Clinical trial NCT04023396
Conditions: Ulcerative Colitis
Keywords: moderate to severe ulcerative colitis
Sponsor: Abivax S.A.
Start date: 2020-01-13; Completion date: 2024-03-15
Enrollment: 217 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
A phase 2b study to evaluate the long-term efficacy and safety study of ABX464 50mg as maintenance therapy in patients with moderate to severe Ulcerative Colitis.

Detailed description:
This study is an open-label study aiming at evaluating the long-term safety and the efficacy profile of ABX464 given once a day (o.d) at 50 mg in subjects who have been previously enrolled in the ABX464-103 clinical study (induction study) and who are willing to continue their treatment. All subjects will receive ABX464 given at 50mg o.d regardless of their previous treatment and dose received in the ABX464-103 study (i.e. ABX464 100mg, ABX464 50mg, ABX464 25mg or Placebo). The enrolment in this follow-up study will be based on the willingness of the subject to carry on his/her participation. Subjects will be treated with ABX464 for an overall period of 48 weeks. Subjects will be followed up on a monthly basis.

Arms: arm 1: All subjects will receive ABX464 administered at 50 mg o.d for an overall period of 96 weeks.
Interventions: intervention 1: ABX464
Intervention descriptions: intervention 1: ABX464

All subjects will receive ABX464 administered at 50 mg o.d for an overall period of 96 weeks.

Protocol documents:
Prot_000.pdf: 
ABIVAX 
Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
Page 1 / 65 
 
 
 
 
 
 
 
 
 
CLINICAL STUDY PROTOCOL 
ABX464-104 
 
Sponsor: 
 
ABIVAX 
 
5, rue de la Baume 
 
 75008 Paris 
 
FRANCE 
Investigational product:  
ABX464 
Product code: 
 
ABX464 
INN: 
 
Obefazimod 
Therapeutic indication:  
Moderate to severe ulcerative colitis 
Study code: 
 
 
ABX464-104 
EudraCT number: 
 
2019-000733-39 
IND number: 
 
 
141396 
Protocol title: 
 
A phase 2b, open-label, efficacy and safety study of ABX464 as maintenance 
therapy in patients with moderate to severe Ulcerative Colitis. 
Version number: 
 
5.1  
Version date: 
 
 
July 11th, 2022 
 
 
CONFIDENTIALITY STATEMENT 
Information and data contained herein are proprietary and confidential. 
This information should not be disclosed to any third party without the prior written consent of ABIVAX 
 
 
 
 
 
 


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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
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CLINICAL STUDY PROTOCOL VALIDATION PAGE 
Study code 
ABX464-104 
EU CT number 
2019-000733-39 
IND number 
141396 
Detailed Title 
A phase 2b, open-label, efficacy and safety study of ABX464 as maintenance 
therapy in patients with moderate to severe Ulcerative Colitis. 
Document date & version 
July 11th, 2022/ Final Version 5.1 
Validation 
Sophie BIGUENET (CMO):  
 
 
 
 
 
 
Date: 
Paul GINESTE (VP, Clin Ops): 
 
 
 
 
 
 
Date:  
Mary MANTOCK (VP, Regulatory Affairs) 
 
 
 
 
 
 
Date: 
 


ABIVAX 
Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
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CLINICAL STUDY PROTOCOL 
Study code 
ABX464-104 
Investigational product  
ABX464 
Investigational product 
code 
ABX464 
INN 
Obefazimod 
EudraCT number 
2019-000733-39 
Detailed Title 
A phase 2b, open-label, efficacy and safety study of ABX464 as 
maintenance therapy in patients with moderate to severe Ulcerative Colitis. 
Study Phase 
Phase 2b 
Coordinating Investigator 
Prof. Severine Vermeire 
University Hospitals Leuven - campus Gasthuisberg 
Gastroenterology 
UZ Herestraat 49 - box 7003 08 
3000 Leuven 
Belgium 
Sponsor 
ABIVAX 
5 rue de la Baume 
75008 Paris 
Tel: +33 (0) 1 53 83 08 41 
Fax: +33 (0) 1 53 83 07 48 
Date/Version 
July 11th, 2022 / Version 5.1 
 
 
 


ABIVAX 
Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
Page 4 / 65 
 
Contacts 
Sponsor 
ABIVAX 
5 rue de la Baume 
75008 PARIS - France 
Dr Sophie Biguenet 
Chief Medical Officer 
Tel: + 33 (0) 6 3648 7644 
 
Dr Paul GINESTE 
VP, Clinical Operations 
Tel: + 33 (0) 1 53 83 09 61 
 
Coordinating investigator 
Prof. Severine Vermeire 
University Hospitals Leuven - campus Gasthuisberg 
Gastroenterology 
Herestraat 49 - box 7003 08 
3000 Leuven - Belgium 
Study Conduct, Data management 
and Statistical Analysis 
IQVIA RDS France 
TOUR D2, 17 bis Place des Reflets 
TSA 64567 
92099 La Défense Cedex France 
miRNA-124 determination  
Biogazelle 
Technologiepark-Zwijnaarde 82,  
9052 Gent - Belgique 
Histopathology (RHI) 
Cerba Research 
126, rue Emile Baudot 
Le Millénaire – 34000 Montpellier -France 
Central Laboratory 
Eurofins Central Laboratory  
Bergschot 71  
4817 PA Breda  
The Netherlands 
Imaging Central Review 
Clario Medical Imaging and Cardiac Safety Services 
72 Hammersmith Road, 6th Floor  
London, W14 8UD- United Kingdom 
Pharmacovigilance 
Voisin Consulting (VCLS) 
64 Av. Pierre Grenier, 92100 Boulogne-Billancourt - 
France 
 
 


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INVESTIGATOR AGREEMENT PAGE 
 
EudraCT number 
 
2019-000733-39 
IND number 
 
 
141396 
Detailed Title:  
A phase 2b, open-label, efficacy and safety study of ABX464 as maintenance 
therapy in patients with moderate to severe Ulcerative Colitis. 
 
 
I have carefully read all the pages of this clinical study protocol and I agree to the following:  
• 
To conduct the study as outlined in the protocol, any mutually agreed future protocol amendments and 
with all the terms and conditions set out by ABIVAX. 
• 
Not to implement any changes in the procedures described in the protocol without the prior approval of 
the sponsor and prior to review and written approval by the Ethics Committee and/or Regulatory 
Authorities, unless instructed otherwise by the Regulatory Authorities or the wellbeing of patients is 
jeopardized. 
• 
To conduct the study in accordance with the ICH GCP (R2) guidelines, US 21 Code of Federal Regulations 
dealing with clinical studies (including parts 50 and 56 concerning informed consent and IRB regulations), 
the European Union Clinical Trials Directive 2005/28/EC, EudraLex GMP guidelines Annex 13, the 
provisions of the Helsinki Declaration, the EU Regulation 536/2014 of the European Parliament and of 
council, the EU Regulation 2016/679 of the European Parliament and of the Council of 27 April 2016 on 
the protection of natural persons with regard to the processing of personal data and on the free movement 
of such data, and relevant legislation in force.  
 
• 
I am thoroughly aware of the study drug specifications and adverse events as described in the protocol 
and the current Investigator’s Brochure and any other information provided by the Sponsor. 
• 
To ensure that sub-investigator(s) and other relevant members of my staff involved in the study are fully 
aware of their responsibilities regarding this study and will conduct the study according to the protocol.  
 
Investigator’s Name:   
 
________________________________________ 
 
Investigator’s Signature:  
 
________________________________________ 
 
Date:   
 
 
 
________________________________________ 
 
 


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Study code: ABX464-104 
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TABLE OF CONTENTS 
 
CLINICAL STUDY PROTOCOL VALIDATION PAGE 
2 
CONTACTS 
4 
ABBREVIATIONS 
8 
SYNOPSIS 
9 
1. 
INTRODUCTION AND STUDY RATIONALE 
15 
1.1. ULCERATIVE COLITIS (UC) 
15 
1.1.1. 
DISEASE 
15 
1.1.2. 
MANAGEMENT OF PATIENTS 
15 
1.2. ABX464 RATIONALE 
15 
1.2.1. 
INVESTIGATIONAL TREATMENT DESCRIPTION 
15 
1.2.2. 
INVESTIGATIONAL PRODUCT DESCRIPTION 
16 
1.2.3. 
INVESTIGATIONAL PRODUCT MODE OF ACTION 
16 
1.2.4. 
PRECLINICAL DATA OF ABX464 
17 
1.2.5. 
PREVIOUS CLINICAL EXPERIENCE WITH ABX464 
18 
1.3. RATIONALE FOR THE CLINICAL STUDY AND STUDY DESIGN 
20 
2. 
STUDY OBJECTIVES AND ENDPOINTS 
22 
2.1. PRIMARY OBJECTIVE 
22 
2.2. SECONDARY OBJECTIVES 
22 
2.3. PRIMARY ENDPOINT 
22 
2.4. SECONDARY ENDPOINTS 
23 
3. 
INVESTIGATIONAL PLAN 
25 
3.1. STUDY DESIGN 
25 
3.1.1. 
DESIGN AND METHODOLOGY 
25 
3.1.2. 
DATA SAFETY MONITORING BOARD - INDEPENDENT CARDIOVASCULAR SAFETY COMMITTEE (ICVSC) 25 
3.1.3. 
DURATION OF STUDY PARTICIPATION 
26 
4. 
STUDY POPULATION 
27 
4.1. NUMBER OF PATIENTS/CENTERS 
27 
4.2. ELIGIBILITY CRITERIA 
27 
4.2.1. 
INCLUSION CRITERIA 
27 
4.2.2. 
EXCLUSION CRITERIA 
27 
5. 
STUDY ASSESSMENTS AND PROCEDURES 
28 
5.1. STUDY FLOW CHART 
28 
5.2. STUDY CONDUCT 
28 
5.2.1. 
BASELINE VISIT (I.E. DAY 113 OF THE INDUCTION STUDY ABX464-103) 
28 
5.2.2. 
MONTHLY AND QUARTERLY VISITS (W4, WEEK X+4; W48, WEEK X+12 AND W96) 
29 
5.2.3. 
END OF STUDY VISIT (WEEK 52 OR WEEK 100 ± 2 DAYS) 
30 
5.3. DETAIL OF THE STUDY ASSESSMENTS 
31 
5.3.1. 
ECHOCARDIOGRAPHY 
31 
5.3.2. 
CARDIAC ISCHEMIC DISEASE/CONGESTIVE HEART FAILURE MEDICAL/TREATMENT HISTORY REVIEW 
31 
5.3.3. 
PHYSICAL EXAMINATION AND VITAL SIGNS 
31 
5.3.4. 
PREGNANCY 
32 
5.3.5. 
ECG 
32 
5.3.6. 
IBD QUESTIONNAIRE (IBDQ) 
32 
5.3.7. 
MODIFIED MAYO SCORE - STOOL AND RECTAL BLEEDING FREQUENCY 
32 
5.3.8. 
SIGMOIDOSCOPY WITH RECTAL/SIGMOIDAL BIOPSIES 
32 
5.3.9. 
HEMATOLOGY, BIOCHEMISTRY AND CALPROTECTIN EVALUATION 
33 
5.3.10. CYTOKINES ANALYSIS 
33 
5.3.11. MIRNA MODULATION 
33 
5.4. SUMMARY OF BLOOD SAMPLES 
34 
6. 
INVESTIGATIONAL PRODUCT(S) 
35 
6.1. DESCRIPTION OF INVESTIGATIONAL TREATMENT 
35 
6.2. DESCRIPTION OF INVESTIGATIONAL PRODUCT ABX 464 
35 
6.3. ADMINISTRATION AND DOSING 
35 
6.3.1. 
ADMINISTRATION OF THE INVESTIGATIONAL PRODUCT 
35 
6.3.2. 
GUIDELINES FOR TREATMENT POSTPONEMENT AND DOSE MODIFICATIONS 
35 


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6.4. METHOD OF ASSIGNING PATIENT NUMBERS 
35 
6.5. PACKAGING 
36 
6.6. STORAGE 
36 
6.7. PRODUCT ACCOUNTABILITY 
36 
6.8. PRIOR AND CONCOMITANT MEDICATION 
36 
6.8.1. 
ALLOWED CONCOMITANT TREATMENT 
36 
6.8.2. 
PROHIBITED CONCURRENT MEDICATIONS 
36 
7. 
STUDY COMPLETION AND WITHDRAWAL 
37 
7.1. PATIENT COMPLETION 
37 
7.2. PREMATURE TRIAL DISCONTINUATION 
37 
7.3. STUDY DISCONTINUATION 
38 
7.4. BASELINE FAILURES 
38 
7.5. END OF TRIAL 
38 
8. 
ADVERSE EVENTS (AE), ADVERSE EVENT OF SPECIAL INTEREST (AESI) AND SERIOUS ADVERSE EVENTS (SAE)39 
8.1. DEFINITION OF AN AE 
39 
8.2. DEFINITION OF AN AESI 
39 
8.3. DEFINITION OF AN ADVERSE DRUG REACTIONS (ADR) 
41 
8.4. DEFINITION OF A SUSPECTED UNEXPECTED SERIOUS ADVERSE REACTION (SUSAR) 
41 
8.5. DEFINITION OF A SAE 
41 
8.6. EVENTS AND/OR OUTCOMES NOT QUALIFYING AS SAES 
42 
8.7. EVENTS OR OUTCOMES QUALIFYING AS AES OR SAES 
42 
8.7.1. 
CLINICAL LABORATORY PARAMETERS 
42 
8.7.2. 
PREGNANCY REPORT 
42 
8.8. TIME PERIOD, AND FREQUENCY OF DETECTING AES, AESIS AND SAES 
42 
8.9. RECORDING AES AND SAES 
43 
8.10. 
REPORTING OF AESIS AND SAES TO ABIVAX OR ITS DESIGNEE 
43 
8.11. 
REPORTING OF SAES TO REGULATORY AUTHORITIES 
44 
9. 
DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
45 
9.1. STATISTICAL AND ANALYTICAL PLANS 
45 
9.1.1. 
PROTOCOL DEVIATIONS 
45 
9.1.2. 
DEFINITION OF STUDY ANALYSIS SETS 
45 
9.1.3. 
PATIENTS/PATIENTS DISPOSITION 
45 
9.1.4. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
45 
9.1.5. 
TREATMENT COMPLIANCE 
45 
9.1.6. 
INTERIM ANALYSIS 
45 
9.2. EFFICACY ANALYSIS 
45 
9.3. SAFETY ANALYSES 
46 
9.4. DETERMINATION OF SAMPLE SIZE 
46 
10. STUDY CONDUCT CONSIDERATION 
47 
10.1. 
REGULATORY AND ETHICAL CONSIDERATIONS 
47 
10.1.1. GENERAL REQUIREMENTS 
47 
10.1.2. INDEPENDENT ETHICS COMMITTEE/INSTITUTIONAL REVIEW BOARD 
47 
10.1.3. PATIENT INFORMED CONSENT 
47 
10.1.4. COMPENSATION TO PATIENTS 
49 
11. STUDY MANAGEMENT 
50 
11.1. 
REMOTE DATA ENTRY 
50 
11.2. 
DATA MANAGEMENT 
50 
11.3. 
DATA CODING 
50 
11.4. 
STUDY MONITORING 
50 
11.5. 
RECORDS RETENTION 
51 
11.6. 
QUALITY ASSURANCE AND INSPECTION BY AUTHORITIES 
51 
11.7. 
STUDY AND SITE CLOSURE 
51 
11.8. 
STUDY REPORT AND PUBLICATION 
52 
11.9. 
OWNERSHIP AND CONFIDENTIALITY 
52 
12. REFERENCES 
53 
13. APPENDICES 
54 
 


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ABBREVIATIONS 
Abbreviation or Term 
Definition 
ABX 
Abivax 
ABX464-N-Glu 
ABX464-N-Glucoronide (ABX464 main metabolite) 
AE 
AESI 
adverse event 
Adverse Event of Special Interest 
ALT/SGPT 
alanine aminotransferase/serum glutamic pyruvate transaminase 
AST/SGOT 
aspartate aminotransferase/serum glutamic oxaloacetic transaminase 
AUC0-24 
area under the plasma concentration-versus-time curve from zero to 24 hours 
AUC0-∞ 
area under the plasma concentration-versus-time curve from zero to infinity 
AUC0-t 
area under the plasma concentration-versus-time curve from time zero to the time of the last quantifiable concentration 
BMI 
Body Mass Index  
BOLS 
Baseline of the Open Label Study 
CBC 
Cap Binding Complex 
CI 
Confidence Interval 
Cmax 
peak plasma concentration 
CMV 
Cytomegalovirus 
CNS 
CPK 
Central Nervous System 
Créatine PhosphoKinase 
CRF 
Case Report Form 
CRP 
C-Reactive Protein 
CTC-AE 
Common Terminology Criteria for Adverse Events, version 5.0 
CTFG 
Clinical Trial Facilitation Group 
CYP 
Cytochrome 
DBP 
Diastolic Blood Pressure  
DSS 
Dextran sulfate sodium 
DSMB 
Data and Safety Monitoring Board 
ECCO 
European Crohn’s and Colitis Organization 
ECG 
Electrocardiogram 
EDTA 
ethylenediaminetetraacetic acid 
GCP 
good clinical practice 
GGT 
gamma-glutamyl transferase 
GHAS 
Global Histological Assessment Score 
GLDH 
GLS 
Glutamate Dehydrogenase 
Global Longitudinal Strain 
GM 
Geometric Mean 
H 
Hb 
Hours 
Hemoglobin 
HIV 
Human Immunodeficiency Virus 
HR 
heart rate 
IB 
Investigator’s Brochure 
IBD 
Inflammatory Bowel Disease 
IBDQ 
Inflammatory Bowel Disease Questionnaire 
ICF 
informed consent form  
ICH 
ICVSC 
International Conference on Harmonization 
Independent Cardiovascular Safety Committee 
IEC 
Independent Ethics Committee 
IL-1b 
Interleukine 1b 
IL-6 
Interleukine 6 
IL10 
Interleukine 10 
IMP 
Investigational Medicinal Product 
IRB 
Institutional Review Board 
ISB 
Induction study baseline 
JAK 
LFTs 
LVEF 
Janus Kinase 
Liver Function tests 
Left Ventricular Ejection Fraction 
LLT 
Lowest Level Term 
Max 
Maximum 
MedDRA 
Medical Dictionary for Regulatory Activities (version 22.0) 
mg 
Milligram 
MH 
Mucosal Healing 
Min 
Minimum 
miR 
micro-RNA 
mL 
Milliliter 
mmHg 
millimeters of mercury 
MMS 
Modified Mayo Score 
NOAEL 
NT-proBNP 
pMMS 
No Observed Adverse Effect Level 
N-terminal pro-brain natriuretic peptide 
partial Modified Mayo Score 
PT 
Preferred Term 
QD 
Quaque Die (Latin) ; Once daily 
QoL 
Quality of Life 
QTc 
heart-rate–corrected QT interval (time between the start of the Q wave and the end of the T wave in the heart’s electrical 
cycle) using Bazett’s formula 
R 
Accumulation ratio 
RHI 
Robarts Histopathology Index 
RNA 
RV 
Ribonucleic Acid 
Right Ventricle 
SAE 
serious adverse event 
SBP 
systolic blood pressure 
SD 
standard deviation 
SEM 
standard error of the mean 
SES-CD 
Simple Endoscopic Score for Crohn’s Disease 
SOC 
system organ class 
t1/2 
terminal half-life 
TB 
Tuberculosis 
TEAE 
Treatment Emergent Adverse Event 
tmax 
Time to peak plasma concentration 
TMS 
Total Mayo Score 
TNF 
Tumor Necrosis Factor 
UC 
Ulcerative Colitis 
ULN 
Upper Limit Normal 
Vd/F 
Volume of Distribution 
vs. 
Versus 
W 
Week 


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Synopsis 
Study n° 
ABX464-104 
Clinical Phase 
2b 
Type of Study 
Maintenance therapy in patients with moderate to severe UC 
Study title 
A phase 2b, open-label, efficacy and safety study of ABX464 as maintenance therapy in patients with 
moderate to severe Ulcerative Colitis. 
Investigators and 
study centers 
Sixty-nine sites in Europe and in Canada will participate in this study. 
Study Duration 
Recruitment period: 
Q4 2019 – Q2 2021 
Overall Study period: 
Q4 2019 – Q4 2023 
Investigational 
product 
ABX464 is a small molecule that binds the cap binding complex (CBC), comprised of two proteins 
CBP20 and CBP80, within the cell nucleus. This binding leads to an increased expression of a 
single micro-RNA (miR-124) by impacting the splicing of a single long non-coding RNA. Because of 
its action on this single splicing event, leading to an increase in miR-124, a microRNA with potent 
anti-inflammatory properties, ABX464 potentially has broad applicability across a variety of 
inflammatory diseases. ABX464 is currently under investigation as a potential treatment for 
Rheumatoid Arthritis (RA) and inflammatory bowel diseases (IBD). As of 30 November 2021, 1023 
subjects have received ABX464, according to various administration schedules, in all completed, and 
ongoing open-label clinical studies across all indications. Out of these 1023 subjects, 830 subjects have 
been dosed with ABX464 50mg once daily (od) including 240 subjects for longer than 6 months with 197 
for more than a year. In addition, 36 subjects have received ABX464 or placebo in ongoing blinded 
clinical study (ABX464-921). All doses tested well tolerated. 
Study Design and 
Methodology 
This study is an open-label study aiming at evaluating the long-term safety and the efficacy profile of 
ABX464 given once a day (QD) at 50 mg in patients with moderate to severe ulcerative colitis (UC) who 
have been previously enrolled in the ABX464-103 clinical study (induction study) and who are willing to 
receive their treatment with ABX464 as long-term (maintenance) therapy of remission. All patients who 
have completed the 16-week (± 4 days) induction treatment period (ABX464-103) will be eligible for this 
maintenance study regardless of their clinical response and will receive 1 capsule of ABX464 50mg once 
daily during up to 96 weeks providing the patient has a clinical response at week 48. 
 
The study design is presented below:  
Patients will be treated for a maximum of 96 weeks in this maintenance study. After the treatment period, 
patients will be followed for 4 additional weeks for safety purposes. Alternatively, eligible subjects willing 
to continue study treatment will be offered to take part in a long term follow up safety study 
(ABX464-108) at the end of treatment (ie Week 96). ABX464-108 study is a separate clinical 
study requiring health authorities and ethics committees’ approvals. 
From Day 1 onwards, patients will be seen at the investigational site every 4 weeks up to week 48 and 
then quarterly until weeks 96. Flexible sigmoidoscopy with rectal and/or sigmoidal biopsies will be 
performed, for all patients at week 48 and at week 96. Additional flexible sigmoidoscopies may be 
performed during the open label phase based on medical judgement. 
During the open label maintenance phase, in the event of clinical progression of the disease, defined as 
at least a 2-point increase from the screening partial Modified Mayo Score (pMMS) with a pMMS ≥ 4 
confirmed by an endoscopy sub score of 2 points or higher, the patient will exit the study. 
. 


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Study code: ABX464-104 
11-July -2022 
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Study n° 
ABX464-104 
Clinical Phase 
2b 
Type of Study 
Maintenance therapy in patients with moderate to severe UC 
Study Objectives 
 
Primary Objective 
The primary objective of the study is to assess in all patients the long-term efficacy of ABX464 given at 
50 mg QD on clinical remission at week 48 compared to the induction study (ABX464-103) baseline 
(ISB). 
Secondary Objectives 
Week 24 and 48 secondary objectives are: 
▪ 
To evaluate clinical remission at week 48 compared to the baseline of the open label study 
(BOLS). For patients with endoscopic improvements at week 8 of the induction study (ABX464-
103) and with no endoscopic data at week 16, the clinical remission at week 48 will be compared 
to week 8 of the induction study. 
▪ 
To evaluate the effect of ABX464 50 mg QD on Modified Mayo Score (MMS) at week 48 and on 
partial Modified Mayo Score (pMMS), among all patients, at every study visit compared to ISB. 
▪ 
To evaluate the effect of ABX464 50 mg QD on endoscopic improvement and remission and 
sustained endoscopic improvement and remission, by segment at week 48 compared to ISB and 
BOLS. For patients with endoscopic improvements at week 8 of the induction study (ABX464-
103) and with no endoscopic data at week 16, endoscopic improvement at week 48 will be 
compared to week 8 of the induction study.  
▪ 
To evaluate the proportion of patients with glucocorticoid-free clinical remission at week 48. 
▪ 
To evaluate the effect of ABX464 50 mg QD on stool and rectal bleeding frequency at every study 
visit compared to BOLS. 
▪ 
To evaluate the effect of ABX464 50 mg QD on fecal calprotectin and CRP levels at week 24 and 
week 48 visits compared to BOLS. 
▪ 
To evaluate the effect of ABX464 50 mg QD on clinical response at week 48 compared to ISB 
and BOLS. For patients with endoscopic improvements at week 8 of the induction study (ABX464-
103) and with no endoscopic data at week 16, endoscopic measurements at week 48 will be 
compared to week 8 of the induction study. 
▪ 
To evaluate the effect of ABX464 50 mg QD on miR-124 expression in colon tissue (RNA later) 
at week 48 and in total blood at week 24 and week 48. 
▪ 
To evaluate the effect of ABX464 50 mg QD on patients’ quality of Life (QoL) measured by the 
Inflammatory Bowel Disease Questionnaire (IBDQ) at week 24 and week 48 compared to BOLS. 
▪ 
To evaluate the effect of ABX464 50 mg QD on the rectal/sigmoidal infiltrates using the Robarts 
Histopathology Index (RHI), the Geboes and Nancy Histology Scoring Scales at week 48 
compared to ISB and BOLS. For patients with endoscopic improvements at week 8 of the 
induction study (ABX464-103) and with no endoscopic data at week 16, endoscopic 
measurements at week 48 will be compared to week 8 of the induction study. 
▪ 
To evaluate the long-term safety profile of ABX464 50 mg QD. 
Week 96 secondary objectives are: 
▪ 
To evaluate the effect of ABX464 50 mg QD on partial Modified Mayo Score (pMMS) at every 
study visit (week 48 to 96) compared to ISB and on Modified Mayo Score at week 96. 
▪ 
To evaluate the effect of ABX464 50 mg QD on stool and rectal bleeding frequency at every study 
visit (week 48 to 96) compared to BOLS. 
▪ 
To evaluate the effect of ABX464 50 mg QD on fecal calprotectin and CRP levels at week 60, 72, 
84 and week 96 visits compared to BOLS. 
▪ 
To evaluate the effect of ABX464 50 mg QD on miR-124 expression in colon tissue (RNA later) 
and in total blood at week 96. 
▪ 
To evaluate the long-term safety profile of ABX464 50 mg QD. 
The echocardiography objective is: 
▪ 
To evaluate the effect of ABX464 on cardiac function as assessed through echocardiograms.  
Study Endpoints 
Primary Endpoint: 
Proportion of patients with clinical remission at week 48 compared to induction study baseline. 
Clinical remission, based on the Mayo Scoring system, is defined as stool frequency sub score = 0 or 1 
and rectal Bleeding sub score = 0 and endoscopy sub score = 0 or 1 (modified to exclude friability). 
Secondary Endpoints: 
The week 24 and 48 secondary endpoints are: 


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Study n° 
ABX464-104 
Clinical Phase 
2b 
Type of Study 
Maintenance therapy in patients with moderate to severe UC 
▪ 
Reduction relative to baseline in Modified Mayo Score at week 48 and in partial Modified 
Mayo Score at every study visit among all patients. 
▪ 
Proportion of patients with either endoscopic improvement or/and endoscopic remission by 
segment at week 48 among all patients. 
Endoscopic improvement is defined as a Mayo endoscopic sub score of ≤1 (excluding friability) 
Endoscopic remission is defined as a Mayo endoscopic sub score of 0. 
▪ 
Proportion of patients with sustained endoscopic improvement or/and sustained endoscopic 
remission at week 48.  
Sustained endoscopic improvement is defined as the number of patients with endoscopic 
improvement at week 48 among patients who had endoscopic improvement during the Induction 
study (at week 8 or week 16). Sustained endoscopic remission is defined as the number of 
patients with endoscopic remission at week 48 among patients who had endoscopic remission 
during the Induction study (at week 8 or week 16). 
▪ 
Proportion of patients with glucocorticoid-free clinical remission at week 48. 
Glucocorticoid-free clinical remission is defined as clinical remission in addition to not requiring any 
treatment with glucocorticoids for at least 8 weeks prior to week 48. 
▪ 
Reduction relative to baseline in stool and rectal bleeding frequency at every study visit. 
▪ 
Reduction relative to baseline in fecal calprotectin and CRP levels at week 24 and 48. 
▪ 
Proportion of patients with clinical response at week 48. Clinical response is defined as: a 
reduction in Modified Mayo Score ≥ 2 points and ≥ 30 % from baseline with an accompanying 
decrease in rectal bleeding sub-score ≥ 1 point or absolute rectal bleeding sub-score ≤ 1 point. 
▪ 
Change relative to baseline in miRNA-124 expression in rectal/sigmoidal biopsies at week 48 
and in total blood at week 24 and week 48. 
▪ 
Scores and changes from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) 
domains at week 24 and 48. 
▪ 
Reduction relative to ISB of infiltrate/histopathology (rectal/sigmoidal biopsies) using the 
Robarts Histopathology Index (RHI), the Geboes and Nancy Histology Scoring Scales at 
week 48. 
The week 96 secondary endpoints are: 
▪ 
Reduction relative to baseline in Modified Mayo Score at week 96 and in partial Modified 
Mayo Score at every study visit (week 48 to 96) among all patients. 
▪ 
Proportion of patients with either endoscopic improvement or/and endoscopic remission by 
segment at week 96.  
▪ 
Proportion of patients with sustained endoscopic improvement or/and sustained endoscopic 
remission at week 96.  
▪ 
Reduction relative to baseline in stool and rectal bleeding frequency at every study visit (week 
48 to 96). 
▪ 
Reduction relative to baseline in fecal calprotectin and CRP levels at week 60, 72, 84 and 96. 
▪ 
Proportion of patients with clinical response at week 96. 
▪ 
Change relative to baseline in miRNA-124 expression in rectal/sigmoidal biopsies and in total 
blood at week 96. 
The echocardiography secondary endpoints are: 
▪ 
Absolute (%) change-from-previous echocardiogram of Left ventricle Ejection Fraction 
(LVEF) as measured by 2-dimensional echocardiography. 
▪ 
Number of subjects with a clinically relevant reduction (change-from-previous 
echocardiogram) of LVEF, defined as by > 10% reduction (absolute percentage points) to a 
value < 50%. 
▪ 
Absolute (%) change from-previous echocardiogram in Global Longitudinal Strain (GLS). 
▪ 
Number of subjects with a relative percentage reduction in GLS by > 15% from the previous 
echocardiogram. 
▪ 
Number of subjects with a reduction of LVEF > 10% (absolute percentage points) to a value 
≥ 50% with an accompanying fall in GLS > 15%. 
▪ 
Number of subjects with reduction in LVEF by > 10% (absolute percentage points) to a value 
≥ 50%. 
▪ 
Changes from previous echocardiography of other echocardiographic parameters as 
described in a standard protocol, including 2-dimensional volumes, RV size and systolic 
function and valve function. 


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Study n° 
ABX464-104 
Clinical Phase 
2b 
Type of Study 
Maintenance therapy in patients with moderate to severe UC 
Safety endpoints:  
▪ 
Number and rate of all adverse events, causally related adverse events, all SAE, and causally 
related SAEs classified by severity. 
▪ 
Incidence of treatment-emergent serious adverse event, hospitalizations, total inpatient days. 
▪ 
Incidence of adverse events leading to investigational product discontinuation. 
▪ 
Number of clinically significant laboratory abnormalities. 
Main Selection 
Criteria 
 
Inclusion criteria: 
A patient will be eligible to participate in this study if ALL the following criteria are met: 
▪ 
Patients must have completed the 16-week (± 4 days) induction treatment period (ABX464-103). 
▪ 
Patients are able and willing to comply with study visits and procedures as per protocol. 
▪ 
Patients should understand, sign and date the written voluntary informed consent form prior to any 
protocol-specific procedures are performed. 
▪ 
Patients should be affiliated to a social security regimen (for French sites only). 
▪ 
Females and males receiving the study treatment (potentially in combination with 
immunosuppressant) and their partners must agree to use a highly effective contraceptive method 
during the study and for 6 months (180 days) after end of study or early termination. Contraception 
should be in place at least 2 weeks prior to screening. Women must be surgically sterile (bilateral 
oophorectomy, bilateral salpingectomy, or hysterectomy) or in the postmenopausal state (no 
menses for 12 months without an alternative medical cause) or if of childbearing potential must 
use a highly effective contraceptive method. Women of childbearing potential (WOCBP) will enter 
the study after confirmed menstrual period and a negative pregnancy test. Highly effective 
methods of contraception include true abstinence, intrauterine device (IUD) or hormonal 
contraception aiming at inhibition of ovulation, intrauterine hormone releasing system, bilateral 
tubal ligation, vasectomized partner. True abstinence is defined when this is in line with the 
preferred and usual lifestyle of the patient. In each case of delayed menstrual period (over one 
month between menstruations) confirmation of absence of pregnancy is required. This 
recommendation also applies to WOCBP with infrequent or irregular menstrual cycle. Female and 
male patients must not be planning pregnancy during the trial and for 6 months post completion 
of their participation in the trial. In addition, male patients should use condom during the trial and 
for 6 months (180 days) post completion of their participation in the study. Male patients must not 
donate sperm as long as contraception is required. 
Criteria that should be met by patients at week 48 to be eligible for 48 additional weeks of study 
treatment. 
▪ 
Patients should be in clinical response. Clinical response is defined as: a reduction in Modified 
Mayo Score ≥ 2 points and ≥ 30 % from baseline (induction) with an accompanying decrease in 
rectal bleeding sub-score ≥ 1 point or absolute rectal bleeding sub-score ≤ 1 point. 
▪ 
Patients able and willing to continue the study treatment and who are compliant with study visits 
and procedures and who signed the update of the written voluntary informed consent. 
Exclusion Criteria: 
Patients who meet any of the following exclusion criteria will be excluded from the study: 
▪ 
Patients who permanently discontinued study treatment in induction study (ABX464-103) because 
of an adverse event (AE) regardless of relatedness to investigational product. 
▪ 
Patients who have developed any major illness/condition or evidence of an unstable clinical 
condition (except UC) that, in the investigator’s judgment, will substantially increase the risk to the 
participant if he or she participates in the study. 
▪ 
Patients with any other severe acute or chronic medical or psychiatric condition or laboratory or 
electrocardiogram (ECG) abnormality that may increase the risk associated with study 
participation or investigational product administration or may interfere with the interpretation of 
study results and, in the judgment of the investigator, would make the patient inappropriate for 
entry into this study. 
▪ 
Patients who are participating or plan to participate in other investigational studies (other than 
induction study) during the study. 
Medications 
and 
Corticosteroids 
Tapering  
 
Allowed Concomitant Medications: 
▪ 
Oral 5-aminosalicylic acid at stable dose. 
▪ 
Immunosuppressants in the form of azathioprine, 6-mercaptopurine, or methotrexate at stable 
dose. 


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Study n° 
ABX464-104 
Clinical Phase 
2b 
Type of Study 
Maintenance therapy in patients with moderate to severe UC 
 
▪ 
Antidiarrheals (e.g., loperamide, diphenoxylate with atropine) at stable dose. 
▪ 
For patients on oral corticosteroids at baseline, prednisone or prednisone equivalent ≤20 mg/day; 
beclomethasone diproprionate (≤5mg/day) or budesonide MMX (≤9 mg/day). 
Tapering period: 
For patients on oral corticosteroids at baseline, a tapering of steroids should be performed from baseline 
onwards. The rate of prednisone or prednisone equivalent tapering should not exceed 5 mg/week till 
complete discontinuation. The tapering can be stopped at any time based on medical judgment. No 
further oral corticosteroids dose escalation is allowed. 
Prohibited Concomitant Medications: 
▪ 
Tumor necrosis factor [TNF] inhibitors, vedolizumab or others biologic therapies. 
▪ 
JAK inhibitors. 
▪ 
Topical corticosteroids and topical 5-aminosalicylic acid preparations. 
▪ 
Cyclosporine and tacrolimus. 
▪ 
Vaccination with live components during the study and up to 8 Weeks after the last dosing (COVID 
19 Vaccine is allowed). 
▪ 
Drugs that inhibit or induce CYP1A2 (cf. Appendix #1). 
▪ 
Drugs that inhibit UDP-glucuronosyltransferase (UGT) IA9 activity and inhibitors or substrates of 
organic anion transporter (OAT) P1B1/P1B3 transporters (cf. Appendix #1). 
▪ 
Use of any investigational or non-registered product. 
Premature trial 
discontinuation 
Subjects who are not found eligible for the second year of treatment are not considered as prematurely 
discontinued as they have completed the first-year treatment. Patient’s premature trial discontinuation 
could occur for the following reasons: 
▪ 
Investigator’s decision: subject who would experience a treatment failure during the study 
may be withdrawn at any time. S/he will have to be treated according to standard of care as 
soon as s/he is discontinued from study treatment because of study withdrawal. 
▪ 
An Adverse Event or an intercurrent condition that preclude continuation of treatment; 
Specifically, 
o 
an increase ≥ 3.0 x ULN in liver transaminases (AST/SGOT and/or ALT/SGPT) or 
an increase ≥ 2.0 x ULN in Alkaline phosphatase or in total bilirubin requires close 
observation with repeating liver enzymes and serum bilirubin tests two times weekly 
and clinical investigation to understand the etiology of this elevation. Frequency of 
retesting can decrease to once a month if abnormality stabilizes after this initial two 
weeks of follow-up and if the patient is asymptomatic. Discontinuation of the study 
treatment should occur if: 
▪ 
 ALT or AST > 8xULN 
▪ 
ALT or AST > 5xULN for more than 2 weeks 
▪ 
ALT or AST > 3xULN and total bilirubin > 2xULN or INR>1.5 
▪ 
ALT or AST > 3xULN with appearance of fatigue, nausea, vomiting, right 
upper quadrant pain or tenderness, fever, rash, and/or eosinophilia 
(>5%). 
o 
A severe (grade 3 or higher) infection, a severe (grade 3 or higher) opportunistic 
infection, or sepsis.  
▪ 
Worsening of the UC defined as a 2-point increase in the pMMS, with pMMS ≥ 4 on 2 
separate occasions 7 day-apart and confirmed by an endoscopy sub-score of 2 points or 
higher. 
▪ 
Withdrawal of consent. 
▪ 
Pregnancy. 
▪ 
Any cardiac AESI or condition diagnosed during the course of the study and assessed by the 
clinical adjudication committee as changing the risk/benefit balance for study subjects. 
▪ 
New onset of acute pancreatitis. 
▪ 
Malignancies (including non-melanoma skin cancers). 
▪ 
Medically significant abnormal laboratory results, including new onset anemia (defined 
as a hemoglobin decrease >2 g/dL from baseline or hemoglobin <8 g/dL) - note: 
transient abnormal values, and/or abnormal values related to an existing condition that 
doesn’t constitute a worsening will not be a criteria for discontinuation. 


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Study n° 
ABX464-104 
Clinical Phase 
2b 
Type of Study 
Maintenance therapy in patients with moderate to severe UC 
▪ 
Any relevant toxicity or negative change in the risk/benefit assessment leading to an 
unacceptable risk for the subject or any data deriving from other clinical trials or toxicological 
studies which negatively influence the risk/benefit assessment. This may be applicable but is 
not limited to the following cases: occurrence of AEs which character, severity or frequency 
is new in comparison to the existing risk profile 
▪ 
Patients included with a history of cardiac ischemic disease and/or congestive heart failure 
will be discontinued from the study, will perform the End of Study Visit 4 weeks after last study 
drug administration and will then be treated according to the standard of care upon study 
treatment interruption. 
Data Safety 
Monitoring Board 
(DSMB) – 
Independent 
Cardiovascular 
Safety Committee 
(ICVSC) 
A Data and Safety Monitoring Board (DSMB) with expertise and experience in the management in UC 
will review the safety of the trial every 2 months during the entire study period.  In addition, DSMB will be 
review all potential causally related serious adverse events (SAE) within 7 days of the initial report. 
An Independent Cardiovascular Safety Committee (ICVSC), comprised of 3 cardiologists with experience 
from drug development, will be formed as detailed in the Charter. The ICVSC will be responsible for an 
on-going evaluation of cardiac adverse events of special interest (Cardiac AESIs), for treatment emergent 
echocardiographic findings, and for treatment emergent changes of cardiac safety biomarkers (as 
detailed above). The ICVSC will review cardiac adverse events on an on-going basis, meet regularly and 
provide recommendations to Sponsor and DSMB regarding study procedures and conduct. 
Sample Size 
calculation 
This study is an open label extension study. Sample size calculation is therefore not applicable. 
Statistical Methods 
 
Efficacy Analysis 
Descriptive statistics will be presented for all efficacy variables for each measurement timepoint. In 
addition, subgroup descriptive analysis will be performed according to the patient status at the end of the 
induction study (clinical remission, clinical response, or no clinical response), and the treatment received 
during the induction phase (ABX464 25 mg, 50 mg or 100 mg, or matching placebo). 
Interim analysis: 
An interim analysis will be performed when all the subjects reach W48 visit. The interim analysis will 
include efficacy and safety data such as the following:  
▪ 
Reduction relative to baseline in Modified Mayo Score and in partial Modified Mayo Score at every 
study visit among all patients. 
▪ 
Clinical response and remission, endoscopy improvement and remission. 
▪ 
Glucocorticoid-free clinical remission at week 48. 
▪ 
Fecal calprotectin results. 
▪ 
Safety parameters. 
▪ 
Hematology and biochemistry parameters. 
Safety Analysis 
Adverse events will be coded using the standard dictionary (most recent MedDRA version) down to the 
lower-level term (LLT).  
Analysis of safety will be performed on the safety data set consisting of all patients who received at least 
one dose of ABX464 in the study. The assessment of safety will be based on the frequency of adverse 
events (with and without regard to causality) graded according to the “CTC-AE” (Version 5.0) and also, 
the review of individual values for clinical laboratory data, vital signs and ECG focusing on the detection 
of abnormal values. 
Adverse events will be tabulated (counts and percentages). All adverse events will be listed, and the 
data will be tabulated by body system/organ class. Adverse event tabulations will include all treatment 
emergent adverse events, which will be further classified by severity, and relationship to treatment. 
Frequency and percentage of patients and number of occurrences of adverse events will also be 
presented for serious TEAEs, TEAEs leading to study drug discontinuation, discontinuation from the 
study or death and TEAEs of special interest 
Clinical laboratory parameters, including echocardiography parameters and vital signs, will be 
summarized by using descriptive statistics (n, mean, SD, SEM, median, minimum and maximum). 
Frequency and percentage of patients with normal, abnormal and abnormal clinically significant ECG 
results will also be summarized. The number of patients with at least one abnormal value will be 
tabulated (counts and percentages) for each parameter in summary shift tables. 
 


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1. Introduction and study rationale 
1.1. Ulcerative Colitis (UC)  
1.1.1. Disease 
Ulcerative colitis (UC) is a chronic inflammatory condition causing continuous mucosal inflammation of the 
colon without granulomas on biopsy, affecting the rectum and a variable extent of the colon in continuity, which 
is characterized by a relapsing and remitting course. 
UC is a lifelong disease arising from an interaction between genetic and environmental factors, observed 
predominantly in the developed countries of the world. 
The precise etiology is unknown and therefore medical therapy to cure the disease is not yet available. 
1.1.2. Management of patients 
Patients may live with a considerable symptom burden despite medical treatment (66% describe interference 
with work and 73% with leisure activities) [1]. 
Although most patients present with mild-to-moderate UC, 10% of patients initially present with severe disease. 
Additionally, approximately 15% of patients will develop a severe flare during the course of their lifetime. Both 
the American College of Gastroenterology practice guidelines and the European Crohn’s and Colitis 
Organization position statements define severe colitis as the passage of six or more stools per day with 
evidence of systemic toxicity (e.g., fever, tachycardia, anemia or elevated ESR) [2,3]. 
Patients with acute severe UC require hospitalization for optimal management owing to the seriousness of 
their illness. Although rates of death in severe UC have dropped by up to 25% with the adoption of more 
aggressive monitoring and treatment [4] acute severe colitis is still associated with a measurable mortality [5]. 
The use of intravenous steroids and improved surgical techniques probably explain much of the reduction in 
mortality associated with acute severe UC observed in the decades since their introduction [6] 
Severe UC should be considered a medical emergency, and patients require close monitoring of stool 
frequency and vitals symptoms. Serial abdominal examinations and plain radiographs should be performed. 
The cornerstone of management of severe UC remains the use of intravenous corticosteroids, which are 
effective in the induction of remission in the majority of cases. While many patients with acute severe ulcerative 
colitis will respond to a short course of intravenous corticosteroids, up to a third will fail to improve. In these 
patients with steroid-refractory colitis, the choice is between rescue medical therapy with ciclosporin, anti-TNF 
Alpha, vedolizumab, JAK inhibitors or surgery. Anti-tumor necrosis factor (TNF) therapy is effective for the 
treatment of ulcerative colitis (UC).  
Nevertheless, up to 30% of patients show no clinical benefit despite optimal treatment, while another 40% of 
patients lose response over time and need to escalate or discontinue anti-TNF therapy within one year of 
treatment. 
Thus, there is an unmet medical need for novel treatment options for patients with moderate to severe UC. 
1.2. ABX464 rationale 
1.2.1. Investigational treatment description  
ABX464 is a first-in-class, orally available, small molecule with anti-inflammatory activity which is under 
investigation as a potential treatment for moderate to severe ulcerative colitis and rheumatoid arthritis. 
ABX464 binds the Cap Binding Complex (CBC) comprised of two proteins CBP20 and CBP80, within the cell 
nucleus. This binding leads to an increased expression of a single micro-RNA (miR-124) by impacting the 
splicing of a single long non-coding RNA. Because of its action on this single splicing event, leading to an 
increase in miR-124, a microRNA with potent anti-inflammatory properties, ABX464 potentially has broad 
applicability across a variety of inflammatory diseases. ABX464 is currently under investigation as a potential 
treatment for Rheumatoid Arthritis (RA) and inflammatory bowel diseases (IBD). In humans, ABX464 is 
conjugated via glucuronidation to ABX464-N-Glu, which contributes the majority of ABX464 plasma exposure. 
ABX464-N-Glu is pharmacologically active and also binds to the CBC leading to an increase in miR124 
expression. 


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1.2.2. Investigational product description  
The chemical name of ABX464 molecule is 8-chloro-N-[4-(trifluoromethoxy) phenyl]quinolin-2-amine, or (8-
chloro-quinolin-2-yl)-(4-trifluoromethoxy-phenyl)-amine. Its molecular weight is 338.7 g/mol. The study drug is 
formulated as hard gelatin, powder-filled capsules (size 1). 
1.2.3. Investigational product Mode of Action 
ABX464 upregulates MiR-124 in vitro in several cell types 
MiR-124 induction by ABX464 in Human Peripheral blood mononucleated cells (PBMCs) has been 
demonstrated as follows: 
• 
Affymetrix genechip miRNA array 2.0 which contains 15644 miRNA probes representing 1105 miRNA 
across 131 organisms. The chip also contains 2202 pre-miR probes and 2334 probes for snoRNA and 
scaRNA. 
• 
TaqMan® Array Human MicroRNA which contains 196 miRNAs. 
 
Both approaches demonstrated that only miR-124 was upregulated by ABX464 treatment across species and 
that no miRNAs were downregulated. The expression of miR-124 was significantly increased (about 13-fold) 
by ABX464. MiR-124 was upregulated after ABX464 treatment in both CD4+ and CD8+ T cells. 
The effects of ABX464 on miR-124 expression was tested in Human Monocyte-Derived Macrophages 
(HuMDM). The results demonstrated that using Real Time Taqman quantitative polymerase chain reaction 
(qPCR), ABX464 is able to up-regulate the expression of miR-124 in HuMDM. 
MiR-124 is encoded from three independent genes, miR-124-1, miR-124-2, and miR-124-3, located on human 
chromosomes 8 and 20. The specific upregulation of miR-124 in CD4+ cells was demonstrated to be the result 
of the action of ABX464 on the splicing of long non-coding RNA 0599-205 located in miR-124-1, one of the 
three loci expressing miR-124.  
ABX464 upregulates miR-124 in treated patients with moderate to severe ulcerative colitis  
After 8 weeks of treatment (57 days) with ABX464 at doses of 25, 50 or 100 mg, the number of miR-124 copies 
in rectal biopsies and in blood were significantly higher in all ABX464 groups compared to placebo (Figure 1 
and Figure 2). 
Figure 1: MiR 124 induction in blood and rectal biopsies of patients treated with ABX464 in the phase 2b trial 
(UC) 
 
Figure 2 : MiR 124 induction in blood of patients treated with ABX464 in the phase 2b trial (UC) 


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ABX464 reduces pro-inflammatory cytokines/chemokines 
ABX464 reduced the expression of pro-inflammatory chemokines/cytokines MCP1 (-50%), CXCL1 (-20%), IL-
10 (-30%), IL-1β (-25%), TNFα (-25%) and IL-6 (-20%) within 4 days of treatment of HuMDM polarized to M1 
phenotype. 
In vivo evidence for the role of ABX464 in inflammation 
ABX464 decreases pro-inflammatory cytokines  
The results observed in HuMDM were confirmed in vivo in the mouse model of Dextran Sulfate Sodium (DSS) 
induced colonic inflammation. Following concomitant 10 days of DSS exposure and ABX464 treatment, 
ABX464 induced a significant marked reduction of pro-inflammatory cytokines: TNFα (7.5-fold reduction), IL-
6 (2-fold reduction), and MCP1 (6-fold reduction in the distal and middle regions) in the supernatant of mouse 
colons that were incubated for 24 hours in culture medium. 
ABX464 decreases the pro-inflammatory Th17 CD4+ cell subset  
Th17 cytokines, that include IL-17, IL-23, and IL-22, are often increased in the inflamed intestinal mucosa of 
active UC and Crohn’s disease (CD) patients relative to unaffected regions and healthy controls [10]. In 
PBMCs, ABX464 treatment did not affect the Treg populations but significantly reduced the number of Th17 
and Th1 population and increased Th 2 cells population. Th17 cells are known to differentiate in response to 
IL-1β, IL6 and IL23 through STAT3 pathway, one of the targets of miR-124 [11]. Proinflammatory Th17 cells 
are increased in the mesenteric lymph nodes of DSS-exposed mice, ABX464 prevented this increase of Th17 
in mesenteric lymph nodes of DSS mice. 
IL-17 secretion was also tested during the course of the phase 2b clinical trial in ulcerative colitis (ABX464-
103). A statistically significant decrease in IL-17 in the sera of the patients has been shown for patients dosed 
with ABX464 compared to placebo. 
ABX464 reduces disease severity in an acute DSS-induced colitis model 
Compared with mice untreated with ABX464, a reduced DSS-induced weight loss was observed in mice 
receiving ABX464. The weight of ABX464-treated mice returned to pre-treatment levels and the mice displayed 
decreased disease parameters including smaller and fewer colonic lesions as well as smaller reductions of 
colon length. 
ABX464 decreased macrophages recruitment during acute colitis.  
 
1.2.4. Preclinical data of ABX464 
The toxicity of ABX464 and ABX464-N-Glu was studied in a range of rodent and non-rodent species (rats, 
rabbits, dogs, cynomolgus and marmoset monkeys, and minipigs) with treatment durations ranging from 2-
weeks to 6/9 months. These studies have demonstrated that ABX464 and ABX464-N-Glu are overall well 
tolerated. Vomiting and ptyalism were the major clinical sign, and the main target organs of ABX464 toxicity 
were the gastro-intestinal tract and the liver. The adverse effects noted on these organs were essentially 
mild/moderate but showed reversibility during the recovery phases. 


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Plasma exposure to ABX464 and ABX464-N-Glu in humans (based on predicted steady-state exposure in 
ulcerative colitis patients at the highest proposed dose of 100mg) are calculated as being approximately parity 
(Cmax) to 4-fold (AUC) for ABX464 and 9-fold (Cmax) to 2-fold (AUC) for ABX464-N-Glu exposure as seen in 
pivotal chronic toxicology studies. 
ABX464 had no significant adverse effects on the nervous and respiratory systems, or on cardiovascular 
function. ABX464 was shown to be non-genotoxic and ABX464-N-Glu was shown to be non-mutagenic. 
Genotoxicity  
ABX464 was found to be non-genotoxic. Its main metabolite, the ABX464-N-Glu was not mutagenic as 
assessed by an Ames test, an in vitro and an in vivo micronucleus assay. 
Reproductive toxicity  
Reproductive toxicity was assessed from fertility to postnatal development, in five studies. In rabbits, the 
maternal NOAEL was considered to be 9mg/kg od and the NOAEL for the embryo-fetal development less than 
1mg/kg od. In rats, the maternal NOAEL and the NOAEL for pup development and survival is considered to 
be lower than 15 mg/kg od. The F1 generation NOAEL is considered to be 40mg/kg od. in absence of adverse 
effect at this dose-level. 
Teratogenicity  
ABX464 appears to have teratogenic activity.  
Hepatocellular toxicity 
In minipigs the main adverse finding was centrilobular hepatocellular degeneration/necrosis associated with 
hemorrhage, fibrosis and /or extramedullary hematopoiesis observed at dose levels of 10mg/kg and above. 
The liver lesions observed in one of the animals administered 5mg/kg od, were not considered adverse. Based 
on this observation, the NOAEL is 5mg/kg od.  
No signs of hepatotoxicity related to ABX464 have been observed in any of the subjects treated with ABX464 
in clinical trials and DILISym evaluation did not predict any risk of liver toxicity for ABX464 and ABX464-N-Glu.  
Regarding the other observations made from the pre-clinical toxicology program, please refer to the current 
version of the Investigator’s Brochure. 
1.2.5. Previous clinical experience with ABX464 
The effect of ABX464 in humans has been assessed in eighteen clinical trials: 
▪ Completed clinical studies in healthy volunteers (ABX464-001, ABX464-002, ABX464-901, ABX464-902, 
and ABX464-903) and controlled studies in patients with ulcerative colitis (ABX464-101 and ABX464-
103), in patients with rheumatoid arthritis (ABX464-301), in HIV infected subjects (ABX464-003, ABX464-
004, and ABX464-005), in COVID-19 infected patients (ABX464-401) and in Japanese Healthy 
Volunteers (ABX464-921). 
▪ Ongoing open label studies in ulcerative colitis (ABX464-102, ABX464-104, and ABX464-108) and 
rheumatoid arthritis (ABX464-302).  
▪ A drug product formulation study (ABX464-905) is ongoing in Healthy Volunteers. 
As of 30 November 2021, 1023 subjects have received ABX464, according to various administration 
schedules, in all completed, and ongoing open-label clinical studies across all indications. Out of these 1023 
subjects, 830 subjects have been dosed with ABX464 50mg once daily (od) including 240 subjects for longer 
than 6 months with 197 for more than a year. In addition, 36 subjects have received ABX464 or placebo in 
blinded clinical study ABX464-921. Fourteen patients have received ABX464 50mg od for more than 3 years 
in the UC open label maintenance study (ABX464-102) and 240 patients have received ABX464 50mg for 
more than 6 months.  
ABX464 was rapidly absorbed in healthy volunteers, HIV and UC patients with a Cmax observed approximately 
1.5 to 2.9 hours after dosing. Exposure to ABX464 was comparable in all subjects receiving ABX464 at a given 
dose. PK of ABX464 were linear in the dose range 50-150mg. After repeated administrations of ABX464, an 
initial decrease in ABX464 AUC was observed and steady state was reached after 4 weeks of treatment.  
ABX464 was rapidly metabolised to ABX464-N-Glu. ABX464-N-Glu had a much longer half-life compared to 
ABX464 (about 100 hours) largely contributing to the high exposures observed.  
Food increased ABX464 exposure at least 2.8-fold while exposure to the metabolite was comparable in fed or 
fasted conditions. 


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Clinical Efficacy 
Completed and ongoing studies with ABX464 in UC are:  
▪ Phase 2a program with an 8-week induction (ABX464-101; completed) and a 4-year maintenance 
(ABX464-102; ongoing; 52-week interim analysis completed) studies. 
▪ Phase 2b program including the 16-week induction (ABX464-103; completed) and an open-label 
extension (ABX464-104; ongoing) studies. 
ABX464-103 was a randomized, double-blind and placebo-controlled phase 2b induction study and was 
conducted at 95 study sites in 15 European countries, Canada and the US. It had three once-daily oral ABX464 
treatment groups (25mg, 50mg and 100mg) and one placebo group. A total of 254 patients with moderate to 
severe active ulcerative colitis were enrolled into the trial. 50% of these patients had inadequate response, 
loss of response, or intolerance to tumour necrosis factor alpha (TNF-α) inhibitors, vedolizumab, other biologics 
and/or JAK inhibitors treatments while the other 50% were refractory to conventional treatments. Endoscopies 
were read centrally and blinded by independent reviewers. Electronic patient diaries were used to promote the 
reliability of the collection of stool frequency, rectal bleedings and other patient reported outcomes. Gender, 
clinical, biological and endoscopic parameters were well distributed across placebo and treatment groups at 
enrolment time. The primary endpoint, i.e. the reduction of the modified Mayo Score from baseline after 8 
weeks of treatment was statistically significant for all active treatment groups. ABX464-103 study was 
completed in April 2021 (LPLV = 16 April 2021). 
 
Table 1 Primary and secondary efficacy endpoints  in ABX464-103 study 
Week 8 top-line results  
(ITT1 population / N= 252)  
Placebo  
25mg  
50mg  
100mg  
Primary Endpoint  
Modified Mayo Score  
Mean change from baseline  
All patients  
-1.9  
-3.1 *  
-3.2 *  
-2.9 *  
Bio exposed 
-1.0  
-2.8 *  
-2.9 *  
-2.8*  
*p-values of <0.05 versus placebo for all dose groups (ANCOVA)  
Key Secondary Endpoints (not powered to show statistical significance)  
Endoscopic Improvementa,d 
All patients  
8 (13.6%)  
20 (34.5%) *  
21 (39.6%) *  
24 (44.4%) *  
Bio exposed 
1 (3.7%)  
8 (28.6%) *  
7 (30.4%) *  
8 (26.6%) *  
*p-values of <0.05 versus placebo for all dose groups using a likelihood ratio chi-square test  
Clinical Remission b, d 
All patients  
8 (12.5%)  
17 (27.9%) *  
11 (17.5%)  
16 (25.0%)  
Bio exposed  
1 (3.2%)  
6 (20.0%) *  
2 (6.7%)  
6 (18.8%) *  
*p-values of <0.05 versus placebo using a likelihood ratio chi-square test but not according to the predefined Mantel-Haenszel Chi Square 
test (p<0.1)  
Clinical Response c, d  
All patients  
23 (35.9%)  
40 (65.6%) *  
38 (60.3%) *  
35 (54.7%) *  
Bio exposed 
5 (16.1%)  
17 (56.6%) *  
13 (43.3%) *  
15 (46.8%) *  
*p-values of <0.05 versus placebo using a likelihood ratio chi-square test  
Fecal Calprotectin (μg/g)  
All patients  
-1027.7  
-2192.8 **  
-2316.8 **  
-2280.9 **  


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ABX464 was shown to be effective in patients refractory to conventional treatments and, importantly, also in 
patients with inadequate response, loss of response, or intolerance to biologics and/or JAK inhibitors. These 
efficacy results warrant the continuation of the development of ABX464 in UC indication. 
97.7% of all patients who completed the phase 2b induction study (ABX464-103), irrespective of treatments or 
treatment outcome during the induction study, enrolled into this subsequent open-label maintenance study to 
evaluate the long-term safety and efficacy profile of ABX464 for up to two years.  
 
Clinical Safety 
Overall, the safety profile of ABX464 appears to be safe and well tolerated. The most frequently reported 
adverse events (AEs) were headache, nausea, vomiting, abdominal pain, back pain, and diarrhea which were 
mostly of mild to moderate intensity, occurring after treatment onset and transient in nature.  
A dose relationship in the occurrence of these AEs was observed, especially with respect to headache.  
No signs of hepatotoxicity have been observed in any of the subjects treated with ABX464 in the previously 
conducted or ongoing clinical trials. ABIVAX and its clinical experts consider that subjects treated with ABX464 
are not at increased risk of developing drug-induced hepatotoxicity. A specific liver function monitoring plan 
has been implemented in the present clinical study (see Section 7.2).  
Altogether, ABX464 efficacy and safety results in nonclinical models of inflammation and in subjects with IBD 
warrant the continuation of the clinical development of ABX464 in IBD. For further information regarding the 
nonclinical and clinical data for ABX464, refer to the current Investigator’s Brochure. 
 
1.3. Rationale for the clinical study and study design 
A Phase 2a study (ABX464-101) aimed at evaluating the efficacy and safety of ABX464 given at a fixed dose 
of 50mg once daily versus Placebo in Patients with Moderate to Severe Active Ulcerative Colitis who have 
failed or are Intolerant to immunomodulators, anti-TNFα or Corticosteroids was conducted in Belgium, France, 
Germany, Austria, Poland, Hungary. 
32 patients were randomized (23 ABX464 patients/9 placebo). The principal study results are presented below. 
A strong efficacy signal was observed with ABX464 50 mg: 
▪ Clinical Remission rate of 35.0 % of ABX464 patients (Placebo = 11.1%). 
▪ Endoscopic improvement rate of 50.0 %* (p=0.03) of ABX464 patients (Placebo = 11.1%). 
▪ Clinical Response rate of 70.0 % of ABX464 patients (Placebo = 33.3%). 
No severe or serious adverse reactions reported. Most adverse events were of mild to moderate intensity. 
At the end of the completed 2-month induction study, 22 patients (15 previously treated with ABX464 and 7 
who had received placebo) opted to enroll in the 12-month open-label maintenance study, ABX464-102. At 
month 9, 19 of the 22 patients were still in the study, receiving a once-daily, oral capsule of 50mg ABX464. 
This interim analysis showed that ABX464 continued to have a good efficacy and safety profile when 
administered chronically. 
The interim analysis used the Month 12 Per Protocol (M12 PP) dataset which included all subjects that had a 
Month 12 visit. Of the 22 subjects, 3 subjects were excluded from the M12 PP Set: 2 subjects from the ABX464 
induction group (one who withdrew due to lack of efficacy at M1 of the maintenance study and one who was 
lost to follow-up) and 1 subject from the placebo induction group (grade 2 headache at month 4), resulting in 
Mean change from baseline  
**p-values of <0.01 versus placebo (MMRM) 
1 = Intent-to-treat patient population. Drop-out patients were considered as failure for all binary endpoints. Nearest neighbor imputation (as defined in the 
Statistical Analysis Plan) was used for missing values at week 8 and applied to MMS, clinical remission, and clinical response. Endoscopic improvement rates 
are presented without imputation (data available at time point). 
a = Endoscopic improvement is defined as endoscopic subscore ≤1.    
b = Clinical remission (per Modified Mayo Score) is defined as stool frequency subscore (SFS) ≤1, rectal bleeding subscore (RBS) of 0 and endoscopic 
subscore ≤1. 
c = Clinical response (per Modified Mayo Score) is defined as a decrease from baseline in the Modified Mayo Score ≥2 points and ≥30% from baseline, plus a 
decrease in RBS ≥1 or an absolute RBS ≤1. 
D = Evidence of friability during endoscopy confers an endoscopic subscore of 2 or 3  


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19 subjects analyzed in the efficacy M12 PP set at baseline. Of the nineteen subjects in the set, sixteen had 
had a Month 12 endoscopy performed which forms part of the Total Mayo score (TMS).  
Clinical remissions obtained at the end of the induction study were durable and the rates further improved 
during the maintenance phase, as additional subjects achieved clinical remission during12 months treatment.  
All patients who had an endoscopy performed, had an endoscopic subscore of 0 or 1. 12/16 patients were in 
clinical remission at month 12. 
Mean and median fecal calprotectin and CRP showed continued declines during the maintenance study, 
though the large variability and small patient numbers requires that the results should be interpreted with 
caution.  The measurement of miR124 relative gene expression by qPCR using whole blood samples was 
included in both ABX464-101 and -102.  A total of 19 patients were sampled on day 0, 28, 56 of ABX464-101 
and on day 365 (while in ABX464-102). Statistically significant increases of miR124 expression were observed 
at all these time points. 
No severe or serious adverse reactions were reported. Most adverse events were of mild to moderate intensity. 
These efficacy and safety results warrant the continuation of the clinical development of ABX464 in this 
indication. 
 
 


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2. STUDY OBJECTIVES AND ENDPOINTS 
2.1. Primary Objective 
The primary objective of the study is to assess in all patients the long-term efficacy of ABX464 given at 50 mg 
QD on clinical remission at week 48 compared to the induction study (ABX464-103) baseline (ISB). 
2.2. Secondary Objectives 
Week 24 and 48 secondary objectives are: 
▪ To evaluate clinical remission at week 48 compared to the baseline of the open label study (BOLS). For patients 
with endoscopic improvements at week 8 of the induction study (ABX464-103) and with no endoscopic data at 
week 16, the clinical remission at week 48 will be compared to week 8 of the induction study. 
▪ To evaluate the effect of ABX464 50 mg QD on Modified Mayo Score (MMS) at week 48 and on partial Modified 
Mayo Score (pMMS), among all patients, at every study visit compared to ISB. 
▪ To evaluate the effect of ABX464 50 mg QD on endoscopic improvement and remission and sustained 
endoscopic improvement and remission, by segment at week 48 compared to ISB and BOLS. For patients with 
endoscopic improvements at week 8 of the induction study (ABX464-103) and with no endoscopic data at week 
16, endoscopic improvements at week 48 will be compared to week 8 of the induction study.  
▪ To evaluate the proportion of patients with glucocorticoid-free clinical remission at week 48. 
▪ To evaluate the effect of ABX464 50 mg QD on stool and rectal bleeding frequency at every study visit compared 
to BOLS. 
▪ To evaluate the effect of ABX464 50 mg QD on fecal calprotectin and CRP levels at week 24 and week 48 visits 
compared to BOLS. 
▪ To evaluate the effect of ABX464 50 mg QD on clinical response at week 48 compared to ISB and BOLS. For 
patients with endoscopic improvements at week 8 of the induction study (ABX464-103) and with no endoscopic 
data at week 16, endoscopic measurements at week 48 will be compared to week 8 of the induction study. 
▪ To evaluate the effect of ABX464 50 mg QD on miR-124 expression in colon tissue (RNA later) at week 48 and 
in total blood at week 24 and week 48. 
▪ To evaluate the effect of ABX464 50 mg QD on patients’ quality of Life (QoL) measured by the Inflammatory 
Bowel Disease Questionnaire (IBDQ) at week 24 and week 48 compared to BOLS. 
▪ To evaluate the effect of ABX464 50 mg QD on the rectal/sigmoidal infiltrates using the Robarts Histopathology 
Index (RHI), the Geboes and Nancy Histology Scoring Scales at week 48 compared to ISB and BOLS. For 
patients with endoscopic improvements at week 8 of the induction study (ABX464-103) and with no endoscopic 
data at week 16, endoscopic measurements at week 48 will be compared to week 8 of the induction study. 
▪ To evaluate the long-term safety profile of ABX464 50 mg QD. 
Week 96 secondary objectives are: 
▪ To evaluate the effect of ABX464 50 mg QD on partial Modified Mayo Score (pMMS) at every study visit 
compared to ISB and on Modified Mayo Score at week 96. 
▪ To evaluate the effect of ABX464 50 mg QD on stool and rectal bleeding frequency at every study visit compared 
to BOLS. 
▪ To evaluate the effect of ABX464 50 mg QD on fecal calprotectin and CRP levels at week 60, 72, 84 and week 
96 visits compared to BOLS. 
▪ To evaluate the effect of ABX464 50 mg QD on miR-124 expression in colon tissue (RNA later) and in total blood 
at week 96. 
▪ To evaluate the long-term safety profile of ABX464 50 mg QD. 
Echocardiography objective is: 
▪ To evaluate the effect of ABX464 on cardiac function as assessed through echocardiograms. 
2.3. Primary Endpoint 
The primary endpoint is the proportion of patients with clinical remission at week 48 compared to induction 
study baseline (ABX464-103). Clinical remission, based on the Mayo Scoring system, is defined as stool 


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frequency sub score = 0 or 1 and rectal Bleeding sub score = 0 and endoscopy sub score = 0 or 1 (modified 
to exclude friability). 
2.4. Secondary Endpoints 
The week 24 and 48 secondary endpoints are: 
▪ Reduction relative to baseline in Modified Mayo Score at week 48 and in partial Modified Mayo Score at every 
study visit among all patients. 
▪ Proportion of patients with either endoscopic improvement or/and endoscopic remission by segment at week 48 
among all patients 
Endoscopic improvement is defined as a Mayo endoscopic sub score of ≤1 (excluding friability).  
Endoscopic remission is defined as a Mayo endoscopic sub score of 0. 
▪ Proportion of patients with sustained endoscopic improvement or/and sustained endoscopic remission at week 
48.  
Sustained endoscopic improvement is defined as the number of patients with endoscopic improvement at week 
48 among patients who had endoscopic improvement during the Induction study (at week 8 or week 16). 
Sustained endoscopic remission is defined as the number of patients with endoscopic remission at week 48 
among patients who had endoscopic remission during the Induction study (at week 8 or week 16). 
▪ Proportion of patients with glucocorticoid-free clinical remission at week 48. 
Glucocorticoid-free clinical remission is defined as clinical remission in addition to not requiring any treatment 
with glucocorticoids for at least 8 weeks prior to week 48. 
▪ Reduction relative to baseline in stool and rectal bleeding frequency at every study visit. 
▪ Reduction relative to baseline in fecal calprotectin and CRP levels at week 24 and 48. 
▪ Proportion of patients with clinical response at week 48.  
Clinical response is defined as: a reduction in Modified Mayo Score ≥ 2 points and ≥ 30 % from baseline with an 
accompanying decrease in rectal bleeding sub-score ≥ 1 point or absolute rectal bleeding sub-score ≤ 1 point. 
▪ Change relative to baseline in miRNA-124 expression in rectal/sigmoidal biopsies at week 48 and in total blood 
at week 24 and week 48. 
▪ Scores and changes from baseline in Inflammatory Bowel Disease Questionnaire (IBDQ) domains at week 24 
and 48. 
▪ Reduction relative to ISB of infiltrate/histopathology (rectal/sigmoidal biopsies) using the Robarts Histopathology 
Index (RHI), the Geboes and Nancy Histology Scoring Scales at week 48. 
The week 96 secondary endpoints are: 
▪ Reduction relative to baseline in Modified Mayo Score at week 96 and in partial Modified Mayo Score at every 
study visit (week 48 to 96) among all patients. 
▪ Proportion of patients with either endoscopic improvement or/and endoscopic remission by segment at week 96.  
▪ Proportion of patients with sustained endoscopic improvement or/and sustained endoscopic remission at week 
96.  
▪ Reduction relative to baseline in stool and rectal bleeding frequency at every study visit (week 48 to 96). 
▪ Reduction relative to baseline in fecal calprotectin and CRP levels at week 60, 72, 84 and 96. 
▪ Proportion of patients with clinical response at week 96.  
▪ Change relative to baseline in miRNA-124 expression in rectal/sigmoidal biopsies and in total blood at week 96. 
The echocardiography secondary endpoints are: 
▪ Absolute (%) change-from-previous echocardiogram of Left ventricle Ejection Fraction (LVEF) as measured by 
2-dimensional echocardiography. 
▪ Number of subjects with a clinically relevant reduction (change-from-previous echocardiogram) of LVEF, defined 
as by > 10% reduction (absolute percentage points) to a value < 50%. 
▪ Absolute (%) change from-previous echocardiogram in Global Longitudinal Strain (GLS). 


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▪ Number of subjects with a relative percentage reduction in GLS by > 15% from the previous echocardiogram. 
▪ Number of subjects with a reduction of LVEF > 10% (absolute percentage points) to a value ≥ 50% with an 
accompanying fall in GLS > 15%. 
▪ Number of subjects with reduction in LVEF by > 10% (absolute percentage points) to a value ≥ 50%. 
▪ Changes from previous echocardiogram of other echocardiographic parameters as described in a standard 
protocol, including 2-dimensional volumes, RV size and systolic function and valve function. 
Safety endpoints are: 
▪ Number and rate of all adverse events, causally related adverse events, all SAE and causally related SAEs 
classified by severity. 
▪ Incidence of treatment-emergent serious adverse event, hospitalizations, total inpatient days. 
▪ Incidence of adverse events leading to investigational product discontinuation. 
▪ Number of clinically significant laboratory abnormalities. 
 
 


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3. INVESTIGATIONAL PLAN 
3.1. Study Design 
3.1.1. Design and Methodology 
This study is an open-label study aiming at evaluating the long-term safety and the efficacy profile of ABX464 given 
once a day (QD) at 50 mg in patients with moderate to severe ulcerative colitis (UC) who have been previously enrolled 
in the ABX464-103 clinical study (induction study) and who are willing to receive their treatment with ABX464 as long-
term (maintenance) therapy of remission.  
All patients who have completed the 16-week (± 4 days) induction treatment period (ABX464-103) will be eligible for 
this maintenance study regardless of their clinical response and will receive 1 capsule of ABX464 50mg once daily 
during up to 96 weeks providing the patient has a clinical response at week 48. 
The study design is presented below: 
Patients will be treated for a maximum of 96 weeks in this maintenance study. After the treatment period, patients will 
be followed for 4 additional weeks for safety purposes. Alternatively, eligible patients willing to continue study treatment 
will be offered to take part in a long term follow up safety study (ABX464-108) at the end of treatment (ie Week 96). 
ABX464-108 study is a separate clinical study requiring health authorities and ethics committees’ approvals. 
 
From Day 1 onwards, patients will be seen at the investigational site every 4 weeks up to week 48 and then quarterly 
until weeks 96. Flexible sigmoidoscopy with rectal and/or sigmoidal biopsies will be performed, for all patients at week 
48 and at week 96. Additional flexible sigmoidoscopies may be performed during the open label phase based on 
medical judgement. 
During the open label maintenance phase, in the event of clinical progression of the disease, defined as at least a 2-
point increase from the screening partial Modified Mayo Score (pMMS) with a pMMS ≥ 4 confirmed by an endoscopy 
sub score of 2 points or higher, the patient will exit the study. 
3.1.2. Data Safety Monitoring Board - Independent Cardiovascular Safety Committee 
(ICVSC) 
An independent Data Safety Monitoring Board (DSMB), with expertise and experience in the pathology, and 
without direct involvement in the conduct of the trial, will be set up specifically to guarantee effective protection 
of patients, ensure the ethical conduct of the trial, benefit/risk ratio of the trial, and to ensure the independent 
review of the scientific results during the trial and at the end of the trial. Besides, the DSMB may recommend 
the early termination of the trial at any time if an unacceptable toxicity occurs. The DSMB will meet every two 
months. In addition, DSMB will be review all potential causally related Serious Adverse Events within 7 days 
of the initial report. 
The DSMB has only a consultative role. It will inform the Sponsor who will decide whether the DSMB 
recommendation will be followed. A DSMB charter must be available upon submission of the trial (initial 
protocol) to the respective competent authorities. 
An Independent Cardiovascular Safety Committee (ICVSC), comprised of 3 cardiologists with experience from drug 
development, will be formed as detailed in the Charter. The ICVSC will be responsible for an on-going evaluation 
of cardiac adverse events of special interest (Cardiac AESIs), for treatment emergent echocardiographic findings, 
and for treatment emergent changes of cardiac safety biomarkers (as detailed above). The ICVSC will review 


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cardiac adverse events on an on-going basis, meet regularly and provide recommendations to Sponsor and DSMB 
regarding study procedures and conduct. 
3.1.3. Duration of study participation 
Patients will receive ABX464 50mg QD for up to 96 Weeks. After the last study drug dose, patients will go 
through a safety follow-up of 4 weeks. Therefore, the study participation duration will be up to 100 weeks. For 
subjects who did not meet eligibility at Week 48, the study participation duration will be up to 52 weeks. 
 
 


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4. STUDY POPULATION 
4.1. Number of Patients/Centers 
Patients will be enrolled in 69 sites located in Europe, US and Canada. 
4.2. Eligibility Criteria 
4.2.1. Inclusion Criteria 
A patient will be eligible for inclusion in this study only if ALL of the following criteria apply: 
▪ Patients must have completed the 16-week (± 4 days) induction treatment period (ABX464-103). 
▪ Patients are able and willing to comply with study visits and procedures as per protocol. 
▪ Patients should understand, sign and date the written voluntary informed consent form prior to any 
protocol-specific procedures are performed. 
▪ Patients should be affiliated to a social security regimen (for French sites only). 
▪ Females and males receiving the study treatment (potentially in combination with immunosuppressant) 
and their partners must agree to use a highly effective contraceptive method during the study and for 6 
months (180 days) after end of study or early termination. Contraception should be in place at least 2 
weeks prior to screening. Women must be surgically sterile (bilateral oophorectomy, bilateral 
salpingectomy, or hysterectomy) or in the postmenopausal state (no menses for 12 months without an 
alternative medical cause) or if of childbearing potential must use a highly effective contraceptive method. 
Women of childbearing potential (WOCBP) will enter the study after confirmed menstrual period and a 
negative pregnancy test. Highly effective methods of contraception include true abstinence, intrauterine 
device (IUD) or hormonal contraception aiming at inhibition of ovulation, intrauterine hormone releasing 
system, bilateral tubal ligation, vasectomized partner. True abstinence is defined when this is in line with 
the preferred and usual lifestyle of the patient. In each case of delayed menstrual period (over one month 
between menstruations) confirmation of absence of pregnancy is required. This recommendation also 
applies to WOCBP with infrequent or irregular menstrual cycle. Female and male patients must not be 
planning pregnancy during the trial and for 6 months post completion of their participation in the trial. In 
addition, male patients should use condom during the trial and for 6 months (180 days) post completion 
of their participation in the study. Male patients must not donate sperm as long as contraception is 
required. 
Criteria that should be met by patients at week 48 to be eligible for 48 additional weeks of study treatment. 
▪ Patients should be in clinical response. Clinical response is defined as: a reduction in Modified Mayo 
Score ≥ 2 points and ≥ 30 % from baseline (induction) with an accompanying decrease in rectal bleeding 
sub-score ≥ 1 point or absolute rectal bleeding sub-score ≤ 1 point. 
▪ Patients able and willing to continue the study treatment and who are compliant with study visits and 
procedures and who signed the update of the written voluntary informed consent. 
4.2.2. Exclusion Criteria 
The following criteria should be checked at the time of screening. If ANY exclusion criterion applies, the patient 
will not be included in the study: 
▪ Patients who permanently discontinued study the treatment in induction study (ABX464-103) because of 
an adverse event (AE) regardless of relatedness to investigational product. 
▪ Patients who have developed any major illness/condition or evidence of an unstable clinical condition 
(except UC) that, in the investigator’s judgment, will substantially increase the risk to the participant if he 
or she participates in the study. 
▪ Patients with any other severe acute or chronic medical or psychiatric condition or laboratory or 
electrocardiogram (ECG) abnormality that may increase the risk associated with study participation or 
investigational product administration or may interfere with the interpretation of study results and, in the 
judgment of the investigator, would make the patient inappropriate for entry into this study. 
▪ Patients who are participating in or plan to participate in other investigational studies (other than induction 
study) during the study. 
 


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5. STUDY ASSESSMENTS AND PROCEDURES 
5.1. Study Flow Chart 
A detailed study flow chart (with all assessments) is displayed hereafter.  
 
Treatment period 
EOS 
 
Baseline 
(D113 study 
ABX464-103) 
Week 4 to 20 
(every 4 weeks) 
Week 24 
Week 28 to 44 
(every 4 weeks) 
Week 48 
Week 60 
to 84 
(every 12 
weeks) 
Week 96 
Week 52 or 
100 
Time Window 
 
± 2 days 
± 2 days 
± 2 days 
± 2 days 
± 2 days 
± 2 days 
± 2 days 
Obtained Inform Consent 
X 
 
 
 
X# 
 
 
 
Check of IN/EX Criteria 
X 
 
 
 
X# 
 
 
 
Demographics 
X* 
 
 
 
 
 
 
 
Physical Examination 
X* 
X 
X 
X 
X 
X 
X 
X 
Body Weight (kg) 
X* 
X 
X 
X 
X 
X 
X 
X 
Medical History 
X* 
 
 
 
 
 
 
 
Vital signs 
X* 
X 
X 
X 
X 
X 
X 
X 
ECG (12 lead) 
X* 
 
 
 
X 
 
 
X 
Concomitant medication 
X* 
X 
X 
X 
X 
X 
X 
X 
Blood Pregnancy test 
(WOCBP) 
X* 
X 
X 
X 
X 
X 
X 
X 
Hematology + 
Biochemistry (including 
NT-proBNP blood levels) ꝉ 
X* 
X 
X 
X 
X 
X 
X 
X 
Modified Mayo Score 
(partial MMS/MMS) 
X* 
X 
X 
X 
X 
X 
X 
X 
Diary data collection 
X* 
X 
X 
X 
X 
X 
X 
X 
Treatment compliance 
verification 
 
X 
X 
X 
X 
X 
X 
 
Fecal calprotectin 
X* 
 
X 
 
X 
X 
X 
X 
Serum collection for 
cytokine assessment 
X* 
 
X 
 
X 
 
 
X 
Sigmoidoscopyǂ 
 
 
 
 
X 
 
X 
 
 Cardiac ischemic 
disease/congestive heart 
failure) medical/treatment 
history review 
 
X 
X 
X 
X 
X 
X 
 
Echocardiography 
 
 
X 
 
X 
Xƚ 
X 
 
IBDQ 
X* 
 
X 
 
X 
 
 
 
ABX464 50mg 
dispensation 
X 
X 
X 
X 
X” 
X 
 
 
Samples for miRNA 
(Biopsy RNA Later) 
X‡ 
 
 
 
X 
 
X 
 
Samples for miRNA (Blood 
PAXgene tube) 
X 
 
X 
 
X 
X 
X 
 
Adverse Events recording 
X 
X 
X 
X 
X 
X 
X 
X 
Dermatologist 
Consultation in case of 
skin effect 
(X) 
Assessment with an * are not repeated but used from the D113 visit and just re-entered in the CRF 
# Specific consent and IN/EX for the second year of treatment 
ǂ: Sigmoidoscopy at Week 48 and Week 96 should be performed within a week prior to the visit, to allow the central results to be available at the visit for the 
assessment of the subject eligibility. Local read results could be used at W96 to assess eligibility of subject to enter ABX464-108 study if central read results are not 
available. 
“If patient is eligible for the 2nd treatment year 
ƚ Only at week 72  
ꝉ NT-proBNP blood levels only at Week 24, 48, 72, 96 and at the End of Study Visit 
‡Biopsy sample for miRNA is only taken if the conditional sigmoidoscopy at D113 of the ABX464-103 induction study is performed 
(X) optional 
 
5.2. Study conduct 
It is the Investigator’s responsibility to ensure that all the assessments are carried out during each visit and 
that the intervals between visits/follow-ups are adhered to. 
5.2.1. Baseline Visit (i.e. Day 113 of the Induction study ABX464-103) 
The patient will be informed about the general aspects of the study and will sign the informed consent form. 
Only when consent has been given may further study procedures be carried out. 
During the baseline visit, the following assessments will be performed (NB: if some are already performed as 
per Day 113 of the induction study ABX464-103, results will be captured, but tests must not be repeated): 
▪ Signed informed consent form 
▪ Inclusion/exclusion criteria will be verified 


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▪ Demographic data: date of birth and gender 
▪ IBD Questionnaire (as the first visit procedure) 
▪ Partial Modified Mayo Score 
▪ Hand over paper diary and instruct the patient how to use it 
▪ Medical history 
▪ Record all concomitant medications 
▪ Record previous UC medication without time limitation (Except for conventional treatments such as 
corticosteroids, oral 5-aminosalicylic acid and immunosuppressants which are to be recorded within a 
year prior to baseline) 
▪ Physical examination including body weight and vital signs measurements 
▪ 12 leads ECG 
▪ Hematology and Biochemistry including pregnancy test for all women of childbearing potential 
▪ Serum tube collection (Cytokines) 
▪ Tissue samples for miRNA (Biopsy RNA Later) if conditional sigmoidoscopy performed on Day 113 of 
the induction study ABX464-103 (sampling must not be repeated) 
▪ Blood sample for miR-124 dosage (PAXgene® tube) if performed on Day 113 of the induction study 
ABX464-103, sampling must not be repeated) 
▪ Fecal calprotectin 
▪ Dispense study treatment to patient and instruct to take the first capsule of the ABX464-104 medication 
the next day of the visit due to the PK samplings in the frame of the ABX464-103 study (no PK analysis 
is performed in the frame of the study ABX464-104) 
▪ Adverse Event reporting. In case of a skin effect, please refer to a dermatologist 
▪ Optional: sigmoidoscopy with biopsy (if performed during the D113 visit of ABX464-103, data will be 
recorded for the ABX464-104 study protocol) 
▪ Schedule next patient visit (i.e. week 4). 
5.2.2.  Monthly and Quarterly Visits (W4, week X+4; W48, week X+12 and W96) 
▪ Review of the subject’s medical history at the earliest opportunity to discontinue subjects with history of 
cardiac ischemic disease and/or congestive heart failure 
▪ Physical examination including body weight and vital signs measurements 
▪ Hematology and Biochemistry (Including NT-proBNP levels at week 24, week 48, week 72and week 96) 
▪ Blood pregnancy test for all women of childbearing potential 
▪ Record all concomitant medication change 
▪ Check treatment compliance and review the patient diary 
▪ Partial Modified Mayo Score 
▪ Fecal calprotectin (at week 24 and week 48 and then quarterly) 
▪ Blood sample for miR-124 dosage (PAXgene® tube) (at week 24 and week 48 and then quarterly) 
▪ Adverse Events reporting. In case of a skin effect, please refer to a dermatologist 
▪ Dispense the study treatment needed to cover the period between consecutive visits (except at Week 48 
if patient is not eligible for a second year of treatment; no dispensation of IP at Week 96) 
▪ Schedule next patient visits (At W96 schedule EOS visit if subjects not rolling over to the long term follow 
up safety study (ABX464-108). 
 
To be performed additionally at week 24 and week 48: 
▪ IBD Questionnaire (prior to other study procedures) 


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▪ Serum collection for cytokine assessment 
▪ Echocardiography. 
 
To be performed additionally at week 48 only: 
▪ ECG (12-lead) 
▪ Sigmoidoscopy with rectal/sigmoidal biopsies for miRNA assessment (procedure can also be done at 
interim study visits only if medically justified); Sigmoidoscopy should be performed within a week prior to 
the visit, to allow the central results to be available at the visit for the assessment of the subject eligibility 
to the second year of treatment 
▪ Check of patient’s eligibility for a second year of treatment 
▪ Second year patient consent signature. 
 
To be performed additionally at week 72: 
▪ Echocardiography. 
 
To be performed additionally at week 96: 
▪ Sigmoidoscopy with rectal/sigmoidal biopsies; Sigmoidoscopy should be performed within a week prior 
to the visit, to allow the central results to be available at the visit for the assessment of the subject eligibility 
to the long term follow up safety study (ABX464-108). Local read results could be used at W96 to assess 
eligibility of subject to enter ABX464-108 study, if central read results are not available. 
▪ Echocardiography 
▪ Enrolment of eligible subjects willing to take part to the long term follow up safety study (ABX464-108). 
 
5.2.3. End of Study Visit (Week 52 or Week 100 ± 2 days) 
This EoS visit applies to all premature discontinued patients, to all patients who completed the W48 treatment 
phase and who are found non-eligible for the second year of treatment and for patients not taking part to the 
long term follow up safety study (ABX464-108). Patients will perform an End of Study Visit (EoS) 4 weeks after 
last study drug intake (i.e Week 52 ± 2 days if the patient did not meet eligibility criteria at week 48; Week 100 
± 2 days if the patient completed the study and is not taking part to the long term follow up safety study 
(ABX464-108). 
Following examinations/procedures should be performed: 
▪ 
Physical examination including body weight and vital signs measurements 
▪ 
ECG (12-lead) 
▪ 
Hematology and Biochemistry (Including NT-proBNP levels) 
▪ 
Blood pregnancy test for all women of childbearing potential 
▪ 
Record all concomitant medication change 
▪ 
Check treatment compliance and review the patient diary 
▪ 
Partial Modified Mayo Score 
▪ 
Fecal calprotectin 
▪ 
Serum collection for cytokine assessment 
▪ 
Adverse Events reporting. In case of a skin effect, please refer to a dermatologist 
NB: In case of premature discontinuation occurring during the treatment phase the above examinations should 
be performed as an End of Study Visit 4 weeks after treatment interruption 
After the end of study visit, patients will be treated according to the local standard of care. 
 


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5.3. Detail of the study assessments  
5.3.1.  Echocardiography  
Since enrolment is completed at the time of this amendment, drug-free baseline measurements are not 
available. Echocardiography will be performed at the earliest opportunity (Week 24 or Week 48 or Week 72) 
and will be repeated every six months. Two-dimensional echocardiography measurements will be assessed 
during the study. Echocardiography will be performed locally, and the images will be transmitted to a central 
reading vendor (Clario) for independent read and evaluation. Sites will receive appropriate training as well as 
an Echocardiography Manual that includes detailed instructions regarding image acquisition, test echo 
submission/approval and image upload procedures. 
Central assessments will adhere to the recommendations of the American Society of Echocardiography.  
In addition, local reads must be performed by site in the case central evaluation is not possible and results will be 
recorded in EDC. 
The following standard parameters - pertinent to the assessment of changes in cardiac function will be 
assessed: 
▪ 
Left Ventricular Ejection Fraction (LVEF%) 
▪ 
Left Ventricular end systolic/end diastolic volumes 
▪ 
Left Ventricular septal/posterior wall thickness 
▪ 
Left Ventricular Mass/Mass indexed 
▪ 
Left Ventricular Global Longitudinal Strain (GLS) 
▪ 
Left Atrial volume 
▪ 
Doppler assessment (Mitral E/A ratio, Stroke Volume, Cardiac Output, Tissue Doppler Imaging) 
▪ 
Valvular assessment for regurgitation/stenosis 
▪ 
Right ventricular (RV) size and systolic function assessment 
Specific attention will be brought to potential changes from previous assessment in LVEF and GLS. All 
echocardiographic parameters will be presented descriptively and will be reviewed by the Independent 
Cardiovascular Safety Committee (ICVSC). 
5.3.2. Cardiac ischemic disease/congestive heart failure medical/treatment history review 
A retrospective review of medical history to search for cardiac ischemic disease and/or congestive heart failure 
will be done at the next possible visit of the subject as enrolment is finished at the time of this amendment. 
Patients with a history of or treated for cardiac ischemic disease and/or congestive heart failure will have to be 
discontinued from the study. 
5.3.3. Physical Examination and Vital Signs 
A routine physical examination (including body weight) will be done at each study visit. Physical examinations 
will cover eyes, ears, nose, throat, lungs/thorax, heart/cardiovascular system, abdomen, skin and mucosae, 
nervous system, lymph nodes, musculo-skeletal system, and, if applicable, others. Any new clinically relevant 
finding compared to baseline must be documented as adverse event. 
Measurements of vital signs will be done at each visit (Blood pressure, Heart Rate, Body temperature). The 
patient should rest supine for at least 10 minutes prior to measurements. The measurements can be performed 
either in sitting or supine position of the patient. The right or left arm may be used. However, the position and 
the arm used for measurement should be kept constant throughout the trial for an individual patient.  
The investigator should ensure that each parameter outside the normal range is assessed for clinical 
significance. For any deviation assessed clinically significant, the investigator has to document the change as 
an AE in the CRF.  
In addition, it is at the discretion of the investigator to document any change or trend over time in vital signs as 
an AE if he considers the change to be clinically significant, even if the absolute value is within the alert limit 
or reference range. 


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5.3.4.  Pregnancy 
For all female patients of childbearing potential, a blood pregnancy test (beta human chorionic gonadotropin 
[HCG]) will be performed at every visit. In case of positive pregnancy testing, detailed procedures can be found 
in section 8.7.2. 
Urine pregnancy tests will be supplied to female patients of childbearing potential from week 48 onwards to 
test for potential pregnancy every month. She will be instructed by the site how to use them and to contact 
immediately the site in case of positive result. 
5.3.5.  ECG 
Electrocardiograms will be performed at baseline, week 48 and EoS visits. At least a 12-lead ECG with 
recordings of at least 6 action potentials in lead II (paper speed 25mm/s, amplitude 10mm/mV) will be 
measured at a resting position. Prior to the recording the patient should be at rest for at least five minutes. 
Resting ECG should be performed before any examinations. 
The ECG printout will be reviewed by the Investigator and a signed and dated copy of the ECG will be attached 
to the medical file. The original ECG printouts are considered as source data and should be stored at site. If 
thermal paper is used, a copy of the original ECG must also be kept. All abnormal findings must be documented 
in the CRF. Any clinically relevant findings compared to ECG done at Day 0 must be documented as adverse 
events. 
5.3.6. IBD Questionnaire (IBDQ) 
The Inflammatory Bowel Disease Questionnaire (IBDQ) is a widely used questionnaire for patients’ quality of 
life assessment in patients with inflammatory bowel diseases (IBDs). This questionnaire has been adapted 
and validated into several languages. IBDQ will be filled in by the patients at baseline, week 24 and week 48 
prior to any study procedures. 
5.3.7.  Modified Mayo Score - Stool and Rectal Bleeding Frequency 
The Stool and Rectal Bleeding frequency assessment will be based on the Mayo scoring system which is the 
most commonly used index in clinical trials.  
While Total Mayo score consists of 4 items: stool frequency, rectal bleeding, flexible sigmoidoscopic 
examination, and a physician global assessment (Appendix #3), in this study and according to regulatory 
guidance, the physician global assessment has been removed to define the Modified Mayo Score (MMS). 
Partial Modified Mayo Score (pMMS) consists of only 2 items (stool frequency, rectal bleeding). Stool 
frequency and rectal bleeding frequency will be recorded from the patient diary at each patient visit by the 
Investigator. 
Instruction for Mayo Score Calculation (MMS/pMMS) is provided in appendices (Appendix #6). 
Attention: Investigators should train his/her patient how to record stool frequency and rectal bleedings in the 
diary. Instruction booklet, detailing the FDA requirements for Patient Reported Outcomes, will be provided to 
patients and investigators.  
5.3.8.  Sigmoidoscopy with rectal/sigmoidal biopsies 
Sigmoidoscopies procedures (or colonoscopies if applicable) will be performed by the site endoscopist. Bowel 
preparation is mandatory. Patients will be instructed to follow the site standard of care. 
Procedures will be standardized for optimized video acquisition at clinical sites. Sigmoidoscopies should be 
performed according to the Central Imaging Management System Charter.  
Central Imaging Management System will be provided including a central image database. Once uploaded, 
video data will be analyzed for quality and resolution prior to independent review by an expert central reader. 
Study videos will be scored separately using the Mayo Clinic Score (excluding friability) for all time points by 
central readers and visit sequence of the recordings.  
The central reader’s score at baseline (ABX464-103 / W8 or W16), week 48 and week 96 will be entered 
directly into the eCRF. All procedure videos collected for outcome evaluation will be scored and results 
communicated within five (5) business days.  
Two rectal biopsies (plus optionally two sigmoidal biopsies, if the inflammation of the sigmoid is observed) will 
be performed at week 48 and 96. The biopsies (1+1 back-up for each test) will be sent to central laboratories 


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for assessment according to Robarts Histopathology Index (RHI), the Geboes and Nancy Histology Scoring 
Scales (please refer to the lab manual) and for miRNA-124 determination (RNA later). 
RHI score ranges from 0 (no disease activity) to 33 (severe disease activity) and is based on the evaluation of 
four main parameters: chronic inflammatory infiltrate, lamina propria neutrophils and eosinophils, neutrophils 
in the epithelium and erosion/ulceration. Overall, this histological index has been reported to be reproducible, 
responsive and valid and will be used for confirmation of the mucosal healing. The patient’s biopsies will be 
also read according to the Geboes and Nancy Histology Scoring Scales for completeness purposes. 
5.3.9.  Hematology, biochemistry and calprotectin evaluation 
For hematology and biochemistry central laboratory will be used (i.e. Eurofins). All lab dosages will be done 
centrally (except with prior approval). Sampling kits and transportation information and devices will be provided 
by Eurofins.  
Regarding the calprotectin measurement, the site might be asked to keep back-up samples at -80°C till the 
end of the study. 
Any hematology and biochemistry safety sample (Total bilirubin, AST/ALT, Alkaline phosphatase, Lipase INR, 
Prothrombin, Troponin I & T, CPK and NT-proBNP) that does not have a result reported at any visit must be 
repeated by the central lab (or locally if preferred). 
For the containment and countering against the spread of the COVID-19 virus (coronavirus disease 19), safety 
blood tests (such as but not limited to LFTs, WBC and hemoglobin) may be performed in other facilities. 
Laboratory reports should be reviewed, dated and signed by the principal investigator and kept in the medical 
file of the subjects. This waiver should also be extended to additional safety procedures for the subject, 
including, for example, cardiological and radiological tests and procedures. 
Each laboratory value that is outside of the institution’s normal range will be identified. The Investigator will be 
responsible for assessing the clinical significance of laboratory abnormalities. If the Investigator is uncertain 
about the clinical significance of a laboratory abnormality, he/she will consult with the Sponsor medical monitor. 
The Investigator should follow any clinically significant laboratory abnormalities until resolution. 
Table 2 displays the clinical laboratory parameters that must be measured. 
Table 2: Laboratory Tests 
HEMATOLOGY 
PANEL 
BIOCHEMISTRY PANEL 
IMMUNOCHEMISTRY 
STOOLS 
Hemoglobin 
Hematocrit 
WBC 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
Platelet count 
Fibrinogen 
Prothrombin 
time 
Sodium 
Potassium 
Chloride 
Calcium 
Phosphate 
Glucose  
BUN or urea  
Creatinine 
CPK  
AST  
ALT 
Total, HDL and LDL 
cholesterol 
Lipase 
Alkaline 
phosphatase 
gammaGT 
Total 
bilirubin  
Total protein  
Albumin  
LDH  
CRP 
GLDH 
NT-proBNP  
Amylase 
Troponin I & T 
T3, T4, TSH 
β-hCG 
 
Fecal calprotectin 
 
5.3.10. Cytokines analysis 
Cytokines (such as IL-6, TNFα, IL-1b, IL-10, MCP-1 but not limited to) will be assessed by a central laboratory. 
All samples will be kept on site (-20°C/-80°C) until sponsor’s notification for shipment to the central laboratory. 
The process for samples preparation, storage and shipment will be fully defined in the laboratory manual. 
5.3.11. miRNA modulation 
ABX464 up-regulates miRNA in PBMCs, making of this micro-RNA a potentially useful biomarker for ABX464 
treatment monitoring. Determination of miRNA level in tissue and in total blood will be performed in order to 
assess treatment effect by comparing before and after treatment. Assays for miRNA determination will be 
conducted by BIOGAZELLE. 


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The rectal/sigmoidal biopsies will be stored in RNA later, total blood in PAXgene® tubes according to lab 
manual instructions. 
5.4. Summary of blood samples 
The table 3 below summarizes the volume of blood to be sampled at each study visit. A total of 316 ml should 
be needed if the patient does not take part to the second year of study treatment or a total of 418 ml for the 
whole study duration including the second year. 
Table 3: Blood Volume 
  
Collection tube 
Baseline* 
Week 4 to Week 
20 
(5 visits) 
Week 
24 
Week 28 to 
Week 44 
(5 visits) 
Week 
48 
EOS  
D52/week 
52 or 
week 100 
Total 
Per Panel 
Hematology (Hemoglobin, 
Hematocrit, Red Cell Count, 
MCV, MCHC, Platelets, White 
cell count with diff.) 
EDTA tube 
2 
2 
2 
2 
2 
2 
12 
Biochemistry panel incl CRP, 
GLDH, CPK, Serum Pregnancy 
test and lipids 
Serum gel tube 
8,5 
8,5 
8,5 
8,5 
8,5 
8,5 
51 
Fibrinogen and Prothrombin 
Time 
Na-citrate tube 
4,5 
4,5 
4,5 
4,5 
4,5 
4,5 
27 
NT-proBNP 
K2 EDTA tube 
2 
 
2 
 
2 
2 
8 
Troponin (I&T) 
SST tube with 
gel 
3,5 
3,5 
3,5 
3,5 
3,5 
3,5 
21 
Cytokines (IL-6, TNFa, IL-1b, IL-
10) 
Serum gel tube 
8,5 
  
8,5 
  
8,5 
8,5 
34 
PAXgene Tube (miRNA) 
PAXgene 
  
  
5 
  
5 
5 
15 
  
Total per visit 
29 
18,5 
34 
18,5 
34 
34 
  
 
*To be done if testing was not performed in the ABX464-103 study. Otherwise, results are to be collected only. 
 
  
Collection tube 
Week 60 to Week 96 
(4 visits) 
Total 
Per Panel 
Hematology (Hemoglobin, Hematocrit, Red 
Cell Count, MCV, MCHC, Platelets, White 
cell count with diff.) 
EDTA tube 
2 
8 
Biochemistry panel incl CRP, CPK, GLDH, 
Serum Pregnancy tests, amylase and lipids 
Serum gel tube 
8,5 
34 
NT-proBNP 
K2 EDTA tube 
2 
8 
Fibrinogen and Prothrombin Time 
Na-citrate tube 
4,5 
18 
Troponin (I&T) 
SST tube with gel 
3,5 
14 
miRNA 
PAXgene Tube 
5 
20 
  
Total per visit 
25.5 
102 
 
 


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6. INVESTIGATIONAL PRODUCT(S) 
All investigational products to be used in this study have been manufactured, packaged and labelled by 
contract manufacturers for ABIVAX, according to GMP standards and are supplied to investigators free of 
charge. 
6.1. Description of investigational treatment 
The study treatment that will be administrated to patients enrolled in this phase 2b study consists of capsules 
containing ABX464 50mg given orally once daily for a maximum of 96 weeks. 
6.2. Description of investigational Product ABX 464 
The ABX464 investigational medicinal product (IMP) is a hard gelatin capsule intended for oral administration. 
For the proposed clinical trial, the IMP consists of size 01 capsules containing 50mg of ABX464 drug substance 
in the form of granulate prepared with a number of common excipients (microcrystalline cellulose, 
polyvinylpyrrolidone, magnesium stearate and colloidal silica).  
It is supplied in high-density polyethylene (HDPE) bottles closed with child-resistant polypropylene screw caps. 
ABX464 manufacturing and packaging will be performed at the following site:  
DELPHARM Lille SAS 
Parc d’activité Roubaix Est 
22, rue de Toufflers 
CS 50070 
59 452 Lys-Lez-Lannoy France 
Labelling activities, as well as Qualified Person release of the IMP will be performed at the following site: 
Creapharm S.A.S. 
Z.A. Air Space 
Avenue de Magudas CS 2007 
33187 Le Haillan 
France 
6.3. Administration and Dosing 
6.3.1. Administration of the investigational product 
Patients will be treated with a daily dose of 50mg of ABX464. Patients will receive 1 capsule every day. starting 
the day after the baseline visit. All patients will be orally dosed in a fed condition (regular meal) with a glass of 
water. A patient diary, in which the patient should report the daily number of capsules taken and the intake 
time will be given to the patient at baseline.  
6.3.2. Guidelines for treatment postponement and dose modifications 
No intra-patient dose escalation/dose adjustment are allowed.  
6.4. Method of Assigning Patient Numbers 
All patients will be assigned a unique and incremental Patient Identification (ID) number (same number as the 
one used in the ABX464-103 study). Patient IDs will be unique (i.e. reallocation of the ID will not be permitted). 
The format will be a seven-digit number as follows: site number (4 digits) – Patient number (3 digits). The latter 
3-digit Patient number will be assigned according to the patient’s order of inclusion in the center. 
Eligible patients (i.e. those who fulfil all inclusion/exclusion criteria) will all receive active treatment. In all cases, 
patients should return his/her used and unused HPDE bottles at each study visit for a compliance check. 
Patient’s compliance to treatment (including capsule count) will be recorded on the eCRF. Insufficient 
treatment compliance (compliance < 80% and non-respect of administration scheme) will be reported as 
deviations. 


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6.5. Packaging 
The IMP consists in hard gelatin, powder-filled capsules (size 01) containing 50 mg of ABX464 supplied in 
HDPE (high-density polyethylene) bottles closed with child-resistant polypropylene screw caps (30 capsules 
per bottle). 
6.6. Storage 
ABX464 capsules will be shipped to the investigational site at a temperature not above 25°C (77°F). 
Storage conditions: Do not store above 30°C (86°F). Do not refrigerate or freeze. 
The IMP must not be used beyond the expiration date. Drug supplies are to be stored in a secure, limited-
access location under the storage conditions as specified in the IMP manual.  
6.7. Product Accountability 
An accurate and current accounting of the dispensing and return of IMP(s) will be maintained on an ongoing 
basis by the pharmacist or member of the study site staff in the Accountability Log and case report form and 
will be verified by the study’s monitor. 
6.8. Prior and Concomitant Medication 
6.8.1.  Allowed concomitant treatment 
Allowed Concomitant Medications are: 
▪  Oral 5-aminosalicylic acid at stable dose [9]; 
▪ Immunosuppressants in the form of azathioprine, 6-mercaptopurine, or methotrexate at stable dose; 
▪ Antidiarrheals (e.g., loperamide, diphenoxylate with atropine) at stable dose; 
▪ For patients on oral corticosteroids at baseline, prednisone or prednisone equivalent ≤20 mg/day; 
beclomethasone diproprionate (≤5mg/day) or budesonide MMX (≤9 mg/day). 
Tapering period: 
For patients on oral corticosteroids at baseline, a tapering of steroids should be performed from baseline 
onwards. The rate of prednisone or prednisone equivalent tapering should not exceed 5 mg/week till complete 
discontinuation. The tapering can be stopped at any time based on medical judgment. No further oral 
corticosteroids dose escalation is allowed. 
Potential other concomitant medications should be kept at constant dose during the course of the study and 
properly reported in the medical file of the patient and the eCRF. 
This information should include the name of the medication (international nonproprietary name), daily dosage, 
treatment duration, and indication. 
6.8.2. Prohibited concurrent medications 
The following drugs are prohibited during the course of the study.  
▪ Tumor necrosis factor [TNF] inhibitors, vedolizumab or others biologic therapies. 
▪ JAK inhibitors. 
▪ Topical corticosteroids and topical 5-aminosalicylic acid preparations. 
▪ Cyclosporine and tacrolimus. 
▪ Vaccination with live components during the study and up to 8 Weeks after the last dosing (COVID 19 
vaccines are allowed). 
▪ Drugs that inhibit or induce CYP1A2 (Appendix #1). 
▪ Drugs that inhibit UDP-glucuronosyltransferase (UGT) IA9 activity and inhibitors or substrates of organic 
anion transporter (OAT) P1B1/P1B3 transporters (Appendix #1). 
▪ Use of any investigational or non-registered product. 
 


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7. STUDY COMPLETION AND WITHDRAWAL 
7.1. Patient Completion 
Treatment with ABX464 shall continue until Week 48 (if the patient did not meet eligibility at week 48 to continue 
treatment until Week 96) or until week 96, except if a patient fulfils a premature discontinuation criterion 
(defined below). 
7.2. Premature trial discontinuation 
Subjects who are not found eligible for the second year of treatment are not considered as prematurely 
discontinued as they have completed the first-year treatment. A patient can be withdrawn at any time from the 
study for the following reasons: 
▪ Investigator’s decision: subject who would experience a treatment failure during the study may be 
withdrawn at any time. S/he will have to be treated according to standard of care as soon as s/he is 
discontinued from study treatment because of study withdrawal 
▪ An Adverse Event or an intercurrent condition that preclude continuation of treatment; Specifically, 
o 
An increase ≥ 3.0 x ULN in liver transaminases (AST/SGOT and/or ALT/SGPT) or an 
increase ≥ 2.0 x ULN in Alkaline phosphatase or in total bilirubin requires close observation 
with repeating liver enzymes and serum bilirubin tests two times weekly and clinical 
investigation to understand the etiology of this elevation. Frequency of retesting can decrease 
to once a month if the abnormality stabilizes after this initial two weeks of follow-up and if the 
patient is asymptomatic. Discontinuation of the study treatment should occur if: 
▪ 
 ALT or AST > 8xULN 
▪ 
ALT or AST > 5xULN for more than 2 weeks 
▪ 
ALT or AST > 3xULN and total bilirubin > 2xULN or INR>1.5 
▪ 
ALT or AST > 3xULN with appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (>5%). 
▪ A severe (grade 3 or higher) infection, a severe (grade 3 or higher) opportunistic infection, or sepsis.  
▪ Any cardiac AESI or condition diagnosed during the course of the study and assessed by the clinical 
adjudication committee as changing the risk/benefit balance for study subjects; 
▪ New onset of acute pancreatitis; 
▪ Malignancies (including non-melanoma skin cancers); 
▪ Medically significant abnormal laboratory results, including new onset anemia (defined as a hemoglobin 
decrease >2 g/dL from baseline or hemoglobin <8 g/dL) - note: transient abnormal values, and/or 
abnormal values related to an existing condition that doesn’t constitute a worsening will not be a criteria 
for discontinuation. 
▪ Any relevant toxicity or negative change in the risk/benefit assessment leading to an unacceptable risk 
for the subject or any data deriving from other clinical trials or toxicological studies which negatively 
influence the risk/benefit assessment. This may be applicable but is not limited to the following cases: 
occurrence of AEs which character, severity or frequency is new in comparison to the existing risk profile.  
▪ Worsening of the UC defined, from the baseline visit of the maintenance phase onwards, as a 2-point 
increase in the partial MMS, with pMMS ≥ 4 on 2 separate occasions 7 day-apart and confirmed by an 
endoscopy sub-score of 2 points or higher. In such a case the patient will be withdrawn from the study. 
▪ Withdrawal of consent. 
▪ Pregnancy. 
▪ Patients included with a history of cardiac ischemic disease and/or congestive heart failure will be 
discontinued from the study, will perform the End of Study Visit 4 weeks after last study drug 
administration and will then be treated according to the standard of care upon study treatment 
interruption. 
A patient who prematurely exits the study will not be replaced.  


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7.3. Study Discontinuation 
All patients, regardless of the completion or premature discontinuation, should perform the End of Study Visit 
according to the study flow-chart. 
7.4. Baseline Failures 
A patient is considered to be a baseline failure if the patient signs the informed consent but withdraws before 
first dosing in the maintenance phase. Reasons for exclusion will be recorded for potential patients who do not 
enter the study. 
7.5. End of Trial 
The ABX464-104 is the maintenance phase of the ABX464-103 protocol (induction study). ABX464-104 End 
of Trial will occur once the last patient from the induction study completes the last study visit. 


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8. ADVERSE EVENTS (AE), ADVERSE EVENT OF SPECIAL INTEREST (AESI) AND SERIOUS 
ADVERSE EVENTS (SAE) 
The investigator is responsible for the detection and documentation of events meeting the criteria and definition 
of an AE, AESI or SAE. During the study, in case of a safety evaluation, the investigator or site staff will be 
responsible for reporting AEs, AESIs and SAEs, as detailed in this section of the protocol.  
Any disease progression will be reported in the eCRF both as an adverse event and documented in the efficacy 
section. 
8.1. Definition of an AE 
Any untoward medical occurrence in a subject or clinical investigation subject administered a pharmaceutical product 
and which does not necessarily have to have a causal relationship with this treatment. 
An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or 
disease (new or exacerbated) temporally associated with the use of a medicinal product, whether or not considered 
related to the medicinal product. 
Note: The official definition also extends to AEs occurring in the placebo arm. For monitoring purpose, events occurring 
during pre-and post-treatment periods will also be designated as AEs. Therefore, reporting of such events, AEs and 
SAEs, will start when the subject is enrolled into the study (date of signature of the informed consent) up to 4 weeks 
after the end of the treatment visits. The period after discontinuing IMP may be extended if there is a strong suspicion 
that the drug has not yet been eliminated. 
8.2. Definition of an AESI 
The following events will be considered AESIs and must be reported using the AESI forms. 
Skin Lesions (regardless of its severity) 
The AESI “skin lesion” should be broadly captured by the site physician. Subjects are informed via the ICF that oral 
administration of ABX464-N-Glu was phototoxic in a nonclinical model at clinically relevant exposure levels.  To 
mitigate this risk, subjects must comply with usual public recommendations for sun protection, such as:  use shade 
wisely, wear protective clothing (hat, sunglasses), use sunscreen (with a sun protective factor [SPF] of 15 or higher), 
and limit time spent in mid-day sun or strong sunlight.  Subjects experiencing skin lesion(s) will be instructed to contact 
the site study coordinator or investigator and to take a picture of the skin lesion for medical assessment. The site 
investigator will complete a specific skin lesion AESI reporting form (Appendix # 4). Additionally, the skin lesion AESI 
form may be supplemented by pictures of the affected skin region(s) taken by the subject, at their discretion. The 
pseudonymized skin lesion AESI form will be reviewed by a central dermatologist, to investigate a potential for 
photosensitivity. A pseudonymized medical report will be provided by the central dermatologist. 
Headaches 
Headaches are frequently reported by subjects dosed with ABX464. In specific situations (i.e. the headache lasts more 
than 72 hours AND is not resolved by standard painkillers), the AE will be closely monitored by means of an individually 
adapted questionnaire (Appendix #5), and sent to VCLS together with the AESI form. 
Anemia 
Some degree of anemia was found in the 9-month marmoset study with ABX464-N-Glu. Although it has not been 
reproduced clinically, Abivax performs surveillance for anemia by means of regular determination of haemoglobin and 
haematocrit levels. 
Anemia defined as a Hemoglobin drop > 2 g/dL from baseline or Hemoglobin < 8g/dL will be reported as AESI. 
Hepatic enzymes 
ABX464 showed hepatoxicity findings in pre-clinical studies, hence attention is paid to identification of liver enzymes 
elevations in subjects. No human predictors of hepatoxicity for ABX464 or its metabolite (ABX464-N-Glu), have been 
identified. Based upon available data, a DILIsym evaluation of ABX464 and ABX464-N-Glu has indicated no predictors 
of toxicity. A signal detection analysis of ALT/AST changes in subjects treated with ABX464, did not reveal any 
meaningful variation of the mean ALT/AST measurement throughout treatment nor an increased incidence of any liver 


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function testes (LFTs). No Hy’s Law cases have been observed in ABX464 subjects. Sporadic cases of isolated 
alkaline phosphatase increase have been reported in subjects dosed with ABX464. 
An increase ≥ 3.0 × ULN in liver transaminases (AST and/or ALT) or an increase ≥ 2.0 × ULN in total bilirubin without 
initial findings of cholestasis (elevated alkaline phosphatase) will be reported as an AESI. 
Severe (grade≥ 3) infections and opportunistic infections  
Immunosuppression has been observed during the 9-month cynomolgus monkey study with ABX464-N-Glu dosed 
directly by oral gavage. Therefore, serious (grade 3) infections and opportunistic infections due to bacterial, 
mycobacterial, invasive fungal, viral, or parasitic organisms (including aspergillosis, blastomycosis, candidiasis, 
coccidioidomycosis, histoplasmosis, legionellosis, listeriosis, pneumocystosis, and tuberculosis) will be reported as 
AESIs. Subjects will be monitored for the development of signs and symptoms of infection during treatment with 
ABX464. ABX464 will be discontinued if a subject develops a severe (grade 3 or higher) infection, a severe (grade 3 
or higher) opportunistic infection, or sepsis. 
Acute pancreatic adverse events 
Cases of transient increase in lipase serum levels, have been observed in ABX464 clinical studies in ulcerative colitis 
subjects as well as in subjects with COVID-19 infection (blinded placebo/ABX464 treatment). Therefore, lipase and 
amylase will be monitored in the clinical studies.  
An elevation of serum lipase and/or amylase at least three times greater than the upper limit of normal will be reported 
as AESI and a workup for a diagnosis of pancreatitis will be performed according to the Atlanta criteria for the definition 
of acute pancreatitis. 
Definition of diagnosis of acute pancreatitis [12]. 
The diagnosis of acute pancreatitis requires two of the following three features: (1) abdominal pain consistent with 
acute pancreatitis (acute onset of a persistent, severe, epigastric pain often radiating to the back); (2) serum lipase 
activity (or amylase activity) at least three times greater than the upper limit of normal; and (3) characteristic findings 
of acute pancreatitis on contrast-enhanced computed tomography (CECT) and less commonly magnetic resonance 
imaging (MRI) or transabdominal ultrasonography. If abdominal pain suggests strongly that acute pancreatitis is 
present, but the serum amylase and/or lipase activity is less than three times the upper limit of normal, as may be the 
case with delayed presentation, imaging will be required to confirm the diagnosis. If the diagnosis of acute pancreatitis 
is established by abdominal pain and by increases in the serum pancreatic enzyme activities, a CECT is not usually 
required for diagnosis in the emergency room or on admission to the hospital. 
Malignancies including Non-Melanoma Skin Cancers 
Despite a lack/paucity of reported events in non-clinical and clinical trials, a potential impact on both innate and adaptive 
immune responses and the novel mechanism of action, could be a concern with regards to malignancies, mainly in 
the long-term. 
All malignancies including non-melanoma skin cancers will be reported as an AESI.  
Cardiac Fibrosis 
Two cases of cardiac fibrosis, likely associated with the marmoset wasting syndrome, have been observed in a 9-
month study with marmoset monkeys exposed to high doses of ABX464-N-Glucuronide. These findings were 
considered to be spontaneous. A review of the safety database for ABX464 has revealed no changes in troponin level 
compared with placebo or any increased reporting of cardiovascular adverse events compared with placebo.  
However, the following cardiac monitoring will be performed in all patients:  
▪ 
Monitoring of AST, Troponin, and creatine phosphokinase blood levels at each study visit, including baseline 
visit and End of Study Visit. 
▪ 
Monitoring of N-terminal pro b-type natriuretic peptide blood levels at baseline, and week 8. A relative change 
of more than 20% from baseline values will be reported as an AESI. 
Two-dimensional echocardiography will be performed in subset of subjects. 


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An independent Cardiovascular Safety Committee (ICVSC) will evaluate cardiac AESIs, treatment emergent 
echocardiographic findings, and treatment emergent changes of cardiac safety biomarkers (as detailed above). 
The following TEAEs will be also categorized as cardiac AESI: Aortic valve disease, Asystole, Atrial fibrillation, Atrial 
flutter, 3rd degree AV block (AV block complete), Cardiac arrest, Chest pain – cardiac, Heart failure, Left ventricular 
systolic dysfunction, Mitral valve disease, Mobitz (type) II atrioventricular block (type 2, 2nd degree AV block), 
Myocardial infarction, Myocarditis, Pericardial effusion, Pericardial tamponade, Pericarditis, Pulmonary valve disease, 
Restrictive cardiomyopathy, Right ventricular dysfunction, Sick sinus syndrome, Tricuspid valve disease, Ventricular 
fibrillation, Ventricular tachycardia. 
8.3. Definition of an Adverse Drug Reactions (ADR) 
All untoward and unintended responses to an investigational medicinal product related to any dose administered. The 
definition covers also medication errors and uses outside what is foreseen in the protocol, including misuse and abuse 
of the product. The definition implies a reasonable possibility of a causal relationship between the event and the IMP. 
This means that there are facts (evidence) or arguments to suggest a causal relationship. 
8.4. Definition of a Suspected Unexpected Serious Adverse Reaction (SUSAR) 
A Suspected Unexpected Serious Adverse Reaction (SUSAR), is a serious adverse reaction (SAR) for which a 
reasonable causal relationship with the medicine use is suspected but not confirmed. Unexpected in this context 
means not consistent with the applicable product information (e.g. investigator’s brochure for an unapproved 
investigational product or SmPC for an authorized product). 
8.5. Definition of a SAE 
A serious adverse event (experience) or reaction is any untoward medical occurrence that, at any dose: 
a) Results in death 
NOTE: Death is an outcome of an AE, and not an AE in itself. Event which led to death should be recorded 
with fatal outcome. 
b) Is life-threatening 
NOTE: The term 'life-threatening' in the definition of 'serious' refers to an event in which the patient was at risk 
of death at the time of the event. It does not refer to an event, which hypothetically might have caused death, 
if it were more severe. 
c) Requires hospitalization or prolongation of existing hospitalization 
NOTE: In general, hospitalization means that the patient has been detained at the hospital or emergency ward 
for observation and/or treatment that would not have been appropriate in the physician’s office or out-patient 
setting. Complications that occur during hospitalization are AEs. If a complication prolongs hospitalization or 
fulfills any other serious criteria, the event is serious. When in doubt as to whether “hospitalization” occurred, 
or was necessary, the AE should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen after informed consent was 
given is not considered serious. 
d) Results in persistent or significant disability/incapacity,  
NOTE: The term disability means a substantial disruption of a person’s ability to conduct normal life functions. 
This definition is not intended to include experiences of relatively minor medical significance such as 
uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (e.g. sprained ankle) 
which may interfere or prevent everyday life functions but do not constitute a substantial disruption. 
e) Is a congenital anomaly/birth defect 
f) 
Is another medically important condition: This refers to an AE that may not be immediately life-
threatening or results in death or hospitalization but may jeopardize the patient or may require 
intervention to prevent one of the outcomes listed above. Based on medical and scientific judgment 
this should usually be considered serious. 
If there is any doubt about whether or not an AE is serious, the investigator should contact the sponsor. 


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8.6. Events and/or Outcomes Not Qualifying as SAEs 
Any hospitalization, or prolongation of hospitalization due to the circumstances listed below, will not be reported 
as SAE: 
▪ planned medical/surgical procedure 
▪ planned medical/surgical admission (planned prior to entry into study, appropriate documentation 
required), for the disease under study 
▪ Administrative or social reasons (e.g. lack of housing, economic inadequacy, care-giver respite, family 
circumstances).  
8.7. Events or Outcomes Qualifying as AEs or SAEs 
8.7.1. Clinical laboratory parameters  
Abnormal laboratory findings (e.g., clinical chemistry, hematology) or other abnormal assessments (e.g. vital 
signs) that are judged by the investigator as clinically significant will be recorded as AEs or SAEs if they 
meet the definitions of sections 8.1 and 8.5 respectively. Clinically significant abnormal laboratory findings or 
other abnormal assessments that are detected during the study or are present at informed consent and 
significantly worsen during the study will be reported as AEs or SAEs. Clinically significant abnormal laboratory 
findings or other abnormal assessments that are associated with the disease being studied and are present at 
the start of the study but do not worsen, will not be reported as AEs or SAEs. However, if these findings or 
assessments are judged by the investigator to be more severe than expected considering the patient’s 
condition, then they may be reported as AEs or SAEs. 
8.7.2. Pregnancy report 
Patients who become pregnant at any time will be immediately withdrawn from participation in the study. All 
appropriate withdrawal assessments may be performed at the discretion of the investigator. 
The investigator will collect pregnancy information on any woman patient or partner of a male patient, who 
becomes pregnant and their partner while participating in this study. The partner of a male patient will sign an 
Informed Consent Form before the pregnancy data can be collected. The investigator will record pregnancy 
information on a specific pregnancy notification form and submit it to ABIVAX or its designee within 24 hours 
after knowledge of a patient's or partner’s pregnancy. The patient or partner will also be followed to determine 
the outcome of the pregnancy, be it full-term or prematurely terminated. Information on the status of the mother 
and child will be forwarded to ABIVAX or its designee. Follow-up will normally end 6 to 8 Weeks following the 
estimated delivery date but could last up to one year after the delivery. 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or elective 
termination of a pregnancy for medical reasons will be recorded as an SAE. A spontaneous abortion is always 
considered to be an SAE and will be reported as such. 
The time period for collecting pregnancy information is identical to the time period for collecting AEs, as stated 
in Section 8.8, Time Period, Frequency, and Method of Detecting AEs and SAEs. Pregnancy information is 
collected from the signing of Pregnancy Follow up Inform Consent or Pregnant Partner Informed Consent to 
the end of the pregnancy follow-up. 
8.8. Time Period, and Frequency of Detecting AEs, AESIs and SAEs 
All AEs, AESI and SAEs occurring from the time a patient consents to participate in the study until the end of 
study visit or until 4 weeks after he or she has completed or discontinued the investigational product must be 
recorded in the Patient’s eCRF.  
Moreover, any occurrence of pregnancy within 6 months post stopping dosing must be reported by using the 
specific pregnancy reporting form and sent to VOISIN CONSULTING LIFE SCIENCES (VCLS). 
Importantly, SAEs and AESI will have to be reported, either by email to VCLS immediately after becoming 
aware of the SAE/AESI, within 24 hours of awareness at the very latest. 
VOISIN CONSULTING LIFE SCIENCES (VCLS) 
E-mail: abivaxsafety@voisinconsulting.com 
Legislative guidance requires the investigator to also ensure that any related SAEs are reported after the 
patient finished the study if the investigator becomes aware of them. 


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8.9. Recording AEs and SAEs 
Severity of AEs will be assessed according to CTC-AE Classification Version 5.0. 
Any ongoing AE from the ABX464-103 study is reported as medical history, any worsening of condition that 
started as an AE in the 103 study is to be reported as a new AE.  
Patients will be asked to report all AEs as part of the procedures performed at each study visit. The site 
personnel will document all AEs in the patient’s medical record. All AEs subsequently must be recorded in the 
appropriate eCRF sections. 
The following points must be recorded for each event: 
▪ A description of the event in medical terms, not as reported by the patient 
▪ Date of onset (start date) 
▪ Date of resolution (stop date) 
▪ The time of onset with respect to administering the investigational product 
▪ The severity of the sign/symptom or clinically significant abnormal laboratory value according to CTC-AE 
Classification (v5.0) 
▪ The causal relationship between the investigational product and the occurrence of each AE. This will be 
assessed by each investigator using clinical judgment. Alternative causes, such as natural history of the 
underlying diseases, concomitant medications, other risk factors and the temporal relationship of the 
event to the investigational product will have to be considered. The causality of all AEs should be 
assessed by the investigator with the following question: Is there a reasonable possibility that the AE may 
have been caused by the investigational product? And answered “NO” (if not related) and “YES” (if 
related) 
▪ Action taken regarding the investigational product:  
o No action; 
o Temporary discontinuation 
o Permanent discontinuation. 
▪ AE outcome: 
o Recovered without sequelae / resolved without sequelae 
o Recovered with sequelae / resolved with sequelae 
o Recovering/Resolving 
o On-going 
o Fatal (for SAEs only). 
If in any one patient, the same AE occurs on several occasions, the AE in question must be documented and 
assessed anew each time. 
8.10. 
Reporting of AESIs and SAEs to ABIVAX or its designee 
Throughout the study, the reporting of AESIs/SAEs to the Sponsor or its designee will be done through the 
SAE and AESI forms. 
It is the investigator’s responsibility to ensure that the SAE/AESI report is submitted to VCLS immediately after 
becoming aware of the SAE/AESI, within 24 hours of awareness at the very latest.  
The study specific SAE/AESI form should be completed as thoroughly as possible, with all the available details 
of the event and signed by the investigator or designee. The investigator will assess causality between the 
study drug and the adverse event of special Interest (AESI) / serious adverse event (SAE) according to the 
table outlined below: 
Related  
A clinical event, including laboratory test abnormality, occurs in a plausible time 
relationship to treatment administration, and which concurrent disease or other 
drugs or chemicals cannot explain.  


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Probably related  
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the treatment, unlikely to be attributed to 
concurrent disease or other drugs or chemicals.  
Possibly related  
A clinical event, including laboratory test abnormality, with a reasonable time 
sequence to administration of the treatment, but which could also be explained 
by concurrent disease or other drugs or chemicals.  
Unlikely to be related  
A clinical event, including laboratory test abnormality, with a temporal relationship 
to treatment administration which makes a causal relationship improbable, and in 
which other drugs, chemicals or underlying disease provide plausible 
explanations.  
Unrelated  
A clinical event, including laboratory test abnormality, with little or no temporal 
relationship with treatment administration. Typically explained by extraneous 
factors (e.g., concomitant disease, environmental factors or other drugs or 
chemicals).  
 
An assessment of causality must always be provided at the time of the initial report. If the investigator or 
designee does not have all information regarding the SAE/AESI, he/she must not wait to receive additional 
information before completing the form and notifying VCLS.  
Additional or follow-up information relating to the initial SAE/AESI report, will be requested, if necessary. Again, 
this information is to be completed and submitted through the SAE/AESI forms within 24 hours of receipt of 
the information.  
In the rare occasion when the facsimile equipment does not work and in the absence of, the investigator must 
notify VCLS by telephone within the given timeframe and send a copy of the SAE/AESI report form by email. 
8.11. 
Reporting of SAEs to Regulatory Authorities  
ABIVAX has a legal responsibility to notify, as appropriate, both the local regulatory authorities and other 
regulatory agencies about the safety of the investigational medicinal product. It is therefore important that the 
investigator notifies promptly (immediately after becoming aware of the SAE/AESI, within 24 hours of 
awareness at the very latest) ABIVAX or designee of any SAEs, in order for legal obligations and ethical 
responsibilities towards other patients to be met.  
In addition, the investigator or designee, will comply with the local regulatory requirements (when applicable) 
in reporting of SAEs to the ethics committee and, if required, to the relevant government authority. 
Safety reports on adverse events that are serious AND unexpected AND causally associated with the 
investigational product are prepared according to ABIVAX’s policy and applicable regulations and are 
forwarded to the investigators. These reports are filed with the investigator brochure or other appropriate study 
documentation. It is the Sponsor or its designee and/or investigator’s responsibility to notify the IRB or IEC of 
these reports, if applicable according to local requirements.  
 
 


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9. DATA ANALYSIS AND STATISTICAL CONSIDERATIONS 
A summary of the principal features of the statistical analysis of the data will be described here, in the statistical 
section of the protocol. A more technical and detailed elaboration of the principal features stated in the protocol 
will be given in the first version of the statistical analysis plan (SAP). 
Any amendments to the SAP will be clearly documented and signed prior to the final database lock including 
justifications and details of their potential impact on the interpretation of the study results. 
9.1. Statistical and Analytical Plans 
An interim analysis is planned once all the subjects have completed the Week 48 visit. The final study analysis 
will be performed following database lock upon the completion of the last patient or upon its early 
discontinuation whichever occurs first.  
9.1.1. Protocol deviations 
Protocol deviations will be reviewed and classed as critical, major or minor during the blind-review meeting. 
9.1.2. Definition of study analysis sets 
The following datasets will be defined and used for the analyses: 
▪ The Safety dataset (SAF population) is defined as those patients included in the study, who have 
received at least one dose of the study treatment. 
▪ The Full Analysis dataset (FAS population) is defined as those patients included in the study, who 
have received at least one dose of the study treatment, and who have at least one efficacy baseline data. 
▪ The Per Protocol dataset (PP population) is defined as those patients of the FAS population without 
any major protocol deviation. 
9.1.3. Patients/Patients disposition 
The number and the percentages of patients enrolled and included will be tabulated. The reason for patient 
exclusions from each of the populations will also be listed. In addition, the number of discontinued patients 
with their reason for discontinuation will be tabulated. 
9.1.4. Demographic and other baseline characteristics 
Demographics and other baseline characteristics will be summarized. This analysis will be conducted on the 
FAS population. 
9.1.5. Treatment compliance 
Subject’s compliance to treatment (including capsule count) will be recorded on the eCRF. Number of daily 
doses will be presented on the FAS population. Insufficient treatment compliance (compliance < 80% and non-
respect of administration scheme) will be reported as deviations. 
9.1.6. Interim analysis 
An interim analysis will be performed when all the subjects reach Week 48 visit. The interim analysis will 
include safety and efficacy data such as the following data: (a) Reduction relative to baseline in Modified 
Mayo Score and in partial Modified Mayo Score at every study visit among all patients (b) Clinical response 
and remission, endoscopy improvement and remission (c) Glucocorticoid-free clinical remission at week 
48 (d) Fecal calprotectin results (e) Safety parameters (f) Hematology and biochemistry parameters. 
9.2. Efficacy Analysis 
Descriptive statistics will be presented for all efficacy variables for each measurement timepoint. 
In addition, subgroup descriptive analysis will be performed according to the patient status at the end of the 
induction study (remitter, responder or non-responder), and the treatment received during the induction phase 
(ABX464 25 mg, 50 mg or 100 mg, or matching placebo). 
 
 


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9.3. Safety Analyses 
Adverse events will be coded using the standard dictionary (most recent MedDRA) down to the lower level 
term (LLT).  
Analysis of safety will be performed on the safety data set consisting of all patients who received at least one 
dose of ABX464 in the study. The assessment of safety will be based on the frequency of adverse events (with 
and without regard to causality) graded according to the “CTC-AE” (Version 5.0) and also, the review of 
individual values for clinical laboratory data, vital signs and ECG focusing on the detection of abnormal values. 
Adverse events will be tabulated (counts and percentages). All adverse events will be listed and the data will 
be tabulated by body system/organ class. Adverse event tabulations will include all treatment emergent 
adverse events, which will be further classified by severity, and relationship to treatment. Frequency and 
percentage of patients and number of occurrences of adverse events will also be presented for serious TEAEs, 
TEAEs leading to study drug discontinuation, discontinuation from the study or death and TEAEs of special 
interest. 
Clinical laboratory parameters, including echocardiography parameters, and vital signs will be summarized by 
using descriptive statistics (n, mean, SD, SEM, median, minimum and maximum). Frequency and percentage 
of patients with normal, abnormal and abnormal clinically significant ECG results will also be summarized. The 
number of patients with at least one abnormal value will be tabulated (counts and percentages) for each 
parameter in summary shift tables. 
Descriptive statistics for laboratory parameters will be computed at each scheduled assessment. If relevant for 
some parameter, change from baseline will also be tabulated. 
In addition, shift tables from baseline will be presented. 
 
9.4. Determination of Sample Size 
This study is an open label extension study. Sample size calculation is therefore not applicable. 
 
 


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10. STUDY CONDUCT CONSIDERATION 
10.1. 
Regulatory and Ethical Considerations 
10.1.1. General Requirements 
The study will be conducted in compliance with the study protocol, ABIVAX / IQVIA Standard Operating 
Procedures and in accordance with any local regulatory requirements, to ensure adherence to Good Clinical 
Practice (GCP) as described in the following documents: 
▪ ICH Harmonized Tripartite Guidelines for Good Clinical Practice (ICH E6 (R2)). 
▪ US 21 Code of Federal Regulations dealing with clinical studies (including parts 50 and 56 concerning 
informed consent and IRB regulations). 
▪ Directive 2005/28/EC on the approximation of the laws, regulations and administrative provisions of the 
Member States relating to the implementation of good clinical practice in the conduct of clinical studies 
on medicinal products for human use and its guidance. 
▪ Declaration of Helsinki and its amendments. 
▪ EudraLex GMP guidelines Annex 13 related to shipment, storage and handling of investigational 
products. For the containment and countering against the spread of the COVID-19 virus (coronavirus 
disease 19), alternative delivery methods of the medicinal product(s) (IMP) from the Hospital Pharmacy 
to trial subjects may be arranged to guarantee the access to the IMP and the treatment continuity to the 
subjects; for example, by using couriers dedicated to delivering to the subject’s home or by delivering the 
medicinal product(s) to the caregiver/family members or delegates of the subject, if going to the clinical 
site is considered impossible or high risk for the subject. If a specialized courier is used for the transport 
of the medicinal product to the subject’s home, the use of personal data will be guaranteed according to 
the applicable regulations on Privacy. Suitable remote communication mechanisms with the trial subjects 
will be guaranteed and adequate documentation of the procedures put in place will be maintained and 
described in the appropriate procedure and documented in subjects’ medical source and Investigators’ 
Site Files. 
▪ EU Regulation 536/2014 of the European Parliament and of council, which introduces the Clinical Trials 
Information System (CTIS) that harmonizes the submission, assessment and supervision processes for 
clinical trials throughout Europe. 
▪ Regulation (EU) 2016/679 of the European Parliament and of the Council of 27 April 2016 on the 
protection of natural persons with regard to the processing of personal data and on the free movement 
of such data. 
 
Upon signing the protocol, the investigator agrees to adhere to the instructions and procedures described in it 
and thereby to adhere to the principles of Good Clinical Practice that it conforms to. 
Written informed consents will be obtained for each patient before he or she can participate in the study. 
ABIVAX will obtain favorable opinion/approval to conduct the study from the appropriate regulatory agencies 
in accordance with any applicable country-specific regulatory requirements prior to a site initiating the study in 
that country. 
10.1.2. Independent Ethics Committee/Institutional Review Board 
Prior to the start of the study, the study protocol and amendments if applicable as well as other appropriate 
study-related documents will be submitted to an independent Institutional Review Board (IRB) or independent 
Ethics Committee (IEC), respectively. 
For each center it will be individually specified, who (investigator or sponsor) will be responsible for informing 
the IRB or IEC, respectively of any protocol amendments or new relevant information that require an ethical 
reconsideration of the study protocol. 
If the investigator is responsible for obtaining approval, he/she should also obtain a statement from the IRB or 
IEC, respectively that it is organized and operates according to GCP and applicable laws and regulations. 
10.1.3. Patient Informed Consent  
It is the responsibility of the investigator to give each patient full and adequate verbal and written information 
regarding the aims, methods, anticipated benefits and potential hazards. The patient must be informed that 


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participation is voluntary, and that they are free to withdraw from the study at any time without any 
disadvantages for their subsequent care. Although a patient is not obliged to give her/his reason(s) for 
withdrawing prematurely from the trial, the investigator should make a reasonable effort to ascertain the 
reason(s), while fully respecting the patient's rights. Written consent (signed and dated by the patient and the 
investigator) must be obtained prior to admission. The patient must be provided with a copy of the patient 
information and informed consent.  
The Investigator will be responsible for obtaining an ICF signed by the subject in accordance with ICH GCP 
guidelines to collect pregnancy information on any woman patient or partner of a male patient, who becomes 
pregnant while participating in this study. 
The data collected in this study will be processed anonymously at ABIVAX. Patients should be informed about 
the purpose of the planned computer data processing and the publication of the data (e.g. at scientific 
meetings). The patient must give consent to the computer processing and to the publishing of anonymous 
data.  
The patient must be informed of and consent in writing that personal data relating to the trial may be subject 
to audits by Health Authorities and the sponsor. However, personal data will be kept strictly confidential and 
will not be made publicly available. 
 
 


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10.1.4. Compensation to Patients 
Insurance coverage will be provided for all patients enrolled in the study from the time of the patient’s inclusion 
in the study (i.e. date of signing the ICF). The insurance coverage will be provided by the Sponsor and will be 
in line with GCP guidance and legal requirements, but also in accordance with local regulations. A confirmation 
of insurance and corresponding insurance conditions should be archived in the Investigator File. 
Besides, due to the cumbersome procedures related to the study (number of visits, sigmoidoscopies…) 
patients could be financially compensated by the Sponsor in accordance with the national regulations and the 
approval of the Ethics Committees. 
 
 


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11. STUDY MANAGEMENT 
11.1. 
Remote Data Entry 
An electronic case report form (eCRF) will be used to record all data required by the protocol. Remote Data 
Entry (RDE) will be used for data collection, i.e. the Patient’s information pertaining to the study, will be entered 
into the eCRF via a computer at the investigational site. 
Prior to the start of the study, the investigator will complete an "Investigator site staff signature and task 
delegation log" form, showing the signatures and initials of any person who is authorized to make or change 
entries in the eCRF and any person authorized to electronically sign the eCRF. 
The eCRF used for this study is validated and fulfils the GCP ICH E6 (R2) requirements, European and FDA 
(21 CFR Part 11) regulations.  
Training sessions will be held for all the participants who will use this tool (e.g. investigators, ABIVAX staff and 
contract research organization [CRO] staff, including project managers, CRAs and data managers). 
Several supports are available to help all users with this tool including eCRF User Guide and five days a Week 
/ working hours helpdesk (support line). 
All of the information will be recorded through transcription from source documents into the eCRF by an 
authorized person.  
The investigator is responsible for the management and accuracy of the information in the eCRF. At each 
monitoring visit, the patient medical files should be at the clinical research associate's (CRA) disposal for 
review. 
11.2. 
Data management 
Data management will be outsourced to a Contract Research Organization (CRO). The data managers will 
issue electronic edit checks via EDC, and modification of the data will be permitted by the investigator to 
achieve accuracy with source documents and eliminate all inconsistencies in the data.  
The data will be reviewed for completeness and logical consistency. Automated validation programs will 
identify missing data, out of range data and other data inconsistencies at the time of entry. 
All new/updated information will be reviewed and verified by the appointed monitor.  
11.3. 
Data coding 
Adverse events, concomitant diseases, medical/surgical histories will be coded using the Medical Dictionary 
for Regulatory Activities (MedDRA). Concomitant medication will be coded using the WHO-DRUG dictionary. 
11.4. 
Study Monitoring 
The study will be conducted in accordance with the related topic of the ICH E6 (R2) GCP guidelines. The 
appointed monitor will contact the site prior to the start of the study to review with the site staff the protocol, 
study requirements, and their responsibilities to satisfy regulatory, ethical, and ABIVAX requirements. 
Throughout the study, the monitor will arrange visits to the study center at appropriate intervals to assess the 
progress of the study and review the completed eCRFs. For the containment and countering against the spread 
of the COVID-19 virus (coronavirus disease 19), remote subjects visit and remote monitoring methods may be 
implemented, including the ability to phone or video call the trial site staff, for the purpose of source data 
verification. These methods will be described in the appropriate procedure and documented in subjects’ 
medical source and Investigators’ Site Files. 
During the monitoring visits, the monitor will: 
▪ Ensure that the safety and the rights of patients are being protected; 
▪ Check that the data are authentic, accurate, and complete and discuss any inconsistencies; 
▪ Ensure that all study materials are correctly stored and dispensed with particular emphasis to the 
investigational product; 
▪ Verify that the site staff and facilities continue to be adequate for the proper conduct of the study; 
▪ Ensure that the study is conducted in accordance with the currently approved protocol and any other 
study agreements, GCP, and all applicable regulatory requirements; 
▪ Help resolve any problems that may have arisen. 


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Study code: ABX464-104 
11-July -2022 
V5.1 
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In line with the ICH E6 (R2) GCP guidelines, monitoring will include verification of data entered in the CRF 
against the original patient records. Therefore, for the purpose of monitoring review, direct access to all study-
related site and source documents is mandatory. Data items for which the eCRF will serve as the source 
document will be identified, agreed upon and documented. The investigator must also ensure provision of 
sufficient time, space and qualified personnel for the monitoring visits. 
11.5. 
Records Retention 
Following closure of the study, the investigator or the head of the medical institution (where applicable) must 
maintain all site study records, except for those required by local regulations to be maintained by someone 
else, in a safe and secure location. The records must be maintained to allow easy and timely retrieval, when 
needed (e.g., audit or inspection), and, whenever feasible, to allow any subsequent review of data in 
conjunction with assessment of the facility, supporting systems, and staff. 
ABIVAX will inform the investigator/institution of the required time period for retaining these records in order to 
be compliant with all applicable regulatory requirements. The minimum retention time will meet the strictest 
standard applicable to that study site, as dictated by ICH E6 (R2) section 4.9, any institutional requirements or 
local laws and regulations, or ABIVAX standards/procedures; otherwise, by default the retention period will be 
15 years. 
The investigator must notify ABIVAX of any changes in the archival arrangements, including, but not limited 
to, the following: archival at an off-site facility, transfer of ownership of the records in the event the investigator 
leaves the site. In addition, the investigator should seek the written approval of the Sponsor prior to disposing 
any of the archived records. 
11.6. 
Quality Assurance and Inspection by Authorities 
To ensure compliance with GCP and all applicable regulatory requirements, ABIVAX may conduct quality 
assurance audits. Regulatory agencies may also conduct a regulatory inspection of this study. Such 
audits/inspections can occur at any time during or after completion of the study. By signing the protocol 
agreement page, the investigator agrees to permit drug regulatory agencies and ABIVAX audits. If an audit or 
inspection occurs, the investigator and institution will allow the auditor/inspector direct access to all relevant 
documents and to allocate his/her time and the time of his/her staff to the auditor/inspector to discuss findings 
and any relevant issues. Items of particular interest in case of an audit are, but not limited to, the following: 
▪ IRB/IEC and regulatory authority approvals. 
▪ Informed consent forms of the patients. 
▪ Approved study protocol and amendments and investigator brochure. 
▪ Treatment accountability. 
▪ Safety reporting. 
▪ Study file. 
▪ Study personnel. 
▪ Log of monitoring visits and monitoring process. 
▪ Medical records and other source documents. 
▪ Site facilities. 
▪ Reports to the IRB/IEC and the sponsor. 
▪ Record retention. 
11.7. 
Study and Site Closure 
If the study is terminated prematurely or suspended for any reason, the investigator/institution should promptly 
inform the study patients and should assure appropriate therapy and follow-up for the patients 
ABIVAX reserves the right to temporarily suspend or prematurely discontinue this study, at any time for reasons 
including, but not limited to, safety or ethical issues or severe non-compliance. For multicenter studies, this 
can occur at one or more or at all sites. If such action is required, the Sponsor will discuss this with the 
investigator or the head of the medical institution (where applicable), including the reasons for taking such 
action, at that time. Advance notification will be provided to the site(s) when feasible, on the impending action 
prior to it taking effect. 


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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
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All investigators and/or medical institutions conducting the study will be informed in writing should the Sponsor 
decide to suspend or prematurely discontinue the study for safety reasons. The regulatory authorities will also 
be informed of the suspension or premature discontinuation of the study and the reason(s) for the action. If 
required by local regulations, the investigator must inform the IRB/IEC promptly and provide the reason for the 
suspension or premature discontinuation. 
Upon premature discontinuation of the study, the monitor will conduct site closure activities with the investigator 
or site staff, as appropriate, in accordance with applicable regulations, GCP, and ABIVAX procedures. All data 
must be returned to ABIVAX. Arrangements will be made for any unused investigational product based on the 
relevant ABIVAX procedures for the study. 
11.8. 
Study report and Publication 
Upon conclusion of the study, an integrated clinical and statistical study report will be written by the Sponsor 
in consultation with the Coordinating Investigator. This report will be based on the items detailed in this study 
protocol. When the clinical study report is completed, ABIVAX will provide the investigators with a full summary 
of the study results. The investigators are encouraged to share the summary results with the patients, as 
appropriate. 
The first resulting publication will be a full publication of all data from all participating sites, coordinated by 
ABIVAX. Any secondary publications by the investigators (abstracts in journals, oral presentations etc.) will 
reference the original publication and will require pre-submission review by the Sponsor. Note that the Sponsor 
is entitled to delay any proposed secondary publication, in order to obtain patent protection, if required. 
The Coordinating Investigator as well as other members of the study committee will be authors on the first 
publication. The principal investigator of the trial will be the first author. Authorship for other investigators will 
be assigned on the basis of their recruitment contribution, as well as intellectual and administrative input. 
Ranking will be according to the number of patients randomized as well as contribution to the study conduct 
and preparation of final manuscript.  
11.9. 
Ownership and Confidentiality 
All information provided by ABIVAX and all data and information generated by the sites, as parts of the study 
(excluding the patients’ medical records) are property of ABIVAX.  
All potential investigators must be aware of and agree in writing (confidentiality agreement) to the confidential 
nature of the information pertaining to this study. Furthermore, all information provided by ABIVAX and all data 
and information generated by the sites during the study must be kept confidential by the investigator and other 
site staff and may not be used for any purpose other than conducting this study. 


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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
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12. REFERENCES  
1. 
Ghosh S. Mitchell R. Results of the European Federation of Crohn's and Colitis Associations (EFCCA) Patient 
survey: prevalence and impact on quality of life Gut 55 Suppl V 2006 A72. 
2. 
Kornbluth A, Sachar DB. Ulcerative colitis practice guidelines in adults (update): American College of 
Gastroenterology, Practice Parameters Committee. Am. J. Gastroenterol. 99(7), 1371–1385 (2004). 
3. 
Travis SPL, Stange EF, Lémann M et al. European evidence-based consensus on the management of ulcerative 
colitis: current management. J. Crohn's Colitis (2), 24–62 (2008). 
4. 
Truelove SC, Witts LJ. Cortisone in ulcerative colitis; final report on a therapeutic trial. Br. Med. J. 2(4947), 1041–
1048 (1955). 
5. 
Jess T, Riis L, Vind I et al. Changes in clinical characteristics, course, and prognosis of inflammatory bowel 
disease during the last 5 decades: a population-based study from Copenhagen, Denmark. Inflamm. Bowel Dis. 
13(4), 481–489 (2007). 
6. 
Sonnenberg A. Time trends of mortality from Crohn's disease and ulcerative colitis. Int. J. Epidemiol. 36(4), 890–
899 (2007). 
7. 
Koukos, G. et al. MicroRNA-124 regulates STAT3 expression and is down-regulated in colon tissues of pediatric 
patients with ulcerative colitis. Gastroenterology 145, 842–52.e2 (2013) 
8. 
Sugimoto, K. et al. IL-22 ameliorates intestinal inflammation in a mouse model of ulcerative colitis. J. Clin. Invest. 
118, 534–544 (2008) 
9. 
Schroeder KW, Tremaine WJ, Ilstrup DM. Coated oral 5-aminosalicylic acid therapy for mildly to moderately active 
ulcerative colitis. A randomized study. NEngl J Med 1987; 317: 1625–9 
10. Leal, R. F., Planell, N., Kajekar, R., Lozano, J. J., Ordás, I., Dotti, I., Esteller, M., Masamunt, M. C., Parmar, H., 
Ricart, E., Panés, J., & Salas, A. (2015). Identification Of Inflammatory Mediators In Patients With Crohn’s Disease 
Unresponsive To Anti-Tnfα Therapy. Gut, 64(2), 233–242. Https://Doi.Org/10.1136/Gutjnl-2013-306518 
11. Yang, X. O., Panopoulos, A. D., Nurieva, R., Seon, H. C., Wang, D., Watowich, S. S., & Dong, C. (2007). Stat3 
Regulates Cytokine-Mediated Generation Of Inflammatory Helper T Cells. Journal Of Biological Chemistry, 
282(13), 9358–9363. Https://Doi.Org/10.1074/Jbc.C600321200 
12. Banks PA, Bollen TL, Dervenis C, Gooszen HG, Johnson CD, Sarr MG, et al. Classification of acute pancreatitis-
-2012: revision of the Atlanta classification and definitions by international consensus. Gut. 2013;62(1):102-11 
 
 
 
 


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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
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13. APPENDICES 
Appendix 1: CYPIA2 inhibitors/inducers, OATP1B1/P1B3 inhibitors and substrates, UGT1A9 inhibitors  
CYP1A2 inhibitors/inducers (in bold: prohibited concomitant medications) 
Inhibitors: 
Artemisinin, Atazanavir, Ciprofloxacin, Enoxacin, Ethinyl Estradiol, Fluvoxamine, Mexiletine, 
Tacrine, Thiabendazole, Zileuton 
Inducers: 
Montelukast, Phenytoin, Rifampicin, Ritonavir, Teriflunomide 
OATP1B1/P1B3 inhibitors and substrates (prohibited concomitant medications) 
Substrates: 
Asunaprevir, Atorvastatin, Atrasentan, Bosentan, Caspofungin, Cerivastatin, Daprevir, 
Docetaxel, Eluxadoline, Empagliflozin, Erythromycin, Fexofenadine, Fimasartan, Fluvastatin, 
Glecaprevir, Glyburide, Grazoprevir, Letermovir, Lopinavir, Lovastatin, Nateglinide, Nelfinavir, 
Olmesartan, Paritaprevir, Pitavastatin, Pravastatin, Repaglinide, Rosuvastatin, Simvastatin, 
Telmisartan, Torsemide, Voxilaprevir 
Inhibitors: 
Cyclosporine, Eltrombopag, Lapatinib, Lopinavir, Rifampicin, Ritonavir 
 
UGT1A9 inhibitors (prohibited concomitant medications) 
Inhibitors: 
Regorafenib, Fosphenytoin, Phenytoin, Eltrombopag, Mefenamic acid, Diflunisal, Niflumic 
acid, Sorafenib, Isavuconazole, Deferasirox, Morniflumat, Rifampicin 
 
 
 


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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
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Appendix 2: IBD Questionnaire 
 
IBD Questionnaire (English Version) 
 
 


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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
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Appendix 3: Mayo Score (Ulcerative Colitis) 
 
 


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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
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Appendix 4 : SKIN LESION QUESTIONNAIRE (for Investigators) 
Subjects should be asked to take picture of any skin lesion 
Study/Subject Details 
 Study number:  
 Subject number:       
Age at Onset of Event:       
Gender:  Male  Female  
 
Additional Medical History, please mention if  
o Photosensitivity?                                      Yes      No 
 
o Drug(s) allergy?                                         Yes      No 
 
o Cutaneous adverse drug reaction?       Yes      No 
 
Other Dermatologic Medical History 
                             
 
 
 
 
 
 Last intake of ABX464 before the event  Date:                              Hour:                                 
 
Skin lesion(s): 
o Start date                             Hour:          
 
o End date                       
   Ongoing 
 
Type of skin lesions:  
o Rash, macular                  Yes      No 
o Rash popular                    Yes      No 
o Rash maculopapular       Yes      No 
o Rash vesicular                  Yes      No 
o Urticaria                            Yes      No 
o Eczematous                      Yes      No 
o Pustules                            Yes      No 
 Please precise the size and the color of the lesions: 
        
o Other: Precise 
                             
 
 
 
 
 
 
Skin lesion associated with sun exposure?                                      Yes      No 
If Yes: 
How long after sun exposure did this occur? 


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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
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      Minutes 
   Later that day 
   Next day 
   Within 1 week 
Which parts of the body are affected?  
   Exposed areas 
   Unexposed areas (remember that thin 
clothes have only a low SPF) 
Topography of skin lesions:  
 
 
 
 
Were pictures taken?                                           Yes      No 
(If answer is Yes, please join pseudonymized pictures) 
Consultation with a dermatologist?                  Yes      No 
(If answer is Yes, please join the pseudonymized dermatologist consultation report) 
Skin biopsy?                                                            Yes      No 
(If answer is Yes, please join the pseudonymized skin biopsy report) 
 
Medications and medical measures (which have been taken) to treat the skin lesions 
 
                             
 
Study drug discontinued or interrupted due to this event?        Yes      No 
If Yes, dates of study drug discontinuation/interruption: 
                             
 
 
 
 
 Reporter Details 


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Clinical Study Protocol 
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11-July -2022 
V5.1 
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Title:       Name:       
Role:       
 
Date:       
 
Pseudonymized picture of the skin lesion 
(Date and hour should be outlined on each picture) 
 
 
 
Picture 1 
 
Picture Date :      /     /      time:      :      
 
Skin Lesion Start Date :      /     /      time:      :      
 
          
 
 
Picture  
 


ABIVAX 
Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
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Evolution of the skin lesion 
 
 
 
Picture 2 
 
Picture Date :      /     /      time:      :      
 
Skin Lesion Start Date :      /     /      time:      :      
 
 
 
 
 
 
 
 
Picture  
 


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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
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Appendix 5: Headache Questionnaire 
 


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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
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Appendix 6 : MAYO Score Calculation 
 
 
 
 
 
 
 
Components of the MAYO score: 
Partial modified Mayo Score (pMMS) calculation includes the “Stool frequency” and “Rectal bleeding” components
but does not include the “Mucosal appearance at endoscopy” component. 
Modified Mayo Score (MMS) calculation includes the Stool Frequency”, Rectal bleeding” and the “Mucosal appearance 
at endoscopy” components. MMS is calculated at the visit where the sigmoidoscopy is performed.  
Mayo score (modified, partial modified) is to be calculated at indicated study visits. 
Stool Frequency and Rectal Bleed sub-score: Instructions and Calculation  
I. 
NORMAL number of stools for the subject. 
At the screening visit (during the 103 study), the subject filled in the average number of stools per day while he/she 
was in remission as the baseline number of stools.  If the subject has never been in remission, then he/she will enter
the average number of stools per day before he/she was diagnosed with Ulcerative Colitis. This number will be 
considered as the “normal” number of stools for the subject and this number is taken from the ABX464-103 study. 
II. 
Stool Frequency and Rectal Bleeding scores calculation rules: 
 
- 
The calculation of Stool frequency and Rectal bleeding sub-scores at a visit are based on stool number and
rectal bleeding of the most 3 recent last values within last 7 days prior to the visit. 
- 
At visits where there is endoscopy performed, the most recent consecutive 3 days preceding the
sigmoidoscopy and excluding the day of bowel preparation should be considered for the calculation of the
average number of stool and the rectal bleeding.  
- 
Only days when the number of stool and the rectal bleeding are available will be considered for the calculation.
- 
If some of the data are missing from the most recent consecutive 3 days preceding the visit, then data from 
the next closest days within the week before the visit will be used for the calculation. 
- 
For the calculation of Stool frequency and Rectal bleed sub score usual rounding rules apply. 
III. 
Stool frequency and rectal bleeding scores calculation: 
 
- 
Sub scores of Stool Frequency are calculated based on the Number of stools/days more than the normal
number. The average of the most recent 3 days within the week before the visit will be used for the calculation
of the sub score of Stool Frequency. 
- 
Sub scores of Rectal Bleeding are based on Categories of Rectal Bleeding. The worst category of the most
recent 3 days within the week before the visit will be used for the calculation of the sub score of Rectal
Bleeding. 


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Clinical Study Protocol 
Study code: ABX464-104 
11-July -2022 
V5.1 
Page 65 / 65 
 
 
 
IV. 
RB and SF Sub scores calculation: Example 
N= 1 
 
 
 
 
 
 
Day 
Day 
- 7 
Day 
- 6 
Day 
- 5 
Day 
- 4 
Day 
- 3 
Day 
- 2 
Day 
- 1 
Visit Day 
Date (DD/MM) 
 
 
Nb of stool for each 
day 
 
 
 
 
No blood seen  
 
 
Visible blood with stool 
less than half the time 
 
 
Obvious blood (more 
than just streaks) or 
streaks of blood with 
stool most of the time 
 
 
Blood alone passed  
 
 
For the calculation of Stool frequency sub score: 
In this example above: 
− 
N (Normal stool frequency) = 1  
− 
Stool frequency = Mean (Day -1; Day -2; Day -3) = Mean (2; 3; 1) = (2+3+1)/3 = 6/3 = 2 
o Stool Frequency = [(mean of Stool Frequency) – (the normal number)] = [(2)-(1)] = 1 
o Stool Frequency Subscore = 1 on the Mayo scale which corresponds to “1-2 stools/day more than
normal”.  
− 
Hence, the sub score for Stool Frequency = 1  
For the calculation of Rectal bleeding sub score: 
− 
The worst score of the 3 days (Day -1, Day -2 and Day -3) is used. In this case, “obvious blood (more than just
streaks), or streaks of blood with stool more of the time” on Day -2. 
− 
The Rectal bleeding sub score = Worst bleeding category = 2 = “obvious blood (more than just streaks), or
streaks of blood with stool more of the time””  
 
o Hence the Rectal bleeding sub score = 2 
1 
3 
X 
X 
X 
2 

SAP_001.pdf: 
Abivax 
PROTOCOL ABX464-104 
Statistical Analysis Plan 
Page 1 of 48 
 
Document: 
\\ieedc-vnasc01\BIOSdata\Abivax\ABX464\KZA43696\Biostatistics\Documentation\SAP\ABX464-
104_SAP_V1.0_28MAR2023.docx 
Author: 
LYNDA OLINGER, GANESH L 
Version Number: 
1.0 
 
Version Date:  
28MAR2023 
Template No.:  CS_TP_BS016 Revision 7 
Reference:  CS_WI_BS005 
Effective Date: 01Nov2021 
 
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and proprietary to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
 
 
 
 
 
 
 
STATISTICAL ANALYSIS PLAN 
 
ABX464-104 
A phase 2b, open-label, efficacy, and safety study of ABX464 as maintenance therapy in patients 
with moderate to severe Ulcerative Colitis 
 
AUTHOR: LYNDA OLINGER, GANESH L 
VERSION NUMBER AND DATE: V1.0, 28 MAR 2023 
 
 
 


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PROTOCOL ABX464-104 
Statistical Analysis Plan 
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104_SAP_V1.0_28MAR2023.docx 
Author: 
LYNDA OLINGER, GANESH L 
Version Number: 
1.0 
 
Version Date:  
28MAR2023 
Template No.:  CS_TP_BS016 Revision 7 
Reference:  CS_WI_BS005 
Effective Date: 01Nov2021 
 
Copyright © 2009, 2010, 2012, 2016, 2018, 2019, 2021 IQVIA. All rights reserved. The contents of this document are confidential 
and proprietary to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
Statistical Analysis Plan V1.0 (Dated 28 March 2023) for Protocol ABX464-104 version 5.1, dated 11th July 2022. 
 
 
Name 
Signature 
Date  
              Author: 
Ganesh L 
 
 
 
Position: 
Manager, Biostatistics 
 
Company: 
IQVIA 
 
Upon review of this document, the undersigned approves this version of the Statistical Analysis Plan, authorizing 
that the content is acceptable for the reporting of this study. 
 
Name 
Signature 
Date  
Approved By: 
Josianne Nitcheu 
 
 
 
Position: 
Project Coordinator 
 
Company: 
Abivax 
 
Approved By: 
Paul Gineste 
 
 
 
Position: 
Vice President, Clinical Operations  
 
Company: 
Abivax 
 


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PROTOCOL ABX464-104 
Statistical Analysis Plan 
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Document: 
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104_SAP_V1.0_28MAR2023.docx 
Author: 
LYNDA OLINGER, GANESH L 
Version Number: 
1.0 
 
Version Date:  
28MAR2023 
Template No.:  CS_TP_BS016 Revision 7 
Reference:  CS_WI_BS005 
Effective Date: 01Nov2021 
 
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and proprietary to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
MODIFICATION HISTORY 
 
Unique 
Identifier 
for this 
Version 
Date of the 
Document Version Author 
Significant Changes from  
Previous Authorized Version 
0.1 
8 April 2020 
Lynda Olinger 
Not Applicable – 1st Version 
0.2 
24 February 2022 
Ganesh L 
Revised based on amended protocol 4.1.0 
specifically for interim analysis. 
0.3 
01 April 2022 
Ganesh L 
- Updated to latest template CS_TP_BS016 
Revision 7 
- Updated section 4.2 by adding loss and newly 
clinical remission/response and endoscopic 
remission/improvement. 
0.4 
28 Oct 2022 
Ganesh L 
Updated as per Protocol amendment version 5.1 
1.0 
28 March 2023 
Ganesh L 
Updated as per additional comments 
 
 
 


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Version Number: 
1.0 
 
Version Date:  
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Effective Date: 01Nov2021 
 
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and proprietary to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
LIST OF ABBREVIATIONS  
AE  
adverse event  
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
AST  
aspartate aminotransferase  
ATC 
Anatomical Theoretical Chemical 
β-hCG 
Beta human chorionic gonadotropin 
BLQ 
below the lower limit of quantification 
BMI  
Body Mass Index  
BOLS 
baseline of the open label study 
bpm 
beats per minute 
CI  
Confidence Interval  
CM 
concomitant medicine 
CONS 
All Subjects Consented Analysis Set 
CRT 
Core Review Team 
CRP 
C-Reactive Protein 
CS 
clinically significant 
CTC-AE  
Common Terminology Criteria for Adverse Events, version 4.0  
CTMS 
Clinical Trial Management System 
DA 
drug accountability 
DBL 
database lock 
DBP  
Diastolic Blood Pressure  
DHD 
data handling database 
DM 
Demography 
DOV 
day of visit 
DR 
data review 
DSMB  
Data and Safety Monitoring Board  
DTL 
data team lead 
EC 
Exposure 
ECG  
electrocardiogram  
eCRF  
electronic Case Report Form  
EOS 
end of study 
FAS 
Full Analysis Set 
GLDH 
glutamate dehydrogenase 
HR  
heart rate  
IBD  
Inflammatory Bowel Disease  
IBDQ 
Inflammatory Bowel Disease Questionnaire 
ICF  
informed consent form  
ISB 
induction study baseline 
LDH 
lactate dehydrogenase 
LLT 
lower level term 
LOCF 
Last Observation Carried Forward 
Max  
maximum  
MedDRA  
Medical Dictionary for Regulatory Activities  
mg  
milligram  
MH 
medical history 


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Version Number: 
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Version Date:  
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Effective Date: 01Nov2021 
 
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Min  
minimum  
miR  
micro-RNA  
mL  
milliliter  
mmHg  
millimeters of mercury  
MMS  
Modified Mayo Score  
msec 
millisecond 
MW 
medical writing 
NCS 
not clinically significant 
o.d.  
Once Daily  
PD  
pharmacodynamics  
PD 
protocol deviation 
PK  
pharmacokinetics  
PL 
project lead 
pMMS  
Partial Modified Mayo Score  
PPAS 
Per Protocol Analysis Set 
PR 
procedure history 
PREG 
pregnancy test 
PT  
Preferred Term  
QA 
quality assurance 
QC 
quality control 
QoL 
Quality of Life 
RHI  
Robarts Histopathology Index  
RNA 
ribonucleic acid 
SAE  
serious adverse event  
SAF 
Safety Analysis Set 
SAP 
Statistical Analysis Plan 
SBP  
systolic blood pressure  
SD  
standard deviation  
SEM  
standard error of the mean  
SOC  
system organ class  
STL 
Statistics team lead 
TEAE  
treatment emergent adverse event  
TMS  
Total Mayo Score  
TNF  
Tumor Necrosis Factor  
TSH 
Thyroid Stimulating Hormone 
UC  
Ulcerative Colitis  
UCHX 
Ulcerative colitis history 
ULN  
Upper Limit Normal  
ULQ 
upper limit of quantification 
WHO 
World Health Organization 
 
 
 
 
 


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Version Number: 
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Version Date:  
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Effective Date: 01Nov2021 
 
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and proprietary to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
TABLE OF CONTENTS 
1. 
INTRODUCTION............................................................................................................. 10 
2. 
STUDY OBJECTIVES ..................................................................................................... 10 
2.1. 
Primary Objective ......................................................................................................................................... 10 
2.2. 
Secondary Objectives .................................................................................................................................... 10 
2.3. 
Estimands ....................................................................................................................................................... 11 
3. 
STUDY DESIGN ............................................................................................................... 14 
3.1. 
General Description ....................................................................................................................................... 14 
3.2. 
Schedule of Events ......................................................................................................................................... 15 
3.3. 
Changes to Analysis from Protocol .............................................................................................................. 15 
4. 
PLANNED ANALYSES ................................................................................................... 15 
4.1. 
Data Safety Monitoring Board (DSMB) – Independent Cardiovascular Safety Committee (ICVSC) .. 15 
4.2. 
Interim Analysis ............................................................................................................................................. 16 
4.3. 
Final Analysis ................................................................................................................................................. 17 
5. 
ANALYSIS SETS.............................................................................................................. 17 
5.1. 
Process for Analysis Set Assignment ............................................................................................................ 17 
5.2. 
All Patients Consented Analysis Set [CONS] .............................................................................................. 18 
5.3. 
Safety Analysis Set [SAF] .............................................................................................................................. 18 
5.4. 
Full Analysis Set [FAS] ................................................................................................................................. 18 
5.5. 
Per Protocol Analysis Set [PPAS] ................................................................................................................. 18 
6. 
GENERAL CONSIDERATIONS ................................................................................... 20 


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6.1. 
Reference Start Date and Study Day ........................................................................................................... 20 
6.2. 
Baseline ........................................................................................................................................................... 20 
6.3. 
Retests, Unscheduled Visits and Early Termination Data ......................................................................... 21 
6.4. 
Windowing Conventions ............................................................................................................................... 21 
6.5. 
Statistical Tests .............................................................................................................................................. 21 
6.6. 
Common Calculations ................................................................................................................................... 21 
6.7. 
Software Version ............................................................................................................................................ 22 
6.8. 
Statistical Considerations .............................................................................................................................. 22 
6.9. 
Multicenter Studies ........................................................................................................................................ 22 
6.10. 
Missing Data ............................................................................................................................................... 23 
6.11. 
Multiple Comparisons/ Multiplicity ......................................................................................................... 23 
6.12. 
Examination of Subgroups ........................................................................................................................ 23 
7. 
OUTPUT PRESENTATIONS ......................................................................................... 23 
8. 
DISPOSITION, WITHDRAWALS AND PROTOCOL DEVIATIONS ..................... 24 
9. 
DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS ....................... 25 
9.1. 
Derivations ..................................................................................................................................................... 25 
9.2. 
Medical and Procedure History .................................................................................................................... 25 
10. 
PRIOR AND CONCOMITANT MEDICATIONS........................................................ 25 
11. 
STUDY MEDICATION EXPOSURE ............................................................................ 26 
11.1. 
Derivations ................................................................................................................................................. 26 
12. 
STUDY MEDICATION COMPLIANCE ...................................................................... 27 
12.1. 
Derivations ................................................................................................................................................. 27 
13. 
EFFICACY OUTCOMES................................................................................................ 28 


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13.1. 
Primary Efficacy ........................................................................................................................................ 28 
13.1.1. 
Primary Efficacy Variable & Derivation ................................................................................................. 28 
13.1.2. 
Missing Data handling for Primary Efficacy Variable ............................................................................ 28 
13.1.3. 
Primary Analysis of Primary Efficacy Variable ...................................................................................... 28 
13.2. 
Secondary Efficacy .................................................................................................................................... 29 
13.2.1. 
Secondary Efficacy Variables & Derivations .......................................................................................... 29 
13.2.2. 
Missing Data Handling for Secondary Efficacy Variables ...................................................................... 33 
13.2.3. 
Analysis of Secondary Efficacy Variables............................................................................................... 33 
14. 
SAFETY OUTCOMES .................................................................................................... 34 
14.1. 
Adverse Events ........................................................................................................................................... 35 
14.1.1. 
All TEAEs ............................................................................................................................................... 35 
14.1.1.1. 
Severity ............................................................................................................................................ 35 
14.1.1.2. 
Relationship to Study Medication .................................................................................................... 35 
14.1.2. 
TEAEs Leading to Discontinuation of Study Medication ....................................................................... 36 
14.1.3. 
Serious Adverse Events ........................................................................................................................... 36 
14.1.4. 
TEAEs leading to discontinuation from study ......................................................................................... 36 
14.1.5. 
Adverse Events Leading to Death............................................................................................................ 37 
14.1.6. 
Adverse Events Of Special Interest ......................................................................................................... 37 
14.2. 
Laboratory Evaluations ............................................................................................................................ 38 
14.3. 
ECG Evaluations ....................................................................................................................................... 39 
14.4. 
Vital Signs ................................................................................................................................................... 39 
14.5. 
Physical Examination ................................................................................................................................ 40 
15. 
REFERENCES .................................................................................................................. 41 
APPENDIX 1. PROGRAMMING CONVENTIONS FOR OUTPUTS .............................. 42 
IQVIA Output Conventions...................................................................................................................................... 42 
Dates & Times ............................................................................................................................................................ 42 
Spelling Format.......................................................................................................................................................... 42 
Presentation of Visits ................................................................................................................................................. 42 
Listings ....................................................................................................................................................................... 43 
APPENDIX 2. MAYO SCORE ............................................................................................... 44 


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APPENDIX 3. PARTIAL DATE CONVENTIONS ............................................................. 45 
Algorithm for Treatment Emergence of Adverse Events: ..................................................................................... 45 
Algorithm for Prior / Concomitant Medications: ................................................................................................... 46 
 
 


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1. INTRODUCTION 
This document describes the rules and conventions to be used in the presentation and analysis of efficacy 
and safety data for protocol ABX464-104. It describes the data to be summarized and analyzed, including 
specifics of the statistical analyses to be performed.  
 
This statistical analysis plan (SAP) is based on protocol version 5.1, dated 11 July 2022. 
2. STUDY OBJECTIVES 
2.1. 
Primary Objective 
The primary objective of this study is to assess in all patients the long-term efficacy of ABX464 given at 50 mg once 
daily (QD) on clinical remission at Week 48 compared to the induction study (ABX464 -103) baseline (ISB). 
2.2. 
Secondary Objectives 
For all secondary objectives, baseline of the open label study (BOLS) will be Week 16 of the induction 
study, or Week 8 of the induction study if no endoscopy results are available for Week 16. 
The secondary objectives are: 
• 
To evaluate clinical remission at Week 48 compared to BOLS  
• 
To evaluate the effect of ABX464 50mg QD on: 
o Modified Mayo Score (MMS) at Week 48 and Week 96 and on partial Modified Mayo 
Score (pMMS), among all patients at every study visit compared to ISB 
o Endoscopic improvement and remission and sustained endoscopic improvement and 
remission, by segment, at Week 48 compared to ISB and BOLS 
o Stool and rectal bleeding frequency at every study visit compared to BOLS 
o Proportion of patients with Glucocorticoid-free Clinical Remission at Week 48  


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o Fecal calprotectin and C-reactive Protein (CRP) levels at Week 24, Week 48, Week 60, 
Week 72, Week 84, and Week 96 visits compared to BOLS  
o Clinical response at Week 48 compared to ISB and BOLS 
o miR-124 expression in colon tissue (Ribonucleic Acid [RNA] later) at Week 48 and in 
total blood at Week 24, Week 48, and Week 96 
o Rectal/sigmoidal infiltrates using the Robarts Histopathology Index (RHI), Geboes and 
Nancy Histology Scoring Scales at Week 48 compared to ISB and BOLS 
o Patient’s quality of Life (QoL) measured by the Inflammatory Bowel Disease 
Questionnaire (IBDQ) at Week 24 and Week 48 compared to BOLS  
• 
To evaluate the long-term safety profile of ABX 464 50 mg QD 
• 
Echocardiography objective:  To evaluate the effect of ABX464 on cardiac function as assessed 
through echocardiograms. 
2.3. 
Estimands 
The primary, and secondary estimands to support regulatory decisions are described in Table A below. The 
intercurrent event is the early discontinuation of patients from the study and/or missing Week 48 efficacy 
assessments. 
Table A: 
List of Estimands 
Estimand 
Definition 
Attributes 
Population 
Variable/Endpoi
nt 
Intercurrent event handling 
strategy 
Population-level 
summary measure 
Primary 
Long term 
efficacy of 
ABX464 50 mg 
dose on clinical 
All patients 
randomized, 
received at least 
one dose of study 
Clinical 
remission 
achieved at Week 
48 compared to 
Patients with missing Week 48 
assessment including discontinued 
patients will be considered to not 
have achieved clinical remission  
Proportion of patients 
achieving clinical 
remission 


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remission at 
Week 48 
drug and provided 
at least one 
efficacy data point 
ISB 
Secondary 
The effect of 
ABX464 50 mg 
dose on 
secondary 
variables 
All patients 
randomized, 
received at least 
one dose of study 
drug and provided 
at least one 
efficacy data point 
Clinical 
Response, 
Endoscopic 
improvement, 
and Endoscopic 
remission at 
Week 48 
Patients with missing Week 48 
assessment including discontinued 
patients will be considered as non-
responders  
Proportion of patients 
achieving Clinical 
Response, 
Endoscopic 
improvement, and 
Endoscopic remission 
Secondary 
The effect of 
ABX464 50 mg 
dose on 
secondary 
variables 
All patients 
randomized, 
received at least 
one dose of study 
drug and provided 
at least one 
efficacy data point 
Clinical 
Remission, 
Clinical 
Response, 
Endoscopic 
improvement, 
and Endoscopic 
remission at 
Week 96 
Patients discontinued prior to Week 
96 are considered as non-
responders. LOCF method is used 
to impute completers (not 
discontinued). The value will be 
carried forward from Week 48.  
Proportion of patients 
achieving Clinical 
Remission, Response, 
Endoscopic 
improvement, and 
Endoscopic remission 
Secondary 
The effect of 
ABX464 50 mg 
dose on 
secondary 
variables 
All patients 
randomized, 
received at least 
one dose of study 
drug and provided 
at least one 
efficacy data point 
Mean change 
from ISB to 
Week 48 in 
pMMS, MMS, 
stool frequency 
and rectal 
bleeding sub 
scores 
 
 
Missing pMMS components (stool 
frequency and rectal bleeding sub 
scores) and endoscopy scores at 
Week 48, pMMS and MMS will not 
be imputed. 
Mean change from 
ISB  
Mean change 
from baseline to 
Missing Fecal calprotectin and CRP 
values will not be imputed. 
Mean change from 
baseline 


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Week 48 in Fecal 
calprotectin and 
CRP levels 


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3. STUDY DESIGN 
3.1. 
General Description 
This study is an open-label study to evaluate the long-term safety and efficacy profile of ABX464 50 mg 
QD in patients with moderate to severe ulcerative colitis (UC) who have been previously enrolled in the 
ABX464-103 clinical study (induction study) and who are willing to continue their treatment with 
ABX464 as long-term (maintenance) remission therapy. All patients who have completed the 16-week (± 
4 days) induction treatment period (ABX464-103) will be eligible for this maintenance study regardless 
of their clinical response and will receive 1 capsule of ABX464 50 mg once daily during up to 96 weeks 
providing the patient has a clinical response at week 48. Patients will be treated for a maximum of 96 
weeks in this maintenance study. After the treatment period, patients will be followed for 4 more weeks 
for safety purposes.  
Patients will be enrolled at approximately 69 sites located in Europe, US, and Canada. 
The study design is presented below: 
 
 
From Day 1 onwards, patients will be seen at the investigational site every 4 weeks up to Week 48 and then 
quarterly until Week 96. Flexible sigmoidoscopy with rectal and/or sigmoidal biopsies will be performed, for all 
patients at week 48 and at Week 96. Additional flexible sigmoidoscopies may be performed during the open-
label phase based on medical judgement.  
In the event of clinical progression of the disease during the open-label maintenance phase, defined as at least a 2-


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point increase from the baseline partial Modified Mayo Score (pMMS) with a pMMS ≥ 4 confirmed by an 
endoscopy sub-score of 2 points or higher, the patient will be withdrawn from the study. 
3.2. 
Schedule of Events 
Schedule of events can be found in Section 5.1 of the protocol. 
3.3. 
Changes to Analysis from Protocol 
Analyses of infiltrate/histopathology and miRNA-124 levels in blood and tissue will be analysed and 
reported separately by an independent vendor and will be excluded from the final outputs and analysis 
conducted by IQVIA. 
The analysis of the following secondary endpoints will not be addressed in this SAP: 
• 
Change relative to baseline in miRNA-124 expression in rectal/sigmoidal biopsies at Week 48 
and Week 96 and in total blood at Week 24, Week 48, and Week 96 
• 
Reduction relative to ISB of infiltrate/histopathology (rectal/sigmoidal biopsies) using RHI, the 
Geboes and Nancy Histology Scoring Scale at Week 48 
4. PLANNED ANALYSES 
The following analyses will be performed for this study: 
• 
Analyses for Data Safety Monitoring Board (DMSB) meetings 
• 
Interim Analysis 
• 
Final Analysis  
4.1. 
Data Safety Monitoring Board (DSMB) – Independent Cardiovascular 
Safety Committee (ICVSC) 
A DSMB will review the safety of the trial during the entire study period. A DSMB charter describing the 
methodology and presentation of results and access to results will be provided by Abivax as a separate 


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document. 
The ICVSC will be responsible for an on-going evaluation of cardiac adverse events of special interest 
(Cardiac AESIs), for treatment emergent echocardiographic findings, and for treatment emergent changes 
of cardiac safety biomarkers (as detailed above). The ICVSC will review cardiac adverse events on an on-
going basis. 
4.2. 
Interim Analysis  
An interim analysis will be performed when all the patients have completed the Week 48 visit for SAF and FAS. 
The interim analysis will summarize efficacy and safety data descriptively for the following:  
• Reduction relative to ISB and BOLS in Modified Mayo Score and in partial Modified Mayo Score at every 
study visit till Week 48  
• Mean change in Stool Frequency, and Rectal Bleeding Score from BOLS to Week 48 
• Proportion of patients with Clinical remission/response and Endoscopic remission /improvement at Week 48 
will be summarized for the following categories as well 
a) With/without clinical remission/response or endoscopic remission/improvement at the BOLS 
b) Induction study arms (100 mg, 50 mg, 25 mg, Placebo) 
c) With/without Previous Biologics/JAK exposure  
d) Sustained clinical remission/response and endoscopic remission/improvement: Sustained 
remission/response/improvement at Week 48 from Week 8 and Week 16 of Induction Study. 
e) Glucocorticoid free (at least 8 weeks) clinical remission (not applicable for Endoscopic 
remission/improvement)  
f) Loss of clinical remission/response and endoscopic remission/improvement: Lost 
remission/response/improvement at Week 48 compared to Week 8 and Week 16 of the 
Induction Study. 
g) Newly 
clinical 
response/remission 
and 
endoscopic 
remission/response: 
New 
remission/response/improvement at Week 48 compared to Week 8 and Week 16 of the 
Induction Study. 


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• Fecal calprotectin results: Along with the descriptive statistics of actual values and change from baseline, 
percentage of patients with FCP level <50µg/g, <150µg/g, <250µg/g, and < Median will be presented for 
each visit.  
• Safety parameters 
• Hematology and biochemistry parameters: Clinically significant abnormalities will be listed and 
summarized. 
 
4.3. 
Final Analysis  
All final, planned analyses identified in this SAP will be performed by IQVIA Biostatistics following 
Abivax Authorization of this SAP, Abivax Authorization of Analysis Sets and Database Lock (DBL).  
5. ANALYSIS SETS 
Agreement and authorization of patients included/excluded from each analysis set will be conducted prior 
to DBL. To facilitate this, a Data Review (DR) process will be co-ordinated by the IQVIA Statistical 
Team Lead (STL).  
5.1. 
Process for Analysis Set Assignment 
A data review meeting will be conducted prior to the Database Lock, to review Critical/Major protocol 
deviations referencing the Blind Data Review plan of Induction study, along with the exclusion reasons 
mentioned below in section 5.5. Analysis of assignment spreadsheet will be authorized by sponsor before 
Database lock and incorporated in the final analysis. 
 
 
 


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5.2. 
All Patients Consented Analysis Set [CONS] 
The All Patients Consented (CONS) Analysis Set will contain all patients who provided written informed 
consent (IC) to the Open label study. 
The following patients will be excluded from this Analysis Set: 
• 
Patients who did not provide written informed consent at the BOLS visit 
 
5.3. 
Safety Analysis Set [SAF] 
The Safety Analysis Set (SAF) will include all patients who have received at least one dose of the study 
medication. If there is any doubt as to whether a patient was treated or not, it will be assumed that the 
patient was treated for the purposes of analysis. The SAF will be used for all safety analyses.  
The following patients will be excluded from this Analysis Set: 
• 
All patients excluded from the CONS Analysis Set 
• 
Patients who have not received at least one dose of the study medication: 
 
5.4. 
Full Analysis Set [FAS] 
The Full Analysis Set (FAS) will include all patients included in the study who have received at least one 
dose of the study medication, and who have BOLS data for at least one efficacy variable. 
 
The following patients will be excluded from this Analysis Set: 
• 
All patients excluded from the SAF 
• 
All patients who do not have baseline data for at least one efficacy variable 
5.5. 
Per Protocol Analysis Set [PPAS] 
The Per Protocol Analysis Set (PPAS) will include all patients in the FAS who do not have critical/major 
PDs that would affect the evaluation of the primary efficacy endpoint. From a statistical analysis 


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perspective, the reason(s) for exclusion of patients from the PPAS may be a PD or other factors affecting 
the primary efficacy outcome. PDs identified during the clinical conduct of the study, as authorized in the 
final PD log, will also be taken into consideration in the final assignment of patients to the analysis sets.  
 
Reasons for exclusion include: 
• 
Insufficient essential efficacy data i.e. no MMS score or its components at Week 48 
• 
Non-compliance with the inclusion or exclusion criteria, including completing procedures as per 
protocol 
• 
Non-compliance with the study medication up to Week 48 (Compliance < 80%) 
• 
Intake of prohibited medication up to Week 48 
• 
Non-compliance with time window up to Week 48 (+/- 7 days) (to be confirmed at Data Review 
meeting) 
• 
Induction Study Per Protocol definition not met, i.e. excluded from per protocol based on 
Induction Study Blind Data Review meeting. 
 
 
 
 
 
 
 
 
 


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6. GENERAL CONSIDERATIONS 
6.1. 
Reference Start Date and Study Day 
Study Day will be calculated from the reference start date and will be used to show start/stop day of 
assessments and events.  
 
Reference start date is defined as the day of the first dose of maintenance study medication and is Day 1 
of the maintenance study. Patients will take the first dose of ABX464-104 medication the day after Day 
113 of the induction study.  
• 
If the date of the event is on or after the reference start date, then:  
 
 
Study Day = (date of event – reference start date) + 1 
 
• 
If the date of the event is prior to the reference start date, then:  
Study Day = (date of event – reference start date) 
 
In the situation where the event date is partial or missing, Study Day and any corresponding durations 
will appear missing in the listings. 
6.2. 
Baseline 
ISB (Induction Study Baseline) is the baseline measurement for the Induction (ABX464-103) study. 
BOLS (Baseline of Open Label Study) is the Day 113 (Week 16) measurement of the Induction 
(ABX464-103) study. Week 48 is considered as baseline for Echocardiography parameters. 
In the case where the last non-missing measurement and the reference start date coincide, such 
measurement will be considered as the baseline measurement, but adverse events (AEs) and concomitant 
medications commencing on the reference start date will be considered post-baseline. 


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6.3. 
Retests, Unscheduled Visits and Early Termination Data 
In general, for by-visit summaries, data recorded at the nominal visit will be presented. Unscheduled 
measurements will not be included in by-visit summaries but will contribute to the best/worst case value 
where required (example: shift table). In the case of a retest (same visit number assigned), the last 
available measurement for that visit will be used for by-visit summaries.  
 
Early discontinuation data will be mapped to the next available visit number for by-visit summaries. 
Listings will include scheduled, unscheduled, retest and early discontinuation data. 
6.4. 
Windowing Conventions  
There will be no visit windowing applied in this study.  
6.5. 
Statistical Tests 
Only descriptive analyses of safety and efficacy variables will be conducted in this study.  
6.6. 
Common Calculations 
For quantitative measurements,  
• 
Change from baseline of the open label study (BOLS) = Test Value at Visit X – Open Label 
(Maintenance) Study Baseline Value  
Open label study baseline value will be determined at Week 16 (Day 113) of the induction study for all 
variables except MMS, which can be determined at Week 8 (Day 57) of the induction study if no 
Week 16 data are available. 
• 
Change from induction study baseline (ISB) = Test Value at Visit X – Induction Study Baseline 
Value  
 


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A patient will be considered to have a reduction relative to baseline (ISB or BOLS) in variable X at 
Visit X when change from the respective baseline for variable X is less than zero.  
6.7. 
Software Version 
All derivations, statistical analyses, summaries, and listings will be generated using SAS® version 9.4 or 
higher (SAS® Institute, Inc., Cary, North Carolina). Graphics will be prepared using the same versionof 
SAS®. 
6.8. 
Statistical Considerations 
Summaries will include descriptive statistics for continuous variables (sample size [n], mean, standard 
deviation [SD], standard error of the mean [SEM], median, minimum and maximum) and for categorical 
variables (frequency [n] and percentage). SEM will only be determined for laboratory, vital signs, and 
ECG assessments. Percentages will be based on the number of patients within the relevant analysis set, or 
the number of patients with data available where relevant (e.g. shift tables). Proportions will be expressed 
as percentages. 
 
If the original data has N decimal places, then the summary statistics will have the following decimal 
places: 
Minimum and maximum: N 
Mean, median, confidence intervals, ratios: N + 1 
SD, SEM: N + 2 
Percentages will be reported to one decimal place. 
 
6.9. 
Multicenter Studies 
This study will be conducted by multiple investigators at multiple centres internationally. As only 
descriptive statistics will be determined for this study, there will be no pooling of data with other 


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countries or into regions (example: Western Europe, Eastern Europe).  
6.10. Missing Data 
Analysis of missing primary and secondary efficacy data is explained in sections Error! Reference 
source not found. and Error! Reference source not found..  Missing safety data will not be imputed. 
Percentages based on the number of patients with data available will not take missing observations into 
account. 
6.11. Multiple Comparisons/ Multiplicity 
No adjustment for multiple comparisons is needed, as only descriptive statistics will be presented. 
6.12. Examination of Subgroups 
Subgroup analyses will be conducted as stated in the relevant analysis sections.  
The following subgroups will be assessed for the primary efficacy variable, the proportion of patients 
with clinical remission at Week 48, and secondary efficacy variables, MMS and pMMS: 
• 
Patient efficacy status at the end of the induction study (Week 16) 
o Remitter (patients with clinical remission) 
o Responder/non-responder (patients with/without clinical response) 
• 
Treatment received during the induction phase 
o ABX464 25 mg 
o ABX464 50 mg 
o ABX464 100 mg 
o Placebo 
 
7. OUTPUT PRESENTATIONS 
APPENDIX 1 shows conventions for presentation of data in outputs. The templates provided with this 


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SAP describe the presentations for this study and therefore the format and content of the summary tables, 
figures, and listings to be provided by IQVIA Biostatistics. 
8. DISPOSITION, WITHDRAWALS AND PROTOCOL DEVIATIONS 
All patients who provide informed consent will be accounted for in this study. The number of patients who are 
baseline failures and the reasons for failure will be presented. A patient is a baseline failure if the patient signs 
informed consent but withdraws before first dosing in the maintenance phase. The number and percentage of 
consented patients and included in each of the analysis sets, as well as reasons for exclusion from each of the 
analysis sets, will be presented. In addition, the number and percentage of discontinued patients with their reason 
for discontinuation will be presented.  
 
 
Listings will include completion or early discontinuation, and the reason for early discontinuation for 
each patient, as well as details of protocol deviations, inclusion/exclusion criteria and analysis sets.. 
 
 
 
 


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9. DEMOGRAPHIC AND OTHER BASELINE CHARACTERISTICS 
Demographic data and other baseline characteristics will be presented for the CONS, FAS, and PPAS. 
Age (years), age categories (<30 years, 30 to < 60 years, >= 60 years), country, gender, child-bearing 
potential, baseline weight and BMI (BOLS) and baseline height (ISB) will be reported for this study. 
MMS (BOLS) will be presented descriptively and in categories of scores 0 to 4, 5 to 6 and 7 to 9. Patient 
status at the end of the induction study, treatment received during the induction study, corticosteroid 
usage, and previous exposure to biologics/JAK inhibitors will also be presented. No statistical testing will 
be carried out for demographic or other baseline characteristics. 
 
9.1. 
Derivations 
𝐵𝑀𝐼= 𝑊𝑒𝑖𝑔ℎ𝑡 (𝑘𝑔)
{𝐻𝑒𝑖𝑔ℎ𝑡 (𝑚) 2} 
9.2. 
Medical and Procedure History 
Medical and Procedure History information will be listed for the SAF analysis set. Conditions or 
procedures which stop prior to the BOLS visit will be recorded as Medical and Procedure History. Any 
other medical condition or procedure occurring on or after BOLS will be recorded as an AE. 
 
Medical and Procedure History will be coded using version 25.0 of the Medical Dictionary for Regulatory 
Activities (MedDRA) (latest). Data captured on the Medical and Procedure History pages of the eCRF 
will be listed by patient and will include System Organ Class (SOC) and Preferred Term (PT) coding.  
 
 
10. 
PRIOR AND CONCOMITANT MEDICATIONS 
Prior and concomitant medications will be listed by the Anatomical Therapeutic Chemical (ATC) Level 2 


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and PT for the SAF and coded using the latest version of the World Health Organization (WHO) Drug 
Dictionary. Prior and concomitant medications will be listed, without time limit for medications used to 
treat UC, and medications used prior to the start of the study or during the study for all other medications.  
• 
‘Prior’ medications are medications which started and stopped prior to the first dose of 
maintenance study medication.  
• 
‘Concomitant’ medications are medications which started prior to, on or after the first dose 
of maintenance study medication, but before the last dose of maintenance study medication, 
and ended on or after the date of first dose of maintenance study medication or were ongoing 
at the end of the study. 
 
See Error! Reference source not found. for handling of partial dates for medications. In the case where 
it is not possible to define a medication as prior or concomitant, the medication will be classified by the 
worst case, i.e. concomitant.  
11. 
STUDY MEDICATION EXPOSURE 
Exposure to study medication in days and the total number of daily doses taken during the study will be 
summarized for the FAS.   
The dates of first study medication administration and last study medication administration will be 
obtained from the eCRF Exposure form (EC).  
 
11.1. Derivations 
• 
Overall duration of study medication exposure (days) = Stop date of last study medication 
administration – Start date of first study medication administration + 1.  
 
• 
Duration of study medication exposure (days) at Visit X measures the treatment duration from 
Visit X to Visit X+1 and is calculated as follows: 


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Duration of study medication exposure (days) at Visit X = (Stop date of study medication issued 
at Visit X) – (Start date of study medication issued at Visit X) +1 
12. 
STUDY MEDICATION COMPLIANCE  
Compliance to study medication will be presented for the FAS  
 
Overall compliance with study medication will be calculated as the number of capsules taken (total 
dispensed – total returned) divided by the expected number of capsules expressed as a percentage.  
 
Patients will take 1 capsule daily from Day 1 to the end of treatment and will receive 30 capsules at each 
dosing visit. The number of capsules dispensed and returned will be obtained from the Drug 
Accountability eCRF page. For patients who permanently stop the study medication, the last visit will be 
replaced by the date of study withdrawal. 
12.1. Derivations 
Overall Compliance to study medication will be calculated as follows: 
𝑇𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑎𝑝𝑠𝑢𝑙𝑒𝑠 𝑡𝑎𝑘𝑒𝑛 𝑑𝑢𝑟𝑖𝑛𝑔 𝑡ℎ𝑒 𝑠𝑡𝑢𝑑𝑦
𝑇𝑜𝑡𝑎𝑙 𝑒𝑥𝑝𝑒𝑐𝑡𝑒𝑑 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑐𝑎𝑝𝑠𝑢𝑙𝑒𝑠 𝑓𝑜𝑟 𝑡ℎ𝑒 𝑝𝑒𝑟𝑖𝑜𝑑  x 100 % 
If a patient permanently discontinues study medication, compliance will be determined from Day 1 to the 
last day of study participation. 


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13. 
EFFICACY OUTCOMES  
13.1. Primary Efficacy 
13.1.1. 
Primary Efficacy Variable & Derivation 
The primary efficacy variable is the proportion of patients with clinical remission at Week 48.  Clinical 
remission is defined as: 
• 
A rectal bleeding sub-score = 0, and 
• 
Endoscopy sub-score = 0 or 1 (excluding friability) and 
• 
A stool frequency sub-score = 0 or 1 
 
The rectal bleeding, endoscopy and stool frequency sub-scores will be obtained from the MMS eCRF 
page variables MMSRB, MMSMA and MMSST respectively.  
13.1.2. 
Missing Data handling for Primary Efficacy Variable 
. Missing data for clinical remission at Week 48 will be imputed as non-responder i.e. not achieved 
clinical remission. The components used to determine clinical remission will not be imputed. 
13.1.3. 
Primary Analysis of Primary Efficacy Variable 
The primary efficacy analysis will be performed for the FAS population. 
 
• 
Proportion of patients in clinical remission at Week 48 =   
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑃𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑤𝑖𝑡ℎ 𝐶𝑙𝑖𝑛𝑖𝑐𝑎𝑙 𝑅𝑒𝑚𝑖𝑠𝑠𝑖𝑜𝑛 𝑎𝑡 𝑊𝑒𝑒𝑘 48
𝑇𝑜𝑡𝑎𝑙 𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑃𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑖𝑛 𝐹𝐴𝑆
  
Clinical remission at Week 48 will be summarized and graphically presented according to treatment 
received during the induction study and patient status at the end of the induction study. The proportion of 
patients in clinical remission at Week 48 with a stool frequency sub score of 0 versus 1 will also be 


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determined. 
13.2. Secondary Efficacy 
The secondary efficacy analyses will be performed for the FAS population. Descriptive statistics, 
excluding SEM, will be presented for all secondary efficacy variables for each measurement timepoint. 
Change from baseline will also be determined where relevant and is defined in Section Error! Reference 
source not found.. 
13.2.1. 
Secondary Efficacy Variables & Derivations 
13.2.1.1. 
Reduction Relative to Baseline in pMMS at every Visit and MMS at Week 48 and 
week 96 
The MMS ranges from 0 to 9 and is derived from the sum of 3 sub-scores ranging from 0 to 3 for stool 
frequency, rectal bleeding and mucosal appearance at endoscopy respectively, with a lower score 
indicating less severe or no UC (See Error! Reference source not found.).  
 
Partial MMS is the sum of the stool frequency and rectal bleeding sub-scores of the MMS and will be 
assessed at every visit.  
 
Descriptive statistics for MMS, pMMS and mean change from baseline (both ISB and BOLS) will be 
summarized and the number of patients with a reduction in MMS or pMMS relative to ISB and BOLS at 
each visit will be recorded. Reduction relative to baseline is defined in Section Error! Reference source 
not found..  
 
Mean MMS at ISB, BOLS, Week 48, and Week 96 will be graphically presented according to treatment 
received during the induction study and patient efficacy status (remitter, responder/non-responder) at 
Week 8 of the Induction phase.  
Mean pMMS will be graphically plotted by visit. 


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13.2.1.2. 
Proportion of Patients with Endoscopic Improvement and/or Endoscopic Remission 
by Segment at Week 48 and week 96 
Endoscopic improvement is defined as an endoscopic sub-score ≤ 1 (excluding friability) and endoscopic 
remission is defined as an endoscopic sub-score = 0. The improvement and remission will be summarized 
by segment (descending colon, sigmoid colon, rectum) as well as overall endoscopic improvement and 
remission for Week 48 and week96. 
• 
Proportion of patients with endoscopic improvement/remission by segment at Week 48/Week 96   
= 
 𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑤𝑖𝑡ℎ 𝑒𝑛𝑑𝑜𝑠𝑐𝑜𝑝𝑖𝑐 𝑖𝑚𝑝𝑟𝑜𝑣𝑒𝑚𝑒𝑛𝑡 (𝑜𝑟 𝑟𝑒𝑚𝑖𝑠𝑠𝑖𝑜𝑛)𝑎𝑡 𝑊𝑒𝑒𝑘 48 / 𝑊𝑒𝑒𝑘 96 𝑖𝑛 𝑠𝑒𝑔𝑚𝑒𝑛𝑡 𝑋
𝑇𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑖𝑛 𝐹𝐴𝑆 
  
 
Overall mucosal appearance at endoscopy subscore is equal to the worst segment sub-score. The 
proportion of patients with overall endoscopic improvement or remission at Week 48/ Week 96 will be 
calculated as follows: 
• 
Proportion of patients with overall endoscopic improvement/remission at Week 48/Week 96 = 
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑤𝑖𝑡ℎ 𝑜𝑣𝑒𝑟𝑎𝑙𝑙 𝑒𝑛𝑑𝑜𝑠𝑐𝑜𝑝𝑖𝑐 𝑖𝑚𝑝𝑟𝑜𝑣𝑒𝑚𝑒𝑛𝑡 (𝑜𝑟 𝑟𝑒𝑚𝑖𝑠𝑠𝑖𝑜𝑛) 𝑎𝑡 𝑊𝑒𝑒𝑘 48 / 𝑊𝑒𝑒𝑘 96
𝑇𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑖𝑛 𝐹𝐴𝑆
 
13.2.1.3. 
Proportion of Patients with Sustained Endoscopic Improvement and/or Remission 
at Week 48 and Week 96     
Sustained endoscopic improvement (or remission) is defined as the number of patients with endoscopic 
improvement (or remission) at Week 48 among patients who had endoscopic improvement (remission) at 
Week 8 or Week 16 of the induction study. 
Proportion of patients with sustained endoscopic improvement at Week 48/Week 96 =  
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑤𝑖𝑡ℎ 𝑒𝑛𝑑𝑜𝑠𝑐𝑜𝑝𝑖𝑐 𝑖𝑚𝑝𝑟𝑜𝑣𝑒𝑚𝑒𝑛𝑡 𝑎𝑡 𝑊𝑒𝑒𝑘 48/𝑊𝑒𝑒𝑘 96
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑤𝑖𝑡ℎ 𝑒𝑛𝑑𝑜𝑠𝑐𝑜𝑝𝑖𝑐 𝑖𝑚𝑝𝑟𝑜𝑣𝑒𝑚𝑒𝑛𝑡 𝑑𝑢𝑟𝑖𝑛𝑔 𝑡ℎ𝑒 𝑖𝑛𝑑𝑢𝑐𝑡𝑖𝑜𝑛 𝑠𝑡𝑢𝑑𝑦 (𝑊𝑒𝑒𝑘 8 ) 


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• 
Proportion of patients with sustained endoscopic remission at Week 48/Week 96 =  
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑤𝑖𝑡ℎ 𝑒𝑛𝑑𝑜𝑠𝑐𝑜𝑝𝑖𝑐 𝑟𝑒𝑚𝑖𝑠𝑠𝑖𝑜𝑛 𝑎𝑡 𝑊𝑒𝑒𝑘 48/Week 96
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑤𝑖𝑡ℎ 𝑒𝑛𝑑𝑜𝑠𝑐𝑜𝑝𝑖𝑐 𝑟𝑒𝑚𝑖𝑠𝑠𝑖𝑜𝑛 𝑑𝑢𝑟𝑖𝑛𝑔 𝑡ℎ𝑒 𝑖𝑛𝑑𝑢𝑐𝑡𝑖𝑜𝑛 𝑠𝑡𝑢𝑑𝑦 (𝑊𝑒𝑒𝑘 8 ) 
13.2.1.4. 
Proportion of Patients with Glucocorticoid-free Clinical Remission at Week 48  
Glucocorticoid-free clinical remission is defined as clinical remission in addition to not requiring any 
treatment with glucocorticoids for at least 8 Weeks.  Patients using concomitant glucocorticoid 
medications after Week 40 will be identified using ATC code value H02AB of WHODRUG. 
Corticosteroids used for treating UC(glucocorticoid) can be identified from CS form of eCRF based 
on the status. 
• 
Proportion of patients with glucocorticoid-free clinical remission at Week 48 = 
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑤𝑖𝑡ℎ 𝑔𝑙𝑢𝑐𝑜𝑐𝑜𝑟𝑡𝑖𝑐𝑜𝑖𝑑 𝑓𝑟𝑒𝑒 𝑐𝑙𝑖𝑛𝑖𝑐𝑎𝑙 𝑟𝑒𝑚𝑖𝑠𝑠𝑖𝑜𝑛 𝑎𝑡 𝑊𝑒𝑒𝑘 48
𝑇𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑖𝑛 𝐹𝐴𝑆
 
13.2.1.5. 
Reduction Relative to Baseline in Stool and Rectal Bleeding Frequency at every 
Study Visit 
Frequency and percentage of patients in each stool frequency and rectal bleeding category (see Error! 
Reference source not found.) relative to the number of patients in the FAS will be obtained from the 
eCRF and summarized for each visit. The number of patients with reduction in stool frequency or 
improvement in rectal bleeding categories relative to ISB and BOLS will also be presented. 
13.2.1.6. 
Reduction Relative to Baseline (BOLS) in Fecal Calprotectin and CRP Levels at 
Week 24,Week 48, Week 60, Week 72,Week 84 and Week 96 
Change from BOLS in Fecal calprotectin and CRP levels will be determined at Week 24, Week 48, Week 
60, Week 72, Week 84, and Week 96. The number of patients with a reduction from BOLS in Fecal 
calprotectin and CRP levels will also be recorded. Reduction relative to baseline is defined in Section 


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Error! Reference source not found.. 
13.2.1.7. 
Proportion of Patients with Clinical Response at Week 48 and Week 96 
Clinical response is defined as a reduction in MMS ≥ 2 points and ≥ 30 % from baseline MMS (BOLS or 
ISB) with an accompanying decrease in rectal bleeding sub-score ≥ 1 point or absolute rectal bleeding sub-score 
≤ 1 point. 
• 
Proportion of patients with clinical response at Week 48 / Week 96 = 
𝑁𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑤𝑖𝑡ℎ 𝑐𝑙𝑖𝑛𝑖𝑐𝑎𝑙 𝑟𝑒𝑠𝑝𝑜𝑛𝑠𝑒 𝑎𝑡 𝑊𝑒𝑒𝑘 48 / Week 96
𝑇𝑜𝑡𝑎𝑙 𝑛𝑢𝑚𝑏𝑒𝑟 𝑜𝑓 𝑝𝑎𝑡𝑖𝑒𝑛𝑡𝑠 𝑖𝑛 𝐹𝐴𝑆
 
13.2.1.8. 
The Inflammatory Bowel Disease Questionnaire Scores and Change from BOLS at 
Week 24 and Week 48 
The IBDQ assesses QoL in patients with inflammatory bowel diseases (IBD). It contains 32 questions 
covering four health domains (bowel symptoms, systemic symptoms, emotional function and social 
function) and scores for each question range from 1 (worst case) to 7 (best case). The total IBDQ score is 
the sum of the individual question scores and ranges from 32 to 224, with higher scores reflecting better 
well-being. The total scores and change in total score from BOLS IBDQ score will be determined at 
Week 24 and Week 48 and summarized. 
13.2.1.9. 
Cardiac function as assessed through Echocardiograms 
Echocardiography will be performed at the earliest opportunity (Week 24 or Week 48 or Week 72) and 
will be repeated every six months. 
Absolute (%) change-from-previous echocardiogram of Left ventricle Ejection Fraction (LVEF) and in 
Global Longitudinal Strain (GLS) is calculated. 
Clinically relevant reduction (change-from-previous echocardiogram) of LVEF is defined as by > 10% 
reduction (absolute percentage points) to a value < 50%.  


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Number of subjects with clinically relevant reduction of LVEF, Number of subjects with a relative 
percentage reduction in GLS by > 15% from the previous echocardiogram, Number of subjects with a 
reduction of LVEF > 10% (absolute percentage points) to a value ≥ 50% with an accompanying fall in 
GLS > 15%. and Number of subjects with reduction in LVEF by > 10% (absolute percentage points) to a 
value ≥ 50% will be calculated and displayed. 
Summary of Actual and Changes from previous echocardiography of other echocardiographic parameters 
as described in the standard protocol, including 2-dimensional volumes, RV size and systolic 
function and valve function will also be presented. 
All echocardiographic parameters will be presented descriptively and will be reviewed by the Independent 
Cardiovascular Safety Committee (ICVSC). 
13.2.2. 
Missing Data Handling for Secondary Efficacy Variables 
Imputation will not be performed for missing Stool Frequency, Rectal Bleeding and Endoscopy sub score, 
hence pMMS, and MMS will not be imputed. Missing Fecal calprotectin, CRP scores and IBDQ scores 
will not be imputed.  
Clinical Remission, Clinical Response, Endoscopic Improvement, and Endoscopic remission:  
Patients with missing Week 48 assessment will be considered as non-responders i.e. not achieving clinical 
endpoint at Week 48.  
Patients discontinued prior to Week 96 are considered as non-responders at Week 96 i.e. not achieving 
clinical endpoint at Week 96. LOCF method is used to impute completers (not discontinued but missing 
Week 96 assessment) by carrying forward the results from Week 48. 
13.2.3. 
Analysis of Secondary Efficacy Variables 
Descriptive statistics as described in Section Error! Reference source not found. will be presented for 
the following secondary variables:  
• 
pMMS and MMS scores and change from baseline summary at every visit assessed for overall 
and by induction study treatment subgroup 
• 
The number and percentage of patients with reduction relative to baseline in pMMS and MMS in 


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every visit assessed for overall and by induction study treatment subgroup 
• 
The number and proportion of patients with endoscopic improvement and remission, by segment 
at Week 48 and Week 96 
• 
The number and proportion of patients with sustained endoscopic improvement and remission at 
Week 48 and Week 96 
• 
The number and proportion of patients with glucocorticoid-free clinical remission at Week 48 
• 
Mucosal appearance at endoscopy by segment at every visit assessed 
• 
Stool frequency and change from baseline at every visit assessed 
• 
 Number and percentage of patients with reduction relative to baseline in stool frequency at every 
study visit 
• 
Rectal Bleeding and change from baseline at every visit assessed 
• 
 Number of patients with reduction relative to baseline in rectal bleeding sub-score at each visit 
• 
Frequencies and percentages for rectal bleeding and stool frequency categories  (Stool Frequency 
– 0 or 1 and Rectal Bleeding – 0). Percentages will be plotted graphically by visit. 
• 
Fecal calprotectin and CRP levels and change from baseline summary at every visit assessed for 
overall and by induction study treatment subgroups 
• 
Number and proportion of patients with reduction relative to baseline in fecal calprotectin and 
CRP levels at Week 24, Week 48, Week 60, 72, 84, and 96, for overall and by induction study 
treatment subgroups 
 
• 
The number and percentage of patients with clinical response at Week 48 and Week 96 
• 
IBDQ scores and change from baseline at Week 24 and Week 48 
 
In addition, the above variables will be included in a listing by patient.  
Additionally, loss, new, and sustained responses are also analysed for clinical response and remission.  
 
 


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14. 
SAFETY OUTCOMES 
All outputs for safety outcomes will be based on the SAF. There will be no statistical comparisons 
between the treatment groups for safety data.  
14.1. Adverse Events 
Adverse Events (AE) will be coded using the version 25.0 of MedDRA, down to the lower level term 
(LLT). Only AEs ongoing at the end of the ABX464-103 study and AEs starting on or after the first dose 
of study medication in the ABX464-104 study will be included in the analysis and description of AEs. 
 
Treatment emergent adverse events (TEAEs) are defined as AEs that started or worsened in severity 
either on or after the first dose of study medication in the ABX464-104 study.  
 
An overall summary of number of patients within each of the categories described in the sub-sections 
below, as well as the number of occurrences of the AE will be provided as specified in the templates. 
Listings will be prepared and will include TEAEs and non-TEAEs. 
 
See Error! Reference source not found. for handling of partial dates for AEs. In the case where it is not 
possible to define an AE as treatment emergent or not, the AE will be classified by the worst case, i.e. 
treatment emergent.  
14.1.1. 
All TEAEs 
Incidence of TEAEs will be presented by SOC and PT and broken down further by maximum severity 
and relationship to study medication. 
14.1.1.1. 
SEVERITY 
Severity is classed as mild, moderate, severe, life-threatening, and fatal corresponding to the Common 
Terminology Criteria of Adverse Events (CTCAE) grades 1 to 5 (increasing severity) (Version 5.0 or 


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most recent version). TEAEs starting after the first dose of study medication with a missing severity will 
be classified as severe. If a patient reports a TEAE more than once within that SOC/PT, the AE with the 
worst-case severity will be used in the corresponding severity summaries. 
14.1.1.2. 
RELATIONSHIP TO STUDY MEDICATION 
Relationship, as indicated by the Investigator, is classed as Unrelated, Unlikely to be Related, Possibly 
Related, Probably Related and Related (increasing severity of relationship). TEAEs will be summarized 
as “Related” or “Unrelated. A “related” TEAE is defined as a TEAE with a relationship to study 
medication as “possibly related”, “probably related” or “related” to study medication, and an 
“unrelated” TEAE is either “unrelated” or “unlikely to be related” to study medication. TEAEs with a 
missing relationship to study medication will be regarded as “probably related” to study medication. If a 
patient reports the same AE more than once within that SOC/ PT, the AE with the worst-case relationship 
to study medication will be used in the corresponding relationship summaries.  
 
14.1.2. 
TEAEs Leading to Discontinuation of Study Medication 
TEAEs leading to permanent discontinuation of study medication will be identified by using the response 
“Permanent discontinuation” to the question “Action taken with study medication” on the AE page of the 
eCRF. For TEAEs leading to discontinuation of study medication, summaries of incidence rates 
(frequencies and percentages) by SOC and PT will be prepared. 
 
14.1.3. 
Serious Adverse Events 
Serious adverse events (SAEs) are those events recorded as “Serious” on the Adverse Events page of the 
eCRF. A summary of serious TEAEs by SOC and PT, as well as related treatment-emergent SAEs by 
maximum severity will be prepared. Incidence of hospitalization and number of inpatient days will also 
be summarized. A listing of all SAEs will also be presented. 


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14.1.4. 
TEAEs leading to discontinuation from study 
TEAEs causing the patient to discontinue from the study will be identified by a positive response to the 
question “Did the AE cause the patient to discontinue from the study?” and will be summarized by SOC 
and PT. 
14.1.5. 
Adverse Events Leading to Death 
TEAEs leading to death are those events which are recorded as 'Fatal' on the Adverse Events page of the 
eCRF. A summary of TEAEs leading to death by SOC and PT will be prepared. 
14.1.6. 
Adverse Events Of Special Interest  
Treatment-emergent adverse events of special interest (AESI) include skin lesions (regardless of its 
severity), headache episodes, Anaemia, Hepatic enzymes, Serious (grade 3) infections and opportunistic 
infections, Acute pancreatic adverse events, Malignancies including Non-Melanoma Skin Cancers, More 
Than 20% Change from Baseline at Week 8 in N-terminal pro b-type Natriuretic Peptide Blood Levels 
and Cardiac AESIs (See section 8.2 of the protocol for details regarding each of these.). and several 
Cardiac SOC including Atrial flutter will be recorded as Cardiac AESI.  The following TEAEs are 
recorded as Cardiac AESI:  
• 
Aortic valve disease,  
• 
Asystole,  
• 
Atrial fibrillation,  
• 
Atrial flutter,  
• 
3rd degree AV block (AV block complete),  
• 
Cardiac arrest,  
• 
Chest pain – cardiac,  
• 
Heart failure,  
• 
Left ventricular systolic dysfunction,  
• 
Mitral valve disease,  
• 
Mobitz (type) II atrioventricular block (type 2, 2nd degree AV block), 
• 
Myocardial infarction,  
• 
Myocarditis, Pericardial effusion,  
• 
Pericardial tamponade,  
• 
Pericarditis, 


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• 
Pulmonary valve disease, 
• 
Restrictive cardiomyopathy,  
• 
Right ventricular dysfunction,  
• 
Sick sinus syndrome,  
• 
Tricuspid valve disease,  
• 
Ventricular fibrillation,  
• 
Ventricular tachycardia. 
A summary of AESIs by SOC and PT will be prepared, as well as a further summary and listing of 
information on all AESI and Cardiac AESI. 
14.2. Laboratory Evaluations 
The central laboratory test results will be included in the reporting of this study. A list of laboratory 
assessments to be included in the outputs is presented in Table E below. Presentations will use Systeme 
International (SI) Units.  
 
Quantitative laboratory measurements reported as “< X”, i.e. below the lower limit of quantification 
(BLQ), or “> X”, i.e. above the upper limit of quantification (ULQ), will be converted to X for 
quantitative summaries, but will be presented as recorded, i.e. as “< X” or “> X” in the listings. 
 
The following summaries will be provided for laboratory data: 
• 
Shift from baseline according to laboratory approved normal ranges (Low, Normal, 
High) for quantitative measurements  
• 
Incidence of clinically significant abnormalities as determined by Site Investigator 
• 
Listing of abnormal laboratory results 
 
The following clinical laboratory parameters, except for β-hCG, will be summarized using descriptive 
statistics as described in section 6.8: 
Table E Laboratory Tests 
HEMATOLOGY  
BIOCHEMISTRY  
 
STOOLS  


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Hemoglobin  
Sodium  
Lipase 
Fecal calprotectin  
Hematocrit  
Potassium  
Alkaline phosphatase  
 
WBC  
Chloride  
gammaGT  
IMMUNOCHEMISTRY 
Neutrophils  
Calcium  
Total bilirubin  
Troponin I & T 
Lymphocytes  
Phosphate  
Total protein  
T3, T4, TSH 
Monocytes  
Glucose  
Albumin  
β-hCG 
Eosinophils  
BUN or urea  
LDH 
 
Basophils  
Creatinine  
CRP  
 
Platelet count  
AST  
NT-proBNP 
 
Prothrombin time 
GLDH 
Amylase 
 
 Fibrinogen 
ALT  
CPK 
 
 
 
Total, HDL, and LDL 
cholesterol 
 
 
Blood pregnancy results (β-hCG) will be listed by patient for every assessment. 
14.3. ECG Evaluations 
Results from the central ECG Reading Centre will be included in the reporting of this study. The overall 
assessment of ECG results will be summarized by frequency and percentage of patients in each 
assessment category for every visit assessed.  
Overall assessment of ECG (Investigator’s judgment) will be reported as follows: 
• 
Normal 
• 
Abnormal NCS 
• 
Abnormal CS 
The following summaries will be provided for ECG data: 
• 
Incidence of overall assessments (normal, abnormal NCS, abnormal CS) included in shift 
table as an overall count 
• 
Shift from baseline according to overall assessment of ECG (for quantitative 
measurements and categorical measurements) 
• 
Listing of all ECG results, including those meeting abnormal and CS or NCS criteria 


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14.4. Vital Signs 
Descriptive statistics as described in Section 6.8 will be summarized for all vital sign parameters. 
The following vital signs measurements will be reported for this study: 
• 
Systolic Blood Pressure (SBP) (mmHg) 
• 
Diastolic Blood Pressure (DBP) (mmHg) 
• 
Heart Rate (bpm) 
• 
Body Temperature (⁰C) 
• 
Weight (kg) 
• 
Baseline (ISB) Height (cm) 
• 
BMI (kg/m2) 
The following summaries will be provided for vital signs data: 
• 
Actual and change from baseline (BOLS) by visit  
• 
Incidence of abnormal CS/NCS results for each parameter and visit 
• 
Shift table for number of patients with at least one abnormal result 
• 
Listing of results by patient, including abnormal CS or NCS observations 
14.5. Physical Examination  
The following assessments will be taken at every physical examination: eyes, ears, nose and throat, 
lungs/thorax, heart/cardiovascular system, abdomen, skin and mucosae, nervous system, lymph nodes, 
and Musculo-skeletal system. 
 
Results will be captured by the following categories: 
• 
Normal 
• 
Abnormal, NCS 
• 
Abnormal, CS 
Only abnormal findings will be presented in a listing. 
 


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15. 
REFERENCES  
1. A phase 2b, open-label, efficacy and safety study of ABX464 as maintenance therapy in patients 
with moderate to severe Ulcerative Colitis. Abivax. Protocol ABX464-104 Version 5.1., 11Jul 
2022 
 
2. Abivax. eCRF ABX464-104 Version 10. 
 
 


Abivax 
PROTOCOL ABX464-104 
Statistical Analysis Plan 
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Document: 
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104_SAP_V1.0_28MAR2023.docx 
Author: 
LYNDA OLINGER, GANESH L 
Version Number: 
1.0 
 
Version Date:  
28MAR2023 
Template No.:  CS_TP_BS016 Revision 7 
Reference:  CS_WI_BS005 
Effective Date: 01Nov2021 
 
Copyright © 2009, 2010, 2012, 2016, 2018, 2019, 2021 IQVIA. All rights reserved. The contents of this document are confidential 
and proprietary to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
APPENDIX 1. PROGRAMMING CONVENTIONS FOR OUTPUTS 
IQVIA Output Conventions 
Outputs will be presented according to the guidelines in the IQVIA Biostatistics Output Conventions. 
 
Dates & Times 
Depending on data available, dates and times will take the form yyyy-mm-ddThh:mm:ss. 
 
Spelling Format 
English US  
Presentation of Visits 
For outputs, visits will be represented as follows and in that order: 
Long Name (default) 
Short Name  
Day 1 (Baseline) 
Baseline 
Week 4 
W4 
Week 8 
W8 
Week 12 
W12 
Week 16 
W16 
Week 20 
W20 
Week 24 
W24 
Week 28 
W28 


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PROTOCOL ABX464-104 
Statistical Analysis Plan 
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Document: 
\\ieedc-vnasc01\BIOSdata\Abivax\ABX464\KZA43696\Biostatistics\Documentation\SAP\ABX464-
104_SAP_V1.0_28MAR2023.docx 
Author: 
LYNDA OLINGER, GANESH L 
Version Number: 
1.0 
 
Version Date:  
28MAR2023 
Template No.:  CS_TP_BS016 Revision 7 
Reference:  CS_WI_BS005 
Effective Date: 01Nov2021 
 
Copyright © 2009, 2010, 2012, 2016, 2018, 2019, 2021 IQVIA. All rights reserved. The contents of this document are confidential 
and proprietary to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
Long Name (default) 
Short Name  
Week 32 
W32 
Week 36 
W36 
Week 40 
W40 
Week 44 
W44 
Week 48 
W48 
Week 60 
 W60 
Week 72 
W72 
Week 84 
W84 
Week 96 
W96 
Week 52 (EOS) or Week 100 
(EOS) 
W52 EOS or W100 EOS 
Listings 
All listings will be ordered by the following (unless otherwise indicated in the template): 
i. Site-Patient ID  
ii. Date (where applicable) 
 
 


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PROTOCOL ABX464-104 
Statistical Analysis Plan 
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Document: 
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104_SAP_V1.0_28MAR2023.docx 
Author: 
LYNDA OLINGER, GANESH L 
Version Number: 
1.0 
 
Version Date:  
28MAR2023 
Template No.:  CS_TP_BS016 Revision 7 
Reference:  CS_WI_BS005 
Effective Date: 01Nov2021 
 
Copyright © 2009, 2010, 2012, 2016, 2018, 2019, 2021 IQVIA. All rights reserved. The contents of this document are confidential 
and proprietary to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
APPENDIX 2. MAYO SCORE 
 


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PROTOCOL ABX464-104 
Statistical Analysis Plan 
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Author: 
LYNDA OLINGER, GANESH L 
Version Number: 
1.0 
 
Version Date:  
28MAR2023 
Template No.:  CS_TP_BS016 Revision 7 
Reference:  CS_WI_BS005 
Effective Date: 01Nov2021 
 
Copyright © 2009, 2010, 2012, 2016, 2018, 2019, 2021 IQVIA. All rights reserved. The contents of this document are confidential 
and proprietary to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
APPENDIX 3. PARTIAL DATE CONVENTIONS 
Imputed dates will NOT be presented in the listings. 
Algorithm for Treatment Emergence of Adverse Events: 
 
START DATE 
STOP DATE 
ACTION 
Known 
Known/Partial/Missing 
If start date < ABX464-103 study med start date (from eCRF 
raw.AE.AEPRIOR = Yes) then not TEAE. 
If start date >= ABX464-103 study med start date (from 
eCRF raw.AE.AEPRIOR = No) and: 
1) Stop date known to be before ABX464-104 study 
med start date then not TEAE.   
2) If stop date is known or partial and is after 
ABX464-104 study med start date and severity of 
AE has worsened on or before start of ABX464-104 
study med, then TEAE. If severity has not 
worsened, then not TEAE. 
3) If stop date is not known, then worst-case severity 
is assumed i.e. TEAE 
If start date >= ABX464-104 study med start date, then 
TEAE. 
 
 
 
Partial, but known 
components show that it 
cannot be on or after 
ABX464-104 study med 
start date 
Known/Partial/Missing 
Not TEAE 
 
 
 
Partial, could be on or 
after ABX464-103 study 
med start date, but before 
ABX464-104 study med 
start date 
Known 
If stop date < ABX464-104 study med start date, then not 
TEAE. 
If stop date >= ABX464-104 study med start date and 
severity worsened on or after start of ABX464-104 study 
med, then TEAE. If severity did not worsen then not TEAE. 
 
Partial 
Impute stop date as latest possible date (i.e. last day of 
month if day unknown or 31st December if day and month 
are unknown), then: 
If stop date < ABX464-104 study med start date, then not 
TEAE. 
If stop date >= ABX464-104 study med start date and 
severity worsened on or after start of ABX464-104 study 
med, then TEAE. If severity did not worsen then not TEAE. 
 
Missing 
Assumed TEAE 


Abivax 
PROTOCOL ABX464-104 
Statistical Analysis Plan 
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Document: 
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104_SAP_V1.0_28MAR2023.docx 
Author: 
LYNDA OLINGER, GANESH L 
Version Number: 
1.0 
 
Version Date:  
28MAR2023 
Template No.:  CS_TP_BS016 Revision 7 
Reference:  CS_WI_BS005 
Effective Date: 01Nov2021 
 
Copyright © 2009, 2010, 2012, 2016, 2018, 2019, 2021 IQVIA. All rights reserved. The contents of this document are confidential 
and proprietary to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
START DATE 
STOP DATE 
ACTION 
 
 
 
Partial, could be on or 
after ABX464-104 study 
med start date, 
Known/Partial/Missing 
TEAE 
 
 
 
Missing 
Known 
If stop date < ABX464-104 study med start date, then not 
TEAE. 
If stop date >= ABX464-104 study med start date, then 
TEAE. 
 
Partial 
Impute stop date as latest possible date (i.e. last day of 
month if day unknown or 31st December if day and month 
are unknown), then: 
If stop date < ABX464-104 study med start date, then not 
TEAE 
If stop date >= ABX464-104 study med start date, then 
TEAE. 
 
Missing 
Assumed TEAE 
 
Algorithm for Prior / Concomitant Medications:  
START DATE 
STOP DATE 
ACTION 
Known 
Known 
If stop date < ABX464-104 study med start date, assign as prior  
If stop date >= ABX464-104 study med start date and start date <= end of 
treatment, assign as concomitant  
 
Partial 
Impute stop date as latest possible date (i.e last day of month if day 
unknown or 31st December if day and month are unknown), then: 
If stop date < ABX464-104 study med start date, assign as prior 
If stop date >= ABX464-104 study med start date and start date <= end of 
treatment, assign as concomitant 
 
Missing 
If stop date is missing could never be assumed a prior medication 
If start date <= end of treatment, assign as concomitant 
 
 
 


Abivax 
PROTOCOL ABX464-104 
Statistical Analysis Plan 
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Document: 
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104_SAP_V1.0_28MAR2023.docx 
Author: 
LYNDA OLINGER, GANESH L 
Version Number: 
1.0 
 
Version Date:  
28MAR2023 
Template No.:  CS_TP_BS016 Revision 7 
Reference:  CS_WI_BS005 
Effective Date: 01Nov2021 
 
Copyright © 2009, 2010, 2012, 2016, 2018, 2019, 2021 IQVIA. All rights reserved. The contents of this document are confidential 
and proprietary to IQVIA Holdings Inc. and its subsidiaries. Unauthorized use, disclosure or reproduction is strictly prohibited. 
START DATE 
STOP DATE 
ACTION 
Partial 
Known 
Impute start date as earliest possible date (i.e first day of month if day 
unknown or 1st January if day and month are unknown), then: 
If stop date < ABX464-104 study med start date, assign as prior 
If stop date >= ABX464-104 study med start date and start date <= end of 
treatment, assign as concomitant 
 
Partial 
Impute start date as earliest possible date (i.e. first day of month if day 
unknown or 1st January if day and month are unknown) and impute stop 
date as latest possible date (i.e. last day of month if day unknown or 31st 
December if day and month are unknown), then: 
If stop date < ABX464-104 study med start date, assign as prior 
If stop date >= ABX464-104 study med start date and start date <= end of 
treatment, assign as concomitant 
 
Missing 
Impute start date as earliest possible date (i.e. first day of month if day 
unknown or 1st January if day and month are unknown), then: 
If stop date is missing could never be assumed a prior medication 
If start date <= end of treatment, assign as concomitant 
 
 
 
Missing 
Known 
If stop date < ABX464-104 study med start date, assign as prior 
If stop date >= ABX464-104 study med start date, assign as concomitant 
 
Partial 
Impute stop date as latest possible date (i.e. last day of month if day 
unknown or 31st December if day and month are unknown), then: 
If stop date < ABX464-104 study med start date, assign as prior 
If stop date >= ABX464-104 study med start date, assign as concomitant 
 
Missing 
Assign as concomitant 
 
 


Statistical Analysis Plan - SAP Final Ver1.0 - 28-Mar-2023
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Ganesh L
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education, training and experience to perform this 
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Nitcheu
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education, training and experience to perform this 
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Paul 
GINESTE
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education, training and experience to perform this 
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