% of patients. In the completed phase I clinical 
study on CBP-307, ALT levels slightly increased in individual subjects but were all 
below 3 times the ULN; and this side effect was also milder than that of fingolimod. In 
this study, blood chemistry analysis will include measurement of LFT levels. Subjects 
with abnormal LFT levels will be continuously followed up until the LFT values returns 
to the normal/baseline level. 
d. Macular edema: In the preclinical and clinical phase I studies of CBP-307, no eye-related 
toxicity was observed yet. In this trial, OCT examination will be included. Subjects with 
macular edema must discontinue the investigational product and undergo examinations 
including a dilated fundus examination. Every subject whose ophthalmic evaluations 
reveal abnormalities will be followed until values return to baseline. 
e. Opportunistic infection or severe infection: Tuberculosis, serious bacterial infections, 
systemic fungal infections, viral infections such as herpes infections (including herpes 


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zoster and disseminated herpes simplex) and protozoal infections during the study should 
be reported as AESI. 
f. Basal cell carcinoma: In a 2-year placebo-controlled clinical study on fingolimod (a 
similar drug), the incidences of basal cell carcinoma are 2.0% in the group treated with 
fingolimod 0.5 mg and 0.1% in the placebo control group, respectively. Subjects should 
be observed for suspected skin lesions, and a specialist assessment should be performed 
immediately if any suspected skin lesions are noted. 
g. Posterior reversible encephalopathy syndrome and progressive multifocal 
leukoencephalopathy. 
The following steps should be followed: 
a. At every visit, vital signs should be measured in the supine position. 
b. Subjects will be closely monitored in the clinic after their first dose of the initial dose 
titration regimen for a period of 6 hours after administration. ECGs will be performed 
predose and at 4 and 6 hours after drug administration, with more frequent assessments as 
clinically indicated. Vital signs will be measured before administration and at every hour 
in 6 hours after administration. During titration period, continuous overnight cardiac 
monitoring should be performed in patients who experience symptomatic bradycardia that 
requires pharmacologic intervention. In these patients, the first-dose monitoring strategy 
will continue the following days until the symptoms improve by investigator's 
assessment, even if the study drug is discontinued. If anyone has prolonged QTc interval 
during 6-hour observation after dosing, repeated cardiac monitoring in the following days 
will be conducted until the abnormity improves. 
c. Prior to drug administration in the clinical study, clinicians should pay attention to 
subjects with a lower heart rate (occurring spontaneously or being induced by β-blockers) 
at baseline. Atropine IV is recommended as the first line therapy for bradycardia, with a 
daily maximum dose of 3 mg. Furthermore, the common guidelines for treatment of 
bradycardia (e.g., Advanced Cardiac Life Support-ACLS guidelines) should be followed 
as appropriate:). 
- 
In case of clinical symptoms or hypotension, give subjects atropine 1 mg and 
repeated doses within 3-5 minutes. 
- 
If the heart rate and/or blood pressure remain unresponsive, consider administration 
of dopamine drip 5-20 µg/kg/min or epinephrine drip 2-10 µg/min can be given.  
- 
Performance Transcutaneous pacing can also be considered. 
- 
In the condition of decreased blood pressure, isoproterenol should be avoided or 
used with caution. 
d. If there is any condition that may affect the pulmonary function test results (FEV1, FVC, 
and DLCO), including infections, respiratory symptoms, occupational exposure 
(including asbestos) and smoking, it is required to collect information and document it in 


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the eCRF before each pulmonary function test. If the subject's pulmonary function test 
results (FEV1 and/or FVC) fall below 50% of the predicted values, the investigational 
product treatment should be discontinued. If a subject discontinues due to respiratory AE, 
the investigator should ensure that the subject has adequate evaluations as clinically 
indicated by a pulmonologist (consider PFTs, chest X-ray or high-resolution computed 
tomography, based on findings of the other examinations) at the time of the AE. For 
subjects with pulmonary nodules, lung biopsy should be taken into account. Follow up 
the subject (for at least 3 months) until a resolution is confirmed or no further aggravation 
or improvement is expected by investigators. 
e. If the subject’s LFT (ALT or/and AST) is elevated and greater than 3 times the ULN, a 
retest should be performed within a week. Upon confirmation of the abnormality, retests 
should be performed weekly until the elevated LFT decreases below 3 times the ULN. If 
the LFTs increase is confirmed to be above 5 times the ULN the study drug must be 
permanently discontinued. 
f. All subjects diagnosed with macular edema must discontinue the investigational product. 
Based on the judgment by the ophthalmologist, follow up subjects with macular edema 
monthly or more frequently if needed. Follow up the subject (for at least 3 months) until a 
resolution is confirmed or no further aggravation or improvement is expected by 
investigators. If the subject does not show definite signs of improvement on examination 
6 to 8 weeks after discontinuation of study drug, then therapy for macular edema in 
conjunction with an ophthalmologist experienced in the management of this condition 
should be initiated. 
g. Examination of the skin for lesions will be performed as part of the physical examination 
at screening and at the end of study. If skin lesions are noted, the subject will be referred 
to a dermatologist for evaluation and follow-up care. 
h. Nervous system physical examinations are required for each visit, and the investigators 
should actively query about nervous system symptoms such as cephalgia, convulsions, 
confusion, vision loss, speech disturbances, facial drooping, weakness, problems with 
coordination, gait and sensory loss, and mental impairment. If any of the above symptoms 
appears, a neurology consult would be ordered for further assessment, and extra 
examinations including CT scanning, MRI examination and other related tests will be 
conducted by neurologists’ judgment. 
8 DEFINITION, MONITORING AND REPORTING OF A SAFETY 
EVENT 
All AEs will be managed and reported in accordance with applicable regulations. If an AE 
occurs, the first thing that needs attention is the safety of the subject. If necessary, the subject 
needs to be treated accordingly. AEs will be summarized in the final clinical study report. 
The informed consent form signed by the subject should include the name of the investigator 


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and the contacts used to report AEs and medical emergencies. 
8.1. Adverse event 
8.1.1. Definition and recording of adverse events 
Definition: An adverse event refers to any untoward medical occurrence that occurs after the 
subjects signs the ICF, which does not necessarily have a causal relationship with the 
investigational product. Thus, an AE can be any unfavorable and unintended symptom, sign, 
disease or condition, or an abnormal test finding, whether or not it is related to the 
investigational product. AEs include: 
● 
Symptoms described by the subject, or signs observed by the investigator, and 
● 
Abnormal findings (involving laboratory tests, ECG, and an X-ray) that result in changes 
in medical care (diagnostic or therapeutic). 
● 
Exacerbation of chronic or intermittent pre-existing diseases, including increased 
incidence and/or diseases severity. 
An abnormality found at screening visit is not an AE unless it has reappeared after 
disappearance or is worsened during the trial. 
Note: Regarding a heart rate decrease (bradycardia) and decreased lymphocyte count in 
peripheral blood in this study, please report them as follows: 
• 
Since a decreased lymphocyte count in peripheral blood is due to the mechanism of action 
of the drug, it itself is not to be reported as an AE. However, clinical diagnosis related to 
a decreased lymphocyte count in peripheral blood indicates AE reporting (if no diagnosis 
is available, it is required to report related clinical symptoms or signs). 
• 
The heart rate decrease (bradycardia) in this study is defined as a heart rate of <50 beats 
per minute in the awake state or a heart rate of  ≥50 beats per minute in the awake state 
whereas subjects experience clinical symptoms due to a reduced heart rate (if subjects 
have a heart rate <50 beats per minute in the awake state and need clinical treatment, such 
condition is considered a grade II AE). 
In this study, AE data will be collected after subjects sign informed consent forms, and AEs 
will be persistently monitored throughout the study, i.e., until 28 days after the last dose. 
The investigator will ask the subject at each follow-up visit if any AE has occurred since the 
last visit. All AEs will be recorded in medical records and eCRFs, including the AE terms, 
severity of AEs, the start date and time of occurrence, the stop date and time of occurrence, 
seriousness (i.e., whether it is a SAE), CTCAE grade, the relationship to the investigational 
product, actions taken on the investigational product, medications/treatments given, and 
outcomes of AEs. Once a written ICF is signed by the subject, the investigator will start 
recording the AE until 4 weeks after the last dose. 


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Outcome of an AE: 
● 
Death: end of life as the result of the AE. 
● 
Unrecovered/unresolved: subjects fail to recover, or an AE is not improved. 
● 
Recovering/resolving: subjects are recovering, or an AE is improving. 
● 
Recovered/resolved: subject has recovered or an AE has been resolved. 
● 
Recovered/resolved with a sequela: an AE has been resolved, but subjects have been left 
with symptoms or pathological manifestations. 
● 
Unknown: no detail, not observed, not recorded, or refusal to provide relevant 
information. 
8.1.2. Grading of adverse events 
All AEs in the trial will be graded according to the Common Terminology Criteria for Adverse 
Events (CTCAE), version 5.0. NCI CTCAE is originally a standard term designed to report 
AEs that occur during cancer clinical trials. CTCAE contains a grading scale representing the 
severity of an event, from grade 1 to grade 5. 
● 
Grade 1: mild; asymptomatic or mild symptoms; clinically or diagnostically observed; 
no intervention required. 
● 
Grade 2: moderate; indicating minimal local non-invasive intervention; instrumental 
activity of daily living corresponding to age is restricted (applicable to AEs involving 
metabolism, nutrition and immunity). 
● 
Grade 3: a severe or medically important event, but not immediately life-threatening; 
resulting in hospitalization or prolonged hospital stay; disability; restriction of self-care 
activity of daily living. 
● 
Grade 4: a life-threatening consequence; indicating emergency treatment. 
● 
Grade 5: deaths related to AE. 
Note: The CTCAE provides specific grading scales for abnormalities shown in a laboratory 
test. Grade 4 abnormality shown by a laboratory test does not automatically represent a 
life-threatening event. An abnormal result shown by a laboratory test still needs to be evaluated 
before it is determined whether such result is an AE or not. 
The safety data from the ongoing trial will be submitted to the medical monitor for review. 
8.1.3. Determination of causality between adverse events and investigational product 
According to the categories below, a causal relationship between the AE and investigational 


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product will be evaluated as definitely related, possibly related, unlikely related and not related. 
A drug-related AE is defined as an AE that is definitely related or possibly related. 
● 
Definitely related: the type of an AE has been identified as a known type of reaction to 
the investigational product and cannot be explained by other reasons, such as 
concomitant medications or comorbidities. The time of occurrence of an event strongly 
suggests a causal relationship (e.g., based on the outcome following drug withdrawal and 
restart). 
● 
Possibly related: an AE occurs with a reasonable time sequence to the administration of 
the investigational product, indicating that the occurrence of such AE may be caused by 
the investigational product. The possibility that the AE is caused by other factors, such 
as a concomitant medication or comorbidity, cannot be ruled out. The drug is not 
withdrawn or re-administered orally. 
● 
Unlikely related: no evidence shows a causal relationship between the occurrence of the 
event and the investigational product. The occurrence of the AE is more possibly related 
to other factors, such as a concomitant medication or comorbidity. There is a negative or 
ambiguous reaction after drug withdrawal. However, the relation between the drug and 
the event cannot be ruled out. 
● 
Not related: the subject does not take the investigational product; the occurrence of the 
AE is not consistent with the time sequence of administration; or such event can be 
caused by other significant factors. 
The investigator should re-assess the causal relationship based on subsequent follow-up 
information and update the corresponding AE/SAE report as required. 
8.2. Serious adverse event 
8.2.1. Definitions of serious adverse events 
An SAE is any adverse medical event that meets any of the following criteria at any dose: 
● 
Results in death; 
● 
Life-threatening; 
Note: "life-threatening" refers to the risk for death in the subject at the time when an 
event occurs. It does not mean that a more serious event may cause death. 
● 
Hospitalization or prolongation of existing hospitalization is required.  
Note: Generally, hospitalization means that due to adverse medical events, subjects receive 
unscheduled observation and/or treatment (not indicated in outpatient clinics) in the hospital's 
inpatient department (going through the hospitalization procedure) or emergency wards 
(usually, subjects need to stay there for at least 24 hours for observation). A complication that 


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appears during hospitalization is an AE; if the complication prolongs hospitalization or satisfy 
any other serious criteria, the event is serious. If hospitalization or extended hospital stay is not 
related to an AE, it is not within the scope of reporting. For example: 
a. Previous illness indicates hospitalization for examination or selective treatment, no new 
AE occurs, and also, the previous disease does not get worse; 
b. Hospitalization for observation not due to relevant AE, e.g. for social and/or 
convenience; 
c. Hospitalization required by the study procedure as indicated in the protocol; 
d. Scheduled hospitalization not due to relevant AE, such as scheduled elective surgery; 
● 
Results in persistent or significant disability/incapacity; 
● 
Congenital anomaly or birth defects; 
● 
Important medical events: These AEs may not be immediately life-threatening or result 
in death, or hospitalization, but may jeopardize the subject and needs intervention to 
prevent the occurrence of any of the above consequences. These important medical 
events include intensive treatment in the emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, or 
drug dependence or drug abuse. 
8.2.2. Reporting and follow-up of serious adverse events 
SAEs will be collected after subjects sign the informed consent form and throughout the entire 
study, i.e., until 28 days after the last dose of investigational product. 
For any SAEs in the study, whether related to investigational product or not, the investigator 
should provide timely emergency treatment, and must immediately (within a maximum of 
24 hours after becoming aware of the event) inform the sponsor or its designee, and complete 
the SAE Report Form following specific completion instructions. In the meantime, the 
investigator should record the SAE in the medical records and eCRF in a timely manner. The 
investigator must provide causality assessment when reporting SAEs. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSARs) according to local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. 
For all SAEs, the investigator needs to conduct follow-up until subjects recover, have stable 
condition or returns to baseline condition, and provide detailed follow-up information. The 
timeline and procedure for the follow-up report are the same as the initial report, namely, the 
investigator should report any follow-up information about the SAEs within 24 hours after 
awareness. 
Regarding follow-up: 


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● 
The investigator needs to take appropriate measures to protect the safety of the subject, 
and it is particularly required that each subject with AEs (abnormal clinical signs, 
laboratory test results, or others) should be followed up until he/she returns to normal or 
has stable condition. 
● 
Subjects experiencing SAEs must be followed up until they recover clinically, return to 
normal or have stable condition. This may require follow-up visits after subjects leave 
the study and require additional investigation by sponsor. 
The original report in written form should be presented in time with details, including a copy 
of the hospital medical record, a discharge summary, autopsy report (if applicable) and other 
necessary documents. 
8.3. Reporting of adverse events of special interest 
In a phase I clinical study on CBP-307 conducted in Australia, potential risk for cardiovascular 
events was observed in the high-dose group (treated with a dose more than 10 times the 
therapeutic dose to be administered in this study). Besides, in the post marketing studies of the 
marketed S1P1 agonist fingolimod and other clinical studies of S1P1 agonists, other potential 
safety risks were also observed, including pulmonary toxicity, hepatotoxicity, macular edema, 
severe and opportunistic infections, and skin tumors. Although these potential risks were not 
observed in the phase I clinical study of CBP-307, special attention is still needed in this study. 
AEs that require special attention include (see Section 7.5 for detail): 
a. 
bradycardia and cardiac conduction abnormalities: significant bradycardia (heart 
rate ≤ 45 beats/min), Mobitz type II or third degree atrioventricular block, and other 
significant cardiac conduction abnormalities, 
b. 
pulmonary toxicity: difficulty in breathing and clinically significant wheezing, and 
c. 
hepatotoxicity: e.g., two consecutive liver function tests in a subject suggesting elevated 
liver enzymes, AST or ALT > 3 times the ULN, or other clinically significant liver 
dysfunction.  
d. 
Macular edema 
e. 
Opportunistic infection or severe infection: tuberculosis, serious bacterial infections, 
systemic fungal infections, viral infections such as herpes infections (including herpes 
zoster and disseminated herpes simplex) and protozoal infections.  
f. 
Malignant neoplasm of skin 
All AEs of special interest specified in the protocol (see Section 7.5) have to be reported to 
sponsor and CRO, regardless of seriousness and relationship to the investigational product. 


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• 
For events conforming to the requirements of SAE, report according to expedited 
reporting procedures for SAE (see Section 8.2); 
• 
Regarding an event that does not meet the criteria for a SAE, it is only needed to be 
recorded in the eCRF. 
8.4. Follow up of subjects with adverse events/serious adverse events 
The investigator should closely monitor every subject experiencing an AE, including 
monitoring the clinical changes in the subjects. The investigator needs to proactively follow up 
each subject and provide sponsor and CRO with more detailed information about AE/SAE. 
During the study, all AEs/SAEs should be followed up until resolved, stabilized or returned to 
baseline status, unless the investigator believes that given the subject’s underlying condition, 
there is little hope that the AEs/SAEs will be resolved.  
8.5. Handling of abnormal laboratory test results 
If the laboratory test data is abnormal and cannot be explained, the test should be repeated 
immediately. If retest confirms that a result is abnormal and clinically significant, it should be 
recorded as an AE (except a decreased lymphocyte count, see Section 8.1 for details). 
8.6. Clinical laboratory parameters and abnormal laboratory test results 
Regarding major abnormal changes in laboratory parameters, which are judged by the 
investigator to be clinically significant, they will be recorded as AEs (except a decreased 
lymphocyte count, see section 8.1.1 for details). 
During treatment, both the total white blood cell count and the white blood cell classification 
data is blinded. 
If any of the following results are observed, the investigator will need to repeat the test: 
● 
Absolute lymphocyte count < 0.2 × 10 9/L 
● 
Absolute neutrophil count < 1.0 × 10 9/L 
● 
Total white blood cell count > 20 × 10 9/L 
If the value of the repeated test also exceeds the above numerical limit, the investigator should 
be informed of the abnormal results of the subject. 
If the absolute lymphocyte count or total white blood cell count is determined to be below an 
acceptable threshold, the medical monitor will contact the investigator responsible for 
treatment to ask him/her to closely monitor the event that may lead to serious infection and to 
follow up the subject appropriately. 


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If the absolute lymphocyte count is < 0.2 × 10 9/L, the subject should temporarily discontinue 
the investigational product. The absolute lymphocyte count should be retested every 3 days. If 
the retest result shows that the lymphocyte count rises to > 0.5 × 10 9/L, the investigator will be 
informed that the value is within the acceptable range, and the investigational product can be 
restarted (the statement of investigational product restart after interruption is shown in Section 
6.2). If the lymphocyte count could not return to at least 0.5 × 10 9/L after 2 weeks, the 
investigator should discuss with sponsor and the medical director of CRO whether subjects can 
continue participating in the study. 
Bradycardia 
The results of the completed phase I clinical trial showed that at clinically relevant dose levels, 
heart rate decrease was observed on the first two days of single and multiple dosing. This effect 
on heart rate was observed in other S1P1 modulators. Given that this is due to the mechanism 
of action of the drug, the AE of heart rate decrease (bradycardia) in this study is defined as a 
heart rate of <50 beats per minute in the awake state or a heart rate of ≥50 beats per minute in 
the awake state whereas subjects experience clinical symptoms due to a reduced heart rate (if 
subjects have a heart rate <50 beats per minute in the awake state and need clinical treatment, 
such condition is considered a grade II AE). In the completed Australian Phase I clinical study, 
it was defined that a heart rate of < 45 beats per minute in the awake state was required to be 
reported as an AE, and this adverse event does not serve as a criterion for termination of the 
trial/treatment. 
Reduction of peripheral blood lymphocyte count 
The results of the completed Australian Phase I clinical trial indicate that at clinically relevant 
dose levels, the drug may reduce the peripheral blood lymphocyte count, which is the efficacy 
indicator of the drug. It itself is not to be reported as an AE. However, clinical diagnosis related 
to a decreased lymphocyte count in peripheral blood indicates AE reporting (if no diagnosis is 
available, it is required to report related clinical symptoms or signs). 
Reduction of peripheral blood lymphocyte count 
A reduction in the peripheral blood lymphocyte count directly leads to a reduction in the WBC 
count. 
Note: In this study, heart rate decrease (bradycardia), a reduction in the peripheral blood 
lymphocyte count and a reduction in the peripheral WBC count (a reduction in the peripheral 
blood lymphocyte count directly leads to a reduction in the WBC count) are not considered as 
criteria for termination of the trial/treatment. 


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8.7. Treatment of overdose 
Overdose refers to the oral administration of the drug in any CBP-307 group at a dose higher 
than that required in the protocol. Any overdose, whether AEs occur or not, should be reported 
to sponsor/CRO. Because the effect of CBP-307 on the heart rate is directly related to the dose, 
subjects should be fully informed of the risks caused by an overdose, which should be 
contraindicated. If subjects experience an overdose in the study, they should immediately 
contact the investigator for an ECG test, heart rate monitoring and even emergency observation. 
Generally, an overdose event will not be recorded as an AE, but in cases where an overdose 
may be related to an AE, it should be recorded in the medical record and the AE/SAE page of 
eCRF. 
8.8. Pregnancy report 
Pregnancy in itself is not considered an AE/SAE unless it is suspected that the investigational 
product has affected the efficacy of a contraceptive. However, any adverse pregnancy outcome 
(e.g., stillbirth, spontaneous abortion, fetal malformation) is considered a SAE and needs to be 
reported in accordance with the requirements for SAE reporting. 
Within 24 hours after being informed of pregnancy of a subject or a subject's partner, the 
investigator should notify sponsor/CRO monitor and complete a pregnancy report form. 
Subjects should stop taking the investigational product immediately if pregnant. The 
investigator is required to follow up the outcome of the pregnancy and make records in the 
pregnancy report forms. 
9 DATA MANAGEMENT AND STATISTICAL ANALYSIS 
9.1. Data management 
In this study, the study data will be documented in the eCRF, and the data management solution 
will be provided by the CRO. 
9.2. Determination of sample size 
Approximately 134 subjects with moderate to severe UC will be randomized in the study. 
Among them, there are approximately 30 subjects in the CBP-307 0.1 mg once daily group. In 
protocol version 5.0 or earlier, 195 patients with moderate to severe UC were planned to be 
randomized at 1:1:1 into any of the following 3 groups: CBP-307 0.1 mg once daily, CBP-307 
0.2 mg once daily, placebo. Approximately 65 subjects were planned to be in each group. 
However, protocol amendment happens during the treatment period. The primary endpoint 
analysis is based on the comparison between the 0.2 mg CBP-307 group and the placebo group, 


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and protocol version 6.0 keeps only these two groups, and sample size is re-calculated. The 0.1 
mg group is not applicable in protocol version 6.0, and there will be no further subjects enrolled 
in the 0.1 mg group. The 30 subjects already randomized with protocol version 5.0 or earlier 
are kept and analyzed for exploratory purpose. 
The sample size re-calculation is based on the comparison between CBP-307 0.2 mg once daily 
group and placebo group on the primary efficacy endpoint, namely the change in adapted Mayo 
score from baseline at week 12 after treatment. Assuming that the difference between the 0.2 
mg group and the placebo group of the change from baseline at week 12 after treatment in 
adapted Mayo score is 1.2, and the common standard deviation is 2.0, a significance level of 
α=0.05 (two-sided), and a dropout rate is 15%, then each group needs to enroll at least 52 
subjects (104 subjects in two groups) to provide a power of 80% to detect the difference 
between the 0.2 mg group and the placebo group on the primary efficacy endpoint. Based on 
this estimation, the eligible subjects with moderate to severe UC will be randomized at 1:1 into 
CBP-307 0.2 mg once daily group or placebo group until 52 subjects are enrolled into each 
group. 
9.3. Statistical analysis plan 
Details of the statistical methods will be provided in the statistical analysis plan (SAP) 
according to the study protocol. 
Statistical analysis will be conducted using SAS® 9.4 or higher version (SAS Institute Inc., 
Cary, NC, USA). 
9.4. Randomization 
Subjects meeting all inclusion/exclusion criteria will be randomized into the study stage 1 and 
stratified according to whether the previous treatment with a tumor necrosis factor (TNF)-α 
antagonist failed. Sub-study 1 of the study stage 2 will include subjects who have achieved 
clinical response to 12-week induction therapy in study stage 1 as shown by efficacy evaluation 
and meet eligibility criteria for the study stage 2: they will undergo blinded maintenance 
treatment with the regimen used during the stage 1. Sub-study 2 of the study stage 2 will include 
subjects who have no clinical response to induction therapy in the stage 1 and meet eligibility 
criteria for the study stage 2: they will undergo open-label treatment with CBP-307 0.2 mg 
once daily. 
9.5. Analysis population 
Statistical analysis will include the following populations: 


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Stage 1 analysis populations 
All Subjects Screened in stage 1: The all subjects screened set will contain all subjects who 
signed informed consent for stage 1. 
All Randomized Set in stage 1: The all randomized set will contain all subjects who are 
randomized into stage 1, no matter treated or not. 
Full Analysis Set (FAS) in stage 1: The FAS will contain all randomized subjects who receive 
at least 1 dose of study medication or placebo in stage 1. FAS will be based on the planned 
drug taken.  
Per-Protocol Set (PPS) in stage 1: The PPS will contain a subset of FAS subjects who do not 
have major protocol deviation in stage 1. 
Safety Set (SS) in stage 1: The SS will contain all randomized subjects who receive at least 
1 dose of study medication or placebo. SS will be based on the actual drug taken. 
PK analysis set: The PK analysis set will include all subjects who has both baseline and post-
baseline PK evaluation. 
Stage 2 analysis populations 
All Subjects Screened in stage 2: The all subjects screened will contain all subjects who signed 
informed consent for stage 2. 
Full Analysis Set (FAS) in stage 2: The FAS will contain all screened subjects who receive at 
least 1 dose of study medication or placebo in stage 2. FAS will be based on the planned drug 
taken. 
Per-Protocol Set (PPS) in stage 2: The PPS will contain a subset of FAS subjects who do not 
have major protocol violation in stage 2. 
Safety Set (SS) in stage 2: The SS will contain all randomized subjects who receive at least 
1 dose of study medication or placebo in stage 2. SS will be based on the actual drug taken. 
Efficacy analysis will be performed in the FAS and PPS according to treatment assignment. 
Safety analysis will be performed based on the SS. According to the SAP, data locking and 
primary analysis methods will be predefined by project statisticians (summarizing results in a 
blinded fashion). 


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9.6. Demographic and baseline data 
Demographic data and baseline data will be summarized. 
9.7. Subjects treatment 
The subject treatment should be summarized. 
9.8. Efficacy analysis 
9.8.1. Study endpoints 
Primary study endpoint  
The primary efficacy analysis is based on the primary efficacy endpoint: change in adapted 
Mayo score from baseline at week 12 compared between CBP-307 0.2 mg and placebo. 
Secondary study endpoints 
The secondary efficacy endpoints include: 
● 
Change in adapted Mayo score from baseline at week 12 compared between CBP-307 
0.1 mg and placebo 
● 
Change in complete Mayo score from baseline at week 12 after treatment 
● 
Comparison of clinical response rate at week 12 by adapted Mayo score (defined as a 
decrease of ≥ 2 points and at least 30% from baseline, accompanied with a decrease of ≥ 
1 point from baseline in the rectal bleeding subscore or an absolute rectal bleeding 
subscore of ≤ 1 point) 
● 
Comparison of clinical response rate at week 12 by complete Mayo score (defined as a 
decrease of ≥ 3 points and at least 30% from baseline, accompanied with a decrease of ≥ 
1 point from baseline in the rectal bleeding subscore or an absolute rectal bleeding 
subscore of ≤ 1 point) 
● 
Comparison of clinical remission rate at week 12 by adapted Mayo score (defined as a 
rectal bleeding subscore = 0 and stool frequency sub score ≤ 1, with an Endoscopy 
subscore ≤ 1 [excluding friability]) 
● 
Comparison of clinical remission rate at week 12 by complete Mayo score (defined as a 
total Mayo score of ≤ 2 points with no individual subscore > 1 point) 
● 
Mucosal healing rate at week 12 after treatment (mucosal healing is defined as Mayo 
endoscopic subscore ≤ 1) 
Exploratory study endpoint  
Exploratory endpoints include: 
● 
Changes in the total IBDQ score and subscore from baseline at week 12 after treatment 
(in study stage 1), at week 24, and week 48 (in study stage 2) after treatment 
● 
To explore the following efficacy endpoints in subjects with moderately to severely 
active UC who respond after 12 weeks of induction therapy in study stage 1: 
o 
Percentage of subjects who maintain clinical response at week 48  


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o 
Percentage of subjects who achieve clinical remission at week 48 
o 
Percentage of subjects who achieve mucosal healing under endoscope at week 48  
o 
Percentage of subjects who take corticosteroids orally at baseline and discontinue 
the treatment with corticosteroids at week 48 and achieve clinical remission. 
o 
Change in the complete Mayo score at week 48 from baseline 
o 
Change in the adapted Mayo score at week 48 from baseline 
● 
To explore the following efficacy endpoints in 
subjects with moderately to severely active UC who do not achieve response after 12 weeks 
of induction therapy in study stage 1: 
o 
Percentage of subjects who achieve clinical response at week 24 (at week 12 after 
treatment in sub-study 2 of study stage 2)  
o 
Percentage of subjects who achieve clinical remission at week 24 (at week 12 after 
treatment in sub-study 2)  
o 
Percentage of subjects who achieve mucosal healing under endoscope at week 24 
(at week 12 after treatment in sub-study 2) 
o 
Change in the complete Mayo score at week 24 (at week 12 after treatment in sub-
study 2) from week 12 
o 
Change in the adapted Mayo score at week 24 (at week 12 after treatment in sub-
study 2) from week 12 
o 
Percentage of subjects who maintain clinical response at week 48 (at week 36 after 
treatment in sub-study 2) (i.e., have clinical response at both week 24 and week 48) 
o 
Percentage of subjects who achieve clinical remission at week 48 (at week 36 after 
treatment in sub-study 2) 
o 
Percentage of subjects who achieve mucosal healing under endoscope at week 48 
(at week 36 after treatment in sub-study 2) 
o 
Change in the complete Mayo score at week 48 (at week 36 after treatment in sub-
study 2) from week 12 
o 
Change in the adapted Mayo score at week 48 (at week 36 after treatment in sub-
study 2) from week 12 
9.8.2. Efficacy analysis 
9.8.2.1 Analysis for primary study endpoints 
The primary efficacy analysis will be based on FAS and PPS. The primary efficacy analysis 
will be performed after all subjects complete (or possibly complete) the treatment with the 
investigational product. 
The covariance (ANCOVA) model with baseline as covariate will be used to analyze the 
changes in adapted Mayo score from baseline at week 12 between the CBP-307 0.2 mg group 
and the placebo group stratified by whether the previous treatment with a tumor necrosis factor 
(TNF)-α antagonist failed (Yes or No). The superiority of the CBP-307 0.2 mg group to placebo 
on change in adapted Mayo score from baseline at week 12 after treatment will be tested at a 


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significance level of 0.025 with one-sided. If the significance level is reached, then superiority 
of the CBP-307 0.2 mg will be statistically significant. 
9.8.2.2 Analysis for secondary study endpoints 
For all categorical secondary efficacy endpoints, their statistical summaries need to be made 
based on the treatment group: number of cases, percentage, and 95% confidence interval. The 
stratified Cochran-Mantel-Haenszel (CMH) χ2 test will be used with a 95% confidence interval 
for the difference in each category of rates. 
For the quantitative secondary efficacy endpoints, the statistical method is similar to that for 
primary efficacy endpoint. 
All secondary efficacy analyses will be performed between treatment groups (0.2 mg, 0.1 mg) 
and placebo and based on FAS and PPS. All results of these comparative analyses are used for 
exploratory purpose. More details of analyses are provided in the SAP. 
9.8.2.3 Analysis of exploratory study endpoints 
The content about exploratory analysis will be detailed in SAP. 
9.9. Pharmacokinetic analysis 
PK data will be analyzed using PK analysis set based on individual CBP-307 concentration-
time curve data collected to PK (Section 9.5). 
Listing and descriptive statistics will be used to summarize the CBP-307 individual plasma 
concentration at each sampling point, including arithmetic mean, minimum, median, maximum, 
standard deviation, coefficient of variation. Moreover, scatter plot (linear/semilog) will be 
provided for the CBP-307 plasma concentration at each sampling point. In addition, descriptive 
statistics of concentration of blood medicine valley (Cmin) will be performed by arithmetic 
mean, geometric mean, median, reference range, standard deviation and coefficient of variation. 
Details will be provided in the statistical analysis plan (SAP). If other PK parameters have to 
be calculated, details will also be provided in SAP. 
In cases where the data are sufficient, a population pharmacokinetic (PopPK) analysis of the 
plasma concentration-time profile of CBP-307 will be performed based on existing data from 
other clinical trials. In addition, the PK parameters of CBP-307, such as the apparent clearance 
and apparent volume of distribution, will be estimated using a model. If a PopPK analysis can 
be performed, more details will be specified in PopPK SAP, and the analysis results will be 
described in a separate report. 


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9.10. Pharmacodynamics and biomarker analysis  
Exploratory analysis on dose-effect relationship of exposure quantity (dose) and safety of CBP-
307, efficacy and pharmacodynamics is performed for the first time. The relationship between 
CBP-307’s efficacy and the changes in the following indicators will be evaluated: 
● 
Absolute lymphocyte count 
● 
Total Igs: IgA, IgG, IgM 
● 
CRP 
● 
Fecal calprotectin 
In cases where the data are sufficient, an exploratory PK/PD analysis will be conducted for the 
relation between the exposure to CBP-307 and indicators of its efficacy (such as a change in 
the absolute lymphocyte count from baseline). The studies will be described in SAP. 
9.11. Safety analysis 
AEs will be summarized based on their severity and their relationship to the investigational 
product. SAEs will be recorded. The incidence of each event will be summarized. If the same 
subject experiences the same AEs more than once, only the worst-case severity will be counted. 
When an event related to the investigational product occurs, it is only recorded once. 
Laboratory data, vital signs, ECG, and pulmonary function tests data are listed in the summary 
table. 
9.12. Missing data 
For the analysis based on FAS for the quantitative efficacy endpoints, the Last Observation 
Carried Forward (LOCF) imputation will be applied for missing data. For the analysis based 
on PPS for these endpoints, no imputation will be applied for missing data. 
In the trial, the endoscopic score of the clinical center will be used as the Mayo score to assess 
clinical efficacy. The endoscopic score read by the investigator will be used as the SES-CD 
score in the event of loss of data from one major endoscope. 
For all secondary categorical efficacy endpoints, subjects who have no data at a specific time 
point will be considered as non-responders. 
The effect of missing data on the efficacy evaluation results will be studied through the 
sensitivity analysis of the primary and secondary efficacy indicators, including completed 
events, observed events, and multiple model-based analysis. 
Methods for calculating some or all missing data regarding time will be explained in SAP. 


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9.13. Interim analysis 
One interim analysis will take place for this study once all the subjects have completed week 12 
(visit 11, last dose/early discontinue visit) in stage 1, the unblinded study team will carry out 
the analysis on primary efficacy endpoint after database lock. The primary efficacy endpoint is 
the change in adapted Mayo score from baseline at week 12 compared between CBP-307 
0.2 mg and placebo in stage 1 while the stage 2 analysis will be exploratory, and no α reserved 
for stage 2. Exclusive of primary efficacy analysis in stage 1, all other comparative analysis 
results of the treatment groups and the placebo group are used for exploratory purpose. 
9.14. Independent Data Monitoring Committee 
The Independent Data Monitoring Committee (IDMC) will be responsible for monitoring data 
of this study, including the main aspects of the study implementation process. 
The IDMC will meet regularly during the study trial to monitor enrollment of subjects into the 
treatment groups, treatment compliance, compliance with follow-up plans, and safety data of 
the study. It may propose to amend or terminate the study based on the safety concerns during 
study data review. It will also review the primary efficacy indicators and give recommendations 
based on efficacy results and safety. 
The double-blinded plan of this study will be clearly clarified to the IDMC to ensure that 
relevant information is blinded to sponsor and study personnel. 
10 DATA QUALITY ASSURANCE 
The investigator is responsible for verifying that data entries are accurate and correct by 
physically or electronically signing the CRF. The investigator must maintain accurate 
documentation (source data) that supports the information entered in the CRF. Sponsor has the 
obligation of ethical, legal and scientific to carry out this study in accordance with the 
established clinical trial protocol, GCP and ICH-GCP guidelines. In order to fulfill these 
obligations and achieve study progress, in addition to ensuring telephone and written 
communication, sponsor's monitor or representative will visit the study site throughout the 
study. Sponsor's monitor or representative will conduct site monitoring visit, making calls, and 
do regular eCRF review, to evaluate subject enrollment, study protocol compliance, and 
integrity and accuracy of data entered into EDC system, and conduct source data verification 
and AE checking according to the original documents. Investigator must provide the monitor 
with all resources and study documents. 


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10.1. Electronic case report form 
The eCRF will be used to save and record subject information. Sponsor or other representative 
will provide the file structure and format of the eCRF and record according to the 
corresponding rules. 
The investigator should review, sign and date the eCRF. 
The eCRF access permission should be strictly protected and should be provided to only those 
directly involved in the study. The study data should be entered into the eCRF by qualified 
personnel or study coordinators. After study assessments, relevant information should be 
recorded into the eCRF as soon as possible. If data needs to be modified due to entry errors or 
any other reasons, there will be a corresponding electronic audit trail. The monitoring agency 
and other regulatory departments must have access to the eCRF and the computer where the 
eCRF is saved. 
10.2. Data collection 
At each visit, the study site will record all important observations of each subject. These records 
should contain at least the visit date time and the scheduled visit time on the study flow sheet 
(e.g., at screening, day 0, etc.); the overall status and important indicators of the subjects, 
including any important medical findings; severity, frequency, duration and coping methods of 
the reported AEs, and information whether these events are judged by the investigator as a 
drug-related AE; concomitant medications or dose changes; main reference for completion of 
procedures; and signature and date of medical data recording by all physicians. 
In addition, any agreement to provide important clinical information, reached by telephone or 
other means, will also be recorded in the medical records (progress notes) as described above. 
The information recorded on the medical records (progress notes) and other original documents 
will be entered into the eCRF. 
Modifications to the medical records (progress notes), eCRF, and other original documents 
should be signed & dated by the investigator or appointee. If there is no significant reason for 
these modifications, an explanation should be attached to these modifications. 
10.3. Monitoring and source data review 
The monitor designated by sponsor will conduct regular on-site monitoring of the study site to 


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monitor all aspects of the clinical trial. If required, the investigator must agree to give the 
personnel authorized by sponsor a direct access to clinical (or related) documents clinical trial 
supplies (drug distribution & storage areas) to validate data entered in the eCRF.  
In addition to monitoring visits, the monitor will make frequent communications (by letter, 
phone and fax) to ensure that the study is carried out according to the protocol design and 
regulatory requirements. 
Monitoring will be carried out as determined by the risk assessment process conducted on the 
study. 
10.4. Audit and inspection 
Domestic and foreign regulatory agencies, ethic committees, and auditor/inspector authorized 
by sponsor may request direct access to all original documents, case report forms and other 
study documents for on-site audits or inspections. The investigator must ensure 
auditor/inspector direct access to these documents and support audits or inspections at any time. 
During audits or inspections, if the subject name has been blacked out to make it confidential, 
it will be allowed to copy medical records and other study documents. 
The audits or inspections are made to assess whether the clinical trial meets ethical, regulatory 
and quality requirements. 
10.5. Storage of original documents and records 
The original documents include the original observation records and the clinical study results. 
The original documents include but are not limited to medical records (progress notes), 
computer printouts, screening logs, and data recorded by automated instruments. 
The investigator cannot destroy any study records unless he/she obtains the written approval 
from sponsor. 
Study records must be saved in accordance with the ICH-GCP and local guidelines. All 
necessary documents, including subject records, original documents, eCRF, and certificates 
about storage of the investigational product, will be archived. Source documents should be 
retained for at least 2 years after obtainment of the last approval for marketing in the ICH 
regions and until no pending or anticipated application for marketing in the ICH regions; or at 
least 2 years after the clinical development of the investigational product is officially stopped, 
however, sponsor may request an extension of the retention period due to international 
regulations or country-specific requirements. 
11 TRIAL MANAGEMENT 


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11.1. Protocol compliance or deviations 
The dosing date and time of investigational product and any deviations from any protocol 
procedure need to be recorded in the subject's eCRF. 
11.2. Publication policy 
The investigator can work with sponsor to make preparation for the publication of the study 
related content after the study is completed. Without written consent from sponsor, the 
investigator must ensure that no data of the study is published. 
11.3. Clinical study report 
The final clinical study report will be prepared according to the ICH guidelines. The report 
submitted to each regulatory authority should comply to the language and format requirements 
of that regulatory authority. The final study report must be prepared no matter whether the 
study is completed or prematurely terminated. Sponsor will provide each investigator with a 
final study report for archiving. 
11.4. Contract and financial details 
Prior to the beginning of the study, the investigator must disclose to sponsor any property right 
or financial interest he/she has related to the investigational product or sponsor’s company, as 
shown in the financial disclosure form provided by sponsor. The investigator must agree to 
update this information if significant changes occur during the study or within 1 year after 
study ended. The investigator also must agree that sponsor can submit this financial 
information to a domestic or foreign regulatory agency to apply for a marketing approval if 
required by laws or regulations. 
If required by regulations, sponsor will also submit the financial arrangements for the study to 
the regulatory agencies. 
Co-investigators who are authorized by the investigator to perform important study 
responsibilities should provide similar information. 
11.5. Insurance, compensation and remuneration 
The provisions on responsibilities and insurance of this study are given in a separate agreement. 
Sponsor has already signed an insurance contract, whose terms and conditions involve 
compensation for injuries that the subjects suffer from in this study that is executed in strict 
accordance with the study protocol and applicable laws and professional standards. 


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11.6. Clinical trial termination 
Sponsor has the right to terminate the study. In view of assurance of the subject’s best interests 
and medical & ethical considerations, the study can be prematurely terminated at any time, 
with the consent from the investigator and sponsor. When the study is terminated, sponsor, 
CRO, and the investigator will ensure that the subject’s interests are protected. 
11.7. Management of study site documents 
The investigator is responsible for the management of investigator site file. The investigator 
site file include but not limited to, Investigator’s Brochure, eCRF (sample form), clinical study 
agreement (signed), clinical study-related normal values for lab tests, shipping orders for the 
investigational product and study-related materials, updates to Investigator’s Brochure, updates 
to normal values for medical or lab tests or operations, mid-term or annual reports, investigator 
signature samples, and other documents (updates to the protocol, eCRF, ICF, written 
notifications). 
12 REFERENCES 
1. 
Loftus EV, Jr. Clinical epidemiology of inflammatory bowel disease: Incidence, 
prevalence, and environmental influences. Gastroenterology 2004; 126 (6): 150417. 2. 2.  
2. 
Shivananda S, Lennard-Jones J, Logan R, Fear N, Price A, Carpenter L, et al. Incidence 
of inflammatory bowel disease across Europe: is there a difference between north and 
south? Results of the European Collaborative Study on Inflammatory Bowel Disease 
(EC-IBD). Gut 1996; 39 (5): 690-7. 
3. 
Trallori G, Palli D, Saieva C, Bardazzi G, Bonanomi AG, d'Albasio G, et al. A 
population-based study of inflammatory bowel disease in Florence over 15 years (1978-
92). Scand J Gastroenterol 1996; 31 (9): 892-9.  
4. 
Asakura K, Nishiwaki Y, Inoue N, Hibi T, Watanabe M, Takebayashi T. Prevalence of 
ulcerative colitis and Crohn's disease in Japan.J Gastroenterol 2009; 44 (7): 659-65.  
5. 
Zheng JJ, Zhu XS, Huangfu Z, et al.  Prevalence and incidence rates of Crohn's disease 
in mainland China: A meta-analysis of 55 years of research. J Dig Dis, 2010, 11: 161-
166. 
6. 
Wang YF, Ouyang Q, Hu Rw. Progression of inflammatory bowel disease in China. J 
Dig Dis, 2010, 11: 76-82. 
7. 
Ouyang Q, Tangdon R, Goh KL, Pan GZ, Fock KM, Fiocchi C, et al. Management 


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consensus of inflammatory bowel disease for the Asia-Pacific region. J Gastroenterol 
Hepatol 2006: 21 (12): 1772-82. 
8. 
Leong RW, Lau JY, Sung JJ. The epidemiology and phonotype of Crohn’s disease in the 
Chinese population. Inflamm Bowel Dis 2004; 10(5):646-51. 
9. 
Kandiel A, Fraser AG, Korelitz BI, Brensinger C, Lewis JD. Increased risk of lymphoma 
among inflammatory bowel disease patients treated with azathioprine and 6-
mercaptopurine. Gut 2005; 54 (8): 1121-5. 
10. 
Hanauer SB, Feagan BG, Lichtenstein GR. Maintenance infliximab for Crohn's disease: 
the ACCENT I randomised trial. Lancet 2002; 359(9317):1541-9. 
11. 
Colombel JF, Sandborn WJ, Rutgeerts P, Adalimumab for maintenance of clinical 
response and remission in patients with Crohn's disease: the CHARM trial. 
Gastroenterology 2007;132(1):52-65. 
12. 
Remicade (infliximab) 100 mg powder for concentrate for solution for infusion. 
Summary of Product Characteristics.Leiden, The Netherlands: Janssen Biologics B.V., 
06 August 2013.  
13. 
Humira 
(adalimumab) 
injection, 
for 
subcutaneous 
use. 
Full 
Prescribing 
Information.North Chicago, IL: AbbVie Inc., Revised May 2013. 
14. 
Investigator’s Brochure, CBP-307: A Class 1.1 New Drug for Treatment of Autoimmune 
Diseases; Version 1.0; April 19, 2017. 


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13 ANNEXES 
ANNEX 1 INFLAMMATORY BOWEL DISEASE QUESTIONNAIRE (IBDQ) 
 


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ANNEX 2: AMENDMENTS TO THE STUDY PROTOCOL 
 
Version No. 
Version Date 
2.0 
19 Apr 2018 
3.0 
24 Jul 2018 
3.1 
17 Sep 2018 
4.0 
10 Apr 2019 
5.0 
17 Dec 2019 
6.0 
25 Dec 2020 
 


Protocol Amendment (Study Level) - Version 6 - 05-Jan-2021
Electronic Signature Manifestation
This page is a manifestation of the electronic signature(s) used in compliance with the organization's
electronic signature policies and procedures.
Page 130 - Object 1000551A00000000320BD885
Signer Full Name
Meaning of Signature
Date and Time
Boran Zheng
Document Approval (I certify that I have
the education, training and experience to
perform this task)
05 Jan 2021 07:27:50 UTC

SAP_001.pdf: 
PROTOCOL CBP-307CN002 
Statistical Analysis Plan 
Page 1 of 68 
Document: 
Statistical Analysis Plan 
Author: 
Boran Zheng 
Version Number: 
1.1 
Version Date: 
18Jan2023 
Template No.:  CS_TP_BS016 Revision 5 
Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
Statistical Analysis Plan 
CBP-307CN002 
Multicenter, randomized, double-blind, placebo-controlled phase II 
clinical trial to evaluate the effectiveness and safety of CBP-307 in 
subjects with moderate to severe ulcerative colitis (UC) 
AUTHOR: BORAN ZHENG 
VERSION NUMBER AND DATE: V1.1, 18JAN2023 
NCT04700449


PROTOCOL CBP-307CN002 
 
Statistical Analysis Plan 
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Document: 
Statistical Analysis Plan 
Author: 
Boran Zheng 
Version Number: 
1.1 
 
Version Date:  
18Jan2023 
Template No.:  CS_TP_BS016 Revision 5 
Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
Statistical Analysis Plan V1.1 (Dated 18Jan2023) for Protocol CBP-307CN002 V6.0 (Dated 
25Dec2020). 
 
Name 
Signature 
Date 
Author: 
Boran Zheng 
 
 
 
Position: 
Biostatistician 2 
 
Company: 
IQVIA 
 
Upon review of this document, the undersigned approves this version of the Statistical Analysis 
Plan, authorizing that the content is acceptable for the reporting of this study. 
 
 
Name 
Signature 
Date 
Approved By: 
Aiqin Zhang 
 
 
 
Position: 
Statistical Scientist 
 
Company: 
IQVIA 
 
Approved By: 
Jang Yun 
 
 
 
Position: 
Senior Director, Biostatistics 
 
Company: 
Suzhou Connect Biopharmaceuticals, Ltd. 
 
 
 
 


PROTOCOL CBP-307CN002 
 
Statistical Analysis Plan 
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Document: 
Statistical Analysis Plan 
Author: 
Boran Zheng 
Version Number: 
1.1 
 
Version Date:  
18Jan2023 
Template No.:  CS_TP_BS016 Revision 5 
Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
Output Templates Signature Page 
Output Templates V1.1 (Dated 18Jan2023) for Protocol CBP-307CN002 V6.0 (Dated 
25Dec2020). 
 
 
Name 
Signature 
Date 
Author: 
Boran Zheng 
 
 
 
Position: 
Biostatistician 2 
 
Company: 
IQVIA 
 
Upon review of this document, the undersigned approves this version of the Output Templates, 
authorizing that the content is acceptable for the reporting of this study. 
 
 
Name 
Signature 
Date 
Approved By: 
Aiqin Zhang 
 
 
 
Position: 
Statistical Scientist 
 
Company: 
IQVIA 
 
Approved By: 
Jang Yun 
 
 
 
Position: 
Senior Director, Biostatistics 
 
Company: 
Suzhou Connect Biopharmaceuticals, Ltd. 


PROTOCOL CBP-307CN002 
 
Statistical Analysis Plan 
Page 4 of 68 
 
Document: 
Statistical Analysis Plan 
Author: 
Boran Zheng 
Version Number: 
1.1 
 
Version Date:  
18Jan2023 
Template No.:  CS_TP_BS016 Revision 5 
Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
MODIFICATION HISTORY 
 
Unique 
Identifier for 
this Version 
Date of the 
Document 
Version 
Author 
Significant Changes from  
Previous Authorized Version 
1.0 
15FEB2022 
Boran Zheng 
Not Applicable – First Version 
1.1 
18Jan2033 
Boran Zheng 
Add definition of per-protocol set and 
0.2mg only analysis sets 
 
 


PROTOCOL CBP-307CN002 
 
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Document: 
Statistical Analysis Plan 
Author: 
Boran Zheng 
Version Number: 
1.1 
 
Version Date:  
18Jan2023 
Template No.:  CS_TP_BS016 Revision 5 
Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
Contents 
1. 
Introduction 
13 
2. 
Study Objectives 
13 
2.1. 
Primary Objective 
13 
2.2. 
Secondary Objectives 
13 
2.3. 
Exploratory Objectives 
14 
3. 
Study Design 
14 
3.1. 
General Description 
14 
3.2. 
Schedule of Events 
18 
3.3. 
Changes from Protocol 
18 
4. 
Planned Analyses 
20 
4.1. 
Data Monitoring Committee (DMC) 
20 
4.2. 
Interim Analysis (Primary Analysis) 
20 
4.3. 
Final Analysis 
22 
5. 
Analysis Population 
22 
5.1. 
Stage 1 Population 
22 
5.2. 
Stage 2 Population 
24 
5.3. 
All Stages (0.2mg only) Population 
25 
6. 
General Considerations 
25 


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Author: 
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Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
6.1. 
Reference Start Date and Study Day 
26 
6.2. 
Baseline 
27 
6.3. 
Retests, Unscheduled Visits 
27 
6.4. 
Common Calculations 
28 
6.5. 
Software Version 
28 
7. 
Statistical Considerations 
28 
7.1. 
Multicenter Studies 
28 
7.2. 
Missing data 
28 
7.3. 
Subgroup Analyses 
28 
7.4. 
Sample Size 
29 
8. 
Disposition and Withdrawals 
29 
9. 
Demographic and Other Baseline Characteristics 
32 
10. 
Medical History 
33 
11. 
Medications and Procedures 
34 
12. 
Study Medication Exposure 
36 
13. 
Study Medication Compliance 
39 
14. 
Efficacy Outcomes 
39 
14.1. 
Efficacy Assessment 
39 
14.2. 
Primary Efficacy 
41 


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Effective Date: 01Apr2018 
 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
14.2.1. 
Primary Efficacy endpoint 
41 
14.2.2. 
Primary Analysis of Primary Efficacy Endpoint 
42 
14.2.3. 
Missing Imputation for Primary Efficacy 
42 
14.2.4. 
Sensitivity Analysis of Primary Efficacy 
44 
14.3. 
Secondary Efficacy 
44 
14.3.1. 
Secondary analyses on Efficacy endpoints 
44 
14.3.2. 
Missing Data Methods for Secondary Efficacy Variables 
45 
14.3.3. 
Analysis of Secondary Efficacy Variables 
46 
14.4. 
Exploratory Efficacy 
47 
14.4.1. 
Exploratory Efficacy Variable & Derivations 
47 
14.4.2. 
Analysis of Exploratory Efficacy Variables 
50 
15. 
Safety Analyses 
51 
15.1. 
Adverse Events 
51 
15.1.1. 
All TEAEs 
53 
15.1.1.1. Severity 
53 
15.1.1.2. Relationship to Study Medication 
53 
15.1.2. 
TEAEs Leading to Discontinuation of Study Medication 
53 
15.1.3. 
Serious Adverse Events 
53 
15.1.4. 
Adverse Events Leading to Death 
54 


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Effective Date: 01Apr2018 
 
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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
15.1.5. 
Adverse Events Of Special Interest 
54 
15.2. 
Deaths 
54 
15.3. 
Laboratory Evaluations 
55 
15.4. 
ECG Evaluations 
58 
15.4.1. 
ECG Markedly Abnormal Criteria 
59 
15.5. 
Vital Signs 
59 
15.6. 
Physical Examination 
61 
15.7. 
Other Safety Assessments 
61 
15.7.1. 
Pulmonary Function Test 
61 
15.7.2. 
Ophthalmologic Examination 
62 
15.7.3. 
Optical Coherence Tomography 
62 
15.7.4. 
Dermatologic Examination 
62 
15.7.5. 
Pregnancy Test 
62 
15.7.6. 
Chest Imaging Examination 
62 
16. 
References 
63 
APPENDIX 1. 
Programming Conventions for Outputs 
64 
IQVIA Output Conventions 
64 
Spelling Format 
64 
Presentation of Treatment Groups 
64 


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Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
Presentation of Visits 
64 
Listings will be ordered by the following (unless otherwise indicated in the template): 
66 
APPENDIX 2. 
Listing of Efficacy Parameters and Study Populations Analysed in Stage 1 
67 
 
 
 
 
 


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Effective Date: 01Apr2018 
 
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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
Abbreviations 
 Abbreviation 
Meaning 
AE 
Adverse event 
ALC 
Absolute lymphocyte count 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
ANC 
Absolute neutrophil count 
AST 
Aspartate aminotransferase 
BLQ 
Below the lower limit of quantification 
BMI 
Body mass index 
CI 
Confidence interval 
CMH 
Cochran-Mantel-Haenszel 
CRP 
C-reactive protein 
CS 
Clinically Significant 
CTCAE 
Common terminology criteria for adverse events 
DBP 
Diastolic Blood Pressure 
DLCO 
Diffusing capacity of the lung for carbon monoxide 
DMC 
Data monitoring committee 
ECG 
Electrocardiogram 
eCRF 
Electronic case report form 
EMA 
European Medicines Agency 
FAS 
Full analysis set 
FCS 
Fully Conditional Specification 
FEV1 
Forced expiratory volume in 1 second 
FVC 
Forced vital capacity 
HBcAb 
Hepatitis B core antibody 
HBsAb 
Hepatitis B surface antibody 
HBsAg 
Hepatitis B surface antigen 
HBV 
Hepatitis B virus 
HCV 
Hepatitis C virus 


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Document: 
Statistical Analysis Plan 
Author: 
Boran Zheng 
Version Number: 
1.1 
 
Version Date:  
18Jan2023 
Template No.:  CS_TP_BS016 Revision 5 
Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
HIV 
Human immunodeficiency virus 
HR 
Heart Rate 
IBDQ 
Inflammatory bowel disease questionnaire 
ICH 
International Conference on Harmonization 
Ig 
Immunoglobulin 
LOCF 
Last observation carried forward 
LSMEANS 
Least square mean 
MAR 
Missing at Random 
MCMC 
Markov Chain Monte Carlo 
MedDRA 
Medical Dictionary for Regulatory Activities 
mFAS 
Modified Full Analysis Set 
MI 
Multiple Imputation 
MNAR 
Missing Not at Random 
n 
Number of subjects 
NCS 
Not Clinically Significant  
NE 
Not Evaluable 
NRI 
Non Responder Imputation 
OCT 
Optical coherence tomography 
PD 
Pharmacodynamics 
PFT 
Pulmonary Function Test 
PK 
Pharmacokinetics 
PPS 
Per protocol set 
PT 
Preferred term 
Q1 
First quartile 
Q3 
Third quartile 
QD 
Once a day 
QTcF 
Fridericia’s corrected QT interval 
RR 
Respiratory Rate 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 


PROTOCOL CBP-307CN002 
 
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Document: 
Statistical Analysis Plan 
Author: 
Boran Zheng 
Version Number: 
1.1 
 
Version Date:  
18Jan2023 
Template No.:  CS_TP_BS016 Revision 5 
Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
SBP 
Systolic Blood Pressure 
SD 
Standard deviation 
SE 
Standard error 
SOC 
System organ class 
SS 
Safety set 
TEAE 
Treatment-emergent adverse event 
TNF 
Tumor necrosis factor 
UC 
Ulcerative colitis 
VZV 
Varicella zoster virus 
WBC 
White blood cell count 
WHO 
World Health Organization 
 
 
 


PROTOCOL CBP-307CN002 
 
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Document: 
Statistical Analysis Plan 
Author: 
Boran Zheng 
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Version Date:  
18Jan2023 
Template No.:  CS_TP_BS016 Revision 5 
Reference:  CS_WI_BS005 
Effective Date: 01Apr2018 
 
Copyright © 2009, 2010, 2012, 2016, 2018 IQVIA. All rights reserved. The contents of this document are confidential and proprietary 
to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
1. INTRODUCTION 
This document describes the rules and conventions to be used in the presentation and analysis of 
efficacy and safety data for Protocol CBP-307CN002. It describes the data to be summarized and 
analyzed, including the specific statistical analyses to be performed. The Pharmacokinetics 
(PK)/Pharmacodynamics (PD) will be performed by the third-party vendor. A separate analysis 
plan will be provided for PK/PD analysis by the third-party vendor. 
This statistical analysis plan (SAP) is based on protocol version 6.0, dated 25Dec2020. Protocol 
version 5.0, dated 17Dec2019, will be also mentioned. 
2. STUDY OBJECTIVES 
2.1. 
PRIMARY OBJECTIVE 
To compare clinical efficacy of CBP-307 vs placebo by evaluating the change of adapted Mayo 
score after 12 consecutive weeks treatment in subjects with moderate to severe UC. 
2.2. 
SECONDARY OBJECTIVES 
The secondary objectives are: 
• To compare clinical efficacy of CBP-307 vs placebo by evaluating the clinical response 
rate, clinical remission rate and mucosal healing rate after 12 consecutive weeks 
treatment in subjects with moderate to severe UC 
• To compare the clinical safety and tolerability of CBP-307 with those of placebo 
administered for 12 weeks in subjects with moderate to severe UC 


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2.3. 
EXPLORATORY OBJECTIVES 
The exploratory objectives are: 
• To evaluate the PK/PD of CBP-307 orally administered in subjects with moderate to 
severe UC in study stage 1 
• To evaluate inflammatory bowel disease questionnaire (IBDQ) in study stage 1 and stage 
2 
• To evaluate the safety and tolerability of CBP-307 after medium or long-term 
administration (in study stage 2) in subjects with moderate to severe UC 
• To evaluate clinical remission, clinical response and mucosal healing in subjects with 
moderately to severely active UC who respond after 12 weeks of induction therapy in the 
stage 1 study, thereby to evaluate the efficacy of CBP-307 orally administered for 
maintenance treatment compared with placebo in sub-study 1 of the study stage 2 
• To evaluate clinical remission, clinical response and mucosal healing in subjects with 
moderately to severely active UC who do not achieve clinical response after 12 weeks of 
induction therapy in the study stage 1, thereby to evaluate the efficacy of CBP-307 when 
orally administered for treatment in the sub-study 2 of the study stage 2. 
3. STUDY DESIGN 
3.1. 
GENERAL DESCRIPTION 
This study is a multicenter, randomized, double-blind, placebo-controlled phase II clinical trial to 
evaluate the efficacy and safety of CBP-307 in subjects with moderate to severe ulcerative colitis 
(UC). This study includes stage 1 and stage 2. 
Stage 1:  
 
After screening, subjects will enter randomized, double-blind, placebo-controlled induction 


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therapy for 12 weeks, i.e.,  stage 1. Subjects will be given CBP-307 capsules 0.2 mg (or placebo) 
orally once daily for 12 consecutive weeks. The eligible patients are planned to be enrolled and 
randomized at a ratio of 1:1 into the 2 groups (approximately 52 subjects per each group) and stratified 
according to whether the subject failed in a previous tumor necrosis factor (TNF)-α antagonist therapy. 
Subjects will be screened at 1-21 days prior to the baseline visit. Subjects with moderate to severe UC 
(adapted Mayo score >= 4) who meet all inclusion criteria and do not meet any exclusion criteria will 
be randomized into one of the following 2 groups at the baseline visit: a group treated with CBP-307 
0.2 mg once daily (2 capsules of CBP-307 0.1 mg), and a placebo group (treated with 2 capsules of 
placebo). Placebo capsules are completely identical with the CBP-307 capsules in appearance and 
weight.  
 
The study includes a one-week titration period: 
For the subjects 0.2 mg group: subjects will be given 0.05mg CBP-307 till day 4, and 0.1 mg CBP-
307 for the following 3 days, from day 8, the subjects will be given 0.2 mg CBP-307.  
The subjects in placebo group will perform simulated titration. Both CBP-307 and placebo are 
administered through the oral route. 
Those patients who were randomized to 0.1mg according to protocol 5.0 or earlier should continue 
the previously assigned treatment till week 12. 
Subjects will be screened at 1-21 days prior to the baseline visit. Administration will be continued 
for 12 weeks. At the same time, if subjects who complete 12 weeks of induction therapy in stage 
1 study meet the criteria, they can be selected to enter stage 2 study to further evaluate the safety 
and efficacy of CBP-307 after medium or long-term administration in subjects with moderate to 
severe UC. 4 weeks of safety follow-up will be performed in subjects who complete stage 1 study 
but not enter stage 2 study or early withdraw from the study. 
Stage 2: 
All subjects who complete 12 weeks of induction therapy (with CBP-307 or placebo) in stage 1 


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study and complete all examinations (including colonoscopy) at visits week 12 can be selected to 
enter stage 2 for a total of 40 weeks, including 36 weeks of continuous administration and 4 weeks 
of safety follow-up after the last dose. Subjects selected to enter stage 2 will be required to sign an 
updated informed consent form and be rescreened for eligibility. 
Stage 2 contains two sub-studies: sub-study 1 and sub-study 2. Subjects entering stage 2 will enter 
one of sub-studies based on their results of efficacy evaluation in stage 1. 
Sub-study 1: Subjects who have clinical response shown by efficacy evaluation at week 12 in 
stage 1 and meet the eligibility criteria for stage 2 will enter sub-study 1 and continue on the 
double-blind maintenance treatment for 36 weeks (weeks 13 to 48), i.e., the therapeutic regimen 
for them in stage 1 study will be maintained. Safety follow-up is scheduled at 4 weeks after the 
last dose. Subjects who present with UC relapse during maintenance treatment period are required 
to terminate treatment and be withdrawn from the study. 
Note: Patients previously enrolled by protocol 4.0/5.0 would have the chance to receive 0.1mg, 
then they will continue 0.1mg in stage 2 sub-study 1. But there is no 0.1 mg group in protocol 
version 6.0 now. 
Definition of disease relapse (UC recurrence): Increased activity of UC, defined as  
a repeated (occurring at 2 consecutive visits) partial Mayo score that is at least 5 points and is 
also >=3 points higher than the score at week 12 (the end of induction therapy), and where the 
possibility of increased disease activity being due to other potential factors unrelated to UC can be 
excluded (e.g., infection, medication changes). 
Sub-study 2 : Subjects who do not achieve clinical response at week 12 efficacy evaluation in 
stage 1 and meet the eligibility criteria for stage 2 will enter open-label treatment with CBP-307 
0.2 mg. Subjects who receive CBP-307 0.2 mg or placebo in stage 1 study will receive CBP-307 
once daily an oral dose of 0.2 mg in sub-study 2 of stage 2. 
For subjects who enter sub-study 2 of stage 2, one-week dose titration will be performed at the 
first week (week 13) of stage 2. Dose titration involves administration of CBP 0.05 mg initiated 
on day 1 and used for 4 consecutive days, followed by administration of CBP-307 0.1 mg for 3 


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days, and administration of CBP-307 at a target dose of 0.2 mg initiated on day 8. After dose 
titration is completed, subjects will receive oral treatment with CBP-307 0.2 mg once daily, for 36 
weeks. Safety follow-up of is scheduled at 4 weeks after the last dose. 
At week 24, subjects will undergo efficacy evaluation involving colonoscopy. If the subjects have 
not achieved clinical response, the treatment will be discontinued, and the subjects will be 
withdrawn from the study. See Figure 1 for the overall design of the clinical study. 
Note: Patients previously enrolled by protocol 4.0/5.0 would have the chance to receive 0.1mg, 
then they will receive open-label 0.2 mg treatment in stage 2 sub-study 2. But there is no 0.1 mg 
group in protocol version 6.0 now. 
Figure 1 Overall design of the clinical trial 
 
For protocol version 5.0 or earlier: 
 
For protocol version 6.0: 


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3.2. 
SCHEDULE OF EVENTS 
Schedule of events can be found in table 2 (study flow chart), table 3 (Sub-study 1 of stage 2) 
and table 4 (Sub-study 2 of stage 2) of the protocol. 
3.3. 
CHANGES FROM PROTOCOL 
1. Add modified full analysis set (mFAS) for efficacy endpoints in stage 1 to exclude 
impact of COVID-19 on week 12 adapted mayo score. For CBP-307CN002 Phase II UC 
study, approximately 20% missing data is anticipated for the adapted mayo score at Week 
12. One major reason is that subjects could not come to site due to COVID-19. mFAS is 
added to reduce the bias due to those subjects. 
2. A Phase II UC study does not have as strict criteria as a pivotal Phase III study. In recent 
years regulators have been critical of last observation carried forward (LOCF) and similar 


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approaches for handling missing data and have advocated using more scientifically 
justifiable (e.g. multiple imputation methods) in primary analyses of Phase III studies 
alongside testing assumptions. Recommendation of The Prevention and Treatment of 
Missing Data in Clinical Trials states, “Single imputation methods like last observation 
carried forward and baseline observation carried forward should not be used as the 
primary approach to the treatment of missing data unless the assumptions that underlie 
them are scientifically justified”. The European Medicines Agency (EMA) Guideline on 
Missing Data in Confirmatory Clinical Trials states, “The risk of underestimating the 
variance of treatment effect when imputing can be reduced by proper implementation of 
techniques such as multiple imputation.” 
For CBP-307CN002 Phase II UC study, approximately 20% missing data is anticipated 
for the adapted mayo score at Week 12. With 20% missing data, the balance in the 
original FAS population could be lost which could result in biased estimates. Multiple 
Imputation (MI) can reduce bias arising from missing data. 
Therefore, multiple imputation will be used to handle missing data in the analysis of the 
primary efficacy endpoints at Week 12 for CBP-307CN002 study. The original planned 
efficacy analysis in the protocol therefore becomes a sensitivity analysis in support of the 
new primary efficacy analysis, as well as LOCF imputed efficacy analysis. 
3. Exploratory clinical remission rate by adapted mayo score is added for clinical discussion 
as exploratory efficacy endpoint. Exploratory clinical remission rate by adapted mayo 
score is defined as a rectal bleeding subscore <= 1 and a stool frequency subscore <= 1, 
with an Endoscopy subscore <= 1 [excluding friability]. 
4. 0.2 mg (all stages) analysis is added for a new population to analyse those patients who 
received 0.2 mg from initial - administration until end of treatment in the study. 


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4. PLANNED ANALYSES 
The following analyses will be performed for this study: 
• Analyses for Data Monitoring Committee (DMC) meetings 
• Interim Analysis 
• Final Analysis 
4.1. 
DATA MONITORING COMMITTEE (DMC)  
A DMC SAP, describing the methodology and presentation of results and access to results will 
be provided by IQVIA as a separate document. 
4.2. 
INTERIM ANALYSIS (PRIMARY ANALYSIS) 
One interim analysis (also primary analysis for this study) will take place for this study once all 
the subjects have completed week 12 (visit 11, last dose/early discontinue visit) in stage 1, the 
unblind study team will produce the analysis on primary endpoint after database lock. The primary 
endpoint is to compare clinical efficacy of CBP-307 vs placebo by evaluating the change of 
adapted Mayo score after 12 consecutive weeks treatment in subjects with moderate to severe UC. 
Interim analysis will only analyze stage 1 part (including 4-week safety follow-up for early 
withdrawal subjects). All analysis is used at interim analysis, or week 12. 
The interim analysis focuses on efficacy analysis, including change from baseline of adapted Mayo 
score, complete Mayo score, and IBDQ, and clinical response rate, clinical remission rate, and 
mucosal healing rate. 
The following will be performed in interim analysis: 
• 
Disposition part: patient disposition (details in section 8), major protocol deviation (details in 
section 8), and analysis sets (details in section 5) summary table in Stage 1 and reference 
listings. 


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• 
Baseline Characteristics: demographics (details in section 9), medical history (details in 
section 10), prior medications and procedures (details in section 11) summary table in Stage 
1 and reference listings. 
• 
Study Exposure: exposure (details in section 12) and compliance (details in section 13) 
summary table in Stage 1 and reference listings. 
• 
Efficacy: clinical response rate  by adapted mayo score and complete mayo score at week 12; 
clinical remission rate by adapted mayo score and complete mayo score at week 12; analysis 
of change in adapted mayo score and complete mayo score from baseline at week 12; 
mucosal healing rate at week 12; analysis of change in IBDQ score from baseline at week 12 
(details in section 14). 
• 
Adverse Events: overall summary table in Stage 1; treatment emergent adverse events 
(TEAEs), drug-related TEAEs, grade>=3 TEAEs, serious TEAEs, TEAEs leading to drug 
withdrawal, TEAEs leading to death, and TEAEs of special interest by system organ class 
(SOC) and preferred term (PT) in Stage 1; TEAEs by maximum CTCAE grade, SOC and PT 
in Stage 1; death details in Stage 1. 
• 
Laboratory: absolute value and change from baseline by visit of hematology, biochemistry, 
fasting lipids, coagulation, and urinalysis; shift from baseline to worst post-baseline common 
terminology criteria for adverse events (CTCAE) grade for hematology, biochemistry, fasting 
lipids, and coagulation; abnormalities in hematology and liver function test. The above 
summary tables are in Stage 1 as well as their reference listings. 
• 
12-Lead ECG: absolute value and change from baseline by visit of ECG; shift from baseline 
to worst post-baseline ECG overall assessment; abnormalities in QT internal and QTcF; shift 
from baseline to maximum post baseline value and maximum increase from baseline in Stage 
1 
• 
Other safety findings: vital signs (VS) part, including absolute value and change from 
baseline by visit and incidence of markedly abnormal values, and shift from baseline to worst 
post-baseline overall assessment; pulmonary function test data’s absolute value and change 


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from baseline; ophthalmologic examination part, including overall assessment by visit and 
change from baseline; optical coherence tomography part, including overall assessment by 
visit and change from baseline; dermatologic examination part, including overall assessment 
by visit and change from baseline in Stage 1. 
• 
Concomitant medications and procedures (details in section 11) in Stage 1. 
If a decision is made to perform the primary or main analysis, in order to maintain study integrity 
with respect to the follow-up visits, safety visits and analyses, a Blind Maintenance Plan will be 
written. This plan will clearly identify the team (including the statistician) that will perform the 
primary or main analysis and all related activities, restrict other clinical team members and other 
Sponsor personnel from access to individual subject treatment allocation and site level analysis 
results, and ensure that the dedicated team will not participate in the data decisions for the 
following analyses. However, the dedicated team can participate in the analysis following the final 
database lock. 
 
4.3. 
FINAL ANALYSIS  
All final, planned analyses identified in this SAP will be performed by IQVIA Biostatistics 
following final analysis database lock (all subjects have completed the study, outstanding data 
queries have been resolved and the database has been cleaned and finalized.). The PK/PD analysis 
will be conducted by the PK group, a separate analysis plan will be provided by PK group. 
5. ANALYSIS POPULATION 
5.1. 
STAGE 1 POPULATION 
Screened Set (Screened) in stage 1 
The screened set will contain all subjects who signed informed consent for stage 1. 


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All Randomized Set (Randomized) in stage 1 
The randomized set will contain all subjects who are randomized into stage 1, no matter treated or 
not. 
Full Analysis Set (FAS) in stage 1 
The full analysis population (FAS) will contain all randomized subjects who receive at least one 
dose of study medication or placebo in stage 1.  FAS will be based on the planned drug taken.  
Modified Full Analysis Set (mFAS) in stage 1 
The modified full analysis population (mFAS) will contain all randomized subjects who receive 
at least one dose of study medication or placebo in stage 1 except subjects without week 12 adapted 
mayo score due to COVID-19.  mFAS will be based on the planned drug taken.  
Per Protocol Set (PPS) in stage 1 
The per-protocol set (PPS) will contain a subset of FAS subjects who do not have major protocol 
deviation in stage 1. 
Definition of major protocol deviation in stage 1: 
1. Any Major clinical protocol deviation of Randomization Criteria 
2. Any Major clinical protocol deviation of Eligibility and Entry Criteria  
3. Any prohibited concomitant medication in clinical protocol deviation 
4. IP compliance below 80% or over 120% 
5. Have no baseline Adapted Mayo score 
6. Have no Week12 Adapted Mayo score  
7. Week 12 Adapted Mayo Score is out of visit window 
8. Any unblinding during stage 1  
9. Any other critical clinical protocol deviations in stage 1 
 
Definition of minor protocol deviation in stage 1: 
Clinical protocol deviation except major protocol deviation happened in stage 1. 
 


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Safety Set (SS) in stage 1 
The safety set (SS) will contain all randomized subjects who receive at least one dose of study 
medication or placebo. SS will be based on the actual drug taken.  
5.2. 
STAGE 2 POPULATION 
All Subjects Screened (Screened) in stage 2 
The all subjects screened will contain all subjects who signed informed consent for stage 2. 
 
Full Analysis Set (FAS) in stage 2 
The full analysis set (FAS) will contain all screened subjects who receive at least one dose of study 
medication or placebo in stage 2.  FAS will be based on the planned drug taken. 
 
Per-Protocol Analysis Set (PPS) in Stage 2 
The per-protocol set (PPS) will contain a subset of FAS subjects who do not have major protocol 
deviation in stage 2. 
Definition of major protocol deviation in stage 2 sub-study 1: 
1. Any Major clinical protocol deviation of Randomization Criteria 
2. Any Major clinical protocol deviation of Eligibility and Entry Criteria  
3. Any prohibited concomitant medication in clinical protocol deviation 
4. IP compliance below 80% or over 120% 
5. Have no baseline Adapted Mayo score 
6. Have no Week48 Adapted Mayo score  
7. Week48 Adapted Mayo Score is out of visit window 
8. Any unblinding during stage 2 
9. Any other critical clinical protocol deviations in stage 2 
 


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Definition of minor protocol deviation in stage 2: 
Clinical protocol deviation except major protocol deviation happened in stage 2. 
 
 
Safety Set (SS) in stage 2 
The safety set (SS) will contain all randomized subjects who receive at least one dose of study 
medication or placebo in stage 2. SS will be based on the actual drug taken. 
 
5.3. 
ALL STAGES (0.2MG ONLY) POPULATION 
All Subjects Screened (Screened) 
The Screened Set includes all subjects who signed informed consent for stage 1 and stage 2 in 
0.2mg treatment group. 
 
Full Analysis Set (FAS) 
The full analysis set includes all randomized subjects who receive at least one dose of 0.2 mg study 
medication in stage 1 and stage 2, either sub-study 1 or sub-study 2.  
6. GENERAL CONSIDERATIONS 
Analysis results will be presented using descriptive statistics. For categorical variables, the number 
and percentage of subjects in each category will be presented; for continuous variables, the number 
of subjects [n], mean, standard deviation [SD] or standard error [SE], median,  minimum, and 
maximum will be presented. Statistical comparisons will be tested at two-sided alpha of 0.05 
significance level, unless otherwise specified. Data collected in the study will be presented in by-
subject listings for all subjects in the full analysis set (efficacy analysis) and safety analysis set 


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(safety analysis), unless otherwise specified. All by subject listings will be presented by treatment 
group, subject identification number in ascending order, unless otherwise specified. 
For stage 1 analysis, the analysis period for subjects who enroll stage 2 will be from screening 
(baseline visit) in stage 1 until before the first dose of stage 2. And for subjects who will not enroll 
stage 2 (including screen failed subjects before randomization, randomized subjects but not treated, 
and subjects early discontinued in stage 1), the analysis period will be from screening (baseline 
visit) in stage 1 until end of study in stage 1. For stage 2 sub-study 1 analysis, the full/safety 
analysis population will be the randomized subjects who receive at least one dose of study 
medication or placebo in stage 2, but the analysis period will be from screening (baseline visit) in 
stage 1 until the end of study in stage 2. But for subjects who will enroll stage 2 sub-study 2, the 
analysis period will be the date of first dose of the open-label CBP307 0.2mg in stage 2 until the 
end of study in stage 2 since treatment is changed to open-label CBP307 0.2 mg QD. 
For 0.2mg (all stages) group, the analysis period will be the date of first dose of initial 
administration until the end of stage 2 study, including stage 2 sub-study 1 and stage 2 sub-stage 
2.  
6.1. 
REFERENCE START DATE AND STUDY DAY 
Study Day will be calculated from the reference start date and will be used to show start/ stop day 
of assessments and events.  
Reference start date is defined as the day of the first dose of study medication, (Day 1 is the day 
of the first dose of study medication) and will appear in every listing where an assessment date or 
event date appears.  
• If the date of the event is on or after the reference date, then:  
Study Day = (date of event – reference date) + 1. 
• 
If the date of the event is prior to the reference date, then:  
Study Day = (date of event – reference date). 


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In the situation where the event date is partial or missing, the date will be imputed based on the 
imputation rules specified in section 11. The original value will be listed in the listings. The study 
day and any corresponding durations for this record will be calculated based on the imputed date. 
6.2. 
BASELINE 
For stage 1: Unless otherwise specified, baseline is defined as the last non-missing measurement 
taken prior to the first treatment date (including unscheduled assessments) in stage 1. In the case 
where the last non-missing measurement and the reference start date coincide, and no time 
collected, that measurement will be considered pre-dose, except that the protocol specifies the 
measurement is post-dose.   
For subject randomized but not treated, baseline is defined as the last non-missing measurement 
on or before randomization date.  
For subjects entered into stage 2 sub-study 1: the baseline will be the same as in stage 1. 
For subjects entered into stage 2 sub-study 2: the baseline is defined as the last non-missing 
measurement taken prior to the first treatment date (including unscheduled assessments) in stage 
2 sub-study 2. 
For all stages (0.2mg only) analysis, baseline will be the same as in stage 1. 
6.3. 
RETESTS, UNSCHEDULED VISITS  
In general, for by-visit summaries, data recorded at the nominal visit will be presented. 
Unscheduled measurements will not be included in by-visit summaries but will contribute to the 
minimum, maximum, best or worst case value where required (e.g. shift table).  
Unless otherwise specified, in the case there are more than one records in the same visit, the latest 
available measurement for that visit will be used for by-visit summaries.  
Listings will include scheduled, unscheduled, retest data. 


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6.4. 
COMMON CALCULATIONS 
For quantitative measurements, change from baseline will be calculated as: 
 
• Change from baseline =Value at Week X – Baseline Value 
Percentage change from baseline will be calculated as:  
• Percentage change from Baseline= (Value at Week X – Baseline Value) / Baseline Value 
× 100% 
6.5. 
SOFTWARE VERSION 
All analyses will be conducted using SAS 9.4 or higher version.  
7. STATISTICAL CONSIDERATIONS 
7.1. 
MULTICENTER STUDIES 
Center pooling will not be carried out for use in analyses for this study. 
7.2. 
MISSING DATA 
Missing safety data will be handled as described in separated section (concomitant medication 
missing data rule in section 11, and adverse event missing data rule in section 15.1).  
Missing efficacy data will be handled as described in section 14.1.2 of this analysis plan.  
7.3. 
SUBGROUP ANALYSES 
No planned subgroup analyses will be performed for this study. 


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7.4. 
SAMPLE SIZE 
Approximately 134 subjects with moderate to severe UC will be randomized in the study. Among 
them, there are approximately 30 subjects in the CBP-307 0.1 mg once daily group. In protocol 
version 5.0 or earlier, 195 patients with moderate to severe UC were planned to be randomized at 
1:1:1 into any of the following 3 groups: CBP-307 0.1 mg once daily, CBP-307 0.2 mg once daily, 
placebo. Approximately 65 subjects were planned to be in each group. However, protocol 
amendment happens during the treatment period. The primary endpoint analysis is based on the 
comparison between the 0.2 mg CBP-307 group and the placebo group, and protocol version 6.0 
keeps only these two groups, and sample size is re-calculated. The 0.1 mg group is not applicable 
in protocol version 6.0, and there will be no further subjects enrolled in the 0.1 mg group. The 
nearly 30 subjects already randomized with protocol version 5.0 or earlier are kept and analyzed 
for exploratory purpose.  
The sample size re-calculation is based on the comparison between CBP-307 0.2 mg once daily 
group and placebo group on the primary efficacy endpoint, namely the change in adapted Mayo 
score from baseline at week 12 after treatment. Assuming that the difference between the 0.2 mg 
group and the placebo group of the change from baseline at week 12 after treatment in adapted 
Mayo score is 1.2, and the common standard deviation is 2.0, a significance level of α=0.05 (two-
sided), and a dropout rate is 15%, then each group needs to enroll at least 52 subjects (104 subjects 
in two groups) to provide a power of 80% to detect the difference between the 0.2 mg group and 
the placebo group on the primary efficacy endpoint. Based on this estimation, the eligible subjects 
with moderate to severe UC will be randomized at 1:1 into CBP-307 0.2 mg once daily group or 
placebo group until 52 subjects are enrolled into each group. 
8. DISPOSITION AND WITHDRAWALS 
Disposition of all screened subjects, Screen failure, screened but not randomized will be 


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summarized by count and percentage.  
Disposition of all randomized subjects will be tabulated by randomized treatment. The categories 
will include:  
Stage 1: 
• All subjects screened 
• Screen Failed  
• Screen success but not randomized  
• All randomized subjects  
• Subjects who were randomized but not treated with study medication  
• Status of study treatment  
➢ completed 
➢ Ongoing 
➢ Discontinued 
• Primary reason for treatment discontinuation   
• Entered stage 2  
 
• Study Status 
➢ Early discontinued in stage 1 
➢ Stage 1 treatment ongoing 
➢ Stage 1 post treatment follow-up 
➢ Completed stage 1 but not entered stage 2 
➢ Entered stage 2 
• Primary reason for study discontinuation 
Stage 2: 
• Subjects archived clinical response by adapted mayo score (for sub-study 1)/ Subjects not 
archived clinical response by adapted mayo score (for sub-study 2) 


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• All subjects screened  
• Status of study treatment 
➢ Completed 
➢ Ongoing 
➢ Discontinued 
• Primary reason for treatment discontinuation 
• Study Status  
➢ Early Discontinued in Stage 2 
➢ Stage 2 Treatment Ongoing 
➢ Stage 2 Post Treatment Follow-Up 
➢ Completed 
• Primary reason for study discontinuation 
Primary reasons for treatment discontinuation, as entered on the eCRF, will be tabulated; the 
reasons include adverse event, significant protocol deviation, death, non-compliance problems, 
lost to follow-up, withdrawal by subject, study terminated by sponsor, pregnancy, lack of efficacy 
or disease progression, or other. COVID-19 will be presented separately after selected from other 
reasons in ‘Other, Specify’ category. 
Primary reasons for study discontinuation, as entered on the eCRF, will be tabulated; the reasons 
include subject didn't meet eligibility criteria(s), adverse event, significant protocol deviation, 
death, non-compliance problems, lost to follow-up, withdrawal by subject, study terminated by 
sponsor, pregnancy, lack of efficacy or disease progression, or other. COVID-19 will be presented 
separately after selected from other reasons in ‘Other, Specify’ category. 
0.2mg only for all stages will present both stage 1 and stage 2 disposition. 
Completed or discontinued from study, duration of study, and the reason for study withdrawal will 
be listed for each safety subject in the listings.  
Major protocol deviation leading to subject being excluded from FAS in PPS and summary of all 
analysis sets will be presented for the safety set and be listed in the listings.  Listing of 


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inclusion/exclusion criteria responses by subject will also be provided. 
9. DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic data and other baseline characteristics will be presented for randomized population. 
The following demographic and other baseline characteristics will be reported for this study: 
• Age (years) - calculated relative to date of consent 
• Sex, including childbearing potential for female subjects 
• Race  
• Ethnicity 
• Weight (kg) 
• Height (cm) 
• BMI (kg/m2) 
• Alcohol use 
• Drug abuse 
• Tobacco use 
• If Treatment with a Tumor Necrosis Factor (TNF)-α Antagonist Failed? 
• Ulcerative colitis history 
➢ Years since UC diagnosis (years) 
➢ Stool frequency (times/day) 
➢ Rectal bleeding 
➢ Endoscopy score - investigator 
➢ Endoscopy score - central 
➢ Physician’s global assessment 
➢ Location and extent of subject’s UC 
• Family history of colon cancer  


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• Family history of premature coronary heart disease 
• Chest imaging examination results at baseline 
BMI (kg/ m2) = weight (kg)/ height (m2) 
Age (Years) = (date of informed consent – date of birth+1)/365.25 
Years since UC diagnosis = (date of informed consent-date of diagnosis+1)/365.25 
10. MEDICAL HISTORY 
Medical History/ Ulcerative Colitis Medical History will be presented for the FAS.  
Medical history collected at screening will be coded using the Medical Dictionary for Regulatory 
Activities (MedDRA) V21.1 or higher. 
Medical history will be summarized by system organ system (SOC) and preferred term (PT) for 
each treatment group and overall. The tables will be sorted in descending order by SOC and in 
decreasing frequency based on the total number of subjects by PT (sorted in alphabetic order in 
case the frequency coincident) in each SOC. The number and percentage of subjects with any 
medical history will be summarized for each SOC and PT. The denominator used for calculating 
the percentages will be the total number of subjects included in each treatment group. For the 
tables, if a subject report the same PT multiple times, then that PT will be counted only once for 
that subject. Similarly, if a subject reports multiple conditions within the same SOC, then that SOC 
will be counted only once for that subject in the tables.  
No inferential statistics will be generated. 
Medical history will be listed by treatment group, study center and subject number. A by-subject 
listing of ulcerative colitis medical history will be provided by subject number (in ascending order) 
and medical history of abnormalities (in chronological order). 


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11. MEDICATIONS AND PROCEDURES 
Medications will be presented for the FAS and coded using World Health Organization Drug 
Dictionary Global (Enhanced WHO Herbal Dictionary) 01Sep2018 or higher. Medications will be 
presented by Preferred name. Procedures recorded will be coded using MedDRA Version 21.1 or 
higher. All procedures will be presented by SOC and PT. 
All medications and procedures will be presented in a listing. 
The following rule is used for handling of partial dates for medications, in the case where it is not 
possible to define a medication as prior, concomitant, or post treatment, the medication will be 
classified by the worst case; i.e. concomitant. For concomitant medications, incomplete (i.e., 
partial missing) start date and/or stop date will be imputed. When the start date and the stop date 
are both incomplete for a subject, consider imputing the start date first. 
Missing day and month 
• If the year of the incomplete start date is the same as the year of the date of the treatment 
start date, then the day and month of the treatment start date will be assigned to the missing 
fields. 
• If the year of the incomplete start date is before the year of the date of the treatment start 
date, then December 31 will be assigned to the missing fields. 
• If the year of the incomplete start date is after the year of the date of the treatment start 
date, then January 1 will be assigned to the missing fields. 
Missing month only 
• The day will be treated as missing and both month and day will be replaced according to 
the above procedure. 
Missing day only 
• If the month and year of the incomplete start date are the same as the month and year of 


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the treatment start date, then the treatment start date will be assigned to the missing day. 
• If either the year is before the year of the treatment start date or if both years are the 
same, but the month is before the month of the treatment start date, then the last day of 
the month will be assigned to the missing day. 
• If either the year is after the year of the date of the treatment start date or if both years are 
the same, but the month is after the month of the treatment start date, then the first day of 
the month will be assigned to the missing day. 
If the stop date is not missing and the start date is after the stop date after missing value calculation, 
the stop date will be used for the start date.   
Incomplete Stop Date 
Missing day and month 
• If the year of the incomplete stop date is the same as the last treatment date, then the day 
and month of the last treatment date will be assigned to the missing fields. 
• If the year of the incomplete stop date is before the year of the last treatment date, then 
December 31 will be assigned to the missing fields. 
• If the year of the incomplete stop date is after the year of the last treatment date, then 
January 1 will be assigned to the missing fields. 
Missing month only 
• The day will be treated as missing and both month and day will be replaced according to 
the above procedure. 
Missing day only 
• If the month and year of the incomplete stop date are the same as the month and year of 
the last treatment date, then the day of the last treatment date will be assigned to the 
missing day. 


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• If either the year is before the year of the last treatment date or if both years are the same, 
but the month is before the month of the last treatment date, then the last day of the 
month will be assigned to the missing day. 
• If either the year is after the year of the date of the last treatment date or if both years are 
the same, but the month is after the month of the last treatment date, then the first day of 
the month will be assigned to the missing day. 
If the start date is not missing and the stop date is before the start date after missing value 
calculation, the start date will be used for the stop date.   
‘Prior’ medications are medications which started and stopped prior to the first dose of study 
medication.  
‘Concomitant’ medications are medications which:  
➢ started prior to, on or after the first dose of study medication and started no later than 
end of study medication,  
➢ AND ended on or after the date of first dose of study medication or were ongoing at 
the end of the study. 
12. STUDY MEDICATION EXPOSURE 
Exposure to study medication in days will be presented for the FAS. 
The extent of exposure to study medication will be presented for the following summaries by 
treatment group and overall: 
• Duration of exposure (days) during regular treatment period: 
Duration of exposure (days) during regular treatment = date of last dose during the regular 
treatment period – date of first dose during the regular treatment period +1; 
• Actual duration of exposure (days) is defined as the total number of days on the study drug 
during the treatment phase (excluding the periods of dose break or dose interruptions). 
• Planned cumulative dose (mg) during the regular treatment period: 


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Planned cumulative dose (mg) is defined as the sum of the total planned dosage that the 
subject should take during the regular treatment period. (subjects are planned to take drug 
after coming to site). 
 
Stage 1 and Stage 2 Sub-study 1 
Treatment 
Group 
Target Visit Day 
Planned 
Daily 
Dose (mg) 
Target 
Duration 
Target Dose 
Level in the 
Target Visit (mg) 
Planned 
Cumulativ
e Dose 
(mg) 
0.2 mg 
QD 
W1D5 
0.05 
4 
0.2 
0.2 
W2D8 
0.1 
3 
0.3 
0.5 
W4D28 
0.2 
21 
4.2 
4.7 
W8D56 
0.2 
28 
5.6 
10.3 
W12D84 
0.2 
28 
5.6 
15.9 
W18D126 
0.2 
42 
8.4 
24.3 
W24D168 
0.2 
42 
8.4 
32.7 
W32D224 
0.2 
56 
11.2 
43.9 
W40D280 
0.2 
56 
11.2 
55.1 
W48D336 
0.2 
56 
11.2 
66.3 
0.1 mg 
QD (for 
protocol 
version 
5.0 or 
earlier) 
W1D5 
0.05 
4 
0.2 
0.2 
W2D8 
0.1 
3 
0.3 
0.5 
W4D28 
0.1 
21 
2.1 
2.6 
W8D56 
0.1 
28 
2.8 
5.4 
W12D84 
0.1 
28 
2.8 
8.2 
W18D126 
0.1 
42 
4.2 
12.4 
W24D168 
0.1 
42 
4.2 
16.6 
W32D224 
0.1 
56 
5.6 
22.2 
W40D280 
0.1 
56 
5.6 
27.8 
W48D336 
0.1 
56 
5.6 
33.4 
Placebo 
W1D5 
1 tablet 
4 
4 tablets 
4 tablets 
W2D8 
2 tablets 
3 
6 tablets 
10 tablets 
W4D28 
2 tablets 
21 
42 tablets 
52 tablets 
W8D56 
2 tablets 
28 
56 tablets 
108 tablets 
W12D84 
2 tablets 
28 
56 tablets 
164 tablets 
W18D126 
2 tablets 
42 
84 tablets 
248 tablets 
W24D168 
2 tablets 
42 
84 tablets 
332 tablets 
W32D224 
2 tablets 
56 
112 tablets 
444 tablets 


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W40D280 
2 tablets 
56 
112 tablets 
556 tablets 
W48D336 
2 tablets 
56 
112 tablets 
668 tablets 
 
Stage 2 Sub-stage 2 
Treatment 
Group 
Target 
Visit Day 
Mappe
d Visit 
Day 
Planned 
Daily 
Dose 
(mg) 
Target 
Duration 
Target Dose 
Level in the 
Target Visit 
(mg) 
Planned 
Cumulative 
Dose (mg) 
0.2 mg QD W13D5 
5 
0.05 
4 
0.2 
0.2 
 
W14D8 
8 
0.1 
3 
0.3 
0.5 
 
W16D112 
28 
0.2 
21 
4.2 
4.7 
 
W24D168 
84 
0.2 
56 
11.2 
15.9 
 
W32D224 
140 
0.2 
56 
11.2 
27.1 
 
W40D280 
196 
0.2 
56 
11.2 
38.3 
 
W48D336 
252 
0.2 
56 
11.2 
49.5 
 
• Actual cumulative dose (mg) during the regular treatment period: 
Actual cumulative dose (mg) is defined as the sum of the total dosage that the subject taken during 
the regular treatment period. 
• Planned dose Intensity (mg/day) during the regular treatment period:  
Planned dose intensity (mg/day) during the regular treatment period = planned cumulative dose 
(mg) during the regular treatment period/duration of exposure (days) during regular treatment 
period*100. 
• Dose intensity (mg/day) during the regular treatment period:  
Dose intensity (mg/day) during the regular treatment period = actual cumulative dose (mg) during 
the regular treatment period/duration of exposure (days) during regular treatment*100. 
• Relative dose intensity (mg/day) during the regular treatment period:  
Relative dose intensity (mg/day) during the regular treatment period=dose intensity during the 
regular treatment period/planned dose intensity during the regular treatment period*100. 
Duration of exposure during the  regular treatment period, total duration of exposure,  planned 
cumulative dose during the regular treatment period, planned cumulative dose, actual cumulative 


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dose during the regular treatment period, total actual cumulative dose, planned dose intensity 
during the regular treatment period, dose intensity during the regular treatment period, relative 
dose intensity (mg/day) during the regular treatment period will be summarized using descriptive 
statistics, i.e., number of subjects (n), mean, median, standard deviation (SD), 25th and 75th 
percentiles (Q1, Q3), minimum and maximum.  
In addition, the exposure data for the SS will be included in a listing.                      
13. STUDY MEDICATION COMPLIANCE  
Compliance during the regular treatment period will be assessed using relative dose intensity 
during the regular treatment period. 
Compliance during the regular treatment period will be summarized using descriptive statistics, 
i.e., number of subjects (n), mean, median, standard deviation (SD), 25th and 75th percentiles (Q1, 
Q3), minimum and maximum.  
The compliance will also be summarized by the number of subjects in each of following categories: 
➢ <80% 
➢ 80% to 120% (including the 80% and 120%) 
➢ >120% 
The compliance categories will be summarized by count(s) and percentages (%). 
Subjects with missing compliance information will be presented in a separate category, if 
applicable. 
14. EFFICACY OUTCOMES  
14.1. 
EFFICACY ASSESSMENT 
Complete Mayo Score 


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The Mayo score is a standard, widely accepted, digital assessment of UC severity in subjects. The 
Mayo scores range from 0 to 12 and consist of 4 sub-items, each with the score range from 0 to 3. 
The higher the score is, the more severe the disease is: 
1. 
Stool frequency a 
0 = Normal numbers of stools for this patient 
1 = 1-2 stools more than normal  
2 = 3-4 stools more than normal  
3 = 5 or more stools than normal  
2. 
 Rectal bleeding b 
0 = No blood seen 
1 = Streaks of blood with stool less than half the time 
2 = Obvious blood with stool most of the time 
3 = Blood alone passes 
3. 
Endoscope findings 
0 = Normal or inactive disease  
1 = Mild disease (erythema, decreased vascular pattern, mild friability) 
2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions)  
3 = Severe disease (spontaneous bleeding, ulceration) 
4. 
Physician’s global assessment c 
0 = Normal 
1 = Mild disease 
2 = Moderate disease 
3 = Severe disease 
Notes: 
a. Each patient serves as his or her own control to establish the degree of abnormality of the stool 


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frequency. 
b. The daily bleeding score represents the most severe bleeding of the day.  
c. The physician’s global assessment acknowledges the 3 other criteria, the patient’s daily 
recollection of abdominal discomfort and general sense of well-being, and other 
observations, such as physical findings and the patient’s performance status. 
Complete Mayo scores at baseline and at week 12 are calculated based on the results in the above 
items 1, 2, 3, and 4 (stool frequency, rectal bleeding, endoscopic findings, and physician’s global 
assessment). 
Adapted Mayo score 
Adapted Mayo score is calculated based on the above assessment 1, 2 and 3 (Stool frequency, 
Rectal bleeding and Endoscopic findings). The Adapted Mayo score will be calculated at the visit 
at screening and week 12 (or early termination visit) during stage 1 study as well as at week 24 
(only sub-study 2) and week 48 (or early termination visit) during stage 2 study. 
Partial Mayo scores 
Partial Mayo scores will be calculated at weeks 2, 4, 8 and 12 (i.e., Mayo score without 
colonoscopy findings) in study stage 1. In sub-study 1 of study stage 2, partial Mayo scores will 
be calculated at weeks 18, 24, 32 and 40. In sub-study 2 of study stage 2, partial Mayo scores will 
be calculated at weeks 16, 32 and 40. 
Partial Mayo scores will be calculated based on assessment in the items 1, 2, and 4 of section 
14.1.1 (Stool frequency, Rectal bleeding and Physician’s global assessment). 
 
14.2. 
PRIMARY EFFICACY 
14.2.1. 
PRIMARY EFFICACY ENDPOINT   
The primary efficacy analysis is based on the primary efficacy endpoint: change in adapted Mayo 


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score from baseline at week 12 compared between CBP-307 0.2 mg and placebo. 
14.2.2. 
PRIMARY ANALYSIS OF PRIMARY EFFICACY ENDPOINT 
The primary efficacy analysis will be based on FAS, mFAS, and PPS.  
The covariance (ANCOVA) model with baseline as covariate will be used to analyze the changes 
in adapted Mayo score from baseline at week 12 between the CBP-307 0.2 mg group and the 
placebo group stratified by whether the previous treatment with a tumor necrosis factor (TNF)-α 
antagonist failed (Yes or No). The superiority of the CBP-307 0.2 mg group to placebo on change 
in adapted Mayo score from baseline at week 12 after treatment will be tested at a significance 
level of 0.025 with one-sided. If the significance level is reached, then superiority of the CBP-307 
0.2 mg will be statistically significant. For subjects enrolled in protocol version 5.0 or earlier in 
0.1 mg group, they will be compared with placebo group with same method as 0.2mg QD group, 
but only results of 0.1 mg group will be presented as supportive results. 
The least square mean (LSMEANS), together with the p values and the 95% confidence intervals, 
between 0.2 mg vs. placebo will be reported using the ANCOVA model (SAS PROC MIXED), 
with the stratification factor as the confounding factor in the ANCOVA model and the baseline 
values as covariate.  
The change from baseline over time on the Adapted Mayo score will also be plotted by each 
treatment group for exploratory purpose.  
 
14.2.3. 
MISSING IMPUTATION FOR PRIMARY EFFICACY 
Multiple Imputation 
Multiple imputation has 3 distinct phases: Imputation, Analysis and Combining. During the 
Imputation Phase, the missing data values are filled-in to form a complete dataset. This is done 
‘m’ times. For the Analysis Phase, each of the ‘m’ complete datasets are analysed by a statistical 


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model (as specified in Section 14.2.2). The Combining Phase pools the parameter estimates with 
their standard errors across the ‘m’ complete datasets and produces an average estimate with a 
standard error calculated using Rubin’s formula this allows for the uncertainty between 
imputations as well as the variability within each analysis. 
Multiple imputation assumes that the data are missing at random (MAR). MAR assumes that the 
missingness does not depend on the actual missing values, but that the missing data can be 
completely explained by the observed data. To test the robustness of the multiple imputation 
strategy a tipping point analysis may be implemented. 
In the case of mayo scores, a multiple imputation approach is implemented for the missing 
individual adapted mayo score. 
Each individual mayo score is imputed and then the composite endpoint measures are created 
(see list of endpoints in APPENDIX 2). 
There are 4 steps to this process: 
1. Create a dataset with one record per subject, containing all values of each mayo score for 
all visits (baseline and  week 12 on one record) in stage 1. These variables are included 
because they are correlated with the endpoint and/or missingness. The multiple 
imputation process creates complete datasets using PROC MI in SAS 9.4. During post-
processing, the endpoints are derived in each of the complete datasets. The endpoints and 
analysis model in APPENDIX 2. 
2. Run ‘m’ times Markov Chain Monte Carlo (MCMC) imputations to make the missing 
values in the dataset have a full missingness pattern. This will produce a dataset with an 
index variable _imputation_ and otherwise the same variables as the input dataset. It will 
have one record per imputation per subject. 
3. Run analysis of covariance model (the method in section 14.2.2) with imputation on each 
imputed dataset from Step 2. This will generate a dataset with the same structure as the 
input dataset, but will have the missing values filled in. 
4. Combine all estimated statistics into one using PROC MIANALYZE. 


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14.2.4. 
SENSITIVITY ANALYSIS OF PRIMARY EFFICACY   
The primary efficacy analysis will be performed after all subjects complete (or possibly complete) 
the treatment with the investigational product. Baseline adapted Mayo score is required. For 
missing primary efficacy endpoint (changes in the Adapted Mayo score at week 12), the latest 
post-baseline changes before week 12 will be carried forward if the Mayo score is missing. 
Imputed week 12 adapted mayo score with last observation carried forward (LOCF) method will 
be used in sensitivity analysis for FAS and mFAS subjects. The format on the summary statistics 
will keep the same as primary analysis. Complete case analysis without any imputation will be 
also summarized with same method in primary analysis for FAS mFAS subjects. 
 
14.3. 
SECONDARY EFFICACY 
The secondary efficacy analyses will be performed in the FAS, mFAS, and PPS. The same 
analyses as primary endpoints will be performed on the secondary quantitative efficacy 
endpoints.  
14.3.1. 
SECONDARY ANALYSES ON EFFICACY ENDPOINTS  
• Change in adapted Mayo score at week 12 from baseline: 0.1 mg vs placebo (only 0.1 mg 
group presented) 
• Change in complete Mayo score at week 12 from baseline: 0.2 mg vs placebo 
• Change in complete Mayo score at week 12 from baseline: 0.1 mg vs placebo (only 0.1 
mg group presented) 
• Clinical response rate by Adapted Mayo Score at week 12: 0.2 mg vs placebo (defined as 
a decrease of >= 2 points and at least 30% from baseline, accompanied with a decrease 
of >= 1 point from baseline in the rectal bleeding subscore or an absolute rectal bleeding 


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subscore of <= 1 point) 
• Clinical response rate by Adapted Mayo Score at week 12: 0.1 mg vs placebo  
• Clinical response rate by Complete Mayo Score at week 12: 0.2 mg vs placebo (defined 
as a decrease of >= 3 points and at least 30% from baseline, accompanied with a decrease 
of >= 1 point from baseline in the rectal bleeding subscore or an absolute rectal bleeding 
subscore of <= 1 point) 
• Clinical response rate by Complete Mayo Score at week 12: 0.1 mg vs placebo 
• Clinical remission rate by Adapted Mayo score at week 12: 0.2 mg vs placebo (defined as 
a rectal bleeding subscore = 0 and stool frequency sub score <= 1, with an Endoscopy 
subscore <=1 [excluding friability]) 
• Clinical remission rate by Adapted Mayo score at week 12: 0.1 mg vs placebo  
• Clinical remission rate by Complete Mayo score at week 12: 0.2 mg vs placebo (defined 
as a total Mayo score of <= 2 points with no individual subscore > 1 point) 
• Clinical remission rate by Complete Mayo score at week 12: 0.1 mg vs placebo 
• Mucosal healing rate at week 12: 0.2 mg vs placebo (defined as Mayo endoscopic 
subscore <= 1) 
• Mucosal healing rate at week 12: 0.1 mg vs placebo 
14.3.2. 
MISSING DATA METHODS FOR SECONDARY EFFICACY 
VARIABLES 
For the quantitative efficacy endpoint (changes in the Mayo score at week 12), the MI, LOCF, 
and complete case analysis will be presented if the Mayo score is missing in FAS and mFAS 
population. 
For the qualitative efficacy analyses, subjects with any missing individual rating at week 12 will 
be considered as non-responders. 
Endoscopy video will be obtained during each endoscopy and will be sent to Bioclinica for 


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central reading and determination of the Mayo endoscopy score. The result of the central reading 
of the endoscopy will be used to ensure subject eligibility prior to randomization and to calculate 
the Mayo score at analysis time points specified in the SAP. The Mayo score used for clinical 
endpoints in the study will utilize the Mayo endoscopy score derived from the central reader. The 
Mayo endoscopic score read by the investigator will be used as the Mayo score for clinical 
endpoints in case central reading endoscope data is missing. 
14.3.3. 
ANALYSIS OF SECONDARY EFFICACY VARIABLES 
Unless otherwise specified, all secondary efficacy analyses will be performed between treatment 
group and placebo and based on FAS and PPS. All results of these comparative analyses are used 
for exploratory purpose. 
The clinical response rate at week 12, clinical remission rate at week 12, and mucosal healing rate 
at week 12 will be analysed 
Summary statistics of qualitative statistic will be provided by each treatment group. Statistical 
comparison between the 0.2 mg CBP-307 group versus the placebo group and between 0.1 mg 
versus placebo group will be conducted using the Cochran Mantel Haenszel (CMH) test, 
stratified by whether treatment with a tumor necrosis factor (TNF)-α antagonist failed (Yes or 
No). The p-value on the rate difference and the 95% Newcombe confidence interval (CI) will be 
provided. 
For example: 
The null hypothesis to be tested is that the clinical response rate at week 12 is not different 
between the 0.2 mg treatment group and the placebo treatment group; i.e.,  
H0: clinical response rate at week 120.2 mg = clinical response rate at week 12placebo  
The alternative hypothesis is that clinical response rate at week 12 in the 0.2 mg treatment group 
is higher than that of the placebo treatment group, i.e.,  
HA: clinical response rate at week 120.2 mg≠ clinical response rate at week 12placebo  


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for quantitative summary statistics, the least square mean (LSMEANS), together with the p values 
and the 95% confidence intervals, between 0.2 mg vs. placebo and between 0.1 mg vs. placebo 
will be reported using the ANCOVA model (SAS PROC MIXED), with the stratification factor as 
the confounding factor in the ANCOVA model and the baseline values as covariate.  
14.4. 
EXPLORATORY EFFICACY  
14.4.1. 
EXPLORATORY EFFICACY VARIABLE & DERIVATIONS  
14.4.1.1 IBDQ Score 
The Inflammatory Bowel Disease Questionnaire (IBDQ) (see Appendix 1 in protocol) is a 
psychometrically validated subject self-assessment scale used to measure the disease-specific 
quality of life in subjects with inflammatory bowel diseases including UC. IBDQ contains 32 items 
related to four aspects: intestinal function, emotional status, systemic symptoms, and social ability. 
The four aspects are scored as follows: 
• Intestinal symptoms (10-70): question 1, 5, 9, 13, 17, 20, 22, 24, 26, 29 
• Systemic symptoms (5-35): question 2, 6, 10, 14, 18 
• Emotional function (12-84): question 3, 7, 11, 15, 19, 21, 23, 25, 27, 30, 31, 32  
• Social ability (5-35): question 4, 8, 12, 16, 28 
For each aspect, the higher the score is, the better the quality of life is. IBDQ is used as an endpoint 
indicator of the study and will be completed by the subjects themselves at baseline and at week 12 
(or early termination visit). 
The exploratory efficacy variable regarding to IBDQ is: 
• Change from baseline at week 12 (stage 1) in IBDQ total and subscale scores (Bowel 
Systems, Emotion Health, Systemic Systems, and Social Function): 0.2 mg vs placebo 
• Change from baseline at week 12 (stage 1) in IBDQ total and subscale scores: 0.1 mg vs 


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placebo 
• Change from baseline at week 24 (stage 2) in IBDQ total and subscale scores: 0.2 mg vs 
placebo 
• Change from baseline at week 24 (stage 2) in IBDQ total and subscale scores: 0.1 mg vs 
placebo 
• Change from baseline at week 48 (stage 2) in IBDQ total and subscale scores: 0.2 mg vs 
placebo 
• Change from baseline at week 48 (stage 2) in IBDQ total and subscale scores: 0.1 mg vs 
placebo 
Other efficacy endpoints in stage 1 
• Exploratory cinical remission rate at week 12 by adapted Mayo score: 0.2 mg vs placebo 
(defined as a rectal bleeding subscore <= 1 and a stool frequency subscore <= 1, with an 
Endoscopy subscore <= 1 [excluding friability]. 
• Exploratory cinical remission rate at week 12 by adapted Mayo score: 0.1 mg vs placebo 
 
Efficacy endpoint in stage 2 sub-study 1 
• Percentage of subjects who maintain clinical response at week 48: 0.2 mg vs placebo  
• Percentage of subjects who maintain clinical response at week 48: 0.1 mg vs placebo 
• Percentage of subjects who achieve clinical remission at week 48: 0.2 mg vs placebo 
• Percentage of subjects who achieve clinical remission at week 48: 0.1 mg vs placebo 
• Percentage of subjects who achieve mucosal healing under endoscope at week 48: 0.2 mg 
vs placebo 
• Percentage of subjects who achieve mucosal healing under endoscope at week 48: 0.1 mg 
vs placebo 


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• Percentage of subjects who take oral corticosteroids at baseline, has discontinued 
treatment with corticosteroids at week 48 and achieved clinical remission: 0.2 mg vs 
placebo 
• Percentage of subjects who take oral corticosteroids at baseline, has discontinued 
treatment with corticosteroids at week 48 and achieved clinical remission: 0.1 mg vs 
placebo 
• Change in the complete Mayo score at week 48 from baseline: 0.2 mg vs placebo 
• Change in the complete Mayo score at week 48 from baseline: 0.1 mg vs placebo 
• Change in the adapted Mayo score at week 48 from baseline: 0.2 mg vs placebo 
• Change in the adapted Mayo score at week 48 from baseline: 0.1 mg vs placebo 
• Percentage of Subjects Who Take Oral Corticosteroids at Baseline, Has Discontinued 
Treatment with Corticosteroids at Week 48 and Achieved Clinical Remission 
 
Efficacy endpoint in stage 2 sub-study 2 
• Percentage of subjects who achieve clinical response at week 24 (at week 12 after 
treatment in sub-study 2) 
• Percentage of subjects who achieve clinical remission at week 24 (at week 12 after 
treatment in sub-study 2) 
• Percentage of subjects who achieve mucosal healing under endoscope at week 24 (at 
week 12 after treatment in sub-study 2) 
• Change in the adapted Mayo score at week 24 (at week 12 after treatment in sub-study 2) 
from week 12 
• Change in the complete Mayo score at week 24 (at week 12 after treatment in sub-study 
2) from week 12 
• Percentage of subjects who maintain clinical response at week 48 (at week 36 after 
treatment in sub-study 2) (i.e., have clinical response at both week 24 and week 48)  


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• Percentage of subjects who achieve clinical remission at week 48 (at week 36 after 
treatment in sub-study 2) 
• Percentage of subjects who achieve mucosal healing under endoscope at week 48 (at 
week 36 after treatment in sub-study 2) 
• Change in the complete Mayo score at week 48 (at week 36 of treatment in sub-study 2) 
from week 12: 
• Change in the adapted Mayo score at week 48 (at week 36 after treatment in sub-study 2) 
from week 12 
• Percentage of Subjects Who Take Oral Corticosteroids at Baseline, Has Discontinued 
Treatment with Corticosteroids at Week 48 and Achieved Clinical Remission 
 
Efficacy endpoint in all stages for 0.2mg only: 
• Change in the adapted Mayo score  from baseline 
• Change in the complete Mayo score from baseline 
• Percentage of subjects who achieve clinical response at week 12 and week 48  
• Percentage of subjects who achieve clinical remission at week 12 and week 48 
• Percentage of subjects who achieve mucosal healing under endoscope  at week 12 and 
week 48 
Change from Baseline by Visit in IBDQ Total and Subscale Scores by VisitSummary of Percentage of Subjects Who 
Take Oral Corticosteroids at Baseline, Has Discontinued Treatment with Corticosteroids at Week 48 and Achieved 
Clinical Remission 
14.4.2. 
ANALYSIS OF EXPLORATORY EFFICACY VARIABLES 
Unless otherwise specified, exploratory efficacy analyses will be performed between treatment 
group and placebo and based on FAS, mFAS (only for stage 1), and PPS. All results of these 
comparative analyses are used for exploratory purpose.  


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The change in IBDQ total and subscale scores at week 12 will be summarized by treatment group. 
The least square mean (LSMEANS), together with the p values and the 95% confidence intervals, 
between 0.2 mg vs. placebo and between 0.1 mg vs. placebo will be reported using the ANCOVA 
model (SAS PROC MIXED), with the stratification factor as the confounding factor in the 
ANCOVA model. The change from baseline over time on the IBDQ total and subscale scores will 
also be plotted by each treatment group for exploratory purpose. If the individual score is missing 
at week 12 or week 12 is out of visit window, the latest observation carried forward (LOCF) 
method will be applied. The latest record before week 12 will be used for imputation. 
For the endpoint clinical response rate, clinical remission rate, mucosal healing rate, change in 
complete Mayo score and change in adapted Mayo score of stage 2 sub-study 1 will be same as 
secondary endpoint in stage 1. But for stage 2 sub-study 2 and 0.2mg only analysis, only 
descriptive statistics will be presented for single arm. 
15. SAFETY ANALYSES 
All safety analyses will be based on the SS by treatment group. Only the descriptive statistics will 
be reported on the safety endpoints and no statistical comparisons will be conducted on safety data, 
unless otherwise specified.  
15.1. 
ADVERSE EVENTS 
Adverse Events (AEs) will be coded using the Medical Dictionary for Regulatory Activities 
(MedDRA), version 21.1 or higher. 
Treatment emergent adverse events (TEAEs) are defined as AEs that started, or worsened in 
severity, on or after the date of the first dose to the last dose date plus 28 days; it does not 
necessarily need to have a causal relationship with this treatment.   
Missing date will be imputed following the blow rule: 


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When the AE start date is incomplete (i.e., partially missing), then the following rules will be 
applied: 
Missing day and month 
• If the year is the same as the year of the date of the treatment start date, then the day and 
month of the date of the treatment start date will be assigned to the missing fields. 
• If the year is before the year of the treatment start date then December 31 will be assigned 
to the missing fields. 
• If the year is after the year of the date of the treatment start date, then January 1 will be 
assigned to the missing fields. 
Missing month only 
• The day will be treated as missing and both month and day will be replaced according to 
the above procedure. 
Missing day only 
• If the month and year are the same as the month and year of the treatment start date, then 
the day of the treatment start date will be assigned to the missing day. 
• If either the year is before the year of the date of the treatment start date or if both years 
are the same, but the month is before the month of the treatment start date, then the last day 
of the month will be assigned to the missing day. 
• If either the year is after the year of the date of the treatment start date or if both years are 
the same, but the month is after the month of the treatment start date, then the first day of 
the month will be assigned to the missing day. 
If the stop date is not missing and the start date is after the stop date after missing value calculation, 
the stop date will be used for the start date.   
An overall summary table for all AEs will be provided by the count and percentage. An overall 
summary of number of subjects within each of the categories described in the sub-section below, 


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will be provided as specified in the templates.  
Listings will include TEAEs and Non-TEAEs. TEAEs (Y/N) will be flagged in the listings. 
15.1.1. 
ALL TEAES  
Incidence of TEAEs will be presented by SOC and PT and broken down further by maximum 
severity and relationship to study medication. 
15.1.1.1. 
Severity 
Severity is classed per CTCAE grade.  If a subject report a TEAE more than once within that SOC/ 
PT, the AE with the worst-case severity will be used in the corresponding severity summaries. 
15.1.1.2. 
Relationship to Study Medication 
Relationship, as indicated by the Investigator, is classed as “Related”, “Possibly Related”, 
“Unlikely Related”, “Not Related”, A” Related” TEAE is defined as a TEAE with a relationship 
to study medication as “Related”, “Possibly Related” to study medication. TEAEs with a missing 
relationship to study medication will be regarded as “Related” to study medication. If a subject 
report the same AE more than once within that SOC/ PT, the AE with the worst-case relationship 
to study medication will be used in the corresponding relationship summaries.  
15.1.2. 
TEAES LEADING TO DISCONTINUATION OF STUDY MEDICATION 
TEAEs leading to permanent discontinuation of study medication will be identified by using the 
“Drug Withdrawal” to the item “Action Taken with Study Drug/ Placebo ” on the “Adverse Events” 
form of eCRF.  
For TEAEs leading to discontinuation of study medication, summaries of incidence rates 
(frequencies and percentages) by SOC and PT will be prepared. 
15.1.3. 
SERIOUS ADVERSE EVENTS 
Serious adverse events (SAEs) are those events recorded as” Yes” to the item “Serious Event?” on 


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the adverse events page of the (e)CRF. A summary of serious TEAEs by SOC and PT will be 
presented. 
15.1.4. 
ADVERSE EVENTS LEADING TO DEATH 
TEAEs leading to Death are those events which are recorded as” Fatal” to the item “Outcome” on 
the Adverse Events page of the (e)CRF. A summary of TEAEs leading to death by SOC and PT 
will be presented. 
15.1.5. 
ADVERSE EVENTS OF SPECIAL INTEREST  
Adverse events of special interest are those events which are recorded as “Yes” to the item “Is 
This an Adverse Event of Special Interest?” on the Adverse Events page of the eCRF. The adverse 
event of special interest will include the following: 
• Bradycardia and cardiac conduction abnormalities 
• Pulmonary toxicity 
• Hepatotoxicity  
• Macular Edema 
• Opportunistic or serious infections 
• Malignant neoplasm of skin 
• Posterior reversible encephalopathy syndrome 
• Progressive multifocal leukoencephalopathy. 
A summary of adverse event of special interest by SOC and PT will be presented. 
15.2. 
DEATHS 
If any subjects die during the study as recorded on the “death” page of the eCRF, the information 
will be presented in a summary table and a data listing. 


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15.3. 
LABORATORY EVALUATIONS 
Laboratory tests include the following: 
Laboratory test item 
Parameter 
Hematology 
Red blood cell (RBC) count, HGB, hematocrit 
(HCT), white blood cell count, blood platelet 
count, 
leukocyte 
differential 
count 
(lymphocyte 
count, 
neutrophil 
count, 
monocyte count, eosinophil count, basophil 
count) 
Blood biochemistry 
 
  Liver function test 
Total bilirubin, conjugated bilirubin, ALT, 
AST, γ-GT, alkaline phosphatase, albumin, 
total protein, lactate dehydrogenase 
  Kidney function test 
Urea, creatinine, uric acid, Na, K, Cl, Ca, P, 
amylase 1 
  Blood glucose examination 
Fasting blood glucose (FBG) 
  Fasting blood fat 2 
Total cholesterol, low-density lipoprotein 
cholesterol, 
high-density 
lipoprotein 
cholesterol and triglycerides 
  Coagulation 
Prothrombin 
time 
activated 
partial 
thromboplastin 
time, 
and 
international 
normalized ratio 
Urinalysis/microscopy 3 
Specific gravity, pH, nitrite, protein, glucose, 
ketone bodies, urobilinogen, bilirubin, occult 
blood, esterase leukocyte/erythrocyte, and 


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white blood cells 
Fecal culture/microscopy 4 
Fecal culture, C.difficile, eggs and parasites, 
and fecal calprotectin 
Others 
 
  Virological and serological tests 
   
Anti-VZV IgG, HIV antibody, HBsAg, 
HBsAb, HBcAb and HCVAb 
Syphilis antibody 
HBV DNA, HCV viral loads 
  Detection of immunoglobulin 
Immunoglobulin A, G, M 
  Detection of C-reactive protein 
C-reactive protein 
  Pregnancy test 5 
Blood  β-human chorionic gonadotropin and 
urine pregnancy test 
  Quantiferon or Quantiferon Plus test 6 
TB 
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; γ-GT=γ-
glutamyltransferase; HBcAb=hepatitis B core antibody; HBsAb=hepatitis B surface antibody; 
HBsAg=hepatitis 
B 
surface 
antigen; 
HCVAb=hepatitis 
C 
antibody; 
HIV=human 
immunodeficiency virus; IgG=immunoglobulin G; TB=tuberculosis; VZV=varicella zoster 
virus.  
1. Abnormal laboratory parameters or potential medical condition inconsistent with the 
clinical manifestations of UC should be repeatedly measured. At any follow-up after drug 
administration, if the amylase level is significantly higher than the clinical reference range 
(>=300 U/L), the lipase level should be measured to determine the source of elevated 
amylase (outside the pancreas). 
2. Subjects must fast within 9 hours before a laboratory test. 
3. If urinalysis show occult blood or abnormal urine protein in subjects' urine samples, a 
microscopy needs to be performed. A microscopy mainly refers to a blood test that measures 


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white blood cells and red blood cells. All other tests are tests with test strips. 
4. Fecal culture/microscopy (involving fecal culture, C.difficile, eggs and parasites) is required 
to be performed at screening. During the screening period and any time point during the 
study if the subject has symptoms including aggravation of the disease condition or disease 
activity before recovery, stool samples can be collected for fecal culture/microscopy and 
C.difficile analysis. 
5. Women with fertility are required to undergo a pregnancy test (involving blood β-human 
chorionic gonadotropin and urine pregnancy test). At screening, subjects with amenorrhea 
for <5 years are required to undergo measurement of follicle stimulating hormone to confirm 
postmenopausal condition. 
6. Subjects can be enrolled in the study if it is evidenced that TB was treated successfully and 
Quantiferon or Quantiferon Plus test result is negative. If Quantiferon or Quantiferon Plus 
test result was uncertain at screening, the retest may be carried out during screening period. 
If Quantiferon or Quantiferon Plus retest result was uncertain, the subject should not 
participate in the study. If Quantiferon or Quantiferon Plus retest result is negative, the 
subject can be enrolled in the study. 
Hematology, blood chemistry, and coagulation test results will be summarized at each study visit 
by treatment group. 
Subjects with abnormalities in hematology assessments, defined as absolute lymphocyte count 
(ALC) <200 cells/uL, absolute neutrophil count (ANC) < 500 cells/uL as well as ANC <1000 
cells/uL and total WBC >20,000 cells/uL will be summarized for each treatment group. 
In addition, the change and percent change from baseline in complete blood count with Differential 
will be summarized for each treatment group. 
The incidence of subjects with abnormalities for ALT/AST/ALP will be summarized overall and 
at each visit for each treatment group for the following categories: 
>= 3 x ULN 
            >= 5 x ULN  


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>= 8 x ULN 
The incidence of subjects with abnormalities for total bilirubin and conjugated bilirubin will be 
summarized overall and at each visit for each treatment group for the following categories: 
> 1 x upper limit of normal (ULN) 
>= 2 x ULN 
 
Shift Tables from Baseline to Worst Post-baseline CTCAE Grade are presented. 
 
15.4. 
ECG EVALUATIONS 
The following ECG parameters will be reported for this study: 
• 
Heart Rate (bpm) 
• 
PR Interval (msec) 
• 
RR Interval (msec) 
• 
QRS Interval (msec) 
• 
QT Interval (msec) 
• 
QTcF Interval (msec)  
• 
Overall assessment of ECG (Investigator’s judgment): 
➢ Normal 
➢ Abnormal, Not Clinically Significant (NCS) 
➢ Abnormal, Clinically Significant (CS) 
➢ Not Evaluable 
The following summaries will be provided for ECG data: 
• 
Actual value and change from baseline by visit 
• 
Shift from baseline to worst post baseline for overall evaluation 
• 
Incidence of subjects with abnormalities for QT Internal/QTcF by visit 
• 
Shift from baseline according to post-baseline maximum value category for QT Interval 


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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
and QTcF  
• 
Shift from baseline according to post-baseline maximum increase category for QT 
Interval and QTcF  
• 
Listing of ECG 
• 
Listing of Holter ECG 
15.4.1. 
ECG MARKEDLY ABNORMAL CRITERIA 
Markedly abnormal quantitative ECG measurements will be identified in accordance with the 
following predefined markedly abnormal criteria: 
• 
Absolute values for QT interval and QTcF will be classified as: 
➢ > 450 msec  
➢ > 480 msec  
➢ > 500 msec 
• 
Change from Baseline for QT interval and QTcF will be classified as: 
➢ >30 msec increase from baseline 
➢ >60 msec increase from baseline 
15.5. 
VITAL SIGNS 
The following Vital Signs measurements will be reported for this study: 
• 
Systolic Blood Pressure (SBP) (mmHg) 
• 
Diastolic Blood Pressure (DBP) (mmHg) 
• 
Systolic Blood Pressure(mmHg) (SBP) (Upright Position) 
• 
Diastolic Blood Pressure(mmHg) (DBP) (Upright Position) 
• 
Respiratory Rate (RR) (resp/min) 
• 
Heart Rate (HR) (bpm) 
• 
Temperature (⁰C) 


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• 
Weight (kg) 
• 
Height (cm) 
The following summaries will be provided for vital signs data: 
• 
Actual and change from baseline by visit  
• 
Incidence Markedly Abnormal Values of vital signs: 
➢ SBP (mmHg) Low is defined as observed value less or equal to 90 and change 
from baseline less or equal to -20. 
➢ SBP (mmHg) High is defined as observed value greater or equal to 180 and 
change from baseline greater or equal to 20. 
➢ DBP (mmHg) Low is defined as observed value less or equal to 50 and change 
from baseline less or equal to -15. 
➢ DBP (mmHg) High is defined as observed value greater or equal to 105 and 
change from baseline greater or equal to 15. 
➢ HR (Bpm) Low is defined as observed value less or equal to 50 and change from 
baseline less or equal to -15. 
➢ HR (Bpm) High is defined as observed value greater or equal to 120 and change 
from baseline greater or equal to 15. 
➢ Temperature (˚C) High is defined as observed value greater or equal to 38.3 and 
change from baseline greater or equak to 1.1. 
➢ Weight (kg) Low is defined as percentage change from baseline less or equal to -
7.0%. 
➢ Weight (kg) High is defined as percentage change from baseline greater or equal 
to 7.0%. 
• 
Listing of vital signs 


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15.6. 
PHYSICAL EXAMINATION  
The following summaries will be provided for physical examination results: 
• 
 Overall assessment of physical examination 
• 
Listing of physical examination 
The following specific assessments will be conducted:  neck/thyroid, chest/lung, heart, lymph, 
nodes, abdomen, nervous system, and other (if applicable). Each measurement will be categorized 
as normal/abnormal, NCS/abnormal, CS/NE.  Nervous System Physical Examination result will 
be also summarized by symptoms.  
15.7. 
OTHER SAFETY ASSESSMENTS 
15.7.1. 
PULMONARY FUNCTION TEST 
The following pulmonary function test measurements will be reported for this study: 
• 
FEV1 Results 
• 
FEV1 Predicted Results 
• 
FEV1% Predicted Results 
• 
FVC Results 
• 
FVC  Predicted Results 
• 
FVC % Predicted Results 
• 
DLCO Results 
• 
DLCO  Predicted Results 
• 
DLCO % Predicted Results 
The following summaries will be provided for pulmonary function test data: 
• 
Actual value, change, percent change and change in percent predicted from baseline by 
visit  
• 
PFT test results will also be listed. 


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15.7.2. 
OPHTHALMOLOGIC EXAMINATION 
The following summaries will be provided for ophthalmologic examination data: 
• 
Ophthalmologic examination result by visit  
• 
Shift from baseline to worst post baseline 
• 
Listing of ophthalmologic examination data 
15.7.3. 
OPTICAL COHERENCE TOMOGRAPHY 
The following summaries will be provided for optical coherence tomography data: 
• 
Optical coherence tomography result by visit  
• 
Shift from baseline to worst post baseline  
• 
Listing of optical coherence tomography data 
15.7.4. 
DERMATOLOGIC EXAMINATION 
The following summaries will be provided for dermatologic examination data: 
• 
Dermatologic examination result by visit  
• 
Shift from baseline to worst post baseline  
• 
Listing of dermatologic examination data 
15.7.5. 
PREGNANCY TEST 
Pregnancy test data will only be listed. 
15.7.6. 
CHEST IMAGING EXAMINATION 
Chest imaging examination data will only be listed. 
 
 


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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
16. REFERENCES  
Dobson, A. J. (2002). An introduction to generalized linear models, 2nd ed. Chapman & 
Hall/CRC. 
EMA. (n.d.). Guideline on Missing Data in Confirmatory Clinical Trials. Retrieved December 
15, 2011, from European Medicines Agency: 
http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/09/WC500
096793.pdf 
 
 
 
 
 
 
 


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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
APPENDIX 1. PROGRAMMING CONVENTIONS FOR OUTPUTS 
IQVIA OUTPUT CONVENTIONS 
Outputs will be presented according to the Shells. 
 
SPELLING FORMAT 
English US.  
 
PRESENTATION OF TREATMENT GROUPS 
For outputs, treatment groups will be represented as follows and in that order: 
Treatment Group 
For Tables and Graphs 
For Listings (include if different 
to tables) 
0.1 mg 
0.1 mg 
 
0.2 mg 
0.2 mg 
 
Placebo 
Placebo 
 
PRESENTATION OF VISITS 
For outputs, visits will be represented as follows and in that order: 
Long Name (default) 
Short Name  
Stage 1 
 
Screening (Visit 1) 
Scr (V1) 
Baseline (Visit 2) 
BL (V2) 


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Long Name (default) 
Short Name  
Week 1 day 1 (Visit 3) 
W1D1 (V3) 
Week 1 day 5 (Visit 4) 
W1D5 (V4) 
… 
… 
Week 16 (Visit 12) 
W16 (V12) 
Stage 2 sub-study 1 
 
Week 13 (Visit 12) 
W13 (V12) 
Week 18 (Visit 13) 
W18 (V13) 
Week 24 (Visit 14) 
W24 (V14) 
Week 32 (Visit 15) 
W32 (V15) 
Week 40 (Visit 16) 
W40 (V16) 
Week 48 (Visit 17) 
W48 (V17) 
Week 52 (Visit 18) 
W52 (V18) 
Stage 2 sub-study 2 
 
Week 13 (Visit 12) 
W13 (V12) 
Week 13 day 1 (Visit 13) 
W13D1 (V13) 
Week 13 day 5 (Visit 14) 
W13D5 (V14) 
Week 14 (Visit 15) 
W14(V15) 
Week 16 (Visit 16) 
W16(V16) 
Week 24 (Visit 17) 
W24(V17) 
Week 32 (Visit 18) 
W32 (V18) 
Week 40 (Visit 19) 
W40 (V19) 
Week 48 (Visit 20) 
W48 (V20) 
Week 52 (Visit 21) 
W52 (V21) 
 
 
 


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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
LISTINGS WILL BE ORDERED BY THE FOLLOWING (UNLESS OTHERWISE INDICATED 
IN THE TEMPLATE): 
• 
Randomized treatment group (or treatment received if it’s a safety output), first by active 
dose [by ascending dose group] and then control/ placebo. 
• 
center-subject ID,  
• 
date (where applicable), 
• 
For listings where non-randomized subjects are included, these will appear in a category after 
the randomized treatment groups labeled ‘Not Randomized’. 
 
 


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to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
APPENDIX 2. LISTING OF EFFICACY PARAMETERS AND STUDY 
POPULATIONS ANALYSED IN STAGE 1 
Efficacy 
Parameters 
Response 
Analyzed 
Comparison Groups 
Visit 
Study 
Populations 
Analyzed 
Imputation 
Method 
Group1 
Group2 
Statistical 
Method 
Primary Endpoint (Stage 1) 
Adapted 
Mayo 
Score 
Change 
from 
Baseline 
0.2mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
MCMC 
MI, LOCF 
 
Secondary Endpoints (Stage 1) 
Adapted 
Mayo 
Score 
Change 
from 
Baseline 
0.1mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
MCMC 
MI, LOCF 
Complete 
Mayo 
Score 
Change 
from 
Baseline 
0.2mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
MCMC 
MI, LOCF 
Complete 
Mayo 
Score 
Change 
from 
Baseline 
0.1mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
MCMC 
MI, LOCF 
Adapted 
Mayo 
Score 
Clinical 
Response 
Rate 
0.2mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
NRI 
Adapted 
Mayo 
Score 
Clinical 
Response 
Rate 
0.1mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
NRI 
Complete 
Mayo 
Score 
Clinical 
Response 
Rate 
0.2mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
NRI 
Complete 
Mayo 
Score 
Clinical 
Response 
Rate 
0.1mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
NRI 
Adapted 
Mayo 
Score 
Clinical 
Remission 
Rate  
0.2mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
NRI 


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Adapted 
Mayo 
Score 
Clinical 
Remission 
Rate  
0.1mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
NRI 
Complete 
Mayo 
Score 
Clinical 
Remission 
Rate  
0.2mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
NRI 
Complete 
Mayo 
Score 
Clinical 
Remission 
Rate  
0.1mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
NRI 
Mayo 
Endoscopic 
Subscore 
Mucosal 
Healing 
Rate 
0.2mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
NRI 
Mayo 
Endoscopic 
Subscore 
Mucosal 
Healing 
Rate 
0.1mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS,  
PPS 
NRI 
 
Exploratory Endpoints (Stage 1) 
IBDQ 
Change 
from 
Baseline 
0.2mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS 
MCMC 
MI, LOCF 
IBDQ 
Change 
from 
Baseline 
0.1mg 
QD 
Placebo 
ANCOVA Week 
12 
FAS, 
mFAS 
MCMC 
MI, LOCF