Clinical trial NCT04294667
Conditions: Systemic Lupus Erythematosus
Keywords: Systemic lupus erythematosus Dapirolizumab pegol SLE DZP
Sponsor: UCB Biopharma SRL
Start date: 2020-08-12; Completion date: 2024-06-04
Enrollment: 321 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to evaluate the ability of dapirolizumab pegol (DZP) as an add-on treatment to standard of care (SOC) medication to achieve clinically relevant long term improvement of moderate to severe disease activity.

Detailed description:

Arms: arm 1: Subjects will receive dapriolizumab pegol througout the Treatment Period. arm 2: Subjects will receive placebo througout the Treatment Period.
Interventions: intervention 1: DZP intervention 2: Placebo
Intervention descriptions: intervention 1: Subjects will receive dapirolizumab pegol at prespecified time-points. intervention 2: Subjects will receive placebo at prespecified time-points.

Protocol documents:
Prot_000.pdf: 
UCB 
 
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Clinical Study Protocol Amendment 4 
Dapirolizumab pegol 
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A MULTICENTER, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, PARALLEL-GROUP STUDY TO 
EVALUATE THE EFFICACY AND SAFETY OF 
DAPIROLIZUMAB PEGOL IN STUDY PARTICIPANTS WITH 
MODERATELY TO SEVERELY ACTIVE SYSTEMIC LUPUS 
ERYTHEMATOSUS 
 
PROTOCOL SL0043 AMENDMENT 4 
PHASE 3 
SHORT TITLE: 
A randomized placebo-controlled study to evaluate the efficacy and safety of dapirolizumab 
pegol in study participants with moderately to severely active systemic lupus erythematosus 
 
Sponsor: 
UCB Biopharma SRL 
Allée de la Recherche 60 
1070 Brussels 
BELGIUM 
 
Regulatory agency identifying number(s): 
Eudra CT Number: 
2019-003406-27 
IND Number: 
100807 
Confidential Material 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 
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PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE 
Protocol/Amendment number 
Date 
Type of amendment 
Protocol Amendment 4 
16 Mar 2023 
Substantial 
Protocol Amendment 3 
14 Jan 2022 
Substantial 
Protocol Amendment 2.3 (UK) 
07 Jul 2021 
Substantial 
Protocol Amendment 2.2 (Hungary) 
06 Jul 2021 
Nonsubstantial 
Protocol Amendment 2.1 (Germany) 
06 Jul 2021 
Nonsubstantial 
Protocol Amendment 2 
29 Jun 2021 
Nonsubstantial 
Protocol Amendment 1.4 (Denmark) 
08 Apr 2021 
Nonsubstantial 
Protocol Amendment 1.3 (UK) 
15 Oct 2020 
Substantial 
Protocol Amendment 1.2 (Hungary) 
15 Oct 2020 
Substantial 
Protocol Amendment 1.1 (Germany) 
15 Oct 2020 
Substantial 
Protocol Amendment 1 
14 Oct 2020 
Substantial 
Protocol Amendment 0.5 (Italy) 
25 Sep 2020 
Nonsubstantial 
Protocol Amendment 0.4 (Portugal) 
08 Sep 2020 
Nonsubstantial 
Protocol Amendment 0.3 (UK) 
26 Aug 2020 
Nonsubstantial 
Protocol Amendment 0.1 (Hungary) 
21 Jul 2020 
Nonsubstantial 
Protocol Amendment 0.1 (Germany) 
29 Jun 2020 
Nonsubstantial 
Original Protocol 
03 Dec 2019 
Not applicable 
Amendment 4: 16 Mar 2023 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union.  
Overall Rationale for the Amendment 
The primary purpose of this amendment is to reduce the sample size and consequently remove 
the interim analysis. Other updates have been incorporated based on Investigators, the 
independent data monitoring committee (IDMC) and regulatory feedback, to provide further 
clarity on the protocol or to correct errors. The table below does not include correction of minor 
typographical errors and formatting/stylistic changes. 
 
Section # and Name 
Description of Change 
Brief Rationale 
Seious Adverse Event 
Reporting 
Text was added on how all SAEs are to 
be reported. 
Updated to provide further 
clarity. 
1.1 Synopsis, Overall 
design 
4.1 Overall design 
IDMC review information was 
removed. 
Due to reduced sample size 
no interim analysis will be 
conducted. 
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Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis, Number of 
participants 
1.2 Schema 
Participant numbers were updated. 
Updated for consistency 
within the protocol. 
1.3 Schedule of activities 
The following text has been added to 
footnote f: In case of a pregnancy after 
initiation of study treatment, weight 
measurement will be performed at 
every study visit. 
 
Footnote x was updated with the option 
of administering paracetamol. 
Updated to enhance 
monitoring of a pregnant 
study participant. 
 
 
 
Clarification. 
2.3 Benefit/risk assessment 
Text describing the important risks was 
amended. 
To ensure consistency with 
the content of the 
Investigator’s Brochure (IB, 
section 6, Summary of Data 
and Guidance for 
Investigator). 
6.1 Treatments administered Text was added to emphasize the 
potential risk of infusion reactions and 
the potential benefit of using 
premedication under certain 
circumstances at the discretion of the 
Investigator. 
To align with other sections 
of the protocol referring to 
study medication 
administration and 
preparation and to ensure 
awareness. 
6.5.1.3 Other 
immunosuppressants/ 
immunomodulatory agents 
The list after the first paragraph in the 
section was removed. 
 
 
Tacrolimus was added to Table 6-6. 
Information in the bulleted 
list is the same as in Table 6-
6 so duplication removed. 
 
Correction. 
Tacrolimus was deleted from 
Table 6-7 during Protocol 
Amendment 3 and was not 
added to Table 6-6. 
7.1.3 Permanent and 
temporary study drug 
discontinuation due to other 
reasons 
Bullet 5 was updated to remove the 
word “severe”. 
 
 
 
Text was added about the timing of 
upcoming surgery after last infusion of 
study medication. 
Updated to align with 
therapeutic guidances and the 
Sampson criteria in Appendix 
10.14. 
 
Updated to provide further 
clarity. 
8.1.1.1 BILAG 2004 
Text was added on grading being 
subject to adjudication. 
To clarify that centralized 
grading includes 
adjudication. 
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Section # and Name 
Description of Change 
Brief Rationale 
8.1.3.1 BILAG 2004-based 
Composite Lupus 
Assessment 
Text was added that if a treatment 
change represents an intercurrent event, 
it will be confirmed by a blinded 
independent adjudicator. 
Additional clarification on 
how the intercurrent event of 
use of escape medication is 
handled. 
8.1.3.2 Severe BILAG flare 
Clarification that flares will be seen as 
such only if there was at least 1 period 
with stable or improving disease 
activity and that flares will be 
adjudicated. 
Updated to provide clarity 
based on regulatory 
feedback. 
8.2.2 Vital signs 
Text was added for the option of taking 
blood pressure and pulse readings in a 
sitting position. 
The requirements for 3 blood pressure 
measurements was removed. 
Updated to simplify the study 
procedure and to clarify 
current practice. 
8.2.7 SARS-CoV-
2/COVID-19 
Text regarding COVID-19 was 
updated. 
Addition of IDMC 
recommended language and 
updated text regarding risks 
of the COVID-19 infection 
for study participants to 
reflect emerging evidence. 
8.3 AEs and SAEs 
Text was added regarding disclosure of 
results on public registries. 
Updated to align with current 
practice. 
8.3.8 Anticipated SAEs, 
Table 8-4 Anticipated SAEs 
for study participants with 
SLE 
 was 
removed from the table. 
Correction. 
8.6.1 Assessment of PK 
variables 
Text regarding the 
 
 
 
 
 
Text regarding the 
 
 
 
 
 
 
 
 
 
 
 
Correction. 
9.3.1 Analysis of the 
primary efficacy/primary 
endpoint 
Details regarding the null and 
alternative hypotheses were updated. 
Primary estimand information was 
updated. 
Based on regulatory 
feedback, the primary 
estimand was updated to 
estimate and test the 
difference between 
proportions meeting the 
primary endpoint, instead of 
the odds ratio. 
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Section # and Name 
Description of Change 
Brief Rationale 
9.3.1.1 Sensitivity analysis 
Text was added on how a logistic 
regression model will be used to 
analyze BICLA. 
Given the change in the 
primary estimand to analysis 
of the difference between 
proportions, the originally 
planned analysis of odds ratio 
via a logistic regression 
model was added as a 
sensitivity analysis. 
9.4.2.1 Pharmacokinetic 
analyses 
Text was added to make clear that 
 
 data will be generated if required. 
Clarification. 
9.7 Planned interim analysis 
and data monitoring 
Added text that there will be no interim 
analysis. 
There will no longer be an 
interim analysis since the 
sample size is reduced. 
9.8 Determination of sample 
size 
The sample size was reduced. 
This section was updated to 
provide the power calculation 
for the reduced sample size. 
10.2 Appendix 2: Clinical 
laboratory tests 
10.15 Appendix 15: 
Suggested management 
guidelines for suspected 
infusion reactions 
Serum tryptase was added to the table 
and a new section was added with 
tryptase information. 
Updated to enhance 
monitoring of a suspected 
infusion reaction. 
10.4 Appendix 4: 
Contraceptive guidance and 
collection of pregnancy 
information 
Information to be collected by 
Investigators from participants who 
become pregnant was updated. 
Updated to align with current 
practice. 
10.11 Appendix 11: 
Protocol Amendment 
History 
Added a summary of the changes made 
in Amendment 3. 
Intra-document 
cross-reference. 
Section 10.15, Appendix 
15: Suggested management 
guidelines for suspected 
infusion reactions 
Text regarding suspected infusion 
reactions, 
 and 
anaphylactic reactions was updated. 
Clarification. 
11 References 
The following 2 references were added: 
Muraro et al, 2022 
Platzgummer et al, 2020 
Update. 
 
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SERIOUS ADVERSE EVENT REPORTING 
Serious adverse event reporting (24h) 
All serious adverse events (SAEs) will be reported and transmitted to Patient 
Safety through the electronic Case Report form (eCRF) system. The numbers 
below are to be used to send ancillary documentation only (eg, discharge 
summaries, death certificates) or in the event that the eCRF is not available. 
Fax 
Europe and Rest of the World: +32 2 386 24 21 
US and Canada: +1 800 880 6949 or +1 866 890 3175 
Email 
Global: DS_ICT@ucb.com  
 
 
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TABLE OF CONTENTS 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ...................................... 2 
TABLE OF CONTENTS ........................................................................................................... 7 
1 
PROTOCOL SUMMARY ............................................................................................... 13 
1.1 
Synopsis ....................................................................................................................... 13 
Protocol title  ..................................................................................................................... 13 
Short Title 
 ..................................................................................................................... 13 
Rationale  
 ..................................................................................................................... 13 
Objectives and endpoints ..................................................................................................... 13 
Overall design  ..................................................................................................................... 19 
Number of participants ........................................................................................................ 20 
Treatment groups and duration ............................................................................................ 21 
1.2 
Schema ......................................................................................................................... 22 
1.3 
Schedule of activities ................................................................................................... 23 
2 
INTRODUCTION ........................................................................................................... 32 
2.1 
Study rationale ............................................................................................................. 32 
2.2 
Background .................................................................................................................. 32 
2.3 
Benefit/risk assessment ................................................................................................ 34 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 35 
4 
STUDY DESIGN ............................................................................................................. 40 
4.1 
Overall design .............................................................................................................. 40 
4.2 
Scientific rationale for study design ............................................................................ 42 
4.3 
Justification for dose .................................................................................................... 42 
4.4 
End of study definition................................................................................................. 43 
5 
STUDY POPULATION .................................................................................................. 43 
5.1 
Inclusion criteria .......................................................................................................... 43 
5.2 
Exclusion criteria ......................................................................................................... 45 
5.3 
Lifestyle restrictions..................................................................................................... 49 
5.3.1 
Meals and dietary restrictions .............................................................................. 49 
5.3.2 
Caffeine, alcohol, and tobacco ............................................................................. 49 
5.3.3 
Activity ................................................................................................................ 49 
5.4 
Screen failures .............................................................................................................. 50 
6 
STUDY TREATMENTS ................................................................................................. 50 
6.1 
Treatments administered .............................................................................................. 50 
6.2 
Preparation, handling, storage, and accountability requirements ................................ 51 
6.2.1 
Drug accountability ............................................................................................. 52 
6.3 
Measures to minimize bias: randomization and blinding ............................................ 52 
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6.3.1 
Procedures for maintaining and breaking the treatment blind ............................. 53 
6.3.1.1 
Maintenance of study treatment blind ....................................................... 53 
6.3.1.2 
Breaking the treatment blind in an emergency situation ........................... 54 
6.4 
Treatment compliance .................................................................................................. 54 
6.5 
Concomitant medication(s)/treatment(s) ..................................................................... 55 
6.5.1 
Permitted concomitant treatments (medications and therapies) .......................... 55 
6.5.1.1 
Corticosteroids ........................................................................................... 55 
6.5.1.2 
Antimalarials ............................................................................................. 61 
6.5.1.3 
Other immunosuppressants/immunomodulatory agents ........................... 62 
6.5.1.4 
Analgesics, medications including natural or synthetic cannabinoids 
(approved in line with local regulations), NSAIDs, HMG-CoA reductase 
inhibitors (statins), ACE inhibitors, and other anti-hypertensive drugs. ... 63 
6.6 
Dose modification ........................................................................................................ 63 
6.6.1 
Prohibited concomitant treatments (medications and therapies) ......................... 63 
6.6.2 
Escape medication ............................................................................................... 65 
6.7 
Criteria for study hold or dosing stoppage ................................................................... 66 
6.8 
Treatment after the end of the study ............................................................................ 66 
7 
DISCONTINUATION OF STUDY MEDICATION AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL ........................................................................ 67 
7.1 
Discontinuation of study medication ........................................................................... 67 
7.1.1 
Liver chemistry stopping criteria ......................................................................... 67 
7.1.2 
QTc stopping criteria ........................................................................................... 67 
7.1.3 
Permanent and temporary study drug discontinuation due to other reasons ....... 68 
7.2 
Participant discontinuation/withdrawal from the study ............................................... 69 
7.3 
Lost to follow up .......................................................................................................... 70 
8 
STUDY ASSESSMENTS AND PROCEDURES ........................................................... 70 
8.1 
Efficacy assessments .................................................................................................... 71 
8.1.1 
Clinical assessments of disease activity .............................................................. 71 
8.1.1.1 
BILAG 2004 .............................................................................................. 71 
8.1.1.2 
SLEDAI-2K ............................................................................................... 73 
8.1.1.3 
S2K RI-50 .................................................................................................. 73 
8.1.1.4 
Physician’s Global Assessment ................................................................. 74 
8.1.1.5 
SELENA Flare Index (2009 revision) ....................................................... 74 
8.1.1.6 
Cutaneous Lupus Erythematosus Disease Area and Severity Index ......... 74 
8.1.1.7 
Tender and Swollen Joint Counts .............................................................. 75 
8.1.1.8 
Lupus Arthritis and Musculoskeletal Disease Activity score ................... 76 
8.1.1.9 
SLICC/ACR Damage Index ...................................................................... 76 
8.1.2 
Patient-reported outcomes ................................................................................... 77 
8.1.2.1 
FATIGUE-PRO ......................................................................................... 77 
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8.1.2.2 
FACIT-F .................................................................................................... 78 
8.1.2.3 
PGI  ............................................................................................................ 78 
8.1.2.4 
LupusQoL .................................................................................................. 78 
8.1.2.5 
EQ-5D-5L .................................................................................................. 78 
8.1.2.6 
PHQ-9 ........................................................................................................ 78 
8.1.3 
Derived endpoints ................................................................................................ 79 
8.1.3.1 
BILAG 2004-based Composite Lupus Assessment .................................. 79 
8.1.3.2 
Severe BILAG flare ................................................................................... 80 
8.1.3.3 
Moderate BILAG flare .............................................................................. 80 
8.1.3.4 
LLDAS ...................................................................................................... 80 
8.1.3.5 
Systemic Lupus Erythematosus Responder Index-4 ................................. 80 
8.1.3.6 
DORIS (Definitions of Remission in SLE) complete remission on 
treatment .................................................................................................... 81 
8.2 
Safety assessments ....................................................................................................... 81 
8.2.1 
Physical examination ........................................................................................... 81 
8.2.2 
Vital signs ............................................................................................................ 82 
8.2.3 
ECG ..................................................................................................................... 82 
8.2.4 
Clinical safety laboratory assessments ................................................................ 82 
8.2.5 
Suicidal risk monitoring ...................................................................................... 83 
8.2.6 
Assessment and management of TB and TB risk factors .................................... 83 
8.2.6.1 
Assessment and reporting of TB and TB risk factors during the study..... 85 
8.2.6.2 
TB questionnaire ....................................................................................... 87 
8.2.6.3 
TB management ........................................................................................ 87 
8.2.7 
SARS-CoV-2/COVID-19 .................................................................................... 87 
8.3 
AEs and SAEs .............................................................................................................. 89 
8.3.1 
Time period and frequency for collecting AE and SAE information .................. 89 
8.3.2 
Method of detecting AEs and SAEs .................................................................... 90 
8.3.3 
Follow-up of AEs and SAEs ................................................................................ 90 
8.3.4 
Regulatory reporting requirements for SAEs ...................................................... 90 
8.3.5 
Pregnancy ............................................................................................................ 90 
8.3.6 
AEs of special interest ......................................................................................... 91 
8.3.7 
AEs of special monitoring ................................................................................... 91 
8.3.8 
Anticipated SAEs ................................................................................................. 92 
8.3.9 
Suspected transmission of an infection agent via a medicinal product ............... 92 
8.4 
Safety signal detection ................................................................................................. 92 
8.5 
Treatment of overdose ................................................................................................. 93 
8.6 
Pharmacokinetics ......................................................................................................... 93 
8.6.1 
Assessment of PK variables ................................................................................. 94 
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8.7 
Immunogenicity assessments ....................................................................................... 94 
8.8 
Pharmacodynamics ...................................................................................................... 95 
8.9 
Immune system markers .............................................................................................. 95 
8.10 
Biomarkers ................................................................................................................... 95 
8.11 
Genetics........................................................................................................................ 96 
8.12 
Medical resource utilization and health economics ..................................................... 96 
9 
STATISTICAL CONSIDERATIONS ............................................................................. 96 
9.1 
Definition of analysis sets ............................................................................................ 96 
9.2 
General statistical considerations ................................................................................. 97 
9.2.1 
General presentation of summaries and analyses ................................................ 97 
9.2.2 
Analysis time points ............................................................................................ 97 
9.2.3 
Definition of Baseline values ............................................................................... 98 
9.3 
Planned efficacy/outcome analyses ............................................................................. 98 
9.3.1 
Analysis of the primary efficacy/primary endpoint ............................................. 98 
9.3.1.1 
Sensitivity analysis .................................................................................. 100 
9.3.2 
Analysis of secondary efficacy endpoints ......................................................... 100 
9.3.2.1 
Analysis of key secondary endpoints ...................................................... 100 
9.3.2.2 
Analysis of other secondary endpoints .................................................... 102 
9.3.3 
Analysis of tertiary efficacy endpoints .............................................................. 103 
9.3.4 
Primary efficacy subgroup analyses .................................................................. 103 
9.4 
Planned safety and other analyses.............................................................................. 104 
9.4.1 
Safety analyses ................................................................................................... 104 
9.4.2 
Other analyses .................................................................................................... 105 
9.4.2.1 
Pharmacokinetic analyses ........................................................................ 105 
9.4.2.2 
Immunogenicity analyses ........................................................................ 105 
9.5 
Handling of protocol deviations................................................................................. 105 
9.6 
Handling of dropouts or missing data ........................................................................ 105 
9.7 
Planned interim analysis and data monitoring ........................................................... 106 
9.8 
Determination of sample size ..................................................................................... 106 
10 SUPPORTING DOCUMENTATION AND OPERATIONAL CONSIDERATIONS. 106 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations ....................... 106 
10.1.1 
Regulatory and ethical considerations ............................................................... 106 
10.1.2 
Financial disclosure ........................................................................................... 107 
10.1.3 
Informed consent process .................................................................................. 107 
10.1.4 
Data protection ................................................................................................... 108 
10.1.5 
Committees structure ......................................................................................... 108 
10.1.6 
Data quality assurance ....................................................................................... 109 
10.1.6.1 
Case Report form completion .................................................................. 109 
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10.1.6.2 
Apps ......................................................................................................... 109 
10.1.7 
Source documents .............................................................................................. 110 
10.1.8 
Study and site closure ........................................................................................ 111 
10.1.9 
Publication policy .............................................................................................. 111 
10.2 
Appendix 2: Clinical laboratory tests ........................................................................ 112 
10.3 
Appendix 3: AEs – definitions and procedures for recording, evaluating, follow-up, 
and reporting .............................................................................................................. 115 
10.4 
Appendix 4: Contraceptive guidance and collection of pregnancy information ....... 121 
10.5 
Appendix 5: Genetics ................................................................................................. 126 
10.6 
Appendix 6: Liver safety – suggested actions and follow-up assessments ............... 127 
10.7 
Appendix 7: Medical device AEs, ADEs, SAEs and device deficiencies: definition 
and procedures for recording, evaluating, follow-up, and reporting ......................... 130 
10.8 
Appendix 8: Rapid alert procedures .......................................................................... 131 
10.9 
Appendix 9: Country-specific requirements .............................................................. 132 
10.9.1 
Poland ................................................................................................................ 132 
10.9.2 
Romania ............................................................................................................. 132 
10.10 Appendix 10: Abbreviations and trademarks ............................................................ 133 
10.11 Appendix 11: Protocol amendment history ............................................................... 137 
10.12 Appendix 12: Endpoint rationale ............................................................................... 152 
10.13 Appendix 13: Inclusion and exclusion criteria rationale ........................................... 161 
10.14 Appendix 14: Criteria for diagnosis of anaphylaxis .................................................. 176 
10.15 Appendix 15: Suggested management guidelines for suspected infusion reactions .. 177 
10.15.1 
Tryptase ............................................................................................................. 177 
10.16 Appendix 16: Criteria for diagnosis of sepsis ............................................................ 179 
10.17 Appendix 17: Criteria for Antiphospholipid Syndrome (APS) ................................. 180 
11 REFERENCES .............................................................................................................. 181 
SPONSOR DECLARATION ................................................................................................ 185 
 
LIST OF TABLES 
Table 1-1: 
Objectives and endpoints ................................................................................. 13 
Table 1-2: 
Schedule of activities ....................................................................................... 23 
Table 3-1: 
Objectives and endpoints ................................................................................. 35 
Table 6-1: 
Characteristics of IMP ..................................................................................... 51 
Table 6-2: 
Prednisone equivalent doses of systemic corticosteroids ................................ 55 
Table 6-3: 
Corticosteroid dose equivalent to 1mg prednisone .......................................... 56 
Table 6-4: 
Recommended corticosteroid tapering schedule ............................................. 58 
Table 6-5: 
Maximum doses of permitted concomitant antimalarials ................................ 61 
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Table 6-6: 
Maximum doses of permitted concomitant immunosuppressants ................... 62 
Table 6-7: 
Prohibited medications and required wash-out periods prior to Screening 
(Visit 1) ............................................................................................................ 64 
Table 8‒1: 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
activity and damage scoring............................................................................. 75 
Table 8‒2: 
Joint tenderness and swelling grades ............................................................... 76 
Table 8‒3: 
SLICC/ACR Damage Index organ system scoring ......................................... 77 
Table 8‒4: 
Anticipated SAEs for study participants with SLE.......................................... 92 
Table 10-1: 
Phase 3-4 liver chemistry stopping criteria and follow-up assessments ........ 127 
 
LIST OF FIGURES 
Figure 7-1: 
Phase 3-4 Liver Chemistry Stopping Criteria and Increased Monitoring 
Algorithm ......................................................................................................... 67 
Figure 8-1: 
Schematic diagram of TB test results and study eligibility ............................. 85 
Figure 9-1: 
Multiplicity strategy figure ............................................................................ 102 
 
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1 
PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol title 
A multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate 
the efficacy and safety of dapirolizumab pegol in study participants with moderately to severely 
active systemic lupus erythematosus 
Short Title 
A randomized placebo-controlled study to evaluate the efficacy and safety of dapirolizumab 
pegol in study participants with moderately to severely active systemic lupus erythematosus 
Rationale 
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease which can 
present with a chronic disease course but has more often a relapsing-remitting disease course. 
The majority of patients develop tissue and organ damage over time with current standard of care 
(SOC) medication due to either lack of well-controlled disease activity or due to toxicities of the 
SOC medications. Therefore, new therapies are needed to achieve long-term control of the 
disease activity of SLE with well-tolerated SLE medication. The study aims to evaluate the 
efficacy of dapirolizumab pegol (DZP) in study participants who have persistent active or 
frequently relapsing-remitting SLE with moderate to severe disease activity despite being on 
stable non-biological SOC medication and therefore have an unmet medical need for a treatment 
intervention with new therapies. 
Objectives and endpoints 
Table 1-1: 
Objectives and endpoints 
Objectives 
Endpoints 
Primary 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication 
to achieve clinically relevant 
long-term improvement of moderate 
to severe disease activity 
• Achievement of BICLA response at Week 48 
Key Secondary 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication 
to achieve fast, clinically relevant 
improvement of moderate to severe 
disease activity 
• Achievement of BICLA response at Week 24 
• Achievement of BICLA response at Week 12 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication 
• Achievement of prevention of severe BILAG 
flares (severe BILAG flare-free) through 
Week 48 
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Objectives 
Endpoints 
to achieve long-term control of 
disease activity 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication 
to achieve and maintain the treat-to-
target goal: low disease activity with 
low/acceptable corticosteroid dose 
over time 
• Achievement of LLDAS in ≥50% of 
post-Baseline visits through Week 48 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication 
to achieve improvement of disease 
activity as measured by numerical 
disease state score commonly used in 
clinical practice 
• Change from Baseline in SLEDAI-2K at 
Week 48 
Secondary 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication 
to achieve components of the 
composite primary endpoints 
• Achievement of BILAG improvement without 
worsening at Week 48 
• Change from Baseline in PGA at Week 48 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication 
to achieve alternative responder 
endpoint 
• Achievement of SRI4 response at Week 48 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication 
to achieve endpoints supporting other 
key secondary endpoints 
• Achievement of prevention of moderate/severe 
BILAG flares (moderate/severe BILAG flare-
free) through Week 48 
• Time to severe BILAG flare through Week 48 
• Time to moderate/severe BILAG flare through 
Week 48 
• To evaluate the safety and tolerability 
of DZP as add-on treatment to SOC 
medication 
• TEAEs, serious TEAEs, TEAEs of special 
interest, and TEAEs of special monitoring 
Tertiary 
• To evaluate the ability of DZP as 
add-on treatment to SOC to achieve 
endpoints which support the primary 
and secondary objectives and/or 
• Achievement of reduction of corticosteroid 
dose from >7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day 
prednisone equivalent by visit 
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Objectives 
Endpoints 
support the interpretation of the 
primary and secondary endpoints 
• Achievement of reduction of corticosteroid 
dose from >7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day 
prednisone equivalent at Week 24 and 
maintaining low corticosteroid dose afterwards 
and achievement of BICLA response at 
Week 48 
• Achievement of reduction of corticosteroid 
dose from >7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day 
prednisone equivalent at Week 24 and 
maintaining low corticosteroid dose and 
achievement of prevention of moderate/severe 
BILAG flares (moderate/severe BILAG 
flare-free) at Week 48 
• Achievement of reduction in corticosteroid 
dose from ≥7.5mg/day prednisone equivalent 
dose at start of study to ≤5mg/day prednisone 
equivalent at Week 24 and maintaining low 
corticosteroid dose and achievement of 
BICLA response at Week 48 
• Achievement of reduction of corticosteroid 
dose from ≥7.5mg/day prednisone equivalent 
dose to ≤5mg/day prednisone equivalent at 
Week 24 and maintaining low corticosteroid 
dose and achievement of prevention of 
moderate/severe BILAG flares 
(moderate/severe BILAG flare-free) at Week 
48 
• Total corticosteroid dose through Week 24, 
through Week 48, and from Week 24 through 
Week 48 
• Achievement of BICLA response by visit 
• Achievement of BILAG 2004 improvement 
without worsening by visit 
• Change from Baseline in BILAG 2004 score 
by visit 
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Objectives 
Endpoints 
• Achievement of BILAG 2004 shifts by visit 
• Achievement of BILAG 2004 improvement by 
organ system by visit 
• Achievement of maintained BICLA response 
by visit 
• Achievement of persistent BICLA response 
between Week 24 and Week 48 
• Worsening of any organ system with a BILAG 
2004 B, C, D, E at Baseline to BILAG 2004 A 
or worsening of >1 organ system with a 
BILAG 2004 C, D, E at Baseline to BILAG 
2004 B by visit 
• Achievement of BILAG 2004 C, D, E in all 
organ systems by visit 
• Change from Baseline in SLEDAI-2K by visit 
• Achievement of SRI 4, 6, 8 response by visit 
• Change from prior visits in S2K RI50 by visit 
• Change from Baseline in PGA by visit 
• Achievement of LLDAS status by visit 
• Cumulative number of visits in LLDAS 
through Week 48 
• Achievement of LLDAS Variant (demand for 
≤5mg/day prednisone equivalent) in >50% of 
post-Baseline visits through Week 48 
• Achievement of prednisone equivalent dose 
≤7.5mg/day by visit 
• Prednisone equivalent dose by visit 
• Occurrence of severe BILAG 2004 flares by 
visit 
• Occurrence of moderate BILAG flares by visit 
• Occurrence of severe SFI flares by visit 
• Occurrence of moderate SFI flares by visit 
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Objectives 
Endpoints 
• Time to severe SFI flare 
• Time to moderate SFI flare 
• Change from Baseline in ACR/SLICC damage 
score by visit 
• Achievement of DORIS remission by visit 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication 
to achieve organ specific endpoints 
• Change from Baseline in CLASI activity score 
by visit for all study participants and for subset 
of study participants with high CLASI score 
• Achievement of a meaningful improvement in 
CLASI activity score by visit for all study 
participants and for subset of participants with 
high CLASI score 
• Change from Baseline in TJC and SJC by visit 
for all study participants and for subset of 
participants with moderate to severe arthritis 
• Achievement of a meaningful decrease in 
TJC/SJC by visit for all study participants and 
for a subset of participants with moderate to 
severe arthritis 
• Change from Baseline in Lupus Arthritis and 
Musculoskeletal Disease Activity score by 
visit 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication 
to achieve important patient reported 
outcomes 
• Change from Baseline in FACIT-F by visit 
• Change from Baseline in PHQ-9 score by visit 
• Change from Baseline in FATIGUE-PRO 
'Physical Fatigue', 'Mental Fatigue' and 
'Fatigability' scores by visit 
• Change from Baseline in LupusQoL by visit 
• Change from Baseline in EQ-5D-5L by visit 
• To evaluate the PK 
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Objectives 
Endpoints 
• To evaluate immunogenicity of DZP 
as an add-on treatment to SOC 
medication 
• Incidence of anti-drug antibodies: 
 
 
• To evaluate the PD and 
immunological parameters of DZP as 
an add-on treatment to SOC 
medication 
• Observed values and change from baseline in 
 
 
 
 
 in all study participants by visit 
and in study participants ‘positive’ at Baseline 
by visit 
• Seroconversion of: 
 
 
 
status by visit 
• To evaluate the safety and tolerability 
of DZP as an add-on treatment to 
SOC medication 
• TEAEs leading to study withdrawal, TEAEs 
leading to permanent study medication 
discontinuation, TEAEs with start day on day 
or up to 1 day after infusion, other identified 
TEAE clusters 
• Summary of participants withdrawn from the 
study due to TEAEs 
• Summary of participants who permanently 
discontinued study medication 
• Change from Baseline in vital sign parameters 
by visit 
• Observed values and change from Baseline in 
safety laboratory tests (hematology, serum 
chemistry, urinalysis) by visit, % study 
participants achieving critical threshold for 
selected lab parameters by visits 
• To evaluate changes in exploratory 
biomarkers  
• Change from Baseline in biomarkers selected 
for analysis 
• 
 
 
 
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Objectives 
Endpoints 
• To evaluate risk for anti-phospholipid 
associated events 
• Change from Baseline in APS score by visit 
ACR/SLICC=American College of Rheumatology/Systemic Lupus International Collaborating Clinics; 
; APS=antiphospholipid antibody syndrome; 
BICLA=BILAG 2004-based Composite Lupus Assessment; BILAG= British Isles Lupus Assessment Group 
Disease Activity Index 2004; CLASI=Cutaneous Lupus Erythematosus Disease Area and Severity Index; 
DORIS=definitions of remission in SLE; DZP=dapirolizumab pegol; 
 
 EQ-5D-5L=Euro Quality of life 5-Dimensions 5-Level; Fab'=fragment antigen-binding; 
FACIT-F=Functional Assessment of Chronic Illness Therapy Fatigue; FATIGUE-PRO=Fatigue patient reported 
outcome; Ig=immunoglobulin; LLDAS=low lupus disease activity state; PD=pharmacodynamics; 
PEG=polyethylene glycol; PGA=Physician’s Global Assessment of Disease; PHQ-9=Patient Health 
Questionnaire-9; PK=pharmacokinetic(s); QoL=quality of life; RNA=ribonucleic acid; SFI=SELENA Flare Index; 
SJC=swollen joint count; SLE=systemic lupus erythematosus; SLEDAI-2K=Systemic Lupus Erythematosus 
Disease Activity Index 2000; sm=Smith antigen; SOC=standard of care; SRI=Systemic Lupus Erythematosus 
Responder Index; 
; S2K RI50=Systemic 
Lupus Erythematosus Disease Activity Index-2000 Responder Index-50; TEAE=treatment-emergent adverse 
event; TJC=tender joint count 
Overall design 
The study will be conducted to assess the efficacy, safety and tolerability of DZP in study 
participants with active SLE despite standard therapy and its results will support regulatory 
filing. 
This study is a randomized, double-blind, placebo-controlled, parallel group, Phase 3 study in 
study participants 16 years of age and older with moderately to severely active SLE who are 
receiving stable SOC medication (ie, antimalarials, corticosteroids, and/or immunosuppressants) 
in line with local and international guidances at Screening Visit (V1). It will primarily 
investigate the improvement of SLE disease activity in study participants treated with DZP as 
add-on to nonbiological SOC treatment over 48 weeks. Key secondary objectives will be to 
investigate early improvement at Weeks 12 and 24, long-term disease control as evidenced by 
prevention of severe British Isles Lupus Assessment Group Disease Activity Index 2004 
(BILAG) flares (severe BILAG flare-free) through Week 48, achievement of a treat-to-target 
endpoint (low disease activity state in conjunction with low/acceptable corticosteroid dose [low 
lupus disease activity state LLDAS]) through Week 48, and long-term improvement of disease 
activity as assessed with an instrument commonly used in clinical practice (Systemic Lupus 
Erythematosus Disease Activity Index 2000 [SLEDAI-2K]) at Week 48. 
The study consists of a 2-week Screening Period, 48-week Treatment Period, and 6-week Safety 
Follow-up (SFU) Period. Due to the required moderate to severe disease activity at screening 
visit (V1), a short Screening Period is planned. At the start of the study, eligible study 
participants will be randomized (2:1) to DZP 24mg/kg or to placebo administered by intravenous 
(iv) infusion every 4 weeks (Q4W). The initial dose will be administered as a 2-hour infusion 
while each subsequent dose will be administered as a 1-hour infusion. Study participants who 
complete the 48-week Treatment Period may be eligible to participate in the open-label 
extension (OLE) study (SL0046). Study participants who withdraw early from the 48-week 
Treatment Period or choose not to enter the OLE will be followed up for at least 10 weeks after 
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their final dose of study medication (also referred to as investigational medicinal product [IMP] 
in the document). 
Eligible study participants will have persisting active or relapsing-remitting SLE at screening 
visit (V1) despite stable SOC treatment (ie, antimalarials, corticosteroids, and/or 
immunosuppressants), in line with local and international guidance at screening visit (V1). Study 
participants considered to have a monophasic or an infrequent relapsing-remitting disease course 
(defined as no evidence for frequently flaring disease course and low risk to have frequent flares) 
will be excluded as their disease likely does not correspond to a persistent active or frequently 
relapsing SLE despite SOC treatment. 
During the study, participants with a corticosteroid dose above a long-term tolerable level 
(7.5mg/day prednisone equivalent) will have to start corticosteroid tapering no later than the 
Week 8 Visit (Visit 4) to reach a target of 7.5mg/day or below. Investigators will be encouraged 
to start steroid tapering earlier if the condition of the study participant suggests improvement. 
Guidance will be provided on how to taper but the exact tapering regimen will be at the 
discretion of the Investigator to be adapted to the individual study participant’s disease activity. 
Other SLE SOC treatment will have to be kept stable unless a reduction is indicated due to side 
effects. In case of insufficient improvement of disease activity, or a clinically relevant worsening 
of the disease activity, Investigators may initiate an escape treatment (Section 6.6.2) by 
increasing the dose of concomitant SOC medication. Depending on the nature of an escape 
treatment intervention, DZP may have to be discontinued if there is a safety concern. 
Investigators should discuss the impact of escape treatment use on study conduct with the 
Medical Monitor before initiation. In case of an initiation of escape treatment, study participants 
may be declared as nonresponders for the primary endpoint; however, they do not have to be 
withdrawn from the study. 
Study participants will be encouraged to stay in the study under observation even if the study 
medication is discontinued (see Section 7.1). A study participant will have to be withdrawn from 
the study only if the study participant withdraws consent or a regulator, Institutional Review 
Board/Independent Ethics Committee (IRB/IEC), or the independent data monitoring committee 
(IDMC) requests a withdrawal for justified reasons (see Section 7.2). 
An IDMC will be established to monitor the benefit-risk profile of study participants during the 
study. The IDMC will regularly review data and will have access to unblinded data as needed. 
The review will include observations in the BILAG 2004 neuropsychiatric body organ system in 
order to monitor potential neuropsychiatric events falsely assigned to SLE. Details are described 
in the IDMC charter. The IDMC will provide recommendation if the study should be stopped, 
should be adapted or can proceed as planned. 
Number of participants 
Approximately 700 participants will be screened at approximately 230 sites in approximately 
31 countries to achieve approximately 312 participants randomly assigned (2:1) to DZP 24mg/kg 
or to placebo for an estimated total of 208 and 104 participants in the DZP 24mg/kg and placebo 
groups, respectively. 
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Treatment groups and duration 
This study consists of a 2-week Screening Period, a 48-week Placebo-controlled Period, and a 
6-week SFU Period after Week 48 (>60 days [5 half-lives] after the final dose at Week 44), for a 
total of up to 56 weeks for study participants not entering the OLE study. 
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1.2 
Schema 
 
BICLA=BILAG 2004-based Composite Lupus Assessment; BILAG=British Isles Lupus Assessment Group Disease Activity Index; BL=Baseline; 
CS=corticosteroid; DZP=dapirolizumab; EOS=End of Study; EOT=End of Treatment; N=number of study participants planned; OLE=open-label extension; 
PBO=placebo; Q4W=every 4 weeks; Scr=Screening; SFU=Safety Follow-up; SOC=standard of care; V=Visit; W/wk=week 
a The CS tapering should start no later than the Week 8 Visit (V4) with a targeted prednisone equivalent dose ≤7.5mg/day (in line with current treatment 
guidelines), guidance on how to taper will be provided but dynamic of dose-reduction is finally in the discretion of the Investigators to be adapted to the 
patient’s individual needs.  
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1.3 
Schedule of activities 
Table 1-2: 
Schedule of activities 
Period 
Scr 
Treatment (all visits in Treatment Period ±3 days) 
SFUa 
Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
Week 
Scr 
Bsl 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44 
EOTb 
W48 
EOS 
W54 
Day c 
D-14 to -1d 
D1c 
D28 
D56 
D84 
D112 
D140 
D168 
D196 
D224 
D252 
D280 
D308 
D336 
D378 
Procedures 
Written informed 
consent 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Genetic informed 
consent e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Demographics and 
Baseline 
characteristics f 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
 
 
Thrombophilia 
diagnostic g,dd 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Inclusion/exclusion 
criteria h 
X  
X i 
 
 
 
 
 
 
 
 
 
 
 
 
 
General 
medical/procedures 
history 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medication history j 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Vaccination history j 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Concomitant 
medications (inc. 
vaccines) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy serum test 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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Table 1-2: 
Schedule of activities 
Period 
Scr 
Treatment (all visits in Treatment Period ±3 days) 
SFUa 
Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
Week 
Scr 
Bsl 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44 
EOTb 
W48 
EOS 
W54 
Day c 
D-14 to -1d 
D1c 
D28 
D56 
D84 
D112 
D140 
D168 
D196 
D224 
D252 
D280 
D308 
D336 
D378 
Procedures 
Pregnancy urine test 
(for WOCBP) k,dd 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Antimalarial blood 
levelsdd 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
 
Chest x-ray l 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
12-lead ECG m 
X 
X 
X 
 
 
 
 
X 
 
 
 
 
 
X 
 
Vital signs  
X 
Xn 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X n 
X 
X 
Study participant 
Identification Card 
assigned 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Infection serology o 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IGRA TB Test 
(QuantiFERON® at 
central lab)dd
X p 
 
 
 
 
 
 
 
 
 
 
 
X 
 
 
TB questionnaire 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
Complete physical 
examination and 
anamnesis q 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Table 1-2: 
Schedule of activities 
Period 
Scr 
Treatment (all visits in Treatment Period ±3 days) 
SFUa 
Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
Week 
Scr 
Bsl 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44 
EOTb 
W48 
EOS 
W54 
Day c 
D-14 to -1d 
D1c 
D28 
D56 
D84 
D112 
D140 
D168 
D196 
D224 
D252 
D280 
D308 
D336 
D378 
Procedures 
Study withdrawal 
and study medication 
discontinuation 
criteria review 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
BILAG 2004 r 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
SLEDAI-2K r 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
S2K-RI50 
 
 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
PGA r 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
CLASI 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
TJC/SJC 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
Lupus Arthritis and 
Musculoskeletal 
Disease Activity 
(LAMDA) score 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
SFI 
X 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
SLICC Damage 
Index 
 
X 
 
 
 
 
 
 
 
 
 
 
 
X 
 
FATIGUE-PRO s 
X 
X 
X 
X 
X 
 
 
X 
 
 
X 
 
 
X 
X 
FACIT-F s 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
LupusQOL s 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
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Table 1-2: 
Schedule of activities 
Period 
Scr 
Treatment (all visits in Treatment Period ±3 days) 
SFUa 
Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
Week 
Scr 
Bsl 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44 
EOTb 
W48 
EOS 
W54 
Day c 
D-14 to -1d 
D1c 
D28 
D56 
D84 
D112 
D140 
D168 
D196 
D224 
D252 
D280 
D308 
D336 
D378 
Procedures 
PGI-S, PGI-S 
Fatigues 
X 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
PGI-C, PGI-C 
Fatigues 
 
 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
EQ-5D-5L s 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
 
PHQ-9 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
C-SSRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation assay 
(pTT, INR, quick), if 
indicateddd 
X 
X u 
X u 
X u 
X u 
X u 
X u 
X u 
X u 
X u 
X u 
X u 
X u 
X u 
 
Adhoc diagnostic as 
clinically 
appropriate, 
including SARS-
CoV-2 testing v,dd 
X  
X 
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
X  
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Table 1-2: 
Schedule of activities 
Period 
Scr 
Treatment (all visits in Treatment Period ±3 days) 
SFUa 
Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
Week 
Scr 
Bsl 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44 
EOTb 
W48 
EOS 
W54 
Day c 
D-14 to -1d 
D1c 
D28 
D56 
D84 
D112 
D140 
D168 
D196 
D224 
D252 
D280 
D308 
D336 
D378 
Procedures 
TSH, T3, T4dd 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
IMP infusion x 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
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Table 1-2: 
Schedule of activities 
Period 
Scr 
Treatment (all visits in Treatment Period ±3 days) 
SFUa 
Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
Week 
Scr 
Bsl 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44 
EOTb 
W48 
EOS 
W54 
Day c 
D-14 to -1d 
D1c 
D28 
D56 
D84 
D112 
D140 
D168 
D196 
D224 
D252 
D280 
D308 
D336 
D378 
Procedures 
Study participant 
diary 
completion/review cc 
 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Recording of 
AEs/medical 
procedures 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
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Table 1-2: 
Schedule of activities 
Period 
Scr 
Treatment (all visits in Treatment Period ±3 days) 
SFUa 
Visit 
V1 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
Week 
Scr 
Bsl 
W4 
W8 
W12 
W16 
W20 
W24 
W28 
W32 
W36 
W40 
W44 
EOTb 
W48 
EOS 
W54 
Day c 
D-14 to -1d 
D1c 
D28 
D56 
D84 
D112 
D140 
D168 
D196 
D224 
D252 
D280 
D308 
D336 
D378 
Procedures 
Contact IWRS 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Study medication 
accountability 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
 
AE=adverse event; 
 
BILAG 2004=British Isles Lupus Assessment Group Disease Activity Index 2004; BMI=body mass index; Bsl=Baseline; CD=cluster of differentiation antigen; 
CK-MB=creatine kinase- myocardial band; CLASI=Cutaneous Lupus Erythematosus Disease Area and Severity Index; COVID-19=Coronavirus disease 2019; 
; C-SSRS=Columbia Suicide Severity Rating Scale; CT=computerized tomography; CXR=chest x-ray; D=Day; 
DZP=dapirolizumab; 
; ECG=electrocardiogram; 
; EOS=End of Study; 
EOT=End of Treatment; EQ-5D-5L=Euro Quality of life 5-Dimensions 5-Level; Fab'=fragment antigen-binding; FACIT-F=Functional Assessment of Chronic 
Illness Therapy-Fatigue; FATIGUE-PRO=Fatigue patient reported outcome; F/U=follow-up; HIV=human immunodeficiency virus; ICF=Informed Consent 
form; IEC=Independent Ethics Committee; Ig=immunoglobulin; IGRA= interferon-γ release assay; IMP=investigational medicinal product; INR=international 
normalized ratio; IWRS= Interactive Web Response System; LAMDA= Lupus Arthritis and Musculoskeletal Disease Activity; LLDAS=low lupus disease 
activity state; LTBI=latent tuberculosis infection; PEG=polyethylene glycol; PGA=Physician’s Global Assessment of Disease; PGI-C= Patient Global 
Impression of Change; PGI-S=Patient Global Impression of Severity; PHQ-9=Patient Health Questionnaire-9; PK=pharmacokinetic; pTT=partial thromboplastin 
time; Q4W=every 4 weeks; QoL=quality of life; RNA=ribonucleic acid; Scr=Screening; SFI=SELENA Flare Index; SFU=safety follow-up; SJC=swollen joint 
count; SLE=systemic lupus erythematosus; SLEDAI-2K=Systemic Lupus Erythematosus Disease Activity Index 2000; SLICC =Systemic Lupus International 
Collaborating Clinics; S2K RI50=Systemic Lupus Erythematosus Disease Activity Index-2K Responder Index-50; TB=tuberculosis; TJC=tender joint count; 
TSH=thyroid-stimulating hormone; V=Visit; VAS=visual analog scale; W=Week; WOCBP=women of childbearing potential 
Note: If study participants have a missed or delayed visit, they should return to their original visit schedule. 
Note: For study participants prematurely terminating or completing the study, final disposition is recorded at Week 48 (V14, EOT). All study participants 
prematurely terminating from the study should be encouraged to undergo final evaluation procedures, in accordance with the Week 48 (V14, EOT) schedule as 
soon as possible after the final dose of study medication. 
Note: Pandemic Situation: In case a study participant is unable to attend a scheduled visit due to pandemic related situations, all efforts will be taken by the 
Investigator to maintain contact with study participant remotely through telephone/video contact, monitor and support participant’s safety and collect relevant 
study data.  
The data collected during telephone/video contact will be recorded in the medical records and/or the electronic data capture system (EDC), accordingly. The 
procedures which cannot be performed will be recorded in EDC as “not done”. 
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a If the study drug is discontinued >10 weeks before Week 48/EOT visit and the study participant attends the Week 48/EOT visit, no SFU is required.  
b In the case of early study termination. 
c Day 1 is the first day of Week 1; for all other weeks, the day shown is the final day of the week indicated. 
d If the 14 day Screening Period is exceeded, an additional 7 days may be allowed after consultation with the Medical Monitor. 
 
 
 
f Collected data includes information about lifestyle, childbearing potential (as applicable), height, weight, and BMI. Weight will be measured again at Week 24. 
For study participants screened under the initial protocol (ie, before Amendment 1), the Baseline (Visit 2) body weight is to be used to determine study drug 
dosing (Section 6.1) through Week 20 (Visit 7). In case of a pregnancy after initiation of study treatment, weight measurement will be performed at every study 
visit.  
g  Thrombophilia diagnostic includes assessment of protein C, S, antithrombin deficiency, homocysteine, factor V Leiden, and prothrombin Gene G20210A. 
h Inclusion/exclusion criteria will be reviewed in addition centrally in accordance with the Central Eligibility Review Plans. Laboratory values obtained within 
4 weeks of the Screening Visit will be considered for BILAG 2004. 
i Confirmation of inclusion/exclusion criteria will be limited to the clinical assessments (eg, SLEDAI without laboratory assessments). Laboratory assessments 
will not be available and therefore will not be considered.  
j All medications, vaccinations and SLE medication history. For SLE medications, record all biologic treatment and antimalarials the study participant has ever 
taken and all other nonbiologic SLE treatments (ie, corticosteroids, immunosuppressants) taken in the prior 6 months. Record known vaccinations (including 
vaccinations against COVID-19) received by study participant. 
k If a study participant is pregnant and stays in the study for observation, no pregnancy testing will be performed as long as the pregnancy lasts. 
l Unless a CXR or chest CT scan is available within 3 months prior to Screening. 
m The 12—lead ECGs at Baseline, Week 4, Week 24, and Week 48 will be read centrally. Screening ECGs will be assessed by Investigators to determine 
eligibility. Post screening ECGs will be assessed by Investigators to detect change from the baseline and significant abnormalities. 
n Will be assessed predose; then every 15 min from start of infusion to end of infusion; then every 30 min until 1 hour after the end of infusion. Refer to 
Section 8.2.2 and Section 10.15 Appendix 15. 
o HIV, hepatitis B, and hepatitis C. 
p In the case of rescreening due to prior LTBI diagnosis and initiation of prophylactic treatment, the IGRA TB test does not have to be performed. 
q To include lung and heart auscultation. If a participant has cutaneous SLE manifestations at V1, photodocumentation as part of source documents may be 
needed at V1, V2, V8, and V14 for adjudication of BILAG 2004 grading. Photodocumentation of cutaneous SLE manifestations may also be needed at other 
visits.  
r To be conducted after physical examination and before study participant questionnaire. The PGA should be re-evaluated after review of laboratory parameters. 
To minimize bias, the same Investigator should perform the key efficacy assessments whenever possible and this will be documented in the database. 
s To be conducted after efficacy assessments are completed. 
 
 
 
 
u Only performed if study participant receives anticoagulant therapy or in the case of significantly increased liver enzymes. 
v Adhoc diagnostic(s) may include but are not limited to the following as medically indicated: procalcitonin, thrombophilia diagnostic, hepatitis/liver injury 
diagnostic, CK-MB, and troponin I. These diagnostics will only be performed in the event of a specified medical event(s), which will be discussed with the 
Investigator and Medical Monitor. SARS-CoV-2 testing will be performed in participants when SARS-CoV-2 infection is suspected by Investigator (in line 
with Section 8.2.7). 
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x The initial dose (Baseline; Day 1) will be administered as a 2-hour infusion as this will be the initial exposure to DZP. All other doses will be administered as a 
1-hour infusion. Study participants will remain in the clinic for 1 hour post-infusion for observation. In study participants with an increased risk for allergic 
reactions premedication with antihistamines with or without paracetamol can be applied at the discretion of the Investigator. In case a study participant cannot 
attend a scheduled study visit or drug cannot be administered as planned at a scheduled visit the study drug should be administered as soon as possible but not 
less than 14 days before the next scheduled visit at a separate day. If procedures assigned to a certain visit have to be done on 2 separate days both days will be 
assigned to the same visit.  
cc Study participants will receive a smart phone with the MyUCB4me tool to enter their corticosteroid use. 
 
 
 
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2 
INTRODUCTION 
2.1 
Study rationale 
Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory disease which can 
present with a chronic disease course but has more often a relapsing-remitting disease course. 
The majority of patients develop tissue and organ damage over time with current SOC 
medication due to either lack of well controlled disease activity or due to toxicities of the SOC 
medications. Therefore, new therapies are needed to achieve long-term control of the disease 
activity of SLE with well tolerated SLE medication. The study aims to evaluate the efficacy of 
DZP in study participants who have persistent active or frequently relapsing-remitting SLE with 
moderate to severe disease activity despite being on stable non-biological SOC medication and 
therefore have an unmet medical need for a treatment intervention with new therapies. 
2.2 
Background 
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2.3 
Benefit/risk assessment 
The totality of the evidence from studies with clinical and immunological outcome parameters 
suggests a signal of superior efficacy of DZP in combination with SOC as compared with SOC 
alone in patients with persisting active or frequent relapsing-remitting SLE. 
Risks from taking part in the studies will be minimized through the selection of an appropriate 
dose level, selection of appropriate study participants defined by the inclusion/exclusion criteria, 
an independent data monitoring committee (IDMC), regular safety monitoring, and regular 
blinded assessments of study data assessments. 
Overall, the benefit-risk profile of DZP is considered favorable for further clinical development 
in a Phase 3 program. Further information can be found in the Investigator’s Brochure (IB). 
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3 
OBJECTIVES AND ENDPOINTS 
Table 3-1: 
Objectives and endpoints 
Objectives 
Endpoints 
Primary 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication to 
achieve clinically relevant long term 
improvement of moderate to severe 
disease activity 
• Achievement of BICLA response at Week 48 
Key Secondary 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication to 
achieve fast, clinically relevant 
improvement of moderate to severe 
disease activity 
• Achievement of BICLA response at Week 24 
• Achievement of BICLA response at Week 12 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication to 
achieve long term control of disease 
activity 
• Achievement of prevention of severe BILAG 
flares (severe BILAG flare-free) through 
Week 48 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication to 
achieve and maintain the treat-to-target 
goal: low disease activity with 
low/acceptable corticosteroid dose over 
time 
• Achievement of LLDAS in ≥50% of post 
Baseline visits through Week 48 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication to 
achieve improvement of disease 
activity as measured by numerical 
disease state score commonly used in 
clinical practice 
• Change from Baseline in SLEDAI-2K at 
Week 48 
Secondary 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication to 
achieve components of the composite 
primary endpoints 
• Achievement of BILAG improvement 
without worsening at Week 48 
• Change from Baseline in PGA at Week 48 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication to 
achieve alternative responder endpoint 
• Achievement of SRI4 response at Week 48 
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Objectives 
Endpoints 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication to 
achieve endpoints supporting other key 
secondary endpoints 
• Achievement of prevention of 
moderate/severe BILAG flares 
(moderate/severe BILAG flare-free) through 
Week 48 
• Time to severe BILAG flare through 
Week 48 
• Time to moderate/severe BILAG flare 
through Week 48 
• To evaluate the safety and tolerability 
of DZP as add-on treatment to SOC 
medication 
• TEAEs, serious TEAEs, TEAEs of special 
interest, and TEAEs of special monitoring 
Tertiary 
• To evaluate the ability of DZP as add-
on treatment to SOC to achieve 
endpoints which support the primary 
and secondary objectives and/or 
support the interpretation of the 
primary and secondary endpoints 
• Achievement of reduction of corticosteroid 
dose from >7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day 
prednisone equivalent by visit 
• Achievement of reduction of corticosteroid 
dose from >7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day 
prednisone equivalent at Week 24 and 
maintaining low corticosteroid dose 
afterwards and achievement of BICLA 
response at Week 48 
• Achievement of reduction of corticosteroid 
dose from >7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day 
prednisone equivalent at Week 24 and 
maintaining low corticosteroid dose and 
achievement of prevention of 
moderate/severe BILAG flares 
(moderate/severe BILAG flare-free) at Week 
48 
• Achievement of reduction in corticosteroid 
dose from ≥7.5mg/day prednisone equivalent 
dose at start of study to ≤5mg/day prednisone 
equivalent at Week 24 and maintaining low 
corticosteroid dose and achievement of 
BICLA response at Week 48 
• Achievement of reduction of corticosteroid 
dose from ≥7.5mg/day prednisone equivalent 
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Objectives 
Endpoints 
dose to ≤5mg/day prednisone equivalent at 
Week 24 and maintaining low corticosteroid 
dose and achievement of prevention of 
moderate/severe BILAG flares 
(moderate/severe BILAG flare-free) at Week 
48 
• Total corticosteroid dose through Week 24, 
through Week 48, and from Week 24 
through Week 48 
• Achievement of BICLA response by visit 
• Achievement of BILAG 2004 improvement 
without worsening by visit 
• Change from Baseline in BILAG 2004 score 
by visit 
• Achievement of BILAG 2004 shifts by visit 
• Achievement of BILAG 2004 improvement 
by organ system by visit 
• Achievement of maintained BICLA response 
by visit 
• Achievement of persistent BICLA response 
between Week 24 and Week 48 
• Worsening of any organ system with a 
BILAG 2004 B, C, D, E at Baseline to 
BILAG 2004 A or worsening of >1 organ 
system with a BILAG 2004 C, D, E at 
Baseline to BILAG 2004 B by visit 
• Achievement of BILAG 2004 C, D, E in all 
organ systems by visit 
• Change from Baseline in SLEDAI-2K by 
visit 
• Achievement of SRI 4, 6, 8 response by visit 
• Change from prior visits in S2K RI50 by 
visit 
• Change from Baseline in PGA by visit 
• Achievement of LLDAS status by visit 
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Objectives 
Endpoints 
• Cumulative number of visits in LLDAS 
through Week 48  
• Achievement of LLDAS Variant (demand 
for ≤5mg/day prednisone equivalent) in 
>50% of post-Baseline visits through 
Week 48 
• Achievement of prednisone equivalent dose 
≤7.5mg/day by visit 
• Prednisone equivalent dose by visit 
• Occurrence of severe BILAG 2004 flares by 
visit 
• Occurrence of moderate BILAG flares by 
visit 
• Occurrence of severe SFI flares by visit 
• Occurrence of moderate SFI flares by visit 
• Time to severe SFI flare 
• Time to moderate SFI flare 
• Change from Baseline in ACR/SLICC 
damage score by visit 
• Achievement of DORIS remission by visit 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication to 
achieve organ specific endpoints 
• Change from Baseline in CLASI activity 
score by visit for all study participants and 
for subset of study participants with high 
CLASI score 
• Achievement of a meaningful improvement 
in CLASI score by visit for all study 
participants and for subset of study 
participants with high CLASI score 
• Change from Baseline in TJC and SJC by 
visit for all participants and for subset of 
participants with moderate to severe arthritis 
• Achievement of a meaningful decrease in 
TJC/SJC by visit for all participants and for a 
subset of participants with moderate to 
severe arthritis 
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Objectives 
Endpoints 
• Change from Baseline in Lupus Arthritis and 
Musculoskeletal Disease Activity score by 
visit 
• To evaluate the ability of DZP as an 
add-on treatment to SOC medication to 
achieve important patient reported 
outcomes 
• Change from Baseline in FACIT-F by visit  
• Change from Baseline in PHQ-9 score by 
visit 
• Change from Baseline in FATIGUE-PRO 
'Physical Fatigue', 'Mental Fatigue' and 
'Fatigability' scores by visit 
• Change from Baseline in LupusQoL by visit 
• Change from Baseline in EQ-5D-5L by visit 
• To evaluate the PK 
• To evaluate immunogenicity of DZP as 
an add-on treatment to SOC 
medication 
• Incidence of anti-drug antibodies: 
 
 
• To evaluate the PD and immunological 
parameters of DZP as an add-on 
treatment to SOC medication 
• Observed values and change from baseline in 
 
 
 
 
 in all study participants by visit 
and in study participants ‘positive’ at 
Baseline by visit 
• Seroconversion of: 
 
 
 
status by visit 
• To evaluate the safety and tolerability 
of DZP as an add-on treatment to SOC 
medication 
• TEAEs leading to study withdrawal, TEAEs 
leading to permanent study medication 
discontinuation, TEAEs with start day on day 
or up to 1 day after infusion, other identified 
TEAE clusters 
• Summary of participants withdrawn from the 
study due to TEAEs 
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Objectives 
Endpoints 
• Summary of participants who permanently 
discontinued study medication 
• Change from Baseline in vital sign 
parameters by visit 
• Observed values and change from Baseline 
in safety laboratory tests (hematology, serum 
chemistry, urinalysis) by visit, % study 
participants achieving critical threshold for 
selected lab parameters by visits 
• To evaluate changes in exploratory 
biomarkers  
• Change from Baseline in biomarkers selected 
for analysis 
• To evaluate risk for anti-phospholipid 
associated events 
• Change from Baseline in APS score by visit 
ACR/SLICC=American College of Rheumatology/Systemic Lupus International Collaborating Clinics; 
; APS=antiphospholipid antibody syndrome; BICLA= 
BILAG 2004-based Composite Lupus Assessment; BILAG=British Isles Lupus Assessment Group Disease Activity 
Index 2004; CLASI=Cutaneous Lupus Erythematosus Disease Area and Severity Index; DORIS=definitions of 
remission in SLE; DZP=dapirolizumab pegol; 
; EQ-5D-5L=Euro 
Quality of life 5-Dimensions 3-Level; Fab'=fragment antigen-binding; FACIT-F=Functional Assessment of Chronic 
Illness Therapy Fatigue; FATIGUE-PRO=Fatigue patient reported outcome; Ig=immunoglobulin; LLDAS=low 
lupus disease activity state; PD=pharmacodynamics; PEG=polyethylene glycol; PGA=Physician’s Global 
Assessment of Disease; PHQ-9=Patient Health Questionnaire-9; PK=pharmacokinetic(s); SFI=SELENA Flare 
Index; SJC=swollen joint count; SLE=systemic lupus erythematosus; SLEDAI-2K=Systemic Lupus Erythematosus 
Disease Activity Index 2000; sm=Smith antigen; SOC=standard of care; SRI4, 6, 8=Systemic Lupus Erythematosus 
Responder Index-4, 6, 8; 
;S2K RI50=Systemic Lupus Erythematosus Disease 
Activity Index-2000 Responder Index-50; TEAE=treatment-emergent adverse event; TJC=tender joint count 
4 
STUDY DESIGN 
4.1 
Overall design 
The study will be conducted to assess the efficacy, safety and tolerability of DZP in study 
participants with active SLE despite standard therapy and its results will support regulatory 
filing. 
This study is a randomized, double-blind, placebo-controlled, parallel group, Phase 3 study in 
study participants 16 years of age and older with moderately to severely active SLE who are 
receiving stable SOC medication (ie, antimalarials, corticosteroids, and/or immunosuppressants) 
in line with local and international guidances at screening visit (V1). It will primarily investigate 
the improvement of SLE disease activity in study participants treated with DZP as add-on to 
nonbiological SOC treatment over 48 weeks. Key secondary objectives will be to investigate 
early improvement at Weeks 12 and 24, long-term disease control as evidenced by prevention of 
severe BILAG flares (severe BILAG flare-free) through Week 48, achievement of a 
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treat-to-target endpoint (low disease activity state in conjunction with low/acceptable 
corticosteroid dose [LLDAS]) through Week 48, and long-term improvement of disease activity 
as assessed with an instrument commonly used in clinical practice (SLEDAI-2K) at Week 48. 
The study consists of a 2-week Screening Period, 48-week Treatment Period, and 6-week SFU 
Period (if the participant completes the study but decides not to enter the open-label extension 
study SL0046). Due to the required moderate to severe disease activity at screening visit (V1) 
and limited allowed treatment possibilities during the screening phase, a short Screening Period 
is planned. At the start of the study, eligible study participants will be randomized (2:1) to 
DZP 24mg/kg or to placebo administered by iv infusion Q4W. The initial dose will be 
administered as a 2-hour infusion while each subsequent dose will be administered as a 1-hour 
infusion. Study participants who complete the 48-week Treatment Period may be eligible to 
participate in the OLE study (SL0046). Study participants who withdraw early from the 48-week 
Treatment Period or choose not to enter the OLE will be followed up for at least 10 weeks SFU 
after their final dose of study medication. 
Eligible study participants will have persisting active or relapsing-remitting SLE at screening 
visit (V1) despite stable SOC treatment (ie, antimalarials, corticosteroids, and/or 
immunosuppressants), in line with local and international guidance at screening visit (V1). Study 
participants considered to have a monophasic or an infrequent relapsing-remitting disease course 
(defined as no evidence for frequently flaring disease course and low risk to have frequent flares) 
will be excluded as their disease likely does not correspond to a persistent active or frequently 
relapsing SLE despite SOC treatment. 
During the study, participants with a corticosteroid dose above a long-term tolerable level 
(7.5mg/day prednisone equivalent) will have to start corticosteroid tapering no later than the 
Week 8 Visit (Visit 4) to reach a target of 7.5mg/day or below. Investigators will be encouraged 
to start steroid tapering earlier if the condition of the study participant suggests improvement. 
Guidance will be provided on how to taper but the exact tapering regimen will be at the 
discretion of the Investigator to be adapted to the individual study participant’s disease activity. 
Other SLE SOC treatment will have to be kept stable unless a reduction is indicated due to side 
effects. In case of insufficient improvement of disease activity, or a clinically relevant worsening 
of the disease activity, Investigators may initiate an escape treatment (Section 6.6.2) by 
increasing the dose of concomitant SOC medication. Depending on the nature of an escape 
treatment intervention, DZP may have to be discontinued if there is a safety concern. 
Investigators should discuss the impact of escape treatment use on study conduct with the 
Medical Monitor before initiation. In case of an initiation of escape treatment, study participants 
may be declared as nonresponders for the primary endpoint; however, they do not have to be 
withdrawn from the study. 
Study participants will be encouraged to stay in the study under observation even if the study 
medication is discontinued (see Section 7.1). A study participant will have to be withdrawn from 
the study only if the study participant withdraws consent or a regulator, Institutional Review 
Board/Independent Ethics Committee (IRB/IEC), or the independent data monitoring committee 
(IDMC) requests a withdrawal for justified reasons (see Section 7.2). 
An IDMC will be established to monitor the benefit-risk profile of study participants during the 
study. The IDMC will regularly review data and will have access to unblinded data as needed. 
The review will include observations in the BILAG 2004 neuropsychiatric body organ system in 
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order to monitor potential neuropsychiatric events falsely assigned to SLE. Details are described 
in the IDMC charter. The IDMC will provide recommendation if the study should be stopped, 
should be adapted or can proceed as planned. 
4.2 
Scientific rationale for study design 
A randomized, double-blind, placebo-controlled, parallel-group study design has been selected to 
demonstrate efficacy and safety of DZP to support regulatory filing. The study population will 
include study participants 16 years of age and older with moderately to severely active SLE who 
are receiving stable SOC medication (ie, antimalarials, corticosteroids, and/or 
immunosuppressants) at screening visit (V1). The primary efficacy outcome measures and other 
efficacy assessments included in this study are consistent with those used for some other SLE 
studies and are considered appropriate for establishing efficacy of DZP. Clinically relevant 
improvement of moderate to severe disease activity over 48 weeks will be used to demonstrate 
the efficacy of DZP over placebo long term. Early clinically relevant improvement from 
moderate to severe disease activity will be assessed after 12 and 24 weeks. Long-term disease 
control will be demonstrated by assessment of flare prevention (flare-free), the achievement of 
the treat-to-target endpoint LLDAS, and the reduction in SLEDAI-2K score. 
4.3 
Justification for dose 
The selection of the dose is based on the Phase 2b study, SL0023. Efficacy and safety of DZP 
was assessed in 3 dose arms in SL0023. The lowest dose of 6mg/kg was selected based on 
non-clinical data on a non-human primate tetanus toxoid (TT) model showing minimal reduction 
of 
 titers suggesting some immunomodulation. 
 
 
 
 
 
 
 
. 
SL0023 Study participants who received 24mg/kg or 45mg/kg DZP showed overall similar 
clinical response rates across all clinical endpoints and majority of time points as well as similar 
reduction in 
, therefore the 45mg/kg dose is not considered to provide 
added benefit as compared to the 24mg/kg. This was also applicable in subgroups of participants 
with higher disease activity and/or more severe disease. While similarities were seen between 
24mg/kg and 45mg/kg doses, response rates in study participants receiving 6mg/kg were 
inconsistent. Moreover, generation of anti-drug antibodies was increased in study participants 
receiving 6mg/kg as compared to study participants receiving 24mg/kg or 45mg/kg. Therefore, 
6mg/kg is considered as a dose with inferior efficacy while 24mg/kg is considered as dose with 
maximum observed effect. As doses between 6mg/kg and 24mg/kg overlap pharmacokinetically 
with the 24mg/kg dose, a clear assignment of benefit/risk to dosages below 24mg/kg is difficult. 
Therefore, in view of the aforementioned information, 24mg/kg was selected as a dose with a 
maximum effect and an acceptable safety profile. 
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4.4 
End of study definition 
A study participant is considered to have completed the study if she/he has completed the 
Week 48 Visit. 
The end of the study is defined as the date of the final visit of the last study participant in the 
study. 
5 
STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also known as 
protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion criteria 
Rescreening will be allowed once during the study in case there is new evidence for an inclusion 
criterion that was not fulfilled at the first screening or in case a study participant no longer meets 
an exclusion criterion (Section 5.4) or screening period exceeded the maximum duration due to 
delays in screening processes. 
Study participants are eligible to be included in the study only if all of the following criteria 
apply: 
Age 
1. Study participant must be ≥16 years of age, unless restricted by local regulation, at the time 
of signing the Informed Consent form (ICF). 
Type of participant and disease characteristics 
2. Study participants who have moderate to severe disease activity due to either persisting 
active SLE or due to an acute worsening of SLE in the scope of frequent flaring/relapsing-
remitting SLE despite stable SOC medication defined as: 
a1. Diagnosed with SLE at least 24 weeks before the Screening Visit (Visit 1) by a 
qualified physician (eg, rheumatologist, internal medicine expert, nephrologist, or 
dermatologist) 
b. Classified by 2019 SLE European League Against Rheumatism/American College of 
Rheumatology (EULAR/ACR) classification criteria for SLE 
c1. With serological evidence for SLE at Screening as demonstrated by at least 1 of the 
following: 
i) Evidence for 
 (defined as evidence for 
 in central 
laboratory) 
ii) Either 
 < lower limit of normal (LLN) OR 
 <LLN OR 
elevated erythrocyte-bound complement 
 (where available) as measured by 
central laboratory 
iii) 
 with a titer of at least 1:80 confirmed by central laboratory in 
combination with evidence of at least 1 of the following SLE typical autoantibodies: 
1. 
 (central laboratory) 
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2. 
 
 (central laboratory) 
3. Historic evidence for anti-dsDNA antibodies (at least 2 historical positive tests 
[>upper limit of normal (ULN) of lab assay with an interval of at least 12 weeks 
between tests]) 
d. Moderately to severely active defined as  
-British Isles Lupus Assessment Group Disease Activity Index 2004 (BILAG 2004) 
Grade B in ≥2 organ systems and/or a BILAG 2004 Grade A in ≥1 organ systems at 
Screening and Baseline Visit AND 
-SLEDAI-2K ≥6 at Screening Visit AND  
-SLEDAI-2K without labs ≥4 at Baseline Visit 
e3. Receiving the following SOC medication at stable dose: 
◦ 
Antimalarial treatment in combination with corticosteroids and/or 
immunosuppressants or as stand-alone treatment if justified (ie, if for other SLE SOC 
medications there is documented intolerance in medical history, documented lack of 
efficacy, contraindications, or lack of availability) OR 
◦ 
Treatment with corticosteroids and/or immunosuppressants if anti-malarial treatment 
is not possible (ie, documented intolerance in medical history or antimalarials not 
available locally) 
Stable dose is defined for: 
◦ 
Antimalarials as no change to dose within 8 weeks prior to Screening and during 
Screening Period and a start date at least 12 weeks before Screening. Maximum doses 
are described in Section 6.5.1.2. 
◦ 
Corticosteroids as no change in dose for 2 weeks prior to Screening, no change during 
Screening Period, and no iv pulse therapy (>500mg x 1 to 3 days) within 4 weeks 
prior to screening. The maximum dose allowed at screening is 40mg/day prednisone 
or equivalent (see Section 6.5.1.1). 
◦ 
Immunosuppressants as no change in dose for 12 weeks prior to Screening Visit and 
during Screening Period. Maximum doses are described in Section 6.5.1.3. 
Weight 
3. Body weight ≥40kg and ≤160kg. 
Sex 
4a. Female and/or male 
• A male study participant must agree to use contraception, as detailed in Section 10.4, during 
the Treatment Period and for at least 17 weeks after the final dose of study medication and 
refrain from donating sperm during this period. 
• A female study participant is eligible to participate if she is not pregnant, not breastfeeding 
(including pumping breast milk to feed to a child), and at least 1 of the following conditions 
applies: 
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− Not a woman of childbearing potential (WOCBP) as defined in Section 10.4 of the 
protocol, or 
− A WOCBP who agrees to follow the contraceptive guidance in Section 10.4 of the final 
protocol during the treatment period and for at least 17 weeks after the final dose of study 
medication. 
Informed consent 
5. Capable of giving signed informed consent as described in Section 10.1.3, which includes 
compliance with the requirements and restrictions listed in the ICF and in this protocol. 
5.2 
Exclusion criteria 
Study participants are excluded from the study if any of the following criteria apply: 
Medical conditions 
General 
1. 
Study participant has any medical or psychiatric condition (including conditions due to 
neuropsychiatric SLE) that, in the opinion of the Investigator, could jeopardize or would 
compromise the study participant’s ability to participate in this study. This includes study 
participants with a life threatening condition (eg, CTCAE grade 4 conditions, CAPS, acute 
severe renal failure, acute severe central nervous system [CNS] manifestations) 
2a. Study participant has moderate to severe disease activity (as defined per inclusion criterion 
2.d) at the Screening Visit (V1) due to an acute flare but does not fulfill at least one of the 
following criteria in addition to the Screening Visit: 
− ≥1 additional disease flare within the last 24 weeks prior to Screening (as per medical 
record) OR 
−
 positivity in combination with 
 <LLN as per central laboratory OR 
−
 <LLN as per central laboratory OR 
− African-American OR 
− Age <25 years 
3. Study participant has a history of chronic alcohol or drug abuse within the previous 
24 weeks.  
4. Study participant has a known 
 to any components of DZP including PEG or 
comparative drugs (and/or an investigational device) as stated in this protocol. 
5a. Study participant has a history of an anaphylactic reaction to parenteral administration of 
contrast agents, human or murine proteins, or monoclonal antibodies. This includes systemic 
reactions due to latex allergy. 
6a. Study participant has a history of malignancy, except the following treated cancers: cervical 
carcinoma in situ (after complete resection [eg, curettage, electrodesiccation] not later than 
4 weeks prior to the Screening Visit [V1]), basal cell carcinoma, or dermatological 
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squamous cell carcinoma (after complete resection not later than 24 weeks prior to the 
Screening Visit [V1]). 
7. Study participants who have had major surgery (including joint surgery) within the 24 weeks 
prior to Screening, or planned surgery within 24 weeks after entering the study. 
8. Study participants who have had significant blood loss or have donated or received 1 or 
more units (450mL) of blood within 30 days prior to the Screening Visit or have donated 
plasma or platelets within 14 days prior to the Screening Visit. 
9. Study participants with a history of thromboembolic events within 52 weeks of Screening 
(Visit 1), including but not limited to the following: deep venous thrombosis, pulmonary 
embolism, cortical sinus thrombosis, myocardial infarction, stroke, transient ischemic attack, 
or arterial insufficiency causing digital gangrene or tissue necrosis. 
Note:  
1) In case of anti-phospholipid antibodies present at the Screening Visit, a prophylactic 
treatment should be considered in line with local or international guidelines and considering 
the individual risk profile of the patient for thromboembolic events 
2) Study participants with antiphospholipid syndrome (APS) can be enrolled if they are on 
stable anticoagulation therapy at an effective dose (eg, International Normalized Ratio [INR] 
target 2 to 3 depending on clinical situation) and did not have a thromboembolic event 
and/or obstetric morbidity within the 52 weeks prior to Screening (Visit 1).Obstetric 
morbidity is defined as 1 or more unexplained deaths of a morphologically normal fetus at 
or beyond the tenth week of gestation with the latest incidence within 52 weeks prior to 
Screening (Visit 1) OR 1 or more preterm births of a morphologically normal neonate before 
the 34th week of: (i) eclampsia or severe pre-eclampsia or (ii) recognized features of 
placental insufficiency with the latest incidence within 52 weeks prior to Screening (Visit 1). 
10. Study participants with a history of catastrophic APS or saddle pulmonary embolism. 
11a. Study participant has an increased risk for thromboembolic events due to an ongoing heart 
disease or due to a medical device, including but not limited to vascular graft, valvular heart 
disease, atrial fibrillation, or a heart rhythm disorder. 
12. Study participant has a BILAG 2004 Grade A in the musculoskeletal system due to severe 
arthritis only AND no BILAG 2004 Grade A or B in any other organ system AND no 
current (within the past 4 weeks) evidence for synovitis based on imaging methods such as 
magnetic resonance imaging or doppler-sonography. 
13a. Study participant has a mixed connective tissue disease, scleroderma, and/or overlap 
syndrome of these diseases with SLE. 
− Clarification: Study participants with rheumatoid arthritis in their medical history are not 
considered as having an overlap syndrome and are therefore eligible. 
Infection related risks: 
14. Study participant has evidence of human immunodeficiency virus infection, 
agammaglobulinemias, T-cell deficiencies, or human T-cell lymphotropic virus-1 infection 
at any time prior to or during the study. 
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15a. Study participant has clinically significant active or latent infection (eg, chronic viral 
hepatitis B or C, or SARS CoV-2 infection [see Section 8.2.7]). 
16a. Study participant has a history of a serious infection within the last 60 days prior to the first 
study medication infusion (Visit 2) that required iv/intramuscular antibiotics, systemic 
antiviral treatment or required hospitalization/prolonged hospitalization. Study participants 
must have completed any prior anti-infective therapy for serious infections prior to the first 
study medication infusion. 
17b. Study participant had a reactivated latent infection (eg, cytomegalovirus, herpes simplex 
virus, or herpes zoster infection) or opportunistic infection (including but not limited to 
pneumocystis, cytomegalovirus, or severe herpes zoster infection) within 12 weeks prior to 
the first study medication infusion (Visit 2), or is currently receiving suppressive therapy 
for an opportunistic infection. 
18. Study participant has a clinically relevant recurrent (more than 3 times a year) infection. 
19. Study participant with any of the following tuberculosis (TB) exclusion criteria: 
• Known active TB infection. 
• History of active TB infection involving any organ system or findings in other organ 
systems consistent with TB, unless adequately treated according to WHO/CDC 
therapeutic guidance and proven to be fully recovered upon consult with a TB specialist. 
• Latent TB infection (LTBI) unless appropriate prophylaxis is initiated at least 4 weeks 
prior to study medication dosing and will be continued to completion of prophylaxis. 
• High risk of acquiring TB infection, eg, known close exposure to another person with 
active TB infection within 3 months prior to Screening or significant time spent in a 
health care delivery setting or institution where individuals infected with TB are housed 
and where the risk of transmission is high within 3 months prior to Screening. 
• Current nontuberculous mycobacterial (NTM) infection or history of NTM infection 
unless proven to have fully recovered upon consult with a TB specialist. 
20a. Study participants who have received live/live attenuated vaccines within 6 weeks prior to 
the first study medication infusion (Visit 2) or who plan to receive these vaccines during the 
study or up to 12 weeks after the final dose of study medication will be excluded. Use of 
nonlive vaccines is allowed during the study; however, based on current evidence, it cannot 
be excluded that the effectiveness of these vaccines may be compromised by the study 
medication. Investigator should consider local and international guidance on vaccination in 
immunosuppressed patients and discuss risks, benefits and administration options with 
participants (for more details see also Section 6.6.1 and Section 8.2.7). 
Prior/Concomitant therapy 
21. Study participant has active lupus that, in the opinion of the Investigator or according to local 
or international guidances, requires an increase in SOC therapy outside of that permitted in 
Section 6.5.1. 
22. Study participants requiring plasma exchange or immunoadsorption in the 16 weeks prior to 
Visit 2 or at any time during the study. 
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23. Study participant has used the prohibited medications listed in Table 6-7, regardless of route 
(with the exception of eye drops), within the time frame (Wash-Out Period) listed in the table 
prior to Screening (Visit 1). Study participant has used investigational agents not included in 
Table 6-7, including other investigational or recently approved biologics, off-label use of 
immunomodulators, or device products, within 12 weeks or 5 times the half-life prior to 
Screening (Visit 1), whichever is longer. Concomitant participation in studies where no 
product or device is administered/used may be allowed if discussed and approved by the 
Medical Monitor/UCB. If there are any questions regarding acceptable wash-out periods not 
mentioned, the Investigator should contact the Medical Monitor. 
24. Hormone replacement therapy is allowed provided it is not initiated within the 4 weeks prior 
to Screening (Visit 1) or during the study. The hormone replacement therapy may be 
decreased and/or discontinued at any time during the study. 
25. Study participant should, if possible, stay on stable doses of the following other concomitant 
medications for the treatment of SLE during the study unless changes in these treatments are 
clinically indicated: analgesics, non-steroidal anti-inflammatory drugs (NSAIDs), 3-hydroxy-
3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase inhibitors (statins), angiotensin 
converting enzyme (ACE) inhibitors, and other anti-hypertensive drugs. 
Prior/Concurrent clinical study experience 
26a. Study participant has previously been randomized within this study or has previously been 
assigned to treatment with DZP in a study evaluating DZP. 
27. 
Study participant has participated in another study of an IMP (and/or an investigational 
device) within the previous 12 weeks or 5 half-lives of the IMP whatever is longer (see 
Table 6-7) or is currently participating in another study of an IMP. 
Diagnostic assessments 
28a. Study participant has history of a suicide attempt within the 5 years prior to the Screening 
Visit or has had suicidal ideation in the past 6 months as indicated by a positive response 
(“Yes”) to either Question 4 or Question 5 of the “Screening/Baseline” version of the 
Columbia Suicide Severity Rating Scale (C-SSRS) at Screening. 
Note: 
− In case a study participant responds to Question 9 in Patient Health Questionnaire-9 
(PHQ-9) 
 
 the severity of 
the suicidal ideation needs to be adequately assessed with the C-SSRS rating scale. 
− In case of history of a suicide attempt more than 5 years ago the absence of concurrent 
suicidal ideation and/or severe depression should be confirmed by a mental healthcare 
practitioner before enrolling into the study. 
29a. Study participant has ≥3x the ULN alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), or alkaline phosphatase (ALP), or >ULN bilirubin (≥1.5xULN 
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bilirubin if known Gilbert’s syndrome), except in the case where the abnormal test values 
are ascribed to SLE hepatitis 
− If study participant only has >ULN, but <1.5xULN bilirubin, fractionate bilirubin to 
identify possible undiagnosed Gilbert’s syndrome (ie, direct bilirubin<35%) should be 
assessed, except in the case where the abnormal test values are ascribed hemolytic 
anemia, in the opinion of the Investigator. 
− In case of a suspected SLE hepatitis, eligibility must be discussed with the Medical 
Monitor. 
− If study participant has a result of ALT, AST, or ALP that is >ULN but that does not 
meet the exclusion limit at Screening, a repetition of the lab assessment is recommended 
to judge the dynamic of the increase, but is in the Investigator’s discretion, considering 
the medical history of the participant. In case of a further clinically relevant increase 
(with a value that still doesn’t meet the exclusion limit), inclusion of the study participant 
must be discussed with the Medical Monitor. 
30a. Study participant has chronic kidney failure stage 4, manifested by estimated glomerular 
filtration rate (eGFR) <30mL/min/1.73m2, or serum creatinine >2.5mg/dL, or participant 
has proteinuria >3g/day, or protein:creatinine ratio >340mg/mmol at the Screening Visit. 
31a. Study participant has any significant hematologic abnormalities at the Screening Visit 
(Visit 1) as follows:  
a. 
Hemoglobin <7.0g/dL 
b. 
T-lymphocytes <200/mm3 
c. 
Absolute neutrophil count <500/mm3 
d. 
 T lymphocytes <500/mm3 in combination with neutrophil count <1000/mm3  
e. 
Platelets <25,000/mm3. Study participants with a higher platelet count should also be 
excluded if they have a clinical risk of bleeding for reasons other than SLE. 
Note: Study participants with an isolated laboratory parameter outside of the normal range at the 
Screening Visit may have a repeat test. If the repeat laboratory parameter is within normal range, 
the study participant may be randomized at the Baseline Visit, provided they meet all other 
eligibility criteria. 
5.3 
Lifestyle restrictions 
No restrictions required. 
5.3.1 
Meals and dietary restrictions 
No restrictions required. 
5.3.2 
Caffeine, alcohol, and tobacco 
No restrictions required. 
5.3.3 
Activity 
No restrictions required. 
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5.4 
Screen failures 
Screen failures are defined as participants who consent to participate in the clinical study but are 
not subsequently randomly assigned to study medication. A minimal set of screen failure 
information is required to ensure transparent reporting of screen failure participants to meet the 
Consolidated Standards of Reporting Trials publishing requirements and to respond to queries 
from regulatory authorities. Minimal information includes demography, screen failure details, 
eligibility criteria, and any serious adverse event (SAE). 
Individuals who do not meet the criteria for participation in this study (screen failure) may be 
rescreened once, in this case the study participant will be assigned a new number; information on 
the previous number must be recorded. 
Study participants who require prophylaxis for LTBI must be on treatment for at least 4 weeks 
prior to initiation of IMP. These study participants may be rescreened once they have completed 
the first 4 weeks of prophylaxis treatment after consultation with the Medical Monitor. 
Study participants who initiated treatment for latent TB infection (LTBI) during the Screening 
Period will be screening failures as TB treatment needs to be stable at least 4 weeks prior to first 
DZP dose. In the scope of rescreening the study participant must repeat initial screening 
laboratory parameters (except the interferon-γ release assay [IGRA] TB test), all physical 
examinations, and questionnaires (after completing at least 4 weeks of treatment for LTBI) at the 
rescreening visit prior to randomization in the study and must continue the full course of TB 
prophylactic therapy. 
The Investigator must assess that the study participant’s likelihood of completing the full course 
of TB prophylactic therapy is high and duly record their opinion in the study participant’s record 
prior to randomizing the study participant. 
6 
STUDY TREATMENTS 
Study treatment is defined as any investigational treatment(s), marketed product(s), placebo, or 
medical device(s) intended to be administered to a study participant according to the study 
protocol. 
6.1 
Treatments administered 
Study participants will receive IMP by iv administration as a 2-hour infusion at the first 
administration Visit (V2, Baseline Visit), and then as a 1-hour infusion Q4W thereafter. Study 
participants will be observed for at least 1 hour after dosing for safety surveillance. 
Serious 
 reactions (including 
) and other infusion-related reactions 
have been reported following the initial and subsequent DZP and blinded study medication 
administrations [see IB Section 6.2.2]. Consider premedication by administration of an 
antihistamine, with or without paracetamol, before infusion of study medication, specifically 
before the first infusion and for study participants with a history of these reactions (see also 
Section 8.3.7 and Table 1-2, footnote x). However, available evidence is insufficient to 
determine to what extent premedication diminishes the frequency or severity of 
 
reactions. Study medication must be administered by healthcare providers prepared to manage 
 reactions, including 
, and infusion-related reactions (see Table 1-2, 
footnote x). If a serious infusion-related or 
 reaction (eg, 
) occurs, 
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immediately interrupt the administration of study medication and initiate appropriate therapy. In 
case of a suspected infusion reaction, blood samples should be obtained for a serum tryptase test 
(see Section 10.15.1). 
Body weight will be measured at Screening to determine dosing through Week 20 and will be 
measured again at Week 24 to determine dosing for the rest of the study. (Exceptions: For 
participants screened under the initial protocol [ie, before Amendment 1], dosing through 
Week 20 will be determined using the Baseline body weight.) 
Characteristics of the IMP are provided in Table 6-1. 
Table 6-1: 
Characteristics of IMP 
ARM Name 
DZP 
PBO 
Intervention name 
DZP 
PBO 
Type 
Biologic 
PBO 
Dose formulation 
Lyophilized drug product in vial 
Liquid 
Dosage level(s) 
24 mg/kg 
NA 
Route of 
administration 
iv infusion 
iv infusion 
Infusion duration 
Initial dose: 2 hours 
Follow up doses: 1 hour 
Initial dose: 2 hours 
Follow up doses: 1 hour 
Use 
Experimental 
Placebo comparator 
Sourcing 
Provided centrally by Sponsor 
Provided centrally by Sponsor 
Packaging and labeling 
Packaging will be described in the 
IP Handling Manual 
Labeling will be as per country 
requirements 
Packaging will be described in the 
IP Handling Manual 
Labeling will be as per country 
requirements 
Current/Former 
name(s) or alias(es) 
CDP7657 
NA 
DZP=dapirolizumab pegol; IMP=investigational medicinal product; IP=investigational product; iv=intravenous; 
NA=not applicable; PBO=placebo 
6.2 
Preparation, handling, storage, and accountability requirements 
In order to maintain blinding, an unblinded pharmacist or other suitably qualified site personnel 
will prepare each dose of IMP and provide the blinded and sealed infusion bag to the qualified 
site personnel performing the administration. The used blinded and sealed infusion bag is to be 
returned to the pharmacy or other unblinded designee to confirm the seal is not broken and blind 
is ensured outside the pharmacy. Complete preparation instructions will be outlined in the IP 
Handling Manual. 
The Investigator or designee must confirm appropriate temperature conditions have been 
maintained during transit for all study medication received and any discrepancies are reported 
and resolved before use of the study medication. 
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Only participants randomized in the study may receive study medication and only authorized site 
staff may supply or administer study medication. All study medication must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in accordance 
with the labeled storage conditions with access limited to the Investigator and authorized site 
staff. 
The Investigator, institution, or the head of the medical institution (where applicable) is 
responsible for study treatment accountability, reconciliation, and record maintenance 
(ie, receipt, reconciliation, and final disposition records). 
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IP Handling Manual. 
Further guidance and information for the final disposition of unused study treatment are provided 
in the IP Handling Manual. 
6.2.1 
Drug accountability 
The electronic Case Report Form (eCRF) will be used to record study medication dispensing and 
return information on a by-participant basis. Details of any study medication lost, damaged (due 
to breakage or wastage), not used, partially used, disposed of at the study site, or returned to the 
Sponsor or designee must also be recorded on the appropriate forms. All supplies and pharmacy 
documentation must be made available throughout the study for UCB (or designee) to review. 
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of study medication until returned or destroyed. 
The Investigator may assign some of the Investigator’s duties for drug accountability at the study 
site to an appropriate pharmacist/designee. 
The Investigator must ensure that the study medication is used only in accordance with the 
protocol. 
Periodically, and/or after completion of the clinical phase of the study, all used (including empty 
containers)/partially used, unused, damaged, and/or expired study medication must be reconciled 
and either destroyed at the site according to local laws, regulations, and UCB standard operating 
procedures or returned to UCB (or designee). Investigational medicinal product intended for the 
study cannot be used for any other purpose than that described in this protocol. 
6.3 
Measures to minimize bias: randomization and blinding 
All participants will be centrally assigned to randomized study medication using an Interactive 
Web Response System (IWRS). Before the study is initiated, the log in information and 
directions for the IWRS will be provided to each site. 
The IWRS will assign eligible participants to a treatment regimen based on a predetermined 
production randomization and/or packaging schedule provided by UCB (or designee). The 
randomization schedule will be produced by the IWRS vendor. The IWRS will generate 
individual assignments for participant kits of IMP, as appropriate, according to the visit schedule. 
Participants’ treatment assignment will be stratified by Pooled Region (North America vs 
Western Europe/Asia-Pacific vs Latin America/Eastern Europe), Screening disease activity 
(chronic active vs acute flaring) and Screening SLEDAI score (<10 vs ≥10), to ensure balanced 
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treatment allocation across the 12 subgroups. Each site enrollment of study participants will be 
limited to 5% of the total study population. 
At Screening, each candidate participant will be assigned a 5-digit number that serves as the 
participant identifier throughout the study. The participant number will be required in all 
communication between the Investigator or designee and the IWRS regarding a particular 
participant. 
Eligible participants will be randomized to treatment groups at the Baseline Visit (Day 1). The 
IWRS will allocate kit numbers to the participant based on the participant number during the 
course of the study. Participant numbers and kit numbers will be tracked via the IWRS. 
Study medication will be dispensed at the study visits summarized in Schedule of Activities 
(Section 1.3). 
To minimize bias, the same Investigator should perform the key efficacy assessments BILAG 
2004 and SLEDAI-2K whenever possible and this will be documented in the database. 
6.3.1 
Procedures for maintaining and breaking the treatment blind 
6.3.1.1 
Maintenance of study treatment blind 
All study participant treatment details will be allocated and maintained by the IWRS. 
The following individuals will receive the randomization code at the start of the study: 
• Sponsor and designated contract research organization (CRO) bioanalytical staff analyzing 
pharmacokinetic (PK) and ADA samples. 
• Sponsor clinical trial supply staff 
• IWRS provider 
Study site pharmacists or other suitably qualified site personnel who are responsible for 
preparation of IMP treatments and any necessary assistants will have access to treatment 
allocations for individual study participants via the IWRS. The unblinded pharmacy monitors 
from the CRO, the Clinical Supply Manager, and the unblinded Clinical Project Manager (CPM) 
(or designee) will also have access to the treatment allocations and to the drug accountability 
records, if applicable. 
The following individuals may have access to the randomization code as indicated: 
• Sponsor Drug Safety staff as needed for reporting SAEs to regulatory authorities. 
• On request, members of the IDMC (Section 9.7) who participate in unblinded (closed) 
sessions will be given information about the IMP allocation for those study participants for 
whom data are provided at these sessions. 
• Sponsor and/or CRO staff supporting preparation of the initial biomarker analysis. 
• Sponsor and/or CRO staff supporting preparation of the data outputs for the IDMC review. 
• A Quantitative Clinical Pharmacologist/Modeling & Simulation Scientist may have access to 
the randomization code if PK data are requested for review by the IDMC. 
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Beside the exception of emergency unblinding of individual participants as described in 
Section 6.3.1.2, the following individuals will be unblinded to the treatment assignment. All 
other study personnel will remain blinded to the treatment assignment until the end of the study. 
Key unblinded study personnel include: 
• Study site pharmacists or other qualified site personnel who are responsible for the 
preparation and handling of IMP treatments 
• Unblinded pharmacy monitors from the CRO 
• Clinical Supply Manager 
• Unblinded CPM 
• Members of the IDMC who participate in unblinded sessions, and statistical team members 
who provide unblinded outputs (and are not involved in the study in any other way) 
• A Quantitative Clinical Pharmacologist/Modeling & Simulation Scientist (separate from 
study team) 
• Laboratory staff analyzing blood samples for 
 
and ADA 
• Sponsor pharmacovigilance staff reporting SUSARs to regulatory authorities 
Should other study with DZP be performed at the same site, all efforts will be made to maintain 
the blinding at the site level as defined in this protocol as long as the study will be performed. 
Under normal circumstances, the blinded treatment must not be revealed. It will be possible to 
break the blind, if medically indicated (Section 6.3.1.2). The impact on study conduct of this 
should be discussed in advance with the Medical Monitor or the Sponsor’s Study Physician 
whenever possible. 
6.3.1.2 
Breaking the treatment blind in an emergency situation 
If a situation arises in which it is medically indicated to determine the treatment (ie, knowledge 
of the nature and/or dose of the applied study medication determines decisions on further 
diagnostic procedures or treatment), it will be possible to determine to which treatment arm the 
study participant has been allocated during the Double-Blind Treatment Period by contacting the 
IWRS. All sites will be provided with details of how to contact the system for code breaking at 
the start of the study. Unblinding can be initiated by the Investigator at any time as medically 
indicated; however, whenever possible, the Medical Monitor or the Sponsor’s Study Physician 
should be consulted prior to unblinding to discuss the impact on the study conduct.  
The study team will be informed immediately via the IWRS when a code is broken, but will 
remain blinded to specific treatment information. Any unblinding of the IMP performed by the 
Investigator must be recorded in the source documents and on the Study Termination eCRF 
page. 
6.4 
Treatment compliance 
The IMP will be administered by designated study site staff. The unblinded monitor will review 
the pharmacy records at each site, including the Drug Dispensing Record Form. The unblinded 
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monitor will compare the dispensing record and vials to the individual study participant’s 
identifiers and visit schedule to assure that the study participant received the correct treatment 
and dose, and that the dosing schedule is correct. The unblinded monitor’s report will include 
details of any missed doses, errors in dose, treatment errors or schedule errors, and reasons for 
these. All supplies and pharmacy documentation must be made available throughout the study 
for the unblinded monitor to review. 
Study participants are expected to receive all doses of IMP as detailed in the schedule of 
assessments. Any study participants who deviate from the dosing schedule or miss any scheduled 
treatment should be reported to the Medical Monitor as soon as possible for determination of 
possible schedule adjustments and continued eligibility; these study participants should return to 
their original visit schedule. These instances will be handled on a case-by-case basis. 
6.5 
Concomitant medication(s)/treatment(s) 
6.5.1 
Permitted concomitant treatments (medications and therapies) 
6.5.1.1 
Corticosteroids 
Corticosteroids are permitted during the study at any dose in the sense of escape medication, if 
medically indicated (see Section 6.6.2). At the screening visit (V1) corticosteroid dose must not 
exceed 40mg/day prednisone equivalent and must be stable for 2 weeks prior to Screening 
(approximately 4 weeks prior to Baseline Visit). Further, the dose must remain stable during 
Screening Period and should be kept stable onwards, if possible, or tapered. In case of a high 
corticosteroid dose (>20mg/day) an early start of tapering should be considered depending on the 
individual patient’s condition. If the corticosteroid dose exceeds 7.5mg/day prednisone 
equivalent, it should be tapered in line with international treatment guidance as soon as possible, 
but must be initiated at the latest at Week 8 (V4). The timepoint and speed of tapering should be 
adapted to the individual study participant’s condition (see below). Steroid doses should be 
converted to prednisone equivalent doses prior to the assessment of study participant inclusion 
criteria and initiation of corticosteroid tapering (regardless of route, except for intraocular, nasal, 
and topical). The list of corticosteroids and their corresponding prednisone equivalent doses can 
be found in Table 6-2. 
Table 6-2: 
Prednisone equivalent doses of systemic corticosteroids 
Corticosteroids 
Prednisone equivalent dose to 1mg of the listed corticosteroid dose 
Cortisone 
0.2mg 
Hydrocortisone 
0.25mg 
Deflazacort 
0.75mg 
Prednisolone 
1mg 
Prednisone 
1mg  
Methylprednisolone 
1.25mg 
Triamcinolone 
1.25mg 
Dexamethasone 
6.7mg 
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Table 6-2: 
Prednisone equivalent doses of systemic corticosteroids 
Betamethasone 
8.3mg 
To determine the prednisone equivalent dose of the corticosteroids shown on the left, multiply 
the mg dose of corticosteroid on the left by the dose amount in the corresponding right hand 
column. For example, a 0.8mg dose of methylprednisolone is equivalent to 1mg (0.8mg × 1.25) 
of prednisone. 
The dose of a specified corticosteroid that is equivalent to 1mg prednisone is given in Table 6-3. 
Table 6-3: 
Corticosteroid dose equivalent to 1mg prednisone 
Corticosteroids 
Corticosteroid dose equivalent to 1mg prednisone 
Cortisone 
5mg 
Hydrocortisone 
4mg 
Deflazacort 
1.3mg 
Prednisolone 
1mg 
Prednisone 
1mg  
Methylprednisolone 
0.8mg 
Triamcinolone 
0.8mg 
Dexamethasone 
0.15mg 
Betamethasone 
0.12mg 
A pulse dose (>500mg x 1 to 3 days) of iv corticosteroids should not have been given within the 
4 weeks before screening. 
Study participants not receiving concomitant corticosteroids or who were previously receiving 
corticosteroids on an as-needed basis must have stopped the treatment or been assigned to a 
continuous corticosteroid dose at least 2 weeks prior to Screening (Visit 1). 
In study participants receiving concomitant corticosteroid doses >7.5mg/day prednisone or 
equivalent, a mandatory corticosteroid taper must be initiated as early as possible but no later 
than 8 weeks after the first study medication infusion (Day 56). The tapering regimen will aim to 
reduce the daily prednisone equivalent dose to 7.5mg/day or lower by Week 18. 
If such a rapid tapering is not considered by the Investigator to be appropriate for the individual 
study participant, a slower tapering regimen can be used. 
Study participants achieving a dose of 7.5mg/day or lower may remain on this dose or continue 
to taper at the discretion of the Investigator. It is recommended to reduce the dose further in a 
slow manner. 
Study participants whose disease is worsening after initiation of tapering and therefore cannot 
fulfill the taper based on the Investigator’s judgment or whose corticosteroid dose has to be 
increased, if indicated, should remain in the study and receive corticosteroids at an appropriate 
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dose as determined by the Investigator. Study participants will be considered nonresponders for 
the primary endpoint in case of the intercurrent event escape treatment intervention with 
corticosteroids as outlined in Section 8.1.3.1. 
Study participants will be issued a daily diary in which to record corticosteroid doses taken on a 
daily basis at home in between visits. Investigators are advised to contact the Medical Monitor or 
Sponsor's Study Physician upfront, if possible, to discuss the potential impact on the further 
study conduct in case use of oral or parenteral steroids for non-SLE related conditions is needed. 
In case the corticosteroid dose at screening visit (V1) is not shown in the recommended tapering 
regimen table (Table 6-4), the tapering regimen of the next higher dose in the table should be 
used. Reduction of corticosteroids between Weeks 44 and 48 should be avoided. 
 
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Table 6-4: 
Recommended corticosteroid tapering schedule 
Week 
Day 
Corticosteroid dosea (mg/day; prednisone equivalent) 
Starting 
Dose 
 
40 a 
35 a 
30 a 
25 a 
20 a 
15 a 
10 a 
7.5 b 
5 b 
2.5 b 
0 
1 
Day 1 to 
Day 7 
30 
30 
30 
25 
20 
15 
10 
7.5 
5 
2.5 
0 
2 
Day 8 to 
Day 14 
30 
20 
30 
25 
20 
15 
10 
7.5 
5 
2.5 
0 
3 
Day 15 to 
Day 21 
20 
20 
20 
20 
20 
15 
10 
7.5 
5 
2.5 
0 
4 
Day 22 to 
Day 28 
20 
15 
20 
20 
20 
15 
10 
7.5 
5 
2.5 
0 
5 
Day 29 to 
Day 35 
15 
15 
15 
15 
15 
10 
10/7.5 b,c 
7.5b 
5b 
NAb 
NAb 
6 
Day 36 to 
Day 42 
15 
10 
15 
15 
15 
10 
10/7.5 b,c 
7.5b 
5b 
NAb 
NAb 
7 
Day 43 to 
Day 49 
10 
10 
10 
10 
10 
10b 
10/7.5 b,c 
7.5/5b,c 
5b 
NAb 
NAb 
8 
Day 50 to 
Day 56 
10 
10 
10 
10 
10 
10b 
10/7.5 b,c 
7.5/5b,c 
5b 
NAb 
NAb 
9 
Day 57 to 
Day 63 
10 
10/7.5b,c 
10 
10 
10 
10/7.5b,c 
7.5b 
7.5/5b,c 
5b 
NAb 
NAb 
10 
Day 64 to 
Day 70 
10/7.5b,c 
10/7.5b,c 
10/7.5b,c 
10/7.5b,c 
10/7.5b,c 
10/7.5b,c 
7.5b 
7.5/5b,c 
5b 
NAb 
NAb 
11 
Day 71 to 
Day 77 
10/7.5b,c 
10/7.5b,c 
10/7.5b,c 
10/7.5b,c 
10/7.5b,c 
10/7.5b,c 
7.5b 
7.5/5b,c 
5b 
NAb 
NAb 
12 
Day 78 to 
Day 84 
10/7.5b,c 
10/7.5b,c 
10/7.5 b,c 
10/7.5b,c 
10/7.5b,c 
10/7.5b,c 
7.5b 
7.5/5b,c 
5b 
NAb 
NAb 
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Table 6-4: 
Recommended corticosteroid tapering schedule 
Week 
Day 
Corticosteroid dosea (mg/day; prednisone equivalent) 
13 
Day 85 to 
Day 91 
10/7.5b,c 
7.5b 
10/7.5 b,c 
10/7.5b,c 
10/7.5b,c 
7.5b 
7.5/5b,c 
5b 
5b 
NAb 
NAb 
14 
Day 92 to 
Day 98 
7.5b 
7.5b 
7.5b 
7.5b 
7.5b 
7.5b 
7.5/5b,c 
5b 
5b 
NAb 
NAb 
15 
Day 99 to 
Day 105 
7.5b 
7.5b 
7.5b 
7.5b 
7.5b 
7.5b 
7.5/5b,c 
5b 
5b 
NAb 
NAb 
16 
Day 106 
to 
Day 112 
7.5b 
7.5b 
7.5b 
7.5b 
7.5b 
7.5b 
7.5/5b,c 
5b 
5b 
NAb 
NAb 
17 
Day 113 
to 
Day 119 
7.5b 
7.5/5b,c 
7.5b 
7.5b 
7.5b 
7.5/5b,c 
7.5/5b,c 
5b 
5b 
NAb 
NAb 
18 
Day 120 
to 
Day 126 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
5b 
5b 
NAb 
NAb 
19 
Day 127 
to 
Day 133 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
5b 
5b 
5b 
NAb 
NAb 
20 
Day 134 
to 
Day 140 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
5b 
5b 
5b 
NAb 
NAb 
21 
Day 141 
to 
Day 147 
7.5/5b,c 
5b 
7.5/5b,c 
7.5/5b,c 
7.5/5b,c 
5b 
5b 
5b 
5b 
NAb 
NAb 
22 
Day 148 
to 
Day 154 
5b 
5b 
5b 
5b 
5b 
5b 
5b 
5b 
5b 
NAb 
NAb 
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Table 6-4: 
Recommended corticosteroid tapering schedule 
Week 
Day 
Corticosteroid dosea (mg/day; prednisone equivalent) 
23 
Day 155 
to 
Day 161 
5b 
5b 
5b 
5b 
5b 
5b 
5b 
5b 
5b 
NAb 
NAb 
24 
Day 162 
to 
Day 168 
5b 
5b 
5b 
5b 
5b 
5b 
5b 
5b 
5b 
NAb 
NAb 
 
NA=not applicable 
a Corticosteroid tapering is only required in those study participants receiving continuous corticosteroids at doses >7.5/day prednisone equivalent at the time of 
enrollment into the study. 
b Study participants starting at or achieving a dose of 7.5mg/day or lower may remain on this dose or taper at the discretion of the Investigator. This is indicated 
by cells with light grey font. 
c Alternating dosing every other day recommended to allow slow reduction based on standard tablet sizes 
 
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6.5.1.2 
Antimalarials 
Antimalarials (eg, hydroxychloroquine, chloroquine, and quinacrine) are permitted during the 
study (see inclusion criteria and maximum dose restrictions in Table 6-5). 
Treatment with antimalarials must have been started or stopped at least 12 weeks prior to 
screening visit (V1). In study participants receiving concomitant antimalarials used for the 
treatment of SLE, doses must have been stable for at least 8 weeks prior to screening visit (V1) 
and should be kept stable through the study. Increases in doses of antimalarials are not permitted 
during the study, unless absolutely clinically indicated (dose reductions are allowed, if medically 
indicated [eg, due to toxicity], per the Investigator’s discretion). Investigators are advised to 
contact the Medical Monitor or Sponsor's Study Physician, upfront if possible, to discuss the 
potential impact on the further study conduct in case a dose change is needed. 
Table 6-5: 
Maximum doses of permitted concomitant antimalarials 
Antimalarial (generic name) 
Maximum dose allowed 
Hydroxychloroquine 
400mg/day 
Chloroquine 
500mg/day 
Quinacrine 
200mg/day 
Quinine 
Any dose allowed 
Antimalarial blood levels will be measured at Screening and at selected visits during the study to 
serve as source for drug intake adherence in order to verify the documented dose of 
antimalarials. 
If blood levels are inconsistent with the dose taken as reported by the participant this must be 
discussed with the participant and documentation of concomitant antimalarials must be adapted 
accordingly. In this case eligibility of the study participant must be reevaluated with respect to if 
the study participant indeed took a stable antimalarial dose as described in inclusion criterion 
2.e3. If the dose is not considered as stable in the past 8 weeks prior to screening the study 
participant is not eligible at this time point. 
In case a participant reports based on the conversation about antimalarial blood levels to have 
stopped or reduced intake of antimalarials due to intolerance more than 12 weeks before 
Screening, the actual intake needs to be documented appropriately. Based on the adequately 
documented concomitant medications it must be evaluated if the participant fulfills the inclusion 
criterion 2.e3. and no exclusion criterion before randomization. In case the participant is eligible 
they should be clearly instructed not to restart or increase antimalarial intake in this case. 
Investigators are advised to contact the Medical Monitor or Sponsor's Study Physician upfront, if 
possible, to discuss the potential impact on the further study conduct in case a dose change is 
needed. 
In case blood levels suggest a change in intake during the study, which was not reported by the 
participant, this should be discussed with the participant and the true intake should be 
documented on the concomitant medication page. 
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6.5.1.3 
Other immunosuppressants/immunomodulatory agents 
Other immunosuppressant or immunomodulatory agents are permitted during the study (see 
inclusion criteria and maximum dose restrictions in Table 6-6). 
In study participants receiving concomitant immunosuppressants for the treatment of SLE, doses 
must have been stable for at least 12 weeks prior to the screening visit (V1) and should be kept 
stable through the study. If immunosuppressants permitted during the study were stopped before 
study entry, they must have been stopped no later than 8 weeks prior to the Screening Visit. 
Increases in doses of immunosuppressant or immunomodulatory agents are not permitted during 
the study, unless absolutely clinically indicated, per the Investigator’s discretion but should not 
occur between Week 44 and Week 48. A temporary hold or dose reduction is allowed if 
medically indicated (eg, due to vaccination [ACR 2021] or due to toxicity), per the Investigator’s 
discretion. Investigators are advised to contact the Medical Monitor or Sponsor's Study 
Physician, upfront, if possible, to discuss the potential impact on the further study conduct in 
case a dose change is needed. 
Table 6-6: 
Maximum doses of permitted concomitant immunosuppressants 
Immunosuppressant (generic name) 
Maximum dose allowed 
Azathioprine 
300mg/day oral 
Mycophenolate mofetil (including mycophenolate mofetil hydrochloride) 
3000mg/day oral 
Coated mycophenolate sodium 
2200mg/day 
Leflunomide 
40mg/day oral 
Methotrexate 
25mg/week any route 
Cyclosporine 
4mg/kg/day 
Voclosporin 
47.4mg/day 
Tacrolimus 
3mg/day 
Caution should be exercised in the co-administration of calcineurin inhibitors (cyclosporine and 
voclosporin) and the study drug. Local guidance(s) should be followed regarding monitoring of 
plasma levels when calcineurin inhibitors are administered. Additionally, when calcineurin 
inhibitors are administered concomitantly with DZP, special benefit-risk considerations and 
enhanced monitoring for infections are advised since the potential for synergistic 
immunomodulatory effects on T-cells (affecting both efficacy and safety) cannot be excluded. 
Please refer to Section 7.1.3 regarding recommended temporary discontinuation of study drug in 
case of infection. 
It cannot be excluded that mycophenolate mofetil (MMF) could reduce effectiveness of 
combined hormonal contraceptives including levonorgestrel. Investigators are advised to 
regularly counsel patients who are of childbearing potential on the risk of MMF treatment for 
adverse pregnancy outcomes and the possibility of reduced effectiveness of hormonal 
contraceptives due to interaction with MMF. Please refer to Section 10.4 for further information. 
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6.5.1.4 
Analgesics, medications including natural or synthetic cannabinoids 
(approved in line with local regulations), NSAIDs, HMG-CoA 
reductase inhibitors (statins), ACE inhibitors, and other 
anti-hypertensive drugs. 
Study participants should stay on stable doses of the following other concomitant medications 
for the treatment of SLE during the study including the Screening Period, unless changes in these 
treatments are clinically indicated: analgesics, NSAIDs, medications including natural or 
synthetic cannabinoids (approved in line with local regulations), HMG-CoA reductase inhibitors 
(statins), ACE inhibitors, and other anti-hypertensive drugs. 
6.6 
Dose modification 
Not applicable for the IMP. 
6.6.1 
Prohibited concomitant treatments (medications and therapies) 
The following concomitant medications will be prohibited at screening visit (V1) and as 
concomitant medication to the IMP during the study (Table 6-7) with the exception of 
immunoglobulins which are allowed to be used concomitantly with DZP after randomization if 
medically indicated. In case one of these medications has to be initiated during the study the IMP 
needs to be permanently discontinued (with the exception of immunoglobulins).  
The impact of initiation of prohibited medications on the study conduct should be discussed 
upfront, if possible, with the Medical Monitor and/or Sponsor’s Study Physician. 
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Table 6-7: 
Prohibited medications and required wash-out periods prior to 
Screening (Visit 1) 
Generic  
(trade) names 
Wash-out period  
prior to Screeninga 
Generic  
(trade) names 
Wash-out period  
prior to Screening 
Biologics (mAbs and Fusion Proteins) 
Immunosuppressants 
Abatacept (CTLA4-Ig) 
(Orencia®) 
High-dose 
cyclophosphamide 
(Cytoxan®) 
Belimumab (Benlysta™) 
(iv and sc) 
Pimecrolimus 
(Elidel®) 
Blisibimod 
Sirolimus 
(Rapamune®) 
Eculizumab (Soliris®) 
--- 
ETI–201 (Elusys 
Heteropolymer Product) 
Others 
Rituximab (Rituxan®), 
Ofatumumab (Arzerra®), 
Obinutuzimab 
(Gazyva®), Ocrelizumab, 
Veltuzumab 
Intravenous 
immunoglobulin 
Rigerimod 
(Lupuzor™) 
Minocycline 
Natalizumab (Tysabri®) 
Thalidomide or 
lenalidomide 
(Thalomid®, 
Revlimid®) 
Vedolizumab (Entyvio®) 
Tabalumab 
JAK inhibitors 
(eg, Baricitinib) 
TACI-Ig (atacicept) 
TYK 2 Inhibitors (eg, 
BMS-986165) 
Tocilizumab (Actemra®, 
MRA) 
BIIB059 (anti-BDCA2) 
IFN kinoid 
Anifrolumab 
 
 
Sifalimumab (MEDI 
545) 
Ustekinumab (Stelara) 
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Table 6-7: 
Prohibited medications and required wash-out periods prior to 
Screening (Visit 1) 
Generic  
(trade) names 
Wash-out period  
prior to Screeninga 
Generic  
(trade) names 
Wash-out period  
prior to Screening 
Any other investigational 
drug or off-label drug 
used to treat SLE, 
cutaneous Lupus or 
 but not 
mentioned in this table 
Contact Medical 
Monitor before 
using 
 
 
a The wash-out period refers to the last administration of the relevant medication. 
BDACA2=blood dendritic cell antigen 2; IFN=interferon; JAK=Janus kinase; mAbs=monoclonal antibodies; 
MRA=myeloma receptor antibody; SLE=systemic lupus erythematosus; TYK 2=tyrosine kinase 2 
Note: Topical formulations (eg, eye drops) are permitted without wash-out, unless otherwise indicated. 
Vaccines 
Administration of live vaccines should not occur during the conduct of the study. If a study 
participant receives a live vaccine, temporary or permanent discontinuation of study medication 
may be needed. In case of considered application of live vaccines the Medical Monitor and/or 
Sponsor’s Study Physician should be contacted to discuss the impact on further study conduct.  
Administration of non-live vaccines is allowed during the study at the discretion of the 
Investigator and should be documented. Local and international guidance on vaccination in 
immunocompromised patients (Furer et al, 2020; Van Assen et al, 2011; Murdaca et al 2016; 
Mason et al, 2021, ACR 2021, Geisen et al, 2021) should be considered.  
According to local and international guidance approved SARS-CoV-2 vaccines are endorsed to 
be used in patients receiving immunosuppressant treatment (ACR 2021; EULAR 2021).  
It cannot be excluded that the effectiveness of some vaccines may be compromised by DZP or 
any other concomitant immunosuppressant drug as part of standard of care. Therefore, blood 
samples will be collected to be able to determine the effect of DZP on the immune response to 
vaccines, eg, 
 as indicated. 
The potential benefits and risks and vaccine administration options should be discussed with the 
study participant.  
In case of administration of investigational Coronavirus Disease 2019 (COVID-19) vaccine 
(vaccines without regulatory authorization or emergency authorization) study medication should 
not be administered within 2 weeks after vaccination. 
6.6.2 
Escape medication 
Although the use of escape medications is allowed at any time of the study, it should be delayed, 
if possible, for at least 8 weeks following the first administration of study treatment. Data from 
Phase 1 and Phase 2 studies suggest that DZP has a fast onset of action however it can take 
several weeks until the potential therapeutic effect of DZP fully develops. Escape treatment 
should be initiated as clinically indicated by the Investigator or other qualified physicians 
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treating the participant. Investigators should discuss the impact of escape treatment use on study 
conduct with the Medical Monitor before initiation.  
Initiation of escape treatment may be handled as intercurrent event in estimands, which will be 
detailed in the statistical analysis plan (SAP) as described in Section 9.3.1. For the primary 
endpoint, specification of how escape treatment will be handled as an intercurrent event is 
detailed in Section 8.1.3.1, Section 9.3.1, and Section 9.6. 
The date and time of escape medication administration as well as the name and dosage regimen 
of the escape medication must be recorded. 
In case of use of escape treatment the study medication does not have to be automatically 
discontinued, however if the escape treatment in combination with DZP represents a safety 
concern (see Section 6.6) for the study participant the study medication should be discontinued 
but the study participant should remain in the study under observation. Investigators are advised 
to contact the Medical Monitor upfront if possible, to discuss the potential impact on the further 
study conduct in case study medications should be permanently discontinued. 
The following escape medications may be used as indicated: 
• Corticosteroids (new initiation or increase in dose) 
• Immunosuppressants (new initiation or increase in dose): 
− azathioprine 
− methotrexate 
− mycophenolate mofetil 
− tacrolimus 
− low dose cyclophosphamide 
− cyclosporine 
− voclosporin 
6.7 
Criteria for study hold or dosing stoppage 
UCB will hold further dosing if the following criteria are met during the course of the study and 
following case review to confirm causality and seriousness and/or severity of reported events: 
• If regulators request a study hold. 
If the IDMC recommends a study hold, UCB will consider the study hold as outlined in the 
IDMC charter. 
6.8 
Treatment after the end of the study 
Study participants who complete the 48-week Treatment Period may be eligible to participate in 
an OLE study. 
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7 
DISCONTINUATION OF STUDY MEDICATION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of study medication 
Study participants who discontinue study medication will be encouraged to stay in the study 
under observation. They should continue to be followed for all regularly scheduled visits for 
safety and efficacy assessments. 
7.1.1 
Liver chemistry stopping criteria 
Discontinuation of study treatment for abnormal liver function should be considered by the 
Investigator when a participant meets one of the conditions outlined in Figure 7-1 or if the 
Investigator believes that it is in best interest of the participant. 
Figure 7-1: Phase 3-4 Liver Chemistry Stopping Criteria and Increased 
Monitoring Algorithm 
 
 
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; INR=international normalized 
ratio; SAE=serious adverse event; ULN=upper limit of normal. 
Specific assessments and follow up actions for potential drug-induced liver injury are provided 
in Section 10.6. 
7.1.2 
QTc stopping criteria 
If a clinically significant finding is identified (including, but not limited to changes from 
Baseline in QT interval corrected using Fridericia’s formula [QTcF]) after enrollment, the 
Investigator or qualified designee will determine if the participant can continue in the study and 
if any change in participant management is needed. This review of the electrocardiogram (ECG) 
Continue Study Treatment 
Discontinue Study Treatment 
Plus 
Bilirubin≥2x
ULN (>35% 
direct) or plus
INR>1.5, if 
measured*
Possible  
Hy’s Law
ALT≥3xULN
ALT
≥8xULN
Plus
Symptoms of 
liver injury
or 
No
Yes
Yes
Yes
No
No
No
See algorithm 
for continued 
therapy with 
increased liver 
chemistry 
monitoring
Yes
ALT 
≥3xULN 
but 
<8xULN
Yes
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printed at the time of collection must be documented. Any new clinically relevant finding should 
be reported as an AE. 
A participant who develops an ECG finding which meets the bulleted criterion based on the ECG 
readings after first study drug application will be withdrawn from study medication. 
• QTcF >500 msec OR Uncorrected QT >600 msec 
For participants with underlying bundle branch block, follow the discontinuation criteria listed 
below: 
Baseline QTcF with Bundle Branch Block 
Discontinuation QTcF Threshold with Bundle 
Branch Block 
< 450 msec 
> 500 msec 
450 to 480 msec 
≥ 530 msec 
See the Schedule of Activities (Section 1.3) for data to be collected at the time of treatment 
discontinuation and follow-up and for any further evaluations that need to be completed. 
7.1.3 
Permanent and temporary study drug discontinuation due to other 
reasons 
Study participants must be permanently discontinued from study medication (but not necessarily 
from the study) if any of the following occurs: 
1. Study participant experiences a thromboembolic event. 
2. Study participant requires an induction therapy with cyclophosphamide for management of 
acute flare of 
 or other severe manifestation of SLE, in the opinion of the 
Investigator. 
3. Study participant requires an induction of therapy with an approved biological immune 
response modifier or an investigational drug (see Section 6.6). 
4. Potential drug-induced liver injury (pDILI) and related to study medication in the opinion of 
the Investigator, regulators, or the Sponsor. Discontinuation of study treatment for abnormal 
liver function should be considered by the Investigator when a participant meets one of the 
conditions outlined in Figure 7-1 or if the Investigator believes that it is in best interest of the 
participant. 
5. Study participant has an anaphylactic reaction related to study medication (fulfilling 
Sampson criteria as described in Section 10.14). 
6. Study participant develops an active TB or NTM (see Section 8.2.6.3). 
Study participants may be temporarily discontinued from study medication (but not necessarily 
from the study) if any of the following occurs, but may be restarted. Consultation with the 
Medical Monitor is advised before restart: 
1. Study medication will be stopped if the study participant develops a medical condition (or 
laboratory abnormality or ECG change) that, in the opinion of the Investigator, compromises 
the study participant’s ability to proceed with study medication or compromises the study 
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participant’s safety. This includes clinically significant infections such as SARs-Cov-2 (see 
Section 8.2.7) and tuberculosis (Section 8.2.6.3). Caution should be taken to exclude a 
clinically significant infection in case of symptoms (see Section 8.3). Study participants must 
be closely followed up. In case of resolution of the event leading to interruption, study 
medication can be restarted after consultation with the Medical Monitor unless the event 
fulfils the criteria for permanent study drug discontinuation. In case of upcoming surgery, the 
time between the last infusion of study medication administered to the participant and the 
surgery should be at least 4 weeks (if possible 6 weeks). After surgery, study medication can 
be restarted once the proliferative phase of wound healing is completed. 
2. If there is a positive pregnancy test, study medication will be held. If there is confirmed 
pregnancy, study medication must be discontinued until end of the pregnancy. In case the 
participant intends to breastfeed after a pregnancy, study medication must be further 
discontinued until end of breastfeeding (including pumping breast milk to feed to a child). 
3. In case a study participant answers Question 9 of the PHQ-9 with 
 
  and active suicidal ideation is confirmed as indicated by a 
positive response (“Yes”) to Question 4 or 5 of the C-SSRS study medication application 
must be discontinued and study participant must be referred immediately to a mental health 
care professional for further clarification. Permanent study medication discontinuation should 
be considered based upon the Investigator’s judgment of benefit/risk. Consultation with the 
Medical Monitor and/or the Sponsor Study Physician is advised upfront to restart. 
In addition, a participant may discontinue study medication administration at any time at the 
discretion of the Investigator for safety, behavioral, compliance, or administrative reasons. 
However, the participant should be encouraged to stay in the study under observation, continuing 
to be followed for all regularly scheduled safety and efficacy assessments. 
Investigators are advised to contact the Medical Monitor, whenever possible in advance, to 
discuss the potential impact on the further study conduct in case of study drug discontinuation. 
7.2 
Participant discontinuation/withdrawal from the study 
Participants are free to withdraw at her/his own request from the study at any time, without 
prejudice to their continued care. 
If the participant withdraws consent for disclosure of future information, the Sponsor may retain 
and continue to use any data collected before such a withdrawal of consent. 
If a participant withdraws from the study, he/she may request destruction of any samples taken 
and not tested, and the Investigator must document this in the site study records. 
See the Schedule of Activities (Section 1.3) for data to be collected at the time of study 
discontinuation and follow-up and for any further evaluations that need to be completed. 
Participants should be withdrawn from the study if any of the following events occur: 
1. Participant withdraws his/her consent. 
2. The IDMC, the responsible IRB/IEC, or a regulatory agency requests withdrawal of the 
participant for safety, behavioral, compliance, or administrative reasons. 
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Investigators should contact the Medical Monitor, whenever possible, to discuss the withdrawal 
of a participant in advance. 
7.3 
Lost to follow up 
A participant will be considered lost to follow-up if she/he repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study site. 
The following actions must be taken if a participant fails to return to the clinic for a required 
study visit: 
• The site 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 whether or not the participant wishes to and/or should continue in the 
study. 
• Before a participant is deemed lost to follow up, the Investigator or designee must make 
every effort to regain contact with the participant (at least 1 phone call and 1 written message 
to the participant), and document his/her effort (date and summary of the phone call and copy 
of the written message in the source documents), to complete the final evaluation. All results 
of these evaluations and observations, together with a narrative description of the reason(s) 
for removing the participant, must be recorded in the source documents. The eCRF must 
document the primary reason for withdrawal. 
Should the participant continue to be unreachable, he/she will be considered to have withdrawn 
from the study with a primary reason of lost to follow-up documented in the eCRF. 
8 
STUDY ASSESSMENTS AND PROCEDURES 
Study procedures and their timing are summarized in the Schedule of Activities (Table 1-2). 
Protocol waivers or exemptions are not allowed. 
Immediate safety concerns should be discussed with the Medical Monitor or the Sponsor Study 
Physician immediately upon occurrence or awareness to determine if the participant should 
continue or discontinue study treatment. 
Adherence to the study design requirements, including those specified in the Schedule of 
Activities, is essential and required for study conduct. 
All screening evaluations must be completed and reviewed to confirm that potential participants 
meet all eligibility criteria. The Investigator will maintain a screening log to record details of all 
participants screened and to confirm eligibility or record reasons for screening failure, as 
applicable. 
Procedures conducted as part of the participant’s routine clinical management (eg, blood count) 
and obtained before signing of the ICF may be utilized for screening or baseline purposes 
provided the procedures met the protocol-specified criteria and were performed within the time 
frame defined in the Schedule of Activities. 
The amount of blood collected from each participant over the duration of the study will be 
approximately 900mL. Additional extra assessments that may be required for re-screening, 
technical issues with the collected samples or safety evaluations may result in additional blood 
volume to be collected. 
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8.1 
Efficacy assessments 
8.1.1 
Clinical assessments of disease activity 
8.1.1.1 
BILAG 2004 
The BILAG 2004 will be used as a clinical assessment of SLE disease activity 
(Tsokos et al, 2007). 
The Investigators will perform an anamnesis and physical examination at every visit and will 
record present symptoms corresponding to the BILAG 2004 components in the electronic 
clinical outcomes assessment (eCOA). Clinical features attributable to SLE are to be recorded 
and based on the study participant’s condition in the last 4 weeks compared with the previous 
4 weeks. For vital signs and laboratory parameters, Investigators must indicate whether or not 
values are outside the normal range and, if outside the normal range, whether or not they are due 
to SLE. 
Nine body/organ-based systems will be assessed if SLE symptoms are present: 
• Constitutional (fatigue, fever, anorexia, weight loss, etc) 
• Mucocutaneous (rash, alopecia, mucosal ulcers, etc) 
• Neuropsychiatric (headache, seizure, psychosis, etc)  
• Musculoskeletal 
 etc) 
• Cardiorespiratory (coronary vasculitis, cardiac failure, effusion, etc) 
• Gastrointestinal (lupus enteritis, hepatitis, peritonitis, etc) 
• Ophthalmic (keratitis, scleritis, optic neuritis, etc) 
• Renal (proteinuria, urine microscopy for red blood cells, casts, etc) 
• Hematology (cytopenias, coagulopathy, etc) 
The Investigator must maintain/provide independent supporting source documents (eg, chart, 
worksheet, clinic notes, labs, and photodocumentation of cutaneous SLE manifestations) capable 
of withstanding audit: 
• For each SLE symptom present at the visit or present within the past 4 weeks before the visit 
• Indicating if symptom had a new onset, was improving, same, or worse in the past 4 weeks as 
compared to the prior 4 weeks 
• Sufficient descriptive detail to support changes (improved, worsening); eg, number/location 
of arthritic joints, size/location of rashes, etc 
• Information indicating that other symptoms relevant for BILAG were not present at the time 
point of the visit and within the 4 weeks prior to the visit 
The Sponsor will provide centralized grading (A, B, C, D, and E) based on BILAG 2004 eCOA 
pages completed by the Investigator, eCRF pages completed by Investigators, laboratory 
parameters, and may be subject to adjudication. Prior to Visit 2, the site must have received 
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confirmation from the central efficacy reader for BILAG 2004 data that the study participant has 
met BILAG 2004 eligibility for randomization. 
The BILAG 2004 grading is anchored in the physician’s intention to treat. Disease activity is 
graded separately for 9 body systems to 5 different grades (A to E) as follows: 
A (“Active”) 
= 
Severely active disease (sufficient to require systemic immunosuppressant 
or anticoagulant therapy; eg, >20mg/day prednisone, immunosuppressants, 
or cytotoxics) 
B (“Beware”) 
= 
Moderately active disease (requires low dose or local immunosuppressant 
therapy or symptomatic therapy; eg, prednisone ≤20mg/day prednisone, or 
antimalarials) 
C (“Contentment”) 
= 
Mild stable disease (no indication for changes in treatment) 
D (“Discount”) 
= 
Inactive now but previously active 
E (“Excluded”) 
= 
Never affected 
An SLE Assessment Reference Guide will be provided to all study personnel, which contains 
detailed protocol-specific clarifications and extensions of BILAG 2004 clinical parameter 
definitions and guidance for correlating SLEDAI-2K and BILAG 2004 clinical parameters. 
Important extensions of selected BILAG 2004 glossary definitions are included as follows: 
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A shift from BILAG 2004 Grade A or B to a lower grade indicates a clinically relevant change in 
disease activity as the BILAG 2004 grades mirror the decision points for treatment interventions. 
Investigators must complete full certified training on BILAG 2004 assessments ≤2 years before 
conducting their initial BILAG 2004 assessment in this study. Investigators who perform 
BILAG 2004 assessments on an ongoing basis (either in this study or another DZP study) are not 
required to repeat this training unless ≥2 years have elapsed since they last conducted a BILAG 
2004 assessment. Preferably, the same Investigator should evaluate the study participant at each 
BILAG 2004 assessment from Screening to study completion. The assessor will be documented 
in the eCOA and dataset. 
8.1.1.2 
SLEDAI-2K 
The SLEDAI-2K (30 days) measures disease activity. Disease activity in the 30 days prior to and 
at the time point of the assessment shall be considered. It is a global index and includes 
24 clinical symptoms and laboratory variables that are weighted by the type of manifestation, but 
not by severity or dynamic of the individual item. The SLEDAI-2K includes scoring for 
antibodies 
 positive or negative) and low complement, as well as some renal and 
hematologic parameters. The total score falls between 0 and 105, with higher scores representing 
increased disease activity. The SLEDAI-2K has been shown to be a valid and reliable disease 
activity measure in multiple study participant groups (Gladman et al, 2002). 
To confirm study participant eligibility at Baseline (Visit 2), the SLEDAI-2K score without any 
laboratory values is calculated based on all the clinical variables only, without factoring in the 
laboratory variables. At Screening (Visit 1), the SLEDAI-2K will include laboratory parameters. 
8.1.1.3 
S2K RI-50 
The S2K RI-50 is comprised of the same 24 descriptors covering 9 organ systems as the 
SLEDAI-2K and describes the improvement in disease activity of at least 50% compared with 
the previous assessment; the S2K RI-50 reflects disease activity over the 30 days prior to the 
assessment (Touma et al, 2011). 
The S2K RI-50 score corresponds to the sum of each of the 24 descriptor scores on the 
S2K RI-50 data retrieval form. The method of scoring is simple, cumulative, and intuitive and 
similar to the SLEDAI-2K. One of 3 situations could have resulted when a descriptor was 
present at the previous assessment: 
1. The descriptor has achieved complete remission, in which case the score would be “0”; 
2. The descriptor has not achieved a minimum of 50% improvement, in which case the score 
would be identical to its corresponding SLEDAI-2K value; or 
3. The descriptor has improved by ≥50% (according to the S2K RI-50 definition) but has not 
achieved complete remission, in which case the score was evaluated as one-half the score 
that would be assigned for SLEDAI-2K. 
If a descriptor was not present at the previous assessment, the value for the S2K RI-50 was the 
same as that for SLEDAI-2K. This process was repeated for each of the 24 descriptors. 
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8.1.1.4 
Physician’s Global Assessment 
The Investigator will rate the overall status of the study participant in response to the following 
statement: 
“Please mark a vertical line on the scale below to assess the overall status of the study 
participant’s Systemic Lupus Erythematosus signs and symptoms and the functional capacity 
of the study participant. The very far left end is ‘very good, asymptomatic and no limitation 
of normal activities’; the very far right end indicates ‘severe disease’. This refers to the most 
severe possible disease, and does not reflect the most severe ever seen in a particular patient, 
but the most severe disease ever seen in all SLE patients.” 
When scoring the Physician’s Global Assessment (PGA), the assessor should always look back 
at the score from the previous visit. 
8.1.1.5 
SELENA Flare Index (2009 revision) 
The SELENA (Safety of Estrogens in Lupus National Assessment) Flare Index in its 2009 
revision evaluates increases in SLE disease activity within eight organ systems: mucocutaneous, 
musculoskeletal, cardiopulmonary, hematological, constitutional, renal, neurological, and 
gastrointestinal. The Investigator assesses different clinical manifestations within each organ 
system, treatment recommendations and the need for hospitalization. The observed 
manifestations map into a flare categorization as no flare, mild flare, moderate flare, or severe 
flare. In case the assessment of a clinical manifestation and the recommendation for a treatment 
change are discrepant the treatment choice takes precedence in the direction of a higher flare 
definition. Treatment changes recommended because of intolerance, toxicity or safety do not 
count towards a flare definition. 
8.1.1.6 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
The Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) consists of 
2 scores; the first summarizes the activity of the disease and the second is a measure of the 
damage done by the disease (Table 8‒1) (Albrecht et al, 2005). Activity is scored on the basis of 
erythema, scale/hypertrophy of skin and mucous membranes, acute hair loss, and nonscarring 
alopecia. Damage is scored in terms of dyspigmentation and scarring, including scarring 
alopecia. Study participants are asked whether dyspigmentation due to cutaneous lupus 
erythematosus lesions usually remains visible for more than 12 months, which is taken to be 
permanent. Symptoms representing damage can not disappear. If so, the dyspigmentation score 
is doubled. The scores are calculated by simple addition based on the extent of the symptoms. 
The extent of involvement for each of the skin symptoms is documented according to specific 
anatomic areas that are scored according to the worst affected lesion within that area for each 
symptom.  
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Table 8‒1: 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
activity and damage scoring 
Activity 
Damage 
Erythema 
0=absent 
1=pink; faint erythema 
2=red 
3=dark red; purple/ violaceous/ 
crusted/ hemorrhagic 
Dyspigmentation 
0=absent 
1=dyspigmentation 
Scale/ 
Hypertrophy 
0=absent 
1=scale 
2=verrucous/hypertrophic 
Scarring/Atrophy/ 
Panniculitis 
0=absent 
1=scarring 
2=severely atrophic scarring 
or panniculitis 
Mucous 
Membrane 
Involvement 
0=absent 
1=lesion or ulceration 
Duration of 
Dyspigmentation 
(after active lesions 
have resolved) 
0=dyspigmentation usually 
lasts <12 months 
1=dyspigmentation usually 
lasts ≥12 months 
Alopecia a 
 
Alopecia a 
 
Recent Hair 
Loss (within 
the last 
30 days) 
0=no 
1=yes 
Scarring of the 
Scalp (judged 
clinically) 
0=absent 
3=in 1 quadrant 
4=2 quadrants 
5=3 quadrants 
6=affects the whole skull 
Alopecia 
(clinically not 
obviously 
scarred) 
0=absent 
1=diffuse; noninflammatory 
2=focal or patchy in 1 quadrant 
3=focal or patchy in >1 
quadrant 
CLASI=Cutaneous Lupus Erythematosus Disease Area and Severity Index 
a If scarring and nonscarring aspects seem to coexist in 1 lesion, both should be scored. 
8.1.1.7 
Tender and Swollen Joint Counts 
The joint assessment will be carried out on 28 joints, including the shoulders, elbows, wrists 
(radiocarpal, carpal, and carpometacarpal bones were considered as a single unit), 
metacarpophalangeal (MCP) joints (MCP 1, 2, 3, 4, and 5), thumb interphalangeal joint, 
proximal interphalangeal (PIP) joints (PIP 2, 3, 4, and 5), and the knees and must be performed 
by the Investigator, a Subinvestigator or a qualified joint assessor. 
Artificial and ankylosed joints will be excluded from tenderness and swelling assessments. 
Study participants taking maintenance NSAIDs/analgesics, medications including natural or 
synthetic cannabinoids (approved inline with local regulations), or approved narcotics should not 
take a dose of these medications within 12 hours prior to the tender joint count/swollen joint 
count (TJC/SJC) assessment visits in order to allow a true assessment of the joint tenderness and 
swelling to be conducted. 
Tenderness and swelling will be graded on a 2-point scale as described in Table 8‒2. 
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Table 8‒2: 
Joint tenderness and swelling grades 
Grade 
Swelling Response 
Tenderness Response (28) 
0 
Not swollen 
Not tender 
1 
Detectable synovial thickening with or 
without loss of bony contours, or 
bulging synovial proliferation with or 
without cystic characteristics 
Positive response to questioning (tender), 
spontaneous response elicited (tender and 
winced), or withdrawal by study participant on 
examination (tender, winced, and withdrew) 
Every effort should be made to ensure each study participant is evaluated by the same 
Investigator (or qualified assessor) during all study visits. 
The total TJC and SJC are the sum of all individual respective tenderness and swelling grades. If 
there are missing observations in the TJC or SJC, then the remaining observations are assessed 
and weighted by dividing by the number of nonmissing values and multiplying by 28. If a joint is 
not evaluable at Baseline, then that joint is set to missing throughout the study. If more than 50% 
of the tenderness or swelling grades are missing, then no imputation is done and the total TJC or 
SJC are set to missing. The total scores are used to assess the percentage change from Baseline. 
8.1.1.8 
Lupus Arthritis and Musculoskeletal Disease Activity score 
Three different VAS scales will be used to assess musculoskeletal disease activity. The 
participant will be asked to rate their musculoskeletal pain on a first VAS scale, and their early 
morning stiffness on a second VAS scale, and the physician will be asked to rate the overall 
musculoskeletal disease activity on a third VAS scale. 
8.1.1.9 
SLICC/ACR Damage Index 
The Systemic Lupus International Collaborating Clinics (SLICC)/ACR Damage Index (version 
1996) for SLE measures irreversible, accumulated organ damage from either the disease process 
or disease treatment, which has been present for at least 6 months, in 12 organ systems. It is an 
important predictor of long-term mortality and is an independent outcome measure separate from 
the BILAG 2004 and SLEDAI-2K. Only nonreversible change that has occurred since the onset 
of SLE is to be included, rather than change related to active inflammation. Consequently, a 
damage/feature once documented cannot disappear. Otherwise, the original grading must be 
reassessed. 
Definition of damage: 
• Nonreversible change 
• Occurring since onset of lupus  
• Not related to active inflammation 
• Present for at least 6 months 
• Ascertained by clinical assessment/x-rays 
The Investigator (or qualified designee) will perform the SLICC/ACR Damage Index assessment 
for the 12 different organ systems (Table 8‒3), and check “Yes” if the criterion is present (and 
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tick the appropriate box if there is more than 1 choice); or check “No,” or “Unknown,” as 
appropriate. 
Table 8‒3: 
SLICC/ACR Damage Index organ system scoring 
ACR=American College of Rheumatology; SLICC=Systemic Lupus International Collaborating Clinics 
8.1.2 
Patient-reported outcomes 
Study participants will complete 9 patient-reported outcomes (PROs) as per time points 
mentioned in the schedule of study assessments in Section 1.3. 
Study personnel other than the treating physician should administer the PROs. The PROs should 
be completed by the study participants themselves in a quiet place. 
The PROs should be completed in the following order: FATIGUE-PRO, Functional Assessment 
of Chronic Illness Therapy (FACIT-F), PGI-S Fatigue, PGI-C Fatigue, PGI-S, PGI-C, Lupus 
quality of life (QoL), Euro Quality of life 5-Dimensions 5-Level (EQ-5D-5L), and PHQ-9. 
The PROs should only be checked for completeness. If a PRO is incomplete, the study personnel 
may check with the participant that any missing data is involuntary. On dosing days, the PROs 
will be completed prior to dosing. 
8.1.2.1 
FATIGUE-PRO 
The FATIGUE-SLE (Short Form) was renamed recently to FATIGUE-PRO. It consists of 
31 items across 3 scales: Physical Fatigue (items 1-9), Mental Fatigue (items 10-20), and 
Fatigability (items 21-31). The study participant is asked to score each fatigue item based on how 
frequently they experienced the item during the past 7◦days using the following response 
options: 1=none of the time; 2=a little of the time; 3=some of the time; 4=most of the time; 5=all 
of the time. For each scale, a score ranging from 0 to 100 is calculated, with 100 indicating a 
higher level of fatigue.  
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8.1.2.2 
FACIT-F 
Functional Assessment of Chronic Illness Therapy-Fatigue Scale is a 13-item, self-reported tool 
that measures an individual’s level of fatigue during their usual daily activities over the past 
week (Cella, 2002). The level of fatigue is measured on a four-point Likert scale (4=not at all 
fatigued to 0 = very much fatigued). Clinically important difference (CID) estimates of 3.0 points 
were determined using anchor-based and distribution-based methods in three patient samples 
(affected by cancer). 
8.1.2.3 
PGI 
Patient Global Impression of Severity (PGI-S) is a single-state, self-report measure that rates a 
participant's severity of their symptoms over the past week. The PGI-S is a 5-point scale (“none”, 
“mild”, “moderate”, “severe”, “very severe”). 
Patient Global Impression of Fatigue Severity (PGI-S Fatigue) is a single-state, self-report 
measure that rates a participant's severity of their fatigue over the past week. The PGI-S is a 
5-point scale (“none”, “mild”, “moderate”, “severe”, “very severe”). 
Patient Global Impression of Change (PGI-C) is a single-state, self-report measure that reflects a 
participant's belief about the efficacy of treatment. The PGI-C is a 7-point scale (“much 
improved”, “moderately improved”, “a little bit improved”, “no change”, “a little bit worse”, 
“moderately worse”, “much worse”). 
Patient Global Impression of Change in Fatigue (PGI-C Fatigue) is a single-state, self-report 
measure that reflects a participant's belief about the efficacy of treatment on their experience of 
fatigue. The PGI-C is a 7-point scale (“much improved”, “moderately improved”, “a little bit 
improved”, “no change”, “a little bit worse”, “moderately worse”, “much worse”). 
8.1.2.4 
LupusQoL 
The LupusQoL (version 2007) is a disease-specific health-related QoL (HRQoL) instrument 
developed with SLE patient qualitative input (McElhone et al, 2007). It consists of 8 domains: 
physical health (8 items), pain (3 items), planning (3 items), intimate relationships (2 items), 
burden to others (3 items), emotional health (6 items), body image (5 items), and fatigue 
(4 items). Scores are calculated independently for each domain and transformed to a 0 to 
100 point scale with higher scores denoting better HRQoL. A recent study has suggested 
minimal clinically important difference scores for minimally improved (ranging from 1.1 to 
9.2 points) and minimally worse (ranging from -0.5 to -6.4 points) for each of the 8 domains of 
LupusQoL (Devilliers et al, 2015). 
8.1.2.5 
EQ-5D-5L 
The EQ-5D-5L health questionnaire provides a descriptive profile and a single index value for 
health status. The instrument is comprised of a 5-item health status measure and a VAS. The 
EQ-5D-5L VAS records the respondent’s self-rated health status on a vertical 20cm scale, 
graduated from 0 to 100 (0=worst imaginable health status, 100=best imaginable health status). 
8.1.2.6 
PHQ-9 
The PHQ-9 is a validated patient outcome tool for screening depression and is not sufficiently 
accurate to establish a definitive diagnosis for depression. The PHQ-9 is scored 0 to 27, with 
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scores ≥10 indicating a possible depressive disorder. The sensitivity and specificity of the tool is 
88%. It is also used to determine treatment response. 
8.1.3 
Derived endpoints 
8.1.3.1 
BILAG 2004-based Composite Lupus Assessment 
A study participant is considered to be a BILAG 2004-based Composite Lupus Assessment 
(BICLA) responder if all of the following is fulfilled: 
1. BILAG 2004 improvement without worsening, defined as BILAG 2004 Grade As at Baseline 
Visit improved to B/C/D, and BILAG 2004 Grade Bs at Baseline Visit improved to C/D, and 
no BILAG 2004 worsening in other BILAG 2004 organ systems (that had BILAG 2004 
Grade C, D, or E at Baseline) such that there are no new BILAG 2004 Grades A nor greater 
than 1 new BILAG 2004 Grade(s) B; and 
2. No worsening in the SLEDAI-2K total score compared to Baseline Visit (defined as no 
increase in SLEDAI-2K total score); and 
3. No worsening in the PGA compared to Baseline Visit (“no worsening” is defined as either no 
worsening or worsening <10% of the full 100mm VAS, equivalent to less than a 10mm 
increase in the PGA compared to Baseline Visit (V2) score). 
Escape treatment intervention as indicated by Investigator until the assessment time point will be 
defined as intercurrent event for the primary endpoint leading to non-response from the day after 
the event onward. 
Escape treatment intervention is defined as: 
1. Any dose increase or new start of systemic antimalarials or immunosuppressants from 
Screening Visit and during Treatment Period 
2. Any increase in dose or new start of a moderate to high potency topical immunosuppressant 
(eg, Tacrolimus) used for an organ system with SLE disease activity during the study 
3. Any increase of prednisone equivalent dose within the first 4 weeks (up to Week 4) that is 
above the Baseline level by >50% of the Baseline level or of >10mg/day, whichever is 
higher, which does not return to the Baseline level within 7 days after increase above 
Baseline level 
4. Any increase of prednisone equivalent dose for a SLE indication above Baseline level after 
Week 4 
5. Any increase of prednisone equivalent dose by >50% or 5mg/day, whichever is lower, for 
more than 1 day within 8 weeks prior to an assessment for any indication after Week 4. 
6. More than 1 corticosteroid intra-articular injection up to Week 12 
7. Any corticosteroid intra-articular injection after Week 12 for an SLE indication  
8. Any intramuscular administration of corticosteroid for an SLE indication 
9. Any iv administration of corticosteroid for an SLE indication 
If a treatment change represents an intercurrent event, it will be confirmed by a blinded 
independent adjudicator. 
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In addition, study participants who permanently discontinue study medication prematurely or are 
withdrawn from the study are categorized as non-responders for the primary analysis (see 
Section 9.3.1). 
8.1.3.2 
Severe BILAG flare 
BILAG severe flare is defined as a BILAG 2004 Grade A in any system due to individual items 
that are new or worse and are qualifying for the Grade A (Isenberg et al, 2011). Determination of 
items that are new or worse qualifying for the Grade A will be according to the supplementary 
information for the numerical scoring of the BILAG-2004 index (Yee et al, 2010). Worsening of 
symptoms after the Baseline Visit will only be considered as a flare if there was at least 1 post-
Baseline Visit, prior to the worsening, where the symptom remained the same or improved. 
BILAG flares will be confirmed by a blinded review by independent adjudicators. 
8.1.3.3 
Moderate BILAG flare 
BILAG moderate flare is defined as 2 or more BILAG 2004 Grade Bs due to individual items 
that are new or worse and are qualifying for the Grade B in any system (Isenberg et al, 2011). 
Determination of items that are new or worse qualifying for the Grade B will be according to the 
supplementary information for the numerical scoring of the BILAG-2004 index (Yee et al, 
2010). 
8.1.3.4 
LLDAS 
LLDAS is defined as 
• No significant disease activity as per SLEDAI-2K: 
− SLEDAI-2K score ≤4 with no activity in major organ systems (renal, CNS, 
cardiopulmonary, vasculitis, fever) 
• No new and/or worsening disease activity defined as no SLEDAI-2K component 
documented as present that was not documented present at previous visit 
• PGA ≤33mm 
• Prednisone equivalent systemic dose for SLE indication ≤7.5mg per day 
• Stable standard maintenance doses of immunosuppressive drugs as allowed by protocol 
defined as no increase in dose in the past 12 weeks, and no dose higher than allowed as per 
protocol. 
8.1.3.5 
Systemic Lupus Erythematosus Responder Index-4 
The Systemic Lupus Erythematosus Responder Index (SRI)-4 define responders as (ie, all 
criteria must be met): 
• Reduction in SLEDAI-2K score of ≥4 
• No shift from BILAG 2004 Grade B, C, D, or E to A post-Baseline 
• No more than 1 shift from BILAG 2004 Grade C, D, or E to B post-Baseline 
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• No worsening in the PGA compared to Baseline Visit (V2) (“no worsening” is defined as 
either no worsening or worsening <10% of the full 100mm VAS, equivalent to less than a 
10mm increase in the PGA compared to Baseline Visit (V2) score); 
The analysis will be repeated using a cut-off of 6 (SRI-6) and 8 (SRI-8) for reduction in 
SLEDAI. 
8.1.3.6 
DORIS (Definitions of Remission in SLE) complete remission on 
treatment 
SLEDAI-based remission is defined as: 
• Clinical SLEDAI-2K score = 0 (SLEDAI-2K without serology: 
 
items) and 
• PGA ≤16mm and 
• Prednisone equivalent systemic dose for SLE indication ≤5mg per day and 
• 
 ≤ULN and 
• 
 ≥ LLN.   
Other tertiary endpoints will be described in the SAP. 
8.2 
Safety assessments 
Planned time points for all safety assessments are provided in the Schedule of Activities 
(Section 1.3). 
8.2.1 
Physical examination 
The physical examination and the interim medical history (anamnesis) are an important base for 
recognition and appropriate documentation of AEs and is a critical part of disease activity 
assessment instruments, such as the BILAG 2004 or the SLEDAI-2K and will be performed at 
every visit. 
Physical examination findings will be recorded in the eCRF at Screening. Clinically relevant 
changes in subsequent physical examinations will be recorded as AEs if not related to SLE. If 
physical examination findings are considered to be related to SLE, they will be documented 
within the BILAG 2004 and/or SLEDAI-2K assessment eCOA. The outcome of physical 
examinations and the interim medical history must be documented in source documentation. 
A complete physical examination will include, at a minimum, general appearance; ear, nose, 
mouth, and throat; eyes, hair, and skin; and assessments of the respiratory, cardiovascular, 
gastrointestinal, musculoskeletal, hepatic, and neurological (including focused assessment of 
reflexes, sensitivity, and muscle strength) systems and mental status. Height (only at Screening) 
and weight (at applicable visits and if deemed necessary by the Investigator) will also be 
measured and recorded. 
Investigators should pay special attention to clinical signs related to previous serious illnesses. 
Clinically relevant findings or worsening of previous findings will be recorded as AEs. 
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8.2.2 
Vital signs 
Oral, tympanic, or temporal artery temperature, pulse rate, respiratory rate, and blood pressure 
will be assessed. 
Blood pressure and pulse measurements will be assessed in a supine or sitting position with a 
completely automated device. Manual techniques will be used only if an automated device is not 
available. 
Blood pressure and pulse measurements should be preceded by at least 10 minutes of rest for the 
participant in a quiet setting without distractions. 
Vital signs (to be taken before blood collection for laboratory tests) will include oral, tympanic, 
or temporal artery temperature, pulse and blood pressure measurements.  
8.2.3 
ECG 
Single 12-lead ECG will be obtained prior to dosing and prior to obtaining PK or other 
laboratory samples (if applicable) using an ECG machine that automatically calculates the heart 
rate and measures PR, QRS, QT, and QTc intervals. Refer to Section 7 for QTc withdrawal 
criteria and any additional QTc readings that may be necessary. 
All ECG recordings should be taken with the study participant resting in the supine position for 
at least 15 minutes prior to the recording and should be motionless during the recording. 
The Investigator or designee will determine whether the results of the ECG are normal or 
abnormal. All important findings and abnormalities (including their specification) should be 
reported as AEs. Data will be electronically transferred to a third-party vendor. 
8.2.4 
Clinical safety laboratory assessments 
See Section 10.2 for the list of clinical laboratory tests to be performed. Some laboratory 
parameters may be subject to blinding. In case a blinded laboratory parameter is considered 
safety relevant, alert notifications in case of clinically significant levels or changes from baseline 
will be established. 
Some immune system markers (Section 8.9) may also be considered safety markers. 
The Investigator must review the laboratory report, document this review, and record the 
underlying disease or condition of clinically relevant laboratory changes occurring during the 
study or, in case an underlying disease or condition cannot be identified, the laboratory change 
itself in the AE section of the eCRF. The laboratory reports must be filed with the source 
documents. Clinically significant abnormal laboratory findings are those which are not 
associated with the underlying disease, unless judged by the Investigator to be more severe than 
expected for the participant's condition. 
All laboratory tests with values considered clinically significantly abnormal during participation 
in the study or within 5 half-lives (10 Weeks) after the final dose of study medication should be 
repeated until the values return to normal or baseline or are no longer considered clinically 
significant by the Investigator or Medical Monitor. 
If such values do not return to normal/Baseline within a period of time judged reasonable by the 
Investigator, the etiology should be identified and the Sponsor notified. 
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All protocol-required laboratory assessments, as defined in Section 10.2, must be conducted in 
accordance with the laboratory manual and the Schedule of Activities. 
If laboratory values from non-protocol specified laboratory assessments performed at the 
institution’s local laboratory require a change in participant management or are considered 
clinically significant by the Investigator (eg, SAE or AE or dose modification), then the results 
must be recorded in the eCRF. 
8.2.5 
Suicidal risk monitoring 
Suicidal ideation and behavior will be assessed by trained study personnel (preferably the 
Investigator or Subinvestigator in the scope of the mandatory anamnesis) using the C-SSRS. This 
scale will be used for screening as well as to assess suicidal ideation and behavior that may occur 
during the study. All information available to the assessor at the time of assessment should be 
considered. 
8.2.6 
Assessment and management of TB and TB risk factors 
Appropriate rigorous precautions are being taken within this protocol to monitor the risk of TB 
infection in this study (see Section 5.2 [Exclusion Criterion 19] and Section 7.1 [discontinuation 
of study medication]). Any presumptive diagnosis or diagnosis of a TB infection is a reportable 
event. Confirmed active TB must be reported as an SAE (Section 8.3). The Investigator is to 
complete and submit the TB follow-up form provided. 
For the purposes of this study, TB definitions are as follows: 
a. Known TB infection 
− Active TB infection or clinical signs and symptoms suspicious for TB (pulmonary or 
extra-pulmonary). 
− History of active TB infection involving any organ system or findings in other organ 
systems consistent with TB infection, unless adequately treated and proven to be fully 
recovered upon consult with a TB specialist. 
− Any evidence by radiography or other imaging modalities consistent with previously 
active TB infection that is not reported in the study participant’s medical history. 
b. High risk of acquiring TB infection: 
− Known close exposure to another person with active TB infection within the 3 months 
prior to Screening. 
− Time spent in a healthcare delivery setting or institution where individuals infected with 
TB are housed and where the risk of transmission of infection is high. 
c. Latent TB infection (unless appropriate prophylaxis is initiated at least 4 weeks prior to study 
medication dosing and continued to completion of prophylaxis): 
− The absence of signs, symptoms, or physical findings suggestive of TB infection with a 
positive IGRA test (or 2 indeterminate IGRA test results) and a chest x-ray (or other 
imaging) without evidence of TB infection. If the result of the IGRA test is 
indeterminate, the particular IGRA test previously performed may be repeated once; if 
positive or indeterminate on retest, the study participant may not be randomized to IMP 
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without further evaluation by a TB specialist and discussion with the Study Physician, if 
LTB infection is identified. The retest must be done during the protocol-defined 
Screening window. 
Note: If available, respiratory or other specimens must also be smear and culture negative 
for TB (CDC diagnosis of LTB infection) 
http://www.cdc.gov/TB/topic/testing/default.htm). 
d. Pulmonary NTM infection is defined as a clinical infection caused by mycobacterial species 
other than those belonging to the Mycobacterium TB complex. 
Study participant eligibility, retesting requirements, and treatment requirements are depicted in 
Figure 8-1. 
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Figure 8-1: Schematic diagram of TB test results and study eligibility 
 
IGRA=interferon gamma release assay; TB=tuberculosis 
aIGRA retest must be done during the protocol-defined Screening window 
bStudy participants with LTB1 may enter the study only after they have completed least 4 weeks of appropriate 
prophylactic therapy and thereafter, will continue and complete the entire regimen. 
8.2.6.1 
Assessment and reporting of TB and TB risk factors during the study 
8.2.6.1.1 
Physical examination 
The Investigator should consider all potential sites of infection when assessing for TB during the 
physical examination, and other evaluations, and based on the study participant’s medical or 
social history. 
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The most common primary focus of TB is the lung. Other sites may include gastrointestinal 
system, bone/joints, lymph glands and meninges etc. However, in immune compromised 
patients, study participants, and/or patients treated with biologics (especially TNF inhibitors) 
extra-pulmonary manifestations of TB are common compared with the normal population. 
Some common symptoms that the study participant may present are dependent on the primary 
focus of infection and may include cough, blood in sputum, night sweats, lymphadenitis, joint 
pain/swelling, spinal deformity, headache/confusion, abdominal pain (mimicking inflammatory 
bowel disease), etc. Unusual presentations should always be considered. 
8.2.6.1.2 
IGRA test conversion 
Tuberculosis test conversion is defined as a positive or indeterminate (and confirmed 
indeterminate on repeat) IGRA result for the current test when previous IGRA test results were 
negative. All study participants with positive or indeterminate IGRA test results must 
immediately stop study medication administration. In case of an IGRA test conversion, the study 
participant must be considered as having either a suspected new latent or an active TB infection 
and be promptly referred to an appropriate specialist (eg, pulmonologist, infectious disease 
specialist) for further evaluation. Additional assessments (eg, blood tests or IGRA, chest X-rays, 
or other imaging) should be performed where medically relevant and documented. Such 
conversions should be reported as AEs as described in the protocol. The AE term would need to 
be updated with final diagnosis once available. 
8.2.6.1.3 
Latent TB 
In case the evaluation by the appropriate specialist diagnoses a new LTBI, a TB prophylactic 
therapy in accordance with applicable clinical guidelines should be immediately initiated. Study 
medication can be restarted no sooner than 4 weeks after the start of TB prophylactic therapy if it 
is deemed likely that the TB prophylactic therapy will be continued to full completion. If no TB 
prophylactic therapy is initiated for the newly diagnosed LTBI, the study participant must 
permanently stop study medication. Every related action should be discussed in advance with the 
Medical Monitor. 
Study participants who prematurely discontinue treatment for LTBI or who, in the opinion of the 
Investigator or Sponsor, are noncompliant with anti-TB therapy must discontinue further intake 
of study medication immediately. Even though withdrawn from study treatment, study 
participants should still be encouraged to regularly attend scheduled visits (but without IMP 
administration) and in any case should return for the End of Treatment Visit, complete all end of 
treatment assessments, and complete an End of Study Visit (as applicable). LTBI must be 
reported as an AE. Follow-up reports should be completed as per protocol requirement until such 
time as the LTBI resolves. 
8.2.6.1.4 
Active TB or non-TB mycobacterium infection 
Study participants who develop active TB or NTM infection during the study must immediately 
permanently discontinue study medication. Treatment for active TB or NTMB should be started 
immediately. 
Confirmed active TB is always considered an SAE. UCB’s process requires that these must be 
captured on an SAE report form and provided to the Sponsor in accordance with SAE reporting 
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requirements. Follow-up reports should be completed as per protocol requirement until such time 
as the TB infection resolves. 
8.2.6.2 
TB questionnaire 
The questionnaire “Evaluation of signs and symptoms of tuberculosis” should be used as a 
source document. The questionnaire will assist with the identification of study participants who 
may require therapy for TB. A study participant who answers “Yes” to the question “Has the 
study participant been in close contact with an individual with active TB, or an individual who 
has recently been treated for TB?” at Screening is excluded. A “Yes” response to any of the other 
questions within the questionnaire at Screening should trigger further careful assessment to 
determine if study participant has LTB or active TB. A “Yes” response to any of the questions 
during the study should trigger further assessments to determine if the study participant has 
either LTB or active TB infection. 
8.2.6.3 
TB management 
During the study, study participants who develop evidence of LTBI, active TB or NTM infection 
must immediately stop further administration of study medication and will be referred to TB 
specialist (pulmonologist or infectious disease specialist) for further evaluation. Study 
participants diagnosed with active TB or LTBI should receive appropriate TB or prophylaxis 
therapy. If a TB specialist excludes active TB, the study participant can restart the study 
medication no earlier than 4 weeks after the start of an appropriate TB prophylactic therapy. The 
study participant should be transferred to the care of their physician and managed according to 
the standard of care. 
Study participants identified as having active TB during the study must permanently discontinue 
study medication. 
If infection with NTM is identified during the study, the same procedure as for active TB 
acquired during the study and compliant TB treatment shall be followed. 
8.2.7 
SARS-CoV-2/COVID-19 
While the SARS-CoV-2 outbreak coincides with the conduct of the study, and study participants 
are at risk of developing the COVID-19 disease caused by the SARS-CoV-2 virus, to date study 
participants do not appear to be at an increased risk for severe disease. Nevertheless, this 
experience is based on a small number of individual cases, and careful monitoring of study 
participants for SARS-CoV-2 infection is recommended. 
Records on the history of COVID-19 vaccination should be collected and best medical practice 
and applicable local healthcare guidance should be followed to exclude active SARS-CoV-2 
infection for evaluating Exclusion Criterion 15a and to validate the criteria for the temporary 
study drug discontinuation as described in Section 7.1. 
Prior to or at any regular study visit participants need to be evaluated by the Investigator if they 
are at risk for having an active SARS-CoV-2 infection. If participants are considered as at risk to 
have an active SARS-CoV-2 infection adequate testing (polymerase chain reaction [PCR] or 
antigen test) is indicated. 
This is applicable at:  
• The Baseline Visit (V2) to confirm eligibility 
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• All post Baseline visits  
Among the factors described in the literature and in healthcare guidance as increasing the 
possibility to have contracted an active SARS-CoV-2 infection are: 
1. Participant is not vaccinated against SARS-CoV-2 
2. Signs and symptoms suggestive of COVID-19  
3. A close contact with a person diagnosed with SARS-CoV-2 infection/COVID-19 within 
the preceding 14 days 
4. The participant resided or visited an area (county, city) with high prevalence of active 
infection (in line with local guidance). 
Investigators are further advised to carefully consider risk factors for a severe COVID-19 course, 
the individual life situation as well as a potential immunity against SARS-CoV-2 (post infection, 
post vaccination) in the decision for diagnostic measures. 
Among the factors described in the literature as representing an increased risk for severe course 
of COVID-19 are: elder age (>65y), obesity (body mass index [BMI] ≥35), comorbidities such as 
diabetes mellitus, chronic kidney disease, hypertension, significant cardiac or pulmonal disease 
and concurrent treatment with a high dose corticosteroid (≥ 10mg/day prednisone equivalent) 
(Haberman et al 2020, Fernandez et al 2020, Gianfrancesco et al 2020, Pablos et al 2020, Fredi et 
al 2020). However, these factors appear not to represent an increased risk to contract a SARS-
CoV-2 infection. 
In case of a suspected SARS-CoV-2 infection, samples for SARS-CoV-2 test should be drawn as 
close as possible, preferably within 72 hours before the planned dosing, to obtain the most up-to-
date status of the suspected infection prior to the study drug administration. If the test sample 
was collected over 72 hours prior to the study drug administration, risks of a new SARS-CoV-2 
virus exposure since sample collection, should be considered and the arguments for proceeding 
with the dosing recorded in the source documentation. 
In case of a positive test result, study drug administration should be temporarily discontinued. 
Study drug application can be resumed ≥ 7 days after recovery of symptoms or, in case of an 
asymptomatic course, ≥ 14 days after the positive test result. 
In case of a known exposure to a person with COVID-19 study drug administration should be 
suspended until ≥ 14 days after the contact. 
Study drug should be only resumed after consultation with the Medical Monitor (see 
Section 7.1.3). 
In case of a positive test result Investigators are advised to recommend quarantine measures to 
the study participants and report the infection according to the local guidance. 
Investigators are strongly advised to discuss with participants the potential risks associated with 
COVID-19 and to encourage them to take special caution to self-protect – this includes wearing 
of masks in public, following social distancing best practices and early medical consultation in 
case of symptoms of an infection, and reporting such symptoms to the Investigator. 
Local and international guidance on vaccination of immunocompromised patients (Furer et al, 
2020; Van Assen et al, 2011; Murdaca et al 2016; Mason et al, 2021, ACR 2021, Geisen et al, 
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2021) should be considered. Applicable guidance, benefits and risks of COVID-19 vaccination 
as well as the option of being vaccinated during the study (including the screening period) should 
be discussed with the study participant during the informed consent process. In case a patient is 
deciding to be vaccinated during the screening period, the screening period may be prolonged to 
3 weeks (ie, prolonged by 1 extra week). 
8.3 
AEs and SAEs 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative). 
The study participant will be given the opportunity to report AEs spontaneously. A general 
prompt will also be given at each study visit to detect AEs. For example: 
“Did you notice anything unusual about your health (since your last visit)?” 
In addition, the Investigator should review any self-assessment procedures (eg, diary cards) 
employed in the study for potential AEs. 
The Investigator and any designees are responsible for detecting, documenting, and recording 
events that meet the definition of an AE or SAE and remain responsible for following up AEs 
that are serious, considered related to the study treatment or study procedures, or that caused the 
participant to discontinue the study treatment (see Section 7). 
New or worsening manifestations of SLE should be recorded as AEs only if they are assessed as 
serious. 
All efforts should be taken to clarify the origin of the AE. This may require at any time point 
additional assessments including but not limited to additional laboratory assessments, imaging 
methods, EMGs and ECGs as medically indicated. Special caution should be taken on signs and 
symptoms of severe infections such as COVID-19. 
For results disclosure on public registries (eg, ClinicalTrials.gov), TEAEs and treatment-
emergent SAEs will be published. 
8.3.1 
Time period and frequency for collecting AE and SAE information 
All AEs and SAEs will be collected from the signing of the ICF until the follow-up visit at the 
time points specified in the Schedule of Activities (Section 1.3). 
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the ICF), including any pretreatment and posttreatment periods required by the 
protocol, must be reported in the eCRF even if no study medication was taken but specific study 
procedures were conducted. This includes all AEs not present prior to the initial visit and all AEs 
that recurred or worsened after the initial visit. 
All SAEs will be recorded and reported to the Sponsor or designee within 24 hours, as indicated 
in Section 10.3. The Investigator will submit any updated SAE data to the Sponsor within 
24 hours of it being available. 
The Investigator is specifically requested to collect and report to UCB (or its representative) any 
SAEs (even if the Investigator is certain that they are in no way associated with the study 
medication), up to from the end of the study for each participant, and to also inform participants 
of the need to inform the Investigator of any SAE within this period. Serious AEs that the 
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Investigator thinks may be associated with the study medication must be reported to UCB 
regardless of the time between the event and the end of the study. 
The method of recording, evaluating, and assessing causality of AE and SAE and the procedures 
for completing and transmitting SAE reports are provided in Section 10.3. 
8.3.2 
Method of detecting AEs and SAEs 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended and 
non-leading verbal questioning of the participant is the preferred method to inquire about 
AE occurrences. 
8.3.3 
Follow-up of AEs and SAEs 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs, treatment-emergent adverse events (TEAEs) 
of special interest and non-serious AEs of special monitoring (as defined in Section 8.3.6 and 
Section 8.3.7, respectively), will be followed until resolution, stabilization, the Investigator 
determines that it is no longer clinically significant, the event is otherwise explained, or the 
participant is lost to follow-up (as defined in Section 7.3). Further information on follow-up 
procedures is given in Section 10.3. 
8.3.4 
Regulatory reporting requirements for SAEs 
Prompt notification by the Investigator to the Sponsor of a SAE is essential so that legal 
obligations and ethical responsibilities towards the safety of participants and the safety of a study 
treatment under clinical investigation are met. 
The Sponsor has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study treatment under clinical investigation. The 
Sponsor will comply with country-specific regulatory requirements relating to safety reporting to 
the regulatory authority, the IRB/IEC, and Investigators. 
Investigator safety reports must be prepared for suspected unexpected serious adverse reactions 
(SUSAR) according to local regulatory requirements and Sponsor policy and forwarded to 
Investigators as necessary. 
An Investigator who receives an Investigator safety report describing a SAE or other specific 
safety information (eg, summary or listing of SAEs) from the Sponsor will review and then file it 
along with the IB and will notify the IRB/IEC, if appropriate according to local requirements. 
8.3.5 
Pregnancy 
Details of all pregnancies in female participants and female partners of male participants will be 
collected after the start of study treatment and until 12 months after the delivery date. 
If a pregnancy is reported, the Investigator must immediately inform the Sponsor within 24 hours 
of learning of the pregnancy and should follow the procedures outlined in Section 10.4. 
Study medication must be discontinued as soon as a pregnancy is suspected (eg, by positive urine 
pregnancy test). Study participants can remain in the study under observation and should attend 
to scheduled visits regularly as their condition allows. Blood sample collection will be adapted as 
indicated considering the study participant's condition during the study and at the end of the 
study visit. Caution is required with respect to concomitant medication if not contraindicated in 
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pregnancy. As indicated Investigators are advised to discuss the case with medical monitors or 
the sponsor's study physician to gain feedback on protocol defined actions. 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs. 
8.3.6 
AEs of special interest 
An AE of special interest is any AE that a regulatory authority has mandated be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE to the 
administration of a UCB product/compound.For DZP, the following events require immediate 
reporting (within 24 hours regardless of seriousness) to UCB: 
• Hy’s Law 
− Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total 
bilirubin in the absence of ≥2xULN ALP, with no alternative explanation for the 
biochemical abnormality (ie, without waiting for any additional etiologic investigations 
to have been concluded). Follow-up information should be reported if an alternative 
etiology is identified during investigation and monitoring of the participant. 
− Malignancies 
8.3.7 
AEs of special monitoring 
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8.3.8 
Anticipated SAEs 
8.3.9 
Suspected transmission of an infection agent via a medicinal 
product 
For the purposes of reporting, any suspected transmission of an infectious agent via a medicinal 
product should be considered as an SAE (Section 8.3); such cases must be reported immediately, 
recorded in the AE module of the eCRF, and followed as any other SAE. Any organism, virus, or 
infectious particle (eg, prion protein transmitting transmissible spongiform encephalopathy), 
pathogenic or nonpathogenic, is considered an infectious agent. 
8.4 
Safety signal detection 
Selected data from this study will be reviewed periodically to detect as early as possible any 
safety concern(s) related to the study medication so that Investigators, clinical study participants, 
regulatory authorities, and IRBs/IECs will be informed appropriately and as early as possible. 
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The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the Patient Safety 
representative. 
As appropriate for the stage of development and accumulated experience with the study 
medication, medically qualified personnel at UCB may identify additional safety measures 
(eg, AEs, vital signs, laboratory or ECG results) for which data will be periodically reviewed 
during the course of the study. 
8.5 
Treatment of overdose 
For this study, any dose of DZP greater than that prescribed in the protocol will be considered an 
overdose. Overdose events are only considered AEs or SAEs if there are associated clinical signs 
and symptoms or if the act of taking the excess study medication itself is an AE or SAE (eg, 
suicide attempt). 
UCB does not recommend specific treatment for an overdose. 
In the event of an overdose, the Investigator should: 
1. Contact the Medical Monitor immediately. 
2. Closely monitor the participant for any AE/SAE and laboratory abnormalities until study 
treatment can no longer be detected systemically (at least 84 days). 
3. Obtain a plasma sample for PK analysis within 84 days from the date of the final dose of 
study medication if requested by the Medical Monitor (determined on a case-by-case basis). 
4. Document the quantity of the excess dose as well as the duration of the overdose in the 
eCRF. 
Decisions regarding dose interruptions or modifications will be made by the Investigator in 
consultation with the Medical Monitor based on the clinical evaluation of the participant. 
8.6 
Pharmacokinetics 
 
 
 
. Additional samples may be 
collected at additional time points during the study if warranted and agreed upon between the 
Investigator and the Sponsor. 
Instructions for the collection and handling of biological samples will be provided in the 
Laboratory Manual. The actual date and time (24-hour clock time) of each sample will be 
recorded. 
 
 
 
 
Drug concentration information that would unblind the study will not be reported to investigative 
sites or blinded personnel until the study has been unblinded. 
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Any changes in the timing or addition of time points for any planned study assessments must be 
documented and approved by the relevant study team member and then archived in the Sponsor 
and site study files, but will not constitute a protocol amendment. The IRB/IEC will be informed 
of any safety issues that require alteration of the safety monitoring scheme or amendment of the 
ICF. 
Study participants are to rest in a supine position for at least 10 min before blood samples are 
taken. Blood samples are to be taken in the arm opposite the one used for infusion and be drawn 
at the time points and sampling windows designated in Table 1-2. Blood samples must not be 
drawn through the infusion cannula. 
Samples may be stored for a maximum of 20 years (or according to local regulations) following 
the last participant’s last visit for the study at a facility selected by the Sponsor to enable further 
analysis of PK of DZP and PEG. 
8.6.1 
Assessment of PK variables 
8.7 
Immunogenicity assessments 
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8.8 
Pharmacodynamics 
Some immune system markers (Section 8.9) may also be considered pharmacodynamic (PD) 
markers. 
8.9 
Immune system markers 
8.10 
Biomarkers 
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If samples are not used immediately, they will be stored frozen for later analysis (reflected in a 
separate report as applicable) for a maximum of 20 years (or according to local regulations) 
following the last participant’s last visit for the study at a facility selected by the Sponsor. They 
will only be used in the context of understanding the molecular taxonomy of SLE and/or 
response to treatment with DZP. 
As required, unused PK back-up samples may also be used for research to develop methods and 
to further investigate the biology of SLE and its treatment with DZP. 
Some immune system markers (Section 8.9) may also be considered biomarkers. 
8.11 
Genetics 
A blood sample for potential future exploratory DNA analysis/genetics research will be collected 
and stored from consenting participants in the study. This sampling is optional for study 
participants and requires a separate informed consent. A decision not to consent does not exclude 
the study participant from the study. 
These samples will only be used to further our understanding of SLE and/or how genetic 
variation may affect response or be affected by treatment with DZP and/or concomitant 
medications on SLE. Blood samples will be stored frozen in a UCB-appointed secure Biobank 
and they may be stored for up to 20 years. 
See Section 10.5 for Information regarding genetic research. Details on processes for collection 
and shipment of these samples can be found in the Laboratory Manual. 
8.12 
Medical resource utilization and health economics 
Not applicable. 
9 
STATISTICAL CONSIDERATIONS 
A description of statistical methods follows and will be described in more detail in the SAP. 
9.1 
Definition of analysis sets 
The Enrolled Set (ES) will consist of all study participants who have given informed consent. 
The Full Analysis Set (FAS) will consist of all study participants randomized into the study. The 
FAS is the primary analysis set for efficacy analyses. 
The Safety Set (SS) will consist of all study participants who are randomized and have received 
at least 1 dose (any amount) of study medication. Safety variables will be analyzed using the SS. 
The Per-Protocol Set (PPS) will consist of study participants in the FAS who have received at 
least 1 full dose of study medication and have no important protocol deviations (such as not 
under stable SOC treatment at Baseline) during the Treatment Period that may influence the 
validity of the data for the primary efficacy variable. 
The Pharmacokinetic Per-Protocol Set (PK-PPS) consists of all study participants who received 
at least 1 dose of study medication and provided at least one quantifiable plasma concentration 
post-dose without important protocol deviations that would affect the concentration. 
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9.2 
General statistical considerations 
9.2.1 
General presentation of summaries and analyses 
Statistical analysis and generation of tables, figures, study participant data listings, and statistical 
output will be performed using SAS® Version 9.4 or higher. 
All original and derived parameters will be listed and described using summary statistics. For 
continuous parameters, number of participants with available measurements, mean, standard 
deviation (SD), median, minimum and maximum and for categorical parameters, number of 
participants and percentages (to one decimal place) in each category will be presented. 
All descriptive statistics will be presented by treatment where applicable, including columns for 
all treated participants and all participants on demographics, baseline characteristics, and AE 
displays, and using the available data for the study population as observed. Summaries of 
concentration data will be based on geometric mean and geometric standard deviation instead of 
arithmetic versions. All tabulations will be sorted by treatment, parameter and visit (including 
time relative to dosing if applicable, unless otherwise stated). Only scheduled visits and times 
relative to dosing will be included in the tabulation. 
Categorical data will be summarized by visit and treatment group, including columns for all 
treated study participants and all study participants on demographics, baseline characteristics, 
and AE displays, using the number and percent of study participants in each category. 
Percentages will be based on the corresponding population size (ie, the denominator of 
percentages should match the sample size in the column header), unless otherwise noted via 
footnote in the applicable summary table. 
Statistical tests of efficacy variables will be presented as 2-sided p-values. P-values will be 
rounded to 4 decimal places. P-values less than 0.0001 will be presented as “<0.0001” and 
p-values greater than 0.9999 will be presented as “>0.9999.” 
Handling of multiplicity for the primary and key secondary efficacy variables is discussed in 
Section 9.4. All other efficacy variables will be considered secondary or exploratory and will be 
assessed at a nominal 2-sided α=0.05 significance level. 
9.2.2 
Analysis time points 
The timeframe for this protocol compasses the entire study, which extends from Screening to 
10 weeks after the final dose, ie, 48 weeks of Double-Blind Treatment Period and 6 weeks of 
SFU Period. 
The following study periods will be included in the analysis: 
• Screening Period: up to 14 days (Day -14 through Day -1). 
• Double-Blind Treatment Period: 48 weeks, starts with the randomization (1:2) of eligible 
participants to 1 of 2 treatment arms (SOC+PBO or SOC+DZP 24mg/kg), stratified in 
accordance with the 3 stratification factors. Study medication will be administered by iv 
infusion every 4 weeks, starting on Day 1. 
• Safety Follow-up Period: 6 weeks, participants who complete the 48-week Double-Blind 
Treatment Period will continue into this 6-week SFU Period. During this period, participants 
will not receive study medication but will be able to receive SOC treatment, as indicated. 
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The time points for individual assessments are provided in Table 1-2. 
Analyses conducted by visit will include each planned study visit at which the assessment was 
scheduled. Data for planned study visits will be based on the nominal time point and will not 
include any unplanned visits. Usually, efficacy data will not be obtained at unscheduled visits, 
with the following exceptions: labs in BILAG and SLEDAI-2K. Here labs that are obtained up to 
2 weeks after the original visit are used to replace missing lab data. 
Study participant data listings will include all time points for collected data, including all 
assessments (planned or unplanned). Data for derived time points Last Visit and Early 
Withdrawal will be included in study participant data listings. 
9.2.3 
Definition of Baseline values 
Unless otherwise specified, the last value obtained prior to the first infusion of study medication 
(Visit 2) will be used as the Baseline value. If a Baseline measurement is missing, and a 
Screening value available, the Screening value will be utilized as Baseline instead. 
For vital signs, a measurement prior to, or at the moment of, the start of the first infusion will be 
available for each visit. The last measurement prior to, or at the moment of, the start of the first 
infusion of study medication will be used as the baseline value. An additional analysis will be 
performed using the pre-infusion values as baseline values and determine the changes from pre-
infusion to post-infusion for each infusion visit. At each post-Baseline Visit, the pre-infusion 
value will be one taken prior to, or at the moment of, the start of the infusion of study 
medication. 
For Baseline assessments, if the BILAG 2004 is completed, but the grade for 1 or more 
individual system(s) is missing, the grade for the system will be set to a grade of BILAG 2004 D 
if no value can be imputed from the Screening Visit. This is a conservative approach for study 
participants on active doses, since no improvement can occur following a baseline grade of 
BILAG 2004 D level disease. 
9.3 
Planned efficacy/outcome analyses 
9.3.1 
Analysis of the primary efficacy/primary endpoint 
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9.3.1.1 
Sensitivity analysis 
The primary analysis described in Section 9.3.1 will be repeated using the PPS as a sensitivity 
analysis. In addition to this, the following sensitivity analyses will also be performed. 
The primary endpoint will also be analyzed using a logistic regression model for BICLA 
response at Week 48 as a function of treatment group, controlling for randomization stratification 
factors. Odds ratio, 95% CI, and 2-sided p-value based on the Wald Chi-square statistic will be 
presented. 
Study participants who have a missing value for the Week 48 treatment response assessment 
(including those who withdraw/dropout prior to the Week 48 Visit), will be included in the 
primary efficacy analysis as non-responders. To examine the impact of such missing data on the 
primary analysis, tipping point analyses that systematically vary assumptions about the missing 
outcomes on the two treatment groups will be performed as a sensitivity analysis. 
The details of all of the above sensitivity analyses and any additional sensitivity analyses will be 
included in the SAP. 
9.3.2 
Analysis of secondary efficacy endpoints 
The handling of intercurrent events for all secondary efficacy endpoints will be described in the 
SAP. 
9.3.2.1 
Analysis of key secondary endpoints 
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9.3.2.1.1 
Multiplicity control strategy 
The multiplicity control strategy of the overall Type-I error rate α (2-sided 5%) is described 
below and presented in Figure 9-1. 
Step 1: First perform the primary endpoint comparison of BICLA responder rate at Week 48 
comparison for SOC+DZP 24mg/kg versus SOC+PBO at the α level (2-sided 0.05), this serves 
as a gatekeeping step. 
If it is not significant at the α level, then stop the rest of the comparison procedure, that is, no 
other formal comparisons will be performed. 
If it is significant at the α level, then proceed to perform key secondary endpoint comparisons as 
follows. 
Step 2: Perform the first key secondary efficacy endpoint comparison of BICLA responder rate 
at Week 24 for SOC+DZP 24mg/kg versus SOC+PBO. 
If it is not significant at the α level, then stop the rest of the comparisons. 
If it is significant at the α level, then continue to: 
Step 3: Perform the second key secondary efficacy endpoint comparison of severe BILAG 2004 
flare prevention responder rate at Week 48 for SOC+DZP 24mg/kg versus SOC+PBO. 
If it is not significant at the α level, then stop the rest of comparisons. 
If it is significant at the α level, continue to: 
Step 4: Apply Hochberg Method for the next 2 key secondary endpoint comparisons in parallel 
(concurrently). 
If the larger p-value is ≤α, then both comparisons are statistically significant. 
Otherwise (ie, the larger p-value is > α), if the smaller p-value is ≤ α/2, then the corresponding 
comparison is statistically significant. 
Otherwise (ie, the smaller p-value is > α/2), then neither comparison is statistically significant. 
Step 5: Only if both of these 2 key secondary endpoint comparisons are significant (ie, the larger 
p-value is ≤ α), will proceed to the fifth key secondary endpoint BICLA responder rate at 
Week 12 and it will be tested at the α significance level. 
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Figure 9-1: Multiplicity strategy figure 
 
EP=endpoint; KSE=key secondary endpoint; NS=not significant; sig=significant. 
This strategy combines gatekeeping procedures and the Hochberg method to assure the overall 
Type-I error rate is controlled at the α (2-sided 0.05) level. 
All other efficacy/outcome analyses will either be other-secondary or exploratory in nature 
without multiplicity adjustments. 
9.3.2.2 
Analysis of other secondary endpoints 
Other secondary efficacy endpoints are the following: 
• Achievement of BILAG improvement without worsening at Week 48 
• Change from Baseline in PGA at Week 48 
• Achievement of SRI4 response at Week 48 
• Achievement of prevention of moderate/severe BILAG flares (moderate/severe BILAG flare-
free) through Week 48 
• Time to severe BILAG flare through Week 48 
• Time to moderate/severe BILAG flare through Week 48 
The analysis methods for these endpoints are described below and details will be included in the 
SAP. 
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For response rate type of endpoints such as achievement of BILAG improvement without 
worsening at Week 48, they will be analyzed the same way as for the primary efficacy endpoint 
without sensitivity analyses. 
For change from Baseline in PGA at Week 48, it will be analyzed the same way as for the key 
secondary endpoint of change from Baseline in SLEDAI-2K at Week 48. 
Time to event endpoints (eg, time to severe BILAG flare through Week 48) will be analyzed 
using statistical survival analysis methods. The time to event will be defined as the time until the 
start of the event. Participants who do not achieve an event by Week 48 or the early termination 
visit will be censored at the date of the last assessment during study period. Survival curves will 
be generated using the Kaplan-Meier product limit estimate. The treatment difference between 
SOC+DZP and SOC+PBO will be analyzed using the stratified log-rank statistic, adjusting for 
stratification factors (if feasible). Median time to event values for each treatment group will be 
summarized and Kaplan-Meier survival curves will be presented by treatment group on a single 
graph. 
9.3.3 
Analysis of tertiary efficacy endpoints 
The tertiary efficacy endpoints are listed Table 3-1. The analysis methods for these endpoints are 
briefly described by categories below and more details will be included in the SAP. 
For response rate type of endpoints such as achievement of BICLA response by visit, they will 
be analyzed the same way as for the primary efficacy endpoint without sensitivity analyses. 
For change from Baseline type of endpoints where the continuous variable analysis methods can 
be applied, they will be analyzed the same way as for the key secondary endpoint of change from 
Baseline in SLEDAI-2K at Week 48. 
For time to event endpoints, they will be analyzed using statistical survival analysis methods as 
described for time to severe BILAG flare through Week 48. 
9.3.4 
Primary efficacy subgroup analyses 
The following subgroup analyses are intended to be performed for the primary efficacy endpoint 
using descriptive statistics, however the list of pre-specified subgroup analyses will be finalized 
in the SAP: 
• Subgroups defined by prior use of biological response modifier vs no prior use 
• Subgroups defined by prior use of belimumab vs. no prior use 
• Subgroups representing stratification factors (Pooled regions, chronic active vs. acute flaring, 
SLEDAI-2K <10 vs ≥10) 
• Subgroups defined by study participants on antimalarials and corticosteroids vs. other 
(EULAR treatment guidance subgroup) 
• Subgroups defined by 
 positive AND low complement vs. other 
• Subgroups defined by 
 positive AND low complement AND SLEDAI 
≥10 vs other 
• Subgroups defined by activity (grade) in BILAG organ systems 
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• Subgroups defined by region 
• Subgroups defined by ethnicity 
• Subgroups by presence of any organ system with a BILAG A vs. other 
• Subgroups defined by low complement vs. other 
• Subgroup defined by young age (<25) vs. other 
• Subgroups defined by gender 
• Subgroup by evidence for at least 1 additional flare in medical history within the past 
24 weeks vs. other 
• Subgroups defined by: 
− Antimalarials at Baseline: yes/no 
− Immunosuppressants at Baseline: yes/no 
− Corticosteroid dose at Baseline: >7.5mg/day yes/no 
9.4 
Planned safety and other analyses 
9.4.1 
Safety analyses 
Safety variables will be analyzed for all study participants in the SS. 
Adverse events will be coded according to the Medical Dictionary for Regulatory Activities 
(MedDRA®). The frequency of all AEs during the study period will be presented for each 
treatment group separately by System Organ Class, high level term, and preferred term. The data 
will be displayed as number of study participants experiencing the AEs, percentage of study 
participants, and number of AEs. Data will also be corrected for exposure and reported by 
100 patient-years. 
The incidence of study participants with AEs will be presented by treatment group and total 
treatment. Additional tables will summarize AEs leading to permanent discontinuation of study 
medication, AEs by maximum intensity, AEs by intensity, and AEs by relationship to study 
medication by treatment group and total treatment. Adverse events will be categorized by 
severity. The countermeasures taken for each AE, the time of onset of AEs after dosing, and AE 
duration will be listed. Additional tables with respect to all categories of AEs will also include 
the numbers of study participants who experienced the respective AE. 
All TEAEs (serious and nonserious), including TEAEs of special interest, TEAEs of special 
monitoring, and deaths will also be tabulated and listed. Other laboratory safety parameters will 
also be tabulated and listed. 
Laboratory evaluations, vital signs, and ECGs will be analyzed in the SS for observed cases. 
Descriptive statistics will be presented by treatment group at each time point: change from 
Baseline in vital signs, serum chemistry, hematology, and urinalysis.  For laboratory data, 
changes between the Baseline (predose) or, if missing, Screening value and each posttreatment 
assessment may be presented in shift tables or using other summaries as detailed in the SAP. 
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9.4.2 
Other analyses 
9.4.2.1 
Pharmacokinetic analyses 
Pharmacokinetic variables will be analyzed for all study participants in the PK-PPS. 
Individual study participant concentrations of DZP and PEG will be displayed graphically. They 
will be summarized using the statistics described for continuous variables (number of available 
observations, mean, median, standard deviation, minimum, and maximum) and in addition by the 
geometric mean and the geometric coefficient of variation (assuming log normally distributed 
data). 
 
 
If data merit, a population PK analysis and PK/PD analyses may be conducted for the clinical 
efficacy endpoints and PD variables of interest. All population PK and PK/PD analyses will be 
described in more detail in a separate Data Analysis Plan, and results will be reported in a 
separate report. 
9.4.2.2 
Immunogenicity analyses 
 incidence will be tabulated. More detailed specifications will 
be presented in the SAP. 
9.5 
Handling of protocol deviations 
Important protocol deviations are a subset of protocol deviations that may significantly impact 
the completeness, accuracy, and/or reliability of the study data or that may significantly affect a 
study participant’s rights, safety, or well-being. The criteria for identifying important protocol 
deviations will be defined within the appropriate protocol-specific document. Important protocol 
deviations will be reviewed as part of the ongoing data cleaning process and data evaluation. All 
important deviations will be identified and documented prior to unblinding to confirm exclusion 
from analysis sets. 
9.6 
Handling of dropouts or missing data 
As the primary efficacy variable is treatment responder rate in BICLA at Week 48, the handling 
of missing data, dropouts and intercurrent events is described as follows. 
• In case of the use of escape treatment as an intercurrent event prior to the Week 48 Visit 
(ie, the escape treatment initiation is at least 1 day before), study participants will be included 
for the primary analysis as non-responders per the composite strategy handling of this 
intercurrent event. 
• Study participants who prematurely withdraw from the study or permanently discontinue 
study medication prior to the Week 48 Visit, will be included for the primary analysis as non-
responders per the composite strategy handling of this intercurrent event. 
• Study participants who have a missing BICLA response for the Week 48 assessment for any 
other reason besides defined intercurrent events will be imputed as non-responders for the 
primary efficacy analysis. 
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• A modified non-responder imputation (mNRI)for missing data will be applied to its 
components, in order to obtain the BICLA response. If the Week 48 assessment was 
performed but the value for a single component (BILAG 2004, SLEDAI-2K, or PGA) is not 
available, then the missing component value will be imputed from the respective previous 
visit value prior to computing the BICLA treatment response variable (limited to 1 visit 
back). In the case where the predose laboratory result is missing (at Screening and at 
Baseline and there is no other unscheduled predose laboratory result), the BILAG 2004 
body/organ system Baseline score for the body system requiring the missing laboratory result 
will be set to a score of BILAG 2004 D level disease. More details will be included in the 
SAP. 
9.7 
Planned interim analysis and data monitoring 
There will be an IDMC that will meet periodically to monitor safety on an ongoing basis. In 
addition to safety data, this IDMC will review disposition, demographics and other Baseline 
characteristics, protocol deviations and compliance, as well as efficacy data to allow for benefit-
risk assessment. The IDMC can recommend terminating enrollment and stopping dosing if it is 
in the interest of patient safety, but the study cannot be stopped prematurely for overwhelmingly 
positive efficacy results. Thus, there will be no risk of increasing the false positive (Type I error) 
rate due to IDMC monitoring, and no alpha-level adjustment for the final analysis will be made. 
Further details of the IDMC will be specified in the IDMC Charter.  
There is no planned interim analysis. 
9.8 
Determination of sample size 
The statistical power and sample size consideration is based on the objective to detect a 20% 
improvement in BICLA responder rate compared with SOC+PBO at Week 48. Given 104 study 
participants in SOC+PBO and 208 study participants in SOC+DZP 24mg/kg groups and an 
assumed SOC+PBO responder rate of 0.32, there will be 90% power to confirm an SOC+DZP 
24mg/kg responder rate of 0.52 (ie, a 0.20 improvement), corresponding to a 2-sided 0.05 
significance level test (SAS® v9.4 POWER procedure, Fisher’s exact). The sample size 
assumptions for SOC+PBO and SOC+DZP 24mg/kg responder rates are based on the Phase 2b 
study SL0023 responder data at Week 24. 
Participants who withdraw from the study prior to the Week 48 Visit will be included in the 
primary efficacy analysis as non-responders. Therefore, no additional participants are planned to 
be randomized in order to make up for early withdrawers. 
10 
SUPPORTING DOCUMENTATION AND OPERATIONAL 
CONSIDERATIONS 
10.1 
Appendix 1: Regulatory, ethical, and study oversight 
considerations 
10.1.1 
Regulatory and ethical considerations 
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
International Council on Harmonisation-Good Clinical Practice (ICH-GCP), and in accordance 
with the ethical principles that have their origin in the Declaration of Helsinki. 
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The Investigator/UCB will ensure that an appropriately constituted IRB/IEC that complies with 
the requirements of the current ICH-GCP version or applicable country-specific regulations will 
be responsible for the initial and continuing review and approval of the clinical study. Prior to 
initiation of the study, the Investigator/UCB will forward copies of the protocol, ICF, IB, 
Investigator’s curriculum vitae (if applicable), advertisement (if applicable), and all other 
participant-related documents to be used for the study to the IRB/IEC for its review and 
approval. 
Before initiating a study, the Investigator will have written and dated full approval from the 
responsible IRB/IEC for the protocol. 
The Investigator will also promptly report to the IRB/IEC all changes in the study, all 
unanticipated problems involving risks to participants or others, and any protocol deviations, to 
eliminate immediate hazards to participants. 
The Investigator will not make any changes in the study or study conduct without IRB/IEC 
approval, except where necessary to eliminate apparent immediate hazards to the participants. 
For minor changes to a previously approved protocol during the period covered by the original 
approval, it may be possible for the Investigator to obtain an expedited review by the IRB/IEC as 
allowed. 
As part of the IRB/IEC requirements for continuing review of approved studies, the Investigator 
will be responsible for submitting periodic progress reports to the IRB/IEC (based on IRB/IEC 
requirements), at intervals appropriate to the degree of participant risk involved, but no less than 
once per year. The Investigator should provide a final report to the IRB/IEC following study 
completion. 
UCB (or its representative) will communicate safety information to the appropriate regulatory 
authorities and all active Investigators in accordance with applicable regulatory requirements. 
The appropriate IRB/IEC will also be informed by the Investigator or the Sponsor, as specified 
by the applicable regulatory requirements in each concerned country. Where applicable, 
Investigators are to provide the Sponsor (or its representative) with evidence of such IRB/IEC 
notification. 
10.1.2 
Financial disclosure 
Insurance coverage will be handled according to local requirements. 
Finance and insurance are addressed in the Investigator and/or CRO agreements, as applicable. 
10.1.3 
Informed consent process 
Participant’s informed consent/assent must be obtained and documented in accordance with local 
regulations, ICH-GCP requirements, and the ethical principles that have their origin in the 
principles of the Declaration of Helsinki. 
Prior to obtaining informed consent, information should be given in a language and at a level of 
complexity understandable to the participant in both oral and written form by the Investigator (or 
designee). Each participant will have the opportunity to discuss the study and its alternatives 
with the Investigator. 
Prior to participation in the study, the ICF should be signed and personally dated by the 
participant, or his/her legal representative, and by the person who conducted the informed 
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consent discussion (Investigator or designee). The participant or his/her legal representative must 
receive a copy of the signed and dated ICF. The study participant of legal age who is incapable 
of comprehending the nature, significance and implications of the clinical trial and of 
determining his/her will in the light of these facts, must not be included in the study. The ICF 
should be signed and personally dated by the participant, or, in case of minors, the informed 
assent must be obtained in addition to his/her legal representative’s consent.  
As part of the consent process, each participant must consent to direct access to his/her medical 
records for study-related monitoring, auditing, IRB/IEC review, and regulatory inspection. 
If the ICF is amended during the study, the Investigator (or the Sponsor, if applicable) must 
follow all applicable regulatory requirements pertaining to the approval of the amended Informed 
Consent form by the IRB/IEC and use of the amended form. 
All studies conducted at centers in the United States must include the use of a Health Insurance 
Portability and Accountability Act Authorization form. 
The participant may withdraw his/her consent to participate in the study at any time. A 
participant is considered as enrolled in the study when he/she has signed the ICF. An eCRF must 
not be started, nor may any study specific procedure be performed for a given participant, 
without having obtained his/her written consent to participate in the study. 
10.1.4 
Data protection 
UCB staff (or designee) will affirm and uphold the participant’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the participant number 
assigned at Screening. 
The Investigator agrees that representatives of UCB, its designee, representatives of the relevant 
IRB/IEC, or representatives of regulatory authorities will be allowed to review that portion of the 
participant’s primary medical records that directly concerns this study (including, but not limited 
to, laboratory test result reports, ECG reports, admission/discharge summaries for hospital 
admissions occurring during a participant’s study participation, and autopsy reports for deaths 
occurring during the study). 
The participant must be informed that his/her personal study-related data will be used by the 
Sponsor in accordance with local data protection law. The level of disclosure must also be 
explained to the participant. 
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by the Sponsor, by 
appropriate IRB/IEC members, and by inspectors from regulatory authorities. 
10.1.5 
Committees structure 
The IDMC regularly reviewing data snapshots will be comprised of 3 independent medical 
experts (voting), an unblinded statistician, and the Sponsor's medical representatives (not voting 
and not part of open session). Other experts may be included in this group as voting or 
non-voting members or consulted at the discretion of the Sponsor. Further details are described 
in the IDMC Charter. 
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10.1.6 
Data quality assurance 
All participant data relating to the study will be recorded on printed, eCOA or eCRF unless 
transmitted to the Sponsor or designee electronically (eg, laboratory data). The Investigator is 
responsible for verifying that data entries are accurate and correct by physically or electronically 
signing the eCRF or eCOA. 
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the eCRF or eCOA. 
The Investigator must permit study-related monitoring, audits, IRB/IEC review, and regulatory 
agency inspections and provide direct access to source data documents. 
The Sponsor or designee is responsible for the data management of this study including quality 
checking of the data. 
Study monitors will perform ongoing source data verification to confirm that data entered into 
the eCRF by authorized site personnel are accurate, legible, contemporaneous, original, and 
attributable from source documents; that the safety and rights of participants are being protected; 
and that the study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH-GCP, and all applicable regulatory requirements. 
All essential documents must be retained by the Investigator for the minimum retention period 
mandatory under the applicable local laws and regulations. The Investigator will contact UCB 
for authorization prior to the destruction of any study records or in the event of accidental loss or 
destruction of any study records. The Investigator will also notify UCB should he/she relocate or 
move the study-related files to a location other than that specified in the Sponsor’s trial master 
file. 
Quality tolerance limits will be established for the study using parameters related to patient 
safety reporting and reliability of study results. The parameters will be monitored throughout the 
study to identify systemic issues. Parameters used, parameter values, important deviations from 
the quality tolerance limits, and actions taken will be summarized in the clinical study report.   
10.1.6.1 
Case Report form completion 
The Investigator is responsible for prompt reporting of accurate, complete, and legible data in the 
eCRFs or eCOA and in all required reports. 
Any change or correction to the eCRF or eCOA after saving must be accompanied by a reason 
for the change. 
Corrections made after the Investigator’s review and approval (by means of a 
password/electronic signature) will be reapproved by the Investigator. 
The Investigator should maintain a list of personnel authorized to enter data into the eCRF or 
eCOA. 
Detailed instructions will be provided in the eCRF/eCOA Completion Guidelines. 
10.1.6.2 
Apps 
Study participants will be given a smart phone with the MyUCB4me tool to enter their 
corticosteroid use. 
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The data recorded in the MyUCB4me tool are not intended to be used to influence the treatment 
decisions of study participants during the conduct of this study. Rather, the data will be analyzed 
at the end of the study to determine whether the design of the app enables the collection of 
information that has potential benefit in the future treatment of SLE. 
Furthermore, this app is designed to only record data associated with the participant’s disease 
state, and therefore it is neither designed nor intended to be used to collect or report 
safety-related information about the participant. 
To ensure the confidence in the reliability, quality, and integrity of the data, several security 
measures have been put in place. The MyUCB4me tool itself is protected by a Personal 
Identification Number that is known only to the participant in SL0043. Furthermore, the 
MyUCB4me tool also allows for qualified and trained site personnel to personalize the 
configuration for each participant. The access to the personalized configuration within the 
MyUCB4me tool is password protected, and the password is only known to the site personnel. 
All data entered by the study participant are fully encrypted within the MyUCB4me tool and its 
transmission to UCB Systems. 
The participant responds to the questions and acts on the requested activities in the MyUCB4me 
tool. All data collected as part of these activities will be stored locally in the MyUCB4me tool. 
All data are reviewable for the Investigator while the participant is at the site. The data collected 
are synchronized with UCB Systems. All data in the MyUCB4me tool will be erased upon 
configuration for a new participant. All data collected will be provided back to the sites in a 
human readable way. 
10.1.7 
Source documents 
All source documents must be accurate, clear, unambiguous, permanent, and capable of being 
audited. They should be made using some permanent form of recording (ink, typing, printing, 
optical disc). They should not be obscured by correction fluid or have temporary attachments 
(such as removable self-stick notes). Photocopies and/or printouts of eCRFs are not considered 
acceptable source documents. 
Source documents are original records in which raw data are first recorded. These may include 
hospital/clinic/general practitioner records, charts, diaries, x-rays, laboratory results, printouts, 
pharmacy records, care records, ECG or other printouts, completed scales, QoL questionnaires, 
or video, for example. Source documents should be kept in a secure, limited access area. 
Source documents that are computer generated and stored electronically must be printed for 
review by the monitor (eg, ECG reports). Once printed, these copies should be signed and dated 
by the Investigator and become a permanent part of the participant’s source documents. The 
Investigator will facilitate the process for enabling the monitor to compare the content of the 
printout and the data stored in the computer to ensure all data are consistent. 
Electronic data records, such as Holter monitor records or electroencephalogram records, must 
be saved and stored as instructed by UCB (or designee). 
Source documents including clinical notes, doctor’s letters, histology reports, reports of technical 
medical assessments (ie, imaging, electrography, ultrasound, laboratory reports), or photographs 
of cutaneous SLE manifestations may be requested in indicated cases and provided after 
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pseudonymization to a medical team established by the Sponsor for central source review of AEs 
and efficacy outcomes (see Section 8.1.1 and Section 10.3). 
10.1.8 
Study and site closure 
The Sponsor designee reserves the right to close the study site or terminate the study at any time 
for any reason at the sole discretion of the Sponsor. Study sites will be closed upon study 
completion. A study site is considered closed when all required documents and study supplies 
have been collected and a study-site closure visit has been performed. 
The Investigator may initiate study-site closure at any time, provided there is reasonable cause 
and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study site by the Sponsor or Investigator may include but are 
not limited to: 
• Failure of the Investigator to comply with the protocol, the requirements of the IRB/IEC or 
local health authorities, the Sponsor's procedures, or GCP guidelines 
• Inadequate recruitment of participants by the Investigator 
• Discontinuation of further study medication development 
10.1.9 
Publication policy 
The results of this study may be published or presented at scientific meetings. If this is foreseen, 
the Investigator agrees to submit all manuscripts or abstracts to the Sponsor before submission. 
This allows the Sponsor to protect proprietary information and to provide comments. 
The Sponsor will comply with the requirements for publication of study results. In accordance 
with standard editorial and ethical practice, the Sponsor will generally support publication of 
multicenter studies only in their entirety and not as individual site data. In this case, a 
coordinating Investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International Committee of 
Medical Journal Editors authorship requirements. 
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10.2 
Appendix 2: Clinical laboratory tests 
• The tests detailed in the table below will be performed by the central laboratory with the 
exception of urine pregnancy tests and ESR. 
• Local laboratory results are only required in the event that the central laboratory results are 
not available in time for either study treatment administration and/or response evaluation. If a 
local sample is required, it is important that the sample for central analysis is obtained at the 
same time. Additionally, if the local laboratory results are used to make either a study 
treatment decision or response evaluation, the results must be entered into the eCRF. 
• Protocol-specific requirements for inclusion or exclusion of participants are detailed in 
Section 5.1 and Section 5.2. 
• Additional tests may be performed at any time during the study as determined necessary by 
the Investigator or required by local regulations. 
• Study participants are to rest in a supine position for at least 10min before blood samples are 
taken. Blood samples are to be taken in the arm opposite the one used for infusion. Blood 
samples must not be drawn through the infusion cannula. 
• At visits for which serum creatinine values are available, eGFR will be calculated using the 
Modification of Diet in Renal Disease formula modified for race. 
Protocol-Required Safety Laboratory Assessments 
Laboratory 
Assessments 
Parameters 
Hematology 
Platelet Count  
RBC Indices: 
MCV 
MCH 
%Reticulocytes 
MCH concentration 
WBC Count with 
Differential: 
Neutrophils 
Lymphocytes 
Monocytes 
Eosinophils 
Basophils 
 
RBC Count 
Hemoglobin 
Hematocrit 
Erythrocyte sedimentation 
rate 
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Laboratory 
Assessments 
Parameters 
Clinical 
Chemistrya 
Blood Urea 
Nitrogen 
(BUN) 
Potassium 
Sodium 
Chloride 
Calcium 
Phosphate 
Aspartate Aminotransferase 
(AST)/ Serum glutamic-
oxaloacetic transaminase 
(SGOT) 
Total and direct 
bilirubin 
 
Creatinine 
Alanine (ALT)/ serum 
glutamic-pyruvic transaminase 
(SGPT) 
Total protein 
and albumin 
 
Glucose 
(nonfasting) 
Alkaline phosphatase 
GGT 
LDH 
Lipase 
Total 
cholesterol and 
triglycerides 
Lipase 
Creatine 
phosphokinase, 
CK-MB and 
Troponine I 
from serum in 
case of 
increased CPK 
Routine 
Urinalysis 
• 
Specific gravity 
• 
pH, glucose, protein, blood, ketones, bilirubin, urobilinogen, nitrite, 
leukocyte esterase by dipstick 
• 
Protein, albumin, and creatinine (for protein:creatinine ratio [mg/mmol] and 
albumin:creatinine [mg/mmol] ratios) 
• 
Microscopy of sediment for RBCs, RBC casts, WBCs, and WBC casts 
Other Screening 
Tests 
• 
Follicle-stimulating hormone and estradiol (as needed in women of 
non-childbearing potential only) 
• 
Serum or urine human chorionic gonadotropin (hCG) pregnancy test (as 
needed for women of childbearing potential)b 
• 
Serology (hepatitis B surface antigen, hepatitis B core antibody, and 
hepatitis C virus antibody), plasma HIV antibody, and reflex testing 
• 
Tuberculosis test (IGRA): Quantiferon test 
All study-required laboratory assessments will be performed by a central laboratory. 
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Laboratory 
Assessments 
Parameters 
Additional 
assessments 
NOTES : 
a Details of liver chemistry stopping criteria and required actions and follow-up assessments after liver stopping 
or monitoring event are given in Section 10.6. All events of ALT 3×upper limit of normal (ULN) and bilirubin 
2 ×ULN (>35% direct bilirubin) or ALT 3×ULN and international normalized ratio (INR) >1.5, if INR 
measured, may indicate severe liver injury (possible Hy’s Law) and must be reported as an SAE (excluding 
studies of hepatic impairment or cirrhosis). 
b Local urine testing will be standard for the protocol (for all assessments after Screening) unless serum testing is 
required by local regulation or IRB/IEC. 
Investigators must document their review of each laboratory safety report. 
Laboratory results that could unblind the study will not be reported to investigative sites or other 
blinded personnel until the study has been unblinded. 
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10.3 
Appendix 3: AEs – definitions and procedures for recording, 
evaluating, follow-up, and reporting 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a patient or clinical study participant, temporally 
associated with the use of study medication, whether or not considered related to the study 
medication. 
• 
NOTE: An AE can therefore be any unfavorable and unintended sign (including an abnormal 
laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of study medication. 
 
Events Meeting the AE Definition 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) not related 
to SLE or other safety assessments (eg, ECG, radiological scans, vital signs measurements not 
related to SLE, including those that worsen from baseline, considered clinically significant in 
the medical and scientific judgment of the Investigator (ie, not related to progression of 
underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition other than SLE including either 
an increase in frequency and/or intensity of the condition. 
• 
New conditions not SLE related detected or diagnosed after study medication administration 
even though it may have been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug-drug interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study medication or 
a concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
• 
"Lack of efficacy" or "failure of expected pharmacological action" per se will not be reported 
as an AE or SAE. Such instances will be captured in the efficacy assessments. However, the 
signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as 
SAE if they fulfil the definition of a SAE. 
 
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Events NOT Meeting the AE Definition 
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments 
which are associated with the underlying disease (SLE) except it fulfills seriousness criteria. 
• 
SLE or expected progression, signs, or symptoms of the SLE except they fulfill seriousness 
criteria. 
• 
Medical or surgical procedure (eg, endoscopy, appendectomy): the condition that leads to the 
procedure is the AE. 
• 
Situations in which an untoward medical occurrence did not occur (social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or 
detected at the start of the study that do not worsen. 
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Definition of SAE 
If an event is not an AE per definition above, then it cannot be an SAE even if serious conditions 
are met (eg, hospitalization for signs/symptoms of the disease under study, death due to 
progression of disease). 
An SAE is defined as any untoward medical occurrence that, at any dose: 
a. Results in death 
b. Is life-threatening 
The term 'life-threatening' in the definition of 'serious' 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, which hypothetically might have 
caused death, if it were more severe. 
c. Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is 
not considered an AE. 
d. Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance 
such as uncomplicated headache, nausea, vomiting, diarrhea, 
, and accidental trauma 
(eg, sprained ankle) which may interfere with or prevent everyday life functions but do not 
constitute a substantial disruption. 
e. Is a congenital anomaly/birth defect 
f. Important medical events: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately 
life-threatening or result in death or hospitalization but may jeopardize the participant or may 
require medical or surgical intervention to prevent one of the other outcomes listed in the 
above definition. These events should usually be considered serious. 
• 
Examples of such events include, but are not limited to, potential Hy’s law, invasive or 
malignant cancers, intensive treatment in an emergency room or at home for allergic 
bronchospasm, blood dyscrasias or convulsions that do not result in hospitalization, or 
development of drug dependency or drug abuse. 
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Recording and Follow-Up of AE and/or SAE 
AE and SAE Recording 
• 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all 
documentation (eg, hospital progress notes, laboratory reports, and diagnostics reports) related 
to the event. 
• 
The Investigator will then record all relevant AE/SAE information in the eCRF. 
• 
It is not acceptable for the Investigator to send photocopies of the participant’s medical records 
to UCB in lieu of completion of the UCB/AE/SAE eCRF page. 
• 
There may be instances when copies of medical records for certain cases are requested by 
UCB. In this case, all participant identifiers, with the exception of the participant number, will 
be redacted on the copies of the medical records before submission to UCB. 
• 
The Investigator will attempt to establish a diagnosis of the event based on signs, symptoms, 
and/or other clinical information. Whenever possible, the diagnosis (not the individual 
signs/symptoms) will be documented as the AE/SAE. 
Assessment of Intensity 
The Investigator will make an assessment of intensity for each AE and SAE reported during the study 
and assign it to 1 of the following categories: 
• 
Mild: An event that is easily tolerated by the participant, causing minimal discomfort and not 
interfering with everyday activities. 
• 
Moderate: An event that causes sufficient discomfort and interferes with normal everyday 
activities. 
• 
Severe: An event that prevents normal everyday activities. An AE that is assessed as severe 
should not be confused with a SAE. Severe is a category utilized for rating the intensity of an 
event; and both AEs and SAEs can be assessed as severe. 
• 
An event is defined as ‘serious’ when it meets at least 1 of the predefined outcomes as 
described in the definition of an SAE, NOT when it is rated as severe (eg, a severe AE may be 
either serious or not serious, depending on whether these criteria are also met). 
The National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) or the 
Rheumatology Common Terminology Criteria (RCTC) should be used as a supportive standardization 
instrument to evaluate AEs and SAEs but the final intensity grading by the Investigator must be mild, 
moderate, or severe. 
 
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Assessment of Causality 
• 
The Investigator is obligated to assess the relationship between study medication and each 
occurrence of each AE/SAE. 
• 
A "reasonable possibility" of a relationship conveys that there are facts, evidence, and/or 
arguments to suggest a causal relationship, rather than a relationship cannot be ruled out. 
• 
The Investigator will use clinical judgment to determine the relationship. 
• 
Alternative causes, such as underlying disease(s), concomitant therapy, and other risk factors, 
as well as the temporal relationship of the event to study medication administration will be 
considered and investigated. 
• 
The Investigator will also consult the IB and/or Product Information, for marketed products, in 
his/her assessment. 
• 
For each AE/SAE, the Investigator must document in the medical notes that he/she has 
reviewed the AE/SAE and has provided an assessment of causality. 
• 
There may be situations in which an SAE has occurred and the Investigator has minimal 
information to include in the initial report to UCB. However, it is very important that the 
Investigator always make an assessment of causality for every event before the initial 
transmission of the SAE data to UCB. 
• 
The Investigator may change his/her opinion of causality in light of follow-up information and 
send a SAE follow-up report with the updated causality assessment. 
• 
The causality assessment is one of the criteria used when determining regulatory reporting 
requirements. 
 
Follow-up of AEs and SAEs 
• 
The Investigator is obligated to perform or arrange for the conduct of supplemental 
measurements and/or evaluations as medically indicated or as requested by UCB to elucidate 
the nature and/or causality of the AE or SAE as fully as possible. This may include additional 
laboratory tests or investigations, histopathological examinations, or consultation with other 
health care professionals. 
• 
An AE should be followed until it has resolved, has a stable sequelae, the Investigator 
determines that it is no longer clinically significant, or the participant is lost to follow up. This 
follow-up requirement applies to AEs, SAEs, and AEs of special interest. 
• 
If a participant dies during participation in the study or during a recognized follow-up period, 
the Investigator will provide UCB with a copy of any post-mortem findings including 
histopathology. 
• 
New or updated information will be recorded in the originally completed eCRF. 
• 
The Investigator will submit any updated SAE data to the Sponsor within 24 hours of receipt of 
the information. 
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Reporting of SAEs 
SAE Reporting to UCB via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to UCB will be the electronic data collection 
tool. 
• 
If the electronic system is unavailable for more than 24 hours, then the site will use the paper 
SAE data collection tool (see next section). 
• 
The site will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given site, the electronic data collection tool will be taken off-
line to prevent the entry of new data or changes to existing data. 
• 
If a site receives a report of a new SAE from a study participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then 
the site can report this information on a paper SAE form (see next section) or to the UCB 
Study Physician by telephone. 
• 
Contacts for SAE reporting can be found in SERIOUS ADVERSE EVENT REPORTING.  
 
SAE Reporting to UCB via Paper CRF 
• 
Facsimile transmission of the SAE paper CRF is the preferred method to transmit this 
information to the UCB Study Physician. 
• 
In rare circumstances and in the absence of facsimile equipment, notification by telephone is 
acceptable with a copy of the SAE data collection tool sent by overnight mail or courier 
service. 
• 
Initial notification via telephone does not replace the need for the Investigator to complete and 
sign the SAE CRF pages within the designated reporting time frames. 
• 
Contacts for SAE reporting can be found in SERIOUS ADVERSE EVENT REPORTING.  
AEOIs and AESMs should be reported to UCB within 24 hours irrespective of seriousness using 
the same procedures as reporting SAEs. 
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10.4 
Appendix 4: Contraceptive guidance and collection of 
pregnancy information 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming post-menopausal unless 
permanently sterile (see below). 
Women in the following categories are not considered WOCBP: 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
− Documented hysterectomy 
− Documented bilateral salpingectomy 
− Documented bilateral oophorectomy 
Note:  Documentation can come from the site personnel’s review of the participant’s medical 
records, medical examination, or medical history interview. 
3. Postmenopausal female 
− A postmenopausal state is defined as no menses for 12 months without an alternative 
medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal 
range may be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence of 
12 months of amenorrhea, a single FSH measurement is insufficient. 
− Females on HRT and whose menopausal status is in doubt will be required to use one of 
the non-estrogen hormonal highly effective contraception methods if they wish to 
continue their HRT during the study. Otherwise, they must discontinue HRT to allow 
confirmation of postmenopausal status before study enrollment. 
Contraception Guidance 
Male participants 
Male participants with female partners of childbearing potential (including partners who are 
pregnant or breastfeeding [including pumping breast milk to feed to a child]) must use 
contraception if any of the following criteria are met: 
• Genotoxic study medication 
• Study medication where reproductive toxicology studies have not yet been conducted 
• Study medication with demonstrated or suspected human teratogenicity/fetotoxicity at 
subtherapeutic exposure levels if relevant systemic concentrations may be achieved in 
WOCBP from exposure to seminal fluid 
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Male participants with female partners of childbearing potential are eligible to participate if they 
agree to ONE of the following during the protocol-defined time frame in Section 5.1: 
• Are abstinent from penile-vaginal intercourse as their usual and preferred lifestyle (abstinent 
on a long-term and persistent basis) and agree to remain abstinent. 
• Agree to use a male condom plus partner use of a contraceptive method with a failure rate of 
<1% per year as described in the table below when having penile-vaginal intercourse with a 
WOCBP who is not currently pregnant. 
• Agree to use a male condom when having penile-vaginal intercourse WOCBP who is 
currently pregnant. 
In addition male participants must refrain from donating sperm for the duration of the study and 
for 17 weeks after the final dose of study medication. 
Male participants with a pregnant or breastfeeding (including pumping breast milk to feed to a 
child) partner must agree to remain abstinent from penile-vaginal intercourse or use a male 
condom during each episode of penile penetration during the study and for at least 17 weeks after 
the final dose of study medication. 
Female participants 
Female participants of childbearing potential are eligible to participate if they agree to use a 
highly effective method of contraception consistently and correctly as described in the table 
below. If the Investigator considers another contraception method not listed below but is proven 
to have a failure rate <1/100 patient-years (PEARL index) or participants use a combination of 
contraceptives with a failure rate <1/100 patient-years, then this method may be considered as 
effective contraception after discussion with the Medical Monitor or Sponsor Study Physician. 
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Highly Effective Contraceptive Methodsa 
Highly Effective Contraceptive Methods That Are User Dependentb 
Failure rate of <1% per year when used consistently and correctly. 
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulationc 
• 
Oral 
• 
Intravaginal 
• 
Transdermal 
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral 
• 
Injectable 
Highly Effective Methods That Are User Independent 
 
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device (IUD) 
• 
Intrauterine hormone-releasing system (IUS) 
• 
Bilateral tubal occlusion 
Vasectomized partner 
A vasectomized partner is a highly effective contraception method provided that the partner is the sole 
male sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional 
highly effective method of contraception should be used. 
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from 
heterosexual intercourse during the entire period of risk associated with the study medication. The 
reliability of sexual abstinence needs to be evaluated in relation to the duration of the study and the 
preferred and usual lifestyle of the participant. 
NOTES: 
a) In case of newly started contraception pills/IUDs, PI should consider the correct timing of starting/applying 
such methods in relation to the menstrual cycle and the manufacturing instruction as when these newly started 
methods would become effective. 
b) Typical use failure rates may differ from those when used consistently and correctly. Use should be consistent 
with local regulations regarding the use of contraceptive methods for participants participating in clinical studies. 
Potential drug-drug interactions of medicinal products or medical conditions (eg, gastrointestinal 
disturbances like diarrhea, vomiting) which could impact the effectiveness of oral contraceptives 
need to be considered as well. Respective prescribing information of concomitant medications 
needs to be consulted and guidance (SmPC, local/national or international guidance) on the need 
of additional contraceptive methods be followed.  
Female participants using mycophenolate treatment 
As per current EMA recommendations for contraception for men and women during 
mycophenolate treatment (EMA/828208/2017) patients who can get pregnant must use at least 
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one reliable form of contraception before, during, and for 6 weeks after stopping treatment. Two 
forms of contraception are preferred. 
As per current FDA label information (Cellcept [package insert] 2019), females of reproductive 
potential taking mycophenolate must receive contraceptive counseling and use acceptable 
contraception. Patients must use acceptable birth control during the entire mycophenolate 
therapy, and for 6 weeks after stopping mycophenolate, unless the patient chooses abstinence. 
Unless patients are abstinent, acceptable contraceptive methods for females of reproductive 
potential during, and for 6 weeks after, treatment with mycophenolate are shown below (Cellcept 
[package insert] 2019, Table 7): 
Option 1 
Methods to 
use alone 
Intrauterine devices (IUDs) 
Tubal sterilization 
Patient’s partner vasectomy 
 
OR 
 
Option 2 
Hormone Methods 
Choose 1 
 
Barrier Methods 
Choose 1 
Choose one 
 
AND 
 
hormone 
Estrogen and progesterone 
 
method AND 
• 
Oral contraceptive pill 
Diaphragm with spermicide 
one barrier 
• 
Transdermal patch 
Cervical cap with spermicide 
method 
• 
Vaginal ring 
Contraceptive sponge 
 
 
Male condom 
 
Progesterone-only 
Female condom 
 
• 
Injection 
 
 
• 
Implant 
 
 
OR 
 
Option 3 
Barrier Methods 
choose 1 
 
Barrier Methods 
choose 1 
Choose one 
barrier 
method from 
each column 
(must choose 
two methods) 
 
Diaphragm with spermicide 
Cervical cap with spermicide 
Contraceptive sponge 
AND 
 
Male condom 
Female condom 
Pregnancy testing 
• Women of childbearing potential should only be included after a confirmed menstrual period 
and a negative highly sensitive serum pregnancy test. 
• Additional urine pregnancy testing should be performed at monthly intervals during the 
treatment period and at End of Treatment/End of Study, after the final dose of study 
medication and as required locally. 
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• Pregnancy testing will be performed when pregnancy is suspected 
• Pregnancy testing will be performed at Screening and at every post-Screening visit before 
study medication application. 
• If a study participant is pregnant and stays in the study for observation no pregnancy testing 
will be performed as long as the pregnancy lasts. 
Male participants with partners who become pregnant 
• The Investigator will attempt to collect pregnancy information on any male participant’s 
female partner who becomes pregnant while the male participant is in this study. This applies 
only to male participants who receive study medication. If the study participant is later found 
to be on placebo, then pregnancy data collection can stop. 
• After obtaining the necessary signed informed consent from the pregnant female partner 
directly, the Investigator will record pregnancy information on the appropriate form and 
submit it to the Sponsor within 1 working day of learning of the partner’s pregnancy. The 
female partner will also be followed to determine the outcome of the pregnancy. Information 
on the status of the mother and child will be forwarded to the Sponsor. Generally, the 
follow-up will be at least 12 months after the delivery date. Any termination of the pregnancy 
will be reported regardless of fetal status (presence or absence of anomalies) or indication for 
the procedure. 
Female Participants who become pregnant 
• Any female participant who becomes pregnant while participating in the study will 
discontinue study medication. 
• The Investigator will collect pregnancy information on any female participant who becomes 
pregnant while participating in this study. Information will be recorded on the appropriate 
form and submitted to the Sponsor within 1 working day of learning of a participant's 
pregnancy. The participant will be followed to determine the outcome of the pregnancy. The 
Investigator will collect follow-up information on the participant and the neonate and the 
information will be forwarded to the Sponsor. Generally, the follow-up will be at least 
12 months after the delivery date. Any termination of pregnancy will be reported, regardless 
of fetal status (presence or absence of anomalies) or indication for the procedure. 
• While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy will be reported as an AE or SAE. A spontaneous 
abortion is always considered to be an SAE and will be reported as such. Any post-study 
pregnancy related SAE considered reasonably related to the study medication by the 
Investigator will be reported to the Sponsor as described in Section 8.3.5. While the 
Investigator is not obligated to actively seek this information in former study participants, he 
or she may learn of an SAE through spontaneous reporting. 
• The Investigator should obtain obstetric history of the study participant, outcomes of prior 
pregnancies, complications of pregnancy and parturition, birth defects and health problems in 
infancy in earlier offspring and known family history of birth defects. 
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10.5 
Appendix 5: Genetics 
Use and Analysis of DNA 
• Genetic variation may impact a participant’s response to study medication, susceptibility to, 
and severity and progression of disease. Variable response to study medication may be due to 
genetic determinants that impact drug absorption, distribution, metabolism, and excretion; 
mechanism of action of the drug; disease etiology; and/or molecular subtype of the disease 
being treated. Therefore, where local regulations and IRB/IEC allow, a blood sample will be 
collected for DNA analysis from participants who have provided a separate informed 
consent. 
• DNA samples may be used for research related to DZP or SLE and related diseases. They 
may also be used to develop tests/assays including diagnostic tests related to DZP and/or 
interventions of this drug class and SLE. Genetic research may consist of the analysis of one 
or more candidate genes or the analysis of genetic markers throughout the genome (as 
appropriate). 
• The samples may be analyzed as part of a multi-study assessment of genetic factors involved 
in the response to DZP or study medications of this class to understand study disease or 
related conditions. 
• The results of genetic analyses will be reported separately from the clinical study report or in 
a separate study summary. 
• The Sponsor will store the DNA samples in a secure storage space with adequate measures to 
protect confidentiality. 
• The samples will be retained while research on DZP or SLE continues but no longer than 
20 years or other period as per local requirements. 
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10.6 
Appendix 6: Liver safety – suggested actions and follow-up 
assessments 
Participants with potential drug-induced liver injury must be assessed to determine if study 
medication must be discontinued. In addition, all concomitant medications and herbal 
supplements that are not medically necessary should also be discontinued. 
Investigators should attempt to obtain information on study participants in the case of study 
medication discontinuation to complete the final evaluation. 
Study participants with potential drug-induced liver injury should not be withdrawn from the 
study until investigation and monitoring are complete. All results of these evaluations and 
observations, as well as the reason(s) for study medication discontinuation and/or participant 
withdrawal (if applicable), must be recorded in the source documents. The eCRF must document 
the primary reason for discontinuation of study medication. 
A specific monitoring plan must be agreed between the UCB study physician and the 
Investigator for study participants who have ALT >5 ULN. The monitoring plan should include 
any necessary follow-up assessments (until resolution of the abnormal lab values). 
Table 10-1: Phase 3-4 liver chemistry stopping criteria and follow-up 
assessments 
Liver Chemistry Stopping Criteria 
ALT-absolute 
ALT 8xULN 
ALT Increase 
ALT 5xULN but <8xULN persists for 2 weeks 
ALT 3xULN but <5xULN persists for 4 weeks 
Bilirubina,b 
ALT 3xULN and bilirubin 2xULN (>35% direct bilirubin) 
INR b 
ALT 3xULN and international normalized ratio (INR) >1.5, if INR measured 
Cannot 
Monitor 
ALT 5xULN but <8xULN and cannot be monitored weekly for 2 weeks 
ALT 3xULN but <5xULN and cannot be monitored weekly for 4 weeks 
Symptomaticc 
ALT 3xULN associated with symptoms (new or worsening) believed to be related 
to liver injury or 
 
Suggested Actions and Follow up Assessments 
Actions 
Follow Up Assessments 
• 
Immediately discontinue study medication. 
• 
Report the event to the UCB within 24 hours. 
• 
Complete the liver event case report form 
(eCRF), and complete a serious adverse event 
(SAE) data collection tool if the event also met 
the criteria for an SAE. b 
• 
Perform liver chemistry follow-up assessments. 
• 
Viral hepatitis serologyd 
• 
Obtain INR and recheck with each liver 
chemistry assessment until the 
transaminases values show downward trend 
• 
Only in those with underlying chronic 
hepatitis B at screening visit (V1) (identified 
by positive hepatitis B surface antigen or 
hepatitis B core antibodies), quantitative 
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Liver Chemistry Stopping Criteria 
• 
Monitor the participant until liver chemistry 
test abnormalities resolve, stabilize, or return to 
baseline (see MONITORING). 
• 
Do not restart/rechallenge participant with 
study medication unless allowed per protocol 
and UCB approval is granted. 
• 
If restart/rechallenge not allowed per protocol 
or not granted, permanently discontinue study 
medication and continue participant in the 
study for any protocol specified follow up 
assessments.Consider the need for a toxicology 
screening. 
 
MONITORING: 
For bilirubin or INR criteria 
• 
Repeat liver chemistry tests (include ALT, 
aspartate transaminase [AST], alkaline 
phosphatase, bilirubin) and perform liver event 
follow-up assessments within 24 hours. 
• 
Monitor participant twice weekly until liver 
chemistry test abnormalities resolve, stabilize, 
or return to baseline. 
• 
A specialist or hepatology consultation is 
recommended. 
For all other criteria 
• 
Repeat liver chemistry tests (include ALT, 
AST, alkaline phosphatase, bilirubin) and 
perform liver chemistry follow-up assessments 
within 24 to 72 hours. 
• 
Monitor participants weekly until liver 
chemistry abnormalities resolve, stabilize, or 
return to baseline. 
hepatitis B deoxyribonucleic acid (DNA) 
and hepatitis delta antibodye 
• 
Obtain blood sample for pharmacokinetic 
(PK) analysis after the most recent dosef 
• 
Serum creatine phosphokinase (CPK) and 
lactate dehydrogenase (LDH) 
• 
Fractionate bilirubin, if total bilirubin 
 2xULN 
• 
Obtain complete blood count with 
differential to assess eosinophilia 
• 
Record the appearance or worsening of 
clinical symptoms of liver injury (eg, 
fatigue, nausea, vomiting, right upper 
quadrant pain), or 
, on the 
adverse event (AE) report form 
• 
Record use of concomitant medications 
(including acetaminophen, herbal remedies, 
and other over-the-counter medications) on 
the concomitant medications eCRF. 
• 
Record alcohol use on the liver event 
alcohol intake eCRF 
• 
Exclude pregnancy 
For bilirubin or INR criteria: 
• 
Anti-nuclear antibody, anti-smooth muscle 
antibody, Type 1 anti-liver kidney 
microsomal antibodies, and quantitative 
total 
 
 
• 
Serum acetaminophen adduct high 
performance liquid chromatography (HPLC) 
assay (quantifies potential acetaminophen 
contribution to liver injury in participants 
with definite or likely acetaminophen use in 
the preceding week [James, 2009]). 
NOTE: Not required in China. 
• 
Liver imaging (ultrasound, magnetic 
resonance, or computerized tomography) 
and or liver biopsy to evaluate liver disease; 
complete Liver Imaging and/or Liver 
Biopsy eCRFs. 
a Serum bilirubin fractionation should be performed if testing is available. If serum bilirubin fractionation is not 
immediately available, discontinue study medication if ALT ≥3xULN and bilirubin ≥2xULN. Additionally, if 
serum bilirubin fractionation testing is unavailable, record the absence/presence of detectable urinary bilirubin 
on dipstick which is indicative of direct bilirubin elevations suggesting liver injury.  
b All events of ALT ≥3xULN and bilirubin ≥2xULN (>35% direct bilirubin) or ALT ≥3xULN and INR >1.5 may 
indicate severe liver injury (possible ‘Hy’s Law’) and must be reported as an SAE (excluding studies of 
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hepatic impairment or cirrhosis). The INR measurement is not required and the stated threshold value will not 
apply to participants receiving anticoagulants.  
c New or worsening symptoms believed to be related to liver injury (such as fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, or jaundice) or 
 (such as fever, rash or eosinophilia). 
d Includes: Hepatitis A 
; HBsAg and HBcAb; hepatitis C RNA; cytomegalovirus 
 Epstein-Barr viral capsid antigen 
 (or if unavailable, heterophile antibody or monospot 
testing); and hepatitis E 
 
e If hepatitis delta antibody assay cannot be performed, it can be replaced with a polymerase chain reaction (PCR) of 
hepatitis D RNA virus (where needed) (Le Gal, 2005). 
f PK sample may not be required for participants known to be receiving placebo or non-comparator interventions. 
Record the date/time of the PK blood sample draw and the date/time of the last dose of study medication prior to 
the PK blood sample draw on the eCRF. If the date or time of the last dose is unclear, provide the participant’s 
best approximation. If the date/time of the last dose cannot be approximated OR a PK sample cannot be collected 
in the time period indicated above, do not obtain a PK sample. Instructions for sample handling and shipping are in 
the Laboratory Manual. 
 
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10.7 
Appendix 7: Medical device AEs, ADEs, SAEs and device 
deficiencies: definition and procedures for recording, 
evaluating, follow-up, and reporting 
Not applicable. 
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10.8 
Appendix 8: Rapid alert procedures 
Not applicable. 
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10.9 
Appendix 9: Country-specific requirements 
10.9.1 
Poland 
The Polish Health Authority’s and Clinical Trial Facilitation Group have made recommendations 
related to contraception and pregnancy testing in a clinical study with IMP where the human data 
for exposure at pregnancy and nonclinical reproductive toxicology data are not available. As a 
mitigation measure, pregnancy testing is to be implemented monthly up to 2 months after the 
final dose of study medication. A urine pregnancy test is added at 4 weeks after final study 
medication administration at Week 44 (Visit 13) for sites located in Poland, thus it meets the 
above requirement. Based on the short half-life of the study medication and because genotoxicity 
is not a class effect of the monoclonal antibody, it is considered 
 to reduce the duration of 
post-study medication administration requirement on contraception for female study participants 
of childbearing potential from 3 months to 2 months, with implementation of monthly pregnancy 
testing during this period. 
10.9.2 
Romania 
The Romanian authorities introduced the following specific requirement for Romania: change in 
duration for the use of permitted oral corticosteroids (prednisolone) from a stable dose of 
2 weeks to 4 weeks prior to the Baseline Visit (Visit 2). It is recommended for sites located in 
Romania, that oral corticosteroids (prednisolone) need to be stable for 4 weeks, rather than 
2 weeks as mentioned in Section 5.1 of this protocol. 
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10.10 
Appendix 10: Abbreviations and trademarks 
ACR 
American College of Rheumatology 
ACE 
angiotensin converting enzyme 
ADL 
activities of daily living 
AE 
adverse event 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
aPL 
antiphospholipid 
APS 
antiphospholipid syndrome 
 
 
AST 
aspartate aminotransferase 
BICLA 
BILAG 2004-based Composite Lupus Assessment 
BILAG 2004 
British Isles Lupus Assessment Group Disease Activity Index 2004 
CAPS 
catastrophic APS 
CI 
confidence interval 
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
CNS 
central nervous system 
COVID-19 
Coronavirus disease 2019 
CPM 
Clinical Project Manager 
CRO 
contract research organization 
C-SSRS 
Columbia Suicide Severity Rating Scale 
DNA 
deoxyribonucleic acid 
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DZP 
dapirolizumab pegol 
 
 
ECG 
electrocardiogram 
eCOA 
electronic clinical outcomes assessment form 
eCRF 
electronic Case Report Form 
EQ-5D-5L 
Euro Quality of life 5-Dimensions 5-Level 
eGFR 
estimated glomerular filtration rate 
ES 
Enrolled Set 
EULAR/ACR 
European League Against Rheumatism/American College of Rheumatology 
Fab´ 
fragment antigen-binding 
FAS 
Full Analysis Set 
Fc 
fragment crystallizable 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEE 
Generalized Estimating Equation 
HIV 
human immunodeficiency virus 
HMG-CoA 
3-hydroxy-3-methyl-glutaryl-coenzyme A 
HRQoL 
health-related quality of life 
 
 
IB 
Investigator’s Brochure 
ICF 
Informed Consent form 
ICH 
International Council for Harmonisation 
IDMC 
independent data monitoring committee 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IGRA 
interferon-γ release assay 
IMP 
investigational medicinal product 
INR 
International Normalized Ratio 
IP 
investigational product 
IRB 
Institutional Review Board 
iv 
intravenous(ly) 
IWRS 
interactive web response system 
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LLDAS 
low lupus disease activity state 
LLN 
lower limit of normal 
LTBI 
latent tuberculosis infection 
LupusQoL 
Lupus Quality of Life questionnaire 
MCP 
metacarpophalangeal 
MMF 
mycophenolate mofetil 
NHP 
nonhuman primate 
NSAID 
nonsteroidal anti-inflammatory drug 
NTM 
non-tuberculosis mycobacterial 
OLE 
open label extension 
PBO 
placebo 
PCR 
polymerase chain reaction 
PD 
pharmacodynamics(s) 
PEF 
peak expiratory flow 
PEG 
polyethylene glycol 
PGA 
Physician’s Global Assessment of Disease 
PHQ-9 
Patient Health Questionnaire-9 
PIP 
proximal interphalangeal 
PK 
pharmacokinetic(s) 
PK-PPS 
Pharmacokinetic Per Protocol Set 
PPS 
Per Protocol Set 
PRO 
patient-reported outcome 
QoL 
quality of life 
qSOFA 
Quick Sequential Organ Failure Assessment 
Q4W 
every 4 weeks 
 
 
RNA 
ribonucleic acid 
RS 
Randomized Set 
SAE 
serious adverse event 
SAP 
Statistical Analysis Plan 
SARS CoV-2 
severe acute respiratory syndrome coronavirus 2  
SFI 
SELENA (Safety of Estrogens in Lupus National Assessment) Flare 
Index 
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SFU 
Safety Follow-up 
SJC 
swollen joint count 
SLE 
systemic lupus erythematosus 
SLEDAI-2K 
Systemic Lupus Erythematosus Disease Activity Index 2000 
SLICC 
Systemic Lupus International Collaborating Clinics 
SOC  
standard of care 
SRI 
Systemic Lupus Erythematosus Responder Index 
SS 
Safety Set 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse event 
TJC 
tender joint count 
TT 
tetanus toxoid 
ULN 
upper limit of normal 
VAS 
visual analog scale 
WOCBP 
woman of childbearing potential 
 
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10.11 
Appendix 11: Protocol amendment history 
Amendment 3: 14 Jan 2022 
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union.  
Overall Rationale for the Amendment 
The primary purpose of this amendment is to provide recommendations for contraception during 
mycophenolate treatment, as requested by regulatory authorities. Additional guidance on 
Coronavirus disease 2019 (COVID-19) vaccinations in immunosuppressed patients has been 
added, as recommend by the Independent Data Monitoring Committee. Other updates have been 
incorporated based on Investigators feedback, to provide further clarity on the protocol or to 
correct errors. The table below does not include correction of minor typographical errors and 
formatting/stylistic changes. 
 
Section # and Name 
Description of Change 
Brief Rationale 
1.3 Schedule of activities 
“COVID-19=Coronavirus disease 
2019;” has been added to the table of 
abbreviations. 
Updated for consistency 
within the table. 
1.3 Schedule of activities 
Footnote j: “(including vaccinations 
against COVID-19)” has been added. 
Updated for consistency 
within the protocol. 
1.3 Schedule of activities 
The following text has been added to 
Updated to provide 
clarification of collection 
specifications. 
1.3 Schedule of Activities 
Clarification of when blood 
samples are collected. 
5.2 Exclusion criteria 
Exclusion criterion #20a: “Investigator 
should consider local and international 
guidance on vaccination in 
immunosuppressed patients and discuss 
risks, benefits and administration options 
with participants (for more details see 
also Section 6.6.1 and Section 8.2.7).” 
has been added. 
To provide additional 
guidance on COVID-19 
vaccinations in 
immunosuppressed patients. 
6.5.1.3 Other 
immunosuppressants/ 
immunomodulatory agents 
The following text has been added to: 
Other immunosuppressant or 
immunomodulatory agents are 
permitted during the study (see 
Updated to provide further 
clarity. 
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inclusion criteria and maximum dose 
restrictions in Table 6-6) 
6.5.1.3 Other 
immunosuppressants/ 
immunomodulatory agents  
“If immunosuppressants permitted 
during the study were stopped before 
study entry, they must have been stopped 
no later than 8 weeks prior to the 
Screening Visit.” has been added. 
Updated to provide clarity and 
consistency with other 
systemic lupus erythematosus 
medications, as so far for 
immunosuppressants only a 
required minimum time 
interval participants had to be 
on a stable dose was defined, 
but no timeframe was defined 
in case immunosuppressants 
were stopped before 
screening. 
6.5.1.3 Other 
immunosuppressants/ 
immunomodulatory agents 
New wording was included to clarify 
that if a participant has a vaccination a 
temporary hold or a reduction in dose of 
concomitant immunosuppressant or 
immunomodulatory agents are 
permitted. 
Updated to provide clarity. 
6.5.1.3 Other 
immunosuppressants/ 
immunomodulatory agents 
Table 6-6: Maximum doses of permitted 
concomitant immunosuppressants: 
“Coated mycophenolate mofetil” 
changed to “Coated mycophenolate 
sodium”. 
Correction. 
6.5.1.3 Other 
immunosuppressants/ 
immunomodulatory agents 
“It cannot be excluded that 
mycophenolate mofetil (MMF) could 
reduce effectiveness of combined 
hormonal contraceptives including 
levonorgestrel. Investigators are advised 
to regularly counsel patients who are of 
childbearing potential on the risk of 
MMF treatment for adverse pregnancy 
outcomes and the possibility of reduced 
effectiveness of hormonal contraceptives 
due to interaction with MMF. Please 
refer to Section 10.4 for further 
information.” has been added. 
To address a regulatory 
authority request. 
6.5.1.4 Analgesics, 
medications including 
natural or synthetic 
cannabinoids (approved in 
line with local regulations), 
NSAIDs, HMG-CoA 
reductase inhibitors (statins), 
ACE inhibitors, and other 
anti-hypertensive drugs 
The sub-heading number (6.5.1.4) was 
added. 
Editorial correction. 
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6.6.1 Prohibited concomitant 
treatments (medications and 
therapies) 
“with the exception of immunoglobulins 
which are allowed to be used 
concomitantly with DZP after 
randomization if medically indicated.” 
has been added to the end of the first 
sentence. 
To clarify that use of 
immunoglobulins in parallel 
to DZP does not represent a 
safety concern (in difference 
to other drugs) and is thereby 
not prohibited. 
6.6.1 Prohibited concomitant 
treatments (medications and 
therapies) 
The following text has been added to: In 
case one of these medications has to be 
initiated during the study, the IMP needs 
to be permanently discontinued (with 
the exception of immunoglobulins). 
Updated to provide further 
clarity. 
6.6.1 Prohibited concomitant 
treatments (medications and 
therapies) 
Table 6-7: Prohibited medications and 
required wash-out periods prior to the 
Screening Visit (V1): Updates were 
made to some of the prohibited 
medications and their wash-out periods. 
To adapt washout periods 
based on recent 
pharmacokinetic and 
pharmacodynamic data for 
approved biologics (see 
Section 10.13). 
6.6.1 Prohibited concomitant 
treatments (medications and 
therapies) 
Table 6-7: Prohibited medications and 
required wash-out periods prior to the 
Screening Visit (V1): The routes of 
administration (iv and sc) have been 
added for Belimumab (Benlysta™). 
Added to provide further 
clarity. 
6.6.1 Prohibited concomitant 
treatments (medications and 
therapies) 
Table 6-7: Prohibited medications and 
required wash-out periods prior to the 
Screening Visit (V1): Tacrolimus 
(FK506) (Prograf®) has been removed 
from the table. 
Tacrolimus is approved and is 
a permitted escape medication 
(see Section 6.6.2). 
6.6.1 Prohibited concomitant 
treatments (medications and 
therapies) 
Table 6-7: Prohibited medications and 
required wash-out periods prior to the 
Screening Visit (V1): Footnote a has 
been added: The wash-out period refers 
to the last administration of the relevant 
medication. 
Added to provide further 
clarity. 
6.6.1 Prohibited concomitant 
treatments (medications and 
therapies) 
Table 6-7: Prohibited medications and 
required wash-out periods prior to the 
Screening Visit (V1): the definition for 
MRA in the footnote has been changed 
to “myeloma receptor antibody”. 
Correction. 
6.6.1 Prohibited concomitant 
treatments (medications and 
therapies) 
Details have been added to provide 
vaccination guidance for non-live 
vaccines. 
To provide additional 
guidance on COVID-19 
vaccinations in 
immunosuppressed patients. 
6.6.1 Prohibited concomitant 
treatments (medications and 
therapies) 
“In case of administration of 
investigational Coronavirus Disease 
2019 (COVID-19) vaccine (vaccines 
without regulatory authorization or 
To clarify how DZP 
administration should be 
handled in case of 
administration of 
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emergency authorization) study 
medication should not be administered 
within 2 weeks after vaccination.” has 
been added to the vaccines subsection. 
investigational COVID-19 
vaccines.  
8.1.3.2 Severe BILAG flare 
The definition of a severe flare was 
amended. 
Corrected to be aligned with 
the definition as published by 
Isenberg et al, 2011. 
8.1.3.3 Moderate BILAG 
flare 
The definition of a moderate flare was 
amended. 
Corrected to be aligned with 
the definition as published by 
Isenberg et al, 2011. 
8.2.6.1.3 Latent TB 
Wording was modified to clarify that 
study participants who prematurely 
discontinue treatment for LTBI or who, 
in the opinion of the Investigator or 
Sponsor, are noncompliant with anti-TB 
therapy are withdrawn from study 
treatment, but are still encouraged to 
regularly attend scheduled visits (but 
without IMP administration). 
Updated for consistency 
within the protocol. 
8.2.7 SARS-CoV-2/ 
Coronavirus Disease 2019 
Details have been added to provide 
reference to local and international 
guidance on vaccination of 
immunocompromised patients. 
To provide additional 
guidance on COVID-19 
vaccinations in 
immunosuppressed patients. 
8.3.8 Anticipated SAEs 
New wording was included to provide 
clarity for the Investigators regarding 
anticipated SAEs and reporting of SAEs. 
Updated to reduce ambiguity 
and considerations from the 
recently released FDA 
guidance. 
9.3.1 Analysis of the primary 
efficacy/primary endpoint 
Details regarding the covariate 
“corticosteroid dose at Baseline 
(≤7.5mg/day vs >7.5mg/day)” have been 
removed. 
To clarify that any covariate 
be described and justified in 
the Statistical Analysis Plan 
before unblinding. 
9.7 Planned interim analysis 
and data monitoring 
Noted that other key secondary and 
secondary efficacy endpoints will be 
provided at the interim analysis for 
consideration by the IDMC in the 
recommendation regarding futility. In 
addition, stated that the SAP will address 
considerations around ensuring the blind 
with regards to the interim futility 
analysis. 
Correction to data provided to 
IDMC, and to approach for 
documentation of ensuring the 
blind with regards to the 
interim futility analysis. 
10.2 Appendix 2: Clinical 
laboratory tests 
Protocol-required safety laboratory 
assessments: Footnote a removed from 
the Additional assessment: aPL 
antibodies including 
 
 
 
 
Correction. 
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Footnote a added to the Additional 
assessment: Hepatitis/liver injury 
diagnostic. 
10.4 Appendix 4: 
Contraceptive guidance and 
collection of pregnancy 
information 
Female participants: Clarified that the 
PEARL index is used. 
Updated to correct an error 
and provide clarity. 
10.4 Appendix 4: 
Contraceptive guidance and 
collection of pregnancy 
information 
Details added to note that potential 
drug-drug interactions of medicinal 
products or medical conditions could 
impact the effectiveness of oral 
contraceptives and therefore prescribing 
information and guidance’s should be 
followed. 
Updated to provide clarity and 
reference to guidances and 
labels. 
10.4.1 Female participants 
using mycophenolate 
treatment 
A section has been added to provide 
contraceptive guidance for female 
participants using mycophenolate 
treatment. 
To address a regulatory 
authority request. 
10.10 Appendix 10: 
Abbreviations and 
Trademarks 
One addition (MMF) was made to the 
list of abbreviations. 
Updated to reflect the 
parameters measured in the 
study. 
10.11 Appendix 11: Protocol 
Amendment History 
Added a summary of the changes made 
in Amendment 2. 
Intra-document 
cross-reference. 
10.13 Appendix 13: 
Inclusion and exclusion 
criteria rationale 
Exclusion criterion #20a: “Investigator 
should consider local and international 
guidance on vaccination in 
immunosuppressed patients and discuss 
risks, benefits and administration options 
with participants (for more details see 
also Section 6.6.1 and Section 8.2.7).” 
has been added. 
To provide additional 
guidance on COVID-19 
vaccinations in 
immunosuppressed patients. 
10.13 Appendix 13: 
Inclusion and exclusion 
criteria rationale 
The following text has been added to the 
justification for exclusion criteria #23: 
To adapt washout periods 
based on recent 
pharmacokinetic and 
pharmacodynamic data for 
approved biologics. 
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11 REFERENCES 
Nine new references have been added. 
Updated to reflect the 
additional publications used 
within the document. 
Amendment 2: 29 Jun 2021 
Overall Rationale for the Amendment 
The primary purpose of this amendment is to clarify that repeat certified BILAG 2004 training 
for Investigators who have used the assessment within 2 years in any DZP study that requires 
BILAG 2004 assessments is not required as continued use supports maintenance of skills; to 
clarify that photodocumentation of cutaneous SLE manifestations as part of source documents 
may be needed for adjudication of BILAG 2004 grading; to update the recommendations about 
the concomitant use of calcineurin inhibitors (including newly authorized voclosporin) and to 
add cautionary statements about co-administration of these products with the study drug; and to 
remove references to the IF-IDMC as a group separate from the IDMC, as the members are the 
same. These and other secondary changes are summarized in the following table. The table does 
not include correction of minor typographical errors and formatting/stylistic changes. 
Section # and Name 
Description of Change 
Brief Rationale 
1.1 Synopsis 
4.1 Overall design 
9.7 Planned interim analysis and data 
monitoring 
Removed text referring to 
and describing IF-IDMC as 
a group separate from the 
IDMC. 
Clarification that 
IF-IDMC and IDMC 
members are the same and 
function under 1 charter 
(ie, the IDMC charter). 
1.3 Schedule of activities 
6.1 Treatments administered 
Added that Baseline body 
weight is used to determine 
dosing through Week 20 for 
study participants screened 
under the initial protocol 
(ie, before Amendment 1). 
Clarification. Baseline 
body weight was specified 
in the protocol prior to 
Amendment 1 and 
changed to Screening with 
Amendment 1. 
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1.3 Schedule of activities 
8.1.1.1 BILAG 2004 
10.1.7 Source documents 
Added text regarding 
photodocumentation of 
cutaneous SLE 
manifestations. 
Clarification regarding 
need for source 
documentation to support 
external adjudication of 
BILAG 2004 grading.  
5.1 Inclusion criteria 
7.1.3 Permanent and temporary study drug 
discontinuation due to other reasons 
10.4 Appendix 4: Contraceptive guidance 
and collection of pregnancy information 
10.13 Appendix 13: Inclusion and 
exclusion criteria rationale 
Added “including pumping 
breast milk to feed to a 
child” to “breastfeeding” 
(Criterion 4; with 
amendment “4” becomes 
“4a”). 
Clarification. 
 
 
 
 
5.2 Exclusion criteria 
10.13 Appendix 13: Inclusion and 
exclusion criteria rationale 
Reordered examples of 
latent and opportunistic 
infections. 
(Criterion 17a; with 
amendment “17a” becomes 
“17b”). 
Clarification that herpes 
simplex virus and, unless 
severe, herpes zoster are 
not considered as 
opportunistic infections 
but rather as latent 
infections. 
5.2 Exclusion criteria 
10.13 Appendix 13: Inclusion and 
exclusion criteria rationale 
Clarification of criteria for 
fractionation of bilirubin. 
(Criterion 29; with 
amendment becomes 29a). 
Consistency with existing 
Gilbert’s syndrome text in 
this criterion.  
6.3.1.2 Breaking the treatment blind in an 
emergency situation 
Addition of text stating that 
unblinding can be initiated 
by the Investigator at any 
time as medically indicated. 
Clarification and 
emphasis. 
6.5.1.3 Other 
immunosuppressants/immunomodulatory 
agents 
6.6.2 Escape medication  
Added voclosporin. 
Voclosporin approved for 
active renal SLE in US. 
6.5.1.3 Other 
immunosuppressants/immunomodulatory 
agents 
Added cautionary text 
about administration of 
calcineurin inhibitors. 
To emphasize the need for 
compliance with local 
guidance(s) and caution 
for concomitant use with 
study drug due to potential 
risks that cannot be 
excluded at this time.  
6.6.1 Prohibited concomitant treatments 
(medications and therapies) 
 
Clarified that only high-
dose cyclophosphamide is 
prohibited. 
Correction. 
8.1.1.1 BILAG 2004 
Eliminated the requirement 
for repeat certified BILAG 
Investigators who have 
completed full certified 
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2004 training for 
Investigators who have 
used the assessment within 
2 years in any DZP study 
that requires BILAG 2004 
assessments. 
BILAG 2004 training, and 
who have ongoing and 
recent (within 2 years) use 
of the BILAG 2004 
assessment are considered 
to be in continuous 
training. 
9.7 Planned interim analysis and data 
monitoring 
Removed reference to 
interim SAP. 
Plans for the interim 
futility analysis are 
included in the main SAP. 
10.11 Appendix 11: Protocol Amendment 
History 
Added a summary of the 
changes made in 
Amendment 1. 
Intra-document 
cross-reference. 
 
Amendment 1: 14 Oct 2020  
This amendment is considered to be substantial based on the criteria set forth in Article 10(a) of 
Directive 2001/20/EC of the European Parliament and the Council of the European Union. 
Overall Rationale for the Amendment 
This amendment addresses questions and comments from regulators, Investigators, and other 
reviewers. Included are updates to the planned analysis, addition of exploratory biomarker 
analysis on the
 
 clarification regarding handling of protocol-defined criteria and 
actions respect to the SARS-CoV-2 pandemic, clarification of unclear or miss-interpretable text, 
and resolution/clarification of inconsistencies between different sections. In addition, minor 
editorial changes have been made and minor errors corrected. 
Section # and Name 
Description of Change 
Brief Rationale 
The following changes were made 
throughout the protocol: 
 
Added BILAG 2004 score of B at 
baseline to be included in 
assessments of worsening 
Clarified that “prevention of 
severe BILAG flares” means 
severe BILAG flare-free 
Clarified that “prevention of 
moderate/severe BILAG flares” 
means moderate/severe BILAG 
flare-free 
To clarify based on regulator 
feedback 
 
 
1.1 Synopsis – Objectives and Endpoints 
3 Objectives and Endpoints 
10.12 Endpoint rationale 
Tertiary endpoints: 
FATIGUE-SLE replaced with 
FATIGUE-PRO throughout 
document 
 
Changes in exploratory 
biomarkers updated: 
Name of scale recently 
changed. 
 
 
 
To add exploratory biomarker 
analysis to be able to assess 
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 added. 
 
 
 
   
1.1 Synopsis and 4.1 Overall design 
 
 
 
9.7 Planned interim analysis and data 
monitoring 
BILAG 2004 neuropsychiatric 
body organ system to monitor 
potential neuropsychiatric events 
falsely assigned to SLE added to 
IDMC review 
Clarification added on IF-IDMC 
determination if the study should 
be stopped. 
Details added of regular IDMC 
meetings 
Additional text to clarify that 
the IDMC will also review 
neuropsychiatric outcomes as 
defined by BILAG 2004 in 
line with the Investigator's 
Brochure. 
Editorial change to provide 
more details on the planned 
interim analysis. 
1.3 Schedule of Activities, Table 1-1 
Updated schedule of events table 
and footnotes  
Editorial change to provide 
more information and/or 
correct errors  
2.2 Background 
Data from the 3 clinical studies 
(SL0013, SL0014, and SL0023) 
added. 
To provide information 
included in the IB  
5.1 Inclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Clarified timing of the “study 
entry” as appeared in the original 
protocol. (number changed from 
2.a to 2.a1) 
To clarify that in the original 
criterion “study entry” was 
intended to mean at the 
Screening Visit, not the 
signature date of the ICF 
5.1 Inclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Added that serological evidence 
for SLE is only applicable for the 
Screening Visit (number changed 
from 2.c to 2.c1) 
 
 
Clarification that 
 will be 
measured where available 
(number changed from 2.c to 
2.c1) 
To clarify that serological 
evidence for SLE only applies 
for Screening Visit data as 
blood samples for baseline will 
not be available at time point 
of randomization 
To clarify that 
 will be 
only available in certain 
regions due to logistic reasons 
5.1. Inclusion criteria Appendix 13: 
Inclusion and exclusion criteria rationale 
Added clarification for when 
antimalarial monotherapy is 
acceptable 
(number changed from 2.e to 
2.e3) 
Clarification 
5.1 Inclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Added maximum corticosteroid 
doses and no iv pulse therapy 
(>500 mg x 1-3 days) within 4 
weeks prior to screening and no 
change in CS allowed during the 
Screening period (number 
changed from 2.e to 2.e3) 
To clarify additional rules 
regarding corticosteroid pulse 
iv treatment, originally not 
defined, and to provide 
maximum doses in alignment 
with other sections of the 
protocol 
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5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Added clarification for anti-
dsDNA positivity and 
measurements as per central 
laboratory (number changed from 
2 to 2a) 
Editorial changes to provide 
more clarity, based on 
feedback from investigators 
5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Added systemic reactions due to 
latex allergy (number changed 
from 5 to 5a) 
To clarify that systemic 
reactions to latex (eg, contact 
allergy) was the intent of the 
original inclusion criterion 
5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Clarified timing of the “study 
entry” as appeared in the original 
protocol. (number changed from 
6 to 6a) 
To clarify that in the original 
criterion “study entry” was 
intended to mean at the 
Screening Visit, not the 
signature date of the ICF 
5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Added clarification for 
thromboembolic events (number 
changed from 11 to 11a) 
Editorial change to clarify that 
this exclusion criteria is 
generally linked to heart 
diseases with an increased risk 
for thromboembolic events 
based on feedback from 
Investigators    
5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Deleted text referring to erosive 
arthritis (number changed from 
13 to 13a) 
Editorial change as erosive 
arthritis is not a symptom 
5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Added “or SARS CoV-2” 
(number changed from 15 to 15a) 
To clarify that SARS CoV-2 
infection is considered a 
clinically significant infection  
5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Added systemic antiviral 
treatment (number changed from 
16 to 16a) 
To include systemic antiviral 
treatment (eg, for SARS CoV-
2) 
5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Added reactivated latent infection 
(number changed from 17 to 17a) 
Change to clarify this refers to 
reactivated latent and not to 
silent latent infections (eg, 
herpes zoster, herpes simplex) 
5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Added clarification on study 
participant previously 
randomized within this study 
(number changed from 26 to 26a) 
Change to clarify that study 
participants gave consent but 
were a screening failure can be 
rescreened, however, study 
participants who were 
randomized before cannot.  
5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Added text to include absence of 
concurrent suicidal ideation 
and/or severe depression (number 
changed from 28 to 28a) 
Clarification added to 
diagnostic assessment  
5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Updated chronic kidney failure to 
stage 4 (number changed from 30 
to 30a) 
Clarification added to chronic 
kidney failure  
5.2 Exclusion criteria and Appendix 13: 
Inclusion and exclusion criteria rationale 
Clarification that all assessments 
are per Screening (Visit 1) 
Clarification 
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(number changed from 31 to 31a) 
6.2 Preparation, handling, storage, and 
accountability requirements 
Clarification to blinding of the 
infusion bag and maintenance of 
blind. 
 
To provide clarity on the 
process of IMP preparation 
and to clarify that study 
participant will not store study 
medication. 
6.4 Treatment compliance 
Deleted text referring to ‘blinded 
fashion’  
To clarify as Investigators and 
medical monitors are usually 
blinded  
6.5.1.1 Corticosteroids 
Corticosteroid tapering scheme 
revised, including update of 
Table 6-3 and Table 6-4  
To clarify that tapering for 
participants receiving high 
dose corticosteroid therapy 
should be initiated as soon as 
possible and to clarify that no 
maximum dose of 
corticosteroid treatment is 
defined for its administration 
as escape treatment in the 
study 
6.5.1.2 Antimalarials  
Additional wording added in case 
a dose change is needed and to 
provide details on antimalarial 
intake. 
To clarify that Investigators 
are advised to contact medical 
monitors to discuss the 
potential impact of an 
intervention on the future 
study conduct not the 
intervention itself, based on 
feedback from a regulator 
6.5.1.3 Other 
immunosuppressants/immunomodulatory 
agents 
Use of concomitant 
immunosuppressants clarified 
and wording added in case a dose 
change is needed.  
Updated text to include natural 
and synthetic cannabinoids 
Change to provide clarification 
consistent with other sections 
of the protocol and to clarify 
that Investigators are advised 
to contact medical monitors to 
discuss the potential impact of 
an intervention on the future 
study conduct not the 
intervention itself, based on 
feedback from a regulator 
6.6 Dose modification 
Added clarification that dose 
modification was not applicable  
Change to clarify that no dose 
change to the study drug is 
foreseen, based on feedback 
from Investigators 
6.6.1 Prohibited concomitant treatments 
(medications and therapies 
 
Clarification added for prohibited 
medications 
 
 
Vaccines:Text added on blood 
collection to determine immune 
response to vaccines.  
Changes to be consistent with 
other sections of the protocol 
and to describe additional 
sample collection for potential 
future analysis of the impact of 
DZP on the immune response 
to infectious antigens 
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6.6.2 Escape medication 
Wording added to clarify when 
escape treatment represents a 
safety risk 
Change to clarify that study 
drug only needs to be 
discontinued if escape 
treatment in combination with 
DZP could represent a safety 
risk based on Investigator 
feedback. 
7.1 Discontinuation of study medication 
 
Added clarification on study 
medication discontinuation and 
observation 
Change to be consistent with 
other sections and to underline 
the need to keep participants in 
the study based on feedback 
from a regulator 
7.1.2 QTc stopping criteria 
Clarification on single ECG 
collection 
Change to align with other 
sections of the protocol 
describing that only single 
ECGs are foreseen and to 
clarify that this withdrawal 
criteria applies for new 
findings after eligibility 
review/randomization. 
7.1.3 Permanent and temporary study 
drug discontinuation due to other reasons 
New sub-section created to 
include clinically significant 
infections, impact on study 
conduct and observation for 
study participants who 
discontinue study drug  
 
Addition of text to clarify 
discontinuation of study 
medication in case of a new 
tuberculosis infection 
Changes to provide more 
clarity under which 
considerations a study 
participant should discontinue 
study drug, stay in the study 
and be withdrawn, based on 
feedback from a regulator and 
Investigators. 
To clarify existing guidance in 
Section 8.2.6.3 
8 Study assessments and procedures 
Changed blood volume to 900mL 
Change to fix error due to 
wrong calculation 
8.1.1.1 BILAG 2004 
Corrected reference guide title  
Change to reflect correct title 
of the document 
8.1.1.2 SLEDAI 2K 
Updated SLEDAI 2K definition. 
Change to fix error on the 
exact definition of the 
SLEDAI 2K to be used 
8.1.1.3 S2K RI 50 
Updated S2K RI 50 assessment   
Change to fix error and to be 
consistent with the published 
way how to analyze the data 
8.1.1.6 Cutaneous Lupus Erythematosus 
Disease Area and Severity Index 
Updated CLASI assessment  
Change to fix error as VAS 
scores described here are not 
part of CLASI 
8.1.1.7 Tender and Swollen Joint Counts 
Clarification added on 
qualification of assessor 
 
 
Updated text on cannabinoids  
Change to provide clarification 
on who is qualified to do the 
assessment, based on 
Investigator feedback. 
Change to provide clarity that 
only locally approved drugs 
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Clarification on assessments to 
be performed by the same 
Investigator (or qualified 
assessor)  
including cannabinoids are 
allowed but not illegal drugs, 
based on feedback from a 
regulator 
Change to underline that key 
efficacy assessments should be 
done by same assessor through 
the study 
8.1.1.8 Lupus Arthritis and 
Musculoskeletal Disease Activity score 
Updated VAS scale 
Change to provide more clarity 
on exploratory endpoint 
8.1.2.1 FATIGUE-PRO (Short Form) 
Updated to FATIGUE-PRO  
Change to update naming 
convention 
8.1.3.1 BILAG 2004-based Composite 
Lupus Assessment 
Updated BICLA assessment  
Change to the planned analysis 
based on feedback from a 
regulator 
8.1.3.4 LLDAS 
Deleted ‘BILAG 2004’ 
Change to clarify that no 
BILAG items are part of the 
referenced definition of 
LLDAS 
8.1.3.5 Systemic Lupus Erythematosus 
Responder Index-4 
Updated assessment  
Change to provide more clarity 
on planned exploratory 
analysis 
8.1.3.6 DORIS (Definitions of 
Remission in SLE) complete remission 
on treatment 
New sub-section added to 
describe analysis 
Change to add only 
exploratory endpoint which 
was not described in the 
protocol  
8.2.1 Physical examination 
Clarification on weight 
measurement collection 
Change to clarify that in case 
of certain SLE specific 
symptoms (weight loss) weight 
may have to be also measured 
at other Visits than BL and 
Week 24 
8.2.2 Vital signs 
 
Updated assessment procedure 
Change to provide more 
details on vitals assessment 
based on feedback from 
Investigators 
8.2.4 Clinical safety laboratory 
assessments 
Clarification added on blinding 
Change to clarify, consistent 
with other section  
8.2.5 Suicidal risk monitoring 
Updated assessment procedure 
Change to provide clarity 
about the expected 
qualification of assessor 
8.2.6 Assessment and management of 
TB and TB risk factors 
Clarification that prophylactic 
therapy for LTB1 should be 
initiated 4 weeks prior to study 
medication. 
Change to fix error, consistent 
with other section 
8.2.7 SARS-CoV-2/COVID-19 
New section added to include 
monitoring of study participants 
for SARS-CoV-2 infection. 
Change to provide more clarity 
on monitoring of study 
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participants for SARS-CoV-2 
infection 
8.3 AEs and SAEs 
Clarification on additional 
assessments assess infections 
such as COVID-19. 
Change to provide more clarity 
on expected actions to report 
adverse events  
8.3.5 Pregnancy 
Updated assessment  
Change to clarify that 
concomitant medications need 
to be assessed in case a study 
participant becomes pregnant  
8.3.7 AEs of special monitoring 
8.6.1 Assessment of PK variables 
Added wording on 
 
   
Change to clarify details of 
planned analysis 
8.9 Immune system markers 
 added 
Change to clarify that 
 is 
part of the assessed 
autoantibodies consistent with 
other section of the protocol 
8.10 Biomarkers 
Clarification on analysis of the 
immune response against 
vaccines or infection related 
antigens and stored samples. 
Change to describe planned 
additional exploratory analysis 
on impact of DZP on the 
immune response to infectious 
antigens 
9.1 Definition of analysis sets 
Updated to clarify the FAS 
Change to planned analysis 
based on feedback from a 
regulator 
9.2.2 Analysis time points 
Updated timepoints to remove 
Early Withdrawal Visit (EWV) 
Change to clarify that study 
participants who withdrew 
their consent and therefore 
leave the study do not have to 
return for another visit. Last 
visit is the EOT visit. 
9.3.1 Analysis of the primary 
efficacy/primary endpoint 
Updated analysis  
Change to provide clarity as 
sensitivity analysis using the 
PPS is described elsewhere 
9.3.1.1 Sensitivity analysis 
Updated analysis 
Changes to provide clarity on 
analysis based on feedback 
from a regulator 
9.3.2.1 Analysis of key secondary 
endpoints 
Updated to remove Early 
Withdrawal Visit (EWV) 
Change as no EWV is 
foreseen. The final visit if a 
patient withdrew consent and 
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leaves the study will be the 
EOT (End of treatment) visit 
9.5 Handling of protocol deviations 
Updated section 
Change to fix error and 
duplication text 
9.6 Handling of dropouts or missing data 
Text updated to clarify study 
participants who will be 
considered non-responders. 
Change to planned analysis 
based on feedback from a 
regulator 
10.1.3 Informed consent process 
Updated process.  
Change to clarify informed 
consent process based on 
feedback from a regulator 
10.1.6 Data quality assurance 
Wording added to clarify the 
quality tolerance limits.  
Change to describe the process 
of planned quality 
management.  
10.2 Clinical laboratory tests 
 
Section updated to match tests in 
the Schedule of Activities 
Addition of hepatitis B core 
antibody testing 
Change to reflect planned 
laboratory analysis and fix 
errors 
10.3 Appendix 3: AEs – definitions and 
procedures for recording, evaluating, 
follow-up, and reporting 
Additional text added to clarify 
reporting of AEOIs and AESMs.  
Change to describe details of 
the process to report AESMs 
and AESIs  
10.4 Appendix 4: Contraceptive 
guidance and collection of pregnancy 
information 
Clarification added to pregnancy 
testing  
Change to clarify that a 
pregnancy test is not required 
in study participants who are 
known to be pregnant and 
editorial change create 
consistency with other sections 
of the protocol 
10.6 Appendix 6: Liver safety – 
suggested actions and follow-up 
assessments 
Addition of hepatitis B core 
antibody testing  
To improve sensitivity of 
chronic hepatitis B screening 
10.17 Appendix 17: Criteria for 
Antiphospholipid Syndrome (APS) 
New appendix for criteria for 
APS syndrome 
Change to provide clarity on 
criteria recommend to classify 
APS 
6.5. Permitted concomitant 
medication(s)/treatments(s) 
 
Rearrangement of headers with 
movement of associated text, as 
applicable 
Editorial change to improve 
presentation 
1.1 Synopsis 
4.1 Overall design 
6.3.1.1 Maintenance of study treatment 
blind 
6.3.1.2 Breaking the treatment blind in 
an emergency situation 
6.6.1 Prohibited concomitant treatments 
(medications and therapies) 
6.6.2 Escape medication 
Wording added to specify impact 
of study conduct 
Change to clarify that 
Investigators are advised to 
contact medical monitors to 
discuss the potential impact of 
an intervention on the future 
study conduct not the 
intervention itself, based on 
feedback from a regulator  
Global 
Minor administrative, formatting, 
and typographical changes have 
been made. 
To provide clarity and be 
consistent with remainder of 
protocol. 
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10.12 
Appendix 12: Endpoint rationale 
Objectives 
Endpoints 
Rationale 
Primary 
To evaluate the ability 
of DZP as an add-on 
treatment to SOC 
medication to achieve 
clinically relevant 
long-term improvement 
of moderate to severe 
disease activity 
Achievement of BICLA response at 
Week 48 
BICLA is a composite endpoint which 
measures improvement of disease 
activity based on improvement by 
BILAG 2004 grades across all organ 
systems with relevant disease activity 
at screening visit (V1)/start of 
treatment. BILAG 2004 is developed 
and validated based on intention to 
treat principles. A change 
(improvement or worsening) by at 
least 1 grade represents a change in 
the need for and nature of a 
therapeutic intervention as determined 
by SLE experts and therefore 
represents a clinically relevant change 
in disease activity. This can be either 
a clinically relevant improvement as 
demanded by BICLA or a clinically 
relevant worsening (flare) as 
demanded to not occur by BICLA. As 
the BICLA demands improvement 
across all organ systems with disease 
activity suggesting the need for a 
therapeutic intervention, it represents 
clinically relevant improvement as to 
be demanded from a potent systemic 
immune response modifier. BICLA is 
inline with EMA regulatory guidance. 
BILAG as the driving component of 
the BICLA is in line with FDA 
regulatory guidance. 
Key Secondary 
To evaluate the ability 
of DZP as an add-on 
treatment to SOC 
medication to achieve 
fast, clinically relevant 
improvement of 
moderate to severe 
disease activity 
Achievement of BICLA response at 
Week 24 
Achievement of BICLA response at 
Week 12 
Phase 2 data suggest a fast onset of 
response within 12-24 weeks. This is 
relevant for study 
participants/prescribers to make 
informed treatment decisions as soon 
as possible including further change in 
therapy or further escalation of 
treatment. 
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Objectives 
Endpoints 
Rationale 
To evaluate the ability 
of DZP as an add-on 
treatment to SOC 
medication to achieve 
long-term control of 
disease activity 
Achievement of prevention of 
severe BILAG flares (severe 
BILAG flare-free) through Week 
48 
Phase 2 data suggest a substantial 
prevention of severe flares. Prevention 
of disease flares is an intuitive 
measure if the disease is well 
controlled over time which is one of 
the primary objectives of treatment in 
SLE according to international 
treatment guidances. Severe flares are 
associated with poor long-term 
prognosis. 
To evaluate the ability 
of DZP as an add-on 
treatment to SOC 
medication to achieve 
and maintain the treat-
to-target goal: low 
disease activity with 
low/acceptable 
corticosteroid dose 
over time 
Achievement of LLDAS in ≥50% 
of post-Baseline visits through 
Week 48 
Phase 2 data suggest that more 
patients achieve and maintain over 
time the treat-to-target endpoint 
LLDAS. LLDAS represents low 
disease activity at a low/acceptable 
corticosteroid background medication 
dose level. It appears to be correlated 
with long-term outcomes including 
damage prevention and flare 
prevention. It is therefore considered 
as highly clinically relevant. The 
LLDAS is based on achievement of a 
low SLEDAI-2K score which is a 
commonly used instrument to 
measure disease activity state in 
clinical practice. As it combines the 
achievement of a steroid tapering 
target with the demand for a 
well-controlled disease, it represents 
clinically successful steroid sparing.  
International treatment guidances 
refer to LLDAS as treatment target. 
To evaluate the ability 
of DZP as an add-on 
treatment to SOC 
medication to achieve 
improvement of 
disease activity as 
measured by numerical 
disease state score 
commonly used in 
clinical practice 
Change from Baseline in SLEDAI-
2K at Week 48 
While the BILAG 2004 as the main 
component of BICLA adequately 
describes clinically relevant 
improvement across all organ 
systems, the BILAG 2004 instrument 
is not broadly used in clinical practice 
due to its complexity. The SLEDAI-
2K is an often-used instrument in 
clinical practice. Information on this 
endpoint will provide valuable 
information to prescribers based on an 
instrument they are familiar with from 
daily practice. Further SLEDAI-2K 
represents a component of the BICLA 
and the LLDAS. 
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Objectives 
Endpoints 
Rationale 
Secondary 
To evaluate the ability 
of DZP as an add-on 
treatment to SOC 
medication to achieve 
components of the 
composite primary 
endpoints 
Achievement of BILAG 
improvement without worsening at 
Week 48 
This endpoint represents the first and 
driving component of BICLA. 
Analysis of the components of 
composite endpoints like the BICLA 
are recommended by regulatory 
guidance 
Change from Baseline in PGA at 
Week 48 
This endpoint represents a component 
of BICLA. Analysis of the 
components of composite endpoints 
like the BICLA are recommended by 
regulatory guidance. 
To evaluate the ability 
of DZP as an add-on 
treatment to SOC 
medication to achieve 
alternative responder 
endpoint 
Achievement of SRI4 response at 
Week 48 
This endpoint represents the primary 
endpoint of the only approved drug in 
SLE in the past decades. It is added to 
allow indirect comparison. 
To evaluate the ability 
of DZP as an add-on 
treatment to SOC 
medication to achieve 
endpoints supporting 
other key secondary 
endpoints 
Achievement of prevention of 
moderate/severe BILAG flares 
(moderate/severe BILAG flare-free) 
through Week 48 
Support to Key secondary endpoint 
prevention of severe flares, 
recommended by regulatory guidance. 
Time to severe BILAG flare 
through Week 48 
Support to key secondary endpoint 
prevention of severe flares, 
recommended by regulatory guidance. 
Time to moderate/severe BILAG 
flare through Week 48 
Support to Key secondary endpoint 
prevention of severe flares, 
recommended by regulatory guidance. 
To evaluate the safety 
and tolerability of DZP 
as add-on treatment to 
SOC medication 
TEAEs, serious TEAEs, TEAEs of 
special interest, and TEAEs of 
special monitoring 
To evaluate the safety profile of DZP. 
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Objectives 
Endpoints 
Rationale 
Tertiary 
To evaluate the ability 
of DZP as add-on 
treatment to SOC to 
achieve endpoints 
which support the 
primary and secondary 
objectives and/or 
support the 
interpretation of the 
primary and secondary 
endpoints 
Achievement of reduction of 
corticosteroid dose from 
>7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day 
prednisone equivalent by visit 
Support to all primary and key 
secondary endpoints, component of 
LLDAS, recommended by regulatory 
guidance 
Achievement of reduction of 
corticosteroid dose from 
>7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day 
prednisone equivalent at Week 24 
and maintaining low corticosteroid 
dose afterwards and achievement of 
BICLA response at Week 48 
Support to primary endpoint, 
recommended by regulatory guidance 
Achievement of reduction of 
corticosteroid dose from 
>7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day 
prednisone equivalent at Week 24 
and maintaining low corticosteroid 
dose and achievement of prevention 
of moderate/severe BILAG flares 
(moderate/severe BILAG flare-free) 
at Week 48 
Support to key secondary endpoint, 
recommended by regulatory guidance 
Achievement of reduction in 
corticosteroid dose from 
≥7.5mg/day prednisone equivalent 
dose at start of study to ≤5mg/day 
prednisone equivalent at Week 24 
and maintaining low corticosteroid 
dose and achievement of BICLA 
response at Week 48 
Support to key secondary endpoint, 
recommended by regulatory guidance 
Achievement of reduction of 
corticosteroid dose from 
≥7.5mg/day prednisone equivalent 
dose to ≤5mg/day prednisone 
equivalent at Week 24 and 
maintaining low corticosteroid dose 
and achievement of prevention of 
moderate/severe BILAG flares 
(moderate/severe BILAG flare-free) 
at Week 48 
Support to primary endpoint, 
recommended by regulatory guidance 
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Objectives 
Endpoints 
Rationale 
Total corticosteroid dose through 
Week 24, through Week 48, and 
from Week 24 through Week 48 
Support to all primary and key 
secondary endpoints, component of 
LLDAS, recommended by regulatory 
guidance 
Achievement of BICLA response 
by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Achievement of BILAG 2004 
improvement without worsening by 
visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Change from Baseline in BILAG 
2004 score by visits 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Achievement of BILAG 2004 shifts 
by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Achievement of BILAG 2004 
improvement by organ system by 
visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Achievement of maintained BICLA 
response by visit 
To evaluate if achieved BICLA 
response is maintained for more than 
one visit, to provide supportive 
information for better understanding 
of the primary and key secondary 
endpoints, due to regulatory guidance 
Achievement of persistent BICLA 
response between Week 24 and 
Week 48 
To evaluate if achieved BICLA 
response is maintained from Week 24 
on through end of study in majority of 
visits, to provide supportive 
information for better understanding 
of the primary and key secondary 
endpoints, due to regulatory guidance 
Worsening of any organ system 
with a BILAG 2004 B, C, D, E at 
Baseline to BILAG 2004 A or 
worsening of >1 organ system with 
a BILAG 2004 C, D, E at baseline 
to BILAG 2004 B by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Achievement of BILAG 2004 C, D, 
E in all organ systems by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
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Objectives 
Endpoints 
Rationale 
Change from Baseline in SLEDAI-
2K by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Achievement of SRI 4, 6, 8 
response by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints and to 
provide information on alternative 
definitions of the SRI 
Change from prior visits in S2K 
RI50 by visit 
To provide information on from visit 
to visit dynamic of disease activity 
and to provide supportive information 
for better understanding of the 
primary and key secondary endpoints 
Change from Baseline in PGA by 
visit 
To provide information on a global 
assessment of disease activity and to 
provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Achievement of LLDAS status by 
visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Cumulative number of visits in 
LLDAS through Week 48 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Achievement of LLDAS Variant 
(demand for ≤5mg/day prednisone 
equivalent) in >50% of post-
Baseline visits through Week 48 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Achievement of prednisone 
equivalent dose ≤7.5 mg/day by 
visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Prednisone equivalent dose by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Occurrence of severe BILAG 2004 
flares by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Occurrence of moderate BILAG 
flares by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
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Objectives 
Endpoints 
Rationale 
Occurrence of severe SFI flares by 
visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Occurrence of moderate SFI flares 
by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Time to severe SFI flare 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Time to moderate SFI flare 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Change from Baseline in 
ACR/SLICC damage score by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
Achievement of DORIS remission 
by visit 
To provide supportive information for 
better understanding of the primary 
and key secondary endpoints 
To evaluate the ability 
of DZP as an add-on 
treatment to SOC 
medication to achieve 
organ specific 
endpoints 
Change from Baseline in CLASI 
activity score by visit for all study 
participants and for subset of study 
participants with high CLASI score 
To provide information on organ 
specific improvement of disease 
activity 
Achievement of a meaningful 
improvement in CLASI score by 
visit for all study participants and 
for subset of study participants with 
high CLASI score 
To provide information on organ 
specific improvement of disease 
activity 
Change from Baseline in Tender 
joint count (TJC), swollen joint 
count (SJC) by visit for all study 
participants and for subset of study 
participants with moderate to severe 
arthritis 
To provide information on organ 
specific improvement of disease 
activity 
Achievement of a meaningful 
decrease in TJC/SJC by visit for all 
study participants and for a subset 
of participants with moderate to 
severe arthritis 
To provide information on organ 
specific improvement of disease 
activity 
Change from Baseline in Lupus 
Arthritis and Musculoskeletal 
Disease Activity score by visit 
To provide information on organ 
specific improvement of disease 
activity 
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Objectives 
Endpoints 
Rationale 
To evaluate the ability 
of DZP as an add-on 
treatment to SOC 
medication to achieve 
important patient 
reported outcomes 
Change from baseline in Functional 
Assessment of Chronic Illness 
Therapy Fatigue (FACIT-F) by visit 
To provide information on organ 
specific improvement of disease 
activity 
Change from Baseline in PHQ-9 
score by visit 
To provide information on depression 
as important comorbidity, regulatory 
guidance 
Change from Baseline in FATIGUE 
PRO 'Physical Fatigue', 'Mental 
Fatigue' and 'Fatigability' scores by 
visit 
To provide information on study 
participants' perception on their 
disease activity. 
Change from Baseline in 
LupusQoL by visit 
To provide information on study 
participants' perception on their 
disease activity. 
Change from Baseline in EQ-5D-
5L by visit 
To provide information on study 
participants' perception on their 
disease activity. 
To evaluate the 
pharmacokinetics (PK) 
To evaluate 
immunogenicity of 
DZP as an add-on 
treatment to SOC 
medication 
Incidence of anti-drug antibodies: 
 
To provide information on antibody 
generation against components of 
DZP with possible impact on efficacy 
and study participant's safety 
To evaluate the PD and 
immunological 
parameters of DZP as 
an add-on treatment to 
SOC medication 
Observed values and change from 
baseline in
 
 
 
 
 
 
 
 
 
in all study participants by 
visit and in study participants 
‘positive’ at Baseline by visit 
To provide information on 
pharmacodynamic, information on 
important biomarkers of SLE possible 
predictive of clinical outcomes, likely 
important information for study 
participant's safety 
Seroconversion of:
 
 
 
To provide information on PD, 
information on important biomarkers 
of SLE possible predictive of clinical 
outcomes, likely important 
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Objectives 
Endpoints 
Rationale 
 status by 
visit 
information for study participant's 
safety 
To evaluate the safety 
and tolerability of DZP 
as an add-on treatment 
to SOC medication 
TEAEs leading to study 
withdrawal, TEAEs leading to 
permanent study medication 
discontinuation, TEAEs with start 
day on day or up to 1 day after 
infusion, other identified TEAE 
clusters 
To provide information on study 
participants' safety outcomes 
Summary of participants withdrawn 
from the study due to TEAEs 
 
Summary of participants who 
permanently discontinued study 
medication 
To provide information number of 
participants who were withdrawn 
from study or whose study medication 
was discontinued 
Change from Baseline in vital sign 
parameters by visit 
To provide information on study 
participants' safety outcomes 
Observed values and change from 
Baseline in safety laboratory tests 
(hematology, serum chemistry, 
urinalysis) by visit, % study 
participants achieving critical 
threshold for selected lab 
parameters by visits 
To provide information on study 
participants' safety outcomes 
To evaluate changes in 
exploratory biomarkers  
Change from Baseline in 
biomarkers selected for analysis 
 
 
 
 
To provide information on biomarkers 
of SLE comorbidity and potential 
additional PD endpoints, possibly 
predictive of clinical outcomes 
To evaluate risk for 
anti-phospholipid 
associated events 
Change from Baseline in APS score 
by visit 
To provide information on change in 
risk profile for thromboembolic 
events. Antiphospholipid antibodies 
are common in SLE and substantially 
contribute to comorbidity such as 
cardiovascular events, other 
thromboembolic events, adverse 
pregnancy outcomes. Phase 2 data 
suggest a reduction of these antibodies 
which would be of substantial value 
for study participants. 
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10.13 
Appendix 13: Inclusion and exclusion criteria rationale 
Criterion 
N 
Content 
Justification 
Inclusion 
1 
Study participant must be ≥16 years 
of age, unless restricted by local 
regulation, at the time of signing the  
Informed Consent form (ICF). 
SLE is a disease with a common onset 
with puberty. It is estimated that up to 
30% of study participants have first 
symptoms before they are 18 years old. 
The unmet medical need is high in this 
young population due to the high toxicity 
of existing standard of care (high dose 
corticosteroids, cyclophosphamide, MTX, 
Azathioprine). 
Further SLE in adolescents has a similar 
etiology, pathogenesis, clinical 
manifestations, and laboratory findings but 
is often described to have a more severe 
disease course. Study participants ≥16 
years of age are expected to have a 
comparable pharmacokinetic as study 
participants ≥18 years of age. Therefore, 
the risk-benefit is considered as 
comparable to adults 
Inclusion 
2 
Study participants who have 
moderate to severe disease activity 
due to either persisting active SLE or 
due to an acute worsening of SLE in 
the scope of frequent 
flaring/relapsing-remitting  SLE 
despite stable SOC medication 
defined as: 
DZP is intended to provide a treatment 
option for study participants whose disease 
is not well controlled on SOC treatment at 
a well-tolerated dose. SLE is considered 
not well controlled over time if there is 
residual disease activity and/or frequently 
flaring/relapsing remitting disease despite 
SOC. Sporadic flares need a short time 
treatment intervention but do not need 
automatically modification of long-term 
immunomodulatory therapy if not 
occurring frequently. 
Inclusion 
2.a1 
Diagnosed with SLE at least 24 
weeks before the Screening Visit 
(Visit 1) by a qualified physician (eg, 
rheumatologist, internal medicine 
expert, nephrologist, or 
dermatologist) 
SLE is a highly complex disease which 
can involve almost all organs and is 
therefore covering the full spectrum of 
internal medicine. However due to its 
complexity diagnosis should be done by a 
well-trained expert in the field with a 
specialty training in rheumatology, 
dermatology, or any specialty within the 
spectrum of internal medicine including 
nephrology. The diagnosis should have 
been done at least 24 weeks prior to 
screening visit (V1) to ensure that there 
was an appropriate attempt to keep the 
disease well-controlled on conventional 
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Content 
Justification 
standard of care treatment at well-tolerated 
dose. 
Inclusion 
2.b 
Classified by 2019 European League 
Against Rheumatism/American 
College of Rheumatology 
(EULAR/ACR) classification criteria 
for SLE 
The 2019 EULAR/ACR criteria are 
considered to have high sensitivity, 
specificity and a high positive predictive 
value, and represent the state of the art of 
current clinical and scientific knowledge 
Inclusion 
2.c1 
With serological evidence for SLE at 
Screening as demonstrated by at least 
1 of the following: 
i) Evidence for 
 (defined 
as evidence for 
 
 in central laboratory) 
ii) Either 
 < lower 
limit of normal (LLN) OR 
 <LLN OR 
elevated erythrocyte-bound 
complement 
 (where 
available) as measured by central 
laboratory 
iii)
 with a titer 
of at least 1:80 confirmed by 
central laboratory in combination 
with evidence of at least 1 of the 
following SLE typical 
autoantibodies: 
1. 
 
(central laboratory) 
2. 
 
 
 
 autoantibodies (central 
laboratory) 
3. Historic evidence for 
 
 (at least 2 historical 
positive tests [>upper limit of 
normal (ULN) of lab assay with 
an interval of at least 12 weeks 
between tests]) 
The 2019 EULAR/ACR criteria are 
demanding evidence for anti-nuclear 
antibodies at any time as mandatory. 
These criteria shall assure that there is also 
sufficient evidence for SLE typical 
autoantibodies or a decrease in 
complement, which is also typical for SLE 
and an important risk factor at screening 
visit (V1).
 and low 
complement are also part of EULAR/ACR 
criteria. 
Inclusion 
2.d 
Moderately to severely active defined 
as 
- British Isles Lupus Assessment 
Group Disease Activity Index 2004 
(BILAG 2004) Grade B in ≥2 
organ systems and/or a BILAG 
Study participant should have an 
indication for a systemic treatment 
intervention with a biotherapeutic 
immunomodulator. A BILAG A represents 
the medical indication for a treatment 
intervention with high potent 
immunomodulatory therapy, a BILAG B 
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2004 Grade A in ≥1 organ systems 
at Screening and Baseline Visit 
AND 
- SLEDAI-2K ≥6 at Screening Visit 
AND 
- SLEDAI-2K without labs ≥4 at 
Baseline Visit 
represents also an indication to change the 
immunomodulatory therapy; however, 
could also indicate local therapy. When at 
least 2 BILAG Bs are present this 
medically indicates to alter the 
immunomodulatory therapy with a 
systemic treatment to cover all affected 
organ systems. SLEDAI ≥6 also represent 
moderately to severely active disease and 
is an entry criteria which is in line with 
other programs to define study participants 
with the need for a treatment intervention 
with investigational immunomodulatory. 
As both BILAG 2004 and SLEDAI-2K are 
partially depending on lab parameters 
which are not available at baseline, the 
disease activity shall be performed at 
baseline by considering only clinical 
symptoms to assure that indication for 
treatment intervention is still present when 
the investigational drug is first applied. 
Inclusion 
2.e3 
Receiving the following SOC 
medication at stable dose: 
• 
Antimalarial treatment in 
combination with corticosteroids 
and/or immunosuppressants or as 
stand-alone treatment if justified 
(ie, if for other SLE SOC 
medications there is documented 
intolerance in medical history, 
documented lack of efficacy, 
contraindications, or lack of 
availability) OR 
• 
Treatment with corticosteroids 
and/or immunosuppressants if 
antimalarial treatment is not 
possible (ie, documented 
intolerance in medical history or 
antimalarials not available 
locally) 
Stable dose is defined for: 
• 
Antimalarials as no change to 
dose within 8 weeks prior to 
Screening and during Screening 
Period and a start date at least 
12 weeks before Screening. 
DZP is intended to provide a treatment 
option for study participants with residual 
disease and/or frequently 
flaring/relapsing-remitting SLE despite 
SOC treatment. Therefore, study 
participants should be on optimized but 
also stable SOC medication to judge 
adequately how well the study participants' 
disease is controlled and therefore to judge 
if there is a need for a treatment 
intervention at all which is the prerequisite 
to qualify for an interventional study. 
 
In line with international and local 
treatment guidance documents and overall 
expert opinion, antimalarials are accepted 
as the cornerstone of treatment in study 
participants with SLE accompanied with 
corticosteroids at the lowest dose possible 
and/or immunosuppressants (if 
corticosteroids cannot be reduced to a 
well-tolerated level). However, some 
study participants do not tolerate 
corticosteroids and/or conventional 
immunosuppressants due to side effects 
and are therefore treated by antimalarials 
as stand-alone treatment. 
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Maximum doses are described in 
Section 6.5.1.2  
• 
Corticosteroids as no change in 
dose for 2 weeks prior to 
Screening, no change during 
Screening Period, and no iv pulse 
therapy (>500mg x 1 to 3 days) 
within 4 weeks prior to 
screening. The maximum dose 
allowed at screening is 40mg/day 
prednisone or equivalent (see 
Section 6.5.1.1). 
Immunosuppressants as no change in 
dose for 12 weeks prior to Screening 
Visit and during Screening Period. 
Maximum doses are described in 
Section 6.5.1.3  
 
Further a certain proportion of study 
participants do have to stop antimalarial 
treatment or are not intake adherent due to 
side effects. In rare cases antimalarials 
may also be not available to study 
participants. In this case study participants 
should still be on either corticosteroids or 
immunosuppressants or both. 
 
In terms of dosage for these treatments, 
changes in corticosteroid therapy can 
influence significantly and short term the 
disease activity in both direction - 
worsening and improvement of disease 
activity. Antimalarials and 
Immunosuppressants have a treatment 
effect with more latency, changes could 
interfere with the disease activity also 
longer after changes to the medication 
itself. The demand for stable corticosteroid 
therapy at least 2 weeks before screening 
visit (V1) and consequently approx. 4 
weeks before randomization (Baseline 
Visit) as well as the demand for stable 
antimalarial and immunosuppressant 
therapy longer term shall ensure the 
adequate qualification for this 
interventional trial (residual disease and/or 
frequent flaring disease despite SOC) and 
at the same time rescue bias on the 
assessment of the investigational drug. 
 
Any treatment intervention with SOC 
treatment will be possible at any time 
during the study if medically indicated. 
However, if this is needed during the 
Screening Period study participants will be 
considered as not eligible. If it occurs 
during the study participants may be 
considered as non-responders but should 
remain in the study. 
Inclusion 
3 
Body weight ≥40kg and ≤160kg 
Weight range as usually in this population 
and based on toxicity margins 
Inclusion 
4a 
Female and/or male 
• 
A male study participant must 
agree to use contraception, as 
As DZP lacks a Fc’ part it is expected 
analogue to other drugs with the same 
structure not to pass the placental barrier. 
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Justification 
detailed in Section 10.4, during 
the Treatment Period and for at 
least 17 weeks after the final 
dose of study treatment and 
refrain from donating sperm 
during this period. 
• 
A female study participant is 
eligible to participate if she is not 
pregnant, not breastfeeding 
(including pumping breast milk 
to feed to a child), and at least 1 
of the following conditions 
applies: 
- Not a woman of childbearing 
potential (WOCBP) as defined 
in Section 10.4 of the final 
protocol, or 
- A WOCBP who agrees to 
follow the contraceptive 
guidance in Section 10.4 of the 
final protocol during the 
treatment period and for at 
least 17 weeks after the final 
dose of study medication. 
However, there is no evidence, neither 
from in vitro experiments, nor from animal 
experiments, nor from humans if DZP can 
pass the placental barrier or can do any 
harm to embryos or fetus. Therefore, a 
substantial contraception is needed at this 
point in time. 
Inclusion 
5 
Capable of giving signed informed 
consent as described in 
Section 10.1.3, which includes 
compliance with the requirements 
and restrictions listed in the ICF and 
in this protocol. 
To protect study participants’ rights 
Exclusion 
1 
Study participant has any medical or 
psychiatric condition (including 
conditions due to neuropsychiatric 
SLE) that, in the opinion of the 
Investigator, could jeopardize or 
would compromise the study 
participant’s ability to participate in 
this study. This includes study 
participants with a life threatening 
condition (eg, CTCAE grade 4 
conditions, CAPS, acute severe renal 
failure, acute severe central nervous 
system [CNS] manifestations) 
To protect study participants' well-being as 
under this conditions adherence to study 
procedures are expected to be affected 
which could put study participants at risk 
Exclusion 
2a 
Study participant has moderate to 
severe disease activity (as defined 
per Inclusion Criterion 2.d) at the 
Screening Visit (V1) due to an acute 
Study participants are required to have 
signs and symptoms of SLE qualifying for 
moderate to severe disease activity at 
screening visit (V1) defined as at least 2 
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flare but does not fulfill at least one 
of the following criteria in addition to 
the Screening Visit: 
• 
≥1 additional disease flare within 
the last 24 weeks prior to 
Screening (as per medical 
record) OR 
• 
 positivity in 
combination with 
< LLN as 
per central laboratory OR 
• 
< LLN as per 
central laboratory OR 
• 
African-American OR 
• 
Age <25 years 
organ systems with a BILAG B or at least 
1 organ system with a BILAG A in 
combination with a SLEDAI ≥6. 
 
Participants could have these signs and 
symptoms due to residual/chronic disease 
activity or due to an acute worsening of 
disease activity (acute flare). 
If signs and symptoms at screening visit 
(V1) are due to an acute flare, it cannot be 
distinguished if these occurred in the 
setting of frequent flares or is a sporadic 
flare in a study participant who is indeed 
overall well controlled on  SOC treatment. 
In fact, the sporadic flare can occur due to 
external events such as UV irradiation, 
infections, drug intake or in adherence to 
SOC treatment but may not represent an 
overall not controlled disease state. 
To avoid introducing a biological 
treatment in study participants that may be 
controlled with SOC, an assessment is 
needed to ensure a well-documented 
medical history of multiple flares. In case 
no substantial documentation of the 
medical history is available (eg, in case of 
referrals to investigational site), several 
risk factors for frequent flares have been 
well described and would also be used to 
assess the need for biologic treatment 
(Fanouriakis, 2019). 
Exclusion 
3 
Study participant has a history of 
chronic alcohol or drug abuse within 
the previous 24 weeks. 
To protect patents' well-being as under this 
conditions adherence to study procedures 
are expected to be affected which could 
put study participants at risk 
Exclusion 
4 
Study participant has a known 
 to any components 
of DZP including PEG or 
comparative drugs (and/or an 
investigational device) as stated in 
this protocol. 
To protect study participants' well-being. 
DZP is a PEGylated fab' fragment. Both 
PEG as well as the fab' fragment are 
proteins which can cause allergic reactions 
under certain circumstances. Study 
participants who have a history for such 
reactions are considered as having a high 
risk to have a severe allergic reactions 
again. 
Exclusion 
5a 
Study participant has a history of an 
anaphylactic reaction to parenteral 
administration of contrast agents, 
To protect study participants' well-being. 
Study participants who had severe 
reactions against proteins or other 
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human or murine proteins, or 
monoclonal antibodies. This includes 
systemic reactions due to latex 
allergy. 
molecules have a high risk to react again 
against a molecule such as DZP 
Exclusion 
6a 
Study participant has a history of 
malignancy, except the following 
treated cancers: cervical carcinoma in 
situ (after complete resection [eg, 
curettage, electrodessication] not 
later than 4 weeks prior to the 
Screening Visit [V1]), basal cell 
carcinoma, or dermatological 
squamous cell carcinoma (after 
complete resection not later than 
24 weeks prior to the Screening Visit 
[V1]). 
to protect study participants'' well-being as 
any immunomodulation could interfere 
with the capability of the immune system 
to keep preexisting tumors under control 
which could lead to exacerbation of the 
tumor 
Exclusion 
7 
Study participants who have had 
major surgery (including joint 
surgery) within the 24 weeks prior to 
Screening, or planned surgery within 
24 weeks after entering the study. 
To protect study participants' well-being as 
major surgeries, increase the risk of 
infections and as an immunomodulator 
DZP could increase the risk of such 
infections further. 
Exclusion 
8 
Study participants who have had 
significant blood loss or have 
donated or received 1 or more units 
(450mL) of blood within 30 days 
prior to the Screening Visit or have 
donated plasma or platelets within 14 
days prior to the Screening Visit. 
To protect study participants' well-being as 
a relevant amount of blood will be taken at 
the Screening and Baseline Visit 
Exclusion 
9 
Study participants with a history of 
thromboembolic events within 52 
weeks of Screening (Visit 1), 
including but not limited to the 
following: deep venous thrombosis, 
pulmonary embolism, cortical sinus 
thrombosis, myocardial infarction, 
stroke, transient ischemic attack, or 
arterial insufficiency causing digital 
gangrene or tissue necrosis. 
Note: 
1) In case of anti-phospholipid 
antibodies present at the 
Screening Visit, a prophylactic 
treatment should be considered in 
line with local or international 
guidelines and considering the 
To protect study participants' well-being. 
In vitro, animal data and limited data in 
humans suggest no increased risk for 
thromboembolic events in contrast to the 
full antiCD40 antibody including the Fc’ 
part (see DZP IB). However, the data so 
far in humans are still limited. Study 
participants with recent thromboembolic 
events in the medical history are 
considered to be of increased risk to have 
an adverse event such as another 
thromboembolic event or a bleeding event 
(if on anti-coagulation). As an increased 
risk for such events associated with DZP 
cannot be excluded at this time exposure 
to DZP could increase the risk further. 
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individual risk profile of the 
patient for thromboembolic events 
2) Study participants with 
antiphospholipid syndrome (APS) 
can be enrolled if they are on 
stable anticoagulation therapy at 
an effective dose (ie, International 
Normalized Ratio [INR] target 2 
to 3 depending on clinical 
situation) and did not have a 
thromboembolic event and/or 
obstetric morbidity within the 52 
weeks prior to Screening (Visit 1). 
Obstetric morbidity is defined as 1 
or more unexplained deaths of a 
morphologically normal fetus at 
or beyond the tenth week of 
gestation with the latest incidence 
within 52 weeks prior to 
Screening (Visit 1) OR 1 or more 
preterm births of a 
morphologically normal neonate 
before the 34th week of: (i) 
eclampsia or severe pre-eclampsia 
or (ii) recognized features of 
placental insufficiency with the 
latest incidence within 52 weeks 
prior to Screening (Visit 1). 
Exclusion 
10 
Study participants with a history of 
catastrophic APS or saddle 
pulmonary embolism 
To protect study participants' well-being. 
In vitro, animal data and limited data in 
humans suggest no increased risk for 
thromboembolic events in contrast to the 
full antiCD40 antibody including the Fc’ 
part. However, the data so far in humans 
are still limited. If DZP does promote 
thromboembolism, then the combination 
of a history of thromboembolism and DZP 
may be too high risk. 
Exclusion 
11a 
Study participant has an increased 
risk for thromboembolic events due 
to an ongoing heart disease or due to 
a medical device, including but not 
limited to vascular graft, valvular 
heart disease, atrial fibrillation, or a 
heart rhythm disorder. 
To protect study participants' well-being. 
In vitro, animal data and limited data in 
humans suggest no increased risk for 
thromboembolic events in contrast to the 
full antiCD40 antibody including the Fc’ 
part. However, the data so far in humans 
are still limited.  If DZP does promote 
thromboembolism, then the combination 
of a history of thromboembolism and DZP 
may be too high risk. 
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N 
Content 
Justification 
Exclusion 
12 
Study participant has a BILAG 2004 
Grade A in the musculoskeletal 
system due to severe arthritis only 
AND no BILAG 2004 Grade A or B 
in any other organ system AND no 
current (within the past 4 weeks) 
evidence for synovitis based on 
imaging methods such as magnetic 
resonance imaging or doppler-
sonography 
To ensure study participants have an 
unmet medical need for a treatment 
intervention with a systemic potent 
immunomodulator. Severe arthritis as 
defined by BILAG is defined as active 
synovitis ≥ 2 joints with marked loss of 
functional range of movements and 
significant impairment of activities of 
daily living, that has been present on 
several days (cumulatively) over the last 4 
weeks. 
As the latter is based on a subjective and 
not well-defined assessment, the 
reproducibility and generalizability of the 
assessment in study participants who have 
no other objective symptoms of SLE 
present could be impaired, specifically if 
synovitis is only based on a subjective 
joint assessment by the assessor either. 
Exclusion 
13a 
Study participant has a mixed 
connective tissue disease, 
scleroderma, and/or overlap 
syndrome of these diseases with 
SLE. 
- 
Clarification: Study participants 
with rheumatoid arthritis in their 
medical history are not considered as 
having an overlap syndrome and are 
therefore eligible. 
To assure study participants indeed have 
the indicated disease 
Exclusion 
14 
Study participant has evidence of 
human immunodeficiency virus 
infection, agammaglobulinemias, T-
cell deficiencies, or human T-cell 
lymphotropic virus-1 infection at any 
time prior to or during the study. 
To protect study participants' well-being as 
DZP as a potent immunomodulator can 
increase the risk for severe exacerbations 
of preexisting chronic infections. 
Exclusion 
15a 
Study participant has clinically 
significant active or latent infection 
(eg, chronic viral hepatitis B or C, or 
SARS CoV-2 infection [see 
Section 8.2.7]). 
To protect study participants' well-being as 
DZP as a potent immunomodulator can 
increase the risk for severe exacerbations 
of ongoing or preexisting chronic 
infections. 
Exclusion 
16a 
Study participant has a history of a 
serious infection within the last 60 
days prior to the first study 
medication infusion (Visit 2) that 
required iv/intramuscular antibiotics, 
systemic antiviral treatment or 
To protect study participants' well-being as 
DZP as a potent immunomodulator can 
increase the risk for severe exacerbations 
of preexisting chronic or ongoing acute 
infections. 
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required hospitalization/prolonged 
hospitalization. Study participants 
must have completed any prior anti-
infective therapy for serious 
infections prior to the first study 
medication infusion. 
Exclusion 
17b 
Study participant had a reactivated 
latent infection (eg, cytomegalovirus, 
herpes simplex virus, or herpes zoster 
infection) or opportunistic infection 
(including but not limited to 
pneumocystis, cytomegalovirus, or 
severe herpes zoster infection) within 
12 weeks prior to the first study 
medication infusion (Visit 2) or is 
currently receiving suppressive 
therapy for an opportunistic 
infection. 
To protect study participants' well-being as 
DZP as a potent immunomodulator can 
increase the risk for severe exacerbations 
of preexisting chronic or ongoing acute 
infections. 
Exclusion 
18 
Study participant has a clinically 
relevant recurrent (more than 3 times 
a year) infection 
To protect study participants' well-being as 
DZP as a potent immunomodulator can 
increase the risk for severe exacerbations 
of preexisting chronic or ongoing acute 
infections. 
Exclusion 
19 
Study participant with any of the 
following tuberculosis (TB) 
exclusion criteria: 
• 
Known active TB infection. 
• 
History of active TB infection 
involving any organ system or 
findings in other organ systems 
consistent with TB, unless 
adequately treated according to 
WHO/CDC therapeutic guidance 
and proven to be fully recovered 
upon consult with a TB 
specialist. 
• 
Latent TB infection (LTBI) 
unless appropriate prophylaxis is 
initiated at least 4 weeks prior to 
study medication dosing and will 
be continued to completion of 
prophylaxis. 
• 
High risk of acquiring TB 
infection eg. known close 
exposure to another person with 
active TB infection within 3 
To protect study participants' well-being as 
DZP as a potent immunomodulator can 
increase the risk for severe exacerbations 
of preexisting chronic or ongoing acute 
infections. 
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months prior to Screening or 
significant time spent in a health 
care delivery setting or 
institution where individuals 
infected with TB are housed and 
where the risk of transmission is 
high within 3 months prior to 
Screening 
• 
Current nontuberculous 
mycobacterial (NTM) infection 
or history of NTM infection 
unless proven to fully recovered 
upon consult with a TB 
specialist. 
Exclusion 
20a 
Study participants who have received 
live/live attenuated vaccines within 6 
weeks prior to the first study 
medication infusion (Visit 2) or who 
plan to receive these vaccines during 
the study or up to 12 weeks after the 
final dose of study medication will be 
excluded. Use of nonlive vaccines is 
allowed during the study; however, 
based on current evidence, it cannot 
be excluded that the effectiveness of 
these vaccines may be compromised 
by the study medication. Investigator 
should consider local and 
international guidance on vaccination 
in immunosuppressed patients and 
discuss risks, benefits and 
administration options with 
participants (for more details see also 
Section 6.6.1 and Section 8.2.7). 
To protect study participants' well-being as 
DZP as potent immunomodulator could 
lead to exacerbation of infection by live 
vaccines 
Exclusion 
21 
Study participant has active lupus 
that, in the opinion of the 
Investigator or according to local or 
international guidances, requires an 
increase in SOC therapy outside of 
that permitted in Section 6.5.1. 
To protect study participants' well-being 
by assuring that study participants receive 
adequate and indicated treatment for their 
SLE if prohibited by this study. 
Exclusion 
22 
Study participants requiring plasma 
exchange or immunoadsorption in 
the 16 weeks prior to Visit 2 or at 
any time during the study. 
To protect study participants' well-being as 
plasma exchange or immunoadsorption 
leads to significant immunosuppression 
which could be further exacerbated by 
DZP and therefore increase the risk for 
serious infections. 
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Content 
Justification 
Exclusion 
23 
Study participant has used the 
prohibited medications listed in 
Table 6-7, regardless of route (with 
the exception of eye drops), within 
the time frame (Wash-Out Period) 
listed in the table prior to Screening 
(Visit 1). Study participant has used 
investigational agents not included in 
Table 6-7, including other 
investigational or recently approved 
biologics, off-label use of 
immunomodulators, or device 
products, within 12 weeks or 5 times 
the half-life prior to Screening 
(Visit 1), whichever is longer. 
Concomitant participation in studies 
where no product or device is 
administered/used may be allowed if 
discussed and approved by the 
Medical Monitor/UCB. If there are 
any questions regarding acceptable 
wash-out periods not mentioned, the 
Investigator should contact the 
Medical Monitor. 
To protect study participants' well-being as 
prohibited medications as mentioned lead 
to significant immunosuppression which 
could be further exacerbated by DZP and 
therefore increase the risk for serious 
infections.  
Exclusion 
24 
Hormone replacement therapy is 
allowed provided it is not initiated 
within the 4 weeks prior to Screening 
(Visit 1) or during the study. The 
hormone replacement therapy may be 
decreased and/or discontinued at any 
time during the study 
To ensure the diagnostic value of the FSH 
test to determine if a study participant is of 
childbearing potential 
Exclusion 
25 
Study participant should, if possible, 
stay on stable doses of the following 
other concomitant medications for 
the treatment of SLE during the study 
unless changes in these treatments 
are clinically indicated: analgesics, 
non-steroidal anti-inflammatory 
drugs (NSAIDs), 3-hydroxy-3-
methyl-glutaryl-coenzyme A (HMG-
To assure integrity of data by reducing 
bias by other background medication. 
Study participants should receive 
treatment which is indicated at any time, 
however if this happens before 
randomization it should be considered to 
not include the study participant in the 
study. 
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Content 
Justification 
CoA) reductase inhibitors (statins), 
angiotensin converting enzyme 
(ACE) inhibitors, and other anti-
hypertensive drugs. 
Exclusion 
26a 
Study participant has previously been 
randomized within this study or 
participant has previously been 
assigned to treatment with DZP in a 
study evaluating DZP. 
To protect study participants' well-being as 
prior participation in a study by which the 
study participants received DZP could 
increase the risk for severe allergic 
reactions. 
Exclusion 
27 
Study participant has participated in 
another study of an IMP (and/or an 
investigational device) within the 
previous 12 weeks or 5 half-lives of 
the IMP whatever is longer (see 
Table 6-7) or is currently 
participating in another study of an 
IMP. 
To protect study participants' well-being as 
prohibited medication as mentioned lead 
to significant immunosuppression which 
could be further exacerbated by DZP and 
therefore increase the risk for serious 
infections. Also, to ensure integrity of data 
controlling for bias by medication with 
impact on SLE. 
Exclusion 
28a 
Study participant has history of a 
suicide attempt within the 5 years 
prior to the Screening Visit or has 
had suicidal ideation in the past 6 
months as indicated by a positive 
response (“Yes”) to either Question 4 
or Question 5 of the 
“Screening/Baseline” version of the 
Columbia Suicide Severity Rating 
Scale (C-SSRS) at Screening.  
Note: 
• 
In case a study participant 
responds to Question 9 in PHQ9 
 
 
 
 
’ the 
severity of the suicidal ideation 
needs to be adequately assessed 
with the C-SSRS rating scale 
• 
In case of history of a suicide 
attempt more than 5 years ago 
the absence of concurrent 
suicidal ideation and/or severe 
depression should be confirmed 
by a mental healthcare 
practitioner before enrolling into 
the study. 
To protect study participants' well-being. 
Study participants with SLE have an 
increased risk for depression and 
suicidality. Some biotherapeutic 
immunomodulators are suspected to 
increase the risk for suicidality. 
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Criterion 
N 
Content 
Justification 
Exclusion 
29a 
Study participant has ≥3x the ULN 
alanine aminotransferase (ALT), 
aspartate aminotransferase (AST), or 
alkaline phosphatase (ALP), or 
>ULN bilirubin (≥1.5xULN bilirubin 
if known Gilbert’s syndrome), except 
in the case where the abnormal test 
values are ascribed to SLE hepatitis. 
• 
If study participant only has 
>ULN, but <1.5xULN bilirubin, 
fractionate bilirubin to identify 
possible undiagnosed Gilbert’s 
syndrome (ie, direct bilirubin 
<35%) should be assessed, 
except in the case where the 
abnormal test values are ascribed 
to SLE hepatitis or hemolytic 
anemia, in the opinion of the 
Investigator.  
• 
In case of a suspected SLE 
hepatitis, eligibility must be 
discussed with the Medical 
Monitor. 
• 
If study participant has a result of 
ALT, AST, or ALP that is >ULN 
but that does not meet the 
exclusion limit at Screening, a 
repetition of the lab assessment is 
recommended to judge the 
dynamic of the increase but is in 
the Investigator’s discretion 
considering the medical history 
of the study participant. In case 
of a further clinically relevant 
increase (with a value that still 
doesn’t meet the exclusion limit), 
inclusion of the study participant 
must be discussed with the 
Medical Monitor. 
To protect study participants' well-being. 
Severe liver dysfunction could impact the 
metabolization of DZP 
Exclusion 
30a 
Study participant has chronic kidney 
failure stage 4, manifested by 
estimated glomerular filtration rate 
(eGFR) <30mL/min/1.73m2, or 
serum creatinine >2.5mg/dL, or 
participant has proteinuria >3g/day, 
or protein:creatinine ratio 
>340mg/mmol at the Screening Visit. 
To protect study participants' well-being. 
Components of DZP are secreted through 
the renal system. So far there are only data 
up to a creatinine clearance of 
≥45mL/min/1.73m2 and proteinuria 
≤3g/day and no impact could be detected. 
As Proteinuria is common in SLE study 
participants this was extended to not 
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Criterion 
N 
Content 
Justification 
exclude study participants with high unmet 
medical need but only by a justifiable 
range 
Exclusion 
31a 
Study participant has any significant 
hematologic abnormalities at the 
Screening Visit (V1) as follows: 
a. Hemoglobin <7.0g/dL 
b. 
 T-lymphocytes <200/mm3 
c. Absolute neutrophil count 
<500/mm3 
d. 
 T lymphocytes <500/mm3 
in combination with neutrophil 
count <1000/mm3 
e. Platelets <25,000/mm3. Study 
participants with a higher platelet 
count should also be excluded if 
they have a clinical risk of 
bleeding for reasons other than 
SLE. 
To protect study participants' well-being. 
Hematological alterations are common in 
SLE however severe anemia (Hb <7g/dL) 
and/or thrombopenia (CTCAE grade 4, 
<25,000/µL) is associated with an 
increased risk for cardiovascular, 
constitutional and bleeding events. Severe 
lymphopenia and granulocytopenia or 
combination is increasing the risk for 
serious infections which could be 
exacerbated by DZP. 
 
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10.14 
Appendix 14: Criteria for diagnosis of anaphylaxis 
Anaphylaxis is highly likely when any of the following 3 criteria is fulfilled 
(Sampson et al, 2006): 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal 
tissue, or both (eg, generalized hives, pruritus or flushing, swollen lips-tongue-uvula) 
AND at least 1 of the following: 
− Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow [PEF], hypoxemia) 
− Reduced blood pressure or associated symptoms of end-organ dysfunction (eg, hypotonia 
[collapse], syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that 
study participant (minutes to several hours): 
− Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen 
lips-tongue-uvula) 
− Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia) 
− Reduced blood pressure or associated symptoms (eg, hypotonia [collapse], syncope, 
incontinence) 
− Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 
3. Reduced blood pressure after exposure to known allergen for that study participant (minutes 
to several hours): systolic blood pressure of <90mmHg or >30% decrease from the study 
participant’s Baseline. 
 
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10.15 
Appendix 15: Suggested management guidelines for suspected 
infusion reactions 
10.15.1 
Tryptase 
In case of a suspected infusion reaction, samples should be taken as follows to determine serum 
tryptase levels to support the differential diagnosis (Muraro et al, 2022; Platzgummer et al, 
2020): 
• The first blood sample should be taken 30 minutes to 2 hours after the start of the 
reaction (if not feasible during this time period, a sample may be taken up to 6 hours after 
the start of the reaction). 
• The second blood sample should be taken 24 or more hours after complete resolution of 
symptoms. If obtaining the second blood sample on one of the following days after the 
Type of reaction 
Sponsor recommendations for management 
Acute – Mild 
Eg, flushing; dizziness; 
headache; sweating; 
palpitations; nausea 
Slow infusion rate to 5mL/h 
Infuse 0.9% NaCl 500-1000mL/h iv 
Antihistamine iv/im  
Paracetamol 1g po 
Monitor vital signs every 10min until back to baseline 
Wait 20min, then increase infusion rate to 8mL/h for 15min, then 16mL/h, 
20mL/h, 25mL/h every 15min, as tolerated until intended dose has been 
given 
Acute – Moderate 
eg, flushing; chest 
tightness; dyspnea; 
hypo/hypertension 
(change >20mmHg in 
SBP); raised temperature; 
palpitations; urticaria 
Stop infusion 
Infuse 0.9% NaCl 500-1000mL/h iv 
Antihistamine iv/im 
Paracetamol 1g po  
Monitor vital signs every 5min until back to baseline 
Wait 20min 
If there is no indication of anaphylaxis (eg, generalized urticaria and/or 
bronchospasm), and if clinically appropriate, consider restarting the 
infusion at a lower rate following this suggested regimen: 
Restart infusion at 5mL/h for 15min 
Increase infusion rate to 8mL/h for 15min, then 16mL/h, 20mL/h, 25mL/h 
every 15min, as tolerated until intended dose has been given 
Acute – Severe  
Eg, hypo/hypertension 
(change >40mmHg in 
SBP); raised temperature 
with rigors; chest 
tightness; dyspnoea with 
wheezing; stridor 
Stop infusion definitively 
Alert crash team 
Maintain airway, ensure oxygen is available 
If wheezing, give epinephrine 0.5mg im (0.5mL 1:1000 epinephrine) 
Antihistamine iv/im  
Corticosteroids iv  
Monitor vital signs every 2min until back to baseline 
im=intramuscular; NaCl=sodium chloride; iv=intravenous; po=oral; SBP=systolic blood pressure 
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suspected infusion reaction is not feasible, a sample should be taken at the next regular 
contact with the study participant (eg, next study visit). 
 
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10.16 
Appendix 16: Criteria for diagnosis of sepsis 
In line with the 2016 Society of Critical Care Medicine/European Society of Intensive Care 
Medicine recommendation, Quick Sequential Organ Failure Assessment (qSOFA) scoring 
should be used to determine if a participant likely has a sepsis. Study participants with suspected 
infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if 
they have at least 2 of the following clinical criteria: 
• Respiratory rate ≥22/min 
• Altered mentation 
• Systolic blood pressure ≥100mmHg 
In a hospital setting, the more comprehensive qSOFA score should be considered to determine if 
an event meets the criteria for sepsis. 
 
 
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10.17 
Appendix 17: Criteria for Antiphospholipid Syndrome (APS) 
Clinical criteria (1 or more of the following) 
Laboratory criteria (1 or more of the following 
present on 2 or more occasions at least 
12 weeks apart using recommended 
procedures) 
Vascular thrombosis: 1 or more objectively 
conﬁrmed episodes of arterial, venous or small 
vessel thrombosis occurring in any tissue or organ 
detected according to the guidelines of the 
ISTH 
Pregnancy morbidity: 1 or more unexplained 
deaths of a morphologically normal fetus at or 
beyond the 10th week of gestation; or 1 or more 
premature births of a morphologically normal 
neonate before the 34th week of gestation because 
of eclampsia, preeclampsia, or placental 
insufﬁciency; or 3 or more unexplained 
consecutive spontaneous abortions before the 10th 
week of gestation 
ACL antibody of 
 isotype, present 
in medium or high titer (> 40 
 
phospholipid units or > the 99th percentile) 
measured by a standardized ELISA 
 
 isotype present in 
titer > the 99th percentile measured by a 
standardized ELISA 
ACL = anticardiolipin; APS= antiphospholipid syndrome; 
 I; ELISA= enzyme-linked 
immunosorbent assay; 
 M; ISTH= International Society on 
Thrombosis and Haemostasis; 
 
Adapted from Lim, 2013 
 
 
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11 
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SPONSOR DECLARATION 
I confirm that I have carefully read and understand this protocol and agree to conduct this 
clinical study as outlined in this protocol and according to current Good Clinical Practice. 
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Approval Signatures
Name:
sl0043-protocol-amend-4-16Mar2023
Version:
1. 0
Document Number:
CLIN-000213926
Title:
SL0043 Protocol - Amendment 4 - Placebo-controlled Double-blind
Approved Date:
16 Mar 2023
Document Approvals
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 16-Mar-2023 12:46:54 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Subject Matter Expert
Date of Signature: 16-Mar-2023 14:27:54 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 16-Mar-2023 17:53:55 GMT+0000
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SAP_001.pdf: 
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Statistical Analysis Plan  
Dapirolizumab pegol 
SL0043 
 
 
 
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STATISTICAL ANALYSIS PLAN 
Study: SL0043 
Product: Dapirolizumab pegol 
 
A multicenter, randomized, double-blind, placebo-controlled, parallel-group study to evaluate 
the efficacy and safety of dapirolizumab pegol in study participants with moderately to severely 
active systemic lupus erythematosus. 
SAP/Amendment Number 
Date 
Final SAP 
16DEC2020 
Amendment 1 
14JAN2022 
Amendment 2 
18DEC2023 
Amendment 3 
19Jul2024 
Confidentiality Statement 
Confidential 
This document is the property of UCB and may not – in full or in part – be passed on, 
reproduced, published, or otherwise used without the express permission of UCB. 
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TABLE OF CONTENTS 
LIST OF ABBREVIATIONS .................................................................................................... 8 
1 
INTRODUCTION ........................................................................................................... 11 
2 
PROTOCOL SUMMARY ............................................................................................... 11 
2.1 
Study objectives ........................................................................................................... 11 
2.1.1 
Primary objective ................................................................................................. 11 
2.1.2 
Secondary objectives ........................................................................................... 11 
2.1.2.1 
Key Secondary objectives ......................................................................... 11 
2.1.2.2 
Secondary objectives ................................................................................. 12 
2.1.3 
Tertiary objectives ............................................................................................... 12 
2.2 
Endpoints ..................................................................................................................... 12 
2.2.1 
Primary Endpoint ................................................................................................. 12 
2.2.2 
Key Secondary Endpoints .................................................................................... 12 
2.2.3 
Secondary Endpoints ........................................................................................... 13 
2.2.4 
Tertiary Endpoints ............................................................................................... 13 
2.3 
Study design and conduct ............................................................................................ 16 
2.3.1 
Study description ................................................................................................. 16 
2.4 
Determination of sample size ....................................................................................... 17 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 18 
3.1 
General presentation of summaries and analyses ........................................................ 18 
3.2 
Analysis time points ..................................................................................................... 18 
3.3 
Relative day ................................................................................................................. 19 
3.4 
Definition of Baseline values ....................................................................................... 20 
3.5 
Protocol deviations....................................................................................................... 20 
3.6 
Analysis sets................................................................................................................. 21 
3.6.1 
Enrolled Set ......................................................................................................... 21 
3.6.2 
Randomized Set ................................................................................................... 21 
3.6.3 
Full Analysis Set .................................................................................................. 21 
3.6.4 
Safety Set ............................................................................................................. 21 
3.6.5 
Per-Protocol Set ................................................................................................... 21 
3.6.6 
The Pharmacokinetic Per-Protocol Set ................................................................ 22 
3.7 
Treatment assignment and treatment groups ............................................................... 22 
3.8 
Center pooling strategy ................................................................................................ 22 
3.9 
Coding dictionaries ...................................................................................................... 22 
3.10 
Changes to protocol-defined analyses ......................................................................... 22 
4 
STATISTICAL/ANALYTICAL ISSUES ....................................................................... 25 
4.1 
Adjustments for covariates .......................................................................................... 25 
4.2 
Handling and definition of the corticosteroid prednisone equivalent dose .................. 26 
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4.3 
Handling of Missing Data ............................................................................................ 27 
4.3.1 
Missing data strategy for missing items within scales and missing components of 
composite endpoints such as BICLA response .................................................... 27 
4.3.2 
Non-Responder Imputation (NRI) ....................................................................... 28 
4.3.3 
Multiple imputation (MI) assuming Missing at Random (MAR) – (MI-MAR) of 
BICLA, No Worsening in PGA, SLEDAI and BILAG Improvement at Week 
48  ..................................................................................................................... 29 
4.3.4 
Multiple imputation (MI) assuming Missing at Random (MAR) – (MI-MAR) of 
SLEDAI-2K at Week 48 ...................................................................................... 30 
4.3.5 
Multiple imputation (MI) assuming Missing at Random (MAR) – (MI-MAR) of 
Severe BILAG Flares Through week 48 ............................................................. 31 
4.3.6 
Dates and times .................................................................................................... 32 
4.4 
COVID-19.................................................................................................................... 34 
4.5 
Escape Treatment Interventions – Definitions ............................................................. 34 
4.5.1 
Escape Treatment Intervention 1 (Landmark endpoints, Flare endpoints) .......... 34 
4.5.2 
Escape Treatment Intervention 2 (Severe Flares only) ........................................ 35 
4.5.3 
Escape Treatment Intervention 3 (Moderate flares only) .................................... 35 
4.5.4 
Escape Treatment Intervention 4 (LLDAS) ........................................................ 35 
4.6 
Interim analyses and data monitoring .......................................................................... 35 
4.6.1 
Data Monitoring ................................................................................................... 35 
4.6.1.1 
Independent Data Monitoring Committee (IDMC) ................................... 35 
4.6.1.2 
Data Evaluation Meetings (DEMs) ........................................................... 35 
4.6.2 
Interim Analyses .................................................................................................. 36 
4.7 
Multicenter studies ....................................................................................................... 36 
4.8 
Multiple comparisons/testing strategy ......................................................................... 36 
4.9 
Examination of subgroups ........................................................................................... 38 
4.9.1 
Subgroup analyses on the primary efficacy endpoint .......................................... 38 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 39 
5.1 
Participant disposition .................................................................................................. 39 
5.2 
Protocol deviations....................................................................................................... 40 
5.3 
2019 EULAR/ACR Classification Criteria for SLE .................................................... 40 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 40 
6.1 
Demographics .............................................................................................................. 40 
6.2 
Baseline characteristics ................................................................................................ 41 
6.3 
Procedure History and Concomitant Medical procedures ........................................... 44 
6.4 
Medical history conditions ........................................................................................... 44 
6.5 
Prior and concomitant medications .............................................................................. 45 
6.5.1 
Escape Treatment Medications ............................................................................ 45 
6.6 
Lifestyle ....................................................................................................................... 45 
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6.7 
Childbearing Potential ................................................................................................. 45 
6.8 
Immunosuppressant, Antimalarial and Corticosteroid at Baseline .............................. 46 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 46 
................................................................................................ 46 
46 
47 
47 
48 
49 
51 
52 
57 
59 
61 
66 
66 
67 
69 
70 
71 
72 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS .......................................... 73 
9.1 
Pharmacokinetics (PK) ................................................................................................ 73 
9.2 
Immunogenicity analyses............................................................................................. 74 
9.2.1 
ADA and Nab Sample Status .............................................................................. 74 
9.2.2 
ADA/Nab Participant Status ................................................................................ 75 
9.3 
Pharmacodynamics (PD) and Immunological analyses ............................................... 79 
10 SAFETY ANALYSES ..................................................................................................... 83 
10.1 
Adverse events ............................................................................................................. 83 
10.1.1 
Evaluation of relationship of ADA with TEAEs ................................................. 87 
10.2 
Extent of exposure ....................................................................................................... 87 
10.2.1 
Calculation of planned and actual dose received ................................................. 88 
10.3 
Clinical laboratory evaluations .................................................................................... 89 
10.4 
Vital signs, physical findings, and other observations related to safety ...................... 90 
10.4.1 
Vital signs ............................................................................................................ 90 
10.4.2 
Electrocardiograms .............................................................................................. 91 
10.4.3 
Physical examination ........................................................................................... 92 
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10.4.4 
Assessment of Suicidal Ideation and Behavior ................................................... 92 
10.5 
Tuberculosis (TB) Questionnaire: Evaluation of Signs and Symptoms of Tuberculosis93 
11 COVID-19 IMPACT ....................................................................................................... 93 
12 REFERENCES ................................................................................................................ 95 
... 98 
... 98 
... 99 
. 100 
. 112 
. 114 
. 115 
. 119 
. 120 
. 121 
. 123 
. 124 
. 125 
. 126 
. 127 
. 130 
. 131 
. 140 
. 141 
. 142 
. 143 
. 143 
. 143 
. 143 
. 145 
. 148 
14 AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN (SAP) .................... 149 
14.1 
Amendment 1 ............................................................................................................. 149 
14.2 
Amendment 2 ............................................................................................................. 150 
14.3 
Amendment 3 ............................................................................................................. 152 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ................................................... 154 
 
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LIST OF TABLES 
Table 3-1: 
Changes to the protocol defined analyses ........................................................ 22 
Table 4-1: 
Prednisone equivalent doses of systemic Corticosteroids Steroids Dose 
equivalent to 1mg Prednisone .......................................................................... 27 
Table 8-1: 
Intercurrent Events (ICE) ................................................................................. 47 
Table 8-2: 
Sensitivity analyses of the primary efficacy endpoint ..................................... 49 
Table 8-3: 
Supplementary analyses for the primary efficacy endpoint ............................. 52 
Table 8-4: 
Supplementary analyses for the primary efficacy endpoint (continued) ......... 53 
Table 8-5: 
Estimand’s attributes to be considered for the analysis of the key 
secondary endpoints. ........................................................................................ 57 
Table 8-6: 
Intercurrent events and missing data strategies for the evaluation of the 
key secondary endpoints (sensitivity analysis) ................................................ 59 
Table 8-7: 
Secondary Endpoints ....................................................................................... 61 
Table 8-8: 
Tertiary Endpoints – Group 1 .......................................................................... 66 
Table 8-9: 
Tertiary Endpoints – Group 2 .......................................................................... 67 
Table 8-10: 
Tertiary endpoints – Group 2 Intercurrent Events and Missing Data 
Strategy ............................................................................................................ 69 
Table 8-11: 
Tertiary Endpoints – Group 3 (cumulative achievement of disease status 
endpoints) ......................................................................................................... 69 
Table 8-12: 
Tertiary Endpoints – Group 3 Intercurrent Events, Intercurrent Events 
Strategy and Missing Data Strategy ................................................................. 69 
Table 8-13: 
Tertiary Endpoints – Group 4 Intercurrent Events, Intercurrent Events 
Strategy and Missing Data Strategy ................................................................. 70 
Table 8-14: 
Tertiary endpoints Group 5 .............................................................................. 71 
Table 8-15: 
Tertiary endpoints Group 6 .............................................................................. 72 
Table 8-16: 
Intercurrent Events, Intercurrent Events Strategy and Missing Data 
Strategy for Tertiary endpoints Group 6 .......................................................... 72 
Table 10-1: 
Abnormality criteria for vital sign parameters ................................................. 91 
Table 10-2: 
Abnormality criteria for body weight .............................................................. 91 
Table 10-3: 
Abnormal criteria for ECG parameters ............................................................ 92 
Table 13-1: 
SLEDAI-2K Scoring ...................................................................................... 113 
 
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LIST OF FIGURES 
Figure 2-1: 
Schema ............................................................................................................. 17 
Figure 4-1: 
Multiplicity strategy figure .............................................................................. 38 
 
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LIST OF ABBREVIATIONS 
ACR   
 
 
American College of Rheumatology 
ADA   
 
 
Anti-drug antibody 
AE  
 
 
 
Adverse event 
ALT 
 
 
 
Alanine aminotransferase 
aPL  
 
 
 
Antiphospholipid antibody 
APS 
 
 
 
Antiphospholipid syndrome 
AST   
 
 
Aspartate aminotransferase 
BICLA  
 
 
BILAG 2004-based Composite Lupus Assessment 
BILAG 2004   
British Isles Lupus Assessment Group Disease Activity Index 2004 
CI  
 
 
 
Confidence interval 
CLASI  
 
 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
CMH  
 
 
Cochran-Mantel-Haenszel 
CSR   
 
 
Clinical study report 
C-SSRS   
 
Columbia Suicide Severity Rating Scale 
CTCAE   
 
Common Terminology Criteria for Adverse Events 
DBP   
 
 
Diastolic blood pressure 
DEM   
 
 
Data Evaluation Meeting 
DNA   
 
 
Deoxyribonucleic acid 
DORIS  
 
 
Definitions of Remission in SLE 
DZP   
 
 
Dapirolizumab pegol 
ECG   
 
 
Electrocardiogram 
eCRF   
 
 
Electronic Case Report Form 
eGFR   
 
 
Estimated glomerular filtration rate 
eCOA  
 
 
Electronic clinical outcomes assessment form 
eLAS  
 
 
Electronic Lupus assessment suite 
ES  
 
 
 
Enrolled Set 
ESR   
 
 
Erythrocyte Sedimentation Rate 
EULAR/ACR  
European League Against Rheumatism/American College of Rheumatology 
EOT   
 
 
End of Treatment 
EQ-5D-5L  
 
Euro Quality of life 5-Dimensions 5-Level 
FAS   
 
 
Full Analysis Set 
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FACIT-F  
 
Functional Assessment of Chronic Illness Therapy-Fatigue Scale 
FCS 
 
 
 
Fully conditional specification 
FDA   
 
 
Food and Drug Administration 
GCP  
 
 
Good clinical practice 
GGT   
 
 
Gamma-glutamyltransferase 
HIV   
 
 
Human immunodeficiency virus 
HR  
 
 
 
Heart Rate 
HRQoL   
 
Health-related quality of life 
ICH   
 
 
International Council for Harmonization 
IDMC  
 
      Independent Data Monitoring Committee 
Ig   
 
 
 
Immunoglobulin 
IMP   
 
 
Investigational medicinal product 
IPD  
 
 
 
Important Protocol Deviation 
Iv   
 
 
 
Intravenous(ly) 
KSE 
 
 
 
Key Secondary Endpoint 
LLDAS   
 
Lupus Low Disease Activity State 
LLN   
 
 
Lower limit of normal 
LOE 
 
 
 
Lack of efficacy 
Lupus QoL 
 
Lupus Quality of Life Questionnaire 
MAR   
 
 
Missing at random 
MACE  
 
 
Major Adverse Cardiovascular Event 
MCAR  
 
 
Missing completely at random 
MedDRA  
 
Medical Dictionary for Regulatory Activities coding dictionary 
MI  
 
 
 
Multiple imputation 
MNAR 
 
 
Missing not at random 
mNRI   
 
 
Modified non-responder imputation  
MMRM  
 
 
Mixed Model for Repeated Measurement 
MSR   
 
 
Minimum Significant Ratio 
Nab 
 
 
 
Neutralizing antibodies 
NRI 
 
 
 
Non-responder imputation 
OLE 
 
 
 
Open label extension 
OR  
 
 
 
Odds ratio 
PBO   
 
 
Placebo 
PD  
 
 
 
Pharmacodynamics(s) 
PEG   
 
 
Polyethylene glycol 
PGA   
 
 
Physician’s Global Assessment of Disease 
PHQ-9  
 
 
Patient Health Questionnaire-9 
PI  
 
 
 
Principal investigator 
PK  
 
 
 
Pharmacokinetic(s) 
PK-PPS 
 
 
Pharmacokinetic Per Protocol Set 
PPS 
 
 
 
Per Protocol Set 
PR  
 
 
 
Pulse rate 
PRO   
 
 
Patient-reported outcome 
Q4W  
 
 
Every 4 weeks 
QRS  
 
 
QRS complex (Ventricular depolarization) 
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QTcF  
 
 
QT Interval Corrected for Heart Rate (Fridericia’s Formula) 
RBC   
 
 
Red blood cell 
SAE   
 
 
Serious adverse event 
SAP   
 
 
Statistical Analysis Plan 
SBP   
 
 
Systolic blood pressure 
SD  
 
 
 
Standard deviation 
SFI 
 
 
 
SELENA (Safety of Estrogens in Lupus National Assessment) Flare Index 
SFU   
 
 
Safety Follow-up 
SJC  
 
 
 
Swollen joint count 
SLE   
 
 
Systemic lupus erythematosus 
SLEDAI-2K   
Systemic Lupus Erythematosus Disease Activity Index 2000 
SLICC  
 
 
Systemic Lupus International Collaborating Clinics 
SMQ   
 
 
Standardized MedDRA Queries 
SRI 
 
 
 
The Systemic Lupus Erythematosus Responder Index 
S2K RI-50  
 
SLEDAI-2K Responder Index-50 
SOC  
 
 
Standard of care 
SS   
 
 
 
Safety Set 
TB  
 
 
 
Tuberculosis 
TEAE   
 
 
Treatment-emergent adverse event 
TJC  
 
 
 
Tender joint count 
ULN   
 
 
Upper limit of normal 
uPCR   
 
 
Urine protein-creatinine ratio 
VAS   
 
 
Visual analog scale 
WBC   
 
 
White blood cell 
WHO-DD  
 
World Health Organization Drug dictionary 
 
 
 
 
 
 
 
 
 
 
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1 
INTRODUCTION 
The purpose of this Statistical Analysis Plan (SAP) is to provide all information necessary to 
perform the final statistical analysis of SL0043 supporting the final clinical study report (CSR). 
It also defines the summary tables, listings and figures to be included in the CSR according to 
protocol. The SAP is based on the following study document: Protocol amendment 4.0 dated 16 
March 2023. The content of this SAP is compatible with the International Conference on 
Harmonization (ICH)/ Food and Drug Administration (FDA) E9 Guidance documents. UCB is 
the Sponsor and PAREXEL is the Contract Research Organization (CRO) for this study. 
In this document, the following estimands’ attributes will be considered:  
(1) Treatment condition is standard of care (SOC) medication + dapirolizumab pegol (DZP) 
intravenous (iv) every 4 weeks (q4w) 24mg/kg and the alternative treatment condition is 
SOC medication + Placebo (PBO) iv q4w. 
(2) Population: The population includes participants with moderately to severely active SLE 
despite stable nonbiological SOC medications (standard SLE therapy) and a persistent 
active or frequently relapsing remitting disease course or risk factors for relapsing 
remitting disease course. As defined in the protocol-specified inclusion/exclusion criteria 
reflecting the target study participant population for approval. 
(3) Endpoints (Variables) are described in Section 2.2. 
(4) Intercurrent events and specifications of how they will be handled for analysis purposes 
will be detailed in the sections related to the analysis of each endpoint. 
(5) Population-level summaries for each endpoint will be detailed in the sections related to 
the analysis of each endpoint. 
2 
PROTOCOL SUMMARY 
2.1 
Study objectives 
2.1.1 
Primary objective 
To evaluate the ability of DZP as an add-on treatment to SOC medication to achieve clinically 
relevant long-term improvement of moderate to severe disease activity 
2.1.2 
Secondary objectives 
2.1.2.1 
Key Secondary objectives 
The key secondary objectives of the study are: 
• To evaluate the ability of DZP as an add-on treatment to SOC medication to achieve fast, 
clinically relevant improvement of moderate to severe disease activity 
• To evaluate the ability of DZP as an add-on treatment to SOC medication to achieve long-
term control of disease activity 
• To evaluate the ability of DZP as an add-on treatment to SOC medication to achieve and 
maintain the treat-to-target goal: low disease activity with low/acceptable corticosteroid dose 
over time 
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• To evaluate the ability of DZP as an add-on treatment to SOC medication to achieve 
improvement of disease activity as measured by numerical disease state score commonly 
used in clinical practice 
2.1.2.2 
Secondary objectives 
The secondary objectives of the study are: 
• To evaluate the ability of DZP as an add-on treatment to SOC medication to achieve 
components of the composite primary endpoint 
• To evaluate the ability of DZP as an add-on treatment to SOC medication to achieve 
alternative responder endpoint 
• To evaluate the ability of DZP as an add-on treatment to SOC medication to achieve 
endpoints supporting other key secondary endpoints 
• To evaluate the safety and tolerability of DZP as add-on treatment to SOC medication 
2.1.3 
Tertiary objectives 
The tertiary objectives of the study are: 
• To evaluate the ability of DZP as add-on treatment to SOC to achieve endpoints which 
support the primary and secondary objectives and/or support the interpretation of the primary 
and secondary endpoints 
• To evaluate the ability of DZP as an add-on treatment to SOC medication to achieve organ 
specific endpoints 
• To evaluate the ability of DZP as an add-on treatment to SOC medication to achieve 
important patient reported outcomes (PRO) 
• To evaluate the Pharmacokinetic (PK)  
• To evaluate immunogenicity of DZP as an add-on treatment to SOC medication 
• To evaluate the Pharmacodynamic (PD) and immunological parameters of DZP as an add-on 
treatment to SOC medication 
• To evaluate the safety and tolerability of DZP as an add-on treatment to SOC medication 
• To evaluate changes in exploratory biomarkers  
• To evaluate risk for anti-phospholipid associated events 
2.2 
Endpoints 
2.2.1 
Primary Endpoint 
Achievement of BILAG (British Isles Lupus Assessment Group Disease Activity Index) 2004-
based Composite Lupus Assessment (BICLA) response at Week 48 
2.2.2 
Key Secondary Endpoints 
• Achievement of BICLA response at Week 24 
• Achievement of BICLA response at Week 12 
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• Achievement of prevention of severe BILAG flares (severe BILAG flare-free) through Week 
48 
• Achievement of Lupus Low Disease Activity State (LLDAS) in ≥50% of post Baseline visits 
through Week 48 
• Change from Baseline in Systemic Lupus Erythematosus Disease Activity Index (SLEDAI-
2K) at Week 48 
2.2.3 
Secondary Endpoints 
• Achievement of BILAG improvement without worsening at Week 48 
• Change from Baseline in Physician’s Global Assessment of Disease (PGA) at Week 48 
• Achievement of SRI-4 response at Week 48 
• Achievement of prevention of moderate/severe BILAG flares (moderate/severe BILAG flare-
free) through Week 48  
• Time to severe BILAG Flare through Week 48 
• Time to moderate/severe BILAG flare through Week 48 
• Treatment Emergent Adverse Events (TEAEs), serious TEAEs, TEAEs of special interest, 
and TEAEs of special monitoring 
2.2.4 
Tertiary Endpoints 
• Achievement of reduction of corticosteroid dose from >7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day prednisone equivalent by visit 
• Achievement of reduction of corticosteroid dose from >7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day prednisone equivalent at Week 24 and maintaining low 
corticosteroid dose afterwards and achievement of BICLA response at Week 48 
• Achievement of reduction of corticosteroid dose from >7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day prednisone equivalent at Week 24 and maintaining low 
corticosteroid dose and achievement of prevention of moderate/severe BILAG flares 
(moderate/severe BILAG flare-free) through Week 48 
• Achievement of reduction in corticosteroid dose from >5mg/day prednisone equivalent dose 
at start of study to ≤5mg/day prednisone equivalent at Week 24 and maintaining low 
corticosteroid dose and achievement of BICLA response at Week 48 
• Achievement of reduction of corticosteroid dose from >5mg/day prednisone equivalent dose 
to ≤5mg/day prednisone equivalent at Week 24 and maintaining low corticosteroid dose and 
achievement of prevention of moderate/severe BILAG flares (moderate/severe BILAG flare-
free) through Week 48 
• Total corticosteroid dose through Week 24, through Week 48, and from Week 24 through 
Week 48 
• Achievement of BICLA response by visit 
• Achievement of BILAG 2004 improvement without worsening by visit 
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• Change from Baseline in BILAG 2004 score by visit 
• Achievement of BILAG 2004 shifts by visit 
• Achievement of BILAG 2004 improvement by organ system by visit 
• Achievement of maintained BICLA response by visit 
• Achievement of persistent BICLA response between Week 24 and Week 48 
• Worsening of any organ system with a BILAG 2004 B, C, D, E at Baseline to BILAG 2004 
A or worsening of >1 organ system with a BILAG 2004 C, D, E at Baseline to BILAG 2004 
B by visit 
• Achievement of BILAG 2004 C, D, E in all organ systems by visit 
• Change from Baseline in SLEDAI-2K by visit 
• Change from Baseline in Clinical SLEDAI-2K by visit 
• Achievement of SRI 4, 6, 8 response by visit 
• Change from prior visits in S2K RI50 by visit 
• Change from Baseline in PGA by visit 
• Achievement of LLDAS status by visit 
• Cumulative number of visits in LLDAS through Week 48 
• Achievement of LLDAS Variant (demand for ≤5mg/day prednisone equivalent) in >50% of 
post-Baseline visits through Week 48 
• Achievement of prednisone equivalent dose ≤7.5mg/day by visit 
• Prednisone equivalent dose by visit 
• Occurrence of severe BILAG 2004 flares by visit 
• Occurrence of moderate BILAG flares by visit 
• Occurrence of severe SFI flares by visit 
• Occurrence of moderate SFI flares by visit 
• Time to severe SFI flare 
• Time to moderate SFI flare 
• Change from Baseline in American College of Rheumatology (ACR)/ Systemic Lupus 
International Collaborating Clinics (SLICC) damage score by visit 
• Achievement of Definitions of Remission in SLE (DORIS) remission by visit 
• Change from Baseline in Cutaneous Lupus Erythematosus Disease Area and Severity Index 
(CLASI) activity score by visit for all study participants and for subset of study participants 
with high CLASI score 
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• Achievement of a meaningful improvement in CLASI activity score by visit for all study 
participants and for subset of study participants with high CLASI score 
• Change from Baseline in tender joint count (TJC) and swollen joint count (SJC) and tender 
and swollen joint count (T&SJC) by visit for all study participants and for subset of 
participants with moderate to severe 
 
• Achievement of a meaningful decrease in TJC/SJC by visit for all participants and for a 
subset of participants with moderate to severe
 
• Change from Baseline in Lupus 
and Musculoskeletal Disease Activity (LAMDA) 
score and it's components by visit 
• Change from Baseline in Functional Assessment of Chronic Illness Therapy-Fatigue Scale 
(FACIT-F) by visit 
• Change from Baseline in Patient Health Questionnaire-9 (PHQ-9) score by visit 
• Change from Baseline in FATIGUE-PRO 'Physical Fatigue', 'Mental Fatigue' and 
'Fatigability' scores by visit 
• Change from Baseline in Lupus QoL by visit 
• Change from Baseline in EQ-5D-5L by visit 
• 
• 
• Incidence of anti-drug antibodies (ADA): 
 
• Observed values and change from Baseline in 
 
 
 in all study participants 
by visit and in study participants ‘positive’ at Baseline by visit 
• Seroconversion of 
 
 status by visit 
• TEAEs leading to study withdrawal, TEAEs leading to permanent study medication 
discontinuation, TEAEs with start day on day or up to 1 day after infusion, other identified 
TEAE clusters 
• Summary of participants withdrawn from the study due to TEAEs 
• Summary of participants who permanently discontinued study medication 
• Change from Baseline in vital sign parameters by visit 
• Observed values and change from Baseline in safety laboratory tests (hematology, serum 
chemistry, urinalysis) by visit, % study participants achieving critical threshold for selected 
lab parameters by visits 
• Change from Baseline in biomarkers selected for analysis 
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• 
 
 
• 
 
• Achievement of a meaningful improvement in CLASI activity sub score – erythema by visit 
for all study participants and for subset of study participants with high CLASI 
• Achievement of a meaningful improvement in CLASI activity sub score – scaling by visit for 
all study participants and for subset of study participants with high CLASI 
• Achievement of a meaningful improvement in CLASI activity sub score – alopecia by visit 
for all study participants and for subset of study participants with high CLASI 
2.3 
Study design and conduct 
2.3.1 
Study description 
The study will be conducted to demonstrate efficacy, safety and tolerability of DZP in study 
participants with moderately to severely active SLE despite stable nonbiological SOC 
medications (standard SLE therapy) and a persistent active or frequently relapsing remitting 
disease course or risk factors for relapsing remitting disease course to support regulatory filing. 
The study is a randomized, double-blind, placebo-controlled, parallel group, Phase 3 study in 
study participants 16 years of age and older with moderately to severely active SLE who are 
receiving stable SOC medication (ie, antimalarials, corticosteroids, and/or immunosuppressants) 
in line with local and international guidance at Screening Visit (V1).  
The study consists of a 2-week Screening Period, 48-week Treatment Period, and 6-week Safety 
Follow-up (SFU) Period (if the participant completes the study but decides not to enter the open-
label extension (OLE) study SL0046). Due to the required moderate to severe disease activity at 
Screening visit (V1) and limited allowed treatment possibilities during the Screening phase, a 
short Screening Period is planned, see Figure 2-1 below. At the start of the study, eligible study 
participants will be randomized (2:1) to DZP 24mg/kg or to placebo administered by iv infusion 
Q4W. The initial dose will be administered as a 2-hour infusion while each subsequent dose will 
be administered as a 1-hour infusion. Study participants who complete the 48-week Treatment 
Period may be eligible to participate in an OLE study (SL0046). Study participants who 
withdraw early from the 48-week Treatment Period will be followed up for at least 10 weeks 
after their final dose of study medication. Study participants who complete the study but choose 
not to enter the OLE will be followed up for at least 10 weeks after their final dose of study 
medication (ie, 10 weeks after last infusion at Week 44 which includes a 6-week SFU period). 
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Figure 2-1: 
Schema 
 
BICLA=BILAG 2004-based Composite Lupus Assessment; BILAG=British Isles Lupus Assessment Group Disease 
Activity Index; BL=Baseline; CS=corticosteroid; DZP=dapirolizumab; EOS=End of Study; EOT=End of 
Treatment; N=number of study participants planned; OLE=open-label extension; PBO=placebo; Q4W=every 4 
weeks; Scr=Screening; SFU=Safety Follow-up; SOC=standard of care; V=Visit; W/wk=week 
a The CS tapering should start no later than the Week 8 Visit (V4) with a targeted prednisone equivalent dose 
≤7.5mg/day (in line with current treatment guidelines), guidance on how to taper will be provided but dynamic of 
dose-reduction is finally in the discretion of the investigators to be adapted to the patient’s individual needs. 
Please see the schedule of activities in Section 1.3, Table 1-2 in the SL0043 protocol for details. 
2.4 
Determination of sample size 
The statistical power and sample size consideration is based on the objective to detect a 
meaningful improvement in BICLA responder rate compared with SOC+PBO at Week 48. 
Given 104 study participants in SOC+PBO and 208 study participants in SOC+DZP 24mg/kg 
groups and an assumed SOC+PBO responder rate of 0.32, there will be 90% power to confirm an 
SOC+DZP 24mg/kg responder rate of 0.52 (ie, a 0.20 improvement), to achieve statistical 
significance using a 2-sided 0.05 significance level test (SAS® version 9.4 POWER procedure, 
Fisher’s exact). The sample size assumptions for SOC+PBO and SOC+DZP are based on the 
Phase 2b study SL0023 responder data at Week 24 in the population fulfilling SL0043 eligibility 
criteria. 
Participants who withdraw from the study prior to the Week 48 Visit will be included in the 
primary efficacy analysis as non-responders (see Section 4.3.2 for additional details about the 
non-responder imputation). Therefore, no additional participants are planned to be randomized in 
order to make up for early withdrawers. 
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3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
Statistical analysis and generation of tables, figures, study participant data listings, and statistical 
outputs will be performed using SAS® Version 9.4 (SAS Institute, Cary, NC, USA). 
For continuous parameters, number of participants with available measurements, mean, standard 
deviation (SD), median, minimum and maximum, and for categorical parameters, number of 
participants and percentages (to one decimal place) in each category will be presented in the 
summary tables. Changes from Baseline and/or percentage changes from Baseline will be 
presented where required. 
All descriptive statistics will be presented by treatment group where applicable. All tabulations 
will be sorted by treatment, parameter and visit (including time relative to dosing if applicable, 
unless otherwise stated). Only scheduled visits and times relative to dosing will be included in 
the tabulation. The number of decimal places for continuous summary statistics should be based 
on level of precision captured in the source (eg, case report form (CRF), lab transfer, etc.) for 
non-derived variables. In general, for derived variables, min/max will be presented as collected 
in the source, and mean, SD, median have 1 additional decimal place with respect to the source. 
Categorical data will be summarized by visit and treatment group, including column for all study 
participants in certain outputs (see Section 3.7 for details). Percentages will be based on the 
corresponding population size (ie, the denominator of percentages should match the sample size 
in the column header), unless otherwise noted via footnote in the applicable summary table. 
Percentages will be presented to 1 decimal place. For data points with n=0 (ie, no participants in 
the applicable category), no value for percentage of participants will be displayed. 
Missing observations will be counted and described in the reports unless otherwise specified. For 
the shift tables, the percentages will be based on non-missing records at Baseline and the related 
post Baseline time points. 
Statistical tests of efficacy variables will be presented as 2-sided p-values. P-values will be 
rounded to 4 decimal places. P-values less than 0.0001 will be presented as “<0.0001” and p-
values greater than 0.9999 will be presented as “>0.9999.” 
Handling of multiplicity for the primary and key secondary efficacy variables is discussed in 
Section 4.8. All other efficacy variables will be considered exploratory in nature, hence 
inferential analysis will be assessed at 0.05 alpha level. 
Unless otherwise noted, each table will be supported by a corresponding participant data listing 
and each figure will be supported by a corresponding table or listing. Participant data listings 
should use the largest logical analysis set in which the data is captured, in most cases this will be 
Enrolled Set for items collected in all study participants, the Full Analysis Set or Safety Set for 
all assessments collected only for randomized study participants. 
3.2 
Analysis time points 
The timeframe encompasses the entire study duration, which extends from Screening to 10 
weeks after the final dose, ie, 48 weeks of the Double-Blind Treatment Period and 6 weeks of the 
SFU Period. 
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The following study periods will be included in the analysis (see Section 3.3 for the definition of 
Relative day): 
• Screening Period: up to 14 days (Day -14 through Day -1). 
• Double-Blind Treatment Period: 48 weeks, starts with the randomization (1:2) of eligible 
participants to 1 of 2 treatment arms (SOC + placebo [PBO] or SOC + DZP 24mg/kg), 
stratified in accordance with the 3 stratification factors (see Section 4.1). Study medication 
will be administered by iv infusion every 4 weeks, starting on Day 1. 
• Safety Follow-up Period (SFU):  
− Participants who withdraw from the study prematurely will be followed up for at least 10 
weeks after the last infusion. 
− Participants who complete the 48-week Double-Blind Treatment Period, but do not enter 
the OLE study will continue into a 6-week SFU Period (10 weeks after last infusion at 
Week 44). During this period, study participants will not receive study medication, but 
will be able to receive SOC treatment, as indicated. 
The time points for individual assessments are provided in the schedule of activities in Section 
1.3, Table 1-2 in the SL0043 protocol. 
Analyses conducted by visit will include each planned study visit at which the assessment was 
scheduled. Data for planned study visits will be based on the nominal time point and will not 
include any unplanned visits. Usually, efficacy data will not be obtained at unscheduled visits, 
with the exception of lab data used in the BILAG grading process and for SLEDAI-2K. Here, 
labs that are obtained prior to the visit or up to 2 weeks after the original visit could be used to 
replace missing lab data (see separate Central BILAG Grading and Adjudication Plan for details 
on the BILAG grading process). 
All data collected, including assessments (planned or unplanned) will be reported in participant 
data listings. Data from participants withdrawing from the study early at end of treatment (EOT) 
visits will be mapped to the next scheduled visit per assessment for purpose of analyses and 
inclusion in summary tables but will be presented in terms of nominal visit in listings.  
3.3 
Relative day 
 Relative days for an event or measurement occurring before a reference date (generally the date 
of the first dose of study drug) are calculated as follows:  
• Relative Day = (Event Date-Reference Date) 
Relative days for an event or measurement occurring on or after the reference date to the last day 
of dose administration are calculated as follows:  
• Relative Day = (Event Date-Reference Date) + 1  
For events or measurements occurring after the date of last dose of study drug the relative day 
will be calculated with the date of last dose administration as reference. Relative day in this case 
will be prefixed with ‘+’ in the data listings and will be calculated as follows:  
• Relative Day = + (Event Date-Reference Date) 
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Note: relative day will be computed for fully reported dates only (for imputed dates it will not be 
computed) 
3.4 
Definition of Baseline values 
Unless otherwise specified, the last value collected prior to the first infusion of study medication 
(Visit 2) will be used as the Baseline value. If a Baseline measurement is missing, and a 
Screening value is available, then the available Screening value will be utilized as Baseline. If a 
Baseline measurement is missing and there are multiple Screening lab values, then the most 
recent lab value prior to Baseline will be considered as the Baseline value. Unscheduled lab 
measurements taken before Baseline will be labelled as Screen Re-test values. 
• For vital signs, a measurement prior to, or at the moment of, the start of the first infusion will 
be available for each visit. The last measurement prior to, or at the moment of, the start of the 
first infusion of study medication will be used as the Baseline value. An additional analysis 
will be performed using the pre-infusion values as Baseline values to determine the changes 
from pre infusion to post-infusion for each infusion visit. At each post-Baseline visit, the pre-
infusion value will be one taken prior to, or at the moment of, the start of the infusion of 
study medication. 
• For BILAG 2004 assessments, if the assessment is completed at Baseline, but the Grade for 1 
or more individual system(s) is missing, the Grade for the system will be imputed as the 
Grade observed at the Screening visit. If there is no Grade available for the individual system 
at the Screening visit, then the Grade for that system at Baseline will be set to a Grade of 
BILAG 2004 D or E (in case no organ involvement ever before is documented). 
• For SLEDAI-2K assessments, if a lab component for SLEDAI is missing at Baseline, the 
following methods will be applied. 
− If the last observation is present the last observation will be carried forward. 
− If there is no last observation the next observation will be carried backwards when there 
is one within the next 2 weeks. 
− If there are no observations under above two conditions the Baseline value will be set to 
‘not present’. 
− Missing lab values that determine hematuria, pyuria or proteinuria at Baseline and at 
Screening will be imputed to 0. 
3.5 
Protocol deviations 
Important protocol deviations (IPDs) are a subset of protocol deviations that may significantly 
impact the completeness, accuracy, and/or reliability of the study data or that may significantly 
affect a participant’s rights, safety, or well-being. 
The criteria for identifying IPDs will be defined within the Protocol Deviation Specification 
Form. IPDs will be reviewed as part of the ongoing data cleaning process and data evaluation. 
All IPDs will be identified and documented prior to unblinding to confirm exclusion from 
analysis sets. 
Sources for identifying protocol deviations will include the clinical database and a cumulative 
protocol deviation log from the clinical sites. Protocol deviations will be classified at blinded 
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data cleaning and data evaluation meetings. Any exclusion of participants from analysis sets or 
individual data from summary outputs will be documented in the meeting minutes. 
For participants enrolled under different versions of the protocol, the programming of protocol 
deviations should be performed according to the version of the Protocol Deviation Specification 
Form relevant to the specific protocol version. The Protocol Deviation Specification Form will 
provide further details with regards to which version of the protocol the specific Protocol 
Deviation Specification Form version is applicable to. The version of the protocol to be followed 
for each participant will be provided by the Project Manager. 
3.6 
Analysis sets 
The population of interest defined in Section 1, will be managed for statistical/reporting purposes 
using the following analysis datasets: 
3.6.1 
Enrolled Set 
The Enrolled Set (ES) will consist of all study participants who have given informed consent. 
3.6.2 
Randomized Set 
The Randomized Set (RS) will consist of all randomized study participants. 
3.6.3 
Full Analysis Set 
The Full Analysis Set (FAS) will consist of all study participants randomized into the study 
following the intent to treat principle. The FAS is the primary analysis set for efficacy analyses 
and will be based on the planned treatment (assigned during randomization). 
Based on concerns pertaining to persistent GCP non-compliance related to primary investigator 
(PI) oversight and study conduct, site 50273 was closed on 08 August 2023. It was discussed and 
agreed by the study team at the final Data Evaluation Meeting prior to database lock that efficacy 
data collected at site 50273 is not reliable and will be excluded from efficacy analyses by 
excluding participants randomized at this site from the FAS. There were 6 participants 
randomized at site 50273. Five of the participants completed the study at site 50273. One of the 
participants, 1327, had the Baseline visit and subsequent visits through Visit 6 at site 50273, but 
then transferred to site 50339 and completed the study at site 50339. All 6 participants will be 
excluded from the FAS. 
3.6.4 
Safety Set 
The Safety Set (SS) will consist of all study participants who are randomized and have received 
at least 1 dose (any amount) of study medication. Safety endpoints will be analyzed using the SS. 
In the case of any mistreated participants, participants will be analyzed 'as randomized' unless 
there is evidence the participant consistently received incorrect treatment, in which case an 'as 
treated' approach will be followed (which will consider the actual treatment received). 
Note that site 50273 is included in the SS. 
3.6.5 
Per-Protocol Set 
The Per-Protocol Set (PPS) will consist of study participants in the FAS who have received at 
least 1 full dose of study medication and have no important protocol deviations during the 
Treatment Period that may influence the validity of the data for the primary efficacy variable. 
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3.6.6 
The Pharmacokinetic Per-Protocol Set 
The Pharmacokinetic Per-Protocol Set (PK-PPS) consists of all study participants who received 
at least 1 dose of study medication and provided at least one quantifiable plasma concentration 
post-dose without important protocol deviations that would affect the concentration.  
Note that site 50273 is included in the PK-PPS. 
 
3.7 
Treatment assignment and treatment groups 
For all analyses (where applicable) the results will be presented by treatment group: 
• SOC + PBO iv q4w 
• SOC + DZP 24mg/kg iv q4w 
Selected parameters (where stated in the following sections) may be summarized also by 
subgroup (definition of subgroups, Section 4.9.1). A column for ‘All Participants’ will be added 
to group all participants regardless of treatment group, in the disposition, demographics, Baseline 
characteristics, prior and concomitant medications, corticosteroid dose at Screening and 
Baseline, exposure and Adverse Events (AEs) summary tables.  
3.8 
Center pooling strategy 
There is no pooling strategy (by sites) defined for this study. Results will be combined across all 
sites, or by region according to the specified analysis. 
3.9 
Coding dictionaries 
All AEs, concomitant diseases, and medical history will be coded for analysis according to the 
Medical Dictionary for Regulatory Activities (MedDRA)® coding dictionary, version 24.0 Prior 
and concomitant medications will be coded for analysis using the World Health Organization 
Drug dictionary (WHO-DD), Sep/2020 B3. The version number of coding dictionary will be 
displayed within the table. The coding dictionaries used to code adverse events (AEs), medical 
history, concomitant medications and concomitant diseases will be specified.  
3.10 
Changes to protocol-defined analyses 
Table 3-1: 
Changes to the protocol defined analyses 
Current in the protocol 
Change 
Tertiary endpoints: 
Observed values and change from Baseline in 
 
 
 
 
 levels in all 
Observed values and change from 
Baseline in 
 
 
 
 
 levels in all study 
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Table 3-1: 
Changes to the protocol defined analyses 
study participants by visit and in study 
participants ‘positive’ at Baseline by visit 
participants by visit and in study 
participants ‘positive’ at Baseline by visit. 
Tertiary endpoints: 
Achievement of a meaningful improvement in 
CLASI Index by visit for all study 
participants and for subset of study 
participants with high CLASI  
Achievement of a meaningful 
improvement in CLASI activity score by 
visit for all study participants, for subset 
of study participants with high CLASI, 
and study participants with a CLASI ≥10 
Tertiary endpoints: 
Observed values and change from Baseline in 
 
 
 
 
 levels in all study participants by 
visit and in study participants ‘positive’ at 
Baseline by visit 
Added 
 
 conversion to the 
immunological parameters of DZP that 
will be evaluated 
 
Tertiary endpoints: 
Achievement of reduction in corticosteroid 
dose from ≥7.5mg/day prednisone equivalent 
dose at start of study to ≤5mg/day prednisone 
equivalent at Week 24 and maintaining low 
corticosteroid dose and achievement of 
BICLA response at Week 48 
Achievement of reduction in 
corticosteroid dose from >5mg/day 
prednisone equivalent dose at start of 
study to ≤5mg/day prednisone equivalent 
at Week 24 and maintaining low 
corticosteroid dose and achievement of 
BICLA response at Week 48 
Tertiary endpoints: 
Achievement of reduction of corticosteroid 
dose from >7.5mg/day prednisone equivalent 
dose at start of study to ≤7.5mg/day 
prednisone equivalent at Week 24 and 
maintaining low corticosteroid dose and 
achievement of prevention of moderate/severe 
BILAG flares (moderate/severe BILAG flare-
free) at Week 48 
Achievement of reduction of 
corticosteroid dose from >7.5mg/day 
prednisone equivalent dose at start of 
study to ≤7.5mg/day prednisone 
equivalent at Week 24 and maintaining 
low corticosteroid dose and achievement 
of prevention of moderate/severe BILAG 
flares (moderate/severe BILAG flare-free) 
through Week 48 
Tertiary endpoints: 
Achievement of reduction in corticosteroid 
dose from >5mg/day prednisone equivalent 
dose at start of study to ≤5mg/day prednisone 
Achievement of reduction in 
corticosteroid dose from >5mg/day 
prednisone equivalent dose at start of 
study to ≤5mg/day prednisone equivalent 
at Week 24 and maintaining low 
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Table 3-1: 
Changes to the protocol defined analyses 
equivalent at Week 24 and maintaining low 
corticosteroid dose and achievement of 
BICLA response at Week 48 
 
 
corticosteroid dose and achievement of 
BICLA response at Week 48 
 
Tertiary endpoints: 
Achievement of reduction of corticosteroid 
dose from ≥7.5mg/day prednisone equivalent 
dose to ≤5mg/day prednisone equivalent at 
Week 24 and maintaining low corticosteroid 
dose and achievement of prevention of 
moderate/severe BILAG flares 
(moderate/severe BILAG flare-free) at Week 
48 
Achievement of reduction of 
corticosteroid dose from >5mg/day 
prednisone equivalent dose to ≤5mg/day 
prednisone equivalent at Week 24 and 
maintaining low corticosteroid dose and 
achievement of prevention of 
moderate/severe BILAG flares 
(moderate/severe BILAG flare-free) 
through Week 48 
To the current tertiary endpoints: 
 
Added: 
• Achievement of a meaningful 
improvement in CLASI activity sub 
score – erythema by visit for all study 
participants and for subset of study 
participants with high CLASI 
• Achievement of a meaningful 
improvement in CLASI activity sub 
score – scaling by visit for all study 
participants and for subset of study 
participants with high CLASI 
• Achievement of a meaningful 
improvement in CLASI activity sub 
score – alopecia by visit for all study 
participants and for subset of study 
participants with high CLASI 
• Change from Baseline in Clinical 
SLEDAI-2K by visit 
 
Revised definition of DORIS:  
- Clinical SLEDAI-2K score =0 
(SLEDAI-2K without serology: 
 
- PGA ≤16mm 
- Prednisone equivalent systemic dose for 
a SLE indication ≤5mg per day at >50% 
of the last 28 days (>14 of the last 28 
days) and the prednisone dose is 
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Table 3-1: 
Changes to the protocol defined analyses 
≤5mg/day at all days in the 7 days before 
a visit, at the day of the visit and at the day 
after the visit 
- 
≤ULN 
- 
 ≥LLN 
To the current primary efficacy subgroup 
analyses: 
4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Adjustments for covariates 
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4.2 
Handling and definition of the corticosteroid prednisone equivalent 
dose 
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4.3 
Handling of Missing Data  
4.3.1 
Missing data strategy for missing items within scales and missing 
components of composite endpoints such as BICLA response 
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4.3.2 
Non-Responder Imputation (NRI) 
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4.3.3 
Multiple imputation (MI) assuming Missing at Random (MAR) – (MI-
MAR) of BICLA, No Worsening in PGA, SLEDAI and BILAG 
Improvement at Week 48 
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4.3.4 
Multiple imputation (MI) assuming Missing at Random (MAR) – (MI-
MAR) of SLEDAI-2K at Week 48 
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4.3.5 
Multiple imputation (MI) assuming Missing at Random (MAR) – (MI-
MAR) of Severe BILAG Flares Through week 48 
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4.3.6 
Dates and times 
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4.4 
COVID-19 
4.5 
Escape Treatment Interventions – Definitions 
4.5.1 
Escape Treatment Intervention 1 (Landmark endpoints, Flare 
endpoints) 
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4.6 
Interim analyses and data monitoring 
4.6.1 
Data Monitoring 
4.6.1.1 
Independent Data Monitoring Committee (IDMC) 
An IDMC will be established to monitor safety and the benefit-risk profile of study participants. 
The composition and operation of the IDMC will be defined in the IDMC Charter. The 
presentation and analysis of data for the IDMC meetings will focus on safety data, but efficacy 
data will be provided to support benefit-risk assessment, and is described within the Appendix of 
this SAP in Section 13.19. The IDMC data review will occur at least every six months, with the 
first data cut (for the IDMC meeting) scheduled at the latest after the first participant in SL0043 
has completed 6 months on treatment. The last data review meeting will be scheduled after all 
participants have finished treatment, and the data have been appropriately prepared for final 
IDMC review. At each meeting, the IDMC will provide a recommendation as to whether the 
study should be stopped, should be adapted, or can proceed as planned. 
4.6.1.2 
Data Evaluation Meetings (DEMs) 
Four DEMs are planned for assessment of blinded aggregate data throughout the study: 
(1) DEM-1 will take place after approximately 15 to 20% of the enrolled participants have 
completed the Week 12 assessment. Objectives: Evaluation of aggregate data in order to 
identify systemic data errors and potential trends in important protocol deviations, and 
review of aggregate data to detect outliers and to evaluate relevant data distributions. 
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(2) DEM-2a will take place after approximately 25% - 30% of randomized participants have 
completed the Week 24 assessments or have withdrawn from study medication in the 
study. Objectives: Evaluation of aggregate data in order to identify systemic data errors 
and potential trends in important protocol deviations, discussion of dry-run tables, listings 
and figures, and finalization of the content of outputs defined in the SAP.  
(3) DEM-2b will take place after approximately 30 to 60% of the enrolled participants have 
complete data of the primary variable. Objectives: Evaluation of aggregate data in order to 
identify systemic data errors and potential trends in important protocol deviations, 
discussion of dry-run tables, listings and figures, and finalization of the content of outputs 
defined in the SAP. 
(4) DEM-3 will take place after 100% of the enrolled participants have complete data of the 
primary variable, all data are entered and approximately 95% to 100% of the data are 
clean. Objectives: confirmation of statistical assumptions, discussion of any outstanding 
analysis topics and finalization of rules for exclusion from analysis set. 
4.6.2 
Interim Analyses 
An interim analysis to assess futility was specified within the original protocol and was removed 
for protocol Amendment 4. Therefore, an interim analysis is no longer planned. 
4.7 
Multicenter studies 
This is a multicenter study with participation of approximately 230 sites in approximately 31 
countries. 
4.8 
Multiple comparisons/testing strategy  
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4.9 
Examination of subgroups 
 
4.9.1 
Subgroup analyses on the primary efficacy endpoint 
Summary tables on the primary efficacy endpoint variable (BICLA) by visit using descriptive 
statistics in the FAS, will be presented in the following subgroups: 
• Prior use of biological response modifier (Yes/No)  
• Pooled regions (North America vs. Western Europe/Asia-Pacific vs. Latin America/Eastern 
Europe) 
• Chronic active vs. acute flaring at Screening 
• SLEDAI-2K Total Score (<10 vs. ≥10) at Screening 
• 
antibody positive (yes/no) at Baseline 
• 
antibody positive AND low complement (yes/no) at Baseline 
• Region   
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• Ethnicity 
• Age group 2 at Baseline 
− <median age 
− ≥median age 
• Antimalarial use at Baseline (yes/no) 
• Immunosuppressant use at Baseline (yes/no) 
• Corticosteroid dose at Baseline >7.5mg/day (yes/no) 
• Low complement at Baseline 
− Low
(yes/no) 
− Low
(yes/no) 
− Low
and/or 
 (yes/no) 
5 
STUDY POPULATION CHARACTERISTICS 
5.1 
Participant disposition 
The following summary tables using descriptive statistics will be created: 
(1) Disposition of participants screened (using the ES)  
(2) Disposition and discontinuation reasons (using the RS)  
(3) Reasons for Screen Failures (using the ES) 
(4) Discontinuation Due to AE (using the RS) 
Note:  
The number of screened participants, as well as screening events (to account for rescreened 
participants), will be presented, as well as the number of re-screened participants, the number of 
participants randomized after first screening and the number of participants randomized after re-
screening.  
The time to permanent study drug discontinuation or premature withdrawal, whichever event 
occurs first will be plotted using Kaplan-Meier methods by treatment group in RS. Time until 
permanent discontinuation of study drug or premature withdrawal from the study will be 
calculated using the date at which a participant is considered a non-responder in efficacy 
analyses due to study withdrawal or permanent study treatment discontinuation determined as 
per the algorithm in Section 4.3. 
If a participant has not prematurely withdrawn from the study nor discontinued study drug 
permanently by Week 48, she/he should be censored on the day of the Week 48 visit date (or 
final visit date if Week 48 visit was missed).  
The following listings will be also created: 
(1) Study Participants Disposition (using the ES) 
(2) Study Participants Eligibility Criteria Text (using the ES) 
(3) Study Participants Who Did Not Meet Study Eligibility Criteria (using the ES) 
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(4) Participants Completions and Discontinuations during the Study (using the RS) 
(5) Visit Dates (RS) 
(6) Study Participants Analysis Sets 
(7) Study Participants Who Were Re-Screened (using the ES) 
(8) Randomization Scheme and Codes (using the RS) 
A listing of the actual treatment received for each participant will be produced separately for 
each participating study site. This listing will not be produced as part of the listings for the CSR 
and is instead generated to support external reporting obligations. 
 
5.2 
Protocol deviations 
A summary of IPDs (described in Section 3.5) will be provided on the FAS by treatment group 
and overall to tabulate the number study participants excluded from the PPS and the PK-PPS due 
to IPD by categories (eg, inclusion criteria, exclusion criteria and all other categories included in 
the Protocol Deviation Specification document).  
5.3 
2019 EULAR/ACR Classification Criteria for SLE  
A summary of past or present fulfillment of 2019 EULAR/ACR classification criteria for SLE 
(single items) will be provided on the FAS by treatment group and overall. Information on 
fulfillment of 2019 EULAR/ACR classification criteria (single items and overall score) for SLE 
will be listed by participant.  
6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
6.1 
Demographics 
Demographics information below, will be summarized (using descriptive) for the FAS (and the 
SS should these analysis sets differ) by treatment and overall. The demographic summary will 
include country information grouped into pooled regions, which are defined as North America, 
Western Europe/Asia-Pacific, and Latin America/Eastern Europe. Demographics information 
will also be listed for the ES. Please see below for additional information about categories that 
will be reported: 
Age (years) 
Age Category 1:  
 <65 years 
 ≥65 to <75 years 
 ≥75 years.  
Age Category 2 (clinicaltrials.gov age categories):  
≤18 years 
19 to <65 years 
≥65 years  
Age Category 3 (EudraCT age categories) 
12 to <18 years 
18 to <65 years 
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65 to <85 years 
 ≥85 years  
Gender 
Race Group 
Ethnicity 
Weight (Kg) 
Height (cm) 
BMI (kg/m2) 
BMI (kg/m2) 
<25 
≥25 
BMI (kg/m2) 
 <25 
 25 to <30 
 ≥30 
      Missing 
Country 
Region 
North America  
Eastern Europe 
Western Europe 
Asia-Pacific  
Latin America 
Pooled Region  
North America   
Western Europe/Asia-Pacific 
Latin America/Eastern Europe 
For patients randomized in the USA: 
Race group 
Ethnicity. 
6.2 
Baseline characteristics 
Baseline (BL) Characteristics summary using the FAS will display the following (by treatment 
group): 
Disease history 
1)  Time since first diagnosis of SLE (years) 
2)  Number of Flares in the 6 Months Prior to Screening (0,1,2,>2, missing) 
3)  The number of participants with a thromboembolic event in the medical history (based on 
Thromboembolic Standardized MedDRA Queries (SMQs) and tabulated overall) 
4)  The number of participants with Urine Protein-Creatinine Ratio (uPCR) >113mg/mmol at 
Baseline 
5)  The number of participants with antiphospholipid antibodies (aPLs) in central lab: 
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− Any aPLs: any participant with >0 aPLs (as documented in Section 9.3) >ULN OR 
 
 >ULN 
− Triple positivity (any): as defined in Section 9.3 
− Double positivity: as defined in Section 9.3 
− Single positivity: as defined in Section 9.3 
− 
 >ULN 
6)  The number of participants with renal dysfunction (defined as estimated 
GFR<60mL/min/1.73m2) 
Disease Activity 
1)  
BILAG 2004 total score at baseline 
2)  
BILAG total score <20 vs. >=20 at baseline 
3)   Number of participants with BILAG A, B, C, D or E by Body/Organ system 
4)  
Number of participants with  
− Moderate to severe disease activity as defined per protocol: BILAG 2004 Grades either 
>=1 BILAG Grade A and/or >=2 BILAG Grade Bs 
− One organ with moderate disease activity: 1 BILAG Grade B Only, No BILAG Grade A 
− No moderate or severe disease activity: No BILAG Grade A, No BILAG Grade B 
− At least 1 organ system severely active: ≥1 BILAG Grade A 
− Only 1 (severely) involved organ system: 1 BILAG Grade A and no other organ system 
with BILAG Grade A, Grade B 
− Multi-organ involvement: ≥2 organ systems with BILAG Grade A or Grade B 
− Multiple severely active organs: ≥2 organ systems with BILAG Grade A 
− Multiple organ involvement but no severely active: ≥2 organ systems with BILAG Grade 
B, no organ system with BILAG Grade A 
5)  
Summaries of SLEDAI-2K scores at baseline as follows: 
− SLEDAI-2K total score at baseline 
− SLEDAI-2K total score (<10 vs. ≥10) at baseline 
− Clinical SLEDAI-2K (SLEDAI-2K without serology: 
 items) at 
baseline 
− Clinical SLEDAI-2K total score (≥6 vs. <6) at baseline 
− SLEDAI-2K without laboratory dependent descriptors (urinary casts, hematuria, 
proteinuria, pyuria, low complement, increased DNA binding, thrombocytopenia, 
leucopenia) (>=4 vs. <4) 
6)  
Physician Global Assessment score 
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7) 
SELENA (Safety of Estrogens in Lupus National Assessment) Flare Index (SFI) 
− Baseline SFI (No flare, Mild flare, Moderate flare and Severe flare) 
8)   Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) 
− CLASI: Disease activity score (continuous) 
− CLASI: Damage scores score (continuous) 
− CLASI disease activity score >0 
− CLASI disease activity score ≥8 
 9)    
Cutaneous SLE Manifestations: Percent Body Surface Skin Eruption (<5% vs. ≥5%)   
10)  
Tender Joint Count/Swollen Joint Count (TJC/SJC) 
− Swollen joints count 
− Tender joint count 
− Count of joints that are both swollen and tender at the same time 
− >=4 joints that are both swollen and tender at the same time 
11)     Lupus 
and Musculoskeletal Disease Activity (LAMDA) Physician Assessment 
12) Systemic Lupus International Collaborating Clinics/American College of Rheumatology 
(SLICC/ACR) Damage Index 
− Total score (continuous) 
− SLICC/ACR =0 
− SLICC/ACR =1 
− SLICC/ACR >1 
SLE Serology 
1) 
The number of participants with  
2) 
The number of participants with 
 antibody  
a) ELISA (<30 IU (negative), 30 – 75 IU (indeterminate) and >75 IU (positive)) at 
Screening 
b) CLIFT (negative vs. positive) at Screening 
c) EliA (negative vs. positive) at Baseline 
3) 
The number of participants with low complement  
a) 
 <LLN 
b) 
 <LLN 
c) 
 >ULN 
d) 
 <LLN   
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e) 
 <LLN 
Baseline Patient-Reported Outcome Characteristics 
1) 
FATIGUE-PRO  
a) Physical Fatigue Score 
b) Mental Fatigue Score 
c) Fatigability Score  
2) 
FACIT Fatigue Scale Version 4 Total Score  
3) 
PGI-S by Symptoms Over the Past Week (None, Mild, Moderate, Severe, Very Severe) 
4) 
PGI-S – Fatigue by Severity Over the Past Week (None, Mild, Moderate, Severe, Very 
Severe) 
5) 
Lupus QOL  
a) Physical Health Score 
b) Pain Score 
c) Planning Score 
d) Intimate Relationships Score 
e) Burden to Others Score 
f) Emotional Health Score 
g) Body Image Score 
h) Fatigue Score  
6) 
PHQ-9 
7) 
EQ-5D UK Tariff 
8) 
EQ-5D-5L Scores by Domain (Mobility, Self-Care, Usual Activities, Pain/Discomfort, 
Anxiety/Depression) and Visual Analog Scale 
Stratification Factors at Screening 
Note that below are the stratification factors reported to IXRS for randomization. 
9) 
Pooled region (North America vs. Western Europe/Asia-Pacific vs. Latin 
America/Eastern Europe). 
10) Screening disease activity pattern (chronic active vs. acute flaring, as collected in the 
stratification electronic case report form (eCRF)). 
11) Screening SLEDAI score (<10 vs. ≥10), 
6.3 
Procedure History and Concomitant Medical procedures  
Procedure history and concomitant medical procedures will be listed chronologically for all 
participants in the SS including the reported term for the procedure, the date of the procedure 
and, for concomitant medical procedures only, what the procedure is primarily related to. 
Concomitant medical procedures will also be summarized for the SS.  
6.4 
Medical history conditions  
Medical history will be listed for all participants in the SS including the reported term, start date, 
end date (or ongoing if applicable).  
A glossary of all medical conditions will also be presented including the reported term, the 
preferred term and the system organ class. The classification of medical history and concomitant 
medical conditions will be done according to the MedDRA coding system using system organ 
class, high level term and preferred term. This data will be summarized for the SS using 
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frequency tables for participant count by MedDRA system organ class, high level term and 
preferred term. 
6.5 
Prior and concomitant medications 
Prior medications include any medications with an end date prior to the start date of study 
medication. Concomitant medications are medications taken at least 1 day in common with the 
study medication dosing period up to 10 weeks after the last infusion.  
Details of imputation methods for missing or partial dates are described in Section 4.3.5. 
Prior and concomitant medications that are SLE-related will be summarized for participants in 
the SS and FAS. In addition, SLE-related concomitant medications taken at the Baseline visit 
will be summarized in the FAS. SLE-related prior and concomitant medications taken at the 
Baseline visit will also be summarized in a single table in the FAS. Prior and concomitant 
medications that are not SLE-related will be summarized for participants in the SS only. All prior 
and concomitant medications will be listed for the SS.  
The number and percentage of participants taking prior medications will be summarized by 
treatment group, overall and by ATC class, presenting Anatomical Main Group (ATC Level 1), 
Pharmacological Subgroup (ATC level 3), and preferred term. Prior corticosteroid medications 
will be summarized similarly. 
The number and percentage of participants taking concomitant medications will be summarized 
similarly for the Treatment Period.  
The prednisone equivalent dose at Baseline and Week 48 as well as the Change from Baseline in 
prednisone equivalent dose will be presented as a cumulative distribution function plot by dose 
level. Further the mean prednisone dose will be plotted by visit. Note that all analyses on 
corticosteroid (prednisone equivalent) doses will be restricted to those for a SLE indication only.   
The classification of the medication will be done according to the WHO-DD ATC classification, 
version Sep/2020 B3. The data will be classified by SLE-related/not SLE-related (information 
about (no) SLE-relation will be provided by investigator using specified tick box in CRF). The 
number and percentage will be summarized separately by treatment group, overall, and by ATC 
class, presenting Anatomical Main Group (ATC Level 1), Pharmacological Subgroup (ATC 
level 3), and PT for the Initial Treatment Period and Maintenance Treatment Period separately. 
6.5.1 
Escape Treatment Medications 
Concomitant medications fulfilling criteria of intercurrent events “escape treatment intervention” 
as described in Section 4.4 will be tabulated and listed in the FAS. 
In general, every medication change which fulfills the criteria of the escape treatment 
intervention 1 will be summarized using the FAS. 
6.6 
Lifestyle 
Lifestyle data collected in the eCRF will be summarized and listed using the SS. 
6.7 
Childbearing Potential 
Childbearing Potential data collected in the eCRF will be listed using the SS 
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6.8 
Immunosuppressant, Antimalarial and Corticosteroid at Baseline 
The following categories will be summarized using descriptive statistics on the SS (Note: All 
analyses on corticosteroid (prednisone equivalent) doses will be restricted to those for a SLE 
indication only). 
− Systemic Corticosteroid use: 0mg/day vs. >0mg/day 
− Systemic Corticosteroid dose Category 1 (≤7.5mg/day vs. >7.5mg/day) 
− Systemic Corticosteroid dose Category 2 (≤10mg/day vs. >10mg/day) 
− Systemic Corticosteroid use only, no antimalarial or immunosuppressant (Yes/No) 
− Antimalarial use (Yes/No) 
− Antimalarial use only, no corticosteroid or immunosuppressant (Yes/No) 
− Immunosuppressant use (Yes/No) 
− Immunosuppressant use only, no corticosteroid or antimalarial (Yes/No) 
− Immunosuppressant and antimalarial use only (Yes/No) 
− Corticosteroid and immunosuppressant use only (Yes/No) 
− Corticosteroid and antimalarial only (Yes/No) 
− Corticosteroid, antimalarial and immunosuppressant use (Yes/No) 
- 
Receive immunosuppressant or have received immunosuppressant in the past 
(Yes/No) 
- 
Receive antimalarial or have received antimalarial in the past (Yes/No) 
- 
Receive corticosteroid or have received corticosteroid in the past (Yes/No) 
− Mean corticosteroid dose at Baseline  
For both antimalarials and immunosuppressants, the systemic or non-systemic classification will 
be determined by medical review. 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE 
Please see Section 10.2 for details for treatment exposure and compliance. 
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9 
PHARMACOKINETICS AND PHARMACODYNAMICS  
9.1 
Pharmacokinetics (PK) 
The following PK endpoints will be evaluated using the PK-PPS: 
Samples from SOC+PBO participants will not be analyzed, except for the Week 48 assessment 
which will be considered the baseline for the OLE study SL0046. This data will be included in 
tables and figures of study SL0046 but not in SL0043. Individual study participant 
 
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 will be displayed graphically in linear and log scales. Geometric 
means with 95% confidence interval per visit will also be displayed graphically in linear and log 
scales. These values will be summarized per visit using the statistics described for continuous 
variables and in addition the number of participants with quantifiable samples, the geometric 
mean and the geometric coefficient of variation (assuming log normally distributed data). Tables 
and figures will only include data from the SOC+DPZ arm. Additional concentration by ADA 
participant status will be also generated. A listing will include all the data. 
  
The lower limit of quantification (LLOQ) for DZP concentration in plasma is 0.2μg/mL , 
 
For the 
summary statistics, if a sample is BLQ, it will be considered as half of the LLOQ.  
Descriptive summary statistics will be calculated only if 2/3 of the values are above the LLOQ at 
a given visit. If this is not case, only median, minimum and maximum values will be presented. 
If data merit, a population PK analysis and PK/PD/Efficacy analyses may be conducted for the 
clinical efficacy endpoints and PD variables of interest. All population PK and PK/PD/Efficacy 
analyses will be described in more detail in a separate Data Analysis Plan, and results will be 
reported in a separate report. 
9.2 
Immunogenicity analyses  
9.2.1 
ADA and Nab Sample Status 
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9.2.2 
ADA/Nab Participant Status 
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9.3 
Pharmacodynamics (PD) and Immunological analyses 
Markers of the immune system will be assessed, including: 
All summaries of immunological variables will be produced on the SS, unless otherwise 
specified. 
All immunological parameters will be listed by participant and time point including changes 
from Baseline for numeric variables and flags for measurements outside the clinical reference 
ranges (where applicable). Values that are below the lower limit of the reference range will be 
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flagged as ‘L’ (low) and values that are above the upper limit of the reference range will be 
flagged as ‘H’ (high) and listed as well. 
Summary tables and figures will be presented for both absolute values, changes from Baseline 
and percentage changes from Baseline for the following immunological parameters in all 
patients:
 
 
For the following immunological parameters 
 
 
 with a defined upper limit normal (ULN), a defined 
lower limit normal (LLN), or both, the number of participants and percentages who are within 
and outside of these normal ranges will be tabulated by treatment group and visit. This will be 
done in separate tables for ULN and for LLN, with pages for each immunological parameter 
within these, such that there are distinct displays for each of the following: 
− Values ≤ULN and values >ULN 
− Values ≥LLN and values <LLN  
− Values ≤ULN and values >ULN for the subgroup of participants for each parameter 
whose value was >ULN for that parameter at Baseline  
− Values ≥LLN and values <LLN for the subgroup of participants for each parameter 
whose value was <LLN for that parameter at Baseline  
A shift table will be presented for each of the following selected immunological parameters with 
number and percentages provided by visit for participants with: 
In addition to the overall summary tables and figures for values, changes from Baseline and 
percentage changes from Baseline values by visit, for selected parameters there will also be 
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summary tables and figures for values, changes from Baseline values and percentage changes 
from Baseline values for the subgroup of participants who had an abnormality for that parameter 
at Baseline. Each selected parameter and the subgroup of participants to be used for the 
additional summary of that parameter are listed below: 
Antiphospholipid (aPL) 
The additional following tables will be created using the SS: 
− Shift table on aPL positivity from Screening to post Screening (Week 24 and Week 48)   
The aPL analysis will be done using two different approaches for defining aPL positivity. A first 
analysis (aPLs based on Criteria tests) will be done using Criteria tests only, which includes 
 test results. A second analysis (aPLs expanded to include PS/PT) 
will incorporate the results of Criteria tests and also the 
 assessments.  
The following criteria apply for the aPLs based on Criteria tests analysis: 
Triple positivity is defined as meeting all 3 of the following criteria: 
 
     
 
 
                                       
Double positivity is defined as not meeting triple positivity and meeting at least one "set" (a 
AND b) of criteria below: 
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Single positivity is defined as not meeting triple positivity nor double positivity, and meeting 
at least one of the criteria below: 
  
The following criteria apply for aPLs expanded to include PS/PT analysis: 
Triple positivity is defined as: 
 and at least 2 of the following: 
 
    
 
 
 
    
 
 
 
 
                  
 
Double positivity is defined as not meeting triple positivity and meeting at least one "set" (a 
AND b) of criteria below: 
Single positivity is defined as not meeting triple positivity nor double positivity, and 
meeting at least one of the criteria below: 
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The criteria for double positivity in both analyses (aPLs based on Criteria tests only, and aPLs 
expanded to include PS/PT) require that the isotype of both aPLs considered in an individual 
criterion must be the same.  
Note: see Section 13.16 for details about aPL scoring. 
10 
SAFETY ANALYSES 
10.1 
Adverse events 
All Adverse Events (AEs) occurring during the study (ie, after signature of the informed consent 
document) will be recorded in the eCRF and reported using the SS. 
For each AE the following information will be recorded in the eCRF: AE term (verbatim term), 
date of onset, whether or not the AE was an infusion reaction, if yes, whether this infusion 
reaction fulfills the Sampson criteria (for the definition of Sampson criteria, see Sampson et al, 
2006), pattern of event, whether or not the AE was classified as a SAE or as an AE of special 
interest or special monitoring, intensity, relationship to concomitant medications, relationship to 
the investigational medicinal product (IMP), action taken with IMP, other action taken, outcome, 
date of outcome and whether the AE led to study premature termination. All AE data will be 
listed. 
AEs are characterized as either pre-treatment or treatment-emergent according to the following 
criteria: 
- 
Pre-treatment AEs are the events with onset date prior to the first administration of study 
medication (DZP or PBO). 
- 
Treatment-emergent AEs are those with onset date on or after the first administration of 
study drug, and up to 60 days after last dose. The events that emerge after the final drug 
administration up to 60 days after last dose, will therefore also be considered as treatment-
emergent even if recorded during the SFU period. 
Time to onset of AE (noted as “Days Since First Dose” on AE listings) is calculated as the time 
(in days) between first dose and onset of AE. Time to onset of AE is not calculated for pre-
treatment AEs.  
The time to onset for each AE (relative to the first dose) will be calculated as follows for all 
TEAEs: 
- 
Time to onset since first dose (Date of AE onset − Date of first dose of IMP). 
- 
If the date of AE onset and date of first dose of IMP are the same, then the time to onset since 
first dose will be shown as <1 day.   
In addition, the time to onset (in days) since the most recent dose prior to the TEAE will be 
calculated: 
- 
Time to onset since most recent dose = (Date of AE onset − Date of most recent dose of IMP 
prior to the TEAE start) . 
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- 
If the date of AE onset and date of most recent dose of IMP prior to the TEAE start are the 
same, Time to onset since most recent dose will be shown as <1 day.   
- 
The duration of each AE will be calculated as follows: 
AE Duration (days) = (Date of outcome − date of onset) 
- 
Imputations for missing start dates will be handled according to the 'Imputation of Partial 
Start Dates' rules in Section 4.3.5. 
- 
 Imputations for missing end dates will not be performed for classification as treatment 
emergent and for calculation of time to onset as this is not required. 
- 
In the listings, where AE onset and end date are the same, AE duration will be presented as 
<1 day. 
- 
For AEs with end date >onset date, the duration will be presented in days. For the calculation 
of duration for AEs with missing start dates, the dates will be imputed as described in 
Section 4.3.5. 
- 
In case of uncoded AEs, these AEs should be designated as “UNCODED” at all MedDRA 
levels, and such AEs will be included in summary tables and participant listings based on this 
classification.  
- 
All TEAEs will be flagged in the listings. In addition, all TEAEs will be summarized, but 
pre-treatment and post-treatment AEs will only be listed. 
- 
The following summaries will be created: 
(1) 
Incidence of treatment-emergent adverse events (TEAEs) by MedDRA system organ 
class, high level term, and preferred term  
(2) 
Exposure adjusted incidence rate of TEAEs (incidence rate/event rate) to include the 
number of events, number and proportion of participants with the event (ie, incidence 
proportion), the exposure-adjusted incidence rate per 100 participant years with the 
associated 95% confidence interval, and the exposure adjusted event rate per 100 
participant years. 
 
For exposure adjusted incidence rate, the numerator will be the total number of 
participants experiencing the AE, each participant counted only once even if the 
participant has the event multiple times. The denominator will be in 100 participant-
years. That is, the total summation of individual participant-years at risk up to the first 
occurrence of the TEAE for participants with that AE, and the total participant-years at 
risk for those participants not experiencing that AE, divided by 100. Incidence rates 
will be presented with a 95% confidence interval. Exact Poisson 95% CIs for 
incidence rates are calculated using the relationship between the Poisson and the Chi-
square distribution (Ulm, 1990). 
 
For exposure adjusted event rate, the numerator will be the number of AEs including 
repeat occurrences in individual participants. The denominator will be in 100 
participant-years. That is, the total summation of individual participant-years at risk 
(total sum of "time at risk (last dose – first dose + 60)" for all participants) divided by 
100. No confidence interval will be computed. 
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(3) 
Incidence of Serious TEAEs  
(4) 
Incidence of serious TEAEs by relationship 
(5) 
Incidences of TEAEs by intensity, maximum intensity and by relationship at any time 
during the study 
(6) 
Incidence of TEAE of special interest (AESI)  
Defined as any TEAE that a regulatory authority has mandated be reported on an 
expedited basis, regardless of the seriousness, expectedness, or relatedness of the AE 
to the administration of a UCB product/compound. For DZP, the following events 
require immediate reporting (within 24 hours regardless of seriousness) to UCB: 
Hy’s Law: 
− Potential Hy’s Law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN total 
bilirubin in the absence of ≥2xULN ALP, with no alternative explanation for the 
biochemical abnormality (ie, without waiting for any additional etiologic 
investigations to have been concluded). Follow-up information should be reported if 
an alternative etiology is identified during investigation and monitoring of the 
participant. 
− Malignancies: haematological malignant tumours (SMQ), haematological tumours of 
unspecified malignancy (SMQ), non-haematological malignant tumours (SMQ) and 
non-haematological tumours of unspecified malignancy (SMQ). 
(7) 
Incidence of TEAE of special monitoring (AESM) as determined by the investigator. 
These are events of interest defined by the sponsor to be reported on an expedited 
basis to the sponsor, regardless of seriousness, expectedness, or relatedness of the AE 
to the administration of DZP 
(8) 
Incidence of TEAEs leading to temporary study drug discontinuation 
(9) 
Incidence of TEAEs leading to permanent study drug discontinuation or withdrawal 
from the study 
(10) Incidence of TEAEs occurring during treatment period (defined as last infusion + 28 
days) 
(11) Incidence of opportunistic infection TEAEs (based on narrow SMQ for opportunistic 
infection) 
(12) Incidence of thromboembolic TEAEs (based on the “Embolic and thrombotic events” 
SMQ) (Note: this incidence table will be presented by maximum intensity) 
(13) Incidence of thromboembolic TEAEs as confirmed by the adjudication committee 
(14) Incidence of TEAEs fulfilling the definition of MACE, defined as events coded to 
MedDRA PTs under the narrow SMQ Central nervous system haemorrhages and 
cerebrovascular conditions, narrow SMQ Ischaemic heart disease, and narrow SMQ 
Cardiac failure, as well as the following additional MedDRA PTs: Cardiac death, 
Angioplasty, Arterial angioplasty, Atherosclerotic plaque rupture and Intra-aortic 
balloon placement 
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(15) Incidence of TEAEs starting on the day or the day after an infusion. 
(16) Incidence of infusion reaction TEAEs in participants with infusion reactions (as 
indicated by the investigator on the CRF)  
(17) Incidence of infusion reactions meeting Sampson’s criteria of Anaphylaxis as 
determined by the investigator 
(18) Incidence of TEAEs suggestive of 
 based on the narrow SMQ for 
 
(19) Incidence of 
 TEAEs based on narrow SMQ for
 
starting on the day or the day after an infusion 
(20) Incidence of 
 TEAEs based on narrow SMQ for
 
starting later than the day after an infusion 
(21) Incidence of TEAEs in SMQ Anaphylactic reaction where scope='Narrow' 
(22) Incidence of TEAEs suggestive of suicidal events based on Suicide/self-injury (SMQ) 
(23) Incidence of TEAEs suggestive of depressive or suicidal events based on depression 
and suicide/self-injury (SMQ) 
(24) Incidence of TEAEs in the SMQ depression and suicide/self-injury where 
scope=narrow 
(25) Incidence of non-serious TEAEs occurring in ≥5% of participants within any 
individual treatment group (incidence is compared to the threshold prior to any 
rounding) 
(26) Incidence of non-serious TEAEs by relationship 
(27) Incidence of TEAEs leading to permanent study drug discontinuation or withdraw 
from the study, by relationship 
(28) Incidence of fatal TEAEs by relationship  
(29) Incidence of TEAEs excluding adverse events related to COVID-19 vaccines as 
determined by the investigator 
(30)  Incidence of TEAEs by Decreasing Incidence of MedDRA Preferred Term 
(31)  Incidence of TEAEs Suggestive of Herpes Zoster TEAEs by Medication Subgroup 
 
 
Figures: 
- 
Relative Risk of Most Frequent AEs (Preferred Term) – All TEAEs 
- 
Relative Risk of Most Frequent AEs (Higher Level Term) – All TEAEs 
 
Note: most frequent will include top 30 most frequent TEAEs 
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10.1.1 
Evaluation of relationship of ADA with TEAEs 
10.2 
Extent of exposure 
Study medication administration and extent of exposure to the IMP as captured in the Study 
Medication Administration eCRF and treatment percent compliance (see note below for 
derivation) will be summarized and listed using the SS. The kit number and batch number 
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corresponding to each infusion will also be included within a listing of study medication 
administration. 
The following categories will be included:  
− Number of infusions received by study participant 
− The duration of infusion will be calculated as follows:  
Duration of infusion (min) = Stop time of infusion – start time of infusion + 1 
− The total duration of exposure will be calculated as follows: 
Exposure (days) = (Date of last dose − Date of first dose) + 28 
− Time at risk (days) = (Date of last dose − Date of first dose) + 60 
− Compliance: Compliance (%) will be defined as (Total volume delivered (mL) /volume 
planned) x 100% by visit. The following categories will be also included in the summary: 
Compliance <80%, ≥80 to ≤-120 and >120% by visit  
− Percentage of missed doses vs. the complete number of infusions intended per the 
protocol (12 infusions) 
− Percentage of infusions where the length of infusion was too short. The length of infusion 
at Baseline is planned for the first dose 120 min (number and percentage of participants 
with length of infusion too short will be defined as <90 minutes). For all the post 
Baseline visit it is planned to be 60 minutes (number and percentage of participants with 
length of infusion too short will be defined as <45 minutes) 
When SL0043 initially began, the planned infusion volume was 150mL. This was later 
changed to 200mL. Sites adopted the change from 150mL to 200mL infusions between Oct 
2020 and April 2021. 
10.2.1 
Calculation of planned and actual dose received 
The total planned dose given at each visit will then be calculated to 1 decimal place as follows: 
Planned dose (mg) = Body weight (kg) x Randomized Dose (mg/kg). 
The actual dose (mg) received will be calculated to 1 decimal place, and is based on the infusion 
volume given (mL) and the actual concentration of DZP in the infusion bag (mg/mL): 
Actual dose (mg) = Infusion volume given (mL) x Concentration DZP in infusion (mg/mL). 
The concentration of DZP in the infusion IV bag (mg/mL) is based on the number of mL of 
reconstituted solution from vials of DZP that were included in the IV bag and the total volume of 
the IV bag. There were 100mg DZP per every 1 mL of reconstituted solution from the vials. 
Concentration DZP in infusion (mg/mL) =  
      { [Sum across all vials used (amount of reconstituted solution taken from the vial (mL)) x 
           100mg/mL (DZP in the reconstituted solution)] / Total volume of IV bag prepared (mL) } 
Percent of planned dose administered (%) is based on the actual dose compared to the planned 
dose, thus representing both the volume of infusion given as well as the actual contents of the IV 
bag, and will be calculated to 1 decimal place for each visit. 
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10.3 
Clinical laboratory evaluations 
Laboratory evaluations will be analyzed in the SS for observed cases, where all data is included.  
Measurements outside the clinical reference ranges will be assessed by the investigator. In 
addition, laboratory values will be graded (where possible) according to CTCAE Version 5.0. 
All laboratory data will be listed by participant and time point including changes from Baseline 
and percentage changes from Baseline for numeric variables, as well as flags for measurements 
outside the normal ranges (to flag markedly abnormal results). 
Values that are below the lower limit of the reference range will be flagged as ‘L’ (low) and 
values that are above the upper limit of the reference range will be flagged as ‘H’ (high). The 
flag and the CTCAE grade will be included in the listings. 
Any laboratory parameters that are given as ‘<xx’ or ‘>xx’ in the database will be imputed with 
the absolute value of the number without the sign (<2.2 will be imputed as 2.2) for the 
calculation of the changes from Baseline. 
Summary tables will be provided for both absolute values, changes from Baseline and percent 
changes from Baseline. Shift tables by markedly abnormal lab parameters (see Section 13.18) 
will be presented for clinical chemistry, hematology parameters. For each of clinical chemistry 
and hematology, there will be: 
− One table for lab parameters that have marked abnormal value based on values that are 
<LLN. This table will show the number and percentage of participants who have a 
marked abnormal value at any time of the study post Baseline compared to Baseline  
− One table for lab parameters that have marked abnormal value based on values that are 
>ULN. This table will show the number and percentage of participants who have a 
marked abnormal value at any time of the study post Baseline compared to Baseline  
The denominator for the percentages in both types marked abnormal lab value shift tables 
will be the number of participants in the SS. 
The number and percentage of participants with a treatment-emergent markedly abnormal result 
will be presented for each parameter where markedly abnormal criteria are defined, by visit and 
treatment group, including a tabulation of incidence at any post-BL time point (regardless of 
visit). 
Urinalysis and urine sediment results will be listed.  
Furthermore, figures will be provided both for the mean value by visit and for the mean changes 
from Baseline by visit for continuous laboratory parameters (as observed). 
The urinary albumin: creatinine ratio (mg/mmol) and urinary protein: creatinine ratio (mg/mmol) 
will be calculated by the laboratory from the corresponding urinary albumin, protein and 
creatinine measurements obtained at Visit 1 (Screening) to 15/EOS (Week 54). A summary table 
showing descriptive statistics for the change from Baseline values by visit for urinary protein: 
creatinine ratio and urinary albumin: creatinine ratio will be provided for the subset of 
participants with a urinary protein: creatinine ratio >56mg/mmol at Baseline. 
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Laboratory results for participants meeting the criteria for potential drug induced liver injury (see 
Figure 7-1 in the protocol) will be displayed in a table and a listing. A listing for participants 
who meet Hy’s Law Criteria will also be provided. 
HIV test at Screening, hepatitis test at Screening and Tuberculosis test are done as part of the 
inclusion/exclusion criteria, therefore, they will only be listed. 
Local laboratory results are only required in the event that the central laboratory results are not 
available in time for either study treatment administration and/or response evaluation. If a local 
sample is required, it is important that the sample for central analysis is obtained at the same 
time. Additionally, if the local laboratory results are used to make either a study treatment 
decision or response evaluation, the results must be entered into the eCRF. If central labs are 
unavailable, local labs will be utilized for evaluating the efficacy response (such as BILAG). 
However, the findings from local labs will only be included in listings and not in safety 
summaries. 
 
10.4 
Vital signs, physical findings, and other observations related to safety 
10.4.1 
Vital signs 
The following vital signs measurements will be assessed: 
− Pulse rate (PR) (bpm) 
− Systolic blood pressure (SBP) (mmHg) 
− Diastolic blood pressure (DBP) (mmHg) 
− Respiratory Rate (breaths per minute) 
− Body temperature (ºC) 
− Body weight (kg) 
− Body height (cm) 
− BMI (kg/m2) 
Vital sign will be analyzed in the SS for observed cases, where all data is included. Absolute 
values and Changes from Baseline for pre-infusion vital signs measurements will be presented 
by visit. Additionally, changes from pre-infusion to post-infusion time points at infusion visits 
will be summarized. 
Listings will be provided of vital sign measurements by visit and timing relative to dosing. It will 
include the change from the Baseline visit for pre-infusion vitals at each post-Baseline visit, as 
well as changes from pre-infusion to post-infusion time points within visits. The listing will also 
include details of abnormal values.  
Vital signs with values below the lower limit of normal and a decrease greater than the limit 
given in the following table or vital signs with values above the upper limit of normal and an 
increase greater than the given value in the table will be classified as abnormal. 
A summary of the number and percentage of participants with a vital sign abnormality will also 
be provided by vital sign measurement, by visit and overall. 
Please see below for abnormality criteria for vital sign and body weight parameters:  
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Table 10-1: 
Abnormality criteria for vital sign parameters 
PARAMETER 
AGE RANGE 
ABNORMALITY CRITERIA 
Pulse Rate (beats/minute) 
≥16y 
<45 and a decrease from Baseline of ≥15 
>90 and an increase from Baseline of ≥15 
Systolic Blood Pressure 
(mmHg) 
≥16y 
<90 and a decrease from Baseline of ≥15 
>140 and an increase from Baseline of ≥15 
Diastolic Blood Pressure 
(mmHg) 
≥16y 
<40 and a decrease from Baseline of ≥15 
>90 and an increase from Baseline of ≥15 
Respiratory Rate 
(breaths/min) 
≥16y 
<10 
>25 
Body Temperature (°C) 
≥16y 
<35.9 
>37.6 
Abbreviations: m = month, y = year. A month is defined as 30.44 days; a year is defined as 365.25 days. 
Table 10-2: 
Abnormality criteria for body weight 
PARAMETER 
AGE RANGE 
ABNORMALITY CRITERIA 
Body weight (kg) 
≥16y 
≥10% decrease from Baseline 
≥10% increase from Baseline  
10.4.2 
Electrocardiograms  
Electrocardiogram data are collected at Visit 1, Visit 2, Visit 3, Visit 8 and Visit 14. ECGs will 
be analyzed in the SS for observed cases, where all data is included. ECG outcomes (as 
determined by investigators) will be listed by participant, visit, and timing relative to dosing.  
A summary table of treatment emergent ECGs values (quantitative parameters as provided by 
central readers, including observed value and change from Baseline) will be presented displaying 
descriptive statistics by visit. This data will also be listed. 
Outlier analysis (eg, QTcF, PR, QRS and HR) using central readers data will be provided (see 
Table 10-3 for details). The number and percentage of participants with an outlier at any post-BL 
time point will be presented by treatment group for each parameter. 
A summary of the number and percentage of participants with a treatment emergent ECG finding 
(as provided by central readers) at the Baseline visit, and any post-Baseline time point by 
treatment will also be provided.  
Abnormal ECGs and findings (as determined by central reader) will be listed by participant, 
visit, and timing relative to dosing. 
The overall assessment provided by sites (investigators) will not be used for table summaries but 
will be presented in participant data listings. 
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Table 10-3: 
Abnormal criteria for ECG parameters 
PARAMETER 
AGE RANGE 
ABNORMALITY CRITERIA 
QTcF 
≥16y 
Treatment-emergent value of >450 and ≤480 ms when not present 
at Baseline (new onset) 
Treatment-emergent value of >480 and ≤500 ms when not present 
at Baseline (new onset) 
Treatment-emergent value of >500 ms when not present at 
Baseline (new onset) 
Increase of QTcF from Baseline of >30 and ≤60 ms 
Increase of QTcF from Baseline >60 ms 
PR 
≥16y 
Increase of PR from Baseline >25% resulting in PR >200 ms 
QRS 
≥16y 
Increase of QRS from Baseline >25% resulting in QRS >100 ms 
HR 
≥16y 
Decrease of HR from Baseline >25% resulting in HR <50 bpm 
Increase of HR from Baseline >25% resulting in HR >100 bpm 
10.4.3 
Physical examination 
Physical examination findings will be recorded in the eCRF at Screening. Clinically relevant 
changes in subsequent physical examinations will be reflected as AEs if not related to SLE. If 
physical examination findings are related to SLE, they will be documented within the 
BILAG 2004 and/or SLEDAI-2K assessment eCOA. The outcome of physical examinations and 
the interim medical history must be documented in source documentation. 
A complete physical examination will include, at a minimum, general appearance; ear, nose, and 
throat; eyes, hair, and skin; and assessments of the respiratory, cardiovascular, gastrointestinal, 
musculoskeletal, hepatic, and neurological (including focused assessment of reflexes, sensitivity, 
and muscle strength) systems and mental status. Height (only at Screening) and weight will also 
be measured and recorded. 
Results of physical examination abnormalities will be listed. 
10.4.4 
Assessment of Suicidal Ideation and Behavior 
Suicidal ideation and behavior will be assessed using the C-SSRS (Columbia Suicide Severity 
Rating Scale). This scale will be used at Screening and Visits 2 through 15 to assess suicidal 
ideation and behavior. 
At Screening, participants will be asked to assess suicidal ideation and behavior for their lifetime 
and for the past 6 months and for the past 2 years (respectively) prior to Screening.   
At Visit 2 through Visit 15, participants will be asked to assess suicidal ideation and behavior 
since the last study visit. 
The C-SSRS includes 10 categories with binary responses (yes/no): 
Category 1: Wish to be dead 
Category 2: Non-specific Active Suicidal Thoughts 
Category 3: Active Suicidal Ideation with Any Methods (Not Plan) without Intent to Act 
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Category 4: Active Suicidal Ideation with Some Intent to Act, without Specific Plan 
Category 5: Active Suicidal Ideation with Specific Plan and Intent 
Category 6: Preparatory Acts or Behavior 
Category 7: Aborted Attempt 
Category 8: Interrupted Attempt 
Category 9: Actual Attempt (non-fatal) 
Category 10: Completed Suicide 
The C-SSRS also includes the following: 
- 
Features (which should be rated with respect to the most severe type of ideation (ie, 1-5 
from above, with 1 being the least severe and 5 being the most severe), since last visit 
which defines the intensity of ideation (frequency, duration, controllability, deterrents 
and the reason for ideation) 
- 
Suicidal behavior (actual attempts, has subject engaged in non-suicidal self-injurious 
behavior?, interrupted attempt, aborted attempt, preparatory acts or behavior, suicidal 
behavior, suicide and for actual attempts only: actual lethality/medical damage, potential 
Lethality). 
Endpoints based on the above categories are defined as: 
Suicidal ideation: A “yes” answer at any time during treatment to any one of the 5 suicidal 
ideation questions (Categories 1-5) on the C-SSRS. 
Suicidal behavior: A “yes” answer at any time during treatment to any one of the 5 suicidal 
behavior questions (Categories 6-10) on the C-SSRS. 
Suicidal ideation or behavior: A “yes” answer at any time during treatment to any one of the 10 
suicidal ideation and behavior questions (Categories 1-10) on the C-SSRS. 
A listing will be provided including all data for only those participants who have a ‘Yes’ 
response in any category at any visit. The listing will be by visit and will indicate the reference 
timepoint upon which each C-SSRS category was evaluated (eg, 'Lifetime' for Screening visit, 
and 'Previous visit' for all visits after Screening). 
10.5 
Tuberculosis (TB) Questionnaire: Evaluation of Signs and Symptoms 
of Tuberculosis 
TB questionnaire data collected in the eCOA will be listed using the SS. 
11 
COVID-19 IMPACT 
The following data to evaluate the impact of COVID-19 global pandemic on the study will be 
captured in the COVID-19 eCRF: 
1. Impacted Visit  
2. Impact Category  
• 
Visit not done  
• 
Visit performed out of window  
• 
Visit performed by video call  
• 
Visit performed by telephone  
• 
Temporary discontinuation of study drug  
• 
Permanent discontinuation of study drug  
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• 
Termination of study participation  
• 
Other, specify  
3. Relationship to COVID-19  
• 
Confirmed COVID-19 infection  
• 
Suspected COVID-19 infection  
• 
General circumstances around COVID-19 without infection  
• 
Other, specify  
- 
A summary and a listing of impact of COVID-19 for any reason (including impact 
category and visit (timepoint)) by treatment arm using the FAS will be created 
- 
A summary of impact of COVID-19 due to confirmed or suspected COVID-19 infection 
(including impact category and visit (ie, timepoint)) by treatment arm using the FAS will 
be created 
- 
Summary of Overall Missed or Discarded Assessments (visits) by Key Endpoints 
(primary, key secondary and secondary endpoints) 
- 
Summary of Covid-19 Impact by Impact Category: number of visits performed by video 
call or by phone  
 will be assessed in the scope of exploratory biomarker 
analysis as a separate analysis outside the scope of the SAP and will be summarized in a separate 
report. 
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12 
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Erthematosus Disease Activity Index 200 Responder Index-50 enhances the ability of SLE 
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van Vollenhoven R, Voskuyl A, Bertsias G, et alA framework for remission in SLE: consensus 
findings from a large international task force on definitions of remission in SLE (DORIS) Annals 
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the BILAG-2004 index. Rheumatology. 2010; 49:1665-9. 
 
 
 
 
 
 
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14 
AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN (SAP)  
14.1 
Amendment 1 
Rationale for the Amendment 
The SAP has been amended for the following reasons: 
• To update the protocol amendment version to v2.0 dated June 2021 
• To clarify that data from participants withdrawing from the study early at end of treatment 
(EOT) visits will be mapped to the next scheduled visit per assessment 
• To indicate that if a Baseline measurement is missing and there are multiple Screening lab 
values, then the most recent lab value prior to Baseline will be considered as the Baseline 
value. Unscheduled lab measurements taken before Baseline will be labelled as Screen Re-
test values 
• To clarify that the assessment of cumulative corticosteroid (prednisone equivalent) doses by 
visit will be limited to medications for a SLE indication only. Corticosteroid doses for 
indications other than SLE are considered for escape treatment interventions 
• To describe the presentation and analysis of data for the regular IDMC meetings   
• To add a listing for study participants who were re-screened (using the ES) 
• To clarify which Baseline PRO characteristics will be assessed   
• To add a sensitivity analysis to exclude those participants who were either unblinded or 
potentially unblinded to the investigator and/or study team from the FAS 
• To clarify the groups of participants considered for Supplementary analysis 3 
• To update the supportive analysis for the change from Baseline in SLEDAI-2K at Week 48 
• To define the severe, moderate, and mild SFI flare categories across body systems 
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• To update the Pharmacokinetics (PK) section in accordance with standardized UCB text. 
Changes include updates to analyses of immunogenicity (ie, ADA and Nab sample and 
participant status), and correlation of ADA with PK, PD and/or efficacy 
• To define antiphospholipid (aPL) single, double, and triple positivity 
• To include an analysis on the incidence of TEAEs by intensity, and incidence of TEAEs 
excluding adverse events related to COVID-19 vaccines as determined by the investigator 
• To define the calculation of planned and actual dose received 
• To update the planned dose as when SL0043 initially began, the planned infusion volume 
was 150mL. This was later changed to 200mL. Sites adopted the change from 150mL to 
200mL infusions between Oct 2020 and April 2021 
• To include an output summarizing the impact of COVID-19 due to confirmed or suspected 
COVID-19 infection (including impact category and visit (ie, timepoint)) by treatment arm 
using the FAS 
• To clarify what will happen if BILAG SLE-relatedness is missing post-Baseline 
• To define the EULAR/ACR classification criteria  
• To define the EQ-5D total score across the 5 individual items and the VAS (denoted as the 
EQ-5D UK Tariff) 
• To include the revised definition of DORIS 
• To state the mapping of each country to the respective region and pooled region used for 
analysis 
• To update the CTCAE grade version from 4.3 to 5.0 
• To add BMI in vital signs analyses 
• To add tertiary endpoint “Change from Baseline in Clinical SLEDAI-2K by visit” 
• To update the analysis of tertiary endpoint BILAG worsening from handling with NRI to 
observed cases 
• To update the analyses of prednisone equivalent dose from probability plot to cumulative 
distribution function plot 
In addition, a few clarifications, inconsistencies, acronyms, and typographical errors have been 
made/defined/corrected within the SAP text. 
14.2 
Amendment 2 
Rationale for the Amendment 
The primary reasons for this amendment are to reduce the sample size and consequently remove 
the interim analysis, and to change the population-level summary of the primary efficacy 
estimand from an odds ratio for the proportion achieving BICLA response at Week 48 in each 
treatment group to the difference in proportion achieving BICLA response at Week 48. Other 
updates have been incorporated for reasons including addressing regulatory feedback, removing 
multiple imputation for data impacted by COVID-19, providing further clarity and correcting 
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errors. In addition to the changes listed below, correction of minor typographical errors, 
inconsistencies, acronyms, and formatting/stylistic changes have been made within the SAP text. 
• To update the protocol amendment version to v4.0 dated 16 March 2023 in Section 1. 
• To update the power calculation for the reduced sample size in Section 2.4. 
• To clarify that data from participants withdrawing from the study early at end of treatment 
(EOT) visits will be mapped to the next scheduled visit per assessment for purpose of 
analyses and inclusion in summary tables but will be presented in terms of nominal visit in 
listings in Section 3.2. 
• To define the baseline values for SLEDAI-2K assessments when a lab component for 
SLEDAI is missing at Baseline in Section 3.4. 
• To remove COVID-19 impacted data as a special case of missing data and modify the 
analyses accordingly due to rare occurrence of missed visits due to COVID-19 impact in 
Section 4.3 and 8. 
• To update the multiple imputation steps for CMH test in Section 4.3.3, 8.3.1 and 8.3.2. 
• To add the strategy of handling data impacted by COVID-19 in Section 4.4, if data is missing 
due to COVID-19 it will be treated the same as other missing data. 
• To clarify that if a treatment change represents an intercurrent event in the category of escape 
treatment intervention 1, it will be confirmed by a blinded independent adjudicator in Section 
4.5. 
• To update the definition of escape treatment intervention 2 per EULAR guidance in Section 
4.5.2. 
• To indicate that there will be no interim analysis since sample size is reduced in Section 4.6.2 
and to remove appendices of Interim Futility Analysis Outputs and Choice of Endpoint for 
SL0043 Futility Assessment. 
• To update the number of sites for the study since sample size is reduced in Section 4.7. 
• To remove some subgroup analyses due to low numbers in the subgroup or due to 
redundancy with other subgroups in Section 4.9.1. 
• To display additional demographics information from subjects recruited in the USA in 
Section 6.1. 
• To update the primary analysis from using logistic regression model to CMH based on 
regulatory feedback and to remove COVID-19 impacted data as an intercurrent event in 
Section 8. 
• To update the definition of observed cases in Section 8.2.1. 
• To remove the primary efficacy endpoint sensitivity analysis of GEE and add sensitivity 
analysis to evaluate the impact of partially available data (ie, one component missing) being 
imputed via multiple imputation rather than carrying forward the component value from prior 
visit in Section 8.3.1. 
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• To update sensitivity analysis 2 (tipping point) for CMH given the change in the primary 
estimand in Section 8.3.1. 
• To add a sensitivity analysis overview (forest plot) in Section 8.3.1.1. 
• To update supplementary analysis 4 of BICLA using odds ratio via a logistic regression 
model given the change in the primary estimand to analysis of the difference between 
proportions in Section 8.3.2. 
• To clarify the definition of the additional analyses in Section 8.3.2. 
• To clarify that BILAG flares will be adjudicated and that worsening of symptoms after the 
Baseline Visit will only be considered as a flare if there was at least 1 post-Baseline Visit, 
prior to the worsening, where the symptom remained the same or improved in Section 8.4, 
8.5 and 13.2.1. 
• To specify the analysis of achievement of severe BILAG flare free through Week 48 
endpoint in Section 8.4. 
• To remove the supportive analysis of change from Baseline in SLEDAI-2K at Week 48 and 
add sensitivity analyses of the endpoint per regulatory feedback in Section 8.4.1. 
• To remove the analysis of BILAG grades and shifts from Baseline corresponding to the 
Neuropsychiatric domain in Section 8.6.1.3 and 13.19. 
• To specify that two definitions of the LAMDA score will be computed in Section 8.6.1.4. 
• To update the immunogenicity analysis per latest standard in Section 9.2. 
• To state that Nab analysis will not be included in the study CSR but in a separate report in 
Section 9.2.2. 
• To clarify the use of narrow or broad AE SMQ in Section 10.1 and 13.19. 
• To clarify the definition of SLEDAI-2K and S2K RI-50 in Section 13.3. 
 
14.3 
Amendment 3 
Rationale for the Amendment 
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STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution. 
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Approval Signatures
Name:
sl0043-sap-amend-3
Version:
1. 0
Document Number:
CLIN-000261282
Title:
sl0043-sap-amend-3
Approved Date:
19 Jul 2024
Document Approvals
Approval
Verdict: Approved
Name:
Capacity: Clinical
Date of Signature: 19-Jul-2024 14:44:19 GMT+0000
Approval
Verdict: Approved
Name: 
Capacity: Clinical
Date of Signature: 19-Jul-2024 14:46:13 GMT+0000
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