Clinical trial NCT04996797
Conditions: Ulcerative Colitis
Keywords: ARTEMIS-UC ARTEMIS Ulcerative Colitis
Sponsor: Prometheus Biosciences, Inc., a subsidiary of Merck & Co., Inc. (Rahway, New Jersey USA)
Start date: 2021-07-14; Completion date: 2025-07-14
Enrollment: 178 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to assess the safety and efficacy of tulisokibart in participants with moderately to severely active Ulcerative Colitis (UC). After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.

Detailed description:

Arms: arm 1: Participants who are CDx+ and CDx- will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0, and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. arm 2: Participants who are CDx+ and CDx- will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. arm 3: Participants who are CDx+ will receive tulisokibart administered by intravenous (IV) infusion at 1000 mg on Day 1, Week 0 and 500 mg on the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks. arm 4: Participants who are CDx+ will receive placebo administered by intravenous (IV) infusion on Day 1, Week 0 and the first day of Weeks 2, 6, and 10. After the completion of the 12-week induction, all participants have the option to continue in the open-label extension for up to 170 weeks.
Interventions: intervention 1: Tulisokibart intervention 2: Companion Diagnostic (CDx) Testing intervention 3: Placebo
Intervention descriptions: intervention 1: Administered by IV infusion intervention 2: PRA023 CDx Genotyping Assay intervention 3: Placebo administered by IV infusion

Protocol documents:
Prot_000.pdf: 
Official Protocol Title: 
NCT number: 
NCT04996797 
Document Date: 
14-Jun-2023
A Phase 2, Multi-Center, Double-Blind, Placebo-Controlled Study
to Evaluate the Safety, Efficacy, and Pharmacokinetics of
Induction Therapy with PRA023 in Subjects with
Moderately to Severely Active Ulcerative Colitis


Clinical Protocol PR200-102
A Phase 2, Multi-Center, Double-Blind, Placebo-Controlled Study 
to Evaluate the Safety, Efficacy, and Pharmacokinetics of 
Induction Therapy with PRA023 in Subjects with 
Moderately to Severely Active Ulcerative Colitis
The ARTEMIS-UC Study
EudraCT: 2021-000091-11
Version 5.0 (14 June 2023)
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: PR200-102 
A Phase 2, Multi-Center, Double-Blind, Placebo-Controlled Study 
to Evaluate the Safety, Efficacy, and Pharmacokinetics of 
Induction Therapy with PRA023 in Subjects with 
Moderately to Severely Active Ulcerative Colitis 
Version 5.0 (14 June 2023) 
Approved by: 
 
 
 
 
 
, MD 
Executive Director, Clinical Development 
Prometheus Biosciences, Inc. 
 
Date 
 
 
 
 
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PROTOCOL SIGNATURE PAGE 
Prometheus Biosciences, Inc. 
Protocol: PR200-102 
Version 5.0 (14 June 2023) 
By my signature I confirm that I have read, and I understand this protocol “A Phase 2, Multi-
Center, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, Efficacy, and 
Pharmacokinetics of Induction Therapy with PRA023 in Subjects with Moderately to Severely 
Active Ulcerative Colitis”, dated 14 June 2023, 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. 
Tel: 
 
Email: mm@prometheusbiosciences.com 
PHARMACOVIGILANCE CONTACT: 
Alimentiv, Inc. 
Email: 
 
Fax: 
 
CLINICAL OPERATIONS CONTACT: 
Email:
 
 
 
 
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PROTOCOL VERSION AND AMENDMENT TRACKING 
Version Number/Amendment 
Date 
Version 1.0 
11 March 2021 
Version 1.1 
10 May 2021 
Version 2.0 
18 June 2021 
Version 2.1 for Belgium and Hungary 
21 June 2021 
Version 2.2 for Russia 
21 October 2021 
Version 2.3 for Italy 
21 October 2021 
Version 3.0 
21 October 2021 
Version 4.0 
27 June 2022 
Version 5.0 
14 June 2023 
 
 
 
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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 ................................................................................................. 28 
1.1 
Background .............................................................................................................. 28 
1.2 
Study Rationale ........................................................................................................ 29 
1.3 
PRA023 Mechanism of Action and Nonclinical Data ............................................... 30 
1.3.1 
Pharmacology ............................................................................................. 30 
1.3.2 
Toxicology .................................................................................................. 31 
1.4 
Previous Human Experience .................................................................................... 32 
1.4.1 
Pharmacokinetic Results (PR200-101 Healthy Volunteer Study) ................. 33 
1.4.2 
Safety Results ............................................................................................. 33 
1.5 
Dose Rationale ......................................................................................................... 34 
1.6 
Overall Benefit/Risk Assessment ............................................................................. 35 
2 
Study Objectives ................................................................................................................ 36 
2.1 
Primary Objective .................................................................................................... 36 
2.2 
Secondary Objectives ............................................................................................... 36 
2.3 
Exploratory Objectives ............................................................................................. 37 
3 
Study Endpoints ................................................................................................................. 38 
3.1 
Primary Objective Evaluation .................................................................................. 38 
3.2 
Secondary Objective Evaluation ............................................................................... 38 
3.3 
Exploratory Objective Evaluation ............................................................................ 39 
4 
Investigational plan ............................................................................................................ 41 
4.1 
Study Design............................................................................................................ 41 
4.1.1 
Study Schema ............................................................................................. 42 
4.1.2 
Number of Subjects ..................................................................................... 43 
4.1.3 
Subject Participation Duration ..................................................................... 43 
4.1.4 
Subject Numbering and Randomization ...................................................... 44 
4.1.4.1 
Screening Numbers ..................................................................... 44 
4.1.4.2 
Randomization Numbers............................................................. 44 
4.1.4.3 
Blinding/Unblinding Procedures ................................................. 44 
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4.2 
Study Subjects/Population ........................................................................................ 45 
4.2.1 
Inclusion/Exclusion Criteria ........................................................................ 45 
4.2.1.1 
Inclusion Criteria ........................................................................ 45 
4.2.1.2 
Exclusion Criteria ....................................................................... 47 
4.3 
Contraception Guidelines ......................................................................................... 50 
4.4 
Concomitant Treatments and Restrictions ................................................................ 51 
4.4.1 
Prior and Concomitant Medications ............................................................ 51 
4.4.2 
Permitted Medications with Restrictions ..................................................... 51 
4.4.3 
Prohibited Medications ............................................................................... 52 
4.4.4 
Corticosteroid and Budesonide Tapering Schedule During Open-Label 
Period ......................................................................................................... 52 
4.4.5 
Other Restricted Medications ...................................................................... 52 
4.4.6 
Rescue Medication ...................................................................................... 53 
4.5 
Removal of Subjects from Study .............................................................................. 53 
4.6 
Modification of Study Drug Dosing ......................................................................... 54 
5 
Investigational Product....................................................................................................... 55 
5.1 
Dosing Form and Preparation ................................................................................... 55 
5.2 
Storage ..................................................................................................................... 55 
5.3 
Accountability.......................................................................................................... 55 
5.4 
Study Drug Administration ...................................................................................... 56 
6 
Study Procedures ............................................................................................................... 57 
6.1 
Study Visit Procedures ............................................................................................. 57 
6.1.1 
Schedule of Study Assessments ................................................................... 58 
6.2 
Other Information for Study Visits ........................................................................... 69 
6.3 
Safety Assessment Description................................................................................. 69 
6.3.1 
Medical History, Physical Examination, Height and Weight ........................ 69 
6.3.2 
Vital Signs .................................................................................................. 69 
6.3.3 
Chest X-Ray ............................................................................................... 70 
6.3.4 
Electrocardiogram (ECG) ............................................................................ 70 
6.3.5 
Clinical Laboratory Evaluations .................................................................. 70 
6.3.5.1 
Stool Evaluation ......................................................................... 72 
6.4 
Efficacy Assessment Description ............................................................................. 72 
6.4.1 
Modified Mayo Scoring System .................................................................. 73 
6.4.2 
Endoscopy Subscore of the Modified Mayo Scoring System ....................... 74 
6.4.3 
Collection of Biopsy Samples ..................................................................... 75 
6.4.4 
Quality of Life (QoL) .................................................................................. 76 
6.5 
Pharmacodynamics .................................................................................................. 76 
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6.6 
Pharmacokinetics ..................................................................................................... 76 
6.6.1 
Pharmacokinetic Sub-Study ........................................................................ 77 
6.7 
Immunogenicity (Anti-Drug Antibody) .................................................................... 77 
6.8 
Pharmacogenomics .................................................................................................. 77 
6.9 
Potential Future Research ......................................................................................... 78 
7 
Adverse Events and Serious Adverse Events ...................................................................... 79 
7.1 
Pre-Treatment-Emergent Events............................................................................... 80 
7.2 
Laboratory Abnormalities as Adverse Events ........................................................... 80 
7.3 
Grading/Severity of Adverse Events......................................................................... 81 
7.4 
Relationship of Adverse Events ................................................................................ 82 
7.4.1 
Relationship of Adverse Events to Study Drug Administration .................... 82 
7.4.2 
Relationship of Adverse Events to Study Procedures ................................... 82 
7.5 
Recording and Reporting of Adverse Events ............................................................ 82 
7.5.1 
Recording Adverse Events .......................................................................... 82 
7.5.2 
Investigator Reporting of a Serious Adverse Event ...................................... 82 
7.5.3 
Investigator Reporting of a Pregnancy ......................................................... 83 
7.6 
Additional Investigator Responsibilities for Serious Adverse Events ........................ 84 
7.7 
Post-Study Follow-Up of Adverse Events ................................................................ 84 
7.8 
Notification of Post-Study Serious Adverse Events .................................................. 84 
7.9 
IRB/IEC Notification of Serious Adverse Events ..................................................... 84 
7.10 Health Authority Safety Reports............................................................................... 85 
7.11 Data Monitoring Committee (DMC) ........................................................................ 85 
8 
Assessment of Study Variables .......................................................................................... 86 
8.1 
Randomization ......................................................................................................... 86 
8.2 
Justification of Sample Size ..................................................................................... 86 
8.3 
Evaluation of Safety Variables ................................................................................. 86 
9 
Statistical Methodology ..................................................................................................... 88 
9.1 
Analysis Populations ................................................................................................ 88 
9.1.1 
Safety Analysis Set (SAS) Population ......................................................... 88 
9.1.2 
Full Analysis Set (FAS) Populations ........................................................... 88 
9.2 
Interim Analysis ....................................................................................................... 88 
9.3 
Statistical Analysis ................................................................................................... 89 
9.3.1 
Demographics and Baseline Characteristics................................................. 89 
9.3.2 
Evaluation of Efficacy Parameters ............................................................... 89 
9.3.3 
Evaluation of Pharmacodynamic Parameters ............................................... 89 
9.3.4 
Evaluation of Immunogenicity .................................................................... 89 
9.3.5 
Evaluation of Exploratory Parameters ......................................................... 90 
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9.3.6 
Evaluation of Pharmacokinetic Parameters .................................................. 90 
9.3.7 
Evaluation of Safety Parameters .................................................................. 90 
9.3.7.1 
Adverse Events and Adverse Events of Special Interest .............. 90 
9.3.7.2 
Medical History, Chest X-ray, ECGs and Physical 
Examination ............................................................................... 90 
9.3.7.3 
Clinical Laboratory and Vital Signs ............................................ 91 
9.3.7.4 
Previous and Concomitant Medication ........................................ 91 
10 Ethics and Regulatory Requirements .................................................................................. 92 
10.1 General Requirements for Study Conduct................................................................. 92 
10.2 Regulatory and Institutional Review Board Approval/ Independent Ethics 
Committee ............................................................................................................... 92 
10.3 Written Informed Consent ........................................................................................ 92 
10.4 Confidentiality ......................................................................................................... 92 
10.5 Protocol Modification/Amendments ......................................................................... 93 
10.6 Direct Access to Source Data/Documents................................................................. 93 
11 Definition of End of Trial ................................................................................................... 94 
11.1 End of Trial in a Member State ................................................................................ 94 
11.2 End of Trial in All Other Participating Countries...................................................... 94 
12 Data Management .............................................................................................................. 95 
12.1 Coding of Adverse Events, Concomitant Medication, and Medical History .............. 95 
13 Documentation and Administrative Considerations ............................................................ 96 
13.1 Recordkeeping ......................................................................................................... 96 
13.2 Disclosure of Data.................................................................................................... 96 
13.3 Publication Policy .................................................................................................... 96 
14 Quality Control and Quality Assurance .............................................................................. 98 
15 References ......................................................................................................................... 99 
16 Appendix ......................................................................................................................... 102 
16.1 Modified Mayo Scoring System for Assessment of Ulcerative Colitis Activity ...... 102 
16.1.1 Partial Mayo Scoring System for Assessment of Ulcerative Colitis 
Activity ..................................................................................................... 103 
16.1.2 3-Component Modified Mayo Score ......................................................... 103 
 
 
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LIST OF TABLES 
Table 1 
Schedule of Study Assessments – Screening Period ................................................. 58 
Table 2 
Schedule of Study Assessments – Induction Period .................................................. 60 
Table 3 
Schedule of Study Assessments – Open-Label Extension Period for 1st Induction 
Responders .............................................................................................................. 62 
Table 4 
Schedule of Study Assessments – Open-Label Extension Period for 1st Induction 
Non-Responders ...................................................................................................... 65 
Table 5 
Post Dosing Follow-Up Period ................................................................................. 68 
Table 6 
Description of Biopsy Sample Collection ................................................................. 75 
Table 7 
Severity of Adverse Events ...................................................................................... 81 
LIST OF FIGURES 
Figure 1 
Study Schema for Induction Period .......................................................................... 42 
Figure 2 
Study Schema for Open-Label Extension Period ...................................................... 43 
 
 
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LIST OF ABBREVIATIONS 
Abbreviation or specialist term 
Explanation 
5-ASA 
Aminosalicylate 
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 
AUC0-t 
Area under the concentration time curve from hour zero to the last 
measurable concentration, estimated by the linear trapezoidal rule 
AZA 
Azathioprine 
AUC 
Area under curve 
BUN 
Blood urea nitrogen 
CD 
Crohn’s disease 
CDx 
Companion diagnostic 
CDC 
Complement-dependent cytotoxicity 
CFR 
Code of Federal Regulations 
CK 
Creatine kinase 
Cmax 
Maximum concentration 
CMH 
Cochran-Mantel-Haenszel 
CMV 
Cytomegalovirus 
CNS 
Central nervous system 
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 
DO 
Doctor of osteopathy 
DR3 
Death receptor 3 
DSS 
Dextran sodium sulfate 
eCRF 
Electronic case report form 
eDiary 
Electronic diary 
FcR 
Fc receptor 
FDA 
Food and Drug Administration 
FSH 
Follicle stimulating hormone 
ET 
Early termination 
GCP 
Good Clinical Practice 
GGT 
Gamma-glutamyl transferase 
GLP 
Good Laboratory Practice 
GM 
Geometric mean 
HBsAg 
Hepatitis B surface antigen 
HBcAb 
Hepatitis B core antibody 
HCV 
Hepatitis C virus 
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Abbreviation or specialist term 
Explanation 
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-Ȗ 
Interferon gamma 
IgG 
Immunoglobulin G 
IgG1N 
Immunoglobulin G subtype G1 kappa 
ILC 
Innate lymphoid cell 
IP 
Induction Period 
IRB 
Institutional Review Board 
IRT 
Interactive response technology 
IUD 
Intrauterine device 
IV 
Intravenous  
JAK 
Janus kinase 
KLH 
Keyhole limpet haemocyanin 
LDH 
Lactic dehydrogenase 
LDL 
Low density lipoprotein 
LSLV 
Last subject last visit 
MAD 
Multiple ascending dose 
MD 
Doctor of medicine 
MedDRA 
Medical Dictionary for Regulatory Activities 
mRNA 
Messenger ribonucleic acid 
msec 
Millisecond  
MTX 
Methotrexate  
Nab 
Neutralizing antibody 
NCI 
National Cancer Institute 
NCS 
Not clinically significant 
NK 
Natural killer 
NOAEL 
No observed adverse effect level 
NP 
Nurse practitioner 
NS 
Normal saline 
NSAIDs 
Nonsteroidal anti-inflammatory agents 
OLE 
Open-label extension 
PCR 
Polymerase Chain Reaction 
PG 
Pharmacogenomic 
PD 
Pharmacodynamic 
PK 
Pharmacokinetic 
PSC 
Primary sclerosing cholangitis 
PT 
Preferred term 
Q2W 
Every 2 weeks 
Q4W 
Every 4 weeks 
Q8W 
Every 8 weeks 
QoL 
Quality of life 
RBC 
Red blood cell 
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Abbreviation or specialist term 
Explanation 
RHI 
Robarts histopathology index 
S1PR 
Sphingosine 1-phosphate receptor 
SAD 
Single ascending dose 
SAE 
Serious adverse event 
SAP 
Statistical analysis plan 
SD 
Standard deviation 
SOC 
System organ class 
sTL1A 
Soluble tumor necrosis factor-like cytokine 1A 
SUSAR 
Suspected, unexpected serious adverse reaction 
t1/2 
Half-life 
TB 
Tuberculosis 
TCR 
T-cell receptor 
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 2, Multi-Center, Double-Blind, Placebo-Controlled Study to Evaluate 
the Safety, Efficacy, and Pharmacokinetics of Induction Therapy with 
PRA023 in Subjects with Moderately to Severely Active Ulcerative Colitis 
PROTOCOL NUMBER: PR200-102 
PROJECT PHASE: 
Phase 2 
OBJECTIVE: 
Primary: 
x 
To assess the safety and tolerability of PRA023 following 12 weeks of 
induction therapy  
x 
To compare the efficacy of PRA023 vs placebo for induction of clinical 
remission at Week 12 
Secondary: 
All objectives below refer to comparison of PRA023-treated subjects vs 
placebo-treated subjects in Cohort 1. For the objectives where the 
companion diagnostic (CDx) status is a variable, a comparison of subjects in 
both Cohort 1 and Cohort 2 will be conducted. 
x 
To compare the efficacy of PRA023 vs placebo for induction of 
endoscopic improvement at Week 12 
x 
To compare the efficacy of PRA023 vs placebo for induction of clinical 
response at Week 12 
x 
To compare the efficacy of PRA023 vs placebo in CDx positive (CDx+) 
subjects (Cohort 1 + Cohort 2) for induction of clinical remission at 
Week 12 
x 
To compare the efficacy of PRA023 vs placebo for induction of 
symptomatic remission at Week 12 
x 
To compare the efficacy of PRA023 vs placebo for induction of 
histologic remission at Week 12  
x 
To compare the efficacy of PRA023 vs placebo for induction of 
histologic-endoscopic mucosal improvement at Week 12 
x 
To compare the efficacy of PRA023 vs placebo in CDx+ subjects 
(Cohort 1 + Cohort 2) for induction of endoscopic improvement at Week 
12 
x 
To compare the efficacy of PRA023 vs placebo in CDx+ subjects 
(Cohort 1 + Cohort 2) for induction of clinical response at Week 12 
x 
To compare the efficacy of PRA023 vs placebo in CDx+ subjects 
(Cohort 1 + Cohort 2) for induction of symptomatic remission at Week 
12 
x 
To compare the efficacy of PRA023 vs placebo in CDx+ subjects 
(Cohort 1 + Cohort 2) for induction of histologic remission at Week 12 
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x 
To compare the efficacy of PRA023 vs placebo in CDx+ subjects 
(Cohort 1 + Cohort 2) for induction of histologic-endoscopic mucosal 
improvement at Week 12 
x 
To compare the efficacy of PRA023 in CDx+ (Cohort 1 + Cohort 2) vs 
CDx negative (CDx-) subjects for induction of clinical remission at 
Week 12 
x 
To compare the efficacy of PRA023 vs placebo for induction of mucosal 
healing at Week 12 
x 
To compare the efficacy of PRA023 vs placebo in CDx+ subjects 
(Cohort 1 + Cohort 2) for induction of mucosal healing at Week 12 
x 
To compare the efficacy of PRA023 vs placebo for change in 
Inflammatory Bowel Disease Questionnaire (IBDQ) at Week 12 
x 
To compare the efficacy of PRA023 vs placebo in CDx+ subjects 
(Cohort 1 + Cohort 2) for change in IBDQ at Week 12 
x 
To compare the efficacy of PRA023 vs. placebo in subjects who are 
CDx+ per alternative algorithm (Cohort 1 + Cohort 2) for clinical 
remission at Week 12 
Exploratory: 
x 
To assess the pharmacokinetics (PK) of PRA023 in subjects with 
ulcerative colitis (UC) over time 
x 
To assess the effects of PRA023 on tissue and serum pharmacodynamic 
(PD) markers, including total TL1A concentrations over time 
x 
To assess the effect of PRA023 on inflammatory biomarkers including 
fecal calprotectin and high sensitivity C-reactive protein (hsCRP) over 
time 
x 
To assess the proportion of subjects in 3-component Modified Mayo 
Score response, 3-component Modified Mayo Score remission, 
endoscopic improvement, Robarts histopathology index (RHI) histologic 
remission, Geboes score histologic remission, and mucosal healing at 
Week 50  
x 
To assess the change in Partial Mayo Score over time 
x 
To assess the change in Geboes Index and RHI from Baseline to 
Week 12 and Week 50  
x 
To assess the exposure-response relationship of PRA023 on PD markers 
over time 
x 
To assess the proportion of subjects achieving corticosteroid-free-
remission at Week 50  
x 
To assess long-term safety, tolerability, and efficacy of PRA023  
STUDY DESIGN: 
This is a multi-center, double-blind, randomized, placebo-controlled proof 
of concept study designed to assess the safety, tolerability, and efficacy of 
PRA023 following 12 weeks of induction therapy in subjects with UC. This 
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study will be conducted under the aegis of a Data Monitoring Committee 
(DMC).  
 
The study has 4 periods (Screening Period, Induction Period [IP], Open-
Label Extension [OLE] Period, and Follow-Up [FU] Period). The study will 
have 2 Cohorts that will enroll subjects in a sequential fashion utilizing an 
adaptive design as described below. 
 
Cohort 1: Following the Screening Period, approximately 120 eligible 
subjects with moderately to severely active UC will enter the IP and be 
randomized in a 1:1 fashion to receive intravenous (IV) administration of 
PRA023 1000 mg on Week 0/Day 1, followed by 500 mg on Weeks 2, 6, 
and 10, or placebo at the same timepoints. Randomization will be stratified 
by CDx status of positive (CDx+) or negative (CDx-) and prior biologic 
experience (yes/no) at Week 0/Day 1. Subjects who discontinue from the 
study drug will have a follow-up period of 12 weeks after last dose. 
 
Cohort 2: Enrollment will continue into Cohort 2 when any stratification 
limit of Cohort 1 enrollment is completed. When approximately 80% of 
Cohort 1 subjects (i.e., ~96 subjects) have reached Week 12 or early 
terminated from the study, the DMC will conduct an unblinded analysis of 
clinical efficacy in CDx+ subjects and will recommend whether enrollment 
into Cohort 2 should continue. The planned sample size for CDx+ subjects 
(combining Cohort 1 and Cohort 2) will be approximately 40, in the case 
where Cohort 2 completes enrollment as planned. For Cohort 2, eligible 
subjects (who must be CDx+) will enter the IP and be randomized in a 1:1 
fashion to receive IV administration of PRA023 1000 mg on Week 0/Day 1, 
followed by 500 mg on Weeks 2, 6, and 10, or placebo at the same 
timepoints. Randomization will be stratified by prior biologic experience 
(yes/no) at Baseline. Subjects who discontinue from the study drug will have 
a follow-up period of 12 weeks after last dose. 
 
Subjects who complete the 12-week IP from either Cohort will have the 
option to enter OLE. During OLE, starting at Week 14 visit: 
x 
Responders (defined as reduction from Baseline points and  30% in 
3-component Modified Mayo 6FRUHDFFRPSDQLHGE\DUHGXFWLRQLQ
UHFWDOEOHHGLQJVXEVFRUHRUDEVROXWHUHFWDOEOHHGLQJVXEVFRUH) will be 
re-randomized, stratified by CDx status of CDx+ or CDx-, to either 
250 mg IV Q4W or 100 mg IV Q4W, starting at Week 14 until Week 
170. 
x 
Nonresponders will receive an open-label induction regimen of 1000 mg 
of PRA023 on Week 14, followed by 500 mg on Weeks 16, 20, and 24. 
Nonresponders who do not respond at Week 28 (per investigator 
discretion) should be discontinued from the study. Nonresponders who 
respond at Week 28 (per investigator discretion) will be re-randomized 
to either 250 mg IV Q4W or 100 mg IV Q4W, starting at Week 28 until 
Week 168. 
 
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For subjects assigned to the 100 mg Q4W OLE arm, the dose may be 
escalated to 250 mg Q4W if disease activity is not adequately controlled in 
the Investigator’s opinion. 
 
The study is being amended by the Sponsor to extend the OLE period 
beyond 132/134 weeks to Week 168/170 based on emerging safety data in 
both this study as well as a concurrent open-label Phase 2 study in Crohn’s 
disease.  This extension is to obtain safety data for at least 2 years’ of 
PRA023 drug exposure for at least 100 subjects in this study, assuming 20% 
annual dropout rate.  The OLE period may be further extended beyond 
168/170 weeks based on emerging safety data in a future amendment. 
 
The study also includes an optional PK sub-study during the IP for subjects 
who consent to additional PK sampling. 
SAMPLE SIZE: 
The study is planned to randomize up to approximately 170 subjects, 
approximately 120 in Cohort 1 and up to 50 in Cohort 2. A sample size of 60 
per arm in Cohort 1 will enable a statistical power of > 80% for the primary 
endpoint at 1-sided significance level of 0.025 using Cochran-Mantel-
Haenszel (CMH), assuming clinical remission rate of 5% for placebo and 
24% for PRA023. Additionally, the sample size will confer > 80% power to 
achieve statistical significance for the 1st secondary endpoint of endoscopic 
improvement with an overall 1-sided alpha level of 0.025, assuming the 
endoscopic improvement rates are 15% and 38% for placebo and PRA023 
groups, respectively.  
 
Additionally, for analyses of the CDx population (combining CDx+ subjects 
from Cohort 1 and Cohort 2), a sample size of 40 per arm will provide a 
statistical power of 80% at a 1-sided alpha level of 0.025, according to a 
group sequential design with a non-binding futility interim analysis when 
approximately 18 subjects per arm are anticipated to reach Week 12, 
assuming clinical remission rate of 5% for placebo and 31% for PRA023.  
SUBJECT TYPE: 
Male or female subjects  18 years of age with moderately to severely active 
UC. 
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: 
Subjects will be stratified by CDx+/CDx- status and prior biologic 
experience (yes/no) in a 1:1 ratio to: 
x 
PRA023 1000 mg IV on Week 0/Day 1, followed by 500 mg IV on 
Weeks 2, 6, and 10 
x 
Placebo IV on Week 0/Day 1, followed by placebo IV on Weeks 2, 6, 
and 10 
During OLE: 
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x 
Responders at the end of Week 12 re-randomized to receive one of the 
following regimens (and subjects from Cohort 1 will be stratified by 
CDx status of CDx+ or CDx-): 
o PRA023 250 mg IV on Week 14 then Q4W until Week 170 
o PRA023 100 mg IV on Week 14 then Q4W until Week 170 
x 
Nonresponders at the end of Week 12 will receive open-label PRA023 
1000 mg IV on Week 14, followed by PRA023 500 mg IV on Weeks 
16, 20, and 24. Subjects who do not respond by Week 26 should be 
discontinued from the study. Subjects who respond by Week 26 will be 
re-randomized to receive one of the following regimens (and subjects in 
Cohort 1 will be stratified by CDx status of CDx+ or CDx-): 
o PRA023 250 mg IV on Week 28 then Q4W until Week 168 
o PRA023 100 mg IV on Week 28 then Q4W until Week 168 
 
x 
A subject may have the dose escalated from 100 mg IV Q4W to 250 mg 
IV Q4W during OLE if the subject’s disease is not adequately 
controlled in the Investigator’s opinion. 
ROUTE OF 
ADMINISTRATION: 
All study drug will be reconstituted in 250 mL of 0.9% normal saline (NS) 
and will be administered IV over 30 minutes.  
STUDY ENDPOINTS: 
x 
Primary endpoints: 
x The proportion of subjects reporting adverse events (AEs), serious 
adverse events (SAEs), AEs leading to discontinuation, and 
markedly abnormal laboratory values. 
x The proportion of subjects in the 3-component Modified Mayo Score 
clinical remission (as defined by endoscopic subscore of 0 or 1, 
rectal bleeding subscore of 0, and stool frequency subscore of 0 or 1 
and not greater than Baseline) at Week 12. The 3-component 
Modified Mayo Score ranges from 0-9 and includes rectal bleeding, 
stool frequency and endoscopic assessment domains. 
x 
Secondary endpoints: 
x The proportion of subjects with endoscopic improvement, as defined 
E\HQGRVFRS\VXEVFRUH 1 with no friability, at Week 12. 
x The proportion of subjects in 3-component Modified Mayo Score 
clinical response at Week 12. The 3-component Modified Mayo 
Score clinical response is defined by reduction from Baseline  2 
points and  30% in 3-component Modified Mayo Score, 
DFFRPSDQLHGE\DUHGXFWLRQLQUHFWDOEOHHGLQJVXEVFRUHRU
DEVROXWHUHFWDOEOHHGLQJVXEVFRUH 1. 
x The proportion of subjects in the 3-component Modified Mayo Score 
clinical remission (as defined by endoscopic subscore of 0 or 1, 
rectal bleeding subscore of 0, and stool frequency subscore of 0 or 1 
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and not greater than Baseline), in CDx+ subjects (Cohort 1 + Cohort 
2) treated with PRA023 compared to CDx+ placebo-treated subjects 
at Week 12. The 3-component Modified Mayo Score ranges from 0-
9 and includes rectal bleeding, stool frequency, and endoscopic 
assessment domains. 
x The proportion of subjects in symptomatic remission (as defined by 
rectal bleeding score = 0 and stool frequency score = 0) at Week 12. 
x The proportion of subjects with histologic remission (defined as 
*HERHVVFRUHDW:HHN 
x The proportion of subjects with histologic-endoscopic mucosal 
impURYHPHQWGHILQHGDV*HERHVVFRUHand endoscopy subscore 
 1 with no friability) at Week 12. 
x The proportion of subjects with endoscopic improvement, as defined 
E\HQGRVFRS\VXEVFRUH 1 with no friability, in CDx+ subjects 
(Cohort 1 + Cohort 2) treated with PRA023 compared to CDx+ 
placebo-treated subjects at Week 12. 
x The proportion of subjects in 3-component Modified Mayo Score 
clinical response in CDx+ subjects treated with PRA023 compared to 
CDx+ placebo-treated subjects at Week 12. The 3-component 
Modified Mayo Score clinical response is defined by reduction from 
Baseline points and LQ3-component Modified Mayo 
6FRUHDFFRPSDQLHGE\DUHGXFWLRQLQUHFWDOEOHHGLQJVXEVFRUHRU
DEVROXWHUHFWDOEOHHGLQJVXEVFRUH 
x The proportion of subjects with symptomatic remission (as defined 
by rectal bleeding score = 0 and stool frequency score = 0) in CDx+ 
subjects (Cohort 1 + Cohort 2) treated with PRA023 compared to 
CDx+ placebo-treated subjects at Week 12. 
x The proportion of subjects with histologic remission, defined as 
*HERHVVFRUH, in CDx+ subjects (Cohort 1 + Cohort 2) treated 
with PRA023 compared to CDx+ placebo-treated subjects at Week 12. 
x The proportion of subjects with histologic-endoscopic mucosal 
improvement (defined as Geboes scorHand endoscopy subscore 
 1 with no friability), in CDx+ subjects (Cohort 1 + Cohort 2) 
treated with PRA023 compared to CDx+ placebo-treated subjects at 
Week 12. 
x The proportion of subjects with clinical remission (defined as 
endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, and 
stool frequency subscore of 0 or 1 and not greater than Baseline) in 
CDx+ subjects (Cohort 1 + Cohort 2) treated with PRA023 compared 
to in CDx- subjects treated with PRA023 at Week 12. 
x The proportion of subjects with mucosal healing (defined as Geboes 
VFRUH 2B.1 and endoscopy subscore RIDW:HHN 
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x The proportion of subjects with mucosal healing (defined as Geboes 
VFRUH 2B.1 and endoscopy subscore RILQ&'[VXEMHFWV
(Cohort 1 + Cohort 2) treated with PRA023 compared to CDx+ 
placebo-treated subjects at Week 12. 
x 7KHSURSRUWLRQRIVXEMHFWVZLWK,%'4UHVSRQVHDVGHILQHGE\-
point increase from Baseline at Week 12. 
x 7KHSURSRUWLRQRIVXEMHFWVZLWK,%'4UHVSRQVHDVGHILQHGE\-
point increase from Baseline, in CDx+ subjects (Cohort 1 + Cohort 
2) treated with PRA023 compared to CDx+ placebo-treated subjects 
at Week 12. 
x The proportion of subjects in the 3-component Modified Mayo Score 
clinical remission (as defined by endoscopic subscore of 0 or 1, rectal 
bleeding subscore of 0, and stool frequency subscore of 0 or 1 and 
not greater than Baseline), in CDx+ subjects per alternative algorithm 
(Cohort 1 + Cohort 2) treated with PRA023 compared to CDx+ 
placebo-treated subjects per alternative algorithm at Week 12. The 3-
component Modified Mayo Score ranges from 0-9 and includes 
rectal bleeding, stool frequency, and endoscopic assessment domains. 
x 
Exploratory endpoints: 
x The pharmacokinetics of PRA023 in subjects with UC after multiple 
doses 
x The change from Baseline in serum and fecal inflammatory 
biomarkers (PD markers) 
x The proportion of subjects in 3-component Modified Mayo Score 
response, 3-component Modified Mayo Score remission, endoscopic 
improvement, RHI histologic remission, Geboes score histologic 
remission, and mucosal healing at Week 50  
x The change in Partial Mayo Score (with or without PGA component) 
over time 
x The change in Geboes Index and RHI from Baseline to Week 12 and 
Week 50 
x The exposure-response relationship of PRA023 on PD markers 
x Within subpopulation of subjects on corticosteroid at study entry, the 
proportion of subjects in clinical remission and off of corticosteroid 
at Week 50 
x Long-term safety, tolerability, and efficacy of PRA023 through week 
168/170 
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. 
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2. Subjects must have had a diagnosis of UC at least 3 months before 
Screening (confirmed by endoscopy + histology) to be eligible for study 
participation. For subjects with no documented confirmation of UC 
diagnosis or if previous diagnosis is not deemed conclusive, UC 
diagnosis must be confirmed at time of screening colonoscopy. Note that 
mention of “chronic inflammation” or “ulcerative colitis” or equivalent 
on histology report is acceptable. 
3. Moderately to severely active UC as defined by 3-component Modified 
Mayo score (3 components of rectal bleeding, stool frequency, and 
endoscopy) of 4 to 9, inclusive, with Modified Mayo endoscopic 
VXEVFRUHand UHFWDOEOHHGLQJVXEVFRUH 
4. 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: 
x 2UDOSUHGQLVRQHPJGD\RUHTXLYDOHQWRU EXGHVRQLGH
mg/day or equivalent or beclomethasone  5 mg/day for at least 
2 weeks  
x 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  
x ImmunosuppUHVVDQWVD]DWKLRSULQHPJNJGD\RU
6-PHUFDSWRSXULQHPJNJGD\>RUGRFXPHQWDWLRQRID
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) 
x An approved anti-TNF agent at an approved labeled dose for at 
least 8 weeks 
x Vedolizumab at the approved labelled dose for at least 8 weeks  
x An approved JAK inhibitor (e.g., tofacitinib, upadacitinib, or 
filgotinib) at an approved labelled dose for at least 8 weeks 
x An approved anti-IL-12/23 (e.g., ustekinumab) at an approved 
labelled dose for at least 8 weeks 
x An approved sphingosine 1-phosphate receptor (S1PR) 
modulator (e.g., ozanimod) at an approved labelled dose for least 
12 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]).  
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OR 
c) Currently receiving one or more of the following treatments: 
x Oral Prednisone t 10 mg/day (or equivalent) for at least 3 months 
x Immunosuppressants [azathioprine PJNJGD\RU
6-mercaptopurine t 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 biologic/biologic-like therapy(ies) 
(anti-TNF, JAK inhibitor, S1PR modulator, anti-IL-12/23, and/or 
vedolizumab):  
x 
The study will include a maximum of 70% and a minimum of 
approximately 50% subjects who have had prior biologic/biologic-
like therapy(ies) experience. Upon reaching the maximum number 
of allowed biologic/biologic-like experienced subjects (70%), 
subjects who have had prior biologic/biologic-like experience will 
no longer be allowed to enter the study. Upon reaching the 
maximum number of allowed biologic/biologic-like naïve subjects 
(approximately 50%), subjects who have never been exposed to a 
prior biologic/biologic-like will no longer be allowed to enter the 
study. 
x 
Subject cannot have failed (no response, insufficient response, loss 
of response, and/or intolerance) > 3 classes or > 4 individual 
biologic/biologic-like therapies (refer to exclusion criterion #26). 
5. 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 
effective methods of contraception until at least 12 weeks after the last 
dose of study drug.  
6. 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. 
7. Subject must meet drug stabilization requirements, as applicable: 
a) Oral corticosteroid treatment must be equivalent RI20 mg 
SUHGQLVRQHRU 9 mg budesonide or beclomethasone  5 mg daily at 
a stable dose for at least 2 weeks prior to randomization 
b) Oral aminosalicylates should be at a stable dose for at least 2 weeks 
prior to randomization 
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c) Azathioprine and 6-mercaptopurine should be at a stable dose for at 
least 4 weeks prior to randomization 
8. Able to provide written informed consent and understand and comply 
with the requirements of the study. 
9. For Cohort 2 only: Subjects must be CDx+. 
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 
randomization. 
Target Disease Exceptions 
4. Diagnosis of Crohn’s disease or indeterminate colitis. 
5. UC limited to the rectum (< 15 cm from anal verge). 
6. Current evidence of fulminant colitis, toxic megacolon, or bowel 
perforation. 
7. Current or impending need for colostomy or ileostomy. 
8. Previous total proctocolectomy or partial colectomy.  
9. Surgical bowel resection within 3 months before screening. 
10. Concomitant primary sclerosing cholangitis (PSC) 
Medical History and Concurrent Diseases 
11. Past or current evidence of definite low-grade or high-grade colonic 
dysplasia that has not been completely removed. 
12. Subjects who are scheduled or anticipate the need for surgery, aside 
from dermatologic procedures. 
13. Subjects who have a history of clinically significant drug or alcohol 
abuse. 
14. 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). 
15. 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. 
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16. 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. 
17. 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 randomization, and no evidence of active TB 
on chest x-ray during Screening. 
18. 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). 
19. 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. 
20. Subjects with any active infections (excluding fungal infections of nail 
beds) including, but not limited to, those that require intravenous (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, but subjects with 
successfully treated HHSDWLWLV&ZLWKQRUHFXUUHQFHIRU\HDU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. 
21. Subjects with herpes zoster reactivation or cytomegalovirus (CMV) that 
resolved less than 2 months prior to signing informed consent. 
22. 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 
23. Positive stool studies [e.g., by Polymerase Chain Reaction (PCR), 
bacterial culture, toxin, etc.] if Investigator deems this positivity reflects 
infection rather than colonization.  Subjects who have an infection can 
be retested after the completion of a full course of treatment, if treatment 
is deemed medically indicated. 
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24. 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. 
25. 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 
26. Failed (no response, insufficient response, loss of response, and/or 
intolerance) > 3 classes (anti-TNF, anti-integrin, anti-IL12/23, JAK 
inhibitor, S1PR modulator) or > 4 individual biologic/biologic-like 
therapies. 
27. Any marketed biologic or biologic-like within 2 weeks for JAK 
inhibitors (e.g., tofacitinib, upadacitinib, or filgotinib, 8 weeks for anti-
TNF agents, 10 weeks for S1PR modulators (e.g., ozanimod), and 12 
weeks for vedolizumab and anti-IL-12/23 (e.g., ustekinumab) prior to 
randomization or if drug level per therapeutic dose monitoring is greater 
than lower limit of detection. 
28. Any biologic immunomodulators not covered in exclusion criterion 27, 
used for UC or other conditions within 8 weeks or 5 half-lives, 
whichever is longer, prior to randomization or if drug level per 
therapeutic dose monitoring is greater than lower limit of detection. 
29. Rituximab within 1 year prior to randomization. 
30. Parenteral corticosteroids within 4 weeks or rectal administration of 
corticosteroids within 2 weeks prior to randomization. 
31. Rectal administration of 5-ASA within 2 weeks prior to randomization. 
32. Tacrolimus, methotrexate, cyclosporine, mycophenolate mofetil 
(CellCept®), immunoadsorption columns (such as Prosorba columns), d-
penicillamine, leflunomide, thalidomide, fish-oil preparations, 
probiotics, fecal transplantation, non-steroidal anti-inflammatory agents 
(NSAIDs), aspirin > 81 mg/day within 2 weeks prior to randomization.  
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33. Other investigational chemical agent within 30 days or other 
investigational biologic agent within 8 weeks or 5 half-lives (whichever 
is longer) of randomization.  
34. Prior exposure to PRA023. 
Other Exclusion Criteria 
35. Prisoners or subjects who are compulsorily detained (involuntarily 
incarcerated) for treatment of either a psychiatric or physical (e.g., 
infectious disease) illness must not be enrolled into this study. 
36. Legal or mental incapacitation, or inability to understand and comply 
with the requirements of the study. 
37. Known allergies, hypersensitivity, or intolerance to PRA023 or its 
excipients.ௗ 
Statistical Methods: 
Statistical methods will be detailed in the Statistical Analysis Plan. The SAP 
will provide details about the method of analysis and specific planned 
analyses, and will be prepared and approved by Prometheus Biosciences and 
its designees before study database lock and unblinding of subject treatment 
assignments. 
The analysis populations are defined as follows: 
x 
Full analysis set (FAS) from Cohort 1: all subjects randomized and 
treated in Cohort 1  
x 
FAS for CDx+: all CDx+ subjects who are randomized and treated in 
both Cohort 1 and Cohort 2  
x 
Safety analysis set: all subjects treated 
The following analyses will be performed: 
Efficacy: 
The efficacy assessment will test for the difference between PRA023 and 
placebo groups in FAS.  
The primary endpoint will be analyzed and compared between PRA023 and 
placebo treatment groups in FAS from Cohort 1. The primary endpoint, the 
proportion of subjects achieving clinical remission, will be tested between 
the 2 treatment groups at 1-sided significance level of 0.025 using CMH 
with stratification factors at randomization. If significant, the 1st secondary 
endpoint of proportion of subjects achieving endoscopic improvement will 
be tested between the 2 treatment groups at 1-sided significance level of 
0.025. If significant, the 2nd, 3rd, 4th, and 5th secondary endpoints will be 
tested sequentially, each at 1-sided significance level of 0.025. Testing for 
statistical significance will stop when the first endpoint is not statistically 
significant at level of 0.025 and all remaining p values will be nominal.  
Treatment difference for primary and secondary endpoints for Cohort 1 will 
be estimated along with 95% CI for all subjects in FAS. The secondary 
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endpoints in CDx+ subjects will be summarized and compared between 
PRA023 and placebo groups in FAS for CDx+, while the treatment 
difference will be estimated with 95% CI. Additional efficacy analysis will 
be detailed in SAP. 
Interim Efficacy Analysis: 
An interim analysis will be carried out when approximately 80% of subjects 
(approximately 96 subjects) in Cohort 1 have reached Week 12 or early 
terminated from the study. The DMC will review the unblinded efficacy and 
safety data and recommend whether to continue enrollment into Cohort 2. 
Decision rules to continue Cohort 2 are to be determined according to the 
futility bounds of group sequential design of a sample size of 40 per arm 
with one interim analysis at the information fraction of 45%.  Because the 
exact bounds will be calculated using the actual number of subjects with 
CDx+ included in the interim analysis, the final decision rules, along with 
sensitivity analysis, will be specified in the DMC SAP, prior to the interim 
analysis. 
 
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 for 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 anti-drug antibody 
(ADA) by visit and by CDx+ and CDx-.  
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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, it 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 (IgG1N) 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 
hsCRP) at Week 14. PF-06480605 appeared to have an acceptable safety and tolerability profile. 
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 
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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 is a Phase 2, multi-center, double-blind, randomized, placebo-controlled proof of concept 
study designed to assess the safety, tolerability, and efficacy of PRA023 following 12 weeks of 
induction therapy in subjects with moderately to severely active UC. 
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, IFNJ, 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. While intestinal fibrosis is a well-recognized complication of CD, clinical colonic 
strictures has been reported in up to 11% of patients with UC (De Dombal 1966, Gumaste 1992). 
In a study that examined 89 consecutive UC colectomy specimen from Cleveland Clinic, 
submucosal fibrosis was detected in 100% of the specimen (Gordon 2018). The degree of 
fibrosis was associated with the severity of chronic mucosal injury but not acute inflammation. 
Subclinical fibrosis in the colonic wall may have significant clinical implications such as 
abnormalities leading to symptoms such as diarrhea, abdominal pain, urgency, and incontinence 
(Bassotti 2006). It has long been speculated that intestinal fibrosis may be the underlying cause 
of persistent UC symptoms, after the resolution of inflammation, that is commonly misclassified 
as irritable bowel syndrome (Hirten 2017). To date, no approved therapies for IBD address or 
treat the intestinal fibrosis. 
Furthermore, 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), Janus kinase 
(JAK) inhibitors (tofacitinib), and anti-IL12/23 (ustekinumab) has improved the care of moderate 
to severe UC. 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 
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treatment of UC 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 placebo-
controlled Phase 2 induction study is designed to demonstrate the efficacy of PRA023 in subjects 
with moderately to severely active UC. In addition, this induction 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.  
In parallel to this study, an open-label CD study (PRA200-103) will be conducted to demonstrate 
the proof of concept of PRA023 for induction therapy in subjects with moderately to severely 
active CD. 
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 toxicological studies conducted to date). 
1.3.1 
Pharmacology 
PRA023 is a humanized IgG1N 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 
 nM and 
 nM, 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 
 nM. Similarly, 
PRA023 blocked monkey TL1A-induced caspase activation with an IC50 of 
 nM. In a monkey 
whole blood assay, PRA023 inhibited the immune complex/TL1A enhancement of IFN-ȖUHOHDVH
with an IC50 of 
 nM and IC90 (90% maximal inhibitory concentration) of 
 nM. 
A single dose pharmacokinetic/pharmacodynamic (PK/PD) study in cynomolgus monkeys 
demonstrated a dose-dependent pharmacologic effect of PRA023 on the inhibition of TL1A-
mediated IFN-J release from peripheral blood mononuclear cells (PBMCs) in whole blood at 
GRVHVRI 
 mg/kg. The observation that greater concentrations (approximately 
fold) 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 
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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 and a definitive GLP embryo-fetal development 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] and complement-dependent cytotoxicity [CDC], and 
antibody-dependent phagocytosis cytotoxicity [ADCP]) assays, human 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 d 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 d300 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.  
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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] on repeat dosing; 
Pg*hr/mL) at the NOAEL is 
-fold, 
relative to the projected AUC0-672hr (
 Pg*hr/mL) after the last 500 mg induction dose (i.e., 
highest predicted exposure due to accumulation with repeat dosing) in the dosing regimen. 
Similarly, for maximum concentration (Cmax), the exposure margin (based on Cmax after repeat 
dosing; 
 Pg/mL) at the NOAEL is 
-fold, relative to the projected exposure (
 Pg/mL) 
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 intravenous 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 variations or malformations were observed. The maternal and fetal no 
observed adverse effect levels (NOAELs) are 
 mg/kg/dose (Cmax of 
 g/mL and AUC0-inf 
of 
 g*hr/mL). The exposure margins, based on Cmax and AUC0-inf, at the NOAEL are 
and 
-fold, 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 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 an 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 1000ௗPJDVDVLQJOHGRVHDQGPJDVPXOWLSOHGRVHV7KHVWXG\GUXJZDVZHOO-
tolerated, and no subjects met the study stopping criteria. 
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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 DWGRVHVRIPJWKHH[SRVXUHLQFUHDVHVDWGRVHVRIPJ
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 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-HPHUJHQW$(VWKDWRFFXUUHGLQVXEMHFWVGRVHG with PRA023 
(regardless of dose) were: headache (5 subjects [14%] in PRA023 and 1 subject [9%] on 
placebo), followed by fatigue (2 subjects [ 6%] on PRA023, 0 on placebo), back pain (2 subjects 
[6%] on PRA023, 0 on placebo), and cough (2 subjects [ 6%] on PRA023, 0 on placebo). All 
other AEs were reported in no more than 1 subject. There was 1 event of headache that was 
assessed as related to placebo that was moderate in severity. The only other AE that was assessed 
as related to PRA023 (600 mg) was somnolence, mild in severity.   
In the MAD portion of the study, treatment-HPHUJHQW$(VWKDWRFFXUUHGLQVXEMHFWVGRVHG 
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%] in PRA023, 0 in 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. 
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For the ongoing Phase 2 studies PR200-102 ARTEMIS-UC (this protocol) and PR200-103 
APOLLO-CD, ongoing review of unblinded efficacy and safety data by the 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 
the APOLLO-CD (open-label) study 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 
in monkeys will provide a safety margin of ~
-fold and ~
-fold 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 
 ± 
g/mL and an AUC0-672hr of 
 ± 
 g*hr/mL 
after the last 500 mg induction dose.  
Of note, the predicted Cmax after the initial 1000 mg dose in the IP is expected to be the highest 
concentration obtained during the PR200-102 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 PR200-102 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 PK 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. 
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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 
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 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 parallel open-label study in CD (PR200-103). 
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2 
STUDY OBJECTIVES 
2.1 
Primary Objective 
x To assess the safety and tolerability of PRA023 following 12-weeks of induction 
therapy  
x To compare the efficacy of PRA023 vs placebo for induction of clinical remission at 
Week 12 
2.2 
Secondary Objectives 
All objectives below refer to comparison of PRA023-treated subjects vs placebo-treated 
subjects in Cohort 1. For the objectives where the CDx status is a variable, a comparison 
of subjects in both Cohort 1 and Cohort 2 will be conducted. 
x To compare the efficacy of PRA023 vs placebo for induction of endoscopic 
improvement at Week 12 
x To compare the efficacy of PRA023 vs placebo for induction of clinical response at 
Week 12 
x To compare the efficacy of PRA023 vs placebo in CDx+ subjects (Cohort 1 + Cohort 2) 
for induction of clinical remission at Week 12 
x To compare the efficacy of PRA023 vs placebo for induction of symptomatic 
remission at Week 12 
x To compare the efficacy of PRA023 vs placebo for induction of histologic remission at 
Week 12  
x To compare the efficacy of PRA023 vs placebo for induction of histologic-
endoscopic mucosal improvement at Week 12 
x To compare the efficacy of PRA023 vs placebo in CDx+ subjects (Cohort 1 + Cohort 
2) for induction of endoscopic improvement at Week 12 
x To compare the efficacy of PRA023 vs placebo in CDx+ subjects (Cohort 1 + Cohort 
2) for induction of clinical response at Week 12 
x To compare the efficacy of PRA023 vs placebo in CDx+ subjects (Cohort 1 + Cohort 
2) for induction of symptomatic remission at Week 12 
x To compare the efficacy of PRA023 vs placebo in CDx+ subjects (Cohort 1 + Cohort 
2) for induction of histologic remission at Week 12 
x To compare the efficacy of PRA023 vs placebo in CDx+ subjects (Cohort 1 + Cohort 
2) for induction of histologic-endoscopic mucosal improvement at Week 12 
x To compare the efficacy of PRA023 in CDx+ (Cohort 1 + Cohort 2) vs CDx negative 
(CDx-) subjects for induction of clinical remission at Week 12 
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x To compare the efficacy of PRA023 vs placebo for induction of mucosal healing at 
Week 12 
x To compare the efficacy of PRA023 vs placebo in CDx+ subjects (Cohort 1 + Cohort 
2) for induction of mucosal healing at Week 12 
x To compare the efficacy of PRA023 vs placebo for change in Inflammatory Bowel 
Disease Questionnaire (IBDQ) at Week 12 
x To compare the efficacy of PRA023 vs placebo in CDx+ subjects (Cohort 1 + Cohort 
2) for change in IBDQ at Week 12 
x To compare the efficacy of PRA023 vs placebo in CDx+ subjects per alternative 
algorithm (Cohort 1 + Cohort 2) for induction of clinical remission at Week 12 
2.3 
Exploratory Objectives 
x To assess the PK of PRA023 in subjects with UC over time 
x To assess the effects of PRA023 on tissue and serum PD markers, including total 
TL1A concentrations over time 
x To assess the effect of PRA023 on inflammatory biomarkers including fecal 
calprotectin and high sensitivity C-reactive protein (hsCRP) over time 
x To assess the proportion of subjects in 3-component Modified Mayo Score response, 
3-component Modified Mayo Score remission, endoscopic improvement, Robarts 
histopathology index (RHI) histologic remission, Geboes score histologic remission, 
and mucosal healing at Week 50 
x To assess the change in Partial Mayo Score over time 
x To assess the change in Geboes Index and RHI from Baseline to Week 12 and Week 
50 
x To assess the exposure-response relationship of PRA023 on PD markers over time 
x To assess the proportion of subjects achieving corticosteroid-free-remission at Week 
50 
x 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 Objective Evaluation 
x The proportion of subjects reporting adverse events (AEs), serious adverse events 
(SAEs), AEs leading to discontinuation, and markedly abnormal laboratory values. 
x The proportion of subjects in the 3-component Modified Mayo Score clinical 
remission (as defined by endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, 
and stool frequency subscore of 0 or 1 and not greater than Baseline) at Week 12. The 
3-component Modified Mayo Score ranges from 0-9 and includes rectal bleeding, 
stool frequency and endoscopic assessment domains. 
3.2 
Secondary Objective Evaluation 
x The proportion of subjects with endoscopic improvement, as defined by endoscopy 
VXEVFRUH 1 with no friability) at Week 12. 
x The proportion of subjects in 3-component Modified Mayo Score clinical response at 
Week 12. The 3-component Modified Mayo Score clinical response is defined by 
UHGXFWLRQIURP%DVHOLQH 2 points and  30% in 3-component Modified Mayo Score, 
DFFRPSDQLHGE\DUHGXFWLRQLQUHFWDOEOHHGLQJVXEVFRUHRUDEVROXWHUHFWDO
EOHHGLQJVXEVFRUH 1. 
x The proportion of subjects in the 3-component Modified Mayo Score clinical 
remission (as defined by endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, 
and stool frequency subscore of 0 or 1 and not greater than Baseline), in CDx+ 
subjects (Cohort 1 + Cohort 2) treated with PRA023 compared to CDx+ placebo-
treated subjects at Week 12. The 3-component Modified Mayo Score ranges from 0-9 
and includes rectal bleeding, stool frequency and endoscopic assessment domains. 
x The proportion of subjects in symptomatic remission at Week 12. 
x 7KHSURSRUWLRQRIVXEMHFWVZLWKKLVWRORJLFUHPLVVLRQGHILQHG*HERHVVFRUH 3.1) at 
Week 12. 
x The proportion of subjects with histologic-endoscopic mucosal improvement (defined 
DV*HERHVVFRUH 3.1 and HQGRVFRS\VXEVFRUH 1 with no friability) at Week 12. 
x The proportion of subjects with endoscopic improvement, as defined by endoscopy 
VXEVFRUH 1 with no friability, in CDx+ subjects (Cohort 1 + Cohort 2) treated with 
PRA023 compared to CDx+ placebo-treated subjects at Week 12. 
x The proportion of subjects in 3-component Modified Mayo Score clinical response in 
CDx+ subjects treated with PRA023 compared to CDx+ placebo-treated subjects at 
Week 12. The 3-component Modified Mayo Score clinical response is defined by 
UHGXFWLRQIURP%DVHOLQH 2 points and LQ3-component Modified Mayo Score, 
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DFFRPSDQLHGE\DUHGXFWLRQLQUHFWDOEOHHGLQJVXEVFRUHRUDEVROute rectal 
EOHHGLQJVXEVFRUH 
x The proportion of subjects with symptomatic remission in CDx+ subjects (Cohort 1 + 
Cohort 2) treated with PRA023 compared to CDx+ placebo-treated subjects at Week 
12. 
x The proportion of subjects with histologic remission, dHILQHGDV*HERHVVFRUH 3.1, 
in CDx+ subjects (Cohort 1 + Cohort 2) treated with PRA023 compared to CDx+ 
placebo-treated subjects at Week 12.  
x The proportion of subjects with histologic-endoscopic mucosal improvement (defined 
DV*HERHVVFRUH 3.1 and endRVFRS\VXEVFRUH 1 with no friability), in CDx+ 
subjects (Cohort 1 + Cohort 2) treated with PRA023 compared to CDx+ placebo-
treated subjects at Week 12. 
x The proportion of subjects with clinical remission (defined as endoscopic subscore of 
0 or 1, rectal bleeding subscore of 0, and stool frequency subscore of 0 or 1 and not 
greater than Baseline) in CDx+ subjects (Cohort 1 + Cohort 2) treated with PRA023 
compared to in CDx- subjects treated with PRA023 at Week 12. 
x The proportion of subjects with mucosal heaOLQJGHILQHGDV*HERHVVFRUH 2B.1 and 
endoscopy subscore of  1) at Week 12. 
x 7KHSURSRUWLRQRIVXEMHFWVZLWKPXFRVDOKHDOLQJGHILQHGDV*HERHVVFRUH 2B.1 and 
endoscopy subscore of  1), in CDx+ subjects (Cohort 1 + Cohort 2) treated with 
PRA023 compared to CDx+ placebo-treated subjects at Week 12. 
x 7KHSURSRUWLRQRIVXEMHFWVZLWK,%'4UHVSRQVHDVGHILQHGE\-point increase 
from Baseline at Week 12. 
x 7KHSURSRUWLRQRIVXEMHFWVZLWK,%'4UHVSRQVHDVGHILQHGE\-point increase 
from Baseline, in CDx+ subjects (Cohort 1 + Cohort 2) treated with PRA023 
compared to CDx+ placebo-treated subjects at Week 12. 
x The proportion of subjects in the 3-component Modified Mayo Score clinical 
remission (as defined by endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, 
and stool frequency subscore of 0 or 1 and not greater than Baseline), in CDx+ 
subjects per alternative algorithm (Cohort 1 + Cohort 2) treated with PRA023 
compared to CDx+ placebo-treated subjects per alternative algorithm at Week 12. 
The 3-component Modified Mayo Score ranges from 0-9 and includes rectal bleeding, 
stool frequency, and endoscopic assessment domains. 
3.3 
Exploratory Objective Evaluation 
x The pharmacokinetics of PRA023 in subjects with UC after multiple doses. 
x The change from Baseline in serum and fecal inflammatory biomarkers (PD markers). 
x The proportion of subjects in 3-component Modified Mayo Score response, 3-
component Modified Mayo Score remission, endoscopic improvement, RHI 
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histologic remission, Geboes score histologic remission, and mucosal healing at 
Week 50. 
x The change in Partial Mayo Score (with or without PGA component) over time. 
x The change in Geboes Index and RHI from Baseline to Week 12 and Week 50. 
x The exposure-response relationship of PRA023 on PD markers. 
Within subpopulation of subjects on corticosteroid at study entry, the proportion of 
subjects in clinical remission and off of corticosteroid at Week 50. 
x The long-term safety, tolerability, and efficacy of PRA023 through Week 168/170. 
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4 
INVESTIGATIONAL PLAN 
4.1 
Study Design 
This is a multi-center, double-blind, randomized, placebo-controlled proof of concept study 
designed to assess the safety, tolerability, and efficacy of PRA023 following 12 weeks of induction 
therapy in subjects with UC. 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 multiple ascending dose study in normal healthy volunteers (Study PR200-101). 
The study has 4 periods (Screening Period, Induction Period [IP], Open-Label Extension [OLE] 
Period, and Follow-Up [FU] Period). The study will have 2 Cohorts that will enroll subjects in a 
sequential fashion utilizing an adaptive design as described below. 
Cohort 1: Following the Screening Period, approximately 120 eligible subjects with moderately 
to severely active UC will enter the IP and be randomized in a 1:1 fashion to receive IV 
administration of PRA023 1000 mg on Week 0/Day 1, followed by 500 mg on Weeks 2, 6, and 
10, or placebo at the same timepoints. Randomization will be stratified by CDx status of positive 
(CDx+) or negative (CDx-) and prior biologic experience (yes/no) at Week 0/Day 1. Subjects 
who discontinue from the study drug will have a follow-up period of 12 weeks after last dose. 
Cohort 2:  Enrollment will continue into Cohort 2 when any stratification limit of Cohort 1 
enrollment is completed.  When approximately 80% of subjects in Cohort 1 (i.e., ~96 subjects) 
have reached Week 12 or early terminated from the study, the DMC will conduct an unblinded 
analysis of clinical efficacy in CDx+ subjects and will recommend whether to continue 
enrollment into Cohort 2. The sample size for CDx+ subjects (combining Cohort 1 and Cohort 2) 
will be approximately 40, in the case where Cohort 2 completes enrollment as planned. For 
Cohort 2, eligible subjects who are CDx+ will enter the IP and be randomized in a 1:1 fashion to 
receive IV administration of PRA023 1000 mg on Week 0/Day 1, followed by 500 mg on Weeks 
2, 6, and 10, or placebo at the same timepoints. Randomization will be stratified by prior biologic 
experience (yes/no) at Baseline. Subjects who discontinue from the study drug will have a 
follow-up period of 12 weeks after last dose.  
Subjects who complete the 12-week IP from either Cohort will have the option to enter OLE. 
During OLE, starting at Week 14 visit: 
x 5HVSRQGHUVGHILQHGDVUHGXFWLRQIURP%DVHOLQHSRLQWVand LQ3-component 
MRGLILHG0D\R6FRUHDFFRPSDQLHGE\DUHGXFWLRQLQUHFWDOEOHHGLQJVXEVFRUHRU
absolute rectal bleedLQJVXEVFRUHZLOOEHUH-randomized, stratified by CDx status of 
CDx+ or CDx-, to either 250 mg IV every 4 week (Q4W) or 100 mg IV Q4W, starting at 
Week 14 until Week 170 
x Nonresponders will receive an open-label induction regimen of 1000 mg of PRA023 on 
Week 14, followed by 500 mg of PRA023 on Weeks 16, 20, and 24. Nonresponders who 
do not respond at Week 26 (per investigator discretion) should be discontinued from the 
study. Nonresponders who respond at Week 26 (per investigator discretion) will be re-
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randomized to either 250 mg IV Q4W or 100 mg IV Q4W, starting at Week 28 until
Week 168.
x
For subjects assigned to the 100 mg Q4W OLE arm, the dose may be escalated to 
250 mg Q4W if disease activity is not adequately controlled in the Investigator’s 
opinion.
The study also includes an optional PK sub-study during the IP for subjects who consent to 
additional PK sampling.
4.1.1
Study Schema
The overall schema for the study is noted below.
Figure 1
Study Schema for Induction Period
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Figure 2
Study Schema for Open-Label Extension Period
Q4W = every 4 weeks; ® = Randomization
4.1.2
Number of Subjects
Approximately 120 subjects with moderately to severely active UC will initially be randomized
in Cohort 1. Enrollment will continue into Cohort 2 when any stratification limit of Cohort 1 
enrollment is completed. Following interim analysis when approximately 80% of subjects in 
Cohort 1 (i.e., ~96 subjects) have reached Week 12 or early terminated from the study, the DMC 
will make a recommendation on the continuation of enrollment into Cohort 2. The planned
sample size for CDx+ subjects (combining Cohort 1 and Cohort 2) will be approximately 40 in 
the case where Cohort 2 enrollment is completed as planned.
4.1.3
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 
168/170
Follow-Up:
12 weeks
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4.1.4 
Subject Numbering and Randomization 
4.1.4.1 
Screening Numbers 
All subjects will be assigned a unique six-digit identification 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 subject on all screening documents and during their study 
participation. 
4.1.4.2 
Randomization Numbers 
Subject enrollment and assignment of treatment will be managed through the use of a centralized 
Interactive Response Technology (IRT) system or another suitable system. Subjects who meet 
the required criteria for study participation will be assigned a subject randomization number which 
will be captured in the IRT. Subjects who are re-randomized in OLE will retain their original 
randomization numbers. 
4.1.4.3 
Blinding/Unblinding Procedures 
The Investigators and the Medical Monitor(s) will be able to unblind subjects through the IRT 
when it is medically imperative to know whether a subject is receiving PRA023 or placebo. In 
case of an emergency, the Investigator has the sole responsibility to assess and make the decision 
to unblind the subject’s drug assignment if he/she feels this is warranted. Each Investigator will 
make arrangements to ensure that access to the secure internet site (i.e., individual user name and 
password) is maintained in strict confidence to prevent a compromise of subject blinding by non-
study or unauthorized individuals. 
Only in the event of an adverse event (AE) that the Investigator feels cannot be adequately 
treated without knowing the identity of the study drug should the medication code be broken for 
an individual subject. Every effort must be made to contact the Sponsor and/or the Medical 
Monitor as soon as possible thereafter if it is an emergency (no later than 24 hours after 
emergency unblinding). Similarly, if the Medical Monitor breaks the blind for the purpose of 
evaluating an emergent safety issue, the Medical Monitor will document within study 
correspondence the rationale, circumstances, and the person or persons being informed about the 
unblinding. 
Access to randomization codes and corresponding treatment assignment will also be made 
available through the IRT to the appropriate Sponsor designee(s) and individual(s) who are 
responsible for reporting serious adverse events (SAEs) and suspected unexpected serious 
adverse reactions (SUSARs) to the regulatory authorities and should be accessed only in the 
event of a medical emergency. No other Sponsor personnel will have access to blinded subject 
treatment codes until all study data have been entered onto the study database and validated, and 
the database locked. 
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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 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 study 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. 0DOHRUIHPDOH 18 years of age. 
2. Subjects must have had a diagnosis of UC at least 3 months before screening (confirmed by 
endoscopy + histology) to be eligible for study participation. For subjects with no 
documented confirmation of UC diagnosis or if previous diagnosis is not deemed conclusive, 
UC diagnosis must be confirmed at time of screening colonoscopy. Note that mention of 
“chronic inflammation” or “ulcerative colitis” or equivalent on histology report is acceptable. 
3. Moderately to severely active UC as defined by 3-component Modified Mayo score 
(3 components of rectal bleeding, stool frequency, and endoscopy) of 4 to 9, inclusive, with 
Modified 0D\RHQGRVFRSLFVXEVFRUH 2 and rectal bleHGLQJVXEVFRUH 
4. 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: 
x 2UDOSUHGQLVRQHPJGD\RUHTXLYDOHQWRUEXGHVRQLGHPJGD\ or equivalent 
or beclRPHWKDVRQHPJGD\ for at least 2 weeks 
x 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 
x ,PPXQRVXSSUHVVDQWVD]DWKLRSULQHPJNJGD\RU-PHUFDSWRSXULQHPJNJGD\ 
[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) 
x An approved anti-TNF agent at an approved labeled dose for at least 8 weeks 
x Vedolizumab at the approved labelled dose for at least 8 weeks 
x An approved JAK inhibitor (e.g., tofacitinib, upadacitinib, or filgotinib) at an 
approved labelled dose for at least 8 weeks 
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x An approved anti-IL-12/23 (e.g., ustekinumab) at an approved labelled dose for at 
least 8 weeks 
x An approved sphingosine 1-phosphate receptor (S1PR) modulator (e.g., ozanimod) at 
an approved labelled dose for least 12 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: 
x Oral Prednisone t 10 mg/day (or equivalent) for at least 3 months 
x ,PPXQRVXSSUHVVDQWV>D]DWKLRSULQHPJNJGD\RU-mercaptopurine t 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 biologic/biologic-like therapy(ies) (anti-TNF, JAK 
inhibitor, S1PR modulator, anti-IL-12/23, and/or anti-integrin): 
x The study will include a maximum of 70% and a minimum of approximately 50% 
subjects who have had prior biologic/biologic-like therapy(ies) experience. Upon 
reaching the maximum number of allowed biologic/biologic-like experienced subjects 
(70%), subjects who have had prior biologic/biologic-like experience will no longer be 
allowed to enter the study. Upon reaching the maximum number of allowed 
biologic/biologic-like naïve subjects (approximately 50%), subjects who have never been 
exposed to a prior biologic/biologic-like will no longer be allowed to enter the study. 
x Subject cannot have failed (no response, insufficient response, loss of response, and/or 
intolerance) > 3 classes or > 4 individual biologic/biologic-like therapies (exclusion 
criterion #26). 
5. 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 
effective methods of contraception until at least 12 weeks after the last dose of study drug. 
6. 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. 
7. Subject must meet drug stabilization requirements, as applicable: 
a) Oral corticosteroid treatment must be WKHHTXLYDOHQWRI20 PJSUHGQLVRQHRUPJ
budesonide or beclomethasone  5 mg daily at a stable dose for at least 2 weeks prior to 
randomization. 
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b) Oral aminosalicylates should be at a stable dose for at least 2 weeks prior to 
randomization. 
c) Azathioprine and 6-mercaptopurine should be at a stable dose for at least 4 weeks prior to 
randomization. 
8. Able to provide written informed consent and understand and comply with the requirements 
of the study. 
9. For Cohort 2 only: Subjects must be CDx+. 
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 randomization. 
Target Disease Exceptions 
4. Diagnosis of CD or indeterminate colitis. 
5. UC limited to the rectum (< 15 cm from anal verge). 
6. Current evidence of fulminant colitis, toxic megacolon, or bowel perforation. 
7. Current or impending need for colostomy or ileostomy. 
8. Previous total proctocolectomy or partial colectomy.  
9. Surgical bowel resection within 3 months before screening. 
10. Concomitant primary sclerosing cholangitis (PSC). 
Medical History and Concurrent Diseases 
11. Past or current evidence of definite low-grade or high-grade colonic dysplasia that has 
not been completely removed. 
12. Subjects who are scheduled or anticipate the need for surgery, aside from dermatologic 
procedures. 
13. Subjects who have a history of clinically significant drug or alcohol abuse. 
14. 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). 
15. Current symptoms of severe, progressive, or uncontrolled renal, hepatic, hematological, 
pulmonary, cardiac, neurological, ophthalmologic or cerebral disease. Concomitant 
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medical conditions that in the opinion of the Investigator might place the subject at 
unacceptable risk for participation in this study. 
16. 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. 
17. 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 randomization, and no evidence of active TB on 
chest x-ray during screening. 
18. 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). 
19. 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. 
20. 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, but subjects with successfully treated Hepatitis C 
ZLWKQRUHFXUUHQFHIRU\HDU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. 
21. Subjects with herpes zoster reactivation or cytomegalovirus (CMV) that resolved less 
than 2 months prior to signing informed consent. 
22. 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 
23. Positive stool studies [e.g., by Polymerase Chain Reaction (PCR), bacterial culture, toxin, 
etc.] if Investigator deems this positivity reflects infection rather than colonization. 
Subjects who have an infection can be retested after the completion of a full course of 
treatment, if treatment is deemed medically indicated. 
24. 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. 
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25. 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 > 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 
26. Failed (no response, insufficient response, loss of response, and/or intolerance) > 3 
classes (anti-TNF, anti-integrin, anti-IL12/23, JAK inhibitor, S1PR modulator) or > 4 
individual biologic/biologic-like therapies. 
27. Any marketed biologic or biologic-like within 2 weeks for JAK inhibitors (e.g., 
tofacitinib, upadacitinib or filgotinib), 8 weeks for anti-TNF agents, 10 weeks for S1PR 
modulators (e.g., ozanimod), and 12 weeks for vedolizumab and anti-IL-12/23 (e.g., 
ustekinumab) prior to randomization or if drug level per therapeutic dose monitoring is 
greater than lower limit of detection. 
28. Any biologic immunomodulators not covered in exclusion criterion 27, used for UC or 
other conditions within 8 weeks or 5 half-lives, whichever is longer, prior to 
randomization or if drug level per therapeutic dose monitoring is greater than lower limit 
of detection. 
29. Rituximab within 1 year prior to randomization. 
30. Parenteral corticosteroids within 4 weeks or rectal administration of corticosteroids 
within 2 weeks prior to randomization. 
31. Rectal administration of 5-ASA within 2 weeks prior to randomization. 
32. Tacrolimus, methotrexate, cyclosporine, mycophenolate mofetil (CellCept®), 
immunoadsorption columns (such as Prosorba columns), d-penicillamine, leflunomide, 
thalidomide, fish-oil preparations, probiotics, fecal transplantation, non-steroidal anti-
inflammatory agents (NSAIDs), aspirin > 81 mg/day within 2 weeks prior to 
randomization.  
33. Other investigational chemical agent within 30 days or other investigational biologic 
agent within 8 weeks or 5 half-lives (whichever is longer) of randomization.  
34. Prior exposure to PRA023. 
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Other Exclusion Criteria 
35. Prisoners or subjects who are compulsorily detained (involuntarily incarcerated) for 
treatment of either a psychiatric or physical (e.g., infectious disease) illness must not be 
enrolled into this study. 
36. Legal or mental incapacitation, or inability to understand and comply with the 
requirements of the study. 
37. 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 
nonchildbearing 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 randomization, 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 randomization. 
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. 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 IP. 
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 
adequate period of time to ensure effectiveness 
2. Correctly placed copper-containing intrauterine device (IUD) 
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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 nonchildbearing potential must meet at least one of the following criteria: 
x 
Have had surgical sterilization (hysterectomy, bilateral oophorectomy, or bilateral 
salpingectomy) 
x 
Have medically confirmed ovarian failure 
x 
Female who are postmenopausal with amenorrhea without an alternative medical cause 
for at least 1 year prior to the first dose and have 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 UC medications, including 5-ASA, corticosteroids, immunosuppressives 
(AZA, 6-MP, and MTX), anti-TNFs, anti-integrins, JAK inhibitors, S1PR modulators, 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, daily 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: 
x A stable dose of 5-ASA for at least 2 weeks prior to randomization and throughout 
the IP 
x A stable dose of oral corticosteroids (prednisone  20 mg/day or equivalent) for UC 
for at least 2 weeks prior to randomization and during the IP. During the OLE, a 
tapering schedule should be followed if the subject’s condition allows (see Section 
4.4.4) 
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x $VWDEOHGRVHRIRUDOEXGHVRQLGH 9 mg/day or equivalent) or beclomethasone  5 
mg/day for at least 2 weeks prior to randomization and during the IP. During the 
OLE, a tapering schedule should be followed if the subject’s condition allows (see 
Section 4.4.4) 
x A stable dose of immunosuppressants (AZA or 6-MP) for 4 weeks prior to 
randomization and during the IP. 
4.4.3 
Prohibited Medications 
x Any marketed biologic or biologic-like therapy throughout the study 
x IV corticosteroid for treatment of UC during the Induction period 
x Oral corticosteroid (prednisone > 20 mg/day or equivalent) for treatment of UC 
during the IP 
x Oral budesonide > 9 mg/day or equivalent or beclomethasone > 5 mg/day 
during the IP 
x Any per rectal therapy including enema (e.g., 5-ASA, budesonide, corticosteroid), 
other than that required for endoscopy preparation during the IP) during the IP 
x Systemic tacrolimus, methotrexate, systemic cyclosporine, oral mycophenolate 
mofetil (MMF), immunoadsorption columns (such as Prosorba columns), D-
penicillamine, leflunomide, Thalidomide, purified medicinal probiotics throughout 
the study 
x Chronic use of non-steroidal anti-inflammatory agents (NSAIDs or aspirin > 100 
mg/day) during the Induction period 
x 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) 
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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 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 
During OLE, high-dose steroids for UC, increases in oral aminosalicylates, rectal 
aminosalicylates, and rectal corticosteroids are permitted as rescue medications. Other UC 
treatments will not be permitted during this period 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 UC, 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: 
x 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. 
x 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. 
x Persistent non-compliance of the subject.  
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x Pregnancy. 
x Use of any investigational drug therapy for UC excluding study treatment. 
x Treatment with biologic or biologic-like therapy for UC. 
x Colectomy. 
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/placebo 
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. 
There are no matching placebo vials for this study. As such, the unblinded site pharmacist(s) or 
designee will need to prepare the study drug for infusion. Subjects randomized to placebo will 
receive normal saline infusions. Both the study drug and placebo infusion bags will be prepared 
in such manner that the Investigator and the subject will not know whether the subject is 
receiving PRA023 or placebo. Detailed study drug preparation and handling instructions will be 
provided 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’s unblinded monitor 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 
Study Drug Administration 
All doses of PRA023 or placebo 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, Table 3, and Table 4). 
Some of the major safety concerns associated with immunogenicity are anaphylaxis, cytokine 
release syndrome, “infusion reactions”, and non-acute reactions such as delayed hypersensitivity; 
and manifestations may be common among these events. 
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: 
x 
Generalized hives, pruritis/itching, flushing, swollen lips/tongue/uvula 
x 
Symptoms of respiratory compromise (e.g., dyspnea, wheeze/bronchospasm, stridor, 
reduced peak expiratory flow, hypoxemia) 
x 
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) 
x 
Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
If a subject experiences anaphylaxis, study drug 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), 
study drug 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 the stop of 
infusion. If symptoms return, study drug should be discontinued immediately and permanently. 
In the event that there is an infusion interruption, the entire duration of study drug 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 endoscopy. The endoscopy should be performed after all 
other eligibility criteria have been met and within 28-5 days of randomization to allow 
3-component Modified Mayo score calculation. 
Subjects may be re-screened one time at the discretion of the Sponsor if they fail their initial 
screening. 
For Cohort 2 - the first screening test after informed consent has been obtained should be buccal 
swab for CDx status identification, unless already known from study PR100-105 (global sample 
collection study).  If the buccal swab testing shows a result of CDx+, the subject may complete 
all other screening procedures as per Table 1. If the buccal swab is CDx- the subject will be 
screen failed. The 35-day screening window additional study assessments need not begin until 
the first study assessment post ICF and CDx status is obtained.  
After randomization, 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 
Table 1 
Schedule of Study Assessments – Screening Period 
Procedure 
Study Visit 
Screening 
NOTES 
Screening duration is up to 35 days (5 weeks) *NOTE: for Cohort 
2, the 35-day window should start after informed consent and CDx  
status is known 
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 
 
Interim Physical Examination  
 
 
Vital Signs 
X 
Including height and weight 
ECG 
X 
 
Chest X-Ray 
X 
Must be performed within 6 months of the screening visit with 
documentation on file. 
Adverse Events Assessment 
X 
 
Subject training on electronic diary (eDiary) 
completion 
X 
 
Issue eDiary to subject 
X 
 
Endoscopy with biopsy 
X 
Endoscopy should be performed between 28 to 6 days prior to the 
Week 0/Day 1 visit. Note that subject will need at least 3 consecutive 
evaluable days or 4 non-consecutive evaluable days of symptoms 
before Day 1. For subjects who have not had a screening 
colonoscopy for malignancy per local guideline, a surveillance 
colonoscopy should be performed. Refer to Section 6.4.2. 
Endoscopy should be performed after all other eligibility criteria 
have been met.  
Laboratory Tests 
Pharmacogenomics (buccal swab and blood) 
X 
For Cohort 2, a buccal swab should be collected and result 
obtained before all other screening assessments, unless CDx status 
already known from Study PR100-105 
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 
Should be repeated if result indeterminate. If indeterminate twice, 
then either screen fail or be considered for treatment for latent TB, 
unless deemed not necessary by infectious disease or pulmonary 
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Procedure 
Study Visit 
Screening 
NOTES 
Screening duration is up to 35 days (5 weeks) *NOTE: for Cohort 
2, the 35-day window should start after informed consent and CDx  
status is known 
specialist. 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 centrally or locally per 
country/regional regulations. Confirmation and documentation of 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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Table 2 
Schedule of Study Assessments – Induction Period 
 
Study Visit 
NOTES 
Study Week 
0 
2 
6 
10 
12 
Early 
Termination 
 
Study Day 
1 
15 
43 
71 
85 
Visit window (days) 
0 
±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 
Xa 
X 
X 
X 
Xa 
X 
Heart rate, temperature, blood pressure; Take pre-dose (no more than 
30 minutes pre-infusion), end of infusion, and end of observation 
period 
a Weight needed  
ECG 
X 
 
 
 
X 
X 
 
Adverse Events Assessment 
X 
X 
X 
X 
X 
X 
 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
 
Efficacy Assessments 
Endoscopy with Biopsy 
 
 
 
 
X 
X 
Endoscopy to be performed 7 or 6 days prior to or within +3 days after 
the Week 12 visit, or at the early termination visit. Refer to Section 
6.4.2. 
Review eDiary Data from Subjects 
X 
X 
X 
X 
X 
X 
Remind subjects to record in their eDiary daily 
Physician Global Assessment 
X 
X 
X 
X 
X 
X 
 
Partial Mayo Score 
 
X 
X 
X 
 
 
Include stool frequency, rectal bleeding, and physician’s global 
assessment (PGA) 
Total Modified Mayo Score 
Xa 
 
 
 
X 
X 
Include 4 components of stool frequency, rectal bleeding, endoscopy 
from Screening Perioda, and PGA 
3-Component Modified Mayo Score 
Xa 
 
 
 
X 
X 
Include 3 components of stool frequency, rectal bleeding, and 
endoscopy from Screening Perioda 
IBDQ 
X 
 
 
 
X 
X 
 
Laboratory Testing 
CBC 
X 
 
X 
 
X 
X 
 
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Study Visit 
NOTES 
Study Week 
0 
2 
6 
10 
12 
Early 
Termination 
 
Study Day 
1 
15 
43 
71 
85 
Visit window (days) 
0 
±3 
±3 
±3 
±3 
 
Procedure 
 
 
 
 
 
 
Chemistry Panel 
X 
 
X 
 
X 
X 
 
Fasting Lipid Panel 
X 
 
 
 
X 
X 
 
Urinalysis 
X 
 
X 
 
X 
X 
 
Urine Pregnancy Test (WOCBP only) 
X 
 
X 
 
X 
X 
 
Pharmacokinetics 
Xa 
Xb 
Xb 
Xa 
X 
X 
a. The PK samples at Week 0/Day 1 and Week 10 must be taken pre-
dose, and immediately following the end of infusion (within 30 
minutes) 
b. The PK sample taken at Weeks 2 and 6 must be taken pre-dose 
(within 30 minutes prior to dosing) 
Pharmacokinetic Sub-Study (Optional) 
Xa 
 
 
Xa 
 
 
a. In addition to the PK samples obtained in all subjects, PK sub-study 
subjects will have the following samples obtained: Week 0/Day 1 
and Week 10:  4 days (96±5 hours) and 1 week (168±5 hours) after 
completion of infusion.  
Refer to Section 6.6.1 for additional details. 
Immunogenicity 
X 
X 
X 
 
X 
X 
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 
 
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. 
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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Table 3 
Schedule of Study Assessments – Open-Label Extension Period for 1st Induction Responders  
 
Study Visit 
NOTES 
Study Week 
14 
18 
26 
34 
42 
50 
Quarterly 
(Q12w)* 
Office Visits 
after Week 50 
Early 
Termination 
Infusion 
Visits 
(excluding 
Office Visits) 
Note: Subjects who are responders after the First 
Induction Period proceed to re-randomization at Week 
14  
*Weeks 62, 74, 86, 98, 110, 122, 134, 146, 158, and 
170 
Study Day 
99 
127 
183 
239 
295 
351 
Visit window (days) 
±7 
±7 
±14 
±14 
±14 
±14 
±14 
 
±7/±14 
Procedure 
 
 
 
 
 
 
 
 
 
Enter subject into IRT for OLE 
X 
 
 
 
 
 
 
 
 
 
Complete Physical Examination 
 
 
 
 
 
X 
Xa 
X 
 
a. Yearly after week 50 
Targeted Physical Examination 
X 
X 
X 
X 
X 
 
Xa 
 
 
a. Except when the yearly complete exam is done 
Vital Signs 
X 
X 
Xa 
X 
X 
Xa 
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 
ECG 
 
 
X 
 
 
X 
 
X 
 
 
Adverse Events Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Efficacy Assessments 
Review Diary Data from Subjects 
X 
X 
X 
X 
X 
X 
X 
X 
 
Electronic or paper diaries may be used 
Physician Global Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Partial Mayo Score  
X 
X 
X 
X 
X 
 
X 
 
 
Include stool frequency, rectal bleeding, and 
physician’s global assessment (PGA) 
Total Modified Mayo Score  
 
 
 
 
 
X 
Xa 
X 
 
Include 4 components of stool frequency, rectal 
bleeding, endoscopy, and PGA 
a. Only if endoscopy is performed 
3-component Modified Mayo Score 
 
 
 
 
 
X 
Xa 
X 
 
Include 3 components of stool frequency, rectal 
bleeding, and endoscopy 
a. Only if endoscopy is performed 
Endoscopy with Biopsy 
 
 
 
 
 
Xa 
Xab 
Xc 
 
Endoscopy can be performed 14 to 6 days prior to 
Week 50 and Week 98 visits or within 7 days after Week 
50, Week 98, or ET visit 
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Study Visit 
NOTES 
Study Week 
14 
18 
26 
34 
42 
50 
Quarterly 
(Q12w)* 
Office Visits 
after Week 50 
Early 
Termination 
Infusion 
Visits 
(excluding 
Office Visits) 
Note: Subjects who are responders after the First 
Induction Period proceed to re-randomization at Week 
14  
*Weeks 62, 74, 86, 98, 110, 122, 134, 146, 158, and 
170 
Study Day 
99 
127 
183 
239 
295 
351 
Visit window (days) 
±7 
±7 
±14 
±14 
±14 
±14 
±14 
 
±7/±14 
Procedure 
 
 
 
 
 
 
 
 
 
a. )RUVXEMHFWVZKRKDYHKDGDGLDJQRVLVRI8&IRU
years and have been treated in OLE, the Week 50 and 
Week 98 endoscopies should also be a malignancy 
surveillance colonoscopy (rather than sigmoidoscopy). 
Refer to Section 6.4.2.  
b. Done annually (11-13 months from prior endoscopy) 
c. Required if >3 months since prior endoscopy 
IBDQ 
 
 
X 
 
 
X 
Xa 
X 
 
a. Every 6 months 
Laboratory Testing 
CBC 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Chemistry Panel 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Fasting Lipid Panel 
 
 
X 
 
 
X 
Xa 
X 
 
a. Every 6 months 
Urinalysis 
X 
X 
X 
X 
X 
X 
Xa 
X 
 
a. Every 6 months 
Urine Pregnancy Test (WOCBP only) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testing must be done once a month 
Pharmacokinetics 
Xa 
 
Xa 
 
Xa 
Xa 
Xb 
X 
 
a. To be taken pre-infusion 
 b. To be taken pre-infusion; every 6 months 
Immunogenicity 
 
 
Xa 
 
Xa 
Xa 
Xb 
X 
 
a To be taken pre-infusion 
b To be taken pre-infusion; every 6 months 
Biomarkers 
Biomarkers 
X 
X 
X 
X 
X 
X 
Xa 
X 
 
Additional whole blood at Week 50 and Week 98 
a Every 6 months 
Soluble TL1A  
X 
X 
X 
X 
X 
X 
 
X 
 
 
hsCRP 
X 
X 
X 
X 
X 
X 
Xa 
X 
 
a. Every 6 months 
Fecal Calprotectin 
 
 
X 
X 
X 
X 
Xa 
X 
 
a. Every 6 months 
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Study Visit 
NOTES 
Study Week 
14 
18 
26 
34 
42 
50 
Quarterly 
(Q12w)* 
Office Visits 
after Week 50 
Early 
Termination 
Infusion 
Visits 
(excluding 
Office Visits) 
Note: Subjects who are responders after the First 
Induction Period proceed to re-randomization at Week 
14  
*Weeks 62, 74, 86, 98, 110, 122, 134, 146, 158, and 
170 
Study Day 
99 
127 
183 
239 
295 
351 
Visit window (days) 
±7 
±7 
±14 
±14 
±14 
±14 
±14 
 
±7/±14 
Procedure 
 
 
 
 
 
 
 
 
 
Infusion 
X 
X 
X 
X 
X 
X 
X 
 
Xa 
a Q4 week infusion visits 
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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Table 4 
Schedule of Study Assessments – Open-Label Extension Period for 1st Induction Non-Responders  
 
Study Visit 
NOTES 
 
Study Week 14 
16 
20 
24 
26 
28 
36 
44 
48 
Quarterly 
(Q12w)* 
Office Visits 
after Week 48 
Early 
Termination 
Infusion 
Visits 
(excluding 
Office Visits) 
Note: Subjects showing a response after 
second induction per Investigator 
discretion should proceed to re-
randomization at Week 28 
*Weeks 60, 72, 84, 96, 108, 120, 132, 144, 
156 and 168 
Study Day 99 
113 141 169 183 
197 
253 309 337 
Visit window (days) ±7 
±7 
±7 
±7 
±14 
±14 
±14 ±14 ±14 
±14 
 
±7/±14 
Procedure 
 
 
 
 
 
 
 
 
 
 
 
 
Enter subject into IRT for OLE 
 
 
 
 
X 
 
 
 
 
 
 
 
Applicable for non-responders who 
complete second induction 
Subject Response is registered as part of 
Week 28 
Complete Physical Examination 
 
 
 
 
 
 
 
 
X 
Xa 
X 
 
a. Yearly after Week 48  
Targeted Physical Examination 
X 
X 
X 
X 
X 
X 
X 
X 
 
Xa 
 
 
a. Except when the yearly complete exam is 
not done  
Vital Signs 
X 
X 
X 
X 
Xa 
X 
X 
X 
Xa 
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 
ECG 
 
 
 
 
X 
 
 
 
X 
 
X 
 
 
Adverse Events Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Concomitant Medication 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Efficacy Assessments 
Review Diary Data from 
Subjects 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Electronic or paper diaries may be used 
Physician Global Assessment 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
Partial Mayo Score  
X 
X 
X 
X 
X 
X 
X 
X 
 
X 
 
 
Include stool frequency, rectal bleeding, 
and physician’s global assessment (PGA) 
Total Modified Mayo Score  
 
 
 
 
 
 
 
 
X 
Xa 
X 
 
Include 4 components of stool frequency, 
rectal bleeding, endoscopy, and PGA 
a. Only if endoscopy is performed 
3-component Modified Mayo 
Score 
 
 
 
 
 
 
 
 
X 
Xa 
X 
 
Include 3 components of stool frequency, 
rectal bleeding, and endoscopy 
a. Only if endoscopy is performed 
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Study Visit 
NOTES 
 
Study Week 14 
16 
20 
24 
26 
28 
36 
44 
48 
Quarterly 
(Q12w)* 
Office Visits 
after Week 48 
Early 
Termination 
Infusion 
Visits 
(excluding 
Office Visits) 
Note: Subjects showing a response after 
second induction per Investigator 
discretion should proceed to re-
randomization at Week 28 
*Weeks 60, 72, 84, 96, 108, 120, 132, 144, 
156 and 168 
Study Day 99 
113 141 169 183 
197 
253 309 337 
Visit window (days) ±7 
±7 
±7 
±7 
±14 
±14 
±14 ±14 ±14 
±14 
 
±7/±14 
Procedure 
 
 
 
 
 
 
 
 
 
 
 
 
Endoscopy with Biopsy 
 
 
 
 
 
 
 
 
Xa 
Xab 
X 
 
(QGRVFRS\FDQEHSHUIRUPHGWR
days prior to Week 48 and Week 96 visits or 
within 7 days after Week 48, Week 96, or 
ET visit 
a. For subjects who have had a diagnosis of 
8&IRU\HDUVDQGKDYHEHHQWUHDWHGLQ
OLE, the Week 48 and Week 96 
endoscopies should also be a malignancy 
surveillance colonoscopy (rather than 
sigmoidoscopy). Refer to Section 6.4.2.  
b. Done annually 
IBDQ 
 
 
 
 
X 
 
 
 
X 
Xa 
X 
 
a. Every 6 months  
Laboratory Testing 
CBC 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Chemistry Panel 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
 
 
Fasting Lipid Panel 
 
 
 
 
X 
 
 
 
X 
Xa 
X 
 
a.Every 6 months 
Urinalysis 
X 
X 
X 
 
X 
X 
X 
X 
X 
Xa 
X 
 
a Every 6 months 
Urine Pregnancy Test (WOCBP 
only) 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testing must be done once a 
month 
Pharmacokinetics 
Xa 
Xa 
 
 
Xa 
Xa 
 
Xa 
Xa 
Xb 
X 
 
a. To be taken pre-infusion 
 
b. To be taken pre-infusion; every 6 months 
Immunogenicity 
 
Xa 
 
 
Xa 
Xa 
 
Xa 
Xa 
Xb 
X 
 
a. To be taken pre-infusion 
b. To be taken pre-infusion; every 6 months  
Biomarkers 
Biomarkers 
X 
X 
X 
 
X 
X 
X 
X 
X 
Xa 
X 
 
Additional whole blood at Week 48 and 
Week 96 
a Every 6 months 
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Study Visit 
NOTES 
 
Study Week 14 
16 
20 
24 
26 
28 
36 
44 
48 
Quarterly 
(Q12w)* 
Office Visits 
after Week 48 
Early 
Termination 
Infusion 
Visits 
(excluding 
Office Visits) 
Note: Subjects showing a response after 
second induction per Investigator 
discretion should proceed to re-
randomization at Week 28 
*Weeks 60, 72, 84, 96, 108, 120, 132, 144, 
156 and 168 
Study Day 99 
113 141 169 183 
197 
253 309 337 
Visit window (days) ±7 
±7 
±7 
±7 
±14 
±14 
±14 ±14 ±14 
±14 
 
±7/±14 
Procedure 
 
 
 
 
 
 
 
 
 
 
 
 
Soluble TL1A  
X 
X 
X 
 
X 
X 
X 
X 
X 
 
X 
 
 
hsCRP 
X 
X 
X 
 
X 
X 
X 
X 
X 
Xa 
X 
 
a. Every 6 months 
Fecal Calprotectin 
 
X 
 
 
X 
X 
X 
X 
X 
Xa 
X 
 
a. Every 6 months 
Infusion 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
Xa 
a. Q4 week infusion visits 
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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Table 5 
Post Dosing Follow-Up Period 
 
Study Visit 
28 Days Post Dosing  
56 Days Post Dosing  
84 Days Post Dosing  
Visit window (days) 
±7 
±7 
±7 
Procedure 
 
 
 
Adverse Events Assessment 
X 
X 
X 
Concomitant Medication 
X 
X 
X 
Urine/Serum Pregnancy Test (WOCBP only) 
X 
X 
X 
Pharmacokinetics 
X 
X 
X 
Immunogenicity 
X 
X 
X 
If the Early Termination (ET) visit occurs within the same timeframe as a Post Dosing visit, the ET assessments should be completed over the Post Dosing 
assessments. 
 
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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 UC history, will be collected at the Screening Visit. 
The Investigator will perform a complete physical examination at the Screening Visit and at the 
at the Week 12/Early Termination (ET), Week 50/ET, and yearly thereafter, at a minimum. The 
complete physical examination must include the following: 
x General appearance 
x Hair and skin 
x Lymph nodes 
x Head 
x Eyes 
x Ears, nose, and throat 
x Neck 
x Respiratory 
x Cardiovascular 
x Abdominal 
x Musculoskeletal 
x Mental status 
x 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 timepoints 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 various timepoints (Section 6.1.1). 
6.3.2 
Vital Signs 
Vital signs to be assessed are heart 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). The 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 procedures (SOP) of the testing facility, for the following according to the schedule of 
study procedures (Section 6.1.1): 
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Hematology 
Chemistry 
x Hemoglobin 
x Hematocrit 
x Total and differential leukocyte count 
x Red blood cell count (with indices) 
x Platelet count 
x Blood Urea Nitrogen (BUN)/urea 
x Bilirubin (total and direct) 
x Uric acid 
x Alkaline phosphatase 
x Aspartate aminotransferase (AST) 
x Alanine aminotransferase (ALT) 
x Albumin 
x Sodium 
x Potassium 
x Chloride 
x Carbon dioxide/bicarbonate 
x Calcium 
x Phosphorus (inorganic)/phosphate 
x Total protein 
x Glucose 
x Lactate dehydrogenase (LDH) 
x Creatinine 
x Creatine kinase (CK)** 
x Gamma-glutamyl transferase (GGT) 
x Lipid panel (total cholesterol, LDL, HDL and 
VLDL fractions and triglycerides)*** 
Urinalysis 
x pH 
x Specific gravity 
x Protein* 
x Glucose 
x Ketones 
x Bilirubin 
x Blood* 
x Nitrite* 
x Urobilinogen 
x Leukocyte esterase* 
Serology 
Other Tests 
x HbsAg 
x HbcAb 
x HIV 
x HCV 
 
x Follicle stimulating hormone (FSH) for 
postmenopausal females only**** 
x QuantiFERON-TB 
x 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 collection time points. 
****If needed 
 
The Investigator must review the screening visit laboratory results for all the measured analytes 
for each subject prior to Qualification Visit. The subject must not be randomized 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. 
6.3.5.1 
Stool Evaluation 
6.3.5.1.1 
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. 
6.3.5.1.2 
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 can be retested after the completion of a full course of 
treatment for C. difficile infection. 
Refer to the Laboratory Manual for further guidance and instruction for C. difficile screening. 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. 
6.4 
Efficacy Assessment Description 
The 3-component Modified Mayo Score (stool frequency, rectal bleeding, and endoscopy) will 
be used to evaluate disease activity for primary and secondary endpoints. The Modified Mayo 
scoring system is a composite index consisting of 3 disease variables (each scored on a scale of 
0 to 3, with higher scores indicating greater frequency or severity): stool frequency, rectal 
bleeding, and findings on endoscopy. The 3-component Modified Mayo Score range from 0 to 9 
points and utilize 3 disease variables, with higher scores indicating more severe disease. The 4th 
component of the Modified Mayo Score, physician’s global assessment (PGA, scored on a scale 
of 0 to 3, with higher score indicating greater severity of disease), will be collected and the fully 
Modified Mayo Score will be used as an exploratory assessment only. The Partial Mayo score 
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ranges from 0 to 9 points and utilizes the Mayo scoring system of stool frequency, rectal 
bleeding, and PGA without the endoscopy subscore. See Appendix 16.1 for a description of 
Modified Mayo Scoring Assessment. 
For the current study, the following definitions will apply: 
x The 3-component Modified Mayo Score Clinical Response (Clinical Response) – a reduction 
IURP%DVHOLQH SRLQWVDQG 30% in Modified Mayo Score, accompanied by a reduction 
 1 LQUHFWDOEOHHGLQJVXEVFRUHRUDEVROXWHUHFWDOEOHHGLQJVXEVFRUH 1. 
x The 3-component Modified Mayo Score Clinical Remission (Clinical Remission) – 
endoscopic subscore of 0 or 1, rectal bleeding subscore of 0, and stool frequency 
subscore of 0 or 1 and not greater than Baseline. 
x Symptomatic remission – rectal bleeding subscore = 0 and stool frequency subscore = 0.  
x Endoscopic improvement – (QGRVFRS\VXEVFRUH 1 with no friability. 
x Histologic Remission – *HERHVVFRUH .1. 
x Histologic-endoscopic mucosal improvement – *HERHVVFRUH 3.1 and endoscopy 
VXEVFRUH 1 with no friability. 
x Mucosal Healing – *HERHVVFRUH 2B.1 and endoscopy subscore of  1. 
Every effort must be made to ensure the same evaluator(s) will complete the assessment for each 
subject. Visits should be scheduled with the availability of the evaluator(s) taken into account. If 
the evaluator(s) is unable to complete the evaluation, then a qualified individual, with 
overlapping experience may perform the evaluation. Documentation of who performed the 
evaluation is to be recorded in source notes. 
The clinical assessor(s) should be a different person from the one preparing the study medication 
infusion. Personnel cannot have been involved in preparing study medications in one visit and 
serve as an assessor at another visit. 
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 vendor. 
6.4.1 
Modified Mayo Scoring System 
The Modified Mayo Scoring system will be reviewed and discussed with the investigational staff 
at the Investigators’ Meeting or other forum as a method of standardizing the grading between 
the investigational staff. For each of the visit where partial Mayo score or 3-component Modified 
Mayo score/Total Modified Mayo score is collected, subject should complete the eDiary or paper 
diary entries at least 7 days immediately preceding each study visit.  
The eDiary/paper diary will collect the following information on a daily basis during the study: 
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x ‘Normal’ number of stools per day (when not having a flare). This question will be asked 
only at the screening visit. 
x Number of times needed to visit the toilet to have a bowel movement (per day). 
x Presence of blood in the stools (if any). 
x Description of blood in the stools (if any). 
eDiary/paper diary entries completed by the subject from the most recent 3 consecutive 
evaluable days (or the most recent 4 non-consecutive evaluable days, if there are no 3 
consecutive evaluable days available) during the preceding 7 days prior to the visit will be used 
to calculate the Mayo score. For Day 1/Week 0, subject should not be randomized unless there 
are adequate evaluable symptom days (3 consecutive evaluable days or 4 non-consecutive 
evaluable days during the preceding 7 days). Note that symptoms on days of the bowel 
preparation, endoscopy, and 2 days post endoscopy are not considered evaluable.   
Each subject serves as their own control to establish the degree of abnormality of stool 
frequency. The physician’s global assessment acknowledges the three other criteria (i.e., stool 
frequency, rectal bleeding, and endoscopy subscore where Mayo score is required), the subject’s 
daily recollection of number of stools per day and presence of blood in the stools, as well as 
other observations, such as physical findings and subject’s performance status. 
The PGA used to determine the Modified Mayo score must be performed by a Doctor of 
Medicine (MD), Doctor of Osteopathy (DO), Physician’s Assistant, or a qualified Endoscopist. 
The physician’s global assessment used to determine the Partial Mayo score may also be 
performed by a Nurse Practitioner (NP). See Appendix 16.1 for details and calculation of the 
Modified Mayo score. The PGA will be entered with the electronic data capture (EDC) tool by 
the investigational site staff. The eDiaries or paper diaries and Mayo Score worksheets will be 
source documents for this study. 
6.4.2 
Endoscopy Subscore of the Modified Mayo Scoring System 
The Week 0/Day 1 Visit and Week 12/ET and Week 50/ET will require a 3-component Modified 
Mayo Score and a Modified Mayo score, both of which include an endoscopy. The Screening, 
Week 12, Week 50 and yearly endoscopies and bowel preparation should not occur within 2 days 
before the eDiary or paper diary window (e.g., endoscopy must occur at least 6 days prior to the 
study visits on Week 0/Day 1). The windows for each of the endoscopy is specified in Section 
6.1.1. A Partial Mayo Score is sufficient for all other visits. The Partial Mayo Score will not 
include the endoscopy subscore since endoscopy is not performed.  
The endoscopy performed during Screening should be a malignancy surveillance colonoscopy 
for subjects ZKRKDYHDGLDJQRVLVRI8&IRU 7 years and have not had a screening colonoscopy 
for > \HDU,QDGGLWLRQIRUVXEMHFWVZKRKDYHKDGDGLDJQRVLVRI8&IRU 7 years and have 
been treated in OLE, the Week 50 endoscopy should also be a malignancy surveillance 
colonoscopy. Subjects should continue to undergo colon cancer surveillance with a full 
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colonoscopy thereafter as per local guidelines. For all other subjects and all other visits, a 
sigmoidoscopy should be performed, unless a colonoscopy should be performed per standard of 
care at the site. Regardless of the type of endoscopy performed, only the 30 cm on retraction of 
the scope should be used for Modified Mayo scoring purposes (range from 0 to 3 points). 
Both the centrally and locally read endoscopy subscores will be used during the study. The central 
endoscopy subscores will be used to derive the Modified Mayo score for study eligibility. The 
adjudication of any disagreement between the locally and centrally read endoscopy score will be 
specified in the central endoscopy reading charter. For purpose of locally read endoscopy subscore, 
photographs depicting examples of each of the 4 endoscopic subscores will be provided to sites for 
standardization purposes and the endoscopist should refer to these photos during the procedure to 
guide assignment of the endoscopy subscore based on best-match to the photos. 
6.4.3 
Collection of Biopsy Samples 
During each of the endoscopies (colonoscopy or sigmoidoscopy) performed during the study 
(during Screening, Week 12, Week 50, and Year 2), biopsies of 8 samples, 4 at the most severely 
affected and 4 at an unaffected (if present) colonic site distal to 30 cm during retraction of the 
endoscope, will be performed. If the most affected area is ulcerated, the sample should be 
obtained from the edge of the ulcer. In the absence of any visible lesions characteristic of UC, 4 
samples should be collected from the region of 10 cm on retraction of the endoscope. Two (2) of 
the 4 affected and unaffected biopsy specimens should be placed into the formalin-fixed bottles 
and 2 of the 4 affected and unaffected biopsy specimens should be placed into the RNAlater 
solution as indicated in Table 6. The formalin-fixed bottles are pre-filled with 10% neutral 
buffered formalin and the RNAlater bottles are pre-filled with RNAlater solutions. 
Table 6 
Description of Biopsy Sample Collection 
Formalin-fixed 
RNAlater 
Affected Area Labeled 
“Disease” 
Unaffected Area Labeled 
“Normal” 
Affected Area Labeled 
“Disease” 
Unaffected Area 
Labeled “Normal” 
2 samples 
2 samples 
2 samples 
2 samples 
 
All samples should be labeled prior to shipment, as instructed in the Laboratory Manual. 
All samples will be sent to the central laboratory for the study and processed by a designated 
central pathology site, which will be blinded to the treatment assignment and endoscopic status. 
Immunohistochemistry of the formalin-fixed samples may include the following antigens per 
standard procedure: Foxp3, TL1A, fibrinogen, and DR3. Samples may also be used for study of 
additional antigens listed above as discovery of new antigens related to the disease become 
available. Samples will not be stored beyond the end of the study when all analyses have been 
completed. 
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6.4.4 
Quality of Life (QoL) 
Subjects will be asked to complete Inflammatory Bowel Disease Questionnaire (IBDQ) at visits 
specified in Section 6.1.1 to measure disease specific quality of life. The questionnaires 
completed by subjects will serve as the source documents for this study. 
The IBDQ will be used to measure disease specific quality of life (QoL). 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 UC disease activity. Blood samples for PD 
are to be drawn at the time points specified in the protocol (see Section 6.1.1). Stool sample for 
fecal calprotectin can be collected up to 3 days prior to visit but must be collected prior to any 
bowel preparation for endoscopy. 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: 
Cytokines 
Stool 
x Soluble TL1A 
x Fecal calprotectin 
 
 
Biomarkers  
 
x hsCRP 
x 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 pharmacokinetics are to be drawn at the time points specified in the protocol 
(see Section 6.1.1). Blood samples for PK analysis of PRA023 concentrations will be collected 
from each subject and 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. 
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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). 
6.6.1 
Pharmacokinetic Sub-Study 
To better understand the PK of PRA023 in subjects with UC and to evaluate the PK of PRA023 at 
steady state during the IP, subjects have the option to participate in the PK sub-study. If subjects 
consent to the PK sub-study, additional PK samples will be obtained during the IP as specified in 
Table 2 (see Section 6.1.1). 
6.7 
Immunogenicity (Anti-Drug Antibody) 
Antibodies to PRA023 will be evaluated in blood samples collected from all subjects at time 
points specified in the protocol (see Section 6.1.1). These samples will be tested 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. Other analyses may be performed to verify the stability of 
antibodies to PRA023 and/or further characterize the immunogenicity of PRA023. 
The detection and characterization of antibodies to PRA023 will be performed using a validated 
assay method by or under the supervision of the Sponsor. All samples collected for detection of 
antibodies to PRA023 will also be evaluated for PRA023 serum concentration to enable 
interpretation of the antibody data. If confirmed positive, antibodies may be further characterized 
and/or evaluated for their ability to neutralize the activity of PRA023. 
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 pharmacogenetics (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 
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protect confidentiality. Each 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 completion of study 
(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: 
x Any symptom or condition not previously reported by the subject (medical history). 
x An exacerbation of a pre-existing symptom or condition. 
x A significant increase in frequency or intensity of a pre-existing episodic event or condition. 
x A drug interaction. 
x 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: 
x 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). 
x 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: 
x Death 
x A life-threatening adverse event 
x Inpatient hospitalization or prolongation of existing hospitalization 
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x A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
x A congenital anomaly/birth defect 
x Disability/incapacity that is persistent and significant 
x 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. 
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 
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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 7 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. 
Table 7 
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 
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. 
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 SAEs to Alimentiv Clinical Safety. The Investigator (or designee) is 
required to complete the SAE page in the eCRF enabling transmission to Alimentiv Safety using 
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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 
Alimentiv Clinical Safety by emailing or faxing a completed paper SAE form to: 
Fax: 
 
Email: 
 
All SAEs must be reported to Alimentiv Clinical Safety 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 the Alimentiv Clinical Safety 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 Alimentiv Clinical Safety 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 Alimentiv Clinical Safety 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 Alimentiv Clinical Safety via fax to 
, or by email to 
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. 
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 
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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 Alimentiv Clinical 
Safety if such events are attributable to the study drug. The notification to Alimentiv Clinical 
Safety of a post-study SAE by the Investigator should occur within 24 hours of becoming aware 
of the SAE. 
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. 
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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 
RI35$DWDGRVHRIPJLQPXOWLSOHDVFHQGLQJGRVHVWXG\LQStudy PR200-101. 
A formal DMC meeting will occur when approximately 80% of Cohort 1 subjects reached Week 
12 and data are cleaned. The purpose of this DMC review is to recommend whether the 
expansion of Cohort 2 is warranted according to the decision rules pre-specified in DMC charter 
and based on the assessment of benefit risk of PRA023 for CDx+ subjects. 
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 
Subjects will be randomized in a 1:1 ratio based on two stratification factors: CDx status (+/-) 
and prior biologic experience (yes/no) in Cohort 1. If the study is expanded in Cohort 2, only 
CDx+ subjects will be randomized in a 1:1 ratio based on prior biologic experience (yes/no). 
Eligible subjects will be assigned a subject randomization number at baseline by the IRT system 
upon confirmation of study eligibility. Subjects who are re-randomized in OLE will retain their 
original subject numbers. 
8.2 
Justification of Sample Size 
The study is planned to randomize up to approximately 170 subjects, approximately 120 in 
Cohort 1 and up to 50 in Cohort 2. A sample size of 60 per arm in Cohort 1 will enable a 
statistical power of > 80% for the primary endpoint at 1-sided significance level of 0.025 using 
Cochran-Mantel-Haenszel (CMH), assuming clinical remission rate of 5% for placebo and 
24% for PRA023. Additionally, the sample size will confer > 80% power to achieve statistical 
significance for the 1st secondary endpoint of endoscopic improvement with an overall 1-sided 
alpha level of 0.025, assuming the endoscopic improvement rates are 15% and 38% for placebo 
and PRA023 groups, respectively. 
Additionally, for analyses of the CDx+ population (combining CDx+ subjects from Cohort 1 and 
Cohort 2), a sample size of 40 per arm will provide a statistical power of t 80% at a 1-sided 
alpha level of 0.025, according to a group sequential design with a non-binding futility interim 
analysis when approximately 18 subjects are anticipated per arm reach Week 12, assuming 
clinical remission rate of 5% for placebo and 31% for PRA023. 
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. 
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: 
x Hematology, chemistry, coagulation, and urinalysis 
x Vital signs 
x ECG parameters 
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x Physical examination 
x 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. 
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) Populations 
The FAS population for Cohort 1: will be a subset of the Safety population and will include all 
subjects who have been randomized and treated in Cohort 1. 
The FAS population for CDx+: will be all CDx+ subjects who are randomized and treated in 
both Cohort 1 and Cohort 2. 
9.2 
Interim Analysis 
An interim analysis will be carried out when approximately 80% of subjects (approximately 96 
subjects) in Cohort 1 have reached Week 12 or early terminated from the study. The DMC will 
review the unblinded efficacy and safety data and recommend on the continuation of enrollment 
into Cohort 2. Decision rules to continue Cohort 2 enrollment are to be determined according to 
the futility bounds of group sequential design of a sample size of 40 per arm with one interim 
analysis at the information fraction of 45%.  Because the exact bounds will be calculated using 
the actual number of subjects with CDx+ included in the interim analysis, the final decision 
rules, along with sensitivity analysis, will be specified in the DMC SAP, prior to the interim 
analysis. 
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9.3 
Statistical Analysis 
9.3.1 
Demographics and Baseline Characteristics 
Demographic data (height, weight, age, sex, race, ethnic origin), and baseline characteristics 
including CDx status will be listed by subject and summarized by treatment group and for the 
overall FAS population.  
9.3.2 
Evaluation of Efficacy Parameters 
The efficacy assessment will test for the difference between PRA023 and placebo groups in FAS. 
The primary endpoint will be analyzed and compared between PRA023 and placebo treatment 
groups in FAS from Cohort 1. The primary endpoint, the proportion of subjects achieving 
clinical remission, will be tested between the 2 treatment groups at 1-sided significance level of 
0.025 using CMH with stratification factors at randomization. If significant, the 1st secondary 
endpoint of proportion of subjects achieving endoscopic improvement will be tested between the 
2 treatment groups at 1-sided significance level of 0.025. If significant, the 2nd, 3rd, 4th, and 5th 
secondary endpoints will be tested sequentially, each at 1-sided significance level of 0.025. 
Testing for statistical significance will stop when the first endpoint is not statistically significant 
at level of 0.025 and all remaining p values will be nominal.  
 
Treatment difference for primary and secondary endpoints for Cohort 1 will be estimated along 
with 95% CI for all subjects in FAS. The secondary endpoints in CDx+ subjects will be 
summarized and compared between PRA023 and placebo groups in FAS for CDx+, while the 
treatment difference will be estimated with 95% CI. Additional efficacy analysis will be detailed 
in SAP. 
9.3.3 
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 dose level. 
Any p-values that will be calculated according to the analysis plan will be interpreted in view of 
the exploratory nature of the study. 
9.3.4 
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 using descriptive statistics. The PK parameters of 
all subjects and subjects with no sample positive for ADA will be summarized to assess whether 
ADA has an impact on PK. 
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9.3.5 
Evaluation of Exploratory Parameters 
Changes from baseline in 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. 
9.3.6 
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.  
9.3.7 
Evaluation of Safety Parameters 
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. 
9.3.7.1 
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 adverse events (all, serious, 
related) will be 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. 
9.3.7.2 
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. 
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9.3.7.3 
Clinical Laboratory and Vital Signs 
All clinical laboratory results and vital signs measurements, and their change from baseline, will 
be summarized by treatment and time point of collection. 
A shift table describing out-of-normal range shifts will be provided for clinical laboratory results. 
9.3.7.4 
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 or designee 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 and FDA 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 (, 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 
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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. 
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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 
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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. 
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Bassotti G, Villanacci V, Mazzocchi A, Castellani D, Giuliano V, Corsi S, Morelli A. Colonic 
propulsive and postprandial motor activity in patients with ulcerative colitis in remission. 
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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. 
De Dombal FT, Watts JM, Watkinson G, Goligher JC. Local complications of ulcerative colitis: 
stricture, pseudopolyposis, and carcinoma of colon and rectum. Br Med J. 1966;1(5501):1442-7. 
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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. 
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Gordon IO, Agrawal N, Willis E, Goldblum JR, Lopez R, Allende D, Liu X, Patil DY, Yerian L, 
El-Khider F, Fiocchi C, Rieder F. Fibrosis in ulcerative colitis is directly linked to severity and 
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chronicity of mucosal inflammation. Alimentary pharmacology & therapeutics. 
ဩGRLDpt.14526. 
Gumaste V, Sachar DB, Greenstein AJ. Benign and malignant colorectal strictures in ulcerative 
colitis. Gut. 1992;33(7):938-41. doi: 10.1136/gut.33.7.938. 
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. 
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Hirten R, Colombel JF. Need for Caution in Diagnosis of Irritable Bowel Syndrome in Patients 
With Inflammatory Bowel Disease. Clin Gastroenterol Hepatol. 2017;15(8):1315. 
doi: 10.1016/j.cgh.2017.04.008. 
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. 
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. 
5REHUWVဩ7KRPVRQ,&)RQ-8\ODNL:&XPPLQV$*%DUUy 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. 
Schroeder KW, Tremaine WJ, Ilstrup DM. Coated Oral 5-Aminosalicylic Acid Therapy for 
Mildly to Moderately Active Ulcerative Colitis. New England Journal of Medicine. 
1987;317(26):1625-9. doi: 10.1056/nejm198712243172603. 
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. 
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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. 
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: Mဩ[ 
 
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16 APPENDIX 
16.1 
Modified Mayo Scoring System for Assessment of Ulcerative Colitis 
Activity 
The Modified Mayo score ranges from 0 to 12, with higher scores indicating more severe 
disease. Data are from Schroeder et al. (Schroeder 1987). 
Stool frequency† 
0 = Normal no. of stools for this subject  
1 = 1 to 2 stools more than normal 
2 = 3 to 4 stools more than normal 
3 = 5 or more stools more than normal  
Subscore, 0 to 3 
 
Rectal bleeding‡ 
0 = no blood  
1 = visible blood with stool less than half of the time 
2 = visible blood with stool half of the time or more 
3 = passing blood alone  
Subscore, 0 to 3 
 
Findings on endoscopy: 
0 = Normal or inactive disease 
1 = Mild disease* (erythema, decreased vascular pattern) 
2 = Moderate disease (marked erythema, lack of vascular pattern, friability, erosions)  
3 = Severe disease (spontaneous bleeding, ulceration) 
Subscore, 0 to 3 
 
Physician’s global assessment§ 
0 = Normal 
1 = Mild disease 
2 = Moderate disease  
3 = Severe disease  
Subscore, 0 to 3 
 
† Each subject serves as his or her own control to establish the degree of abnormality of the stool frequency. 
‡ The daily bleeding score represents the most severe bleeding of the day. 
§ The physician’s global assessment acknowledges the three other criteria, the subject’s daily recollection of abdominal discomfort 
and general sense of wellbeing, and other observations, such as physical findings and the subject’s performance status. 
* Modified Mayo score considers mild disease (endoscopy score of 1) to be without any friability. 
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PRA023 
Protocol PR200-102 
Version 5.0 (14 June 2023) 
Prometheus Biosciences, Inc. 
Confidential 
Page 103 of 103 
16.1.1 
Partial Mayo Scoring System for Assessment of Ulcerative Colitis Activity 
For calculation of Partial Mayo score, the mucosal appearance on endoscopy (i.e., findings on 
endoscopy component of Mayo score) is not included. 
16.1.2 
3-Component Modified Mayo Score 
For calculation of the 3-component Modified Mayo Score, the physician’s global assessment 
component of Mayo score is not included. 
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SAP_001.pdf: 
Official Protocol Title: 
NCT number: 
NCT04996797 
Document Date: 
29-Nov-2022
A Phase 2, Multi-Center, Double-Blind, Placebo-Controlled Study
to Evaluate the Safety, Efficacy, and Pharmacokinetics of
Induction Therapy with PRA023 in Subjects with
Moderately to Severely Active Ulcerative Colitis


 
Statistical Analysis Plan - Addendum 
Version: 01 
 
Status: Final 
 
PR200-102-StatisticalAnalysisPlan(Induction)-V01addendum 
Page 1 of 8 
 
 
A Phase 2, Multi-Center, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, 
Efficacy, and Pharmacokinetics of Induction Therapy with PRA023 in Subjects with 
Moderately to Severely Active Ulcerative Colitis 
 
STATISTICAL ANALYSIS PLAN 
Addendum to SAP V01 
 
Protocol No.: 
PR200-102 
Analysis Type: 
Primary Analysis of Induction Period 
Version/Date: 
01 / 29 November 2022 
Development Phase: 
2  
IND No.: 
150117 
EudraCT No.: 
2021-000091-11 
Sponsor: 
Prometheus Biosciences, Inc. 
3050 Science Park Road 
San Diego, CA 92121 
United States of America 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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. 
 
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Statistical Analysis Plan - Addendum 
Version: 01 
 
Status: Final 
 
PR200-102-StatisticalAnalysisPlan(Induction)-V01addendum 
Page 2 of 8 
 
APPROVAL 
 
A Phase 2, Multi-Center, Double-Blind, Placebo-Controlled Study to Evaluate the Safety, 
Efficacy, and Pharmacokinetics of Induction Therapy with PRA023 in Subjects with 
Moderately to Severely Active Ulcerative Colitis 
 
STATISTICAL ANALYSIS PLAN 
Primary Analysis (Induction Period) 
 
Addendum to SAP V01 
Version/Date: 01 / 29 November 2022 
 
Name 
Position 
Signature 
Date 
 
 
 
 
 
 
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3 Approver, signs for the release of the document 
 
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Statistical Analysis Plan - Addendum 
Version: 01 
 
Status: Final 
 
PR200-102-StatisticalAnalysisPlan(Induction)-V01addendum 
Page 3 of 8 
 
 
DEFINITIONS / ABBREVIATIONS  
CDx  
companion diagnostic  
CI 
confidence interval 
CMH 
Cochran–Mantel–Haenszel test 
DMC  
Data Monitoring Committee  
FAS  
full analysis set  
GM 
geometric mean 
hsCRP  
high sensitivity C-reactive protein  
LS 
least square 
IBDQ  
Inflammatory Bowel Disease Questionnaire  
SAP  
statistical analysis plan  
TL1A 
tumor necrosis factor-like cytokine 1A 
 
 
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Statistical Analysis Plan - Addendum 
Version: 01 
 
Status: Final 
 
PR200-102-StatisticalAnalysisPlan(Induction)-V01addendum 
Page 4 of 8 
 
Table of Contents 
DEFINITIONS / ABBREVIATIONS ......................................................................................... 3 
1  INTRODUCTION..................................................................................................................... 5 
2  MODIFICATION TO APPROACH FOR MULTIPLICITY .............................................. 5 
3  ANALYSIS OF CDX+ SUBPOPULATIONS IN COHORT 1 ............................................. 7 
4  CHANGES FROM PROTOCOL ............................................................................................ 8 
5  REVISION HISTORY ............................................................................................................. 8 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
3.1 
DEFAULT CDX+ ........................................................................................................ 7 
3.2 
CDX+ BASED ON ALTERNATIVE ALGORITHMS ......................................................... 8 
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Statistical Analysis Plan - Addendum 
Version: 01 
 
Status: Final 
 
PR200-102-StatisticalAnalysisPlan(Induction)-V01addendum 
Page 5 of 8 
 
1  INTRODUCTION 
This statistical analysis plan (SAP) addendum describes the additions or modifications to the 
approved SAP V01 dated 10 August 2022 and is based on the study protocol version 4.0. 
The SAP addendum covers the following topics of statistical analyses of the Induction Period for 
Cohort 1 following the corresponding database lock: 
• Modification of Section 6.10, for the approach to multiplicity adjustment.  
• Addition of an interim analysis for subjects with CDx+ based on protocol specified 
algorithm and the alternative algorithms.  
2  MODIFICATION TO APPROACH FOR MULTIPLICITY 
The following text will replace the content of Section 6.10 of the SAP V01.  
A closed hierarchical procedure will be used to control for multiple comparisons of primary and 
key secondary endpoints. The order of testing will be primary endpoint, followed by the key 
secondary endpoints in the order as displayed in Table 1. If at any point in this sequential procedure 
the null hypothesis is not rejected, the testing procedure will be terminated. All subsequent 
analyses would be considered exploratory. 
The primary endpoint will be analyzed and compared between PRA023 and placebo treatment 
groups in FAS from Cohort 1. The primary endpoint, the proportion of subjects achieving clinical 
remission, will be tested between the 2 treatment groups at 1-sided significance level of 0.025 
using CMH. If significant, the secondary endpoints will be tested sequentially between the 2 
treatment groups at significance level indicated in the table.  
Table 1 
Primary and Key Secondary Endpoints in Cohort 1 
Endpoints 
Analysis Population  
(1-sided alpha) 
Primary 
Proportion of subjects in 3-component Modified Mayo Score clinical 
remission (as defined by endoscopic subscore of 0 or 1, rectal bleeding 
subscore of 0, and stool frequency subscore of 0 or 1 and not greater 
than Baseline) at Week 12 
FAS (0.025) 
Secondary 
• 
Proportion of subjects with endoscopic improvement (as defined 
by endoscopy subscore ≤ 1 with no friability) at Week 12 
 
FAS (0.025) 
• 
Proportion of subjects in 3-component Modified Mayo Score 
clinical response (as defined by a reduction from Baseline ≥ 2 
points and ≥ 30% in 3-component Modified Mayo Score, 
accompanied by a reduction ≥ 1 in rectal bleeding subscore or 
absolute rectal bleeding subscore ≤ 1) at Week 12 
FAS (0.025) 
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Status: Final 
 
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Endpoints 
Analysis Population  
(1-sided alpha) 
• 
Proportion of subjects with symptomatic remission (as defined by 
stool frequency (SF) subscore = 0 and rectal bleeding (RB) 
subscore = 0) at Week 12 
FAS (0.025) 
• 
Proportion of subjects with histologic-endoscopic mucosal healing 
(defined as Geboes score ≤ 2B.1 and endoscopy subscore ≤ 1 with 
no friability) at Week 12 
Histology Analysis Set (0.025) 
• 
Proportion of subjects with histologic improvement (defined as 
Geboes score ≤ 3.1) at Week 12  
Histology Analysis Set (0.025) 
• 
Proportion of subjects with histologic-endoscopic mucosal 
improvement (defined as Geboes score ≤ 3.1 and endoscopy 
subscore ≤ 1 with no friability) at Week 12 
Histology Analysis Set (0.025)  
• 
Proportion of subjects with IBDQ response, as defined by ≥ 16-
point increase from Baseline at Week 12 
FAS (0.025) 
• 
Proportion of subjects in 3-component Modified Mayo Score 
clinical remission at Week 12 in CDx+ subjects (Cohort 1 + 
Cohort 2)  
CDx+ FAS (0.0245) 
• 
Proportion of subjects with endoscopic improvement, as defined 
by endoscopy subscore ≤ 1 with no friability) at Week 12 in CDx+ 
subjects (Cohort 1 + Cohort 2) 
CDx+ FAS (0.0245) 
• 
Proportion of subjects in 3-component Modified Mayo Score 
clinical response at Week 12 in CDx+ subjects (Cohort 1 + 
Cohort 2) 
CDx+ FAS (0.0245) 
• 
Proportion of subjects with symptomatic remission (as defined by 
rectal bleeding score = 0 and stool frequency score = 0) at Week 
12 in CDx+ subjects (Cohort 1 + Cohort 2) 
CDx+ FAS (0.0245) 
• 
Proportion of subjects with histologic-endoscopic mucosal healing 
(defined as Geboes score ≤ 2B.1 and endoscopy subscore ≤ 1 with 
no friability) at Week 12 in CDx+ subjects (Cohort 1 + Cohort 2) 
CDx+ Histology Analysis Set 
(0.0245) 
• 
Proportion of subjects with histologic improvement (defined as 
Geboes score ≤ 3.1) at Week 12 in CDx+ subjects (Cohort 1 + 
Cohort 2) 
CDx+ Histology Analysis Set 
(0.0245) 
• 
Proportion of subjects with histologic-endoscopic mucosal 
improvement (defined as Geboes score ≤ 3.1 and endoscopy 
subscore ≤ 1 with no friability) at Week 12 in CDx+ subjects 
(Cohort 1 + Cohort 2) 
CDx+ Histology Analysis Set 
(0.0245) 
• 
Proportion of subjects with IBDQ response, as defined by ≥ 16-
point increase from Baseline at Week 12 in CDx+ subjects 
(Cohort 1 + Cohort 2) 
CDx+ FAS (0.0245) 
 
The alpha reduction by 0.001 (2-sided) is due to the added Sponsor unblinded interim analysis of CDx+ 
population based on Cohort 1. This analysis of the CDx based on Cohort 1 is considered interim because 
data from Cohort 1 CDx+ subjects are considered interim results of CDx+ FAS (Cohort 1 + Cohort 2).  
While Section 3 of this addendum will detail the analyses, the interim analysis intends to estimate the effect 
size of PRA023 comparing to the placebo in CDx+ subjects. A minimal alpha level is allocated to the 
interim analysis, as no efficacy early stopping is expected.    
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Version: 01 
 
Status: Final 
 
PR200-102-StatisticalAnalysisPlan(Induction)-V01addendum 
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3  ANALYSIS OF CDX+ SUBPOPULATIONS IN COHORT 1 
3.1 
DEFAULT CDX+  
The protocol specified CDx status, called default UC algorithm, was used for stratification of the 
randomization in Cohort 1. As designed, CDx+ subjects will be enrolled in Cohort 2 following the 
completion of Cohort 1 enrollment. The analysis for CDx+ related secondary endpoints will be 
analyzed when all subjects in Cohort 2 complete Week 12 or early discontinue. The combined CDx+ 
subjects across Cohort 1 and Cohort 2 will consistitute the CDx+ FAS for these secondary endpoints.  
At the time of this SAP addendum, the planned interim analysis when approximately 80% of subjects 
in Cohort 1 (i.e., ~96 subjects) have reached Week 12 or early terminated from the study has been 
completed. DMC reviewed the unblinded interim efficacy and safety data for all available subjects and 
CDx+ subjects on 19 October 2022. Following the review, DMC recommended to continue the 
enrollment of Cohort 2, and informed a total sample size of 48 for the cohort.  
Based on the emerging information related to CDx development and validation, the Sponsor has made 
the decision to conduct an additional analysis for CDx+ subpopulation based on Cohort 1 data to assess 
the effect size of PRA023 in CDx+ subjects.  In addition to the subgroup analysis based on CDx status 
for the primary endpoint, Table 2 lists endpoints that will be assessed for the Cohort 1 CDx+ 
subpopulation. The methods of analysis are similar to those specified in SAP V01, with the following 
exceptions:  
• 
The analysis sets are defined as CDx+ subjects who are randomized and treated in Cohort 1. 
• 
No statistical hypothesis testing will be performed between PRA023 and Placebo treatment 
groups, while 95% confidence intervals will be presented for the estimation of treatment 
difference.  
Table 2 
Analyses for CDx+ Population in Cohort 1 
Endpoints 
Treatment Difference 
Proportion of subjects in 3-component Modified Mayo Score 
clinical remission at Week 12 
Included in subgroup analysis of 
the primary endpoint 
Proportion of subjects with endoscopic improvement, as defined 
by endoscopy subscore ≤ 1 with no friability) at Week 12 
 
Risk difference and 95% CI 
Proportion of subjects in 3-component Modified Mayo Score 
clinical response at Week 12  
Risk difference and 95% CI 
Mean change in Partial Mayo Score over time 
Mean change in PRO-2 Score over time 
Difference of LS mean and 95% 
CI 
Fold change in hsCRP over time 
Fold change in fecal calprotectin over time 
Ratio of geometric means and 95% 
CI 
 
 
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3.2 
CDX+ BASED ON ALTERNATIVE ALGORITHMS 
To evaluate whether a CDx call can render a different treatment effect of PRA023 comparing to 
placebo, alternative algorithms (Table 3) will also be assessed.   
Table 3 
Alternative CDx Algorithms 
Algorithm Name 
Description 
entrocyte.RDS 
Score and predicted label (high/low) based on Ileum-
derived entrocytes from subject’s germline genetics 
colon.bma.model.cluster 
Resident.macrophages.RDS 
Score and predicted label (high/low) based on Colon-
derived resident macrophages from subject’s germline 
genetics 
colon.bma.model.cluster.TA.RDS 
Score and predicted label (high/low) based on Colon-
derived Transit-Amplifying (TA) cells from subject’s 
germline genetics 
colon.bma.model.cluster.Goblet.cell.RDS 
Score and predicted label (high/low) based on Colon-
derived Goblet cells from subject’s germline genetics 
modc.RDS 
Score and predicted label (high/low) based on Ileum-
derived monocyte-derived dendritic cells (moDC) from 
subject’s germline genetics 
 
For each CDx+ call, descriptive statistics for the endpoints listed in Table 2 will be provided by 
treatment group. Additionally, the point estimate and multiplicity controlled 95% CI for the 
treatment difference in clinical remission at Week 12 will be plotted against the estimated overall 
treatment effect in Cohort 1. Given the number of alternative CDx algorithms to be evaluated, the 
conventional confidence intervals are subject to an inflation of the alpha. A re-sampling based 
method [1] will be used to construct the 95% CI for each CDx+ call subpopulation with an overall 
alpha level of 0.05 (2-sided) across alternative algorithms.   
 
4  CHANGES FROM PROTOCOL 
The analyses outlined in Section 3 of this addendum are additions to the analyses defined by the 
protocol.  
5  REVISION HISTORY 
Version 
Reason  
V01 
New 
 
6  REFERENCES 
1. Westfall, P. H., & Young, S. S. (1993). Resampling-based multiple testing: Examples and 
methods for p-value adjustmen. John Wiley & Sons. 
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