A Multicenter,Open-label,Single Arm,Multiple-dose Study to Evaluate the Safety,Tolerability,Pharmacokinetics and Pharmacodynamics of Cenerimod in Adult Chinese Participants With Moderate-to-severe Systemic Lupus Erythematosus (SLE) on Top of Background Therapy
Phase: PHASE2
Conditions: SLE - Systemic Lupus Erythematosus
Sponsor: Viatris Pharmaceuticals Co., Ltd.

 
 
 
 
 Cenerimod (ACT-334441) 
Systemic lupus erythematosus 
Protocol ID-064A204 
 
A multicenter, open-label, single arm, multiple-dose study to evaluate the safety, 
tolerability, pharmacokinetics and pharmacodynamics of cenerimod in adult 
Chinese participants with moderate-to-severe systemic lupus erythematosus (SLE) 
on top of background therapy 
 
Study Phase: 
2 
EudraCT Number: 
Not applicable 
Status and version: 
Final Version 3.0 
Date: 
16 Sep. 2025 
Document type: 
Clinical study protocol  
Viatris Innovation document 
number (Doc No.): 
V-25.095 
 
 
The information contained in this document, especially unpublished data, is the property of the sponsor of 
this study, Viatris Innovation GmbH. It is therefore provided to you in confidence as an investigator, potential 
investigator, or consultant, for review by you, your staff, and an independent ethics committee(s) or 
institutional review board(s). It is understood that this information will not be disclosed to others without 
written authorization from Viatris Innovation GmbH, except to the extent necessary to obtain informed 
consent from those persons to whom the study treatment(s) may be administered. 
 
 

Cenerimod (ACT-334441) 
Systemic lupus erythematosus 
Protocol ID-064A204 
 
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SPONSOR CONTACT DETAILS 
Sponsor 
Viatris Innovation GmbH 
Gewerbestrasse 14 
CH-4123 Allschwil 
Switzerland  
Clinical Trial Physician  
Contact details of the Clinical Trial Physician can 
be found in the Investigator Site File 
Local Sponsor in China 
Viatris Pharmaceuticals Co., Ltd. 
Units 1-2, 5-9, F10 (9F actual floor), 669 Xinzha 
Road, Jing'an District, Shanghai, China 
Medical Emergency Hotline 
Toll Telephone Number  
Site-specific toll telephone numbers and toll-free 
telephone numbers for the Medical Emergency 
Hotline can be found in the Investigator Site File 
 
CONTRACT RESEARCH ORGANIZATION INFORMATION 
Some key study activities are delegated to Contract Research Organizations. A list of 
site-specific contact details can be found in the Investigator Site File. 
Contract Research Organization 
Information 
Frontage Laboratories (Shanghai) Co., Ltd. 
No. 13, Lane 67, Libing Road, Pilot Free Trade 
Zone, Shanghai, China 
Central Laboratory 
GOBROAD LABORATORIES CO., LTD. 
No. 6 Zhengwangfen South, Fengtai District, 
Beijing, China 
 
Q Squared Solutions (Beijing) Co., Ltd. 
Unit 302, Building 15, No. 8 Liangshuihe 2nd 
Street Han’s Enterprise Bay, BDA Beijing, 100176 
China 
 
Frontage Laboratories (Suzhou) Co., Ltd. 
3/F, Block C, 1336 Wuzhong Avenue, Wuzhong 
District, Suzhou 
 
 
 

Cenerimod (ACT-334441) 
Systemic lupus erythematosus 
Protocol ID-064A204 
 
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SIGNATURE PAGE FOR VIATRIS INNOVATION GmbH 
Hereinafter called Sponsor 
 
Compound name / number 
Cenerimod / ACT-334441 
 
Indication 
Systemic lupus erythematosus 
 
Protocol number, study acronym, study title 
ID-064A204 
A multicenter, open label, single arm, multiple-dose study to evaluate the safety, 
tolerability, pharmacokinetics and pharmacodynamics of cenerimod in adult Chinese 
participants with moderate-to-severe systemic lupus erythematosus (SLE) on top of 
background therapy. 
 
Name (Title)  
Date 
 
Signature 
 
 
ZhiJun Zhang, Clinical 
Project Physician 
Sponsor Medical Expert
 
 
Mark Liu 
Head of Clinical 
Pharmacology Statistics & 
Data Management 
Global Clinical 
Pharmacology 
Viatris
 
 
 
Mark 
Shiyao Liu
Digitally signed by Mark Shiyao Liu 
DN: c=US, st=Pennsylvania, l=Canonsburg, 
2.5.4.97=LEIXG-254900ZZTSW7NL773X71, 
sn=Shiyao Liu, givenName=Mark, o=Viatris 
Inc., cn=Mark Shiyao Liu, 
email=shiyao.liu@viatris.com 
Reason: I am approving this document 
Date: 2025.09.16 15:55:25 -04'00'
Zhi Jun 
Zhang
数字签名者：Zhi Jun Zhang 
DN：c=US, st=Pennsylvania, 
l=Canonsburg, 
2.5.4.97=LEIXG-254900ZZTSW7NL773
X71, o=Viatris Inc., cn=Zhi Jun Zhang, 
email=zhijun.zhang@viatris.com 
原因：我正在审批本文档 
日期：2025.09.17 10:04:53 +08'00'

Confidential
V-25.095
Cencrimod (ACT-334441)
Systemic lupus erythematosus
Protocol ID-064A204
Final Version 3.0
16 Sep. 2025, Page 4/15()
INVESTIGATOR SIGNATURE PAGE
Compound name / number
Cencrimod / ACT-334441
Indication
Systemic lupus erythematosus
Protocol number, study acronym, study title
ID-064A204
A multicenler, open label, single arm, multiple-dose study to evaluate the safety,
tolerability, pharmacokinetics and pharmacodynamics of cenerimod in adult Chinese
participants with modcratc-to-severc systemic lupus erythematosus (SLE) on top of
background therapy.
I agree to the terms and conditions relating to this study as defined in this protocol and any
other protocol-related documents. I fully understand that any changes instituted by the
investigator(s) without previous agreement with the sponsor would constitute a protocol
deviation, including any ancillary studies or procedures performed on participants (other
than those procedures necessary fbr the well-being of the participants).
I agree to conduct this study in accordance with the Declaration of Helsinki principles, ICH
GCP guidelines, and applicable local GCP guidelines, regulations and laws.
Location
Principal Investigator
(Site number)
Date
Signature
2

Cenerimod (ACT-334441) 
Systemic lupus erythematosus 
Protocol ID-064A204 
 
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AMENDMENT DETAILS 
Current Amendment 
Amendment 
Number 
ID-064A204 
Version No. 
V3.0 
Version Date 
16 Sep. 2025 
Number of 
participants 
enrolled 
Fifteen (15) participants to be enrolled and none enrolled at present 
Reason(s) for 
Amendment 
Primary Reason: 
Select from the following (multiple 
selections allowed): 
• 
Regulatory agency request to 
amend 
• 
New regulatory guidance 
• 
IRB/IEC feedback 
• 
New safety information available 
• 
Manufacturing change 
• 
Adaptive 
clinical 
trial 
IMP 
addition 
✓ 
Change in strategy: 3-month 
interim analysis and report 
submitted 
to 
CDE 
is 
not 
required 
• 
Change in standard of care 
• 
New data available (other than 
safety data) 
• 
Investigator/site feedback 
• 
Recruitment difficulty 
• 
Inconsistency and/or error in the 
protocol 
• 
Protocol design error 
✓ 
Other: 
Change 
of 
sponsor 
information 
Other: 
Select from the following (multiple 
selections allowed): 
• 
Regulatory agency request to 
amend 
• 
New regulatory guidance 
• 
IRB/IEC feedback 
• 
New 
safety 
information 
available 
• 
Manufacturing change 
• 
Adaptive clinical trial IMP 
addition 
• 
Change in strategy 
• 
Change in standard of care 
• 
New data available (other than 
safety data) 
• 
Investigator/site feedback 
• 
Recruitment difficulty 
• 
Inconsistency and/or error in 
the protocol 
• 
Protocol design error 
✓ 
Other: A few updates for the 
scale in Appendix 6 
Specify the exclusion criteria 
18 
Revision in section 2.4.3 
Summary of 
the 
Amendment 
1) Deletion of contents about 3-month interim analysis; 
2) Change of sponsor information; 
3) Change of Appendix 6 in Protocol according to the scale to be used; 
4) Specification of the varicella-zoster virus antibody type as IgG in 
exclusion criteria 18; 

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Systemic lupus erythematosus 
Protocol ID-064A204 
 
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5) Revision of the blood amount to be collected at each visit on average in 
section 2.4.3 Study procedures and associated potential risks. 
Is this amendment likely to have a substantial impact on 
• 
Safety or rights of the participants, or 
• 
On the reliability and robustness of the data 
generated in the clinical trial? 
No 
 
Summary of Changes in the Current Amendment 
Section and Name  
Description of Change  
Brief Rationale for 
Change 
1.1 Protocol synopsis ID-
064A204  
 
1.2 Schema 
 
2.3 Study rationale 
 
3.1 List of objectives and 
endpoints –  
 
9.3 Planned analyses 
Delete content on “The Month-3 interim 
analysis will be performed when all 
enrolled participants have completed the 
3-month treatment period or permanently 
discontinued the study” and “The Month-
3 interim report will be submitted to CDE 
for decision to allow the continuation of 
this Phase 2 study and initiation of the 
Phase 3 study in China”. 
In addition, “The safety of the participants 
will be closely monitored. Safety review 
will be conducted regularly and on 
demand during the study” is clarified for 
safety monitoring. 
Based on the review 
comments on 
cenerimod data from 
CDE, the development 
strategy would be 
changed: The 3-month 
interim analysis and 
report submitted to 
CDE is not required. 
The safety of the 
participants will be 
closely monitored and 
further decision on the 
clinical studies would 
be based on periodical 
safety results.  
COVER PAGE 
 
SPONSOR CONTACT 
DETAILS 
 
SIGNATURE PAGE FOR 
SPONSOR 
 
Protocol header 
Delete 
information 
about 
Idorsia 
pharmaceuticals Ltd., and change the 
global sponsor to Viatris Innovation 
GmbH 
Change global sponsor 
according to the 
transfer of the 
cenerimod development 
program 
12 APPENDICES 
Change of Appendix 6 SLEDAI-2K: Data 
collection sheet 
A few description 
content updates to be 
consistent with the 
scale to be used 
1.1 Protocol synopsis ID-
064A204  
 
5.3 Exclusion criteria 
Clarify the varicella-zoster virus antibody 
type as IgG in exclusion criteria 18 
Specify the requirement 

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Systemic lupus erythematosus 
Protocol ID-064A204 
 
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Section and Name  
Description of Change  
Brief Rationale for 
Change 
2.4.3 Study procedures and 
associated potential risks 
Revise the blood amount to be collected at 
each visit on average 
Update the planned 
blood amount to be 
collected according to 
the trial design and the 
requirement by the test 
laboratory 
 
 

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AMENDMENT DETAILS 
Amendment Version 2.0 
Amendment 
Number 
ID-064A204 
Version No. 
V2.0 
Version Date 
11 Jul. 2025 
Number of 
participants 
enrolled 
Fifteen (15) participants to be enrolled and none enrolled at present 
Reason(s) for 
Amendment 
Primary Reason: 
Select from the following (multiple 
selections allowed): 
• 
Regulatory agency request to 
amend 
• 
New regulatory guidance 
• 
IRB/IEC feedback 
• 
New safety information available 
• 
Manufacturing change 
• 
Adaptive 
clinical 
trial 
IMP 
addition 
• 
Change in strategy 
• 
Change in standard of care 
• 
New data available (other than 
safety data) 
• 
Investigator/site feedback 
• 
Recruitment difficulty 
• 
Inconsistency and/or error in the 
protocol 
• 
Protocol design error 
✓ 
Other: details optimization 
Other: 
Select from the following (multiple 
selections allowed): 
• 
Regulatory agency request to 
amend 
• 
New regulatory guidance 
• 
IRB/IEC feedback 
• 
New 
safety 
information 
available 
• 
Manufacturing change 
• 
Adaptive clinical trial IMP 
addition 
• 
Change in strategy 
• 
Change in standard of care 
• 
New data available (other than 
safety data) 
• 
Investigator/site feedback 
• 
Recruitment difficulty 
• 
Inconsistency and/or error in 
the protocol 
• 
Protocol design error 
• 
Other: [Describe] 
Summary of 
the 
Amendment 
1) Protocol description optimization; 
2) Update detailed operation as applicable. 
Is this amendment likely to have a substantial impact on 
• 
Safety or rights of the participants, or 
• 
On the reliability and robustness of the data 
generated in the clinical trial? 
No 

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Summary of Changes in the Amendment Version 2.0 
Section and Name  
Description of Change  
Brief Rationale for Change 
Full text 
Update “subject” to “participant” or “patient” 
Update according to the latest 
Declaration of Helsinki and 
guidance e.g. ICH M11 
SPONSOR CONTACT DETAILS 
Add CRO and central lab unit information 
Important unit information 
added 
LIST OF ABBREVIATIONS AND 
ACRONYMS 
Revision, adding and deleting as applicable 
Update abbreviations as used 
actually in protocol 
1.1 Protocol synopsis ID-064A204 
5.2 Inclusion criteria 
Delete the requirement “BILAG Grade B in ≥ 2 
organ systems or a BILAG Grade A in ≥ 1 organ 
system” for enrollment on Day 1. 
Based on the study objective, 
the limitation on BILAG for 
enrolled participants is not 
required 
1.1 Protocol synopsis ID-064A204 
Description of core protocol was deleted 
There was no core protocol 
and the information not 
applicable was deleted 
1.1 Protocol synopsis ID-064A204 
9.1 Analysis sets 
Update the abbreviation of safety analysis set to SS 
from SAF. 
Update according to the 
domestic operation and 
guidance 
1.1 Protocol synopsis ID-064A204 
Add 
analysis 
of 
efficacy 
endpoints 
in 
STATISTICAL METHODOLOGY:  
Analysis of efficacy endpoints 
Efficacy data will be analyzed descriptively. These 
analyses are detailed in the statistical methods 
section. 
List all endpoints and the 
statistical methods 
1.3 Schedule of activities 
Adjust the location of the superscript remarks: 
superscript remarks 3, 4, 5, and 6 were involved in 
table 1; 
all superscript remarks were involved in table 2; 
Improve readability 

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Section and Name  
Description of Change  
Brief Rationale for Change 
superscript remarks 2 and 3 were involved in table 
3. 
1.3 Schedule of activities 
The SLE biomarkers in PAXgene samples was 
deleted in table 1. 
The test results on Day 1 
predose will be considered as 
baseline values 
1.3 Schedule of activities 
9.2.2 Analysis of pharmacokinetic endpoints 
The timepoint of 24 h postdose for PK sampling 
was added at Month 2 visit. 
To obtain more accurate PK 
results 
1.3 Schedule of activities 
7.2.3.3.2 Additional cardiac monitoring on 
Day 1 
Clarify the hourly frequency of 12-lead ECGs 
monitoring within 12 hours postdose on Day 1 or 
the day of treatment re-initiation. 
Clarify the operation to guide 
clinical implementation 
1.3 Schedule of activities 
Clarify the body weight should be measured under 
fasting conditions in the morning. 
Clarify the operation to guide 
clinical implementation 
2.4.2 Known and potential risks 
Classify the embryo-fetal toxicity to potential risks. 
Only pre-clinical data 
indicated the embryo-fetal 
toxicity and no human data 
was reported 
2.4.3 Study procedures and associated 
potential risks 
The CT scan is also allowed for eligibility to 
exclude latent TB in table 4 
CT is more sensitive 
5.8.1.4.1 Day 1 specific stopping criteria 
Update the criteria of permanent discontinuation of 
study treatment on Day 1 and on the first day of re-
initiation of study treatment 
To better ensure participant 
safety 
7.2.2.4 Physician’s Global Assessment of 
disease 
Clarify 1, 2, and 3 are indicative of SLE disease 
activity assessment and correspond to upper limits 
of “mild”, “moderate”, and “severe”, respectively. 
The upper limits of disease 
activity were clarified to avoid 
confusion 
7.2.3.2 Weight and height 
The participant body weight will be measured with 
heavy clothing removed rather than in underwear 
To be more operable 
7.2.3.3.1 Cardiac monitoring applicable to all 
participants 
The 
ECG 
findings 
(e.g., 
rhythm, 
ectopy, 
conduction, and morphology) and the overall 
interpretation of the ECG (normal/abnormal) will 
The ECG findings and 
interpretation will also be sent 
to sponsor in actual operation 

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Section and Name  
Description of Change  
Brief Rationale for Change 
be provided by the ECG central vendor to the study 
site and to sponsor. 
7.2.3.5 Ophthalmological examination 
7.2.3.6 Optical coherence tomography 
Update the results record from “Yes/No for 
abnormality” to “Normal, NCS abnormal and CS 
abnormal” 
The latter is more conformed 
with the clinical assessment for 
the results in actual operation 
7.2.5.1 Pharmacokinetic assessments 
Add the allowed time window for PK sampling 
Clarify the operation to guide 
clinical implementation 
7.2.5.1 Pharmacokinetic assessments 
Delete the description of “The plasma samples will 
be destroyed upon signature of the CSR” 
The samples will be processed 
according to the actual 
agreement 
8.2.2 Reporting serious adverse events 
8.3.1 Reporting of pregnancy 
8.3.2 Follow-up of pregnancy 
AEs and pregnancy will be sent to sponsor’s “Drug 
Safety department” rather than “Global Drug 
Safety department” 
Update protocol to consistent 
with the actual operations 
9.2.2 Analysis of pharmacokinetic endpoints 
Delete the detailed rule for statistical description of 
“If more than 50% of the values at a given time 
point are BLQ, no mean (including 95% CI), SD, or 
SE will be calculated for this time point”; 
Update the software for PK calculation 
The actual statistical analysis 
methods shall prevail 
9.2.3 Analysis of PD endpoints 
Clarify that PD parameters will be calculated and 
summarized based on Lymphocyte counts 
Clarify the PD endpoint to be 
analyzed 
10.12 Inspections 
Delete the specific way in which the inspection 
should be inform to sponsor 
The actual operation shall 
prevail 
Appendix 1 Clinical laboratory tests 
Revise “Blood urea nitrogen” to “Blood urea 
nitrogen or urea, urea (mg/dL) = urea nitrogen 
(mg/dL) * 2.14”; 
Delete “leukocyte esterase” in Urinalysis; clarify 
the items in urinalysis–blood (hemoglobin, white 
blood 
cells) 
and 
Microscopic 
examination-
sediment (red blood cells, white blood cells and 
casts) 
Update according to the actual 
items to be tested 

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Section and Name  
Description of Change  
Brief Rationale for Change 
Appendix 2 2019 EULAR/ACR Classification 
criteria for SLE 
Appendix 6 SLEDAI-2K: Data collection 
sheet 
Appendix 7 BILAG-2004 index 
Appendix 8 SLE Flare Index 
Appendix 9 Physician’s Global Assessment 
Visual Analog Scale 
Appendix 11 Tender/swollen joints count 
Make 
notes 
to 
clarify 
that 
“The 
actual 
scale/assessment to be used will prevail” 
The actual scale/assessment to 
be used will prevail 
Appendix 10 CLASI 
Update the scale 
Update according to the actual 
scale to be used 
 
 
 

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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS AND ACRONYMS ..........................................................19 
1 
PROTOCOL SUMMARY ..........................................................................................23 
1.1 
Protocol synopsis ID-064A204 ....................................................................23 
1.2 
Schema ..........................................................................................................41 
1.3 
Schedule of activities ....................................................................................42 
2 
INTRODUCTION .......................................................................................................51 
2.1 
Indication ......................................................................................................51 
2.2 
Investigational treatment ..............................................................................52 
2.3 
Study rationale ..............................................................................................53 
2.4 
Benefit/risk assessment of cenerimod ..........................................................54 
2.4.1 
Potential benefits ...............................................................................54 
2.4.2 
Known and potential risks ................................................................55 
2.4.3 
Study procedures and associated potential risks ...............................57 
2.4.4 
Assessment of benefit -risk ...............................................................57 
3 
STUDY OBJECTIVES AND ENDPOINTS ..............................................................58 
3.1 
List of objectives and endpoints – ................................................................58 
3.2 
Appropriateness of endpoints .......................................................................60 
4 
STUDY DESIGN AND PLAN ...................................................................................61 
4.1 
Study design .................................................................................................61 
4.1.1 
Study periods for an individual participant .......................................61 
4.2 
Study duration and End-of-Study definition ................................................62 
4.3 
Study design rationale ..................................................................................62 
4.4 
Study committees .........................................................................................63 
5 
STUDY POPULATION .............................................................................................63 
5.1 
Participant population description ................................................................63 
5.2 
Inclusion criteria ...........................................................................................63 
5.3 
Exclusion criteria ..........................................................................................65 
5.4 
Rationale for the selection of the study population ......................................70 
5.5 
Contraception requirements for women of childbearing potential ...............70 
5.5.1 
Definition of childbearing potential ..................................................70 
5.5.2 
Methods of contraception .................................................................71 

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5.6 
Contraception for male participants with a partner who is of 
childbearing potential ...................................................................................72 
5.7 
Screen failures and re-screening ...................................................................73 
5.8 
Criteria for withdrawal of participants .........................................................73 
5.8.1 
Study treatment interruption and permanent discontinuation of 
study treatment ..................................................................................73 
5.8.1.1 
Principles ................................................................................ 73 
5.8.1.2 
Pregnancy ............................................................................... 74 
5.8.1.3 
Lack of compliance with methods of contraception .............. 74 
5.8.1.4 
Cardiovascular ........................................................................ 75 
5.8.1.5 
Infections ................................................................................ 75 
5.8.1.6 
Lymphocyte count monitoring ............................................... 76 
5.8.1.7 
Liver enzyme abnormalities ................................................... 77 
5.8.1.8 
Ocular abnormalities .............................................................. 79 
5.8.1.9 
Initiation of forbidden concomitant medication during 
the study ................................................................................. 79 
5.8.1.10 
Other potential permanent treatment discontinuation ............ 79 
5.8.1.11 
Other study-specific criteria for re-initiation after 
temporary treatment interruption ............................................ 79 
5.8.2 
Measures for participant retention ....................................................80 
5.8.3 
Withdrawal from the study ...............................................................80 
5.8.4 
Lost to follow-up ..............................................................................81 
6 
TREATMENTS ..........................................................................................................81 
6.1 
Study treatment .............................................................................................81 
6.1.1 
Investigational treatment ...................................................................81 
6.1.2 
Study treatment dosing and administration ......................................82 
6.1.2.1 
Study treatment dose adjustments .......................................... 82 
6.1.3 
Justification for dose .........................................................................82 
6.1.4 
Treatment assignment .......................................................................82 
6.1.5 
Study treatment handling/preparation/storage/accountability ..........82 
6.1.5.1 
Study treatment packaging and labeling ................................ 83 
6.1.5.2 
Study treatment distribution and storage ................................ 83 
6.1.5.3 
Study treatment dispensing .................................................... 83 
6.1.5.4 
Study treatment accountability ............................................... 83 
6.1.5.5 
Study treatment return and destruction .................................. 84 
6.1.6 
Study treatment compliance ..............................................................84 
6.2 
Previous and concomitant medications ........................................................84 
6.2.1 
Auxiliary medicinal products ............................................................85 
6.2.1.1 
SLE background therapy (except OCS background 
therapy) conditions of use ...................................................... 85 

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6.2.1.2 
OCS background therapy conditions of use ........................... 86 
6.2.2 
Allowed concomitant therapy ...........................................................89 
6.2.2.1 
CS burst conditions of use ...................................................... 89 
6.2.2.2 
NSAIDs conditions of use ...................................................... 90 
6.2.3 
Forbidden concomitant therapy ........................................................90 
6.3 
Medical care of participants after study completion / withdrawal from 
study ..............................................................................................................91 
7 
VISIT SCHEDULE AND STUDY ASSESSMENTS AND PROCEDURES ...........91 
7.1 
General information ......................................................................................91 
7.1.1 
Screening ..........................................................................................92 
7.1.2 
Unscheduled visits ............................................................................93 
7.1.3 
Study completion ..............................................................................93 
7.2 
Study assessments and procedures ...............................................................93 
7.2.1 
Demographics / baseline characteristics ...........................................93 
7.2.2 
Disease activity assessments .............................................................94 
7.2.2.1 
Systemic Lupus Erythematosus Disease Activity 
Index-2000 .............................................................................. 95 
7.2.2.2 
British Isles Lupus Assessment Group ................................... 95 
7.2.2.3 
SLE Flare Index ...................................................................... 97 
7.2.2.4 
Physician’s Global Assessment of disease ............................. 98 
7.2.2.5 
Cutaneous Lupus Erythematosus Disease Area and 
Severity Index ......................................................................... 98 
7.2.2.6 
Tender/swollen joints count ................................................... 98 
7.2.3 
Safety assessments ............................................................................99 
7.2.3.1 
Physical examination .............................................................. 99 
7.2.3.2 
Weight and height ................................................................ 100 
7.2.3.3 
Electrocardiograms ............................................................... 100 
7.2.3.4 
Clinical laboratory assessments ............................................ 102 
7.2.3.5 
Ophthalmological examination ............................................ 104 
7.2.3.6 
Optical coherence tomography ............................................. 105 
7.2.3.7 
Chest X-ray or CT scan ........................................................ 105 
7.2.3.8 
Test for tuberculosis ............................................................. 105 
7.2.3.9 
Skin examination .................................................................. 106 
7.2.4 
Blood pressure assessments ............................................................106 
7.2.5 
Pharmacokinetic and pharmacodynamic assessments ....................106 
7.2.5.1 
Pharmacokinetic assessments ............................................... 106 
7.2.5.2 
Pharmacodynamic assessments ............................................ 107 
7.2.6 
Biomarker assessments ...................................................................107 
7.2.6.1 
Disease activity biomarkers .................................................. 107 

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8 
SAFETY DEFINITIONS AND REPORTING REQUIREMENTS .........................107 
8.1 
Safety definitions ........................................................................................107 
8.1.1 
Definition of adverse events ...........................................................107 
8.1.2 
Definition of adverse events of specific interest .............................108 
8.1.3 
Definition of serious adverse events ...............................................109 
8.1.4 
Intensity of adverse events ..............................................................109 
8.1.5 
Relationship to study treatment ......................................................110 
8.1.6 
Relationship to study design or protocol-mandated procedure ......110 
8.1.7 
Definition of study treatment overdose, misuse, and abuse ...........110 
8.2 
Reporting procedures ..................................................................................110 
8.2.1 
Reporting adverse events ................................................................110 
8.2.2 
Reporting serious adverse events ....................................................111 
8.2.3 
Reporting procedure for SUSARs ..................................................112 
8.2.4 
Reporting medical or surgical intervention ....................................112 
8.3 
Pregnancy ...................................................................................................112 
8.3.1 
Reporting of pregnancy ..................................................................112 
8.3.2 
Follow-up of pregnancy ..................................................................113 
9 
STATISTICAL METHODS .....................................................................................113 
9.1 
Analysis sets ...............................................................................................113 
9.1.1 
Screened set ....................................................................................113 
9.1.2 
Safety Analysis Set (SS) .................................................................113 
9.1.3 
Pharmacokinetic Analysis Set (PKS) .............................................113 
9.1.4 
Pharmacodynamic Analysis Set (PDS) ...........................................113 
9.2 
Description of statistical analyses ...............................................................113 
9.2.1 
Analysis of safety endpoints ...........................................................114 
9.2.2 
Analysis of pharmacokinetic endpoints ..........................................115 
9.2.3 
Analysis of PD endpoints ...............................................................116 
9.2.4 
Analysis of efficacy endpoints ........................................................116 
9.3 
Planned analyses .........................................................................................117 
9.4 
Sample size .................................................................................................117 
10 REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS ................................................................................................117 
10.1 
Regulatory and ethical considerations ........................................................117 
10.2 
Informed consent process ...........................................................................118 
10.3 
Data protection and privacy ........................................................................119 
10.4 
Indemnification, compensation, and refund of expenses to participants 
and investigators .........................................................................................120 
10.5 
Essential documents and retention of documents .......................................120 

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10.5.1 
Investigator Site File .......................................................................120 
10.5.2 
Source documents ...........................................................................121 
10.6 
Data handling ..............................................................................................122 
10.6.1 
Data collection, data transfer procedure, and data access ...............122 
10.6.2 
Database management and quality control .....................................122 
10.7 
Protocol deviations .....................................................................................123 
10.8 
Clinical monitoring .....................................................................................123 
10.9 
Study safety oversight ................................................................................124 
10.10 
Premature termination or suspension of the study ......................................124 
10.11 
Audit ...........................................................................................................125 
10.12 
Inspections ..................................................................................................125 
10.13 
Reporting of study results and publication .................................................125 
11 REFERENCES ..........................................................................................................126 
12 APPENDICES ...........................................................................................................131 
 
 
LIST OF TABLES 
 
Table 1 
Schedule of activities at Screening ............................................................ 42 
Table 2 
Schedule of activities after Screening ....................................................... 44 
Table 3 
Schedule of activities: PTOP (applicable to participants who 
permanently discontinue study treatment .................................................. 49 
Table 4 
Study procedures and associated potential risks ....................................... 57 
Table 5 
Objectives and endpoints .......................................................................... 58 
Table 6 
Example of background OCS therapy forced tapering schedule .............. 88 
Table 7 
Relationship among laboratory tests for proteinuria ............................... 102 
 
 
LIST OF FIGURES 
 
Figure 1 
Study design  ............................................................................................. 41 
Figure 2 
Guidance for re-test results of lymphocytes < 200 cells/µL ..................... 77 
Figure 3 
Guidance for monitoring liver test abnormalities ..................................... 78 
Figure 4 
OCS management overview ...................................................................... 86 
 
 

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LIST OF APPENDICES 
 
Appendix 1 
Clinical laboratory tests ........................................................................... 131 
Appendix 2 
2019 EULAR/ACR Classification criteria for SLE ................................ 133 
Appendix 3 
Forbidden anti-arrhythmic or heart rate lowering medications ............... 134 
Appendix 4 
Forbidden medications with risk of torsade de pointes ........................... 135 
Appendix 5 
Criteria for discharge from monitored setting on Day 1 and on the 
first day of re-initiation following treatment interruptions ..................... 136 
Appendix 6 
SLEDAI-2K: Data collection sheet ......................................................... 137 
Appendix 7 
BILAG-2004 index ................................................................................. 139 
Appendix 8 
SLE Flare Index ...................................................................................... 140 
Appendix 9 
Physician’s Global Assessment Visual Analog Scale ............................. 141 
Appendix 10 CLASI ..................................................................................................... 142 
Appendix 11 Tender/swollen joints count .................................................................... 143 
Appendix 12 Conversion table from glucocorticoids to Prednisone ............................ 145 
Appendix 13 Notable abnormalities for ECG, BP, and laboratory variables ............... 146 
Appendix 14 New York Heart Association Classes of Heart Failure ........................... 150 
 
 
 

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LIST OF ABBREVIATIONS AND ACRONYMS 
 
ACR  
American College of Rheumatology 
ADL  
Activities of daily living 
AE  
Adverse event 
AESI  
Adverse event of special interest 
AI  
Accumulation index 
ALT  
Alanine aminotransferase 
ANA  
Antinuclear antibodies 
Anti-dsDNA  
Anti-double-stranded deoxyribonucleic acid 
Anti-Sm  
Anti-Smith 
AST  
Aspartate aminotransferase 
AUC  
Area under the plasma concentration-time curve 
AUC  
Area under the plasma concentration-time curve during a dose 
interval at steady state 
AUC0-24  
Area under the plasma concentration-time curve from zero to 24 h 
after dosing 
AV  
Atrioventricular 
BICLA  
BILAG-based Composite Lupus Assessment 
BILAG  
British Isles Lupus Assessment Group-2004 
BLQ  
Below the limit of quantification 
BP  
Blood pressure 
bpm  
Beats per minute 
CDE  
Center for Drug Evaluation  
CFR  
Code of Federal Regulations (US) 
CI  
Confidence interval 
CLASI  
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
Cmax  
Maximum plasma concentration 
CNS  
Central nervous system 
COVID-19  
Coronavirus disease 2019 
CRA  
Clinical Research Associate 
CRO  
Contract Research Organization 
CS  
Corticosteroid(s) 
CSR  
Clinical study report 

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CT  
Computed tomography 
DBP  
Diastolic blood pressure 
ECG  
Electrocardiogram 
eCRF  
Electronic case report form 
EDTA  
Ethylenediaminetetraacetic acid 
eGFR  
Estimated glomerular filtration rate 
EOS  
End-of-Study 
EOT  
End-of-Treatment 
EULAR  
European League Against Rheumatism 
FDA  
Food and Drug Administration (US) 
FSV  
Final study visit 
FU  
Follow-up 
GCP  
Good Clinical Practice 
HAV  
Hepatitis A virus 
HbA1c  
Glycated hemoglobin 
HBsAg  
Hepatitis B surface Antigen 
HCV  
Hepatitis C virus 
HEV  
Hepatitis E virus 
HIV  
Human immunodeficiency virus 
HR  
Heart rate 
i.v.  
Intravenous(ly) 
ICF  
Informed consent form 
ICH  
International Council for Harmonisation 
IEC  
Independent ethics committee 
IFN  
Interferon 
IFN-1  
Type 1 interferon 
Ig  
Immunoglobulin 
IGRA  
IFN gamma release assay 
IL  
Interleukin 
INR  
International normalized ratio 
IOSB  
Independent Ophthalmology Safety Board 
IRB  
Institutional review board 
IRT  
Interactive Response Technology 

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ISF  
Investigator Site File 
MCP  
Metacarpophalangeal 
MedDRA  
Medical Dictionary for Drug Regulatory Activities 
MRL/lpr  
Murphy Roths large lymphoproliferation 
mRNA  
Messenger ribonucleic acid 
mSLEDAI-2K  
Modified Systemic Lupus Erythematosus Disease Activity 
Index-2000 
NSAID  
Nonsteroidal anti-inflammatory drug 
o.d.  
Once daily 
OCS  
Oral corticosteroid(s) 
OCT  
Optical coherence tomography 
PCR  
Polymerase chain reaction 
PD  
Pharmacodynamic(s) 
PDS  
Pharmacodynamic analysis set 
pEOT  
Premature End-of-Treatment 
PGA  
Physician’s Global Assessment 
PIP  
Proximal interphalangeal 
PK  
Pharmacokinetic(s) 
PKS  
Pharmacokinetic analysis set 
PT  
Preferred Term 
PTOP  
Post-treatment observation period 
QTcB  
QT interval corrected according to Bazett’s formula 
QTcF  
QT interval corrected according to Fridericia’s formula 
RBC  
Red blood cell count 
RNA  
Ribonucleic acid 
s.c.  
Subcutaneousl(ly) 
S1P  
Sphingosine-1-phosphate 
S1P1  
Sphingosine-1-phosphate receptor 1 
SAE  
Serious adverse event 
SAP  
Statistical analysis plan 
SARS-CoV-2  
Severe acute respiratory syndrome coronavirus 2 
SBP  
Systolic blood pressure 
SD  
Standard deviation 

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SE  
Standard error 
SELENA  
Safety of Estrogens in Lupus Erythematosus National Assessment 
SFI  
SLE Flare Index 
SLE  
Systemic lupus erythematosus 
SLEDAI-2K  
Systemic Lupus Erythematosus Disease Activity Index-2000 
SmPC  
Summary of Product Characteristics 
SoA  
Schedule of Assessments 
SOC  
System Organ Class 
SOP  
Standard Operating Procedure 
SRI  
Systemic Lupus Erythematosus Responder Index 
SS  
Safety analysis set 
SUSAR  
Suspected unexpected serious adverse reaction 
t½  
Terminal half-life 
TB  
Tuberculosis 
TBIL  
Total bilirubin 
TEAE  
Treatment-emergent adverse event 
tmax  
Time to reach maximum plasma concentration 
TNF  
Tumor necrosis factor 
ULN  
Upper limit of normal 
US  
United States 
VAS  
Visual analog scale 
WBC  
White blood cell  
WHO  
World Health Organization 
WoCBP  
Women of childbearing potential 
 
 

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1 
PROTOCOL SUMMARY 
1.1 Protocol synopsis ID-064A204  
TITLE 
A multicenter, open label, single arm, multiple-dose study to 
evaluate 
the 
safety, 
tolerability, 
pharmacokinetics 
and 
pharmacodynamics of cenerimod in adult Chinese participants 
with moderate-to-severe systemic lupus erythematosus (SLE) on 
top of background therapy 
OBJECTIVES 
Primary objectives 
• To evaluate the safety and tolerability of cenerimod 4 
mg in Chinese participants.  
• To evaluate the PK of cenerimod 4 mg in Chinese 
participants.  
• To evaluate the PD of cenerimod 4 mg in Chinese 
participants. 
Other objective 
• To preliminarily evaluate the efficacy of cenerimod 4 
mg in Chinese participants. 
ENDPOINTS 
Safety endpoints 
The following endpoints will be evaluated. 
• Occurrence of treatment-emergent adverse events (AEs), 
serious AEs (SAEs) and AEs of special interest (AESIs)  
• Occurrence of AEs leading to permanent discontinuation of 
study treatment. 
• Changes in vital signs (systolic blood pressure [SBP], 
diastolic blood pressure [DBP]) and body weight from 
baseline to each post-baseline assessment. 
• Changes in hourly 12-lead electrocardiogram (ECG) variables 
(hear rate [HR] and the QTcB and QTcF intervals) and 
SBP/DBP assessments at Day 1 cardiac monitoring.  
• Changes in 12-lead ECG variables (HR and the PR, QRS, 
QTcB, and QTcF intervals) from baseline to each post-
baseline assessment. 
• Treatment-emergent medically relevant ECG abnormalities 
from baseline to each post-baseline assessment. 

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• Changes in laboratory variables (hematology, blood 
chemistry, and urinalysis) from baseline to each post-baseline 
assessment. 
• Treatment-emergent marked laboratory abnormalities from 
baseline to each post-baseline assessment. 
The treatment-emergent period for the study is defined as the time 
from first study treatment intake until the end of the safety follow-
up period, i.e., up to last study treatment intake + 180 days.  
PK endpoints  
• Cenerimod plasma concentrations at all scheduled time points 
(see Table 2). 
• The plasma PK parameters of 4 mg cenerimod will be derived 
by non-compartmental analysis of the plasma concentration-
time profiles and calculated based on the actual PK sampling 
time points. The following endpoints will be determined:  
− Cmax, tmax, and AUC0-24 during the first dosing interval 
on Day 1, 
− Cmax, tmax, and AUC  during a dosing interval at steady 
state (i.e., at Month 2), 
− Accumulation index (AI) between Day 1 and Month 2. 
PD endpoints 
• Change in total blood lymphocyte count from baseline to each 
post-baseline assessment. 
Efficacy endpoints 
• Response on SRI-4 from baseline to Month 12. 
• Response on mSLEDAI-2K from baseline to Month 12. 
• Response on BICLA from baseline to Month 12. 
• Response on CLASI from baseline to Month 12. 
• Change in tender and swollen joints from baseline to Month 
12. 
• Changes in OCS dosage from baseline to Month 12. 

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DESIGN 
This is a multicenter, single arm, open label, multiple dose, study 
in adult Chinese participants with moderate-to-severe SLE with 
cenerimod 4 mg being administered on top of background SLE 
therapy. 
The safety of the participants will be closely monitored. Safety 
review will be conducted regularly and on demand during the 
study. 
PERIODS 
The study comprises the following consecutive periods: 
Screening period: Lasts up to 30 days; starts with the full 
signature of the informed consent form (ICF; participant, 
investigator/delegate and/or any other applicable third party) and 
ends with the administration of the study treatment on Day 1 or 
screening failure. 
Treatment period: Starts with the administration of the first dose 
of study treatment and ends on the day of the last dose of study 
treatment. It is planned that participants will be treated for up to 
12 months.  
Post-treatment observation period (PTOP; only applicable to 
participants who permanently discontinue study treatment): Starts 
the day after the last dose of study treatment and participants will 
complete visits until at least 6 months after last study treatment 
intake as follows:  
• Participants who permanently discontinue study treatment 
before or at Month 6 will complete study visits until Month 12 
and the final study visit (FSV) will be at Month 12 (i.e., 
PTOP-Visit 14).  
• Participants who permanently discontinue study treatment 
between Month 7 and Month 12 (inclusive), will complete 
PTOP follow-up visit(s). The FSV will be one of the monthly 
PTOP FU visits, as applicable. 
Follow-up period: Starts on the day after the last dose of study 
treatment and ends 6 months, i.e., 180 days, thereafter with FSV.  
The visit schedule and protocol-mandated procedures are 
performed according to the schedule of activities (SoA) [see 
Table 1, Table 2, and Table 3]. 

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The study design is depicted in Figure 1. 
PLANNED 
DURATION 
Approximately 22 months from first participant first visit to 
last participant last visit. 
SITES / 
COUNTRIES 
Approximately 5 -10 sites in China. 
PARTICIPANTS / 
GROUPS 
Approximately 15 adult participants diagnosed with generalized 
moderate-to-severe SLE and concurrently receiving SLE 
background therapy will receive 4 mg of cenerimod once daily for 
12 months. 
INCLUSION 
CRITERIA 
Screening criteria 
1. 
Signed and dated ICF prior to any study-mandated 
procedure. 
2. 
Male and female Chinese participants aged from 18 to 75 
years old (inclusive) at the time of signing the ICF. 
3. 
Diagnosis of SLE made at least 6 months prior to Screening, 
according to 2019 European League Against Rheumatism / 
American College of Rheumatology Criteria.  
4. 
An mSLEDAI-2K score ≥ 6 and clinical mSLEDAI-2K 
score ≥ 4 with at least 2 points for musculoskeletal or 
mucocutaneous manifestations (i.e., myositis, arthritis, rash, 
alopecia, mucosal ulcers).  
Note: 
The mSLEDAI-2K score does 
not include 
“leukopenia”. 
The 
clinical 
mSLEDAI-2K 
is 
the 
mSLEDAI-2K assessment score without the inclusion of 
points attributable to hematuria, proteinuria, pyuria, urinary 
casts, low complement, increased DNA binding, and 
thrombocytopenia. 
5. 
PGA score ≥ 1.0 on a 0 to 3 VAS. 
6. 
Currently treated with one or more of the following SLE 
background medications: 
• Antimalarials: (≤ 400 mg/day hydroxychloroquine, 
≤ 500 mg/day chloroquine, ≤ 100 mg/day quinacrine), 
• Mycophenolate mofetil (≤ 2 g/day) / mycophenolic acid 
(≤ 1.44 g/day), 
• Azathioprine (≤ 2 mg/kg/day), 

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• Methotrexate (≤ 25 mg/week), 
• Oral corticosteroid(s) (OCS): 
– If OCS is the only SLE background medication: 
≥ 7.5 mg/day and ≤ 30 mg/day prednisone or 
equivalent.  
– If OCS is not the only SLE background medication: 
≤ 30 mg/day prednisone or equivalent. 
• Belimumab (≤ 10 mg/kg every 4 weeks intravenously 
[i.v.] or ≤ 200 mg/week subcutaneously [s.c.]). 
• Telitacicept (≤ 240 mg/week subcutaneously). 
Treatment 
with 
antimalarials, 
mycophenolate 
mofetil, 
mycophenolic acid, azathioprine, methotrexate, belimumab, or 
telitacicept must have been started at least 90 days prior to 
Screening.  
Treatment with OCS must have been started at least 30 days prior 
to Screening. 
7. 
For women of childbearing potential (WoCBP): 
• Negative serum pregnancy test at Screening. 
• Agreement to undertake monthly urine pregnancy tests 
from Day 1 up to 6 months after study treatment 
discontinuation. 
• Agreement to use a highly effective method of 
contraception from Screening (Visit 1) up to 6 months 
after study treatment discontinuation. 
Day 1 pre-dose criteria 
8. 
A clinical mSLEDAI-2K score ≥ 4 with at least 2 points for 
musculoskeletal or mucocutaneous manifestations (i.e., 
myositis, arthritis, rash, alopecia, mucosal ulcers). 
9. 
PGA score ≥ 1.0 on a 0 to 3 VAS. 
10. Presence of at least one of the following biomarkers of 
serological evidence of active SLE (in a Screening sample as 
measured by central laboratory): 
• Anti-dsDNA antibodies elevated above normal. 
• Antinuclear antibodies (ANA) with a titer of at least 1:160. 

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• Anti-Smith (anti-Sm) antibody elevated above normal. 
11. Currently treated with one or more of the following SLE 
background medications that must be stable for at least 
30 days prior to Day 1 (except OCS, which must be stable 
for at least 15 days prior to Day 1): 
• Antimalarials (≤ 400 mg/day hydroxychloroquine, 
≤ 500 mg/day chloroquine, ≤ 100 mg/day quinacrine), 
• Mycophenolate mofetil (≤ 2 g/day) / mycophenolic acid 
(≤ 1.44 g/day), 
• Azathioprine (≤ 2 mg/kg/day), 
• Methotrexate (≤ 25 mg/week), 
• OCS: 
– If OCS is the only SLE background medication: 
≥ 7.5 mg/day and ≤ 30 mg/day prednisone or 
equivalent.  
– If OCS is not the only SLE background medication: 
≤ 30 mg/day prednisone or equivalent. 
• Belimumab (≤ 10 mg/kg every 4 weeks i.v. or 
≤ 200 mg/week s.c.);  
• Telitacicept (≤ 240 mg/week subcutaneously). 
12. WoCBP must have a negative urine pregnancy test.  
EXCLUSION 
CRITERIA 
Pregnancy and breastfeeding 
1. 
Pregnant, planning to be become pregnant up to 6 months 
after the last dose of cenerimod in this study, or lactating 
women.  
SLE and other immune diseases 
2. 
Active severe SLE-driven renal disease (within 90 days prior 
to Screening or during Screening) where, in the judgment of 
the investigator, protocol-specified SLE background therapy 
is insufficient and the use of a more aggressive therapeutic 
approach or other treatments not permitted in the protocol is 
indicated.  
3. 
Urine 
protein/creatinine 
ratio 
> 3000 mg/g 
(i.e., > 339.45 mg/mmol) at Screening assessment based on 
central assessment. 

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4. 
Severe active central nervous system lupus or active severe 
or unstable neuropsychiatric SLE including but not limited 
to: aseptic meningitis; cerebral vasculitis; myelopathy; 
demyelination syndromes (ascending, transverse, acute 
inflammatory demyelinating polyradiculopathy); acute 
confusional state; impaired level of consciousness; 
psychosis; acute stroke or stroke syndrome; cranial 
neuropathy; status epilepticus; cerebellar ataxia; or 
mononeuritis multiplex: 
• That would make the participant unable to fully 
understand the ICF.  
 
or  
• Where, in the opinion of the investigator/delegate, 
protocol-specified standard of care is insufficient and the 
use of a more aggressive therapeutic approach, such as 
adding i.v. cyclophosphamide and/or high dose i.v. pulse 
corticosteroid (CS) therapy or other treatments not 
permitted in the protocol is indicated. 
5. 
Severe forms of vasculitis (e.g., retinal vasculitis, coronary 
vasculitis, pulmonary vasculitis, mesenteric vasculitis) 
requiring systemic immunosuppressive treatment within 
90 days prior to Screening or during Screening. 
6. 
A diagnosis of mixed connective tissue disease or any history 
of overlap syndromes of SLE with psoriasis, rheumatoid 
arthritis, 
erosive 
arthritis, 
scleroderma, 
autoimmune 
hepatitis, or uncontrolled autoimmune thyroid disease.  
Cardiovascular 
7. 
History or presence of Mobitz type II or third-degree 
atrioventricular block, sick sinus syndrome, symptomatic 
bradycardia, or syncope associated with cardiac disorders. 
8. 
Participants 
who 
experienced 
myocardial 
infarction, 
unstable angina pectoris, stroke, transient ischemic attack, 
vascular thrombosis, decompensated heart failure requiring 
hospitalization, or heart failure defined by the New York 
Heart Association Class III/IV (see Appendix 14) within 6 
months prior to Screening.  

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9. 
Resting HR < 50 beats per minute as measured by the 12-lead 
ECG at Screening or at Day 1 prior to study treatment 
administration. 
10. An elevated QTcF interval of > 470 ms (females) / > 450 ms 
(males) at Screening or at Day 1 prior to study treatment 
administration.  
Pulmonary 
11. History or presence of severe respiratory disease or 
pulmonary fibrosis, based on medical history, lung function, 
and chest X-ray (or CT scan as per local guidelines), 
performed at Screening or within 6 months prior to 
Screening. 
12. History of clinically relevant bronchial asthma or chronic 
obstructive pulmonary disease that has required treatment 
with oral or parenteral CS for more than a total of 2 weeks 
within the last 6 months prior to Screening. 
Infection and infection risk 
13. Have had household contact with a person with active 
Tuberculosis (TB) and did not receive appropriate and 
documented prophylaxis for TB.  
14. Have evidence of active TB or latent TB 
a. Active TB: Have evidence of active TB, defined in this 
study as the following: 
• Medical history, clinical features, and abnormal chest X-
ray at Screening indicating the presence of TB. 
• IFN gamma release assay (IGRA): participants are 
excluded from the study if the test is not negative and there 
is clinical evidence of active TB.  
 
Exception 1: participants with a history of active TB who 
have documented evidence of appropriate treatment, have no 
history of re-exposure since their treatment was completed, 
have no clinical features of active TB, and have a Screening 
chest X-ray with no evidence of active TB may be enrolled 
if other entry criteria met. Such participants would not be 
required to undergo the IGRA test, but must have a chest X-
ray at Screening (i.e., chest imaging performed within the 
past 6 months will not be accepted).  
 

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b. Latent TB: Have evidence of untreated/inadequately or 
inappropriately treated latent TB, defined in this study as the 
following:  
• An IGRA test which is not negative, no clinical features 
consistent with active TB, and a chest X-ray with no 
evidence of active TB at Screening;  
• If the IGRA test results are positive, the participant will 
be considered to have latent TB. If the test is not negative, 
the test may be repeated once within approximately 2 
weeks of the initial value. If the repeat test results are 
again not negative, the participant will be considered to 
have latent TB (for purposes of this study). 
 
Exception 2: participants with a history of latent TB who 
have documented evidence of appropriate treatment, have no 
history of re-exposure since their treatment was completed, 
have no clinical features of active TB, and have a Screening 
chest X-ray with no evidence of active TB may be enrolled 
if other entry criteria met. Such participants would not be 
required to undergo the IGRA test, but must have a chest X-
ray at Screening (i.e., chest imaging performed within the 
past 6 months will not be accepted). 
15. Ongoing bacterial, viral, parasitic, or fungal infection that is 
of clinical concern according to the investigator or any of the 
following:  
• Clinically 
significant 
chronic 
infection 
(e.g., 
osteomyelitis, bronchiectasis, etc.) within 8 weeks prior to 
Screening (chronic nail infections are allowed). 
• Any infection requiring hospitalization or treatment with 
i.v. anti-infectives not completed at least 4 weeks prior to 
Screening.  
16. Positive results for serological markers for hepatitis A, B, C, 
and E indicating acute or chronic infection: 
• Anti-hepatitis A virus (HAV) immunoglobulin M (IgM). 
• Hepatitis B surface antigen. 
• Anti-hepatitis C virus (HCV) IgG or IgM (if positive IgM 
and/or IgG, to be confirmed by HCV-RNA polymerase 

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chain reaction assessment, and if this assessment is 
negative, participant can be enrolled). 
• Anti-hepatitis E virus (HEV) IgG or IgM (if positive IgM 
and/or IgG, to be confirmed by HEV-RNA polymerase 
chain reaction, and if this assessment is negative, 
participant can be enrolled). 
17. Participants who have congenital or acquired severe 
immunodeficiency or known human immunodeficiency 
virus (HIV) infection or positive HIV testing.  
18. Negative IgG antibody test for varicella-zoster virus. 
Malignancy 
19. History or presence of malignancy (except for surgically 
excised and non-recurrent cutaneous basal cell carcinoma, 
squamous 
cell 
carcinoma, 
or 
cervical 
carcinoma), 
lymphoproliferative disease, or history of total lymphoid 
irradiation within 10 years prior to Screening. 
Transplantation 
20. History or presence of homologous (allogenic) bone marrow 
or solid organ transplantation. 
Ophthalmologic 
21. Presence of macular edema or active uveitis detected by 
optical coherence tomography (OCT) during Screening. 
Metabolic 
22. Documented poorly controlled diabetes mellitus (i.e., 
glycated hemoglobin > 8.0% at Screening as reported by the 
central laboratory or unstable blood sugar control/treatment 
adherence as per investigator’s judgment) or diabetes 
mellitus complicated with organ involvement, such as 
diabetic nephropathy or retinopathy as assessed by 
investigator. 
Hepatic 
23. History of chronic liver or biliary disease (other than 
Gilbert’s 
Syndrome) 
or 
participants 
with 
alanine 
aminotransferase or aspartate aminotransferase > 3 × upper 

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limit of normal or total bilirubin > 1.5 × upper limit of 
normal (unless in the context of known Gilbert’s Syndrome). 
Hematology 
24. Significant 
hematology 
abnormality 
at 
screening 
assessment:  
• Lymphocyte count < 500 /μL (0.5 × 109/L); 
• Hemoglobin < 7 g/dL;  
• White blood cell count < 2000/μL (2.0 × 109/L) or  
• Platelets < 25,000/μL (25 × 109/L). 
Renal 
25. Estimated glomerular filtration rate < 15 mL/min/1.73 m2. 
Medications 
26. Treatment with the following medications within 15 days or 
5 half-lives of the medication (whichever is longer) prior to 
Day 1: 
• β-blockers, diltiazem, verapamil, digoxin, digitoxin, or 
any other anti-arrhythmic or HR-lowering systemic 
therapy. 
• QT-prolonging drugs with known risk of torsade de 
pointes irrespective of indication. 
27. Treatment with the following medications within 30 days or 
5 half-lives of the medication (whichever is longer) prior to 
Day 1: 
• Cyclophosphamide, cyclosporine, voclosporin, 
tacrolimus, sirolimus, etc. 
• Pulse methylprednisolone. 
• Vaccination with live vaccines. 
28. Intra-articular, intramuscular or i.v. CS within 6 weeks prior 
to Day 1. 
29. Treatment with the following medications within 90 days or 
5 half-lives of the medication (whichever is longer) prior to 
Day 1: 
• Leflunomide. 

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• i.v. immunoglobulins. 
30. Treatment with any investigational agent within 90 days or 
5 half-lives of the drug (whichever is longer) prior to Day 1. 
31. Treatment with B cell-depleting biological agents (e.g., 
rituximab or ocrelizumab) or biological immunosuppressive 
agents (e.g., anti-tumor necrosis factor, anti-interleukin-
[IL]1, anti-IL-6 therapies), within 12 months prior to Day 1. 
32. Treatment with anifrolumab within 6 months prior to Day 1. 
33. Treatment with any of the following medications any time 
prior to Screening: 
• Alemtuzumab. 
• Sphingosine-1-phosphate (S1P) receptor modulators (e.g., 
fingolimod). 
• Participants previously randomized to cenerimod or 
placebo in any trial involving cenerimod. 
Other categories 
34. Recent clinically significant drug or alcohol abuse as per 
investigator’s judgment. 
35. Known allergy to S1P receptor modulators or any of the 
cenerimod formulation excipients. 
36. Any other clinically relevant medical condition that would 
put the participant at risk if participating in the study, or any 
other diseases that may confound the disease activity 
assessments. 
37. Participants with body weight < 40 kg at Screening or Day 1. 
STUDY 
TREATMENTS 
Investigational treatment  
Cenerimod is supplied as film-coated tablets at the dose of 4 mg.  
Study treatment dosing and administration 
One tablet of cenerimod will be taken orally once daily, 
irrespective of food intake. The tablet should be taken each day in 
the morning. 
CONCOMITANT 
THERAPY 
Allowed background SLE therapy  
See inclusion criteria 6 and 11. 

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SLE background therapy (except OCS) 
Background SLE therapy must have been started at least 90 days 
prior to Screening and must be stable for at least 30 days prior to 
Day 1.  
Any post-Day 1 change of background medication has the 
potential to obviate the treatment effect and efforts should be 
made to adjust background medication during the screening 
period prior to Day 1.  
After Day 1 study treatment administration, SLE background 
medications and route of administration must not change. Dose 
must remain stable from Day 1 to the completion of Month 12 but 
may be decreased for toxicity reasons or to optimize management 
of an AE, such as infection. The toxicity/event must be reported 
as an AE and the change of dose entered in the electronic case 
report form (eCRF). The dose can be returned to the Day 1 level 
if the toxicity/event resolves and if clinically indicated.  
Antimalarials/immunosuppressants (including dose, frequency, 
and route of administration) should not be changed if a participant 
has increased SLE disease activity during the OCS tapering 
period. 
OCS management 
OCS management and dose optimization during Screening 
(Visit 1 up to Visit 2): 
Participants will be eligible if background OCS dose is ≤ 30 
mg/day of prednisone or equivalent. If OCS is the only SLE 
background medication, OCS dose must be ≥ 7.5 mg/day and ≤ 
30 mg/day of prednisone or equivalent (see inclusion criteria 6 
and 11). Treatment with OCS must have been started at least 30 
days prior to Screening and must be stable for at least 15 days 
prior to Day 1.  
Investigators are encouraged to enroll participants that have 
optimized OCS usage prior to Screening. 
Dose reductions are at the investigator’s discretion. The OCS dose 
must be stable for 15 days prior to Day 1. For the purpose of 
standardization, background OCS therapy is recommended to be 

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prednisone, methylprednisolone, or prednisolone during the 
study.  
At Day 1 
When OCS is not the only SLE background medication, the OCS 
dose must be ≤ 30 mg/day background prednisone or equivalent 
(see inclusion criteria 6 and 11). 
When OCS is the only SLE background medication, the OCS dose 
must be between ≥ 7.5 mg/day and ≤ 30 mg/day prednisone or 
equivalent.  
During study treatment period 
Change in OCS dose should be restricted to:  
• medically justified safety reasons, and  
• protocol-specified rules (see below).  
The justification and nature of any change in OCS dose should be 
thoroughly documented in the participant’s medical records. 
Protocol-specified rules for changes in CS dose 
From Visit 2 up to Visit 5: Recommended stable OCS dose 
The OCS dose should be kept stable. The investigator is 
encouraged to only change the OCS dose in the following 
situation: 
• In participants with SLE disease activity improvement for at 
least 4 consecutive weeks (i.e., between 2 consecutive visits), 
an OCS dose decrease is allowed using the tapering schedule 
detailed in the protocol but is not mandatory. SLE disease 
activity improvement is defined as the British Isles Lupus 
Assessment Group-2004 (BILAG) reduction of all A scores to 
B/C/D scores and the reduction of all B scores to C/D scores, 
and no worsening score in other organ systems, as defined by 
≥ 1 new A score or ≥ 2 new B score. 
From Visit 5 up to Visit 10: Mandatory OCS tapering 
For participants with OCS dose ≥ 10 mg/day at Day 1, steroid 
tapering to an OCS dose of ≤ 7.5 mg/day MUST be attempted as 
per the algorithm in the protocol and started within 14 days after 

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Visit 5. Tapering should not be attempted if at least 1 of the 
following criteria is met:  
• Worsening of SLE disease activity defined as ≥ 1 new 
BILAG A or ≥ 2 new BILAG B scores (except 
mucocutaneous and musculoskeletal domains). 
• Moderate-to-severe skin disease as reflected by a Cutaneous 
Lupus Erythematosus Disease Area and Severity Index 
activity score of ≥ 10. 
• Moderate-to-severe arthritis disease as reflected by an active 
joint count of ≥ 4 tender and/or swollen joints. 
If a participant fails tapering down on the first attempt, an increase 
of OCS dose up to the dose before the start of the forced tapering 
is allowed. Another attempt to taper down OCS might be done 
unless at least 1 of the above criteria is met. 
If steroid tapering is not attempted in an eligible participant, the 
sponsor must be contacted immediately. The recommended 
steroid tapering regimen is detailed in the protocol, but due to 
variability in participant responses to steroid treatment and 
tolerability of taper, investigators will have flexibility in how the 
OCS dose is reduced at each visit.  
Investigators will not be required, but may continue, to taper the 
OCS dose below 7.5 mg/day up to Visit 10.  
From Visit 2 to Visit 10, participants who experience an increase 
in SLE disease activity may receive one (and only one) CS burst 
as follows: 
• OCS increase up to a maximum daily dose of 40 mg/day 
prednisone or equivalent up to a total of 14 days. This OCS 
increase must be fully administered and tapered to less than or 
equal to the Day 1 (Visit 2) by no later than Visit 10. 
or 
• Intramuscular methylprednisolone (≤ 80 mg or equivalent) 
administered as a single dose. 
or 
• A maximum of 2 intra-articular / tendon sheath / bursal 
injections (for a total methylprednisolone ≤ 80 mg or 
equivalent) at the same visit.  

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Steroid tapering will not be permitted after Visit 10. 
From Visit 10 to Visit 14: Mandatory stable OCS dosage  
OCS dosage must be stable unless medically justified by the 
investigator. No increase in OCS is allowed after Visit 10 except 
for managing AEs or as prophylaxis for adrenal insufficiency.  
Other allowed concomitant therapies: 
• Atropine (i.v.) in the event of symptomatic bradycardia. 
• Topical ocular therapy (e.g., chronic treatment for glaucoma, 
ocular inflammation, allergy), including dilating eye drops, 
mydriatics, parasympathetic antagonists (e.g., tropicamide) or 
sympathetic agonists (e.g., phenylephrine). 
• Vaccination with non-live vaccines. 
• Topical treatment therapy including topical (skin), inhaled, 
and nasal use of CS. 
• Nonsteroidal anti-inflammatory drugs (NSAIDs). 
– If used for treatment of SLE, NSAIDs must be stable for 
a period of at least 30 days prior to Day 1 and must 
remain stable throughout the study but can be reduced for 
reasons of toxicity but not efficacy. 
– Temporary use and/or dose change for treatment of 
non-SLE-related conditions (e.g., headache, menstrual 
cramps) is allowed.  
– NSAIDs cannot be used in combination with another 
NSAID at any dose, except low-dose aspirin 
(≤ 325 mg/day). 
– Topical NSAIDs may be used in combination with one 
oral NSAID. 
– On a given scheduled visit day, NSAIDs should not be 
taken until after all assessments have been completed. 
• Stable long-term use of low-dose aspirin (maximum of 
325 mg/day) for cardiovascular disease is permitted.  
• Temporary 
use 
of 
pain 
medications 
(e.g., 
acetaminophen/paracetamol or other non-NSAID pain 
medication) may be used for pain as required, based on the 
investigator judgment for up to 1 week at a time and should 
not be taken on the day of a scheduled visit until all 
assessments have been completed.  

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• All other medications that are not forbidden. 
Forbidden concomitant therapies:  
• Immunosuppressive agents not listed as allowed concomitant 
medications, such as cyclophosphamide, cyclosporine, 
voclosporin, leflunomide, sirolimus, tacrolimus, etc.  
• Immunosuppressive or immunomodulatory biological agents 
(e.g., i.v. immunoglobulin, anifrolumab, rituximab, etc.). 
• S1P receptor modulators other than cenerimod. 
• β-blockers, diltiazem, verapamil, digoxin, digitoxin, or any 
other anti-arrhythmic or HR-lowering therapy. 
• QT-prolonging drugs with known risk of torsade de pointes. 
• Vaccination with live vaccines. 
• Inhibitors of the breast cancer resistance protein transporter: 
curcumin, cyclosporine, eltrombopag, elacridar, gefitinib, 
teriflunomide. 
• Cannabidiol and other derivatives of marijuana. 
• Investigational agents. 
STATISTICAL 
METHODOLOGY 
Analysis of safety endpoints 
Descriptive analysis of safety endpoints will be performed using 
the safety analysis set (SS). The SS includes all participants who 
received at least 1 dose of study treatment. 
Adverse events  
AEs will be coded using the Medical Dictionary for Drug 
Regulatory Activities (MedDRA). The number (%) of 
participants experiencing a treatment-emergent AE (including 
SAEs, AESIs, and AEs leading to premature discontinuation of 
the study treatment) will be summarized by system organ class 
(SOC) and/or preferred term (PT), and maximum intensity. A 
participant with multiple occurrences of an AE is counted only 
once in the AE category (e.g., SOC, PT).  
Vital signs and electrocardiograms during post-dose cardiac 
monitoring on Day 1 
Observed values and changes in vital signs (SBP and DBP) and 
12-lead ECG variables, including HR and QTcB and QTcF 
intervals, from baseline to all post-dose assessments will be 

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summarized. The number (%) of participants with a marked ECG 
abnormality will be tabulated. The number of participants 
discharged at 12 h will be summarized. For participants not 
discharged, reasons for not being discharged will be summarized.  
Vital signs and body weight  
Observed values and changes in vital signs (SBP and DBP) and 
body weight from baseline to all scheduled post-baseline visits 
will be summarized. 
Electrocardiograms  
Observed values and changes for each 12-lead ECG variable (HR 
and the PR, QRS, QTcB, and QTcF intervals) from baseline to all 
scheduled post-baseline visits will be summarized. The number 
(%) of participants with a marked ECG abnormality will be 
tabulated. 
Laboratory data  
Observed values for all scheduled post-baseline visits in 
hematology, blood chemistry, and urinalysis laboratory variables 
will be summarized. The number (%) of participants with a 
marked laboratory abnormality will be tabulated. 
Analysis of PK and PD endpoints 
PK and PD data will be analyzed descriptively. These analyses 
are detailed in the statistical methods section. 
Analysis of efficacy endpoints 
Efficacy data will be analyzed descriptively. These analyses are 
detailed in the statistical methods section. 
STUDY 
COMMITTEE 
An Independent Ophthalmology Safety Board (IOSB) will 
receive all information related to suspected cases of macular 
edema and will perform a central review of OCT images and 
participants’ data of suspected cases of macular edema as per the 
IOSB charter. 
 

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1.2 Schema 
The study design is depicted in Figure 1. 
Figure 1 
Study design  
 
 
 
 
OCS = oral corticosteroid(s) 
 
Screening 
Up to 30 days 
OCS 
optimization 
OCS stable 
(3 months) 
OCS tapering 
(5 months) 
OCS stable 
(4 months) 
6-month follow-up period 
Cenerimod 4 mg o.d. 
Treatment up to 12 months 

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1.3 Schedule of activities 
The visit schedule and protocol-mandated activities are performed according to the SoA 
Table 1 Table 2 and Table 3 and are described in Section 7. 
Table 1 
Schedule of activities at Screening  
PERIODS 
Name 
SCREENING 
 
Duration 
Up to 30 days 
VISITS 
Number 
1 
 
Time window 
Day –30 to Day –1 
Contact IRT 
X 
Informed consent and participant’s lupus history 
 
Informed consent 
X 
Eligibility 
X 
Demographics 
X 
Medical history and SLE history (including 2019 EULAR/ACR criteria questionnaire) 
X 
SLE and previous/concomitant therapies 
X 
Medical examination and SLE disease activity 
 
Physical examination1, body weight 2 and height 
X 
Vital signs3  
X 
12-lead ECG3  
X 
Ophthalmological examinations 
X 
OCT 
X 
Chest X-ray / CT scan 4 
X 
SAEs / AEs  
X 
SLE disease activity 
 
mSLEDAI-2K 
X 
SFI 
X 
PGA 
X 
CLASI 
X 
Tender/swollen joint count 
X 
BILAG 
X 
Laboratory tests 
 
Serum pregnancy test 5 
X 
Labs (hematology/serum chemistry, coagulation and urine analyses)6,  
X 
HbA1c 
X 
Anti b2GP1 
X 
Blood test for TB 
X 
Hepatitis A, B, C, E 
X 
Varicella-zoster virus 
X 
HIV test 
X 
Anti-dsDNA, complement (C3, C4, CH50), ANA, anti-Smith 
X 

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1 Physical examination will only be performed at Visits 1, 2, 3, 5, 8, 11, 14, and 15. For all other visits, a symptom-driven 
abbreviated physical examination will be performed to capture assessments needed for the SLEDAI-2K, the PGA, 
the CLASI and the SFI. 
2 Body weight (measured under fasting conditions in the morning) should be recorded in the BILAG assessment page in 
the paper sheets at all visits in which this assessment is performed. It should also be recorded in the eCRF at Visits 
1, 14, and 20. 
3 At all visits, a single pre-dose 12-lead ECG will be performed and transmitted to the central reader. A pre-dose SBP/DBP 
will be performed at all visits (including Screening) in duplicate and both values, including the arm and position used, 
will be entered into the eCRF. 
4 If a chest X-ray or CT scan has been performed within 6 months prior to Screening and the results are available, there 
is no need to repeat the chest X-ray or CT scan at Screening. 
5 Only applicable for WoCBP. The serum pregnancy test at Visit 1 must be performed at least 3 weeks before the urine 
dipstick pregnancy test performed at Visit 2 prior to cenerimod intake. 
6 A central laboratory will be used for all protocol-mandated laboratory tests, including retests due to laboratory 
abnormalities and laboratory tests performed at unscheduled visits. Local laboratory tests may be required under 
exceptional circumstances and results should be recorded as unscheduled local laboratory in eCRF.  
AE = adverse event; ANA = antinuclear antibodies; anti-dsDNA = anti-double-stranded deoxyribonucleic acid; BILAG 
= British Isles Lupus Assessment Group-2004; CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity 
Index; CT = computed tomography; ECG = electrocardiogram; EULAR/ACR = European League Against 
Rheumatism/American College of Rheumatology; HbA1c = glycated hemoglobin; HIV = human immunodeficiency 
virus; IRT = Interactive Response Technology; mSLEDAI-2K = Modified Systemic Lupus Erythematosus Disease 
Activity Index-2000; OCT = Optical coherence tomography; PGA = Physician’s Global Assessment; SAE = serious 
adverse event; SFI = SLE Flare Index; SLE = systemic lupus erythematosus; TB = tuberculosis. 
 

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Table 2 
Schedule of activities after Screening  
PERIODS 
Name 
TREATMENT 
 
Duration 
12 months 
VISITS 
Number 
2 
3 
4, 6, 7, 9, 10, 12, 13 
5, 8, 11 
14 
 
Name 
1st  
 study drug 
administration 
Month 1 Months 2, 4, 5, 7, 8, 
10, 11  
Months 3, 6, 9 
Month 12 (EOT) / Premature 
EOT (pEOT)12, 13 
 
Time window 
Day 1 
Day 30  
(±2 days) 
Days 60, 120, 150, 
210, 240, 300, 330 
(±7 days) 
Days 90, 180, 270 
(±7 days) 
Day 360 (±7 days) / pEOT  
(from next day up to 7 days after 
last study treatment intake) 
To be performed at Day 1 only 
Eligibility 
X 
 
 
 
 
Day 1 cardiac monitoring 1 
X 
 
 
 
 
To be performed at all visits 
SLE and previous/concomitant therapies 
X 
X 
X 
X 
X 
Physical examination2 
X 
X 
X 
X 
X 
Body weight 3 
X 
X 
X 
X 
X 
mSLEDAI-2K, BILAG, SFI, PGA, CLASI, 
Tender/swollen joint count 2 
X 
X 
X 
X 
X 
Vital signs, 12-lead ECG 4, * 
X1 
X 
X 
X 
X 
Labs (hematology/serum chemistry5, 
coagulation and urine analyses)6, * 
X 
X 
X 
X 
X 
BILAG associated blood and urine samples 
(anti-cardiolipin, lupus anticoagulant 
haptoglobin, and Coombs) 7 
X 
X 
X 
X 
X 
Urine pregnancy test 8 
X 
X 
X 
X 
X 
Contact IRT 
X 
X 
X 
X 
X 
Study treatment dispensing/return and 
accountability 
X 
X 
X 
X 
X 
SAEs/AEs9 
X 
X 
X 
X 
X 

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PERIODS 
Name 
TREATMENT 
 
Duration 
12 months 
VISITS 
Number 
2 
3 
4, 6, 7, 9, 10, 12, 13 
5, 8, 11 
14 
 
Name 
1st  
 study drug 
administration 
Month 1 Months 2, 4, 5, 7, 8, 
10, 11  
Months 3, 6, 9 
Month 12 (EOT) / Premature 
EOT (pEOT)12, 13 
 
Time window 
Day 1 
Day 30  
(±2 days) 
Days 60, 120, 150, 
210, 240, 300, 330 
(±7 days) 
Days 90, 180, 270 
(±7 days) 
Day 360 (±7 days) / pEOT  
(from next day up to 7 days after 
last study treatment intake) 
To be performed at specific visits 
Site visit study treatment administration10 
X 
X 
X  
X 
 
Ophthalmological examinations11 
 
 
 
X (Months 3, 6 only) 
X 
OCT11 
 
 
 
X (Months 3 and 6 only) 
X 
PK sampling 
Pre-dose*, and 1, 
2, 3, 4, 5, 6, 7, 8, 
10, 12, and 24 h 
after the first dose 
Pre-dose* 
Pre-dose*, and 1, 2, 
3, 4, 5, 6, 7, 8, 10, 12 
and 24 h after dosing 
(Month 2 only); 
Pre-dose* (Month 4 
only)  
Pre-dose* (Month 6 only) 
X 
SLE biomarkers in PAXgene samples  
X 
 
 
X (Month 6 only) 
X 
Anti-dsDNA, complement (C3, C4, CH50)  
X 
X 
X 
X 
X 
ANA 
X 
 
 
X 
X 
Anti-Smith 
X 
 
 
 
 
IFN-alpha sample 
X 
 
 
X (Month 6 only) 
X 
 

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PERIODS 
Name 
FOLLOW-UP6 
UNSCHEDULED 
 
Duration 
6 months 
NA 
VISITS 
Number 
15 
16, 17, 18, 19 
20 (FSV) 
U1, U2, … 
RI 
 
Name 
FU1 
FU2, FU3, FU4, 
FU5 
Phone call 
Final study 
visit 
Unscheduled15 
Re-initiation 
 
Time window 
1 month after 
last study 
treatment 
intake 
(±7 days) 
Monthly after FU1  
(±7 days) 
6 months after 
last study 
treatment 
intake 
(±7 days) 
Any day between ICF 
signature and FSV 
(assessments to be 
performed as applicable) 
Re-initiating study treatment 
after interruption lasting more 
than 7 days between Day 1 and 
Day 14 
To be performed at all visits 
SAEs/AEs9 
X 
X 
X 
X 
X 
To be performed at specific visits 
SLE and concomitant therapies 
X 
X 
X 
X 
X 
Physical examination2 
X 
 
X 
X 
X 
Body weight3 
 
 
X 
X 
 
mSLEDAI-2K, BILAG, SFI, PGA, 
CLASI, Tender/swollen joint count  
 
 
 
X 
 
Vital signs, 12-lead ECG 4 
X 
 
X 
X 
X1 
Ophthalmological examinations 
 
 
X 
X 
 
OCT 
 
 
 
X 
 
Labs (hematology/blood chemistry5, 
urine analyses)6 
X 
 
X 
X 
 
Labs (coagulation)6 
 
 
 
X 
 
BILAG associated blood and urine 
samples (anti-cardiolipin, lupus 
anticoagulant, haptoglobin, and 
Coombs) 7 
 
 
 
X 
 
Serum pregnancy test 8 
 
 
X 
X 
 
Urine pregnancy test14 
X 
X 
 
 
 
Viral serology / TB test 
 
 
 
X 
 
PK sampling 
 
 
X 
 
 

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PERIODS 
Name 
FOLLOW-UP6 
UNSCHEDULED 
 
Duration 
6 months 
NA 
VISITS 
Number 
15 
16, 17, 18, 19 
20 (FSV) 
U1, U2, … 
RI 
 
Name 
FU1 
FU2, FU3, FU4, 
FU5 
Phone call 
Final study 
visit 
Unscheduled15 
Re-initiation 
 
Time window 
1 month after 
last study 
treatment 
intake 
(±7 days) 
Monthly after FU1  
(±7 days) 
6 months after 
last study 
treatment 
intake 
(±7 days) 
Any day between ICF 
signature and FSV 
(assessments to be 
performed as applicable) 
Re-initiating study treatment 
after interruption lasting more 
than 7 days between Day 1 and 
Day 14 
SLE biomarkers in PAXgene samples 
 
 
X 
X 
 
IFN-alpha sample 
 
 
X 
X 
 
Anti-dsDNA, complement (C3, C4, 
CH50) 
 
 
X 
X 
 
ANA 
 
 
X 
X 
 
Anti-Smith 
 
 
X 
X 
 
Study treatment dispensing/return and 
accountability 
 
 
 
 
X 
One month is considered to be 30 days. 
Day 1 is to be used as the reference date for the purpose of calculating the subsequent visit dates (and time windows). 
* Study treatment should not be taken before the assessment (i.e., SBP/DBP, ECGs, laboratory tests and PK sampling). 
1 The post dose 12-lead ECGs assessments will be measured once at each hourly time point within 12 hours post-dose, while SBP/DBP assessments will be measured once 
at each hourly time point within 6 hours post-dose and at 12 hours post-dose at Visit 2 (Day 1) and at study treatment re-initiation. At the 12-hour post-dose timepoint, 
participants may be discharged from the monitored setting if they meet the pre-specified discharge criteria. For discharge criteria see Appendix 5. 
2 Physical examination will only be performed at Visits 1, 2, 3, 5, 8, 11, 14, and 15. For all other visits, a symptom-driven abbreviated physical examination will be 
performed to capture assessments needed for the SLEDAI-2K, the PGA, the BILAG, the CLASI and the SFI. 
3 Body weight (measured under fasting conditions in the morning) should be recorded in the BILAG assessment page in the paper sheets at all visits in which this assessment 
is performed. It should also be recorded in the eCRF at Visits 1, 14, and 20. 
4 At all visits, a single pre-dose 12-lead ECG will be performed and transmitted to the central reader. A pre-dose SBP/DBP will be performed at all visits (including 
Screening) in duplicate and both values, including the arm and position used, will be entered into the eCRF. 
5 Aldolase to be measured only at investigator’s request. 
6 A central laboratory will be used for all protocol-mandated laboratory tests, including retests due to laboratory abnormalities and laboratory tests performed at unscheduled 
visits. Local laboratory tests may be required under exceptional circumstances and results should be recorded as unscheduled local laboratory in eCRF. 

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7 For some tests associated with BILAG, samples will be collected and sent to the central laboratory. The analysis of the sample will only be done upon request of the 
investigator. The following blood tests must be performed at Day 1 pre-dose but are optional at all other visits: cardiolipin IgA, IgG and IgM antibodies and lupus 
anticoagulant. Haptoglobin is optional at all visits. 
8 Only applicable for WoCBP. The serum pregnancy test at Visit 1 must be performed at least 3 weeks before the urine dipstick pregnancy test performed at Visit 2. 
9 All AEs and SAEs that occur after signing the informed consent form and up to 6 months after study treatment discontinuation must be reported. 
10 Study treatment should be administered at the site from study treatment dispensed on the day of the visit, after study assessments have been performed. 
11 Ophthalmological examination and OCT may be performed up to 7 days prior to the visit date but no later than 7 days after the visit. 
12 All participants will be asked to return for an EOT visit. For participants who permanently discontinued study treatment, the pEOT visit will occur within 7 days of last 
intake of study treatment and participants will thereafter attend PTOP visits [see Table 3]. If a pEOT visit occurs within 7 days of a scheduled PTOP visit, this PTOP 
visit should be skipped. For all other participants, the EOT visit will coincide with Visit 14. 
13 After completion of the Month 12 visit, participants will be asked to complete the follow-up period. 
14 For Visits 16–19, the site will dispense urine pregnancy kits to WoCBP and collect the results during the scheduled phone call. If a urine test is positive, the participant 
will be instructed to return to the site for a serum pregnancy test. 
15 During unscheduled visits, any additional assessments considered necessary by the investigator may be performed. 
 
AE = adverse event; ANA = antinuclear antibodies; anti-dsDNA = anti-double-stranded deoxyribonucleic acid; BILAG = British Isles Lupus Assessment Group-2004; 
bpm = beats per minute; CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index; DBP = diastolic blood pressure; ECG = electrocardiogram; 
eCRF = electronic case report form; EDTA = ethylenediaminetetraacetic acid; EOT = End-of-Treatment; FSV = final study visit; FU = follow-up; IFN-1 = Type 1 
interferon; IRT = Interactive Response Technology; mSLEDAI-2k = modified Systemic Lupus Erythematosus Disease Activity Index-2000; OCT = optical 
coherence tomography; pEOT = premature End-of-Treatment or permanent discontinuation of study treatment; PGA= Physician’s Global Assessment; 
PK = pharmacokinetic; PTOP = post-treatment observation period; RI = re-initiation; SAE = serious adverse event; SBP = systolic blood pressure; SFI = SLE Flare 
Index; SLE = systemic lupus erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index-2000; TB = tuberculosis, WoCBP = women of 
childbearing potential. 
 

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Table 3 
Schedule of activities: PTOP (applicable to participants who permanently discontinue study treatment 
PERIODS 
Name 
POST-TREATMENT OBSERVATION 
 
Duration 
Up to 12 months1 
Up to 6 months1 
PTOP VISITS1 
Number 
PTOP 3, 4, 6, 7, 9, 10, 
12, 131 
PTOP 5, 8, 11, 141 
PTOP 151 
PTOP 16, 17, 18, 191 
PTOP 20 / FSV1 
 
Name 
Months 1, 2, 4, 5, 7, 8, 
10, 11 
Months 3, 6, 9, 12 
FU Month 1 
FU Months 2, 3, 4 and 5 
Phone call 
FU Month 6 
 
Time window 
Days 30, 60, 120, 150, 
210, 240, 300, 330 
(±7 days) 
Days 90, 180, 270, 360 
(±7 days) 
1 month after last 
dose 
(±7 days) 
Monthly after PTOP 
FU1 
(±7 days) 
6 months after last 
dose 
(±7 days) 
To be performed at all visits 
Pregnancy test 2 
X 
X 
X 
X 
X 
SAEs/AEs 
X 
X 
X 
X 
X 
SLE concomitant therapies 
X 
X 
X 
X 
X 
To be performed at specific visits 
Physical examination 
X 
X 
X 
 
X 
Body weight3 
X 
X (Month 12) 
 
 
X 
mSLEDAI-2K, BILAG, SFI, PGA, 
CLASI, tender/swollen joint count,  
X 
X 
 
 
 
Vital signs, 12-lead ECG 
X 
X 
X 
 
X 
Ophthalmological examinations 
 
X (Months 3, 6, 12) 
 
 
X 
OCT 
 
X (Months 3, 12) 
 
 
 
Labs (hematology/blood chemistry, 
urine analyses)4 
X 
X 
X 
 
X 
Anti-dsDNA, complement (C3, C4, 
CH50) 
X 
X 
 
 
X 
ANA 
 
X 
 
 
X 
Anti-Smith 
 
 
 
 
X 
1 Participants who permanently discontinue study treatment will attend PTOP visits starting at the visit following the permanent treatment discontinuation as follows:  
• 
Participants who permanently discontinue before or at Month 6 will complete study visits until Month 12 and the FSV will be at Month 12 (i.e., PTOP Visit 
14).  
• 
Participants who permanently discontinue between Month 7 and Month 12 (both inclusive), will complete PTOP FU visits until at least 6 months after last 
study treatment intake and the FSV will be one of the monthly PTOP FU visits, as applicable. 

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2 Only applicable for WOCBP. A serum pregnancy test for participants who permanently discontinue study treatment before or at Month 6 will be performed and analyzed 
centrally at Month 12 (i.e., PTOP Visit 14). A serum pregnancy test for participants who permanently discontinue study treatment between Month 7 and Month 12 
(both inclusive) will be performed and analyzed centrally at FSV, i.e., 6 months after last study treatment intake. Urine pregnancy tests will be performed at all other 
visits with kits provided by the site. 
3 Body weight should be measured as part of BILAG assessment at each applicable visit and recorded in the source documentation. It should also be recorded in the 
eCRF at PTOP 14 and 20. 
4 A central laboratory will be used for all protocol-mandated laboratory tests, including retests due to laboratory abnormalities and laboratory tests performed at 
unscheduled visits. 
AE = adverse event; ANA = antinuclear antibodies; anti-dsDNA = anti-double-stranded deoxyribonucleic acid; BILAG = British Isles Lupus Assessment Group-2004; 
CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index; ECG = electrocardiogram; eCRF = electronic case report form; FU = follow-up; 
FSV = final study visit; mSLEDAI-2k = modified Systemic Lupus Erythematosus Disease Activity Index-2000; OCT = optical coherence tomography; 
PGA = Physician’s Global Assessment; PTOP = post-treatment observation period; SAE = serious adverse event; SFI = SLE Flare Index; SLE = systemic lupus 
erythematosus; SLEDAI-2K = Systemic Lupus Erythematosus Disease Activity Index-2000; WoCBP = women of childbearing potential. 
 
 
 

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2 
INTRODUCTION 
2.1 Indication 
Systemic lupus erythematosus 
SLE is an autoimmune disease of unknown etiology, characterized by the production of 
pathogenic autoantibodies, tissue deposition of immune complexes, and tissue damage 
across multiple organ systems. This heterogeneous, chronic, debilitating, autoimmune 
inflammatory disorder characterized by diverse clinical manifestations can affect any organ 
or system in the body simultaneously or sequentially [Kaul 2016]. The adaptive T and 
B cells and the innate immune system are considered to play a major pathophysiological 
role in this disease [Carroll 2004, Kaul 2016].  
Despite many treatment advances and improved diagnostics, SLE continues to cause 
substantial morbidity and premature mortality. Current management strategies are limited 
by high failure rates and toxicity. An overreliance on CS therapy contributes to much of 
the long-term organ damage [Durkan 2019]. 
Medical need for new targeted therapies 
The current treatment of SLE comprises NSAIDs, antimalarials, CS, and 
immunosuppressive drugs, often prescribed in that order as the disease progresses 
[Xiong 2014]. Belimumab (an inhibitor of soluble B-cell-activating factor), approved by 
the FDA in 2011, anifrolumab (an IFN-1 receptor antagonist), approved by the FDA in 
2021, and telitacicept (a novel human recombinant fusion protein) conditionally approved 
in China in 2021 are the only treatments approved for SLE in over 60 years [Furie 2019, 
Morand 2020, Navarra 2011, Dhillon 2021]. Clinical experience with anifrolumab and 
telitacicept is limited to date. Other medications currently used to treat SLE, such as 
azathioprine, cyclophosphamide, and mycophenolate mofetil / mycophenolic acid, have 
not been approved for the disease by regulatory authorities. Antimalarials and CS are also 
used to control some manifestations of lupus (e.g., arthralgia, arthritis, and rashes). All 
these drugs have well-documented and substantial safety profiles and are not effective in 
all patients and/or on all SLE manifestations. Furthermore, it is difficult to taper 
participants with moderate or severe disease completely off CS, which cause long-term 
morbidity and may contribute to early cardiovascular mortality [Petri 2001, Urowitz 1976]. 
Even small daily doses of 5 to 10 mg prednisone used long term carry increased risks of 
side effects such as cataracts, osteoporosis, and coronary artery disease [Petri 2001]. 
In China there is a large population of SLE patients with a clinical presentation that may 
differ from that reported in other ethnicities [Tian et al 2022]. Guidelines developed by 
Chinese rheumatologists and other experts have made several recommendations for the 
diagnosis, treatment and follow-up of disease activity, including disease monitoring using 
the SLEDAI-2K which will be used in this clinical study [Li et al 2020]. It has been shown 

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that Chinese SLE patients that experience severe flares have associated costs 5 times 
greater than those with non-severe flares [He et al 2023]. This suggests that aside from the 
medical rational to reduce flares and thus subsequent organ damage there is also an 
economic reason.  
There is thus a medical need to identify new targeted therapies, particularly agents that may 
reduce the requirement for CS and cytotoxic agents. 
Though recent improvements in care have dramatically enhanced the survival of patients 
with SLE, increased morbidity and mortality remain a major concern. Many patients have 
partially controlled disease and progression to end-stage organ involvement continues, and 
the therapies carry risks of debilitating side effects [Lateef 2012]. Therefore, it is important 
to continue the development of medical products that have the potential to be more 
effective and/or less toxic. 
2.2 Investigational treatment 
Cenerimod is a potent, orally active, selective S1P1 receptor modulator that blocks the 
egress of lymphocytes from lymphoid organs and thus reduces the tissue availability of 
circulating lymphocytes (T and B cells). This PD effect, observed in both healthy 
volunteers and SLE patients, is sustained with continued daily oral dosing. After study 
treatment discontinuation, a gradual return towards baseline levels in lymphocyte counts 
was observed [Cenerimod IB, Hermann 2019]. The compound was selected based on its 
potential for o.d. oral administration, its long t½ allowing a built-in natural up titration, and 
its high selectivity for the S1P1 receptor [Juif 2016, Juif 2017].  
Cenerimod has unique S1P1 receptor-signaling properties, and an improved safety profile 
compared to other S1P modulators. For instance, the absence of broncho- and 
vaso-constrictor effects ex vivo and in vivo was notable [Piali 2017]. Cenerimod 
dose-dependently lowered circulating lymphocyte counts in animal models (mice, rats, 
dogs) and in human participants, leaving Natural Killer cell and monocyte counts 
unaffected. Cenerimod effectively attenuated disease variables in a mouse experimental 
autoimmune encephalitis model and was effective in the treatment of lupus-like disease in 
the MRL/lpr mouse model of SLE [Cenerimod IB, section 1.3.1].  
The PK of cenerimod in healthy participants were characterized by a slow absorption 
(median tmax: 5–6 and 6–7 h after single- and multiple-dosing, respectively) and elimination 
(t½ approximately 33 days measured after the last dosing under steady-state conditions), 
dose-proportional exposure in the range of 0.5–4 mg, and steady-state conditions reached 
within 50 days. Cenerimod showed an accumulation of approximately 8-fold at steady state 
when compared to the first day of treatment. The PK of cenerimod support o.d. dosing and 
no dose adjustment is required for sex, ethnicity, or fed/fasted state. Cenerimod can be 
concomitantly administered with drugs that are inhibitors, inducers, or substrates of 

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cytochrome proteins without dose adjustment. Further details on the PK characteristics of 
cenerimod are provided in the IB [Cenerimod IB]. 
The first study performed in adult participants with moderate-to-severe SLE (AC-064A201) 
met its primary objective by establishing the dose-response relationship of cenerimod 
based on the reduction of lymphocyte count in peripheral blood. The AC-064A201 study 
demonstrated that cenerimod significantly reduced lymphocyte counts in a dose-dependent 
manner (p < 0.01) as expected from its primary mode of action [Cenerimod IB, 
sections 1.4.2.2 and 5.3.1.1]. The exploratory analysis of efficacy suggested clinical 
improvement, particularly with the higher cenerimod doses [Cenerimod IB, 
section 5.3.1.1]. Cenerimod treatment was well tolerated in patients with SLE at all doses 
tested [Cenerimod IB, section 5.3.2.2].  
In adult participants with moderate-to-severe SLE (Phase 2b study ID-064A202), 
cenerimod 4 mg showed a clinically significant reduction in disease activity characterized 
by an improvement in the mSLEDAI-2K score from baseline to Month 6 (the primary 
efficacy endpoint). [Cenerimod IB, sections 1.4.3 and 5.3.1.2]. The subgroup analyses of 
change from baseline to Month 6 in mSLEDAI-2K in participants with a more severe or 
more active disease categorized by daily dose of CS (≥ 7.5 mg/day) and by mSLEDAI-2K 
score (≥ 10) at baseline revealed that efficacy of the 4 mg dose appeared to be greater (vs 
placebo and lower doses) in participants receiving higher doses of prednisone or with a 
more active disease. [Cenerimod IB, section 5.3.1.2]. The cenerimod safety profile did not 
show any unexpected findings and safety areas of special interest related to class did not 
raise any concerns with any dose, up to and including 4 mg [Cenerimod IB, section 5.3.2.3]. 
Post-hoc analyses were made by immunological status at baseline with regards to IFN-1, 
anti-dsDNA, and complement C4 and C3 levels at baseline. The placebo-corrected changes 
in mSLEDAI-2K score for the cenerimod 4 mg dose were consistently larger compared to 
placebo in participants with high disease activity assessed by the immunological variables. 
Based on these data, the same analytes will be measured in this clinical study to compare 
the results with previous studies. 
In participants with high IFN-1 status at entry, representing 50.7% of the overall study 
population, the placebo-corrected mSLEDAI-2K change from baseline to Month 6 in 
participants on cenerimod 4 mg was greater than that observed in the overall population.  
2.3 Study rationale 
Despite recent improvements in treatment regimens and medical care in reducing mortality 
and morbidity, many patients have partially controlled disease and progression to end-stage 
organ involvement, and the therapies carry risks of side effects [Lateef 2012]. Effective 
control of SLE is still difficult due to disease heterogeneity and variability in disease 
manifestations among individuals. 

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Results of recently conducted clinical studies in SLE patients have demonstrated a 
favorable effect of cenerimod on mediators of inflammation and on lupus efficacy clinical 
outcome measures [see Section 2.2]. In the Phase 2b dose-finding study (ID-064A202), 
cenerimod 4 mg was well tolerated over a treatment period of 6 months with limited side 
effects vs placebo.  
The nonclinical safety data and the resulting safety margins / exposure ratios are considered 
adequate to support the safe use of cenerimod in humans at the dose of 4 mg selected for 
the ID-064A204 study.  
Cenerimod exposure in the Chinese population has not yet been evaluated and, while 
differences in drug response due to intrinsic or extrinsic factors in the Chinese ethnic 
population are not expected based on cenerimod properties, it should be assessed. For 
Chinese participants, a staggered approach will therefore be implemented with the limited 
ID-064A204 study started first to mitigate the risk of exposing a large number of Chinese 
patients to cenerimod 4 mg. Study ID-064A204 will evaluate the safety, tolerability, PK 
and PD of cenerimod in Chinese participants.  
The safety of the participants will be closely monitored and safety review will be conducted 
regularly and on demand. 
2.4 Benefit/risk assessment of cenerimod 
Currently there is limited clinical data to assess the benefit/risk ratio of cenerimod. In the 
following sub-sections, the potential and known risks and potential benefits of treatment 
with cenerimod are discussed. 
2.4.1 Potential benefits 
In the Phase 2b study (ID-064A202), the primary analysis of efficacy at 6 months revealed 
a clinically and nominally statistically significant improvement (p = 0.029) in 
mSLEDAI-2K score from baseline to Month 6 in cenerimod 4 mg vs placebo. From 
Month 4 onwards, the change from baseline and the difference to placebo was consistently 
larger in the cenerimod 4 mg group than for lower doses and placebo. For the secondary 
endpoints, a numerically greater response in SRI-4 was observed at Month 6 in the 4 mg 
group than in the placebo group. The effect was greater in participants with more 
serologically or clinically active disease. The selection criteria for the population in the 
current study are aimed at enrolling a population with a clinically and serologically active 
disease, as this population will potentially derive greater benefit from treatment.  
Based on available data, cenerimod may have the potential to be a new oral therapeutic 
approach for patients with SLE [see Cenerimod IB, section 5.3]. 

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2.4.2 
Known and potential risks 
Safety areas of special interest were identified in the nonclinical program and were 
considered in the clinical development of cenerimod. Compared to other S1P receptor 
modulators, the S1P1-selective cenerimod did not show a negative effect on 
bronchoconstriction or vasoconstriction, which are known class effects; the spirometry 
data showed no significant worsening of the pulmonary function in participants treated 
with cenerimod compared to placebo. Nonclinical pharmacological studies concluded that 
the QT prolongation potential of cenerimod is low; this was later confirmed in humans 
[Cenerimod IB, section 5.3.2.1.3]. Furthermore, the results of the ECG monitoring and 
echocardiography sub-study performed during the ID-064A202 study were not suggestive 
of any clinically relevant effect in humans.  
Accordingly, and taking into consideration the safety results from the Phase 2b study 
(ID-064A202), the following risk-minimization measures for identified and potential risks 
will be implemented for participants participating in this study: 
Identified risks: 
• Cardiovascular variables: cenerimod shows a transient effect on HR at the time of first 
dose intake, with a maximum decrease of 9 beats per minute (bpm) observed 6 h 
post-dose. To mitigate the risk of cardiac events, participants will be excluded from 
this Phase 2 study if they have certain cardiac rhythm disorders, ECG abnormalities 
indicative of increased risk for arrhythmia, and/or low resting HR [see Section 5.3]. 
Participants will be excluded or discontinued if receiving medications likely to reduce 
HR (e.g., beta-blockers) or to increase the risk of cardiac arrhythmia [see Sections 5.3 
and 6.2.3]. All participants in this clinical study will undergo cardiac monitoring on 
Day 1 for 12 hours. Since the effects on HR are expected to be transient and related to 
initial dosing, no treatment of sinus bradycardia and/or atrioventricular (AV) block is 
anticipated, unless the symptoms or the seriousness of the condition mandate 
therapeutic intervention in the view of the treating physician. 
Potential risks: 
• Embryo-fetal animal toxicity studies showed that cenerimod is embryotoxic and 
teratogenic in rats and rabbits. Therefore, pregnant women are excluded from this study 
[see Section 5.3]. Cenerimod should be given to WoCBP only when the absence of 
pregnancy has been verified, appropriate advice on contraception has been provided, 
and highly effective contraception is practiced [see Section 5.5]. Women should not 
become pregnant while on treatment and for 6 months after discontinuation of 
cenerimod. During these periods, the absence of pregnancy is monitored monthly [see 
Table 2]. Occurrence of pregnancy will result in immediate discontinuation of the study 
treatment and monitoring of the pregnancy [see Section 5.8.1.2]. 

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• Liver: a slightly higher incidence of hepatic AEs (mostly denoting liver enzyme 
increase) and liver enzyme marked abnormalities with no dose-related trends were 
observed in participants treated with cenerimod compared to placebo in the ID-
064A202 study [Cenerimod IB, section 5.3.2.3]. Overall, the incidence of hepatobiliary 
disorders was lower than seen with other S1P receptor modulators. Participants with 
signs of ongoing liver disease will not be enrolled into this study and 
monitoring/discontinuation criteria are applied [see Sections 5.3 and 5.8.1.7]. 
• Abnormal Immunomodulation: cenerimod reduces the number of circulating 
lymphocytes. Because of reduced immune surveillance, the risk of infections and 
malignancy may be increased. Participants with low lymphocytes and/or presenting 
certain types of malignancies at Screening are excluded from this study [see Section 
5.3]. Monitoring/discontinuation criteria are applied [see Section 5.8.1.6]. 
• Infections: heightened vigilance is required for opportunistic infections, particularly for 
potentially serious viral infections with neurological symptoms, such as reactivation of 
human herpes viruses, and of John Cunningham polyoma virus, the causative agent of 
progressive multifocal leukoencephalopathy. If findings raise suspicion of an 
opportunistic infection, the participant must discontinue the study treatment. 
Study -specific eligibility/discontinuation criteria and proper clinical monitoring are 
applied in the study [see Sections 5.3 and 5.8.1.5]. Results from the ID-064A202 study 
did not reveal an increased rate of infection in participants treated with cenerimod 
compared to placebo [Cenerimod IB, section 5.3.2.3]. 
• Vaccination: no clinical data are currently available on vaccination efficacy under 
cenerimod. The currently registered S1P receptor modulators (i.e., fingolimod, 
siponimod, ozanimod, ponesimod) may reduce vaccine effectiveness [Gilenya® SmPC, 
Mayzent® SmPC, Ponvory® SmPC, Zeposia® SmPC ]. Patients with SLE hospitalized 
because of COVID-19 have significantly higher risks of death and poor outcomes than 
patients without comorbidities and patients with other comorbidities [Bertoglio 2021]. 
COVID-19 vaccination induced humoral and cellular responses against SARS-CoV-2 
variants in SLE [Moyon 2021] and appears well tolerated in patients with SLE, with 
only a minimal risk of flare, if any, including after the mRNA vaccines [Felten 2021]. 
Altogether, vaccination of participants participating in this study may be recommended 
by the investigator, except for vaccination with live vaccines, which is not allowed 
within 30 days prior to Day 1 and up to 6 months post last study dose.  
• Macular edema: clinical experience with other S1P receptor modulators indicates that 
participants treated with these drugs may be at increased risk of developing macular 
edema. Participant safety is ensured by implementation of appropriate eligibility and 
discontinuation criteria as well as monitoring during this study [see Sections 5.3 and 
5.8.1.8]. Participants presenting with a suspicion of macular edema, as reported by 

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investigators, will be temporarily discontinued from study treatment while an IOSB 
reviews and assesses the suspected cases [see Section 4.4]. 
2.4.3 
Study procedures and associated potential risks 
The following procedures shown in Table 4 will be performed during the study, with their 
associated potential risks. 
Table 4 
Study procedures and associated potential risks 
Procedure 
Standard 
of Care  
Associated potential risk  
Physical exam 
Yes 
No associated potential medical risks. 
Blood sampling 
No 
 
 
 
 
 
 
 
On 
 
average 
 
between
 
7
 
and
 
63.5
 
mL 
 
of 
 
blood 
 
will 
 
be
sampled
 
(planned)
 
at each
 
monthly
 
visit for the different
assessments.
 
The amount
 
of
 
blood drawn
 
at each visit and
in 
 
total
 
(19
 
months)
 
is
 
considered 
 
acceptable.
 
Potential
medical
 
risks include bruising.
 
Additional blood sample
maybe required for AE re-test or unscheduled visit. 
Urine sampling 
Yes 
No associated potential medical risks. 
12-lead ECG  
No 
Possible discomfort and transient erythema of ECG 
patches. 
Vital signs 
Yes 
No associated potential medical risks. 
Ophthalmological exam and 
OCT 
No 
No associated potential medical risks. 
Chest X-ray (or CT scan) for 
eligibility to exclude latent TB 
No 
Single low radiation exposure. Performed only at 
Screening. 
ECG = electrocardiogram; OCT = optical coherence tomography; TB = tuberculosis.  
 
2.4.4 
Assessment of benefit -risk  
In the ID-064A202 study, there was no participant discontinuation due to low HR on Day 
1, no relevant findings in the echocardiography sub-study, no difference in pulmonary 
function tests compared to placebo. Three cases of macular edema were reported but none 
were related to cenerimod with one each being present at baseline, due to retinitis 
pigmentosa or related to chloroquine therapy, and considered to be due to a branch retinal 
vein occlusion (refer to Investigator Brochure). Second‑degree AV block Mobitz I was 
reported in 2 participants; all AV blocks were transient, asymptomatic, resolved within 
24 h without therapeutic intervention, and did not require study treatment discontinuation. 
Finally, there was no imbalance in AEs compared to placebo denoting infections and no 
consistent or dose-dependent change in SBP or DBP over time. Although 4 mg cenerimod 
was administered for a total of 6 months only, followed by either placebo or 2 mg for 
another 6 months, there is currently no indication that prolonged use of 4 mg cenerimod 

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(12 months of 4 mg) would create further risks. However, caution is advised for the 
longer-term treatment at this dose in study ID-064A204 due to the limited data generated 
so far. 
Safety data (AEs, SAEs, laboratory assessments, ECGs, vital signs, and other study-
specific examinations) will be monitored on a regular basis by the sponsor.  
It is the investigator/delegate’s responsibility to monitor the benefit -risk ratio of study 
treatment administration, as well as the degree of distress caused by study procedures, at 
an individual participant level, and to discontinue study treatment or the study for that 
individual if, on balance, they believe that continuation would be detrimental to the 
participant’s wellbeing. 
3 
STUDY OBJECTIVES AND ENDPOINTS 
3.1 List of objectives and endpoints –  
The objectives are: 
Primary objectives 
• To evaluate the safety and tolerability of cenerimod 4 mg in Chinese participants. 
• To evaluate the PK of cenerimod 4 mg in Chinese participants  
• To evaluate the PD of cenerimod 4 mg in Chinese participants.  
Other objective 
• To preliminarily evaluate the efficacy of cenerimod 4 mg in Chinese participants. 
All endpoints and their relationship to the objectives are shown in Table 5. Baseline is 
defined as the last available measurement before the start of treatment. These endpoints 
will be evaluated according to the protocol once the last participant completes the 6-month 
safety follow-up visit or withdraws from the study.  
Table 5 
Objectives and endpoints 
Objectives 
Endpoints 
To evaluate the safety and 
tolerability of cenerimod 4 mg in 
Chinese participants 
 
 
 
• Occurrence of TEAEs1, SAEs and AESIs up to FSV. 
• Occurrence of AEs leading to permanent discontinuation of 
study treatment. 
• Changes in vital signs (SBP, DBP) and body weight from 
baseline to each post-baseline assessment. 
• Changes in hourly 12-lead ECG variables (HR and the 
intervals: QTcB, and QTcF) and in SBP/DBP assessments at 
Day 1 cardiac monitoring.  

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Objectives 
Endpoints 
 
 
 
 
 
 
• Changes in 12-lead ECG variables (HR and the intervals: PR, 
QRS, QTcB, and QTcF) from baseline to each post-baseline 
assessment. 
• Treatment-emergent medically relevant ECG abnormalities 
from baseline to each post-baseline assessment. 
• Changes in laboratory variables (hematology, blood chemistry, 
and urinalysis) from baseline to each post-baseline assessment. 
• Treatment-emergent marked laboratory abnormalities from 
baseline to all assessed time points. 
To evaluate the PK of cenerimod 
4 mg in Chinese participants. 
PK endpoints  
• 
Cenerimod plasma concentrations at all scheduled time points 
(see Table 2). 
• 
The plasma PK parameters of 4 mg cenerimod will be derived 
by 
non-compartmental 
analysis 
of 
the 
plasma 
concentration-time profiles and calculated based on the actual 
PK sampling time. The following endpoints will be 
determined:  
− 
Cmax, tmax, and AUC0-24 during the first dosing interval 
on Day 1, 
− 
Cmax, tmax, and AUC during a dosing interval at 
steady state (i.e., at Month 2), 
− 
AI between Day 1 and Month 2. 
To evaluate the PD of cenerimod 4 
mg in Chinese participants. 
PD endpoints 
• 
Change in total blood lymphocyte count from baseline to each 
post-baseline assessment.  

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Objectives 
Endpoints 
To preliminarily evaluate the 
efficacy of cenerimod 4 mg in 
Chinese participants. 
Efficacy endpoints 
• 
Response on SRI-4 from baseline to Month 12 
• 
Response on mSLEDAI-2K from baseline to Month 12. 
• 
Response on BICLA from baseline to Month 12 
• 
Response on CLASI from baseline to Month 12 
• 
Change in tender and swollen joints from baseline to Month 
12 
• 
Changes in OCS dosage from baseline to Month 12 
1 A TEAE is any AE temporally associated with the use of study treatment (from study treatment start until 180 days 
after study treatment discontinuation) whether or not considered by the investigator as related to study treatment.  
AE = adverse event, AESI = adverse event of special interest, AI = Accumulation index, BICLA = BILAG-based 
Composite Lupus Assessment, CLASI = Cutaneous Lupus Erythematosus Disease Area and Severity Index, 
DBP = diastolic blood pressure, ECG = electrocardiogram, FSV = final study visit, HR = heart rate, 
mSLEDAI = Modified Systemic Lupus Erythematosus Disease Activity Index, OCS= oral corticosteroids, 
PK = pharmacokinetic(s), QTcB = QT corrected for heart rate using Bazett’s formula, QTcF = QT corrected for 
heart rate using Fridericia’s formula, SAE = serious adverse event, SBP = systolic blood pressure, SRI = Systemic 
Lupus Erythematosus Responder Index, TEAE = treatment-emergent adverse event. 
 
3.2 Appropriateness of endpoints 
The safety endpoints are well established and typically reported in studies at this stage of 
clinical development, such as safety laboratory data, ECGs and vital signs. Due to the 
known class effects of S1P receptor modulators, ophthalmology examinations and OCT 
assessments are being performed at regular intervals during the clinical study. 
S1P receptor modulators, including cenerimod, have been shown to have an effect on HR. 
In Phase 2 studies, cenerimod has been shown to have a clinically non-significant decrease 
in HR at the first dose. In the current study, all participants will have HR, BP and ECG 
monitored at the first dose to determine if cenerimod has the same effect in Chinese SLE 
patients.  
The PK endpoints are well established for evaluating the extent of systemic exposure (AUC) 
and rate of systemic absorption (Cmax and tmax) of a drug [FDA 2014b]. Obtaining a plasma 
concentration-time profile at Month 2 will allow to assess the PK endpoints at steady-state 
conditions and, thus, to evaluate the accumulation of cenerimod. 
The efficacy endpoints are based on previous clinical studies conducted in SLE and have 
regulatory precedent. Due to the open-label nature of this clinical study, no placebo group 
will be available for comparison, and the post-dose values of these endpoints will be 
compared to the baseline values. Multiple efficacy endpoints are included to allow 

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comparison between other studies and to act as an internal control between the disease 
assessments, e.g., the CLASI rash is a detailed evaluation of rash on the body and therefore 
can be used to determine if the rash reported in the mSLEDAI is correct.  
4 
STUDY DESIGN AND PLAN  
4.1 Study design 
This is a multicenter, open label, single arm, multiple-dose study in adult Chinese 
participants with moderate-to-severe SLE on top of background therapy. 
It is planned that approximately 15 adult Chinese participants concurrently receiving SLE 
background therapy will receive cenerimod 4 mg o.d. for 12 months.  
The study will be conducted at approximately 5-10 sites in China.  
4.1.1 Study periods for an individual participant 
The screening period will last up to 30 days. Participants will receive cenerimod for a 
maximum of 12 months. For participants that permanently discontinue study treatment, 
they will enter the post-treatment observation period. Participants that complete the 12-
month treatment period will enter a 6-month safety follow-up period until FSV. 
Post-treatment observation period (only applicable to participants who permanently 
discontinue study treatment): starts the day after the last dose of study treatment and 
participants will complete visits until at least 6 months after last study treatment intake as 
follows:  
• Participants who permanently discontinue study treatment before or at Month 6 will 
complete study visits until Month 12 and the FSV will be at Month 12 (i.e., PTOP 
Visit 14).  
• Participants who permanently discontinue study treatment between Month 7 and 
Month 12 (inclusive) will complete PTOP FU visit(s) until 6 months after last study 
treatment intake and the FSV will be one of the monthly PTOP FU visits, as applicable. 
Follow-up period: Starts on the day after the last dose of study treatment and ends 
6 months, i.e., 180 days, thereafter with FSV.  
A participant’s participation in the study ends with the completion of the FSV. The 
participant will participate in the study for a duration of up to 19 months. 
The visit schedule and protocol-mandated procedures are performed according to the SoA 
[Table 1, Table 2, and Table 3] and are described in Section 7.2. 
The study design is depicted in Figure 1. 

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4.2 Study duration and End-of-Study definition 
The study starts with the recruitment of the first participant. A participant is considered 
recruited when the participant’s ICF has been fully signed.  
The study’s primary completion date is the date of the last participant’s FSV (i.e., 
completion of the 6-month safety follow-up). 
The End-of-Study (EOS) is defined as completion of the last FSV. The study is expected 
to last approximately 22 months. 
4.3 Study design rationale 
This study is a multicenter, open label, single arm, multiple-dose study evaluating the 
safety, PK and PD of cenerimod 4 mg in adult Chinese patients with moderate-to-severe 
SLE in addition to background SLE therapy.  
A treatment period of 12 months is an appropriate study duration to evaluate cenerimod’s 
long-term safety profile.  
Open label treatment is considered adequate to evaluate the PK of cenerimod in Chinese 
participants based on the quantitative nature of these measurements. As cenerimod has 
been evaluated in a number of other clinical studies, the safety endpoints can also be 
evaluated in an open label manner to avoid treating SLE patients with a placebo for 12 
months. 
To ensure adequate treatment, all participants will receive SLE standard of care treatment 
with at least 1 of the following: OCS, antimalarial, or immunosuppressants, in addition to 
study treatment [see Sections 5.2 and 6.2]. This is consistent with the Chinese guidelines 
for the treatment of moderate-to-severe SLE [Li et al 2020]. 
Given the associated side effects of OCS, an important goal of new therapies is to reduce 
the chronic use of CS. In this study OCS tapering is mandatory to investigate if cenerimod 
can reduce the usage of OCS in Chinese patients. Tapering will start after the Month 3 visit 
(see section 6.2.1.2.3for details), when cenerimod is expected to have a clinical effect but 
is not allowed after Month 9 to allow interpretation of the efficacy measurements. 
Overexpression of IFN-1, IFN-1 gene signature, and proteins induced by Type 1 IFNs have 
all been associated with greater disease activity and organ system involvement in SLE. 
Recent clinical studies have demonstrated that between 50 and 90% of SLE patients show 
the consistent presence of an IFN-1 high signature based on blood analyses, and that this 
signal is stable over time [Kirou 2004, Northcott 2022, Oke 2019, Ronnblom 2019]. 
Therefore, in this study, we will evaluate the IFN-1 gene signature in participants at 
baseline, during and after treatment. 

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4.4 Study committees 
An IOSB will receive all information related to suspected cases of macular edema and will 
perform a central, review of OCT images and participants’ data of suspected cases of 
macular edema as per the IOSB charter. 
5 
STUDY POPULATION 
5.1 Participant population description 
The target population of this study is adult participants diagnosed with generalized 
moderate-to-severe SLE who are receiving SLE background therapy.  
5.2 Inclusion criteria 
Participants must meet all the following inclusion criteria: 
Screening criteria 
1. Signed and dated ICF prior to any study-mandated procedure. 
2. Male or female Chinese participants aged from 18 to 75 years old (both inclusive) at 
the time of signing the ICF. 
3. Diagnosis of SLE made at least 6 months prior to Screening, according to 
2019 EULAR/ACR Criteria [see Appendix 2]. 
4. An mSLEDAI-2K score ≥ 6 and clinical mSLEDAI-2K score ≥ 4 with at least 2 points 
for musculoskeletal or mucocutaneous manifestations (i.e., myositis, arthritis, rash, 
alopecia, mucosal ulcers) [see Appendix 6].  
Note: The mSLEDAI-2K score does not include “leukopenia”. The clinical mSLEDAI-2K 
is the mSLEDAI-2K assessment score without the inclusion of points attributable to 
hematuria, proteinuria, pyuria, urinary casts, low complement, increased DNA binding, 
and thrombocytopenia. 
5. PGA score ≥ 1.0 on a 0 to 3 VAS [see Appendix 9]. 
6. Currently treated with one or more of the following SLE background medications: 
• Antimalarials: (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, 
≤ 100 mg/day quinacrine) 
• Mycophenolate mofetil (≤ 2 g/day) / mycophenolic acid (≤ 1.44 g/day) 
• Azathioprine (≤ 2 mg/kg/day) 
• Methotrexate (≤ 25 mg/week) 
• OCS 
– if OCS is the only SLE background medication: ≥ 7.5 mg/day and ≤ 30 mg/day 
prednisone or equivalent 

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– if OCS is not the only SLE background medication: ≤ 30 mg/day prednisone or 
equivalent 
• Belimumab (≤ 10 mg/kg every 4 weeks i.v. or 200 mg/week s.c.). 
• Telitacicept (≤ 240 mg/week subcutaneously). 
Treatment with antimalarials, mycophenolate mofetil, mycophenolic acid, azathioprine, 
methotrexate, belimumab, or telitacicept must have been started at least 90 days prior to 
Screening.  
Treatment with OCS must have been started at least 30 days prior to Screening.  
7. For WoCBP [see definition in Section 5.5.1]: 
• Negative serum pregnancy test at Screening. 
• Agreement to undertake monthly urine pregnancy tests from Day 1 up to 6 months 
after study treatment discontinuation. 
• Agreement to use a highly effective method of contraception as described in 
Section 5.5.2 from Screening (Visit 1) up to 6 months after study treatment 
discontinuation. 
Day 1 pre-dose criteria 
8. A clinical mSLEDAI-2K score ≥ 4 with at least 2 points for musculoskeletal or 
mucocutaneous manifestations (i.e., myositis, arthritis, rash, alopecia, mucosal ulcers).  
9. PGA score ≥ 1.0 on a 0 to 3 VAS. 
10. Presence of at least one of the following biomarkers of serological evidence of active 
SLE (in a Screening sample as measured by central laboratory):  
• Anti-dsDNA antibodies elevated above normal. 
• ANA with a titer of at least 1:160. 
• Anti-Sm antibody elevated above normal. 
11. Currently treated with one or more of the following SLE background medications that 
must be stable for at least 30 days prior to Day 1 (except OCS that must be stable for 
at least 15 days prior to Day 1): 
• Antimalarials (≤ 400 mg/day hydroxychloroquine, ≤ 500 mg/day chloroquine, 
≤ 100 mg/day quinacrine), 
• Mycophenolate mofetil (≤ 2 g/day) / mycophenolic acid (≤ 1.44 g/day), 
• Azathioprine (≤ 2 mg/kg/day), 
• Methotrexate (≤ 25 mg/week), 
• OCS: 

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– if OCS is the only SLE background medication: ≥ 7.5 mg/day and ≤ 30 mg/day 
prednisone or equivalent 
– if OCS is not the only SLE background medication: ≤ 30 mg/day prednisone or 
equivalent 
• Belimumab (≤ 10 mg/kg every 4 weeks i.v. or 200 mg/week s.c.), 
• Telitacicept (≤ 240 mg/week subcutaneously). 
12. WoCBP must have a negative urine pregnancy test. 
5.3 Exclusion criteria 
Participants must not meet any of the following exclusion criteria: 
Pregnancy and breastfeeding 
1. Pregnant, planning to be become pregnant up to 6 months after the last dose of 
cenerimod in this study, or lactating women.  
SLE and other immune diseases 
2. Active severe SLE-driven renal disease (within 90 days prior to Screening or during 
Screening) where, in the judgment of the investigator, protocol-specified SLE 
background therapy is insufficient and the use of a more aggressive therapeutic 
approach or other treatments not permitted in the protocol, is indicated. 
3. Urine protein/creatinine ratio > 3000 mg/g (i.e., > 339.45 mg/mmol) at screening 
assessment based on central assessment. 
4. Severe active CNS lupus or active severe or unstable neuropsychiatric SLE including 
but not limited to aseptic meningitis; cerebral vasculitis; myelopathy; demyelination 
syndromes 
(ascending, 
transverse, 
acute 
inflammatory 
demyelinating 
polyradiculopathy); acute confusional state; impaired level of consciousness; psychosis; 
acute stroke or stroke syndrome; cranial neuropathy; status epilepticus; cerebellar 
ataxia; and mononeuritis multiplex. 
• That would make the participant unable to fully understand the ICF.  
or  
• Where, in the opinion of the investigator/delegate, protocol-specified standard of 
care is insufficient and the use of a more aggressive therapeutic approach, such as 
adding i.v. cyclophosphamide and/or high dose i.v. pulse CS therapy or other 
treatments not permitted in the protocol, is indicated.  
5. Severe forms of vasculitis (e.g., retinal vasculitis, coronary vasculitis, pulmonary 
vasculitis, mesenteric vasculitis) requiring systemic immunosuppressive treatment 
within 90 days prior to Screening or during Screening. 

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6. A diagnosis of mixed connective tissue disease or any history of overlap syndromes of 
SLE with psoriasis, rheumatoid arthritis, erosive arthritis, scleroderma, autoimmune 
hepatitis, or uncontrolled autoimmune thyroid disease. 
Cardiovascular 
7. History or presence of Mobitz type II or third-degree AV block, sick sinus syndrome, 
symptomatic bradycardia, or syncope associated with cardiac disorders. 
8. Participants who experienced myocardial infarction, unstable angina pectoris, stroke, 
transient ischemic attack, vascular thrombosis, decompensated heart failure requiring 
hospitalization, or heart failure defined by the New York Heart Association Class III/IV 
within 6 months prior to Screening.  
9. Resting HR < 50 bpm as measured by the 12-lead ECG at Screening or at Day 1 prior 
to study drug administration.  
10. An elevated QTcF interval of > 470 ms (females) / > 450 ms (males) at Screening or at 
Day 1 prior to study drug administration. 
Pulmonary 
11. History or presence of severe respiratory disease or pulmonary fibrosis, based on 
medical history, lung function, and chest X-ray (or CT scan as per local guidelines) 
performed at Screening or within 6 months prior to Screening. 
12. History of clinically relevant bronchial asthma or chronic obstructive pulmonary 
disease that has required treatment with oral or parenteral CS for more than a total of 
2 weeks within the last 6 months prior to Screening. 
Infection and infection risk 
13. Have had household contact with a person with active TB and did not receive 
appropriate and documented prophylaxis for TB. 
14. Have evidence of active TB or latent TB 
a. Active TB: Have evidence of active TB, defined in this study as the following: 
Medical history, clinical features, and abnormal chest x-ray at screening indicating 
the presence of TB. 
IFN gamma release assay (IGRA): Participants are excluded from the study if the test 
is not negative and there is clinical evidence of active TB.  
 
Exception 1: participants with a history of active TB who have documented evidence 
of appropriate treatment, have no history of re-exposure since their treatment was 
completed, have no clinical features of active TB, and have a screening chest x-ray 
with no evidence of active TB may be enrolled if other entry criteria met. Such 
participants would not be required to undergo the IGRA test but must have a chest x-

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ray at screening (i.e., chest imaging performed within the past 6 months will not be 
accepted).  
 
b. Latent TB: Have evidence of untreated/inadequately or inappropriately treated 
latent TB, defined in this study as the following:  
An IGRA test which is not negative, no clinical features consistent with active TB, 
and a chest x-ray with no evidence of active TB at screening;  
If the IGRA test results are positive, the participant will be considered to have latent 
TB. If the test is not negative, the test may be repeated once within approximately 2 
weeks of the initial value. If the repeat test results are again not negative, the 
participant will be considered to have latent TB (for purposes of this study).  
Exception 2: participants with a history of latent TB who have documented evidence 
of appropriate treatment, have no history of re-exposure since their treatment was 
completed, have no clinical features of active TB, and have a screening chest x-ray 
with no evidence of active TB may be enrolled if other entry criteria met. Such 
participants would not be required to undergo the IGRA test, but must have a chest x-
ray at screening (i.e., chest imaging performed within the past 6 months will not be 
accepted 
15. Ongoing bacterial, viral, parasitic, or fungal infection that is of clinical concern 
according to the investigator or history of any of the following:  
• Clinically significant chronic infection (e.g., osteomyelitis, bronchiectasis, etc.) 
within 8 weeks prior to Screening (chronic nail infections are allowed). 
• Any infection requiring hospitalization or treatment with i.v. anti-infectives not 
completed at least 4 weeks prior to Screening.  
16. Positive results for serological markers for hepatitis A, B, C, and E indicating acute or 
chronic infection: 
• Anti-HAV IgM. 
• HBsAg. 
• Anti-HCV IgG or IgM (if positive IgM and/or IgG, to be confirmed by HCV-RNA 
PCR assessment, and if this assessment is negative, participant can be enrolled). 
• Anti-HEV IgG or IgM (if positive IgM and/or IgG, to be confirmed by HEV-RNA 
PCR assessment and if this assessment is negative participant can be enrolled). 
17. Participants who have congenital or acquired severe immunodeficiency or known HIV 
infection or positive HIV testing. 
18. Negative IgG antibody test for varicella-zoster virus. 

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Malignancy 
19. History or presence of malignancy (except for surgically excised and non-recurrent 
cutaneous basal cell carcinoma, squamous cell carcinoma, or cervical carcinoma), 
lymphoproliferative disease, or history of total lymphoid irradiation within 10 years 
prior to Screening. 
Transplantation 
20. History or presence of homologous (allogenic) bone marrow or solid organ 
transplantation. 
Ophthalmologic 
21. Presence of macular edema or active uveitis detected by OCT during Screening. 
Metabolic 
22. Documented poorly controlled diabetes mellitus (i.e., HbA1c > 8.0% at Screening as 
reported by the central laboratory or unstable blood sugar control/treatment adherence 
as per investigator’s judgment) or diabetes mellitus complicated with organ 
involvement, such as diabetic nephropathy or retinopathy as assessed by investigator. 
Hepatic 
23. History of chronic liver or biliary disease (other than Gilbert’s Syndrome) or 
participants with ALT or AST > 3 × ULN or TBIL > 1.5 × ULN (unless in the context 
of known Gilbert’s Syndrome). 
Hematology 
24. Significant hematology abnormality at screening assessment:  
• Lymphocyte count < 500 /μL (0.5 × 109/L);  
• Hemoglobin < 7 g/dL;  
• WBC count < 2000/μL (2.0 × 109/L) or  
• Platelets < 25,000/μL (25 × 109/L). 
Renal 
25. eGFR < 15 mL/min/1.73 m2.  
Medications 
26. Treatment with the following medications within 15 days or 5 half-lives of the 
medication (whichever is longer) prior to Day 1: 
• β-blockers, diltiazem, verapamil, digoxin, digitoxin, or any other anti-arrhythmic 
or HR-lowering systemic therapy [list of drugs provided in Appendix 3]. 

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• QT-prolonging drugs with known risk of torsade de pointes irrespective of 
indication [list of drugs provided in Appendix 4]. 
27. Treatment with the following medications within 30 days or 5 half-lives of the 
medication (whichever is longer) prior to Day 1:  
• Cyclophosphamide, cyclosporine, voclosporin, tacrolimus, sirolimus, etc. 
• Pulse methylprednisone. 
• Vaccination with live vaccines. 
28. Intra-articular, intramuscular, or i.v. CS within 6 weeks prior to Day 1. 
29. Treatment with the following medications within 90 days or 5 half-lives of the 
medication (whichever is longer) prior to Day 1:  
• Leflunomide. 
• i.v. immunoglobulins. 
30. Treatment with any investigational agent within 90 days or 5 half-lives of the drug 
(whichever is longer) prior to Day 1. 
31. Treatment with B cell-depleting biological agents (e.g., rituximab or ocrelizumab) or 
biological immunosuppressive agents (e.g., anti-TNF, anti-IL1, anti-IL6 therapies) 
within 12 months prior to Day 1. 
32. Treatment with anifrolumab within 6 months prior to Day 1. 
33. Treatment with any of the following medications any time prior to Screening: 
• Alemtuzumab.  
• S1P receptor modulators (e.g., fingolimod). 
• Participants previously randomized to cenerimod or placebo in any trial involving 
cenerimod. 
Other categories 
34. Recent clinically significant drug or alcohol abuse as per investigator’s judgment. 
35. Known allergy to S1P receptor modulators or any of the cenerimod formulation 
excipients. 
36. Any other clinically relevant medical condition that would put the participant at risk if 
participating in the study, or any other diseases that may confound the disease activity 
assessments. 
37. Participants with body weight < 40 kg at Screening or Day 1. 

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5.4 Rationale for the selection of the study population 
The target population of this study is similar to the participant population from the Phase 
2b ID-064A202 study as it consists of adult participants with generalized SLE who are 
receiving background therapy.  
Participants must have at least a 6-month history of SLE and must be classified as SLE 
according to 2019 EULAR/ACR criteria [Aringer 2019]. This study is being performed in 
patients with SLE in order to evaluate the PK and PD effects in the target population which 
may benefit from cenerimod. Healthy volunteers would not allow for the same evaluation, 
as for example lymphopenia is often more prevalent in SLE as compared to healthy people. 
Participants will be included in the study if they have a sufficient level of disease activity 
to justify therapeutic intervention.  
However, since only limited efficacy data are available to date, it is premature to test 
cenerimod in the most severe spectrum of the disease. In line with our exclusion criteria, 
participants with active lupus nephritis and CNS lupus requiring additional 
immunosuppressive therapies are excluded [see Section 5.3].  
Given the heterogeneity in SLE disease manifestations, treatment is often not standardized. 
In order not to confound the results of the study, participants should have initiated SLE 
background treatment (except OCS) at least 3 months prior to Screening and need to have 
stable doses at least 30 days prior to Day 1 and throughout the study. Background OCS 
therapy should have been initiated at least 30 days prior to Screening and the dose must be 
stable at least 15 days prior to Day 1 [see Section 5.2 and 6.2.1.2]. The inclusion of 
participants with background therapies commonly used to treat SLE in China will allow 
the evaluation of safety in a smaller number of patients prior to starting a large clinical 
study in China. 
5.5 Contraception requirements for women of childbearing potential 
5.5.1 Definition of childbearing potential 
A woman is considered to be of childbearing potential, i.e., fertile, following menarches 
and until becoming post-menopausal unless permanently sterile. 
Permanent sterilization methods include hysterectomy, bilateral salpingectomy, and 
bilateral oophorectomy.  
Post-menopausal state is defined as 12 consecutive months with no menses without an 
alternative medical cause (ICH M3 definition).  

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5.5.2 Methods of contraception 
Cenerimod is embryotoxic and teratogenic in animal studies. WoCBP [see definition in 
Section 5.5.1 must use an uninterrupted highly effective method of contraception from 
Screening (Visit 1) up to at least 6 months after study treatment discontinuation due to the 
long half-life of the study treatment (33 days). 
Contraceptive methods with low user dependency should preferably be used, in particular 
when contraception is introduced as a result of participation in the study.  
Highly effective methods of contraception are defined as those, alone or in combination, 
resulting in a failure rate of  1% per year when used consistently and correctly. Such 
methods include: 
• Hormonal contraceptives: Combined (containing estrogen and progestogen) or 
progestogen-only hormonal contraception associated with inhibition of ovulation using 
one of the following routes of administration: 
– Oral 
– Intravaginal 
– Transdermal 
– Injectable 
– Implantable (low user dependency) 
If a hormonal contraceptive is chosen from this group, it must be taken for at least 30 days 
prior to administration of the first study treatment dose. If, during the study treatment 
period, a participant switches or starts a hormonal contraceptive method, caution must be 
taken to ensure a highly effective method of contraception is used without discontinuation 
in order to ensure continued effective contraception. 
• 
Intrauterine device (low user dependency). 
• 
Intrauterine hormone-releasing system (low user dependency). 
• 
Bilateral tubal occlusion/ligation at least 6 weeks prior to Screening (low user 
dependency). 
• 
Vasectomized partner: this is a highly effective birth control method, provided that the 
partner is the sole sexual partner of the participant and that the vasectomized partner 
has received a medical assessment of the surgical success. 
• 
Sexual abstinence, defined as refraining from heterosexual intercourse during the 
entire period of risk associated with the study treatment. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the clinical study; 
whether it is the preferred and usual lifestyle of the participant; and whether it is locally 
accepted as a highly effective method of contraception. 

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The following contraception schemes used alone are NOT considered highly effective 
methods of contraception: 
• Male or female condom with or without spermicide.  
• Cap, diaphragm, or sponge with or without spermicide. 
The following methods are not allowed as methods of contraception for this study: 
• Progestogen-only oral hormonal contraception (except if inhibition of ovulation is the 
primary mode of action).  
• Periodic abstinence (calendar, symptothermal, post-ovulation methods). 
• Withdrawal (coitus interruptus). 
• Spermicides only. 
• Lactational amenorrhea method. 
• Combination of female condom and male condom. 
The methods of birth control used (including non-pharmacological methods) of the 
WoCBP and/or partner (if applicable) must be recorded in the eCRF. 
The investigator must explain and remind female participants of the importance of using 
methods of contraception at every study visit. 
The investigator/delegate will record in the eCRF at monthly intervals the result of the 
pregnancy test, whether the method of contraception has changed, and will remind the 
participant to follow the protocol-mandated method of contraception up to at least 6 months 
after study treatment discontinuation. 
If the investigator/delegate finds that the protocol-mandated highly effective method of 
contraception is not consistently and correctly followed by the participant, the study 
treatment must be permanently discontinued [see Section 5.8.1.3].  
Note: The documentation of the methods of contraception can be based on the site 
personnel’s review of the participant’s medical records, medical examination, or medical 
history interview of the participant. 
5.6 Contraception for male participants with a partner who is of 
childbearing potential 
Cenerimod is neither genotoxic nor mutagenic [see section 4.3.8.7 of the Cenerimod IB]. 
Thus, no contraceptive methods are needed for male participants participating in this 
clinical study. Based on nonclinical data and human distribution models, it is considered 
very unlikely that a relevant dose of cenerimod would be delivered to the female by seminal 

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fluid transfer. Therefore, despite the teratogenic effect of cenerimod, the risk of harm to a 
human fetus by seminal transfer of cenerimod is very low.  
5.7 Screen failures and re-screening 
Screen failures are defined as participants recruited in the clinical study (i.e., ICF fully 
signed) who are not subsequently enrolled in the study. Participants may have a laboratory 
assessment repeated once during the screening period, if, in the investigator’s medical 
opinion, the value leading to ineligibility is transient and not clinically significant, prior to 
the participant being screen failed.  
A minimal set of screening failure information is required to ensure compliant reporting of 
screening failure participants. For participants who failed Screening, the following data 
will be recorded in the eCRF: 
• ICF signature date; 
• Age, sex, and race; 
• Inclusion criteria not met and/or exclusion criteria met; 
• SAEs. 
Re-screening of participants after screen failure is not allowed. 
5.8  Criteria for withdrawal of participants 
A participant has the right to permanently discontinue the study treatment at any time by 
withdrawing from the study treatment only or by withdrawing from the study treatment 
and any further participation in the study (i.e., premature withdrawal from the study). It is 
recommended that the investigator/delegate makes a reasonable effort to maintain 
participants on treatment, as medically appropriate, and follow the schedule of visits, as 
data robustness depends on such compliance. Should a participant stop treatment or 
withdraw from the study, the investigator/delegate should ascertain the reason(s), while 
fully respecting the participant’s rights. 
5.8.1 
Study treatment interruption and permanent discontinuation of study 
treatment 
5.8.1.1 Principles 
The decision to permanently discontinue the study treatment can be made by the participant, 
the investigator/delegate, or the sponsor personnel.  
The investigator/delegate has the option of temporarily interrupting or permanently 
discontinuing the study treatment for a given participant in response to an AE, a diagnostic 
or therapeutic procedure, a laboratory abnormality, or for administrative reasons. If the 

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study treatment is interrupted by the participant for any reason, he/she must inform the 
investigator/delegate as soon as possible. Any study treatment interruptions (i.e., for a day 
or more) must be recorded in the eCRF. 
The investigator/delegate must permanently discontinue the study treatment for a given 
participant if, on balance, he/she believes that continued administration would be contrary 
to the best interests of the participant.  
Study-specific criteria for temporary interruption and permanent discontinuation of the 
study treatment are described in Sections 5.8.1.2 to 5.8.1.11   
The main reason for permanent discontinuation of the study treatment (e.g., due to 
pre-specified study treatment discontinuation criteria, an AE, lack of efficacy, study 
termination) must be documented in the eCRF.  
A participant who permanently discontinues the study treatment is NOT considered 
withdrawn from the study. The participant will be asked to return for a pEOT visit within 
7 days after the last dose of study treatment intake, and thereafter to attend further planned 
visits as defined in the SoA [Table 2 and Table 3] and in Section 7.2.  
All participants withdrawn from study treatment are encouraged to continue the planned 
study procedures (e.g., visits and questionnaire completion [Table 3]) until planned FSV, 
provided that the participant’s consent for this further limited participation in the study has 
not been withdrawn. This will decrease the amount of missing data, which is important to 
maintain the integrity of the study. 
5.8.1.2 Pregnancy 
If a participant becomes pregnant while on study treatment, the study treatment must be 
permanently discontinued. The investigator/delegate must counsel the participant and 
discuss the risks of continuing with the pregnancy and the possible effects on the fetus. For 
reporting of pregnancies, refer to Section 8.3.1.  
If a participant has a positive urine pregnancy test, the study treatment must be interrupted 
immediately. A serum pregnancy test must be performed as soon as possible. If the 
pregnancy is confirmed, the study treatment must be permanently discontinued. If the 
result of the serum pregnancy test is negative, the study treatment may be resumed.  
5.8.1.3 Lack of compliance with methods of contraception 
If the investigator/delegate considers that the participant is not compliant with the protocol 
methods of contraception instructions, the study treatment must be permanently 
discontinued. 

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5.8.1.4 Cardiovascular 
All clinically relevant ECG or vital sign abnormalities as per investigator’s judgment must 
be recorded as an AE in the eCRF as per protocol AE definitions [see Section 8.1.1]. 
5.8.1.4.1 Day 1 specific stopping criteria 
Cardiac monitoring on the first dose on Day 1 and on the first day of re-initiation of study 
treatment will be required for participants. 
Participants must be permanently discontinued from study treatment if any of the 
following occurred on Day 1 or on the day of re-initiation: 
– 
HR < 40 bpm at two consecutive hourly 12-lead ECG post-dose assessments; 
– 
SBP < 90 mmHg at two consecutive hourly BP measurements post-dose; 
– 
For participants with baseline pre-dose SBP < 90 mmHg: decrease in SBP of > 5 
mmHg from pre-dose SBP value at two consecutive hourly BP measurements post-
dose; 
– 
The participant does not meet the criteria for discharge from the monitored setting at 
12-hour post-dose.  
Close monitoring (ECG or BP, as appropriate) is recommended for participants who meet 
study treatment discontinuation criteria as detailed in Appendix 5. 
5.8.1.4.2 Other cardiovascular stopping criteria 
• If participant presents with a QTcF of > 500 ms (females) or > 480 ms (males) at any 
time throughout the study, as measured and documented by 12-lead ECG, a re-test 
should be performed at the same visit. If at re-test, QTcF is confirmed > 500 ms (females) 
or > 480 ms (males), the participant must be permanently discontinued from study 
treatment. Participants with QTcF prolongation should be monitored until the absence 
of the persisting ECG abnormality can be confirmed. 
• Symptomatic bradycardia or hypotension (e.g., syncope) at any time.  
If any of those criteria are met, it will be recorded as an AE/SAE, and follow-up monitoring 
will have to be provided until the AE resolves and the participant’s condition is stable. 
5.8.1.5 Infections 
In the event of a serious infection as per the investigator’s opinion (e.g., opportunistic 
infection or serious infection requiring i.v. medication or hospitalization), the participant 
should be adequately treated and monitored until resolution of the infection. The 
investigator should consider permanent discontinuation of study treatment. The decision to 

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permanently discontinue study treatment should be made after evaluation of all available 
information concerning all potential causes of infection and based on the clinical status of 
the participant and response to the treatment of the infection. Further diagnostic work-up 
and consultation with an infectious disease specialist or other specialist should be 
considered according to local practice and the clinical situation. 
These AEs must be reported in the eCRF [see Section 8.2]. Concomitant 
immunomodulatory medications may also be discontinued at the discretion of the 
investigator. 
Note: Participants should not receive any of the per-protocol prohibited systemic 
treatments during 6 months after last study treatment intake, unless clinically indicated and 
justifiable in the opinion of the investigator. 
5.8.1.6 Lymphocyte count monitoring 
Lymphocytes are assessed by the central laboratory at each scheduled visit.  
Alert for total lymphocyte < 200 cells/µL (i.e., 0.2 × 109 cells/L or 0.2 × 103 cells/µL) 
At any time throughout the study, when total lymphocyte count is < 200 cells/µL, an alert 
including the lymphocyte count results will be generated by the central laboratory. This 
alert will be distributed to the investigator and to the sponsor. The sponsor will ensure that 
the investigator/delegate has received the alert. The investigator/delegate will take 
appropriate action to ensure the safety of the participant [see Figure 2]. The investigator 
must closely follow up with the participant, especially focusing on signs or symptoms of 
infection. The participant must be instructed to contact the study site if symptoms of 
infection occur [see Section 5.8.1.5]. 
Upon receipt of the first alert, the investigator/delegate will rapidly contact the participant 
to schedule a visit at study site as detailed below, while asking the participant to continue 
taking the study treatment. 
At this visit, a lymphocyte count re-test and necessary clinical assessments will be 
performed. The central laboratory must be used for assessments of the re-test lymphocyte 
count.  
Re-test result is ≥ 200 cells/µL (i.e., 0.2 × 109 cells/L or 0.2 × 103 cells/µL) 
The participant can continue taking study medication and can resume the regular schedule 
of visits as per protocol. 
Re-test result is 100 to < 200 cells/µL  
The participant must be retested within 2 weeks, while continuing to take study treatment. 

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Re-test result is < 100 cells/µL (i.e., 0.1 × 109 cells/L or 0.1 × 103 cells/µL) 
The participant must be permanently discontinued from study treatment, except at the first 
occurrence of a total lymphocyte count at re-test < 100 cells/µL, in which case the 
participant must be re-tested within 1 week. Then, based on the results:  
• If the lymphocyte count at 1-week re-test is confirmed < 100 cells/µL, the participant 
must be permanently discontinued from study treatment. For results of 100 to < 200 
cells/µL or ≥ 200 cells/µL, see instructions above. 
Note: If the lymphocyte count < 200 cells/µL is accompanied by signs of opportunistic 
infection or severe infection (as per investigator’s judgment), the study treatment will be 
permanently discontinued. The participant will be medically followed [see Section 5.8.1.5].  
Figure 2 
Guidance for re-test results of lymphocytes < 200 cells/µL 
 
 
Total lymphocyte count at final study visit 
If the lymphocyte count is < 500 cells/μL at FSV (i.e., after 6 months FU period or at the 
end of PTOP/FU period for participants who permanently discontinued study treatment), 
monitoring of clinical status and total lymphocyte count in local laboratory should be 
performed on a regular basis (e.g., every 2–4 weeks) until the lymphocyte count has 
returned to ≥ 500 cells/µL.  
5.8.1.7 Liver enzyme abnormalities 
In the event of elevated transaminase > 3 × ULN, the participant will be closely observed, 
liver tests will be repeated, and study treatment must be permanently discontinued, 
according to the guidance provided in Figure 3. 

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Figure 3 
Guidance for monitoring liver test abnormalities 
 
 
* Symptoms include unusual lethargy or fatigue, nausea, vomiting, right upper quadrant pain or tenderness, jaundice, 
anorexia, dark urine, fever, rash, itching and/or eosinophilia (> 5%). 
** See details below for participants receiving or not receiving anticoagulants. 
ALT = alanine aminotransferase; AST = aspartate aminotransferase; INR = international normalized ratio; LT = liver 
test; TBIL = total bilirubin; ULN = upper limit of normal.  
 
When marked abnormalities for AST, ALT, TBIL, or INR are reached as indicated in 
Figure 3, an alert will be sent by the central laboratory to the site/investigator and the 
sponsor. If a participant has ALT or AST ≥ 3 × ULN and is not receiving an anti-coagulant, 
then the threshold to permanently discontinue study treatment is 1.5 × ULN for INR. If a 
participant has ALT or AST ≥ 3 × ULN and is receiving an anti-coagulant (e.g., coumadin), 
then the threshold for INR is 1.5 × the upper INR target set for the participant (for example, 
if a participant is receiving coumadin with an INR target of 2 to 3, the marked abnormality 
for the INR would be 4.5 for this participant). The sponsor will contact the site/investigator 
to ensure that he/she will immediately contact the participant to enquire about symptoms 
and ask the participant to permanently discontinue study treatment or to return to the site 
within 72 h at the latest to repeat the test at the central laboratory (unless the clinical 
situation mandates immediate local testing) as applicable. 
In the event of repeated abnormal liver tests within 72 h, the participant will be closely 
monitored, and liver enzyme and bilirubin tests will be repeated by the central laboratory 
**

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or locally according to the scheme illustrated in Figure 3. Further diagnostic work-up and 
consultation with a hepatologist or other specialist should be considered according to local 
practice. Preferably, the central laboratory should be used. If the local laboratory is used 
for testing in some situations (e.g., laboratory result needed immediately by treating 
physician), please ensure that an additional sample is sent to the central laboratory at the 
same time.  
In all cases of permanent study treatment discontinuation, follow-up monitoring must be 
conducted until abnormalities in the liver assessments have resolved or are steadily 
improving. 
5.8.1.8 
Ocular abnormalities 
Suspected macular edema cases will be submitted to the IOSB [see Section 4.4]. 
The study treatment must be temporarily interrupted during the case assessment. If the 
IOSB confirms or suspects macular edema, study treatment must be permanently 
discontinued. If the IOSB assesses the case as not being a macular edema, the study 
treatment can be re-started. The participant must be followed up until resolution or until 
the condition is considered not clinically significant by the investigator.  
5.8.1.9 
Initiation of forbidden concomitant medication during the study 
At any time throughout the study, study treatment will be permanently discontinued if the 
participant starts taking a forbidden concomitant therapy [see Section 6.2.3]. 
5.8.1.10 Other potential permanent treatment discontinuation 
In the event of malignancy, study treatment will be permanently discontinued and the 
participant must be medically followed up as appropriate. 
5.8.1.11 Other study-specific criteria for re-initiation after temporary treatment 
interruption 
The following guidance is provided for re-initiation of study treatment after study treatment 
interruptions.  
A study visit to re-initiate treatment is only required after a study treatment interruption 
lasting more than 7 consecutive days and occurring between Day 1 and Day 14 of the study.  
• During the period between Day 1 and Day 14, if the participant fails to take the dose for 
more than 7 consecutive days, the participant must inform the investigator and a re-
initiation visit should take place no later than 7 days after the investigator is aware of 
the treatment interruption. Re-initiation of study treatment must be monitored on site 
following the cardiac assessment schedule and applying the discharge criteria as on Day 
1 [see Appendix 5]. 

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• If, at any visit (scheduled or unscheduled), the participant reports to the investigator that 
he/she missed taking the dose for one or more days during the initial 2 weeks of 
treatment (Day 1 to Day 14) but then resumed study treatment without reporting the 
interruption promptly, information on any event potentially related to the study 
treatment interruption should be collected. The participant should be counseled on the 
risks of non-compliance. Information on the treatment interruption must be recorded in 
the eCRF. No re-initiation visit needs to be performed in such a case. 
If the participant misses doses after Day 14, a re-initiation visit is not required. Information 
on any event potentially related to the interruption should be collected and the participant 
should be counseled on the risks of non-compliance. Information on the treatment 
interruption must be recorded in the eCRF. Participants must be instructed to contact the 
investigator immediately if they experience any symptoms that may be related to 
bradycardia (e.g., dizziness, vertigo, syncope). 
5.8.2 
Measures for participant retention 
Participants withdrawn from study treatment are encouraged to remain in the study until 
its completion. 
In order to ensure study data integrity and completeness, participants that are prematurely 
discontinued from study treatment should perform the subsequent visits as per PTOP 
schedule [see Table 3].  
The investigator is encouraged to explain to the participants the importance of remaining 
in the study for data accuracy purposes and scientific relevance of the study results. The 
ICF will also highlight the scientific importance of the participant’s data. 
5.8.3 Withdrawal from the study  
Participants may voluntarily withdraw from the study without justification for any reason 
at any time. Participants are considered withdrawn if they state an intention to withdraw 
further participation in all components of the study (i.e., withdrawal of consent), die, or are 
lost to follow-up [see Section 5.8.4. If a participant withdraws consent for further study 
participation, no further data will be collected in the eCRF from the date of withdrawal 
onward.  
If, for whatever reason (except death or lost to follow-up), a participant withdraws from 
the study, the investigator/delegate should make their best effort to schedule a last 
appointment / telephone call to assess the safety and wellbeing of the participant, collect 
unused study treatment, and discuss follow-up medical care. Data obtained during this last 
appointment / telephone call will be recorded in the participant’s medical records but will 
not be collected in the eCRF.  

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The main reason for premature withdrawal from the study must be documented in the eCRF.  
The investigator must provide follow-up medical care for all participants who withdraw 
from the study, or must refer them for appropriate ongoing care, as described in Section 
6.3. 
5.8.4 Lost to follow-up 
A participant will be considered as lost to follow-up if he/she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the site. 
The site must take preventive measures to avoid a participant being lost to follow-up (e.g., 
document different ways of contact, such as telephone number, home address, email 
address, contact person if the participant cannot be reached).  
The following actions must be taken if a participant fails to return to the site for a scheduled 
study visit: 
• The site staff must attempt to contact the participant and reschedule the missed visit as 
soon as possible and counsel the participant on the importance of maintaining the 
assigned visit schedule and ascertain if the participant wishes to and/or should continue 
in the study. 
• If the participant cannot be reached, the site must make a reasonable effort to contact 
the participant and document all attempts in the participant’s medical chart. Reasonable 
efforts include, when possible, 3 telephone calls to the last available telephone number 
and 1 registered/certified letter to the participant’s last known mailing address or local 
equivalent methods. 
• If the participant is still unreachable after all contact attempts listed above, he/she will 
be considered lost to follow-up. 
The date of last successful contact with the participant will be collected in the eCRF. 
6 
TREATMENTS 
6.1 Study treatment 
6.1.1 
Investigational treatment  
Cenerimod is supplied as film-coated tablets at a 4 mg dose.  
The inactive ingredients of the cenerimod film-coated tablet formulation are: 
hydroxypropyl methylcellulose, polyvinylpyrrolidone, mannitol, colloidal silicon dioxide, 
and magnesium stearate. The film coating consists of hydroxypropyl methylcellulose, 
propylene glycol, titanium dioxide, iron oxide yellow, iron oxide red, and iron oxide black. 

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6.1.2 
Study treatment dosing and administration 
One tablet of cenerimod will be taken orally irrespective of food intake. The tablet will be 
swallowed whole. It is preferable that the tablet is taken each day in the morning.  
Participants must be instructed not to take study treatment in the morning of study visit 
days. On the day of the study visits, study treatment must be administered only after the 
completion of the pre-dose assessments (i.e., vital signs, ECGs, laboratory tests, and PK 
sampling). The dose prior to the Month 2 visit must be administered by the participant 24 
h (±3 h) prior to the anticipated dosing at the Month 2 visit. Date and time of study 
treatment intake will be recorded in the eCRF for Day 1, the day before Month 2, and 
Month 2. 
To ensure compliance, the study personnel must remind participants at each visit of the 
study treatment intake requirements. 
6.1.2.1 Study treatment dose adjustments  
Study treatment dose adjustments are not permitted. 
Note that under no circumstances should a participant take more than 1 tablet per day. 
6.1.3 Justification for dose 
The selection of a 4 mg (o.d.) dose of cenerimod for this study is based on the safety and 
efficacy results from the Phase 2b study (ID-064A202), where cenerimod did not show any 
safety signals/concerns at any tested dose (0.5, 1, 2, and 4 mg), and was not associated with 
any clinically relevant safety findings. In that study, cenerimod 4 mg was well tolerated 
and was the only dose to show a clinically significant reduction on the primary endpoint 
(change from baseline to Month 6 in mSLEDAI-2K score) [Cenerimod IB, section 5.3.1.2]. 
These results are in line with those of the anifrolumab Phase 3 study (TULIP-1) conducted 
in SLE patients and using similar endpoints [Furie 2019]. 
6.1.4 Treatment assignment 
All participants will receive cenerimod. An IRT system will be used to assign the kit 
numbers to the individual participants. 
6.1.5 Study treatment handling/preparation/storage/accountability 
Manufacture, labeling, packaging, and supply of study treatments is conducted according 
to Good Manufacturing Practice. 
All study treatment supplies are to be used only in accordance with this protocol, and not 
for any other purpose. 

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6.1.5.1 Study treatment packaging and labeling 
Study treatment is provided as tablets and supplied in childproof bottles. 
Study treatment is labeled to comply with the applicable laws and regulations of the 
countries in which the study sites are located. 
6.1.5.2 Study treatment distribution and storage  
Study treatment supplies must be kept in an appropriate, secure area and stored according 
to the conditions specified on the label. The storage conditions must be explained to the 
participant. 
6.1.5.3 Study treatment dispensing 
The participants will receive sufficient study treatment to cover the period up to the next 
scheduled visit. Participants are asked to return all used, partially used, and unused study 
treatment bottles at each visit. Should the treatment bottle dispensed at a scheduled visit be 
lost or damaged, a replacement bottle can be requested via the IRT system. 
Protocol-mandated study treatment dispensing procedures may not be altered without prior 
written approval from the sponsor. In exceptional circumstances (e.g., if the participant lost 
the study treatment between 2 visits, or if the participant is unable to return to the site due 
to a medical emergency / hospitalization at another hospital / long distance to travel / 
pandemic restrictions), unscheduled dispensing and delivery of study treatment may occur 
outside of a scheduled visit. 
An accurate record of the date and amount of study treatment dispensed to each participant 
must be available for inspection at any time. 
6.1.5.4 Study treatment accountability 
The inventory of study treatment dispensed to and returned by the participant (i.e., study 
treatment accountability) must be performed by site personnel on the day of the visit and 
before dispensing further study treatment. The inventory is to be recorded by site personnel 
in the site documentation and in the eCRF. The study treatment accountability log in the 
eCRF will include the following information for each study treatment bottle dispensed to 
the participant: 
• Dispensed bottles number. 
• Date dispensed / number of tablets dispensed. 
• Date returned / number of tablets returned. 
All study treatment supplies, including partially used or empty bottles must be retained at 
the site. 

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If the participant forgets to bring the remaining study treatment to a study visit, he/she must 
be instructed to not take any tablets from the remaining study treatment bottle and to return 
it at the next visit. 
6.1.5.5 Study treatment return and destruction 
On an ongoing basis and/or upon termination of the study, the CRA will collect used and 
unused treatment kits, which will be sent to the warehouse, where the sponsor / depot 
personnel or a deputy will check treatment reconciliation.  
In certain circumstances (e.g., local hospital procedures), used and unused study treatment 
containers may be destroyed at the site. In general, this can only be done once study 
treatment accountability is finalized and has been checked by the sponsor personnel 
representative, and written permission for destruction has been obtained from the sponsor. 
Exceptions might occur if a local process requires immediate destruction of the study 
treatment. Such local study treatment destruction processes must be provided and approved 
by the sponsor. 
6.1.6 Study treatment compliance 
Study treatment compliance with the prescribed study treatment dose regimen is based on 
study treatment accountability. Study treatment compliance will be calculated by site 
personnel at each monthly visit during the study treatment period using the formula below: 
Compliance = [(number of tablets dispensed – number of tablets returned) / total number 
of tablets that should have been taken during the period*] × 100 
*The period is defined as the number of days between the respective visits. 
During the entire study treatment period, the study treatment compliance is expected to be 
80% or above. At each monthly visit during the study treatment period, the study treatment 
compliance is also expected to be 80% or above. If below 80% without a medical 
justification (e.g., AE), this will be considered as a protocol deviation. 
The investigator/delegate must discuss the non-compliance with the participant to clarify 
the reason(s) and to take appropriate actions to avoid re-occurrence. This discussion and 
its outcome must be documented in the source documents. 
6.2 Previous and concomitant medications 
A previous therapy is any treatment for which the end date is prior to start of study 
treatment. Relevant previous therapies (e.g., SLE treatment) for which the end date is less 
than 12 months prior to ICF signature will be recorded in the eCRF. 

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A study-concomitant therapy is any treatment (including methods of contraception and 
traditional and alternative medicines, i.e., plant-, animal-, or mineral-based medicines) 
given for any reason including the background SLE therapy that is either ongoing at the 
start of study treatment or is initiated during the study treatment period, or during the 
follow-up period up to FSV. All study-concomitant therapies administered will be reported 
in the eCRF.  
The generic name, start/end dates of administration (as well as whether it started prior to 
first study treatment administration and/or was ongoing at FSV), route, dose, frequency, 
and indication for use will be recorded in the eCRF. 
6.2.1 
Auxiliary medicinal products 
An auxiliary medicinal product is a medicinal product used for the purpose of the clinical 
study but not as an Investigational Medicinal Product (e.g., a mandatory background 
therapy or a medicinal product used for a study-mandated procedure). 
Auxiliary therapy includes background SLE therapy as requested for a participant to be 
eligible in the study. Any post-Day 1 change of background medication has the potential 
to obviate the treatment effect and efforts should be made to adjust background medication 
during the screening period.  
Allowed auxiliary therapy 
Conditions of use 
Antimalarials (hydroxychloroquine, 
chloroquine, quinacrine) 
See Section 6.2.1.1 
Mycophenolate mofetil / mycophenolic acid 
Azathioprine 
Methotrexate 
Belimumab 
Telitacicept 
OCS background therapy 
See Section 6.2.1.2 
 
6.2.1.1 
SLE background therapy (except OCS background therapy) conditions of 
use 
For eligibility, SLE background medication must have been started at least 90 days prior 
to Screening. 
Dose, frequency, and route of administration must be stable for at least 30 days prior to 
Day 1. 

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Treatment, dose, and route of administration should remain identical from Day 1 to the 
completion of Visit 14 (Month 12).  
The dose may be decreased by the investigator/delegate for toxicity reasons, or to optimize 
management of an AE, such as an infection. The toxicity/event must be reported as an AE 
and the change of dose entered in the eCRF. The dose can be returned to the Day 1 level if 
the toxicity/event resolves and as clinically indicated.  
Antimalarials/immunosuppressants (including dose, frequency, and route of administration) 
should not be changed if a participant has increased SLE disease activity during the OCS 
tapering period. 
6.2.1.2 OCS background therapy conditions of use 
Figure 4 
OCS management overview 
 
 
CS = corticosteroid(s); OCS = oral corticosteroid(s). 
 
6.2.1.2.1 OCS eligibility criteria 
• OCS must have been started at least 30 days prior to Screening.  
• Participants will be eligible at Screening and Day 1 under the following conditions: 
– when OCS is the only SLE background medication: ≥ 7.5 mg/day and 
≤ 30 mg/day prednisone or equivalent.  
– when OCS is not the only SLE background medication: ≤ 30 mg/day prednisone 
or equivalent. 
6.2.1.2.2 OCS management and dose optimization during Screening (Visit 1 up to 
Visit 2) 
For the purpose of standardization, it is recommended to use either prednisone, 
methylprednisolone, or prednisolone during the study [see Appendix 12]. If a participant 
is treated with another background OCS therapy, it is recommended to switch to 1 of the 
3 OCS mentioned above during the Screening period. 

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For participants treated with OCS prior to enrollment, it is recommended to optimize the 
background OCS therapy during the Screening period to the minimal effective dose by 
performing a cautious tapering [Table 6]. This will allow for minimal OCS changes during 
the treatment period outside of the mandatory OCS tapering period (Visit 5 up to Visit 10), 
which is the preferred approach. 
Dose reductions are at the investigator’s discretion; however, the OCS dose must be kept 
stable for 15 days prior to Day 1.  
6.2.1.2.3 OCS management during treatment period 
The OCS dose should be kept stable. Any change in the OCS dose should be restricted to 
2 different situations: a) medically justified safety reason and b) protocol-specified rules 
(see below). The justification and nature of any change should be thoroughly documented 
in the participants’ medical records. 
Protocol-specified rules for changes in OCS dose 
From Visit 2 up to Visit 5: Recommended stable OCS dose 
The OCS dose should be kept stable. The investigator is encouraged to only change the 
OCS dose in the following situation: 
• OCS dose decrease is allowed for participants with SLE disease activity improvement 
for at least 4 consecutive weeks (i.e., between 2 consecutive visits), but is not 
mandatory. Table 6 describes a recommended tapering schedule. SLE disease activity 
improvement is defined as BILAG reduction of all A scores to B/C/D scores and 
reduction of all B scores to C/D scores, and no score worsening in other organ systems, 
as defined by ≥ 1 new A score or ≥ 2 new B score. 
From Visit 5 up to Visit 10: Mandatory OCS tapering  
For participants with an OCS dose ≥ 10 mg/day at Day 1, steroid tapering to an OCS dose 
of ≤ 7.5 mg/day MUST be attempted [see the recommended tapering schedule in Table 6] 
and started within 14 days after Visit 5.  
Tapering should not be attempted if at least 1 of the following criteria is met:  
• Worsening of SLE disease activity defined as ≥ 1 new BILAG A or ≥ 2 new BILAG B 
scores (except mucocutaneous and musculoskeletal domains).  
• Moderate-to-severe skin disease as reflected by a CLASI activity score of ≥ 10.  
• Moderate-to-severe arthritis disease as reflected by an active joint count of ≥ 4 tender 
and/or swollen joints.  

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If a participant fails tapering down at the first attempt, an increase of the OCS dose up to 
the dose before the start of the forced tapering is allowed. Another attempt to taper down 
OCS might be done unless at least 1 of the above criteria is met. 
If steroid tapering is not attempted in an eligible participant, the sponsor must be contacted 
immediately. The recommended steroid-tapering regimen is provided in Table 6, but due 
to variability in participant responses to steroid treatment and tolerability of taper, 
investigators will have flexibility in how the OCS dose is reduced at each visit. 
Investigators will not be required but may continue to taper OCS dose beyond 7.5 mg/day 
up to Visit 10.  
Steroid tapering will not be permitted after Visit 10. The dose may be optimized for 14 days 
after Visit 9 but the OCS dose must be stable for 14 days prior to the scheduled Visit 10. 
Table 6 
Example of background OCS therapy forced tapering schedule  
 
1 OCS dose in [mg/day] prednisone equivalent. 
2 Day 0 = first day of OCS tapering. 
OCS = oral corticosteroid(s). 
 
Participants who experienced increased SLE disease activity may receive one CS burst 
(after study visit assessments) during the first 8 months of treatment [see Section 6.2.2.1].  
From Visit 10 to Visit 14: Mandatory stable OCS dosage  
OCS dosage must be stable unless medically justified by the investigator.  
No increase in OCS is allowed after Visit 10 except for managing AEs or as prophylaxis 
for adrenal insufficiency. 

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6.2.2 Allowed concomitant therapy 
Allowed concomitant therapy include medications allowed under certain conditions.  
Allowed medication 
Conditions of use 
CS burst 
See Section 6.2.2.1. 
NSAIDs 
See Section 6.2.2.2. 
Low-dose aspirin 
Stable long-term use of low-dose aspirin (maximum of 325 mg/day) for 
cardiovascular disease is permitted. 
Non-NSAIDs pain 
medications 
Temporary use of pain medications (e.g., acetaminophen/paracetamol or other 
non-NSAID pain medication) may be used for pain management as required, 
based on Investigator judgment for up to 1 week at a time and should not be taken 
on the day of a scheduled visit until all assessments have been completed.  
Topical therapy 
Topical ocular therapy (e.g., chronic treatment for glaucoma, ocular 
inflammation, allergy), including dilating eye drops, mydriatics, parasympathetic 
antagonists (e.g., tropicamide) or sympathetic agonists (e.g., phenylephrine). 
Topical skin therapy, inhaled and nasal therapy, including topical use of CS. 
Atropine 
Permitted i.v. in the event of symptomatic bradycardia. 
Vaccination 
Only non-live vaccines. 
 
6.2.2.1 CS burst conditions of use 
From Visit 2 to Visit 10  
Participants who experienced increased SLE disease activity may receive one CS burst 
(after study visit assessments). Only one burst can be administered between Visit 2 and 
Visit 10, as follows: 
• OCS dose increase up to a maximum daily dose of 40 mg/day prednisone or equivalent 
[see Appendix 12] up to a total of 14 days. This OCS increase must be fully 
administered and tapered to less than or equal to the Day 1 (Visit 2) dose by no later 
than Visit 10. 
or 
• Intramuscular methylprednisolone (≤ 80 mg or equivalent) administered as a single 
dose. 
or 
• A maximum of 2 intra-articular / tendon sheath / bursal injections (for a total 
methylprednisolone ≤ 80 mg or equivalent) at the same visit.  

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From Visit 10 to Visit 14 
No CS burst allowed.  
6.2.2.2 NSAIDs conditions of use 
For the treatment of SLE, NSAIDs dose and frequency must be stable for at least 30 days 
prior to Day 1 and must remain stable throughout the study. The dose may be reduced for 
reasons of toxicity but not efficacy. 
For the treatment of non-SLE-related conditions (e.g., headache, menstrual cramps), 
temporary use and/or dose change is allowed. 
Of note, NSAIDs cannot be used in combination with another NSAID at any dose, except 
low-dose aspirin (≤ 325 mg/day) and topical NSAIDs may be used in combination with 
1 oral NSAID. 
On a given visit day, NSAIDs should not be taken until after all assessments have been 
completed. 
6.2.3 
Forbidden concomitant therapy 
The following concomitant therapies are forbidden during the treatment period and until 
6 months after last study treatment intake. Initiation of any of these medications will result 
in the permanent discontinuation of study treatment. 
• Immunosuppressive agents not listed in allowed concomitant medications, such as 
cyclophosphamide, cyclosporine, voclosporin, leflunomide, sirolimus, tacrolimus, etc.  
• Immunosuppressive 
or 
immunomodulatory 
biological 
agents 
(e.g., 
i.v. 
immunoglobulin, anifrolumab, rituximab). 
• S1P receptor modulators other than cenerimod. 
• β-blockers, diltiazem, verapamil, digoxin, digitoxin, or any other anti-arrhythmic or 
HR-lowering therapy [list of drugs provided in Appendix 3]. 
• QT-prolonging drugs with known risk of torsade de pointes [list of drugs provided in 
Appendix 4]. 
• Vaccination with live vaccines. 
• Inhibitors of the breast cancer resistance protein transporter: curcumin, cyclosporine, 
eltrombopag, elacridar, gefitinib, teriflunomide. 
• Cannabidiol and other derivatives of marijuana. 
• Investigational agents. 
Note: due to the long half-life of cenerimod, in the event of permanent discontinuation 
from study treatment for any reason, participants should not receive any of the forbidden 

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therapies during the follow-up period of 6 months after last study treatment intake, unless 
clinically indicated in the judgment of the investigator.  
6.3 Medical care of participants after study completion / withdrawal from 
study  
After the participant’s study completion or premature withdrawal from the study, the 
investigator/delegate will explain to participants what treatment(s) / medical care is 
necessary and available according to local medical practice and applicable guidelines. 
Female participants of childbearing potential must be reminded of the contraception 
requirements as described in Section 5.5.2. In the event of premature discontinuation from 
the study, WoCBP must be instructed to continue the use of contraception for at least 
6 months after the last dose of study treatment to prevent any pregnancy. These reminders 
and instructions must be documented in the source documents of these female participants. 
7 
VISIT SCHEDULE AND STUDY ASSESSMENTS AND PROCEDURES  
7.1 General information 
The study visits and their respective time windows are listed in the SoA [Table 1, Table 2, 
and Table 3]. If it is not possible to complete all assessments on the same day, a visit may 
extend over more than 1 day within the permitted time window.  
All efforts should be made to keep participants on schedule based on the date of their Day 
1 (Visit 2), which is the day of the first study drug treatment. 
When scheduling the different assessments for a study site visit, the following should be 
considered: 
• The participant must come to the clinic in a fasted condition for all protocol scheduled 
visits.  
• Participants should be instructed not to take the study medication in the morning of the 
day of the visit.  
• At Visit 2 (i.e., Day 1) and at the re-initiation visit if applicable [see Section 5.8.1.11], 
assessments during the visits will be divided into 2 parts: before (pre-dose) and after 
(post-dose) the administration of the study treatment, which will be taken at the site. 
• Resting time: 
– When a participant must perform a specific protocol-mandated test at another 
department within the hospital, sufficient time should be allowed for the participant 
to rest prior to the examination. 

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– Sufficient time between blood drawing and cardiac assessments (i.e., ECGs and/or 
BP measurement) is to be allowed. Blood drawing should preferably be done after 
cardiac assessments. 
• All PK samples are to be collected at the time points outlined in Table 2. The actual 
date and time of each PK sample collection will be collected in the eCRF. 
• Follow-up information will be collected during the FU1 visit; FU2, FU3, FU4, and FU5 
visits (telephone call visits), and at the FSV visit (6 months after last study treatment 
intake).  
• To minimize the risk of non-compliance with contraception requirements, the study 
personnel must remind WoCBP at each visit to use the methods of contraception 
defined for this study. 
Calibration certificates or evidence of equipment maintenance for the below-listed 
equipment used to perform study assessments will be collected for the study trial master 
file by the sponsor:  
• OCT machine.  
• BP device. 
Calibration certificates or evidence of equipment maintenance of other equipment must be 
available as per local requirements.  
7.1.1 
Screening  
A participant who agrees to be part of the study and the investigator/delegate must both 
sign the ICF prior to participation in the study. The ICF must be fully signed see 
Section 10.2 for informed consent procedure on the day of Screening.  
A dated and timed signature must be available prior to any study-specific procedures are 
performed. 
Procedures or assessments conducted as part of the participant’s routine clinical 
management (e.g., laboratory sample, vital signs) obtained before signing the ICF may be 
used for screening or baseline purposes, provided the procedures met the protocol-specified 
criteria and were performed within the time frame defined in the SoA [Table 1, Table 2, 
and Table 3]. In such cases, it must be clear from the source documents when and for which 
reason the assessment was done prior to the signing of the ICF. 
After the ICF has been fully signed, the investigator/delegate contacts the IRT system to 
get a participant identification number allocated to the participant. 

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For convenience reasons, study-specific procedures or assessments can take place on 
different days during the screening period. 
For participants who are being treated with CS prior to enrollment in this study, an 
optimization period aiming to reduce the doses of background OCS therapy to (or as close 
as possible to) the minimum effective dose, should be considered during the screening 
period [see Section 6.2.1.2]. 
Once the enrollment target (defined as completed Day 1 and received cenerimod) has been 
met, participants who have signed the ICF may not be allowed to enroll. 
7.1.2 
Unscheduled visits 
Unscheduled visits may be performed at any time during the study and will be recorded in 
the eCRF. Depending on the reason for the unscheduled visit (e.g., AE), appropriate 
assessments will be performed based on the judgment of the investigator and the results 
will be recorded in the eCRF. After an unscheduled visit, the regular scheduled study visits 
must continue according to the SoA [Table 2]. 
7.1.3 
Study completion  
A participant who completes 12 months of treatment and the follow-up period is considered 
to have completed the study. A participant who permanently discontinued the study 
treatment and who agreed to still follow planned study procedures thereafter see Section 
5.8.1 or was withdrawn from the study because of study closure or study premature 
termination or suspension of the study [see Section 10.10 is also considered to have 
completed the study. 
7.2 Study assessments and procedures 
The study assessments and procedures and their timing are summarized in the SoA [Table 1, 
Table 2, and Table 3]. All study assessments performed during study visits (scheduled or 
unscheduled) are carried out by the investigator/delegate physician or a healthcare 
professional with an advanced practice role, if allowed by local regulations, and are 
recorded in the eCRF, unless otherwise specified.  
7.2.1 
Demographics / baseline characteristics 
Demographic and baseline characteristic data to be collected in the eCRF for all 
participants that received study medication include age, sex, and race. Relevant medical 
history and/or current medical conditions based on the investigator/delegate’s judgment 
(e.g., chronic and ongoing acute conditions, serious past conditions) present before and/or 
at the time of signing informed consent will be recorded in the eCRF. Where possible, 
diagnoses and not symptoms will be recorded. 

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The following medical history and/or current medical conditions are considered relevant 
for this study and must always be reported in the eCRF: 
• Valvular heart disease, arrhythmias, tachycardia, bradycardia, atrial fibrillation, atrial 
flutter, PR interval shortened, QTc prolonged, left ventricular hypertrophy, right 
ventricular hypertrophy, angina pectoris, myocardial infarction, coronary artery disease, 
heart failure (current New York Heart Association class should be provided), 
cardiomegaly, pericarditis, myocarditis, endocarditis, idiopathic cardiomyopathy, 
congenital heart disease, previous heart surgery, stroke, transient ischemic attack, 
peripheral vascular disease, deep vein thrombosis. 
• Chronic medical conditions including pulmonary, CNS, liver function, renal function, 
eye disorder, and skin conditions at any time in the past. 
• New acute medically relevant conditions in the past 6 months including any serious 
infection defined as life-threatening or requiring i.v. antibiotics or hospitalization. 
• Exposure to healthcare settings in the past 3 months (e.g., hospitalization, emergency 
care admissions, visit to emergency medical services facility). 
• Any history of pregnancy morbidity (e.g., fetus loss, spontaneous abortion, premature 
birth). 
• Previous and concomitant therapy [see Section 6.2]. 
• Any history of chemotherapy, radiotherapy, operations, immunosuppression, or any 
other relevant medical treatment.  
SLE disease characteristics as defined below, evidenced by documentation in the 
participant charts, will be recorded in the eCRF: 
• Date of SLE diagnosis. 
• SLE symptoms according to 2019 EULAR/ACR Criteria [see Appendix 2]. 
For women, the reason for not being of childbearing potential will be recorded in the eCRF. 
7.2.2 
Disease activity assessments 
Unless otherwise specified, the date of each assessment will be collected in the eCRF. 
Investigators and designated site personnel must be trained and certified for all the 
assessments required in this study prior to participants entering Screening at their 
respective sites. If there is a change in site personnel over the course of the study, new 
investigators or physicians must be trained and certified prior to performing these 
assessments. 

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The investigator/delegate will record data for the disease assessment scores on the paper 
scoring sheets which replicate those contained in the appendices. Data from the physical 
examination, weight, clinical symptoms, and the medical evaluation of the participant will 
also be collected by the investigator or delegate. These data will be used to complete 
relevant aspects of the disease assessment scores.  
The instructions for the scoring of the disease activity assessments will be provided in form 
of instructions manual. 
7.2.2.1 Systemic Lupus Erythematosus Disease Activity Index-2000 
The SLEDAI-2K [see Appendix 6] will be assessed by the investigator or delegate as per 
the schedule of assessments [see Section 1.3]. 
The SLEDAI-2K is a validated clinical index for the measurement of disease activity in 
SLE. It was developed as a modification of SLEDAI to reflect persistent, active disease in 
descriptors (i.e., proteinuria, rash, alopecia, and mucous membrane lesions) that were 
previously only considered if new or recurrent. 
The investigator will perform physical examinations, question the participant on his/her 
current state and about any potential SLE symptoms and/or manifestations that were 
“present” or “absent” during the last 10 days, and collect all laboratory variables relevant 
to the scoring (e.g., protein-to-creatinine ratio, anti-dsDNA titer, dipstick urinalysis). If the 
dipstick results are positive, the urine sample will be further analyzed as clinically indicated 
(i.e., microscopic analysis of WBC, RBC, casts, and protein quantification). If the 
participant reports symptoms of myositis, the investigator should request aldolase analysis 
to be performed from the collected blood sample. 
Notes: 
• Reduction in total WBC count due to reduction of lymphocytes is the main PD effect 
of S1P1 receptor modulators including cenerimod. Therefore, leukopenia is excluded 
from the SLEDAI-2K scoring to define the mSLEDAI-2K (i.e., mSLEDAI-2K score 
does not consider “leukopenia”.) 
• The clinical mSLEDAI-2K score is only used to evaluate inclusion criteria for 
eligibility, as visit laboratory assessment from central laboratory will not be available 
at the time of Day 1. The clinical mSLEDAI-2K excludes points attributable to any 
urine or laboratory results including immunologic measures. 
7.2.2.2 British Isles Lupus Assessment Group 
The BILAG will be assessed by the investigator or delegate as per the schedule of 
assessments [see Section 1.3]. 

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The scoring system for the BILAG index of disease activity is based upon the principle of 
the physician’s intention to treat, and the main feature of the BILAG index is that disease 
activity in different organs/systems is reported separately. The investigator will record 
clinical features covered by the BILAG index of lupus disease activity and relevant data 
will be recorded in the BILAG form. There are 9 systems: constitutional, mucocutaneous, 
neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, 
and hematological. Immunological data do not contribute to BILAG scores, but basic 
hematology and assessment of renal function determine the scores of the relevant systems 
[see Appendix 7]. As cenerimod causes a reduction in the peripheral blood lymphocyte 
count, and hence the complete WBC count, these data will not contribute to the scoring.  
A score is calculated for each system depending on the clinical features present and whether 
they are “not present”, “new”, “worse”, “the same” or “improving” in the last 4 weeks 
compared to previous assessment. Of note, the “improving” score MUST respect the 
following definition: 
• The amount of improvement is sufficient for consideration of reduction in therapy and 
would not justify escalation in therapy, 
and 
• Improvement must be present currently and for at least 2 weeks out of the last 
4 weeks,  
or 
• The manifestation has completely resolved and remained absent over the whole last 
1 week. 
The scoring categorizes disease activity into 5 different grades from A to E: 
• 
Grade A represents very active disease requiring a prednisone dose of > 20 mg/day or 
equivalent and/or immunosuppressive drugs. 
• 
Grade B represents moderate disease activity requiring a prednisone dose of 
< 20 mg/day 
or 
equivalent, 
topical 
steroids, 
topical 
immunosuppressives, 
antimalarials, or NSAIDs. 
• 
Grade C represents mild stable disease. 
• 
Grade D represents no current disease activity, but the system has been previously 
affected. 
• 
Grade E represents no current or previous disease activity. 
Important extensions of selected BILAG glossary and SLEDAI-2K clinical variable 
definitions are detailed below. Of note, protocol-specific extensions for BILAG are 
highlighted in italic below: 

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• BILAG A or B score in the musculoskeletal organ system due to active polyarthritis, 
defined as follows:  
– “BILAG-2004 A”: severe arthritis (BILAG #41) with observed active synovitis in 
≥ 2 joints with marked loss of functional range of movements and significant 
impairment of basic activities of daily living (ADL), that has been present on 
several days cumulatively over the past 4 weeks, including at the time of the 
Screening visit. Basic ADLs are defined as the following activities which require 
assistance or assistive devices (at least 1 must be present and documented in 
source): ambulation, dressing, eating, toileting, grooming including bathing.  
– “BILAG-2004 B”: moderate arthritis or tendonitis or tenosynovitis (BILAG #42) 
defined as tendonitis/tenosynovitis or active synovitis in ≥1 joint (observed or 
through history) with some loss of functional range of movements which leads to 
some loss of functional range of motion as manifested by effects on instrumental 
ADLs (including cooking, driving, using the telephone or computer, shopping, 
cleaning, etc.), which has been present on several days over the last 4 weeks, 
including at the time of the Screening visit.  
• BILAG and SLEDAI-2K “lupus headache”: lupus headache is rare and is considered a 
manifestation of lupus cerebritis. Migraine, tension, or cluster headaches should not be 
recorded as a lupus headache. Lupus headache should only be recorded if it is disabling, 
lasts at least 3 days, and does not respond to narcotics. It is expected that its severity 
would prompt formal testing (lumbar puncture, magnetic resonance imaging, CT, etc.) 
and require CS and/or immunosuppressants and potentially hospitalization for 
treatment. 
7.2.2.3 SLE Flare Index 
The SFI will be assessed by the investigator or delegate as per the schedule of assessments 
[see Section 1.3], using paper sheets. 
The classic SELENA-SLEDAI Flare Index was originally developed specifically for the 
SELENA study [Buyon 2005, Petri 2005] with the aim of sensitively capturing flares of all 
types as well as distinguishing severe flares. Mild and moderate flares are not discriminated 
in the classic SELENA-SLEDAI Flare Index. 
The SFI assessment [see Appendix 8] will be scored by the investigator/delegate in 
comparison to the participant’s previous visit (i.e., over the past 28 days) and will only 
include findings which are due to SLE disease activity within that timeframe and as per 
investigator opinion. Flare will be defined as any 1 criterion present in either the 
Mild/Moderate Flare or Severe Flare categories. New or worsened manifestations should 
only be reported for manifestations of SLE. The increase in SLEDAI score used to 
determine the SFI will be evaluated in comparison with the previous visit. 

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7.2.2.4 Physician’s Global Assessment of disease 
The PGA will be assessed by the investigator or delegate as per the schedule of assessments 
[see Section 1.3] using paper sheets.  
The PGA is a visual 100 mm analog scale for assessment of disease activity by the 
physician ranging from 0 to 100, with 0 indicating inactive disease and 100 indicating 
severe disease [see Appendix 9]. Pre-defined vertical marks with numbers 0, 1, 2, and 3 
are indicative of SLE disease activity assessment and correspond to “none”, upper limits 
of “mild”, “moderate”, and “severe”, respectively. These marks aim to guide the evaluator 
in his/her assessment. 
The investigator will rate the overall state of the participant and make a vertical mark on 
the scale that will automatically be translated into a length in mm. When scoring the PGA, 
the score from the last visit should be reviewed and the mark should be moved relative to 
the score from the last visit. The PGA is a global assessment for the participant’s lupus 
disease activity. It should not consider non-lupus medical conditions. 
7.2.2.5 Cutaneous Lupus Erythematosus Disease Area and Severity Index  
The CLASI will be assessed by the investigator or delegate as per schedule of assessments 
[see Section 1.3] using paper sheets. 
The CLASI consists of 2 scores: the first summarizes the activity of the disease and the 
second measures the damage done by the disease [see Appendix 10]. Activity is scored 
based on erythema, scale / hyperkeratosis, mucous membrane involvement, acute hair loss 
and non-scarring alopecia. Damage is scored based on dyspigmentation and scarring, 
including scarring alopecia. The scores are calculated by simple addition based on the 
extent of the symptoms. The CLASI is designed as a table where the rows denote 
anatomical areas, and the columns score major clinical symptoms. The extent of 
involvement for each of the skin symptom is documented according to specific anatomic 
areas that are scored according to the worst affected lesion within that area for each 
symptom [Albrecht 2005]. 
7.2.2.6 Tender/swollen joints count 
The tender/swollen joint count will be assessed by the investigator or delegate with 
adequate experience (minimum of 1 year) and training qualifications as per schedule of 
assessments [see Section 1.3] using paper sheets. 
The tender/swollen joint count was originally proposed for rheumatoid arthritis patients. 
Because joint involvement is a common manifestation of SLE, it was later validated and 
used to assess the joint disease activity in SLE patients. 

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The tender/swollen joint count is based on left and right shoulder, elbow, wrist, MCP1, 
MCP2, MCP3, MCP4, MCP5, PIP1, PIP2, PIP3, PIP4, PIP5 joints of the upper extremities 
and left and right knee of the lower extremities [see Appendix 11]. Each of 28 joints will 
be evaluated separately for tenderness (by palpating the joint) and swelling. Joints with 
intra-articular injection within 4 weeks are not evaluable for the assessment. 
7.2.3 
Safety assessments 
Unless otherwise specified, the date of each assessment will be collected in the eCRF. 
The definitions, reporting, and follow-up of AEs, SAEs, and pregnancies are described in 
Section 8. 
7.2.3.1 Physical examination 
A full and complete physical examination will be performed at Visits 1, 2, 3, 5, 8, 11, 14, 
and 15. Full and complete physical examination includes the examination of the following 
body parts/systems: 
• Head, ear, nose, mouth, and throat 
• Eyes 
• Neck 
• Cardiovascular system 
• Respiratory system 
• Abdomen 
• Skin 
• Extremities 
• Neurological system 
• Musculoskeletal system  
Other exams will be performed if indicated, based on medical history and/or symptoms. 
For all other visits, a symptom-driven abbreviated physical examination will be performed 
to capture assessments needed for the SLEDAI-2K, the PGA, the BILAG, and the SFI. 
For details on skin examination, please refer to Section 7.2.3.9. 
Information for all physical examinations must be included in the source documentation at 
the study site.  
All findings, including clinically not relevant findings that are present prior to signing the 
ICF, must be recorded as medical history or SLE-relevant disease history in the eCRF. 

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Physical examination findings after signing the ICF which meet the definition of an AE 
[Section 8.1.1] must be recorded as an AE in the eCRF. 
7.2.3.2 Weight and height 
Height will be measured and recorded in the eCRF at Visit 1 (Screening). Participant body 
weight will be measured (heavy clothing should be removed) and recorded in the eCRF at 
Visit 1 (Screening), Visit 14 (EOT), and Visit 20 (FSV). For further body weight 
measurements as part of the BILAG assessment at each applicable visit [see Section 
7.2.2.2], the weights will be recorded in the source documentation and if clinically relevant, 
the body weight collected outside Visit 1 (Screening), Visit 14 (EOT) and Visit 20 (FSV) 
may be reported as an unscheduled assessment in the eCRF. 
7.2.3.3 Electrocardiograms 
7.2.3.3.1 Cardiac monitoring applicable to all participants 
ECGs will be performed at pre-dose for all participants at all scheduled visits with the 
participant in a fully rested supine position after the participant has been allowed to rest for 
a minimum of 5 minutes prior to the measurement. Single digital 12-lead ECG will be 
performed using the ECG machine provided by the central ECG vendor. The date and 
actual time of ECGs will be recorded in the eCRF. 
A central ECG vendor (see ECG manual for contact details) will be used for the evaluation 
of all protocol-mandated ECGs, including re-tests due to ECG abnormalities and ECGs 
performed at unscheduled visits. The site personnel will electronically transmit the ECGs 
to the central ECG vendor for central reading as soon as possible after the examinations.  
The 12-lead ECG measurements will evaluate the following variables: HR (bpm), PR (ms), 
QRS (ms), QT (ms), QTc (ms), and any ECG findings. The QTc (ms) will be calculated 
according 
to 
Bazett’s 
and 
Fridericia’s 
formula 
(QTcB = QT/(RR)½ 
and 
QTcF = QT/(RR)⅓, respectively). The ECG findings (e.g., rhythm, ectopy, conduction, 
and morphology) and the overall interpretation of the ECG (normal/abnormal) will be 
provided by the ECG central vendor to the study site and to sponsor. 
At Visit 2 Day 1, the pre-dose ECG must be performed for all participants and interpreted 
by the investigator/delegate prior to study drug administration. The applicable cardiac 
exclusion criteria 7, 8, 9 and 10 must be ruled out.  
In addition to transmitting the ECG to the central reader, an ECG record at the Visit 2 must 
be printed, signed, and dated by the person interpreting the ECG and determining that the 
relevant exclusion criteria were not met.  

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ECG reports will be provided by the central ECG vendor to the investigator/delegate. If 
specific (pre-defined in the ECG manual) ECG abnormalities are observed, the central 
ECG vendor will alert the sponsor and the investigator/delegate. 
All ECG reports obtained from the central ECG vendor must be reviewed, signed, and 
dated by the investigator/delegate within 10 calendar days of receipt and filed with the 
source documentation. The investigator/delegate must indicate on the ECG report whether 
abnormal values or findings are considered clinically relevant or not. All ECG findings, 
including clinically not relevant findings, that are present at the time of signing the ICF 
must be recorded on the medical history page in the eCRF. Any clinically relevant ECG 
abnormalities detected after signing the ICF must be reported as an AE or SAE as 
appropriate [see Section 8.2] and must be followed until the finding returns to normal, is 
considered stable, or until the change is no longer clinically relevant. Notable abnormalities 
are detailed in Appendix 13 and marked abnormalities will be detailed in the SAP. 
Details on ECG procedures (recording, transfer of data and reporting) will be provided in 
the ECG manual. 
7.2.3.3.2 Additional cardiac monitoring on Day 1 
To evaluate the possible transient effects on BP and HR after study treatment initiation 
with S1P receptor modulators, 12-lead ECGs and BP assessments will be additionally 
performed as post-dose cardiac monitoring for all participants on Day 1 and at study 
treatment re-initiation visit(s).  
The post-dose cardiac monitoring will consist of post-dose 12-lead ECGs, performed 
hourly within 12 hours post dose, and BP assessments, performed hourly within 6 hours 
post dose and at 12 hours post dose as per the SoA. At 12 hours the participant may be 
discharged from monitored setting if they meet the discharge criteria [see Appendix 5] If 
the participant does not meet the discharge criteria at 12 h post-dose, the participant will 
be permanently discontinued from the study treatment and will be kept in the monitored 
setting for observation. 
Any cardiac events of potential clinical concern on Day 1 and on the first day of 
re-initiation visit must be assessed by the investigator or their delegate for seriousness. In 
addition, the investigator or their delegate should determine the need for medical 
management and decide what actions should be taken on study treatment, if any. The 
investigator or their delegate may consult with a cardiologist. In cases of acute cardiac 
events, and if they are not adequately trained and experienced in cardiology and are not 
equipped to provide emergency treatment, she/he will refer the participant to a cardiologist 
to receive emergency care and treatment. 

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7.2.3.4 Clinical laboratory assessments 
See Appendix 1 for the list of clinical laboratory tests to be performed. See the SoA 
[Table 1, Table 2, and Table 3 for the timing and frequency. 
At unscheduled visits, blood samples will be collected at the investigator’s discretion. 
Sample collection dates will be recorded in the eCRF [for biomarkers see Section 7.2.6]. 
Blood samples will be drawn in the morning under fasted conditions (i.e., before breakfast) 
and when applicable before the morning administration of the study treatment at all 
scheduled and unscheduled visits. However, it is not permitted to request that participants 
are in a fasted state (for the study) at Screening unless the ICF has already been fully signed. 
A midstream, clean-catch urine specimen will be collected according to the SoA [Table 1, 
Table 2, and Table 3 and sent to the central laboratory for analysis using urine dipsticks . 
If the dipstick results are positive for protein, leukocytes, or blood, the urine sample will 
be subject to further analysis (i.e., microscopic analysis). The results will be used for 
assessment of the mSLEDAI-2K and BILAG scores. 
Urine protein-to-creatinine ratio is to be determined using urine samples sent to the central 
laboratory for analysis of protein and creatinine. For the assessment of proteinuria, the 
protein-to-creatinine ratio in a single urine sample has been demonstrated as strongly 
correlated with the protein content of a 24-hour urine collection [Ginsberg 1983, 
KDIGO 2012, Price 2005, Ruggenenti 1998]. For this reason, the result from urine 
protein-to-creatinine ratio can be used in this study for assessment of both the 
mSLEDAI-2K and BILAG scores. The relationship among these laboratory tests for 
proteinuria is provided below in Table 7 [KDIGO 2012]. If the results of the 
protein-to-creatinine ratio are below the lower limit of quantification, this must be recorded 
as “not determined” in the questionnaires and justification has to be provided. 
Table 7 
Relationship among laboratory tests for proteinuria 
Measure 
Unit 
Conversion factor 
24-hour urine protein excretion rate 
g/24 hours 
1 
mg/24 hours 
1000 
Urine protein-to-creatinine ratio 
mg/g 
1000 
mg/mmol 
100* 
* The conversion is rounded for pragmatic reasons. For an exact conversion from mg/g of creatinine to mg/mmol of 
creatinine, multiply by 0.113. 
 

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A serum pregnancy test for WoCBP will be performed at Screening (Visit 1) and a urine 
pregnancy test prior to study drug administration Visit 2. Both must be negative and 
performed at least 3 weeks apart. A second serum pregnancy test is performed at Visit 20 
(FSV). Serum pregnancy tests will be sent to the central laboratory for analysis and the 
result will be sent to the investigator/delegate. 
Urine pregnancy tests will be performed at all other visits with kits provided by the central 
laboratory. Urine pregnancy kits will be provided to WoCBP at follow-up Visit 15 for use 
by the participant during the follow-up phone call Visits 16, 17, 18, 19, and the results 
collected during the scheduled phone calls. The results of the urine pregnancy tests, 
including those performed at home by the participants, will be collected in the eCRF. If 
pregnancy is suspected during the study, i.e., in each case of delayed menstrual period (e.g., 
over 1 month between menstruations), positive urine pregnancy test, etc., a serum 
pregnancy test must be performed as soon as possible. Reporting procedures of pregnancy 
are described in Section 8.3.1.  
A central laboratory (see central laboratory manual for contact details) will be used for all 
protocol-mandated laboratory tests, including retests due to laboratory abnormalities and 
laboratory tests performed at unscheduled visits. 
Exceptional circumstances that may require recording of local laboratory results of the 
variables described in Appendix 1 include hospitalization of the participant due to a 
medical emergency, inability to travel to the study site due to reasonable reasons judged 
by investigators and missing central laboratory results from a scheduled or unscheduled 
visit. The local laboratory results (with the corresponding normal ranges) must be recorded 
in the eCRF.  
If central laboratory samples are lost or cannot be analyzed for whatever reason, the 
investigator/delegate will collect an additional sample as soon as possible for repeat 
analysis, unless a local laboratory sample was collected within the same time frame and 
these test results are available. 
Central laboratory reports will be sent to the investigator/delegate. In the event of specific 
(pre-defined) laboratory abnormalities, the central laboratory will alert the sponsor 
personnel and the concerned site personnel. Alert flags that trigger such notifications will 
be displayed in the laboratory manual. 
All laboratory reports must be reviewed, signed and dated by the investigator/delegate 
within 10 calendar days of receipt and filed with the hospital chart. The 
investigator/delegate must indicate on the laboratory report whether abnormal values are 
considered clinically relevant or not. Laboratory findings that are present at the time of 
signing the ICF must be recorded on the Medical History page in the eCRF. Any clinically 

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relevant laboratory abnormalities detected after signing the ICF must be reported as an AE 
or SAE as appropriate [see Section 8] and must be followed until the value returns to within 
the normal range or is stable, or until the change is no longer clinically relevant. Notable 
abnormalities are detailed in Appendix 13.  
Details about the collection, sampling, storage, shipment procedures, and reporting of 
results and abnormal findings can be found in the laboratory manual. 
7.2.3.5 Ophthalmological examination 
The purpose of the ophthalmology assessment prior to cenerimod treatment is to document 
a baseline assessment as well as to exclude participants with macular edema, retinal 
vasculitis, or active uveitis from the study. Assessments at other visits will ensure that any 
new ophthalmological abnormality is detected and treated at an early stage.  
An ophthalmological examination will be performed by an ophthalmologist at any time 
during the screening period, but results must be available prior to Visit 2. Examinations 
after Screening will be performed as per schedule of assessments [see Table 2]. 
The ophthalmological examination should include previous eye history and ophthalmic 
conditions, any new or current ophthalmological symptoms, assessment of best corrected 
visual acuity per local standard practice, measurement of ocular pressure by the Goldmann 
applanation tonometry (recommended, if not available other tonometer allowed; in case 
the assessment is performed by rebound tonometry and result is abnormal, confirmation by 
applanation tonometer must be performed), slit lamp examination of the anterior segment, 
and fundoscopy. While the visual acuity and applanation tonometry exams may be 
performed by a delegate (e.g., experienced technician, optometrist), the review and 
interpretation must be performed by an ophthalmologist. Conduct, review, and 
interpretation of all other ophthalmological exams must be performed by an 
ophthalmologist. 
In the eCRF, the date of the ophthalmological examination and the presence/absence of 
any abnormality and clinical assessment results (i.e., Normal, NCS abnormal and CS 
abnormal) will be recorded. Clinically relevant findings that are present at the time of 
signature of the ICF must be recorded on the medical history page of the eCRF. Any 
clinically relevant ophthalmological abnormalities (including OCT findings) detected after 
signature of the ICF must be reported as an AE or SAE as appropriate [see Section 8.1.1] 
and must be followed until the value returns to within the normal range or is steadily 
improving. 
For participants with suspected macular edema or retinal vasculitis, the diagnosis should 
be confirmed by diagnostic work-up as recommended by local guidelines (e.g., OCT or 
fluorescence angiography). 

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7.2.3.6 Optical coherence tomography 
OCT will be performed at as per the SoA. Testing at Visit 1 can be performed at any time 
during the screening period. At all other visits, testing may be performed up to 7 days prior 
to the visit date but no later than 7 days after the visit.  
In addition, unscheduled OCT examination must be performed in the event of visual 
symptoms or findings suggestive of macular edema according to the ophthalmologist’s 
decision or if active uveitis is diagnosed during the study. While the OCT exam may be 
performed by a delegate (e.g., experienced technician, optometrist), the review and 
interpretation must be performed by an ophthalmologist.  
The purpose of the assessment prior to Visit 2 is to exclude participants with macular 
edema or active uveitis from the study, and to document a baseline assessment. The site 
will use the OCT device available locally and must ensure it is working properly. A copy 
of the calibration certificate or evidence of equipment maintenance performed prior to the 
assessment must be stored as source documents at the site. To the extent that is logistically 
feasible, the same OCT machine is recommended to be used for each individual participant 
throughout the study.  
In the eCRF, the date of the OCT assessment and the presence/absence of any abnormality 
and clinical assessment results (i.e., Normal, NCS abnormal and CS abnormal) will be 
recorded. Any clinically relevant abnormalities detected after signature of the ICF must be 
reported as an AE or SAE as appropriate [see Section 8.1.1]. 
7.2.3.7 Chest X-ray or CT scan 
A chest X-ray or CT scan will be performed at Visit 1 (Screening) and assessed by the local 
radiologist to support the assessment of eligibility criteria (e.g., exclude any participant 
with active or latent TB). Chest X-ray or CT scan testing can be performed at any time 
during the screening period. If results of a chest X-ray or CT scan that has been performed 
within 6 months prior to Screening do not demonstrate active or latent TB, there is no need 
to repeat the chest X-ray or CT scan at Screening. The report of the chest X-ray or CT scan 
must be recorded in the participant’s file. 
7.2.3.8 Test for tuberculosis 
An IGRA will be performed at Visit 1 (Screening) to screen for active or latent TB, unless 
one of the exceptions as detailed in the exclusion criterion have been met. The test will be 
analyzed and interpreted at the central laboratory and transferred to the investigator. 
Details on the performance of the test for TB will be provided in the specific central 
laboratory manual. 

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7.2.3.9 Skin examination 
Each physical examination must include a complete skin examination performed by the 
investigator/delegate. In the event of findings other than skin findings relevant to SLE, a 
dermatologist will conduct further examination per local standard practice, including 
performing skin biopsies if required to rule out or confirm a diagnosis. 
7.2.4 
Blood pressure assessments 
The investigator/delegate is responsible for BP measurements, including SBP and DBP. 
BP will be assessed as per the SoA. 
For a given participant, BP measurements will be performed using the same type of device 
throughout the study on the same arm with the participant in a fully rested supine position 
after the participant has been allowed to rest for a minimum of 5 minutes prior to the 
measurement. At all visits (including Visit 1/Screening visit), SBP and DBP will be 
measured twice. The SBP/DBP assessment will be performed pre-dose at all visits during 
the study treatment period. Each of the 2 obtained measurements (i.e., 2 SBP measurements 
and 2 DBP measurements) and the position and arm used are to be recorded in the eCRF. 
The means of the 2 obtained measurements will be calculated in the eCRF. Any clinically 
relevant BP abnormalities detected after informed consent signature must be reported as 
an AE or SAE as appropriate [see Section 8.2]. 
At Visit 2 (Day 1) and at study treatment re-initiation, the post-dose SBP/DBP assessments 
will be performed in parallel to 12-lead ECGs.  
The post-dose SBP/DBP assessments will only be measured once at each hourly time point 
until 6 h post-dose and at hour 12 post-dose. At the 12-hour post-dose timepoint, 
participants may be discharged from the monitored setting if they meet the pre-specified 
discharge criteria [see Appendix 5]. Refer to Appendix 5 regarding participant 
discontinuation and monitoring if discharge criteria not met.  
7.2.5 Pharmacokinetic and pharmacodynamic assessments 
7.2.5.1 Pharmacokinetic assessments 
PK samples will be collected at the times indicated in the SoA [Table 2]. 
The date and actual time of collection of each blood sample will be entered in the eCRF. 
In addition, the food status will be recorded in the eCRF for study treatment intake on Day 
1 and at Month 2.  
The allowed time deviation from scheduled post dose PK sampling time points is listed as 
follows: 

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Time point 
Allowed time window 
1-12 hours post dose 
±3 min 
24 hours post dose 
+18 min (Must obtained before the next dosing) 
Details about the collection, sampling, storage, and shipment procedures can be found in 
the laboratory manual. 
The analysis of cenerimod in plasma will be performed by a laboratory approved by the 
Sponsor using a validated bioanalytical method. 
The PK data generated from this study may be used for PPK modeling in future. 
7.2.5.2 Pharmacodynamic assessments 
The PD marker is total lymphocyte counts, which will be measured as part of the 
hematology tests [see Section 7.2.3.4]. 
7.2.6 
Biomarker assessments 
7.2.6.1 Disease activity biomarkers 
Serum, EDTA plasma, and whole blood (PAXgene) samples will be drawn at the indicated 
visits [Table 1, Table 2, and Table 3]. The sample collection date will be recorded in the 
eCRF. 
Details of the collection, labeling, and shipment of the samples can be found in the 
laboratory manual provided to the investigator. 
The following biomarkers will be measured at a central laboratory as per the SoA:  
• Whole blood will be collected in PAXgene tubes to measure the overexpression of 
mRNA of specific IFN-1 inducible genes. Other gene expression signatures will be 
reported to examine T and B cell function, metabolism, and mRNA production. 
• In serum samples: ANA, anti-dsDNA, anti-Sm, CH-50, and complement C3 and C4. 
• In EDTA plasma samples: IFN alpha levels. 
Details of the collection, labeling, and shipment of the samples can be found in the 
laboratory manual provided to the investigator. 
8 
SAFETY DEFINITIONS AND REPORTING REQUIREMENTS 
8.1 Safety definitions 
8.1.1 
Definition of adverse events 

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An AE is any untoward medical occurrence, i.e., any unfavorable and unintended sign, 
including an abnormal laboratory finding, symptom, or disease that occurs in a participant 
during the study, whether or not considered by the investigator/delegate as related to study 
treatment. 
AEs include: 
• Exacerbation of a pre-existing disease if considered medically relevant.  
• Exacerbation of a pre-existing disease except for efficacy endpoints and associated 
symptoms. 
• Increase in frequency or intensity of a pre-existing episodic disease or medical 
condition. 
• Disease or medical condition detected or diagnosed during the study after signing the 
ICF, even though it may have been present prior to the start of the study. 
• Continuous persistent disease or symptoms present at study start that worsen after the 
start of the study. 
• Abnormal change in physical examination or ECG findings, if they represent a 
clinically significant finding that was not present at study start or worsened during the 
study as per investigator medical assessment. 
• Laboratory test abnormalities if they represent a clinically significant finding 
(symptomatic or not) that was not present at study start or worsened during the study 
as per investigator judgment, led to interruption or permanent discontinuation of study 
treatment. 
8.1.2 
Definition of adverse events of specific interest 
AESIs will include the anticipated risks of treatment with cenerimod or the known class 
effects or the events that may be related to SLE comorbidities (e.g., cardiovascular AEs) 
and will address the following safety areas: 
• Effect on HR and rhythm‑related AEs 
• Hypotension-related AEs 
• Hypertension-related AEs 
• Cardiovascular-related AEs 
• Hepatobiliary disorders / liver enzyme abnormality‑related AEs 
• Pulmonary-related AEs  
• Eye disorder-related AEs 
• Infection-related AEs 

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• Skin malignancy-related AEs 
• (Non-skin) malignancy-related AEs 
A list of AESIs (MedDRA preferred terms) will be defined in the SAP. 
8.1.3 
Definition of serious adverse events 
An SAE is defined by the ICH guidelines as any AE fulfilling at least 1 of the following 
criteria: 
• Fatal. 
• Life-threatening: Refers to an event in which the participant was at risk of death at the 
time of the event. It does not refer to an event that hypothetically might have caused 
death had it been more severe. 
• Requiring in-patient hospitalization (i.e., the AE required admission to hospital) or 
prolongation of existing hospitalization. 
• Resulting in persistent or significant disability or incapacity. 
• Congenital anomaly or birth defect. 
• Medically significant: Refers to important medical events that may not immediately 
result in death, be life-threatening, or require hospitalization, but may be SAEs based 
upon appropriate medical judgment, as they may jeopardize the participant, and/or may 
require medical or surgical intervention to prevent 1 of the outcomes listed in the 
definitions above. 
The following reasons for hospitalization are not considered as SAEs: 
• Hospitalization for cosmetic elective surgery, or social and/or convenience reasons. 
• Hospitalization for pre-planned (i.e., planned prior to signing the ICF) surgery or 
standard monitoring of a pre-existing disease or medical condition that did not worsen, 
e.g., hospitalization for coronary angiography in a participant with stable angina 
pectoris. 
8.1.4 Intensity of adverse events 
The intensity of AEs is graded on a 3-point scale—mild, moderate, severe—as follows: 
• Mild 
– The event may be noticeable to the participant. It does not usually influence daily 
activities, and normally does not require intervention. 
• Moderate 

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– The event may make the participant uncomfortable. Performance of daily activities 
may be influenced, and intervention may be needed. 
• Severe 
– The event may cause noticeable discomfort and usually interferes with daily 
activities. The participant may not be able to continue in the study, and treatment 
or intervention is usually needed. 
A mild, moderate, or severe AE may or may not be serious [see Section 8.1.2]. These terms 
are used to describe the intensity of a specific event. Medical judgment should be used on 
a case-by-case basis. 
8.1.5 
Relationship to study treatment  
Each AE/SAE must be assessed by the investigator/delegate as to whether there is a 
reasonable possibility of causal relationship to the study treatment and reported as either 
related or unrelated.  
8.1.6 Relationship to study design or protocol-mandated procedure  
An AE/SAE is defined as related to the study design or protocol-mandated procedure if it 
appears to have a reasonable possibility of a causal relationship to either the study design 
or to a protocol mandated procedure. 
Determining the likelihood that a protocol-mandated procedure caused the AE/SAE will 
be provided by the investigator/delegate. 
8.1.7 
Definition of study treatment overdose, misuse, and abuse 
Study treatment overdose is defined as higher than the dose of study treatment prescribed. 
Study treatment misuse is defined as any intentional and inappropriate use of the study 
treatment which is different from the instruction provided in the protocol. 
Study treatment abuse is defined as any intentional and excessive use of the study treatment, 
with harmful physical or psychological effects. 
In the event of a study treatment overdose, abuse, or misuse, the investigator/delegate must 
contact the sponsor and closely monitor the participant for any AEs/SAEs.  
8.2 Reporting procedures 
8.2.1 
Reporting adverse events 
The occurrence of an AE may come to the attention of study personnel during study visits, 
telephone calls, or interviews with participants presenting for medical care.  

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At each study visit (scheduled or unscheduled), the investigator/delegate will inquire about 
the occurrence of AEs since the last visit. 
All AEs with an onset date after signing the ICF and up to 6 months after study treatment 
discontinuation must be recorded in the eCRF.  
The AE should be reported as a final diagnosis (if possible) rather than a list of symptoms. 
Information to be collected on an AE form in the eCRF includes date of onset, action taken 
with the study treatment (e.g. dose reduction or suspension), outcome of AE, date of 
resolution (if applicable), and investigator/delegate’s assessment of intensity as well as 
relationship to study treatment, study design or protocol-mandated procedures.  
Information on worsening of intensity will be collected on a new AE form. If the AE 
lessens in intensity, no change in the severity is required to be reported. 
AEs still ongoing after study treatment discontinuation must be followed up until resolution, 
until they are no longer considered clinically relevant, or until stabilization.  
8.2.2 
Reporting serious adverse events 
All SAEs must be reported by the investigator/delegate to the sponsor’s Drug Safety 
department within 24 h of site staff first becoming aware of the event. 
All SAEs occurring after signing the ICF and up to 6 months after study treatment 
discontinuation 
must 
be 
recorded 
on 
an 
SAE 
form, 
regardless 
of 
the 
investigator-/delegate 
-attributed 
causal 
relationship 
with 
study 
treatment 
or 
study -mandated procedures. 
The SAE forms must be sent to the sponsor’s Drug Safety department (see contact details 
on the SAE form). The investigator/delegate must complete the SAE form in English and 
must assess the event’s causal relationship to the study treatment. 
Any relevant information from source documents regarding the SAE, e.g., hospital notes 
or discharge summaries, etc., must be summarized on the SAE form. 
Follow-up information about a previously reported SAE must be promptly reported. The 
sponsor’s Drug Safety personnel may contact the investigator/delegate to obtain further 
information. 
If the participant is hospitalized in a hospital other than that of the study site, it is the 
investigator/delegate’s responsibility to contact this hospital to obtain all SAE -relevant 
information and documentation. 

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New SAEs occurring after the 6-month follow-up period must be reported to the sponsor’s 
Drug Safety department within 24 h of site staff first awareness/knowledge of the event, 
only if considered by the investigator/delegate to be causally related to previous exposure 
to the study treatment. 
SAEs still ongoing after study treatment discontinuation must be followed up until 
resolution, stabilization, or until the event outcome is provided. 
8.2.3 
Reporting procedure for SUSARs 
The expectedness of an SAE is determined by the sponsor according to the reference safety 
information section provided in the Investigator’s Brochure.  
Any SAE that is assessed as related and unexpected against the reference safety 
information is considered a SUSAR. 
Any SUSAR must be reported by the sponsor/CRO to relevant health authorities, and 
investigators. Submission to central/local IECs/IRBs will be done as per their requirements. 
8.2.4 Reporting medical or surgical intervention 
At each study visit (scheduled or unscheduled), the investigator/delegate will inquire about 
any medical or surgical intervention performed on the participant. 
All medical or surgical intervention with an onset date after signing the ICF and up to 
6 months after study treatment discontinuation must be recorded in the eCRF.  
8.3 Pregnancy 
If a woman becomes pregnant while on study treatment, study treatment must be 
discontinued see Section 5.8.1.2. The investigator/delegate must counsel the participant 
and discuss the risks of continuing with the pregnancy and the possible effects on the fetus. 
8.3.1 Reporting of pregnancy 
Any pregnancy occurring in a female participant after signing of the ICF and up to 6 
months following study treatment discontinuation must be reported to the sponsor’s Drug 
Safety department within 24 h of site staff first becoming aware of the event. 
All pregnancies must be reported on the sponsor’s Pregnancy form, which is sent to the 
sponsor’s Drug Safety department (see contact details provided on the Pregnancy form). 
The investigator/delegate must complete the Pregnancy form in English.  

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8.3.2 
Follow-up of pregnancy 
Any pregnancies must be followed up to their conclusion and the outcome must be reported 
to the sponsor’s Drug Safety department. If local regulations or IRB/EC decisions mandate 
the reporting of the baby’s health after delivery, this will be performed using the same 
procedure in Section 8.3.1. Any AE associated with the pregnancy of a female participant 
occurring during the AE reporting time must be reported on separate AE forms in the eCRF 
as described in Section 8.2.1.  
Any SAE occurring during the pregnancy must be reported on an SAE form as described 
in Section 8.2.2. 
9 
STATISTICAL METHODS 
All statistical analyses will be conducted by the sponsor/CRO. 
The SAP will provide full details of the analyses, data displays, and algorithms to be used 
for data derivations. 
9.1 Analysis sets 
9.1.1 
Screened set 
The screened set includes all participants who provided informed consent and participated 
in any screening procedures. 
9.1.2 
Safety Analysis Set (SS) 
The SS includes all participants who received at least 1 dose of study treatment.  
9.1.3 
Pharmacokinetic Analysis Set (PKS) 
The PKS includes all participants from the SS who, after initiation of cenerimod treatment, 
have at least one PK sample collected, had evaluable plasma concentrations, and did not 
deviate from the protocol in a way that might affect the evaluation of the PK endpoint. 
9.1.4 
Pharmacodynamic Analysis Set (PDS)  
The PDS includes all participants from the SS who, after initiation of cenerimod treatment, 
have at least one PD sample collected, had evaluable total lymphocyte counts, and did not 
deviate from the protocol in a way that might affect the evaluation of the PD endpoint. 
9.2 Description of statistical analyses 
All available data (regardless of whether collected during scheduled or unscheduled visits) 
for each participant will be used in all statistical analyses unless otherwise specified. 

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9.2.1 Analysis of safety endpoints 
Descriptive analysis of safety endpoints will be performed using the SS (see definition in 
Section 9.1.2). 
If not otherwise stated, only treatment-emergent safety data will be considered in tables 
and figures. Treatment-emergent safety data will be defined as assessments (or events) that 
were performed (or started) on or after the first study treatment intake (inclusive) up to the 
last study treatment intake + 180 days (inclusive).  
Analyses on marked abnormalities for ECG and laboratory variables and Notable BP 
abnormalities will be specified in the SAP. 
Adverse events  
AEs will be coded using MedDRA. The number (%) of participants experiencing a TEAE 
(including SAEs, AESIs, and AEs leading to premature discontinuation of study treatment) 
will be summarized by SOC and/or PT, and maximum intensity. A participant with 
multiple occurrences of an AE is counted only once in the AE category (e.g., SOC, PT).  
Vital signs and electrocardiograms during post-dose cardiac monitoring on Day 1 
On Day 1, observed values and changes from baseline to all post-dose assessments in vital 
signs (SBP and DBP) and for 12-lead ECG variables, including HR and QTcB and QTcF 
intervals will be summarized by hourly timepoint. The number (%) of participants having 
a marked ECG abnormality will be tabulated on Day 1. The number of participants 
discharged at 12 h will be summarized for Day 1. For participants not discharged, reasons 
for not being discharged will be summarized.  
The number of participants who discontinue study treatment after 12 h will also be 
summarized. 
Vital signs and body weight  
Observed values and changes from baseline to all scheduled post-baseline visits in vital 
signs (SBP and DBP) and body weight will be summarized. Treatment-emergent notable 
BP abnormalities will be summarized. 
Electrocardiograms  
Observed values and changes from baseline to all scheduled post-baseline visits for each 
12-lead ECG variable (HR and the PR, QRS, QTcB, and QTcF intervals) will be 
summarized. The number (%) of participants with a marked ECG abnormality will be 
tabulated.  

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Laboratory data  
Observed and change from baseline laboratory variables for hematology, blood chemistry, 
and urinalysis for all scheduled post-baseline visits will be summarized. The number (%) 
of participants with a marked laboratory abnormality (see Appendix 13) will be tabulated. 
9.2.2 
Analysis of pharmacokinetic endpoints 
PK analyses will be performed using the PKS. 
Plasma concentrations of cenerimod will be listed by participant and scheduled time point 
of blood sampling. For samples collected on Day 1/2 and at Month 2, when PK profiles are 
obtained, elapsed actual times will be displayed, too. Elapsed actual time in hours is defined 
as the number of hours elapsed from date and time of last study treatment intake to actual 
date and time of sampling recorded in the eCRF.  
Cenerimod plasma concentrations will be summarized per scheduled timepoint by using 
the number of observations, arithmetic mean, minimum, median, maximum, SD, etc.. 
Concentrations reported as BLQ will be set to zero. 
The arithmetic mean ± SD for the cenerimod plasma concentrations will be represented 
graphically over time for the PK profiles obtained during the first dosing interval (i.e., 
pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 h after dosing on Day 1) and at Month 2 (i.e., 
pre-dose, 1, 2, 3, 4, 5, 6, 7, 8, 10, 12 and 24 h after the dosing at Month 2). In addition, the 
arithmetic mean ± SD for all pre-dose (trough) cenerimod plasma concentrations will be 
displayed graphically per visit. 
PK parameters of cenerimod (AUC, Cmax, tmax*, and AI) will be determined by non-
compartmental methods by the responsible Clinical Pharmacologist using Professional 
WinNonlin version 8.4 or higher, Certara USA Inc and calculated based on the actual blood 
sampling time points. It is assumed that AUC and Cmax are log-normally distributed 
[Julious 2000]. PK parameters will be listed by participant displaying the dosing interval 
(i.e., Day 1/2: first dosing interval, Month 2: dosing interval at steady-state conditions) and 
summarized by dosing interval, with arithmetic mean, minimum, median, maximum, SD, 
SE, geometric mean, coefficient of variation between participants in %, and 95% CIs of 
arithmetic and geometric means. 
*For tmax, the geometric mean and its 95% CI and coefficient of variation will not be 
calculated. 
If appropriate, the steady-state PK parameters such as Cmin,ss, etc. will be derived and 
analyzed similarly as above. 
Further details of these analyses will be provided in the SAP. 

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9.2.3 Analysis of PD endpoints 
Lymphocyte count analyses will be performed using the PDS. Observed and change from 
baseline values for all scheduled post-baseline visits will be summarized. PD parameters 
will be calculated and summarized based on Lymphocyte counts, the details of which will 
be provided in the SAP. 
A listing of lymphocyte counts by participant will be produced using the PDS. 
 
9.2.4 
Analysis of efficacy endpoints 
The following variables will be descriptively analyzed and summarized by month using 
the SS. 
• The observed mSLEDAI-2K total score and change from baseline 
Please refer to Appendix 6 for the detailed information. 
• Observed SRI-4 response. 
A participant will be assessed as a SRI-4 responder if they meet ALL the below 
criteria: 
1. Reduction from baseline of at least 4 points in the mSLEDAI-2K;  
and 
2. No new BILAG A organ domain score and no more than one new BILAG B organ 
domain score compared with baseline;  
and  
3. No increase of more than 0.3 points on the PGA Score since baseline;  
 
If 1 of the 3 components is missing, the SRI-4 response will be missing for this assessment, 
unless 1 of the non-missing components is not met. In that case, the participant will be 
assigned a non-response status for SRI-4. 
• Observed BICLA response. 
A participant will be assessed as a BICLA responder if they meet ALL the below 
criteria: 
1) Improvement from baseline in disease activity as measured by BILAG-2004. 
Improvement is defined as a reduction of all baseline BILAG-2004 A to B/C/D and 
baseline BILAG-2004 B to C/D and no BILAG-2004 worsening in other organ systems, 
where worsening is defined as ≥ 1 new BILAG-2004 A or ≥ 2 new BILAG-2004 B. 

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2) No worsening from baseline in mSLEDAI-2K score, where worsening is defined as an 
increase from baseline of > 0 points. 
3) No worsening from baseline in the participant’s lupus disease activity, where 
worsening is defined as an increase of 0.3 points or more on a 3-point PGA VAS score. 
4) No discontinuation of study treatment. 
If 1 of the 4 components is missing, the BICLA response will be missing for this assessment, 
unless 1 of the non-missing components is not met. In that case, the participant will be 
assigned a non-response status for BICLA. 
•  Response on CLASI from baseline to Month 12. 
Please refer to Appendix 10 for the detailed information. 
• Change from baseline in tender and swollen joints. 
The total tender joint count will be derived at each assessment, by summing the number of 
tender joints (= 1) as derived above. The total tender joint count values range from 0 to 28. 
If at least one joint was not assessed for tenderness or was not evaluable, the total tender 
joint count will be missing. 
The total swollen joint count will be derived at each assessment in the same manner as for 
tender joint count. The total swollen joint count values range from 0 to 28. 
• Changes in OCS dosage from baseline to Month 12. 
9.3 Planned analyses 
The EOS analysis will be performed when all enrolled participants have completed the 
post-treatment follow-up period or discontinued the study.  
9.4 Sample size  
A total of approximately 15 Chinese patients with SLE are planned to be enrolled. 
10 REGULATORY, ETHICAL, AND STUDY OVERSIGHT 
CONSIDERATIONS 
10.1 Regulatory and ethical considerations 
The sponsor personnel and the investigators will ensure that the study is conducted in full 
compliance with ICH GCP guidelines, the principles of the Declaration of Helsinki, and 
with the laws and regulations of the country in which the study is conducted. 
The investigator and/or sponsor/CRO will submit this protocol and any related documents 
provided to the participant (such as the ICF) to an IEC/IRB and to the health authority (as 
applicable). Approval from both the IEC/IRB and the health authority must be obtained 

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before starting the study and must be documented in a dated letter to the investigator and/or 
sponsor/CRO, clearly identifying the study, the documents reviewed, and the date of 
approval. 
Modifications made to the protocol or the ICF after receipt of the approval must also be 
submitted as amendments by the investigator/delegate and/or sponsor/CRO to the IEC/IRB 
and to the health authority in accordance with local procedures and regulations. 
10.2 Informed consent process 
It is the responsibility of the investigator/delegate to obtain informed consent according to 
ICH GCP and Declaration of Helsinki guidelines and local regulations from each 
individual participating in this study. The investigator/delegate must explain to participants 
that they are completely free to refuse to enter the study, or to voluntarily withdraw from 
the study at any time for any reason without having to provide any justification. Special 
attention must be paid to the information needs of specific participant populations and of 
individual participants, as well as to the methods used to deliver the information. Adequate 
time must be given for the participant to consider his or her decision to participate in the 
study and it must be verified that the participant has understood the information (e.g., by 
asking the participant to explain what is going to happen).  
If a revised version of the ICF is approved by health authorities (if applicable) and 
IRBs/IECs:  
• Newly recruited participants must provide consent using the most current version of the 
ICF(s). 
• Participants who are already participating in the study (e.g., already recruited) must 
re-consent using the most current version of the ICF(s), if necessary (e.g., additional 
study procedure, new safety information) and/or requested (e.g., as per IRB/IEC 
requirements). 
The ICF will be provided, at a minimum, in the country’s official local language(s) and as 
requested by health authorities (if applicable) and IRBs/IECs. 
Site personnel authorized (according to local regulation) to participate in the consent 
process and/or to obtain consent from the participant will be listed on the Delegation of 
Authority form. A study physician or a healthcare professional with advanced practice, if 
allowed by local regulations must always be involved in the consent process. 
The participant and authorized site personnel listed on the Delegation of Authority form 
must sign, personally date, and time the ICF before any study-related procedures (i.e., any 
procedures required by the protocol) begin. If the time is not included on the ICF due to 

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local regulations, the time of the ICF signature of the participant and investigator/delegate 
must be documented in the participant’s medical charts. 
A copy of the signed and dated ICF is given to the participant; the original is filed in the 
site documentation. The informed consent process must be fully documented in the 
participant’s medical records. This must include, at a minimum, the study reference, the 
participant identification number, the date and, if applicable, time when the participant was 
first introduced to the study, the language in which the study was explained, the date, the 
time of consent, who participated in the consent discussion, who consented the participant, 
and any additional persons present during the consent process (e.g., participant’s family 
member[s]), and the information that a copy of the signed ICF was given to the participant. 
If a participant becomes pregnant during the study, she will be asked to sign a specific ICF 
to allow the collection of her health information during her pregnancy and from the 
baby(ies) following delivery. The father of the baby, if possible, will also be asked to sign 
the ICF. 
If the site intends to recruit participants who are considered vulnerable (e.g., participant 
cannot read or write, does not speak or understand the ICF language), additional measures 
must be implemented to ensure the participant’s rights are respected and the consent 
obtained is legally valid. The sponsor, the regulatory authorities (if applicable), and the 
IEC/IRB must be informed prior to the recruitment. The consent process (e.g., involvement 
of an impartial witness) must be fully described, submitted to, and approved by the 
IEC/IRB, according to procedures and before participants are recruited. 
10.3 Data protection and privacy 
Participant data confidentiality and privacy are strictly held in trust by the investigators, 
their staff, and the sponsor or delegate.  
The investigator/delegate must ensure that data confidentiality is maintained. On eCRFs or 
other documents (e.g., documents attached to SAE forms / Pregnancy forms) submitted to 
the sponsor and any vendors or CROs, participants must be identified only by number and 
never by their name or initials, date of birth, hospital numbers, or any other personal 
identifier. The investigator/delegate must keep a participant identification code list at the 
site. Documents identifying the participants (e.g., signed ICFs) must not be sent to the 
sponsor or any vendors or CROs, and must be kept in strict confidence by the 
investigator/delegate.  
The participants must be informed that their personal study-related data will be used by the 
sponsor in accordance with local data protection laws.  

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The participants must be informed that their medical records may be inspected by the 
sponsor or sponsor’s delegate, by appropriate IRB/IEC members, and by inspectors from 
regulatory authorities. 
10.4 Indemnification, compensation, and refund of expenses to participants 
and investigators 
The sponsor provides insurance in order to indemnify (with both legal and financial 
coverage) the investigator/site against claims arising from the study, except for claims that 
arise from malpractice and/or negligence. 
The indemnification of the participants in the event of study-related injuries will comply 
with applicable regulations. 
10.5 Essential documents and retention of documents 
The investigator/delegate must maintain adequate records necessary for the reconstruction 
and evaluation of the study. Several attributes are considered to be of universal importance 
to source data and the records that hold those data. These include that the data and records 
are accurate, legible, contemporaneous, original (or a certified copy), attributable, complete, 
consistent, enduring, and available when needed. 
These records will be classified into 2 different categories of document: ISF and 
participants’ source documents. 
These records must be kept by the investigator/site for as long as is necessary to comply 
with the sponsor’s requirements (i.e., as specified in the clinical study agreement), 
ICH GCP and national and/or international regulations, whichever is the longest period. If 
the investigator/site cannot guarantee this archiving requirement at the site for any or all of 
the documents, special arrangements, respecting the data confidentiality, must be made 
between the investigator/site and the sponsor to store these documents off site, so that they 
can be retrieved in the event of a regulatory inspection. Study documents must not be 
destroyed without prior written approval from the sponsor. If the site needs to transfer the 
study records to another location and/or if the site facility can no longer store the study 
records, the investigator/site must immediately inform the sponsor.  
10.5.1 
Investigator Site File 
Each site will maintain an ISF. It will contain all the essential documents that are required 
to be up-to-date and filed at the site as per ICH GCP section 8. 
The ISF must be stored in a secure and access-restricted area during and after the study.  

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10.5.2 Source documents 
All source documents should be completed in a neat and legible manner to ensure accurate 
interpretation and traceability of the data. Data reported in the eCRF derived from source 
documents must be consistent with the source documents. 
If the site is using electronic/computerized system(s) to store participants’ medical records, 
it can be used for the purpose of the clinical study if it is validated (as per 21 CFR Part 11 
or equivalent standard) and if the CRA has been provided personal access to participants’ 
medical records in order to verify consistency between electronic source data and the eCRF 
during monitoring visits. 
If the site is using electronic/computerized system(s) to store participant medical records 
but it cannot be confirmed that the system(s) is/are validated or if the CRA cannot be 
provided access to the system(s), the site is requested to print the complete set of source 
data needed for verification by the CRA. These printouts need to be produced via a 
controlled process in order to be considered as certified copies as defined in the ICH GCP 
(e.g., printout numbered, stapled together with a cover sheet, signed, and dated by the 
investigator / member of site staff to confirm that these certified copies are exact copies 
containing the same information as the original source data). The printouts will be 
considered as the official clinical study records. Once printed and certified, the document 
must not be edited/changed (e.g., manual notes added, clinical value changed) in order not 
to impact the validity of the certification. If the data need to be changed (e.g., correction of 
a mistake) the change(s) must be done in a traceable fashion and a new copy must be 
printed and certified. 
In order to verify that the process the site uses to prepare certified copies is reliable, the 
CRA periodically requests that a site representative logs into the electronic/computerized 
system so the CRA could verify the entries in the system against the printouts. The CRA 
does not need to perform these activities for all participants but at least for some of them 
and for key data (e.g., eligibility criteria and primary endpoints) as per the sponsor/CRO 
instructions. 
Paper source data will be collected by paper sheets: 
• By trained and delegated site staff for clinical outcome assessments (SLEDAI-2K, SFI, 
PGA, BILAG, CLASI, and tender/swollen joint count) and supportive data from 
physical examination, weight, clinical symptoms, and medical evaluation of the 
participants. 

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10.6 Data handling 
10.6.1 
Data collection, data transfer procedure, and data access 
The investigator/delegate is responsible for ensuring the accuracy, completeness, and 
timely reporting of participants’ data.  
Electronic data capture will be used to collect eCRF data. The investigator and site 
personnel will be trained to enter and edit the data via a secure network, with secure access 
features (username, password, and identification—an electronic password system). A 
complete electronic audit trail will be maintained. The investigator/delegate will approve 
the data (i.e., confirm the accuracy and completeness of the data recorded) using an 
electronic signature (as per US 21 CFR Part 11).  
Participant recruitment and enrollment data will be completed for all participants (i.e., 
eligible and non-eligible) through the IRT system and eCRF. 
For each participant recruited, regardless of study treatment initiation, an eCRF must be 
completed and signed by the investigator/delegate. This also applies to those participants 
who fail to complete the study.  
The investigator and site personnel will be trained on the use of the paper sheets [see 
Section 7.2.2]. The data on the paper sheets will be considered source documents. 
10.6.2 Database management and quality control 
The eCRF must be completed in a timely manner as per eCRF completion guidelines. 
While entering the data, the investigator/delegate will be instantly alerted to data queries 
by validated, programmed checks. Additional data review will be performed by the sponsor 
personnel or delegate on an ongoing basis to look for unexpected patterns in data and for 
study monitoring. Should discrepant data be detected, a query specifying the matter and 
requesting clarification will be issued and visible to the investigator/delegate via the eCRF. 
All electronic queries visible in the system either require a data correction (when applicable) 
and a response from the investigator/delegate to clarify the queried data directly in the 
eCRF, or simply a data correction in the eCRF. The investigator/delegate must, on request, 
supply the sponsor with any required background data from the study documentation or 
clinical records. This is particularly important when errors in data transcription are 
suspected. In the event of health authority queries, it is also necessary to have access to the 
complete study records, provided that participant data confidentiality is protected. 
This process will continue until database lock.  
Laboratory samples and 12-lead ECGs will be processed through a central vendor and the 
results of the enrolled participants will be electronically sent to the sponsor at pre-specified 

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intervals with a final transfer prior to database lock. During the study, the site staff and 
sponsor representatives can access the data in view-only mode on the central server of the 
respective vendor see also Section 10.6.1. 
AEs and medical history are coded with MedDRA version 26.0 or later. Medications are 
coded with the WHO Drug Dictionary. 
After the database has been declared complete and accurate, the database will be locked. 
Any changes to the database after that time may only be made as described in the 
appropriate sponsor/CRO Quality System documents. The sponsor is responsible for 
ensuring that the investigator/delegate will have permanent access (either “write” access 
or “read-only” access) to the site eCRF participant data, until receipt of an electronic copy 
of the site eCRFs (including the audit trail). 
10.7 Protocol deviations 
A protocol deviation is any change, divergence, or departure from the study design or 
procedures defined in the protocol. A protocol deviation code list will be available to 
provide guidance on protocol deviations recording. 
Prospective approvals of protocol deviations, also known as protocol waivers or 
exemptions, are not permitted.  
The investigator must conduct the study in compliance with the IEC/IRB-approved and/or 
the regulatory authority-approved version of the protocol and must not implement any 
deviation/change from the protocol, except when deviation is necessary to eliminate an 
immediate hazard to the participant. 
Protocol deviations must be reported to the IEC/IRB and regulatory authorities according 
to local requirements. 
10.8 Clinical monitoring 
Prior to study start at a site, all required approvals must be obtained. A site initiation visit 
will be performed after the required essential study documents are approved by the sponsor. 
The study treatment will be shipped to the site upon approval of the required essential 
documents. 
The investigator must ensure that all key site personnel involved in the study are 
present/available during the site initiation visit and will dedicate sufficient time to it. 
The site initiation visit must be completed before the site can start recruiting participants. 
Following the site initiation visit, a copy of the completed initiation visit report and 
follow-up letter will be provided to the investigator and filed in the ISF. 

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During the study, the CRA will contact and visit the site regularly and must be permitted, 
on request, to have access to study facilities and all source documents needed to verify 
adherence to the protocol and the completeness, consistency, and accuracy of the data being 
entered in the eCRFs and other protocol-related documents. Monitoring activities will be 
performed according to the study-specific monitoring guidelines. The methodology and the 
frequency of the monitoring visits will be mainly based on participant recruitment rate and 
critical data collection times. 
The investigator/delegate must ensure that the eCRF is completed as per the eCRF 
completion guidelines and that all requested participant files (e.g., ICFs, medical 
notes/charts, other documentation verifying the activities conducted for the study) are 
available for review by the CRA. The required site personnel must be available during 
monitoring visits and allow adequate time to meet with the CRA to discuss study-related 
issues. 
The investigator agrees to cooperate with the CRA to ensure that any issues detected during 
these monitoring visits are resolved. 
A close-out visit will be performed for any initiated site when there are no more active 
participants and all follow-up issues have been resolved. If a site does not screen any 
participants, the close-out visit may be performed prior to study closure at the discretion of 
the sponsor. 
10.9 Study safety oversight 
Study safety information (AEs, SAEs, laboratory values, ECGs, vital signs, and study 
specific- examinations, as required) is monitored and reviewed on a continuous basis by 
the sponsor.  
The sponsor may request additional data pertaining to the diagnostic work-up of an AE or 
SAE (e.g., medical imaging, local laboratory values) for the purpose of monitoring safety. 
Such additional data may be shared with external experts. 
10.10 Premature termination or suspension of the study 
The sponsor reserves the right to terminate the study at any time globally or locally. 
Investigators can terminate the participation of their site in the study at any time. 
If the study is suspended or prematurely terminated, the sponsor will promptly inform the 
investigators, the IECs/IRBs, and health authorities, as appropriate, and provide the reasons 
for the suspension or termination. 
If the study is suspended or prematurely terminated for any reason, the investigator—in 
agreement with the sponsor—must promptly inform all recruited participants and ensure 

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their appropriate treatment and follow-up, as described in Section 6.3. The sponsor may 
inform the investigator of additional procedures to be followed in order to ensure that 
adequate consideration is given to the protection of the participants’ interests. 
In addition, if the investigator suspends or terminates the study without prior agreement 
from the sponsor, the investigator must promptly inform the sponsor personnel and the 
IEC/IRB and provide both with a detailed written explanation of the termination or 
suspension.  
If the CDE does not approve the continuation of the study or the continued treatment of the 
participants enrolled in the study, the study will be terminated. The investigators and 
IECs/IRBs will be informed promptly of the CDE’s decision.  
10.11 Audit 
The sponsor representatives may audit the investigator site during the study or after its 
completion. The purpose of this visit will be to determine the investigator’s adherence to 
ICH GCP, the protocol, and applicable regulations. Adherence to the sponsor requirements 
(e.g., SOPs) will also be verified. Prior to initiating this audit, the investigator will be 
contacted by the sponsor to arrange a time for the audit. 
The investigator and site personnel must cooperate with the auditor(s) and allow access to 
all study documentation (e.g., participant records) and facilities. 
10.12 Inspections 
Health authorities and/or the IEC/IRB may also conduct an inspection of this study at the 
site (during the study or after its completion). 
Should an inspection be announced by a health authority and/or the IEC/IRB, the 
investigator must immediately inform the sponsor that such a request has been made. 
The investigator and site personnel must cooperate with the sponsor to handle the 
inspection related to sponsor studies. The investigator and site personnel must also 
cooperate with the inspector(s) to ensure proper performance of the inspection and allow 
access to all study documentation (e.g., participant records) and study facilities. 
10.13 Reporting of study results and publication 
The sponsor will post the key elements of this protocol and the summary of results within 
the required timelines on publicly accessible databases (e.g., clinicaltrials.gov), as required 
by law and regulation. 
Study results will be documented in a CSR that will be signed by the sponsor’s 
representatives and the coordinating investigator. 

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In accordance with the Good Publication Practices and ethical practice as outlined in 
internationally recognized guidance documents (e.g., European Medical Writers 
Association, American Medical Writers Association, International Society for Medical 
Publication Professionals), the results of the study will be submitted for publication in a 
peer-reviewed journal. Study results can be submitted for presentation at a congress before 
submission to a peer-reviewed journal. 
Authorship will be determined in accordance with the International Committee of Medical 
Journal Editors criteria, and be based on: 
• substantial contributions to the conception or design of the study, or the acquisition, 
analysis, or interpretation of data; and 
• drafting of the publication or critical review for important intellectual content; and 
• providing final approval of the version to be published; and 
• agreement to be accountable for all aspects of the work in ensuring that questions 
related to the accuracy or integrity of any part of the work are appropriately investigated 
and resolved. 
The list of authors of any publication of study results may include representatives of the 
sponsor and will be determined by mutual agreement. 
Any study-related publication written independently by investigators must be submitted to 
the sponsor for review at least 60 days prior to submission for publication or presentation 
at a congress. Upon review, the sponsor may provide comments and may also request 
alterations and/or deletions for the sole purpose of protecting its confidential information 
and/or patent rights. Neither the institution nor the investigator is permitted to write a 
publication during such a review period. 
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[Kirou 2004] Kirou KA, Lee C, George S, Louca K, Papagiannis IG, Peterson MGE, et al. 
Coordinate Overexpression of Interferon-α–Induced Genes in Systemic Lupus 
Erythematosus. Arthritis Rheum. 2004;50(12):3958–67. 
[Lateef 2012] Lateef A, Petri M. Unmet medical needs in systemic lupus erythematosus. 
Arthritis Res Ther. 2012;14(Suppl 4):S4. 
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guidelines for the diagnosis and treatment of systemic lupus erythematosus 
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product-information_en.pdf 
[Morand 2020] Morand EF, Furie R, Tanaka Y, Bruce IN, Askanase AD, Richez C, et al. 
Trial of Anifrolumab in Active Systemic Lupus Erythematosus. N Engl J Med. 
2020;382(3):21121. 
[Moyon 2021] Moyon Q, Sterlin D, Makoto M, Anna F, Mathian A, Lhote R, et al. 
BNT162b2 vaccine-induced humoral and cellular responses against SARS-CoV-2 
variants in systemic lupus erythematosus. Ann Rheum Dis. 2021;0:19. 
[Navarra 2011] Navarra SV, Guzmán RM, Gallacher AE, Hall S, Levy RA, Jimenez RE, 
et al. Efficacy and safety of belimumab in patients with active systemic lupus 
erythematosus: a randomised, placebo-controlled, phase 3 trial. Lancet. 
2011;377(9767):72131. 
[Northcott 2022] Northcott M, Jones S, Koelmeyer R, Bonin J, Vincent F, 
Kandane-Rathnayake R, et al. Type 1 interferon status in systemic lupus 
erythematosus: a longitudinal analysis. Lupus Sci Med. 2022;9(1):e000625. 
[Oke 2019] Oke V, Gunnarsson I, Dorschner J, Eketjall S, Zickert A, Niewold TB, et al. 
High levels of circulating interferons type I, type II and type III associate with distinct 
clinical features of active systemic lupus erythematosus. Arthritis Res Ther. 
2019;21(1):107. 
[Petri 2001] Petri M. Long-Term Outcomes in Lupus. Am J Manag Care. 2001;7(16 
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[Petri 2005] Petri M, Kim MY, Kalunian KC, Grossman J, Hahn BH, Sammaritano LR, et 
al; OC-SELENA Trial. Combined Oral Contraceptives in Women with Systemic 
Lupus Erythematosus. N Engl J Med. 2005;353(24):2550–8. 

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[Piali 2017] Piali L, Birker-Robaczewska M, Lescop C, Froidevaux S, Schmitz N, 
Morrison K, et al. Cenerimod, a novel S1P1 receptor modulator with unique 
signaling properties. Pharmacol Res Perspect. 2017;e00370:1–12. 
[Ponvory® SmPC] Ponvory® film-coated tablets. Summary of product characteristics. 
European Medicines Agency [accessed on 6 February 2021]. Available from: 
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product-information_en.pdf  
[Price 2005] Price CP, Newall RG, Boyd JC. Use of Protein:Creatinine Ratio 
Measurements on Random Urine Samples for Prediction of Significant Proteinuria: 
A Systematic Review. Clinical Chemistry. 2005;51(9):1577–86. 
[Ronnblom 2019] Ronnblom L, Leonard D. Interferon pathway in SLE: one key to 
unlocking the mystery of the disease. Lupus Sci Med. 2019;6:e000270. 
[Ruggenenti 1998] Ruggenenti P, Gaspari F, Perna A, Remuzzi G. Cross sectional 
longitudinal study of spot morning urine protein:creatinine ratio, 24 hour urine 
protein excretion rate, glomerular filtration rate, and end stage renal failure in chronic 
renal disease in patients without diabetes. BMJ. 1998;316(7130):504–9. Erratum in 
BMJ 1998;317(7171):1491. 
[Tian 2022] Tian X, Li M, Wang Q, Zhao J, Zeng X. The challenges and future perspective 
for the Management of systemic lupus erythematosus in China: A concise annual 
report of 2020. Rheumatol Immunol Res 2022;3(1):38–44 
[ukkidney.org] UK Kidney Association [Internet]. Bristol (UK): The UK eCKD Guide for 
Proteinuria [cited 29 November 2023]. Available from:  
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guide/proteinuria#sthash.jdT5cPIP.dpbs 
[Urowitz 1976] Urowitz MB, Bookman AA, Koehler BE, Gordon DA, Smythe HA, 
Ogryzlo MA. The bimodal mortality pattern of systemic lupus erythematosus. Am J 
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[Xiong 2014] Xiong W, Lahita RG. Pragmatic approaches to therapy for systemic lupus 
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[Zeposia® SmPC] Zeposia® hard capsules. Summary of product characteristics. European 
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https://www.ema.europa.eu/en/documents/product-information/zeposia-epar-
product-information_en.pdf 
 

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12 APPENDICES 
Appendix 1 
Clinical laboratory tests 
Laboratory 
assessment 
Variables 
Hematology 
Platelet count 
Erythrocyte indices: 
Leukocyte count with 
differential counts: 
 
Erythrocyte count 
MCV 
Neutrophils 
 
Hemoglobin 
MCH 
Lymphocytes 
 
Hematocrit 
Reticulocytes 
Monocytes 
 
 
 
Eosinophils 
 
 
 
Basophils 
Clinical 
chemistry 
Blood urea nitrogen or urea 
urea (mg/dL) = urea 
nitrogen (mg/dL) * 2.14 
AST 
Bilirubin (total and direct) 
 
Creatinine 
ALT 
Total protein 
 
eGFR using the CKD‑EPI 
formulae 
ALP 
Albumin 
 
Glucose  
LDH 
CK 
GGT 
 
Aldolase 
Lipid profile: total 
cholesterol, triglycerides, 
LDL, HDL 
HbA1c 
 
Uric acid 
Electrolytes: sodium, 
potassium, chloride, 
calcium 
 
Coagulation 
tests 
Prothrombin time and INR 
aPTT 
 
Test for 
tuberculosis1 
IFN gamma release assay 
 
 
Virus 
serology2 
Anti-HAV IgM, hepatitis B 
surface antigen, hepatitis C 
antibodies (anti-HCV 
IgG/IgM, HCV-RNA PCR if 
positive anti-HCV IgM or 
IgG) 
Varicella-zoster virus IgG 
antibodies 
Anti-HEV IgG, anti-HEV 
IgM, HEV-RNA PCR (if 
positive anti-HEV IgM 
and/or IgG) 
 
HIV1 and HIV2 antibodies  
 
 

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Laboratory 
assessment 
Variables 
Immunology 
lupus related 
ANA,  
Anti-dsDNA 
 
C3,  
C4,  
CH50, 
Anti-Sm,  
IFN alpha 
Anti-cardiolipin IgA 
anti-cardiolipin IgG,  
anti-cardiolipin IgM, 
antiglobulin (Coombs),  
haptoglobin, 
anti beta-2 glycoprotein 1 
(anti b2GP1), 
lupus anticoagulant 
Urinalysis 
(spot urine) 
Protein (protein/creatine 
ratio) 
 
Dipstick analysis: e.g. pH, 
glucose, protein; blood 
(hemoglobin, white blood 
cells), ketones, nitrite 
 
Albumin 
(albumin-to-creatinine ratio) 
Creatinine 
 
Microscopic examination – 
sediment (red blood cells, 
white blood cells, casts) 
Pregnancy 
test serum 
 
 
Beta hCG 
Pregnancy 
test urine 
Dipstick (performed locally) 
 
 
 
1 An IFN gamma release assay will be performed at Visit 1 (Screening) to screen for active or latent TB [see Sections 5.3 
and 7.2.3.8]. 
2 Virus serology will be assessed in serum at Visit 1 (Screening) (a confirmatory test might be required in the event of 
positive testing results [e.g., positive hepatitis C antibodies]). 
ANA = antinuclear antibodies; anti-dsDNA = anti-double-stranded deoxyribonucleic acid; anti-Sm = anti-Smith; ALP = 
alkaline phosphatase; ALT = alanine aminotransferase; aPTT = activated partial thromboplastin time; AST = 
aspartate aminotransferase; CK = creatine (phospho) kinase; CKD-EPI = chronic kidney disease epidemiology 
collaboration; eGFR = estimated glomerular filtration rate; GGT= gamma glutamyl transferase; HAV = hepatitis A 
virus; HbA1c = glycated hemoglobin; hCG = human chorionic gonadotropin; HCV = hepatitis C virus; HDL = high-
density lipoprotein; HEV = hepatitis E virus; HIV = human immunodeficiency virus; IFN = interferon; 
Ig = immunoglobulin; INR = international normalized ratio; LDH = lactate dehydrogenase; LDL = low-density 
lipoprotein; MCH = mean corpuscular hemoglobin; MCV = mean corpuscular volume; PCR = polymerase chain 
reaction; RNA = ribonucleic acid; TB = tuberculosis; WBC = white blood cell count. 
 
 

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Appendix 2 
2019 EULAR/ACR Classification criteria for SLE  
 
ACR = American College of Rheumatology; ANA = antinuclear antibodies; anti-Sm = anti-Smith; 
ECG = electrocardiogram/graphy; EULAR = European League Against Rheumatism; Ig = immunoglobulin; 
SLE = systemic lupus erythematosus. 
Source: [Aringer 2019]. 
The actual assessment to be used will prevail. 
 
 

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Appendix 3 
Forbidden anti-arrhythmic or heart rate lowering medications 
The use of the following drugs at any time during the study is prohibited [see Section 6.2.3]: 
•         Adenosine 
 
•         Diltiazem 
•         Moracizine 
•         Acebutolol 
 
•         Disopyramide 
•         Nadolol 
•         Ajmaline 
 
•         Dofetilide 
•         Phenytoin 
•         Amiodarone 
 
•         Dronedarone 
•         Pilocarpin 
•         Aprindine 
 
•         Encainide 
•         Prajmalium 
•         Atenolol 
 
•         Esmolol 
•         Procainamide 
•         Azimilide 
 
•         Flecainide 
•         Propafenone 
•         Bepridil 
 
•         Ibutilide 
•         Propranolol 
•         Betaxolol  
 
•         Ivabradine 
•         Quinidine 
•         Bisoprolol  
 
•         Lidocaine 
•         Sparteine 
•         Bretylium 
 
•         Lorajmine 
•         Tedisamil 
•         Bunaftine 
 
•         Lorcainide 
•         Timolol 
•         Cibenzoline 
 
•         Metoprolol 
•         Tocainide 
•        Digoxin 
 
•         Mexiletine 
•         Verapamil 
 
 
 
•         Vernakalant 
 
If, in the judgment of the investigator, it is in the best interests of the participant to receive 
any of the drugs listed above, study treatment must be permanently discontinued. It is 
recommended to wait for 6 months (i.e., 5 half-lives of cenerimod) to initiate any treatment 
with the drug listed above. 
Topically applied therapies are allowed. 
 

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Appendix 4 
Forbidden medications with risk of torsade de pointes 
The use of the following QT-prolonging medications with a known risk of torsade de 
pointes at any time during the study is prohibited [see Section 6.2.3]: 
• Amifampridine 
 
• Disopyramide 
• Ondansetron 
• Amiodarone 
 
• Dolasetron 
• Pentamidine 
• Amisulpride 
 
• Domperidone 
• Pimozide 
• Anagrelide 
 
• Dronedarone 
• Procainamide 
• Apomorphine 
 
• Droperidol  
• Probucol 
• Arsenic trioxide 
 
• Flecainide 
• Quinidine 
• Artenimol 
 
• Fluconazole 
• Sevoflurane 
• Astemizole  
 
• Erythromycin 
• Sildenafil 
• Azithromycin 
 
• Escitalopram 
• Sotalol 
• Bedaquiline 
 
• Halofantrine 
• Sparfloxacin 
• Bepridil  
 
• Haloperidol 
• Sulpiride 
• Chlorpromazine 
 
• Ketoconazole 
• Terfenadine 
• Ciprofloxacin 
 
• Levofloxacin 
• Thioridazine 
• Citalopram 
 
• Levomethadyl 
• Voriconazole 
• Clomipramine 
 
• Mesoridazine 
• Vandetanib 
• Clarithromycin 
 
• Methadone 
• Ziprasidone 
• Cocaine 
 
• Moxifloxacin 
 
 
If, in the judgment of the investigator, it is in the best interests of the participant to receive 
any of the drugs listed above, study treatment must be permanently discontinued. It is 
recommended to wait for 6 months (i.e., 5 half-lives of cenerimod) to initiate any treatment 
with the drug listed above. 
 

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Appendix 5 
Criteria for discharge from monitored setting on Day 1 and on the 
first day of re-initiation following treatment interruptions 
At the 12 hours post-dose on Day 1 and on the first day of re-initiation of study treatment 
following treatment interruptions lasting for at least 7 days in the first 14 days of treatment, 
all the following criteria must be met: 
• ECG-derived resting HR > 45 bpm; and if HR < 50 bpm it must not be the lowest value 
measured post-dose; 
• SBP ≥ 90 mmHg; 
• For participants with baseline pre-dose SBP < 90 mmHg: decrease in SBP of ≤ 5 mmHg 
from pre-dose SBP value; 
• QTcF < 500 ms (females) or < 480 ms (males); 
• No newly occurred persistent clinically significant ECG abnormality (e.g., AV block 
second-degree or higher) or ongoing AE requiring continued hospitalization; 
• No other clinically significant symptoms, signs or abnormalities as per judgment of the 
investigator. 
If at 12 h post-dose the participant does not meet discharge criteria, he/she must be 
permanently discontinued from study treatment. Participants who are permanently 
discontinued should not be discharged from the monitored setting before the HR 
abnormalities and BP return to near baseline values and until there are no persistent ECG 
abnormalities (e.g., AV block second-degree or higher) or ongoing AE requiring continued 
hospitalization, or until a diagnosis is established. 
Discharge criteria will be recorded in the eCRF. 
 
 

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Appendix 6 
SLEDAI-2K: Data collection sheet 
Study No.:_______ 
Patient name:_______ 
Visit name:______ ______ ______ 
 
 
 
 
 
 
 
 
 
d 
m 
yr 
Enter weight in SLEDAI-2K score column if descriptor is present at the time of the visit 
or in the preceding 10 days. 
SLEDAI-2K 
Descriptor 
Definition 
Weight 
SCORE 
8 
 
 
Seizure 
Recent onset, exclude metabolic, infectious or drug causes. 
8 
 
 
Psychosis 
Altered ability to function in normal activity due to severe 
disturbance in the perception of reality. Include 
hallucinations, incoherence, marked loose associations, 
impoverished thought content, marked illogical thinking, 
bizarre, disorganized, or catatonic behavior. Exclude 
uremia and drug causes. 
8 
 
 
Organic brain 
syndrome 
Altered mental function with impaired orientation, memory, 
or other intellectual function, with rapid onset and 
fluctuating clinical features, inability to sustain attention 
to environment, plus at least 2 of the following: 
perceptual disturbance, incoherent speech, insomnia or 
daytime drowsiness, or increased or decreased 
psychomotor activity. Exclude metabolic, infectious, or 
drug causes. 
8 
 
 
Visual 
disturbance 
Retinal changes of SLE. Include cytoid bodies, retinal 
hemorrhages, serous exudate or hemorrhages in the 
choroid, or optic neuritis. Exclude hypertension, 
infection, or drug causes. 
8 
 
 
Cranial nerve 
disorder 
New onset of sensory or motor neuropathy involving cranial 
nerves. 
8 
 
 
Lupus headache 
Severe, persistent headache; may be migrainous, but must be 
nonresponsive to narcotic analgesia. 
8 
 
 
CVA 
New onset of cerebrovascular accident(s). Exclude 
arteriosclerosis. 
8 
 
 
Vasculitis 
Ulceration, gangrene, tender finger nodules, periungual 
infarction, splinter hemorrhages, or biopsy or angiogram 
proof of vasculitis. 
4 
 
 
Arthritis 
> 2 joints with pain and signs of inflammation (i.e., 
tenderness, swelling or effusion). 
4 
 
 
Myositis 
Proximal muscle aching/weakness, associated with elevated 
creatine phosphokinase/aldolase or electromyogram 
changes or a biopsy showing myositis. 
4 
 
 
Urinary casts 
Heme-granular or red blood cell casts. 
 

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4 
 
 
Hematuria 
> 5 red blood cells/high power field. Exclude stone, 
infection or other cause. 
4 
 
 
Proteinuria 
> 0.5 gram/24 hours. 
4 
 
 
Pyuria 
> 5 white blood cells/high power field. Exclude infection. 
2 
 
 
Rash 
Inflammatory type rash. 
2 
 
 
Alopecia 
Abnormal, patchy or diffuse loss of hair. 
2 
 
 
Mucosal ulcers 
Oral or nasal ulcerations. 
2 
 
 
Pleurisy 
Pleuritic chest pain with pleural rub or effusion, or pleural 
thickening. 
2 
 
 
 
Pericarditis 
Pericardial pain with at least 1 of the following: rub, 
effusion, or electrocardiogram or echocardiogram 
confirmation. 
2 
 
 
Low complement 
Decrease in CH50, C3, or C4 below the lower limit of 
normal for testing laboratory. 
2 
 
 
Increased DNA 
binding 
Increased DNA binding by Farr assay above normal range 
for testing laboratory. 
1 
 
 
Fever 
> 38 oC. Exclude infectious cause. 
1 
 
 
Thrombocytopenia 
< 100,000 platelets / × 109/L, exclude drug causes. 
1 
 
 
Leukopenia 
< 3,000 white blood cells / × 109/L, exclude drug causes.  
 
 
TOTAL SCORE:  ______________ 
The actual scale to be used will prevail 
Note that leukopenia will not be evaluated due to the mechanism of action of cenerimod. 
Hematuria, proteinuria and pyuria are evaluated by dipstick at each visit assessing 
SLEDAI-2K. If the dipstick results are positive, urine sample will be further analyzed as 
clinically indicated (i.e., microscopic analysis of WBC, RBC, casts, and protein 
quantification).  
 
 

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Appendix 7 
BILAG-2004 index 
 
The actual scale to be used will prevail 
Total white blood cell count and lymphocyte count will not be evaluated due to the mechanism of action of cenerimod. 

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Appendix 8 
SLE Flare Index 
 
Source: [Petri 2005]. 
The actual scale to be used will prevail 
 
 

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Appendix 9 
Physician’s Global Assessment Visual Analog Scale 
 
The actual scale to be used will prevail 

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Appendix 10 CLASI 
Select the score in each anatomical location that describes the most severely affected 
cutaneous lupus-associated lesion 
 
 
 

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Appendix 11 Tender/swollen joints count 
 
 
 

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The actual assessment to be used will prevail  
 

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Appendix 12 Conversion table from glucocorticoids to Prednisone  
Glucocorticoid 
Approximate 
equivalent dose 
(mg) 
Conversion factor to 
Prednisone 
Half‐life (hs) 
Cortisone  
25  
0.2  
<12 (short)  
Hydrocortisone  
20  
0.25  
<12 (short)  
Deflazacort  
7.5  
0.67  
<12 (short)  
Prednisolone  
5  
1  
12–36 (medium)  
Prednisone  
5  
1  
12–36 (medium)  
Methylprednisolone  
4  
1.25  
12–36 (medium)  
Triamcinolone  
4  
1.25  
12–36 (medium)  
Betamethasone  
0.75  
6.67  
36–72 (long)  
Dexamethasone  
0.75  
6.67  
36–72 (long)  
Conversion: any glucocorticoid x Conversion factor to Prednisone = Prednisone dose  
Example: Triamcinolone 8 mg x 1.25 = Prednisone 10 mg  
Reference:   Goodman & Gilman's The Pharmacological Basis of Therapeutics (2023), chapter 50, page 1013  
Clarifications  
▪ 
These dose relationships only apply to oral or IV administration. Glucocorticoid potencies may differ greatly 
following intramuscular or intra-articular administration.  
o 
Methylprednisolone (MEDROL) → oral  
• 
Methylprednisolone Succinate (SOLU-MEDROL) → IV (FDA label mentions the same conversion factor 
than methylprednisolone)  
• 
Methylprednisolone Acetate (DEPO-MEDROL) → IM, intra-articular or intra-lesional (FDA label 
mentions the same conversion factor than methylprednisolone)  
▪ 
Fludrocortisone, even though is a glucocorticoid, it is used for its mineralocorticoid activity, the anti-
inflammatory activity is negligible at normal therapeutic doses (1/10 that of hydrocortisone)  
 
 

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Appendix 13 Notable abnormalities for ECG, BP, and laboratory variables 
Notable abnormalities for ECG and BP 
Notable abnormalities for ECG and BP that are related to the potential effects of cenerimod 
will address the following variables: 
• Morphological ECG findings (defined as any abnormal finding not present prior to start 
of treatment) 
• HR outliers (bpm), based on ECG 
• PR interval (ms) 
• QT/QTc interval (ms), based on Bazett’s or Fridericia’s formula 
• BP (mmHg) 
The definition of the abnormal values to be reported will be described in the SAP. 
Laboratory abnormalities 
Laboratory values below or above the normal range will be graded at three levels (H, HH, 
HHH for values above normal range and L, LL, LLL for values below the normal range) 
where L stands for “low”, H for “high”. 
The term “marked abnormality” describes laboratory values above or below the thresholds, 
with grading of abnormalities at two levels: LL/HH and LLL/HHH. These thresholds have 
been defined by the sponsor in order to flag and/or communicate abnormal laboratory 
results from the central laboratory to the investigators, and for the purpose of standardized 
data analysis and reporting by the sponsor. The definitions of marked abnormal values are 
based mainly on the Common Terminology Criteria for Adverse Events grading system 
(2017 v5.0) and, in specific cases (e.g., lymphocyte levels), are adjusted based on the 
known PD effect of the study treatments (e.g., LLL threshold for lymphocytes) 
[CTCAE 2017].  
The term ALERT here corresponds to the protocol-defined test result threshold requiring 
action from the investigator as described in the protocol (e.g., repeat the test, interrupt or 
discontinue the study treatment) and should not be confused with the term “call alert” used 
by the central laboratory for laboratory results which will be communicated to the 
investigator. Not all ALERTs listed in this table will be “call alerts” from the central 
laboratory and vice-versa. 
PLEASE NOTE: Thresholds for abnormality of level L or H are not provided in this 
appendix but will be provided in the laboratory manual. 

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Parameter 
LL  
LLL 
HH  
HHH  
Hemoglobin  
< 100 g/L 
(< 10 g/dL; 
< 6.2 mmol/L) 
< 80 g/L (< 8 g/dL; 
< 4.9 mmol/L) 
Increase 
in > 20 g/L above 
ULN or above 
baseline (if 
baseline is above 
ULN)  
Increase 
in > 40 g/L above 
ULN or above 
baseline (if 
baseline is above 
ULN) 
MCH  
n/a 
n/a 
n/a 
n/a 
MCV  
n/a 
n/a 
n/a 
n/a 
Hematocrit 
< 28% (female) 
< 32% (male) 
< 20% 
 
> 60% (male) 
> 55% (female) 
> 65% 
 
Platelet count  
< 75  10 e9/L 
(< 75,000/mm3) 
< 50.0  10 e9/L 
(< 50,000/mm3) 
> 600  10 e9/L 
 
> 999  10 e9/L 
RBC count 
ND 
ND 
ND 
ND 
WBC (leukocytes) 
total count  
ND 
 
 
< 1.9  10 e9/L 
 
 
> 20.0  10 e9/L 
(> 20,000/mm3) 
 
CTCAE (grade 3) 
> 100.0  10 e9/L 
(>100,000/mm3) 
Lymphocyte total  
ND 
< 0.2  10 e9/L  
(< 200/mm3) 
ALERT* 
< 0.2  10 e9/L  
(< 200/mm3) 
> 4.0  10 e9/L 
(> 4000/mm3) 
≥ 8  10 e9/L  
(> 8000/mm3) 
 
 
Neutrophils total 
< 1.5  10 e9/L 
(< 1500/mm3) 
< 1.0  10 e9/L 
(< 1000/mm3) 
ND  
ND 
Eosinophils total 
ND 
ND 
> 5.0  10 e9/L or  
> 5% 
(> 5000 cells/mm3) 
ND 
Monocytes total 
ND 
ND 
ND 
ND 
Basophils total 
ND 
ND 
ND 
ND 
Polymorphonuclear 
leucocyte/Band 
cells 
ND 
ND 
> 90% 
> 95% 
AST  
ND 
ND 
≥ 3 ULN  
ALERT  
≥ 3 ULN 
 
≥ 5 ULN  
ALERT  
≥ 5 ULN 
≥ 8 ULN 
ALT  
ND 
ND 
≥ 3 ULN  
ALERT  
≥ 3 ULN 
≥ 5 ULN  
ALERT  
≥ 5 ULN 
≥ 8 ULN 
GGT 
ND 
ND 
≥ 2 ULN 
≥ 5 ULN  
Total bilirubin  
ND 
ND 
≥ 2 ULN  
ALERT  
≥ 2 ULN 
combined with 
≥ 5 ULN  

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Parameter 
LL  
LLL 
HH  
HHH  
ALT or AST 
≥ 3 ULN 
Alkaline 
Phosphatase 
ND 
ND 
> 2.5 ULN  
> 5 ULN  
INR 
ND 
ND 
≥ 1.5** or 
≥ 1.5 times above 
baseline if on 
anticoagulation 
ALERT  
≥ 1.5 combined 
with ALT or AST 
≥ 3 ULN 
≥ 2.5** or 
≥ 2.5 times above 
baseline if on 
anticoagulation 
aPTT 
ND 
ND 
> 1.5–2.5  ULN  
 
> 2.5  ULN  
 
Lactate 
dehydrogenase 
ND 
ND 
ND 
ND 
Creatinine  
ND 
ND 
> 1.5 ULN or  
> 1.5  baseline  
> 3 ULN or  
> 3  baseline 
Creatinine 
Clearance (eGFR) 
<60 ml/min/1.73m2 
< 30 ml/min/1.73m2 
ND 
ND 
Urea 
ND 
ND 
> 2.5 ULN 
> 5 ULN 
Uric acid 
ND 
ND 
> 590 µmol/L 
(> 10 mg/dL) 
> 720 µmol/L 
(> 12 mg/dL) 
Proteinuria 
ND 
ND 
≥ 1.0 g/24 h  
2+ and 3+ 
proteinuria 
≥ 3.5 g/24 h 
4+ proteinuria 
Protein/creatinine 
ratio 
ND 
ND 
> 100 mg/mmol*** 
> 300 mg/mmol*** 
Albumin  
< 30 (g/L) 
< 20 (g/L) 
ND 
ND 
Protein total 
ND 
ND 
ND 
ND 
Glucose  
(non-diabetic 
Fasting) 
< 3.0 (mmol/L) 
(< 55 mg/dL) 
< 2.2 (mmol/L) 
(< 40 mg/dL) 
> 8.9 (mmol/L) 
(> 160 mg/dL) 
> 13.9 (mmol/L) 
(> 250 mg/dL) 
Potassium  
< 3.2 (mmol/L) 
< 3.0 (mmol/L) 
> 5.5 (mmol/L) 
> 6.0 (mmol/L) 
Sodium  
ND 
< 130 (mmol/L) 
(< 130 mEq/L) 
> 150 (mmol/L) 
(> 150 mEq/L) 
> 155 (mmol/L) 
(> 155 mEq/L) 
Calcium (corrected 
for albumin) 
< 2.0 (mmol/L) 
(< 8.0 mg/dL) 
< 1.75 (mmol/L) 
(< 7.0 mg/dL) 
> 2.9 (mmol/L) 
(> 11.5 mg/dL) 
> 3.1 (mmol/L) 
(> 12.5 mg/dL) 
Chloride  
ND 
ND 
ND 
ND 
Triglyceride  
ND 
ND 
> 3.42 (mmol/L) 
> 11.4 (mmol/L) 
Cholesterol  
ND 
ND 
> 7.75 (mmol/L) 
> 12.92 (mmol/L)  
Creatin (phospho) 
kinase (CK, CPK) 
ND 
ND 
>5 × ULN 
>10 × ULN 
IgG 
Na 
ND 
ND 
ND 
IgM 
ND 
ND 
ND 
ND 

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Parameter 
LL  
LLL 
HH  
HHH  
IgA 
ND 
ND 
ND 
ND 
ANA 
ND 
ND 
ND 
ND 
Anti-dsDNA 
ND 
ND 
ND 
ND 
C3 
ND 
ND 
ND 
ND 
C4 
ND 
ND 
ND 
ND 
Anti-Sm 
ND 
ND 
ND 
ND 
Anti-cardiolipin 
IgA 
ND 
ND 
ND 
ND 
Anti-cardiolipin 
IgG 
ND 
ND 
ND 
ND 
Anti-cardiolipin 
IgM 
ND 
ND 
ND 
ND 
Serum pregnancy 
test 
ND 
ND 
ND 
Positive 
ALERT: Positive 
GENERAL note: this table displays safety alerts for possible drug induced liver disease (DILI), lymphocytopenia as 
per protocol and serum pregnancy test. Additional alerts may be applicable, details are described in a respective 
section of laboratory manual. 
*The ALERT will provide the exact lymphocyte count. In addition, if lymphocyte count < 500 cells/µl at FSV, an 
ALERT will be sent.  
** HH and HHH based on CTCAE 2017 v5.0 [CTCAE 2017]. However, an ALERT will be sent when INR ≥ 1.5 based 
on the guidance for monitoring liver test abnormalities from the FDA [FDA 2009].  
*** Source for protein/creatinine ratio thresholds: [ukkidney.org]. 
ALT = alanine aminotransferase; ANA = antinuclear antibodies; anti-dsDNA = anti-double-stranded deoxyribonucleic 
acid; anti-Sm = anti-Smith; aPTT = activated partial thromboplastin time; AST = aspartate aminotransferase; 
CTCAE = Common Terminology Criteria for Adverse Events; eGFR = estimated glomerular filtration rate; 
FDA = Food and Drug Administration; FSV = Final Study Visit; GGT- gamma glutamyl transferase; 
Ig = immunoglobulin; INR = international normalized ratio; LLN = lower limit of normal; MCH = mean 
corpuscular hemoglobin; MCHC = Mean corpuscular hemoglobin concentration; MCV = mean corpuscular 
volume; ND = not defined; RBC = red blood cell; ULN = upper limit of normal; WBC = white blood cell. 
 
 

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Appendix 14 New York Heart Association Classes of Heart Failure 
 
Adapted from the American Heart Association.