A Multi-center, Randomized, Double-blind, Placebo-controlled, Parallel-group, Dose-ranging Study Followed by an Observational Period to Evaluate the Efficacy and Safety of Dapirolizumab Pegol in Subjects With Moderately to Severely Active Systemic Lupus Erythematosus
Phase: PHASE2
Conditions: Systemic Lupus Erythematosus (SLE)
Sponsor: UCB Biopharma S.P.R.L.

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PROTOCOL SL0023 AMENDMENT 1
A MULTI-CENTER, RANDOMIZED, DOUBLE-BLIND, 
PLACEBO-CONTROLLED, PARALLEL-GROUP, 
DOSE-RANGING STUDY FOLLOWED BY AN 
OBSERVATIONAL PERIOD TO EVALUATE THE EFFICACY 
AND SAFETY OF DAPIROLIZUMAB PEGOL IN SUBJECTS
WITH MODERATELY TO SEVERELY ACTIVE SYSTEMIC 
LUPUS ERYTHEMATOSUS
PHASE 2B
EudraCT Number: 2015-004457-40
IND Number: 100807
Sponsor:
UCB Biopharma SPRL
Allée de la Recherche 60, 1070 
Brussels, Belgium
Protocol/Amendment Number
Date
Type of amendment
Final Protocol
12 Apr 2016
Not applicable
Protocol Amendment 1
14 Dec 2016
Nonsubstantial
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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STUDY CONTACT INFORMATION
Sponsor
UCB Biopharma SPRL
Allée de la Recherche 60, 1070 
Brussels, Belgium
Sponsor Study Physician
Name:
, MD
Address:
UCB BIOSCIENCES GmbH
Alfred-Nobel-Str. 10
40789 Monheim
GERMANY
Phone:
Clinical Project Manager
Name:
Address:
UCB Biosciences Inc.
8010 Arco Corporate Drive, Ste 100
Raleigh, NC 27617
USA
Phone:
Clinical Trial Biostatistician
Name:
Address:
UCB Biosciences Inc.
8010 Arco Corporate Drive, Ste 100
Raleigh, NC 27617
USA
Phone:
Clinical Monitoring Contract Research Organization
Name:
INC Research
Address:
3201 Beechleaf Ct #600
Raleigh, NC 27604
USA
Phone:
+1 919 876 9300
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SERIOUS ADVERSE EVENT REPORTING
Serious adverse event reporting (24h)
Fax
Europe and Rest of the World: +32 2 386 6563
USA: +1 770 970 2494
Canada: +1 877 582 8842
Email
Global: safetyreportingCDP7657@ucb.com
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TABLE OF CONTENTS
LIST OF ABBREVIATIONS..................................................................................................11
1
SUMMARY.....................................................................................................................15
2
INTRODUCTION ...........................................................................................................17
3
STUDY OBJECTIVES....................................................................................................20
3.1 Primary objective.............................................................................................................20
3.2 Secondary objectives .......................................................................................................20
3.3 Other objectives ...............................................................................................................20
4
STUDY VARIABLES.....................................................................................................21
4.1 Efficacy variables.............................................................................................................21
4.1.1
Primary efficacy variable.....................................................................................21
4.1.2
Secondary efficacy variable.................................................................................21
4.1.3
Other efficacy variables.......................................................................................21
4.1.3.1
Clinical assessments of disease activity....................................................21
4.1.3.2
Variables assessing corticosteroid-sparing effects....................................22
4.1.3.3
Patient-reported outcome variables...........................................................23
4.2 Safety variables................................................................................................................23
4.3 Pharmacokinetic variables ...............................................................................................23
4.4 Pharmacodynamic variables ............................................................................................23
4.4.1
Immunological variables .....................................................................................23
4.5 Immunogenicity variables................................................................................................23
4.6 Biomarkers.......................................................................................................................24
5
STUDY DESIGN.............................................................................................................24
5.1 Study description .............................................................................................................24
5.1.1
Study duration per subject ...................................................................................26
5.1.2
Planned number of subjects and sites ..................................................................26
5.1.3
Anticipated regions and countries .......................................................................26
5.1.4
Data Monitoring Committee................................................................................26
5.2 Schedule of study assessments.........................................................................................27
5.3 Schematic diagram...........................................................................................................33
5.4 Rationale for study design and selection of dose.............................................................34
6
SELECTION AND WITHDRAWAL OF SUBJECTS...................................................36
6.1 Inclusion criteria ..............................................................................................................36
6.2 Exclusion criteria .............................................................................................................39
6.3 Withdrawal criteria ..........................................................................................................42
6.3.1
Potential drug-induced liver injury IMP discontinuation criteria........................43
7
STUDY TREATMENTS.................................................................................................44
7.1 Description of IMPs.........................................................................................................44
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7.2 Treatments to be administered.........................................................................................44
7.2.1
Treatment preparation and administration...........................................................45
7.2.1.1
Preparation.................................................................................................45
7.2.1.2
Administration...........................................................................................45
7.3 Packaging.........................................................................................................................46
7.4 Labeling ...........................................................................................................................46
7.5 Handling and storage requirements..................................................................................46
7.6 Drug accountability..........................................................................................................46
7.7 Procedures for monitoring subject compliance................................................................47
7.8 Concomitant medications/treatments...............................................................................47
7.8.1
Permitted concomitant treatments (medications and therapies) for SLE ............47
7.8.2
Permitted concomitant treatments (medications and therapies) other than those 
for SLE.................................................................................................................49
7.8.3
Prohibited concomitant treatments (medications and therapies).........................49
7.8.4
Rescue medication for SLE disease flares...........................................................50
7.8.5
Subject diary........................................................................................................50
7.9 Blinding............................................................................................................................50
7.9.1
Procedures for maintaining and breaking the treatment blind.............................50
7.9.1.1
Maintenance of study treatment blind.......................................................50
7.9.1.2
Breaking the treatment blind in an emergency situation...........................51
7.10 Randomization and numbering of subjects......................................................................51
8
STUDY PROCEDURES BY VISIT ...............................................................................52
8.1 Visit 1 (Week -4 to -1/Day -28 to -1); Screening Visit....................................................52
8.2 Visit 2 (Day 1); Randomization Visit ..............................................................................54
8.3 Visit 3 (Week 2/Day 14 [±3 days])..................................................................................56
8.4 Visit 4 (Week 4/Day 28 [±3 days]) and Visit 6 (Week 8/Day 56 [±3 days]) ..................56
8.5 Visit 5 (Week 6/Day 42 [±3 days])..................................................................................58
8.6 Visit 7 (Week 12/Day 84 [±3 days]), Visit 8 (Week 16/Day 112 [±3 days]), and Visit 9 
(Week 20/Day 140 [±3 days])..........................................................................................58
8.7 Visit 10 (Week 24/Day 168 [±3 days]); Double-Blind Treatment Period End of 
Treatment/Early Withdrawal Visit...................................................................................60
8.8 Visit 11/SFU (Week 28/Day 196 [±3 days]), Visit 13 (Week 36/Day 252 [±3 days]), and 
Visit 15 (Week 44/Day 308 [±3 days])............................................................................62
8.9 Visit 12/SFU (Week 32/Day 224 [±3 days]) and Visit 14 (Week 40/Day 280 [±3 days])63
8.10 Visit 16 (Week 48/Day 336 [± 3days]); Observation Period Final/Early 
Withdrawal Visit..............................................................................................................65
8.11 Unscheduled Visit............................................................................................................66
9
ASSESSMENT OF EFFICACY......................................................................................67
9.1 Clinical assessments of disease activity...........................................................................67
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9.1.1
BILAG 2004 ........................................................................................................67
9.1.2
SLEDAI-2K.........................................................................................................68
9.1.3
PGA .....................................................................................................................68
9.1.4
PtGA ....................................................................................................................69
9.1.5
SLICC/ACR Damage Index ................................................................................69
9.1.6
Tender and Swollen Joint Counts (28 joints) ......................................................70
9.1.7
CLASI..................................................................................................................71
9.1.8
Assessment of flare..............................................................................................72
9.1.9
Responders based on clinical assessments of disease activity.............................72
9.1.9.1
BICLA.......................................................................................................72
9.1.9.2
SRI-4, -5, and -6........................................................................................73
9.1.9.3
SRI-50 .......................................................................................................73
9.2 Patient-reported outcomes ...............................................................................................74
9.2.1
LupusQoL............................................................................................................74
9.2.2
SLE-S...................................................................................................................74
9.2.3
SLE-F...................................................................................................................74
9.2.4
SLE-M .................................................................................................................75
9.2.5
SLE-P...................................................................................................................75
9.2.6
SLE-E ..................................................................................................................75
9.2.7
Subject Experience Interview..............................................................................75
10
ASSESSMENT OF PK AND PD VARIABLES.............................................................75
10.1 Assessment of PK variables.............................................................................................75
10.2 Assessment of PD variables.............................................................................................76
10.3 Handling and shipment of blood and urine samples for PK and PD assessments...........76
11
ASSESSMENT OF IMMUNOGENICITY VARIABLES .............................................76
12
ASSESSMENT OF BIOMARKERS...............................................................................77
13
ASSESSMENT OF SAFETY..........................................................................................77
13.1 Adverse events.................................................................................................................77
13.1.1
Definition of adverse event..................................................................................77
13.1.2
Procedures for reporting and recording adverse events.......................................77
13.1.3
Description of adverse events..............................................................................78
13.1.4
Follow up of adverse events ................................................................................78
13.1.5
Rule for repetition of an adverse event................................................................78
13.1.6
Hypersensitivity and adverse drug reactions .......................................................78
13.1.7
Thromboembolic events ......................................................................................79
13.1.8
Infections .............................................................................................................79
13.1.8.1
Suspected transmission of an infectious agent via a medicinal product ...79
13.1.9
Neurological events .............................................................................................80
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13.1.10
Pregnancy ............................................................................................................80
13.1.11
Overdose of IMP..................................................................................................81
13.1.12
Safety signal detection.........................................................................................81
13.2 Serious adverse events .....................................................................................................81
13.2.1
Definition of serious adverse event .....................................................................81
13.2.2
Procedures for reporting serious adverse events .................................................82
13.2.3
Follow up of serious adverse events....................................................................83
13.3 Adverse events of special interest....................................................................................83
13.4 Immediate reporting of adverse events............................................................................83
13.5 Anticipated serious adverse events ..................................................................................84
13.6 Assessment and management of TB and TB risk factors ................................................84
13.6.1
TB assessments....................................................................................................85
13.6.2
Chest x-ray...........................................................................................................86
13.6.3
TB signs and symptoms questionnaire ................................................................86
13.6.4
TB management...................................................................................................86
13.7 Evaluation of PDILI.........................................................................................................87
13.7.1
Consultation with Medical Monitor and local hepatologist.................................91
13.7.2
Immediate action: determination of IMP discontinuation...................................91
13.7.2.1
IMP restart/rechallenge (if applicable)......................................................91
13.7.3
Testing: identification/exclusion of alternative etiology.....................................92
13.7.4
Follow-up evaluation...........................................................................................93
13.8 Physical examination and interim medical history..........................................................93
13.9 Laboratory measurements................................................................................................94
13.10
Vital signs ..............................................................................................................96
13.11
12-lead ECGs.........................................................................................................96
13.12
Assessment of suicidal ideation and behavior .......................................................96
14
STUDY MANAGEMENT AND ADMINISTRATION.................................................97
14.1 Adherence to protocol......................................................................................................97
14.2 Monitoring .......................................................................................................................97
14.2.1
Definition of source data .....................................................................................97
14.2.2
Source data verification .......................................................................................98
14.3 Data handling...................................................................................................................98
14.3.1
Case Report Form completion.............................................................................98
14.3.2
Database entry and reconciliation........................................................................98
14.3.3
Subject Screening and Enrollment Log/Subject Identification Code list ............98
14.4 Termination of the study..................................................................................................99
14.5 Archiving and data retention............................................................................................99
14.6 Audit and inspection ........................................................................................................99
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14.7 Good Clinical Practice ...................................................................................................100
15
STATISTICS .................................................................................................................100
15.1 Definition of analysis sets..............................................................................................100
15.1.1
Enrolled Set .......................................................................................................100
15.1.2
Randomized Set.................................................................................................100
15.1.3
Safety Set...........................................................................................................100
15.1.4
Full Analysis Set................................................................................................100
15.1.5
Per Protocol Set .................................................................................................100
15.1.6
Pharmacokinetic Set ..........................................................................................101
15.1.7
Completer Set ....................................................................................................101
15.2 General statistical considerations...................................................................................101
15.3 Planned efficacy analyses ..............................................................................................102
15.3.1
Analysis of the primary efficacy variable..........................................................102
15.3.2
Other efficacy analyses......................................................................................103
15.4 Planned safety and other analyses..................................................................................104
15.4.1
Safety analyses...................................................................................................104
15.4.2
PK analyses........................................................................................................104
15.4.3
Immunogenicity analyses ..................................................................................105
15.5 Handling of protocol deviations.....................................................................................105
15.6 Handling of dropouts or missing data............................................................................105
15.7 Planned interim analysis and data monitoring...............................................................106
15.8 Determination of sample size.........................................................................................106
16
ETHICS AND REGULATORY REQUIREMENTS....................................................107
16.1 Informed consent ...........................................................................................................107
16.2 Subject identification cards............................................................................................107
16.3 Institutional Review Boards and Independent Ethics Committees................................108
16.4 Subject privacy...............................................................................................................108
16.5 Protocol amendments.....................................................................................................109
17
FINANCE, INSURANCE, AND PUBLICATION.......................................................109
18
REFERENCES ..............................................................................................................109
19
APPENDICES ...............................................................................................................112
19.1 SLICC classification criteria for SLE............................................................................112
19.2 Equivalent doses of oral steroids ...................................................................................115
19.3 Suggested management guidelines for infusion reactions.............................................116
19.4 Criteria for diagnosis of anaphylaxis .............................................................................117
19.5 Protocol-specific clarification and extension of BILAG 2004 definitions ....................118
19.6 Protocol Amendment 1 ..................................................................................................118
20
DECLARATION AND SIGNATURE OF INVESTIGATOR .....................................143
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21
SPONSOR DECLARATION ........................................................................................144
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LIST OF TABLES
Table 5-1:
Corticosteroid tapering schedule......................................................................25
Table 5‒2:
Schedule of study assessments.........................................................................28
Table 5‒3:
Summary of qualitative evidence leading the selected target DZP Ctrough
and corresponding dose levels for SL0023......................................................35
Table 5‒4:
Pharmacokinetic parameters expected at the dose levels proposed in 
SL0023 (median [5th-95th percentile]) .............................................................35
Table 6-1:
Maximum doses of permitted concomitant antimalarials................................38
Table 6-2:
Maximum doses of permitted concomitant immunosuppressants...................38
Table 7-1:
Prohibited medications and required wash-out periods prior to Screening 
(Visit 1)............................................................................................................49
Table 9‒1:
SLICC/ACR Damage Index organ system scoring .........................................70
Table 9‒2:
Joint tenderness and swelling grades...............................................................70
Table 9‒3:
CLASI activity and damage scoring................................................................71
Table 13‒1:
Anticipated serious adverse events for subjects with SLE ..............................84
Table 13‒2: Required investigations and follow up for PDILI ...............................................89
Table 13‒3:
PDILI laboratory measurements......................................................................92
Table 13‒4:
PDILI information to be collected...................................................................93
Table 13-5:
Laboratory measurements................................................................................95
LIST OF FIGURES
Figure 5-1:
Schematic diagram of SL0023.........................................................................33
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LIST OF ABBREVIATIONS
ACR
American College of Rheumatology
ACE
angiotensin converting enzyme
ADL
activities of daily living
AE
adverse event
ALP
alkaline phosphatase
ALT
alanine aminotransferase
ANA
antinuclear antibody
anti-dsDNA
anti-double-stranded deoxyribonucleic acid
anti-ENA
extractable nuclear antigen antibody
anti-RNP
anti-ribonucleoprotein antibody
anti-SM
anti-Smith antibody
anti-SSA
Sjögren’s syndrome antibody A 
anti-SSB
Sjögren’s syndrome antibody B 
aPL
antiphospholipid
APS
antiphospholipid syndrome
aPTT
activated partial thromboplastin time
AST
aspartate aminotransferase
BICLA
BILAG 2004-based Composite Lupus Assessment
BILAG 2004
British Isles Lupus Assessment Group Disease Activity Index 2004
BST
BILAG 2004 Systems Tally
C3
complement 3
C4
complement 4
CD40L
CD40 ligand
CDMS
clinical data management system
CI
confidence interval
CLASI
Cutaneous Lupus Erythematosus Disease Area and Severity Index
CPM
Clinical Project Manager
CRO
contract research organization
CS
Completer Set
CSR
Clinical Study Report
C-SSRS
Columbia Suicide Severity Rating Scale
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CTSO
Clinical Trial Supply Operations
DMC
Data Monitoring Committee
DNA
deoxyribonucleic acid
DZP
dapirolizumab pegol
ECG
electrocardiogram
eCRF
electronic Case Report Form
EDC
electronic data capture
eGFR
estimated glomerular filtration rate
EHR
Electronic Healthcare Record
ES
Enrolled Set
EWV
Early Withdrawal Visit
Fab´
fragment antigen-binding
FAS
Full Analysis Set
Fc
fragment crystallizable
FDA
Food and Drug Administration
GCP
Good Clinical Practice
HIV
human immunodeficiency virus
HMG-CoA
3-hydroxy-3-methyl-glutaryl-coenzyme A
HRQoL
health-related quality of life
hsCRP
high sensitivity C-reactive protein
IB
Investigator’s Brochure
ICH
International Council for Harmonisation
IEC
Independent Ethics Committee
Ig
immunoglobulin
IGRA
interferon-γ release assay
im
intramuscular(ly)
IMP
investigational medicinal product
IP
interphalangeal
IRB
Institutional Review Board
ITP
idiopathic thrombocytopenic purpura
iv
intravenous(ly)
IVRS
interactive voice response system
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IWRS
interactive web response system
LupusQoL
Lupus Quality of Life questionnaire
LTB
latent tuberculosis
MCID
minimal clinically important difference
MCP
metacarpophalangeal
MCP-Mod
Multiple Comparison Procedure–Modelling
MILES
Michigan Lupus and Epidemiology Surveillance Program
mRNA
messenger ribonucleic acid
NHP
nonhuman primate
NSAID
nonsteroidal anti-inflammatory drug
NTMB
non-tuberculosis mycobacterium
PBO
placebo
PD
pharmacodynamics(s)
PDILI
potential drug-induced liver injury
PEF
peak expiratory flow
PEG
polyethylene glycol
PGA
Physician’s Global Assessment of Disease
PIP
proximal interphalangeal
PK
pharmacokinetic(s)
PK-PPS
Pharmacokinetic Per Protocol Set
PPS
Per Protocol Set
PRO
patient-reported outcome
PS
Patient Safety
PtGA
Patient’s Global Assessment of Disease
QFT-GIT
Quanti-FERON®-TB GOLD in-Tube test
RF
rheumatoid factor
RS
Randomized Set
SAE
serious adverse event
SAP
Statistical Analysis Plan
SFU
Safety Follow-up
SJC
swollen joint count
SLE
systemic lupus erythematosus
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SLEDAI-2K
Systemic Lupus Erythematosus Disease Activity Index 2000
SLE-E
Systemic Lupus Erythematosus-Emotional States Instrument
SLE-F
Systemic Lupus Erythematosus-Fatigue Instrument
SLE-M
Systemic Lupus Erythematosus-Mobility Instrument
SLE-P
Systemic Lupus Erythematosus-Pain Instrument
SLE-S
Systemic Lupus Erythematosus-Symptom Inventory Instrument
SLICC
Systemic Lupus International Collaborating Clinics
SOP
Standard Operating Procedure
SRI-4, -5, and -6
Systemic Lupus Erythematosus Responder Index-4, -5, and -6
SRI-50
Systemic Lupus Erythematosus Disease Activity Index-2K Responder 
Index-50
SS
Safety Set
TB
tuberculosis
TJC
tender joint count
TT
tetanus toxoid
ULN
upper limit of normal
VAS
visual analog scale
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1
SUMMARY
SL0023 is a 2-part study consisting of a randomized, double-blind, placebo (PBO)-controlled, 
parallel-group, dose-ranging period (24-week Double-Blind Treatment Period; Part 1) followed 
by a 24-week Observational Period (Part 2) in adult subjects with moderately to severely active 
systemic lupus erythematosus (SLE) who are receiving stable standard-of-care medications
(ie, corticosteroids, immunosuppressants, and/or antimalarials) at study entry.
The primary objective of SL0023 is to assess the dose-response for the efficacy of intravenous 
(iv) dapirolizumab pegol (DZP; 3 dose groups) at Week 24 of the Double-Blind Treatment 
Period (Part 1). Secondary objectives are to assess the efficacy of the individual dose regimens of 
iv DZP at Week 24 and to assess the safety and tolerability of iv DZP. Other objectives are to 
assess the efficacy of iv DZP at additional time points; to assess the corticosteroid-sparing effect 
of iv DZP; to assess the pharmacokinetics (PK) of iv DZP and polyethylene glycol (PEG); to 
assess the pharmacodynamics (PD) of iv DZP; to assess the immunogenicity of iv DZP and 
PEG; to assess the effects of iv DZP on health-related quality of life (HRQoL), symptoms, 
fatigue, mobility, and pain; to perform exploratory analyses of the effects of iv DZP with
transcriptomic and proteomic biomarkers; to assess durability of the clinical response after 
withdrawal of iv DZP; and to assess PD after withdrawal of iv DZP (including gene transcription 
signature).
The primary efficacy variable is the British Isle Lupus Assessment Group Disease Activity Index 
2004 (BILAG 2004)-based Composite Lupus Assessment (BICLA) responder rate across 3 doses 
of DZP and PBO at Week 24. The secondary efficacy variable is the BICLA responder rate in 
the individual dose groups at Week 24. Several other efficacy variables assessing disease 
activity, corticosteroid-sparing effects, HRQoL, symptoms, fatigue, mobility, and pain are also 
included. 
Safety variables include adverse events (AEs) and serious AEs (SAEs), subject withdrawals due 
to AEs, vital sign parameters, electrocardiograms (ECGs), and safety laboratory tests. Several 
variables evaluating PK, PD, biomarkers, and immunogenicity will also be assessed.
The study consists of a Screening Period of up to 4 weeks, a 24-week Double-Blind Treatment 
Period (Part 1), and a 24-week Observational Period (Part 2). At the start of the 24-week
Double-Blind Treatment Period (Part 1), eligible subjects will be randomized (1:1:1:1) to 1 of 
4 treatment arms (DZP 6mg/kg, 24mg/kg, or 45mg/kg, or PBO) and stratified in accordance with 
corticosteroid dose (≤10mg/day or >10mg/day prednisone equivalent) determined at Screening. 
Study drug will be administered by iv infusion every 4 weeks during Part 1 of the study. Subjects 
who withdraw early from the 24-week Double-Blind Treatment Period (Part 1) will enter an 
8-week Safety Follow-up (SFU) Period (which ends 12 weeks after the final dose of study drug). 
Subjects who complete the 24-week Double-Blind Treatment Period (Part 1) will continue into a 
24-week Observational Period (Part 2), during which subjects will not receive study drug but 
will be able to receive standard-of-care treatment, as indicated. The subjects, Investigators, and 
study site staff will remain blinded to the treatment administered during Part 1 of the study until 
the end of the study. The maximum duration of the entire study (Parts 1 and 2) per subject will 
be approximately 52 weeks.
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Eligible subjects will have active SLE at Baseline despite stable standard-of-care treatment with 
at least 1 of the following, either alone or in combination: corticosteroids (at doses of ≤40mg/day 
prednisone or equivalent), and/or antimalarials, and/or immunosuppressants. In subjects 
receiving concomitant corticosteroids, doses must have been stable for at least 2 weeks prior to 
Screening, must remain stable until Baseline (Visit 2), and should remain stable until 4 weeks 
after the first study drug infusion (until Day 28). Subjects 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 subjects receiving concomitant corticosteroid doses between 10mg/day 
and 40mg/day prednisone or equivalent at Screening, a mandatory corticosteroid taper must be 
initiated no later than 4 weeks after the first study drug infusion (on Day 29). The tapering 
regimen will aim to reduce the daily prednisone equivalent dose to 7.5mg/day or lower by 
Week 12 (Day 84) of the study. Treatment with antimalarials and immunosuppressants must 
have been started or stopped at least 12 weeks prior to dosing with study drug and doses must 
remain stable for at least 4 weeks for antimalarials and at least 8 weeks for immunosuppressants 
prior to the first study drug infusion (Visit 2). In subjects receiving concomitant antimalarials or 
immunosuppressants, doses must not exceed the specified maximum permitted doses (as outlined 
in Table 6-1 and Table 6-2). 
The study is planned to enroll at least 267 subjects in order to randomize approximately 
160 subjects (40 subjects per treatment group). Subjects eligible to enroll in this study are males 
or females, ≥18 years of age, diagnosed with SLE according to the Systemic Lupus International 
Collaborating Clinics (SLICC) Classification Criteria and having moderately to severely active 
disease, defined as having BILAG Grade A level disease activity in ≥1 body/organ system or 
BILAG Grade B in ≥2 body/organ systems if no BILAG Grade A level disease is present and
Systemic Lupus Erythematosus Disease Activity Index-2000 (SLEDAI-2K) score ≥6 at 
Screening. Subjects must have 1 of the following 3 criteria confirmed by the central laboratory at 
Screening: (a) anti-double stranded deoxyribonucleic acid (anti-dsDNA) antibodies by Farr 
assay, or (b) low complement (ie, either low complement 3 [C3], low complement 4 [C4], or 
both), or (c) antinuclear antibody (ANA) titer of ≥1:80. In subjects meeting the latter ANA 
criterion “c,” this must be in combination with at least 1 of the following: (1) historical positivity 
for anti-dsDNA at least twice in the past, or (2) positivity for extractable nuclear antigen 
antibodies (anti-ENA) (anti-Smith antibody [anti-SM], Sjögren’s syndrome antibody A 
[anti-SSA], Sjögren’s syndrome antibody B [anti-SSB], or anti-ribonucleoprotein antibody 
[anti-RNP]).
A Data Monitoring Committee (DMC) will monitor the safety of subjects in SL0023 on an 
ongoing basis, with a particular emphasis on occurrence of thromboembolic events. 
An initial biomarker analysis may be performed on all evaluable biomarker data from Part 1 of 
the study when 25% to 35% of the randomized subjects have completed Visit 7 (Week 12) of the 
Double-Blind Treatment Period. Data from subjects who have prematurely withdrawn from the 
study prior to Visit 7 will be included. The initial biomarker analysis will focus on transcriptomic
biomarker variables (eg, messenger ribonucleic acid [mRNA]), prespecified in a Biomarker Plan, 
in order to provide guidance for the DZP development program, and will not affect the conduct 
of the study.  
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After the last subject completes Part 1 of the study, the data for those subjects will be secured 
and an interim Clinical Study Report (CSR) will be written for the Double-Blind Treatment 
Period (Part 1) of the study; this interim CSR will not include any data from the Observational
Period (Part 2). A biomarker analysis on the full Double-Blind Treatment Period (Part 1) dataset 
will be included in the interim CSR. Subsequently, a complete final CSR will be written for the 
entire study following completion of the Observational Period (Part 2) of the study.
2
INTRODUCTION
Systemic lupus erythematosus is a chronic autoimmune disease that can target nearly all major 
organ systems in the body (Tsokos et al, 2007). In Europe, the incidence rate of SLE varies from 
1.0 per 100,000 person-years in Denmark to 4.7 per 100,000 person-years in the UK 
(Borchers et al, 2010). Studies in the US, Australia, and Canada report a similar incidence, with a 
range of 2 to 5 per 100,000 person-years (Borchers et al, 2010). These areas also have 
nonhomogeneous prevalence rates varying from 28.3 in Denmark to an estimated 149.5 per 
100,000 adults in the US (Borchers et al, 2010). In the Asia Pacific countries, crude incidence 
rates of SLE are reported to be 0.9 to 3.1 per 100,000 patient-years and the crude prevalence is 
reported to be 4.3 to 45.3 per 100,000 people (Jakes et al, 2012). The disease is rarely diagnosed 
in Africa.
The observed regional variation can be partially explained by the racial and ethnic differences in 
SLE occurrence. The prevalence in the US per 100,000 people is estimated to be between 
406 and 694 in blacks, 139 and 244 in Hispanics, 93 and 103 in Asian/Pacific Islanders, and 
164 and 203 in whites (Borchers et al, 2010). Two recent studies were designed to minimize 
many of the limitations in previous US SLE studies (Somers et al, 2014; Lim et al, 2014). These 
studies used Centers for Disease Control funded registries including the Michigan Lupus and 
Epidemiology Surveillance Program (MILES) and the Georgia Lupus Registry. In the MILES 
study, the source population was 2.4 million people (in 2 counties in Michigan). The 
age-adjusted incidence of SLE was 5.5 per 100,000 (95% confidence interval [CI]: 5.0, 6.1) 
person-years, and the prevalence was 72.8 per 100,000 people (95% CI: 70.8, 74.8) 
(Somers et al, 2014). These rates are higher than previously reported but are also calculated from 
more robust data. The study in Georgia found crude and adjusted incidence rates for SLE were 
both 5.6 per 100,000 person-years and the prevalence was 74 and 73 (crude and adjusted) per 
100,000 people (Lim et al, 2014). The more complete case ascertainment in both of these studies 
resulted in the highest incidence and prevalence statistics recorded in the US.
Manifestations of SLE are highly heterogeneous, with the most common organ manifestations 
being musculoskeletal, mucocutaneous, and renal (Nightingale et al, 2006; Cervera et al, 2003). 
There is a large degree of variability in disease activity and organ system involvement seen 
across patients; thus, the instruments to measure disease activity should encompass this range of 
organ systems. The disease often oscillates between periods of active disease (flare), low disease 
activity, and remission, but can also remain chronically active. All disease periods need 
individualized treatments; ie, if a patient flares, the patient needs a treatment intervention with 
high dose immunosuppressant therapy (ie, high dose corticosteroid therapy, potent 
immunosuppressants such as cyclophosphamide) to induce disease control; if a patient achieves a 
low disease activity, the treatment is adapted to lower dose immunomodulatory therapy (ie, low 
dose steroids, antimalarials) and/or symptomatic treatment to maintain disease control. The 
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highest unmet need remains in patients with frequent flares or persistently active disease in spite 
of the use of the currently available treatments.
Corticosteroids are the cornerstone of treatment of SLE, but they are associated with an 
extensive number of side effects most frequently seen during long-term use but also seen during 
short-term high dose induction therapy. Much of the organ damage in SLE is either directly or 
indirectly related to prednisone (Gladman et al, 2003). As the dose of prednisone increases in 
SLE patients, the likelihood of organ damage increases and the pattern of organ damage 
observed may differ depending on how the prednisone is administered (Thamer et al, 2009). For 
example, long-term, low dose prednisone may result in coronary artery disease, cataracts, or 
osteoporotic fractures; whereas high dose iv methylprednisone may additionally result in acute 
psychotic events or avascular necrosis of bone.
High dose corticosteroids (eg, short-term 0.5 to 1.0mg/kg/day oral prednisone [or equivalent] or 
500mg to 1g daily pulse iv methylprednisolone) are used to manage acute SLE flares such as
newly presenting grade III or IV lupus nephritis in combination with immunosuppressants as an 
induction therapy to gain disease control. Immunosuppressants are also generally used in both 
moderate and severe cases when other treatments are ineffective or to limit or prevent long-term 
major organ damage from the disease or corticosteroid use (“steroid-sparing”) 
(Muangchan et al, 2015; Al Sawah et al, 2015). Antimalarials (eg, chloroquine or 
hydroxychloroquine) are generally recommended as standard-of-care maintenance treatment in 
SLE, if tolerated. 
Other common drugs are initially used in the setting of lower-level disease activity, but their use 
continues as the disease progresses; they include analgesics, nonsteroidal anti-inflammatory 
drugs (NSAIDs), and local steroids, with common supportive medications, including 
vasodilators (calcium channel blockers, angiotensin-converting enzyme inhibitors) for systemic
hypertension or Raynaud’s syndrome, local treatments for rashes or sicca syndromes, 
transfusions, anticonvulsants, antimigraine medications, narcotic pain medications, 
anticoagulants for recurrent thromboses, and antidepressants (Muangchan et al, 2015).
The CD40 ligand (CD40L) (also known as CD154) is expressed on various types of cells, 
including activated T cells, and can also be found as a soluble protein. Through interactions with 
its receptor, CD40, CD40L plays an important role in regulating interactions between T cells and 
other immune cells, notably B cells and antigen presenting cells, and thus affects several 
important functional events thought to be involved in autoimmune disease. There is considerable 
pharmacological evidence in the literature (for reviews see Burkly, 2001; 
van Kooten and Banchereau, 2000) showing that blockade of CD40L is efficacious in 
inflammatory and autoimmune conditions. CD40L blockade could, therefore, be an innovative 
approach for the treatment of SLE, specifically to induce disease control in patients experiencing 
flare or persisted disease activity in spite of standard-of-care medication.
The monoclonal anti-CD40L antibodies hu5c8 (also known as BG9588 or ruplizumab 
[Antova®]) and IDEC-131 were developed and previously evaluated by Biogen and IDEC, 
respectively. Both products were humanized immunoglobulin (Ig) G1 antibodies that blocked 
humoral immune responses in nonhuman primate (NHP) models and showed evidence of 
potential efficacy in early clinical studies in idiopathic thrombocytopenic purpura (ITP) and SLE 
(Patel et al, 2008; Kuwana et al, 2004; Boumpas et al, 2003; Kalunian et al, 2002; 
Davis et al, 2001). Administration of hu5c8 was associated with an unusually high incidence of 
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thromboembolic events (approximately 10% of subjects exposed) and further clinical 
development of hu5c8 was discontinued. In over 150 subjects treated with IDEC-131, there was 
1 report in the literature of a thromboembolism; this subject (who had chronic refractory ITP, 
and who was diabetic, overweight, and hypertensive) had a myocardial infarction when their
platelet count increased to >100x109/L. Coronary angiography revealed longstanding 
atherosclerotic changes in the subject’s coronary arteries (Patel et al, 2008).
The underlying mechanism for the induction of thromboembolic events by hu5c8 in humans has 
been investigated. It has been known for some time that human platelets carry both CD40 and 
fragment crystallizable (Fc) γIIA (CD32a) receptors, and that they secrete CD40L and express 
cell surface CD40L after activation. Hypothetically, therefore, administration of anti-CD40L 
antibody may cause platelet activation via CD32a receptor cross-linking by simultaneously 
binding both to CD40/CD40L and to the Fc receptor. Indeed, in a transgenic mouse model, 
administration of anti-CD40L antibodies caused platelet aggregation and thrombosis in an 
Fc-dependent manner (Robles-Carrillo et al, 2010). Thus, it can be hypothesized that removal of 
the Fc receptor binding site might alleviate this risk of thromboembolism and enable further 
assessment of this therapeutic strategy in patients with SLE.
Dapirolizumab pegol (previously referred to as CDP7657) is a purified recombinant, humanized 
fragment antigen-binding (Fab´) antibody fragment covalently bound to PEG that targets CD40L 
and represents a novel approach to the treatment of SLE in patients experiencing flare or 
persistent disease activity in spite of standard-of-care medication. In particular, DZP lacks the Fc 
portion of whole antibody, and instead has a PEG moiety to achieve the PK characteristics to
enable adequate exposure (Fab´ PEG). Both hu5c8 and DZP display cross-reactivity against 
NHP CD40L with comparable affinity and potency in in vitro studies, and both are active in 
mechanistic studies. Extensive in vivo data from studies in NHPs together with data from in vitro 
functional experiments with human and Rhesus macaque platelets suggest that, for 
thromboembolism induction with an anti-CD40L antibody, 2 interactions are required: idiotypic 
binding of CD40L and interaction with the CD32a receptor via the Fc portion. In NHP studies, 
hu5c8 induced significant thromboembolic event-like lesions (thrombi, organized thrombi, and 
intimal hyperplasia) in the lungs of rhesus macaques after repeat dosing. In contrast, DZP does 
not result in any increase in pulmonary thrombi or vascular intimal hyperplasia above the
background incidence level in rhesus macaques. There are no NHP disease models resembling 
SLE. Dapirolizumab pegol displays no cross-reactivity against murine CD40L; however, an 
anti-murine CD40L Fab´ PEG antibody suppresses nephritis and improves renal function 
(proteinuria) in the New Zealand Black/New Zealand White murine lupus model (see the DZP
Investigator’s Brochure [IB] for further details). The nonclinical efficacy and safety data support 
further development of DZP as a potential therapy for patients with SLE.
Two clinical studies have been conducted with DZP. SL0013 was the first-in-human single-dose 
study of DZP. In Part 1 of SL0013, 28 healthy volunteers received either PBO or DZP at doses 
of 0.004mg/kg to 5mg/kg, and in Part 2, 17 subjects with SLE received PBO or DZP at doses of 
5mg/kg to 60mg/kg. Dapirolizumab pegol was well tolerated both in healthy subjects and in 
subjects with SLE in this study and no thromboembolic events were reported. The DZP IB
contains additional information pertaining to data obtained in SL0013.
SL0014 was a Phase 1 study evaluating the safety, tolerability, PK, immunogenicity, and effects 
on disease activity of repeat-dose iv administration of DZP in subjects with active SLE, defined 
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as having a SLEDAI-2K score ≥4. A total of 24 subjects with SLE were randomized (2:1) to 
receive a loading dose of DZP 30mg/kg followed by DZP 15mg/kg every 2 weeks for a total of 
6 doses of DZP or matching PBO on the same dosing schedule. DZP was well tolerated in this 
study, with a safety profile similar to subjects administered PBO, with the exception of a slightly 
higher incidence of nonserious infection in the DZP group. There were no AEs of 
thromboembolism and no laboratory findings suggestive of thromboembolic events. In 
exploratory analyses, numerically greater improvements from Baseline were observed in the 
DZP group compared with the PBO group for the BILAG 2004 total score, SLEDAI-2K, 
Patient’s Global Assessment of Disease, SLEDAI-2K Responder Index-50 (SRI-50) score, and 
BICLA and SLE Responder Index-4 (SRI-4) responders. The BICLA response represents a 
clinically relevant improvement of moderate to severe disease activity, as it represents the 
change from a disease activity with an indication for systemic treatment intervention to a disease 
activity with no or limited indication to change the preexisting therapy; the SRI-4 represents a 
relevant decrease in disease activity. At Week 12, there were more BICLA and SRI-4 responders 
in the DZP group (45.5% and 41.7%, respectively) compared with the PBO group (14.3% for 
both BICLA and SRI-4). There was a small but statistically significant reduction in IgG 
concentrations at Week 12 (p=0.0436) in the DZP group compared with the PBO group. 
Messenger ribonucleic acid analysis demonstrated changes in the expression of genes associated 
with B cell and plasma cell function, as well as reductions in the expression of interferon-
responsive genes (see the DZP IB for further details).
The current study, SL0023, is a Phase 2b, randomized, double-blind, PBO-controlled, 
parallel-group dose-ranging study followed by an observational period that will evaluate the 
efficacy in inducing disease control and safety of DZP in subjects with moderately to severely 
active SLE. Dapirolizumab pegol or PBO will be added to stable standard-of-care medication 
and randomization will be stratified by Screening corticosteroid dose (≤10mg/day or >10mg/day 
prednisone equivalent). Following completion of the 24-week Double-Blind Treatment Period 
(Part 1) of the study, subjects will continue into a 24-week Observational Period (Part 2), during 
which subjects will not receive study drug but will be able to receive standard-of-care treatment,
as indicated.
3
STUDY OBJECTIVES
3.1
Primary objective
The primary objective of SL0023 is to assess the dose-response for the efficacy of iv DZP 
(3 dose groups) at Week 24 of the Double-Blind Treatment Period (Part 1) in adult subjects with 
moderately to severely active SLE receiving stable standard-of-care treatment.
3.2
Secondary objectives
The secondary objectives of SL0023 are:

To assess the efficacy of the individual dose regimens of iv DZP at Week 24

To assess the safety and tolerability of iv DZP
3.3
Other objectives
The other objectives of SL0023 are:

To assess the efficacy of the individual dose regimens of iv DZP at additional time points
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
To assess the corticosteroid-sparing effect of iv DZP

To assess the PK of iv DZP and PEG

To assess the PD of iv DZP

To assess the immunogenicity of iv DZP and PEG

To assess the effects of iv DZP on HRQoL, symptoms, fatigue, mobility, and pain

To perform exploratory analyses of the effects of iv DZP with transcriptomic and proteomic 
biomarkers

To assess durability of the clinical response after withdrawal of study drug

To assess PD after withdrawal of study drug (including gene transcription signature)
4
STUDY VARIABLES
4.1
Efficacy variables
The Baseline value for efficacy variables is defined as the last value obtained prior to the first 
infusion of study drug (Visit 2), unless otherwise noted.
4.1.1
Primary efficacy variable
The primary efficacy variable is the BICLA responder rate across 3 doses of DZP and PBO at 
Week 24 (see Section 9.1.9.1 for a detailed description of this variable).
4.1.2
Secondary efficacy variable
The secondary efficacy variable is the BICLA responder rate in the individual dose groups at 
Week 24.
4.1.3
Other efficacy variables
Other efficacy variables being evaluated by visit will include all scheduled visits for that 
particular variable and will exclude the time points at which the primary and secondary variables 
are assessed, as specified in Section 4.1.1 and Section 4.1.2.
4.1.3.1
Clinical assessments of disease activity

BICLA responder rates by visit

Time to first maintained BICLA response (defined as BICLA response at 2 consecutive study 
visits)

Percentage of subjects with maintained BICLA response from Week 12 to Week 24

Percentage of subjects with maintained BICLA response from Week 24 to Week 48

Number and percent of subjects with BILAG 2004 improvement (all BILAG 2004 Grade A
improved to B, C, or D and all BILAG 2004 Grade B improved to C or D) by visit

Absolute and change from Baseline in total BILAG 2004 score by visit

BILAG 2004 Systems Tally (BST)

Absolute and change from Baseline in SRI-50 score by visit
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
Absolute and change from Baseline in SLEDAI-2K score by visit

Change from Baseline in Physician’s Global Assessment of Disease (PGA) and Patient’s 
Global Assessment of Disease (PtGA) scores by visit

SRI-4 responder rates by visit

SLE Responder Index-5 (SRI-5) responder rates by visit

SLE Responder Index-6 (SRI-6) responder rates by visit

Percentage of subjects in each category in the Systemic Lupus International Collaborating 
Clinics/American College of Rheumatology (SLICC/ACR) Damage Index score at Week 24

Percent change from Baseline in tender joint count (TJC) by visit

Percent change from Baseline in swollen joint count (SJC) by visit

Absolute and change from Baseline in Cutaneous Lupus Erythematosus Disease Area and 
Severity Index (CLASI) by visit

Time to flare (with the occurrence of a flare determined by the Investigator)

Time to flare after Week 24 (with the occurrence of a flare determined by the Investigator)

Time to flare after Week 24 (with the occurrence of a flare defined as: a new sustained 
BILAG 2004 Grade A/B [present at ≥2 consecutive visits] after withdrawal of study drug or 
start of new induction therapy [either corticosteroid dose increase to ≥0.5 mg/kg/day 
prednisone equivalent or initiation of cyclophosphamide, rituximab, iv Ig, or plasma 
exchange] after withdrawal of study drug)
4.1.3.2
Variables assessing corticosteroid-sparing effects

Absolute daily corticosteroid dose (in prednisone equivalent)

Percentage of subjects with a daily corticosteroid dose of 7.5mg prednisone equivalent or less 
and BICLA response at Week 24

Percentage of subjects with a daily corticosteroid dose of 7.5mg prednisone equivalent or less 
and a maintained BICLA response from Week 12 to Week 24

Percentage of subjects with a daily corticosteroid dose of 7.5mg prednisone equivalent or less 
and SRI-4 response at Week 24

Time-weighted area under the curve in corticosteroid dose for the period covering Baseline
to Week 24

Percentage of subjects with a daily corticosteroid dose of 7.5mg or less prednisone 
equivalents by visit

Percentage of subjects with no concomitant corticosteroid treatment by visit
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4.1.3.3
Patient-reported outcome variables

Change from Baseline in Lupus Quality of Life (LupusQoL) questionnaire scores by visit

The following exploratory patient-reported outcome (PRO) variables being developed by 
UCB will be assessed at sites in English- and Spanish-speaking countries (approximately 
45% to 50% of the projected study population):

Change from Baseline in the SLE-Symptom Inventory Instrument (SLE-S) scores by visit

Change from Baseline in the SLE-Fatigue Instrument (SLE-F) scores by visit

Change from Baseline in the SLE-Mobility Instrument (SLE-M) scores by visit

Change from Baseline in the SLE-Pain Instrument (SLE-P) scores by visit

Change from Baseline in the SLE-Emotional States Instrument (SLE-E) scores by visit
4.2
Safety variables

Incidence of AEs, SAEs, and AEs of interest including and not limited to infections, 
infusion-related reactions, thromboembolic events, neurological events, and malignancies

Subject withdrawals due to AEs

Changes from Baseline in vital sign parameters by visit

ECGs (normal/abnormal) by visit

Changes from Baseline in safety laboratory tests (hematology [including lymphocyte 
subsets], blood chemistry, urinalysis) by visit
4.3
Pharmacokinetic variables

Plasma concentrations of DZP and PEG

Urine concentrations of PEG
4.4
Pharmacodynamic variables

Whole blood mRNA signature profiling to characterize potential changes in gene expression 
relevant to the inflammatory and immune response to DZP in SLE
4.4.1
Immunological variables

Lupus Autoantibody Profile: anti-dsDNA antibodies, ANAs, anti-ENA (anti-SM, anti-SSA, 
anti-SSB, and anti-RNP), rheumatoid factor (RF), and antiphospholipid (aPL) antibodies

Ig (total Ig, IgG, IgM, IgA, and IgE)

High sensitivity C-reactive protein (hsCRP)

C3 and C4 levels
4.5
Immunogenicity variables

Anti-DZP and anti-PEG antibodies
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4.6
Biomarkers
In addition to the PD variables (Section 4.4), the following samples will also be taken:

Serum will be taken and stored for protein and lipid analysis to characterize potential changes 
relevant to inflammatory and immune responses and cardiovascular risk in SLE.

Whole blood will be taken and stored to isolate deoxyribonucleic acid (DNA) which may be 
used to examine genetic and epigenetic changes. If samples are not used immediately, they 
will be stored at -80°C for later analysis until the completion of the DZP development 
program. They will be stored at BioStorage Technologies GmbH (Germany) and they will 
only be used in the context of understanding the molecular taxonomy of SLE and/or response 
to treatment with DZP.
5
STUDY DESIGN
5.1
Study description
SL0023 is a 2-part study consisting of a randomized, double-blind, PBO-controlled, 
parallel-group, dose-ranging period (24-week Double-Blind Treatment Period; Part 1) followed 
by a 24-week Observational Period (Part 2) in adult subjects with moderately to severely active 
SLE who are receiving stable standard-of-care medications (ie, corticosteroids, 
immunosuppressants, and/or antimalarials) at study entry.
The study consists of a Screening Period of up to 4 weeks, a 24-week Double-Blind Treatment 
Period (Part 1), and a 24-week Observational Period (Part 2) (see Figure 5-1). At the start of the 
24-week Double-Blind Treatment Period (Part 1), eligible subjects will be randomized (1:1:1:1) 
to 1 of 4 treatment arms (DZP 6mg/kg, 24mg/kg, or 45mg/kg, or PBO) and stratified in 
accordance with Screening corticosteroid dose (≤10mg/day or >10mg/day prednisone 
equivalent). Study drug will be administered by iv infusion every 4 weeks during Part 1 of the 
study. Subjects who withdraw early from the 24-week Double-Blind Treatment Period (Part 1) 
will enter an 8-week SFU Period (which ends 12 weeks after the final dose of study drug).
Subjects who complete the 24-week Double-Blind Treatment Period (Part 1) will continue into a 
24-week Observational Period (Part 2), during which subjects will not receive study drug but 
will be able to receive standard-of-care treatment, as indicated. The subjects, Investigators, and 
study site staff will remain blinded to the treatment administered during Part 1 of the study until 
the end of the study.
Eligible subjects will have active SLE at Baseline despite stable standard-of-care treatment with
at least 1 of the following, either alone or in combination: corticosteroids (at doses of ≤40mg/day 
prednisone or equivalent), and/or antimalarials, and/or immunosuppressants. In subjects 
receiving concomitant corticosteroids, doses must have been stable for at least 2 weeks prior to 
Screening, must remain stable until Baseline (Visit 2), and should remain stable until 4 weeks 
after the first study drug infusion (until Day 28). Subjects 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). Treatment with antimalarials and immunosuppressants must have been 
started or stopped at least 12 weeks prior to dosing with study drug and doses must remain stable 
for at least 4 weeks for antimalarials and at least 8 weeks for immunosuppressants prior to the 
first study drug infusion (Visit 2). In subjects receiving concomitant antimalarials or 
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immunosuppressants, doses must not exceed the specified maximum permitted doses (as outlined 
in Table 6-1 and Table 6-2). 
In subjects receiving concomitant corticosteroid doses between 10mg/day and 40mg/day 
prednisone or equivalent at Screening, a mandatory corticosteroid taper must be initiated no later 
than 4 weeks after the first study drug infusion (on Day 29). The tapering regimen, as
recommended in Table 5-1, will aim to reduce the daily prednisone equivalent dose to 7.5mg/day 
or lower by Week 12 (Day 84) of the study. If such a rapid tapering is not considered by the 
Investigator to be appropriate for the individual subject, a slower tapering regimen can be used.
Subjects achieving a dose of 7.5mg/day or lower may remain on this dose or continue to taper at 
the discretion of the Investigator. Subjects who cannot fulfill the taper based on the 
Investigator’s judgment should remain in the study and receive corticosteroids at an appropriate 
dose as determined by the Investigator. Subjects will be considered nonresponders for the 
primary endpoint if the corticosteroid dose exceeds the prednisone equivalent dose at Baseline. 
Subjects will be issued a daily diary in which to record corticosteroid doses taken on a daily 
basis at home in between visits. Use of oral or parenteral steroids for non-SLE related conditions 
should be discussed in advance with the Sponsor on an individual basis.
Table 5-1:
Corticosteroid tapering schedule
Day
Corticosteroid dose a (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
Day 1 to Day 7
40
35
30
25
20
15
10
7.5
5
2.5
0
Day 8 to Day 14
40
35
30
25
20
15
10
7.5
5
2.5
0
Day 15 to Day 21
40
35
30
25
20
15
10
7.5
5
2.5
0
Day 22 to Day 28
40
35
30
25
20
15
10
7.5
5
2.5
0
Day 29 to Day 35
30
30
20
20
15
10
7.5
NAb
NAb
NAb
NAb
Day 36 to Day 42
30
20
20
15
15
10
NAb
NAb
NAb
NAb
NAb
Day 43 to Day 49
20
20
15
15
10
7.5
NAb
NAb
NAb
NAb
NAb
Day 50 to Day 56
20
15
15
10
7.5
NAb
NAb
NAb
NAb
NAb
NAb
Day 57 to Day 63
15
15
10
7.5
NAb
NAb
NAb
NAb
NAb
NAb
NAb
Day 64 to Day 70
15
10
7.5
NAb
NAb
NAb
NAb
NAb
NAb
NAb
NAb
Day 71 to Day 77
10
7.5
NAb
NAb
NAb
NAb
NAb
NAb
NAb
NAb
NAb
Day 78 to Day 84
7.5
NAb
NAb
NAb
NAb
NAb
NAb
NAb
NAb
NAb
NAb
a Corticosteroid tapering is only required in those subjects receiving continuous corticosteroids at doses ≥10mg/day 
at the time of enrollment into the study.
b Subjects 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.
Eligible subjects who are receiving a corticosteroid dose at Screening that is in between the 
specified starting doses of the corticosteroid tapering schedule (Table 5-1; eg, 12.5mg/day or 
17.5mg/day) should transition to the lowest nearest prespecified starting dose over the first 
2 weeks of Screening and will enter the study on this dose; the dose will be considered stable in 
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this case. This dose should then remain stable until 4 weeks after the first study drug infusion 
(until Day 28).
An initial biomarker analysis may be performed on all evaluable biomarker data from Part 1 of 
the study when 25% to 35% of the randomized subjects have completed Visit 7 (Week 12) of the 
Double-Blind Treatment Period. Data from subjects who have prematurely withdrawn from the 
study prior to Visit 7 will be included. The initial biomarker analysis will focus on transcriptomic 
biomarker variables (eg, mRNA), prespecified in a Biomarker Plan, in order to provide guidance 
for the DZP development program, and will not affect the conduct of the study.
After the last subject completes Part 1 of the study, the data for those subjects will be secured 
and an interim CSR will be written for the Double-Blind Treatment Period (Part 1) of the study. 
A complete final CSR will be written for the entire study following completion of the 
Observational Period (Part 2) of the study. See Section 15.7 for further details regarding these 
analyses.
5.1.1
Study duration per subject
The maximum duration of the entire study (Parts 1 and 2) per subject will be approximately 
52 weeks, including a Screening Period of up to 4 weeks, a 24-week Double-Blind Treatment 
Period (Part 1), and a 24-week Observational Period (Part 2).
The end of the study is defined as the date of the last visit of the last subject in the study.
5.1.2
Planned number of subjects and sites
The study is planned to enroll at least 267 subjects in order to randomize approximately 
160 subjects (40 subjects per treatment group). The study will be conducted at approximately 
70 sites. 
5.1.3
Anticipated regions and countries
This study is anticipated to be conducted in Western Europe, Eastern Europe, Latin America, and 
North America, with possible extension to other regions and countries, as needed. Capping rules 
for regions and sites will be described in detail in the interactive voice response system 
(IVRS)/interactive web response system (IWRS) specifications.
5.1.4
Data Monitoring Committee
A DMC will be formed to monitor the ongoing safety of the study. The DMC will consist of at 
least 3 individuals. These are clinicians knowledgeable about the disease or the treatment and 
1 member may be a statistician. All members will have experience and expertise in clinical trials. 
The DMC members may not participate in the study as principal or coinvestigators, or as study 
subject care physicians. The duration of membership for the DMC will be inclusive of planned 
analyses for SL0023. The DMC will periodically review study data and evaluate the treatments 
for excess adverse effects and other potential safety issues. The DMC may also be asked to 
provide a review of final study results, as deemed appropriate. The detailed role, scope, 
composition, responsibilities, and operation of the DMC, as well as the identity of the DMC
members, will be defined in a separate DMC Charter. 
Safety and tolerability data will be made available to the DMC at each meeting as described in 
the DMC Statistical Analysis Plan (SAP). The data will be provided in a semi unblinded fashion 
(data will be visualized by real treatment groups, but the treatment/dose assigned to each group 
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will remain blinded) and the full unblinding can be requested by the DMC members, if 
appropriate. Pharmacokinetic data may be provided to the DMC at their request. These safety, 
tolerability, and PK data will be presented by individuals not otherwise involved in the conduct 
of the study. The deliberations and decisions of the DMC will be formally minuted/documented.
Ad hoc DMC meetings can be held for other reasons if deemed appropriate by the Sponsor or the 
DMC members.
In addition to ongoing review of safety data and safety signal detection within UCB (see 
Section 13.1.12), the occurrence of AEs of interest including thromboembolic events, in 
particular, will be monitored by the DMC to provide an assessment of the risk of occurrence of 
these events in the study. Statistical modeling will be used to provide estimates for quantification 
of the level of risk in the study based on the risk in the SLE population and in the intended 
patient population in the study (see Inclusion and Exclusion Criteria in Section 6). This analysis 
will inform any decisions regarding changes in study conduct and/or study termination.
The DMC procedures will ensure that the data remain blinded to the study team and investigators 
at all times throughout the conduct of the study until the data for Part 1 of the study have been 
unblinded.
5.2
Schedule of study assessments
A schedule of study assessments is provided in Table 5‒2.
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Table 5‒2:
Schedule of study assessments
Period
Screening
Double-Blind Treatment Period (Part 1)
Observational Period (Part 2)
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10/
EWV
V11/ 
SFU b
V12/ 
SFU b
V13
V14
V15
V16/
EWV
Week a
W-4 to -1
1a
W2
W4
W6
W8
W12 W16 W20
W24
W28b W32b W36
W40
W44
W48
Day a (±3 days for Visits 3 to 16)
D-28 to -1
D1a
D14
D28
D42
D56
D84
D112 D140 D168 D196b D224b D252 D280 D308 D336
Written informed consent
X
Demographic information
X
Lifestyle 
X
History: general medical/procedures
X
TB Signs & Symptoms questionnaire
X
X c
X c
X
Chest x-ray d
X
Verification of eligibility
X
X c,e
C-SSRS
X
X
X f
X
Physical exam/interim medical history
X
X c
X c
X c
X c
X c
X c
X
X
X
X
12-lead ECG
X
X c
X
X
Randomization
X c
Recording of concomitant medications
X
X c
X
X c
X
X c
X c
X c
X c
X
X
X
X
X
X
X
Recording of medical procedures
X c
X
X c
X
X c
X c
X c
X c
X
X
X
X
X
X
X
Adverse events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Withdrawal criteria check
X c
X
X c
X
X c
X c
X c
X c
X
X g
X g
X
X
X
Overnight fast (prior to visit) h
X h
X h
X h
X h
X h
Contact IVRS/IWRS
X
X
X
X
X
X
X
X
X
X
Study drug administration
X
X
X
X
X
X
Dispense daily diary
X
X
X
X
X
X
X
X
X
X
X
X g
X
X
X
Collect/review daily diary/corticosteroid 
taper
X c
X
X c
X
X c
X c
X c
X c
X
X
X
X
X
X
X
Dispense urine collection container i
X
X
X
X
X
X g
X
X
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Table 5‒2:
Schedule of study assessments
Period
Screening
Double-Blind Treatment Period (Part 1)
Observational Period (Part 2)
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10/
EWV
V11/ 
SFU b
V12/ 
SFU b
V13
V14
V15
V16/
EWV
Week a
W-4 to -1
1a
W2
W4
W6
W8
W12 W16 W20
W24
W28b W32b W36
W40
W44
W48
Day a (±3 days for Visits 3 to 16)
D-28 to -1
D1a
D14
D28
D42
D56
D84
D112 D140 D168 D196b D224b D252 D280 D308 D336
Vital signs j:
Unspecified time during visit
X
X
X
X
X
X
X
X
X
X
Predose; every 15min post start of 
infusion; every 30min until 2h post end 
of infusion
X
X
X
X
X
X
Collection of blood samples for:
TB test k
X
HIV and hepatitis screening
X
Serum pregnancy testing (β-hCG) 
(subjects of childbearing potential)
X
Hematology l
X
X c
X
X c
X c
X c
X c
X c
X
X
X
X
X
Clinical chemistry l
X
X c
X
X c
X c
X c
X c
X c
X
X
X
X
X
Additional laboratory assessments:
Anti-dsDNA antibodies
X
X c
X c
X c
X c
X c
X c
X
X
X
X
ANAs, anti-ENAs (anti-SM, 
anti-SSA, anti-SSB, anti-RNP), and 
RF
X
X
X
aPL antibodies (anticardiolipin 
antibodies, lupus anticoagulant, and 
anti-β2 glycoprotein-1)
X
X
X
Anti-DZP, anti-PEG antibodies
X c
X c
X c
X c
X c
X c
X
X
X
X
Coagulation and hemostasis tests m
X
X c
X
X
X
Total Ig, IgG, IgM, IgA, and IgE
X c
X
X c
X c
X c
X c
X c
X
X
X
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Table 5‒2:
Schedule of study assessments
Period
Screening
Double-Blind Treatment Period (Part 1)
Observational Period (Part 2)
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10/
EWV
V11/ 
SFU b
V12/ 
SFU b
V13
V14
V15
V16/
EWV
Week a
W-4 to -1
1a
W2
W4
W6
W8
W12 W16 W20
W24
W28b W32b W36
W40
W44
W48
Day a (±3 days for Visits 3 to 16)
D-28 to -1
D1a
D14
D28
D42
D56
D84
D112 D140 D168 D196b D224b D252 D280 D308 D336
Serum complement (C3, C4)
X
X c
X
X c
X c
X c
X c
X c
X
X
X
X
hsCRP
X
X c
X
X c
X c
X c
X c
X c
X
X
X
X
X
Whole blood mRNA
X c
X
X c
X c
X c
X
X
X
Proteomic signature profile
X
X
X c
X c
X c
X c
X
X
X
Cardiovascular proteins, lipids, lipid 
particles h
X c,h
X h
X c,h
X h
X h
DNA (PGx analysis)
X c
X
X
Plasma PK sampling n:
Unspecified time during visit
X
X
X
X
X
X
X
X
Predose; end of infusion; 30min, 1h, 
2h post end of infusion
X
X
X
Predose; end of infusion
X
X
X
Collection of urine for:
Urine pregnancy testing (β-hCG) 
(subjects of childbearing potential)
X c
X
X c
X
X c
X c
X c
X c
X
X
X
X
X
X
X
Urinalysis, chemistry, microscopy l
X
X c
X
X c
X c
X c
X c
X c
X
X
X
X
X
Urine PK sampling (to be collected at 
home) i
X
X
X
X
X
X
X
X
Clinical assessments of disease activity:
BILAG 2004
X
X c
X c
X c
X c
X c
X c
X
X
X
X
SLEDAI-2K
X
X c
X c
X c
X c
X c
X c
X
X
X
X
SRI-50
X c
X c
X c
X c
X c
X
X
X
X
PGA
X c
X c
X c
X c
X c
X c
X
X
X
X
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Table 5‒2:
Schedule of study assessments
Period
Screening
Double-Blind Treatment Period (Part 1)
Observational Period (Part 2)
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10/
EWV
V11/ 
SFU b
V12/ 
SFU b
V13
V14
V15
V16/
EWV
Week a
W-4 to -1
1a
W2
W4
W6
W8
W12 W16 W20
W24
W28b W32b W36
W40
W44
W48
Day a (±3 days for Visits 3 to 16)
D-28 to -1
D1a
D14
D28
D42
D56
D84
D112 D140 D168 D196b D224b D252 D280 D308 D336
PtGA
X c
X c
X
X
SLICC/ACR Damage Index
X
X
X
TJC, SJC
X
X c
X c
X c
X c
X c
X c
X
X
X
X
CLASI
X
X c
X c
X c
X c
X c
X c
X
X
X
X
Investigator Assessment of Flare
X
X c
X
X c
X c
X c
X c
X
X
X
X
X
X
X
Patient-reported outcomes:
LupusQoL
X c
X c
X c
X c
X c
X c
X
X
X
X
SLE-S o
X c,o
X c,o
X c,o
X c,o
X c,o
X c,o
X o
X o
X o
X o
SLE-F o
X c,o
X c,o
X c,o
X c,o
X c
X c,o
X o
X o
X o
X o
SLE-M o
X c,o
X c,o
X c,o
X c,o
X c
X c,o
X o
X o
X o
X o
SLE-P o
X c,o
X c,o
X c,o
X c,o
X c
X c,o
X o
X o
X o
X o
SLE-E o
X c,o
X c,o
X c,o
X c,o
X c
X c,o
X o
X o
X o
X o
Subject Experience Interview o
X c,o
X o
ANA=antinuclear antibody; anti-dsDNA=anti-double-stranded deoxyribonucleic acid; anti-ENA=extractable nuclear antigen antibody; anti-RNP=anti-ribonucleoprotein antibody; 
anti-SSA=Sjögren’s syndrome antibody A; anti-SSB=Sjögren’s syndrome antibody B; anti-SM=Smith antibody; aPL=antiphospholipid; β-hCG=β-human chorionic 
gonadotropin; BILAG 2004=British Isles Lupus Assessment Group Disease Activity Index 2004; C3=complement 3; C4=complement 4; CLASI=Cutaneous Lupus 
Erythematosus Disease Area and Severity Index; C-SSRS=Columbia Suicide Severity Rating Scale; D=Day; DZP=dapirolizumab pegol; ECG=electrocardiogram; EWV=Early 
Withdrawal Visit; HIV=human immunodeficiency virus; hsCRP=high sensitivity C-reactive protein; Ig=immunoglobulin; IGRA=interferon-γ release assay; 
IVRS/IWRS=interactive voice/web response system; LupusQoL=Lupus Quality of Life questionnaire; mRNA=messenger ribonucleic acid; PEG=polyethylene glycol; 
PGA=Physician’s Global Assessment of Disease; PGx=pharmacogenomics; PK=pharmacokinetic; PtGA=Patient’s Global Assessment of Disease; QFT-GIT=Quanti-FERON®-
TB GOLD in-Tube test; RF=rheumatoid factor; SFU=Safety Follow-up; SJC=swollen joint count; SLEDAI-2K=Systemic Lupus Erythematosus Disease Activity Index 2000; 
SLE-E=Systemic Lupus Erythematosus-Emotional States Instrument; SLE-F=Systemic Lupus Erythematosus-Fatigue Instrument; SLE-M=Systemic Lupus Erythematosus-
Mobility Instrument; SLE-P=Systemic Lupus Erythematosus-Pain Instrument; SLE-S=Systemic Lupus Erythematosus-Symptom Inventory Instrument; SLICC/ACR=Systemic 
Lupus International Collaborating Clinics/American College of Rheumatology Damage Index; SRI-50=Systemic Lupus Erythematosus Disease Activity Index-2K Responder 
Index-50; TB=tuberculosis; TJC=tender joint count; V=Visit; W=Week
Note: Unscheduled visits are described in Section 8.11.
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Table 5‒2:
Schedule of study assessments
Period
Screening
Double-Blind Treatment Period (Part 1)
Observational Period (Part 2)
Visit
V1
V2
V3
V4
V5
V6
V7
V8
V9
V10/
EWV
V11/ 
SFU b
V12/ 
SFU b
V13
V14
V15
V16/
EWV
Week a
W-4 to -1
1a
W2
W4
W6
W8
W12 W16 W20
W24
W28b W32b W36
W40
W44
W48
Day a (±3 days for Visits 3 to 16)
D-28 to -1
D1a
D14
D28
D42
D56
D84
D112 D140 D168 D196b D224b D252 D280 D308 D336
a
Day 1 is the first day of Week 1; for all other weeks, the day shown is the final day of the week indicated.
b
Subjects who withdraw prior to Week 32 (Visit 12) will complete an EWV (Visit 10 assessments if withdrawn prior to Visit 10; Visit 16 assessments if withdrawn after 
Visit 10) as well as Visits 11 and 12 for SFU assessments at 8 and 12 weeks after their final dose of study drug (as applicable). Subjects who withdraw after Week 32 
(Visit 12) do not require additional SFU visits and will complete the Visit 16/EWV assessments only.
c
To be performed before study drug dosing is started.
d
A chest x-ray should be performed if one is not available within 3 months prior to Visit 1 (Screening).
e
Subject must have a SLEDAI-2K score without any laboratory values of ≥4 at Visit 2 in order to be eligible to be randomized.
f
Performed only in subjects who have withdrawn from the study prior to Week 32 (Visit 12) and are undergoing SFU assessments.
g
Performed only in subjects who are continuing into Part 2.
h
Subjects should undergo an overnight fast (at least 8 hours) prior to coming to the site for Visits 2, 5, 7, 10, and 16 for the collection of fasting blood samples for 
cardiovascular proteins, lipids, and lipid particles. Subjects may then eat breakfast after serum samples have been obtained for these assessments and before study drug 
administration (if applicable).
i
For urine PK assessments, a urine collection container will be dispensed to the subject at the designated visits for urine collection at home prior to their next visit. Prior to 
Visits 9 and 10 only, the subject will collect overnight urine samples, which includes the first void after the subject goes to sleep the night before the visit through the first 
morning void the morning of the visit. The subject should note the times for the first and last urine collection. For all other noted visits (Visits 2, 11, 12, 13, 14, and 16), the 
subject will only collect their first morning void.
j
Height will only be measured at Screening. With the exception of weight, which should be measured predose, all other vital signs (pulse rate, blood pressure, and body 
temperature) should be measured at the times indicated. Weight should only be measured at Screening and on dosing visits. Vitals signs should be measured within ±5min of 
the scheduled time point for the every 15min assessments and within ±10min of the scheduled time point for the every 30min assessments. There are no time window 
requirements for vital signs assessments when measured pre-dose or at unspecified times during the visit.
k
Tuberculosis testing should be done using IGRA. The QFT-GIT is the preferred IGRA test (see Section 13.6). It is recommended that the QFT-GIT be the first test performed 
at Screening to reduce the number of screening procedures conducted for any QFT-GIT-positive subjects that may need to be withdrawn from the study.
l
Hematology, clinical chemistry, and urinalysis parameters to be assessed are defined in Section 13.9.
m
As defined in the Laboratory Manual.
n
Blood samples for PK measurements should be drawn within ±10min of the scheduled time point for each post-infusion time point or within 10min after the infusions ends 
for end of infusion time points (ie, not prior to the end of the infusion; further details are provided in the Laboratory Manual). There are no time window requirements for 
blood samples for PK measurements when measured pre-dose or at unspecified times during the visit.
o
The exploratory SLE-S, SLE-F, SLE-M, SLE-P, and SLE-E Instruments and Subject Interview will be assessed at sites in English- and Spanish-speaking countries only.
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5.3
Schematic diagram
A schematic diagram of the study design is provided in Figure 5-1.
Figure 5-1:
Schematic diagram of SL0023
CS=corticosteroids; DZP=dapirolizumab pegol; PBO=placebo; q4w=every 4 weeks; SOC=standard-of-care
a Stratified in accordance with Screening corticosteroid dose (≤10mg/day or >10mg/day prednisone or equivalent).
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5.4
Rationale for study design and selection of dose
Moderately to severely active SLE is a disease area with high unmet need, as, in many patients,
disease remains uncontrolled and poorly managed with current standard-of-care
immunosuppressants and corticosteroids at tolerable doses. Dapirolizumab pegol has been 
evaluated in 2 small Phase 1 studies: 1 single dose study at doses up to 5mg/kg in healthy 
subjects (SL0013, Part 1) and up to 60mg/kg in subjects with SLE (SL0013, Part 2), and 1 repeat 
dose study utilizing a loading dose of 30mg/kg followed by 5 doses of 15mg/kg every 2 weeks in 
subjects with SLE (SL0014). No treatment-limiting safety findings were observed in either 
study, and the results of SL0014 showed a trend for clinical efficacy in subjects with SLE. 
SL0023 is a dose-ranging study in subjects with moderately to severely active SLE (including 
neurological and renal involvement), where a spectrum of DZP doses will be administered over a 
Double-Blind Treatment Period of 24 weeks (Part 1) in subjects who have active disease despite 
stable standard-of-care treatment. Subjects completing the Double-Blind Treatment Period 
(Part 1) will enter a 24-week Observational Period (Part 2).
SL0023 is intended to evaluate 3 dose levels of DZP, 6mg/kg, 24mg/kg, and 45mg/kg,
administered every 4 weeks for 24 weeks. These doses have been selected to explore a 
dose-response curve for DZP in SLE. The clinical data generated thus far for DZP have not 
allowed an exposure-response relationship to be defined in order to aid in the selection of doses 
to be tested in SL0023. Therefore, several target Ctrough values were defined based on qualitative 
evidence from nonclinical and clinical data and dose levels were selected to maintain the DZP 
plasma concentration above the target Ctrough values in more than 90% of subjects for the 
majority of the dosing interval.
The DZP dosing regimen in SL0014 (30 mg/kg loading followed by 15mg/kg every 2 weeks) 
was chosen in order to maintain DZP plasma concentrations above 100μg/mL, and in fact, the 
majority of subjects in SL0014 had Ctrough ≥100μg/mL. The 100μg/mL target was determined 
based on clinical data observed in clinical studies for hu5c8, a full length anti-CD40L 
monoclonal antibody. Study C99-1021 was an open-label, multiple dose study to evaluate the 
efficacy, safety, and PK of hu5c8 in subjects with proliferative lupus glomerulonephritis. 
Pharmacological activity was observed for hu5c8 in terms of meaningful changes in 
anti-dsDNA. Hu5c8 at 20mg/kg was planned to be administered every 2 weeks for 3 doses, and 
then every 28 days for 4 doses. Data from subjects who received at least 3 doses were evaluated. 
Following hu5c8 administration, there was a significant treatment-related decline in anti-dsDNA 
antibody titers, with mean reductions of 25.1% on Day 29 and 23.9% and 18.9%, respectively, 
1 month and 2 months after the last treatment (Boumpas et al, 2003). A limited PK/PD 
relationship (log-linear model) was determined, and it highlighted that to achieve the 25% 
reduction in anti-dsDNA antibody titers, an hu5c8 plasma concentration >100μg/mL was 
required. Therefore, 100μg/mL was set as the target Ctrough to be maintained in SL0014 and this 
study demonstrated greater improvement in clinical measures of disease activity in the DZP 
group compared with the PBO group. For SL0023, the dosing frequency is being reduced to 
every 4 weeks as a more patient-oriented regimen and no loading dose is proposed. A dose level 
of 45mg/kg administered every 4 weeks is predicted to maintain the Ctrough >100μg/mL for the 
majority of the dosing interval.
In order to explore the dose response curve, 2 DZP dose levels below 45mg/kg have been 
selected (24mg/kg and 6mg/kg). The 24mg/kg dose has been selected in consideration of results 
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from the hu5c8 anti-dsDNA antibody PK/PD model demonstrating that minimum changes in 
anti-dsDNA antibody titers could be achieved with an hu5c8 plasma concentration of 40μg/mL. 
The dose of 24mg/kg every 4 weeks was selected to maintain a Ctrough >40μg/mL for the majority 
of the dosing interval.
The lowest DZP dose level in SL0023 (6mg/kg) has been selected based on nonclinical 
pharmacology data. Nonclinical data from a NHP tetanus toxoid (TT) model showed that a
minimal reduction of anti-TT IgG/IgM titers was observed at a dose of DZP 5mg/kg with a 
plasma concentration range of 15 to 31μg/mL. Based on these data, a target DZP Ctrough of 
10μg/mL for minimum pharmacological effect in nonclinical models has been defined and 
corresponds to a dose level of 6mg/kg every 4 weeks in SL0023. 
A summary of the target Ctrough values and corresponding proposed doses in SL0023 is provided 
in Table 5‒3.
Table 5‒3:
Summary of qualitative evidence leading the selected target DZP 
Ctrough and corresponding dose levels for SL0023
Evidence
Target DZP Ctrough
(μg/mL)
SL0023 Dose Level 
(mg/kg every 4 weeks)
DZP plasma concentration for minimum
pharmacological effect in preclinical models
10
6
Hu5c8 plasma concentration to produce minimum 
observed change from baseline in anti-dsDNA
antibodies
40
24
Ctrough in SL0014 that showed evidence of clinical 
efficacy
Hu5c8 plasma concentration to produce 25% 
reduction from baseline in anti-dsDNA antibodies
100
45
anti-dsDNA=anti-double-stranded deoxyribonucleic acid; Ctrough=trough concentration; DZP=dapirolizumab pegol
The expected Cmax, AUCτ (over the last dosing interval of 28 days), and Ctrough at the proposed 
dose levels in SL0023 are presented in Table 5‒4.
Table 5‒4:
Pharmacokinetic parameters expected at the dose levels proposed in 
SL0023 (median [5th-95th percentile])
DZP dose level 
(mg/kg) every 4 weeks
Cmax (μg/mL)
AUCτ (μg.day/mL)
Ctrough (μg/mL)
6
145 (93, 241)
1357 (974, 1384)
20 (10, 36)
24
582 (373, 966)
5429 (3895, 7937)
33 (17, 59)
45
1091 (698, 1811)
10179 (7305, 14882)
149 (75, 267)
AUCτ=area under the curve over the dosing interval; Cmax=maximum concentration; Ctrough=trough concentration; 
DZP=dapirolizumab pegol
At the highest DZP dose level proposed of 45mg/kg every 4 weeks, the expected DZP Cmax is 
1091μg/mL (698-1811μg/mL) and the expected AUCτ over the 28-day dosing interval is 
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10179μg.day/mL (7305-14882μg.day/mL) (median [5th-95th percentiles]). When comparing the 
mean AUCτ with the mean toxicokinetic data at the no-observed-adverse-effect level (NOAEL)
of 50mg/kg obtained in the 26-week toxicology study in Cynomolgus monkeys, there is an 
exposure margin of 4-fold for AUC and 2-fold for Cmax.
6
SELECTION AND WITHDRAWAL OF SUBJECTS
Subjects who initially fail to meet eligibility criteria or for whom eligibility assessments could 
not be completed as planned may be rescreened once on a case-by-case basis after discussion 
with the Medical Monitor (see Section 8.1).
6.1
Inclusion criteria
To be eligible to participate in this study, all of the following criteria must be met:
General
1a. An Institutional Review Board (IRB)/Independent Ethics Committee (IEC) approved written 
Informed Consent form is signed and dated by the subject prior to the initiation of any study-
specific assessment at Screening (Visit 1). 
2. Subject is considered reliable and capable of adhering to the protocol (eg, able to understand 
and complete diaries), visit schedule, and medication intake according to the judgment of the 
Investigator.
3. Subject (male or female) is ≥18 years of age at Screening (Visit 1).
4. Subject has a bodyweight of ≥50kg and ≤160kg.
5. Adequate reading and writing abilities (in native language) such that the subject can 
comprehend and answer the questions on the subject completed assessments.
Disease-specific
6. The subject has SLE diagnosed by a physician, confirmed by the SLICC Classification 
Criteria for SLE (see Appendix 19.1; Petri et al, 2012). 
7. The subject has at least 1 of the following:

Anti-dsDNA antibodies by Farr assay confirmed by the central laboratory at Screening 
(Visit 1)
OR

Low complement (ie, either low C3, or low C4, or both) confirmed by the central 
laboratory at Screening (Visit 1)
OR

ANA titer of ≥1:80 confirmed by the central laboratory at Screening (Visit 1) in 
combination with at least 1 of the following:
◦
Historical positivity for anti-dsDNA (as defined for the SLICC criteria, at least twice
in the past)
or
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◦
Positivity for anti-ENA (anti-SM, anti-SSA, anti-SSB, or anti-RNP) confirmed by the 
central laboratory at Screening (Visit 1)
8. The subject has moderate to severe SLE disease activity as demonstrated by BILAG 2004
Grade A level disease activity in at least 1 body/organ system at Screening (Visit 1) or 
BILAG 2004 Grade B level disease activity in at least 2 body/organ systems if no 
BILAG 2004 Grade A level disease is present.
9. The subject has moderate to severe SLE disease activity as demonstrated by a SLEDAI-2K
total score of ≥6 at Screening (Visit 1) and a SLEDAI-2K score without any laboratory 
values of ≥4 at Baseline (Visit 2).
10. The subject is receiving stable standard-of-care medication, defined as at least 1 of the
following, either alone or in combination: corticosteroids, and/or antimalarials, and/or 
immunosuppressants.

If the subject is receiving concomitant corticosteroids on a continuous regimen, the dose 
must be ≤40mg/day prednisone or equivalent dependent on the Investigator’s assessment 
of disease activity (refer to the list of prednisone equivalents in Appendix 19.2). Doses of 
corticosteroids must have been stable for at least 2 weeks prior to Screening (Visit 1), 
must remain stable until Baseline (Visit 2), and should remain stable until 4 weeks after 
the first study drug infusion (until Day 28). Subjects 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).
◦
Subjects who are receiving a corticosteroid dose at Screening (Visit 1) that is in 
between the specified starting doses of the corticosteroid tapering schedule 
(Table 5-1; eg, 12.5mg/day or 17.5mg/day prednisone or equivalent) should transition 
to the lowest nearest prespecified starting dose over the first 2 weeks of Screening 
and will enter the study on this dose; the dose will be considered stable in this case. 
This dose should then remain stable until 4 weeks after the first study drug infusion 
(until Day 28). 
◦
If iv steroids have been administered for treatment of acute disease flare, this must 
have occurred at least 6 weeks prior to the first study drug infusion (Visit 2). 

Treatment with antimalarials must have been started or stopped at least 12 weeks prior to 
dosing with study drug. If the subject is receiving concomitant antimalarials at Screening, 
doses must remain stable for at least 4weeks prior to the first study drug infusion 
(Visit 2). The maximum doses for allowed antimalarials are specified in Table 6-1.
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Table 6-1:
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

Treatment with immunosuppressants must have been started or stopped at least 12 weeks 
prior to dosing with study drug. If the subject is receiving concomitant 
immunosuppressants at Screening, doses must remain stable for at least 8 weeks prior to 
the first study drug infusion (Visit 2). The maximum doses for allowed 
immunosuppressants are specified in Table 6-2.
Table 6-2:
Maximum doses of permitted concomitant immunosuppressants
Immunosuppressant (generic name)
Maximum dose allowed
Azathioprine
300mg/day oral
Mycophenolate mofetil
3000mg/day oral
Leflunomide
40mg/day oral
Methotrexate
25mg/week any route
11. Subjects receiving memantine, bromocriptine (parlodel), danazol, dapsone,
dehydroepiandrosterone, or retinoids must be on a stable dose for at least 4 weeks prior to the 
first study drug infusion (Visit 2) and the doses should remain stable throughout the 
Treatment Period.
12. Female subjects of childbearing potential must have a negative serum pregnancy test at the
Screening Visit, which is confirmed to be negative by urine testing prior to the first dose of 
study drug at Week 1 (Visit 2) and prior to further dosing at each study visit thereafter. 
13a.Female subjects of childbearing potential must agree to use a highly effective method of 
birth control during the study and for a period of 12 weeks after their final dose of study drug
(ie, through completion of the SFU Period). Highly effective forms of birth control are 
methods which achieve a failure rate of less than 1% per year when used consistently and 
correctly. Highly effective methods of birth control include, but are not limited to:

Combined (estrogen- and progesterone-containing) hormonal contraception (oral, 
implant, or injectable) associated with inhibition of ovulation (which must be stable for at 
least 1 full month prior to Screening [Visit 1], and should remain stable during the study)

Progesterone-only hormonal contraceptives (oral, implant, or injectable) associated with 
inhibition of ovulation (which must be stable for at least 1 full month prior to Screening 
[Visit 1], and should remain stable during the study)

Progesterone-releasing intrauterine systems or the TCu380A intrauterine device
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
Vasectomized partner (provided sole partner and partner has medical proof of surgical 
success)

True heterosexual sexual abstinence is an acceptable form of contraception when this is 
in line with the preferred and usual lifestyle of the person. Periodic abstinence 
(eg, calendar, ovulation, symptothermal, postovulation methods), declaration of 
abstinence for the duration of the study, and withdrawal are not acceptable methods of 
contraception.
Women not agreeing to use birth control must be of nonchildbearing potential, defined as 
being:

Postmenopausal (for at least 2 years before the Screening Visit), verified by serum 
follicle-stimulating hormone level >40mIU/mL at the Screening Visit, or

Permanently sterilized (eg, bilateral tubal occlusion, hysterectomy, bilateral 
salpingectomy), or

Congenitally sterile
14. Contraception methods for male subjects and their female partners:

Male subjects with a partner of childbearing potential must be willing to use a condom 
when sexually active during the study and for 12 weeks after the final administration of 
study drug (ie, through completion of the SFU Period; approximately 5 half-lives).

In addition, the female partner of childbearing potential of a male subject must be willing 
to use a highly effective method of contraception (per Inclusion Criterion #13) during the 
study period and for 12 weeks after the final administration of study drug.
6.2
Exclusion criteria
Subjects are not permitted to enroll in the study if any of the following criteria is met:
General
1. Subject has previously been randomized in this study or has previously participated in a DZP 
clinical study.
2. Subject has any medical or psychiatric condition that, in the opinion of the Investigator, 
could jeopardize or would compromise the subject’s ability to participate in this study.
3. Female subjects who are breastfeeding, pregnant, or plan to become pregnant during the 
study or within 3 months following their final dose of study drug.
4. Subject has a history of malignancy, except the following treated cancers: cervical carcinoma 
in situ, basal cell carcinoma, or dermatological squamous cell carcinoma.
5a. Subject has a mixed connective tissue disease, scleroderma, and/or overlap syndromes of 
SLE.

Subjects with SLE and secondary Sjögren’s syndrome are permitted provided they meet 
the eligibility criteria.
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
Clarification: Subjects with rheumatoid arthritis in their medical history are not 
considered as having an overlap syndrome and are thereby eligible, except when erosive 
arthritis is the only symptom at Screening.
Disease specific
6. Subjects with severe neuropsychiatric SLE or other neurological symptoms that in the 
opinion of the Investigator, would prevent the subject from completing protocol required 
procedures and assessments.
7. Subject has active lupus that, in the opinion of the Investigator, requires an increase in 
standard-of-care therapy outside of that permitted in Table 6-1 and Table 6-2.
8. Subject has new or worsening Class III or IV lupus nephritis.
9. Subject has chronic kidney failure stage 3b, manifested by estimated glomerular filtration 
rate (eGFR) <45mL/min/1.73m2, or serum creatinine >2.5mg/dL, or proteinuria >2g/day, or 
protein:creatinine ratio >226mg/mmol.
10. Subjects requiring plasma exchange or immunoabsorption in the 4 months prior to Visit 2 or 
during the study.
Infection-related risks
11. Subject has evidence of human immunodeficiency virus (HIV) infection, 
agammaglobulinemias, T-cell deficiencies, or human T-cell lymphotropic virus-1 infection at 
any time prior to or during the study.
12. Subject has clinically significant active or latent infection, for example, but not limited to,
chronic viral hepatitis B or C.
13. Subject has a history of a serious infection within the last 60 days prior to the first study drug 
infusion (Visit 2) that required iv/intramuscular (im) antibiotics or required 
hospitalization/prolonged hospitalization. Subjects must have completed any prior 
anti-infective therapy for serious infections prior to the first study drug infusion.
14. Subject had an opportunistic infection (for example, but not limited to, pneumocystis, 
cytomegalovirus, herpes simplex virus, or herpes zoster) within 12 weeks prior to the first 
study drug infusion (Visit 2), or is currently receiving suppressive therapy for an 
opportunistic infection.
15. Subject has a clinically relevant recurrent (more than 3 times a year) infection.
16. Subjects with known tuberculosis (TB) infection, at high risk of acquiring TB infection, or 
latent TB (LTB) infection are excluded.
a.
Known TB infection whether present or past is defined as:

Active TB infection or clinical signs and symptoms suggestive of TB (pulmonary or 
extrapulmonary).

History of active TB infection involving any organ system or findings in other organ 
systems consistent with TB infection.
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
Any evidence by radiography or other imaging modalities consistent with previously 
active TB infection that is not reported in the subject's medical history.
b. High risk of acquiring TB infection is defined as:

Known exposure to another person with active TB infection within the 3 months prior 
to Screening (Visit 1).

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.
LTB infection (refer to Section 13.6 for further details and instructions).
17. Subjects who have received live/live attenuated vaccines within 6 weeks prior to the first 
study drug infusion (Visit 2) or who plan to receive these vaccines during the study or 
12 weeks after the final dose of study drug 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 drug.
Other safety risks
18. Subjects with a history of thromboembolic events within 12 months 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: Subjects 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 12 months prior to Screening (Visit 1).
*Obstetric morbidity is defined as 1 or more unexplained deaths of a morphologically normal fetus at or 
beyond the 10th week of gestation with the latest incidence within 12 months 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 
12 months prior Screening (Visit 1).
19. Subjects with a history of catastrophic APS or saddle pulmonary embolism.
20. Subject has blood laboratory values as follows: significant hematologic abnormalities of 
hemoglobin <7.0g/dL, or lymphocytes <500/mm3, or absolute neutrophil count <500/mm3, or 
platelets <25,000/mm3 at Screening (Visit 1). Subjects with a higher platelet count should 
also be excluded if they have a clinical risk of bleeding for reasons other than SLE.  
Note: Subjects 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 subject may be randomized at the Baseline Visit, provided they meet all other 
eligibility criteria.
21. Subject has a vascular graft, valvular heart disease, or atrial fibrillation.
22. Subject has a known hypersensitivity to any components of the investigational medicinal 
product (IMP), including PEG.
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23. Subject has a history of an anaphylactic reaction to parenteral administration of contrast 
agents, human or murine proteins, or monoclonal antibodies.
24. Subject has 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.
25. Subject has ≥3x the upper limit of normal (ULN) alanine aminotransferase (ALT), aspartate 
aminotransferase (AST), or alkaline phosphatase (ALP), or >ULN bilirubin (≥1.5xULN 
bilirubin if known Gilbert’s syndrome). If subject only has >1.5xULN bilirubin, fractionate 
bilirubin to identify possible undiagnosed Gilbert’s syndrome (ie, direct bilirubin <35%), 
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.
For subjects with a baseline result >ULN, a baseline diagnosis and/or the cause of any 
clinically meaningful elevation must be understood and recorded in the eCRF.
If subject has >ULN that does not meet the exclusion limit for ALT, AST, or ALP at 
Screening, repeat, if possible, prior to dosing to ensure there is no further ongoing clinically 
relevant increase. In case of a clinically relevant increase, inclusion of the subject must be 
discussed with the Medical Monitor. 
An ALT and/or AST result up to 25% above the exclusion limit may be repeated once for
confirmation. This includes rescreening.
Prior and concomitant medications
26. Subject has used the prohibited medications listed in Table 7-1, 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). Subject has used investigational agents not included in Table 7-1,
including other investigational or recently approved biologics or device products, within 
3 months 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.

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.
27. Subject should 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, NSAIDs, 3-hydroxy-3-methyl-glutaryl-coenzyme A (HMG-CoA) reductase 
inhibitors (statins), angiotensin converting enzyme (ACE) inhibitors, and other 
anti-hypertensive drugs.
6.3
Withdrawal criteria
Subjects are free to withdraw from the study at any time, without prejudice to their continued 
care.
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Subjects must be withdrawn from the study if any of the following occurs at any time during the 
study:

Subject withdraws his/her consent.

The Sponsor or a regulatory agency requests withdrawal of the subject.
Subjects must be discontinued from study drug (but not from the study) if any of the following 
occurs during Part 1 of the study (ie, through Visit 10 [Week 24] of the Double-Blind Treatment 
Period):

There is confirmation of an ongoing pregnancy during the study, as evidenced by a positive 
pregnancy test.

Subject experiences a thromboembolic event.

Subject has a TB test that is confirmed positive or any further evidence suggestive of 
potential TB infection (eg, exposure) and further examinations result in a diagnosis of active 
TB or LTB. Refer to Section 13.6 (Assessment and management of TB and TB risk factors) 
for further details and instructions.

Subject receives a live/live attenuated vaccine.

Subject requires an induction therapy with cyclophosphamide for management of acute flare 
of lupus nephritis or other severe manifestation of SLE, in the opinion of the Investigator.
Subjects may be withdrawn from the study, at the Investigator’s discretion, if any of the
following occurs:

Subject develops a clinically meaningful illness that would interfere with his/her continued 
participation, and/or render safety and efficacy data to be unreliable in the opinion of the 
Investigator.

Subject is noncompliant with the study procedures or medications, in the opinion of the 
Investigator, in a manner that impacts the subject’s safety.
Investigators should contact the Medical Monitor, whenever possible, to discuss the 
withdrawal of a subject in advance.
Investigators should attempt to obtain information on subjects in the case of withdrawal. For 
subjects considered as lost to follow up, the Investigator should make an effort (at least 1 phone 
call and 1 written message to the subject), 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 subject, must be recorded in the source documents. The 
electronic Case Report Form (eCRF) must document the primary reason for withdrawal or 
discontinuation.
6.3.1
Potential drug-induced liver injury IMP discontinuation criteria
Subjects with potential drug-induced liver injury (PDILI) must be assessed to determine if IMP 
must be discontinued. In addition, all concomitant medications and herbal supplements that are 
not medically necessary should also be discontinued. 
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The following PDILI criteria require immediate and permanent discontinuation of IMP:

Subjects with any of the following:

ALT or aspartate aminotransferase (AST) ≥8xULN

ALT or AST ≥3xULN and co-existing total bilirubin ≥2xULN
The following PDILI criterion requires immediate discontinuation of IMP: 

Subjects with ALT and/or AST ≥3xULN who exhibit temporally associated symptoms of
hepatitis (excluding SLE-related hepatitis) or hypersensitivity. Hepatitis symptoms include
fatigue, nausea, vomiting, right upper quadrant pain or tenderness. Hypersensitivity 
symptoms include fever (without clear alternative cause), rash, or eosinophilia (ie, >5%).
If a non-drug related cause for the symptoms can be confirmed, these subjects may resume IMP 
administration after discussion with the responsible UCB physician, but only when the 
requirements for rechallenge with IMP as provided in Section 13.7.2.1 are followed.
The following PDILI criteria allows for subjects to continue on IMP at the discretion of the 
Investigator:

ALT or AST ≥3xULN (and ≥2x baseline) and <8xULN, total bilirubin <2xULN, and no 
eosinophilia (ie, ≤5%), with no fever, rash or symptoms of hepatitis (eg, fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness)
Evaluation of PDILI must be initiated as described in Section 13.7. If subjects are unable to 
comply with the applicable monitoring schedule, IMP must be discontinued immediately (see 
Section 8.10). 
Investigators should attempt to obtain information on subjects in the case of IMP discontinuation 
to complete the final evaluation. Subjects with PDILI should not be withdrawn from the study 
until investigation and monitoring are complete. All results of these evaluations and 
observations, together with a narrative description of the reason(s) for IMP discontinuation and 
subject withdrawal (if applicable), must be recorded in the source documents. The eCRF must 
document the primary reason for IMP discontinuation.
7
STUDY TREATMENTS
7.1
Description of IMPs
The DZP IMP will be supplied by UCB Clinical Trial Supply Operations (CTSO) or designee, as 
follows:

DZP 20mL vial lyophilized drug product. Each DZP vial will be labeled.
The PBO IMP will not be supplied by UCB CTSO. The sites will use commercial 0.9% sodium 
chloride aqueous solution (physiological saline, preservative free) of pharmacopoeia 
(US Pharmacopeia/European Pharmacopoeia) quality.
7.2
Treatments to be administered
During the 24-week Double-Blind Treatment Period (Part 1), eligible subjects will be randomly 
allocated in a 1:1:1:1 ratio to receive an iv infusion of DZP (6mg/kg, 24mg/kg, or 45mg/kg) or 
PBO every 4 weeks, for a total of 6 doses (on Day 1 and at Weeks 4, 8, 12, 16, and 20). The 
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subject’s body weight at Baseline (Visit 2) will be used to calculate the individual dose 
throughout the study.
Following completion of the 24-week Double-Blind Treatment Period (Part 1), subjects will 
enter a 24-week Observational Period, during which subjects will not receive study drug but will 
be able to receive standard-of-care treatment, as indicated. The subjects, Investigators, and study 
site staff will remain blinded to the treatment administered during Part 1 of the study until the 
end of the study.
Refer to Table 5‒2 for details regarding the visits at which IMP should be administered.
7.2.1
Treatment preparation and administration
7.2.1.1
Preparation
Only DZP lyophilized drug product will be supplied by UCB CTSO. The lyophilized drug 
product provided in a 20mL vial will be reconstituted by adding 10mL water for injection and 
then diluted with saline to prepare for administration. Complete preparation instructions will be 
outlined in the Pharmacy Manual.
For PBO, commercial 0.9% sodium chloride aqueous solution will be used. Thus, in order to 
maintain blinding, an unblinded pharmacist or other suitably qualified site personnel will prepare 
each dose of IMP and provide it to the blinded site personnel for administration.
All the preparation steps, including the reconstitution of DZP and preparation for infusion, PBO 
material requirements, and dispensing material requirements will be described in full detail in the 
Pharmacy Manual.
7.2.1.2
Administration
The IMP will be administered as an iv infusion through a cannula placed in an easily accessible 
vein of the arm (eg, cephalic vein or median cubital vein); an iv infusion pump will be used for 
IMP administration.
For all subjects, the infusion volume will be 150mL and the infusion time will be approximately 
120min. These timings are provided to allow a slow rise in plasma concentration and for the 
possibility of interrupting the infusion in case of an acute AE. Further instructions on 
administration will be provided in the Pharmacy Manual.
The infusion rate may be reduced at any time at the discretion of the Investigator. If an infusion 
is interrupted, it can be restarted if the Investigator considers it appropriate to do so. In such 
instances, the total infusion time may exceed 120min in order to administer the entire planned 
dose. The chronology of these events should be recorded accurately in the source data and eCRF.
After the infusion is completed, the subject will remain in the clinic for observation and 
assessments for at least 2 hours, or longer at the discretion of the Investigator.
Data from clinical studies SL0013 and SL0014 are limited, and because DZP is an iv
administered protein, an increased risk for infusion-related reactions, including anaphylaxis,
cannot be excluded at this time. A mandatory premedication for prophylaxis of infusion-related
reactions is not planned in this study; however, premedication (with acetaminophen or
antihistamines) is permitted at the discretion of the Investigator considering the individual risk 
profile of the subject (for example, but not limited to, medical history, comorbidities, and 
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concomitant medication) and current knowledge on the risk of DZP to induce anaphylactic 
reactions. Corticosteroids should be avoided as an antiallergic premedication given the protocol 
requirements for stable corticosteroid use and planned tapering (refer to Section 5.1 and 
Section 7.8.1).
7.3
Packaging
Dapirolizumab pegol lyophilized drug product is supplied in 20mL vials. Each vial and each box 
will be labeled and will be for individual use.
The site carton will be suitably packaged in such a way as to protect the product from 
deterioration during transport and storage. Further information regarding storage and transport 
conditions will be provided in the Pharmacy Manual.
The diluent and materials such as syringes and needles, perfusor syringes, and administration 
sets required for reconstitution, dilution, and final administration will be provided in the original 
packaging to the sites by the contract research organization (CRO) or will be sourced by the sites 
based on the material specifications noted in the Pharmacy Manual and provided by UCB. 
7.4
Labeling
Clinical drug supplies will be labeled in accordance with the current International Council for
Harmonisation (ICH) guidelines on Good Clinical Practice (GCP) and Good Manufacturing 
Practice and will include any locally required statements. If necessary, labels will be translated 
into the local language and adapted to the size of the IMP package.
7.5
Handling and storage requirements
The Investigator (or designee) is responsible for the safe and proper storage of IMP at the site. 
Investigational medicinal product stored by the Investigator is to be kept in a secured area with 
limited access according to the storage conditions mentioned in the IMP Handling Manual.
Appropriate storage condition must be ensured by controlled refrigerator temperature either 
using an automated temperature monitoring and recording system or by using a 
minimum/maximum thermometer and completing daily a temperature log in accordance with 
local requirements. Temperature data for IMP should be recorded on each working day with the 
actual and minimum/maximum temperatures reached during this period.
In case an out-of-range temperature is noted, it must be immediately reported as per instructions 
contained in the IMP Handling Manual.
The physiological saline [0/9% sodium chloride] used for administration should be handled per 
specific site requirements and stored according to label requirements.  
7.6
Drug accountability
A Drug Accountability form will be used to record IMP dispensing and return information on a 
by-subject basis and will serve as source documentation during the course of the study. Details of 
any IMP 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 only to
the designated unblinded monitor (or designee) for review. In addition, the site will document all 
materials used for each subject dosing, including water for injection used for reconstitution, 
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saline for PBO, and infusion and other materials. The site will keep a log with the names of those 
individuals with access to IMP, including the names of those who are involved in preparation of 
doses for IMP administration.
The Investigator (or designee) is responsible for retaining all used, unused, and partially used 
containers of IMP until returned or destroyed.
The Investigator must assign duties for drug accountability at the study site to an appropriate 
unblinded pharmacist (or designee).
The Investigator must ensure that the IMP 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 IMP must be reconciled and either 
destroyed at the site according to local laws, regulations, and UCB SOPs 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.
7.7
Procedures for monitoring subject 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 
monitor will compare the dispensing record and vials to the individual subject’s identifiers and 
visit schedule to assure that the subject 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. 
Subjects are expected to receive all doses of IMP as detailed in the schedule of assessments. Any 
subject who deviates from the dosing schedule or misses any scheduled treatment should be 
reported to the Medical Monitor in a blinded fashion for determination of possible schedule 
adjustments and continued eligibility. These instances will be handled on a case-by-case basis.
7.8
Concomitant medications/treatments
7.8.1
Permitted concomitant treatments (medications and therapies) for 
SLE
The following concomitant medications are permitted for the treatment of SLE and SLE 
associated signs and symptoms under certain conditions:

Corticosteroids (≤40mg/day prednisone or equivalent; see Inclusion Criterion #10)

Antimalarials (eg, hydroxychloroquine, chloroquine, and quinacrine) (see Inclusion 
Criterion #10 and maximum dose restrictions in Table 6-1)

Other immunosuppressant or immunomodulatory agents including (see Inclusion 
Criterion #10 and maximum dose restrictions in Table 6-2)

Methotrexate

Azathioprine
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
Mycophenolate (including mycophenolate mofetil, mycophenolate mofetil hydrochloride, 
and mycophenolate sodium)

Leflunomide

Analgesics, NSAIDs, HMG-CoA reductase inhibitors (statins), ACE inhibitors, and other 
anti-hypertensive drugs
In subjects receiving concomitant corticosteroids, doses must have been stable for at least 
2 weeks prior to Screening, must remain stable until Baseline (Visit 2), and should remain stable 
until 4 weeks after the first study drug infusion (until Day 28). Subjects 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 subjects receiving concomitant corticosteroid doses between 10mg/day and 40mg/day 
prednisone or equivalent, a mandatory corticosteroid taper must be initiated no later than 
4 weeks after the first study drug infusion (on Day 29) The tapering regimen, as recommended in 
Section 5.1 and Table 5-1, will aim to reduce the daily prednisone equivalent dose to 7.5mg/day 
or lower by Week 12 (Day 84) of the study. If such a rapid tapering is not considered by the 
Investigator to be appropriate for the individual subject, a slower tapering regimen can be used. 
Subjects achieving a dose of 7.5mg/day or lower may remain on this dose or continue to taper at 
the discretion of the Investigator. Subjects who 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 dose as determined by the 
Investigator (see Section 7.8.4). Subjects will be considered nonresponders for the primary 
endpoint if the corticosteroid dose exceeds the prednisone equivalent dose at Baseline. Subjects 
will be issued a daily diary in which to record corticosteroid doses taken on a daily basis at home 
in between visits (Section 7.8.5). Use of oral or parenteral steroids for non-SLE related 
conditions should be discussed in advance with the Sponsor on an individual basis. 
Treatment with antimalarials or immunosuppressants must have been started or stopped at least 
12 weeks prior to dosing with study drug. In subjects receiving concomitant antimalarials used 
for the treatment of SLE, doses must have been stable for at least 4 weeks prior to the first study 
drug infusion (Visit 2). In subjects receiving concomitant immunosuppressants for the treatment 
of SLE, doses must have been stable for at least 8 weeks prior to the first study drug infusion
(Visit 2). Increases in doses of antimalarials and immunosuppressant or immunomodulatory 
agents above Baseline are not permitted until Visit 10 (Week 24) of the study, unless absolutely 
clinically indicated (dose reductions are allowed, if medically indicated [eg, due to toxicity], per 
the Investigator’s discretion; refer to Section 7.8.4 for further details).
Subjects should stay on stable doses of the following other concomitant medications for the 
treatment of SLE during Part 1 (Double-Blind Treatment Period) of the study, unless changes in 
these treatments are clinically indicated: analgesics, NSAIDs, HMG-CoA reductase inhibitors 
(statins), ACE inhibitors, and other anti-hypertensive drugs.
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7.8.2
Permitted concomitant treatments (medications and therapies) other 
than those for SLE
Concomitant medications for comorbidities are permitted as long as they comply with the 
restrictions imposed in the inclusion criteria (Section 6.1), exclusion criteria (Section 6.2), and 
are not explicitly prohibited (Section 7.8.3). Both ACE inhibitors and angiotensin receptor 
blockers are permitted.
Subjects will record their concomitant corticosteroid doses in the subject diary (Section 7.8.5).
7.8.3
Prohibited concomitant treatments (medications and therapies)
Table 7-1 provides a list of concomitant medications prohibited during the study until Visit 12 
(Week 32) or until 10 weeks after permanent study drug discontinuation. Also included in this 
table are the wash-out periods (and, if applicable, additional requirements) as apply to inclusion 
(Section 6.1) and exclusion (Section 6.2) criteria. 
Table 7-1:
Prohibited medications and required wash-out periods prior to 
Screening (Visit 1)
Generic 
(trade) names
Wash-out period 
prior to Screening
Generic 
(trade) names
Wash-out period 
prior to Screening
Biologics (Mabs and Fusion Proteins)
Immunosuppressants
Abatacept (CTLA4-Ig) 
(Orencia®)
6 months
Cyclophosphamide 
(Cytoxan®)
6 months
Belimumab (Benlysta™)
6 months
Cyclosporine 
(Sandimmune®, Neoral®, 
Gengraf®) (except 
cyclosporine eye drops)
4 weeks
Blisibimod
8 weeks
Pimecrolimus (Elidel®)
4 weeks
Eculizumab (Soliris®)
3 months
Sirolimus (Rapamune®)
4 weeks
ETI – 201 (Elusys 
Heteropolymer Product)
3 months
Tacrolimus (FK506) 
(Prograf®)
4 weeks 
(oral and topical)
Rituximab (Rituxan®), 
Ofatumumab (Arzerra®), 
Obinutuzimab (Gazyva®), 
Ocrelizumab, 
Veltuzumab
12 months
Others
Intravenous 
immunoglobulin
4 weeks
IPP-201101 (Lupuzor™)
3 months
Natalizumab (Tysabri®)
12 weeks
Anifrolumab (MEDI 546)
Sifalimumab (MEDI 545)
3 months
Vedolizumab (Entyvio®)
24 weeks
Tabalumab
12 weeks
Minocycline
4 weeks
TACI-Ig (atacicept)
3 months
Thalidomide or 
lenalidomide (Thalomid®, 
Revlimid®)
2 months
Tocilizumab (Actemra®, 
MRA)
3 months
Note: Topical formulations (eg, eye drops) are permitted without wash-out, unless otherwise indicated.
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7.8.4
Rescue medication for SLE disease flares
Rescue treatment of SLE disease flares with corticosteroids (oral or iv) or with changes to dosing 
of the immunosuppressant medications listed in Section 7.8.1 are allowed at the discretion of the 
Investigator, if clinically indicated. Investigators should carefully evaluate their treatment 
decision, as an increase above the baseline dose between Visit 2 (Baseline) and Visit 10 
(Week 24) will define a subject as a nonresponder with respect to the primary endpoint.
Subjects who receive rescue therapy should continue in the study (at the Investigator’s 
discretion), unless they require one of the prohibited medications listed in Table 7-1 prior to
Visit 12 (Week 32).
7.8.5
Subject diary
Subjects will be issued daily diaries at each visit to record concomitant corticosteroid doses taken 
on a daily basis at home in between visits. Subjects will be instructed to bring the diary to the 
clinic at each visit. Site personnel will collect and review the diary at each visit to ensure that 
subjects are adhering to their prescribed corticosteroid tapering regimen (where applicable), and 
will issue a new diary for the subject to use until their next visit.
7.9
Blinding
7.9.1
Procedures for maintaining and breaking the treatment blind
7.9.1.1
Maintenance of study treatment blind
All subject treatment details will be allocated and maintained by the IVRS/IWRS.
The following individuals will receive the randomization code at the start of the study:

Sponsor and designated CRO bioanalytical staff analyzing PK samples.

Sponsor clinical trial supply staff

IVRS/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 subjects via the IVRS/IWRS. The unblinded pharmacy monitors from 
the CRO, the Clinical Supply Manager, and the unblinded 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 Patient Safety (PS) staff as needed for reporting SAEs to regulatory authorities.

On request, members of the DMC who participate in unblinded (closed) sessions will be 
given information about the IMP allocation for those subjects 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 DMC review.

A Quantitative Clinical Pharmacologist/Modeling & Simulation Scientist may have access to 
the randomization code if PK data are requested for review by the DMC.
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The following individuals may receive access to the randomization code and the first initial 
biomarker analysis:

Quantitative Clinical Pharmacologist/Modeling & Simulation Scientist
If necessary, the results of the initial biomarker analysis during the Double-Blind Treatment 
Period (Part 1) may be shared with key UCB and Biogen personnel in order to facilitate 
additional Clinical Planning or Portfolio Management decisions. Only unblinded summary 
results will be provided, and individual subject data will be kept blinded. Those individuals who 
are not involved in the study conduct, but seeing unblinded summary data, will be documented in 
the Trial Master File. The DMC will also have access to any initial biomarker analysis data, if 
needed.
With the exception of emergency unblinding on a case-by-case basis as described in 
Section 7.9.1.2, the following individuals will remain blinded to the treatment assignment in 
Part 1 until the end of the study:

Investigators

Study site staff

Subjects

CRO staff, with the exception of the unblinded pharmacy monitors and any CRO staff 
supporting preparation of the analyses

Personnel working on the study at the BILAG 2004 central independent efficacy reader
Under normal circumstances, the blinded treatment must not be revealed. It will be possible to 
break the blind, if medically indicated (Section 7.9.1.2). This should be discussed in advance 
with the Medical Monitor or the Sponsor’s Study Physician whenever possible.
7.9.1.2
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 drug determines decisions on further diagnostic 
procedures or treatment), it will be possible to determine to which treatment arm and dose the 
subject has been allocated during the Double-Blind Treatment Period by contacting the 
IVRS/IWRS. All sites will be provided with details of how to contact the system for code 
breaking at the start of the study. The Medical Monitor or the Sponsor’s Study Physician should 
be consulted prior to unblinding, whenever possible.
The CPM will be informed immediately via the IVRS/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.
7.10
Randomization and numbering of subjects
An IVRS/IWRS will be used for assigning eligible subjects to a treatment regimen based on 
predetermined randomization schedules generated by the CRO. The IVRS/IWRS is responsible 
for issuing treatment kit numbers, as appropriate, according to the visit schedule.
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To enroll a subject (Visit 1), the Investigator or designee will contact the IVRS/IWRS and 
provide brief details about the subject to be enrolled. Each subject will receive a unique 5-digit 
subject number assigned at Screening that serves as the subject identifier throughout the study. 
The subject number will be required in all communication between the Investigator or designee 
and the IVRS/IWRS regarding a particular subject. Enrolled subjects who withdraw from the 
study prior to randomization will retain their subject number without receiving a randomization 
number (ie, subject numbers will not be reassigned).
To randomize a subject (Visit 2), the Investigator or designee will contact the IVRS/IWRS and 
provide brief details about the subject to be randomized. The IVRS/IWRS will automatically 
inform the Investigator or designee of the subject’s unique 5-digit randomization number. The 
IVRS/IWRS will allocate treatment kit numbers to the subject based on the subject number 
during the course of the study. Randomization numbers and treatment kit numbers will be 
tracked via the IVRS and also will be required to be entered into the eCRF.
The study is planned to enroll at least 267 subjects in order to randomize approximately 
160 subjects (40 subjects per treatment group). During the 24-week Double-Blind Treatment 
Period (Part 1), subjects will be randomized in a 1:1:1:1 ratio to receive DZP (6mg/kg, 24mg/kg, 
or 45mg/kg) or PBO. The randomization will be stratified by Screening corticosteroid dose 
(≤10mg/day or >10mg/day prednisone equivalent).
During the Observational Period (Part 2), subjects will not receive study drug but will be able to 
receive standard-of-care treatment, as indicated. The subjects, Investigators, and study site staff 
will remain blinded to the treatment administered during Part 1 of the study until the end of the 
study.
8
STUDY PROCEDURES BY VISIT
Table 5‒2 provides a general overview of study assessments to be conducted at each visit. A 
detailed listing of procedures to be undertaken at each visit is presented in the sections that 
follow.
Visit windows of ±3 days on either side of the scheduled date are permitted for Visits 3 to 16
only; however, the Investigator should try to keep the subjects on the original dosing schedule. 
The window of ±3 days is relative to Baseline and applicable for all subsequent visits. Changes
to the dosing schedule outside of the 3-day window must be discussed with the Medical Monitor 
and may result in subject withdrawal. 
8.1
Visit 1 (Week -4 to -1/Day -28 to -1); Screening Visit
The Screening Period lasts a maximum of 28 days (Day -28 to -1). Prior to any study activities, 
subjects will be asked to read and sign an Informed Consent form that has been approved by an 
IEC/IRB and the Sponsor, and which complies with regulatory requirements. Subjects will be 
given adequate time to consider any information concerning the study given to them by the 
Investigator or designee. As part of the informed consent procedure, subjects will be given the 
opportunity to ask the Investigator any questions regarding potential risks and benefits of 
participation in the study. 
It is recommended that the Quanti FERON®-TB GOLD in-Tube test (QFT-GIT) be the first test 
performed at Screening to reduce the number of screening procedures conducted for any 
QFT-GIT positive subjects that may need to be withdrawn from the study. 
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Subjects who initially fail to meet eligibility criteria or for whom eligibility assessments could 
not be completed as planned may be rescreened once after discussion with the Medical Monitor. 
In addition, subjects with an isolated laboratory parameter outside of the normal range (or 
negative in the case of auto-antibody assessments) at the Screening Visit may have a repeat test. 
If the repeat laboratory parameter meets the entry criteria, the subject may be randomized at the 
Baseline Visit, provided they meet all other eligibility criteria.
Assessments at Visit 1 (Screening) include:

Obtain written informed consent(s)

Demographic data (includes date of birth, gender, and race/ethnicity)

Lifestyle (includes alcohol, tobacco, and drug use)

Medical and procedure history and concomitant disease, including SLE disease history

Prior and concomitant medications

TB assessments:

TB test (QFT-GIT)

TB Signs and Symptoms questionnaire

Chest x-ray (if one is not available within 3 months prior to Screening)

Verification of eligibility (inclusion/exclusion criteria)

C-SSRS

Physical examination

HIV and hepatitis screening

Vital signs: systolic and diastolic blood pressure, pulse rate, temperature, body weight, and 
height

12-lead ECG

Serum pregnancy test for women of childbearing potential

Safety laboratories: hematology, clinical chemistry, and urinalysis

Additional laboratories: 

ANAs, anti-ENAs (anti-SM, anti-SSA, anti-SSB, anti-RNP), and RF

anti-dsDNA antibodies

aPL antibodies

coagulation and hemostasis tests

serum complement (C3, C4)

hsCRP

proteomic signature profile
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
BILAG 2004

SLEDAI-2K assessing the past 10 days

SLICC/ACR Damage Index

TJC/SJC 

CLASI

AEs

Dispense subject daily diary

Dispense urine collection container (for first morning urine collection at home on the 
morning of their next visit)

Contact the IVRS/IWRS to indicate the subject has been enrolled
8.2
Visit 2 (Day 1); Randomization Visit
Visit 2 can occur at any time after the laboratory results from the Screening Visit are available, 
but no later than 28 days after the Screening Visit. Prior to Visit 2, the site must have received 
confirmation from the central independent efficacy reader for BILAG 2004 data that the subject 
has met BILAG 2004 eligibility for randomization. The site must confirm whether or not the 
subject is eligible to be randomized prior to contacting the IVRS/IWRS.
Subjects should undergo an overnight fast (at least 8 hours) prior to coming to the site for Visit 2. 
Subjects may then eat breakfast after serum samples have been obtained for the assessment of 
cardiovascular proteins, lipids, and lipid particles, and before study drug administration.
The PRO questionnaires should then be completed in a quiet place by the subjects themselves at 
the start of the study visit and prior to the remaining visit assessments.
All assessments should be performed prior to study drug dosing, unless otherwise indicated.
Assessments at Visit 2 (Randomization) include:

LupusQoL

PROs at sites in English- and Spanish-speaking countries only:

SLE-S

SLE-F

SLE-M

SLE-P

SLE-E

Verification of continued eligibility (inclusion/exclusion criteria; including verification that 
the SLEDAI-2K score without any laboratory values is ≥4 prior to Randomization; see 
below)

TB Signs and Symptoms questionnaire

Concomitant medications
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
Medical procedures

Collect/review subject daily diary

Collect PK urine sample obtained at home (first morning urine collection on the morning of 
the visit)

Physical examination/interim medical history

Urine pregnancy test for women of childbearing potential

Withdrawal criteria check

Vital signs:

systolic and diastolic blood pressure, pulse rate, and temperature: predose; every 15mins 
post start of infusion; every 30mins until 2h post end of infusion

body weight: predose
Note: Blood samples must not be drawn through the infusion cannula.

Safety laboratories: hematology, clinical chemistry, and urinalysis

Additional laboratories: 

anti-dsDNA antibodies

anti-DZP and anti-PEG antibodies

total Ig, IgG, IgM, IgA, and IgE

serum complement (C3, C4)

hsCRP

whole blood mRNA

cardiovascular proteins, lipids, and lipid particles (blood samples should be collected 
under fasting conditions [at least 8 hours])

DNA

PK plasma sampling (predose; end of infusion; and 30min, 1h, and 2h post end of infusion)

BILAG 2004

SLEDAI-2K assessing the past 10 days (including the SLEDAI-2K score without laboratory 
values assessment [defined as any SLEDAI-2K defined features excluding all laboratory 
parameters in the past 10 days prior to Baseline] of ≥4 prior to Randomization)

PGA

PtGA

TJC/SJC

CLASI

Contact the IVRS/IWRS for randomization or to note screen failure
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
Study drug preparation (predose), administration, and accountability (postdose)

AEs (pre and postdose)

Dispense subject daily diary (postdose)
8.3
Visit 3 (Week 2/Day 14 [±3 days])
Assessments at Visit 3 (Week 2) include:

Concomitant medications

Medical procedures

Collect/review subject daily diary

Urine pregnancy test for women of childbearing potential

Withdrawal criteria check

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature)

Safety laboratories: hematology, clinical chemistry, and urinalysis

Additional laboratories: 

total Ig, IgG, IgM, IgA, and IgE

serum complement (C3, C4)

hsCRP

whole blood mRNA

proteomic signature profile

PK plasma sample

Investigator assessment of flare

AEs

Dispense subject daily diary

Contact the IVRS/IWRS
8.4
Visit 4 (Week 4/Day 28 [±3 days]) and Visit 6 (Week 8/Day 56 
[±3 days])
The PRO questionnaires should be completed at the start of the study visit in a quiet place and by 
the subjects themselves.
All assessments should be performed prior to study drug dosing, unless otherwise indicated.
Assessments at Visit 4 (Week 4) and Visit 6 (Week 8) include:

LupusQoL

PROs at sites in English- and Spanish-speaking countries only:

SLE-S
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
SLE-F

SLE-M

SLE-P

SLE-E

Subject Experience Interview (Visit 4 only)

Concomitant medications

Medical procedures

Collect/review subject daily diary

Physical examination/interim medical history

Urine pregnancy test for women of childbearing potential

Withdrawal criteria check

Vital signs:

systolic and diastolic blood pressure, pulse rate, and temperature: predose; every 15mins 
post start of infusion; every 30mins until 2h post end of infusion

body weight: predose

12-lead ECG (Visit 4 only)
Note: Blood samples must not be drawn through the infusion cannula.

Safety laboratories: hematology, clinical chemistry, and urinalysis

Additional laboratories: 

anti-dsDNA antibodies

anti-DZP and anti-PEG antibodies

total Ig, IgG, IgM, IgA, and IgE

serum complement (C3, C4)

hsCRP

whole blood mRNA (Visit 4 only)

proteomic signature profile

PK plasma sampling:

Visit 4: predose; end of infusion; and 30min, 1h, and 2h post end of infusion

Visit 6: predose; end of infusion

BILAG 2004

SLEDAI-2K assessing the past 30 days

SRI-50
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
PGA

TJC/SJC

CLASI

Investigator assessment of flare

Contact IVRS/IWRS

Study drug preparation (predose), administration, and accountability (postdose)

AEs (pre and postdose)

Dispense subject daily diary (postdose)
8.5
Visit 5 (Week 6/Day 42 [±3 days])
Subjects should undergo an overnight fast (at least 8 hours) prior to coming to the clinic for 
Visit 5. Subjects may then eat breakfast after serum samples have been obtained for the 
assessment of cardiovascular proteins, lipids, and lipid particles, and prior to any other 
assessments.
Assessments at Visit 5 (Week 6) include:

Concomitant medications

Medical procedures

Collect/review subject daily diary

Urine pregnancy test for women of childbearing potential

Withdrawal criteria check

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature)

Additional laboratories: 

cardiovascular proteins, lipids, and lipid particles (blood samples should be collected 
under fasting conditions [at least 8 hours])

PK plasma sample

Investigator assessment of flare

AEs

Dispense subject daily diary

Contact the IVRS/IWRS
8.6
Visit 7 (Week 12/Day 84 [±3 days]), Visit 8 (Week 16/Day 112 
[±3 days]), and Visit 9 (Week 20/Day 140 [±3 days])
Subjects should undergo an overnight fast (at least 8 hours) prior to coming to the site for Visit 7
only. Subjects may then eat breakfast after serum samples have been obtained for the assessment 
of cardiovascular proteins, lipids, and lipid particles, and before study drug administration.
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The PRO questionnaires should then be completed in a quiet place by the subjects themselves at 
the start of the study visit and prior to the remaining visit assessments.
All assessments should be performed prior to study drug dosing, unless otherwise indicated.
Assessments at Visit 7 (Week 12), Visit 8 (Week 16), and Visit 9 (Week 20) include:

LupusQoL

PROs at sites in English- and Spanish-speaking countries only:

SLE-S

SLE-F

SLE-M

SLE-P

SLE-E

TB Signs and Symptoms questionnaire (Visit 7 only)

Concomitant medications

Medical procedures

Collect/review subject daily diary

Collect PK urine sample obtained at home (Visit 9 only; overnight void collection at home 
the night before the visit through the first morning void the morning of the visit)

Physical examination/interim medical history

Urine pregnancy test for women of childbearing potential

Withdrawal criteria check

Vital signs:

systolic and diastolic blood pressure, pulse rate, and temperature: predose; every 15mins 
post start of infusion; every 30mins until 2h post end of infusion

body weight: predose
Note: Blood samples must not be drawn through the infusion cannula.

Safety laboratories: hematology, clinical chemistry, and urinalysis

Additional laboratories: 

anti-dsDNA antibodies

anti-DZP and anti-PEG antibodies

coagulation and hemostasis tests (Visit 7 only)

total Ig, IgG, IgM, IgA, and IgE

serum complement (C3, C4)
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
hsCRP

whole blood mRNA (Visits 7 and 8 only)

proteomic signature profile (Visits 7 and 8 only)

cardiovascular proteins, lipids, and lipid particles (Visit 7 only; blood samples should be 
collected under fasting conditions [at least 8 hours])

PK plasma sampling:

Visits 7 and 8: predose; end of infusion

Visit 9: predose; end of infusion; and 30min, 1h, and 2h post end of infusion

BILAG 2004

SLEDAI-2K assessing the past 30 days

SRI-50

PGA

PtGA (Visit 7 only)

TJC/SJC

CLASI

Investigator assessment of flare

Contact IVRS/IWRS

Study drug preparation (predose), administration, and accountability (postdose)

AEs (pre and postdose)

Dispense subject daily diary (postdose)

Dispense urine collection container (postdose; Visits 8 and 9 only; for overnight void 
collection at home the night before their next visit through the first morning void the morning 
of the visit)
8.7
Visit 10 (Week 24/Day 168 [±3 days]); Double-Blind Treatment 
Period End of Treatment/Early Withdrawal Visit
Subjects who withdraw prior to Week 32 (Visit 12) will complete an Early Withdrawal 
Visit (EWV; Visit 10 assessments if withdrawn prior to Visit 10; Visit 16 assessments if 
withdrawn after Visit 10) as well as Visits 11 and 12 for SFU assessments at 8 and 12 weeks 
after their final dose of study drug (as applicable). Subjects who withdraw after Week 32 
(Visit 12) do not require additional SFU visits and will complete the Visit 16/EWV assessments 
only.
Subjects should undergo an overnight fast (at least 8 hours) prior to coming to the site for 
Visit 10. Subjects may then eat breakfast after serum samples have been obtained for the 
assessment of cardiovascular proteins, lipids, and lipid particles, and prior to any other 
assessments.
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The PRO questionnaires should then be completed in a quiet place by the subjects themselves at 
the start of the study visit and prior to the remaining visit assessments.
Assessments at Visit 10 (Week 24) include:

LupusQoL

PROs at sites in English- and Spanish-speaking countries only:

SLE-S

SLE-F

SLE-M

SLE-P

SLE-E

Subject Experience Interview

TB Signs and Symptoms questionnaire 

Concomitant medications 

Medical procedures 

Collect/review subject daily diary 

Collect PK urine sample obtained at home (overnight void collection at home the night 
before the visit through the first morning void the morning of the visit)

C-SSRS

Physical examination/interim medical history

Urine pregnancy test for women of childbearing potential

Withdrawal criteria check

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature)

12-lead ECG

Safety laboratories: hematology, clinical chemistry, and urinalysis

Additional laboratories: 

ANAs, anti-ENAs (anti-SM, anti-SSA, anti-SSB, anti-RNP), and RF

anti-dsDNA antibodies

anti-DZP and anti-PEG antibodies

aPL antibodies

coagulation and hemostasis tests

total Ig, IgG, IgM, IgA, and IgE

serum complement (C3, C4)
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
hsCRP

whole blood mRNA

proteomic signature profile

cardiovascular proteins, lipids, and lipid particles (blood samples should be collected 
under fasting conditions [at least 8 hours])

DNA

PK plasma sampling

BILAG 2004

SLEDAI-2K assessing the past 30 days

SRI-50

PGA

PtGA

SLICC/ACR Damage Index

TJC/SJC

CLASI

Investigator assessment of flare

Contact IVRS/IWRS

AEs

Dispense subject daily diary

Dispense urine collection container (for first morning urine collection at home on the 
morning of their next visit)
8.8
Visit 11/SFU (Week 28/Day 196 [±3 days]), Visit 13 
(Week 36/Day 252 [±3 days]), and Visit 15 (Week 44/Day 308 
[±3 days])
Subjects who withdraw prior to Week 32 (Visit 12) will complete an EWV (Visit 10 assessments 
if withdrawn prior to Visit 10; Visit 16 assessments if withdrawn after Visit 10) as well as 
Visits 11 and 12 for SFU assessments at 8 and 12 weeks after their final dose of study drug (as 
applicable). Subjects who withdraw after Week 32 (Visit 12) do not require additional SFU visits 
and will complete the Visit 16/EWV assessments only.
Assessments at Visit 11 (Week 28), Visit 13 (Week 36), and Visit 15 (Week 44) include:

Concomitant medications

Medical procedures 

Collect/review subject daily diary 
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
Collect PK urine sample obtained at home (first morning urine collection at home on the 
morning of visit; Visits 11 and 13 only)

Urine pregnancy test for women of childbearing potential 

Withdrawal criteria check (only performed in subjects who are continuing in the study)

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature)

Safety laboratories (Visit 11 only): hematology, clinical chemistry, and urinalysis

Additional laboratories: 

anti-DZP and anti-PEG antibodies (Visit 11 only)

hsCRP (Visit 11 only)

PK plasma sampling (Visits 11 and 13 only)

Investigator assessment of flare

AEs

Dispense subject daily diary

Dispense urine collection container (for first morning urine collection at home on the 
morning of their next visit)
8.9
Visit 12/SFU (Week 32/Day 224 [±3 days]) and Visit 14 
(Week 40/Day 280 [±3 days])
Subjects who withdraw prior to Week 32 (Visit 12) will complete an EWV (Visit 10 assessments 
if withdrawn prior to Visit 10; Visit 16 assessments if withdrawn after Visit 10) as well as 
Visits 11 and 12 for SFU assessments at 8 and 12 weeks after their final dose of study drug (as 
applicable). Subjects who withdraw after Week 32 (Visit 12) do not require additional SFU visits 
and will complete the Visit 16/EWV assessments only.
The PRO questionnaires should be completed at the start of the study visit in a quiet place and by 
the subjects themselves.
Assessments at Visit 12 (Week 32) and Visit 14 (Week 40) include:

LupusQoL

PROs at sites in English- and Spanish-speaking countries only:

SLE-S

SLE-F

SLE-M

SLE-P

SLE-E

Concomitant medications 

Medical procedures 
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
Collect/review subject daily diary 

Collect PK urine sample obtained at home (first morning urine collection at home on the 
morning of visit)

C-SSRS (Visit 12; only performed in subjects who have withdrawn from the study and are 
undergoing SFU assessments)

Physical examination/interim medical history

Urine pregnancy test for women of childbearing potential 

Withdrawal criteria check (only performed in subjects who are continuing in the study)

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature)

Safety laboratories: hematology, clinical chemistry, and urinalysis

Additional laboratories: 

anti-dsDNA antibodies

anti-DZP and anti-PEG antibodies (Visit 12 only)

coagulation and hemostasis tests (Visit 12 only)

total Ig, IgG, IgM, IgA, and IgE (Visit 12 only)

serum complement (C3, C4) 

hsCRP

whole blood mRNA (Visit 12 only)

proteomic signature profile (Visit 12 only)

PK plasma sampling 

BILAG 2004

SLEDAI-2K assessing the past 30 days 

SRI-50

PGA

TJC/SJC

CLASI

Investigator assessment of flare

AEs

Dispense subject daily diary (only performed in subjects who are continuing in the study)

Dispense urine collection container (for first morning urine collection at home on the 
morning of their next visit; only performed at Visit 12 in subjects who are continuing in the 
study; not done at Visit 14)
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8.10
Visit 16 (Week 48/Day 336 [± 3days]); Observation Period
Final/Early Withdrawal Visit
Subjects who withdraw prior to Week 32 (Visit 12) will complete an EWV (Visit 10 assessments 
if withdrawn prior to Visit 10; Visit 16 assessments if withdrawn after Visit 10) as well as 
Visits 11 and 12 for SFU assessments at 8 and 12 weeks after their final dose of study drug (as 
applicable). Subjects who withdraw after Week 32 (Visit 12) do not require additional SFU visits 
and will complete the Visit 16/EWV assessments only.
Subjects should undergo an overnight fast (at least 8 hours) prior to coming to the site for 
Visit 16. Subjects may then eat breakfast after serum samples have been obtained for the 
assessment of cardiovascular proteins, lipids, and lipid particles, and prior to any other 
assessments.
The PRO questionnaires should then be completed in a quiet place by the subjects themselves at 
the start of the study visit and prior to the remaining visit assessments.
Assessments at Visit 16 (Week 48) include:

LupusQoL

PROs at sites in English- and Spanish-speaking countries only:

SLE-S

SLE-F

SLE-M

SLE-P

SLE-E

Concomitant medications

Medical procedures

Collect/review subject daily diary

Collect PK urine sample obtained at home (first morning urine collection at home on 
morning of visit)

C-SSRS

Physical examination/interim medical history

Urine pregnancy test for women of childbearing potential

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature)

12-lead ECG

Safety laboratories: hematology, clinical chemistry, and urinalysis

Additional laboratories: 

ANAs, anti-ENAs (anti-SM, anti-SSA, anti-SSB, anti-RNP), and RF
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
anti-dsDNA antibodies

anti-DZP and anti-PEG antibodies

aPL antibodies

coagulation and hemostasis tests

total Ig, IgG, IgM, IgA, and IgE

serum complement (C3, C4)

hsCRP

whole blood mRNA

proteomic signature profile

cardiovascular proteins, lipids, and lipid particles (blood samples should be collected 
under fasting conditions [at least 8 hours])

DNA

PK plasma sample

BILAG 2004

SLEDAI-2K assessing the past 30 days

SRI-50

PGA

PtGA

SLICC/ACR Damage Index

TJC/SJC

CLASI

Investigator assessment of flare

AEs
8.11
Unscheduled Visit
If at any point during the study the Investigator determines that a subject requires additional 
safety evaluations, the subject can return to the site and the Investigator may perform additional 
assessments, as clinically indicated, such as, but not limited to, the following assessments:

Concomitant medications

Medical procedures

Vital signs (systolic and diastolic blood pressure, pulse rate, and temperature)

12-lead ECG

Standard safety laboratories: hematology, serum chemistry, and urinalysis
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
hsCRP

Urine pregnancy test for women of childbearing potential

AEs

Contact the IVRS/IWRS
9
ASSESSMENT OF EFFICACY
9.1
Clinical assessments of disease activity
9.1.1
BILAG 2004
The BILAG 2004 will be used as a clinical assessment of SLE disease activity 
(Tsokos et al, 2007). 
The Investigators will assess 97 BILAG 2004 components and record the assessments in the 
eCRF. Only clinical features attributable to SLE are to be recorded and based on the subject’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 separately:

Constitutional (fatigue, fever, anorexia, weight loss, etc)

Mucocutaneous (rash, alopecia, mucosal ulcers, etc)

Neuropsychiatric (headache, seizure, psychosis, etc) 

Musculoskeletal (arthritis, myalgia, 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 document (chart, 
worksheet, clinic notes, and labs) capable of withstanding audit: 

For each entry indicating activity (and first time prior entry is no longer present)

Indicating why feature new, improving, same, or worse 

Sufficient descriptive detail to support future changes (improved, worsening);
eg, number/location of arthritic joints, size/location of rashes, etc

Information indicating that all other features were not active at the time point of the visit
The Sponsor will provide centralized grading (A, B, C, D, and E) based on BILAG 2004 eCRF 
pages completed by the Investigator. Prior to Visit 2, the site must have received confirmation 
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from the central independent efficacy reader for BILAG 2004 data that the subject 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
Refer to Appendix 19.5 for protocol-specific clarification and extension of BILAG 2004
definitions.
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.
In addition, the BST is a new method of representing the BILAG 2004 scores longitudinally, 
which combines the flexibility and simplicity of numerical scoring with the clinical intuitiveness 
and meaningfulness of the BILAG 2004 categorical score. It was devised using a data-driven 
methodology and is based on counts of the number of systems with active/worsening disease and 
improving disease between 2 assessments. Further details will be provided in the SAP.
Only Investigators that complete BILAG 2004 training will be allowed to perform the 
BILAG 2004 assessments. Preferably, the same Investigator should evaluate the subject at each 
BILAG 2004 assessment from Screening to study completion.
9.1.2
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 and laboratory variables that are weighted by the type of manifestation, but not by 
severity. The SLEDAI-2K includes scoring for antibodies (anti-dsDNA 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 subject groups 
(Gladman et al, 2002).
To confirm subject 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. For both 
Visits 1 and 2, the SLEDAI-2K will assess disease activity in the past 10 days only.
9.1.3
PGA
The Investigator will rate the overall status of the subject in response to the following statement:
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“Please mark a vertical line on the scale below to assess the overall status of the subject’s
Systemic Lupus Erythematosus signs and symptoms and the functional capacity of the
subject. Zero is ‘very good, asymptomatic and no limitation of normal activities’; 100 
indicates ‘severe disease’ and is at the very end of the scale. 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 PGA, the assessor should always look back at the score from the previous 
visit. This assessment by the Investigator must be made blinded to the PtGA performed at the 
same visit.
9.1.4
PtGA
Subjects will rate their global assessment of their SLE disease activity for the day of the visit in 
response to the statement “Considering all the ways your SLE affects you, please mark a vertical
line on the scale below for how you are feeling today” using a 100mm visual analog scale (VAS)
where 0 is “very good, no symptoms” and 100 is “very poor, very severe symptoms.”
9.1.5
SLICC/ACR Damage Index
The 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 9‒1), and check “Yes” if the criterion is present (and 
tick the appropriate box if there is more than 1 choice); or check “No,” or “Unknown,” as 
appropriate.
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Table 9‒1:
SLICC/ACR Damage Index organ system scoring
Organ system
Range of possible scores
Ocular
0–2
Neuropsychiatric
0–6
Renal
0–3
Pulmonary
0–5
Cardiovascular
0–6
Peripheral vascular 
0–5
Gastrointestinal
0–5
Musculoskeletal
0–6
Skin
0–3
Diabetes
0–1
Premature gonadal failure 
0–1
Malignancy
0–2
ACR=American College of Rheumatology; SLICC=Systemic Lupus International Collaborating Clinics
9.1.6
Tender and Swollen Joint Counts (28 joints)
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 (IP) joint, 
proximal interphalangeal (PIP) joints (PIP 2, 3, 4, and 5), and the knees.
Artificial and ankylosed joints will be excluded from tenderness and swelling assessments.
Subjects taking maintenance NSAIDs/analgesics, medical marijuana, or narcotics should not take 
a dose of these medications within 12 hours prior to the 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 9‒2.
Table 9‒2:
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 subject on 
examination (tender, winced, and withdrew)
Every effort should be made to ensure each subject is evaluated by the same Investigator 
(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 
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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.
9.1.7
CLASI
The 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 9‒3) (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. Subjects are asked whether dyspigmentation due to cutaneous lupus 
erythematosus lesions usually remains visible for more than 12 months, which is taken to be 
permanent. 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. Associated symptoms, including itch, 
pain, and fatigue are recorded separately on a 1 to 10 VAS by the subjects.
Table 9‒3:
CLASI 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
aIf scarring and nonscarring aspects seem to coexist in 1 lesion, both should be scored.
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9.1.8
Assessment of flare
The reduction in lupus flares and increase in time to lupus flare is considered an appropriate 
measure to evaluate the efficacy of potential new lupus treatments. However, there is a lack of a 
universally accepted definition of a lupus flare. A recent international initiative involving 
multiple SLE experts led to a proposal for a consensus definition of disease flare in lupus 
(Ruperto et al, 2011):
A flare is a measurable increase in disease activity in 1 or more organ systems involving new 
or worse clinical signs and symptoms and/or laboratory measurements. It must be 
considered clinically significant by the assessor and usually there would be at least 
consideration of a change or an increase in treatment.
Flare will be assessed by the Investigator and by the Sponsor, as follows.
Investigator Assessment of Flare:
To determine if the definition of flare is fulfilled in the opinion of the Investigator, the following 
question will be answered by the Investigator at each visit after Visit 2:
“Do you consider that the SLE disease activity of the patient in 1 or more organ systems 
(involving new or worse clinical signs and symptoms and/or laboratory measurements) 
increased clinically significantly since the last visit and that you considered a change or 
increase the treatment for SLE of your patient?”
Sponsor Assessment of Flare:
The definition of flare according to the Sponsor is: a new sustained BILAG 2004 Grade A/B 
(present at ≥2 consecutive visits) after withdrawal of study drug or start of new induction therapy 
(either corticosteroid dose increase to ≥0.5 mg/kg/day prednisone equivalent or initiation of 
cyclophosphamide, rituximab, iv Ig, or plasma exchange] after withdrawal of study drug.
9.1.9
Responders based on clinical assessments of disease activity
9.1.9.1
BICLA
The primary efficacy variable, the BICLA responder rate across 3 doses of DZP and PBO at 
Week 24, is a categorical response variable (yes/no) incorporating the following criteria for 
achievement of responder status (ie, all criteria must be met to achieve responder status):
1. BILAG 2004 improvement, defined as BILAG 2004 Grade As at study entry improved to 
B/C/D, and BILAG 2004 Grade Bs at study entry improved to C/D, and no 
BILAG 2004 2004 worsening in other BILAG 2004 organ systems such that there are no
new BILAG 2004 Grade As or greater than 1 new BILAG 2004 Grade B(s); and
2. No worsening in the SLEDAI-2K total score compared to study entry (defined as no increase 
in SLEDAI-2K total score); and 
3. No worsening in the Physician’s Global Assessment of Disease Activity compared to study 
entry (“no worsening” is defined as <10% worsening, equivalent to a 10mm increase on a 
100mm VAS); and
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4. No changes in concomitant medications according to the following criteria (all criteria must 
be met):

No increase of (or addition of a new) immunosuppressant nor antimalarial doses over 
Baseline (Visit 2) levels, nor initiation of any medication listed in Table 7-1

No increase in oral corticosteroid dose over Baseline (Visit 2) levels for an SLE-related
indication

No iv, im, nor intra-articular injections of corticosteroids which are SLE related
In addition, subjects who discontinue study drug prematurely are primarily categorized as 
nonresponders.
The BICLA responder rate is based primarily on the BILAG 2004 disease activity measurement 
instrument. The BILAG 2004 was selected as the primary tool for measurement of disease 
activity on the basis of its comprehensiveness, ability to capture incremental changes in disease 
activity, and the clinical relevance of its grading system. The BILAG 2004 grading is anchored 
in the physician’s intention to treat. 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 2004 grades mirror 
the decision points for treatment interventions. Consequently it represents the induction of 
disease control.
It is important to note that for the BILAG 2004 improvement, all As and Bs at entry need to 
improve. If an A improves to a B but a single B remains from entry, then the subject has not 
improved in their BILAG 2004.
9.1.9.2
SRI-4, -5, and -6
The SRI-4, SRI-5, and SRI-6 define responders as (ie, all criteria must be met):

Reduction in SLEDAI-2K score of ≥4, ≥5, and ≥6 points, respectively

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, or from B to A, post-Baseline

Increase in Physician’s Global Assessment of Disease from Baseline of <10% (<10mm)
Assessments of SRI-4, -5, and -6 will include an assessment of nonresponders based on 
concomitant medication rules.
9.1.9.3
SRI-50
The SRI-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 SRI-50 reflects disease activity over the 30 days prior to the 
assessment (Touma et al, 2011). The total score of SLEDAI-2K falls between 0 and 105, with 
higher scores representing increased disease activity. 
The SRI-50 score corresponds to the sum of each of the 24 descriptor scores on the SRI-50 data 
retrieval form. The method of scoring is simple, cumulative, and intuitive and similar to the 
SLEDAI-2K. One of 3 situations can result when a descriptor is present at the initial visit: 
1. The descriptor has achieved complete remission, in which case the score would be “0”; 
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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 SRI-50 definition) but has not 
achieved complete remission, in which case the score is evaluated as one-half the score that 
would be assigned for SLEDAI-2K. 
If a descriptor was not present at the initial visit, the value for the SRI-50 will be the same as that 
for SLEDAI-2K. This process is repeated for each of the 24 descriptors.
Finally, the SRI-50 score is evaluated as the sum of the scores of the 24 individual descriptors.
9.2
Patient-reported outcomes
The administration of the questionnaires for PRO assessments should be performed by study 
personnel other than the treating physician. The questionnaires should be filled in at the start of 
the study visit in a quiet place and by the subjects themselves. 
The LupusQoL will be collected for all subjects at all sites participating in the study. In addition, 
the following exploratory PRO variables being developed by UCB will be assessed at sites in 
English- and Spanish-speaking countries (approximately 45% to 50% of the projected study 
population): SLE-S, SLE-F, SLE-M, SLE-P, and SLE-E. These newly developed instruments are 
being piloted in the current study and the data generated from this study will aid in refining the 
instruments for use in future studies. The Subject Experience Interview will also be assessed at 
sites in English- and Spanish-speaking countries.
The PRO questionnaires should be completed in the following order: LupusQoL, SLE-S, SLE-F, 
SLE-M, SLE-P, SLE-E, and Subject Experience Interview. The questionnaires should only be 
checked for completeness.
The visits at which PRO assessments are to be performed are described in Table 5‒2.
9.2.1
LupusQoL
The LupusQoL (version 2007) is a disease-specific 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 (MCID) 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).
9.2.2
SLE-S
The SLE-S consists of 26 symptom items. The subject is asked to score each symptom item 
based on the severity experienced during the past 7 days using the following scale: 1=none; 
2=mild; 3=moderate; 4=severe. 
9.2.3
SLE-F
The SLE-F consists of 55 fatigue items across 3 scales: 16 physical domain items, 18 mental 
domain items, and 21 fatigability domain items. The subject is asked to score each fatigue item 
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based on how frequently they experienced the item during the past 7 days using the following 
scale: 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.
9.2.4
SLE-M
The SLE-M consists of 12 mobility items. The subject is asked to score each mobility item based 
on how frequently they experienced the item during the past 7 days using the following scale: 
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.
9.2.5
SLE-P
The SLE-P consists of 3 Numeric Rating Scales and 29 items across a Pain and Physical 
Sensations Scale and a Pain Checklist. The subject is asked to indicate on Numeric Rating Scales
the level of pain experienced in the past 7 days at its LEAST, at its WORST, ON AVERAGE, 
and also RIGHT NOW. The subject is then asked to score each of 12 pain and physical 
sensations items based on the severity experienced during the past 7 days using the following 
scale: 1=none; 2=very mild; 3=mild; 4=moderate; 5=severe; 6=very severe. Finally, the subject 
is asked to indicate the locations of the pain experienced in the past 7 days using a checklist 
consisting of 17 body locations.
9.2.6
SLE-E
The SLE-E consists of seven feelings and mood items. The subject is asked to score each item 
based on how frequently they experienced the item during the past 7 days using the following 
scale: 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. 
9.2.7
Subject Experience Interview
Qualitative subject interviews will be conducted by an external third party vendor. The third 
party vendor will call the subject at home to collect the subject's experience with lupus in terms 
of symptoms and impact on daily activities, and the perceived changes during the course of the 
study. The extent to which the exploratory PRO items and scales used fully captured their 
experience will also be assessed.
10
ASSESSMENT OF PK AND PD VARIABLES
Subjects 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 and be drawn at the time 
points and sampling windows designated in Table 5‒2 Blood samples must not be drawn 
through the infusion cannula.
10.1
Assessment of PK variables
The following PK variables will be evaluated:

For plasma samples:

Plasma concentrations of DZP and PEG

For urine samples:

Urine concentration of PEG
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The DZP concentrations in the plasma will be determined by a validated 
electrochemiluminescence-based immunoassay. Concentrations of total PEG (both Fab' PEG and 
PEG) in plasma and of PEG in urine (following ultrafiltration) will be determined by a validated 
assay using 1H nuclear magnetic resonance spectroscopy. Concentrations of DZP in urine may be 
measured depending on the availability of a bioanalytical method. 
There are no time window requirements for blood samples for PK measurements when measured 
pre-dose or at unspecified times during the visit. Blood samples for PK measurements should be 
drawn within ±10min of the scheduled time point for each post-infusion time point or within 
10min after the infusions ends for end of infusion time points. 
For urine PK assessments, urine collection containers will be dispensed to the subjects at the 
designated visits for urine collection at home prior to the next visit. As outlined in Table 5‒2, 
prior to Visits 9 and 10 only, the subject will collect overnight urine samples, which includes the 
first void after the subject goes to sleep the night before the visit through the first morning void 
the morning of the visit. The subject should note the times for the first and last urine collection. 
For all other visits requiring urine PK sample collection (Visits 2, 11, 12, 13, 14, and 16), the 
subject will collect only their first morning void.
10.2
Assessment of PD variables
The following PD assessments will be performed. Additional assessments may also be 
performed, as deemed appropriate.

Whole blood mRNA signature profiling to characterize potential changes in gene expression 
relevant to the inflammatory and immune response in SLE

Immunological variables:

Lupus Autoantibody Profile: anti-dsDNA, ANAs, anti-ENA (anti-SM, anti-SSA, 
anti-SSB, and anti-RNP), RF, and aPL antibodies

Ig (total Ig, IgG, IgM, IgA, and IgE)

hsCRP

C3 and C4 levels
10.3
Handling and shipment of blood and urine samples for PK and 
PD assessments
Sample work-up as well as the handling and shipment of samples should be performed as 
detailed in the Laboratory Manual.
11
ASSESSMENT OF IMMUNOGENICITY VARIABLES
The determination of the following immunogenicity variables will be performed from plasma 
samples (as noted in the Laboratory Manual):

Anti-DZP and anti-PEG antibodies
Table 5‒2 provides the timings for immunogenicity assessments.
Blood samples must not be drawn through the infusion cannula. Sample work-up as well as 
the handling and shipment of samples should be performed as detailed in the Laboratory Manual.
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The detection of anti-DZP antibodies and anti-PEG antibodies will be done using validated 
methods. The details of analytical methods (including validation status) and results will be 
presented in the bioanalytical report.
12
ASSESSMENT OF BIOMARKERS
In addition to the PD variables (Section 10.2), the following samples will also be taken:

Serum will be taken and stored for protein and lipid analysis to characterize potential changes 
relevant to inflammatory and immune responses and cardiovascular risk in SLE.

Whole blood will be taken and stored to isolate DNA which may be used to examine genetic 
and epigenetic changes. If samples are not used immediately, they will be stored at -80°C for 
later analysis until the completion of the DZP development program. They will be stored at 
BioStorage Technologies GmbH (Germany) and they will only be used in the context of 
understanding the molecular taxonomy of SLE and/or response to treatment with DZP.
Table 5‒2 provides the timings for biomarker assessments.
Blood samples must not be drawn through the infusion cannula. Sample work-up as well as 
the handling and shipment of samples should be performed as detailed in the Laboratory Manual.
13
ASSESSMENT OF SAFETY
13.1
Adverse events
13.1.1
Definition of adverse event
An AE is any untoward medical occurrence in a patient or clinical investigation subject 
administered a pharmaceutical product that does not necessarily have a causal relationship with 
this treatment. An AE can therefore be any unfavorable and unintended sign (including an 
abnormal laboratory finding), symptom, or disease temporally associated with the use of a 
medicinal (investigational) product, whether or not related to the medicinal (investigational) 
product. All AEs that occur during the study should be considered related unless clearly 
unrelated.
In order to ensure complete safety data collection, all AEs occurring during the study (ie, after 
the signing of the Informed Consent form), including any pretreatment and posttreatment periods 
required by the protocol, must be reported in the eCRF even if no IMP 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.
New or worsening manifestations of SLE should be recorded as AEs only if they are assessed as 
serious.
13.1.2
Procedures for reporting and recording adverse events
The subject 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.
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13.1.3
Description of adverse events
When recording an AE, the Investigator should use the overall diagnosis of the underlying 
disease, condition, or syndrome using standard medical terminology, rather than recording 
individual symptoms or signs. The eCRF and source documents should be consistent. Any 
discrepancies between the subject’s own words on his/her own records (eg, diary card) and the 
corresponding medical terminology should be clarified in the source documentation.
Details for completion of the Adverse Event eCRF (including judgment of relationship to IMP) 
are described in the eCRF Completion Guidelines.
13.1.4
Follow up of adverse events
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 subject is lost to follow up. This 
follow-up requirement applies to AEs, SAEs, and AEs of special interest; further details 
regarding follow-up of PDILI events are provided in Section 13.7.
If an AE is ongoing at the end of the study for a subject, follow up should be provided until 
resolution/stable level of sequelae is achieved, or until the Investigator no longer deems that it is 
clinically significant, or until the subject is lost to follow up. If no follow up is provided, the 
Investigator must provide a justification. For subjects withdrawn from the study prior to Visit 12 
(Week 32), the follow up will be continued throughout the SFU Period (which ends 12 weeks 
after the final dose of study drug).
Information on SAEs obtained after clinical database lock will be captured through the PS
database without limitation of time.
13.1.5
Rule for repetition of an adverse event
An increase in the intensity of an AE should lead to the repetition of the AE being reported with:

The outcome date of the first AE that is not related to the natural course of the disease being 
the same as the start date of the repeated AE, and the outcome of “worsening”

The AE verbatim term being the same for the first and repeated AE, so that the repeated AE 
can be easily identified as the worsening of the first one
13.1.6
Hypersensitivity and adverse drug reactions
In the event of a serious hypersensitivity reaction, the subject must permanently discontinue IMP 
and be progressed as described in Section 6.3.
In case of occurrence of a hypersensitivity reaction (not determined by the Investigator to be a 
minor local reaction at the infusion site, such as minimal itching) and depending upon its 
severity, appropriate countermeasures will immediately be taken by the Investigator.
In the event of an anaphylactic reaction, the infusion must be discontinued immediately and 
emergency resuscitation measures implemented. If the Investigator does not initially choose to 
discontinue the infusion of IMP and symptoms persist or escalate during continued infusion, the 
infusion should be stopped. In case of any severe infusion reaction(s), the infusion of IMP must 
be stopped immediately and appropriate treatment initiated, as necessary, at the discretion of the 
Investigator and in accordance with the standard-of-care. 
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Suggested guidelines for the management of infusion reactions are provided in Appendix 19.3. 
Refer to Section 7.2.1.2 for details regarding premedication for prophylaxis of infusion-related 
reactions.
Suspected anaphylactic reactions should be classified using Sampson’s Criteria 
(Sampson et al, 2006) as described in Appendix 19.4.
13.1.7
Thromboembolic events
If the Investigator suspects a subject has a thromboembolic event, the Investigator should 
manage the subject in accordance with the standard-of-care and should discuss the event with the 
Medical Monitor. The IMP should be withheld while the suspected thromboembolic event is 
being investigated. After investigation, IMP administration will be addressed as follows:

Suspected thromboembolic event is not confirmed: IMP may be continued

Thromboembolic event is confirmed: IMP should be discontinued permanently
In the unexpected situation in which the study needs to be terminated due to the incidence of 
thromboembolic events, the following will occur:

All Investigators will be informed of the details of the thromboembolic events

All Investigators will be asked to evaluate each subject who received study drug within the 
past 12 weeks, to assess the potential increased risk of thromboembolic event, and to 
consider appropriate management that may include prophylactic anticoagulant therapy in 
case an increased risk cannot be excluded. Before a prophylactic anticoagulant treatment is 
started, the Investigator should break the blind in order to assure that the subject at risk was 
treated with DZP. Based on the half-life of DZP, the Sponsor recommends that the duration 
of anticoagulant therapy be for 18 weeks after the final dose of IMP.

All subjects who are in the Double-Blind Treatment Period (Part 1) will enter and complete 
the SFU Period

All subjects who are in in the SFU Period will complete the period as planned
13.1.8
Infections
Subjects who have the signs or symptoms of any infection should be managed according to local 
guidelines. This may include tests for possible infection with Epstein Barr virus and 
cytomegalovirus, if clinically indicated. The tests for Epstein Barr virus and cytomegalovirus 
will be performed at the central laboratory using blood provided by the site in accordance with 
the directions provided in the Laboratory Manual.
If a subject has an infection that requires parenteral (iv or im) antimicrobial treatment or that 
requires hospitalization, the subject’s continuation in the study should be discussed with the 
Medical Monitor.
13.1.8.1
Suspected transmission of an infectious 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 13.2); such cases must be reported 
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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.
13.1.9
Neurological events
Subjects who develop new neurological signs or symptoms or significantly worsening
preexisting neurological signs or symptoms should be managed appropriately to evaluate the 
underlying disease or condition. This may include involvement of a neurologist, imaging, and 
other diagnostic activities as indicated. In case of severe and/or serious headache, positional 
headache, cranial nerve dysfunction, or signs and symptoms of meningitis, the Medical Monitor
should be contacted immediately and the neurological event must be reported as an AE of 
interest to UCB within 24 hours.
13.1.10
Pregnancy
If an Investigator is notified that a subject has become pregnant after the first intake of any IMP, 
the Investigator must immediately notify UCB’s PS department by providing the completed 
Pregnancy Report and Outcome form (for contact details see Serious Adverse Event Reporting
information at the beginning of this protocol). The subject should be discontinued from the study 
drug as soon as pregnancy is known (by positive pregnancy test), and the following should be 
completed:

The IMP should be immediately discontinued. 

The subject should complete the study per protocol.
If the Investigator becomes aware of a pregnancy only after an abortion, the withdrawal should 
be discussed with a Medical Monitor upfront. The Investigator must inform the subject of 
information currently known about potential risks and about available treatment alternatives.
The pregnancy will be documented on the Pregnancy Report and Outcome form provided to the 
Investigator. The progression of the pregnancy and the eventual birth (if applicable) must be 
followed up using the Pregnancy Report and Outcome form in which the Investigator has to 
report on the health of the mother and of the child. Every reasonable attempt should be made to 
follow the health of the child for 30 days after birth for any significant medical issues. In certain
circumstances, UCB may request that follow up is continued for a period longer than 30 days. If 
the subject is lost to follow up and/or refuses to give information, written documentation of 
attempts to contact the subject needs to be provided by the Investigator and filed at the site. 
UCB’s PS department is the primary contact for any questions related to the data collection for 
the pregnancy, eventual birth, and follow up.
In cases where the partner of a male subject enrolled in a clinical study becomes pregnant, the 
Investigator or designee is asked to contact the subject to request consent of the partner via the 
Partner Pregnancy Consent form that has been approved by the responsible IRB/IEC and should 
be available in the Investigator site file. In case of questions about the consent process, the 
Investigator may contact the UCB/CRO contract monitor for the study. The Investigator will 
complete the Pregnancy Report and Outcome form and send it to UCB’s PS department (for 
contact details see Serious Adverse Event Reporting information at the beginning of this 
protocol) only after the partner has agreed that additional information can be captured and has 
provided the signed Partner Pregnancy Consent form. UCB’s PS department is also the primary 
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contact for any questions related to the data collection for the partner pregnancy, eventual birth, 
and follow up.
A pregnancy becomes an SAE in the following circumstances: miscarriage, abortion (elective or 
spontaneous), unintended pregnancy after hormonal contraceptive failure (if the hormonal 
contraceptive was correctly used), ectopic pregnancy, fetal demise, or any congenital 
anomaly/birth defect of the baby. Those SAEs must be additionally reported using the 
Investigator SAE Report Form.
13.1.11
Overdose of IMP
Any SAE or nonserious AE associated with excessive dosing must be followed as any other SAE 
or nonserious AE. These events are only considered AEs or SAEs if there are associated clinical 
signs and symptoms or if the act of taking the excess medicine itself is an AE or SAE 
(eg, suicide attempt).
13.1.12
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 IMP so that Investigators, clinical study subjects, regulatory 
authorities, and IRBs/IECs will be informed appropriately and as early as possible.
The Study Physician or medically qualified designee/equivalent will conduct an ongoing review 
of SAEs and perform ongoing SAE reconciliations in collaboration with the PS representative.
As appropriate for the stage of development and accumulated experience with the IMP, 
medically qualified personnel at UCB may identify additional safety measures (eg, AEs, vital 
signs, laboratory values, or ECG results) for which data will be periodically reviewed during the 
course of the study.
In addition, a DMC will also monitor the ongoing safety of the study (see Section 5.1.4).
13.2
Serious adverse events
13.2.1
Definition of serious adverse event
Once it is determined that a subject experienced an AE, the seriousness of the AE must be 
determined. An SAE must meet 1 or more of the following criteria:

Death

Life-threatening
(Life-threatening does not include a reaction that might have caused death had it occurred in 
a more severe form.)

Significant or persistent disability/incapacity

Congenital anomaly/birth defect (including that occurring in a fetus)

Important medical event that, based upon appropriate medical judgment, may jeopardize the 
patient or subject and may require medical or surgical intervention to prevent 1 of the other 
outcomes listed in the definition of serious
(Important medical events may include, but are not limited to, potential Hy’s Law [see
Section 13.3], allergic bronchospasm requiring intensive treatment in an emergency room or 
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at home, blood dyscrasias that do not result in inpatient hospitalization, or the development 
of drug dependency or drug abuse.)

Initial inpatient hospitalization or prolongation of hospitalization
(A patient admitted to a hospital, even if he/she is released on the same day, meets the 
criteria for the initial inpatient hospitalization. An emergency room visit that results in 
admission to the hospital would also qualify for the initial inpatient hospitalization criteria. 
However, emergency room visits that do not result in admission to the hospital would not 
qualify for this criteria and, instead, should be evaluated for 1 of the other criteria in the 
definition of serious [eg, life-threatening adverse experience, important medical event].
Hospitalizations for reasons not associated with the occurrence of an AE [eg, preplanned 
surgery or elective surgery for a pre-existing condition that has not worsened or manifested 
in an unusual or uncharacteristic manner] do not qualify for reporting. For example, if a 
subject has a condition recorded on his/her medical history and later has a preplanned surgery 
for this condition, it is not appropriate to record the surgery or hospitalization as an SAE, 
since there is no AE upon which to assess the serious criteria. Please note that, if the 
pre-existing condition has worsened or manifested in an unusual or uncharacteristic manner, 
this would then qualify as an AE and, if necessary, the seriousness of the event would need to 
be determined.)
13.2.2
Procedures for reporting serious adverse events
If an SAE is reported, UCB must be informed within 24 hours of receipt of this information by 
the site (see contact information for SAE reporting listed in the Serious Adverse Event Reporting 
section at the front of the protocol). The Investigator must forward to UCB (or its representative) 
a duly completed “Investigator SAE Report Form for Development Drug” (SAE Report Form) 
provided by UCB, even if the data are incomplete, or if it is obvious that more data will be 
needed in order to draw any conclusions. Information recorded on this form will be entered into 
the global safety database.
An Investigator SAE report form will be provided to the Investigator. The Investigator SAE 
Report Form must be completed in English. 
It is important for the Investigator, when completing the SAE Report Form, to include the 
assessment as to a causal relationship between the SAE and the IMP administration. This insight 
from the Investigator is very important for UCB to consider in assessing the safety of the IMP 
and in determining whether the SAE requires reporting to the regulatory authorities in an 
expedited manner.
Additional information (eg, autopsy or laboratory reports) received by the Investigator must be 
provided within 24 hours. All documents in the local language must be accompanied by a 
translation in English, or the relevant information included in the same document must be 
summarized in the Investigator SAE Report Form.
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 IMP), up to 
30 days from the end of the study for each subject, and to also inform participating subjects 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 IMP must be reported to UCB regardless of the 
time between the event and the end of the study.
Upon receipt of the SAE Report Form, UCB will perform an assessment of expectedness of the 
reported SAE. The assessment of the expectedness of the SAE is based on the list of Anticipated 
SAEs provided in Section 13.5.
13.2.3
Follow up of serious adverse events
An SAE should be followed until it has resolved, has a stable sequelae, the Investigator
determines that it is no longer clinically significant, or the subject is lost to follow up. 
Information on SAEs obtained after clinical database lock will be captured through the PS 
database without limitation of time.
13.3
Adverse events 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. There are currently no AEs of special interest 
identified for DZP; however, in accordance with the Sponsor’s internal guidelines for all drugs in 
development, Potential Hy's Law is to be reported as an AE of special interest as follows:
Potential Hy’s law, defined as ≥3xULN ALT or AST with coexisting ≥2xULN bilirubin in the 
absence of ≥2xULN ALP, with no alternative explanation for the biochemical abnormality, must 
ALWAYS be reported to UCB as an AE of special interest (ie, without waiting for any 
additional etiologic investigations to have been concluded). Follow-up information should then 
be reported if an alternative etiology is identified during investigation and monitoring of the 
subject. Refer to Section 13.7 for details on investigation and monitoring of PDILI.
13.4
Immediate reporting of adverse events
The following AEs must be reported immediately to UCB (or its representative):

SAEs: AEs that the Investigator classifies as serious by the above definitions regardless of 
causality

Suspected transmission of an infectious agent via a medicinal product (see Section 13.1.8.1)

AEs of special interest (see Section 13.3)

AEs of interest (regardless of seriousness):

Moderate to severe infections, including opportunistic infections and TB

Infusion reactions (including hypersensitivity and anaphylaxis)

Thromboembolic events (including but not limited to cardiovascular events, stroke,
myocardial infarction, pulmonary embolism, and deep vein thrombosis)

Prespecified neurological events: Severe and/or serious headache, positional headache, 
cranial nerve dysfunction, or signs and symptoms of meningitis (photophobia, neck 
stiffness)

Malignancies
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13.5
Anticipated serious adverse events
Table 13‒1 lists anticipated SAEs that have been identified as these events are anticipated to 
occur in the population studied in this protocol at some frequency that is independent of drug 
exposure. This original list will remain in effect for the duration of the protocol.
This list does not change the Investigator’s obligation to report all SAEs (including Anticipated 
SAEs) as detailed in Section 13.2.2.
Table 13‒1: Anticipated serious adverse events for subjects with SLE
Thromboembolism
Serious infection
Renal dysfunction
Neuropsychiatric episode
Leucopenia
Anemia
Thrombocytopenia
SLE
SLE=systemic lupus erythematosus
13.6
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 6.2 [Exclusion Criterion #16]) and Section 6.3 [Withdrawal 
Criteria]). Any presumptive diagnosis or diagnosis of a TB infection is a reportable event. 
Confirmed active TB must be reported as an SAE (Section 13.2.2). The Investigator is to 
complete and submit the TB follow-up form provided.
Signs and symptoms
The Investigator should consider all potential sites of infection when assessing for TB during the 
physical examination, and other evaluations, and based on the subject’s history. Sites commonly 
infected by TB include: the lungs, larynx, lymph glands, pleura, gastrointestinal system, 
genitourinary tract (including renal), bones and joints, meninges, peritoneum, pericardium, and 
skin. This is not an exhaustive list and unusual presentations and areas of involvement should 
always be considered.
Common symptoms with which the subject may present with include cough, blood in sputum, 
night sweats, lymphadenitis, joint pain/swelling, spinal deformity, headache/confusion, 
abdominal pain mimicking inflammatory bowel disease, frequent or painful urination, scrotal 
mass in men and pelvic inflammatory disease in women as well as other symptoms, or 
nonspecific symptoms. This is not an exhaustive list and unusual presentations should always be 
considered.
If active TB is identified, the subject must undergo appropriate study specified withdrawal 
procedures.
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Latent TB infection is defined as the absence of signs, symptoms (eg, evidence of organ-specific 
involvement), or physical findings suggestive of TB infection with a positive interferon-γ release 
assay (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 
subject may not be randomized to study drug and, if already randomized, must undergo 
appropriate study specified withdrawal procedures. 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 
(Centers for Disease Control, 2015).
Test conversion
Tuberculosis test conversion is defined as a positive result (IGRA) for the current test but 
previous test results were negative (IGRA). All subjects with TB test conversion must 
immediately stop study drug administration. In case of a TB test conversion, the subject 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. If test conversion indicates LTB infection, active TB, or non-mycobacterial TB 
infection then, per UCB TB working instructions, TB test conversion (confirmed) should be 
classified as due to LTB, active TB infection, or non-TB mycobacterial infection. Additional 
assessments (eg, blood tests or IGRA test, chest x-rays, or other imaging) should be performed as 
medically indicated.
Latent TB: In case the evaluation by the appropriate specialist indicates a new LTB, the subject 
must be withdrawn from the study.
Active TB/non-tuberculosis mycobacterium: Subjects who develop active TB or 
non-tuberculosis mycobacterium (NTMB) infection during the study (conversion demonstrated 
by IGRA) must be withdrawn from the study. The subject must be immediately discontinued 
from study drug and an EWV must be scheduled as soon as possible, but no later than the next 
scheduled visit. The subject should be encouraged to keep the SFU Visits as specified by the 
protocol. The TB must be documented as an SAE. Treatment should be immediately started.
Note that subjects with history of or active NTMB infection are excluded from the study 
regardless of prior or current therapy. 
Confirmed active TB is an SAE and must be captured on an SAE Report Form and provided to 
the Sponsor in accordance with SAE reporting requirements. As with all SAEs, periodic 
follow-up reports should be completed as per protocol requirement until such time as the TB 
infection resolves.
Once withdrawn from study treatment, subjects should return for the End of Treatment/EWV, 
complete all early withdrawal assessments, and complete the SFU Visits.
13.6.1
TB assessments
During conduct of the study, the TB assessment by IGRA (QFT-GIT or Elispot, if QFT-GIT is 
not available locally), should be repeated at Week 48 or early withdrawal for all subjects. The 
test results will be reported as positive, negative, or indeterminate and must be reviewed by an 
experienced TB specialist, radiologist, or a pulmonologist. If the assessment by IGRA is positive 
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or indeterminate on retest for subjects who were previously negative at Screening, the subject 
must undergo appropriate study-specified withdrawal procedures. The retest during Screening 
must be done during the protocol-defined Screening window.
13.6.2
Chest x-ray
A plain posteroanterior chest x-ray (or, if done, computed axial tomography of the chest) should 
be performed during Screening unless one has been done within 3 months prior to the Screening 
Visit. The chest x-ray must be clear of signs of TB infection (previous or current) before first 
study drug administration. The chest x-ray should be repeated only if the TB test was confirmed 
positive or any further evidence is suggestive of potential TB infection (eg, exposure). 
Radiographic findings suggestive of inactive TB or active TB may include but are not limited to: 
apical fibrosis, pleural thickening, pulmonary nodules, fibrotic scars, calcified granulomas, upper 
lobe infiltrates, cavitations and pleural effusions, calcified lung nodules, calcified hilar lymph 
nodes, and pericardial calcification.
The chest x-ray (or, if done, computed axial tomography of the chest) must be negative for TB 
infection as determined by a qualified radiologist and/or pulmonary physician. Any new 
clinically significant findings post-Baseline during physical examination or on chest x-ray must 
be documented in the source documents and eCRF as an AE.
13.6.3
TB signs and symptoms 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 subjects who may 
require therapy for TB. A subject who answers “Yes” to the question
 
 
 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 subject has 
latent or active TB (see Section 6.2, Exclusion Criterion #16). A “Yes” response to any of the
questions during the study should trigger further assessments to determine if the subject has 
either LTB or active TB infection.
Subjects with a LTB or active TB infection must be withdrawn from the study and will have 
further assessments.
13.6.4
TB management
For inclusion in the study, see Section 6.2, Exclusion Criterion #16.
LTB infection and active TB identified during study
During the study, subjects who develop evidence of LTB infection or active TB must 
immediately stop further administration of study drug and will be referred to an appropriate TB 
specialist (pulmonologist or infectious disease specialist) for further evaluation. Evidence of 
LTB infection is defined as the subject’s IGRA test converting to positive or indeterminate (and 
confirmed indeterminate on repeat), or the subject’s questionnaire history or physical 
examination indicating that TB infection or exposure may have occurred. Evidence of active TB 
includes, in addition to the aforementioned tests, signs and symptoms of organ involvement. In 
either situation, the subject should be carefully assessed by a TB specialist for active TB. 
Subjects diagnosed with active TB or LTB infection should receive appropriate TB or 
prophylaxis therapy and must be withdrawn from the study.
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Confirmed active TB must be reported as a SAE. The Investigator is to complete and submit the 
TB follow-up form provided.
The subject should be transferred to the care of their physician and managed according to the 
standard-of-care. Subjects identified as having converted to active TB during the study must be 
withdrawn and scheduled to return for the EWV as soon as possible but no later than the next 
scheduled study visit and complete all EWV assessments. The subject should be encouraged to 
complete the SFU Visits after the final dose of study drug.
If infection with NTMB is identified during the study, the same procedure as for active TB 
acquired during the study must be followed. 
Follow-Up information of suspected and confirmed TB cases should be provided to UCB at least 
after 3, 9, and 12 months of the start date of anti-TB treatment, including hematological and 
biochemical safety parameters, x-ray evolution data, and TB diagnostic procedures used to 
follow-up and confirm recovery of TB.
13.7
Evaluation of PDILI
The PDILI IMP discontinuation criteria for this study are provided in Section 6.3.1, with the 
accompanying required follow-up investigation and monitoring detailed below. All PDILI events 
must be reported as an AE and reported to the study site and Sponsor within 24 hours of learning 
of their occurrence. Any PDILI event that meets the criterion for potential Hy’s Law must be 
reported as an AE of special interest (see Section 13.3), and, if applicable, also reported as an 
SAE (see Section 13.2.2).
Evaluation of PDILI consists of the diagnostic testing and continued monitoring included in
Table 13‒2 (specific tests dependent on lab results and corresponding symptoms) and consult 
with a local hepatologist (if applicable; discussed in Section 13.7.1). The local hepatologist is the 
expert usually consulted by the treating physician for assessment and management of potential 
hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist. 
Additional investigation and monitoring may be required and adapted based on the diagnosis 
after the cause of the liver injury/abnormality is confirmed (details in Section 13.7.3). 
The results of all monitoring, including labs and other testing, should be made available to the 
study site and Sponsor.
All initial abnormal hepatic lab values need to be repeated, but appropriate medical action must 
not be delayed waiting for the repeat result.
If tests are done locally for more rapid results, a concurrent sample should also be sent to the 
central laboratory whenever possible. Medical care decisions are to be made initially using the 
most rapidly available results and a conservative approach must be taken if the results from the 
2 laboratory tests are significantly different. Data from the local and central laboratory are to be 
recorded on the applicable eCRF pages.
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. In these cases, the Investigator should also 
consider dose reduction for medically necessary concomitant medication and consider changing 
any medically required concomitant medication known to be hepatotoxic to a suitable 
alternative.
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When IMP is stopped due to PDILI (as described in Section 6.3.1), IMP must be permanently 
discontinued unless a subsequent alternative diagnosis fully explains the hepatic findings. If a 
subsequent alternative diagnosis fully explains the hepatic findings, and the requirements 
provided in Section 13.7.2.1 are met, rechallenge with IMP may be appropriate. 
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
The table below summarizes the approach to investigate PDILI.
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Table 13‒2: Required investigations and follow up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥3xULN
≥2xULNb
NA
Hepatology consult.c
Medical Monitor 
must be notified 
within 24 hours 
(eg, by laboratory 
alert) and subject 
discussed with 
Medical Monitor 
ASAP.
Immediate, 
permanent IMP 
discontinuation.
Essential: Must 
have repeat liver 
chemistry values 
and additional 
testing completed 
ASAP (see
Section 13.7.3); 
recommended to 
occur at the site 
with HCP.
Monitoring of liver chemistry 
values at least twice per week 
until values normalize, stabilize, 
or return to within baseline 
values.d
≥8xULN
NA
NA
≥3xULN
NA
Yes
Immediate, 
temporary or 
permanent, IMP 
discontinuation.
≥3xULN 
(and ≥2x 
baseline) 
and 
<5xULN
<2xULN
No
Discussion with 
Medical Monitor 
required if the 
criterion that allows 
for IMP continuation 
is met.
Further investigation 
– immediate IMP 
discontinuation not 
required (see
Section 13.7.2).
Not required 
unless otherwise 
medically
indicated (at 
discretion of 
Investigator).
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Table 13‒2: Required investigations and follow up for PDILI
Laboratory value
Immediate
Follow up
ALT or 
AST
Total 
bilirubin
Symptomsa of 
hepatitis or 
hypersensitivity
Consultation 
requirements
Actions
Testing
Evaluation
≥5xULN 
(and ≥2x 
baseline) 
and 
<8xULN
<2xULN
No
Hepatology consult if 
there is no evidence 
of resolution (see 
Follow up 
requirements).c
Discussion with 
Medical Monitor 
required.
IMP discontinuation 
required if any of 
the following occur:
Subject cannot 
comply with 
monitoring 
schedule. 
Liver chemistry 
values continue to 
increase during 
2 week monitoring 
period.
Liver chemistry 
values remain 
≥5xULN (and 
≥2x baseline) after 
2 week monitoring 
period.
Essential: Every 
attempt must be 
made to have 
repeat liver 
chemistry values 
and additional 
testing completed 
within 48 hours 
at the site with 
HCP (see
Section 13.7.3).
Monitoring of liver chemistry 
values at least twice per week 
for 2 weeks.d
Immediate IMP discontinuation required if liver 
chemistry values continue to increase.
After 2 weeks of monitoring liver chemistry 
values:
Discontinue IMP if levels 
remain ≥5xULN (and ≥2x 
baseline); monitor until values 
normalize, stabilize, or return to 
within baseline values. d
Continue IMP if levels are no 
longer ≥5xULN (and ≥2x 
baseline); continue to monitor at 
least twice per week until 
values normalize, stabilize, or 
return to within baseline 
values.d
ALP=alkaline phosphatase; ALT=alanine aminotransferase; ASAP=as soon as possible; AST=aspartate aminotransferase; HCP=healthcare practitioner; 
IMP=investigational medicinal product; NA=not applicable; PDILI=potential drug-induced liver injury; ULN=upper limit of normal 
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, and fever (without clear alternative cause).
b If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Medical Monitor.
.c Details provided in Section 13.7.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of potential 
hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist.
d Unless an alternative monitoring schedule is agreed by the Investigator and UCB responsible physician. Determination of stabilization is at the discretion of the 
Investigator in consultation with the hepatologist (as applicable) and UCB responsible physician, as needed.
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13.7.1
Consultation with Medical Monitor and local hepatologist
Potential drug-induced liver injury events require notification of the Medical Monitor, within 
24 hours (eg by laboratory alert), and the subject must be discussed with the Medical Monitor as 
soon as possible. If required, the subject must also be discussed with the local hepatologist. The 
local hepatologist is the expert usually consulted by the treating physician for assessment and 
management of potential hepatic disease. This would usually be a hepatologist, but may be a 
gastroenterologist. If determined necessary, this discussion should be followed by a full 
hepatology assessment (see Section 13.7.3) and SAE report (if applicable).
13.7.2
Immediate action: determination of IMP discontinuation
All PDILI events require immediate action, testing, and monitoring.
The immediate action is dependent on the laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation of IMP (followed by immediate investigation) to 
immediate and permanent discontinuation (see Section 6.3.1 and Table 13‒2 for details).
When IMP is discontinued, all concomitant medications and herbal supplements that are not 
medically necessary should also be discontinued. The Investigator should also consider dose 
reduction for medically necessary concomitant medication and consider changing any medically 
required concomitant medication known to be hepatotoxic to a suitable alternative.
13.7.2.1
IMP restart/rechallenge (if applicable)
Rechallenge with a substance potentially causing drug-induced liver injury is dangerous, may be 
fatal, and must not occur.
Subjects who are immediately discontinued from IMP due to having met certain criteria for 
PDILI (as described in Section 6.3.1 and Table 13‒2), but for whom an alternative diagnosis is 
confirmed, can rarely restart IMP. Rechallenge with IMP can occur only if ALL of the following 
requirements are met:

The results of additional testing and monitoring described in Section 13.7.3 and 
Section 13.7.4 confirm a nondrug-related cause for the abnormal hepatic laboratory 
parameters and any associated symptoms (ie, a subsequent alternative diagnosis fully 
explains the hepatic findings). 

No alternative treatment options are available to the subject.

The subject has shown clear therapeutic benefit from the IMP.

Subject’s ALT or AST elevations do not exceed ≥3xULN.

Subject’s total bilirubin is <1.5xULN.

Subject has no signs or symptoms of hypersensitivity. 
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
The rechallenge is approved by the UCB responsible physician, DMC, and a hepatologist. 
The hepatologist must be external to UCB but may be a member of the DMC. It is 
recommended that the hepatologist be a local hepatology expert or the hepatologist treating 
the subject.

Subject agrees to the Investigator-recommended monitoring plan.
13.7.3
Testing: identification/exclusion of alternative etiology
The measurements and additional information required for the assessment of PDILI events when 
there is a reasonable possibility that it may have been caused by the IMP are detailed in 
Table 13‒3 (laboratory measurements) and Table 13‒4 (additional information). Results of the 
laboratory measurements and information collected are to be submitted to the Sponsor on the 
corresponding eCRF. If medical history of the subject indicates a requirement for other 
assessments not included below, these additional assessments should be completed and 
submitted, as applicable.
All blood samples should be stored, if possible. If tests are done locally for more rapid results, a 
concurrent sample must also be sent to the central laboratory.
Table 13‒3:
PDILI laboratory measurements
Virology-related
Hematology
Hepatitis A immunoglobulin M (IgM) antibody
Prothombin timea
International Normalized Ratio (INR)
Hepatitis B surface antigen (HBsAg)
Eosinophil count
Hepatitis E IgM antibody
Urinalysis
Hepatitis B core antibody-IgM (HBcAb-IgM)
Urine toxicology screen
Hepatitis C ribonucleic acid (RNA)
Chemistry
Cytomegalovirus IgM antibody
If bilirubin ≥1.5xULN, obtain fractionated bilirubin 
to obtain % direct bilirubin
Epstein Barr viral capsid antigen IgM antibody (if 
unavailable, obtain heterophile antibody or 
monospot testing)
Serum creatine phosphokinase (CPK) and lactate 
dehydrogenase (LDH) to evaluate possible muscle 
injury causing transaminase elevation
Immunology 
Amylase
Anti-nuclear antibody (qualitative and quantitative)
Additional
Anti-smooth muscle antibody (qualitative and 
quantitative)
Serum pregnancy test
Type 1 anti-liver kidney microsomal antibodies 
(qualitative and quantitative)
PK sample
ALT=alanine aminotransferase; PDILI=potential drug-induced liver injury; PK=pharmacokinetic; ULN=upper limit 
of normal
a Measured only for subjects with ALT >8xULN, elevations in total bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or 
tenderness; hypersensitivity symptoms include eosinophilia (>5%), rash, and fever (without clear alternative 
cause).
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The following additional information is to be collected:
Table 13‒4:
PDILI information to be collected
New or updated information
Concomitant prescription and over the counter medications (eg, acetaminophen, herbal remedies, 
vitamins); dosages and dates should be included.
Pertinent medical history, including the following:

history of liver disease (eg, autoimmune hepatitis, nonalcoholic steatohepatitis or other “fatty liver 
disease”)

adverse reactions to drugs

allergies

relevant family history or inheritable disorders (eg, Gilbert’s disease, alpha 1 antitrypsin deficiency)

recent travel and/or progression of malignancy involving the liver (note that metastatic disease to the 
liver, by itself, should not be used as an explanation for significant AST and/or ALT elevations)
The appearance or worsening of clinical symptoms of hepatitis or hypersensitivity (eg, fatigue, nausea, 
vomiting, right upper quadrant pain or tenderness, decreased appetite, abdominal pain, jaundice, fever, or 
rash)
Recent clinically significant hypotension or hypoxemia with compromised cardiopulmonary function
Alcohol and illicit drug use; include dates where available
Results of liver imaging or liver biopsy, if done
Results of any specialist or hepatology consult, if done
Any postmortem/pathology reports
ALT=alanine aminotransferase; AST=aspartate aminotransferase
13.7.4
Follow-up evaluation
All PDILI events require follow-up monitoring as described in Table 13‒2. Monitoring should 
continue until liver chemistry values normalize, stabilize, or return to baseline. Determination of 
stabilization is at the discretion of the Investigator in consultation with the hepatologist (as 
applicable) and UCB responsible physician, as needed.
13.8
Physical examination and interim medical history
The physical examination and the interim medical history is 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. 
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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. The outcome of physical examinations 
and the interim medical history must be documented in source documentation. The following 
body systems will be examined:

General Appearance

Ear, Nose and Throat

Eyes

Hair and Skin

Respiratory

Cardiovascular

Gastrointestinal

Musculoskeletal

Hepatic

Neurological (including focused assessment of reflexes, sensitivity, muscle strength)

Mental Status
13.9
Laboratory measurements
A central laboratory will perform all blood- and urine-based laboratory assessments except urine 
pregnancy tests, which will be performed at the site.
Subjects 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.
Certain coagulation tests (in particular, activated partial thromboplastin time [aPTT]) should only 
be performed using the central laboratory while subjects are receiving study drug as PEG may 
interfere with some aPTT assays leading to false results indicating prolongation of aPTT.
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.
Laboratory parameters that will be measured are listed in Table 13-5.
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Table 13-5: Laboratory measurements
Category
Parameters to be assessed
Clinical chemistry 
Liver function tests: bilirubin, AST, ALT, ALP, GGT, and LDH
Creatinine
Urea nitrogen
Electrolytes (sodium, potassium, calcium, and phosphate)
Total cholesterol and triglycerides
Total protein and albumin
Glucose
Lipase
Creatine phosphokinase
Hematology
Hemoglobin
Hematocrit 
Mean corpuscular volume 
RBC count
Erythrocyte sedimentation rate
Mean corpuscular hemoglobin concentration 
Mean corpuscular hemoglobin 
WBC count with differential (basophils, eosinophils, lymphocytes, monocytes, 
and neutrophils)
Platelet count
T cells (CD3+)
B cells (CD19+)
Additional 
assessments
HIV test
Hepatitis screening
Tuberculosis test (QFT-GIT)
Anti-dsDNA antibodies
ANAs, anti-ENAs (anti-SM, anti-SSA, anti-SSB, and anti-RNP) and RF
aPL antibodies including anticardiolipin antibodies, lupus anticoagulant a, and 
anti-β2 glycoprotein antibodies
Total Ig, IgG, IgM, IgA, and IgE
High sensitivity C-reactive protein
Serum complement (C3, C4)
Whole blood mRNA signature profiling
Proteomic signature profile
Cardiovascular proteins, lipids, lipid particles
Coagulation and hemostasis a
Coombs’ test (reflex testing to be performed by the central laboratory as 
indicated if signs of anemia are observed) a
Pregnancy testing
Serum test (β-hCG) (subjects of childbearing potential) at Screening (Visit 1)
Urine test (β-hCG) (subjects of childbearing potential) at all other visits
Urinalysis
pH
Protein
Glucose
Ketone
Urobilinogen
Bilirubin
Blood
Nitrite
Leukocytes
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Table 13-5: Laboratory measurements
Category
Parameters to be assessed
Urine chemistry and 
microscopy
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
Proteins and metabolites relevant to SLE
ANA=antinuclear antibody; anti-ENA=extractable nuclear antigen antibody; anti-RNP=anti-ribonucleoprotein 
antibody; anti-SSA=Sjögren’s syndrome antibody A; anti-SSB=Sjögren’s syndrome antibody B; anti-SM=Smith 
antibody; aPL=antiphospholipid; ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST=aspartate 
aminotransferase; β-hCG=beta human chorionic gonadotropin; dsDNA=double-stranded deoxyribonucleic acid; 
GGT=gamma-glutamyltransferase; HIV=human immunodeficiency virus; Ig=immunoglobulin; LDH=lactate 
dehydrogenase; mRNA=messenger ribonucleic acid; RBC=red blood cell; RF=rheumatoid factor; SLE=systemic 
lupus erythematosus; WBC=white blood cell
a As defined in the Laboratory Manual.
13.10
Vital signs
Vital sign measurements for all subjects will include height, weight, blood pressure (systolic and 
diastolic), pulse rate, and body temperature. 
Subjects will rest in the position used for dosing for at least 10min before and continue to rest in 
that position while pulse rate and blood pressure are measured. 
Table 5‒2 indicates the timings for vital sign assessments. Vitals signs should be measured 
within ±5min of the scheduled time point for the every 15min assessments and within ±10min of 
the scheduled time point for the every 30min assessments.
13.11
12-lead ECGs
Twelve-lead ECG assessments should be performed prior to dosing (if applicable) and prior to 
obtaining PK or other laboratory samples. Electrocardiograms will be recorded digitally and read 
by the Investigator for recording in the eCRF. 
Care should be taken to assure proper lead placement and quality ECG recording. Subjects 
should rest in a supine position in a controlled, calm environment for at least 15min 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.
Table 5‒2 indicates the visits at which 12-lead ECG assessments will be performed.
13.12
Assessment of suicidal ideation and behavior
Suicidal ideation and behavior will be assessed by trained study personnel 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. Table 5‒2 indicates the visits at which the C-SSRS assessments will be 
performed.
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14
STUDY MANAGEMENT AND ADMINISTRATION
14.1
Adherence to protocol
The Investigator should not deviate from the protocol. However, the Investigator should take any 
measure necessary in deviation from or not defined by the protocol in order to protect clinical 
study subjects from any immediate hazard to their health and safety. In this case, this action 
should be taken immediately, without prior notification of the regulatory authority, IRB/IEC, or 
Sponsor.
After implementation of such measure, the Investigator must notify the CPM of the Sponsor 
within 24 hours and follow any local regulatory requirements.
14.2
Monitoring
UCB (or designee) will monitor the study to meet the Sponsor’s monitoring Standard Operating 
Procedures (SOPs), ICH-GCP guideline, and applicable regulatory requirements, and to ensure 
that study initiation, conduct, and closure are adequate. Monitoring of the study may be 
delegated by UCB to a CRO or a contract monitor.
The Investigator and his/her staff are expected to cooperate with UCB (or designee) and to be 
available during the monitoring visits to answer questions sufficiently and to provide any 
missing information. The Investigator(s)/institution(s) will permit direct access to source 
data/documents for study-related monitoring, audits, IRB/IEC review, and regulatory 
inspection(s).
The Investigator will allow UCB (or designee) to periodically review all eCRFs and 
corresponding source documents (eg, hospital and laboratory records for each study participant). 
Monitoring visits will provide UCB (or designee) with the opportunity to evaluate the progress 
of the study, verify the accuracy and completeness of eCRFs, ensure that all protocol 
requirements, applicable authorities regulations, and Investigator’s obligations are being 
fulfilled, and resolve any inconsistencies in the study records.
14.2.1
Definition of source data
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, ECGs or other printouts, completed scales, or electronic 
questionnaires, 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 subject’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.
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Electronic data records, such as Holter monitor records or electroencephalogram records, must 
be saved and stored as instructed by UCB (or designee).
UCB expects to select approximately 4 to 6 US sites to participate in an Electronic Healthcare 
Record (EHR) pilot, which will test data extraction from the subjects’ EHR into the eCRF to 
populate fields in the Demography, Medical History, Concomitant Medications, and Vital Signs 
eCRFs. UCB stated the intention to pilot the use of EHR data in their response to FDA’s Federal 
Register Notice, Source Data Capture from Electronic Health Records: Using Standardized 
Clinical Research Data. For the purposes of the pilot, the EHR is considered the source for these 
fields. The sites participating in the EHR pilot are not expected to print the subjects’ EHRs.
14.2.2
Source data verification
Source data verification ensures accuracy and credibility of the data obtained. During monitoring 
visits, reported data are reviewed with regard to being accurate, complete, and verifiable from 
source documents (eg, subject files, recordings from automated instruments, tracings [ECG], 
x-ray films, laboratory notes). All data reported on the eCRF should be supported by source 
documents, unless otherwise specified in Section 14.2.1.
14.3
Data handling
14.3.1
Case Report Form completion
The study is performed using electronic data capture (EDC). The Investigator is responsible for 
prompt reporting of accurate, complete, and legible data in the eCRFs and in all required reports.
Any change or correction to the eCRF 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.
Detailed instructions will be provided in the eCRF Completion Guidelines.
14.3.2
Database entry and reconciliation
Case Report Forms/external electronic data will be entered/loaded into a validated electronic 
database using a clinical data management system (CDMS). Computerized data cleaning checks 
will be used in addition to manual review to check for discrepancies and to ensure completeness, 
consistency, and plausibility of the data. 
An electronic audit trail system will be maintained within the CDMS to track all data changes in 
the database once the data have been saved initially into the system or electronically loaded. 
Regular backups of the electronic data will be performed.
14.3.3
Subject Screening and Enrollment Log/Subject Identification Code 
list
The subject’s screening and enrollment will be recorded in the Subject Screening and Enrollment 
Log.
The Investigator will keep a Subject Identification Code list. This list remains with the 
Investigator and is used for unambiguous identification of each subject.
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The subject’s consent and enrollment in the study must be recorded in the subject’s medical 
record. These data should identify the study and document the dates of the subject’s 
participation.
14.4
Termination of the study
UCB reserves the right to temporarily suspend or prematurely discontinue this study either at a 
single site, multiple sites, or at all sites at any time for reasons including, but not limited to, 
safety or ethical issues, inaccurate or incomplete data recording, noncompliance, or
unsatisfactory enrollment with respect to quality or quantity.
If the study is prematurely terminated or suspended, UCB (or its representative) will inform the 
Investigators/institutions and the regulatory authority(ies) of the termination or suspension and 
the reason(s) for the termination or suspension, in accordance with applicable regulatory 
requirement(s). The IRB/IEC should also be informed and provided with reason(s) for the 
termination or suspension by the Sponsor or by the Investigator/institution, as specified by the 
applicable regulatory requirement(s). In addition, arrangements will be made for the return of all 
unused IMP and other material in accordance with UCB procedures for the study.
14.5
Archiving and data retention
The Investigator will maintain adequate records for the study, including eCRFs, medical records, 
laboratory results, Informed Consent documents, drug dispensing and disposition records, safety 
reports, information regarding participants who discontinued, and other pertinent data.
All essential documents are to be retained by the Investigator until at least 2 years after the last 
approval of a marketing application in an ICH region and until there are no pending or 
contemplated marketing applications in an ICH region, or at least 2 years have elapsed since the 
formal discontinuation of clinical development of the IMP. These documents should be retained 
for a longer period, however, if required by the applicable regulatory requirement(s) or by an 
agreement with UCB (CPMP/ICH/135/95, 2002 [Section 4.9.5]). 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 
study master file.
14.6
Audit and inspection
The Investigator will permit study-related audits mandated by UCB, after reasonable notice, and 
inspections by domestic or foreign regulatory authorities.
The main purposes of an audit or inspection are to confirm that the rights and well-being of the 
subjects enrolled have been protected, that enrolled subjects (ie, signing consent and undergoing 
study procedures) are appropriate for the study, and that all data relevant for the evaluation of the 
IMP have been processed and reported in compliance with the planned arrangements, the 
protocol, investigational site, and IRB/IEC SOPs, ICH GCP, and applicable regulatory 
requirements.
The Investigator will provide direct access to all study documents, source records, and source 
data. If an inspection by a regulatory authority is announced, the Investigator will immediately 
inform UCB (or designee).
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14.7
Good Clinical Practice
Noncompliance with the protocol, ICH-GCP, or local regulatory requirements by the 
Investigator, institution, institution staff, or designees of the Sponsor will lead to prompt action 
by UCB to secure compliance. Continued noncompliance may result in the termination of the 
site’s involvement in the study.
15
STATISTICS
A brief description of the planned statistical methods is provided in the sections that follow. Full 
details will be provided in the SAP. An additional interim SAP will describe the complete 
analysis of the Double-Blind Treatment Period (Part 1) of the study.
15.1
Definition of analysis sets
Seven analysis sets will be defined for this study: the Enrolled Set (ES), the Randomized Set 
(RS), the Safety Set (SS), the Full Analysis Set (FAS), the Per Protocol Set (PPS), the 
Pharmacokinetic Per Protocol Set (PK-PPS), and the Completer Set (CS). 
15.1.1
Enrolled Set
The ES will consist of all subjects who have given informed consent.
15.1.2
Randomized Set
The RS will consist of all subjects randomized into the study.
15.1.3
Safety Set
The SS will consist of all subjects who are randomized and have received at least 1 dose (any 
amount) of study drug. Safety variables will be analyzed using the SS.
It is expected that subjects will receive treatment as randomized; hence, safety analyses will be 
based on the randomized treatment group. However, if it is determined that a subject has 
consistently received treatment other than what they were randomized to, then for safety 
analyses, the subject will be allocated to the actual treatment they received.
15.1.4
Full Analysis Set
The FAS will consist of all subjects who have received at least 1 full dose of study drug and have 
at least 1 post-Baseline efficacy measurement during the Double-Blind Treatment Period. The 
FAS is the primary analysis set for efficacy analyses.
In case of mistreatment, subjects will be analyzed as randomized for the FAS. The FAS will only 
be used for subjects in Part 1 of the study (until the end of Double-Blind Treatment Period of the 
study).
15.1.5
Per Protocol Set
The PPS will consist of subjects in the FAS who have received at least 1 full dose of study drug 
and have no important protocol deviations during the Double-Blind Treatment Period that may 
influence the validity of the data for the primary efficacy variable, the BICLA.
Analyses of the primary efficacy variable will be repeated using the PPS.
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15.1.6
Pharmacokinetic Set
The PK-PPS will consist of all subjects in the SS who have provided at least 1 PK sample and 
for whom no important protocol deviations affecting the PK variables have been documented. 
This analysis set will be used for all PK analyses.
15.1.7
Completer Set
The CS will consist of all subjects who did not permanently discontinue study drug during the 
Double-Blind Treatment Period (Part 1), completed Week 24 of Part 1, and continued into the 
Observational Period (Part 2) of the study.
15.2
General statistical considerations
For continuous data in general, summary statistics (n [number of available measurements], 
arithmetic mean, standard deviation, median, minimum, and maximum) will be presented by 
treatment group. 
For descriptive statistics of continuous variables, change from Baseline and the value at the time 
point itself will be displayed.
Frequency tables (frequency counts and percentages) will be presented for categorical data. If 
there are missing values, either a missing category will be included in the display or the number 
of nonmissing results will be used for calculations.
In general, percentages will be calculated based on the utilized analysis set; however, in case any 
analysis subsets are affected then the N of the subset will be used as denominator. Subsets of 
analysis sets will be described more in detail in SAPs.
Unless otherwise specified in the SAPs, the last measurement before study drug infusion will be 
used as the Baseline value. For almost all variables, this will be the Baseline assessment. 
However, for some variables, assessments may be scheduled for Screening only and not for 
Baseline. In this case the Screening value will be utilized as Baseline value. If a Baseline 
measurement is missing, and a Screening value available, the Screening value will be utilized as 
Baseline instead.
In general (if not otherwise specified in the SAPs), tables and figures will be presented by 
randomized treatment during the Double-Blind Treatment Period for the entire study.
The end of the Double-Blind Treatment Period (Part 1) of the study is defined as the date of the 
last Week 24 visit of the last subject in the study or the date of the last SFU Visit of the last early 
terminating subject (before Week 24) in the study, whichever is later. The end of the study is 
defined as the date of the last visit of the last subject in the study.
For the calculation of the SLEDAI-2K, the central laboratory information will be used for 
anti-dsDNA and complement, not the eCRF-derived information.
Assessments of SRI-4, -5, and -6 will include an assessment of nonresponders based on 
concomitant medication rules.
Data from EWVs will be recoded to the closest scheduled treatment period visit (after the last 
nonmissing visit value).
Handling of any mistreatments will be described in more detail in the SAPs.
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Analyses of the primary and secondary efficacy variables will be repeated for the PPS.
15.3
Planned efficacy analyses
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 
level disease if no value can be imputed from the Screening Visit. For post-Baseline assessments, 
if the BILAG 2004 is scored, but the grade for 1 or more individual system(s) is missing or 
scored as “Not applicable,” then the grade for that system will be set to the grade at the previous 
visit. 
The underlying assumption supporting imputation of missing post-Baseline BILAG 2004 grades 
with results from the prior visit is that the value at the preceding visit is the most accurate 
estimate of the value at the current visit. The underlying assumption supporting imputation of 
missing BILAG 2004 grades at Baseline with a grade of BILAG 2004 D level disease is that this 
is a conservative reasonable approach, since no improvement can occur following a Baseline 
grade of BILAG 2004 D level disease.
Missing values for Physician’s Global Assessment of Disease will be imputed via last 
observation carried forward (LOCF).
15.3.1
Analysis of the primary efficacy variable
The primary efficacy variable is the BICLA responder at Week 24 across 3 doses of DZP and 
PBO. The BICLA is a binary efficacy response variable, which is a composite endpoint derived 
from the efficacy components: BILAG 2004, SLEDAI-2K, and the Physician’s Global 
Assessment of Disease Activity. The BILAG 2004 and SLEDAI-2K are themselves composite 
endpoints comprising of multiple assessments of several organ systems affected by SLE. In 
addition, usage of specified concomitant medication as escape treatment is also a factor in 
determining BICLA responder status. See Section 9.1.9.1 for a complete description of the 
BICLA composite variable. Modified nonresponder imputation will be used to impute missing 
data, after applying additional rules within each component, which are further detailed as 
follows:
If 1 of the 3 efficacy components (BILAG 2004, SLEDAI-2K, or Physician’s Global Assessment 
of Disease) is missing, but the visit was performed and all other assessments were completed, the 
missing component will be imputed from the subject’s previous post-baseline assessment, prior 
to computing the treatment response variable, following the last observation carried forward 
principle. 
Furthermore, for BILAG 2004 and SLEDAI-2K, if the assessment was done, but individual 
system or item scores are missing, the respective individual score will be imputed from the 
respective previous post-baseline score, in order to obtain a score for the current visit, prior to 
computing the system or score. If the value at the previous visit is also missing, or if the subject 
has 2 or more missing components at Week 24, then the treatment response value is considered 
to be unknown (ie, left as missing and therefore considered a nonresponder).
In addition, subjects who discontinue treatment prematurely (while still remaining in the study) 
are primarily categorized as nonresponder from that visit and all subsequent visits.
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The Week 24 BICLA dose-response relationship across 3 doses of DZP and PBO will be 
evaluated using the Multiple Comparison Procedure–Modelling (MCP-Mod) methodology 
(Bretz et al, 2005). Monotonic dose-response trends will be tested using the appropriate contrasts 
as determined by the MCP-Mod methodology such that the overall Type 1 error rate is controlled 
at 0.05 (one-sided testing).
The SAP will describe additional features and detail around the MCP-Mod methodology as well 
as handling of missing data.
15.3.2
Other efficacy analyses
The analysis of the secondary and other efficacy responder rates will use a similar approach for 
handling of dropouts as previously described for the primary efficacy variable of treatment 
response at Week 24 (ie, dropouts are included as nonresponders). 
The number and percent of responders in each treatment group will be presented. The crude 
difference in proportions of responders between each DZP treatment group and PBO will also be 
presented along with 95% CIs for the difference in proportions (Fleiss, 1981). Treatment group 
differences between each DZP group and PBO will be computed along with odds ratio and 95% 
CI.
Additionally, an estimate of the treatment differences at Week 24 will be obtained from a 
longitudinal generalized estimating equation model for binary outcome, and with a treatment by 
week interaction term. An unstructured covariance matrix will be used for this analysis. Missing 
values are not explicitly imputed, and remain missing in the model. All available scheduled 
post-Baseline assessments are utilized for deriving Week 24 treatment differences.
Analyses of continuous efficacy variables will be performed using mixed effects models for 
repeat measurement. These models will use all available post-Baseline data at all visits up to and 
including Week 24, and will be incorporated as repeated measures within each subject. Data 
from EWVs (prior to Week 24) will be recoded to the closest scheduled treatment period visit 
(after the last nonmissing visit value). Multiple visits for each subject will be incorporated as 
repeated measures within each subject. An unstructured covariance matrix will be utilized and 
least squares means for changes from Baseline and 95% CIs for each treatment group will be 
presented. Estimated treatment differences for each DZP dose group versus PBO and 
corresponding 95% CIs and p-values will be presented for each scheduled time point. This will 
apply to the following variables: Physician’s Global Assessment of Disease Activity scores and 
SLEDAI-2K scores.
Supportive models of the continuous efficacy variables will involve analysis of covariance 
models with treatment group as a factor and Baseline score as a covariate. Least squares means 
for changes from Baseline at each visit and 95% CIs for treatment groups and treatment 
difference will be presented. These supportive analyses will be performed using as observed case 
models using all available data at each visit.
Analyses of the secondary efficacy variable will be repeated for the PPS for the Double-Blind 
Treatment Period (Part 1).
Patient-reported outcomes variables will be analyzed as continuous efficacy variables. For PRO 
variables that cannot be considered continuous (if any), analysis methods for longitudinal ordinal 
data may be used. Analyses of PRO variables will be performed for the Double-Blind Treatment 
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Period (Part 1) and for the Observational Period (Part 2) of the study. Analysis of the PRO data 
in the Observational Period (Part 2) will aim to explore the maintenance of patient-perceived 
treatment benefits after end of treatment. Analyses to support the interpretation of change in 
PRO variables will be performed (cumulative distribution functions, responder analysis). In 
addition, psychometric analyses of the newly developed measures (SLE-S, SLE-F, SLE-M, 
SLE-P, and SLE-E) will be performed blinded from treatment arms. The association between 
PROs and clinical variables will also be explored, as well as the association between the various 
PROs.
For all efficacy variables, DZP treatment arms, when statistically compared with PBO, will use a 
two-sided α=0.05 level of significance, without any adjustment for multiple comparisons. As 
such, these results are considered exploratory in nature and caution should be exercised in 
interpreting these results. Pairwise treatment comparisons for efficacy variables will be 
performed for the Double-Blind Treatment Period (Part 1) only.
An observed case analysis will be also performed as another sensitivity analysis for responder 
efficacy variables (BICLA, SRI).
15.4
Planned safety and other analyses
All safety summaries will be performed using the SS.
15.4.1
Safety analyses
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 (Medical Dictionary for 
Regulatory Activities). The data will be displayed as number of subjects experiencing the AEs, 
percentage of subjects, and number of AEs. Data will also be corrected for exposure and reported 
by 100 patient-years.
The incidence of subjects with AEs will be presented by treatment group and total treatment. 
Additional tables will summarize AEs leading to permanent discontinuation of study drug (for 
Part 1 only), AEs by maximum intensity, AEs by intensity, and AEs by relationship to study 
drug 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 
subjects who experienced the respective AE.
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.
15.4.2
PK analyses
Individual subject 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). 
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For DZP and PEG, the Cmax and Ctrough per visit will be obtained directly from the plasma 
concentration time profiles. The AUCτ will be derived via a population approach using nonlinear 
mixed effects modeling. Dapirolizumab pegol PK data from SL0023 may be combined with 
other studies in the population PK approach and the analysis will be described in a separate Data 
Analysis Plan. The AUCτ following the last treatment visit in SL0023 will be derived, listed, and 
summarized together with the Cmax and Ctrough values.
The concentration of PEG in urine will also be summarized.
If data merit, PK/PD analyses may be conducted for the clinical efficacy endpoints and PD 
variables of interest. All PK/PD analyses will be described in more detail in a separate Data 
Analysis Plan, and results will be reported in an appendix to the CSRs.
Data Analysis Plans for PK/PD will be created separately for the Double-Blind Treatment Period 
(Part 1) alone, and for the complete study including the Observational Period (Part 2).
15.4.3
Immunogenicity analyses
Anti-DZP and anti-PEG antibodies will be tabulated. More detailed specifications will be 
presented in the SAP.
15.5
Handling of protocol deviations
Important protocol deviations are deviations from the protocol which potentially could have a 
meaningful impact on study conduct or on the primary efficacy, key safety, or PK outcomes for 
an individual subject. 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.
Important protocol deviations for the primary efficacy variable will be identified through 
Week 24.
Further details on the handling of protocol deviations will be described in the SAPs.
15.6
Handling of dropouts or missing data
Handling of missing endpoint data for the primary efficacy analysis is described in Section 15.3
and the analysis of the secondary and other efficacy responder rates will use a similar approach 
for handling of dropouts or missing data. 
In the case where laboratory results are missing at a non-Baseline visit, the laboratory result from 
the central laboratory at the prior visit will be used in determining the BILAG 2004 body/organ 
system score at the visit at which the laboratory value is missing. In the case where the 
laboratory result is missing at the Baseline Visit, the BILAG 2004 body/organ system score for 
the body system requiring the missing laboratory result will be set to a score of BILAG 2004 D 
level disease.
In addition, for purposes of computing a SLEDAI-2K total score, in the case where the 
SLEDAI-2K assessment has been done yet individual items have been left blank (ie, a “Yes” or 
“No” response for the item was not provided), these individual items will be imputed from the 
previous visit value prior to computing the total score. As an additional sensitivity analysis, 
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rather than imputing missing component values from previous visit values, when a total score 
cannot be computed due to 1 or more missing individual items, the total score will be imputed by 
extrapolating from the score based on the nonmissing items at the visit. In this scenario, provided 
that at least 75% of the individual items have a nonmissing response, the total of nonmissing 
items will be computed. This total will then be extrapolated to the equivalent value based on the 
total maximum value of the SLEDAI-2K instrument. Additional sensitivity analyses based on 
alternate approaches for handling of dropouts or missing data may be performed to support the 
robustness of the study results and will be described in the SAPs.
15.7
Planned interim analysis and data monitoring
An initial biomarker analysis may be performed on all evaluable biomarker data from Part 1 of 
the study when 25%-35% of the randomized subjects have completed Visit 7 (Week 12) of the 
Double-Blind Treatment Period. Data from subjects who have prematurely withdrawn from the 
study prior to Visit 7 will be included. The initial biomarker analysis will focus on transcriptomic 
biomarker variables (eg, mRNA), prespecified in a Biomarker Plan, in order to provide guidance 
for the DZP development program, and will not affect the conduct of the study. This initial 
biomarker analysis will not affect the conduct of the study and no adjustment to the final analysis 
is planned.
The tabulations for the initial biomarker analysis will be provided by individuals not otherwise 
involved in the conduct of the study. Blinding aspects of the initial biomarker analysis are 
described in Section 7.9.1.
After the last subject completes Part 1 of the study (including the SFU Period for early 
withdrawals from Part 1 or subjects not continuing into Part 2, if applicable), the data for those 
subjects will be secured and an interim CSR will be written for the Double-Blind Treatment 
Period (Part 1) of the study; this interim CSR will not include any data from the Observational
Period (Part 2). A biomarker analysis on the full Double-Blind Treatment Period (Part 1) dataset 
will be included in the interim CSR. A complete final CSR will be written for the entire study 
following completion of the Observational Period (Part 2) of the study.
15.8
Determination of sample size
The size of this study is governed by determining whether there is a dose-response relationship 
across the 3 doses of DZP and PBO using the MCP-Mod methodology, as described in 
Section 15.3.1. The primary endpoint of the study is a binary indicator of whether the subject
responds to treatment. Four different dose-response models (“candidate models”) were 
identified: a linear model, a logistic model, and 2 Emax models, and the MCP-Mod methodology 
controls for multiplicity.
The sample size assessment was estimated using the “DoseFinding” library in the R statistical 
package (Bretz et al, 2005). This library implements design and analysis aspects of the 
MCP-Mod method. The sample size requirement was obtained for each candidate model in turn 
and the maximum value was taken, thus maintaining the power requirement.
Since the Dose Finding library assumes Normal data with constant variance, and the primary 
endpoint (responder rate) is binary, the Normal approximation was used. This entailed 
calculating the predicted response probabilities at each dose, for each of the candidate models, 
computing the binomial variances and then using these variances in the sample-size calculations. 
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Based upon prior experience in SLE, a placebo responder rate for this study of 25% is postulated. 
The desired clinical effect is 29% above PBO, resulting in a responder rate of 54%. With power 
of 80%, a (multiple-comparison corrected) one-sided type-1 error of 5% and all dose groups of 
the same size, 112 subjects are required to complete Part 1 of the study.
Adjusting for an expected dropout rate of 30% results in the need to randomize 160 subjects 
(40 subjects per treatment group). Assuming a screening failure rate of approximately 40%, it is 
anticipated to enroll around 267 subjects in this study.
16
ETHICS AND REGULATORY REQUIREMENTS
16.1
Informed consent
Subject’s informed consent 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 subject in both oral and written form by the Investigator (or 
designee). Each subject will have the opportunity to discuss the study and its alternatives with 
the Investigator.
Prior to participation in the study, the written Informed Consent form should be signed and 
personally dated by the subject, and by the person who conducted the informed consent 
discussion (Investigator or designee). The subject must receive a copy of the signed and dated 
Informed Consent form. As part of the consent process, each subject must consent to direct 
access to his/her medical records for study-related monitoring, auditing, IRB/IEC review, and 
regulatory inspection.
If the Informed Consent form 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 US must include the use of a Health Insurance Portability 
and Accountability Act Authorization form.
The subject may withdraw his/her consent to participate in the study at any time. A subject is 
considered as enrolled in the study when he/she has signed the Informed Consent form. An eCRF 
must not be started, nor may any study-specific procedure be performed for a given subject, 
without having obtained his/her written consent to participate in the study.
16.2
Subject identification cards
Upon signing the Informed Consent and Assent form (as applicable), the subject will be provided 
with a subject identification card in the language of the subject. The Investigator will fill in the 
subject identifying information and medical emergency contact information. The Investigator
will instruct the subject to keep the card with him/her at all times.
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16.3
Institutional Review Boards and Independent Ethics 
Committees
The study will be conducted under the auspices of an IRB/IEC, as defined in local regulations, 
ICH-GCP, and in accordance with the ethical principles that have their origin in the Declaration 
of Helsinki.
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, Informed 
Consent form, Investigator’s Brochure, Investigator’s curriculum vitae (if applicable), 
advertisement (if applicable), and all other subject-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 human subjects or others, and any protocol deviations, 
to eliminate immediate hazards to subjects.
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 subjects. 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 subject 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.
16.4
Subject privacy
UCB staff (or designee) will affirm and uphold the subject’s confidentiality. Throughout this 
study, all data forwarded to UCB (or designee) will be identified only by the subject 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 
subject’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 
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admissions occurring during a subject’s study participation, and autopsy reports for deaths 
occurring during the study).
16.5
Protocol amendments
Protocol changes may affect the legal and ethical status of the study and may also affect the 
statistical evaluations of sample size and the likelihood of the study fulfilling its primary 
objective.
Significant changes to the protocol will only be made as an amendment to the protocol and must 
be approved by UCB, the IRB/IEC, and the regulatory authorities (if required), prior to being 
implemented.
17
FINANCE, INSURANCE, AND PUBLICATION
Insurance coverage will be handled according to local requirements.
Finance, insurance, and publication rights are addressed in the Investigator and/or CRO 
agreements, as applicable.
18
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LE Disease Area and Severity Index): an outcome instrument for cutaneous lupus erythematosus. 
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Al Sawah S, Zhang X, Zhu B, Magder LS, Foster SA, Iikuni N, et al. Effect of corticosteroid use 
by dose on the risk of developing organ damage over time in systemic lupus erythematosus—the 
Hopkins Lupus Cohort. Lupus Sci Med. 2015;2:e000066.
Borchers AT, Naguwa SM, Shoenfeld Y, Gershwin ME. The geoepidemiology of systemic lupus 
erythematosus. Autoimmun Rev. 2010;9:A277-87.
Boumpas DT, Furie R, Manzi S, Illei GG, Wallace DJ, Balow JE, et al. A short course of 
BG9588 (anti-CD40 ligand antibody) improves serologic activity and decreases hematuria in 
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Bretz F, Pinheiro JC, Branson M. Combining multiple comparisons and modeling techniques in 
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mortality in systemic lupus erythematosus during a 10-year period: a comparison of early and 
late manifestations in a cohort of 1,000 patients. Medicine (Baltimore). 2003;82:299-308.
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erythematosus. J Rheumatol. 2001;28:95-101.
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Devilliers H, Amoura Z, Besancenot JF, Bonnotte B, Pasquali JL, Wahl D, et al. Responsiveness 
of the 36-item Short Form Health Survey and the Lupus Quality of Life questionnaire in SLE. 
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Gladman DD, Urowitz MB, Rahman P, Ibañez D, Tam LS. Accrual of organ damage over time 
in patients with systemic lupus erythematosus. J Rheumatol. 2003;30:1955-9.
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immune complexes potently activate platelets in vitro and cause thrombosis in FCGR2A 
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consensus for a definition of disease flare in lupus. Lupus. 2011;20(5):453-462.
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organ damage. J Rheumatol. 2009;36:560-4.
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Erthematosus Disease Activity Index 200 Responder Index-50 enhances the ability of SLE 
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19
APPENDICES
19.1
SLICC classification criteria for SLE
A subject is classified as having SLE if he or she satisfies 4 of the clinical and immunologic 
criteria used in the SLICC classification criteria, including at least 1 clinical criterion and 
1 immunologic criterion, OR if he or she has biopsy-proven nephritis compatible with SLE in the 
presence of ANAs or anti-dsDNA antibodies. 
The criteria do not need to be present concurrently. A criterion should only be judged as fulfilled 
if better explained by other causal relationships (eg, other disease, drug-site effects).
2012 SLICC SLE Criteria
Clinical Criteria
Has the subject ever experienced any of the following clinical criteria?
1. Acute Cutaneous Lupus
Lupus malar rash (do not count if malar discoid)
Yes
No
Bullous lupus
Yes
No
Toxic epidermal necrolysis variant of SL
Yes
No
Maculopapular lupus rash
Yes
No
Photosensitive lupus rash in the absence of dermatomyosit
Yes
No
Subacute cutaneous lupus (nonindurated psoriaform and/or annular polycyclic lesions that resolve without 
scarring, although occasionally with postinflammatory dyspigmentation or telangiectasias)
Yes
No
2. Chronic Cutaneous Lupus
Localized classical discoid rash (above the neck)
Yes
No
Generalized classical discoid rash (above and below the neck)
Yes
No
Hypertrophic (verrucous) lupus
Yes
No
Lupus panniculitis (profundus)
Yes
No
Mucosal lupus
Yes
No
Lupus erythematosus tumidus
Yes
No
Chillblains lupus
Yes
No
Discoid lupus/lichen planus overlap
Yes
No
3. Oral or nasal ulcers in the absence of other causes, such as vasculitis, Behcets disease, infection 
(herpes), inflammatory bowel disease, reactive arthritis, and acidic foods
Palate
Yes
No
Buccal
Yes
No
Tongue
Yes
No
Nasal
Yes
No
4. Non-scarring alopecia in the absence of other causes such as alopecia areata, drugs that cause alopecia, 
iron deficiency and androgenic alopecia (diffuse thinning or hair fragility with visible broken hairs)
Yes
No
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5. Synovitis involving 2 or more joints, characterized by swelling or effusion OR tenderness in 2 or more 
joints and thirty minutes or more of morning stiffness
Yes
No
6. Serositis
Typical pleurisy for more than 1 day
Yes
No
Pleural effusions
Yes
No
Pleural rub
Yes
No
Typical pericardial pain (pain with recumbency improved by sitting forward) for more than 1 day
Yes
No
Pericardial effusion
Yes
No
Pericardial rub
Yes
No
Pericarditis by ECG in the absence of other causes, such as infection, uremia, and Dressler's pericarditis..........
Yes
No
7. Renal
Urine protein/creatinine ratio (or 24hr urine protein) representing 500mg of protein/24hr
Yes
No
Red blood cell casts
Yes
No
8. Neurologic
Seizures
Yes
No
Psychosis
Yes
No
Mononeuritis multiplex in the absence of other known causes such as primary vasculitis
Yes
No
Myelitis
Yes
No
Peripheral or cranial neuropathy in the absence of other known causes such as primary vasculitis, infection, 
and diabetes mellitus
Yes
No
Acute confusional state in the absence of other causes, including toxic-metabolic, uremia, drugs
Yes
No
9. Hemolytic anemia
Yes
No
10. Leukopenia
Leucocytes <4000/mm3 at least once in the absence of other known causes such as Felty's syndrome, drugs, 
and portal hypertension
Yes
No
Lymphocytes <1000/mm3 at least once in the absence of other known causes such as corticosteroids, drugs 
and infection
Yes
No
11. Thrombocytopenia (<100000/mm3) in the absence of other known causes such as drugs, portal 
hypertension, and thrombotic thrombocytopenic purpura (TTP)
Yes
No
Immunological criteria
1. ANA above laboratory reference range in the absence of drugs known to cause ANA increase......................
Yes
No
2. Anti-dsDNA antibody above laboratory reference range, except enzyme-linked immunosorbent assay 
(ELISA): twice above laboratory reference range
Yes
No
3. Anti-Sm antibod
Yes
No
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4. Antiphospholipid antibody
Positive lupus anticoagulant test
Yes
No
False-positive rapid plasma reagin
Yes
No
Medium or high titer anticardiolipin antibody level (IgA, IgG, or IgM)
Yes
No
Positive test result for anti-β2 glycoprotein I (IgA, IgG, or IgM)
Yes
No
5. Low complement (C3, C4, CH50)
Low C3
Yes
No
Low C4
Yes
No
Low CH50
Yes
No
6. Direct Coombs’ test (in the absence of hemolytic anemia)
Yes
No
Pathohistological Findings
Biopsy proven Nephritis compatible with SLE:
Class I
Yes
No
Class II
Yes
No
Class III
Yes
No
Class IV
Yes
No
Class V
Yes
No
Class VI
Yes
No
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19.2
Equivalent doses of oral steroids
Oral Steroids
Equivalent Dose (mg/day)
Cortisone, oral
25
Hydrocortisone, oral
20
Deflacort, oral
6
Prednisolone, oral
5
Prednisone, oral
5
Methylprednisolone
4
Triamcinolone, oral
4
Dexamethasone, oral
0.75
Betamethasone, oral
0.6
Note: For topically applied corticosteroids and intra-articular, subcutaneous, or ocular steroids, equivalent dose=0.
Cortisol (hydrocortisone) is the standard of comparison for glucocorticoid potency.
Hydrocortisone is the name used for pharmaceutical preparations of cortisol.
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19.3
Suggested management guidelines for infusion reactions
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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19.4
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 
subject (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 subject (minutes to several 
hours): systolic blood pressure of <90mmHg or >30% decrease from the subject’s Baseline.
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19.5
Protocol-specific clarification and extension of BILAG 2004
definitions
A quick 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. Please refer to this 
guide when completing disease activity assessments. Important extensions of selected 
BILAG 2004 glossary definitions are included as follows:
Protocol specific extensions of BILAG 2004 and SLEDAI-2K clinical parameter definitions:
a.
BILAG 2004 A or B score in the musculoskeletal organ system due to active polyarthritis, 
defined as follows:

“BILAG 2004 A”: severe arthritis (BILAG 2004 #41) manifested by observed active 
synovitis in ≥2 joints with marked loss of functional range of movements and significant 
impairment of basic activities of daily living (ADL), that has been present on several 
days cumulatively over the past 4 weeks, including at the time of the Screening Visit. 
Basic ADL are defined as the following activities which require assistance or assistive 
devices (at least 1 must be present and documented in source): ambulation, toileting, 
grooming including bathing, dressing, feeding oneself (not responsive to steroids up to 
10mg/day, antimalarials, NSAIDs).

“BILAG 2004 B”: moderate arthritis or tendonitis or tenosynovitis (BILAG 2004 #42) 
defined as tendonitis/tenosynovitis or active synovitis in ≥1 joint (observed or through 
history) with some loss of functional range of movements which leads to some loss of 
functional range of motion as manifested by effects on instrumental ADLs (such as 
cooking, driving, using the telephone or computer, shopping, cleaning, etc), which has 
been present on several days over the last 4 weeks and is present at the time of the 
Screening Visit.
b. BILAG 2004 and SLEDAI-2K “lupus headache”: lupus headache is rare; migraine, tension 
or cluster headaches should not be recorded. Lupus headache should only be recorded if it is 
disabling, lasts at least 3 days, and does not respond to narcotics. It is expected that its 
severity would prompt formal testing (lumbar puncture, magnetic resonance imaging, 
computed tomography, etc) and require corticosteroids and/or immunosuppressants and 
potentially hospitalization for treatment. Lupus headache is considered a manifestation of 
lupus cerebritis.
19.6
Protocol Amendment 1
Rationale for the amendment
The primary objective for this amendment is to allow for qualitative subject interviews to be 
conducted by an experienced, external third party vendor and to allow for assessments of hsCRP 
at 4-week intervals and serum complement (C3 and C4) at Visit 14. Anti-DZP and anti-PEG 
antibody assessments have been removed from Visits 13 and 14 and additional text has been 
added. The inclusion of subjects who lack capacity to consent mentally or physically has been 
removed since some protocol assessments require mental and physical abilities. The eligibility of 
subjects with an overlap syndrome has been clarified. The protocol has also been updated 
according to the new UCB protocol template (for example, with the update of text regarding 
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PDILI); these changes were strictly template-driven. They do not reflect a change in the liver 
safety signal for DZP and are included only for alignment with updated standard Sponsor text 
across programs.
Modifications and changes
Global changes
“Drug Safety” was changed to “Patient Safety” to reflect the renaming of that functional group 
at UCB.
“International Conference on Harmonisation” was changed to “International Council for 
Harmonisation.”
Minor stylistic and typographical changes were made for consistency within the document (eg, 
“the investigator” was changed to “the Investigator” at all occurrences).
Specific changes
The following table presents specific changes made with Amendment 1. This table does not 
include global changes unless they occur in other changed text.
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Specific changes with SL0023 Amendment 1
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section(s)
impacted
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Key components of amended text
Rationale
Study contact 
information
Sponsor
UCB Biosciences Inc.
8010 Arco Corporate Drive, Ste 100
Raleigh, NC 27617
USA
Sponsor
UCB Biopharma SPRL
Allée de la Recherche 60, 1070 
Brussels, Belgium
Update to match title page.
Update to reflect current 
contact information.
Clinical Project Manager
Clinical Project Manager
Clinical Trial Biostatistician
UCB BIOSCIENCES GmbH
Alfred-Nobel-Str. 10
40789 Monheim
GERMANY
Clinical Trail Biostatistician
UCB Biosciences Inc.
8010 Arco Corporate Drive, Ste 100
Raleigh, NC 27617
USA
SAE
reporting 
Email
Global: safetyreportingCDP7657@ucb.com
(for interventional clinical studies)
Email
Global: safetyreportingCDP7657@ucb.com
Removal of unnecessary 
information about 
interventional studies.
List of 
Abbre-
viations
DS: Drug Safety
ICH: International Conference on 
Harmonisation
PS: Patient Safety
ICH: International Council for Harmonisation
Administrative update.
Table 5-2 and 
Sections 8.8 
and 8.9
Assessment of anti-DZP and anti-PEG 
antibodies included at Visits 13 and 14.
Assessment of anti-DZP and anti-PEG 
antibodies removed/excluded from Visits 13 
and 14.
Removal since extensive 
testing during the observation 
period no longer considered 
necessary.
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Specific changes with SL0023 Amendment 1
Protocol
section(s)
impacted
Key components of previous text
Key components of amended text
Rationale
Table 5-2 and
Section 8.9
No assessment of serum complement (C3, C4) 
included at V14.
Assessment of serum complement (C3, C4) 
added to V14.
Correction of omitted serum 
complement measurement
needed for SLEDAI-2K
calculation.
Table 5-2 and
Sections 8.1, 
8.3, 8.4, 8.6, 
8.8, 8.9, and 
8.11
No assessment of hsCRP included at V1, V3, 
V4, V6, V8, V9, V11, V14, or the 
Unscheduled Visit.
Assessment of hsCRP added to V1, V3, V4, 
V6, V8, V9, V11, V14, and the Unscheduled 
Visit (Section 8.11).
Alignment with other 
laboratory assessments of 
safety.
Section 6.1
1.  An Institutional Review Board 
(IRB)/Independent Ethics Committee (IEC) 
approved written Informed Consent form is 
signed and dated by the subject or legal 
representative prior to the initiation of any 
study-specific assessment at Screening 
(Visit 1). 
1a. An Institutional Review Board 
(IRB)/Independent Ethics Committee 
(IEC) approved written Informed Consent 
form is signed and dated by the subject 
prior to the initiation of any study-specific 
assessment at Screening (Visit 1). 
Revision to not include
subjects who lack capacity to 
consent mentally or 
physically since some 
protocol assessments require 
mental and physical abilities.
13. Female subjects of childbearing 
potential must agree to use a highly 
effective method of birth control during 
the study and for a period of 12 weeks after 
their final dose of study drug (ie, through 
completion of the SFU Period). Highly 
effective forms of birth control are methods 
which achieve a failure rate of less than 1% 
per year when used consistently and 
correctly. Highly effective methods of birth 
control include:
13a.Female subjects of childbearing 
potential must agree to use a highly 
effective method of birth control during 
the study and for a period of 12 weeks 
after their final dose of study drug 
(ie, through completion of the SFU 
Period). Highly effective forms of birth 
control are methods which achieve a 
failure rate of less than 1% per year when 
used consistently and correctly. Highly 
effective methods of birth control include, 
but are not limited to:
Revision to provide clarity 
that the birth control methods
are examples only.
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Specific changes with SL0023 Amendment 1
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impacted
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Section 6.2
5. Subject has a mixed connective tissue 
disease, scleroderma, and/or overlap 
syndromes of SLE.

Subjects with SLE and secondary 
Sjögren’s syndrome are permitted 
provided they meet the eligibility 
criteria.
5a. Subject has a mixed connective tissue 
disease, scleroderma, and/or overlap 
syndromes of SLE.

Subjects with SLE and secondary 
Sjögren’s syndrome are permitted 
provided they meet the eligibility
criteria.

Clarification: Subjects with 
rheumatoid arthritis in their medical 
history are not considered as having an 
overlap syndrome and are thereby 
eligible, except when erosive arthritis 
is the only symptom at Screening.
Clarification provided for the 
eligibility of subjects with a 
medical history of rheumatoid 
arthritis.
Section 6.3

Subject has potential drug-induced 
liver injury (PDILI), as described in 
Section 6.3.1.
Removed.
Update to UCB protocol 
template text.
Section 6.3
Investigators should attempt to obtain 
information on subjects in the case of 
withdrawal or discontinuation.
Investigators should attempt to obtain 
information on subjects in the case of 
withdrawal.
Update to UCB protocol 
template text.
Section 6.3.1
Header: PDILI-related withdrawal criteria
To enable the effective management and 
assessment of any PDILI as outlined in the 
Food and Drug Administration (FDA) 
Guidance for Industry, Drug Induced Liver 
Injury: Premarketing Clinical Evaluation 
Header: Potential drug-induced liver injury 
IMP discontinuation criteria
Subjects with potential drug-induced liver 
injury (PDILI) must be assessed to determine if 
IMP must be discontinued. In addition, all 
concomitant medications and herbal 
Update to UCB protocol 
template text.
Sponsor language for 
monitoring of PDILI events 
added to increase clarity for 
the sites and to align across 
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(2009), UCB has developed prespecified 
criteria for managing any PDILI events and 
discontinuing IMP.
Subjects with PDILI must have IMP 
discontinued. In addition, all concomitant 
medications and herbal supplements that are 
not medically necessary should also be 
discontinued. 
The following PDILI criteria require 
immediate and permanent discontinuation of 
IMP:
Subjects with any of the following:

ALT and/or aspartate aminotransferase 
(AST) ≥8xULN

ALT and/or AST ≥3xULN and co-existing 
total bilirubin ≥2xULN
The following PDILI criterion requires 
immediate discontinuation of IMP: 

Subjects with ALT and/or AST ≥3xULN 
who exhibit a temporally associated 
fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever (without 
clear alternative cause), rash, or 
eosinophilia (ie, >5%) must be 
immediately discontinued from IMP.
If a non-drug related cause for the symptoms 
supplements that are not medically necessary 
should also be discontinued. 
The following PDILI criteria require 
immediate and permanent discontinuation of 
IMP:

Subjects with any of the following:

ALT or aspartate aminotransferase 
(AST) ≥8xULN

ALT or AST ≥3xULN and co-existing 
total bilirubin ≥2xULN
The following PDILI criterion requires 
immediate discontinuation of IMP: 

Subjects with ALT and/or AST ≥3xULN 
who exhibit temporally associated 
symptoms of hepatitis (excluding 
SLE-related hepatitis) or hypersensitivity. 
Hepatitis symptoms include fatigue, 
nausea, vomiting, right upper quadrant 
pain or tenderness. Hypersensitivity 
symptoms include fever (without clear 
alternative cause), rash, or eosinophilia (ie, 
>5%).
If a non-drug related cause for the symptoms 
can be confirmed, these subjects may resume 
IMP administration after discussion with the 
programs. (Exception: 
program-specific exclusion of 
lupus hepatitis from hepatitis 
symptoms requiring 
immediate discontinuation of 
IMP). The addition of PDILI 
language is to align with FDA 
guidance regarding 
monitoring of PDILI events 
and does not reflect a change 
in the liver safety signal for 
DZP.
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Specific changes with SL0023 Amendment 1
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section(s)
impacted
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Key components of amended text
Rationale
can be confirmed, these subjects may resume 
IMP administration after discussion with the 
Medical Monitor. 
The following PDILI criteria allows for 
subjects to continue on IMP at the discretion of 
the investigator:

ALT and/or AST ≥3xULN (and ≥2x 
baseline) and <8xULN, total bilirubin 
<2XULN, and no eosinophilia (ie, ≤5%), 
with no fever, rash or symptoms of 
hepatitis (eg, fatigue, nausea, vomiting, 
right upper quadrant pain or tenderness)
Monitoring and investigation of PDILI must be 
initiated as described in Section 13.7. If 
subjects are unable to comply with the 
applicable monitoring schedule, IMP must be 
discontinued immediately. 
responsible UCB physician, but only when the 
requirements for rechallenge with IMP as 
provided in Section 13.7.2.1 are followed. 
The following PDILI criteria allows for 
subjects to continue on IMP at the discretion of 
the Investigator:

ALT or AST ≥3xULN (and ≥2x baseline) 
and <8xULN, total bilirubin <2xULN, and 
no eosinophilia (ie, ≤5%), with no fever, 
rash or symptoms of hepatitis (eg, fatigue, 
nausea, vomiting, right upper quadrant 
pain or tenderness)
Evaluation of PDILI must be initiated as 
described in Section 13.7. If subjects are 
unable to comply with the applicable 
monitoring schedule, IMP must be 
discontinued immediately (see Section 8.10). 
Section 7.5
The Investigator (or designee) is responsible 
for the safe and proper storage of IMP at the 
site. Investigational medicinal product stored 
by the Investigator is to be kept in a secured 
area with limited access.
Appropriate storage conditions will be 
specified on the label and in the Pharmacy 
Manual. A temperature log will be completed 
in accordance with local requirements on a 
regular basis (eg, once a week), showing 
The Investigator (or designee) is responsible 
for the safe and proper storage of IMP at the 
site. Investigational medicinal product stored 
by the Investigator is to be kept in a secured 
area with limited access according to the 
storage conditions mentioned in the IMP 
Handling Manual.
Appropriate storage condition must be ensured 
by controlled refrigerator temperature either 
Update to UCB protocol 
template text and IMP 
Handling Manual.
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Specific changes with SL0023 Amendment 1
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impacted
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Rationale
minimum and maximum temperatures reached 
over the period of IMP storage in order to 
document that appropriate storage was 
maintained.
In case an out-of-range temperature is noted, it 
must be immediately communicated to the 
unblinded Clinical Project Manager (CPM) (or 
designee) before further use of the IMP.
The unblinded CPM (or designee) will transmit 
the out-of-range temperature (copy of the 
temperature log and duration of the 
out-of-range temperature, if available) to the 
Clinical Supply Manager. Based on discussion 
with a UCB Quality Assurance representative, 
the Clinical Supply Manager will then provide 
the unblinded CPM (or designee) with 
instructions for the site regarding use of the 
IMP.
The PBO and other materials used during 
drug administration will be stored and 
handled per specific requirements of each 
material and site requirements.
using an automated temperature monitoring 
and recording system or by using a 
minimum/maximum thermometer and 
completing daily a temperature log in 
accordance with local requirements. 
Temperature data for IMP should be recorded 
on each working day with the actual and 
minimum/maximum temperatures reached 
during this period. 
In case an out-of-range temperature is noted, it 
must be immediately reported as per 
instructions contained in the IMP Handling 
Manual.
The physiological saline [0/9% sodium 
chloride] used for administration should be 
handled per specific site requirements and 
stored according to label requirements.  
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Specific changes with SL0023 Amendment 1
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impacted
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Rationale
Section 7.6
A Drug Accountability form will be used to 
record IMP dispensing and return information 
on a by-subject basis and will serve as source 
documentation during the course of the study. 
Details of any IMP lost (due to breakage or 
wastage), not used, disposed of at the study 
site, or returned to the Sponsor or designee 
must also be recorded on the appropriate 
forms. 
Periodically, and/or after completion of the 
clinical phase of the study, all used (including 
empty containers) and unused IMP vials must 
be reconciled and returned to UCB (or 
designee), preferably in their original package 
or destroyed at the site following local 
procedures.
A Drug Accountability form will be used to 
record IMP dispensing and return information 
on a by-subject basis and will serve as source
documentation during the course of the study. 
Details of any IMP 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. 
Periodically, and/or after completion of the 
clinical phase of the study, all used (including 
empty containers)/partially used, unused, 
damaged, and/or expired IMP must be 
reconciled and either destroyed at the site 
according to local laws, regulations, and UCB 
SOPs or returned to UCB (or designee).
Update to UCB protocol 
template text.
Section 9.2.7
Qualitative subject interviews will be 
conducted by a study nurse/study personnel to 
collect the subject's experience with lupus in 
terms of symptoms and impact on daily 
activities, and the perceived changes during the 
course of the study. The extent to which the 
exploratory PRO items and scales used fully 
captured their experience will also be assessed.
Qualitative subject interviews will be 
conducted by an external third party vendor. 
The third party vendor will call the subject at 
home to collect the subject's experience with 
lupus in terms of symptoms and impact on 
daily activities, and the perceived changes 
during the course of the study. The extent to 
which the exploratory PRO items and scales 
used fully captured their experience will also 
be assessed.
Provision for collection of 
subject interviews by an 
external third party vendor 
with experience in such 
interviews.
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Specific changes with SL0023 Amendment 1
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Section 11
Not applicable.
The detection of anti-DZP antibodies and anti-
PEG antibodies will be done using validated 
methods. The details of analytical methods 
(including validation status) and results will be 
presented in the bioanalytical report.
Provide information about 
methodology and reporting.
Section 
13.1.4
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 subject is lost to follow up. 
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 subject is lost to follow up. 
This follow-up requirement applies to AEs, 
SAEs, and AEs of special interest; further 
details regarding follow-up of PDILI events are 
provided in Section 13.7.
Information on SAEs obtained after clinical 
database lock will be captured through the PS 
database without limitation of time.
Update to UCB protocol 
template text.
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Specific changes with SL0023 Amendment 1
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section(s)
impacted
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Section 
13.1.8.1
Not applicable.
Header: Suspected transmission of an 
infectious 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 13.2); 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.
Update to UCB protocol 
template requirements.
Section 
13.1.10
The subject should be withdrawn from the 
study as soon as pregnancy is known (by 
positive pregnancy test), and the following 
should be completed:

The IMP should be immediately 
discontinued. 

The subject should return for an EWV.

The subject should complete the SFU 
Period per protocol.
The subject should be discontinued from the 
study drug as soon as pregnancy is known (by 
positive pregnancy test), and the following 
should be completed:

The IMP should be immediately 
discontinued. 

The subject should complete the study per 
protocol.
Update to UCB protocol 
template text.
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Specific changes with SL0023 Amendment 1
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Section 
13.2.1
(Important medical events may include allergic 
bronchospasm requiring intensive treatment in 
an emergency room or at home, blood 
dyscrasias that do not result in inpatient 
hospitalization, or the development of drug 
dependency or drug abuse.)
(Important medical events may include, but are 
not limited to, potential Hy’s Law [see Section 
13.3], allergic bronchospasm requiring 
intensive treatment in an emergency room or at 
home, blood dyscrasias that do not result in 
inpatient hospitalization, or the development of 
drug dependency or drug abuse.)
Update to UCB protocol 
template text.
Section 13.3
There are currently no AEs of special interest 
identified for DZP.
Potential Hy’s law, defined as ≥3xULN ALT 
and/or AST with coexisting ≥2xULN bilirubin 
in the absence of ≥2xULN ALP, with no 
alternative explanation for the biochemical 
abnormality, must ALWAYS be reported to 
UCB as an AE of special interest and a serious 
unexpected AE (ie, without waiting for any 
additional etiologic investigations to have been 
concluded). 
There are currently no AEs of special interest 
identified for DZP; however, in accordance 
with the Sponsor’s internal guidelines for all 
drugs in development, Potential Hy's Law is to 
be reported as an AE of special interest as 
follows:

Potential Hy’s law, defined as ≥3xULN 
ALT or AST with coexisting ≥2xULN 
bilirubin in the absence of ≥2xULN ALP, 
with no alternative explanation for the 
biochemical abnormality, must ALWAYS 
be reported to UCB as an AE of special 
interest (ie, without waiting for any 
additional etiologic investigations to have 
been concluded). 
Update to UCB protocol 
template text with 
clarification regarding 
reporting of Hy’s law. 
Section 13.4

Suspected transmission of an infectious 
agent via a medicinal product

Suspected transmission of an infectious 
agent via a medicinal product (see Section 
13.1.8.1)
Provision of assistance in 
document navigation.
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Section 13.6
Not applicable.
Any presumptive diagnosis or diagnosis of a 
TB infection is a reportable event. Confirmed 
active TB must be reported as an SAE (Section 
13.2.2). The Investigator is to complete and 
submit the TB follow-up form provided.
Restatement of requirements 
for reporting for additional 
emphasis.
Section 13.7
Section header: Investigation and monitoring 
of PDILI 
UCB has developed prespecified procedures 
for managing PDILI events that are consistent 
with the FDA Guidance for Industry, Drug 
Induced Liver Injury: Premarketing Clinical 
Evaluation (2009). All PDILI events must be 
reported as SAEs and reported to the Sponsor 
within 24 hours of learning of its occurrence. If 
a PDILI event meets the criteria for Hy’s law 
(ie, ≥3xULN ALT and/or AST with coexisting 
≥2xULN bilirubin in the absence of ≥2xULN 
ALP, with no alternative explanation for the 
biochemical abnormality), it must also be 
reported as an AE of special interest and a 
serious unexpected AE (ie, without waiting for 
any additional etiologic investigations to have 
been concluded) (see Section 13.3 on AEs of
Special Interest, Hy’s law).
Table 13-2 summarizes the approach to 
investigate PDILI.
Table 13-2: Required testing and follow up for 
Section header: Evaluation of PDILI
The PDILI IMP discontinuation criteria for this 
study are provided in Section 6.3.1, with the 
accompanying required follow-up investigation 
and monitoring detailed below. All PDILI 
events must be reported as an AE and reported 
to the study site and Sponsor within 24 hours 
of learning of their occurrence. Any PDILI 
event that meets the criterion for potential Hy’s 
Law must be reported as an AE of special 
interest (see Section 13.3), and, if applicable, 
also reported as an SAE (see Section 13.2.2). 
If tests are done locally for more rapid results, 
a concurrent sample should also be sent to the 
central laboratory whenever possible. Medical 
care decisions are to be made initially using the 
most rapidly available results and a 
conservative approach must be taken if the 
results from the 2 laboratory tests are 
significantly different. Data from the local and 
central laboratory are to be recorded on the 
Update to UCB protocol 
template text and table.
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PDLI. Replaced. The table that was replaced is 
provided below.
applicable eCRF pages.
When IMP is discontinued, all concomitant 
medications and herbal supplements that are 
not medically necessary should also be 
discontinued. In these cases, the Investigator 
should also consider dose reduction for 
medically necessary concomitant medication 
and consider changing any medically required 
concomitant medication known to be 
hepatotoxic to a suitable alternative.
When IMP is stopped due to PDILI (as 
described in Section 6.3.1), IMP must be 
permanently discontinued unless a subsequent 
alternative diagnosis fully explains the hepatic 
findings. If a subsequent alternative diagnosis 
fully explains the hepatic findings, and the 
requirements provided in Section 13.7.2.1 are 
met, rechallenge with IMP may be appropriate. 
Rechallenge with a substance potentially 
causing drug-induced liver injury is dangerous, 
may be fatal, and must not occur.
The table below summarizes the approach to 
investigate PDILI.
Table 13-2: Required investigations and follow 
up for PDILI. Replacement added.
Section 
13.7.1
Section header: Consultation with local 
hepatologist and/or Sponsor Study Physician
Section header: Consultation with Medical 
Monitor and local hepatologist
Update to UCB protocol 
template.
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All PDILI events, as detailed in Table 13-2, 
require the Investigator to consult with a local 
hepatologist and/or Sponsor Study Physician, 
as applicable, within 24 hours. The local 
hepatologist is the expert usually consulted by 
the treating physician for assessment and 
management of potential hepatic disease. This 
would usually be a hepatologist, but may be a 
gastroenterologist. If deemed necessary, this 
discussion should be followed by a full 
hepatology assessment (see Section 13.7.2) and 
updated SAE report.
Potential drug-induced liver injury events 
require notification of the Medical Monitor, 
within 24 hours (eg by laboratory alert), and 
the subject must be discussed with the Medical 
Monitor as soon as possible. If required, the 
subject must also be discussed with the local 
hepatologist. The local hepatologist is the 
expert usually consulted by the treating 
physician for assessment and management of 
potential hepatic disease. This would usually 
be a hepatologist, but may be a 
gastroenterologist. If determined necessary, 
this discussion should be followed by a full 
hepatology assessment (see Section 13.7.3) and 
SAE report (if applicable).
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Section 
13.7.2
Not applicable.
Header: Immediate action: determination of 
IMP discontinuation
All PDILI events require immediate action, 
testing, and monitoring.
The immediate action is dependent on the 
laboratory values and symptoms of hepatitis or 
hypersensitivity and ranges from continuation 
of IMP (followed by immediate investigation) 
to immediate and permanent discontinuation 
(see Section 6.3.1 and Table 13-2 for details).
When IMP is discontinued, all concomitant 
medications and herbal supplements that are 
not medically necessary should also be 
discontinued. The Investigator should also 
consider dose reduction for medically 
necessary concomitant medication and 
consider changing any medically required 
concomitant medication known to be 
hepatotoxic to a suitable alternative.
Update to UCB protocol 
template.
Section 
13.7.2.1
Not applicable.
Header: IMP restart/rechallenge (if applicable)
Rechallenge with a substance potentially 
causing drug-induced liver injury is dangerous, 
may be fatal, and must not occur.
Subjects who are immediately discontinued 
from IMP due to having met certain criteria for 
PDILI (as described in Section 6.3.1 and Table 
13-2), but for whom an alternative diagnosis is 
confirmed, can rarely restart IMP. Rechallenge 
Update to UCB protocol 
template.
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with IMP can occur only if ALL of the 
following requirements are met:

The results of additional testing and 
monitoring described in Section 13.7.3 and 
Section 13.7.4 confirm a nondrug-related 
cause for the abnormal hepatic laboratory 
parameters and any associated symptoms 
(ie, a subsequent alternative diagnosis fully 
explains the hepatic findings). 

No alternative treatment options are 
available to the subject.

The subject has shown clear therapeutic 
benefit from the IMP.

Subject’s ALT or AST elevations do not 
exceed ≥3xULN.

Subject’s total bilirubin is <1.5xULN.

Subject has no signs or symptoms of 
hypersensitivity. 

The rechallenge is approved by the UCB 
responsible physician, DMC, and a 
hepatologist. The hepatologist must be 
external to UCB but may be a member of 
the DMC. It is recommended that the 
hepatologist be a local hepatology expert 
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or the hepatologist treating the subject.

Subject agrees to the Investigator-
recommended monitoring plan.
Section 
13.7.3
(original 
protocol 
Section
13.7.2)
Header: Immediate testing: 
identification/exclusion of alternative etiology
Header: Testing: identification/exclusion of 
alternative etiology
Update to UCB protocol 
template.
The measurements and additional information 
required for the assessment of PDILI events 
when there is a reasonable possibility that it 
may have been caused by the study drug are 
detailed in Table 13-3 (laboratory 
measurements) and Table 13-4 (additional 
information). Results of the laboratory 
measurements and collection of information is 
to be collected and submitted to the Sponsor on 
the corresponding eCRF. If medical history of 
the subject indicates a requirement for other 
assessments not included below, these should 
be completed and submitted, as applicable.
Table 13-3: Pancreatic amylase specified.
The measurements and additional information 
required for the assessment of PDILI events 
when there is a reasonable possibility that it 
may have been caused by the IMP are detailed 
in Table 13-3 (laboratory measurements) and 
Table 13-4 (additional information). Results of 
the laboratory measurements and information 
collected are to be submitted to the Sponsor on 
the corresponding eCRF. If medical history of 
the subject indicates a requirement for other 
assessments not included below, these 
additional assessments should be completed 
and submitted, as applicable.
All blood samples should be stored, if possible. 
If tests are done locally for more rapid results, 
a concurrent sample must also be sent to the 
central laboratory.
Table 13-3: Prothombin time added to 
hematology assessments.
Table 13-3: Pancreatic amylase changed to 
amylase.
Table 13-3: The following added to the 
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abbreviation list: ALT=alanine 
aminotransferase
Table 13-3: The following footnote (“a”) added 
to prothrombin time: Measured only for 
subjects with ALT >8xULN, elevations in total 
bilirubin, and symptoms of hepatitis or 
hypersensitivity. Hepatitis symptoms include 
fatigue, nausea, vomiting, and right upper 
quadrant pain or tenderness; hypersensitivity 
symptoms include eosinophilia (>5%), rash, 
and fever (without clear alternative cause).
Table 13-4: The following lead-in text added: 
“The following additional information is to be 
collected:”
Section 
13.7.4
(original 
protocol 
Section
13.7.3)
Header: Follow-up monitoring
All PDILI events require follow-up monitoring 
as described in Table 13-3 Monitoring should 
continue until liver chemistry values 
normalize, stabilize, or return to baseline. 
Determination of stabilization is at the 
discretion of the Investigator in consultation 
with the hepatologist and study team.
Header: Follow-up evaluation
All PDILI events require follow-up monitoring 
as described in Table 13-2. Monitoring should 
continue until liver chemistry values 
normalize, stabilize, or return to baseline. 
Determination of stabilization is at the 
discretion of the Investigator in consultation 
with the hepatologist (as applicable) and UCB 
responsible physician, as needed.
Update to UCB protocol 
template.
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Section 
14.2.1
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 of eCRFs are not 
considered acceptable 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. 
Update to UCB protocol 
template.
Section 
15.1.6
The PK-PPS will consist of all subjects in the 
SS who are randomized to 1 of the DZP 
treatment arms, have provided at least 1 PK 
sample, and for whom no important protocol 
deviations affecting the PK variables have been 
documented.
The PK-PPS will consist of all subjects in the 
SS who have provided at least 1 PK sample 
and for whom no important protocol deviations 
affecting the PK variables have been 
documented.
Clarification regarding 
composition of the PK-PPS.
Section 15.3
For purposes of computing a SLEDAI-2K total 
score, in the case where the SLEDAI-2K 
assessment has been done yet individual items 
have been left blank, these individual items 
will be imputed from the previous visit value 
prior to computing the total score. 
Deleted.
Remove repetition of 
information provided in 
Section 15.3.1.
Section 
15.3.1
The primary efficacy variable is the responder 
rate at Week 24 across 3 doses of DZP and 
PBO according to a combined response index 
(BICLA); the analysis will use a modified 
nonresponder imputation (mNRI) for missing 
data.
The primary efficacy variable is the BICLA 
responder at Week 24 across 3 doses of DZP 
and PBO. The BICLA is a binary efficacy 
response variable, which is a composite 
endpoint derived from the efficacy 
components: BILAG 2004, SLEDAI-2K, and 
Update to provide additional 
information about 
methodology.
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If Visit 24 was done but the value for a single 
component (BILAG 2004, SLEDAI-2K, or 
Physician’s Global Assessment of Disease) is 
not available, then the missing component 
value will be imputed from the previous visit 
value prior to computing the treatment 
response variable. In the case where a subject 
has a missing component, but already is known 
to have failed to achieve responder status on 
the basis of the nonmissing components (eg, 
SLEDAI-2K is missing but the nonmissing 
BILAG 2004 may not have demonstrated 
sufficient improvement), the missing value 
does not need to be imputed to know the 
subject’s treatment response classification. 
Thus, imputation only has a role for those 
subjects who have data at Visit 24 with all 
observed components meeting their respective 
criterion for treatment response, and hence the 
imputed missing component will ultimately 
dictate whether or not the subject is classified 
as a responder. If the value at the previous visit 
is also missing, or if the subject has 2 or more 
missing components at the visit, then the 
treatment response value is considered to be 
unknown (ie, left as missing and subject to the 
missing data approach specific to the given 
analysis).
In addition, subjects who discontinue treatment 
prematurely are primarily categorized as 
the Physician’s Global Assessment of Disease 
Activity. The BILAG 2004 and SLEDAI-2K 
are themselves composite endpoints 
comprising of multiple assessments of several 
organ systems affected by SLE. In addition, 
usage of specified concomitant medication as 
escape treatment is also a factor in determining 
BICLA responder status. See Section 9.1.9.1
for a complete description of the BICLA 
composite variable. Modified nonresponder 
imputation will be used to impute missing data, 
after applying additional rules within each 
component, which are further detailed as 
follows:
If 1 of the 3 efficacy components (BILAG 
2004, SLEDAI-2K, or Physician’s Global 
Assessment of Disease) is missing, but the visit 
was performed and all other assessments were 
completed, the missing component will be 
imputed from the subject’s previous post-
baseline assessment, prior to computing the 
treatment response variable, following the last 
observation carried forward principle. 
Furthermore, for BILAG 2004 and SLEDAI-
2K, if the assessment was done, but individual 
system or item scores are missing, the 
respective individual score will be imputed 
from the respective previous post-baseline 
score, in order to obtain a score for the current 
visit, prior to computing the system or score. If 
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nonresponders. In any situation where a subject 
is known to be a nonresponder based on 
available data, imputation will not be 
performed for missing data required to 
determine treatment response status, since the 
subject is known to be a nonresponder 
regardless of the result of the missing 
assessment(s).
The primary efficacy analysis will be tested 
across 3 doses of DZP and PBO using the 
Multiple Comparison Procedure–Modelling 
(MCP-Mod) methodology (Bretz et al, 2005). 
Monotonic dose-response trends will be tested 
using the appropriate contrasts as determined 
by the MCP-Mod methodology such that the 
overall Type 1 error rate is controlled at 0.05 
(one-sided testing).
the value at the previous visit is also missing, 
or if the subject has 2 or more missing 
components at Week 24, then the treatment 
response value is considered to be unknown 
(ie, left as missing and therefore considered a 
nonresponder).
In addition, subjects who discontinue treatment 
prematurely (while still remaining in the study) 
are primarily categorized as a nonresponder 
from that visit and all subsequent visits.
The Week 24 BICLA dose-response 
relationship across 3 doses of DZP and PBO 
will be evaluated using the Multiple 
Comparison Procedure–Modelling (MCP-
Mod) methodology (Bretz et al, 2005). 
Monotonic dose-response trends will be tested 
using the appropriate contrasts as determined 
by the MCP-Mod methodology such that the 
overall Type 1 error rate is controlled at 0.05 
(one-sided testing).
The SAP will describe additional features and 
detail around the MCP-Mod methodology as 
well as handling of missing data.
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Section 16.1
Prior to participation in the study, the written 
Informed Consent form should be signed and 
personally dated by the subject, or his/her legal 
representative, and by the person who 
conducted the informed consent discussion 
(Investigator or designee). The subject or 
his/her legal representative must receive a copy 
of the signed and dated Informed Consent 
form. As part of the consent process, each 
subject must consent to direct access to his/her 
medical records for study-related monitoring, 
auditing, IRB/IEC review, and regulatory 
inspection.
Prior to participation in the study, the written 
Informed Consent form should be signed and 
personally dated by the subject, and by the 
person who conducted the informed consent 
discussion (Investigator or designee). The 
subject must receive a copy of the signed and 
dated Informed Consent form. As part of the 
consent process, each subject must consent to 
direct access to his/her medical records for 
study-related monitoring, auditing, IRB/IEC 
review, and regulatory inspection.
Update to UCB protocol 
template.
Section 16.2
Upon signing the Informed Consent and Assent 
form (as applicable), the subject or legal 
representative will be provided with a subject 
identification card in the language of the 
subject.
Upon signing the Informed Consent and Assent 
form (as applicable), the subject will be 
provided with a subject identification card in 
the language of the subject.
Update to UCB protocol 
template.
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The following table from the original protocol has been replaced by Table 13-2 of Amendment 1 
as noted in the specific changes for Section 13.7 above:
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Original protocol Table 13-2:  Required testing and follow up for PDILI
Lab value
Symptoms a of 
hepatitis or 
hypersensitivity
Consultation requirements
Additional immediate testing
Continued 
monitoring
ALT and/or 
AST
Bilirubin
≥3xULN
NA
No
Subject must be discussed with 
the Sponsor Study Physician 
within 24h
Must have repeat liver chemistries 
and additional testing completed as 
soon as possible (see Section 
13.7.2); recommended to occur 
within 24hrs at site or with HCP
Monitoring of 
liver chemistries 
required at least 
2 times weekly 
until liver 
chemistries 
normalize, 
stabilize, or return 
to within baseline 
values. d
≥3xULN
NA
Yes
Hepatology b consult
Subject must be discussed with 
the Sponsor Study Physician 
within 24h
≥3xULN
≥2xULN c
N/A
Hepatology b consult
Subject must be discussed with 
the Sponsor Study Physician 
within 24h
ALP=alkaline phosphatase; ALT=alanine aminotransferase; AST= aspartate aminotransferase ; HCP=health care practitioner; NA=not applicable; 
PDILI=potential drug-induced liver injury; ULN=upper limit of normal
a Hepatitis symptoms include fatigue, nausea, vomiting, and right upper quadrant pain or tenderness; hypersensitivity symptoms include eosinophilia (>5%), 
rash, fever (without clear alternative cause).
b Details provided in Section 13.7.1. The local hepatologist is the expert usually consulted by the treating physician for assessment and management of potential
hepatic disease. This would usually be a hepatologist, but may be a gastroenterologist.
c If the subject also has ≥2xULN ALP, the possibility of an indication of biliary obstruction should be discussed with the Sponsor Study Physician.
d Unless an alternative monitoring schedule is agreed by the Investigator and Sponsor Study Physician. Determination of stabilization is at the discretion of the 
Investigator in consultation with the hepatologist and study team.
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20
DECLARATION AND SIGNATURE OF INVESTIGATOR
I confirm that I have carefully read and understood this protocol and agree to conduct this 
clinical study as outlined in this protocol, according to current Good Clinical Practice and local 
laws and requirements.
I will ensure that all subinvestigators and other staff members read and understand all aspects of 
this protocol.
I have received and read all study-related information provided to me.
The objectives and content of this protocol as well as the results deriving from it will be treated 
confidentially, and will not be made available to third parties without prior authorization by 
UCB.
All rights of publication of the results reside with UCB, unless other agreements were made in a 
separate contract.
Investigator:
Printed name
Date/Signature
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21
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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ELECTRONIC SIGNATURES 
 
Signed by 
Meaning of Signature 
Server Approval Date 
(dd-mon-yyyy 
(HH:mm)) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
SL0023 Protocol Amendment 1
Clinical Approval
15-Dec-2016 13:40 GMT+01
Clinical Approval
16-Dec-2016 23:17 GMT+01
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