Clinical trial NCT05013905
Conditions: Crohn Disease
Keywords: APOLLO-CD APOLLO Crohn's Disease
Sponsor: Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Start date: 2021-07-28; Completion date: 2025-05-27
Enrollment: 55 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
The purpose of this study is to assess the safety and efficacy of PRA023 in participants with moderately to severely active Crohn's Disease.

After the completion of the 12-week induction period, all participants have the option to continue in the open-label extension for another 38 weeks.

Detailed description:

Arms: arm 1: Participants to receive PRA023 administered by intravenous (IV) infusion.
Interventions: intervention 1: PRA023 IV intervention 2: Companion diagnostic (CDx)
Intervention descriptions: intervention 1: PRA023 administered at timepoints as directed by the protocol intervention 2: CDx+ or CDx-

Protocol documents:
Prot_000.pdf: 
Official Protocol Title:
NCT number:
Document Date:
A Phase 2a, Multi-Center, Open-Label 
Study to Evaluate the Safety, Efficacy, and 
Pharmacokinetics of PRA023 in Subjects 
With Moderately to Severely Active Crohn's 
Disease 
NCT05013905
28-June-2022


 
Clinical Protocol PR200-103 
A Phase 2a, Multi-Center, Open-Label Study to Evaluate 
the Safety, Efficacy, and Pharmacokinetics of PRA023 
in Subjects with Moderately to Severely Active Crohn’s Disease 
 
The APOLLO-CD Study 
 
EudraCT: 2021-000092-37 
 
Version 4.0 (28 June 2022) 
 
 
Study Sponsor: 
Prometheus Biosciences, Inc. 
3050 Science Park Road 
San Diego, CA 92121 
USA 
 
Confidentiality Statement 
The information contained in this document is the property of Prometheus Biosciences, Inc. and 
is provided to you in confidence. The recipient agrees that no information contained herein will be 
published or disclosed without the written approval of Prometheus Biosciences, Inc. This document 
may be disclosed to applicable institutional review boards or other duly authorized regulatory agency 
representatives, as applicable, under the condition that confidentiality is maintained.
 


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PROTOCOL APPROVAL PAGE 
Prometheus Biosciences, Inc. 
Protocol: PR200-103 
A Phase 2a, Multi-Center, Open-Label Study to Evaluate 
the Safety, Efficacy, and Pharmacokinetics of PRA023 
in Subjects with Moderately to Severely Active Crohn’s Disease 
Version 4.0 (28 June 2022) 
Approved by: 
Prometheus Biosciences, Inc. 
Date 
 
 
30Jun2022
PPD


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PROTOCOL SIGNATURE PAGE 
Prometheus Biosciences, Inc. 
Protocol: PR200-103  
Version 4.0 (28 June 2022) 
By my signature I confirm that I have read, and I understand this protocol “A Phase 2a, Multi-
Center, Open-Label Study to Evaluate the Safety, Efficacy, and Pharmacokinetics of PRA023 in 
Subjects with Moderately to Severely Active Crohn’s Disease”, dated 28 June 2022, in its entirety, 
and I agree that it contains all necessary details for carrying out the study as described. I will 
diligently conduct this protocol as outlined herein in full accordance with the Principles of Good 
Clinical Practice and all applicable laws and regulations. 
 
I will provide copies of the protocol and access to all information furnished by Prometheus 
Biosciences, Inc. pertinent to the study to concerned personnel under my supervision. I will 
discuss the material with them to ensure that they are fully informed about the study. 
 
I agree to implement the protocol procedures only after confirming that specimens were 
collected with informed consent/subject information approval from the Institutional Review 
Board/Independent Ethics Committee (IRB/IEC) permitting such use. 
 
I understand that all information supplied by Prometheus Biosciences, Inc. is confidential, and 
I hereby agree to ensure that when this information is submitted to an IRB/IEC, it will be 
submitted with a designation that the material is confidential. 
Investigator Name 
Investigator’s Signature 
Date 
Institution Name 
Institution Address 


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LIST OF STUDY PERSONNEL 
SPONSOR: 
Prometheus Biosciences, Inc. 
3050 Science Park Road 
San Diego, CA 92121 
MEDICAL MONITOR CONTACT: 
Prometheus Biosciences, Inc. 
PHARMACOVIGILANCE CONTACT: 
. 
CLINICAL OPERATIONS CONTACT: 
 
 
 
PPD
PPD
PPD
CCI


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PROTOCOL VERSION AND AMENDMENT TRACKING 
Version Number/Amendment 
Date 
Version 1.1 
30 April 2021 
Version 2.0 
18 June 2021 
Version 2.1 for Belgium 
28 June 2021 
Version 3.0 
21 October 2021 
Version 3.1 for USA 
19 January 2022 
Version 4.0 
28 June 2022 
 
 


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TABLE OF CONTENTS 
Protocol Approval Page .................................................................................................................. 2 
Protocol Signature Page .................................................................................................................. 3 
List of Study Personnel ................................................................................................................... 4 
Protocol Version and Amendment Tracking .................................................................................. 5 
List of Tables ................................................................................................................................ 10 
List of Figures ............................................................................................................................... 10 
List of Abbreviations .................................................................................................................... 11 
Protocol Synopsis.......................................................................................................................... 14 
1 
Background and Rationale .................................................................................................... 25 
1.1 
Background ..................................................................................................................25 
1.2 
Study Rationale ............................................................................................................26 
1.3 
PRA023 Mechanism of Action and Nonclinical Data .................................................27 
1.3.1 
Pharmacology .................................................................................................27 
1.3.2 
Toxicology ......................................................................................................27 
1.4 
Previous Human Experience ........................................................................................29 
1.4.1 
Pharmacokinetic Results (PR200-101 Healthy Volunteer Study) ..................29 
1.4.2 
Safety Results .................................................................................................30 
1.5 
Dose Rationale .............................................................................................................30 
1.6 
Overall Benefit/Risk Assessment .................................................................................31 
2 
Study Objectives .................................................................................................................... 33 
2.1 
Primary Objective ........................................................................................................33 
2.2 
Secondary Objectives ...................................................................................................33 
2.3 
Exploratory Objectives .................................................................................................33 
3 
Study Endpoints..................................................................................................................... 35 
3.1 
Primary Endpoints ........................................................................................................35 
3.2 
Secondary Endpoints ....................................................................................................35 
3.3 
Exploratory Endpoints .................................................................................................35 
4 
Investigational Plan ............................................................................................................... 37 
4.1 
Study Design ................................................................................................................37 
4.1.1 
Study Schema .................................................................................................38 
4.1.2 
Subject Participation Duration ........................................................................38 
4.1.3 
Subject Numbering and Randomization .........................................................38 
4.1.4.1 
Screening Numbers ....................................................................... 38 
4.1.4.2 
Randomization Numbers .............................................................. 39 
4.2 
Study Subjects/Population ...........................................................................................39 
4.2.1 
Inclusion/Exclusion Criteria ...........................................................................39 


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4.2.1.1 
Inclusion Criteria .......................................................................... 39 
4.2.1.2 
Exclusion Criteria ......................................................................... 41 
4.3 
Contraception Guidelines .............................................................................................44 
4.4 
Concomitant Treatments and Restrictions ...................................................................45 
4.4.1 
Prior and Concomitant Medications ...............................................................45 
4.4.2 
Permitted Medications with Restrictions ........................................................45 
4.4.3 
Prohibited Medications ...................................................................................46 
4.4.4 
Corticosteroid and Budesonide Tapering Schedule During Open-Label Period
 ........................................................................................................................46 
4.4.5 
Other Restricted Medications .........................................................................46 
4.4.6 
Rescue Medication ..........................................................................................47 
4.5 
Removal of Subjects from Study .................................................................................47 
4.6 
Modification of Study Drug Dosing ............................................................................48 
5 
Investigational Product .......................................................................................................... 49 
5.1 
Dosing Form and Preparation ......................................................................................49 
5.2 
Storage ..........................................................................................................................49 
5.3 
Accountability ..............................................................................................................49 
5.4 
PRA023 Administration ...............................................................................................50 
6 
Study Procedures ................................................................................................................... 51 
6.1 
Study Visit Procedures .................................................................................................51 
6.1.1 
Schedule of Study Assessments ......................................................................52 
6.2 
Other Information for Study Visits ..............................................................................61 
6.3 
Safety Assessment Description ....................................................................................61 
6.3.1 
Medical History, Physical Examination, Height and Weight .........................61 
6.3.2 
Vital Signs ......................................................................................................61 
6.3.3 
Chest X-Ray ....................................................................................................62 
6.3.4 
Electrocardiogram (ECG) ...............................................................................62 
6.3.5 
Clinical Laboratory Evaluations .....................................................................62 
6.3.6 
Stool Evaluation ..............................................................................................64 
6.3.5.1 
Stool Culture ................................................................................. 64 
6.3.5.2 
Screening for Clostridium Difficile .............................................. 64 
6.4 
Efficacy Assessment Description .................................................................................64 
6.4.1 
Ileocolonoscopy with Biopsy .........................................................................65 
6.4.1.1 
Ileocolonoscopy and SES-CD Score ............................................ 65 
6.4.1.2 
Biopsy ........................................................................................... 66 
6.4.2 
Crohn’s Disease Activity Index (CDAI) Score ..............................................66 
6.4.3 
Perianal Disease Activity Index (PDAI) .........................................................67 


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6.4.4 
Fistula Drainage Assessment ..........................................................................67 
6.4.5 
Quality of Life (QoL) .....................................................................................67 
6.5 
Pharmacodynamics ......................................................................................................67 
6.6 
Pharmacokinetics .........................................................................................................68 
6.7 
Immunogenicity (Anti-Drug Antibody) .......................................................................68 
6.8 
Pharmacogenomics ......................................................................................................69 
6.9 
Potential Future Research ............................................................................................69 
7 
Adverse Events and Serious Adverse Events ........................................................................ 70 
7.1 
Pre-Treatment-Emergent Events ..................................................................................71 
7.2 
Laboratory Abnormalities as Adverse Events ..............................................................72 
7.3 
Grading/Severity of Adverse Events ............................................................................72 
7.4 
Relationship of Adverse Events ...................................................................................73 
7.4.1 
Relationship of Adverse Events to Study Drug Administration .....................73 
7.4.2 
Relationship of Adverse Events to Study Procedures ....................................73 
7.5 
Recording and Reporting of Adverse Events ...............................................................73 
7.5.1 
Recording Adverse Events .............................................................................73 
7.5.2 
Investigator Reporting of a Serious Adverse Event .......................................74 
7.5.3 
Investigator Reporting of a Pregnancy ...........................................................74 
7.6 
Additional Investigator Responsibilities for Serious Adverse Events .........................75 
7.7 
Post-Study Follow-Up of Adverse Events ...................................................................75 
7.8 
Notification of Post-Study Serious Adverse Events ....................................................75 
7.9 
IRB/IEC Notification of Serious Adverse Events ........................................................76 
7.10 Health Authority Safety Reports ..................................................................................76 
7.11 Data Monitoring Committee (DMC) ...........................................................................76 
8 
Assessment of Study Variables ............................................................................................. 77 
8.1 
Randomization .............................................................................................................77 
8.2 
Justification of Sample Size .........................................................................................77 
8.3 
Evaluation of Safety Variables .....................................................................................77 
9 
Statistical Methodology ......................................................................................................... 79 
9.1 
Analysis Populations ....................................................................................................79 
9.1.1 
Safety Analysis Set (SAS) Population ............................................................79 
9.1.2 
Full Analysis Set (FAS) Population ...............................................................79 
9.2 
Statistical Analyses ......................................................................................................79 
9.2.1 
Demographics and Baseline Characteristics ...................................................79 
9.2.2 
Evaluation of Efficacy Parameters .................................................................79 
9.2.3 
Evaluation of Pharmacodynamic Parameters .................................................80 
9.2.4 
Evaluation of Immunogenicity .......................................................................80 


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9.2.5 
Evaluation of Exploratory Parameters ............................................................80 
9.2.6 
Evaluation of Pharmacokinetic Parameters ....................................................80 
9.2.7 
Evaluation of Safety Parameters .....................................................................80 
9.2.7.1 
Adverse Events and Adverse Events of Special Interest .............. 80 
9.2.7.2 
Medical History, Chest X-ray, ECGs and Physical 
Examination .................................................................................. 81 
9.2.7.3 
Clinical Laboratory and Vital Signs ............................................. 81 
9.2.7.4 
Previous and Concomitant Medication ......................................... 81 
10 Ethics and Regulatory Requirements .................................................................................... 82 
10.1 General Requirements for Study Conduct ...................................................................82 
10.2 Regulatory and Institutional Review Board Approval/ Independent Ethics 
Committee ....................................................................................................................82 
10.3 Written Informed Consent ............................................................................................82 
10.4 Confidentiality ..............................................................................................................82 
10.5 Protocol Modification/Amendments ............................................................................83 
10.6 Direct Access to Source Data/Documents ...................................................................83 
11 Definition of End of Trial ...................................................................................................... 84 
11.1 End of Trial in a Member State ....................................................................................84 
11.2 End of Trial in All Other Participating Countries ........................................................84 
12 Data Management .................................................................................................................. 85 
12.1 Coding of Adverse Events, Concomitant Medication, and Medical History ...............85 
13 Documentation and Administrative Considerations .............................................................. 86 
13.1 Recordkeeping ..............................................................................................................86 
13.2 Disclosure of Data ........................................................................................................86 
13.3 Publication Policy ........................................................................................................86 
14 Quality Control and Quality Assurance ................................................................................ 88 
15 References ............................................................................................................................. 89 
16 Appendix ............................................................................................................................... 92 
16.1 Simple Endoscopic Score for Crohn’s Disease (SES-CD) ..........................................92 
16.2 Crohn’s Disease Activity Index (CDAI) ......................................................................93 
16.3 Perianal Disease Activity Index (PDAI) ......................................................................94 
 
 


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LIST OF TABLES 
 
Schedule of Study Assessments – Screening Period ...................................................52 
 
Schedule of Study Assessments – Induction Period ....................................................54 
 
Schedule of Study Assessments – Open-Label Extension Period ...............................56 
 
Schedule of Study Assessments – Open-Label Extension Period (After Week 50) ....58 
 
Post Dosing Follow-Up Period ....................................................................................60 
 
Severity of Adverse Events ..........................................................................................72 
 
Placebo Endoscopic Response Rates in Recent CD Clinical Trials ............................77 
LIST OF FIGURES 
Figure 1 
Study Schema...............................................................................................................38 
 


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LIST OF ABBREVIATIONS 
Abbreviation or specialist term 
Explanation 
5-ASA 
5-Acetylsalicylic acid 
6-MP 
6-Mercaptopurine 
ADA 
Anti-drug antibody 
ADCC 
Antibody-dependent cellular cytotoxicity 
ADCP 
Antibody-dependent cell-mediated phagocytosis 
ADL 
Activities of daily living 
AE 
Adverse event 
ALT 
Alanine aminotransferase 
AST 
Aspartate aminotransferase 
AUC 
Area under the curve 
AUC0-t 
Area under the concentration time curve from hour zero to the last 
measurable concentration, estimated by the linear trapezoidal rule 
AZA 
Azathioprine 
BUN 
Blood urea nitrogen 
CBC 
Complete blood count 
CD 
Crohn’s disease 
CDAI 
Crohn’s disease activity index 
CDC 
Complement-dependent cytotoxicity 
CDx 
Companion diagnostic 
CFR 
Code of Federal Regulations 
CK 
Creatine kinase 
Cmax 
Maximum concentration 
CMV 
Cytomegalovirus 
CNS 
Central nervous system 
COVID-19 
Coronavirus disease 2019 
CRO 
Contract Research Organization 
CS 
Clinically significant 
CTA 
Clinical trial application 
CTCAE 
Common Toxicity Criteria for Adverse Events 
CV 
Coefficient of variation 
DILI 
Drug induced liver injury 
DMC 
Data Monitoring Committee 
DMP 
Data management plan 
DNA 
Deoxyribonucleic acid 
DR3 
Death receptor 3 
DSS 
Dextran sodium sulfate 
EC 
Ethics Committee 
eCRF 
Electronic case report form 
ECG 
Electrocardiogram 
EDC 
Electronic data capture 
eDiary 
Electronic diary 
EFD 
EHI 
Embryo-fetal development 
Endoscopic healing index 
ET 
Early termination 
FAS 
Full Analysis Set 
FcR 
Fc receptor 
FDA 
Food and Drug Administration 


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Abbreviation or specialist term 
Explanation 
FSH 
Follicle stimulating hormone 
FU 
Follow-Up 
GCP 
Good Clinical Practice 
GD 
Gestational day 
GDH 
Glutamate dehydrogenase 
GGT 
Gamma-glutamyl transferase 
GHAS 
Global histological activity score 
GI 
Gastrointestinal 
GLP 
Good Laboratory Practice 
GM 
Geometric mean 
HBsAg 
Hepatitis B surface antigen 
HBcAb 
Hepatitis B core antibody 
HCV 
Hepatitis C virus 
HDL 
High density lipoprotein 
Hgb 
Hemoglobin 
HIV 
Human immunodeficiency virus 
hsCRP 
High sensitivity C-reactive protein 
IBD 
Inflammatory bowel disease 
IBDQ 
Inflammatory Bowel Disease Questionnaire 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
IFN-γ 
Interferon gamma 
IgG 
Immunoglobulin G 
IgG1κ 
Immunoglobulin G subtype G1 kappa 
IgM 
Immunoglobulin M 
IL-12/23 
Interleukin-12/23 
ILC 
Innate lymphoid cell 
INR 
International normalized ratio 
IP 
Induction Period 
IRB 
Institutional Review Board 
IRT 
Interactive response technology 
IUD 
Intrauterine device 
IV 
Intravenous  
KLH 
Keyhole limpet haemocyanin 
LDH 
Lactic dehydrogenase 
LDL 
Low density lipoprotein 
LSLV 
Last subject last visit 
MAD 
Multiple ascending dose 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMF 
Mycophenolate mofetil 
mRNA 
Messenger ribonucleic acid 
MTX 
Methotrexate 
Nab 
Neutralizing antibody 
NCI 
National Cancer Institute 
NCS 
Not clinically significant 
NK 
Natural killer 
NOAEL 
No observed adverse effect level 
NS 
Normal saline 


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Abbreviation or specialist term 
Explanation 
NSAID 
Non-steroidal anti-inflammatory agent 
OLE 
Open-Label Extension 
PBMC 
Peripheral blood mononuclear cell 
PCR 
Polymerase chain reaction 
PD 
Pharmacodynamic 
PDAI 
Perianal Disease Activity Index 
PG 
Pharmacogenomic 
PK 
Pharmacokinetic 
PRO-2 
Two component patient-reported outcome 
PSC 
Primary sclerosing cholangitis 
PT 
Preferred term 
Q2W 
Every 2 weeks 
Q4W 
Every 4 weeks 
QoL 
Quality of life 
RBC 
Red blood cell 
RHI 
Robarts histopathology index 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SES-CD 
Simple endoscopy score for Crohn’s disease 
SOC 
System organ class 
sTL1A 
Soluble tumor necrosis factor-like cytokine 1A 
SOP 
Standard operating procedure 
SUSAR 
Suspected, unexpected serious adverse reaction 
t1/2 
Half-life 
TB 
Tuberculosis 
TCR 
T-cell receptor 
TEAE 
Treatment-emergent adverse event 
Th1 
T helper 1 cells  
Th 2 
T helper 2 cells 
Th 9 
T helper 9 cells 
Th17 
T helper 17 cells 
TL1A 
Tumor necrosis factor-like cytokine 1A 
TLR 
Toll like receptor 
Tmax 
Time to maximum concentration 
TMDD 
Target-mediated drug disposition 
TNF 
Tumor necrosis factor 
UC 
Ulcerative colitis 
ULN 
Upper limit of normal 
VLDL 
Very low density lipoprotein 
WBC 
White blood cell 
WHO-DD 
World Health Organization – Drug Dictionary 
WK 
Week 
WOCBP 
Women of childbearing potential 


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PROTOCOL SYNOPSIS 
TITLE: 
A Phase 2a, Multi-Center, Open-Label Study to Evaluate the Safety, 
Efficacy, and Pharmacokinetics of PRA023 in Subjects with Moderately to 
Severely Active Crohn’s Disease 
PROTOCOL NUMBER: PR200-103 
PROJECT PHASE: 
Phase 2a 
OBJECTIVE: 
Primary: 
• 
To evaluate the safety and tolerability of PRA023 following 12-weeks 
of induction therapy  
• 
To assess the proportion of subjects with endoscopic improvement 
(decrease in simple endoscopy score for Crohn’s disease [SES-CD] 
≥ 50% from Baseline) at Week 12  
Secondary: 
• 
To assess the proportion of subjects with clinical remission (Crohn’s 
disease activity index [CDAI] < 150) at Week 12 
• 
To assess the proportion of subjects with endoscopy and clinical 
improvement (decrease in SES-CD ≥ 50% AND reduction in CDAI 
≥ 100 points from Baseline) at Week 12 
• 
To assess the proportion of subjects with biomarker and clinical 
improvement (decrease in high sensitivity C-reactive protein [hsCRP] 
or fecal calprotectin ≥ 50% from Baseline, among subjects with at least 
one elevated biomarker at Baseline, AND reduction in CDAI ≥ 100 
points from Baseline) at Week 12  
• 
To assess the proportion of subjects with normalization of C-reactive 
protein (hsCRP < upper limit of normal [ULN]), among subjects with 
elevated concentrations at Baseline, at Week 12 
• 
To assess the proportion of subjects with normalization of fecal 
calprotectin (fecal calprotectin < ULN), among subjects with elevated 
concentrations at Baseline, at Week 12 
• 
To assess the proportion of subjects with clinical improvement 
(reduction in CDAI ≥ 100 points from Baseline) at Week 12 
• 
To assess the proportion of subjects with two component patient-
reported outcome (PRO-2) remission (average daily abdominal pain 
score ≤ 1 point and average daily stool frequency ≤ 3 points with 
abdominal pain and stool frequency no worse than Baseline at Week 12) 
• 
To assess the change in SES-CD score from Baseline to Week 12 
• 
To assess the pharmacokinetics (PK) of PRA023 
• 
To assess the immunogenicity of PRA023 


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Exploratory: 
• 
To assess the change in CDAI and component scores over time  
• 
To assess the effects of PRA023 on tissue and serum pharmacodynamic 
(PD) markers, including tumor necrosis factor-like cytokine 1A 
(TL1A) concentrations, endoscopic healing index (EHI), fecal 
calprotectin, and hsCRP in all subjects over time 
• 
To assess the change in SES-CD at Week 50 from Baseline 
• 
To characterize the change in Perianal Disease Activity Index (PDAI) 
score from Baseline to Week 12, Week 28, and Week 50 
• 
To characterize the effect of PRA023 for improvement and remission 
of enterocutaneous and/or perianal fistula during the Induction Period 
(IP) and Open-Label Extension (OLE) 
• 
To assess all secondary endpoints at Week 50 
• 
To assess the change in global histological activity score (GHAS) and 
Robarts histopathology index (RHI) from Baseline to Week 12 and 
Week 50 
• 
To assess the proportion of subjects with histologic response and 
histologic remission at Week 12 and Week 50 
• 
To assess change in PRO-2 over time 
• 
To assess change in extraintestinal manifestations over time 
• 
To assess long-term safety, tolerability, and efficacy of PRA023 
STUDY DESIGN: 
This is a multi-center, open-label, proof of concept study designed to assess 
the safety, tolerability, and preliminary efficacy of PRA023 following 
12 weeks of induction therapy in subjects with Crohn’s disease (CD). This 
study will be conducted under the aegis of a Data Monitoring Committee 
(DMC) and will commence following the demonstration of an acceptable 
safety profile of PRA023 at a dose of ≥ 500 mg in the multiple ascending 
dose study in normal healthy volunteers (Study PR200-101). 
 
The study has 4 periods (Screening, IP, OLE and Follow-Up [FU] Period). 
Following the Screening Period, approximately 50 eligible subjects with 
moderately to severely active CD will enter the IP to receive PRA023 1000 
mg on Week 0/Day 1, followed by 500 mg on Weeks 2, 6, and 10 via 
intravenous (IV) administration. Subjects who discontinue from the study 
drug will have a follow-up period of 12 weeks after the last dose. 
 
Response at Week 12 will be defined as reduction from Baseline in CDAI 
of ≥ 100 points. Non-responders at Week 12 should discontinue from study 
drug treatment. 
 
Subjects who complete the 12-week IP and have responded will have the 
option to enter OLE, where they will be randomized to either 250 mg IV 


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Q4W or 100 mg IV Q4W until Week 134 Subjects will continue in OLE 
until they progress, withdraw from the study, study termination, or Week 
134.  
The study is being amended by the Sponsor to extend the OLE period 
beyond 50 weeks to Week 134 based on emerging safety data in both this 
study as well as a concurrent double-blind Phase 2 study in ulcerative 
colitis. The OLE period may be further extended beyond 134 weeks based 
on emerging safety data in a future amendment. 
SAMPLE SIZE: 
The study is planned to enroll approximately 50 subjects. The sample size 
will enable a statistical power of 80%, at 1-sided significance level of 
0.025, to test against the null hypothesis of endoscopic improvement rate of 
12%, assuming the endoscopic improvement rate for PRA023 is 27%.  
SUBJECT TYPE: 
Male or female subjects ≥ 18 years of age with moderately to severely 
active CD. 
FORMULATIONS: 
PRA023 will be supplied in 10 mL vials each containing 500 mg PRA023 
(60 mg/mL concentrate for solution for infusion) for IV administration after 
reconstitution. 
DOSAGE: 
Induction Period: all subjects will receive PRA023 1000 mg on Week 
0/Day 1, followed by 500 mg IV on Weeks 2, 6, and 10. 
Non-responders at Week 12 should be discontinued from study drug 
treatment. 
Responders at the end of Week 12 have the option to enter the OLE, where 
all subjects will be randomized to receive one of the following regimens 
until disease progression, withdraw from the study, study termination, or 
Week 134. 
• 
PRA023 250 mg IV on Week 14 then Q4W 
• 
PRA023 100 mg IV on Week 14 then Q4W 
ROUTE OF 
ADMINISTRATION: 
The study drug will be reconstituted in 250 mL of 0.9% normal saline (NS) 
and will be administered IV over 30 minutes. 
STUDY ENDPOINTS: 
Primary endpoints: 
• 
Safety and tolerability: the proportion of subjects reporting adverse 
events (AEs), serious adverse events (SAEs), AEs leading to 
discontinuation, and markedly abnormal laboratory values 
• 
The proportion of subjects with endoscopic improvement, as defined by 
decrease in SES-CD ≥ 50% from Baseline at Week 12 
Secondary endpoints: 
• 
The proportion of subjects in clinical remission (CDAI < 150) at 
Week 12 


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• 
The proportion of subjects with endoscopic and clinical improvement, 
as defined by decrease in SES-CD ≥ 50% AND reduction in CDAI 
≥ 100 points from Baseline at Week 12 
• 
The proportion of subjects with both biomarker and clinical 
improvement (decrease in hsCRP OR fecal calprotectin ≥ 50% from 
Baseline, among subjects with at least one elevated biomarker at 
Baseline, AND reduction in CDAI ≥ 100 points from Baseline) at 
Week 12 
• 
The proportion of subjects with normalization of hsCRP (as defined by 
hsCRP < ULN), among subjects with elevated concentrations at 
Baseline, at Week 12 
• 
The proportion of subjects with normalization of fecal calprotectin 
(as defined by fecal calprotectin < ULN), among subjects with elevated 
concentrations at Baseline, at Week 12 
• 
The proportion of subjects in clinical response, as defined by reduction 
in CDAI ≥ 100 points from Baseline at Week 12 
• 
The proportion of subjects with PRO-2 remission (defined as average 
daily abdominal pain score ≤ 1 point and average daily stool frequency 
≤ 3 points with abdominal pain and stool frequency no worse than 
Baseline) at Week 12 
• 
Change in SES-CD score at Week 12 from Baseline 
• 
Descriptive summaries of PK and immunogenicity of PRA023 
• 
Proportion of subjects developing anti-drug antibody (ADA) and 
neutralizing antibody (Nab) 
Exploratory endpoints: 
• 
Change in CDAI and components from Baseline over time 
• 
Change in PD markers including TL1A concentrations, EHI, fecal 
calprotectin, and hsCRP over time 
• 
Change in SES-CD from Baseline at Week 50 
• 
Change in PDAI from Baseline over time 
• 
Proportion of subjects with improvement or remission of 
enterocutaneous and/or perianal fistula at Week 12 and Week 50 
• 
Change in GHAS and RHI from Baseline to Week 12 and Week 50 
• 
The proportion of subjects with GHAS histologic score ≤ 4 at Week 12 
and Week 50 
• 
The proportion of subjects with Robarts histologic score < 5 at Week 
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• 
The proportion of subjects with GHAS histologic remission, defined as 
no neutrophils in the epithelium or subscore of 0, at Week 12 and 
Week 50 
• 
The proportion of subjects with Robarts histologic remission (< 3) at 
Week 12 and Week 50 
• 
Change in PRO-2 over time 
• 
The proportion of subjects with extraintestinal manifestation through 
Week 50 
• 
The long-term safety, tolerability, and efficacy of PRA023 through 
Week 134 
INCLUSION 
CRITERIA: 
Subjects are required to meet the following criteria in order to be included in 
the study: 
1. Male or female ≥ 18 years of age. 
2. Subjects must have had a diagnosis of CD (confirmed by endoscopy + 
histology) at least 3 months prior to screening to be eligible for study 
participation. For subjects with no documented confirmation of CD 
diagnosis or if previous diagnosis is not deemed conclusive, CD 
diagnosis must be confirmed at time of screening colonoscopy. Note 
that mention of “chronic inflammation” or “Crohn’s disease” or 
equivalent on histology report is acceptable. 
3. Moderately to severely active CD as defined by CDAI of ≥ 220 and 
≤ 450. 
4. SES-CD score (per central reading) ≥ 6 if ileocolonic or colonic 
disease; or ≥ 4 if isolated ileal disease only. 
5. Subjects must satisfy at least one of the following criteria: 
a) In the past, had an inadequate response to one or more of the 
following treatments: 
• Oral prednisone ≥ 40 mg/day (or equivalent) or budesonide 
≥ 9 mg/day or equivalent or beclomethasone ≥ 5 mg/day for at 
least 2 weeks  
• Corticosteroid dependence as defined by failed to successfully 
taper to < 10 mg/day of prednisone or equivalent (i.e., had a 
flare of disease) within 3 months of starting therapy, or if 
relapse occurs within 3 months of stopping corticosteroids 
• Immunosuppressants (azathioprine ≥ 2 mg/kg/day or 
6-mercaptopurine ≥ 1.0 mg/kg/day, [or documentation of a 
therapeutic concentration of 6-thioguanine nucleotide] or 
methotrexate ≥ 15 mg/week) for at least 8 weeks. Note: a lower 
dosage of 6-MP or AZA is acceptable if local guidelines specify 
a different treatment regimen (which would need be 
documented in the source document) 


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• An approved anti-TNF agent at an approved labeled dose for at 
least 8 weeks 
• An approved anti-integrin (e.g., vedolizumab) at an approved 
labeled dose for at least 8 weeks 
• An approved anti-IL-12/23 (e.g., ustekinumab) at an approved 
labeled dose for at least 8 weeks 
OR 
b) Had been intolerant to one or more of the above mentioned 
treatments (e.g., unable to achieve doses or treatment durations 
because of dose-limiting side effects [e.g., leukopenia, psychosis, 
uncontrolled diabetes, elevated liver enzymes]) 
OR 
c) Currently receiving one or more of the following treatments: 
• Oral Prednisone ≥ 10 mg/day (or equivalent) or budesonide 
≥ 3 mg/day or beclomethasone ≥ 5 mg/day for at least 3 months 
• Immunosuppressants [azathioprine ≥ 2 mg/kg/day or 
6-mercaptopurine ≥ 1.0 mg/kg/day, (or documentation of a 
therapeutic concentration of 6-thioguanine nucleotide)] for at 
least 8 weeks. Note: a lower dosage of 6-MP or AZA is 
acceptable if local guidelines specify a different treatment 
regimen (which would need be documented in the source 
document) 
Notes on subjects who have had prior approved biologic therapy(ies) 
(e.g., anti-TNF, anti-integrin, and/or anti-IL-12/23):  
• 
The study will include a maximum of 70% and a minimum of 
approximately 50% subjects who have had prior approved biologic 
therapy(ies) experience. Upon reaching the maximum number of 
allowed biologic experienced subjects (70%), subjects who have 
had prior biologic experience will no longer be allowed to enter the 
study. Upon reaching the maximum number of allowed biologic-
naïve subjects (approximately 50%), subjects who have never been 
exposed to a prior biologic will no longer be allowed to enter the 
study.   
• 
Subjects cannot have had failed (no response, insufficient response, 
loss of response, and/or intolerance) > 4 approved biologic 
therapies, whether of same or different mechanism of action 
• 
Subjects previously on clinical trials only (i.e., did not receive 
commercial available therapy post-approval) are not considered to 
have received the approved therapy for purpose of this inclusion 
criteria 
6. For subjects who are women of childbearing potential (WOCBP) 
involved in any sexual intercourse that could lead to pregnancy, the 
subject has used two highly effective methods of contraception for at 
least 4 weeks prior to Day 1 and agrees to continue to use two highly 


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effective methods of contraception until at least 12 weeks after the last 
dose of study drug. 
7. Male subjects must use, with their female partner of childbearing 
potential, two highly effective methods of contraception and refrain 
from sperm donation from screening to 12 weeks after the last dose of 
study drug. 
8. Subjects must meet drug stabilization requirements, as applicable: 
a) Oral corticosteroid treatment must be equivalent of ≤ 20 mg 
prednisone or ≤ 9 mg budesonide or beclomethasone ≤ 5 mg daily 
at a stable dose for at least 2 weeks prior to Day 1 
b) Oral aminosalicylates should be at a stable dose for at least 2 
weeks prior to Day 1 
c) Azathioprine, 6-mercaptopurine, and methotrexate should be at a 
stable dose for at least 4 weeks prior to Day 1 
9. Able to provide written informed consent and understand and comply 
with the requirements of the study. 
EXCLUSION 
CRITERIA: 
Subjects with the following characteristics will be excluded from the study: 
Sex and Reproductive Status 
1. WOCBP and men with female partners of childbearing potential who 
are unwilling or unable to use two highly effective methods of 
contraception to avoid pregnancy for the entire study period and for up 
to 12 weeks after the last dose of study drug. 
2. Women who are pregnant or breastfeeding. 
3. Women with a positive pregnancy test on enrollment or prior to Day 1. 
Target Disease Exceptions 
4. Diagnosis of ulcerative colitis or indeterminate colitis. 
5. CD isolated to the stomach, duodenum, jejunum, or perianal region, 
without colonic and/or ileal involvement. 
6. Suspected or diagnosed intra-abdominal or perianal abscess at 
Screening. 
7. Known symptomatic stricture or stenosis not passable in endoscopy 
(including pediatric colonoscope). 
8. Current stoma or need for colostomy or ileostomy. 
9. Previous small bowel resection with combined resected length of 
> 100 cm or previous colonic resection of > 2 segments. 
10. Currently receiving total parenteral nutrition. 
11. Surgical bowel resection within 3 months before screening. 
12. Concomitant primary sclerosing cholangitis (PSC). 


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Medical History and Concurrent Diseases 
13. Past or current evidence of definite low-grade or high-grade colonic 
dysplasia that has not been completely removed. 
14. Subjects who are scheduled or anticipate the need for surgery, aside 
from dermatologic procedures. 
15. Subjects who have a history of clinically significant drug or alcohol 
abuse. 
16. Concomitant illness that in the opinion of the Investigator, is likely 
to require systemic glucocorticosteroid therapy during the study 
(e.g., moderate to severe asthma). 
17. Current symptoms of severe, progressive, or uncontrolled renal, 
hepatic, hematological, pulmonary, cardiac, neurological, 
ophthalmologic, or cerebral disease. Concomitant medical conditions 
that in the opinion of the Investigator might place the subject at 
unacceptable risk for participation in this study. 
18. Subjects with a history of cancer within the last 5 years (other than 
non-melanoma skin cell cancers cured by local resection). Existing 
non-melanoma skin cell cancers must be removed prior to enrollment. 
Subjects with carcinoma in situ or localized cervical cancer, treated 
with definitive surgical intervention, are allowed. 
19. Subjects at risk for tuberculosis (TB). Specifically, subjects with: 
a) A history of active TB  
b) Current clinical, radiographic, or laboratory evidence of active TB 
c) Latent TB which was not successfully treated. Subjects with a 
positive TB screening test indicative of latent TB will not be 
eligible for the study unless active TB infection has been ruled out, 
and an appropriate course of intervention for latent TB has been 
initiated at least 2 weeks prior to Day 1, and no evidence of active 
TB on chest x-ray during screening. 
20. Subjects with any serious bacterial infection within the last 3 months, 
unless treated and resolved with antibiotics, or any chronic bacterial 
infection (such as chronic pyelonephritis, osteomyelitis, and 
bronchiectasis). 
21. Female subjects who have had a breast cancer screening that is 
suspicious for malignancy, and in whom the possibility of malignancy 
cannot be reasonably excluded following additional clinical, laboratory, 
or other diagnostic evaluations. 
22. Subjects with any active infections (excluding fungal infections of nail 
beds) including, but not limited to, those that require IV antimicrobial 
treatment 4 weeks or oral antimicrobial treatment 2 weeks prior to 
randomization. Subjects with evidence of Human Immunodeficiency 
Virus (HIV), Hepatitis B, or Hepatitis C infection detected during 


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screening are also excluded, but subjects with successfully treated 
Hepatitis C with no recurrence for ≥ 1 year are allowed. Subjects with 
active documented or suspected COVID-19 infection within 4 weeks of 
randomization or asymptomatic SARS-CoV-2 test positivity within 2 
weeks of randomization are excluded. 
23. Subjects with herpes zoster reactivation or cytomegalovirus (CMV) 
that resolved less than 2 months prior to signing informed consent. 
24. Subjects who have received any live vaccines within 3 months of the 
anticipated first dose of study medication or who will have need of a 
live vaccine at any time during the study. 
Physical and Laboratory Test Findings 
25. Positive stool Polymerase Chain Reaction (PCR) if Investigator deems 
this positivity reflects infection rather than colonization or positive 
culture for enteric pathogens.  Subjects who have an infection can be 
retested after the completion of a full course of treatment. 
26. Stool positive for Clostridium difficile (C. difficile) toxin. Subjects who 
are positive can be retested after the completion of a full course of 
treatment for C. difficile infection. 
27. Any of the following lab values: 
a) Hemoglobin (Hgb) < 8.0 g/dL (80 g/L) 
b) White blood cell (WBC) < 2,500/mm3 (2.5 x 109/L) 
c) Neutrophils < 1,000/mm3 (1 x 109/L) 
d) Platelets < 100,000/mm3 (100 x 109/L) 
d) Serum creatinine > 2 times ULN 
e) Serum alanine aminotransferase (ALT) or aspartate 
aminotransferase (AST) > 2 times ULN 
f) Any other laboratory test results that, in the opinion of the 
Investigator, might place the subject at unacceptable risk for 
participation in this study. 
Prohibited Therapies and/or Medications 
28. Failed (no response, insufficient response, loss of response, and/or 
intolerance) > 4 approved biologic therapies (anti-TNF, anti-integrin, 
anti-IL12/23), whether of same or different mechanism of action. 
29. Any marketed biologic within 8 weeks for anti-TNF agents and 12 
weeks for anti-integrin agents (e.g., vedolizumab) and ustekinumab 
prior to Day 1 or if drug level per therapeutic dose monitoring is 
greater than lower limit of detection. 
30. Any biologic immunomodulators used for CD or other conditions 
within 8 weeks or 5 half-lives, whichever is longer, prior to Day 1 or if 


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drug level per therapeutic dose monitoring is greater than lower limit of 
detection. 
31. Rituximab within 1 year prior to Day 1. 
32. Parenteral corticosteroids within 4 weeks or rectal administration of 
corticosteroids within 2 weeks prior to Day 1. 
33. Rectal administration of 5-ASA within 2 weeks prior to Day 1. 
34. Tacrolimus, cyclosporine, mycophenolate mofetil (CellCept®), 
immunoadsorption columns (such as Prosorba columns), D 
Penicillamine, Leflunomide, Thalidomide, chronic use of non-steroidal 
anti-inflammatory agents (NSAIDs), and aspirin > 81 mg/day within 2 
weeks prior to Day 1. 
35. Other investigational chemical agent within 30 days or other 
investigational biologic agent within 8 weeks or 5 half-lives (whichever 
is longer) of entry into the IP. 
36. Prior exposure to PRA023. 
Other Exclusion Criteria 
37. Prisoners or subjects who are compulsorily detained (involuntarily 
incarcerated) for treatment of either a psychiatric or physical 
(e.g., infectious disease) illness. 
38. Legal or mental incapacitation, or inability to understand and comply 
with the requirements of the study. 
39. Known allergies, hypersensitivity, or intolerance to PRA023 or its 
excipients. 
Statistical Methods: 
Statistical methods will be detailed in the Statistical Analysis Plan (SAP). 
The SAP will provide details about methods of analysis and the specific 
planned analyses, and will be prepared and approved by Prometheus 
Biosciences and its designees before study database lock. 
The analysis populations are defined as follows: 
• 
Full analysis set (FAS): all subjects treated with Baseline SES-CD score 
• 
Safety analysis set: all subjects treated 
The following analyses will be performed: 
Efficacy: 
The primary efficacy endpoint, endoscopic improvement at Week 12, will 
be used to assess the efficacy of PRA023. The proportion of subjects in the 
per-protocol population with endoscopic improvement will be tested 
against the null hypothesis of endoscopic improvement rate of 12%, at a 1-
sided significance level of 0.025. If significant, the 1st secondary endpoint 
of proportion of subjects in FAS achieving clinical remission will be tested 
against the null hypothesis of clinical remission rate of 16%, at a 1-sided 
significance level of 0.025.  


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The point estimates for the primary and secondary endpoints will be 
calculated along with 95% confidence interval and by companion 
diagnostic (CDx) status (CDx+ or CDx-).  
Adverse Events: 
AEs will be coded using the most current version of Medical Dictionary for 
Regulatory Activities (MedDRA®). 
A by-subject AE data listing, including verbatim term, preferred term (PT), 
system organ class (SOC), treatment, severity, seriousness criteria, 
relationship to drug, and action taken, will be provided. 
The number of subjects experiencing treatment-emergent adverse events 
(TEAEs) and number of TEAEs will be summarized by treatment using 
frequency counts in safety analysis set. 
Medical History, chest x-ray, electrocardiogram (ECG), and physical 
examination will be listed by subject. 
Changes in ECGs and physical examinations will be described in the text of 
the final report. 
Concomitant Medications: 
Concomitant medications will be coded using the most current World 
Health Organization (WHO) drug dictionary and listed by treatment. 
Pharmacokinetics: 
Summary statistics of PRA023 concentrations and ADA by visit.  


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1 
BACKGROUND AND RATIONALE 
1.1 
Background 
PRA023 is a humanized monoclonal antibody that binds human tumor necrosis factor-like 
cytokine 1A (TL1A) with high affinity and specificity. TL1A is a cytokine which is part of the 
tumor necrosis factor (TNF) superfamily protein and is secreted by both innate and adaptive 
immune cells as well as by endothelial cells. 
TL1A binds to death receptor 3 (DR3) that is found primarily on T cells, natural killer (NK) and 
NK-T cells, innate lymphoid cells (ILC), and epithelial cells (Valatas 2019) and potently drives 
Th1, Th2, Th9, and Th17 responses. In addition, TL1A is induced in antigen-presenting cells by 
toll like receptor (TLR) ligands and FcR (Fc receptor) cross-linking and in T cells by T-cell 
receptor (TCR) stimulation (Prehn 2007). TL1A occurs as both membrane-bound and soluble 
forms (Ferdinand 2018). 
TL1A has been shown to be upregulated in mucosa and serum of patients with inflammatory 
bowel disease (IBD) (Bamias 2003, Bamias 2010). TL1A and DR3 are abundantly localized at 
inflamed intestinal areas of patients with IBD and mice with experimental ileitis or colitis and 
actively participate in the immunological pathways that underlie mucosal homeostasis and 
intestinal inflammation (Valatas 2019). Furthermore, TL1A polymorphisms have been shown to 
be associated with susceptibility to IBD (Yamazaki 2005, Yang 2008) and with disease severity 
(Cleynen 2013, Richard 2015). 
In dextran sodium sulfate (DSS) and adoptive transfer mouse models, antibodies against TL1A led 
to reduced inflammation and reversal of fibrosis, even when treatment was administered late in the 
course of disease, after inflammation and fibrosis has been established (Shih 2014). 
Prometheus Biosciences has developed PRA023, a humanized IgG1 kappa (IgG1κ) monoclonal 
antibody that binds to both membrane-bound and soluble forms of TL1A with high affinity and 
specificity and blocks the binding of TL1A to its functional receptor DR3. Prometheus 
Biosciences is also developing a genetic-based companion diagnostic (CDx) to identify patients 
who are predisposed for increased expression of TL1A and therefore potentially more likely to 
respond to PRA023. By targeting both intestinal inflammation and fibrosis, PRA023 has the 
potential to substantially improve outcomes for moderate to severe IBD patients with increased 
TL1A expression. 
PF-06480605 is an anti-TL1A monoclonal antibody developed by Pfizer and studied in healthy 
volunteers and patients with ulcerative colitis (UC) (Banfield 2020, Danese 2020). Target 
engagement was demonstrated in healthy volunteers as confirmed by dose-dependent increases 
in mean total soluble tumor necrosis factor-like cytokine 1A (sTL1A). In a Phase 2a open-label 
study with centrally read endoscopy in subjects with moderately to severely active UC, treatment 
with the anti-TL1A antibody led to significant endoscopic improvement (38%), clinical 
remission (24%), histologic improvement, and decrease in biomarkers (fecal calprotectin and 
high sensitivity c-reactive protein [hsCRP]) at Week 14. PF-06480605 appeared to have an 
acceptable safety and tolerability profile. 


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Prometheus Biosciences is undertaking a Precision Medicine approach to the development of an 
anti-TL1A therapeutic for treatment of moderate to severe Crohn’s Disease (CD) and UC, using a 
CDx to identify patients most likely to respond to study drug. The advantage of this unique, 
precision-based approach in IBD is the ability to identify patients more likely to respond to our 
therapeutics in targeted clinical trials, with the ultimate goal of bringing therapeutic drugs to 
patients with significantly better clinical efficacy. 
This study is a Phase 2a, open-label study designed to evaluate the safety, efficacy, and 
pharmacokinetics (PK) of PRA023 in subjects with moderately to severely active CD. 
1.2 
Study Rationale 
IBD is a complex disease with many contributing factors including environmental influences, 
genetics, and immunologic factors. UC and CD are two of the most common forms of IBD. Both 
UC and CD are chronic, relapsing, remitting, inflammatory conditions of the gastrointestinal (GI) 
tract that begin most commonly during adolescence and young adulthood. UC involves the mucosal 
layer of the large intestine, and symptoms include abdominal pain and diarrhea, frequently with 
blood and mucus. CD can affect the entire thickness of the bowel wall and all parts of the GI tract 
from mouth to anus. CD symptoms include abdominal pain, diarrhea, and other more insidious 
symptoms such as weight loss, nutritional deficiencies, and fever. The prevalence of IBD globally 
is approximately 5 million and affects over 2 million people in the US (Ananthakrishnan 2020). 
A hallmark of IBD is the cytokine responses that govern the initiation, evolution, and ultimately, 
the resolution of these forms of inflammation. Many immune cells, cytokines, and chemokines of 
the adaptive and innate immune systems play a role in IBD, including but not limited to IL-12, 
IL-23, IFNγ, IL-17, IL-22, and TL1A (Roberts‑Thomson 2011, Strober 2011). 
The current standard of care for the treatment of patients with moderate to severe IBD are 
generally immunomodulatory agents that are anti-inflammatory. None of the therapies address 
fibrosis in IBD. Since the approval of the first anti-TNF agent for the treatment of CD in 1998, 
the availability of newer biological agents, including anti-integrin (vedolizumab and natalizumab) 
and anti-IL-12/23 (ustekinumab) has improved the care of moderate to severe CD. However, 
none of these subsequently approved therapies have demonstrated significant improvement in 
effect size relative to anti-TNF. Moreover, among those patients who do respond, up to 45% will 
lose response over time (Roda 2016). Current therapies used in the treatment of CD apply a 
one-size-fits-all approach without regard to genetic or biologic variations in the patient. Existing 
approaches continue to leave unmet patient need. 
Given established clinical validation of the target with PF-06480605, the current open-label 
Phase 2a study is designed to demonstrate the efficacy of PRA023 in subjects with moderately to 
severely active CD. In addition, this study is designed to assess the effectiveness of the genetic 
CDx for the purpose of selection of subjects whose disease is driven by the TL1A pathway and 
therefore, have a higher response rate to treatment with an anti-TL1A antibody. The study is also 
designed with an open-label extension study to ensure that subjects who benefit from the therapy 
have the option to continue therapy.  


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In parallel, a randomized, placebo-controlled study (PR200-102) will be conducted to demonstrate 
the proof of concept of PRA023 for induction therapy in subjects with moderately to severely 
active UC. 
1.3 
PRA023 Mechanism of Action and Nonclinical Data 
The Investigator’s Brochure should be referenced for a complete summary of data and information 
collected about PRA023 (including the principal data and findings from the nonclinical 
pharmacology, pharmacokinetic, and toxicology studies conducted to date). 
1.3.1 
Pharmacology 
PRA023 is a humanized IgG1κ antibody that binds human TL1A with high affinity and specificity 
and neutralizes TL1A functional activity in vitro and ex vivo cell-based assays. PRA023 binds to 
both human and cynomolgus TL1A with a similar sub-nanomolar EC50 (half maximal effective 
concentration) and with similarly high affinity (KD [dissociation constant] values of 
 and 
 respectively). In addition, PRA023 is specific for TL1A and does not bind to other 
TNF super family members. Together, these data show that PRA023 is a high affinity humanized 
monoclonal antibody with selectivity for human and cynomolgus TL1A. 
PRA023 has the capacity to block human TL1A-induced caspase activation and apoptosis in the 
TF-1 functional assay with an IC50 (half maximal inhibitory concentration) of 
 Similarly, 
PRA023 blocked monkey TL1A-induced caspase activation with an IC50of 
 In a monkey 
whole blood assay, PRA023 inhibited the immune complex/TL1A enhancement of interferon 
gamma (IFN-γ) release with an IC50 of 
 and IC90 (90% maximal inhibitory concentration) 
of
. 
A single dose PK/PD study in cynomolgus monkeys demonstrated a dose-dependent 
pharmacologic effect of PRA023 on the inhibition of TL1A-mediated IFN-γ release from 
peripheral blood mononuclear cells (PBMCs) in whole blood at doses of
. The 
observation that greater concentrations 
 of serum PRA023 were required 
to elicit this effect in animals treated with PRA023 versus when PRA023 was added in vitro to 
monkey whole blood indicates that a higher concentration of drug is required for biologic effect 
in vivo. In addition, a dose-dependent increase in circulating sTL1A concentrations was observed 
at all dose levels. This suggests that systemic sTL1A concentrations may be a useful PD marker 
for target engagement by PRA023. 
1.3.2 
Toxicology 
Six-week and 6-month Good Laboratory Practice (GLP) repeat-dose toxicity studies were conducted 
in cynomolgus monkeys with a 6-week recovery period and a definitive GLP embryo-fetal 
development (EFD) study was conducted in New Zealand White rabbits. The intravenous (IV) 
route of administration was selected for these studies since it is the route of clinical 
administration. In addition, a series of in vitro studies were conducted with PRA023 including Fc 
effector function (i.e., antibody-dependent cellular cytotoxicity [ADCC], complement-dependent 
cytotoxicity [CDC], and antibody-dependent phagocytosis cytotoxicity [ADCP]) assays, human 
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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cytokine release assays, and a GLP tissue cross-reactivity study using human and monkey 
tissues. 
Stand-alone safety pharmacology studies were not conducted with PRA023. Cardiovascular, 
central nervous system (CNS), and respiratory safety pharmacology endpoints were incorporated 
into the repeat-dose IV toxicity studies in monkeys. There were no functional cardiovascular, CNS, 
or respiratory system findings observed in monkeys after once weekly IV administration of 
PRA023 at ≤ 300 mg/kg/week for up to 6 months. 
PRA023 was administered to monkeys once weekly via IV injection for up to 6 months. The no 
observed adverse effect level (NOAEL) in the 6-month study was considered to be 300 
mg/kg/week (the highest dose tested). No PRA023-related mortality; adverse clinical 
observations; body weight or body weight alterations; hematology, coagulation, or urinalysis 
effects; organ weight effects; macroscopic observations; microscopic findings; ECG findings; 
ophthalmic or neurobehavioral observations or findings in body temperature or respiration rates 
were observed at the end of the dosing phase after 6 months of repeat dosing in monkeys. No 
PRA023-related effects were noted in mean absolute counts or relative proportions of 
lymphocyte subsets (total T cells, helper and cytotoxic T cells, B cells, NK cells, monocytes, and 
regulatory helper and cytotoxic T cells) at ≤300 mg/kg/week as measured by 
immunophenotyping, compared with the controls. All animals mounted a robust anti-KLH IgG 
and IgM response, suggesting an intact humoral immunity. There were no organ weight changes, 
or macroscopic or microscopic observations in male or female reproductive organs after 6 
months repeat dosing of PRA023 administration in sexually mature monkeys. A normal 
progression of the spermatogenic cycle and the expected cell associations and proportions in the 
various stages of spermatogenesis were noted in the testes.  
After IV administration of PRA023 to monkeys in the 6-week repeat-dose toxicity study, 
findings that were secondary to generation of ADA and immune complex deposition in response 
to administration of a foreign protein (humanized monoclonal antibody) to immunocompetent 
animals (including the death of one low dose animal) were observed. Similar findings were not 
observed in the 6-month monkey toxicity study using the same dosing regimen and dose levels 
confirming that the findings in the 6-week repeat-dose toxicity study were secondary to ADA 
formation and not directly related to the mechanism of action of PRA023.  
Based on the NOAEL of 300 mg/kg/week, the exposure margin (based on area under the curve from 
0 to 168 hr [AUC0-168hr] after repeat dosing; 
 at the NOAEL is 
, relative 
to the projected AUC0-672hr (
 after the last 500 mg induction dose (i.e., highest 
predicted exposure due to accumulation of repeat dosing) in the dosing regimen. Similarly, for 
maximum concentration (Cmax), the exposure margin (based on Cmax after repeat dosing; 
 
 at the NOAEL is 
 relative to the projected exposure (
 after the last 
500 mg induction dose. 
In the pivotal EFD study, once-weekly administration of 50, 150, or 270 mg/kg/dose PRA023 
via IV injection to pregnant rabbits on gestation days (GDs) 7 and 14 was well tolerated. No 
PRA023-related mortality, clinical observations, or effects on mean body weight gain, mean 
body weight, food consumption, or cesarean section parameters were observed during the period 
of organogenesis (GD7 through 19). No PRA023-related fetal external, visceral, or skeletal 
CCI
CCI
CCI
CCI
CCI
CCI


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variations or malformations were observed. The maternal and the fetal NOAELs are 
 
(Cmax of 
 and AUC0-inf of 
 The exposure margins, 
based on Cmax and AUC0-inf, at the NOAEL are 
 respectively, relative to the 
projected clinical exposures after the last 500 mg induction dose. 
There was no off-target binding of PRA023 noted in the tissue cross-reactivity study in a broad 
range of human or monkey tissues. There was no PRA023-related cytokine release in in vitro 
human PBMC or whole blood cytokine release assays (soluble and plate-bound formats), nor in 
monkeys during the 6-week repeat-dose toxicity study. PRA023 did not cause CDC, ADCC, or 
ADCP of target expressing cells in in vitro Fc effector function assays. 
1.4 
Previous Human Experience 
A single and multiple ascending dose Phase 1 study of PRA023 in healthy volunteers has been 
completed. In this study, doses ranging from 5 mg to 1000 mg given as a single dose or three 
multiple doses given once every two weeks were evaluated (Study PR200-101).  
A total of 69 healthy subjects completed the dosing phase, 46 subjects in single ascending dose 
(SAD) phase (35 subjects received active PRA023 and 11 subjects received placebo) and 23 in 
the multiple ascending dose (MAD) phase (17 subjects received PRA023 and 6 subjects received 
placebo) in Study PR200-101. In the SAD phase, doses of PRA023 tested were 5 mg, 25 mg, 
100 mg, 300 mg, 600 mg, and 1000 mg given as a single IV infusion. In the MAD phase, doses 
of PRA023 tested were 50 mg, 200 mg, and 500 mg given as IV infusion every 2 weeks for a 
total of 3 doses. No clinically significant treatment-related adverse events were reported, and no 
clinically significant laboratory abnormalities, vital signs, or ECGs were noted with PRA023, at 
doses up to 1000 mg as a single dose and 500 mg as multiple doses. The study drug was well-
tolerated, and no subjects met the study stopping criteria. 
1.4.1 
Pharmacokinetic Results (PR200-101 Healthy Volunteer Study) 
PK data from the PR200-101 study indicate that the exposure to serum PRA023 increased in a 
greater than dose-proportional manner following the administration of single and multiple 
PRA023 doses as IV infusions at doses of < 100 mg; the exposure increases at doses of ≥ 100 mg 
were dose-proportionate. This observation is consistent with target mediated drug disposition 
(TMDD) at lower doses (< 100 mg). The half-life of PRA023 after 500 mg every other week 
dosing was approximately 19 days.  
Based on the preliminary PK data available, a population PK model was built to accurately 
simulate and predict PRA023 PK. The PK data were best described by a 2-compartment model 
with linear elimination. Demographic variables (including sex, age, race, and body size related 
variables) and laboratory clinical variables (including hematological, urine, and chemical 
variables) were tested for inclusion in the model for effect on the clearance and the volume of 
distribution in the central compartment. None of these variables were identified as significant 
covariates on the two PK parameters evaluated.  The results of these analyses are presented in 
the Investigator’s Brochure for PRA023. Briefly, evaluation of the model relative to observed 
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data from the healthy volunteer study indicated that the population PK model could adequately 
predict the observed PRA023 concentrations and was suitable to be used to simulate PRA023 
concentrations. 
1.4.2 
Safety Results  
Study PR200-101 has been completed. There were no deaths, SAEs, severe AEs, or subjects who 
had a reduction in dose or discontinued from the study due to AEs during Study PR200-101. 
Additionally, there were no clinically significant laboratory abnormalities, vital signs, or ECGs. 
In the SAD, treatment-emergent AEs that occurred in ≥ 2 subjects dosed with PRA023 
(regardless of dose) were: headache (5 subjects [14%] in PRA023 and 1 subject [9%] on 
placebo), followed by fatigue (2 subjects [6%] on PRA023, 0 on placebo), back pain (2 subjects 
[6%] on PRA023, 0 on placebo), and cough (2 subjects [6%] on PRA023, 0 on placebo). All 
other AEs were reported in no more than 1 subject. There was 1 event of headache that was 
assessed as related to placebo that was moderate in severity. The only other AE that was assessed 
as related to PRA023 (600 mg) was somnolence, mild in severity.    
In the MAD portion of the study, treatment-emergent AEs that occurred in ≥ 2 subjects dosed 
with PRA023 (regardless of dose) were: catheter site bruise (3 subjects [18%] on PRA023, 2 
[33%] on placebo), followed by catheter site pain (2 subjects [12%] on PRA023, 1[17%] on 
placebo), and infusion site extravasation (2 subjects [12%] on PRA023, 0 on placebo). All other 
AEs were reported in no more than 1 subject. All AEs that were assessed as related to study drug 
were mild in severity. Of the AEs assessed as related to study drug by the Investigator, diarrhea 
was reported in 2 subjects (1 subject on PRA023 at 50 mg and 1 subject on placebo) and all other 
AEs (dizziness [PRA023 200 mg], headache [placebo], and somnolence [PRA023 50 mg]) were 
reported in 1 subject. 
For the ongoing Phase 2 studies PR200-102 ARTEMIS-UC and PR200-103 APOLLO-CD (this 
protocol), ongoing review of unblinded efficacy and safety data by the independent external Data 
Monitoring Committee (DMC) has resulted in the committee’s recommendation to continue the 
study. Subjects from the ARTEMIS-UC study have been dosed for up to 10 months (i.e., either 
10 months of PRA023 or 3 months of placebo followed by 7 months of PRA023) and subjects 
from this study (the APOLLO-CD study, which is open-label) have been dosed for up to 9 
months of PRA023 as of the date of this protocol amendment. 
1.5 
Dose Rationale 
PRA023 is a humanized monoclonal antibody that binds human TL1A. It is expected that the 
ultimate goal of PRA023 treatment in humans will be to saturate the TL1A target in 
intestinal/colonic tissue of disease patients to obtain optimal efficacy. Based on the emerging 
safety, tolerability, pharmacodynamic (PD), and PK data from the PR200-101 study and 
modeling, the dosing regimen selected for induction in this study is PRA023 1000 mg on Week 
0/Day 1 followed by 500 mg on Weeks 2, 6, and 10, administered intravenously. This regimen is 
expected to lead to optimal target modulation and confer pharmacologic efficacy. The NOAEL 


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in monkeys will provide a safety margin of 
 for Cmax and AUC0-672hr, 
respectively, after the last 500 mg induction dose (i.e., highest predicted AUC due to 
accumulation with repeat dosing) in this dosing regimen. 
A population PK model was built based on the available data from Study PR200-101. The model 
was adequate to predict and simulate PRA023 exposure and no significant demographic or 
laboratory covariates were identified. Based on the population PK model, assuming the PK is 
similar between healthy volunteers and moderate to severe UC patients, the dosing regimen of 
PRA023 1000 mg on Week 0/Day 1 followed by 500 mg on Weeks 2, 6, and 10 is expected to 
lead to a Cmax (mean ± SD) of 
 and an AUC0-672hr of 
 
after the last 500 mg induction dose.  
Of note, the predicted Cmax after the initial 1000 mg dose in the induction phase is expected to be 
the highest concentration obtained during the PR200-103 clinical dosing regimen. This level of 
exposure has already been evaluated in the 1000 mg SAD cohort of the healthy volunteer study 
(Study PR200-101).  As stated, the highest exposure during the PR200-103 clinical dosing 
regimen based on AUC is expected to be after the last 500 mg induction dose due to 
accumulation with repeat dosing. The predicted AUC is expected to be approximately equivalent 
(within 10%) to that after the Phase 1 dosing regimen of 500 mg every other week.   
From an induction efficacy perspective, assuming clearance of free soluble TL1A (sTL1A) from 
the gut will translate into efficacy, a physiologically based pharmacokinetic model was used to 
predict the impact of various dosing regimen of PRA023 on the level of sTL1A in normal and 
disease states in the central compartment (serum) and gut. The model predicts that the proposed 
induction regimen will lead to sTL1A levels of lower than healthy volunteers if the production 
level of sTL1A in the colon is as high as 60-fold. 
After the 12-week induction, subjects who are in response will continue in the open-label 
extension randomized to 2 maintenance regimens. The maintenance regimen of 250 mg Q4W is 
selected to maintain the sTL1A level to below that of healthy volunteers if the production of 
sTL1A in the colon is up to 20X and the 100 mg Q4W regimen is selected to maintain the 
sTL1A level to below that of healthy volunteers if the production of sTL1A in the colon is up to 
10X. 
1.6 
Overall Benefit/Risk Assessment 
It is the hope that PRA023 will provide comparable or better efficacy than the currently approved 
biologic therapy, with an alternative and novel mechanism of action. There has been no safety 
signal identified based on nonclinical toxicity studies, safety analyses from normal healthy 
volunteers treated with up to 1000 mg of PRA023, and similar therapy in class. Based on the fact 
that PRA023 is a monoclonal antibody and an immunomodulatory agent, theoretical risks 
associated with treatment includes hypersensitivity reaction, infusion site reaction, and infections. 
Since there is limited experience with use of PRA023, several steps will be taken to ensure that 
the benefit-risk relationship of study participation continues to be favorable throughout the study. 
In addition to ongoing safety monitoring of data throughout this study, a formal analysis is 
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planned after all subjects have completed 12 weeks of treatment or early terminated from the 
study. Lastly, the study will be conducted under the aegis of an independent Data Monitoring 
Committee (DMC) which will perform safety and efficacy assessments at regularly scheduled 
times as well as on an ad hoc basis if needed, throughout this and a randomized, placebo-controlled 
study in UC (PR200-102). 


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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
• To evaluate the safety and tolerability of PRA023 following 12-weeks of induction therapy 
• To assess the proportion of subjects with endoscopic improvement (decrease in simple 
endoscopy score for Crohn’s disease [SES-CD] ≥ 50% from Baseline) at Week 12 
2.2 
Secondary Objectives 
• To assess the proportion of subjects with clinical remission (Crohn’s disease activity 
index [CDAI] < 150) at Week 12 
• To assess the proportion of subjects with endoscopy and clinical improvement (decrease 
in SES-CD ≥ 50% AND reduction in CDAI ≥ 100 points from Baseline) at Week 12 
• To assess the proportion of subjects with biomarker and clinical improvement (decrease 
in hsCRP or fecal calprotectin ≥ 50% from Baseline, among subjects with at least one 
elevated biomarker at Baseline, AND reduction in CDAI ≥ 100 points from Baseline) at 
Week 12 
• To assess the proportion of subjects with normalization of hsCRP < ULN), among 
subjects with elevated concentrations at Baseline, at Week 12 
• To assess the proportion of subjects with normalization of fecal calprotectin (fecal 
calprotectin < ULN), among subjects with elevated concentrations at Baseline, at Week 12 
• To assess the proportion of subjects with clinical improvement (reduction in CDAI ≥ 100 
points from Baseline) at Week 12 
• 
To assess the proportion of subjects with two component patient-reported outcome 
(PRO-2) remission (average daily abdominal pain score ≤ 1 point and average daily stool 
frequency ≤ 3 points with abdominal pain and stool frequency no worse than Baseline) 
Week 12 
• To assess the change in SES-CD score from Baseline to Week 12 
• To assess the PK of PRA023 
• To assess the immunogenicity of PRA023 
2.3 
Exploratory Objectives 
• To assess the change in CDAI and component scores over time 
• To assess the effects of PRA023 on tissue and serum PD markers, including TL1A 
concentrations, endoscopic healing index (EHI), fecal calprotectin, and hsCRP in all 
subjects over time 
• To assess the change in SES-CD at Week 50 from Baseline 


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• To characterize the change in PDAI score from Baseline to Week 12, Week 28 and 
Week 50 
• To characterize the effect of PRA023 for improvement and remission of enterocutaneous 
and/or perianal fistula during the Induction Period (IP) and Open-Label Extension (OLE) 
• To assess all secondary endpoints at Week 50 
• To assess the change in GHAS and RHI from Baseline to Week 12 and Week 50 
• To assess the proportion of subjects with histologic response and histologic remission at 
Week 12 and Week 50 
• To assess the change in PRO-2 over time 
• To assess the change in extraintestinal manifestations over time 
• To assess long-term safety, tolerability, and efficacy of PRA023 
 


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3 
STUDY ENDPOINTS 
The following will be measured for the evaluation of the study endpoints. 
3.1 
Primary Endpoints 
• Safety and tolerability: the proportion of subjects reporting AEs, SAEs, AEs leading to 
discontinuation, and markedly abnormal laboratory values 
• The proportion of subjects with endoscopic improvement, as defined by decrease in 
SES-CD ≥ 50% from Baseline at Week 12  
3.2 
Secondary Endpoints 
• The proportion of subjects in clinical remission (CDAI < 150) at Week 12 
• The proportion of subjects with endoscopic and clinical improvement, as defined by 
decrease in SESCD ≥ 50% AND reduction in CDAI ≥ 100 points from Baseline at 
Week 12 
• The proportion of subjects with both biomarker and clinical improvement (decrease in 
hsCRP OR fecal calprotectin ≥ 50% from Baseline, among subjects with at least one 
elevated biomarker at Baseline, AND reduction in CDAI ≥ 100 points from Baseline) at 
Week 12 
• The proportion of subjects with normalization of hsCRP (as defined by hsCRP < ULN), 
among subjects with elevated concentrations at Baseline, at Week 12 
• The proportion of subjects with normalization of fecal calprotectin (as defined by fecal 
calprotectin < ULN), among subjects with elevated concentrations at Baseline, at 
Week 12 
• The proportion of subjects in clinical response, as defined by reduction in CDAI ≥ 100 
points from Baseline at Week 12 
• The proportion of subjects with PRO-2 remission (defined as average daily abdominal 
pain score ≤ 1 point and average daily stool frequency ≤ 3 points with abdominal pain 
and stool frequency no worse than Baseline) at Week 12 
• Change in SES-CD score at Week 12 from Baseline 
• Descriptive summaries of PK and immunogenicity of PRA023 
• Proportion of subjects developing anti-drug antibody (ADA) and neutralizing antibody (Nab) 
3.3 
Exploratory Endpoints 
• Change in CDAI and components from Baseline over time 
• Change in PD markers including TL1A concentrations, EHI, fecal calprotectin, and 
hsCRP over time 


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• Change in SES-CD from Baseline at Week 50 
• Change in PDAI from Baseline over time 
• Proportion of subjects with improvement or remission of enterocutaneous and/or perianal 
fistula at Week 12 and Week 50 
• Change in GHAS and RHI from Baseline to Week 12 and Week 50 
• The proportion of subjects with GHAS histologic score ≤ 4 at Week 12 and Week 50 
• The proportion of subjects with Robarts histologic score < 5 at Week 12 and Week 50 
• The proportion of subjects with GHAS histologic remission, defined as no neutrophils in 
the epithelium or subscore of 0, at Week 12 and Week 50 
• The proportion of subjects with Robarts histologic remission (< 3) at Week 12 and 
Week 50 
• Change in PRO-2 over time 
• The proportion of subjects with extraintestinal manifestation through Week 50 
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4 
INVESTIGATIONAL PLAN 
4.1 
Study Design 
This is a multi-center, open-label, proof of concept study designed to assess the safety, tolerability, 
and preliminary efficacy of PRA023 following 12 weeks of induction therapy in subjects with 
CD. This study will be conducted under the aegis of a DMC and will commence following the 
demonstration of an acceptable safety profile of PRA023 at a dose of ≥ 500 mg in the multiple 
ascending dose study in normal healthy volunteers (Study PR200-101). 
The study has 4 periods (Screening, IP, OLE, and FU Period). An ileocolonoscopy must be 
performed during the Screening Visit between 28 to 10 days prior to the Week 0/Day 1. 
Following the Screening Period, approximately 50 eligible subjects with moderately to severely 
active CD will enter the IP to receive PRA023 1000 mg on Week 0/Day 1, followed by 500 mg 
on Weeks 2, 6, and 10 via IV administration. Subjects who discontinue from the study drug will 
have a follow-up period of 12 weeks after the last dose. 
Response at Week 12 will be defined as reduction from Baseline in CDAI of ≥ 100 points. Non-
responders at Week 12 should be discontinued from study drug treatment. 
Subjects who complete the 12-week IP and have responded will have the option to enter OLE, 
where they will be randomized to either 250 mg IV Q4W or 100 mg IV Q4W until Week 134. 
Subjects will continue in OLE until they progress, withdraw from the study, study termination, 
or Week 134.  
The study may be amended by the Sponsor to extend the OLE beyond 134 weeks based on 
emerging safety data.   
 


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4.1.1 
Study Schema 
The overall schema for the study is noted below. 
Figure 1 
Study Schema 
 
 
 
Q4W = every 4 weeks; ® = Randomization 
Number of Subjects 
Approximately 50 subjects with moderately to severely active CD will be enrolled. 
4.1.2 
Subject Participation Duration 
Time permitted from screening to dosing: 
Up to 5 weeks 
Duration of individual subject participation 
 
 
Induction: 
12 weeks 
 
Open-Label Extension: 
Based on emerging safety data, until Week 134  
 
Follow-Up: 
12 weeks 
4.1.3 
Subject Numbering and Randomization 
4.1.4.1 
Screening Numbers 
All subjects will be assigned a unique six-digit screening number. The first four digits will be the 
site number and the last two digits will be a number sequentially assigned by the site. This 
number will be used to identify the subjects on all screening documents and during their study 
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4.1.4.2 
Randomization Numbers 
Subjects who meet the required criteria for PRA023 treatment will be assigned a subject 
randomization number. Since this is an open-label study, there is no formal randomization per se; 
the randomization number will be captured in the IRT to denote that the subject has been 
allocated to PRA023 treatment and to ensure that appropriate number of subjects have been 
enrolled in the study. Responders who are re-randomized in OLE will retain their original 
randomization numbers. 
4.2 
Study Subjects/Population 
All subjects must meet the study inclusion and exclusion criteria outlined below in order to 
participate in the study. All subjects must also meet other site-specific criteria (e.g., screening 
and on-study criteria established by each site for COVID-19 mitigation) in order to participate in 
the study. These criteria will be amended by the site(s) as situation changes during the course of 
the study and should be documented by each site on a site-specific COVID-19 risk mitigation plan.  
If absolutely necessary, for extenuating circumstances related to COVID-19, study activities may 
also be deviated as described by the Sponsor COVID-19 mitigation plan. 
4.2.1 
Inclusion/Exclusion Criteria 
4.2.1.1 
Inclusion Criteria 
Subjects are required to meet the following criteria in order to be included in the study: 
1. Male or female ≥ 18 years of age. 
2. Subjects must have had a diagnosis of CD (confirmed by endoscopy + histology) at least 3 
months before screening to be eligible for study participation. For subjects with no 
documented confirmation of CD diagnosis or if previous diagnosis is not deemed conclusive, 
CD diagnosis must be confirmed at time of screening colonoscopy. Note that mention of 
“chronic inflammation” or “Crohn’s disease” or equivalent on histology report is acceptable. 
3. Moderately to severely active CD as defined by CDAI of ≥ 220 and ≤ 450. 
4. SES-CD score (per central reading) ≥ 6 if ileocolonic or colonic disease; or ≥ 4 if isolated 
ileal disease only. 
5. Subjects must satisfy at least one of the following criteria: 
a) In the past, had an inadequate response to one or more of the following treatments: 
• Oral prednisone ≥ 40 mg/day (or equivalent) or budesonide ≥ 9 mg/day or equivalent 
or beclomethasone ≥ 5 mg/day for at least 2 weeks 
• Corticosteroid dependence as defined by failed to successfully taper to < 10 mg/day of 
prednisone equivalent (i.e., had a flare of disease) within 3 months of starting therapy, 
or if relapse occurs within 3 months of stopping corticosteroids 


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• Immunosuppressants (azathioprine ≥ 2 mg/kg/day or 6-mercaptopurine ≥ 1.0 mg/kg/day, 
[or documentation of a therapeutic concentration of 6-thioguanine nucleotide] or 
methotrexate ≥ 15 mg/week) for at least 8 weeks. Note: a lower dosage of 6-MP or 
AZA is acceptable if local guidelines specify a different treatment regimen (which 
would need be documented in the source document) 
• An approved anti-TNF agent at an approved labeled dose for at least 8 weeks 
• An approved anti-integrin (e.g., vedolizumab) at an approved labeled dose for at least 
8 weeks 
• An approved anti-IL-12/23 (e.g., ustekinumab) at an approved labeled dose for at least 
8 weeks 
OR 
b) Had been intolerant to one or more of the above mentioned treatments (e.g., unable 
to achieve doses or treatment durations because of dose- limiting side effects 
[e.g., leukopenia, psychosis, uncontrolled diabetes, elevated liver enzymes]) 
OR 
c) Currently receiving one or more of the following treatments: 
• Oral Prednisone ≥ 10 mg/day (or equivalent) or budesonide ≥ 3 mg/day or 
beclomethasone ≥ 5 mg/day for at least 3 months 
• Immunosuppressants [azathioprine ≥ 2 mg/kg/day or 6-mercaptopurine ≥ 1.0 mg/kg/day, 
(or documentation of a therapeutic concentration of 6-thioguanine nucleotide)] for at 
least 8 weeks. Note: a lower dosage of 6-MP or AZA is acceptable if local guidelines 
specify a different treatment regimen (which would need be documented in the source 
document) 
Notes on subjects who have had prior approved biologic therapy(ies) (e.g., anti-TNF, anti-
integrin, and/or anti-IL-23): 
• The study will include a maximum of 70% and a minimum of approximately 50% 
subjects who have had prior approved biologic therapy(ies) experience. Upon reaching 
the maximum number of allowed biologic experienced subjects (70%), subjects who have 
had prior biologic experience will no longer be allowed to enter the study. Upon reaching 
the maximum number of allowed biologic-naïve subjects (approximately 50%), subjects 
who have never been exposed to a prior biologic will no longer be allowed to enter the 
study. 
• Subjects cannot have had failed (no response, insufficient response, loss of response, 
and/or intolerance) > 4 approved biologic therapies, whether of same or different 
mechanism of action. 
• Subjects previously on clinical trials only (i.e., did not receive commercial available 
therapy post-approval) are not considered to have received the approved therapy for 
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6. For subjects who are WOCBP involved in any sexual intercourse that could lead to 
pregnancy, the subject has used two highly effective methods of contraception for at least 
4 weeks prior to Day 1 and agrees to continue to use two highly effective methods of 
contraception until at least 12 weeks after the last dose of study drug. 
7. Male subjects must use, with their female partner of childbearing potential, two highly 
effective methods of contraception and refrain from sperm donation from screening to 
12 weeks after the last dose of study drug. 
8. Subjects must meet drug stabilization requirements, as applicable: 
a) Oral corticosteroid treatment must be equivalent of ≤ 20 mg prednisone or ≤ 9 mg 
budesonide or beclomethasone ≤ 5 mg daily at a stable dose for at least 2 weeks prior to 
Day 1 
b) Oral aminosalicylates should be at a stable dose for at least 2 weeks prior to Day 1 
c) Azathioprine, 6-mercaptopurine, and methotrexate should be at a stable dose for at least 
4 weeks prior to Day 1 
9. Able to provide written informed consent and understand and comply with the requirements 
of the study. 
4.2.1.2 
Exclusion Criteria 
Subjects with the following characteristics will be excluded from the study: 
Sex and Reproductive Status 
1. WOCBP and men with female partners of childbearing potential who are unwilling or unable 
to use two highly effective methods of contraception to avoid pregnancy for the entire study 
period and for up to 12 weeks after the last dose of study drug. 
2. Women who are pregnant or breastfeeding. 
3. Women with a positive pregnancy test on enrollment or prior to Day 1. 
Target Disease Exceptions 
4. Diagnosis of ulcerative colitis or indeterminate colitis. 
5. CD isolated to the stomach, duodenum, jejunum, or perianal region, without colonic and/or 
ileal involvement. 
6. Suspected or diagnosed intra-abdominal or perianal abscess at Screening. 
7. Known symptomatic stricture or stenosis not passable in endoscopy (including pediatric 
colonoscope). 
8. Current stoma or need for colostomy or ileostomy.  
9. Previous small bowel resection with combined resected length of > 100 cm or previous 
colonic resection of > 2 segments.  
10. Currently receiving total parenteral nutrition. 


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11. Surgical bowel resection within 3 months before screening. 
12. Concomitant PSC. 
Medical History and Concurrent Diseases 
13. Past or current evidence of definite low-grade or high-grade colonic dysplasia that has not 
been completely removed. 
14. Subjects who are scheduled or anticipate the need for surgery, aside from dermatologic 
procedures. 
15. Subjects who have a history of clinically significant drug or alcohol abuse. 
16. Concomitant illness that in the opinion of the Investigator, is likely to require systemic 
glucocorticosteroid therapy during the study (e.g., moderate to severe asthma). 
17. Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, 
pulmonary, cardiac, neurological, ophthalmologic, or cerebral disease. Concomitant medical 
conditions that in the opinion of the Investigator might place the subject at unacceptable risk 
for participation in this study. 
18. Subjects with a history of cancer within the last 5 years (other than non-melanoma skin cell 
cancers cured by local resection). Existing non-melanoma skin cell cancers must be removed 
prior to enrollment. Subjects with carcinoma in situ or localized cervical cancer, treated with 
definitive surgical intervention, are allowed. 
19. Subjects at risk for tuberculosis (TB). Specifically, subjects with: 
a) A history of active TB 
b) Current clinical, radiographic or laboratory evidence of active TB 
c) Latent TB which was not successfully treated. Subjects with a positive TB screening test 
indicative of latent TB will not be eligible for the study unless active TB infection has 
been ruled out, and an appropriate course of intervention for latent TB has been initiated 
at least 2 weeks prior to Day 1, and no evidence of active TB on chest x-ray during 
screening. 
20. Subjects with any serious bacterial infection within the last 3 months, unless treated and 
resolved with antibiotics, or any chronic bacterial infection (such as chronic pyelonephritis, 
osteomyelitis, and bronchiectasis). 
21. Female subjects who have had a breast cancer screening that is suspicious for malignancy, 
and in whom the possibility of malignancy cannot be reasonably excluded following 
additional clinical, laboratory, or other diagnostic evaluations. 
22. Subjects with any active infections (excluding fungal infections of nail beds) including, but 
not limited to, those that require IV antimicrobial treatment 4 weeks or oral antimicrobial 
treatment 2 weeks prior to randomization. Subjects with evidence of Human 
Immunodeficiency Virus (HIV), Hepatitis B, or Hepatitis C infection detected during 
screening are also excluded. Subjects with successfully treated Hepatitis C with no 
recurrence for ≥ 1 year are allowed. Subjects with active documented or suspected COVID-


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19 infection within 4 weeks of randomization or asymptomatic SARS-CoV-2 test positivity 
within 2 weeks of randomization are excluded. 
23. Subjects with herpes zoster reactivation or cytomegalovirus (CMV) that resolved less than 
2 months prior to signing informed consent. 
24. Subjects who have received any live vaccines within 3 months of the anticipated first dose of 
study medication or who will have need of a live vaccine at any time during the study. 
Physical and Laboratory Test Findings 
25. Positive stool Polymerase Chain Reaction (PCR) if Investigator deems this positivity reflects 
infection rather than colonization or positive culture for enteric pathogens. 
26. Stool positive for Clostridium difficile (C. difficile) toxin. Subjects who are positive can be 
retested after the completion of a full course of treatment for C. difficile infection. 
27. Any of the following lab values: 
a) Hemoglobin (Hgb) < 8.0 g/dL (80 g/L) 
b) White blood cell (WBC) < 2,500/mm3 (2.5 x 109/L) 
c) Neutrophils < 1,000/mm3 (1 x 109/L) 
d) Platelets < 100,000/mm3 (100 x 109/L) 
e) Serum creatinine > 2 times upper limit of normal (ULN) 
f) Serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) > 2 times ULN 
g) Any other laboratory test results that, in the opinion of the Investigator, might place the 
subject at unacceptable risk for participation in this study 
Prohibited Therapies and/or Medications 
28. Failed (no response, insufficient response, loss of response, and/or intolerance) > 4 approved 
biologic therapies (anti-TNF, anti-integrin, anti-IL12/23), whether of same or different 
mechanism of action. 
29. Any marketed biologic within 8 weeks for anti-TNF agents and 12 weeks for anti-integrin 
agents (e.g., vedolizumab) and ustekinumab prior to Day 1 or if drug level per therapeutic 
dose monitoring is greater than lower limit of detection. 
30. Any biologic immunomodulators used for CD or other conditions within 8 weeks or 5 half-
lives, whichever is longer, prior to Day 1 or if drug level per therapeutic dose monitoring is 
greater than lower limit of detection. 
31. Rituximab within 1 year prior to Day 1. 
32. Parenteral corticosteroids within 4 weeks or rectal administration of corticosteroids within 
2 weeks prior to Day 1. 
33. Rectal administration of 5-ASA within 2 weeks prior to Day 1. 
34. Tacrolimus, cyclosporine, mycophenolate mofetil (CellCept®), immunoadsorption columns 
(such as Prosorba columns), D Penicillamine, Leflunomide, Thalidomide, chronic use of 
non-steroidal anti-inflammatory agents (NSAIDs), and use of aspirin > 81 mg/day within 
2 weeks prior to Day 1. 


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35. Other investigational chemical agent within 30 days or other investigational biologic agent 
within 8 weeks or 5 half-lives (whichever is longer) of entry into the IP. 
36. Prior exposure to PRA023. 
Other Exclusion Criteria 
37. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for 
treatment of either a psychiatric or physical (e.g., infectious disease) illness. 
38. Legal or mental incapacitation, or inability to understand and comply with the requirements 
of the study. 
39. Known allergies, hypersensitivity, or intolerance to PRA023 or its excipients.  
4.3 
Contraception Guidelines 
The Investigator or his/her designee will discuss with the subject the need to use two highly 
effective methods of contraception consistently and correctly according to Schedule of Study 
Assessments (Section 6.1.1) and document such conversation in the subject’s chart. In addition, 
the Investigator or his or her designee will instruct the subject to call immediately if the selected 
contraception methods are discontinued or if pregnancy is known or suspected in the subject or 
the subject’s partner. 
All women who have experienced menarche are WOCBP unless meeting criteria for women of 
non-childbearing potential as described below. This includes women who are using an active 
method of birth control, are practicing abstinence, with same sex partner, have undergone tubal 
ligations, or where the partner is sterile (e.g., vasectomy). 
WOCBP involved in any sexual intercourse that could lead to pregnancy will be eligible for the 
study provided they use two highly effective methods of contraception for at least 4 weeks prior 
to Day 1, throughout the study and until the 12 weeks after the last dose of IP. The dose for 
hormonal contraceptives must have been stable for at least 4 weeks prior to Day 1. 
All male subjects who are able to father children, are sexually active with female partners, and at 
risk for pregnancy must agree to use, with their partners, two highly effective method of 
contraception consistently and correctly for the duration of the active treatment period and 12 
weeks after the last dose of study drug. In addition, all sexually active male subjects must also 
agree to prevent potential transfer of and exposure to study drug through semen to their partners 
by using a condom consistently and correctly, beginning with the first dose of study drug and 
until 12 weeks after the last dose of study drug. 
Highly effective methods of contraception are those that, alone or in combination, result in a 
failure rate of less than 1% per year when used consistently and correctly (i.e., perfect use) and 
include the following: 
1. Established use of oral, inserted, injected, implanted or transdermal hormonal methods of 
contraception is allowed provided the subject plans to remain on the same treatment 
throughout the entire study and has been using that hormonal contraceptive for an 


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adequate period of time to ensure effectiveness 
2. Correctly placed copper-containing intrauterine device (IUD) 
3. Male condom or female condom used WITH a spermicide (i.e., foam, gel, film, cream, or 
suppository). For countries where spermicide is not available and condoms alone are 
considered an effective method of contraception, at the Investigator’s discretion, the use 
of condom alone without spermicide is acceptable and sufficient to meet this 
requirement. 
4. Male sterilization with documented absence of sperm in the post-vasectomy ejaculate 
5. Bilateral tubal ligation/bilateral salpingectomy or bilateral tubal occlusive procedure 
(provided that occlusion has been confirmed in accordance with the device’s label) 
6. Females who meet the criteria for non-childbearing potential, as described below: 
Woman of non-childbearing potential must meet at least one of the following criteria: 
• 
Have had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy) 
• 
Have medically confirmed ovarian failure 
• 
Females who are postmenopausal with amenorrhea without an alternative medical cause 
for at least 1 year prior to the first dose and have follicle stimulating hormone (FSH) 
serum levels consistent with postmenopausal status as per investigator judgment 
4.4 
Concomitant Treatments and Restrictions 
4.4.1 
Prior and Concomitant Medications 
Any prior or ongoing CD medications, including corticosteroids, immunosuppressives (AZA, 
6-MP, and MTX), anti-TNFs, anti-integrins, and anti-IL-12/23 used by the subject will be 
recorded on the eCRF. 
All concomitant medication(s) and treatment(s) administered/taken during the study must be 
recorded with indication, dose, and start and stop dates of administration. All subjects will be 
questioned about concomitant medication at each site visit. 
Medication(s) administered/taken following the first dose of PRA023 will be documented as 
concomitant medication(s). 
4.4.2 
Permitted Medications with Restrictions 
Subjects will be allowed to use the following medications as detailed below: 
• A stable dose of 5-ASA for at least 2 weeks prior to Day 1 and throughout the IP 
• A stable dose of oral corticosteroids (prednisone ≤ 20 mg/day or equivalent) for CD for at 
least 2 weeks prior to Day 1 and during the IP. During the OLE period, a tapering 
schedule should be followed if the subject’s condition allows (see Section 4.4.4). 


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• A stable dose of oral budesonide (≤ 9 mg/day or equivalent) or beclomethasone ≤ 5 
mg/day for at least 2 weeks prior to Day 1 and during the IP. During the OLE period, a 
tapering schedule should be followed if the subject’s condition allows (see Section 4.4.4). 
• A stable dose of immunosuppressants (AZA, 6-MP, or methotrexate) for 4 weeks prior to 
Day 1 and during the IP. 
4.4.3 
Prohibited Medications 
• Any marketed biologic therapy throughout the study 
• IV corticosteroid for treatment of CD during the IP 
• Oral corticosteroid (prednisone > 20 mg/day or equivalent) for the treatment of CD 
during the IP  
• Oral budesonide > 9 mg/day or equivalent or beclomethasone > 5 mg/day during 
the IP 
• Any per rectal therapy including enema (e.g., 5-ASA, budesonide, corticosteroid) during 
IP, other than that required for endoscopy preparation during the IP.  
• Systemic tacrolimus, systemic cyclosporine, oral mycophenolate mofetil (MMF), 
immunoadsorption columns (such as Prosorba columns), D-penicillamine, leflunomide, 
Thalidomide, purified medicinal probiotics throughout the study 
• Chronic use of NSAIDs or aspirin > 100 mg/day during the IP 
• Any investigational drug other than the study medication throughout the study 
4.4.4 
Corticosteroid and Budesonide Tapering Schedule During Open-Label 
Period 
After the completion of all Week 12 assessments, background oral corticosteroid and/or 
budesonide therapy should be tapered if the subject is in remission (as defined in Section 6.4) or 
has a satisfactory response to treatment per Investigator. 
For prednisone or equivalent, dose should be reduced at a rate of 2.5 mg (daily dose) of prednisone 
or equivalent per week; although the Investigator may use an alternative regimen if preferred. For 
budesonide and beclomethasone, tapering schedule per site protocol with goal of completing the 
tapering regimen within 8 weeks. 
4.4.5 
Other Restricted Medications 
Due to the risk of infection, vaccination of subjects with any live vaccine is contraindicated 
during the treatment period of the study (i.e., at any time after randomization into the IP), as is 
the administration of LIVE oral polio vaccine to household contacts. The Centers for Disease 
Control and Prevention Advisory Committee on Immunization Practices (CDC ACIP) 
recommends that subjects should not be administered a live virus vaccination for at least 3 months 
after immunosuppressive therapy. Therefore, study subjects should not be administered a live 


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vaccine for a minimum of 3 months following the last dose of study medication. Check with 
Medical Monitor, if uncertain, regarding use of certain COVID-19 vaccines. 
4.4.6 
Rescue Medication 
High-dose steroids for CD, increases in oral aminosalicylates, rectal aminosalicylates, and rectal 
corticosteroids are permitted as rescue medications only during OLE, and other CD treatments 
will not be permitted during the study and will only be permitted following formal study 
withdrawal. Once a subject permanently discontinues PRA023 treatment and withdraws from the 
study, subjects will no longer need to abstain from the medications that were prohibited. 
However, biologic treatment(s) should not be initiated for 12 weeks after the last dose of 
PRA023 without discussion with the Sponsor due to the long half-life (t1/2) of PRA023. 
Subjects are free to withdraw from the study at any time at their own request, or they may be 
withdrawn at any time at the discretion of the Investigator or Sponsor. If a subject requires 
initiation of a new therapy for CD, the subject should be withdrawn from the study and 
appropriate treatment should be administered at the discretion of the Investigator. 
4.5 
Removal of Subjects from Study 
A genuine effort must be made to determine the reason(s) why a subject fails to return for the 
necessary visits or is discontinued from the study. This information and date must be recorded on 
the appropriate eCRF and on the Termination Sheet. Subjects MUST discontinue from the study 
for any of the following reasons: 
• The subject decides that it is in his/her best interest. It is fully understood that all subjects 
volunteer for the study and that they may withdraw their consent to continue in the study 
at any time. 
• Any AE, laboratory abnormality, or change in medical condition which, in the opinion of 
the Investigator, indicates that continued participation in the study is not in the best 
interest of the subject. 
o For potential drug induced liver injury (DILI), timely confirmation of initial liver-
related laboratory abnormalities should be performed. Potential drug induced liver 
injury is defined as: 
 ALT/AST elevation >3 x ULN, AND 
 Total bilirubin >2 x ULN, without initial findings of cholestasis (elevated serum 
alkaline phosphatase), AND 
 No other immediately apparent possible cause of increased ALT/AST and total 
bilirubin, such as viral hepatitis A, B, or C; preexisting or acute liver disease; or 
other drug capable of causing the observed injury 
o Subjects with suspected DILI should be discontinued from the study 
• Persistent non-compliance of the subject  
• Pregnancy 


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• Use of any investigational drug therapy for CD excluding study treatment 
• Treatment with biologic therapy for CD 
The Investigator must notify the Medical Monitor by telephone or by email as soon as possible if 
any subject prematurely withdraws from the study. The date when the subject is withdrawn and 
the reason for discontinuation must be recorded in the eCRF. If a subject is “lost to follow-up” 
(fails to return for study visits), a reasonable effort should be made to contact the subject in order 
to determine why the subject failed to return. This information must be documented in the eCRF. 
If a subject is withdrawn from the study early (regardless of the cause) all of the end-of-study 
evaluations should be performed at the time of withdrawal, and the subject followed for 12 weeks 
after the last dose of PRA023, if possible, due to the long t1/2 of PRA023. 
It is agreed that, for reasonable cause, either the Investigator or the Sponsor, Prometheus, may 
terminate this study. 
4.6 
Modification of Study Drug Dosing 
Investigators should reference the Investigator’s Brochure (IB) for PRA023 and use their best 
clinical judgment to determine the continuation of dosing during the study. PRA023 doses 
should be withheld until after the resolution of clinically significant infections. Reference 
Section 5.4 for dose modification recommendations related to infusion reaction. 


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5 
INVESTIGATIONAL PRODUCT 
5.1 
Dosing Form and Preparation 
PRA023 concentrate for solution for infusion will be provided as a single-dose glass vial 
containing 500 mg of PRA023 at 60 mg/mL dose strength. PRA023 will be packaged in a box 
containing 6 vials per box. Each vial will contain at minimum 8.4 mL of PRA023. All study drug 
vials will indicate the lot number and the label affixed to the vial will contain the drug 
identification and conditions for storage. The vials do not contain antibacterial preservatives. 
Therefore, any unused portion of the study drug after single use should not be stored for reuse. 
Since this is an open-label study, there is no blinding. The site pharmacist(s) or designee will be 
preparing study drug for infusion. Detailed study drug preparation and handling instructions will 
be provided to the investigational pharmacist in the Pharmacy Manual. 
5.2 
Storage 
The study drug must be stored in a secure, lockable area in 36oF - 46oF (2oC - 8oC) controlled 
storage condition prior to use. All study drug must continue to be stored in a secure, lockable 
area until it is returned to the Sponsor or designee or destroyed upon approval by the Sponsor or 
designee. 
5.3 
Accountability 
The study drug must be used in accordance with the protocol and only under the direction of the 
Investigator. The Investigator or designee shall keep and maintain complete and accurate records 
of all investigational materials. Records showing the receipt and disposition of all study drug 
shall include a master record listing the date of receipt of study drug shipment, the quantities 
received, and a dispensing record, which includes each quantity dispensed, identification of the 
person to whom dispensed, the date of dispensing, and the identification of the dispenser. The 
accountability records must be made available to the Sponsor or designee at any time. 
At the termination of the study or at the request of the Sponsor or designee, the Investigator must 
return any unused study drug to the Sponsor or its designee according to applicable local and 
country regulations, and appropriately destroy any empty or used study drug vials. If return of 
unused study drug is not feasible, the Sponsor or designee will supply instructions as to how the 
supplies may be destroyed. All study drug supply destruction must be clearly documented. The 
Investigator must also provide a written explanation for any missing study drug. 


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5.4 
PRA023 Administration 
All doses of PRA023 will be administered intravenously as a 30-minute infusion using a 
calibrated infusion pump by the appropriately designated study staff at the investigational site. 
Treatment of subjects with monoclonal antibodies may result in inappropriate immune responses 
and range from mild events with no apparent clinical manifestations to life-threatening or 
catastrophic reactions. Signs and symptoms of these events may develop during or shortly after 
infusion. As such, subjects must be closely monitored during administration of PRA023. Post-
infusion observation period during the first 2 infusions (Week 0/Day 1 and Week 2) should be 1* 
hour and subsequent infusions should be 30 minutes (Table 2 and Table 3).  
Some of the major safety concerns associated with immunogenicity are anaphylaxis, cytokine 
release syndrome, “infusion reactions”, and non-acute reactions such as delayed hypersensitivity. 
The information below is provided as guidance to assess anaphylaxis, but the clinical judgment 
of the Investigator should be considered as well. 
Anaphylaxis is a serious, acute allergic reaction characterized by certain clinical features. Signs 
and symptoms of anaphylaxis may include: 
• Generalized hives, pruritis/itching, flushing, swollen lips/tongue/uvula 
• Symptoms of respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, 
reduced peak expiratory flow, hypoxemia) 
• Reduced blood pressure (systolic blood pressure of less than 90 mm Hg or greater than 
30% decrease from baseline) or associated symptoms of end-organ dysfunction 
(e.g., hypotonia [collapse], syncope, incontinence) 
• Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
If a subject experiences anaphylaxis, PRA023 administration should be discontinued 
immediately and permanently. If a subject experiences symptoms that may be attributed to 
hypersensitivity reaction or delayed hypersensitivity (e.g., fever, rash, arthralgia, myalgia, 
hematuria, proteinuria, serositis, central nervous system complications, or hemolytic anemia), 
PRA023 infusion should be stopped. 
In the event that symptoms are mild or minor in severity, at the discretion of the Investigator, the 
infusion may be restarted at a slower rate if symptoms are resolved within 1 hour after stopping 
the infusion. If symptoms return, PRA023 should be discontinued immediately and permanently. 
In the event that there is an infusion interruption, the entire duration of PRA023 infusion, from 
the initial start of infusion, to the completion of infusion, should not exceed 24 hours of PRA023 
dilution. Subjects will receive appropriate treatment at the discretion of the Investigator. 
                                            
* 2 hours for subjects in Czech Republic 


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6 
STUDY PROCEDURES 
A schedule of study procedures is presented in Section 6.1.1. If any discrepancies should be found 
between the text of the protocol and the Schedule of Study Assessments tables, the tables will 
predominate. 
Every effort should be made to ensure that the protocol-required tests and procedures are 
completed as described. However, it is anticipated that from time to time there may be 
circumstances, outside of the control of the Investigator, that may make it unfeasible to perform 
the test. In these cases, the Investigator will take all steps necessary to ensure the safety and well-
being of the subject. When a protocol-required test cannot be performed, the Investigator will 
document the reason for this and any corrective and preventive actions that he or she has taken to 
ensure that normal processes are adhered to as soon as possible. The Sponsor or designee will be 
informed of these incidents in a timely fashion. 
6.1 
Study Visit Procedures 
A written, signed informed consent form (ICF) must be obtained from each subject prior to 
performing any study procedure. Medical/surgical history, medication record (prior and concomitant 
medications and therapy), and a physical examination including vitals will be obtained for all 
subjects at the Screening Visit. A series of laboratory and diagnostic/clinical tests and evaluations 
will be performed. At least two visits to the clinical facility may be necessary to complete all 
screening procedures, including an ileocolonoscopy. The ileocolonoscopy should be performed 
after all other eligibility criteria, including CDAI during Screening, have been met and within 
28-10 days of Day 1 to allow SES-CD score calculation. 
Subjects may be re-screened one time at the discretion of the Sponsor if they fail their initial 
screening. 
After Week 0/Day 1, all subjects will be evaluated frequently through a series of physical 
examinations, and laboratory tests and assessments for safety and efficacy as described in the 
Schedule of Study Assessments tables (Section 6.1.1). 
 


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6.1.1 
Schedule of Study Assessments 
 
Schedule of Study Assessments – Screening Period 
Procedure 
Study Visit 
Screening 
NOTES 
Screening duration is up to 35 days (5 weeks) 
Eligibility Assessments 
Informed Consent 
X 
 
Inclusion/Exclusion Criteria 
X 
 
Medical and Surgical History  
X 
 
Smoking History 
X 
 
Prior and Current Concomitant Medications 
X 
 
Safety Assessments 
Complete Physical Examination 
X 
 
Targeted Physical Examination  
 
 
Vital Signs 
X 
Height at Screening Visit 1 only 
Heart rate, temperature, blood pressure 
Weight 
X 
 
ECG 
X 
 
Chest X-Ray 
X 
Must be performed within 6 months of the Screening Visit 1 
with documentation on file. 
Adverse Events Assessment 
X 
 
Efficacy Assessments 
Subject Training on Electronic Diary (eDiary) 
Completion 
X 
 
Issue eDiary to Subject 
X 
Remind subjects to record in their eDiary daily 
Ileocolonoscopy with Biopsy 
X 
Ileocolonoscopy should be performed between 28 to 10 days 
prior to the Week 0/Day 1 visit. Ileocolonoscopy should be 
performed after all other eligibility criteria have been met. 
Laboratory Tests 
Pharmacogenomics (Buccal Swab and Blood) 
X 
In case of DNA extraction failure, additional sample should be 
collected for CDx testing. 
Stool PCR or Culture 
X 
Can be performed centrally or locally. Ova and parasite 
examination should also be performed based on local 
guidelines. 
C. difficile PCR/Toxin 
X 
Can be performed centrally or locally. 
Fecal calprotectin 
X 
To be performed during screening, prior to Week 0/Day 1 
CBC 
X 
 
Chemistry Panel 
X 
 
hsCRP 
X 
 
Urinalysis 
X 
 
QuantiFERON-TB 
X 
May be repeated if result indeterminate. No need to test if 
negative result available within 90 days of screening. 
HBsAg, HBcAb, and HCV Ab 
X 
If HCV Ab positive, confirmation by undetectable HCV-RNA. . 
If HBcAb is positive and Hep B sAg negative, Hep B DNA will 
be done as reflexive test, and if undetectable, then not 
exclusionary. No need to test if negative result available within 
90 days of screening. 
Human Immunodeficiency Virus (HIV) 
X 
Per local regulations. To be assayed locally or centrally per 
country/regional regulations. Confirmation and documentation of 


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Procedure 
Study Visit 
Screening 
NOTES 
Screening duration is up to 35 days (5 weeks) 
a negative HIV test result within 3 months (except for subjects 
in Czech Republic) prior to screening will be accepted.  
Serum Pregnancy Test (WOCBP only) 
X 
 
 


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Schedule of Study Assessments – Induction Period 
 
Study Visit 
NOTES 
Study Week 
0 
1 
2 
6 
10 
12 
Early 
Termination 
 
Study Day 
1 
8 
15 
43 
71 
85 
Visit window (days) 
0 
±1 
±3 
±3 
±3 
±3 
 
Procedure 
 
 
 
 
 
 
 
Eligibility Confirmation 
X 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
Via IRT system 
Complete Physical Examination 
 
 
 
 
 
X 
X 
 
Targeted Physical Examination 
X 
 
X 
X 
X 
 
 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
Heart rate, temperature, blood pressure; Take pre-dose (no more than 30 
minutes pre-infusion), end of infusion, and end of observation period. 
Weight 
X 
X 
X 
X 
X 
X 
X 
Needed for CDAI assessment 
ECG 
X 
 
 
 
 
X 
X 
 
Adverse Events Assessment 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
 
Efficacy Assessments 
Ileocolonoscopy with Biopsy 
 
 
 
 
 
X 
X 
Ileocolonoscopy to be performed within 10 days after Week 12 visit, or 
at early termination visit 
Review eDiary Data from Subjects 
X 
X 
X 
X 
X 
X 
X 
Remind subjects to record in their eDiary daily  
CDAI Assessment 
X 
X 
X 
X 
X 
X 
X 
 
PDAI 
X 
 
 
 
 
X 
X 
 
Fistula Drainage Assessment 
X 
 
X 
X 
X 
X 
X 
 
IBDQ 
X 
 
 
X 
 
X 
X 
 
Laboratory Testing 
CBC 
X 
X 
X 
X 
X 
X 
X 
 
Chemistry Panel 
X 
 
X 
X 
 
X 
X 
 
Fasting Lipid Panel 
X 
 
 
 
 
X 
X 
 


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Study Visit 
NOTES 
Study Week 
0 
1 
2 
6 
10 
12 
Early 
Termination 
 
Study Day 
1 
8 
15 
43 
71 
85 
Visit window (days) 
0 
±1 
±3 
±3 
±3 
±3 
 
Procedure 
 
 
 
 
 
 
 
Urinalysis 
X 
 
X 
X 
 
X 
X 
 
Urine Pregnancy Test (WOCBP only) 
X 
 
 
X 
 
X 
X 
 
Pharmacokinetics 
Xa 
X 
Xb 
Xb 
Xa 
X 
X 
a.  The PK sample at Week 0/Day 1 and Week 10 must be taken pre-
dose, immediately following the end of infusion (within 30 minutes), 
and 1 hour after the end of infusion. 
b.  The PK sample taken at Weeks 2 and 6 must be taken pre-dose 
(within 30 minutes prior to dosing). 
Immunogenicity 
Xa 
 
Xa 
Xa 
 
X 
X 
a. To be taken pre-infusion 
Biomarkers 
Biomarkers 
X 
 
X 
X 
X 
X 
X 
Serum at all visits; additional whole blood at Weeks 0, 6 and 12 
Soluble TL1A  
X 
 
X 
X 
X 
X 
X 
 
hsCRP 
X 
X 
X 
X 
X 
X 
X 
 
Fecal Calprotectin 
X 
 
 
X 
 
X 
X 
 
Infusion 
X 
 
X 
X 
X 
 
 
Include date, start and stop time, volume infused, and length of the IV 
infusion. 
Infusion observation period at Week 0/Day 1 and Week 2 will be 1 hour 
(2 hours for subjects in Czech Republic); 30 minutes for all subsequent 
infusions thereafter. 
 


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Schedule of Study Assessments – Open-Label Extension Period Up to Week 50 
 
Study Visit 
NOTES 
Visit windows are as follows: +14 day window for Week 14 visit, 
±7 day window from Week 18 to Week 24 visits, and ±14 day 
window if >Week 24 
 
Study Week 14 
18 
26 
34 
42 
50 
Early 
Termination 
Infusion Visits 
Q4W 
(excluding Office 
Visits) 
 
Study Day 99 
127 183 239 295 351 
Visit window (days) +14 
±7 
±14 ±14 ±14 ±14 
 
±7/±14 
Procedure 
 
 
 
 
 
 
 
 
Enter subject into IRT for OLE 
X 
 
 
 
 
 
 
 
 
Complete Physical Examination 
 
 
 
 
 
X 
X 
 
 
Targeted Physical Examination  
X 
X 
X 
X 
X 
 
 
 
 
Vital Signs 
X 
X 
X 
X 
X 
X 
X 
X 
Heart rate, temperature, blood pressure; Take pre-dose (no more 
than 30 minutes pre-infusion) and end of infusion  
ECG 
 
 
 
 
 
X 
X 
 
 
Weight 
X 
X 
X 
X 
X 
X 
X 
 
Needed for CDAI assessment 
Adverse Events Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
 
Efficacy Assessments 
Review eDiary Data from Subjects 
X 
X 
X 
X 
X 
X 
X 
 
Remind subjects to record in their eDiary daily  
CDAI Assessment 
X 
X 
X 
X 
X 
X 
X 
 
 
PDAI 
 
 
X 
 
 
X 
X 
 
 
Fistula Drainage Assessment 
X 
X 
X 
X 
X 
X 
X 
 
 
Ileocolonoscopy with Biopsy 
 
 
Xa,b 
 
 
X 
X 
 
Ileocolonoscopy to be performed between 14 and 8 days before 
Week 26 and Week 50 visits or within 1 week after Week 50 
visit or ET visit 
aIf the investigator feels there is a contraindication, this Week 26 
endoscopy could be considered optional.  
bBiopsies are optional. 


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Study Visit 
NOTES 
Visit windows are as follows: +14 day window for Week 14 visit, 
±7 day window from Week 18 to Week 24 visits, and ±14 day 
window if >Week 24 
 
Study Week 14 
18 
26 
34 
42 
50 
Early 
Termination 
Infusion Visits 
Q4W 
(excluding Office 
Visits) 
 
Study Day 99 
127 183 239 295 351 
Visit window (days) +14 
±7 
±14 ±14 ±14 ±14 
 
±7/±14 
Procedure 
 
 
 
 
 
 
 
 
IBDQ 
 
 
X 
 
 
X 
X 
 
 
Laboratory Testing 
CBC 
X 
X 
X 
X 
X 
X 
X 
 
 
Chemistry Panel 
X 
X 
X 
X 
X 
X 
X 
 
 
Fasting Lipid Panel 
 
 
X 
 
 
X 
X 
 
 
Urinalysis 
X 
X 
X 
X 
X 
X 
X 
 
 
Urine Pregnancy Test (WOCBP only) 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testing must be done once a month 
Pharmacokineticsc 
Xa 
Xa 
Xa 
 
Xa 
Xb 
X 
 
a. To be taken pre-infusion. 
b. To be taken pre-infusion or at the same time as other laboratory 
tests for early termination.. 
Immunogenicity 
 
Xa 
Xa 
 
Xa 
Xa 
X 
 
a. To be taken pre-infusion 
Biomarkers 
Biomarkers 
X 
X 
X 
X 
X 
X 
X 
 
Serum at all visits; additional whole blood at Week 50 
Soluble TL1A  
X 
X 
X 
X 
X 
X 
X 
 
 
hsCRP 
X 
X 
X 
X 
X 
X 
X 
 
 
Fecal Calprotectin 
 
 
X 
 
 
X 
X 
 
 
Infusion 
X 
X 
X 
X 
X 
X 
 
X 
Include date, start and stop time, volume infused, and length of 
the IV infusion. 
Infusion observation period will be 30 minutes 
 
 


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Schedule of Study Assessments – Open-Label Extension Period (After Week 50) 
 
Study Visit 
NOTES 
Visit windows are  ±14 days  
Study Week 
Quarterly* 
Office Visits 
Early 
Termination 
Infusion 
Visits 
(excluding 
Office Visits) 
* Weeks 62, 74, 86, 98, 110, 122, 134 
Procedure 
 
 
 
Complete Physical Examination 
Xa 
X 
 
a. Yearly 
Targeted Physical Examination 
X 
 
 
 
Vital Signs 
Xa 
Xa 
X 
Heart rate, temperature, blood pressure; Take pre-dose (no more than 30 minutes 
pre-infusion) and end of infusion  
a. Weight needed 
Adverse Events Assessment 
X 
X 
X 
 
Concomitant Medication 
X 
X 
X 
 
Efficacy Assessments 
Review Diary Data from Subjects 
X 
 
 
Paper diaries may be used 
CDAI Assessment  
X 
X 
 
 
PDAI   
Xa 
Xa 
 
a. To be performed on every subject every 6 months 
Fistula Drainage Assessment  
X 
X 
 
 
Ileocolonoscopy with Biopsy 
Xa 
Xa 
 
a. Done annually 
Subjects should undergo colon cancer surveillance as per local guidelines, if 
applicable, for clinical management 
IBDQ 
Xa 
X 
 
a.Every 6 months 
Laboratory Testing 
CBC 
X 
X 
 
 
Chemistry Panel 
X 
X 
 
 
Fasting Lipid Panel 
Xa 
X 
 
a. Every 6 months 
Urine Pregnancy Test (WOCBP only)  
X 
X 
X 
Pregnancy testing must be done once a month prior to dosing 
Urinalysis 
Xa. 
X 
 
a. Every 6 months 
Pharmacokinetics 
Xa 
Xb 
 
a. To be taken pre-infusion; every 6 months 


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Study Visit 
NOTES 
Visit windows are  ±14 days  
Study Week 
Quarterly* 
Office Visits 
Early 
Termination 
Infusion 
Visits 
(excluding 
Office Visits) 
* Weeks 62, 74, 86, 98, 110, 122, 134 
Procedure 
 
 
 
b. To be taken at the same time as other laboratory tests for early termination 
Immunogenicity 
Xa 
X 
 
a To be taken pre-infusion; every 6 months 
Biomarkers 
hsCRP 
Xa 
X 
 
a. Every 6 months 
Fecal Calprotectin 
Xa 
X 
 
a. Every 6 months 
Serum biomarkers 
Xa 
X 
 
a. Every 6 months; additional whole blood sample at Week 98 
Infusion 
X 
 
X 
Infusions should be at Q4 week interval 
Include date, start and stop time, volume infused, and length of the IV infusion 
Infusion observation period will be 30 minutes 


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Post Dosing Follow-Up Period 
 
Study Visit 
 
28 Days Post Dosing Period 
56 Days Post Dosing Period 
84 Days Post Dosing Period 
Visit window (days) 
±7 
±7 
±7 
Procedure 
 
 
 
Adverse Events Assessment 
X 
X 
X 
Concomitant Medication 
X 
X 
X 
Urine Pregnancy Test (WOCBP only) 
X 
X 
X 
Pharmacokinetics 
X 
X 
X 
Immunogenicity 
X 
X 
X 


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6.2 
Other Information for Study Visits 
Unscheduled procedures may be required in addition to the procedures detailed above for subject 
safety and/or exacerbation assessments. The additional procedures are at the discretion of the 
Investigator. The details of these unscheduled procedures will be recorded in the source 
documents and entered into the eCRFs. 
6.3 
Safety Assessment Description 
6.3.1 
Medical History, Physical Examination, Height and Weight 
Medical history, including CD history, will be collected at the Screening Visit. 
The Investigator will perform a complete physical examination at the Screening Visit and at the 
visits specified in the schedule of study procedures (Section 6.1.1). The complete physical 
examination must include the following: 
• General appearance 
• Hair and skin 
• Lymph nodes 
• Head 
• Eyes 
• Ears, nose, and throat 
• Neck 
• Respiratory 
• Cardiovascular 
• Abdominal 
• Musculoskeletal 
• Mental status 
• Neurological 
Unless otherwise indicated, following screening visit, physical examinations should be targeted 
(symptom directed). Complete and targeted physical examinations are to be performed at 
specified visits according to the schedule of study procedures (Section 6.1.1). 
Height and weight will be measured without the subject wearing shoes. Height (inches or 
centimeters) will be measured and recorded at the screening visit only and weight (lbs or kg) 
will be measured and recorded at specified visits (Section 6.1.1). 
6.3.2 
Vital Signs 
Vital signs to be assessed are heart rate, respiratory rate, body temperature, and resting blood 
pressure. The body position (sitting or supine) should be recorded. Approved medical devices 
may be used to record these parameters. 


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6.3.3 
Chest X-Ray 
A chest x-ray (posterior-anterior and lateral views are recommended, however, local guidelines 
should be followed) with no evidence of current, active TB or previous inactive TB, general 
infections, heart failure or malignancy is to be taken at screening or within the 6 months prior to 
screening and read by a qualified radiologist. Documentation of the official reading must be 
located and available in the source documentation. 
6.3.4 
Electrocardiogram (ECG) 
A standard 12-lead ECG for all subjects will be performed at Screening and at the subsequent 
visits specified in the schedule of study procedures (Section 6.1.1). Original ECGs with interval 
printouts and rhythm strip run at 25 mm/sec must be provided as source documentation. 
Automatically calculated QT and QTc intervals will be reviewed and checked for gross 
inaccuracies by the Investigator or designated ECG reviewer. If the automatically calculated QT 
or QTc intervals are greater than 480 msec, or if either has increased by 50 msec or more over 
the baseline value, it will be manually over-read by the Investigator or designated ECG reviewer. 
The ECG parameters that will be assessed include heart rate, PR interval, QRS interval, and QT 
interval. If QT or QTc interval prolongation exceeding these limits is verified during treatment, 
the subject’s medical background should be examined closely for risk factors that may have 
contributed to the event, including genotyping for hereditary long QT syndromes, if appropriate. 
Any sign of arrhythmia should be noted. During treatment, any indication of QT prolongation or 
Torsade de Pointes, a polymorphic ventricular tachyarrhythmia that appears on the ECG as 
continuous twisting of the vector of the QRS complex around the isoelectric baseline, must be 
recorded as an adverse event and reported to the Medical Monitor. 
The decision to continue the treatment of any subject with prolonged QT or QTc interval must be 
discussed and agreed upon by the Investigator and the Medical Monitor. All such subjects, 
including subjects with cardiac arrhythmias, should be monitored closely. If appropriate, ECG 
monitoring should be performed until the QT and QTc interval and waveform morphology have 
returned to normal. If the prolongation or abnormal rhythm persists, the Medical Monitor must 
be contacted. 
6.3.5 
Clinical Laboratory Evaluations 
Blood and urine samples will be collected and analyzed or tested, according to the standard 
operating procedure (SOP) of the testing facility, for the following: 


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Hematology 
Chemistry 
• Hemoglobin 
• Hematocrit 
• Total and differential leukocyte count 
• Red blood cell count (with indices) 
• Platelet count 
• Blood Urea Nitrogen (BUN)/urea 
• Bilirubin (total and direct) 
• Uric acid 
• Alkaline phosphatase 
• Aspartate aminotransferase (AST) 
• Alanine aminotransferase (ALT) 
• Albumin 
• Sodium 
• Potassium 
• Chloride 
• Carbon dioxide/bicarbonate 
• Calcium 
• Phosphorus (inorganic)/phosphate 
• Total protein 
• Glucose 
• Lactate dehydrogenase (LDH) 
• Creatinine 
• Creatine kinase (CK)** 
• Gamma-glutamyl transferase (GGT) 
• Lipid panel (total cholesterol, LDL, HDL and 
VLDL fractions and triglycerides)*** 
Urinalysis 
• pH 
• Specific gravity 
• Protein* 
• Glucose 
• Ketones 
• Bilirubin 
• Blood* 
• Nitrite* 
• Urobilinogen 
• Leukocyte esterase* 
Serology 
Other Tests 
• HBsAg 
• HBcAb 
• HIV 
• HCV 
• Follicle stimulating hormone (FSH) for 
postmenopausal females only**** 
• QuantiFERON-TB 
• Serum/urine pregnancy test (for female subjects 
only) 
* If urinalysis is positive for protein, blood, nitrite and/or leukocyte esterase, a microscopic examination 
(for red blood cells, white blood cells, bacteria, casts, and epithelial cells) will be performed. 
** CK-MB reflex test (or Troponin 1) may be performed if CK is elevated. 
***Fasting; refer to schedule of study procedures (Section 6.1.1) for fasting sample collection timepoints. 
****If needed. 
The Investigator must review the screening visit laboratory results for all the measured analytes 
for each subject prior to Week 0/Day 1. The subject must not be enrolled for treatment if any of 
the laboratory values meet the exclusion criteria or in the opinion of the Investigator, might place 
the subject at unacceptable risk for participation in this study. 
Subjects who would not qualify to participate in the study due to a screening laboratory value 
abnormality can repeat the test once within the original screening time window without resulting 
in screen failure, if the Investigator believes there is a reasonable possibility that the subject 
would be eligible if re-tested. 


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All subjects with laboratory tests containing clinically significant abnormal values are to be 
followed regularly until the values return to normal ranges; until a valid reason, other than study 
drug-related AE, is identified; or until further follow-up is deemed medically unnecessary. 
6.3.6 
Stool Evaluation 
6.3.5.1 
Stool Culture 
A stool PCR or culture (per central laboratory or local laboratory availability) is to be performed 
at the screening visit only and can be performed centrally or locally at the Investigator’s 
discretion. Subjects will be provided with instructions for stool sample collection at home and 
will be required to submit the stool sample to the site for testing. Ova and parasite examination, 
if applicable, should be performed based on local guidelines. 
6.3.5.2 
Screening for Clostridium Difficile 
Highly sensitive screening tests, with high negative predictive value, should be employed in 
evaluating subjects for eligibility for the study. The detection of C. difficile by toxigenic stool 
culture [stool culture followed by detection of toxin] is considered the gold standard for the 
diagnosis of the colonization or infection with pathogenic C. difficile. Comparable 
sensitivity may be achieved by direct testing of stool via point of use rapid membrane 
enzyme immunoassay card for both C. difficile toxin A and B and/or glutamate 
dehydrogenase (GDH) antigen on a card. Use of the card for point of care screening is 
encouraged where permitted by local regulation. Molecular techniques such as polymerase 
chain reaction (PCR) for detection of toxin RNA are also acceptable alternatives.  
Subjects who are positive at Screening Visit can be retested after the completion of a full course 
of treatment for C. difficile infection. 
Refer to the Central Laboratory Manual for further guidance and instruction for C. difficile 
screening if sent for central testing. If using the central lab, as the C. difficile PCR may be the 
screening test, a positive PCR test result with a negative toxin result may reflect infection or 
colonization, and the Investigator should decide whether PCR positivity reflects infection, in 
which case, treatment should be administered. Sites should follow the guidance and instructions 
from the local laboratory if tested locally. 
6.4 
Efficacy Assessment Description 
The SES-CD will be used to evaluate disease activity for the primary endpoint. The SES-CD and 
CDAI scores will be used to evaluate disease activity for the secondary endpoints. The SES-CD 
is a validated endoscopic score that is used to describe ileocolonoscopic findings in CD. SES-CD 
assesses the size of mucosal ulcers, the ulcerative surface, the endoscopic extension, and the 
presence of stenosis (Daperno 2004, Moskovitz 2007). 
For the current study, the following definitions will apply:  


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• Endoscopic Improvement – a decrease in SES-CD of ≥ 50% from Baseline 
• Clinical Remission – CDAI < 150 
• Clinical Response – a reduction in CDAI ≥ 100 points from Baseline 
• Biomarker and Clinical Composite Improvement – a decrease in hsCRP or fecal 
calprotectin ≥ 50% from Baseline and reduction in CDAI ≥ 100 points from Baseline 
6.4.1 
Ileocolonoscopy with Biopsy 
6.4.1.1 
Ileocolonoscopy and SES-CD Score 
An ileocolonoscopy with biopsy should be performed during Screening and Visit Week 12/ET 
and Week 50/ET and annually thereafter with whatever cancer surveillance technique is 
recommended as per local guidelines if subject has colonic involvement. The endoscopy during 
Screening should be performed within 28-10 days of Week 0/Day 1 Visit. The bowel preparation 
should be conducted as per local routine. 
While the assessment by the Central Reader will be used to derive the SES-CD score for study 
eligibility, the Investigator should also determine the SES-CD score locally. The ileocolonoscopy 
report should be filed in the subject’s chart. The findings of the ileocolonoscopy, including local 
grading of SES-CD score should be completed at the end of the procedure. 
The endoscopic variables will be evaluated in 5 predefined ileocolonic segments: 
• Ileum - include the full extent for which it is examined. Do not include the ileocecal 
valve or an ileocolonic anastomosis 
• Right colon - include the ileocecal valve, the cecum, and the ascending colon to the 
hepatic flexure 
• Transverse colon - between the hepatic and the splenic flexures 
• Descending colon - from the splenic flexure to the rectosigmoid junction 
• Rectum - distal to the rectosigmoid junction 
The 4 endoscopic variables (each to be scored from 0 to 3 points) to be evaluated are (see 
Appendix 16.1): 
• Ulcers - scored according to size (diameter 0.1 - 0.5 cm, 0.5 - 2 cm, or > 2 cm) 
• Proportion of the surface covered by ulcers according to extent (< 10%, 10 - 30%, or > 30%) 
• Proportion of affected surface with any other lesions according to extent (< 50%, 50 - 75%, 
or > 75%) 
• Stenosis (single or multiple, and whether the colonoscopy could pass through the narrow 
lumen) 


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A study specific video capture kit, which includes the Endoscopy Video Instructions Manual and 
other Quick Reference materials, and a detailed Biopsy Procedural Manual will be provided by 
the Central Reader vendor. 
6.4.1.2 
Biopsy 
During each of the ileocolonoscopies, at least 3 biopsy samples should be obtained from each of 
the 5 ileocolonic segments (rectum, descending colon/sigmoid, transverse colon, ascending 
colon, or ileum). The biopsies should be collected in the vicinity of any lesion or ulcerated area, 
at the edge of the ulcerated area if possible. If no lesions were present in the segment, biopsies 
should be collected from random sites within the segment. Two (2) of the 3 biopsy specimens 
from each segment should be placed into the formalin-fixed bottles pre-filled with 10% neutral 
buffered formalin and the 3rd of the biopsy specimens from each segment should be placed into 
the RNAlater bottles pre-filled with RNAlater solution. 
All biopsy samples will be sent to the central laboratory for the study and processed by a 
designated central pathology site for histological scoring. 
6.4.2 
Crohn’s Disease Activity Index (CDAI) Score 
Subjects will use an eDiary in order to record their CD symptoms on a daily basis. eDiary data 
will be assessed at the clinic from screening until the end of PRA023 treatment. Subjects will 
record the following information: 
• Number of soft/liquid stools each day 
• Daily rating of abdominal pain 
• Daily rating of general well-being 
• Daily fever 
• Daily use of anti-diarrheal medications 
The information extracted will be used for calculation of CDAI score taking into account the 
data recorded over the last 7 days prior to each study visit. If there are less than 7 available days 
reported prior to the study visit, the average will be taken from the limited available data unless 
there is no eDiary/paper diary data reported within 7 days. Note that if there is less than 5 days of 
eDiary/paper diary data prior to the baseline, then the subject cannot be enrolled into the study. 
In case where there are not at least 5 evaluable days of symptoms available in the prior 7 days, a 
look back to 10 days prior to the visit is acceptable, although not preferred. Note that symptoms 
on days of the bowel preparation, endoscopy, and 2 days post endoscopy are not considered 
evaluable.   
In order to encourage consistent diary recording, subjects should enter diary data continuously 
throughout the study. Instructions for completing the eDiary/paper diary will be provided to 
subjects at screening and reviewed at subsequent visits. 


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All other elements of the CDAI not captured in the eDiary/paper diary (Appendix 16.2) should 
be assessed by the site personnel at the time of the visit. The eDiaries or paper diaries and CDAI 
score worksheets will be source documents for this study. 
6.4.3 
Perianal Disease Activity Index (PDAI) 
The PDAI will be used to evaluate severity of perianal disease. The PDAI incorporates 5 items: 
discharge, pain, restriction of sexual activity, type of perianal disease, and degree of induration. 
Each category is graded on a 5-point Likert scale ranging from no symptoms (score of 0) to 
severe symptoms (score of 4). Scores can range from 0 - 20, with higher scores indicating more 
severe perianal disease (Irvine 1995). See Appendix 16.3 for additional details. 
6.4.4 
Fistula Drainage Assessment 
Severity of enterocutaneous and perianal disease will be assessed using the Fistula Drainage 
Assessment. Fistulas will be classified as either (1) open and actively draining or (2) closed, 
based on the Investigator’s physical evaluation of the subject: a fistula is open if the Investigator 
can express purulent material from the fistula with the application of gentle pressure (Present 
1999). Improvement is defined as a reduction ≥50% from baseline in the number of draining 
fistulas observed at 2 or more consecutive visits (at least 21 days apart). Remission is defined as 
the absence of any draining fistulas at 2 consecutive visits (at least 21 days apart). 
6.4.5 
Quality of Life (QoL) 
Subjects will be asked to complete the Inflammatory Bowel Disease Questionnaire (IBDQ) at 
visits specified in Section 6.1.1 to measure disease specific quality of life (QoL). The 
questionnaires completed by subjects will serve as the source documents for this study. 
The IBDQ is a self-administered 32-item questionnaire that evaluates QoL across 4 dimensions: 
(1) Bowel – symptoms related to primary bowel disturbance, (2) Systemic symptoms, 
(3) Emotional function, and (4) Social function. The response to each question can range from 
1 to 7, with 1 indicating severe problem and 7 indicating normal health. The total IBDQ is 
computed as the sum of the responses to the individual IBDQ questions. The total score can 
range between 32 to 224 with higher scores indicating a better QoL (Guyatt 1989). 
6.5 
Pharmacodynamics 
Serum biomarkers will be measured to determine the expression of pro-inflammatory cytokines 
and other soluble biomarkers that may correlate with CD disease activity. Blood samples for PD 
are to be drawn at the time points specified in the protocol (see Section 6.1.1). The actual date 
and time (24-hour clock time) of each sample will be recorded. Instructions for the handling of 
the PD samples will be provided in the Laboratory Manual. 
Evaluations of pharmacodynamics may include, but are not limited to, the following: 


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Cytokines 
Stool 
• Soluble TL1A 
• Fecal calprotectin 
 
Biomarkers  
 
• Endoscopic healing index (EHI) 
• hsCRP 
• mRNA 
 
Any residual serum, following completion of analysis, will be stored frozen at -20°C or colder at 
the testing facility. Additional cytokines or other biomarkers may also be evaluated based on 
emerging data from the study for up to 5 years after the conclusion of the study. 
6.6 
Pharmacokinetics  
Blood samples for the measurement of PRA023 concentration are to be drawn from each subject 
at the time points specified in the protocol (see Section 6.1.1). Blood samples for PK analysis of 
PRA023 concentrations will be analyzed using a validated assay method by or under the 
supervision of the Sponsor. The PK blood samples will be obtained according to the study 
flowchart. The actual date and time (24-hour clock time) of each sample will be recorded. 
Instructions for the handling of the PK samples will be provided in the Laboratory Manual. 
Changes in the timing or addition of time points for any planned study assessments must be 
documented and approved by the relevant study team member and then archived in the Sponsor 
and study center study files, but will not constitute a protocol amendment. The IRB/IEC will be 
informed of any safety issues that require alteration of the safety monitoring scheme or 
amendment of the ICF. PK analysis will be performed as outlined in the PK section of the 
Statistical Analysis Plan (SAP). 
6.7 
Immunogenicity (Anti-Drug Antibody) 
Antibodies to PRA023 will be evaluated in blood samples collected from all subjects at the time 
points specified in the protocol (see Section 6.1.1). The detection and characterization of 
antibodies to PRA023 will be performed using a validated assay method by the Sponsor or 
Sponsor’s designee. Instructions for the handling of ADA samples will be provided in the 
Laboratory Manual. 
Blood samples will be screened for antibodies binding to PRA023 and the titer of confirmed 
positive samples will be reported. If confirmed positive, antibodies may be further characterized 
and/or evaluated for their ability to neutralize the activity of PRA023. Other analyses may be 
performed to verify the stability of antibodies to PRA023 and/or further characterize the 
immunogenicity of PRA023. 


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6.8 
Pharmacogenomics 
Genetic variation may impact a subject’s response to study treatment, susceptibility to, and 
severity and progression of disease. Variable response to study treatment may be due to genetic 
determinants that impact drug absorption, distribution, metabolism, and excretion; mechanism of 
action of the drug; disease etiology; and/or molecular subtype of the disease being treated. 
Therefore, a 4 mL whole blood and buccal (cheek) swab samples for DNA isolation will be 
collected from subjects at the Screening Visit for an assessment of pharmacogenomics (i.e., CDx 
assessment). In the event of DNA extraction failure, a replacement genetic blood and/or buccal 
sample may be requested from the subject during the study. 
After collection, the samples are to be shipped to the Sponsor and/or the central laboratory. 
Instructions for the handling of pharmacogenomic samples will be provided in the Laboratory 
Manual. The DNA samples will be stored in a secure storage space with adequate measures to 
protect confidentiality. Each stored sample will be identified only by its barcode number and will 
otherwise not be individually identifiable. 
6.9 
Potential Future Research 
Blood, biopsy, and DNA samples will be stored for up to 5 years after study completion 
(potential for storage and duration of storage may depend on local guidelines), after which all the 
samples will be destroyed.  Blood and biopsy samples may be tested for levels of biomarker and 
other pharmacodynamic markers.  DNA samples may be used in the future for various 
evaluations, including, but not limited to, the potential association between genotype and drug 
absorption, distribution, metabolism, and excretion; mechanism of action of the drug; disease 
etiology; and/or molecular subtype of the disease. 


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7 
ADVERSE EVENTS AND SERIOUS ADVERSE EVENTS 
The following definitions of terms are guided by the International Conference on Harmonisation 
and the U.S. Code of Federal Regulations [21 CFR 312.32] and are included herein. 
An adverse event (AE) is any untoward medical occurrence associated with the use of a drug in 
humans, whether or not considered drug related. 
AEs include, but are not limited to: 
• Any symptom or condition not previously reported by the subject (medical history). 
• An exacerbation of a pre-existing symptom or condition. 
• A significant increase in frequency or intensity of a pre-existing episodic event or 
condition. 
• A drug interaction. 
• A condition first detected or diagnosed after study drug administration even though it 
may have been present prior to the start of the study. 
An AE does not include: 
• Medical or surgical procedures (e.g., surgery, endoscopy, tooth extraction, or blood 
transfusion); the condition that leads to the procedure is an adverse event (e.g., bleeding 
esophageal varices, dental caries). 
• Overdose of either study drug or concurrent medication without any clinical signs or 
symptoms. 
All identified AEs after signing of informed consent until 84 days after last study drug dose must 
be recorded and described on the appropriate non-serious or serious AE page of the eCRF. If 
known, the diagnosis of the underlying illness or disorder should be recorded, rather than 
individual symptoms. 
Suspected adverse reaction means any AE for which there is a reasonable possibility that the 
drug caused the AE. For the purposes of safety reporting, ‘reasonable possibility’ means there is 
evidence to suggest a causal relationship between the drug and the AE. A suspected adverse 
reaction implies a lesser degree of certainty about causality than adverse reaction, which means 
any AE caused by a drug. 
An adverse reaction is any AE caused by a drug. Adverse reactions are a subset of all suspected 
adverse reactions for which there is reason to conclude that the drug caused the event. 
An AE or suspected adverse reaction is considered “serious” if, in the view of either the 
Investigator or sponsor, it results in any of the following outcomes: 
• Death 
• A life-threatening adverse event 


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• Inpatient hospitalization or prolongation of existing hospitalization 
• A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• A congenital anomaly/birth defect 
• Disability/incapacity that is persistent and significant 
Important medical events that may not result in death, be life-threatening, or require hospitalization 
may be considered serious when, based upon appropriate medical judgment, they may jeopardize 
the subject and may require medical or surgical intervention to prevent one of the outcomes listed 
in this definition. Examples of such medical events include allergic bronchospasm requiring 
intensive treatment in an emergency room or at home, blood dyscrasias or convulsions that do 
not result in inpatient hospitalization, or the development of drug dependency or drug abuse. 
An AE or suspected adverse reaction is considered “life-threatening” if, in the view of either the 
Investigator or sponsor, its occurrence places the subject or subject at immediate risk of death. It 
does not include an AE or suspected adverse reaction that, had it occurred in a more severe form, 
might have caused death. 
An AE or suspected adverse reaction is considered ‘unexpected’ if it is not listed in the 
Investigator’s Brochure or is not listed at the specificity or severity that has been observed; or, if 
an Investigator’s Brochure is not required or available, is not consistent with the risk information 
described in the general investigational plan or elsewhere in the current application. For example, 
under this definition, hepatic necrosis would be unexpected (by virtue of greater severity) if the 
Investigator’s Brochure referred only to elevated hepatic enzymes or hepatitis. Similarly, cerebral 
thromboembolism and cerebral vasculitis would be unexpected (by virtue of greater specificity) 
if the Investigator’s Brochure listed only cerebral vascular accidents. ‘Unexpected,’ as used in 
this definition, also refers to AEs or suspected adverse reactions that are mentioned in the 
Investigator’s Brochure as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug, but are not specifically mentioned as occurring with the 
particular drug under investigation. 
The Sponsor will determine the expectedness of serious adverse reactions and report all suspected, 
unexpected serious adverse reactions (SUSARs) according to statutory requirements. 
7.1 
Pre-Treatment-Emergent Events 
Prometheus considers AEs that occur between the time the subject signs the informed consent 
form for the study and the time when that subject is first administered the study drug as “pre-
treatment-emergent” AEs. Any pre-treatment-emergent event will be recorded as an AE but will 
be clearly documented as pre-treatment emergent event in the data listings. 


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7.2 
Laboratory Abnormalities as Adverse Events 
Many laboratory abnormalities observed during the course of a study will be included under a 
reported AE describing a clinical syndrome (e.g., elevated BUN and creatinine in the setting of 
an AE of renal failure, or decreased hemoglobin in a case of bleeding esophageal varices). In 
such cases, the laboratory abnormality itself (e.g., elevated creatinine in a setting of renal failure) 
does not need to be recorded as an AE. However, isolated laboratory abnormalities should be 
reported as AEs if they are considered to be clinically significant by the Investigator. Criteria for 
a “clinically significant” laboratory abnormality are: 
a) A laboratory abnormality that leads to a dose-limiting toxicity (e.g., an abnormality that 
results in study drug dose reduction, suspension or discontinuation), or 
b) A laboratory abnormality that results in any therapeutic intervention (i.e., concomitant 
medication or therapy), or 
c) Other laboratory abnormality judged by the Investigator to be of any particular clinical 
concern (e.g., significant fall in hemoglobin not requiring transfusion) 
For laboratory abnormalities that do not meet the above criteria but are outside of normal range 
(e.g., < or > normal reference range), the Investigator should indicate whether the value is 
clinically significant (CS) or not clinically significant (NCS) for the subject. 
7.3 
Grading/Severity of Adverse Events 
The Investigator must define the severity of each AE using the NCI’s CTCAE Version 5.0. A 
severity category of mild, moderate, severe, life threatening, or death as defined in Table 6 must 
be entered on the AE eCRF. The Investigator will consider the range of the possible severity of 
the event and identify the severity that is the most appropriate according to her/his medical 
judgment. 
 
Severity of Adverse Events 
Grade 
Clinical Description of Severity 
1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not indicated. 
2 
Moderate; minimal, local or noninvasive intervention indicated; limiting age-appropriate instrumental ADL*. 
3 
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of 
hospitalization indicated; disabling; limiting self care ADL**. 
Note: An experience may be severe but may not be serious, e.g., severe headache). 
4 
Life-threatening consequences; urgent intervention indicated. 
5 
Death related to AE. 
A Semi-colon indicates ‘or’ within the description of the grade. 
Note: Activities of Daily Living (ADL): 
*Instrumental ADL refer to preparing meals, shopping for groceries or clothes, using the telephone, managing money, etc. 
**Self care ADL refer to bathing, dressing and undressing, feeding self, using the toilet, taking medications, and not bedridden. 


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7.4 
Relationship of Adverse Events 
7.4.1 
Relationship of Adverse Events to Study Drug Administration 
The Investigator will determine if there is a reasonable causal relationship between the study drug 
and an AE or not. The Investigator will use her/his best medical judgment and consider all relevant 
factors (e.g., temporal relationship, location of the event, the subject’s relevant medical history, 
concomitant therapies, and concurrent conditions) to determine the relationship of the AE to the 
study drug. The Investigator will define the relationship of an AE to the study drug by selecting 
one of the following categories: 
Related: 
There is a reasonable possibility that there is a causal relationship between the 
study drug and the AE. 
Not Related: There is not a reasonable possibility that there is a causal relationship between 
the study drug and the AE. 
The term “reasonable causal relationship” means there are facts or arguments to suggest a causal 
relationship (International Conference on Harmonisation (ICH) E2A). 
7.4.2 
Relationship of Adverse Events to Study Procedures 
Relationship (causality) to study procedures should be determined for all pre-treatment-emergent 
events and AEs. The relationship should be assessed as Related if the Investigator considers that 
there is reasonable possibility that an event is due to a study procedure. Otherwise, the 
relationship should be assessed as Not Related. 
7.5 
Recording and Reporting of Adverse Events 
7.5.1 
Recording Adverse Events 
All AEs will be recorded in the appropriate section of the eCRF. Subjects withdrawn from the 
study due to AEs will be followed by the Investigator until the outcome is determined and, when 
appropriate, additional written reports and documentation will be provided. The Investigator 
should attempt, if possible, to establish a diagnosis based on the presenting signs and symptoms. 
If the AE meets the definition of an SAE, or if the Investigator becomes aware of an unexpected 
AE event that places the subject at risk, or if there is a pregnancy at any time after the study drug 
administration up to the end of the study follow-up period, the event must be documented and 
reported. 


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7.5.2 
Investigator Reporting of a Serious Adverse Event 
In agreeing to the provisions of this protocol, the Investigator accepts all legal responsibilities for 
prompt notification of serious adverse events (SAEs) to 
 The 
Investigator (or designee) is required to complete the SAE page in the eCRF enabling 
transmission to 
 using the electronic data capture (EDC) system. In the event 
EDC transmission is not possible, (e.g., there are access or system problems), then the 
Investigator (or designee) must report the SAE to 
 by emailing or 
faxing a completed paper SAE form to: 
Fax: 
 
Email: 
 
All SAEs must be reported to 
 within 24 hours after the Investigator 
recognizes/classifies the event as a SAE.  
The initial SAE report should include at a minimum: subject number, a narrative description of 
the event, and an assessment by the Investigator of the intensity of the event and relationship of 
the event to study drug. The initial SAE report received from the site should be as complete as 
possible. A complete follow-up SAE report must be submitted when information not available at 
the time of the initial report becomes available. The Sponsor (or designee) may request SAE 
follow-up information. Copies of any relevant data from the hospital notes (e.g., ECGs, laboratory 
tests, discharge summary, postmortem results) should be sent to the addressee, if requested. 
The Investigator must receive acknowledgement by 
 that the information 
about the SAE has been received. In the event that the Sponsor or designee permits an alternate 
delegate, the Investigator and staff will be notified and provided the alternate’s contact information. 
The Investigator is responsible for continuing to report to the 
 any new or 
relevant follow-up information that he/she learns about the SAE. 
7.5.3 
Investigator Reporting of a Pregnancy 
Investigator (or designee) should notify 
 of all pregnancies occurring 
after start of study drug and 12 weeks after last dose in enrolled female subjects or the female 
partner of male subjects. 
If a pregnancy occurs, a Pregnancy Report Form should be completed by the Investigator (or 
designee) and submitted to 
 via fax to
, or by email to 
.com within 24 hours after learning of the pregnancy. 
Female subjects who become pregnant must discontinue study drug, and the Investigator should 
evaluate the risks and benefits of continuing with the study after discussing the risks of the 
pregnancy and possible effects on the fetus with the subject. A determination regarding study 
drug discontinuation will be made for male subjects with a partner pregnancy based on risks 
involved by the Investigator and/or Sponsor. 
PPD
PPD
PPD
PPD
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI


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Pregnancy is not regarded as an AE unless there is a suspicion that study drug may have interfered 
with the effectiveness of a contraceptive medication. 
The outcome of all pregnancies (spontaneous miscarriage, elective termination, normal birth, or 
congenital abnormality) must be followed up and documented even if the subject was 
discontinued from the study. Female partners of male subjects are asked to sign a separate 
partner pregnancy informed consent form in order to collect pertinent personal and medical 
information regarding the status and outcome of the pregnancy. 
All reports of congenital abnormalities/birth defects are considered SAEs and should be reported 
per Section 7.5.2. Spontaneous miscarriages should also be reported and handled as SAEs. 
Elective abortions without complications should not be handled as AEs unless they were 
therapeutic abortions. The medical reason (e.g., fetal disease) for therapeutic abortion will be 
reported as an SAE. 
7.6 
Additional Investigator Responsibilities for Serious Adverse Events 
The Investigator and supporting personnel responsible for subject care should discuss with the 
Medical Monitor any need for supplemental investigations of SAEs. The results of these 
additional assessments conducted must be reported to the Sponsor. If a subject dies during 
participation in the study and a post-mortem examination is performed, a copy of the autopsy 
report must be submitted to Sponsor or designee. 
7.7 
Post-Study Follow-Up of Adverse Events 
All AEs, including a worsening of clinically significant laboratory values or physical 
examination findings compared with baseline values, must be followed until the event resolves, 
the condition stabilizes, the event is otherwise explained, or the subject is lost to follow-up. 
AEs ongoing at the final visit will be followed for as long as necessary to adequately evaluate the 
subject’s safety or until the event stabilizes or resolves. If resolved, a resolution date should be 
documented on the eCRF or reported to Sponsor or designee if the eCRFs have been collected. 
The Investigator is responsible to ensure that follow-up includes any supplemental investigations 
as may be indicated to elucidate the nature and/or causality of the AE. This may include 
additional laboratory tests or investigations, histopathological examinations, or consultation with 
other health care professionals as is practical. 
7.8 
Notification of Post-Study Serious Adverse Events 
Investigators are not obligated to actively follow subjects after the completion of the study. 
However, if the Investigator becomes aware of an SAE, he/she should notify 
 
 if such events are attributable to the study drug. The notification to 
 
 of a post-study SAE by the Investigator should occur within 24 hours of becoming aware 
of the SAE. 
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7.9 
IRB/IEC Notification of Serious Adverse Events 
The Investigator is responsible for promptly notifying her/his IRB/IEC of all SAEs, including 
any follow-up information, occurring at her/his site and any SAE regulatory report, including 
any follow-up reports that he/she receives from the Sponsor or designee. 
7.10 
Health Authority Safety Reports 
Prometheus or its representatives will submit a safety report to appropriate regulatory agencies, 
for all suspected unexpected serious adverse reactions (SUSARs) and any other applicable SAEs 
to regulatory authorities in accordance with national regulations in the countries where the study 
is conducted. SUSARs will be submitted to the regulatory authorities as expedited report within 
7 days for fatal and life-threatening events and 15 days for other serious events, unless otherwise 
required by national regulations. Prometheus or its representatives will also prepare and distribute 
an expedited report for other safety issues which might alter the current benefit-risk assessment 
of the study drug or impact the overall conduct of the trial. Prometheus or its representatives will 
send copies of each safety report submitted to the regulatory agencies to the Investigators who are 
actively participating in Prometheus-sponsored clinical studies. Safety reports must be submitted 
to the appropriate IRB/IEC according to local regulations and guidelines. Documentation of the 
submission to the IRB/IEC must be retained for each safety report. 
7.11 
Data Monitoring Committee (DMC) 
Prometheus will establish an independent DMC for PRA023 to oversee the benefit-risk profile in 
IBD and safety across the entire program. The DMC will review safety data at periodic intervals 
from this and all other PRA023 studies conducted by Prometheus Biosciences. Members of the 
DMC will not be allowed to participate as Investigators in any of the PRA023 studies. 
A charter, which will include a detailed description of the scope and the extent of its responsibilities 
and procedures, will be implemented prior to any data review. The charter will specify how the 
data will be provided to the committee member (e.g., blinded, unblinded, grouped or not, etc.) 
for review. These documents (charter, open and closed meeting minutes, etc.) will be considered 
part of the study documentation, but not of this protocol. The DMC will review data within its 
general remit to oversee subject safety for the PR200 program and provide recommendations and 
guidance to the Sponsor in accordance with the procedures stated in its charter. 
A formal DMC monitoring meeting will occur prior to the commencement of this study, where 
the DMC will assess all available safety data from the normal healthy volunteer study (Study 
PR200-101). This study will commence following the demonstration of acceptable safety profile 
of PRA023 at a dose of ≥ 500 mg in multiple ascending dose study in Study PR200-101. 
All Investigators, responsible IRB/IECs, and applicable regulatory agencies will be informed of 
any decisions made by Prometheus Biosciences based on recommendations from the DMC 
relating to subject safety and affect the conduct of this study. The Investigators will inform the 
subjects of such actions and the protocol and ICF will be revised, as appropriate. 


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8 
ASSESSMENT OF STUDY VARIABLES 
The data will be analyzed by Prometheus or an official designee (e.g., a contract research 
organization [CRO]). 
8.1 
Randomization 
This is an open-label study where all subjects will receive PRA023. Eligible subjects will be 
assigned a subject randomization number by the IRT system at Week 0/Day 1 upon confirmation 
of study eligibility as a means to track the number of eligible subjects enrolled in the study. 
Subjects who are re-randomized in OLE will retain their original subject numbers. 
8.2 
Justification of Sample Size 
The planned sample size is 50 subjects, which will provide a statistical power of 80% to test 
against the null hypothesis of endoscopic improvement rate of 12%, at 1-sided significance level 
of 0.025, assuming the endoscopic improvement rate for PRA023 is 27%.  
The null hypothesis of an endoscopic improvement (decrease in SES-CD ≥ 50%) rate of 12% is 
based on a meta-analysis estimate of the upper limit of 95% CI of the observed placebo rate 
(95% CI) of 9.5% (7.1, 11.9) from multiple modern-era CD clinical trials with centrally read 
endoscopy and similar eligibility criteria (Table 7). 
 
Placebo Endoscopic Response Rates in Recent CD Clinical Trials 
Clinical Trial 
N 
Placebo Endoscopic Response Rate (%) 
Feagan et al. 2017 
39 
13 
Vermeire et al. 2017 
44 
14 
Sands et al. 2019 
64 
10.9 
Selinger et al. 2018 
59 
3.4 
Advance Study 2021 
175 
12 
Motivate Study 2021 
187 
11 
Average 
10.7 
Sample-size Weighted Average 
568 
9.5 
 
8.3 
Evaluation of Safety Variables 
Data will be summarized with respect to safety observations. Monitoring of AEs, physical 
examinations, vital signs, ECGs, safety and tolerability monitoring evaluations, clinical 
laboratory evaluations, and special procedures are detailed in Section 6.3. 


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All available safety data for all randomized subjects who receive at least one dose of PRA023 
will be included in the safety analysis, which will be primarily descriptive. 
The safety variables will be: 
• Hematology, chemistry, and urinalysis 
• Vital signs 
• ECG parameters 
• Physical examination 
• AEs and SAEs 
o AEs of special interest: infections, acute infusion reaction (within 1 hour of completion 
of infusion), and peri-infusion reaction (within 24 hours of completion of infusion) 
o AEs in subjects who are ADA positive  


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9 
STATISTICAL METHODOLOGY 
This section describes the statistical analysis as it is foreseen at the time of planning the trial. 
Statistical methods will be further detailed in the SAP. The SAP will provide details about 
methods of analysis and the specific planned analyses, and will be prepared and approved by 
Prometheus Biosciences and its designees before study database lock. 
Any deviations from the analysis plan, and the reasons for such deviations, and all alternative or 
additional statistical analyses that may be performed will be justified in the clinical study report. 
No formal statistical evaluation will be applied to the safety and tolerability variables. However, 
a clinical interpretation will be made based on the side effect profile to judge the safety of 
PRA023. All individual data as well as results of statistical analyses will be presented in 
individual subject data listings and statistical summary tables. In general, continuous variables 
will be summarized using the following standard descriptive summary statistics: number of 
observations, arithmetic mean, standard deviation (SD), coefficient of variation (CV), minimum, 
median, and maximum. The geometric mean (GM) will be reported for PK and PD variables 
where appropriate. Categorical data will be summarized as number and percentage of subjects. 
Shift tables will be provided, where appropriate.  
9.1 
Analysis Populations 
9.1.1 
Safety Analysis Set (SAS) Population 
All subjects who received at least one dose of the study drug will be included in the safety 
evaluations. 
9.1.2 
Full Analysis Set (FAS) Population 
The FAS population will be a subset of the Safety population and will include all subjects who 
have been treated with PRA023 with Baseline SES-CD scores. 
9.2 
Statistical Analyses 
9.2.1 
Demographics and Baseline Characteristics 
Demographic data characteristics (height, weight, age, sex, race, and ethnic origin) will be listed 
by subject and summarized by CDx status and for the overall study population.  
9.2.2 
Evaluation of Efficacy Parameters 
The primary efficacy endpoint, endoscopic improvement at Week 12, will be used to assess the 
efficacy of PRA023. The proportion of subjects in the per-protocol population with endoscopic 
improvement at Week 12 will be tested against the null hypothesis of 12%, an observed placebo 


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rate from multiple CD trials. Chi-square test will be used with a 1-sided significance level of 
0.025. If significant, the 1st secondary endpoint of proportion of subjects in FAS achieving 
clinical remission will be tested against the null hypothesis of clinical remission rate of 16% (an 
observed remission rate for the placebo treated patients from multiple CD trials (AbbVie 2021, 
Feagan 2017, Sands 2019, Selinger 2018, Vermeire 2017). 
The point estimates for the primary and secondary endpoints will be calculated along with 95% 
confidence interval for FAS and by CDx status (CDx+ or CDx-). 
9.2.3 
Evaluation of Pharmacodynamic Parameters 
The PD markers, circulating cytokine levels, will be summarized using descriptive statistics: N, 
mean, SD, min, max, median, coefficient of variation as a percent (CV %), and GM by CDx status. 
Any p-values that will be calculated according to the analysis plan will be interpreted in view of 
the exploratory nature of the study. 
9.2.4 
Evaluation of Immunogenicity 
The proportion of samples positive for ADA and the proportion of subjects with any sample 
positive for ADA will be summarized by dose, when appropriate, using descriptive statistics. The 
PRA023 concentrations from all subjects and subjects with no sample positive for ADA will be 
summarized to assess whether ADA has an impact on PRA023 exposure.  
9.2.5 
Evaluation of Exploratory Parameters 
Changes from baseline in exploratory PD parameters will be computed, as appropriate. All 
exploratory parameters will be summarized using descriptive statistics. Graphs of change from 
baseline will be presented, as appropriate. 
9.2.6 
Evaluation of Pharmacokinetic Parameters 
PK parameters will be computed, as appropriate, from the individual serum concentrations using 
a non-compartmental approach. All PK parameters will be summarized using descriptive 
statistics: N, mean, SD, min, max, median, CV %, and GM and GM CV%. Serum concentrations 
of PRA023 will be summarized.  
9.2.7 
Evaluation of Safety Parameters 
9.2.7.1 
Adverse Events and Adverse Events of Special Interest 
All AEs will be coded using most current version of Medical Dictionary for Regulatory 
Activities (MedDRA). All reported adverse events will be assigned to the SOC and PT according 
to MedDRA. The number and percentage of subjects reporting AEs (all, serious, related) will be 


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tabulated by overall and treatment. AEs will be summarized by SOC and PT. AEs will also be 
summarized by relationship to the study drug, seriousness, and severity. 
A treatment-emergent AE (TEAE) will be defined as an AE that began or worsened on or after 
the first treatment dose. AEs recorded prior to the first infusion of study treatment will be 
considered non-treatment-emergent. 
All reported AEs (treatment-emergent or not) will be listed. Only TEAEs will be summarized. 
AEs of special interest including infections, acute infusion reaction (within 1 hour of completion 
of infusion), and peri-infusion reaction (within 24 hours of completion of infusion) will be 
summarized based on a pre-specified MedDRA list. 
AEs occurring in subjects who are considered immunogenicity positive will also be summarized. 
9.2.7.2 
Medical History, Chest X-ray, ECGs and Physical Examination 
Medical history, chest x-ray, ECGs, and physical examination data will be listed by subject. All 
medical history will be coded using the most current version of MedDRA. Changes in ECGs and 
physical examination will be described in the text of the final study report. 
9.2.7.3 
Clinical Laboratory and Vital Signs 
All clinical laboratory results and vital signs measurements, and their change from baseline, will 
be summarized by time point of collection. 
A shift table describing out-of-normal range shifts will be provided for clinical laboratory results. 
9.2.7.4 
Previous and Concomitant Medication 
All previous and concomitant medication will be listed by subject. Prior and concomitant 
medications will be coded using the most current World Health Organization – Drug Dictionary 
(WHO-DD). 


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10 ETHICS AND REGULATORY REQUIREMENTS 
10.1 
General Requirements for Study Conduct 
The Investigator or designee is responsible for ensuring that the study is conducted in accordance 
with the clinical protocol and is in full compliance with regulatory requirements; the basic 
principles outlined in 21 CFR Parts 50, 54, 56, and 312; ICH-guidelines for Good Clinical 
Practice as published in the Federal Register on May 9, 1997; and the Declaration of Helsinki. 
The Investigator is also responsible for protecting the rights, safety, and welfare of subjects 
under the Investigator’s care and for the control of study device under investigation. 
The Investigator(s) (and sub investigators) will provide the Sponsor with her/his/their up-to-date 
scientific Curriculum Vitae (signed and dated) prior to start of the study and when new site 
personnel are added once the study commences. 
10.2 
Regulatory and Institutional Review Board Approval/ Independent 
Ethics Committee 
Regulatory approval will be obtained from the appropriate regulatory authority prior to initiation 
of the study protocol. 
The Investigator is responsible for obtaining IRB/IEC approval for the study protocol and the 
subject informed consent form. A copy of the dated approval letter from the IRB/IEC stating the 
study title, and/or study number must be provided to the Sponsor before the start of screening 
and release of supplies. A list of the names of the committee members will be obtained for the 
Sponsor’s and Investigator’s records. 
10.3 
Written Informed Consent 
The Investigator will inform the subject of the nature, risks, and purpose of the study. A written 
informed consent form will be provided to each subject describing the study information. The 
consent must be reviewed and approved by IRB/IEC before use in the study. Each volunteer 
must sign and date this form prior to their participation in the study. A signed original consent 
form for each subject will be kept on file at the clinical site. A copy of the signed consent will be 
provided to the subject. 
10.4 
Confidentiality 
The Investigator at each site and its designees, employees, and agents involved with the study 
will comply with relevant state and federal laws relating to confidentiality, privacy, and security 
of subject’s health information. Confidential data may be disclosed to the Investigator and 
employees, sponsor, IRB/IEC, FDA, or other authorized representatives during the course of the 


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study or when requested. Information will remain confidential and will not be used for any 
purpose other than the type of review requested. 
10.5 
Protocol Modification/Amendments 
Sponsor modifications made to the experimental design, study parameters, subject selection, or 
any other content in the protocol will be communicated with a protocol amendment(s) to the 
investigator, FDA and other regulatory agencies for review and approval. All amendments will 
require IRB/IEC review and approval prior to implementation.  
10.6 
Direct Access to Source Data/Documents 
Investigator will permit trial-related monitoring, audits, IRB/IEC review, and regulatory 
inspections by providing direct access to source data/documents. 


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11 DEFINITION OF END OF TRIAL 
11.1 
End of Trial in a Member State 
End of trial in a Member State of the European Union is defined as the time at which it is 
deemed that a sufficient number of subjects have been recruited and completed the study as 
stated in the regulatory application (i.e., clinical trial application [CTA]) and ethics application in 
the Member State. Poor recruitment (recruiting less than the anticipated number in the CTA) by a 
Member State is not a reason for premature termination but is considered a normal conclusion to 
the study in that Member State. 
11.2 
End of Trial in All Other Participating Countries 
End of trial in all other participating countries is defined as last subject last visit (LSLV). 
 


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12 DATA MANAGEMENT 
Data will be handled and processed according to CRO’s SOPs, which are written based on the 
principles of GCP. At all times, appropriate backup copies of the database and related software 
files will be maintained and the information will be appropriately protected from unauthorized 
access. 
The eCRF development will be based on the study protocol. All eCRF data, including laboratory 
data, will be included in an integrated database. At the end of the study when the database is 
deemed clean, the integrated database will be locked (i.e., all data entry, quality control, database 
edits, medical coding, SAE reconciliation complete). The data will then be processed, evaluated, 
and stored in anonymous form in accordance with applicable data protection regulations. 
eCRFs will be kept for each subject and will document all study data. The eCRFs must be 
completed for each subject to allow the progress and results of the study to be closely followed 
by the study monitor. 
The study monitor or designee will review the eCRFs for completeness and accuracy via Source 
Document Verification. Study written ICFs and all study specific logs will be verified for 
completeness, accuracy, and plausibility. 
12.1 
Coding of Adverse Events, Concomitant Medication, and Medical 
History 
After data entry, the AEs and medical history will be coded according to the MedDRA®. Where 
required, concomitant medication will be coded according to the WHO-DD. The versions of 
MedDRA® and WHO-DD used in the study will be specified in the data management plan (DMP). 


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13 DOCUMENTATION AND ADMINISTRATIVE CONSIDERATIONS 
13.1 
Recordkeeping 
All essential documents specific to the study (including study file, source documentation, copies 
of eCRF, etc.) should be retained by the Investigator until at least two years after the last approval 
of a marketing application in an ICH region and until there are no pending or contemplated 
marketing applications in an ICH region or at least 25 years have elapsed since completion of 
this clinical trial. These documents should be retained for a longer period if required by the 
applicable regulatory authority or if needed by the Sponsor. 
Every reasonable effort should be made by the Investigator to retain records enabling the follow 
up of subjects who have received study medication. The Investigator should notify the Sponsor 
and obtain approval prior to destroying any material retained from the study. 
13.2 
Disclosure of Data 
The Investigator agrees not to disclose data from this study without the prior written approval of 
the Sponsor. 
13.3 
Publication Policy 
It is intended that the results of the study may be published as scientific literature. Results may 
also be used in submissions to regulatory authorities. The following conditions are to protect 
commercial confidential materials (patents, etc.), not to restrict publication. 
All information concerning the product subsequently generated from this study (such as patent 
applications, formulae, manufacturing processes, basic scientific data, or formulation information 
supplied to the investigator by the Sponsor and not previously published) is considered 
confidential by and shall remain the sole property of the Sponsor. The Investigator agrees not to 
use it for other purposes without the Sponsor’s written consent. 
It is understood by the Investigator that the Sponsor will use the information developed in this 
clinical study in connection with the development of PRA023 and, therefore, may be disclosed as 
required to other Sponsor investigators or any appropriate international regulatory authorities. In 
order to allow for the use of information derived from this clinical study, the Investigator 
understands that he or she has an obligation to provide the Sponsor with complete test results and 
all data developed during this study. 
Prior to submitting the results of this study for publication or presentation, the Investigator will 
allow the Sponsor 60 days in which to review and comment upon the publication manuscript. In 
accordance with generally recognized principles of scientific collaboration, co authorship with 
any Sponsor personnel will be discussed and mutually agreed upon before submission of a 
manuscript to a publisher. The publication of study data may not be performed without the 
written prior approval of the Sponsor, and this approval shall not be unreasonably withheld. 


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During the period for review of a proposed publication from the Investigator, the Sponsor shall 
be entitled to make a reasoned request to the Investigator that publication be delayed for a period 
of up to 6 months from the date of first submission to the Sponsor in order to enable the Sponsor 
to take steps to protect its proprietary information, and the Investigator shall not unreasonably 
withhold consent to such a request. Any intended joint publication must precede any proposed 
individual publication. 


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14 QUALITY CONTROL AND QUALITY ASSURANCE 
The study monitor will maintain a close liaison with the investigational site to clarify any problems 
that may arise, and to ensure that the Investigator is following the protocol. This liaison may 
consist of personal visits before the study is initiated and at appropriate intervals during the study 
and will include communications via telephone, facsimile, email, and letter. During site monitoring 
visits, information recorded on the eCRFs will be verified against source documents. 
The Investigator agrees that Prometheus, its employees or agents, and regulatory health authorities 
will have the right from time to time, both during and after the course of this study, to audit and 
review medical records relating to this study. 
A statement will be obtained from each subject participating in the study permitting the release 
of his/her medical records as necessary for inspection by authorized personnel of Prometheus, 
the FDA, and/or other regulatory health authorities. 


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15 REFERENCES 
AbbVie, Risankizumab (SKYRIZI®) demonstrates significant improvements in clinical 
remission and endocopic response in two Phase 3 induction studies in patients with Crohn’s 
disease [Internet]. Illinois: AbbVie Inc.; 2021; 07 Jan [cited 2021 Feb 2]. Available from: 
https://news.abbvie.com/news/press-releases/risankizumab-skyrizi-demonstrates-significant-
improvements-in-clinical-remission-and-endoscopic-response-in-two-phase-3-induction-studies-
in-patients-with-crohns-disease.htm 
Ananthakrishnan AN, Kaplan GG, Ng SC. Changing Global Epidemiology of Inflammatory 
Bowel Diseases: Sustaining Health Care Delivery Into the 21st Century. Clin Gastroenterol 
Hepatol. 2020;18(6):1252-60. doi: 10.1016/j.cgh.2020.01.028. 
Bamias G, Kaltsa G, Siakavellas SI, Papaxoinis K, Zampeli E, Michopoulos S, Zouboulis-
Vafiadis I, Ladas SD. High intestinal and systemic levels of decoy receptor 3 (DcR3) and its 
ligand TL1A in active ulcerative colitis. Clin Immunol. 2010;137(2):242-9. 
doi: 10.1016/j.clim.2010.07.001. 
Bamias G, Martin C, 3rd, Marini M, Hoang S, Mishina M, Ross WG, Sachedina MA, Friel CM, 
Mize J, Bickston SJ, Pizarro TT, Wei P, Cominelli F. Expression, localization, and functional 
activity of TL1A, a novel Th1-polarizing cytokine in inflammatory bowel disease. J Immunol. 
2003;171(9):4868-74. doi: 10.4049/jimmunol.171.9.4868. 
Banfield C, Rudin D, Bhattacharya I, Goteti K, Li G, Hassan-Zahraee M, Brown LS, Hung KE, 
Pawlak S, Lepsy C. First-in-human, randomized dose-escalation study of the safety, tolerability, 
pharmacokinetics, pharmacodynamics and immunogenicity of PF-06480605 in healthy subjects. 
Br J Clin Pharmacol. 2020;86(4):812-24. doi: 10.1111/bcp.14187. 
Best WR, Becktel JM, Singleton JW, Kern F Jr. Development of a Crohn’s disease activity 
index. National Cooperative Crohn’s Disease Study. Gastroenterology 1976; 70: 439–44. 
Cleynen I, González JR, Figueroa C, Franke A, McGovern D, Bortlík M, Crusius BJ, Vecchi M, 
Artieda M, Szczypiorska M, Bethge J, Arteta D, Ayala E, Danese S, van Hogezand RA, Panés J, 
Peña SA, Lukas M, Jewell DP, Schreiber S, Vermeire S, Sans M. Genetic factors conferring an 
increased susceptibility to develop Crohn's disease also influence disease phenotype: results from 
the IBDchip European Project. Gut. 2013;62(11):1556-65. doi: 10.1136/gutjnl-2011-300777. 
Danese S, Klopocka M, Scherl EJ, Romatowski J, Allegretti JR, Peeva E, Vincent MS, 
Schoenbeck U, Xi L, Ye Z, Hassan-Zahraee M, Rath N, Li G, Neelakantan S, Banfield C, Lepsy 
C, Chandra D, Hung KE. DOP72 Safety, tolerability and efficacy of anti-TL1A antibody PF-
06480605 in treatment of ulcerative colitis: The open-label, multicentre, Phase 2a TUSCANY 
study [abstract]. Journal of Crohn's and Colitis. 2020;14(Supplement_1):S108-S10. 
doi: 10.1093/ecco-jcc/jjz203.111. 
Daperno M, D'Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, Sostegni R, Rocca R, 
Pera A, Gevers A, Mary JY, Colombel JF, Rutgeerts P. Development and validation of a new, 


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simplified endoscopic activity score for Crohn's disease: the SES-CD. Gastrointest Endosc. 
2004;60(4):505-12. doi: 10.1016/s0016-5107(04)01878-4. 
Feagan BG, Sandborn WJ, D'Haens G, Panés J, Kaser A, Ferrante M, Louis E, Franchimont D, 
Dewit O, Seidler U, Kim KJ, Neurath MF, Schreiber S, Scholl P, Pamulapati C, Lalovic B, 
Visvanathan S, Padula SJ, Herichova I, Soaita A, Hall DB, Böcher WO. Induction therapy with 
the selective interleukin-23 inhibitor risankizumab in patients with moderate-to-severe Crohn's 
disease: a randomised, double-blind, placebo-controlled phase 2 study. Lancet. 
2017;389(10080):1699-709. doi: 10.1016/s0140-6736(17)30570-6. 
Ferdinand JR, Richard AC, Meylan F, Al-Shamkhani A, Siegel RM. Cleavage of TL1A 
Differentially Regulates Its Effects on Innate and Adaptive Immune Cells. J Immunol. 
2018;200(4):1360-9. doi: 10.4049/jimmunol.1700891. 
Guyatt G, Mitchell A, Irvine EJ, Singer J, Williams N, Goodacre R, Tompkins C. A new 
measure of health status for clinical trials in inflammatory bowel disease. Gastroenterology. 
1989;96(3):804-10. 
Irvine EJ. Usual therapy improves perianal Crohn's disease as measured by a new disease 
activity index. McMaster IBD Study Group. J Clin Gastroenterol. 1995;20(1):27-32. 
Moskovitz DN, Daperno M, Assche GA. Defining and validating cut-offs for the Simple 
Endocopic Score for Crohn's Disease. Gastroenterology. 2007;132:S1097. 
NCI. Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Bethesda (MD): 
National Cancer Institute; 2017. Available from: 
ttps://ctep.cancer.gov/protocoldevelopment/electronic_applications/ctc.htm#ctc_50. 
Prehn JL, Thomas LS, Landers CJ, Yu QT, Michelsen KS, Targan SR. The T cell costimulator 
TL1A is induced by FcgammaR signaling in human monocytes and dendritic cells. J Immunol. 
2007;178(7):4033-8. doi: 10.4049/jimmunol.178.7.4033. 
Present DH, Rutgeerts P, Targan S, Hanauer SB, Mayer L, van Hogezand RA, Podolsky DK, 
Sands BE, Braakman T, DeWoody KL, Schaible TF, van Deventer SJ. Infliximab for the 
treatment of fistulas in patients with Crohn's disease. N Engl J Med. 1999;340(18):1398-405. 
doi: 10.1056/nejm199905063401804. 
Richard AC, Ferdinand JR, Meylan F, Hayes ET, Gabay O, Siegel RM. The TNF-family 
cytokine TL1A: from lymphocyte costimulator to disease co-conspirator. J Leukoc Biol. 
2015;98(3):333-45. doi: 10.1189/jlb.3RI0315-095R. 
Roberts‑Thomson IC, Fon J, Uylaki W, Cummins AG, Barry S. Cells, cytokines and 
inflammatory bowel disease: a clinical perspective. Expert Rev Gastroenterol Hepatol. 
2011;5(6):703-16. doi: 10.1586/egh.11.74. 
Roda G, Jharap B, Neeraj N, Colombel J-F. Loss of Response to Anti-TNFs: Definition, 
Epidemiology, and Management. Clinical and translational gastroenterology. 2016;7(1):e135. 
doi: 10.1038/ctg.2015.63. 


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Sands B, Sandborn W, Peyrin-Biroulet L, Higgins P, Hirai F, Belin R, Valderas E, Miller D, 
Morgan-Cox M, Naegeli A, Pollack P, Tuttle J, Imaeda H. Efficacy and Safety of Mirikizumab 
(LY3074828) in a Phase 2 Study of Patients with Crohn's Disease. Gastroenterology. 
2019;156:S-216. doi: 10.1016/S0016-5085(19)37335-4. 
Selinger C, Sandborn W, Panes J, Jones J, Hassanali A, Jacob R, Sharafali Z, Oh Y, Tole S. 
Etrolizumab as induction therapy in moderate to severe Crohn's disease: results from 
BERGAMOT cohort 1. Gut. 2018;67(Suppl 1):A1–A304. doi: 10.1136/gutjnl-2018-
BSGAbstracts.106. 
Shih DQ, Zheng L, Zhang X, Zhang H, Kanazawa Y, Ichikawa R, Wallace KL, Chen J, 
Pothoulakis C, Koon HW, Targan SR. Inhibition of a novel fibrogenic factor Tl1a reverses 
established colonic fibrosis. Mucosal immunology. 2014;7(6):1492-503. 
doi: 10.1038/mi.2014.37. 
Strober W, Fuss IJ. Proinflammatory cytokines in the pathogenesis of inflammatory bowel 
diseases. Gastroenterology. 2011;140(6):1756-67. doi: 10.1053/j.gastro.2011.02.016. 
Valatas V, Kolios G, Bamias G. TL1A (TNFSF15) and DR3 (TNFRSF25): A Co-stimulatory 
System of Cytokines With Diverse Functions in Gut Mucosal Immunity. Frontiers in 
immunology. 2019;10:583-. doi: 10.3389/fimmu.2019.00583. 
Vermeire S, Schreiber S, Petryka R, Kuehbacher T, Hebuterne X, Roblin X, Klopocka M, Goldis 
A, Wisniewska-Jarosinska M, Baranovsky A, Sike R, Stoyanova K, Tasset C, Van der Aa A, 
Harrison P. Clinical remission in patients with moderate-to-severe Crohn's disease treated with 
filgotinib (the FITZROY study): results from a phase 2, double-blind, randomised, placebo-
controlled trial. Lancet. 2017;389(10066):266-75. doi: 10.1016/s0140-6736(16)32537-5. 
Yamazaki K, McGovern D, Ragoussis J, Paolucci M, Butler H, Jewell D, Cardon L, Takazoe M, 
Tanaka T, Ichimori T, Saito S, Sekine A, Iida A, Takahashi A, Tsunoda T, Lathrop M, 
Nakamura Y. Single nucleotide polymorphisms in TNFSF15 confer susceptibility to Crohn's 
disease. Hum Mol Genet. 2005;14(22):3499-506. doi: 10.1093/hmg/ddi379. 
Yang SK, Lim J, Chang HS, Lee I, Li Y, Liu J, Song K. Association of TNFSF15 with Crohn's 
disease in Koreans. Am J Gastroenterol. 2008;103(6):1437-42. 
doi: 10.1111/j.1572‑0241.2007.01752.x. 
 


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16 APPENDIX 
16.1 
Simple Endoscopic Score for Crohn’s Disease (SES-CD) 
The Simple Endoscopic Score for Crohn’s Disease (SES-CD) assesses the size of mucosal 
ulcers, the ulcerated surface, the endoscopic extension, and the presence of stenosis. 
Ulcers - scored according to size  
0 = no ulcers 
1 = aphthous (0.1 - 0.5 cm) 
2 = large (0.5 - 2 cm) 
3 = very large (> 2 cm) 
Proportion of the surface covered by ulcers according to extent  
0 = none 
1 = < 10% 
2 = 10 - 30% 
3 = > 30% 
Proportion of affected surface with any other lesions according to extent  
0 = unaffected segment 
1 = < 50% 
2 = 50 - 75% 
3 = > 75% 
Stenosis (single or multiple, and whether the colonoscopy could pass through the narrow 
lumen) 
0 = none 
1 = single, can be passed 
2 = multiple, can be passed 
3 = cannot be passed 
 
 


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16.2 
Crohn’s Disease Activity Index (CDAI) 
The Crohn’s disease activity index (CDAI) scores range from 1 to approximately 600, with 
higher scores indicating more severe disease. Eight variables comprise the components of the 
CDAI score (modified from Best 1976). Modification limits the contribution of the weight 
variable to no more than 10 points in negative contribution.  
 
 
 


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16.3 
Perianal Disease Activity Index (PDAI) 
The perianal disease activity index (PDAI) score includes the evaluation of 5 elements: 
1. discharge 
2. pain 
3. restriction of sexual activity 
4. type of perianal disease 
5. degree of induration 
Each category is graded on a 5-point Likert scale ranging from no symptoms (score of 0) to severe 
symptoms (score of 4), with a range of 0 to 20; a higher score indicates more severe disease. 
 

SAP_001.pdf: 
Official Protocol Title:
NCT number:
Document Date:
A Phase 2a, Multi-Center, Open-Label 
Study to Evaluate the Safety, Efficacy, and 
Pharmacokinetics of PRA023 in Subjects 
With Moderately to Severely Active Crohn's 
Disease 
NCT05013905
19-April-2022


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STATISTICAL ANALYSIS 
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*Confidentiality Statement 
The information contained in this document is privileged and confidential. Any disclosure is prohibited unless such 
disclosure is required by applicable laws and regulations. Persons to whom the information is disclosed must be informed 
that the information is privileged and confidential and it may not be further disclosed by them. 
A Phase 2a, Multi-Center, Open-Label Study to Evaluate the Safety, Efficacy, and 
Pharmacokinetics of PRA023 in Subjects with Moderately to Severely Active Crohn’s 
Disease 
STATISTICAL ANALYSIS PLAN 
 
Protocol No.: 
PR200-103 
Analysis Type: 
Primary Analysis of Induction Period 
Version/Date: 
3.0/21OCT2021 
Development Phase: 
2a 
EudraCT No.: 
2021-000092-37 
Sponsor: 
Prometheus Biosciences, Inc. 
9410 Carroll Park Drive 
San Diego, CA 92121 
United States of America 
Clinical Research 
Organization: 
 
100 Dundas Street Suite 200 
London, Ontario, Canada 
N6A 5B6 
 
 
 
CCI


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STATISTICAL ANALYSIS 
PLAN 
APPROVAL 
 
A Phase 2a, Multi-Center, Open-Label Study to Evaluate the Safety, Efficacy, and 
Pharmacokinetics of PRA023 in Subjects with Moderately to Severely Active Crohn’s 
Disease 
STATISTICAL ANALYSIS PLAN 
Primary Analysis (Induction Period) 
Version/Date: V02/19APR2022 
 
Name 
Position 
Signature 
Date 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
1 Author, signs for correctness and completeness 
2 Reviewer, signs for correctness and completeness 
3 Approver, signs for the release of the document 
PPD


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STATISTICAL ANALYSIS 
PLAN 
Table of Contents 
DEFINITIONS / ABBREVIATIONS 
6 
1 
INTRODUCTION 
8 
2 
STUDY OBJECTIVES AND ENDPOINTS 
8 
3 
STUDY DESIGN 
3.1 
SUMMARY OF STUDY DESIGN .................................................................................. 10 
3.2 
DETERMINATION OF SAMPLE SIZE .......................................................................... 11 
3.3 
RANDOMIZATION ..................................................................................................... 11 
3.3.1 RANDOMIZATION NUMBERS .......................................................................... 11 
3.3.2 BLINDED IMAGE ASSESSMENT ....................................................................... 12 
4 
GENERAL CONSIDERATIONS FOR DATA ANALYSES 12 
4.1 
REPORTING CONVENTIONS ..................................................................................... 12 
4.2 
ANALYSIS SETS ......................................................................................................... 13 
4.2.1 SCREENING SUBJECTS ANALYSIS SET ........................................................... 13 
4.2.2 SAFETY ANALYSIS SET .................................................................................. 13 
4.2.3 FULL ANALYSIS SET (FAS) ........................................................................... 14 
4.2.4 PER-PROTOCOL(PP) ANALYSIS SET ............................................................... 14 
4.2.5 OPEN LABEL EXTENSION ANALYSIS SET ....................................................... 14 
4.3 
HANDLING OF MISSING DATA ................................................................................. 14 
4.4 
ANALYSIS VISIT WINDOW ....................................................................................... 14 
5 
SUBJECT CHARACTERISTICS 15 
5.1 
SUBJECT DISPOSITION ............................................................................................. 15 
5.2 
DEMOGRAPHICS AND BASELINE DISEASE CHARACTERISTICS ............................... 16 
5.3 
TREATMENT EXPOSURE ........................................................................................... 16 
5.3.1 EXPOSURE ...................................................................................................... 16 
5.3.2 COMPLIANCE ................................................................................................. 16 
5.4 
PRIOR AND CONCOMITANT MEDICATION ............................................................... 17 
5.4.1 PRIOR MEDICATION ....................................................................................... 17 
5.4.2 CONCOMITANT MEDICATION ......................................................................... 17 
5.5 
MEDICAL AND SURGICAL HISTORY ........................................................................ 18 
5.6 
PROTOCOL DEVIATIONS .......................................................................................... 18 
6 
EFFICACY ANALYSES 18 
6.1 
DERIVATION OF EFFICACY MEASURMENTS ............................................................ 18 


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6.1.1 SIMPLE ENDOSCOPIC SCORE – CROHN’S DISEASE (SES-CD) ......................... 18 
6.1.2 CROHN’S DISEASE ACTIVITY INDEX (CDAI) ................................................. 19 
6.1.3 PERIANAL DISEASE ACTIVITY INDEX (PDAI) ................................................ 21 
6.1.4 GLOBAL HISTOLOGIC DISEASE ACTIVITY SCORE (GHAS) ............................ 21 
6.1.5 ROBERTS HISTOPATHOLOGY INDEX (RHI) ..................................................... 21 
6.2 
PRIMARY EFFICACY ENDPOINT ............................................................................... 21 
6.2.1 PRIMARY ANALYSIS ....................................................................................... 22 
6.2.2 SENSITIVITY ANALYSIS .................................................................................. 22 
6.3 
SECONDARY EFFICACY ENDPOINTS ........................................................................ 22 
6.3.1 DICHOTOMOUS OR BINARY ENDPOINTS ......................................................... 22 
6.3.2 CONTINUOUS ENDPOINTS ............................................................................... 23 
6.4 
EXPLORATORY EFFICACY ENDPOINTS ..................................................................... 23 
6.4.1 DICHOTOMOUS OR BINARY ENDPOINTS ......................................................... 23 
6.4.2 CONTINUOUS EFFICACY ENDPOINTS .............................................................. 24 
6.5 
EVALUATION OF PHARMACODYNAMIC PARAMETERS ............................................ 25 
6.6 
EVALUATION OF PHARMACOKINETIC PARAMETERS .............................................. 26 
6.7 
EVALUATION OF IMMUNOGENICITY ........................................................................ 26 
6.8 
MISSING DATA HANDLING ....................................................................................... 26 
6.8.1 NON-RESPONDER IMPUTATION (NRI) ............................................................ 26 
6.9 
SENSITIVITY ANALYSES ........................................................................................... 26 
6.10 
MULTIPLICITY ...................................................................................................... 26 
7 
SAFETY ANALYSES 
26 
7.1 
ADVERSE EVENTS .................................................................................................... 27 


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7.1.1 ADVERSE EVENT DICTIONARY ....................................................................... 27 
7.1.2 ADVERSE EVENT SEVERITY ........................................................................... 27 
7.1.3 RELATIONSHIP OF ADVERSE EVENT TO STUDY TREATMENT .......................... 27 
7.1.4 SERIOUS ADVERSE EVENTS ........................................................................... 27 
7.1.5 ADVERSE EVENT OF SPECIAL INTEREST .......................................................... 28 
7.1.6 TREATMENT EMERGENT ADVERSE EVENTS ................................................... 28 
7.1.7 SUMMARIES OF ADVERSE EVENTS ................................................................. 28 
7.2 
PHYSICAL EXAMINATION ........................................................................................ 29 
7.3 
VITAL SIGNS ............................................................................................................. 29 
7.4 
CLINCAL LABORATORY TESTS ................................................................................ 30 
7.5 
ELECTROCARDIOGRAMS .......................................................................................... 31 
8 
OTHER ANALYSES 
31 
8.1 
QUALITY OF LIFE(QOL) .......................................................................................... 31 
9 
NUMBER AND TIMING OF ANALYSES 32 
10 
CHANGES FROM PROTOCOL 32 
11 
REVISION HISTORY 33 
12 
REFERENCES 34 
APPENDICES 35 
APPENDIX A. SIMPLE ENDOSCOPIC SCORE FOR CROHN’S DISEASE (SES-CD) ........... 35 
APPENDIX B. CROHN’S DISEASE ACTIVITY INDEX (CDAI) .......................................... 36 
APPENDIX C. PRO2 CALCULATION ............................................................................... 37 
APPENDIX D. PERIANAL DISEASE ACTIVITY INDEX (PDAI) ......................................... 38 
APPENDIX E. GLOBAL HISTOLOGIC DISEASE ACTIVITY SCORE .................................. 39 
APPENDIX F. ROBARTS HISTOPATHOLOGY INDEX ........................................................ 40 
APPENDIX G. SCHEDULE OF ASSESSMENTS – INDUCTION PERIOD ............................... 41 
APPENDIX H. SCHEDULE OF ASSESSMENTS – OPEN-LABEL EXTENSION PERIOD ........ 42 
APPENDIX I. SCHEDULE OF ASSESSMENTS – POST DOSING FOLLOW-UP PERIOD ........ 44 


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STATISTICAL ANALYSIS 
PLAN 
DEFINITIONS / ABBREVIATIONS 
ADA 
Anti-drug antibody 
AE 
Adverse event 
ATC 
Anatomical therapeutic chemical 
BLQ 
Limit of quantitation 
CD 
Crohn’s disease 
CDAI 
Crohn’s disease activity index 
CDC 
Complement-dependent cytotoxicity 
CDx 
Companion diagnostic 
CFR 
Code of Federal Regulations 
Cmax 
Maximal concentration 
CI 
Confidence interval 
 
 
CTCAE 
Common Terminology Criteria for Adverse Events 
COVID-19 
Coronavirus disease 2019 
CR 
Central Reader 
CRO 
Contract Research Organization 
CSR 
Clinical study report 
DMC 
Data Monitoring Committee 
EC 
Ethics Committee 
ECG 
Electrocardiograms 
eCRF 
Electronic case report form 
EHI 
Endoscopic healing index 
ET 
Early termination 
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
FU 
Follow-Up 
QTcF 
Fridericia’s corrected QT 
GCP 
Good Clinical Practice 
GHAS 
Global histological activity score 
GM 
Geometric Mean 
hsCRP 
High sensitivity C-reactive protein 
IBD 
Inflammatory bowel disease 
IBDQ 
Inflammatory Bowel Disease Questionnaire 
ICF 
Informed consent form 
ICH 
International Conference on Harmonisation 
IP 
Induction Period 
IRB 
Institutional Review Board 
IRT 
Interactive response technology 
IV 
Intravenous 
LOQ 
Limit of quantitation 
LOCF 
Last observation carried forward 
MedDRA 
Medical Dictionary for Regulatory Activities 
Nab 
Neutralizing antibody 
NCI 
National Cancer Institute 
NRI 
Non-Responder Imputation 
OLE 
Open-Label Extension 
CCI
CCI


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STATISTICAL ANALYSIS 
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PD 
Pharmacodynamic 
PDAI 
Perianal Disease Activity Index 
PG 
Pharmacogenomic 
PK 
Pharmacokinetic 
PRO-2 
Two component patient-reported outcome 
PT 
Preferred term 
Q2W 
Every 2 weeks 
Q4W 
Every 4 weeks 
QoL 
Quality of life 
RBC 
Red blood cell 
RHI 
Robarts histopathology index 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SES-CD 
Simple endoscopy score for Crohn’s disease 
SOC 
System organ class 
SOP 
Standard operating procedure 
TEAE 
Treatment-emergent adverse event 
TFLs 
Tables, figures, and listings 
TL1A 
tumor necrosis factor-like cytokine 1A 
ULN 
Upper limit of normal 
WK 
Week 
WHO 
World Health Organization 


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STATISTICAL ANALYSIS 
PLAN 
1 
INTRODUCTION 
This statistical analysis plan (SAP) describes in detail the analyses to be performed for the 
Induction Period (IP) of the study on the safety, efficacy, and pharmacokinetics of PRA023 in 
subjects with moderately to severely active Crohn’s Disease(CD). This SAP describes the 
statistical analysis methods and data presentations to be used in tables, figures, and listings (TFLs) 
in the clinical study report (CSR) for study PR-200-103. This SAP is based on the study protocol 
version 3.0. 
There will be a primary analysis after all subjects have completed 12-week IP. The analysis will 
include complete data for the induction period and interim data for the OLE as of the cutoff date 
for the database lock. Outstanding data queries would have been resolved or adjudicated as 
unresolvable, and data should have been cleaned and finalized before database lock. Following the 
database lock after all subjects have completed Induction Period, the primary analysis of the data 
will be performed. 
The SAP will be finalized and approved before 50% of planned subjects enrolled and initiated 
dosing. Any changes made after the finalization and approval of the SAP will be documented in 
the CSR with the rationale. 
 
2 
STUDY OBJECTIVES AND ENDPOINTS 
This is a Phase 2a, Multi-Center, Open-Label Study to Evaluate the Safety, Efficacy, and 
Pharmacokinetics of PRA023 in Subjects with Moderately to Severely Active Crohn’s Disease. 
The primary, secondary and exploratory study objectives and corresponding endpoints for IP 
analyses are listed in Table 1 below. 
 
Table 1 Study Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
To evaluate the safety and tolerability of 
PRA023 following 12-weeks of induction 
therapy 
• 
Proportion of subjects reporting AEs, SAEs, AEs leading to 
discontinuation, and markedly abnormal laboratory values 
To assess the proportion of subjects with 
endoscopic improvement (decrease in simple 
endoscopy score for Crohn’s disease [SES-CD] 
≥ 50% from Baseline) at Week 12 
• 
Proportion of subjects with endoscopic improvement , as 
defined by decrease in SES-CD ≥ 50% from Baseline at Week 
12 
Secondary 
To assess the proportion of subjects with 
clinical remission (Crohn’s disease activity 
index [CDAI] < 150) at Week 12 
• 
Proportion of subjects in clinical remission (CDAI < 150) at 
Week 12 
To assess the proportion of subjects with 
endoscopy and clinical improvement at Week 
12 
• 
Proportion of subjects with endoscopic and clinical 
improvement, as defined by decrease in SES-CD ≥ 50% AND 
reduction in CDAI ≥ 100 points from Baseline or CDAI <150 
at Week 12 
To assess the proportion of subjects with 
biomarker and clinical improvement, among 
subjects with at least one elevated biomarker at 
Baseline, at Week 12 
• 
Proportion of subjects with both biomarker and clinical 
improvement (decrease in hsCRP OR fecal calprotectin ≥ 50% 
from Baseline, among subjects with at least one elevated 
biomarker at Baseline, AND reduction in CDAI ≥ 100 points 
from Baseline or CDAI <150) at Week 12 


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To assess the proportion of subjects with 
normalization of C-reactive protein (hsCRP < 
upper limit of normal [ULN]), among subjects 
with elevated concentrations at Baseline, at 
Week 12 
• 
Proportion of subjects with normalization of hsCRP (as defined 
by hsCRP < ULN), among subjects with elevated concentrations 
at Baseline, at Week 12 
To assess the proportion of subjects with 
normalization of fecal calprotectin (fecal 
calprotectin < ULN), among subjects with 
elevated concentrations at Baseline, at Week 12 
• 
Proportion of subjects with normalization of fecal calprotectin 
(as defined by fecal calprotectin < ULN), among subjects with 
elevated concentrations at Baseline, at Week 12 
To assess the proportion of subjects with clinical 
improvement at Week 12 
• 
Proportion of subjects in clinical response, as defined by 
reduction in CDAI ≥ 100 points from Baseline or CDAI<150 at 
Week 12 
To assess the proportion of subjects with two 
component patient-reported outcome (PRO-2) 
remission at Week 12 
• 
Proportion of subjects with PRO-2 remission (defined as average 
daily abdominal pain score ≤ 1 point and average daily stool 
frequency ≤ 3 points with abdominal pain and stool frequency no 
worse than Baseline) at Week 12 
To assess the change in SES-CD score from 
Baseline to Week 12 
• 
Change in mean SES-CD score at Week 12 from Baseline 
To assess the pharmacokinetics (PK) of 
PRA023 
• 
Descriptive summaries of PK and immunogenicity of PRA023 
To assess the immunogenicity of PRA023 
• 
Proportion of subjects developing anti-drug antibody (ADA) and 
neutralizing antibody (Nab) 
Exploratory 
To assess endoscopic remission at Week 12 
• 
Proportion of subjects with endoscopic remission, as defined as 
SES-CD <=4 and at least 2-point reduction from baseline and all 
individual score <=1 at Week 12 
To assess ulcer-free at Week 12 
• 
Proportion of subjects with SES-CD ulcerated surface score of 0 
at week 12 among patients with SES-CD ulcerated surface score 
>=1 at baseline 
To assess the change in SES-CD segment score 
from baseline to Week 12 
• 
Change from baseline in SES-CD for each segment at Week 12 
To assess the clinical improvement by PRO-2 
score at Week 12 
• 
Change in PRO-2 over time 
• 
Proportion of subjects with clinical improvement by PRO-2 
score, defined as >=30% reduction of either score and no 
worsening in both scores at Week 12 
• 
Proportion of subjects with enhanced clinical response by PRO- 
2 score, defined as a reduction of >=60% in averge daily stool 
frequency or a reduction of >=35% in average daily abdominal 
pain score, and no worsening in both scores at Week 12 
• 
Proportion of subjects with >=30% reduction of PRO-2 total 
score 
To assess the proportion of subjects with both 
clinical 
improvement 
and 
endoscopic 
improvement at Week 12 
• 
Proportion of subjects who achieve both enhanced clinical 
response by PRO-2 score and endoscopic improvement at Week 
12 
To  assess  the  IBDQ  remission  or  IBDQ 
improvement at Week 12 
• 
Proportion of subjects with IBDQ remission or IBDQ 
improvement at Week 12 
To assess the change from baseline in IBDQ 
scores at Week 12 
• 
Change from baseline in IBDQ scores 
To assess the change in CDAI and component 
scores over time 
• 
Change in CDAI and components from Baseline over time 


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To assess the effects of PRA023 on tissue and 
serum pharmacodynamic (PD) markers, 
including tumor necrosis factor-like cytokine 
1A (TL1A) concentrations, fecal calprotectin, 
and hsCRP in all subjects over time 
• 
Change in PD markers including TL1A concentrations, fecal 
calprotectin, and hsCRP over time 
To characterize the change in Perianal Disease 
Activity Index (PDAI) score from Baseline to 
Week 12 
• 
Change in PDAI from Baseline over time 
To characterize the effect of PRA023 for 
improvement and remission of enterocutaneous 
and/or perianal fistula -Overtime 
• 
Proportion of subjects with improvement or remission of 
enterocutaneous and/or perianal fistula Overtime , among 
patients with fistula at baseline 
To assess the change in global histological 
activity 
score 
(GHAS) 
and 
Robarts 
histopathology index (RHI) from Baseline to 
Week 12 
• 
Change in mean GHAS and RHI scores from Baseline to Week 
12 
• 
Proportion of subjects with GHAS histologic score ≤ 4 at Week 
12 
• 
Proportion of subjects with Robarts histologic score < 5 at Week 
12 
To assess the proportion of subjects with 
histologic response and histologic remission at 
Week 12 
• 
Proportion of subjects with GHAS histologic remission, defined 
as no neutrophils in the epithelium or subscore of 0, at Week 12 
• 
Proportion of subjects with Robarts histologic remission (< 3) at 
Week 12 
 
3 
STUDY DESIGN 
 
3.1 
SUMMARY OF STUDY DESIGN 
This is a multi-center, open-label, proof of concept study designed to assess the safety, tolerability, 
and preliminary efficacy of PRA023 following 12 weeks of induction therapy in subjects with 
Crohn’s disease (CD). This study will be conducted under the aegis of a Data Monitoring 
Committee (DMC) and will commence following the demonstration of an acceptable safety profile 
of PRA023 at a dose of ≥ 500 mg in the multiple ascending dose study in normal healthy volunteers 
(Study PR200-101). 
The study has 4 periods (Screening, IP, OLE and Follow-Up [FU] Period). Following the 
Screening Period, approximately 50 eligible subjects with moderately to severely active CD will 
enter the IP to receive PRA023 1000 mg on Week 0/Day 1, followed by 500 mg on Weeks 2, 6, 
and 10 via intravenous (IV) administration. Subjects who discontinue from the study will have a 
follow-up period of 12 weeks after the last dose. A schema for the study is in Figure 1. 
 
Figure 1 Study Design 


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Q4W=every 4 weeks; R=Randomization. 
 
Response at Week 12 is defined as reduction from Baseline in CDAI of ≥ 100 points , or CDAI < 
150. Non-responders at Week 12 should discontinue from study drug treatment. 
Subjects who complete the 12-week IP and have responded will have the option to enter OLE, 
where they will be randomized to either 250 mg IV Q4W or 100 mg IV Q4W until Week 50. 
Subjects will continue in OLE until they progress, withdraw from the study, study termination, or 
Week 50. 
The study may be amended by the Sponsor to extend the OLE period beyond 50 weeks based on 
emerging safety data. 
For additional details, please see the Schedule of Assessments are described in Appendix G. 
 
3.2 
DETERMINATION OF SAMPLE SIZE 
The study is planned to enroll approximately 50 subjects. The sample size will enable a statistical 
power of 80%, at 1-sided significance level of 0.025, to test against the null hypothesis of 
endoscopic improvement rate of 12%, assuming the endoscopic improvement rate for PRA023 is 
27%. 
The null hypothesis of an endoscopic improvement (decrease in SES-CD ≥ 50%) rate of 12% is 
based on a meta-analysis estimate of the upper limit of 95% CI of the observed placebo rate (95% 
CI) of 9.5% (7.1, 11.9) from multiple modern-era CD clinical trials with centrally read endoscopy 
and similar eligibility criteria. [1] 
 
3.3 
RANDOMIZATION 
3.3.1 RANDOMIZATION NUMBERS 
This is an open-label study where all subjects will receive PRA023. Eligible subjects will be 
assigned a subject number by the IRT system at Week 0/Day 1 upon confirmation of study 
eligibility as a means to track the number of eligible subjects enrolled in the study. Subjects who 
are randomized in OLE will retain their original subject numbers. 


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3.3.2 BLINDED IMAGE ASSESSMENT 
Endoscopy videos and histopathology images will be scored by qualified independent central 
readers (CR) blinded to the visit at which the videos/images were obtained. 
Endoscopic assessments will be scored both locally and centrally and histologic assessments will 
be scored centrally. Study central readers will receive standardized training on 
 
 for assessment of endoscopy and histopathology (qualified 
gastroenterologists and pathologists, respectively). Central readers will enter scores in a study 
database. For histologic assessments, there will be a single central read. For endoscopic 
assessments, two central reader scores will be the primary scores for analyses and for confirming 
eligibility. In the case of adjudication for endoscopy, the third central reader (adjudicator) would 
score the endoscopy video independently. 
Further details are available in the Image Review Charter. 
 
4 
GENERAL CONSIDERATIONS FOR DATA ANALYSES 
 
4.1 
REPORTING CONVENTIONS 
The following reporting conventions apply generally to tables, listings, and graphs: 
• Unless otherwise specified, the baseline value is defined as the last non-missing assessment 
before the first does of study treatment. 
• If the date of interest occurs on or after the first dose date, the study day will be calculated 
as (date of interest – date of first dose) + 1. 
• If the date of interest occurred prior to the first dose date, then study day will be calculated 
as (date of interest – date of first dose). 
• Categorical data will be summarized by treatment group in terms of frequency counts and 
percentages. 
• Continuous variables will be summarized by treatment group using descriptive statistics 
(the number of subjects (n), mean, median, standard deviation (SD), minimum (Min), and 
maximum (Max)) of the values at each visit and the change from baseline to each visit, 
unless specified otherwise. 
• Confidence Intervals (CIs) will be presented as 2-sided 95% CIs. 
• All mean, median and CI values will be formatted to one more decimal place than the 
measured values. SD values will be formatted to two more decimal places than the 
measured value. Min and Max will be formatted to the same number of decimal places as 
the measured value. The maximum number of decimal places reported shall be four for any 
summary statistic. 
• All percentages will be rounded to one decimal place, unless specified otherwise. The 
number and percentage of responses will be presented in the form xx (xx.x), where the 
percentage is in the parentheses. 
• Change from baseline is calculated as a post-baseline value minus the baseline value. 
• All laboratory data will be reported using standard international units. 
• All analysis and summary tables will include the analysis population sample size (ie, 
number of subjects) in the column headings. 
CCI


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• By-subject listings will be presented for all subjects in the relevant analysis sets, and sorted 
by treatment allocation, study site (if applicable), Subject ID, date, and visit. Numeric data 
will be listed to the same number of decimal places as recorded on the eCRF or other data 
source. Data collected on log forms, such as AEs, will be presented in chronological order 
within the subject, and age, and sex will be included in the listing, as space permits. 
• SAS® Software Version 9.4 (SAS Institute Inc., Cary, NC, USA.) is to be used for all 
analyses including tables, listings, and figures. 
• Non-pharmacokinetic and non-biomarker lab data that are continuous in nature but are less 
than the lower limit of quantitation (LOQ) or above the upper LOQ will be imputed as 
follows: 
- 
A value that is 1 unit less than the LOQ will be used for calculation of descriptive 
statistics if the datum is reported in the form of “< x” (where x is considered the 
LOQ). For example, if the values are reported as < 50 and < 5.0, values of 49 and 
4.9, respectively, will be used for calculation of summary statistics. An exception 
to this rule is any value reported as < 1 or < 0.1, etc. For values reported as < 1 or 
< 0.1, a value of 0.9 or 0.09, respectively, will be used for calculation of summary 
statistics. 
- 
A value that is 1 unit above the LOQ will be used for calculation of descriptive 
statistics if the datum is reported in the form of “> x” (where x is considered the 
LOQ). Values with decimal points will follow the same logic as above. The LOQ 
will be used for calculation of descriptive statistics if the datum is reported in the 
form of “≤ x” or “≥ x” (where x is considered the LOQ). 
• PK plasma concentration values that are below the limit of quantitation (BLQ) will be 
treated as 0. PD/biomarker BLQ concentration values will be treated as ½ *LOQ at all time 
points. 
• MedDRA version 24.0 will be used to code adverse events and medical history, World 
Health Organization (WHO) drug dictionary version March 2020 or newest will be used 
for medication coding. 
4.2 
ANALYSIS SETS 
4.2.1 SCREENING SUBJECTS ANALYSIS SET 
All subjects who signed informed consent and participated in screening visit will be included in 
the screening subjects analysis set. The number of subjects screened will be reported, and will be 
used for the presentation of subject disposition. Data collected on subjects who are screened but 
not enrolled, i.e. study medication not received, will not be included in any analyses. 
4.2.2 SAFETY ANALYSIS SET 
All subjects who received at least 1 dose of study drug will be included in the safety analysis set. 
The Safety Analysis Set is the primary analysis set for safety analyses. 


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4.2.3 FULL ANALYSIS SET (FAS) 
All subjects who have been treated with PRA023 with Baseline CDAI and SES-CD scores will be 
included in the FAS. The FAS set will be used for efficacy analysis. 
4.2.4 PER-PROTOCOL(PP) ANALYSIS SET 
The PP analysis set is a subset of FAS. Subjects who had significant protocol deviations will be 
excluded from analysis based on PP analysis set. 
4.2.5 OPEN LABEL EXTENSION ANALYSIS SET 
The OLE analysis set includes subjects who are randomized and received at least 1 dose of OLE 
drug. The analysis will be presented by the randomized treatment group. 
 
4.3 
HANDLING OF MISSING DATA 
In general, missing data will not be imputed for descriptive statistics unless methods for handling 
missing data are specified. The handling of missing or incomplete dates for prior and concomitant 
medications is described in Section 5.4, and for AE onset is described in Section 7.1. 
The handling of missing data in analyses of the efficacy endpoints is discussed in Section 6.2 to 
Section 6.4. 
 
4.4 
ANALYSIS VISIT WINDOW 
The following tables present the visits assigned for efficacy and safety analyses and the 
corresponding ranges of treatment days (window) during which an actual visit may occur. In 
general, data collected at nominal visits will be used for the analysis. In case of missing 
assessments at a nominal visit, data collected from unscheduled visits will be slotted according to 
the Visit Windows of Table 2 for analysis, unless specified otherwise. If multiple unscheduled 
visits are slotted into the same nominal visit, the one closest to the targeted visit date will be used. 
 
Table 2 Analysis Visit Windows 
 
Analysis Visit a 
Assessment 
Target Day of the 
Visit 
Analysis Visit Window 
(Study Day) 
Induction Treatment Period 
Screening 
All assessments 
-35 to 0 
≤ 1 
Randomization (Week 0) 
All assessments 
1 
1 
Week 1 
Vital Signs, CBC, 
hsCRP, CDAI 
8 
2 - 11 
Week 2 
Vital Signs, CBC, 
hsCRP, CDAI 
15 
12 - 28 
Fistula, Chemitry panel, 
Urianalysis, total 
sTL1A, Fecal 
Calprotectin 
15 
2 - 28 
Week 6 
Vital Signs, CBC, 
Chemistry panel, 
Urianalysis, Fistula, 
43 
29 - 57 


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total sTL1A, Fecal 
Calprotectin, CDAI 
IBDQ 
43 
2 - 57 
Week 10 
Vital Signs, CBC, 
Fistula, total sTL1A, 
Fecal Calprotectin, 
CDAI 
71 
58 - 78 
Week 12/ET 
Vital Signs, CBC, 
Fistula, total sTL1A, 
Fecal Calprotectin, 
CDAI 
85 
79 - 92 
Chemistry panel, 
Urianalysis, IBDQ 
85 
58 - 92 
Ileocolonoscopy 
85 
71 - 98 
ECG, Lipid panel, 
PDAI 
85 
2 – 92 
Post Treatment Period 
Safety Follow-up b 
Safety Follow-up 
NA 
Remain as the nominal visit 
a Relative to the date of the first dose of study treatment. Day 1 = the date of the first dose of study treatment. 
b No visit window will be used for the post-treatment period. The nominal CRF visit description of Safety Follow- 
up will be used regardless of when this visit occurs. Presented in analysis tables for safety parameters, including 
but not limited to electrocardiograms, clinical laboratory values, and vital signs. No visit window are needed for 
physical examination or pregnancy test. 
 
5 
SUBJECT CHARACTERISTICS 
 
5.1 
SUBJECT DISPOSITION 
Tabular summaries of subject disposition will be provided for screening and IP. These summaries 
will include the number of subjects screened, the number of subjects screened but not enrolled (for 
screening period only), and the number of subjects enrolled and treated as well as the number of 
subjects who discontinued the respective study period, and reasons for discontinuation. 
The following subject disposition summaries will be provided based on the total number of 
subjects screened: 
• Number of subjects screened (n) 
• Number of subjects screening failures (n) 
• Number of subjects enrolled (n) 
• Number of subjects enrolled and treated (n) 
The following subject disposition summaries will be provided based on Safety Analysis Set: 
• Number of subjects completed IP (n) 
• Number of subjects in FAS 
• Number of subjects in PP Analysis Set 
• Number of subjects discontinued prematurely during IP (n) 
o Reasons for discontinuation 


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The number of subjects in Safety Analysis Set will be summarized by geographic region. A listing 
of subject discontinuation will be provided with a reason of discontinuation indicating period (i.e., 
Screening or IP). 
Geographic region will be defined as follows, based on the locations of sites anticipated to 
participate in these studies: 
• North America: Canada, United States 
• Western Europe: Belgium, France, , 
• Eastern Europe: Poland, Czech, Russia, Georgia, Ukraine 
• Rest of World: Australia 
5.2 
DEMOGRAPHICS AND BASELINE DISEASE CHARACTERISTICS 
The subject’s year of birth, gender, weight, height, companion diagnostic (CDx) status, prior 
biologic experienced, concomitant corticosteroid and immunosuppressant use, and other 
demographic and disease characteristics are collected at the screening visit. Age and body mass 
index will be calculated. 
Only the year of birth is collected at screening. For the purpose of age calculation, the month and 
day of birth will be imputed as July 01, of the year of birth. Age is the computed as follows: 
AGE = (Informed Consent Date − Date of Birth)⁄365.25 
Demographic and baseline characteristics (e.g., age (years), gender(male, female), race/ ethnicity, 
geographic region) will be summarized. The summary of demographic data and baseline disease 
characteristics will be provided for the Safety Analysis Set and OLE analysis set. 
Baseline disease characteristics include duration of disease, CD complication, concomitant CD 
medication use (Steroids, immunomodulators, and aminosalicylates), and data for prior biologic 
use. 
 
5.3 
TREATMENT EXPOSURE 
5.3.1 EXPOSURE 
Since this is an open-label study, there is no blinding. The site pharmacist(s) or designee will be 
preparing study drug for infusion. Detailed study drug preparation and handling instructions will 
be provided to the investigational pharmacist in the Pharmacy Manual. 
Total duration of exposure to study treatment during Induction period is defined as the number of 
days elapsed from date first dose to the date of Week 14 visit for patients who enter OLE, or 
otherwise, to the date of 4 weeks after last dose or the date of data cutoff for the primary analysis, 
whichever is earlier. The total duration of exposure to study treatment and total number of 
infusions received for the IP and OLE will be summarized using descriptive statistics for the Safety 
Analysis Set. 
5.3.2 COMPLIANCE 
The investigator is responsible for accountability of all study supplies, including study treatments, 
at the site and must maintain adequate records of all study treatment received and dispensed. These 
records will be used to evaluate protocol deviation with respect to treatment compliance. 


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The total number of infusions (PRA023) administered will be summarized using descriptive 
statistics during the IP for safety analysis set. Number of subjects with a missing dose during IP 
will be presented. 
A complete infusion is defined as the infusion with at least 80% infusion volume (i.e., 200 mL) 
administered of the total volume (i.e., 250 mL). The total number of complete infusions 
administered will be summarized. 
A by-subject listing of study drug administration and infusion interruption will be provided for the 
Induction Period and OLE period, sorted by subject ID number in ascending order. 
 
5.4 
PRIOR AND CONCOMITANT MEDICATION 
Prior and concomitant medications will be classified into anatomical therapeutic chemical (ATC) 
drug classes using the World Health Organization (WHO) drug dictionary version March 2020 or 
newer. 
A tabular summary showing the number and percentage of subjects taking CD agents (including 
corticosteroids) prior to the enrollment, and concomitant during the Induction period will be 
presented for all subjects in Safety Analysis Set. A similar table will be presented for OLE period 
for subjects in OLE analysis set. 
Summary of prior and concomitant medications, separately for CD medications and non-CD 
medications, will include the number and percentage of subjects by ATC Classification level 2 and 
preferred term. A subject will be counted only once within a given drug class and within a given 
drug name, even if he/she received the same medication at different times. If any prior or 
concomitant medication is classified into multiple ATC classes, the medication will be 
summarized separately under each of these ATC classes. The summary tables will be sorted on 
decreasing frequency of drug class and decreasing frequency of drug name in a given drug class. 
In case of equal frequency regarding drug class (respectively drug name), alphabetical order will 
be used. In case any specific medication does not have ATC classification level 2 coded term, it 
will be summarized under “Unavailable ATC classification” category. Summaries will be based 
on the Safety Analysis Set. No formal statistical testing is planned. 
Listings of prior and concomitant CD medications will be generated. 
5.4.1 PRIOR MEDICATION 
Prior medications are defined as the medication that started and stopped before the first dosing 
date. Only medications where the stop date is prior to the first dosing date will be considered prior. 
If the stop date is unknown or incomplete and the medications cannot definitely be considered as 
stopped prior to first dosing date then the medications will be considered as concomitant 
medications (e.g., partial stop date is May 2021, first dosing date is 15 May 2021, medication will 
be considered as concomitant). 
5.4.2 CONCOMITANT MEDICATION 
Any medication with a start date prior to or on the first dosing date and continuing to take after the 
first dosing date, or started after the first dosing date will be considered concomitant medications. 
In addition, concomitant medications with a start date after the last dosing date (concomitant 
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listing, as appropriate. If the start date of a medication is incomplete or missing, the medication 
will be assumed to be concomitant medication, unless the incomplete start date (month and/or 
year) or the stop date (complete or incomplete) clearly indicate that the medication started prior to 
first dosing date or later than 30 days after the last dosing date. Medication with completely 
missing start and stop dates will be included in the concomitant medication summary. 
Additionally, the use of prohibited medications will be summarized and listed. 
 
5.5 
MEDICAL AND SURGICAL HISTORY 
Medical and surgical history will be coded using the most current available version of Medical 
Dictionary for Regulatory Activities (MedDRA version 24.0) and will include all relevant surgical 
and medical history including CD-related complications, other significant conditions or diseases 
relevant to the disease under study, previous surgeries for CD, and the extent and duration of 
disease at baseline. 
A by-subject listing will be provided for those subjects with any medical/surgical history for the 
Safety Analysis Set. 
 
5.6 
PROTOCOL DEVIATIONS 
Review of all protocol deviations will be performed on an ongoing basis during the conduct of the 
study. The number and percentage of subjects with major protocol deviations will be summarized. 
Subjects with important protocol deviations will be excluded from PP Analysis Set. The important 
protocol deviation could include, but are not limited to: 
• Major protocol deviation related to certain study eligibility 
o Entry criteria that would impact on efficacy analyses: Inclusion criteria 2,3,or 4 
• Major protocol deviation related to study treatment 
o Receiving incorrect investigated products, or 
o Missing ≥2 scheduled infusions during IP 
• Unevaluable or missing Week 12 SES-CD score 
A by-subject listing will be provided for those subjects with any protocol deviations before 
database lock. A separated by-subject listing will be provided for important protocol deviations 
that resulted in exclusion from the PP analysis set. 
 
6 
EFFICACY ANALYSES 
Efficacy analyses for IP will primarily be based on the FAS, and supportive efficacy analysis will 
be based on PP, unless specified otherwise. Demographic data characteristics (height, weight, age, 
sex, race, and ethnic origin) will be listed by subject and summarized by CDx status and for the 
overall study population. Selected efficacy endpoints over time during the OLE will be 
summarized descriptively. 
 
6.1 
DERIVATION OF EFFICACY MEASURMENTS 
6.1.1 SIMPLE ENDOSCOPIC SCORE – CROHN’S DISEASE (SES-CD) 
The SES-CD scores 4 endoscopic items (ulcer size, proportion of ulcerated surface, proportion of 
the surface area affected by any disease lesion, and stenosis) from 0 to 3, with higher scores 


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representing more severe endoscopic disease activity. Each variable is scored for the 5 intestinal 
segments (ileum, right colon, transverse colon, left colon, and rectum) and summed to provide the 
total variable score. The sum of each variable score ranges from 0 to 15, except for stenosis, where 
it ranges from 0 to 11, because 3 represents a stenosis through which a colonoscope cannot be 
passed and therefore, can only be observed once. Total SES-CD score is then calculated by 
summing the item scores (0-56 points). A score of zero is imputed for the missing items within a 
segment; if all components are missing, the total score will also be missing. [2] See Appendix A 
for additional details. 
In general, a total SES-CD score can be calculated if the scores are available for at least 2 segments, 
and the total score is the sum of available segment scores, with the exception that if any segment 
is missing at Baseline, in which event the post-Baseline SES-CD will not include the specific 
segment. 
Post-Baseline endoscopy perfomed out of study window can be used for the study visit (e.g., Week 
12) if the procedure date is within the time window of 2 weeks prior to and 6 weeks after the date 
of study visit. 
 
6.1.1.1 Central Scoring of Endoscopy Videos 
All endoscopy videos are scored for the SES-CD independently by two blinded central readers. If 
adjudication is required, a third central reader will also score the video. Adjudication is required 
if any of the follow are true: 
• Screening Assessment: 
o Central readers do not agree on the subject’s eligibility (SES-CD score of ≥6 for 
ileocolonic and colonic only disease or ≥4 for ileal only disease). 
• End of Induction (Week 12) Assessment: 
o Central readers do not agree on the subject’s response to treatment (≥50% decrease 
in SES-CD score from baseline). 
• All Assessments: 
o Central readers disagree on the inability to score the video due to video quality 
concerns. 
The medians of the two or three central reader scores are used to form the outcome scores. The 
medians of each component (ulcer size, proportion of ulcerated surface, proportion of the surface 
area affected by any disease lesion, and stenosis) within each segment are rounded up to the next 
whole number, the total segmental score is reported as the sum of each component’s unrounded 
median score within the segment reported to one decimal, and the total score is calculated as the 
sum of all resulting segmental totals (reported to one decimal) and rounded to integer. 
6.1.2 CROHN’S DISEASE ACTIVITY INDEX (CDAI) 
The Crohn’s Disease Activity Index(CDAI) consists of 8 items including physical examination 
items, extraintestinal manifestations, the hematocrit, and patient-reported outcome measures 
(number of liquid or very soft stools/day, abdominal pain, fever and general well-being), which 
are recorded by the subject in the electronic diary (or paper diary as backup in case of electronic 
diary not be available). A lookback to the 7 days prior to the clinic visit (Appendix B) will be used 
for CDAI score calculation. [3] Each item is multiplied by a weighting factor and summed to give 


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a total CDAI score, ranging from 0 to over 600 points, with higher scores representing more severe 
disease activity. Evaluable days do not include days of bowel prep, day of colonoscopy, and two 
days after colonoscopy. 
If the full seven evaluable days of daily diary information for any of the patient-reported outcome 
measures (number of liquid stools, abdominal pain, general well-being) are not present, the 
following imputation rules will be applied: 
1. If five or six days are available, the available data will be summed and reweighted for seven 
days. E.g. for five days: Abdominal Pain Score = SUM(five days) × 7⁄5 
2. If four or fewer days are available, then reach back to 10 days rather than 7 days prior to 
the visit. If there are at least 5 evaluable days of symptoms in the 10 day window, the 
available data will be summed and reweighted (if necessary) for the seven day score. 
3. If there are still four or fewer evaluable days of symptoms in 10 days, then the component 
score will be considered missing. 
The resulting days of eDiary used will apply to fever (a part of extraintestinal manifestation) and 
use of antidiarrheal medication. 
 
For the component of extraintestinal manifestation, if the assessment is not done at a visit, data of 
evaluation from visits (including unscheduled visits) within 60 days prior to, or within 7 days after 
the study visit will be used. As fever is captured via eDiary, any presence of fever from the days 
of the eDiaries above will be counted as 1; 0 otherwise. 
For the component of use of antidiarrheal medication, any recorded use of antidiarrheal medication 
from the days of eDiaries above will result in a ‘Yes’; ‘No’ otherwise. 
For the component of abdominal mass, if the assessment is not done at a visit, the last known status 
will be used. 
For lab value of hemacrit, central lab value from the study visit should be used. If the study visit 
hemacrit is not evaluable, value from other visits within 60 days prior to, or within 7 days after the 
study visit will be used. 
For body weight, if weight is not measured at the study visit, the last known weight prior to the 
study visit will be used. 
CDAI score at a study visit will be considered missing if any of these components is missing 
according the rules above. 
 
6.1.2.1  2-item Patient-reported Outcome Measure (PRO-2) 
The PRO2 consists of two CDAI component items: daily stool frequency and abdominal pain. [4] 
Study participants record the number of liquid or very soft stools and rate abdominal pain (from 
0-3) daily, excluding non-evaluable days. The average of the daily entries for the 7-day period is 
calculated and multiplied by a weighting factor to provide a total score for each component item. 
The total PRO2 score is then calculated by summing the component item scores. See Appendix C 
for additional details. The similar imputation rules (without reweighting) will be applied to the 
PRO-2 as in the CDAI. 


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6.1.3 PERIANAL DISEASE ACTIVITY INDEX (PDAI) 
The Perianal Disease Activity Index Activity Index (PDAI) will be used to evaluate severity of 
perianal disease. The PDAI incorporates 5 items: discharge, pain, restriction of sexual activity, 
type of perianal disease, and degree of induration. Each category is graded on a 5-point Likert 
scale ranging from no symptoms (score of 0) to severe symptoms (score of 4). Scores can range 
from 0 - 20, with higher scores indicating more severe perianal disease. See Appendix D for 
additional details. 
6.1.4 GLOBAL HISTOLOGIC DISEASE ACTIVITY SCORE (GHAS) 
The Global Histologic Disease Activity Score (GHAS) assesses the extent and/or severity of 7 
histologic variables (Appendix E). [5] The total GHAS (range: 0-16) per segment is calculated by 
adding up the scores for each histological variable, with higher scores representing more severe 
disease activity. The overall total GHAS is the sum of all affected segments. Disease activity is 
scored separately for colonic (CGHAS) and ileal (IGHAS) biopsies. 
6.1.5 ROBERTS HISTOPATHOLOGY INDEX (RHI) 
The Roberts Histopathology Index (RHI) was developed by selecting items from the Geboes score 
that showed at least moderate intra-rater reliability and best predicted overall microscopic disease 
activity on a visual analogue scale. [6] The 4 items selected for inclusion include: 1) the extent of 
chronic inflammatory cell infiltration, 2) neutrophils in the lamina propria, 3) neutrophils in the 
epithelium, and 4) erosions and ulceration (see Appendix E). Each item is scored from 0 to 3 and 
multiplied by a weighting factor and summed to give the overall RHI score, with total scores 
ranging from 0 (no disease activity) to 33 (severe disease activity). 
 
6.2 
PRIMARY EFFICACY ENDPOINT 
The primary efficacy endpoint, endoscopic improvement at Week 12, will be used to assess the 
efficacy of PRA023. The proportion of subjects in PP analysis set with endoscopic improvement 
at Week 12 will be tested against the null hypothesis of 12%, an upper bound of observed placebo 
rate from multiple CD trials (Table below and Table 6 of study protocol). 
 
Clinical Trial 
N 
Placebo Endoscopic Response Rate (%) 
Feagan et al. 2017 
39 
13 
Vermeire et al. 2017 
44 
14 
Sands et al. 2019 
64 
10.9 
Selinger et al. 2018 
59 
3.4 
Advance Study 2021 
175 
12 
Motivate Study 2021 
187 
11 
Average 
10.7 
Sample-size Weighted Average 
568 
9.5 
95% CI 
(7.1, 11.9) 


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6.2.1 PRIMARY ANALYSIS 
The proportion of subjects with endoscopic improvement in PP analysis set will be estimated by 
the number of subjects who achieved the improvement at Week 12 divided by the total number of 
subjects in PP analysis set. The confidence interval for the proportion will be calculated using 
Wilson-score method (Wilson 1927). If the resulting lower bound of 95% CI is greater than 12%, 
the null hypothesis is, therefore, rejected at a 1-sided significance level of 0. 025. 
6.2.2 SENSITIVITY ANALYSIS 
In the sensitivity analysis, patients in FAS with missing SES-CD score at Week 12 will be 
considered as a non-responder for the endpoint of endoscopic improvement. The 95% confidence 
interval will then be calculated according to Wilson score method. 
 
The proportion of subjects with endoscopic improvement for PP analysis set and associated 95% 
confidence intervals will also be estimated by the following subgroups: 
• CDx status (CDx+ or CDx-) 
• Number of prior biologic use (0, 1, or 2+) 
• Disease extent (ileal only, colonic only, or both) 
• Disease severity (baseline SES-CD<=16, or >16) 
• Concomitant use of immunosuppressive including AZA, 6MP, and MTX (Yes, or No) 
• Concomitant use of oral corticosteroids (Yes, or No) 
• ADA status (positive, negative) 
Given the small sample size of the trial, the results of subgroup analysis should be interpreted with 
caution. The forgoing analysis may be modified when the sample size in a subgroup is deemed too 
small. 
 
6.3 
SECONDARY EFFICACY ENDPOINTS 
6.3.1 DICHOTOMOUS OR BINARY ENDPOINTS 
The definition of the dichotomous secondary efficacy endpoints (i.e., responders) are listed in 
Table 3 below. 
 
Table 3 Definition of Secondary Binary Endpoints 
 
Outcome 
Measure 
Definition 
Analysis Timepoints 
Clinical Remission 
CDAI 
Crohn’s disease activity index [CDAI] < 
150 
Week 12 
Endoscopic and 
clinical improvement 
SES-CD and 
CDAI 
Decrease in SES-CD ≥ 50% AND 
reduction in CDAI ≥ 100 points from 
Baseline, or CDAI<150 
Week 12 
Biomarker and 
Clinical Composite 
Improvement 
hsCRP and 
CDAI 
Decrease in hsCRP or fecal calprotectin ≥ 
50% from Baseline and reduction in 
Week 12 


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CDAI ≥ 100 points from Baseline, or 
CDAI<150 
Clinical Response 
CDAI 
Reduction in CDAI ≥ 100 points from 
Baseline or CDAI<150 
Week 12 
PRO-2 remission 
Abdominal 
pain score and 
Stool 
frequency 
Average daily abdominal pain score ≤ 1 
point and average daily stool frequency ≤ 
3 points with abdominal pain and stool 
frequency no worse than Baseline 
Week 12 
Normalization of 
hsCRP 
hsCRP 
hsCRP < ULN, among subjects whose 
baseline hsCRP ≥ ULN 
Baseline, Week 12 
Normalization of fecal 
calprotectin 
fecal 
calprotectin 
fecal calprotectin < ULN, among subjects 
whose baseline fecal calprotectin ≥ ULN 
Week 12 
Anti-drug antibody 
(ADA) and 
Neutralizing antibody 
(Nab) 
ADA and Nab 
Positive ADA at any time; Posotive Nab 
at any time 
Over time 
Abbreviations: SES-CD, Simple endoscopy score for Crohn’s disease; CDAI, Crohn’s disease activity index; hsCRP, High sensitivity C-reactive 
protein; PRO-2, Two component patient-reported outcome; ADA, Anti-drug antibody; Nab, Neutralizing antibody. 
 
The proportion of clinical remission in FAS will be analyzed according to the method similar to 
the sensitivity analysis for the primary efficacy endpoint, in the case of missing data in CDAI at 
Week 12. If the resulting lower limit of 95% confidence interval is greater than 16%, the observed 
remission rate for the placebo treated patients from multiple prior CD trials ( [1], [7], [8], [9], [10]), 
the null hypothesis for the first secondary endpoint of clinical remission at Week 12 will be rejected 
at a 1-sided significance level of 0.025. 
 
The point estimate and 95% CI for the secondary efficacy endpoints will be calculated for FAS, 
while the missing values in the categorical endpoint will be imputed as non-responders. 
Subgroup analysis (defined in section 6.2.2) may be performed for clinical remission, endoscopic 
and clinical improvement, biomarker and clinical composite improvement, clinical response, and 
PRO-2 remission. 
6.3.2 CONTINUOUS ENDPOINTS 
The mean change from baseline in SES-CD score at Week 12 for PP analysis set will be estimated 
using ANCOVA with baseline SES-CD score as covariates. The 95% confidence interval for the 
LS mean for the change from baseline at Week 12 will be calculated. The median for the change 
from baseline in SES-CD score at Week 12 for PP analysis set will also be estimated and p-value 
for testing against no change will be reported using Wilcoxon rank test. 
 
6.4 
EXPLORATORY EFFICACY ENDPOINTS 
6.4.1 DICHOTOMOUS OR BINARY ENDPOINTS 
The definition of the binary exploratory endpoints are listed in Table 4 below. 


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Table 4 Definition of Exploratory Binary Endpoints 
 
Outcome 
Measure 
Definition 
Analysis Timepoints 
Endscopic Remission 
SES-CD 
SES-CD <=4 and at least 2-point 
reduction from baseline and all individual 
score <=1 
Week 12 
Ulcer-free 
SES-CD 
(Ulcerated 
Surface) 
SES-CD ulcerated surface score of 0, 
among patients with SES-CD ulcerated 
surface score >=1 at baseline 
Week 12 
Clinical response by 
PRO-2 
PRO-2 
>=30% reduction of either score and no 
worsening in both scores 
Over time 
Clinical response by 
PRO-2 total score 
PRO-2 
>=30% reduction of PRO-2 total score 
Over time 
Enhanced Clinical 
response by PRO-2 
PRO-2 
reduction of >=60% in averge daily stool 
frequencies or a reduction of >=35% in 
average daily abdominal pain score, and 
no worsening in both score 
Over time 
Enhanced Clinical 
response and 
Endoscopic 
improvement 
PRO-2 and 
SES-CD 
enhanced clinical response by PRO-2 
score and endoscopic improvement 
Week 12 
IBDQ Remission 
IBDQ 
IBDQ total score of >170 
Week 12 
IBDQ Rresponse 
IBDQ 
>=16-point increase from baseline or an 
absolute score of >170 
Week 12 
Improvement or 
remission of 
enterocutaneous 
and/or perianal fistula 
Fistula 
Fistula Improvement from baseline 
among patients with fistula at baselinef 
Week 12 
GHAS histologic 
remission 
GHAS 
No neutrophils in the epithelium or 
subscore of 0 
Week 12 
GHAS histologic 
response 
GHAS 
GHAS histologic score ≤ 4 
Week 12 
Robarts histologic 
remission 
RHI 
RHI<3 
Week 12 
Robarts histologic 
response 
RHI 
Robarts histologic score < 5 
Week 12 
Abbreviations: SES-CD, Simple endoscopy score for Crohn’s disease; CDAI, Crohn’s disease activity index; hsCRP, High sensitivity C-reactive 
protein; PRO-2, Two component patient-reported outcome; GHAS, Global histological activity score; RHI, Robarts histopathology index; IBDQ, 
Inflammatory Bowel Disease Questionnaire. 
 
The proportion of subjects of meeting the definition of these endpoints will be calculated in FAS, 
though patients with missing data will be excluded from the summary. 
 
6.4.2 CONTINUOUS EFFICACY ENDPOINTS 
The definition of the continue efficacy endpoints (Mean Change from Baseline) by visit are listed 
in Table 5 below. 
 
Table 5 Definition of Exploratory Continuous Endpoints 


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Measure 
Definition 
Analysis 
Timepoint 
SES-CD segment score 
Mean change from baseline 
Week 12 
PD markers (TL1A 
concentrations, fecal 
calprotectin, and hsCRP) 
Mean fold change from baseline 
Over time 
RHI 
Mean change in Robarts Histopathology Index (RHI) from baseline 
Week 12 
GHAS 
Mean change in global histological activity score (GHAS) from 
baseline 
Week 12 
PDAI 
Mean change in Perianal Disease Activity Index(PDAI) subscore 
from baseline 
Week 12 
CDAI 
Mean change in CDAI and components from Baseline over time 
Over time 
PRO-2 
Mean change in PRO-2 over time 
Over time 
IBDQ 
Mean change from baseline in IBDQ score over time 
Over time 
Abbreviations: CDAI, Crohn’s disease activity index; hsCRP, High sensitivity C-reactive protein; PRO-2, Two component patient-reported outcome; 
RHI, Robarts Histopathology Index; GHAS, Global histological activity score; SES-CD, Simple endoscopy score for Crohn’s disease; PDAI, Perianal 
Disease Activity Index; IBDQ, Inflammatory Bowel Disease Questionnaire. 
In general, continuous endpoints will be summarized using descriptive statistics of the values at 
each visit and the change from baseline to each post-baseline visit. Missing data will not be 
imputed for descriptive statistics. 
The mean change in CDAI over time through Week 12, mean change in PRO-2 over time through 
Week 12 and mean change in IBDQ score over time through Week 12 will be estimated according 
to a MMRM model with baseline CDAI, visit as fixed effect and subject as random effect. The 
95% confidence intervals at each time point will be calculated according to the MMRM model. 
This analysis will be conducted by maximum likelihood methods using the SAS PROC MIXED 
procedure. 
Additional descriptive summary over time will be reported for patients who entered OLE based on 
available data as of cutoff date of the DBL for Induction period. 
 
6.5 
EVALUATION OF PHARMACODYNAMIC PARAMETERS 
The PD markers (hsCRP, fecal calprotectin, and total sTL1A) will be summarized using 
descriptive statistics: N, mean, SD, min, max, median, coefficient of variation as a percent (CV 
%), and Geometric Mean (GM) by CDx status. 
 
Stool samples for analysis of fecal calprotectin will be collected prior to any bowel preparation. 
Subjects will receive instructions and stool sample supplies for collection at home. 
Listings and descriptive statistics (n, mean [or geometric mean], median, SD, CV%, min and max) 
will be provided by treatment group for each biomarkers (fecal lactoferrin, hsCRP, total sTL1A) 
specified in the study protocol as follows: 
• Baseline values 
• Values at each post-baseline visit 
• Change from baseline or fold change from baseline at each post-baseline visit, depending 
on the data distribution of a PD marker 


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• % Change from baseline at each post-baseline visit, as appropriate 
In the case of multiple values in an analysis visit, data will be selected for analysis as described in 
Section 4.4. Graphs of change from baseline will be presented, as appropriate. 
 
6.6 
EVALUATION OF PHARMACOKINETIC PARAMETERS 
PK parameters will be computed, as appropriate, from the individual serum concentrations using 
a non-compartmental approach. All PK parameters will be summarized using descriptive statistics: 
N, mean[or geometric mean], SD, min, max, median, CV %, and GM and GM CV%. Serum 
concentrations of PRA023 will be summarized. 
 
6.7 
EVALUATION OF IMMUNOGENICITY 
The proportion of subjects with any sample positive for ADA and the proportion of subjects with 
any sample positive for neutralizing antibody (Nab) will be summarized by the study period and 
dose using descriptive statistics. The PRA023 concentrations from all subjects and subjects with 
no sample positive for ADA will be summarized to assess whether ADA has an impact on PRA023 
exposure. 
 
6.8 
MISSING DATA HANDLING 
6.8.1 NON-RESPONDER IMPUTATION (NRI) 
For the responder analyses as described in Table 3 of Section 6.2, unless specified otherwise, 
subjects who do not have sufficient measurements to determine the endpoint will be considered as 
non-responders (i.e., non-responder imputation (NRI). Specifically, all subjects who discontinue 
from the study at any time prior to the assessment timepoint (regardless of reason) or fail to have 
an adequate efficacy assessment at that timepoint will be considered a non-responder. 
 
6.9 
SENSITIVITY ANALYSES 
To evaluate of the robustness of the primary efficacy analysis, the binary endpoint based on the 
NRI in PP analysis set will use the same analysis methods for FAS as described in Section 6.2.1. 
 
6.10 MULTIPLICITY 
A closed hierarchical procedure will be used to control for multiple comparisons for the primary 
endpoint aand the first secondary endpoint. The order of testing will be primary endpoint, followed 
by the secondary endpoint of clinical remission at Week 12. If the null hypothesis for the primary 
endpoint is not rejected, the testing procedure will be terminated. The subsequent analysis of 
clinical remission would be considered exploratory. 
 
7 
SAFETY ANALYSES 
Safety will be evaluated via descriptive statistics and point estimates for patients in Safety Analysis 
Set. No inferential testing for statistical significance will be performed. 


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7.1 
ADVERSE EVENTS 
7.1.1 ADVERSE EVENT DICTIONARY 
All AEs will be classified according to the Medical Dictionary for Regulatory Activities 
(MedDRA) dictionary. System organ class (SOC) and preferred term (PT) will be provided in the 
AE dataset. 
7.1.2 ADVERSE EVENT SEVERITY 
The severity of AEs will be graded according to the National Cancer Institute (NCI) Common 
Terminology Criteria for Adverse Events (CTCAE) version 5.0 (27 November 2017). The general 
categories for each grade are presented in Table 6. 
 
Table 6 Adverse Event Severity Grading 
 
Grade 
Severity 
Alternate Description 
1 
Mild 
Asymptomatic or mild symptoms; clinical or diagnostic observations only; 
intervention not indicated 
2 
Moderate 
Minimal; local or noninvasive intervention indicated; limiting age appropriate 
instrumental ADL 
3 
Severe 
Severe or medically significant but not immediately life-threatening; 
hospitalization or prolongation of hospitalization indicated; disabling; limiting 
self-care ADL 
4 
Very severe, life- 
threatening, or disabling 
Life-threatening consequences; urgent intervention indicated 
5 
Death related to AE 
Death related to AE 
 
7.1.3 RELATIONSHIP OF ADVERSE EVENT TO STUDY TREATMENT 
The relationship of the AE to study treatment (PRA023) will be assessed by the investigator. The 
Investigator will define the relationship of an AE to the study drug by selecting one of the 
following categories: 
• Related: There is a reasonable possibility that there is a causal relationship between the 
study drug and the AE. 
• Not Related: There is not a reasonable possibility that there is a causal relationship between 
the study drug and the AE. 
Relationship (causality) to study procedures should be determined for all pre-treatment-emergent 
events and AEs. The relationship should be assessed as Related if the Investigator considers that 
there is reasonable possibility that an event is due to a study procedure. Otherwise, the relationship 
should be assessed as Not Related. 
7.1.4 SERIOUS ADVERSE EVENTS 
Serious adverse events will be identified and captured as SAEs if AEs met the definitions of SAEs 
that were specified in the study protocol (Section 10.1.4). 


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7.1.5 ADVERSE EVENT OF SPECIAL INTEREST 
An infusion reaction is defined as adverse events reported within the terms of hypersensitivity 
MedDRA SMQ (20000214 ) that occurred within 1 hour after the end of study drug infusion. A 
peri-infusion reaction is defined as adverse events reported within the terms of hypersensitivity 
SMQ (20000214)that occurred within 24 hours after the end of study drug infusion. 
An infection is defined as those events coded under MedDRA body system of Infection and 
Infestation. 
7.1.6 TREATMENT EMERGENT ADVERSE EVENTS 
7.1.6.1 Definition of Treatment Emergent Adverse Events 
Treatment Emergent Adverse Events (TEAE) are defined as following: 
• AE onset date ≥ 1st study treatment date; or 
• AE worsened on or after the 1st study treatment date 
AEs recorded prior to the first infusion of study treatment will be considered non-treatment- 
emergent. All reported AEs (treatment-emergent or not) will be listed. Only TEAEs will be 
summarized. 
AEs of special interest including infections, acute infusion reaction (within 1 hour of completion 
of infusion), and peri-infusion reaction (within 24 hours of completion of infusion) will be 
summarized based on a pre-specified MedDRA list. 
AEs occurring in subjects who are considered immunogenicity positive will also be summarized. 
 
7.1.6.2 Incomplete Dates 
If the onset date of AE is incomplete and the AE stop date is not prior to the first dosing date of 
study treatment, then the month and year (or year alone if month is not recorded) of onset determine 
whether an AE is treatment emergent. The event is considered treatment emergent if both of the 
following 2 criteria are met: 
• The AE onset/severity worsened is the same as or after the month and year (or year) of 
the first dosing date of study treatment, and 
• The AE onset/severity worsened is the same as or before the month and year (or year) of 
the last dosing date of study treatment 
An AE with completely missing onset and stop dates, or with the onset date missing and a stop 
date later than the first dosing date of study treatment, will be considered to be treatment emergent. 
In addition, an AE with onset date missing and incomplete stop date with the same or later month 
and year (or year alone if month is not recorded) as the first dosing date of study treatment will be 
considered treatment emergent. 
7.1.7 SUMMARIES OF ADVERSE EVENTS 
Treatment Emergent (TE) AEs will be summarized based on the Safety Analysis Set by treatment 
period and post-treatment period, separately. 
Summary tables will be presented to provide the number and percentage of subjects experiencing 
any AEs, any severe AEs, any drug-related AEs, any SAEs, any drug-related SAEs, and any AEs 
leading to study drug interruption or discontinuation. 


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In addition to the above summary table, summary tables and listings of adverse events listed below 
will be provided. 
• 
Summary of TEAEs by SOC and PT 
• 
Summary of TEAEs by SOC, PT and Max Severity 
• 
Summary of Severe (CTCAE Grade ≥ 3) TEAEs by SOC and PT 
• 
Summary of Related TEAEs by SOC and PT 
• 
Summary of TESAEs by SOC and PT 
• 
Summary of Related TESAEs by SOC and PT 
• 
Summary of AEs in Follow-up by SOC and PT 
• 
Listing of All AEs 
• 
Listing of TESAEs or Death 
• 
Listing of TEAEs Leading to Study Drug Interruption or Discontinuation 
 
7.2 
PHYSICAL EXAMINATION 
Physical examination is performed at the screening visit. All abnormal findings will be presented 
in a by-subject listing. 
 
7.3 
VITAL SIGNS 
Descriptive statistics will be provided by treatment group for vital signs (blood pressure (mm Hg), 
heart rate (bpm), respiratory rate, temperature, weight (kg), height (m) and BMI (kg/m2)) as 
follows: 
• Baseline values 
• Values at each post-baseline visit 
• Change from baseline at each post-baseline visit 
Body mass index (BMI) will be calculated from height and weight measurements collected at screening 
and Week 12/EOT using the following formula: 
BMI = Weight (kg) / [Height (m)]2. 
A by-subject listing of vital signs will be provided by treatment group, subject ID number and visit 
in chronological order. 
Subjects with markedly abnormal vital signs (criteria depicted in Table 7) will be summarized by 
study period. 
 
Table 7 Markedly Abnormal Vital Signs 
 
Markedly Abnormal Vital Signs 
Weight 
increase or decrease ≥ 20% from Baseline 
Heart Rate 
(Increase of > 20 bpm from Baseline and >120 bpm) 
OR (decrease of > 20 bpm and <60 bpm) 
SBP 
(Increase of >20 mmHg from Baseline AND >160 
mmHg) OR (decrease of >20 mmHg from Baseline 
AND <80 mmHg) 


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DBP 
(Increase of >20 mmHg from Baseline AND >100 
mmHg ) OR (decrease of >20 mmHg from Baseline 
AND <60 mmHg) 
 
 
7.4 
CLINCAL LABORATORY TESTS 
Descriptive statistics will be provided by treatment group for each laboratory test (hematology, 
serum chemistry, and urinalysis) specified in the study protocol as follows: 
• Baseline values 
• Values at each post-baseline visit 
• Change from baseline at each post-baseline visit 
Tabulated tables will be presented by showing change in lab normal range (low, normal, and high) 
for clinical laboratory values by treatment group. A shift table describing out-of-normal range 
shifts will be provided for clinical laboratory results. 
In the by subject listings, laboratory values which fall outside the reference ranges and abnormal 
findings will be flagged. The listing will include treatment group, subject ID, laboratory collection 
date/time, analyte name, and analyte finding. 
Subjects with markedly abnormal lab values (criteria depicted in Table 8) will be summarized by 
study period. 
 
Table 8 Markedly Abnormal Laboratory 
 
Markedly Abnormal Laboratory 
Hematology 
Hemoglobin 
<8.0 g/dL 
Platelet 
<50,000/mm^3 
WBC 
<2000/mm^3 
Neutrophils (absolute) 
<1000/mm^3 
Lymphocytes (Absolute) 
<500/mm^3 or >200,00/mm^3 
Chemistry 
ALT 
>5 X ULN 
AST 
>5X ULN 
Alkalikne phosphatase 
>5 X ULN 
Total bilirubin 
>3X ULN 
GGT 
>5X ULN 
Potassium 
>6.0 mmol/L or <3.0 mmol/L 
Sodium 
>155 mmol/L or <130 mmol/L 
Cholesterol 
>400 mg/dL 
CPK 
>5X ULN 
Creatinine 
>3X ULN or 3X of Baseline 


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Calcium 
>12.6 mg/dL or <7 mg/dL 
Glucose 
>250 mg/dL or <40 mg/dL 
Triglyceride 
>500 mg/dL 
Albumin 
<2 g/dL 
 
 
 
7.5 
ELECTROCARDIOGRAMS 
ECG measurements are obtained at the screening visit and Week 12. Single 12-lead ECG will be 
obtained using an ECG machine that may automatically report heart rate, PR, QRS, QT, and/or 
Fridericia’s corrected QT (QTcF) intervals. If any of these parameters are not automatically 
reported, they may be measured or calculated. 
The ECG assessment values at each visit and change from baseline to each visit will be 
summarized and shift table using the normal/abnormal classification to compare baseline to the 
post-baseline visit values will be provided. In addition, a by-subject listings, which includes 
treatment group, subject ID, ECG date/time, test name, test result and ECG interpretation (eg, 
clinical interpretation, normal abnormal, not clinically significant, abnormal, clinically significant) 
will be presented. If any clinically significant ECG measurement occurs, it will be recorded as an 
AE. 
 
8 
OTHER ANALYSES 
 
8.1 
QUALITY OF LIFE(QOL) 
The Inflammatory Bowel Disease Questionnaire (IBDQ) is a self-administered, disease-specific 
Health-Related Quality of Life (HRQOL) instrument for patients with IBD. [11] The IBDQ covers 
4 dimensions: bowel symptoms (10 items, questions 1, 5, 9, 13, 17, 20, 22, 24, 26, and 29), 
systemic symptoms (5 items, questions 2, 6, 10, 14 and 18), emotional function (12 items, 
questions 3, 7, 11,15, 19, 21, 23, 27, 30, 31 and 32 ), and social function (5 items, questions 4, 8, 
12, 16, and 28). Items are scored on a 7-point Likert scale, for a total global score in the range 32 
to 224 (with higher scores indicating better HRQOL). 
IBDQ scores will be collected at Week 0 Visit, Week 6 Visit, and Week 12 Visit. Summary 
statistics of the absolute and change from baseline scores for IBDQ total score and each subscale 
score will be displayed by treatment group and visit. 
IBDQ Scores will be calculated as follows: 
• The question on the same day of measurement will be used for calculation of each subscore 
and total score. 
• For each subscore, sum of the questions will be round off to the first decimal place. 
• IBDQ total score: sum of all questions and round off to the first decimal places. 
• The value of each question after imputing missing data will be used for the calculation of 
each subscore. 


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The instructions on how the IBDQ score is calculated in the presence of missing or incomplete 
information is provided below with detailed scenarios given in Table 9. Rules for handing missing 
data: 
1. If no response is given for a particular question and only one response per dimensional 
score is missing, impute the missing value to be equal to the mean score for that other item 
of the subscore 
2. If two or more questions are unanswered for a particular domain, then the subscore will be 
set to missing. 
If after steps 1 and 2, more than 4 questions are missing for the full IBQD, then the total IBDQ 
will be set to missing. 
 
Table 9 IBDQ Missing Data Instructions 
 
Number of Missing Values 
Comments/Actions 
Subscore 1 
Subscore 2 
Subscore 
3 
Subscore 4 
Scenario 
A 
0 
0 
0 
0 
We can compute 4 subscores and the full IBDQ 
Scenario 
B 
1 
0 
0 
0 
We can compute both the full IBDQ and the 4 subscores, by replacing the missing 
value with the average mean (computed on the data available for its own subscore) 
Scenario 
C 
1 
1 
1 
1 
We can compute both the full IBDQ and the 4 subscores, by replacing the missing 
value with the average mean (each one computed on the data available for its own 
subscore) 
Scenario 
D 
2 
0 
0 
0 
We can compute the full IBDQ by replacing the 2 missing values with the average 
mean (computed on the data available for its own subscore). We can compute only 3 
subscores. 
Scenario 
E 
2 
1 
0 
1 
We can compute the full IBDQ by replacing the missing values with the average 
mean (each one computed on the data available for its own subscore). We can 
compute only 3 subscores. 
Scenario 
F 
2 
1 
1 
1 
We cannot compute the full IBDQ (more than 4 missing values). We can compute 
only 3 subscores. 
Scenario 
G 
2 
2 
0 
0 
We cannot compute the full IBDQ because in more than one subscore there are 2 
missing values (even though the total missing value is not exceeding 4). We can 
compute only 2 subscores. 
Scenario 
H 
0 
0 
3 
0 
We cannot compute the full IBDQ because there is one subscore with more than 2 
missing values. We can compute only 3 subscores. 
 
 
9 
NUMBER AND TIMING OF ANALYSES 
There will be a primary analysis after all subjects have completed 12-week IP. During the 
primary analysis, interim results from the OLE will be summarized descriptively. Complete 
analysis for the OLE will be covered in a different SAP. 
 
10 CHANGES FROM PROTOCOL 
Methods in this SAP different form the methods described in the protocol are summarized as 
follow: 
• In Section 2, for objectives and endpoints that has accessing timepoint at Week 50, all 
timepoints at Week 50 were removed from this SAP. The final analysis of OLE data will 
be specified in a separate SAP. 


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• In Section 2 and Section 3.1, the definition for clinical response is refined so that 
responders will also include those patients who achieve clinical remission (CDAI < 150) 
but may not achieve >=100 point reduction in CDAI from baseline. 
• In section 2, additional exploratory endpoints (endoscopic remission, ulcer-free at Week 
12, change in SES-CD segment score from baseline to week 12, clinical improvement by 
PRO-2 score, IBDQ remission or response,(steroid-free clinical remission for CDAI and 
by PRO-2, steroid-free clinical improvement by CDAI and by PRO-2, Clinical response 
by PRO-2 total score,) were add in the overall objectives and endpoints. 
• In section 2, serum PD marker EHI was removed from the SAP. It will be analyzed when 
it becomes available. 
• For analysis populations, PP analysis set was added. 
• For evaluation of primary efficacy endpoint, the analysis specified in SAP V01 based on 
the method of multiple imputation was removed due to the known lack of sufficient 
correlation between SES-CD and CDAI scores in prior CD clinical trials. Instead, PP 
analysis set, which requires evaluable endoscopic score at Week 12, will be used and the 
confidence interval for the proportion will be calculated using Wilson-score method. 
• Sensitivity analysis based on FAS was added to further access the robustness of primary 
analysis. 
• For evaluation of secondary efficacy dichotomous or binary endpoint, the confidence 
interval for the proportion will be calculated using Wilson-score method, while non- 
responder imputation may apply for missing endpoint. 
•  For evaluation of the continuous secondary efficacy endpoint, PP analysis set and 
ANCOVA will be used for the change from baseline in SES-CD at Week 12. The median 
for the change from baseline in SES-CD score at Week 12 for PP analysis set will also be 
estimated and p-value for testing against no change will be reported using Wilcoxon rank 
test 
• For evaluation of continuous exploratory efficacy endpoints, endpoints with multiple 
assessments over time, MMRM will be used. The 95% confidence interval for the LS mean 
for the change from baseline at Week 12 will be calculated. 
• For evaluation of exploratory efficacy endpoint, proportion of subjects of meeting the 
definition will be calculated. For evaluation of continuous exploratory efficacy endpoints, 
MMRM method will be used, where appropriate. 
 
 
11 REVISION HISTORY 
Version 
Effective Date 
Reason 
V01 
28FEB2022 
New 
V02 
19APR2022 
Amendment 


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12 REFERENCES 
 
[1] Feagan, Brian G et al., "Induction therapy with the selective interleukin-23 inhibitor 
risankizumab in patients with moderate-to-severe Crohn's disease: a randomised, double- 
blind, placebo-controlled phase 2 study," The Lancet, pp. P1699-1709, 2017. 
[2] Daperno M, D'Haens G, Van Assche G, Baert F, Bulois P, Maunoury V, et al, 
"Development and validation of a new, simplified endoscopic activity score for Crohn's 
disease: the SES-CD," in Gastrointest Endosc, 2004. 
[3] Best WR, Becktel JM, Singleton JW, Kern F, Jr., "Development of a Crohn's disease 
activity index. National Cooperative Crohn's Disease Study," in Gastroenterology, 1976. 
[4] Khanna R, Zou G, D'Haens G, Feagan BG, Sandborn WJ, Vandervoort MK, et al, "A 
retrospective analysis: the development of patient reported outcome measures for the 
assessment of Crohn's disease activity," in Aliment Pharmacol Ther, 2015. 
[5] D'Haens GR, Geboes K, Peeters M, Baert F, Penninckx F, Rutgeerts P., "Early lesions of 
recurrent Crohn's disease caused by infusion of intestinal contents in excluded ileum," in 
Gastroenterology, 1998. 
[6] Mosli MH, Feagan BG, Zou G, Sandborn WJ, D'Haens G, Khanna R, Shackelton LM, 
Walker CW, Nelson S, Vandervoort MK, Frisbie V, Samaan MA, Jairath V, Driman DK, 
Geboes K, Valasek MA, Pai RK, Lauwers GY, Riddell R, Stitt LW, Levesque BG., 
"Development and validation of a histological index for UC," in GUT, 2017. 
[7] "Risankizumab (SKYRIZI®) Demonstrates Significant Improvements in Clinical 
Remission and Endoscopic Response in Two Phase 3 Induction Studies in Patients with 
Crohn's Disease," 07 01 2021. [Online]. Available: https://news.abbvie.com/news/press- 
releases/risankizumab-skyrizi-demonstrates-significant-improvements-in-clinical- 
remission-and-endoscopic-response-in-two-phase-3-induction-studies-in-patients-with- 
crohns-disease.htm. [Accessed 04 10 2021]. 
[8] William J. Sandborn, et al., "Efficacy and Safety of Mirikizumab (LY3074828) in a 
Randomized Phase 2 Study of Patients with Crohn's Disease," Gastroenterology, vol. 162, 
2022. 
[9] S. W. Selinger C, "Etrolizumab as induction therapy in moderate to severe crohn's disease: 
results from bergamot cohort 1," in Cochrane Library, 2018. 
[10] S. S. Vermeire S, "Clinical remission in patients with moderate-to-severe Crohn's disease 
treated with filgotinib (the FITZROY study): results from a phase 2, double-blind, 
randomised, placebo-controlled trial," in Cochrance Library, Lancet, 2017. 
[11] Guyatt G, Mitchell A, Irvine EJ, Singer J, Williams N, Goodacre R, et al, "A new measure 
of health status for clinical trials in inflammatory bowel disease," Gastroenterology, Vols. 
96(3):804-10, 1989 Mar. 


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STATISTICAL ANALYSIS 
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APPENDICES 
 
APPENDIX A. 
SIMPLE ENDOSCOPIC SCORE FOR CROHN’S DISEASE (SES- 
CD) 
 
The Simple Endoscopic Score for Crohn’s Disease (SES-CD) assesses the size of mucosal ulcers, 
the ulcerated surface, the endoscopic extension, and the presence of stenosis. 
 
Variable 
SES-CD Values 
0 
1 
2 
3 
Size of ulcers 
None 
Aphthous ulcers 
(0.1 < 0.5cm) 
Large ulcers 
(> 0.5 – 2cm) 
Very large ulcers 
(> 2.0cm) 
Ulcerated surface (%) 
None 
< 10% 
10-30% 
> 30% 
Affected surface (%) 
Unaffected 
segment 
< 50% 
50-75% 
> 75% 
Presence of narrowing 
None 
Single, can be 
passed 
Multiple, can be 
passed 
Cannot be passed 
 
Ileum 
Right 
Colon 
Transverse 
colon 
Left 
colon 
Rectum 
Total 
Presence and size of ulcers (0-3) 
Extent of ulcerated surface (0-3) 
Extent of affected surface (0-3) 
Presence and type of narrowings (0-3) 
Total SES-CD = 
Source: Daperno, et al. Gastrointest Endosc. 2004. 
Note: Current Alimentiv scoring conventions are to be used. 


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STATISTICAL ANALYSIS 
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APPENDIX B. 
CROHN’S DISEASE ACTIVITY INDEX (CDAI) 
 
The Crohn’s disease activity index (CDAI) scores range from 1 to approximately 600, with 
higher scores indicating more severe disease. Eight variables comprise the components of the 
CDAI score. Modification limits the contribution of the weight variable to no more than 10 
points in negative contribution. 
 


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STATISTICAL ANALYSIS 
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APPENDIX C. 
PRO2 CALCULATION 
 
The two CDAI items included in the PRO2 are daily stool frequency (SF) and abdominal 
pain(AP). SF consists of the number of liquid or very soft stools that occur per day. AP is rated 
on a 4-point scale (from 0 to 3) of increasing severity (Table a). This information is recorded by 
the subject on the electronic diary (or by paper diary if electronic diary not available. The 
average of the daily entries for the 7-day period prior to each visit is calculated and 
multiplied by weighting factors (X2 for SF and X5 for AP) to provide a total score for 
each component item. The total PRO2 score is the sum of the component item scores (Table b) 
 
Table a. PRO2 Diary Card 
 
Table b. Calculation of the Total PRO2 Score 
 
Source: Khanna, et al. Aliment Pharmacol Ther. 2015. 


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STATISTICAL ANALYSIS 
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APPENDIX D. 
PERIANAL DISEASE ACTIVITY INDEX (PDAI) 
 
The perianal disease activity index (PDAI) score includes the evaluation of 5 elements: 
1) discharge 
2) pain 
3) restriction of sexual activity 
4) type of perianal disease 
5) degree of induration 
Each category is graded on a 5-point Likert scale ranging from no symptoms (score of 0) to severe 
symptoms (score of 4), with a range of 0 to 20; a higher score indicates more severe disease. 
 


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APPENDIX E. 
GLOBAL HISTOLOGIC DISEASE ACTIVITY SCORE 
 
Histological Variable 
Description 
Epithelial damage 
0 
normal 
1 
focal pathology 
2 
extensive pathology 
Architectural changes 
0 
normal 
1 
moderately disturbed (< 50%) 
2 
severely disturbed (> 50%) 
Infiltration of mononuclear cells in the lamina propria 
0 
normal 
1 
moderate increase 
2 
severe increase 
Infiltration of polymorphonuclear cells in the lamina 
propria 
0 
normal 
1 
moderate increase 
2 
severe increase 
Polymorphonuclear cells in epithelium 
0 
absent 
1 
in surface epithelium 
2 
cryptitis 
3 
crypt abscess 
Presence of erosion and/or ulcers 
0 
no 
1 
yes 
Presence of granuloma 
0 
no 
1 
yes 
Number of biopsy specimens affected 
0 
none 
1 
< 33% (1 or 2 of 6) 
2 
33-66% (3 or 4 of 6) 
3 
> 66% (5 or 6 of 6) 
Source: D’Haens, et al. Gastroenterology. 1998 


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STATISTICAL ANALYSIS 
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APPENDIX F. 
ROBARTS HISTOPATHOLOGY INDEX 
 
Histological Variable 
Grading 
Multiplication 
Factor 
Chronic inflammatory infiltrate 
0=No increase 
1=Mild but unequivocal increase 
2=Moderate increase 
3=Marked increase 
X1 
Lamina propria neutrophils 
0=None 
1=Mild but unequivocal increase 
2=Moderate increase 
3=Marked increase 
X2 
Neutrophils in epithelium 
0=None 
1= < 5% crypts involved 
2= < 50% crypts involved 
3= > 50% crypts involved 
X3 
Erosion or ulceration 
0=No erosion, ulceration, or granulation 
tissue 
1=Recovering epithelium + adjacent 
inflammation 
1=Probably erosion-focally stripped 
2=Unequivocal erosion 
3=Ulcer or granulation tissue 
X5 
Source: Mosli, et al. Gut. 2017. 


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STATISTICAL ANALYSIS 
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APPENDIX G. 
SCHEDULE OF ASSESSMENTS – INDUCTION PERIOD 
 
 


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STATISTICAL ANALYSIS 
PLAN 
APPENDIX H. 
SCHEDULE OF ASSESSMENTS – OPEN-LABEL EXTENSION 
PERIOD 
 


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STATISTICAL ANALYSIS 
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STATISTICAL ANALYSIS 
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APPENDIX I. 
SCHEDULE OF ASSESSMENTS – POST DOSING FOLLOW-UP 
PERIOD