Clinical trial NCT02804763
Conditions: Systemic Lupus Erythematosus (SLE)
Keywords: Systemic Lupus Erythematosus (SLE) Dapirolizumab Pegol (DZP)
Sponsor: UCB Biopharma S.P.R.L.
Start date: 2016-06-02; Completion date: 2018-11-19
Enrollment: 182 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose is to evaluate the efficacy and safety of three different doses of Dapirolizumab Pegol (DZP) versus placebo in adult subjects with moderately to severely active systemic Lupus Erythematosus.

Detailed description:

Arms: arm 1: Placebo in a specified sequence for a total of 24 weeks arm 2: Dapirolizumab pegol (DZP) dose 1 in a specified sequence for a total of 24 weeks arm 3: Dapirolizumab pegol (DZP) dose 2 in a specified sequence for a total of 24 weeks arm 4: Dapirolizumab pegol (DZP) dose 3 in a specified sequence for a total of 24 weeks
Interventions: intervention 1: Placebo intervention 2: Dapirolizumab pegol (DZP)
Intervention descriptions: intervention 1: Solution for infusion, 0,9% saline intervention 2: Solution for infusion

Protocol documents:
Prot_000.pdf: 
UCB
14 Dec 2016
Clinical Study Protocol
Dapirolizumab pegol
SL0023
Confidential
Page 1 of 144
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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Clinical Study Protocol
Dapirolizumab pegol
SL0023
Confidential
Page 2 of 144
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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Clinical Study Protocol
Dapirolizumab pegol
SL0023
Confidential
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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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Clinical Study Protocol
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SL0023
Confidential
Page 4 of 144
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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SL0023
Confidential
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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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SL0023
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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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Dapirolizumab pegol
SL0023
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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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Dapirolizumab pegol
SL0023
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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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SL0023
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21
SPONSOR DECLARATION ........................................................................................144
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Clinical Study Protocol
Dapirolizumab pegol
SL0023
Confidential
Page 10 of 144
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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Dapirolizumab pegol
SL0023
Confidential
Page 11 of 144
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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Dapirolizumab pegol
SL0023
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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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SL0023
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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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SL0023
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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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SL0023
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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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SL0023
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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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by dose on the risk of developing organ damage over time in systemic lupus erythematosus—the 
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Borchers AT, Naguwa SM, Shoenfeld Y, Gershwin ME. The geoepidemiology of systemic lupus 
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Devilliers H, Amoura Z, Besancenot JF, Bonnotte B, Pasquali JL, Wahl D, et al. Responsiveness 
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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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SL0023
Confidential
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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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14 Dec 2016
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SL0023
Confidential
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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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Dapirolizumab pegol
SL0023
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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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SL0023
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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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Clinical Study Protocol
Dapirolizumab pegol
SL0023
Confidential
Page 119 of 144
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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14 Dec 2016
Clinical Study Protocol
Dapirolizumab pegol
SL0023
Confidential
Page 120 of 144
Specific changes with SL0023 Amendment 1
Protocol
section(s)
impacted
Key components of previous text
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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14 Dec 2016
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SL0023
Confidential
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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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SL0023
Confidential
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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
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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SL0023
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Specific changes with SL0023 Amendment 1
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section(s)
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Key components of amended text
Rationale
(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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SL0023
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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
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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SL0023
Confidential
Page 125 of 144
Specific changes with SL0023 Amendment 1
Protocol
section(s)
impacted
Key components of previous text
Key components of amended text
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
Protocol
section(s)
impacted
Key components of previous text
Key components of amended text
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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impacted
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Rationale
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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Rationale
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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impacted
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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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impacted
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Rationale
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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SAP_001.pdf: 
UCB 
 
04 Sep 2018 
Statistical Analysis Plan Amendment 1 
Dapirolizumab pegol 
SL0023 
 
 
 
Confidential 
Page 1 of 100 
 
STATISTICAL ANALYSIS PLAN AMENDMENT 1  
Study: SL0023 
Product: Dapirolizumab pegol 
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 
 
 
Confidentiality Statemen
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. 
 
 
 
SAP/Amendment Number Date 
Final SAP 
19 December 2017 
Amendment 1 
04 September 2018 
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UCB 
 
04 Sep 2018 
Statistical Analysis Plan Amendment 1 
Dapirolizumab pegol 
SL0023 
 
 
 
Confidential 
Page 2 of 100 
TABLE OF CONTENTS 
TABLE OF CONTENTS ........................................................................................................... 2 
LIST OF ABBREVIATIONS .................................................................................................... 6 
1 
INTRODUCTION ........................................................................................................... 10 
2 
PROTOCOL SUMMARY ............................................................................................... 10 
2.1 
Study objectives ........................................................................................................... 11 
2.1.1 
Primary objective ................................................................................................. 11 
2.1.2 
Secondary objectives ........................................................................................... 11 
2.1.3 
Other objectives ................................................................................................... 11 
2.2 
Study variables ............................................................................................................. 12 
2.2.1 
Efficacy variables ................................................................................................ 12 
2.2.1.1 
Primary efficacy variable .......................................................................... 12 
2.2.1.2 
Secondary efficacy variable ...................................................................... 12 
2.2.1.3 
Other efficacy variables ............................................................................. 12 
2.2.2 
Safety variables .................................................................................................... 15 
2.2.3 
Pharmacokinetic/pharmacodynamic variables .................................................... 16 
2.2.3.1 
Immunological variables ........................................................................... 16 
2.2.4 
Immunogenicity variables ................................................................................... 16 
2.3 
Study design and conduct ............................................................................................ 16 
2.4 
Determination of sample size ....................................................................................... 17 
3 
DATA ANALYSIS CONSIDERATIONS ...................................................................... 18 
3.1 
General presentation of summaries and analyses ........................................................ 18 
3.2 
Analysis time points ..................................................................................................... 19 
3.3 
Relative study days ...................................................................................................... 20 
3.4 
Definition of baseline values ....................................................................................... 20 
3.5 
Protocol deviations....................................................................................................... 21 
3.6 
Analysis sets................................................................................................................. 21 
3.6.1 
Enrolled Set ......................................................................................................... 21 
3.6.2 
Randomized Set ................................................................................................... 21 
3.6.3 
Safety Set ............................................................................................................. 21 
3.6.4 
Full Analysis Set .................................................................................................. 21 
3.6.5 
Per Protocol Set ................................................................................................... 22 
3.6.6 
Pharmacokinetic Per Protocol Set ....................................................................... 22 
3.6.7 
Completer Set ...................................................................................................... 22 
3.7 
Treatment assignment and treatment groups ............................................................... 22 
3.8 
Center pooling strategy ................................................................................................ 23 
3.9 
Coding dictionaries ...................................................................................................... 23 
3.10 
Changes to protocol-defined analyses ......................................................................... 23 
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4 
STATISTICAL/ANALYTICAL ISSUES ....................................................................... 26 
4.1 
Adjustments for covariates .......................................................................................... 26 
4.2 
Handling and definition of the corticosteroid prednisone equivalent dose .................. 26 
4.3 
Handling of dropouts or missing data .......................................................................... 27 
4.4 
Handling of Retests ...................................................................................................... 29 
4.5 
Interim analyses and data monitoring .......................................................................... 30 
4.6 
Multicenter studies ....................................................................................................... 30 
4.7 
Multiple comparisons/multiplicity ............................................................................... 30 
4.8 
Use of an efficacy subset of subjects ........................................................................... 31 
4.9 
Active-control studies intended to show equivalence .................................................. 31 
4.10 
Examination of subgroups ........................................................................................... 31 
5 
STUDY POPULATION CHARACTERISTICS ............................................................. 33 
5.1 
Subject disposition ....................................................................................................... 33 
5.2 
Protocol deviations....................................................................................................... 34 
6 
DEMOGRAPHICS AND OTHER BASELINE CHARACTERISTICS ........................ 35 
6.1 
Demographics .............................................................................................................. 35 
6.2 
Other Baseline characteristics ...................................................................................... 35 
6.3 
Medical history and concomitant diseases ................................................................... 37 
6.4 
Prior and concomitant medications .............................................................................. 37 
7 
MEASUREMENTS OF TREATMENT COMPLIANCE ............................................... 40 
8 
EFFICACY ANALYSES ................................................................................................ 40 
8.1 
Statistical analysis of the primary efficacy variable .................................................... 41 
8.1.1 
Derivation of primary efficacy variable .............................................................. 41 
8.1.2 
Analysis of the primary efficacy variable ............................................................ 42 
8.1.2.1 
MCP-Mod - Candidate models .................................................................. 42 
8.1.2.2 
MCP-Mod - Analysis ................................................................................ 43 
8.1.2.3 
Sensitivity Analyses of the Primary Efficacy Variable - missing data ..... 44 
8.1.2.4 
Sensitivity Analyses of the Primary Efficacy Variable - candidate models44 
8.2 
Statistical analysis of the secondary efficacy variable ................................................. 45 
8.2.1 
Sensitivity Analyses of the Secondary Efficacy Variable. .................................. 45 
8.3 
Statistical analysis of the other efficacy variables ....................................................... 46 
8.3.1 
Clinical assessment of disease activity ................................................................ 48 
8.3.2 
Variables assessed corticosteroid-sparing effects ................................................ 61 
8.3.3 
Patient-reported outcome variables ..................................................................... 64 
8.4 
Additional Endpoints and Analyses ............................................................................. 65 
8.4.1 
DORIS (Definitions of Remission in SLE) complete remission on treatment .... 65 
8.4.2 
LLDAS (Lupus Low Disease Activity State) ...................................................... 66 
8.4.3 
BILAG 2004 substantial/partial/no response ....................................................... 67 
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8.4.4 
Flare assessment .................................................................................................. 68 
8.4.5 
BICLA variants .................................................................................................... 69 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS .......................................... 70 
9.1 
Pharmacokinetics ......................................................................................................... 70 
9.2 
Pharmacodynamics ...................................................................................................... 71 
9.2.1 
Transcriptomics ................................................................................................... 71 
9.2.2 
Auto-antibody Measurements .............................................................................. 71 
9.2.3 
Immunological Variables ..................................................................................... 72 
10 IMMUNOGENICITY ...................................................................................................... 73 
10.1 
Anti-Dapirolizumab antibodies .................................................................................... 73 
10.2 
Anti-PEG antibodies .................................................................................................... 75 
10.3 
Analyses Done for Both Anti-DZP and Anti-PEG Antibodies ................................... 76 
11 SAFETY ANALYSES ..................................................................................................... 78 
11.1 
Extent of exposure ....................................................................................................... 79 
11.1.1 
Presentation of dosing data .................................................................................. 79 
11.2 
Adverse events ............................................................................................................. 80 
11.2.1 
Adverse events of special interest and adverse events of interest ....................... 84 
11.3 
Clinical laboratory evaluations .................................................................................... 84 
11.3.1 
Routine safety laboratory evaluations.................................................................. 84 
11.3.2 
Additional laboratory evaluations ........................................................................ 86 
11.3.3 
Potential drug-induced liver injury ...................................................................... 87 
11.4 
Vital signs, physical findings, and other observations related to safety ...................... 87 
11.4.1 
Vital signs ............................................................................................................ 87 
11.4.2 
Electrocardiogram ................................................................................................ 88 
11.4.3 
Physical examination ........................................................................................... 88 
11.4.4 
Other safety variables .......................................................................................... 88 
11.4.4.1 
Assessment of suicidal ideation and behavior ........................................... 88 
12 REFERENCES ................................................................................................................ 90 
13 APPENDICES ................................................................................................................. 91 
13.1 
Schedule of study assessments ..................................................................................... 91 
13.2 
SLEDAI-2K and SRI-50 .............................................................................................. 97 
14 AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN (SAP) (IF 
APPLICABLE) ................................................................................................................ 99 
14.1 
AMENDMENT 1......................................................................................................... 99 
STATISTICAL ANALYSIS PLAN SIGNATURE PAGE ................................................... 100 
 
 
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LIST OF TABLES 
Table 4‒1: 
Prednisone equivalent doses of systemic corticosteroids ................................ 26 
Table 11‒1: 
Routine Clinical Laboratory Evaluations ......................................................... 84 
Table 11‒2: 
Additional Laboratory Evaluations .................................................................. 86 
Table 11‒3: 
Reference ranges for vital signs ....................................................................... 88 
Table 13‒1: 
Schedule of study assessments......................................................................... 92 
Table 13‒2: 
SLEDAI-2K and SRI-50 .................................................................................. 97 
 
 
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LIST OF ABBREVIATIONS 
Ab 
Antibody 
ACR 
American College of Rheumatology 
ADA 
Anti-Drug Antibody 
AE 
adverse event 
AESI 
adverse event of special interest 
AEOI 
adverse event of interest 
ALP 
alkaline phosphatase  
ALT 
alanine aminotransferase  
ANA 
antinuclear antibody 
ANCOVA 
Analysis of covariance 
ANOVA 
Analysis of variance 
anti-dsDNA 
anti-double-stranded deoxyribonucleic acid antibody 
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 antibody 
aPTT 
activated partial thromboplastin time 
AST 
aspartate aminotransferase 
AUC 
area under the curve 
AUCτ 
area under the concentration-time curve over the dosing 
interval 
AUCMB 
area under the curve minus baseline 
BICLA 
BILAG 2004-based Composite Lupus Assessment 
BILAG 2004 
British Isles Lupus Assessment Group Disease Activity Index 
2004 
BLQ 
below level of quantification 
BP 
blood pressure 
BST 
BILAG 2004 System Tally 
C3 
complement 3 
C4 
complement 4 
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CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity 
Index 
Cmax 
maximum plasma concentration 
CS 
Completer Set 
CSR 
Clinical Study Report 
C-SSRS 
Columbia Suicide Severity Rating Scale 
CTCAE 
Common Terminology Criteria for Adverse Events 
Ctrough 
predose plasma concentration 
DBP 
diastolic blood pressure 
DEM 
Data Evaluation Meeting 
DMC 
Data Monitoring Committee  
DNA 
deoxyribonucleic acid 
DORIS 
Definitions of Remission in SLE 
DZP 
dapirolizumab pegol 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
eGFR 
estimated glomerular filtration rate 
ES 
Enrolled Set 
EWV 
Early Withdrawal Visit  
FAS 
Full Analysis Set 
FDA 
Food and Drug Administration 
GCP 
Good Clinical Practice 
GEE 
Generalized Estimating Equation 
GGT 
gamma-glutamyltransferase 
HIV 
human immunodeficiency virus 
HRQoL 
health-related quality of life 
hsCRP 
high sensitivity C-reactive protein 
ICH 
International Council for Harmonization 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IMP 
investigational medicinal product 
IPD 
Important Protocol Deviation  
IRB 
Institutional Review Board 
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iv 
intravenous(ly) 
LDH 
lactate dehydrogenase 
LLDAS 
Lupus Low Disease Activity State 
LLN 
lower limit of normal 
LLOQ 
lower limit of quantification 
LOQ 
limit of quantification 
MCAR 
missing completely at random 
MCP-Mod 
Multiple Comparison Procedure–Modeling 
MMRM 
Mixed Models for Repeated Measurement 
mRNA 
messenger ribonucleic acid 
n 
number of observations 
N 
number of subjects 
PBO 
placebo 
PD 
pharmacodynamics(s) 
PDILI 
potential drug-induced liver injury 
PEG 
polyethylene glycol 
PGA  
Physician’s Global Assessment of Disease 
PK 
pharmacokinetic(s) 
PR 
pulse rate 
PRO 
patient-reported outcome 
PtGA 
Patient’s Global Assessment of Disease 
RBC 
red blood cell 
RF 
rheumatoid factor 
RS 
Randomized Set 
SAE 
serious adverse event  
SAP 
Statistical Analysis Plan  
SBP 
systolic blood pressure 
sBST 
simplified BILAG 2004 System Tally 
SD 
standard deviation 
SFU 
Safety Follow-up 
SJC 
swollen joint count 
SLE 
systemic lupus erythematosus 
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SLE-E 
Systemic Lupus Erythematosus Emotional 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 
SLEDAI-2K 
Systemic Lupus Erythematosus Disease Activity Index 2000 
SLICC 
Systemic Lupus International Collaborating Clinics 
SMQ 
Standardized MedDRA Queries 
S2K RI-50 
SLEDAI-2K Responder Index-50 
SS 
Safety Set 
TB 
tuberculosis 
TEAE 
treatment-emergent adverse events 
TJC 
tender joint count 
ULN 
upper limit of normal 
uPCR 
urine protein-creatinine ratio 
VAS 
visual analog scale 
WBC 
white blood cell 
WOCF 
worst observation carried forward 
  
 
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1 
INTRODUCTION 
The purpose of this Statistical Analysis Plan (SAP) is to provide all information that is necessary 
to perform the interim and final statistical analysis of SL0023 to support the interim and final 
clinical study reports (CSRs). It also defines the summary tables, listings and figures to be 
included in the clinical study reports according to protocol. 
The SAP is based on the following study documents: Protocol amendment 1: 14 Dec 2016. 
The content of this SAP is compatible with the International Conference on Harmonization 
(ICH)/ Food and Drug Administration (FDA) E9 Guidance documents. 
2 
PROTOCOL SUMMARY 
This study 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 (i.e., 
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 (potentially 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 Part 1 of the study, 
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. 
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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 maximum 
duration of the entire study (Parts 1 and 2) per subject will be approximately 52 weeks. 
The study is planned to enroll at least 267 subjects in order to randomize approximately 160 
subjects (40 subjects per treatment group). Eligible subjects 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 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. 
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, prespecified in a Biomarker Plan, in order to provide guidance for the DZP 
development program, and will not affect the conduct of the study.  A final analysis of biomarker 
data will be conducted at the end of the study. 
After the last subject completes Part 1 of the study, the data for those subjects will be secured 
and an interim Clinical Study Report 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). 
2.1 
Study objectives 
2.1.1 
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. 
2.1.2 
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 
2.1.3 
Other objectives 
The other objectives of the study are: 
 To assess the efficacy of the individuals dose regimens of iv DZP at additional time points 
 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 
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 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 (potentially including gene transcription 
signature) 
2.2 
Study variables 
The measures employed in this study include variables to explore clinical disease activity and to 
assess organ system function, which may be compromised as a result of disease activity in 
subjects with SLE. 
2.2.1 
Efficacy variables 
2.2.1.1 
Primary efficacy variable 
The primary efficacy variable is the BICLA responder rate across 3 doses of DZP and PBO at 
Week 24 (see Section 8.1.1 for a detailed description of this variable). 
2.2.1.2 
Secondary efficacy variable 
The secondary efficacy variable is the BICLA responder rate in the individual dose groups at 
Week 24. 
2.2.1.3 
Other efficacy variables 
Other efficacy variables being evaluated by visit will include all scheduled visits for that 
particular variable. 
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 S2K RI-50 score by visit 
 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 
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 SLE Responder Index-4 (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 
 Percentage of subjects in each category in the Systemic Lupus International Collaborating 
Clinics/American College of Rheumatology (SLICC/ACR) Damage Index score at Week 48 
 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 up to Week 24 (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 from Baseline up to Week 48 (with the occurrence of a flare determined by the 
Investigator) 
 Time to flare up to Week 24 (with the occurrence of a flare defined as: a new sustained 
BILAG 2004 Grade A/B [present at ≥2 consecutive visits] 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, MMF, MTX, Azathioprin, or plasma exchange]) 
 Time to severe flare up to Week 24 (with the occurrence of a severe flare defined as a 
BILAG severe flare) 
 Time to severe flare after Week 24 (with the occurrence of a severe flare defined as a BILAG 
severe flare) 
 Time to severe flare from Baseline up to Week 48 (with the occurrence of a severe flare 
defined as a BILAG severe flare) 
 Time to moderate flare up to Week 24 (with the occurrence of a moderate flare defined as a 
BILAG moderate flare) 
 Time to moderate flare after Week 24 (with the occurrence of a moderate flare defined as a 
BILAG moderate flare) 
 Time to moderate flare from Baseline up to Week 48 (with the occurrence of a moderate flare 
defined as a BILAG moderate flare) 
 Time to mild flare up to Week 24 (with the occurrence of a mild flare defined as a BILAG 
mild flare) 
 Time to mild flare after Week 24 (with the occurrence of a mild flare defined as a BILAG 
mild flare) 
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 Time to mild flare from Baseline up to Week 48 (with the occurrence of a mild flare defined 
as a BILAG mild flare) 
 Time to severe flare (Variant 1) up to Week 24 (with the occurrence of a severe flare defined 
as a BILAG severe flare - Variant 1: a new BILAG 2004 Grade A since the previous visit) 
 Time to severe flare (Variant 1) after Week 24 (with the occurrence of a severe flare defined 
as a BILAG severe flare - Variant 1: a new BILAG 2004 Grade A since the previous visit) 
 Time to severe flare (Variant 1) from Baseline up to Week 48 (with the occurrence of a 
severe flare defined as a BILAG severe flare - Variant 1: a new BILAG 2004 Grade A since 
the previous visit) 
 Time to moderate/severe flare (Variant 1) up to Week 24 (with the occurrence of a 
moderate/severe flare defined as a BILAG moderate/severe flare - Variant 1: a new BILAG 
2004 Grade A or 2 new BILAG 2004 Grade Bs since the previous visit) 
 Time to moderate/severe flare (Variant 1) after Week 24 (with the occurrence of a 
moderate/severe flare defined as a BILAG moderate/severe flare - Variant 1: a new BILAG 
2004 Grade A or 2 new BILAG 2004 Grade Bs since the previous visit) 
 Time to moderate/severe flare (Variant 1) from Baseline up to Week 48 (with the occurrence 
of a moderate/severe flare defined as a BILAG moderate/severe flare - Variant 1: a new 
BILAG 2004 Grade A or 2 new BILAG 2004 Grade Bs since the previous visit) 
 Variables assessing corticosteroid-sparing effects 
 Absolute daily corticosteroid dose (in prednisone equivalent) 
 Percentage of subjects with a daily corticosteroid dose (prednisone-equivalent) of 7.5mg 
prednisone equivalent or less and BICLA response at Week 24 
 Percentage of subjects with a daily corticosteroid dose (prednisone-equivalent) 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 (prednisone-equivalent) of 7.5mg 
prednisone equivalent or less and SRI-4 response at Week 24 
 Time-weighted area under the curve in corticosteroid dose (prednisone-equivalent) for the 
period covering Baseline to Week 24 
 Percentage of subjects with a daily corticosteroid dose (prednisone-equivalent) of 7.5mg or 
less prednisone equivalents by visit 
Percentage of subjects with no concomitant corticosteroid treatment by visit 
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): 
 SLE-Symptom Inventory Instrument (SLE-S) by visit 
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 SLE-Fatigue Instrument (SLE-F) by visit 
 SLE-Mobility Instrument (SLE-M) by visit 
 SLE-Pain Instrument (SLE-P) by visit 
 SLE-Emotional States Instrument (SLE-E) by visit 
2.2.2 
Safety variables 
The following safety variables will be evaluated in the course of the study: 
 Incidence of adverse events (AEs), serious adverse events (SAEs), AEs leading to 
discontinuation of study drug and/or study, and adverse event of interest (AEOIs) including 
and not limited to infusion reactions, thromboembolic events, neurological events and 
malignancies 
 Vital signs 
 12-lead ECG 
 Hematology:  
 Hemoglobin  
 Hematocrit 
 Mean corpuscular volume (MCV) 
 Red blood cell (RBC) count 
 Mean corpuscular hemoglobin concentration (MCHC) 
 Mean corpuscular hemoglobin (MCH) 
 White blood cell (WBC) count, WBC differential (basophils, eosinophils, lymphocytes, 
monocytes, and neutrophils) 
 Platelet count 
 Clinical chemistry:  
 Liver function tests (bilirubin, aspartate aminotransferase (AST), alanine 
aminotransferase (ALT), alkaline phosphatase (ALP), gamma-glutamyltransferase 
(GGT), and lactate dehydrogenase (LDH)) 
 Creatinine 
 Urea nitrogen 
 Electrolytes (sodium, potassium, calcium, and phosphate) 
 Total cholesterol and triglycerides 
 Total protein and albumin 
 Glucose 
 Lipase 
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 Creatine phosphokinase  
 Additional laboratory assessments 
 Coagulation and hemostasis tests: prothrombin time, activated partial thromboplastin 
time, prothrombin intl. normalized ratio, and fibrinogen (fibrinogen was optional, ordered 
by the sites as needed) 
 Urinalysis: pH, bilirubin, protein, blood, glucose, nitrite, ketone, leukocytes, urobilinogen 
 Urine chemistry and microscopy, as applicable:  
a. Protein, albumin, creatinine (for protein:creatinine ratio (mg/mmol) and 
albumin:creatinine (mg/mmol) ratios) 
b. Microscopy of urine sediment for RBCs, RBC casts, WBCs, and WBC casts 
 Erythrocyte sedimentation rate (ESR) 
 C-SSRS assessment of suicidal ideation and behavior 
2.2.3 
Pharmacokinetic/pharmacodynamic variables 
The following PK variables will be evaluated: 
 For plasma samples: Plasma concentrations of DZP and PEG 
 For urine samples: Urine amount of PEG 
The following PD variable will be evaluated: 
 Whole blood mRNA signature profiling to characterize potential changes in gene expression 
relevant to the inflammatory and immune response to DZP in SLE 
2.2.3.1 
Immunological variables 
 Lupus Autoantibody Profile: anti-double-stranded deoxyribonucleic acid (anti-dsDNA) 
antibodies, antinuclear antibody (ANAs), extractable nuclear antigen antibody (anti-
ENA), anti-Smith antibody (anti-SM), Sjögren’s syndrome antibody A (anti-SSA), 
Sjögren’s syndrome antibody B (anti-SSB), anti-ribonucleoprotein antibody (anti-RNP), 
rheumatoid factor (RF), and antiphospholipid (aPL) antibodies (anticardiolipin 
antibodies, lupus anticoagulant, and anti β2 glycoprotein antibodies) 
 Ig (total Ig, IgG, IgM, IgA, and IgE) 
 High sensitivity C-reactive protein (hsCRP) 
 C3 and C4 levels 
2.2.4 
Immunogenicity variables 
The following immunogenicity variable will be evaluated: 
 Anti-DZP and anti-PEG antibodies 
2.3 
Study design and conduct 
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-
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week Observational Period (Part 2) in adult subjects with moderately to severely active SLE who 
are receiving stable standard-of-care medications (i.e., corticosteroids, immunosuppressants, 
and/or antimalarials) at study entry. Subjects (male or female, ≥18 years of age) who enroll in 
this study must have moderately to severely active SLE, defined as having BILAG 2004 Grade 
A level disease activity in ≥1 body/organ system or BILAG 2004 Grade B in ≥2 body/organ 
systems if no BILAG 2004 Grade A level disease is present and SLEDAI-2K score ≥6 at 
Screening. 
A target size of at least 267 subjects has been selected in order to randomize approximately 160 
subjects (40 subjects per treatment group). The study will be conducted at approximately 70 
sites. 
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). 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 during 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 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. 
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.  
A schedule of study assessments is provided in the Section 13.1. 
2.4 
Determination of sample size 
The sample 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 Multiple Comparison Procedure–
Modelling (MCP-Mod) methodology. The primary endpoint of the study is a binary indicator of 
whether the subject responds to treatment.  
Based upon prior experience in SLE, a PBO 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. 
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Adjusting for an expected dropout rate of 30% results in the need to randomize 160 subjects (40 
subjects per treatment group) and assuming a screening failure rate of approximately 40%, it is 
anticipated to enroll approximately 267 subjects in this study. 
3 
DATA ANALYSIS CONSIDERATIONS 
3.1 
General presentation of summaries and analyses 
All statistical analyses will be performed by UCB. Computations and generation of outputs will 
be performed using SAS® Version 9.4.  
All original and derived parameters will be listed and described using summary statistics 
(number of observations (n), mean, standard deviation (SD), median, minimum and maximum, 
unless otherwise stated) or frequency counts (number of subjects (N) and percentages).  
Unless otherwise stated, listings will be sorted by treatment (PBO, then DZP 6mg/kg, 24mg/kg, 
or 45mg/kg), subject number within treatment group (not randomization number), parameter (if 
applicable) and visit (if applicable; including timing relative to dosing if applicable). For listings 
including non-randomized subjects, the non-randomized subjects will be shown first in the 
listing, ordered by subject number. All listings will include repeated and unscheduled 
measurements. Such measurements will appear in chronological order together with the 
scheduled visits, i.e., a repeated measurement will appear directly after the visit and time relative 
to dosing, for which the repeat measurement was performed. If imputed values will be included 
in the listings, these values have to be flagged. In all the listings dates will be presented in the 
format ‘YYYY-MM-DD’ and times will be presented in 24h clock format as ‘hh:mm’ or 
‘hh:mm:ss’ where appropriate. 
For continuous variables, descriptive statistics will include number of subjects (n), mean, 
standard deviation (SD), median, minimum, and maximum. Decimal places for descriptive 
statistics will always apply the following rules: 
 “n” will be an integer. 
 Mean, SD, and median will use 1 additional decimal place compared to the original data. 
 Minimum and maximum will have the same number of decimal places as the original value. 
All descriptive statistics will be presented by treatment where applicable, including columns for 
all treated subjects and all subjects on demographics, baseline characteristics, and adverse event 
displays, and using the available data for the study population as observed. Summaries of 
concentration data will be based on geometric mean and geometric standard deviation instead of 
arithmetic versions. All tabulations will be sorted by treatment, parameter and visit (including 
time relative to dosing if applicable, unless otherwise stated). Only scheduled visits and times 
relative to dosing will be included in the tabulation.  
Categorical data will be summarized by visit and treatment group, including columns for all 
treated subjects and all subjects on demographics, baseline characteristics, and adverse event 
displays, using the number and percent of subjects in each category. Percentages will be based 
on the corresponding population size (i.e., the denominator of percentages should match the 
sample size in the column header), unless otherwise noted via footnote in the applicable 
summary table. Percentages will be presented to 1 decimal place. For data points with n=0 (i.e., 
no subjects in the applicable category), no value for percentage of subjects will be displayed. 
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Missing observations will be included in the denominator unless otherwise specified on the table. 
For the shift tables, the percentages are based on those with non-missing at both time points. 
Statistical tests of efficacy variables will be presented as 2-sided p-values, except for p-values 
from the 1-sided MCP-Mod testing of the primary efficacy variable. P-values will be rounded to 
4 decimal places. P-values less than 0.0001 will be presented as “<0.0001” and p-values greater 
than 0.9999 will be presented as “>0.9999.” 
Handling of multiplicity for the primary efficacy variable is discussed in Section 4.7. All other 
variables will be considered exploratory and will be assessed at a nominal 2-sided α=0.05 
significance level. 
3.2 
Analysis time points 
The timeframe for this SAP encompasses the entire study, which extends from Screening to 28 
weeks after last dose, i.e. 24 weeks of Double-Blind Treatment Period and 24 weeks of 
Observational Period (up to Week 48). Details of the study periods are given below. All analyses 
described in this SAP will be run for the Double-Blind Treatment Period (up to Week 24) for the 
interim analysis after Part 1 is completed (unless otherwise specified, e.g., analyses of time to 
flare after Week 24, or summaries of AE groupings that include AEs beyond Week 24). All 
analyses described in the SAP will be run again for the entire study, Double-Blind Treatment 
Period (up to Week 24) + Observational Period (up to Week 48), for the final analysis after Part 
2 is completed. However, for a few summaries and analyses it is specifically stated that they are 
run only for the period up to Week 24 or the period after Week 24, and as such they will only 
include those study periods even for the final analysis. 
The following study periods will be included in the analysis: 
 Screening Period: up to 28 days (Day -28 through Day -1). 
 Double-Blind Treatment Period (Part 1): 24 weeks, starts with the randomization (1:1:1:1) of 
eligible subjects to 1 of 4 treatment arms (DZP 6mg/kg, 24mg/kg, or 45mg/kg, or PBO), 
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, starting on Day 1.  
 Observational Period (Part 2): 24 weeks, subjects who complete the 24-week Double-Blind 
Treatment Period will continue into this 24-week Observational Period. During Part 2, 
subjects will not receive study drug but will be able to receive standard-of-care treatment, as  
indicated.  
 Early Withdrawal Visit (EWV)/Safety Follow-up (SFU): 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 time points for individual assessments are provided in Table 13‒1Table 13‒1. 
Analyses conducted by visit will include each planned study visit at which the assessment was 
scheduled. Data for planned study visits will be based on the nominal time point and will not 
Formatte
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include any unplanned visits. Usually, efficacy data will not be obtained at unscheduled visits, 
with the exceptions: labs in BILAG and SLEDAI-2K. Here labs that are obtained up to 2 weeks 
after the original visit are used to replace missing lab data. 
The minimum post-baseline and maximum post-baseline values included in certain analyses by 
visit are not specific time points; rather they are the minimum and maximum observed non-
missing values per subject during SL0023, inclusive of all scheduled and unscheduled visits. 
Analyses which are presented by visit may also include an Early Withdrawal time point for 
subjects prematurely discontinuing the study. For subjects withdrawing on the same calendar day 
as a planned study visit, the assessments planned at that study visit will be summarized with the 
planned study visit and additional assessments not planned for the regular study visit, will be 
mapped to the next planned timepoint for this assessment. For subjects not withdrawing on the 
same calendar day as a planned study visit, the data will also be mapped to the next planned 
study visit. These Early Withdrawal assessments will then be included as observed data with the 
visits to which they are mapped in all analyses, except in the case of mNRI and strict NRI 
imputations, in which a subject is counted as a non-responder at the visit at which they 
discontinue study treatment or withdraw from the study and at all subsequent visits. 
Subject data listings will include all time points for collected data, including all assessments 
(planned or unplanned). Data for derived time points Last Visit and Early Withdrawal will be 
included in subject data listings. 
3.3 
Relative study days 
Relative day will accompany visit dates, sample dates, onset/start dates, and resolution/stop dates 
in data listings, and will be calculated as follows: 
 If the event start (stop) date occurred prior to first infusion, then relative day is calculated as 
start (stop) date minus first dose date. The relative day in this situation should be preceded by 
a ‘-‘. 
 If the event start (stop) date occurred on or after the first infusion and through the date of the 
last infusion, relative day is calculated as start (stop) date minus first dose date + 1. 
 If the event start (stop) date occurred after the last/latest infusion, the relative day is 
calculated as event start (stop) date minus date of last/latest infusion. The relative day in this 
situation should be preceded by a ‘+’. 
3.4 
Definition of baseline values 
Unless otherwise specified in the SAP, the last value obtained prior to the first infusion of study 
drug (Visit 2) will be used as the baseline value. If a baseline measurement is missing, and a 
screening value available, the screening value will be utilized as Baseline instead. 
For vital signs, a measurement prior to, or at the moment of, the start of the first infusion will be 
available for each visit. The last measurement prior to, or at the moment of, the start of the first 
infusion of study drug will be used as the baseline value. An additional analysis will be 
performed using the pre-infusion values as baseline values and determine the changes from pre-
infusion to post-infusion for each infusion visit. At each post-baseline visit, the pre-infusion 
value will be one taken prior to, or at the moment of, the start of the infusion of study drug. 
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For baseline assessments, if the BILAG 2004 is completed, but the grade for 1 or more 
individual system(s) is missing, the grade for the system will be set to a grade of BILAG 2004 D 
if no value can be imputed from the Screening Visit. This is a conservative approach for subjects 
on active doses, since no improvement can occur following a baseline grade of BILAG 2004 D 
level disease. 
3.5 
Protocol deviations 
Important protocol deviations are a subset of protocol deviations that may significantly impact 
the completeness, accuracy, and/or reliability of the study data or that may significantly affect a 
subject’s rights, safety, or well-being.   
Important protocol deviations are defined in the Important Protocol Deviations (IPD) document. 
Sources for identifying protocol deviations will include the clinical database and a cumulative 
protocol deviation log from the clinical sites. Protocol deviations will be classified at blinded 
data cleaning and data evaluation meetings. Any exclusion of subjects from analysis sets or 
individual data from summary outputs will be documented in the meeting minutes. 
For subjects enrolled under different versions of the protocol, the programming of protocol 
deviations should be performed according to the version of the IPD relevant to the specific 
protocol. The IPD will provide further details with regards to which version of the protocol the 
specific IPD version is applicable to. The version of the protocol to be followed for each subject 
will be provided by the Project Manager. 
3.6 
Analysis sets 
3.6.1 
Enrolled Set 
The Enrolled Set (ES) will consist of all subjects who have given informed consent. 
3.6.2 
Randomized Set 
The Randomized Set (RS) will consist of all subjects randomized into the study. 
3.6.3 
Safety Set 
The Safety Set (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 after unblinding it is determined that 
subjects received the incorrect treatment (i.e., not as per the randomization schedule), then for 
safety analyses subjects will be allocated to the actual treatment they received (as-treated) for the 
data summaries, assuming that the incorrect treatment was consistently received throughout the 
study. 
3.6.4 
Full Analysis Set 
The Full Analysis Set (FAS) will consist of all subjects who have received at least 1 full dose of 
study drug and have at least one post-Baseline efficacy measurement during the Double-Blind 
Treatment Period, with the exception of 5 patients who were randomized at site 321, who will be 
excluded from the FAS. Based on medical review of data during the course of the study, 
inconsistencies and implausibilities were identified and could neither be adequately explained by 
source data nor feedback by site personal. These findings put the adequately medically qualified 
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assessment of the disease activity at screening (determination of eligibility), baseline and post-
baseline visits in question.  After careful consideration of the problems identified, UCB feels that 
these findings may seriously compromise the ability to draw valid conclusions from the clinical 
trial. For this reason, all 5 subjects enrolled at Site 321 will be excluded from the FAS. However, 
these 5 subjects will be included for a sensitivity analysis which will be done in addition. 
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 be used for the Interim Analysis of the 
study (up to Week 24).  The FAS will also be used for the Final Analysis of the study (through 
Week 48). 
3.6.5 
Per Protocol Set 
The per Protocol Set (PPS) will consist of subjects in the FAS who have received at least one full 
dose of study drug and have no important protocol deviations during the Screening and Double-
Blind Treatment Period that may influence the validity of the data for the primary efficacy 
variable, the BICLA. 
Analyses of the primary and secondary efficacy variable, as well as BICLA responder by visit 
and SRI-4 response by visit, will be repeated using the PPS for the Double-Blind Treatment 
Period only. 
3.6.6 
Pharmacokinetic Per Protocol Set 
The Pharmacokinetic Per Protocol Set (PK-PPS) will consist of all subjects in the SS with one 
full dose of study drug 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. 
3.6.7 
Completer Set 
The Completer Set (CS) will consist of all subjects in the FAS 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. The CS will only be 
used for the Final Efficacy Analysis of the study (through Week 48). Note that completion of 
Week 24 requires that the subject has completed the efficacy scales, BILAG, SLEDAI, and PGA, 
which are required for determining BICLA response. 
3.7 
Treatment assignment and treatment groups 
For all analyses (where applicable) the results will be presented by treatment group:  
 SOC + PBO iv q4w  
 SOC + DZP 6mg/kg iv q4w  
 SOC + DZP 24mg/kg iv q4w 
 SOC + DZP 45mg/kg iv q4w  
Selected parameters (where stated in the following sections) may be summarized by treatment 
and subgroup (Definition of subgroups, s. Section 4.10). The columns ‘SOC + DZP All Subjects’ 
and ‘All Subjects’ will be included in the tables for disposition, demographic, baseline 
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characteristics, prior and concomitant medications, corticosteroid dose at screening and baseline, 
exposure and AEs. 
3.8 
Center pooling strategy 
Disposition tables will be displayed by region. The results of the secondary efficacy variable, the 
BICLA response rates in the individual dose groups at Week 24, will be displayed by country 
and region. All other results will be summarized across centers and will not be stratified by 
center. There will be no specific pooling strategy. 
3.9 
Coding dictionaries 
All AEs, concomitant diseases, and medical history will be coded for analysis according to the 
Medical Dictionary for Regulatory Activities (MedDRA)® coding dictionary, version 19.1. Prior 
and concomitant medications will be coded for analysis using the World Health Organization 
Drug dictionary (WHO-DD), version SEP/2015. The version number of coding dictionary will 
be displayed within the table. 
3.10 
Changes to protocol-defined analyses 
 A wording clarification (vs. the protocol wording) was made in the definition of a BICLA 
responder point 3, relating to PGA: 
No worsening in the Physician’s Global Assessment of Disease Activity (PGA) compared to 
study entry (“no worsening” is defined as either no worsening or worsening <10% of the 
full 100mm VAS, equivalent to less than a 10 mm increase in the PGA compared to study 
entry score); and 
 For CLASI, the protocol stated that associated symptoms, including itch, pain, and fatigue 
would be recorded separately on a 1 to 10 VAS by the subjects. However, the VAS 
assessments were not collected.  
 The following endpoints have been included as other efficacy variables – clinical assessment 
of disease activity: 
 Percentage of subjects in each category in the Systemic Lupus International Collaborating 
Clinics/American College of Rheumatology (SLICC/ACR) Damage Index score at Week 
48. 
 Time to severe flare up to Week 24 (with the occurrence of a severe flare defined as a 
BILAG severe flare) 
 Time to moderate flare up to Week 24 (with the occurrence of a moderate flare defined as 
a BILAG moderate flare. 
 Time to mild flare up to Week 24 (with the occurrence of a mild flare defined as a 
BILAG mild flare. 
 Time to severe flare (Variant 1) up to Week 24 (with the occurrence of a severe flare 
defined as a BILAG severe flare - Variant 1: a new BILAG 2004 Grade A since the 
previous visit) 
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 Time to moderate/severe flare (Variant 1) up to Week 24 (with the occurrence of a 
moderate/severe flare defined as a BILAG moderate/severe flare - Variant 1: a new 
BILAG 2004 Grade A or 2 new BILAG 2004 Grade Bs since the previous visit) 
 Time to severe flare after Week 24 (with the occurrence of a severe flare defined as a 
BILAG severe flare) 
 Time to moderate flare after Week 24 (with the occurrence of a moderate flare defined as 
a BILAG moderate flare. 
 Time to mild flare after Week 24 (with the occurrence of a mild flare defined as a BILAG 
mild flare. 
 Time to severe flare (Variant 1) after Week 24 (with the occurrence of a severe flare 
defined as a BILAG severe flare - Variant 1: a new BILAG 2004 Grade A since the 
previous visit) 
 Time to moderate/severe flare (Variant 1) after Week 24 (with the occurrence of a 
moderate/severe flare defined as a BILAG moderate/severe flare (Variant 1): a new 
BILAG 2004 Grade A or 2 new BILAG 2004 Grade Bs since the previous visit) 
 Time to severe flare from Baseline up to Week 48 (with the occurrence of a severe flare 
defined as a BILAG severe flare) 
 Time to moderate flare up to Week 48 (with the occurrence of a moderate flare defined as 
a BILAG moderate flare. 
 Time to mild flare up to Week 48 (with the occurrence of a mild flare defined as a 
BILAG mild flare. 
 Time to severe flare (Variant 1) from Baseline up to Week 48 (with the occurrence of a 
severe flare defined as a BILAG severe flare - Variant 1: a new BILAG 2004 Grade A 
since the previous visit) 
 Time to moderate/severe flare (Variant 1) from Baseline up to Week 48 (with the 
occurrence of a moderate/severe flare defined as a BILAG moderate/severe flare - 
Variant 1: a new BILAG 2004 Grade A or 2 new BILAG 2004 Grade Bs since the 
previous visit) 
 Time to flare up to Week 24 (with the occurrence of a flare defined as: a new sustained 
BILAG 2004 Grade A/B [present at ≥2 consecutive visits] or start of new induction 
therapy [either corticosteroid dose increase to ≥0.5mg/kg/day prednisone equivalent or 
initiation of cyclophosphamide, rituximab, iv Ig, MMF, MTX, Azathioprin, or plasma 
exchange])   
 The endpoint of time to flare after Week 24: 
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 ≥0.5mg/kg/day 
prednisone equivalent or initiation of cyclophosphamide, rituximab, iv Ig, or plasma 
exchange] after withdrawal of study drug) 
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was removed  from the analysis because after Week 24 BILAG was only assessed once every 
other visit (every 8 weeks) which would not allow for a valid assessment of sustained 
BILAG Grade A/B at consecutive visits. 
 The specification of patient-reported outcome variables being developed by UCB (SLE-S, 
SLE-F, SLE-M, SLE-P, SLE-E) was edited versus the protocol to remove reference to the 
“Change from Baseline…scores”.  These endpoints do not have continuous numerical scores 
and as such, no change from Baseline score can be calculated.  Only descriptive frequency 
summaries per item will be provided, as stated in Section 8.3.3.  The full analysis of these 
exploratory PRO variables is defined in a stand-alone mixed method analytical plan outside 
the SAP. 
 A new nomenclature was included for SRI-50. To avoid confusion with the SRI response 
SRI-50 was renamed to S2K RI-50. 
 Definition of SRI-4, SRI-5, SRI-6 was changed to: 
 No more than 1 shift from BILAG 2004 Grade C, D, or E to B post-Baseline 
The protocol wording for this criteria was “No more than 1 shift from BILAG 2004 Grade C, 
D, or E to B, or from B to A, post-Baseline”.  However, the allowance of a shift from B to A 
was an error and was in conflict with the second criterion of the definition which states “No 
shift from BILAG 2004 Grade B, C, D, or E to A post-Baseline”. 
 Immunological variables were only included in Section 2.2.3.1 ‘Immunological variables’, 
not additionally in Section 11.3.2 ‘Additional laboratory evaluations’, according to protocol. 
 Additional endpoints were included in the SAP, see Section 8.4. 
 In protocol section 15.6, it states that as an additional sensitivity analysis for SLEDAI-2K 
total score, if items are missing “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.” 
 
It was decided that there was not strong rationale for this approach, because the individual 
items on the SLEDAI-2K scale refer to all different organ systems. Responses for one organ 
system do not indicate what the response in another organ system may have been.  Therefore, 
extrapolating non-missing responses from some organ systems to complete the SLEDAI-2K 
total score for missing responses in other organ systems is not a good approach, and this 
sensitivity analysis was not done.  SLEDAI-2K total score will be analyzed with imputation 
for missing individual items using values from the previous visit, using MMRM and 
ANCOVA.  Additionally, SLEDAI-2K total score will be analyzed using a worst observation 
carried forward approach for missing individual items and missing total scores. 
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4 
STATISTICAL/ANALYTICAL ISSUES 
4.1 
Adjustments for covariates 
Randomization will be stratified by Screening corticosteroid dose (prednisone-equivalent).  
Accordingly, corticosteroid strata will be included in statistical models.  For the primary efficacy 
variable, the corticosteroid strata will be accounted for as detailed in Section 8.1.2.2. For the 
secondary efficacy variable a GEE analysis controlling for corticosteroid strata will be 
performed. The odds ratio of the responder rates at Week 24 will be estimated and presented 
together with the associated 95% confidence interval. 
For the analysis of other efficacy variables, statistical models will include treatment group as a 
factor and control for corticosteroid strata.  GEE and MMRM models will include visit and 
treatment*visit in the models. For models of continuous endpoints, the Baseline value will also 
be included in the model as a covariate. 
4.2 
Handling and definition of the corticosteroid prednisone 
equivalent dose 
For the purposes of further analysis and tabulations, all corticosteroid doses (including both prior 
and concomitant corticosteroids taken for any indication) will be converted to prednisone 
equivalent doses. The conversion table for systemic corticosteroids is presented in Table 4‒
1Table 4‒1. Systemic corticosteroids are those with a route of administration of oral, 
intravenous, or intramuscular.  All others (including topical, ocular, nasal, subcutaneous, intra-
articular, etc.) are non-systemic.  All non-systemic steroids will have a prednisone equivalent 
dose = 0mg/day. Budenoside is considered non-systemic even if taken orally, and will always be 
assigned a prednisone equivalent dose = 0mg/day.  
The prednisone equivalent dose will be included in the listing. For example, if the total daily 
dose of triamcinolone is 8mg, the equivalent total daily dose of prednisone will be 10mg.  
If a new corticosteroid is reported that is not in Table 4‒1Table 4‒1, the appropriate prednisone-
equivalent conversion will be determined and the prednisone equivalent dose will be included in 
the listing.  
Table 4‒1: 
Prednisone equivalent doses of systemic 
corticosteroids 
Steroids 
Dose equivalent to 5mg/day Prednisone 
Cortisone 
25 
Hydrocortisone 
20 
Deflazacort 
6.5 
Prednisolone 
5 
Prednisone 
5 
Methylprednisolone 
4 
Triamcinolone 
4 
Dexamethasone 
0.75 
Formatte
Formatte
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Table 4‒1: 
Prednisone equivalent doses of systemic 
corticosteroids 
Betamethasone 
0.6 
Note: All non-systemic corticosteroids (including topical, ocular, nasal, subcutaneous, intra-articular, etc.) will be 
assigned a prednisone equivalent dose = 0mg/day. 
Cortisol (hydrocortisone) is the standard of comparison for glucocorticoid potency. 
4.3 
Handling of dropouts or missing data 
Imputation of missing data will be done as described for missing dates and/or times for 
concomitant medication and AE data (Section 6.4  and Section 11.2, respectively), and for the 
BILAG 2004 body/organ system score, for the SLEDAI-2K total score, for the Physician’s 
Global Assessment of Disease and the efficacy variables, as described below in this section. All 
calculations and statistical analyses will be performed using the available data (including data for 
subjects who discontinued the study treatment). 
A modified non-responder imputation (mNRI) for missing data will be used for the primary 
efficacy variable (responder rate at Week 24 across 3 doses of DZP and PBO according to a 
combined response index (BICLA)). If Week 24 assessment 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 respective previous visit 
value prior to computing the BICLA treatment response variable (limited to 1 visit back). In the 
case where the predose laboratory result is missing (at Screening and at Baseline and there is no 
other unscheduled predose laboratory result), the BILAG 2004 body/organ system Baseline score 
for the body system requiring the missing laboratory result will be set to a score of BILAG 2004 
D level disease, see Section 3.4. 
If the subject has 2 or more missing components for the visit being analyzed, then the BICLA 
treatment response value is considered to be unknown (ie, left as missing and therefore 
considered a non-responder in the primary analysis approach, and subject to the missing data 
approach specified for other sensitivity analyses). 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 
non-missing components (e.g., SLEDAI-2K is missing but the non-missing 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 which is non-responder. In addition, 
subjects who prematurely withdraw from the study or who discontinue treatment prematurely 
(while still remaining in the study) are categorized as a non-responder on that visit and all 
subsequent visits for the primary analysis, although other approaches will be taken in sensitivity 
analyses.  
For the BILAG 2004 and SLEDAI-2K, if the assessment was done at a visit, but individual item 
scores/grades within the scale are missing, the respective individual item scores/grades will be 
imputed from the respective previous individual item scores/grades (limited to 1 visit back), in 
order to obtain a total score (or total assessment of improvement or worsening for BILAG) for 
the scale at the current visit, which can then be used as a component of the BICLA response 
variable. If the values of the individual item scores/grades are also missing at the previous visit, 
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then they cannot be imputed for the current visit, and the scale score is then missing for the 
current visit.  
The analysis of the secondary and other efficacy responder rates will use a similar approach for 
handling of dropouts or missing data. Note that for analysis of a responder rate at Week 4, if 
imputation from the respective previous visit is required due to missing data, a value from Visit 2 
may be used.  
For the other continuous efficacy variables that are scales made up of multiple individual items 
(BILAG 2004 total score, SLEDAI-2K total score, CLASI Activity Score, CLASI Damage 
Score, and SLICC/ACR Damage Index), observed case data will include limited imputation as 
follows. Assessments completed with one or more individual scores missing will impute 
individual scores/grades from the previous visit (limited to 1 visit back). This will be done so 
that one missing item score will not render the entire scale total score incalculable. Note that for 
analysis at Week 4, if imputation from the respective previous visit is required due to missing 
data, a value from Visit 2 (Visit 1 for SLICC/ACR Damage Index) may be used.  Beyond that, 
no direct imputation will be done for a missing assessment at a visit, and the efficacy response 
will be considered to be unknown (ie, left as missing and subject to the analysis approach applied 
to continuous efficacy variables, mixed effects models for repeat measurement (MMRM) and 
supportive Analysis of Covariance (ANCOVA) using observed case data). For other continuous 
efficacy variables, analyses will be based on observed case data with no imputation of any 
individual items or total scores, unless otherwise noted for the individual endpoint in Section 
8.3.1. 
As stated above, subjects who prematurely withdraw from the study or who discontinue 
treatment prematurely (while still remaining in the study) are categorized as a non-responder on 
that visit and all subsequent visits for the primary analysis. However, there is no date collected 
for discontinuation of study medication when a patient remains in the study. Additionally, the 
date collected for study withdrawal is often long after the decision to withdraw from the study 
due to completion of follow-up visits and documentation. Therefore, the following algorithm will 
be used to determine the date at which a subject is considered a non-responder in efficacy 
analyses due to study withdrawal or study treatment discontinuation: 
If a subject has withdrawn from the entire study (without having previously withdrawn study 
drug), the subject should be considered a non-responder starting on the earliest of these 
dates: 
 the withdraw date given in the Subject Disposition CRF (i.e., stored in SDTM DS 
dataset) 
 if withdrawal during the double-blind period and subject did attend the next 
scheduled infusion visit after the last infusion received, then the date of the next 
scheduled infusion visit after the last infusion, at which the subject should have had 
an infusion but did not 
 if withdrawal during the double-blind period and the next scheduled infusion visit 
was missed/skipped after the last infusion, then the last infusion date+28 days 
 If withdrawal during the observational period, then date of last visit attended  
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If a subject has withdrawn only from study drug, then the subject should be considered a non-
responder starting on the earlier of these dates: 
 the date of the next scheduled visit at which the subject should have had an infusion 
but did not, if the subject did attend the next scheduled infusion visit 
 the last infusion date+28 days (in case the next scheduled infusion visit was 
missed/skipped after the last infusion)  
The above proposed algorithm is for determining at what point the subject is considered a non-
responder for efficacy analyses.   
It also needs to be determined when a subject Discontinued Study Drug or Withdrew from the 
Study relative to study visits for the summary of Discontinuation Reasons by Visit Table. 
Specifically, at each visit, it needs to be determined whether a subject discontinued study drug or 
withdrew from the study prior to that visit. 
If a subject has withdrawn from the entire study, on the Discontinuation Reasons by Visit 
Table the subject is counted as withdrawing from the study prior to visit beginning with: 
 the next scheduled visit after the last visit attended (if the withdraw date in DS >= the 
last visit attended)  
 the next visit attended after the withdraw date in DS (if the withdraw date in DS < the 
date of the last visit attended) 
If a subject has withdrawn only from study drug, on the Discontinuation Reasons by Visit 
Table the subject is counted as discontinuing study drug prior to visit beginning with: 
 the next scheduled visit at which the subject should have had an infusion but did not 
4.4 
Handling of Retests 
All original and retested assessments will be listed. In case of retest of a variable, the following 
rules are applied: 
 The last non-missing value of baseline assessments is used for statistical analyses. 
 The nominal visit value of post-dose assessments (discharge included) is used for statistical 
analyses. Retests of post-dose assessments will not be used in analyses and summaries, but 
will be included in listings. 
These rules imply that: 
 When more than 1 assessment is available for a specific study moment, these assessments are 
organized as first the original assessment, assigned to the nominal visit, and then the retested 
assessment(s), assigned to unscheduled visits. The date and time of measurement are used to 
sort the data. 
 For BP, when selecting the last non-missing value for Baseline, a complete set of both SBP 
and DBP is selected for statistical analyses. 
For laboratory assessments:  
 Not assessable values are excluded from the statistical analyses. 
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 When selecting the last non-missing value for Baseline, a complete set of WBC counts from 
the same laboratory sample assessment is selected (neutrophil count, eosinophil count, 
basophil count, monocyte count, atypical lymphocyte count and lymphocyte count). The 
rounded sum of these counts should be equal to 100, if the individual counts are expressed in 
%. 
4.5 
Interim analyses and data monitoring 
A Data Monitoring Committee (DMC) will be formed to monitor the safety of the study. The 
composition and operation of the DMC will be defined in the DMC Charter. The presentation 
and analysis of data for the DMC meetings is described within a separate SAP. 
In Part 1 (double-blind part) of the study 3 Data Evaluation Meetings (DEMs) are planned for 
assessment of aggregate data throughout the study: 
DEM-1 will take place after 15 to 25% of the enrolled subjects have complete data of primary 
variable. Objectives: Evaluation of aggregate data in order to identify systemic data errors and 
potential trends in important protocol deviations, and review of aggregate data to detect outliers 
and to evaluate relevant data distributions. 
DEM-2 will take place after 50 to 60% of the enrolled subjects have complete data of primary 
variable. Objectives: Evaluation of aggregate data in order to identify systemic data errors and 
potential trends in important protocol deviations, discussion of dry-run tables, listings and 
figures, and finalization of the content of outputs defined in the SAP. 
DEM-3 will take place after 100% of the enrolled subjects have complete data of primary 
variable, all data are entered and approximately 95% to 100% of the data are clean. Objectives: 
confirmation of statistical assumptions, discussion of any outstanding analysis topics and 
finalization of rules for exclusion from analysis set. 
DEM-3a will take place after 100% of the enrolled subjects have complete data through the end 
of the Observational Period of Early Withdrawal, all data are entered and approximately 95% to 
100% of the data are clean. Objectives: Final evaluation of data to ensure readiness for final 
database lock. 
After the last subject completed Part 1 of the study 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) and will include all 
information of the entire study (Double-blind and Observational Period). Final tables should include 
all tables run for the interim analysis, updated to include all study visits where appropriate. In general, 
the interim analysis will cover the visits up to Week 24 and the final analysis will cover all visits 
up to Week 48. All efficacy tables of the final analysis will be run on the FAS and CS. Tables 
that only cover Week 24 to Week 48 will be run on the CS. 
4.6 
Multicenter studies 
The results of the secondary efficacy variable, the BICLA response rates in the individual dose 
groups at Week 24, will be displayed by country and region. The other data from all centers will 
be pooled for the purposes of the final analyses. There will be no formal statistical evaluation of 
the effect of center on the results obtained. 
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4.7 
Multiple comparisons/multiplicity 
Multiple Comparison Procedure-Modeling (MCP-Mod) methodology (Bretz et al, 2005) will be 
used to test the dose-response relationship across 3 doses of DZP and PBO for the BICLA 
responder rate.  Monotonic dose-response trends (as well as non-monotonic dose-response trends 
in one sensitivity analysis) will be tested using the optimal contrasts as determined by the MCP-
Mod methodology such that the overall Type I error rate is controlled at 0.05 (one-sided testing).  
Analyses of secondary and other efficacy variables will not be adjusted for multiple 
comparisons, and as such, p-values are considered descriptive and caution should be exercised in 
interpreting them. 
4.8 
Use of an efficacy subset of subjects 
Not applicable. 
4.9 
Active-control studies intended to show equivalence 
Not applicable. 
4.10 
Examination of subgroups 
The primary efficacy variable will be summarized by treatment group and subgroups of interest, 
as defined below: 
 Region (Western/Central Europe, Eastern Europe, Latin America, North America) 
 Demographic factors at Screening: 
 Age: < median age, ≥ median age (Median age based on the Safety Set) 
 Weight: ≤ 80kg, > 80kg 
 BMI: < median BMI, ≥ median BMI (Median BMI based on the Safety Set) 
 Gender: female, male 
 Race: White vs. non-White  
 Ethnicity: Not Hispanic/Latino vs. Hispanic/Latino 
 Baseline disease activity: 
 High SLEDAI-2K at Baseline: <10, ≥10 
 SLEDAI-2K at Baseline: < median, ≥ median (Median SLEDAI-2K based on the Safety 
Set) 
 BILAG 2004 at Baseline (severely active patients): Subjects with  at least 1 BILAG 2004 
Grade A, subjects with no BILAG 2004 Grade A at Baseline (Visit 2) [a] 
 BILAG 2004 at Baseline (multi-organ moderately to severely active): Subjects with  >2 
BILAG Grade As or Bs, subjects with ≤2 BILAG 2004 Grade As or Bs at Baseline (Visit 
2)  
 Lower BILAG 2004 activity at Baseline: Subjects with maximum 1 BILAG 2004 Grade 
B (BILAG C, D or E allowed) at Baseline, subjects with at least 2 BILAG 2004 Grade Bs 
or ≥1 BILAG 2004 Grade A at Baseline 
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 No significant disease activity at Baseline: Subjects with only BILAG 2004 Grade C, D 
or E in all organ systems, subjects with at least 1 BILAG 2004 Grade B in one organ 
system 
 Musculoskeletal only: BILAG 2004 Grade A in musculoskeletal at Baseline and no 
BILAG 2004 Grade A or B in another organ system, all other 
 BILAG 2004 score at Baseline: ≤12, >12 
 CLASI Activity Score at Baseline: <4, ≥4 
 SLE associated lab parameters 
 Anti ds DNA status at Baseline: anti-dsDNA in Farr assay ≤ 10iU (negative/ 
indeterminate), > 10iU (positive) 
 ANA titer at Screening: ≤1:160, >1:160 (For ANA titer, 1:80 < 1:160, i.e., it is the 
denominators that are assessed to determine whether the ANA titer is < or > a cutoff.) 
 Any low complement at Baseline: Subjects with C3 or C4 < LLN, subjects with both C3 
and C4 ≥LLN 
 Both low complement at Baseline: Subjects with C3 and C4 < LLN, subjects with either 
C3 or C4 ≥LLN 
 Anti-dsDNA and low complement at Baseline: Anti-dsDNA Farr > 10iU and either C3 or 
C4 < LLN, all other 
 Concomitant medications at Baseline (Visit 2) 
 Corticosteroid dose (prednisone-equivalent) randomization strata: ≤10mg/day, 
>10mg/day 
 Corticosteroid dose (prednisone-equivalent) high dose/low dose: ≤7.5mg/day, 
>7.5mg/day 
 Corticosteroid vs. no dose: 0 mg/day, >0mg/day 
 Anti-malarial at Baseline: yes, no 
 Immunosuppressants at Baseline: yes, no 
 Other 
 Unblinded cases: Subjects unblinded during the study for any reason (e.g., qualifying  
safety event) 
 
All subgroup summaries will be provided for BICLA by visit for the FAS for the interim 
analysis, and for the FAS and the CS for the final analysis. Descriptive statistics by subgroup 
will be presented for the BICLA responder by visit. There will be no statistical analyses within 
subgroups. A patient data listing including all subgroups will be provided. 
 
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Furthermore, subgroup summaries will be provided for treatment-emergent AEs (TEAEs). 
Incidences of TEAEs will be presented by the following subgroup: 
 aPL status positive at any time during the study (Screening or Week 24 for Interim Analysis 
assessment of the Double-Blind Period; and Screening, Week 24, or Week 48 for Final 
Analysis assessments including AEs during the Observational Period) vs. negative at all time 
points assessed during the study. aPL positive is defined as subject has ever experienced at 
least 1 of the following immunologic criteria during the study: positive test result for anti-β2 
glycoprotein (IgG>ULN or IgM>ULN), medium or high titer anticardiolipin antibody level 
(IgG>ULN or IgM>ULN), positive lupus anticoagulant test (time (noted as DRVVT in the 
laboratory dataset)>ULN and ratio (noted as DRVVTRT in the laboratory dataset)>ULN).   
There will also be subgroup summaries provided (for the final analysis) for BICLA by visit for 
the FAS and CS and for TEAEs by the following subgroups: 
 anti-DZP: any positive [pre or post] during study vs. negative at all time points analyzed, 
 anti-PEG: any positive [pre or post] during study vs. negative at all time points analyzed. 
5 
STUDY POPULATION CHARACTERISTICS 
5.1 
Subject disposition 
Subject disposition will be listed for all subjects screened and will include the following 
information: subject status (screen failure, study completed or discontinued, study drug 
completed or discontinued, study drug discontinued, but study continued), date of informed 
consent, date of randomization, date of first and last dose of study drug (including relative day 
for last dose, as described in Section 3.3), date of premature study and/or study drug termination 
(if applicable) and primary reason for study and/or study drug termination (if applicable). The 
date of premature study withdrawal is taken from the CRF, however the date of study drug 
termination will be determined as per the algorithm in Section 4.3. The listing will also include 
the date and reason for breaking the randomization code (if applicable) as well as the date of 
final contact for the subject and the previous subject number, if a subject was re-screened. For 
screen failures the date and reason for screen failure will be listed. 
Subject disposition will be summarized for all subjects screened including the reasons for screen 
failure, the number of subjects re-screened and the number of subjects randomized. Subject 
disposition will also be summarized for the Randomized Set by treatment and overall, including 
the reasons for discontinuation of study and/or study drug and the number of subjects with 
premature termination of study drug but not early withdrawn from the study. Details of 
discontinuation due to AEs will be tabulated. Reasons for discontinuation of study and/or of 
treatment and visit of discontinuation will be listed.. Discontinuations will be assigned to visits 
as per the algorithm in Section 4.3.  
A Kaplan Meier figure will display the Kaplan Meier estimates for subjects who were neither 
withdrawn from the study nor permanently withdrawn fromstudy drug vs. time. The time until 
discontinuation of study drug or premature withdrawal from the study will be calculated using 
the date at which a subject is considered a non-responder in efficacy analyses due to study 
withdrawal or study treatment discontinuation determined as per the algorithm in Section 4.3. 
The reason for this approach is that the figure presents the time to study drug discontinuation or 
premature withdrawal, so it should use the time to whichever event occurs first. Similarly, the 
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date at which a subject is considered a non-responder in efficacy analyses due to study 
withdrawal or study treatment discontinuation is the earliest date of either study treatment 
discontinuation or study withdrawal as per the Disposition CRF.  If a subject has not prematurely 
withdrawn from the study nor discontinued study drug by Week 24 (for the interim analysis), 
she/he should be censored on the Week 24 visit date (or the planned Week 24 visit date if the 
visit was missed).  If a subject has not prematurely withdrawn from the study nor discontinued 
study drug by Week 48 (for the final analysis), she/he should be censored on the day of the Week 
48 visit date (or final visit date if Week 48 visit was missed). 
A subject who is rescreened will be counted as 2 screened subjects in disposition tables that 
provide a count of screened subjects. That way each reason for screen failure will be tabulated as 
well. The disposition tables will indicate how many subjects were rescreened and thus counted 
twice in the total number screened. 
Study eligibility criteria will be listed and a separate listing of subjects who did not meet the 
eligibility criteria will be presented. Only failed criteria will be included in the former listing. 
Finally, a listing of study visit dates will be presented by subject including the relative study day 
(calculated as described in Section 3.3) for each visit. 
To further support public disclosure, a summary of the number and percentage of subjects in 
each study defined Analysis Set, by treatment and overall, will be produced for the Final 
Analysis only based on the Enrolled Set. 
5.2 
Protocol deviations 
Important protocol deviations will be identified and classified by the deviation types defined in 
the Important Protocol Deviations (IPD) document, which will include at least the deviation 
types, listed below. A listing of all important protocol deviations identified at the Data 
Evaluation Meeting will be presented for all subjects in the Randomized Set, and will include 
deviation type and description. The number and percentage of subjects in the Randomized Set 
with important protocol deviations will be summarized overall and by treatment. 
The following deviation types are defined in the IPD: 
 Inclusion criteria 
 Exclusion criteria 
 Withdrawal criteria 
 Study drug compliance 
 PK blood sampling deviations 
 PK urine sampling deviations 
 Prohibited concomitant medication use 
Deviation types will be classified according to the following categories as defined in the IPD: 
 Important deviations that may significantly affect a subject's rights or safety 
 Important deviations for the PPS 
 Important deviations for the PK-PPS 
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Subjects are excluded from the PPS if they have an important protocol deviation that may impact 
the results of the primary efficacy analysis.  Subjects are excluded from the PK-PPS if they have 
an important protocol deviation that may impact the results of the PK analysis. The denominator 
for the percentages will be the number of subjects in the Randomized Set for each treatment or 
overall. 
The assignment of subjects to each of the analysis sets will be listed for all subjects screened. In 
addition, a listing of all screened subjects who did not meet study eligibility criteria will be 
presented. 
6 
DEMOGRAPHICS AND OTHER BASELINE 
CHARACTERISTICS 
6.1 
Demographics 
Tables with descriptive statistics and listings will be given for the demographic variables age (at 
time of informed consent), gender, weight and height at Screening, race, ethnicity, and body 
mass index (BMI). Demographic characteristics will be summarized for the FAS, the SS and the 
CS by treatment and overall. Age will be summarized as a continuous variable and as a 
categorical variable based on the following categories: <65 years, ≥65 - <75 years, ≥75 years. 
Age will also be summarized by additional categories required by EudraCT and clinicaltrials.gov 
for public disclosure. 
6.2 
Other Baseline characteristics 
Systemic lupus erythematosus history (BILAG 2004 SLE History) will be listed for subjects in 
the FAS including the date of first diagnosis and whether the subject has ever experienced an 
SLE-related sign or symptom in each body system (constitutional, mucocutaneous, 
neuropsychiatric, musculoskeletal, cardiorespiratory, gastrointestinal, ophthalmic, renal, 
hematology and vasculitis). The number of subjects who ever experienced an SLE sign or 
symptom (BILAG 2004 SLE History) will be tabulated for each Body System for the FAS and 
CS as well. 
Procedure history will be listed chronologically for all subjects in the SS including the reported 
term for the procedure, the date of the procedure and the information whether the procedure is 
related to SLE. 
Information about the SLE disease status at Screening and at Baseline will be summarized in tables 
for the SS, FAS, and CS. Baseline is already defined in Section 3.4 as the last value obtained prior 
to the first infusion of study drug (Visit 2). For the purpose of the display of Baseline 
Characteristics at Screening only, Screening will be defined as the last value obtained prior to 
Visit 2, i.e., it will be the last value obtained at Visit 1 or at an unscheduled visit prior to Visit 2. 
The information about SLE disease status at Screening and at Baseline will include:  
 the frequencies of British Isles Lupus Assessment Group Disease Activity Index 2004 
(BILAG 2004) grades in each system,  
 the descriptive statistics for the BILAG 2004 total score, 
 the number of subjects with BILAG 2004 Total Score <20 or with BILAG 2004 Total Score  
≥20, 
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 the descriptive statistics for the total score of the SLEDAI-2K (with and without inclusion of 
labs as a component of the SLEDAI-2K score) (where labs are excluded, the items excluded 
from the SLEDAI-2K score are: 'low complement ', 'anti-DNA', 'urinary casts', 'hematuria', 
'proteinuria', 'pyuria', 'thrombocytopenia', and 'leukopenia'), 
 the number of subjects with SLEDAI-2K <10 or with SLEDAI-2K  ≥10, 
 the number of subjects with SLEDAI-2K (calculated with dsDNA positivity defined as anti-
dsDNA ≥ 5 iU) < 10 or with SLEDAI-2K (calculated with dsDNA positivity defined as anti-
dsDNA ≥ 5 iU) ≥ 10, 
 , 
 the descriptive statistics for the Physician’s Global Assessment of Disease (PGA) score,  
 the descriptive statistics for the Patient’s Global Assessment of Disease (PtGA) score, 
 the results for the Systemic Lupus International Collaborating Clinics (SLICC) Damage Index: 
the number of subjects with a SLICC score ‘0’ (no organ damaged), a SLICC score ‘1’ (one 
organ damaged) or a SLICC score ‘>1’ (multiple organ damaged).  
Furthermore, the following disease specific baseline parameters will be included in the table:  
 the descriptive statistics for the time since diagnosis,  
 the number of flares in the 6 months prior to Screening, 
 At Screening and at Baseline: the number of subjects 
 fulfilling screening eligibility criteria: either ≥1 BILAG Grade A or ≥2 BILAG Grade Bs 
 who do not fulfill screening eligibility anymore but still are evaluable: 1 BILAG Grade B 
only, no BILAG Grade A 
 who do not fulfill screening eligibility and are not evaluable: no BILAG Grade A, no 
BILAG Grade B 
 with at least 1 organ system severely active: ≥1 BILAG Grade A 
 with only 1 (severely) involved organ system: 1 BILAG Grade A and no other organ 
system with BILAG Grade A, Grade B,  
 with multi-organ involvement: ≥2 organ systems with BILAG Grade A or Grade B 
 with multiple severely active organs: ≥2 organ systems with BILAG Grade A 
 with multiple organ involvement but no severely active: ≥2 organ systems with BILAG 
Grade B, no organ system with BILAG Grade A, 
  the number of subjects with aPLs in central lab (at least ever experienced 1 of the following 
immunologic criteria: positive test result for anti-β2 glycoprotein I, medium or high titer 
anticardiolipin antibody level, positive lupus anticoagulant test), for each criterion and 
combined,  
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 the number of subjects with a thromboembolic event in the medical history (based on 
Thromboembolic Standardized MedDRA Queries (SMQs) plus the additional item 
“antiphospholipid syndrome” and tabulated overall), 
 the number of subjects with anti-dsDNA (based on data from central lab [0 to <5iU 
(negative), ≥5 to ≤ 10iU (intermediate-positive), > 10iU (positive), ≥ 5 iU (intermediate-
positive and positive)] and also based on data from the SLICC classification form which 
reflects whether a patient has ever experienced anti-dsDNA positivity in the past),  
 the number of subjects with ANA titer classified as ANA titer < 1:80, ANA titer ≥ 1:80 and  
≤ 1:160, or ANA titer > 1:160 (For ANA titer, 1:80 < 1:160, i.e., it is the denominators that 
are assessed to determine whether the ANA titer is < or > a cutoff.),   
 the number of subjects with low complement (either low complement 3 (C3), low 
complement 4 (C4), either C3 or C4, or both), and  
 the number of subjects with renal dysfunction (defined as estimated 
GFR<60mL/min/1.73m3), 
 the number of subjects with uPCR >113 mg/mmol 
 the number of subjects on corticosteroids  
 the number of subjects on antimalarials  
 the number of subjects on immunosuppressants 
 the number of subjects on corticosteroids and antimalarials 
 the number of subjects on immunosuppressants and antimalarials  
 the number of subjects on corticosteroids and immunosuppressants 
 the number of subjects on corticosteroids, antimalarials and immunosuppressants 
 the number of subjects in each region, and 
 the number of subjects in each country. 
 
All baseline characteristics will be listed. 
6.3 
Medical history and concomitant diseases 
Medical history and ongoing medical conditions will be listed for all subjects in the SS including 
the reported term, start date (month and year only), end date (month and year only) (or ongoing if 
applicable) and the information whether the reported condition is related to SLE. A glossary of all 
medical conditions will also be presented including the reported term, the preferred term and the 
System Organ Class.  
The classification of medical history and concomitant diseases will be done according to the 
MedDRA coding system (version 19.1) using system organ class (SOC), high level term and 
preferred term. These data will be summarized using frequency tables for subject count by 
classified data.  
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6.4 
Prior and concomitant medications 
Any medication with end date and time before first administration of study drug will be 
considered and labeled as ‘prior medication’. 
Medication started and not stopped before first study drug administration date will be considered 
and labeled as ‘concomitant medication’. Medication for which the start date and time is between 
the start of study drug administration and the end of the Safety Follow-up (SFU) Period (12 
weeks after the final dose of study drug) will be considered and labeled as ‘concomitant 
medication’.  
‘Observational Period medication’ will be defined as any medication taken during the period 
starting at the Week 24 visit and running through the end of the study. In case of early 
withdrawal, medications taken during the period starting at 4 weeks after the final dose of study 
drug and running through the end of the study will be considered as ‘Observational Period 
medication’. As such, some medications will be considered as ‘concomitant medication’ and as 
‘Observational Period medication’. 
Any medications with incomplete start and end dates/times will be handled according to the 
following rules for classification as prior and concomitant and for the calculation of relative 
study days. Such imputations will only be performed for these classifications and calculations; in 
the listings all data will be shown as recorded on the eCRF. 
Imputation of Partial Start Dates: 
 If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of the start date, then use the 1st of the month. 
 If only the month and year are specified and the month and year of first dose is the same as 
the month and year of the start, then use the date of first dose. 
 If only the year is specified, and the year of first dose is not the same as the year of the start 
date, then use January 1 of the year of the start date. 
 If only the year is specified, and the year of first dose is the same as the year of the start date, 
then use the date of first dose. 
 If the date is completely unknown, then use the date of first dose. 
Imputation of Partial End Dates: 
 If only the month and year are specified then use the last day of the month. 
 If only the year is specified then use December 31 of that year. 
 If the date is completely unknown, do not impute the stop date. 
Imputations of missing data will be performed before calculation of relative study days. 
Prior, concomitant and Observational Period medications will be listed for subjects in the SS, 
separately in a listing for SLE medications and an overall listing for all medications. Variables 
will be included which classify the medication as prior, concomitant and/or Observational 
Period. Furthermore, the following information will be included in the listings: reported term, 
dose per intake and dose unit, frequency, formulation, indication (including free text recorded by 
Investigator for non-SLE indications), start and stop dates (including relative study day), and in 
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case of missing stop date, the information whether the intake of medication is ongoing. 
Additionally, for immunosuppressants, anti-malarials, and corticosteroids that are prior 
medications (stopped before the study), the reason for discontinuation or change of dose will be 
included in the listings. A listing of subjects with concomitant medical procedures will also be 
provided. 
Furthermore, the number of subjects with prior, concomitant or Observational Period medication 
will each be analyzed separately using frequency tables based on classified data by SLE-
related/not SLE-related (information about (no) SLE-relation will be provided by tick box in 
CRF). The classification of the medication will be done according to the WHO-DD ATC 
classification, version Sep. 2015. The number of subjects with SLE-related medication at 
Baseline will also be tabulated. Specifically, the number of subjects taking corticosteroids, the 
number of subjects taking antimalarials, and the number of subjects taking immunosuppressants 
at Baseline will be tabulated in the Baseline Characteristics table.  Concomitant medications will 
be manually reviewed by a physician during the study to assign medications to these groups. 
This review will be done in a blinded manner for the Interim Analysis. 
Additionally, the descriptive statistics of the corticosteroid dose (prednisone-equivalent) at 
Baseline will be tabulated for the SS, FAS and CS analysis sets. The number of subjects with 
‘≤10mg/day corticosteroids’ vs. ‘>10mg/day corticosteroids’, with 0mg/day vs. ≤7.5mg/day 
corticosteroids vs. >7.5mg/day corticosteroids, and with <10mg/day corticosteroids vs. 
≥10mg/day corticosteroids will be displayed.  
 
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7 
MEASUREMENTS OF TREATMENT COMPLIANCE 
The IMP will be administered by designated study site staff. The unblinded monitor will review 
the pharmacy records at each site, including the Drug Dispensing Record Form. The unblinded 
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. 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. 
Date and time of start and end of each IMP administration will be listed. Treatment 
administration including total volume infused, estimated fraction of dose remaining, planned and 
actual dose of DZP administered (mg), duration of infusion (min) and compliance (%) (derived 
as described in Section 11.1.1) will be listed (including PBO when applicable). A summary of 
total volume given, actual dose received, and infusion duration (min) and compliance by visit 
and the total duration of exposure will also be provided. Descriptive statistics for the total 
number of infusions administered, for %doses with correct/incorrect (<80%/ >120%) 
administration, for %skipped doses and %infusions with a shorter infusion time as planned (<90 
min) will be tabulated.  
The planned volume to be infused is 150 mL for all subjects and doses. The planned infusion 
time is approximately 120 min. 
8 
EFFICACY ANALYSES 
The efficacy analysis for the Interim Analysis will be based on all subjects of the FAS.  The 
efficacy analysis for the Final Analysis will be based on the FAS and the CS. 
Regarding the BILAG-2004, the SLEDAI-2K total score and the Physician’s Global Assessment 
of Disease, as well as other endpoints, the handling of dropouts and missing data is described in 
Section 4.3. 
All statistical models should be controlling for corticosteroid strata unless the model cannot 
accommodate a covariate or will not converge with a covariate. 
The endpoints BICLA, SRI-4, SRI-5, SRI-6, S2K RI-50 and SLEDAI-2K include the SLEDAI-
2K Total Score as part of their derivation. The SLEDAI-2K Total Score will be re-calculated 
based on central laboratory results:  Although the SLEDAI-2K Total Score is captured on the 
CRF, these values should not be used as the SLEDAI-2K values being analyzed. The SLEDAI-
2K includes several items that are related to lab parameters. While the majority of these items 
include an additional judgment by the assessor, the items connected to 'low complement' and 
'increased DNA binding' are directly related to lab parameters. For these parameters the central 
lab results for the lab sample taken at the same visit will be used to determine if an item is 
considered to be ‘present’, based on the following definitions:   
 'low complement' is defined as either complement C3 or complement C4 or both is below 
LLN 
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 'increased DNA binding' is defined as a Farr assay >10 iU  
If there is no lab sample taken at the same visit, a lab within 14 days after the visit may be used. 
If there is no lab within 14 days after the visit, the lab results from one visit back may be used. 
(Note that this also applies for C3 and C4, such that if one is non-missing and the other is 
missing, the missing one will be imputed as described here using a lab from up to 14 days after 
the visit, or if that is not available then lab results from one visit back.) Only in case there is no 
lab value available at the respective visit, within 14 days after the visit, nor at the previous visit, 
then the data from the CRF will be used if available. The number of points to be added to the 
SLEDAI-2K score if an item is present is the same whether the item is determined to be present 
based on CRF data or central lab data. 
8.1 
Statistical analysis of the primary efficacy variable 
8.1.1 
Derivation of primary efficacy variable 
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 (i.e., all criteria must be met to achieve responder status).  
Note that “study entry” within these criteria refers to Baseline, which is Visit 2 (or an earlier visit 
if the Visit 2 assessment was not done). 
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 
worsening in other BILAG 2004 organ systems (that had BILAG 2004 Grade C, D, or E at 
Baseline) such that there are no new BILAG 2004 Grades A nor greater than 1 new BILAG 
2004 Grade(s) B; and 
2. No worsening in the SLEDAI-2K total score compared to study entry (defined as no increase 
in SLEDAI-2K total score); and 
3. No worsening in the Physician’s Global Assessment of Disease Activity (PGA) compared to 
study entry (“no worsening” is defined as either no worsening or worsening <10% of the full 
100mm VAS, equivalent to less than a 10mm increase in the PGA compared to study entry 
score); and 
4. No changes in specified concomitant medications as escape 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 in the 
protocol. 
 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. 
For subjects known to be non-responders due to changes in concomitant medications, subjects 
will be primarily categorized as non-responders throughout the remainder of the study, 
regardless of visit attendance or assessments performed. A subject will become a non-responder 
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due to a change in concomitant medication that is considered to be escape medication, beginning  
the day after the reported start date of the relevant concomitant medication. 
In addition, subjects who permanently discontinue study drug prematurely are primarily 
categorized as non-responders. Any subject who is withdrawn from the study prior to completing 
the Visit 9 infusion has effectively permanently discontinued study drug prematurely, and is 
therefore primarily categorized as a non-responder. 
8.1.2 
Analysis of the primary efficacy variable 
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 non-
responder imputation (mNRI) for missing data, s. Section 4.3.  The analysis will be run on the 
FAS and the PPS. 
The Week 24 BICLA dose-response relationship across 3 doses of DZP and PBO will be tested 
using the Multiple Comparison Procedure–Modeling (MCP-Mod) methodology (Bretz et al, 
2005). Monotonic dose-response trends will be tested using the optimal contrasts as determined 
by the MCP-Mod methodology such that the overall Type 1 error rate is controlled at 0.05 (one-
sided testing). 
8.1.2.1 
MCP-Mod - Candidate models 
The primary endpoint of the study is a binary indicator of whether the subject responds to 
treatment. Four different dose-response models (‘candidate models’) will be used: a linear 
model, a logistic model, and 2 Emax models, and the MCP-Mod methodology will control for 
multiplicity. 
The analysis will be performed 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.  
 
Three families of models will be considered in the candidate set for representing the expected 
response μd (on the logit scale) at dose d:  
 Linear — μd = e0 + δ*d,  
parameters to estimate: e0 and δ  
 Logistic — μd = e0 + emax /{1+exp([ED50-d]/ δ)} 
parameters to estimate: e0, emax, ED50 and δ 
 Emax — μd = e0 + emax * d/(ED50 + d),  
parameters to estimate: e0, emax and ED50 
where, e0 is the placebo effect (except for in the logistic model), δ is the slope parameter,  
Emax is the asymptotic maximum effect and ED50 is the dose giving half of the asymptotic 
maximum effect. 
 
  
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The pre-specified standardized parameters for each candidate model are from the sample size 
calculations:  
Linear model: µd=d   
Logistic model: µd=1/{1+exp[(17.2-d)/7]}, i.e., ED50=17.2 and δ=7 
Emax model 1: µd=d/(13.5+d), i.e., ED50=13.5 
Emax model 2: µd=d/(25+d), i.e., ED50=25 
8.1.2.2 
MCP-Mod - Analysis 
 
The analysis will be performed using a two-step approach that extends MCP-Mod methodology 
to perform dose-reponse modeling and testing in the context of general parametric models 
(Pinheiro et al, 2014) as follows:  
 Using the R function glm, a logistic regression model (with ANOVA-type 
parametrization), including parameters for dose category and corticosteroid stratum, will 
be fitted to obtain LSmean LogOdds estimates µd for each dose and their associated 
covariance matrix S. The LSmeans for each dose will be averaged over the effect of 
corticosteroid stratum.   
 Then all subsequent inference using the R function MCPMOD depends only on the pre-
defined standardized model shapes, the fitted lsmeans µd and covariance matrix S as 
inputs. The random seed used for MCPMOD analysis will be 123493. 
If at least one model is statistically significant from the multiple contrast test, there is an 
indication of a dose-response effect. 
MCPMOD will also identify the best candidate model using the model selection criteria, lowest 
AIC (Akaike Information Criteria). The MCPMOD selected model will then be used to produce 
an estimate of the MCP-Mod target dose, defined as the minimum dose that achieves the 
protocol design treatment effect, 29% on the probability scale given a placebo response of 25%, 
expressed on the LogOdds scale, i.e., 1.258955. The MCPMOD selected model will also be used 
to produce estimates of the probability of response, difference in probability of response vs. 
placebo, and odds ratio vs. placebo at selected doses. 
The number of BICLA responders and non-responders at Week 24 will be tabulated. The 
assessment of each subject as a responder or as a non-responder and the assessment for each 
criterion the BICLA is based on (see Section 8.1.1) will be tabulated by treatment and subject. 
As the primary efficacy endpoint is a composite variable, reasons for failure to achieve treatment 
response and the exclusive reason for failure to achieve treatment response will also be 
summarized with descriptive statistics. One table includes the subjects who may have more than 
one reason for non-response/adherence to medication, a second table will include the number of 
subjects who have one reason exclusively for non-response/adherence to medication. Analysis of 
the individual components of the composite endpoint is described in Section 8.3. 
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8.1.2.3 
Sensitivity Analyses of the Primary Efficacy Variable - missing data  
Sensitivity analyses to examine the impact of missing data on the primary analysis will be 
conducted. All sensitivity statistical hypothesis tests will be considered descriptive only and will 
be conducted at the nominal level α=0.05 (one-sided testing).  
The primary analysis will be conducted using the FAS. This analysis will be repeated using the 
PPS as a sensitivity analysis. 
To examine the impact of missing data on the primary analysis, missing treatment response 
status at Week 24 will be imputed using the following 3 alternate methods: 
1. mNRI data set where non-missing study response after discontinuation of study drug is used 
for subjects who discontinued study treatment but remained in the study 
2. Observed cases data set (including only observed data at Week 24 with no imputation of any 
missing data in BICLA components [including no imputation of any missing individual items 
in the multiple item scales]) 
3. Strict NRI data set (all/any missing data in BICLA components [including any missing 
individual items in the scales] at Week 24 leads to non-responder status on the BICLA for 
Week 24) 
The MCP-Mod procedure described in Sections 8.1.2.1 and 8.2.1.2 will be re-run for the FAS on 
each of these datasets to examine the selected dose-response model and the MCPMOD estimated 
target dose (defined as the minimum dose that achieves the protocol design treatment effect, 29% 
on the probability scale given a placebo response of 25%, expressed on the LogOdds scale, i.e., 
1.258955) identified by the model. 
8.1.2.4 
Sensitivity Analyses of the Primary Efficacy Variable - candidate 
models  
A sensitivity analysis will be run to explore the impact of the MCP-Mod candidate models on 
identifying a statistically significant dose-response model. The primary analysis MCP-Mod using 
mNRI for missing data will be repeated, exactly as described in Sections 8.1.2.1 and 8.1.2.2, 
except that there will be 3 additional candidate models included in the analysis, in addition to 
those included in the primary efficacy analysis.  The intent is to explore whether there is an 
alternate dose-response model, perhaps non-monotonic, that is a better fit for the primary 
efficacy variable than those considered in the primary efficacy analysis. 
Two additional families of models will be considered in the candidate set for representing the 
expected response μd (on the logit scale) at dose d:  
 Exponential — μd = e0 + e1*[exp(d/δ)-1],  
parameters to estimate: e0, e1 and δ 
 Beta — μd = e0 + emax * B(δ1,δ2)(d/D)δ1(1-d/D)δ2,  
parameters to estimate: e0, emax, δ1 and δ2 
where, e0 is the placebo effect and Emax is the asymptotic maximum effect. For the Exponential 
model, e1 is the slope parameter, and δ controls the convexity of the model.  For the Beta model, 
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δ1 and δ2 are shape parameters, D is a scale parameter that will be fixed at 1.2*maximum tested 
dose (i.e., 1.2*45=54), and B(δ1,δ2)=( δ1+δ2)δ1+δ2/( δ1δ1δ2δ2). 
The pre-specified standardized parameters for each candidate model are from the sample size 
calculations:  
Exponential model: µd=exp(d/0.7)-1, i.e., δ=0.7 
Beta model 1: µd=B(0.3,0.8)(d/D)0.3(1-d/D)0.8, i.e., δ1=0.3, δ2=0.8 
Beta model 2: µd=B(0.6,0.8)(d/D)0.6(1-d/D)0.8, i.e., δ1=0.6, δ2=0.8 
This sensitivity analysis will be run using the FAS. The sensitivity statistical hypothesis tests will 
be considered descriptive only and will be conducted at the nominal level α=0.05 (one-sided 
testing).   
8.2 
Statistical analysis of the secondary efficacy variable 
The secondary efficacy variable is the BICLA responder rate (as defined in Section 8.1.1) in the 
individual dose groups at Week 24. 
The main analysis for the secondary variable will be based on the same mNRI as for the primary 
variable analyzed by a logistic regression model, modeling treatment response at Week 24 as a 
function of treatment group, controlling for corticosteroid strata. Least squares (LS) mean 
proportion responding in each treatment group, as well as LS mean differences in the proportion 
responding, odds ratios, 95% confidence intervals (CIs) for each, and p-values based on the 
Wald Chi-square statistic for the pairwise comparisons of each DZP treatment group with PBO 
will be obtained from the logistic regression model and presented.  Additionally, the crude 
difference in proportion responding and standard Wald asymptotic 95% CI based on the normal 
approximation to the binomial distribution will be presented for each DZP treatment group vs. 
PBO. This analysis will be conducted using the FAS. 
A test for treatment*corticosteroid interaction will be performed in a separate model, and the 
interaction will be explored if significant. 
8.2.1 
Sensitivity Analyses of the Secondary Efficacy Variable.  
Sensitivity analyses to examine the impact of missing data on the secondary analysis will be 
conducted as follows.  
First, the analysis of the secondary efficacy variable will be repeated for the PPS. 
Then, the same logistic regression model with stratification by corticosteroid strata will be 
applied to the following data sets including 3 alternate methods of imputation of missing data:  
1. mNRI data set where non-missing end of study response is used for subjects who 
discontinued study treatment but remained in the study. 
2. Observed cases data set (including only observed data at Week 24 with no imputation of any 
missing data in BICLA components [including no imputation of any missing individual items 
in the multiple item scales]) 
3. Strict NRI data set (all/any missing data in BICLA components [including any missing 
individual items in the scales] at Week 24 leads to non-responder status on the BICLA for 
Week 24) 
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Furthermore, an estimate of the treatment differences at Week 24 will be obtained from a 
Longitudinal Generalized Estimating Equation (GEE) model for binary outcome, controlling for 
corticosteroid strata, and with a treatment by visit interaction. 
The Generalized Estimating Equation (GEE) is only valid under MCAR (missing completely at 
random) assumption, which is generally not reasonable for clinical trials. Therefore, the data 
used for this analysis, which is the observed data at Week 24 with no imputation of any missing 
data in BICLA components (including no imputation of any missing individual items in the 
multiple item scales), will be modified such that informative dropouts are set to non-responder 
for this analysis, which is permitted within the GEE framework. In general, all other missing 
values will be left missing in this model. However, as per the definition of BICLA (Section 
8.1.1), subjects who prematurely discontinue the study but have had disallowed changes in 
concomitant medication dosing prior to discontinuing, and hence would have been a non-
responder at all subsequent visits if those visits had been done, will be set to non-response for all 
subsequent time points even if the visit was not done. In addition, subjects who prematurely 
discontinued the study with primary reason for discontinuation being informative will be set to 
non-response for all subsequent time points as well, such that, following these imputations, the 
only missing values in this analysis are values which are inadvertent missing as opposed to 
clearly informative missing values. Informative reasons for discontinuation include lack of 
efficacy and adverse events other than pregnancy and/or primagravida. 
The number and percent of responders in each treatment group will be presented. LS mean 
proportion responding in each treatment group and LS mean differences and 95% CIs in 
proportion responding between each DZP treatment group and PBO will be computed using the 
GEE model described above. Odds ratios of each DZP treatment group vs PBO along with the 
95% confidence interval and p-value (versus PBO) will be presented. An unstructured 
covariance matrix will be used for this analysis. If the model does not converge, the Toeplitz or 
compound symmetry covariance matrix (Toeplitz should be tried first and then compound 
symmetry) will be used. If the GEE model still does not converge with any of the 3 covariance 
matrices, the reason may be that there are too few responders at Visit 4. In that case, the GEE 
model will be run including data from Visits 6-10 only, using the unstructured covariance matrix 
(or Toeplitz or compound symmetry in that order if needed for convergence). In the GEE 
analysis, missing values are not explicitly imputed, but GEE analysis uses information from the 
observed data to implicitly impute the unobserved data. All available scheduled post-Baseline 
assessments are utilized for deriving Week 24 treatment differences (except if Visit 4 has to be 
excluded to achieve model convergence). Additionally, the crude difference in proportion 
responding and standard Wald asymptotic 95% CI based on the normal approximation to the 
binomial distribution will be presented for each DZP treatment group vs. PBO. 
8.3 
Statistical analysis of the other efficacy variables 
The analyses of the other efficacy variables will be performed for all visits through Week 24 in 
the interim analysis and for all visits through the end of study (Week 48) for the final analysis 
(unless otherwise noted). 
The main analysis of other efficacy responder rates will be based on the same mNRI imputation 
as for the primary efficacy variable analyzed by a logistic regression model, modeling treatment 
response as a function of treatment group, controlling for corticosteroid strata, as detailed in 
Section 8.2 for the secondary efficacy variable. Note that BILAG Improvement and BILAG 
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substantial/partial/no response are both considered responder endpoints and are analyzed using 
mNRI imputation as specified here. (However, BILAG substantial/partial/no response will be 
analyzed using a Cochran-Mantel-Haenszel test due to the 3 ordered levels of response.) 
Additionally, an estimate of the treatment differences will be obtained from a Longitudinal 
Generalized Estimating Equation (GEE) model for binary outcome, controlling for corticosteroid 
strata, and with a treatment by visit interaction.  The details of this GEE model will be the same 
as that used for the sensitivity analysis of the secondary efficacy variable described in Section 
8.2.1.  In general, missing values will be left missing in this model, however informative 
dropouts will be set to non-responder for this analysis, as detailed in Section 8.2.1.  All available 
scheduled post-Baseline assessments will be utilized for deriving treatment differences (except if 
Visit 4 has to be excluded to achieve model convergence).    
Analyses of continuous efficacy variables will be performed using mixed effects models for 
repeated measurement (MMRM) with change from Baseline as dependent variable and fixed 
effects for treatment, visit, and treatment*visit as well as corticosteroid strata and baseline values 
as covariates. These models will use all available post-Baseline data at all visits up to and 
including Week 24, and the data from multiple visits will be incorporated as repeated measures 
within each subject. As detailed in Section 3.2, data from EWVs (prior to Week 24) will be 
recoded to the closest scheduled treatment period visit (after the last non-missing visit value) and 
will be included among the observed data for analysis. An unstructured covariance matrix (or 
Toeplitz or compound symmetry in that order if needed for convergence) will be utilized. LS 
means for changes from Baseline for each treatment group will be presented by visit. LS mean 
differences in the changes from Baseline for each DZP dose group versus PBO and 
corresponding 95% CIs and p-values will also be presented for each scheduled time point. The 
MMRM analysis of continuous efficacy variables will be performed using observed case data. 
This observed case data will include the limited imputation of missing individual scores from 
these multiple-item scales (BILAG 2004 total score, SLEDAI-2K total score, CLASI Activity 
Score, CLASI Damage Score, and SLICC/ACR Damage Index) from the previous visit (limited 
to 1 visit back), but no imputation when an entire scale is missing. In the MMRM analysis, 
missing values for total scale scores (i.e., when the entire scale is missing) will not be explicitly 
imputed, but MMRM analysis uses information from the observed data to implicitly impute the 
unobserved data. 
Supportive models of the continuous efficacy variables will involve analysis of covariance 
(ANCOVA) models with treatment group as a factor and corticosteroid strata and baseline scores 
as covariates. LS means for changes from Baseline at each visit for treatment groups will be 
presented. LS mean differences in the changes from Baseline for each DZP dose group versus 
PBO and corresponding 95% CIs and p-values will also be presented by visit. 
These supportive ANCOVA analyses of continuous efficacy variables will be performed using 
observed case data. This observed case data will include the limited imputation of individual 
scores from these multiple-item scales (BILAG 2004 total score, SLEDAI-2K total score, CLASI 
Activity Score, CLASI Damage Score, and SLICC/ACR Damage Index) from the previous visit 
(limited to 1 visit back), but no imputation when an entire scale is missing. In the ANCOVA 
analysis, missing values for total scale scores are excluded from the analysis. 
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 
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such, these results are considered exploratory in nature and caution should be exercised in 
interpreting these results.  
8.3.1 
Clinical assessment of disease activity 
In addition to the tables and listing, given in for the primary and secondary efficacy variables, the 
BICLA responder rates by visit will be tabulated and listed. The analysis of the responder rates 
by visit will use the same approach as for the secondary efficacy variable. Data will be imputed 
using mNRI and the analysis of each time point will consist of a logistic regression model, 
modeling treatment response at the applicable study visit as a function of treatment group with 
corticosteroid strata included in the model as a covariate, s. Section 8.2. P-values based on Wald 
Chi-square will be generated for the pairwise comparisons of each DZP treatment group with 
PBO.  As an additional analysis approach, a GEE model will be fit, as described in Section 8.2.1. 
Line graphs will be presented to display the responder rate over time by treatment group. A part 
of the assessment of the BICLA responder rate will be based on the SLEDAI-2K Total Score as 
described in Section 8, including the lab criteria for anti-dsDNA positive ‘>10iU’. Additionally, 
as a sensitivity analysis, the table program will be re-run including SLEDAI-2K total scores 
based on anti-dsDNA positive ‘≥5iU’ as ‘positive’.  
Analyses of the number of subjects with maintained BICLA response (defined as BICLA 
response at 2 consecutive study visits) will be provided. These analyses will use the primary 
imputation approach for BICLA, the mNRI data. 
The time to maintained BICLA response will be analyzed with statistical survival methods. The 
time to maintained BICLA response will be defined as the time until the start of the Maintained 
BICLA response (i.e., time until the first visit with BICLA response that is then maintained for at 
least one more consecutive visit thereafter). Subjects who do not achieve a maintained BICLA 
response by Week 24 (interim analysis), Week 48 (final analysis) or early termination visit will 
be censored at the date of the last assessment during study period. Survival curves will be 
generated using the Kaplan-Meier product limit estimate. The treatment differences vs PBO will 
be analyzed using the stratified log-rank statistic, adjusting for corticosteroid strata. Median time 
to event values for each treatment group will be summarized and Kaplan-Meier survival curves 
will be presented by treatment group on a single graph. 
Additionally, the number and percentage of subjects with maintained BICLA response from 
Week 12 to Week 24 for the interim analysis, and from Week 24 to Week 48 for the final 
analysis will be summarized. 
 The BICLA responder rate is primarily based on the BILAG 2004 disease activity measurement 
instrument. The BILAG 2004 was selected as the primary tool for measurement of SLE disease 
activity on the basis of its comprehensiveness, ability to capture incremental changes in disease 
activity, and the clinical relevance of its grading system (Tsokos et al, 2007).  
The Investigator will assess 97 BILAG 2004 components and record the assessments in the 
eCRF. Only features attributable to SLE will be recorded and based on the subject’s condition in 
the last 4 weeks compared with the previous BILAG 2004 assessment. The components of the 
BILAG 2004 Index will assess nine body/organ-based systems:  
 Constitutional 
 Mucocutaneous 
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 Neuropsychiatric  
 Musculoskeletal 
 Cardiorespiratory 
 Gastrointestinal 
 Ophthalmic 
 Renal 
 Hematological 
Disease activity is graded separately for 9 body systems to 5 different grades (A to E) as follows: 
A (“Active”)  
 
Severely active disease 
B (“Beware”)  
 
Moderately active disease 
C (“Contentment”) 
Mild stable disease 
D (“Discount”) 
 
Inactive now but previously active 
E (“Excluded”) 
 
Never affected 
A shift from BILAG 2004 Grade A or B to a lower (less severe/active) grade indicates a 
clinically relevant change in disease activity. It is important to note that for the BILAG 2004 
improvement, all Grades A and Grades B at Baseline need to improve. If a Grade A from 
Baseline improves to a B but a single Grade B from Baseline remains as a B, then the subject has 
not improved in their BILAG 2004. 
Shift tables of BILAG 2004 Grades will be presented by body system showing the number and 
percentage of subjects with Grade A, B, C, D or E at each post-Baseline visit by the Grade A, B, 
C, D or E at Baseline. The denominator for the percentages will be the number of subjects in the 
Full Analysis Set. The shift table will include a missing category, presenting the number of 
subjects with no results at Baseline or subsequent visit. Furthermore, a shift will be presented for 
the BILAG 2004 Grades at Baseline and at the subsequent visits where the grades are combined 
in the categories A/B and C/D/E rather than presenting each grade individually. Here, the 
number and percentage of subjects with Grade A or B at Baseline and with Grade C, D or E at 
each subsequent visit, and conversely, the number and percentage of subjects with Grade C, D or 
E at Baseline and with Grade A or B at each subsequent visit will be presented. In addition the 
number and percentage of subjects with no change in the grade classifications by category A/B 
vs. C/D/E will be presented in the tabulation (subjects with Grade A or B at Baseline and at the 
subsequent visit; subjects with Grade C, D or E at Baseline and at the subsequent visit). 
The responses to the individual BILAG body systems and components and the BILAG 2004 
Grades for each body system will be listed by treatment, subject and visit, after grouping subjects 
by treatment.  
The number and percentage of subjects with BILAG 2004 improvement will be summarized by 
treatment group and visit. BILAG 2004 improvement, analyzed on its own as an ‘other’ 
endpoint, will still be defined the same as it is when it is part of the BICLA.  Specifically, 
BILAG 2004 improvement is 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 
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worsening in other BILAG 2004 organ systems (that had BILAG 2004 Grade C, D, or E at 
Baseline) such that there are no new BILAG 2004 Grades A nor greater than 1 new BILAG 2004 
Grade(s) B. Note that “study entry” within these criteria refers to Baseline, which is Visit 2 (or 
an earlier visit if the Visit 2 assessment was not done).  
BILAG 2004 improvement is considered a responder rate endpoint and analyzed similarly to the 
secondary efficacy variable, using mNRI imputation. Missing individual items (BILAG Grades) 
can be imputed from the previous visit (limited to 1 visit back) and subjects with missing values 
due to premature study discontinuation will be imputed as non-responders (i.e., not improved) 
for this analysis. P-values based on Wald Chi-square will be generated for pairwise comparisons 
of each DZP treatment group with PBO at each visit, using a logistic regression model as 
described in Section 8.2. As an additional approach, a GEE model will be fit as described in 
Section 8.2.1.  
The BILAG 2004 total score is defined as the sum of the numeric scores of each of the 9 
individual body systems, where letter grades A/B/C/D/E are converted to numeric score 
equivalents.  Numeric equivalents for the version of the BILAG used in this study, the BILAG-
2004 Index, are A=12, B=8, C=1, D/E=0 (Yee et al, 2010).  Descriptive statistics for absolute 
values of the BILAG 2004 total score and changes from Baseline will be tabulated by treatment 
and visit on the observed case values as well as the WOCF imputed values. As detailed in 
Section 4.3, the observed case data for BILAG 2004 total score will include the limited 
imputation of individual missing scores (Grades) from this multiple-item scale from the previous 
visit (limited to 1 visit back), but no imputation when an entire scale is missing.  The WOCF 
imputed values will include imputation of individual missing scores (Grades) from this multiple 
item scale by using the worst observation of all previous visits for the individual item, and 
additionally will include imputation of the total score for an entire missing scale using the worst 
observation of all previous visits for the scale. P-values for pairwise comparisons of change from 
baseline in each DZP treatment group to PBO will be generated for each visit based on a mixed 
effects models for repeated measurement (MMRM) run on the observed case values.  In this 
analysis, missing values for total score of the scale will not be explicitly imputed, but MMRM 
analysis uses information from the observed data to implicitly impute the unobserved data, s. 
Section 8.3. Analyses at each time point measured will be repeated using an ANCOVA model 
(detailed in Section 8.3) with the observed case values (i.e., missing values for total score of the 
scale not imputed), as well as an ANCOVA model with WOCF imputed values. Line graphs will 
be presented to display mean observed BILAG total score and mean observed change from 
Baseline BILAG total score, with 95% confidence intervals over time by treatment group. 
Corresponding listings will be provided.  
The BILAG 2004 systems tally is a new method of representing the BILAG-2004 index scores 
longitudinally, which combines the flexibility and simplicity of numerical scoring with the 
clinical intuitiveness and meaningfulness of the BILAG 2004 index categorical score (Yee et al, 
2012). 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 two assessments. It has 2 
forms: the comprehensive BILAG 2004 systems tally (BST) and the simplified BILAG 2004 
systems tally (sBST). 
BST comprises 6 components: 
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1. Number of systems with major deterioration (change of Grade B/C/D/E to A or Grade D/E to 
B) 
2. Number of systems with minor deterioration (change of Grade C to B) 
3.  Number of systems with persistent significant activity (no change from Grade A or B) 
4.  Number of systems with major improvement (change of Grade A to C/D or Grade B to D) 
5.  Number of systems with minor improvement (change of Grade A to B or B to C) 
6. Number of systems with persistent minimal or no activity (change of Grade C/D/E to C/D/E) 
sBST is a simplification of BST with 3 components: 
1. Number of systems with active/worsening disease (systems with major deterioration, minor 
deterioration and persistent significant activity) 
2. Number of systems with improving disease (systems with major improvement and minor 
improvement) 
3. Number of systems with persistent minimal or no activity. 
The shifts described above (major deteriorations, etc.) within BST and sBST are based on 
comparison of BILAG grades at consecutive visits (no comparisons to Baseline, except for the 
first post-Baseline visit which should be compared to Baseline). Additionally, the shifts are 
based on ‘observed’ values of the BILAG only, rather than using any values imputed for missing 
data. This should be applied based on protocol defined visits at which BILAG is assessed (every 
4 weeks). 
BST and sBST results should only be considered if there is a non-missing grade for all 9 systems 
for both time points being compared. If a BILAG 2004 is not done at a visit, then comparisons 
involving that time point would not be possible. For example, if Week 12 is missing, then Week 
8 shifts to Week 12 cannot be assessed, nor can shifts from Week 12 to Week16. Hence a single 
missing time point will result in two ‘paired time points’ having missing values.  
Where ‘two paired time points’ or a ‘visit pair’ is missing due to a missing value for one or more 
of the 9 body systems at one or both of the visits in the ‘visit pair’, then the time interval for that 
‘visit pair’ should not be counted in the denominator for AMsBST. That results in the total time 
for the AMsBST denominator being lower than total time based on subject’s last visit.  
BST and sBST results will be presented cumulatively for the double-blind treatment period for 
the FAS, and cumulatively for observational period for the FAS.  Cumulative presentation in this 
context means presentation of the total number of ‘visit pairs’ across the entire relevant study 
period with X systems meeting a specific component (e.g., major deterioration) of the BST or 
sBST, over the denominator of all non-missing ‘visit pairs’.  sBST results will be analyzed using 
a GEE model for ordinal outcomes outcome with factors for treatment, corticosteroid strata, 
study visit, and treatment by study visit interaction. For this GEE analysis, the model will have to 
be provided with by-visit data (i.e., the number of ‘visit pairs’ at each visit with X systems 
meeting a specific component), although the table will display this information cumulatively 
across all relevant visits. 
Adjusted mean sBST has been advocated as a useful summary of sBST over time. In the same 
way, the component of number of systems with active/worsening disease in sBST might be used 
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to create a comparable measure of ‘adjusted mean sBST - active/worsening’ (AMsBST - 
active/worsening). The formula for AMsBST would be: 
∑
𝑋𝑖𝑡𝑖
𝑛
𝑖=2
∑
𝑡𝑖
𝑛
𝑖=2
 
where  
Xi=sBST component of interest (active/worsening systems in this example) at visit i and  
ti = time interval between visit i and visit i-1. 
This measure would provide an overall measure of burden of disease activity over period of 
study. Hence, it could be used to demonstrate the magnitude of treatment effect between 
treatment arms. Since AMsBST is calculated over the entire duration of study, there would be 
just one value per subject (and not one per time point) for this variable. AMsBST values will be 
analyzed using a nonparametric van Elteren test comparing DZP arm to placebo, adjusted for 
corticosteroid strata. 
 The SLEDAI-2K measures disease activity in the 30 days prior to and at the time point of the 
assessment, but for both Visits 1 and 2, the SLEDAI-2K will assess disease activity in the past 10 
days only, to represent the disease status at study entry (Gladman et al, 2002). It is a global index 
and includes 24 clinical and laboratory variables marked as present or absent, 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. Details of the SLEDAI-2K calculation are given in Section 8.  
The results of the SLEDAI-2K will be listed by treatment, subject and visit, and will include the 
individual component results (Yes or No) and the overall score for each visit. Listings will be 
sorted by visit and then by the individual descriptor, such that results for the same visit appear 
together. Changes from Baseline in total score will be included in the listing.  
As described in Section 8, the SLEDAI-2K total score will be calculated using the central lab 
data to determine the presence or absence of a few items that are directly based on labs.  For 
these few items, both SLEDAI-2K information will be included in the listing - the (not analyzed) 
values from the eCRF and the (analyzed) values based on the central lab information.  
Descriptive statistics for absolute values and changes from Baseline in SLEDAI-2K total score 
will be presented by treatment and visit on observed case values as well as the WOCF imputed 
values. As detailed in Section 4.3, the observed case data for SLEDAI-2K total score will include 
the limited imputation of individual missing scores from this multiple-item scale from the 
previous visit (limited to 1 visit back), but no imputation when an entire scale is missing.  The 
WOCF imputed values will include imputation of individual missing scores from this multiple 
item scale by using the worst observation of all previous visits for the individual item, and 
additionally will include imputation of the score for an entire missing scale using the worst 
observation of all previous visits for that scale. The calculation of SLEDAI-2K Total Score as 
described in Section 8, includes the lab criteria for anti-dsDNA positive ‘>10iU’. Additionally, 
as a sensitivity analysis, the table program will be re-ran including SLEDAI-2K total scores 
based on anti-dsDNA positive ‘≥5iU’ as ‘positive’. Line graphs will be presented to display 
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mean observed SLEDAI-2K total score and mean observed change from Baseline SLEDAI-2K  
total score, with 95% confidence intervals over time by treatment group. 
P-values for pairwise comparisons of change from Baseline in each DZP treatment group 
compared to PBO will be generated for each time point based on a MMRM analysis run on the 
observed case values.  In this analysis, missing values for total score of this scale will not be 
explicitly imputed, but MMRM analysis uses information from the observed data to implicitly 
impute the unobserved data, s. Section 8.3. Analyses at each time point measured will be 
repeated using ANCOVA with the observed case values (i.e., missing values for total score of 
this scale not imputed), as well as using ANCOVA with the WOCF imputed values. Line graphs 
will be presented to display mean observed SLEDAI-2K total score and mean observed change 
from Baseline in SLEDAI-2K total score, with 95% confidence intervals over time by treatment 
group. Corresponding listings will be provided. 
The S2K RI-50 comprises the same 24 descriptors covering 9 organ systems as the SLEDAI-2K 
and in contrast to SLEDAI-2K captures improvement of at least 50% in disease activity 
compared with the previous assessment; the S2K RI-50 reflects disease activity over the 30 days 
prior to the assessment (Touma et al, 2011). The S2K RI-50 score is evaluated as the sum of the 
scores of the 24 individual descriptors. If the S2K RI-50 was not completed for an individual 
item at a visit, then if the SLEDAI-2K score for that same item at the same visit = 0, then the 
S2K RI-50 score for that item at that visit =0.  No other imputation will be made for S2K RI-50 
missing data (including no imputation using previous visit data).  
The determination of S2K RI-50 will be based on the SLEDAI-2K Total Score as described in 
Section 8 and as such, also needs to use central lab results to determine the item score for 'low 
complement' and 'increased DNA binding'.  This will be done as follows: 
 If the Farr assay ≤10 iU then the DNA binding is normal and there is no 'increased DNA 
binding', so the score for this item is 0.  However, if the Farr assay >10 iU, then there is 
‘increased DNA binding’ and it must be determined whether it is <50% or ≥50% 
improved vs. the previous visit as follows: 
o If the Farr assay ≤ (0.5* Farr assay value at previous visit) then there is ≥50% 
improvement vs. the previous visit, so the score for this item is half the total 
points for this item on the SLEDAI-2K scale, i.e., 1. 
o If the Farr assay > (0.5* Farr assay value at previous visit) then there is <50% 
improvement vs. the previous visit, so the score for this item is the total points for 
this item on the SLEDAI-2K scale, i.e., 2. 
o  
 If both the complement C3 ≥ LLN and the complement C4 ≥ LLN, then there is no 'low 
complement', so the score for this item is 0.  However, if either C3 or C4 is < LLN, then 
there is ‘low complement’ and it must be determined whether it is <50% or ≥50% 
improved vs. the previous visit as follows: 
o If there is ≥50% increase in the level of C3 or C4 vs. the previous visit (i.e., C3 
≥1.5* C3 value at previous visit or C4 ≥1.5* C4 value at previous visit), without 
any drop in the value of the other compared to the previous visit  
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OR 
o If one of either C3 or C4 has changed from < LLN to ≥ LLN since the previous 
visit, without any drop in the value of the other compared to the previous visit 
THEN that is considered ≥50% improvement, so the S2K RI-50 score for ‘low 
complement’ is half the total points for this item on the SLEDAI-2K scale, i.e., 1. 
 
ELSE 
o Else there is <50% improvement, so the S2K RI-50 score for ‘low complement’ is 
the total points for this item on the SLEDAI-2K scale, i.e., 2. 
For these parameters, 'low complement' and 'increased DNA binding', the central lab results for 
the lab sample taken at the same visit will be used. If there is no lab sample take on the same day 
as the respective visit, a lab within 14 days after the visit may be used. If there is no lab within 
14 days after the visit, the lab results from one visit back may be used.  Only in case there is no 
lab value available at the respective visit, within 14 days after the visit, nor at the previous visit, 
then the data from the CRF will be used if available. 
The determination of the S2K RI-50 score as described above includes the lab criteria for anti-
dsDNA positive ‘>10iU’ as ‘positive’. Additionally, as a sensitivity analysis, the table program 
will be re-run using the lab criteria for anti-dsDNA positive ‘≥5iU’ as ‘positive’. 
In the protocol, the S2K RI-50 was referred to as the SRI-50.  However, since that time a new 
nomenclature has been adopted for S2K RI-50. To avoid confusion with the SRI-4, SRI-5, and 
SRI-6 response S2KRI-50 was renamed to S2K RI-50. 
The results of the S2K RI-50 will be listed by treatment, subject and visit and will include the 
individual component results and the overall score for each post-Baseline visit. Listings will be 
sorted by visit and then by the individual descriptor, such that results for the same visit appear 
together. Descriptive statistics will be presented for the S2K RI-50 total score and changes from 
previous visit in S2K RI-50 total score (including SLEDAI-2K as Baseline values, i.e., as the 
previous visit for Week 4) by treatment and visit.  
P-values for pairwise comparisons of change from Baseline in each DZP treatment group 
compared to PBO will be generated for each time point based on a mixed effects models for 
repeated measurement (MMRM) run on the observed case values. The observed case data for 
S2K RI-50 will include the limited imputation of an individual missing item score as 0 if the 
SLEDAI-2K score for the same item at the same visit is 0, but will include no other imputation 
of missing item scores and no imputation when an entire scale is missing. In the MMRM 
analysis, missing values for the S2K RI-50 total score will not be explicitly imputed, but MMRM 
analysis uses information from the observed data to implicitly impute the unobserved data, s. 
Section 8.3. Analyses at each time point measured will be repeated using ANCOVA with the 
observed case values (i.e., missing values the S2K RI-50 total score not imputed). Line graphs 
will be presented to display mean observed S2K RI-50 total score and mean observed change 
from Baseline in S2K RI-50 total score, with 95% confidence intervals over time by treatment 
group. 
 
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Physician’s Global Assessment (PGA): The Investigator will assess the overall status of the 
subject’s Systemic Lupus Erythematosus signs and symptoms and the functional capacity of the 
subject using a visual analog scale (VAS): Zero indicates ‘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.  
The results of the VAS scores will be listed by treatment, subject and visit. The Physician’s 
global assessment of disease activity score (using 100mm VAS) and changes vs Baseline in 
physician’s global assessment of disease will be summarized with descriptive statistics by 
treatment group at each time point measured. P-values for pairwise comparisons of each DZP 
treatment group compared to PBO will be generated for each time point based on a MMRM 
analysis run on the observed case values. The observed case data for PGA contains all observed 
data and no imputations. In this MMRM analysis, missing values for PGA score will not be 
explicitly imputed, but MMRM analysis uses information from the observed data to implicitly 
impute the unobserved data, s. Section 8.3. Analyses at each time point measured will be 
repeated using ANCOVA with the observed case values (i.e., missing values not imputed). Line 
graphs will be presented to display mean observed physician’s global assessment of disease and 
mean observed change from Baseline in physician’s global assessment of disease, with 95% 
confidence intervals, over time by treatment group. Line graphs will be presented to display 
mean observed PGA score and mean observed change from Baseline in PGA score, with 95% 
confidence intervals over time by treatment group). 
The SRI-4, SRI-5, and SRI-6 define responders as (i.e., 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 post-Baseline 
 Increase in Physician’s Global Assessment of Disease from Baseline of <10% of the total 
100mm VAS (i.e., increase from Baseline of <10mm) 
Assessments of SRI-4, SRI-5, and SRI-6 will include an assessment of non-responders based on 
the same concomitant medication rules as for the BICLA response: In case of escape treatment 
(s. Section 8.1.1, Derivation of primary efficacy variable), a subject is also considered as a non-
responder for SRI-4, SRI-5 and SRI-6 beginning the day after the reported start date of the 
concomitant medication considered as escape treatment and at all subsequent visits. In case of 
missing data the same mNRI rules as for BICLA will be applied to SRI-4, SRI-5 and SRI-6. 
The number of SRI-4, SRI-5 and SRI-6 responders will be tabulated by visit. A corresponding 
listing will be provided. 
The analysis of the responder rates by visit will use the same approach as for the secondary 
efficacy variable (s. Section 8.2). At each time point, mNRI imputed data will be analyzed using 
a logistic regression model, modeling treatment response at the applicable study visit as a 
function of treatment group with corticosteroid strata included in the model as a covariate. To 
assess for sensitivity to missing data, as for the secondary efficacy variable (s. Section 8.2.1), the 
logistic regression model will also be applied to the following data sets including 3 alternate 
methods of imputation of missing data:  
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1. mNRI data set where non-missing end of study response is used for subjects who 
discontinued study treatment but remained in the study. 
2. Observed cases data set (observed data at Week 24 with no imputation of any missing data in 
SRI-4/5/6 components [including no imputation of any missing individual items in the 
multiple item scales]) 
3. Strict NRI data set (all/any missing data in SRI-4/5/6 components [including any missing 
individual items in the scales] at Week 24 leads to non-responder status on the SRI-4/5/6 for 
Week 24). 
 As an additional approach, for SRI-4, SRI-5 and SRI-6 a GEE model will be fit, as described in 
Section 8.2.1 . Line graphs will be presented for SRI-4 to display the responder rate over time by 
treatment group. 
The determination of SRI-4, SRI-5 and SRI-6 will be based on the SLEDAI-2K Total Score as 
described in Section 8 and includes the lab criteria for anti-dsDNA positive ‘>10iU’. 
Additionally, as a sensitivity analysis, the table program will be re-run including SLEDAI-2K 
total scores based on anti-dsDNA positive ‘≥5iU’ as ‘positive’. 
A sensitivity analysis based on the PPS will be performed for SRI-4.  
Patient’s Global Assessment (PtGA): Subjects will rate their global assessment of their SLE 
disease activity for the day of the visit using a 100 mm visual analog scale (VAS) where 0 is 
“very good, no symptoms” and 100 is “very poor, very severe symptoms.”, i.e., higher scores 
indicate more severe disease. 
The analysis described in the section ‘Physician’s Global Assessment (PGA)‘ will be repeated 
for the Patient’s Global Assessment (PtGA) of disease. 
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.  
Definition of damage: 
 Non-reversible 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, and check if the criterion is present (“Yes” ticked) or not 
(“No”), or “Unknown,” as appropriate. The different organ systems and corresponding ranges of 
possible score are given in Table 9-1 in the protocol.  
Due to the long-term nature of the changes that are measured by the SLICC/ACR Damage Index, 
all summaries, analyses, and listings of SLICC/ACR Damage Index will be done at the time of 
the Final Analysis only, and not for the Interim Analysis. 
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The results of the SLICC/ACR Damage Index will be listed by treatment, subject and visit and 
will include the individual component results (Yes/No) and the corresponding score. The 
SLICC/ACR Damage Index Total Score will be categorized into categories ‘0’, ‘1’, ‘2’, and ‘>2’ 
for summary and analysis. Frequency counts (n and percentage) for the number of subjects with 
a SLICC/ACR Damage Index Total Score in each category, ‘0’, ‘1’, ‘2’, and ‘>2’ will be 
presented.  Cochran-Mantel-Haenszel analysis of the number of subjects in each score category 
by treatment will be performed, adjusting for corticosteroid strata. A shift table which presents 
the shift in the SLICC/ACR Damage Index from Baseline at each visit, including the categories 
‘0’, ‘1’, ‘2’, and ‘>2’ will be provided. Observed case data will be used for these analyses, which 
as detailed in Section 4.3, will include limited imputation of missing individual scores from the 
previous visit (limited to 1 visit back) if the entire scale is not missing. 
Furthermore, tables with descriptive statistics (n, mean, SD, median, min, max) for the 
SLICC/ACR Damage Index scores and their changes from Baseline will also be provided.  P-
values for pairwise comparisons of each DZP treatment group compared to PBO will be 
generated for each time point based on a mixed effects models for repeated measurement 
(MMRM) run on the observed case values. As detailed in Section 4.3, the observed case data for 
SLICC/ACR Damage Index scores will include the limited imputation of individual missing 
scores from this multiple-item scale from the previous visit (limited to 1 visit back), but no 
imputation when an entire scale is missing. In this MMRM analysis, missing values for 
SLICC/ACR Damage Index score will not be explicitly imputed, but MMRM analysis uses 
information from the observed data to implicitly impute the unobserved data, s. Section 8.3. 
Analyses at each time point measured will be repeated using ANCOVA with the observed case 
values (i.e., missing values not imputed).    
 
The joint assessment will be carried out on 28 joints. Tenderness and swelling will be graded on 
a 2-point scale (Grade 0, Grade 1). For details, see Table 9‒2 in the protocol. The total tender 
joint counts (TJC) and swollen joint counts (SJC) are the sum of all individual respective 
tenderness and swelling grades. If the TJC/SJC is completed, but there are missing individual 
observations in the TJC or SJC, then the non-missing observations are assessed and weighted by 
dividing by the number of non-missing values and multiplying by 28. If a joint is not evaluable at 
Baseline, then that joint is set to missing throughout the study. If more than 50% of the 
tenderness or swelling grades are missing, then no imputation is done and the total TJC or SJC 
are set to missing.  
The total scores are used to assess the percentage change from Baseline. Tables with the 
descriptive statistics for the absolute values, the percent changes from Baseline, and the changes 
from Baseline, and the corresponding listing will be provided. 
P-values for pairwise comparisons of change from baseline in each DZP treatment group 
compared to PBO will be generated for each time point based on a mixed effects models for 
repeated measurement (MMRM) run on the observed case values. The observed case data for 
TJC and SJC includes the limited imputation involving weighting for missing individual items 
within an otherwise completed scale as described above, but will include no other imputation of 
missing item scores and no imputation when an entire TJC or SJC scale is missing. In this 
MMRM analysis, missing values for TJC or SJC total score will not be explicitly imputed, but 
MMRM analysis uses information from the observed data to implicitly impute the unobserved 
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data, s. Section 8.3. Analyses at each time point measured will be repeated using an ANCOVA 
with observed case values (i.e., missing values for TJC or SJC total score not imputed).  
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, see Table 9‒3 in the protocol (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 remain visible for more 
than 12 months, which is taken to be permanent.  If so, the dyspigmentation score is doubled. 
The CLASI Activity and Damage Total scores are then calculated by simple addition based on 
the extent of the individual skin 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.  
For both the CLASI Activity Total score and the CLASI Damage Total score, tables with the 
descriptive statistics for the absolute values and the changes versus Baseline and the 
corresponding listing (including the individual responses and scores) will be provided.  
Due to the long-term nature of the changes that are measured by the CLASI Damage Total 
Score, all summaries, analyses, and listings of the CLASI Damage Total Score will be done at 
the time of the Final Analysis only, and not for the Interim Analysis. However, the CLASI 
Activity Total Score will be summarized, analyzed and listed for both the Interim Analysis and 
the Final Analysis. 
For the CLASI Activity Total Score, descriptive statistics for the absolute values and the changes 
from Baseline will also be presented for subjects with CLASI Activity Total Score > 0 at 
Baseline, for subjects with CLASI Activity Total Score ≥ 4 at Baseline, and for subjects with 
CLASI Activity Total Score ≥ 10 at Baseline. 
P-values for pairwise comparisons of each DZP treatment group compared to PBO will be 
generated for each time point based on a mixed effects models for repeated measurement 
(MMRM) run on the observed case values. As detailed in Section 4.3, the observed case data for 
CLASI will include the limited imputation of individual missing scores from this multiple-item 
scale from the previous visit (limited to 1 visit back), but no imputation when an entire scale is 
missing. In this MMRM analysis, missing values for CLASI scores will not be explicitly 
imputed, but MMRM analysis uses information from the observed data to implicitly impute the 
unobserved data, s. Section 8.3. Analyses at each time point measured will be repeated using an 
ANCOVA with observed case values (i.e., missing values not imputed).  
In addition, for subjects with CLASI Activity Total Score ≥ 4 at Baseline and for subjects with 
CLASI Activity Total Score ≥ 10 at Baseline, CLASI Activity Total Score improvement (defined 
as ≥50% improvement in the CLASI Activity Score compared to Baseline) will be summarized 
by treatment group and visit. Subjects with missing values will be imputed as non-responders 
(i.e., not improved) for this analysis. P-values based on Wald Chi-square will be generated for 
pairwise comparisons of each DZP treatment group with PBO at each visit, using logistic 
regression model as described in Section 8.3.  
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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. Flare will be assessed by 
multiple definitions: 
 flare determined by the Investigator (Clinically significant increase of SLE disease 
activity of the patient in 1 or more organ systems since the last visit and consideration of 
a change or increase in the treatment for SLE of your patient)  
 flare determined by the Sponsor (A new sustained BILAG 2004 Grade A/B [present at 
≥2 consecutive visits] or start of new induction therapy [either corticosteroid dose 
increase to ≥0.5mg/kg/day prednisone equivalent or initiation of cyclophosphamide, 
rituximab, iv Ig, MMF, MTX, Azathioprin, or plasma exchange]). For flare assessed by 
the Sponsor, “a new sustained BILAG 2004 Grade A/B [present at ≥ 2 consecutive 
visits]” means that a BILAG Grade A or B must be observed that was not present at the 
previous visit, and then must continue to be observed at the subsequent visit. This 
criteria could be fulfilled by a new BILAG Grade A, which would be a new BILAG 
Grade A at one visit, after having been a BILAG Grade B, C, D or E at the previous 
visit, and then a Grade A at the next consecutive visit as well. This criteria could also be 
fulfilled by a new BILAG Grade B, which would be a new BILAG Grade A or B at one 
visit, after having been a BILAG Grade C, D or E at the previous visit, and then a Grade 
B at the next consecutive visit as well. Or the new BILAG Grade B could be a new 
BILAG Grade B at one visit, after having been a BILAG Grade C, D or E at the previous 
visit, and then a Grade A or B at the next consecutive visit as well.   
 BILAG severe flare - defined as a new BILAG 2004 Grade A since previous visit in any 
system due to individual items that are new or worse qualifying for the Grade A 
(Isenberg et al, 2011). Determination of items that are new or worse qualifying for the 
Grade A will be according to the supplementary information for the numerical scoring of 
the BILAG-2004 index (Yee et al, 2010). Programming details will be documented in a 
programming specification outside the SAP.   
 BILAG moderate flare - defined as 2 or more new BILAG 2004 Grade Bs since previous 
visit in any systems due to individual items that are new or worse qualifying for the 
Grade B (Isenberg et al, 2011). Determination of items that are new or worse qualifying 
for the Grade B will be according to the supplementary information for the numerical 
scoring of the BILAG-2004 index (Yee et al, 2010). Programming details will be 
documented in a programming specification outside the SAP. 
 BILAG mild flare - defined as a single new BILAG 2004 Grade B since previous visit in 
any system due to individual items that are new or worse and qualify for the Grade B, or 
3 or more new BILAG 2004 Grade Cs since previous visit in any systems due to 
individual items that are new or worse and qualify for the Grade C (Isenberg et al, 2011). 
Determination of items that are new or worse qualifying for the Grade B or the Grade C 
will be according to the supplementary information for the numerical scoring of the 
BILAG-2004 index (Yee et al, 2010). Programming details will be documented in a 
programming specification outside the SAP. 
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 BILAG severe flare - Variant 1 (a new BILAG 2004 Grade A since the previous visit). 
For BILAG severe flare - Variant 1 if a new A is observed at a visit, it does not have to 
be due to new or worsening symptoms. 
   
 BILAG moderate/severe flare - Variant 1 (new BILAG 2004 Grade A or 2 new BILAG 
2004 Grade Bs since the previous visit). For BILAG moderate/severe flare - Variant 1 if 
a new A or 2 new Bs are observed at a visit, they do not have to be due to new or 
worsening symptoms. 
For each definition of flare (assessed by Investigator, assessed by Sponsor, BILAG severe flare, 
BILAG moderate flare, BILAG mild flare, BILAG severe flare - Variant 1, and BILAG 
moderate/severe flare - Variant 1): 
 The number and proportion of subjects with >= 1 flare up to and including the visit will 
be presented by visit, since Baseline to Week 24, and since Week 24 (for the 
Observational Period). 
 Descriptive statistics for the number of flares per affected subjects (i.e., subjects with at 
least one flare) will be presented overall per study period (i.e., not by visit). 
 Descriptive statistics, based on statistical analysis survival methods, will be provided for 
time to flare up to Week 24, time to flare after Week 24 (for analyses of the 
Observational Period), and time to flare from Baseline to Week 48 (for analyses of the 
DB Treatment Period and the Observational Period together; and with one exception, 
descriptive statistics for the time to flare as assessed by Sponsor will only be provided for 
time up to Week 24, as explained in Section 3.10). Start time of a flare for all definitions 
that require a BILAG Grade sustained for 2 consecutive visits will be the date of the first 
of two consecutive BILAG Grade of increased intensity. 
For the Interim Analysis (at the end of the DB Treatment Period (Part 1), only the analyses of 
BILAG severe flare – Variant 1 and BILAG moderate/severe flare – Variant 1 for the DB 
Treatment Period will be performed. All other analyses of flare described here will be delivered 
at the time of the Final Analysis and included in the Final CSR, regardless of whether the 
endpoints are focused on the DB Treatment Period or the Observational Period. 
Patients who do not experience a flare by Week 24 (for analyses of the DB Treatment Period), 
Week 48 (for analyses including the Observational Period) or Early Termination will be 
censored at the date of last assessment during the study period (i.e., the last visit date or the study 
discontinuation date). Survival curves will be generated using the Kaplan-Meier product limit 
estimate. The differences versus PBO will be analyzed using the stratified log rank statistic, 
adjusting for corticosteroid strata as randomized. Median time to event values for each treatment 
group will be summarized and Kaplan Meier survival curves will be presented by treatment 
group on a single graph. 
Additional general rules for counting flares are as follows.  
 For all flares based on BILAG Grades, if the BILAG assessment was done at a visit, but 
individual grades within the scale are missing, the respective individual grades will be 
imputed from the respective previous individual item grades (limited to 1 visit back).  
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 For all flares based on BILAG Grades, all visits at which flares start will be identified 
based on BILAG Grades within each organ system individually. Then, no more than one 
flare will be counted per visit for visits that have >=1 organ system with a flare starting at 
that visit.   
 For definitions of flares that consider 2 Grade B’s at the same visit to be a flare, if there is 
no Grade A at a particular visit, the criteria for having a B will have to be met within each 
of >=2 organ systems individually at that visit in order to count a flare at that visit. 
 Additionally for flare as determined by the Sponsor, flares will be counted at a visit based 
on the following criteria. However, if the subject also has a flare at the visit based on 
BILAG Grades, only 1 flare can be counted per visit. 
o Subject has newly begun any systemic corticosteroids for the first time in the 
study or has increased dose of corticosteroids since the last visit, i.e. from the last 
visit day+1 up to and including the visit day being evaluated. 
o Subject has had a plasma exchange since the last visit, i.e. from the last visit 
day+1 up to and including the visit day being evaluated, as recorded in the 
medical procedures. 
o Subject has newly initiated treatment with cyclophosphamide, rituximab, iv Ig, 
MMF, MTX, Azathioprin since the last visit, i.e. from the last visit day+1 up to 
and including the visit day being evaluated. For these treatments, it will not be 
considered initiation of therapy if the subject had already been taking the same 
therapy previously at the same or higher dose, and just had a short gap of ≤ 4 
weeks in that treatment.   
Further details about flare assessment are described in Section 8.4.4  (additional endpoints). 
8.3.2 
Variables assessed corticosteroid-sparing effects 
Subjects will be issued daily diaries at each visit to record concomitant corticosteroid doses taken 
on a daily basis at home in between visits. All reported corticosteroid doses will be converted to 
prednisone equivalent doses (s. Section 4.2), and all summaries and analyses of corticosteroid 
doses will be based on daily prednisone equivalent doses. In order to obtain the daily prednisone 
equivalent dose, in addition to converting corticosteroid doses as per Section 4.2, the reported 
frequency of dosing will be accounted for. For example, to obtain a daily dose, a dose reportedly 
taken ‘BID’ will have to be doubled, and a dose reportedly taken ‘QOD’ will have to be halved. 
If more than one corticosteroid was reportedly taken on a given day, then the daily dose must be 
the sum of the doses of each of those corticosteroids. 
For all summaries and analyses of corticosteroids, only corticosteroids with an indication for 
SLE will be included. For summaries other than time-weighted AUCMB and total AUC, only 
oral corticosteroids taken for SLE will be included. For time-weighted AUCMB and total AUC, 
all corticosteroids taken for SLE will be included regardless of route of administration, although 
non-systemic corticosteroids are assigned a prednisone equivalent dose of 0mg, so effectively all 
systemic corticosteroids taken for SLE will be included for AUC and AUCMB.   
Descriptive statistics for the absolute daily corticosteroid dose (prednisone-equivalent) and 
changes from Baseline by visit will be presented by treatment, based on observed case data. 
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Missing values will not be explicitly imputed and p-values for pairwise comparisons of change 
from baseline in each DZP treatment group to PBO will be generated for each visit based on a 
mixed effects models for repeated measurement (MMRM) analysis. In this MMRM analysis, 
missing values will not be explicitly imputed, but MMRM analysis uses information from the 
observed data to implicitly impute the unobserved data, s. Section 8.3. Analyses at each visit will 
be repeated using an ANCOVA model with the observed case values (i.e., missing values not 
imputed). A line graph will be presented to display mean and mean change in daily corticosteroid 
dose (prednisone-equivalent) from Baseline across visits. All corticosteroid data will be listed by 
treatment, subject and visit. 
Frequency tables will be provided displaying the number of subjects with daily corticosteroid 
dose (prednisone equivalent) in various categories, and in some cases also with responses on 
BICLA or SRI-4. For all of these categorical frequency tables, subjects with a missing daily 
corticosteroid dose at any time point due to premature study discontinuation will have this value 
imputed from the dose of oral corticosteroids with SLE indication at the time of discontinuation 
(i.e., LOCF). If a subject discontinues study drug, but stays in the study and reports a new 
corticosteroid dose (may be in a higher dose or a lower dose) then these values will be included 
in the analysis of corticosteroid data.  
Frequency tables will be provided for subjects with no daily corticosteroid dose (prednisone-
equivalent) vs. subjects with a daily corticosteroid dose (prednisone-equivalent) greater than 
0mg, and for subjects with a daily corticosteroid dose of 7.5mg/day prednisone equivalent or 
less, vs. subjects with a daily corticosteroid dose of more than 7.5mg/day prednisone equivalent. 
Logistic regression will be used to compare the proportion of patients with no concomitant 
corticosteroid treatment for each treatment group vs. placebo. Logistic regression will also be 
used to compare the proportion of subjects with a daily corticosteroid dose (prednisone-
equivalent) of 7.5mg/day or less, for each treatment group vs. placebo.  
Additionally, frequency tables will be provided displaying the proportion of patients from each 
treatment group in each of following categories: subjects with a daily corticosteroid dose 
(prednisone-equivalent) of 7.5mg/day or less at Week 24 and BICLA response at Week 24, 
subjects with a daily corticosteroid dose (prednisone-equivalent) of 7.5mg/day or less at Week 
24 and SRI-4 response at Week 24, and subjects with a daily corticosteroid dose (prednisone-
equivalent) of 7.5mg/day or less at Week 12 that stays ≤7.5mg/day for rest of time through Week 
24 and maintained BICLA response from Week 12 to Week 24. Furthermore, these will each be 
repeated with a daily corticosteroid dose (prednisone-equivalent) cut-off 10mg/day instead of 
7.5mg/day. For each category described here, a logistic regression analysis will be used to 
compare the proportion of patients in the category for each treatment group vs. placebo. 
Cumulative distribution function plots will be presented for the daily corticosteroid dose 
(prednisone-equivalent) at Baseline, at Week 24 (Interim Analysis) and at Week 48 (Final 
Analysis) as well as for the changes vs. Baseline at Week 24 and Week 48. 
Average change from Baseline in corticosteroid dose (prednisone-equivalent) in mg/day 
(including all routes of administration) during the entire treatment period will be summarized via 
time-weighted area under the curve minus baseline (AUCMB), estimated using the trapezoidal 
rule, for the change from Baseline in corticosteroid dose (prednisone-equivalent) through Week 
24/Week 48. Time-weighted AUCMB will be calculated as follows using all available data.  
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𝑡𝑖𝑚𝑒−𝑤𝑒𝑖𝑔ℎ𝑡𝑒𝑑 𝐴𝑈𝐶𝑀𝐵 ≈ 
∑𝑥Δx
2 [𝑓(𝑥) + 𝑓(𝑥+ ∆𝑥)]
𝑥𝑓𝑖𝑛𝑎𝑙−𝑥𝑏𝑎𝑠𝑒𝑙𝑖𝑛𝑒
 
where  
x represents the time point of the assessment,  
f(x) represents the change from Baseline in corticosteroid dose (prednisone-equivalent), and  
Δx represents the elapsed time between time points.  
Δx will be set to one day for this analysis, so that the time-weighted AUCMB will be calculated 
by summing over time intervals of one day in length. This is to increase the precision of the 
AUCMB calculation and to make the approach consistent across subjects who will have had dose 
changes at varying intervals of time. Missing values following premature discontinuation of 
study will not be imputed for this time-weighted AUCMB analysis, so it will be based on the 
study days up until the subject’s last visit.  
The descriptive statistics for the time-weighted AUCMB in corticosteroid dose (prednisone-
equivalent) will be tabulated.  
Additionally, total corticosteroid dose (prednisone-equivalent) in mg (including all routes of 
administration) during the entire treatment period will be summarized via area under the curve 
(AUC), estimated using the trapezoidal rule, for the corticosteroid dose (prednisone-equivalent) 
through Week 24/Week 48.  Total AUC will be calculated as follows,  
𝑡𝑜𝑡𝑎𝑙 𝐴𝑈𝐶 ≈∑𝑥Δx
2 [𝑓(𝑥) + 𝑓(𝑥+ ∆𝑥)]  
where  
x represents the time point of the assessment,  
f(x) represents the change from Baseline in corticosteroid dose (prednisone-equivalent), and  
Δx represents the elapsed time between time points.  
As with the time-weighted AUCMB, Δx will be set to one day for this analysis, so that the total 
AUC will be calculated by summing over time intervals of one day in length. This is to increase 
the precision of the AUC calculation and to make the approach consistent across subjects who 
will have had dose changes at varying intervals of time. However, for the total AUC analysis, 
missing values following premature discontinuation of study will be imputed, so it will be based 
on the total scheduled study days up until Week 24 (i.e. 168 days)/ Week 48 (i.e. 336 days). (The 
imputation is needed for total AUC since it is not a time-weighted (mg/day) value, but rather a 
total (mg) value for the study. Thus, in order for it to be compared across subjects, the length of 
time included needs to be constant for all.) The imputation of missing values will be the same as 
done for frequency tables of corticosteroid categories. Subjects with a missing daily 
corticosteroid dose at any time point due to premature study discontinuation will have this value 
imputed from the dose of oral corticosteroids with SLE indication at the time of discontinuation 
(i.e., LOCF). However, if a subject discontinues study drug, but stays in the study and reports a 
new corticosteroid dose (may be in a higher dose or a lower dose) then these values will be 
included in the analysis of corticosteroid data. 
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The descriptive statistics for the total AUC in corticosteroid dose (prednisone-equivalent) will be 
tabulated.  
For time-weighted AUCMB and total AUC only, corticosteroid dose (prednisone-equivalent) 
will be computed using all routes of administration, not only the daily oral corticosteroids. When 
calculating the area under the curve, the actual date at which each new dose starts must be used 
(not the first visit date that occurs after the new dose has started).  
In the case, when a site has recorded the stop date of one dose equal to the start date of the next 
dose, it incorrectly appears as if the subject was taking a double dose for 1 day. For all 
summaries and analyses of daily corticosteroid dose (prednisone-equivalent), including but not 
limited to time-weighted AUCMB and total AUC, in that special case, the old dose only will be 
assumed to have been taken on the stop date, and the new dose will be assumed to have begun on 
start date + 1.  
 
8.3.3 
Patient-reported outcome variables 
The patient-reported outcome (PRO) questionnaires include LupusQoL, SLE-S, SLE-F, SLE-M, 
SLE-P, SLE-E, and Subject Experience Interview. 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 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 (provided at least 50% of the items in the domain are 
answered) and transformed to a 0 to 100 point scale with higher scores denoting better HRQoL. 
If more than 50% of the items in the domain are missing, then the domain score is missing. A 
“Not Applicable” response is treated as unanswered/missing. 
LupusQoL scores in each of the LupusQoL domains will be summarized by treatment group at 
each time point measured, including change from Baseline. Missing values will not explicitly be 
imputed and p-values for pairwise comparisons of change from Baseline in each treatment group 
compared to PBO will be generated for each time point measured based on a mixed effects 
models for repeated measurement (MMRM) run on the observed case values. The observed case 
data for LupusQoL contains all observed data and no imputations (including no imputations for 
any individual items). In this MMRM analysis, missing values for LupusQoL scores will not be 
explicitly imputed, but MMRM analysis uses information from the observed data to implicitly 
impute the unobserved data, s. Section 8.3. Analyses at each time point measured will be 
repeated using an ANCOVA model with observed case values (i.e., missing values not imputed). 
Line graphs will be presented to display mean and mean change from baseline, with 95% 
confidence intervals, of observed LupusQoL scores over time by treatment group. 
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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. 
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 
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. 
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. 
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. 
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. 
The newly exploratory PROs (SLE-S to SLE-E) do not require a full analysis as they are 
exploratory instruments. All results will be listed. Frequency tables will be provided at item-
level, providing the number and percentage of subjects responding at each level of the scale for 
that item, by visit. Denominators for percentages will be based on the number of subjects who 
completed the item (question) at the specified visit.  Another standalone SAP/psychometric plan 
(accountable party: Modus Outcomes) will be created, which would detail out all the exploratory 
and correlation analyses across these new PROs.  
Qualitative subject interviews will be conducted by a 3rd party vendor 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. The qualitative output of these 
interviews will be analyzed and reported on by the team from Modus Outcomes. 
8.4 
Additional Endpoints and Analyses 
The following additional endpoints, not included in the protocol, will be analyzed: 
8.4.1 
DORIS (Definitions of Remission in SLE) complete remission on 
treatment 
SLEDAI-based remission is defined as:  
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 Clinical SLEDAI-2K score = 0 (SLEDAI-2K without serology: anti-dsDNA and C3/C4 
items) and 
 PGA ≤16mm and  
 Prednisone equivalent systemic dose for SLE indication ≤5mg per day 
 Anti-dsDNA is negative 
 Complement C3 or C4 ≥ LLN 
Note that the prednisone equivalent systemic dose criteria (of ≤5mg/day) has to be met from the 
(last (planned) visit day + 1) through to the current visit day.  i.e., last (planned) visit day+1, and 
every day after last visit day + 1 up to and including current visit day.  
Additionally, if any of the components of DORIS shown above are missing, then the DORIS 
result will be missing, unless the non-missing components determine that the subject has failed 
to achieve DORIS in which case the subject will count as NOT achieving DORIS. However, if 
the SLEDAI-2K assessment was done at a visit, but individual item scores within the scale are 
missing, the respective individual item scores will be imputed from the respective previous 
individual item scores (limited to 1 visit back).     
The SLEDAI based definition of remission will be used to evaluate the endpoint  
 Number of consecutive visits in remission status 
Determine the maximum number of consecutive visits the subject is in remission. If a subject has 
e.g., 2 consecutive visits with remission, and after a break 3 more consecutive visits with 
remission, the maximum number of consecutive visits the subjects is in remission will be 3. The 
analysis of this endpoint will be performed based on DB Treatment Period for interim as well as 
final analysis. Additionally number of consecutive visits in remission will be analyzed based on 
entire study for final analysis.   
8.4.2 
LLDAS (Lupus Low Disease Activity State) 
Australian version/definition 
 No significant disease activity as per SLEDAI-2K and BILAG 2004: 
 SLEDAI-2K score ≤4  
 The following SLEDAI-2K items: urinary casts, hematuria, proteinuria, pyuria, seizure, 
visual disturbance, cranial nerve disorder, lupus headache, CVA, vasculitis, pleurisy, 
pericarditis, fever should not be documented as ‘present’. 
 No evidence for hemolysis (BILAG 2004, Item 96: No) 
Gastrointestinal BILAG 2004 Organ System: no BILAG 2004 disease activity greater 
than BILAG 2004 Grade D.  
 Renal/Neuropsychiatric/Cardiorespiratory BILAG 2004 Organ Systems: no BILAG 2004 
disease activity greater than BILAG 2004 Grade D.  
 Pyrexia and Cutaneous Vasculitis (BILAG 2004 Item 1 and 13): ‘not present’ 
 No new and/or worsening disease activity 
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 No worsening in any BILAG system and no new activity as per SLEDAI-2K since last 
visit. 
Definition of worsening in any BILAG 2004 Organ System: At any time, the BILAG 
2004 Grade at one visit for a particular BILAG 2004 Organ System is greater in severity 
than at the previous visit, ie, A is worse than B, C, D, E. B is worse than C, D, E. C is 
worse than D, E.   
Definition of new activity as per SLEDAI-2K: At any time, the SLEDAI-2K score at one 
visit is higher than at the previous visit. 
 PGA ≤33mm  
 Prednisone equivalent systemic dose for SLE indication ≤7.5mg per day 
 Immunosuppressive therapy: No increase in dose in the past 12 weeks, no dose higher than 
allowed as per protocol. It will not be considered an increase in dose if the subject had 
already been taking the same therapy previously at the same or higher dose and just had a 
short gap of ≤ 1 week in that treatment. 
Note that the prednisone equivalent systemic dose criteria (of ≤7.5mg/day) has to be met from 
the (last (planned) visit day + 1) through to the current visit day.  i.e., last (planned) visit day+1, 
and every day after last visit day + 1 up to and including current visit day.  
Additionally, if any of the components of LLDAS shown above are missing, then the LLDAS 
result will be missing, unless the non-missing components determine that the subject has failed 
to achieve LLDAS in which case the subject will count as NOT achieving LLDAS. However, if 
the BILAG-2004 and/or SLEDAI-2K assessment was done at a visit, but individual item 
scores/grades within the scale are missing, the respective individual item scores/grades will be 
imputed from the respective previous individual item scores/grades (limited to 1 visit back). 
The above definition of low disease activity state would be used to evaluate these endpoints: 
 Number of subjects in LLDAS status by visit 
 Number of visits in LLDAS status/subject 
 Number of subjects with no visits, <25% of visits in LLDAS, ≥25% - <50% of visits in 
LLDAS, ≥50% - <75% of visits in LLDAS, and ≥75% of visits in LLDAS. 
Two Imputation Approaches for the % of Visits in LLDAS: 
 Observed Cases – will use only those visits the subject attended in the denominator, so 
missed visits do not impact the % of visits in LLDAS.   
 Not Achieved Imputation – will use all visits in the denominator even if subject dropped 
out and didn’t attend visit, so that is the same as counting the subject as not achieving 
LLDAS for the missed visits.  
The LLDAS analyses described above will be done for interim and final analysis based on DB 
Treatment Period and for the final analysis based on the entire study in addition. 
8.4.3 
BILAG 2004 substantial/partial/no response 
 Substantial response: all of the following 
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 All BILAG 2004 Grade As and Bs at Baseline have improved to Grade C or D 
 No escape treatment as per BICLA (s. Section 8.1.1, topic 4 of BICLA definition) 
 No organ system worsened from BILAG 2004 Grade C or D/E at Baseline to Grade A or 
B 
 Partial response: all of the following 
 At least one organ system improved from BILAG 2004 Grade A or B at Baseline to 
Grade C or D 
 At least one organ system did not improve from BILAG 2004 Grade A or B at Baseline 
to Grade C or D 
 No organ system worsened from BILAG 2004 Grade C or D/E at Baseline to Grade A or 
B 
 No escape treatment as per BICLA (s. Section 8.1.1, topic 4 of BICLA definition) 
 Non-response 
 No improvement from BILAG 2004 Grade A or B at Baseline to Grade C or D 
or 
 An organ system has worsened from BILAG 2004 Grade C or D/E at Baseline to Grade 
A or B 
or 
 Escape treatment as per BICLA (s. Section 8.1.1, topic 4 of BICLA definition) 
Based on the above definition of BILAG substantial response, partial response, and non-
response, the number and percentage of subjects with response in each categorical response level 
will be summarized by treatment group and visit. This will be a by-visit display, showing the 
number and percentage of subjects in each of the 3 categorical response levels at that visit. 
BILAG substantial/ partial/ no response is considered a responder rate endpoint and therefore 
analysis is based on mNRI BILAG data. At each visit, a Cochran-Mantel-Haenszel test of the 
association between treatment and the ordered response levels, using modified ridit scores, and 
controlling for corticosteroid strata at Baseline will be performed for each treatment group vs. 
placebo.  
8.4.4 
Flare assessment 
Variants of the investigators flare assessment as per protocol 
CRF form “Investigator Assessment of SLE Flare” has 2 questions: 
1. Do you consider that the SLE disease activity of the subject in one or more organ systems 
(involving new or worse clinical signs and symptoms and/or laboratory measurements) 
increased clinically significantly since the last visit? 
2. If ‘yes’, do you consider a change or did you increase the treatment for SLE in your subject? 
Variants:  
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1. Significant worsening only: Only 1st question has to be ticked yes 
2. Full definition + ‘measurable’ worsening: Both questions have to be ticked yes and there is 
any one or more of these: 
 any increase in SLEDAI-2K from previous visit 
 any BILAG 2004 individual item considered as ‘new’ or ‘worsening’  
 worsening of PGA by ≥10mm compared to previous visit score. 
In determining flares as defined above, similar to the determination of other flares in this study, 
if the BILAG 2004 and/or SLEDAI-2K assessment was done at a visit, but individual item 
scores/grades within the scale are missing, the respective individual item scores/grades will be 
imputed from the respective previous individual item scores/grades (limited to 1 visit back). 
Also, no more than one flare can be counted per visit. 
The above definitions of flares would be used to evaluate these endpoints: 
 Time to first flare  
 from Baseline up to Week 24 (for analysis of DB Treatment Period) 
 after Week 24 (for analysis of Observational Period) 
 from Baseline up to Week 48 (for analysis of DB Treatment and Observational Period 
together) 
 Proportion of subjects with at least 1 flare since Baseline up to and including the visit will be 
presented by visit 
 Proportion of subjects with at least 1 flare since Week 24 up to and including the visit will be 
presented by visit (for the Observational Period) 
 Descriptive statistics for the number of flares per affected subject (i.e., subjects with at least 
one flare) overall (per study period) 
All analyses of these variants of the investigators flare assessment will only be delivered at the 
time of the final analysis and included in the final CSR, regardless of whether the endpoints are 
focused on the DB Treatment Period or the Observational Period. 
 
 
Patients who do not experience a flare by Week 24 (for analyses of the DB Treatment Period), 
Week 48 (for analyses of the Observational Period) or Early Termination will be censored at the 
date of last assessment during the study period (i.e., the study discontinuation date). Survival 
curves will be generated using the Kaplan-Meier product limit estimate. 
8.4.5 
BICLA variants 
Below are 3 alternate ways of defining a BICLA responder. Each alternate definition of BICLA 
responder should be analysed using the approach described in SAP section 8.2.1. 
Modified escape treatment criterion (topic 4 of BICLA definition): 
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a) No increase of systemic  (or addition of a new) immunosuppressant nor systemic antimalarial 
doses over Baseline (Visit 2) levels for a duration of > 1 week , nor initiation of any medication 
listed in Table 7-1, s. Section 7.8.3 of Protocol Amendment.  
b) No increase in oral corticosteroid dose over Baseline (Visit 2) levels for an SLE related 
indication 
c) No iv, im, injections of corticosteroids which are SLE related 
d) No intra-articular injections of corticosteroids which are SLE related in patients with a BILAG 
A or B in the musculoskeletal BILAG organ system within 12 weeks before the BICLA visit 
being assessed. (e.g., for a Week 12 BICLA, there must not have been an injection since baseline 
(visit 2).  For a Week 24 BICLA, there must not have been an injection since Week 12.) 
e) No increase in systemic corticosteroid dose for any indication within 8 weeks before the 
BICLA visit  
All other items are unchanged. 
Modification by withdrawing items: 
1. Withdraw SLEDAI-2K and PGA criterion (criterion 2 and 3) from BICLA definition. 
(If a subject did not attend a visit, they will be counted as a non-responder in mNRI 
imputations for that visit.) 
2. Withdraw PGA criterion (criterion 3, keeping in criterion 2) from BICLA definition. 
All other items are unchanged. 
9 
PHARMACOKINETICS AND PHARMACODYNAMICS  
9.1 
Pharmacokinetics 
The following PK variables will be evaluated: 
 For plasma samples: Plasma concentrations of DZP and PEG 
 For urine samples: Urine amount of PEG 
Individual subject concentrations of DZP and of PEG will be listed and summary statistics per 
visit and planned time be provided. Plasma concentration vs. time points will be displayed in 
figures: one figure with the geometric mean plasma concentrations time profile +/- 95% CI (one 
plot with all dose levels), and a spaghetti plot per dose level, for DZP and for PEG, each. All 
plots will be provided in linear and log scale. The lower limit of quantification (LLOQ) for DZP 
concentration in plasma is 0.2μg/mL and for PEG concentration in plasma 20μg/mL. For the 
summary statistics, if a sample is BLQ, it will be considered as half of the LLOQ. Summary 
statistics will only be reported if at least 2/3 of the samples are above the LLOQ for a particular 
time point. 
Additionally, figures with the geometric mean plasma concentrations time profiles for DZP and 
PEG in plasma on the same plot, one plot per dose group, will be provided in linear and log 
scale.  
 Additionally, a figure with the geometric mean ± CIs for Ctrough vs time will be provided by dose 
level for DZP and for PEG.  
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Urine collection for the determination of PEG concentrations will be performed at the visits 
indicated in the schedule of events. For each collection interval the amount of PEG excreted in 
the urine will be calculated using the following formula:  
Amount excreted per interval (μg) = Concentration (μg/mL) x Urine volume (mL) 
The urine concentration of PEG and the amount of PEG excreted per collection interval will be 
tabulated and listed. Urine amount vs. time points will be displayed in figures: one figure with 
the geometric mean urine amount time profile +/- 95% CI (one plot with all dose levels), and a 
spaghetti plot per dose level. All plots will be provided in linear and log scale. The LLOQ for 
PEG concentration in urine is 1 μg/mL. 
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 and 
results reported separately. 
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. 
9.2 
Pharmacodynamics 
9.2.1 
Transcriptomics 
The summary and analysis of the 96-gene transcript profiling will be included in a separate 
report.  That report will be an appendix of the final SL0023 CSR.  There will be a separate 
analysis plan for that summary and analysis. 
 
9.2.2 
Auto-antibody Measurements 
All summaries of auto-antibody measurements will be run on the Safety Set, unless otherwise 
specified. All auto-antibody measurements will be listed as part of the Immunology Listing. 
For anti-dsDNA, the number and percent of subjects with: 
 anti-dsDNA (data from central lab)  
 clear cut (>10 iU) 
 intermediate or clear cut (≥5 iU) 
will be summarized at each visit. For the categories of subjects with anti-dsDNA>10 iU at 
Baseline, and with anti-dsDNA≥5 iU at Baseline, subjects achieving a reduction will also be 
tabulated, where a reduction in anti-dsDNA is defined as a ≥50% decrease from Baseline, or 
reverting to negative. In the case of a value at the upper LOQ, a reduction to less than 50% of the 
numerical LOQ will be considered to be a reduction in anti-dsDNA. 
 
Also, a shift table for anti-dsDNA will be created providing the number and percentage of 
subjects in each anti-dsDNA category at Baseline that have shifted to each anti-dsDNA category 
post-Baseline at Week 24 and Week 48. The anti-dsDNA categories are shown below. 
 anti-dsDNA classified as  
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 anti-dsDNA < 5 iU 
 anti-dsDNA >=5 iU to <=10 iU 
 anti-dsDNA >10 iU 
Further for ANA titers, a shift table will be created providing the number and percentage of 
subjects in each ANA titer category at Baseline that have shifted to each ANA titer post-Baseline 
by visit at which assessments occurred. The ANA titer categories are shown below. 
 ANA titer classified as  
 ANA titer < 1:80 
 ANA titer ≥ 1:80 and ≤ 1:160 
 ANA titer > 1:160. 
(For ANA titer, 1:80 < 1:160, i.e., it is the denominators that are assessed to determine 
whether the ANA titer is < or > a cutoff.) 
Values and change from Baseline values will be summarized by visit, as part of the Immunology 
table. The values and change from Baseline values by visit will be presented for the relevant 
parameter, for subjects with: 
 Anti-dsDNA > 10 iU at Baseline 
 Anti-dsDNA ≥ 5 iU at Baseline 
9.2.3 
Immunological Variables 
All summaries of immunological variables will be run on the Safety Set, unless otherwise 
specified. 
All immunological parameters (s. Section 2.2.3.1) will be listed by subject and time point 
including changes from Baseline for numeric variables and flags for measurements outside the 
clinical reference ranges (where applicable). Values that are below the lower limit of the 
reference range will be flagged as ‘L’ (low) and values that are above the upper limit of the 
reference range will be flagged as ‘H’ (high) and listed as well. 
Note that for the Interim Analysis, Sjögren’s syndrome antibody A (anti-SSA), Sjögren’s 
syndrome antibody B (anti-SSB), and high sensitivity C-reactive protein (hsCRP) will not be 
presented.  These will only be presented in the Final Analysis.   
Summary tables and figures will be presented for both absolute values and changes from 
Baseline.  
The number of subjects and percentages will be tabulated by treatment group and visit for 
subjects with: 
 values ≤ upper limit and analogously, with values above upper limit, 
 value < lower limit, 
 value above the upper limit at Baseline who switch to ≤ upper limit, 
 value < lower limit at Baseline who switch to ≥lower limit.  
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A shift table will be presented for C3/C4 levels showing the number and percentage of subjects 
with low C3/C4 at Baseline changed to normalized C3/C4 post-Baseline. 
Moreover, number and percentages will be provided by visit for subjects with 
 low complement 
 low complement 3 (C3),  
 low complement 4 (C4),  
 both C3 and C4 are low 
 either of C3 or C4 are low 
 evidence for aPLs: 
 Anti-Beta2 glyoprotein positive (IgG>ULN or IgM>ULN) 
 Anti-cardiolipin positive (IgG>ULN or IgM>ULN) 
 Lupus Anticoagulant increased (time (noted as DRVVT in the laboratory dataset)>ULN 
and ratio (noted as DRVVTRT in the laboratory dataset)>ULN) 
 Any of the 3 above. 
The values and change from Baseline values by visit will be presented for the relevant parameter, 
for subjects with: 
 C3 < LLN at Baseline 
 C4 < LLN at Baseline 
 Anti-Beta2 glyoprotein positive (IgG> ULN or IgM> ULN) at Baseline 
 Anti-cardiolipin positive (IgG> ULN or IgM> ULN) at Baseline 
1. 
Lupus Anticoagulant increased (time (noted as DRVVT in the laboratory dataset)>ULN 
and ratio (noted as DRVVTRT in the laboratory dataset)> ULN) at Baseline 
10 
IMMUNOGENICITY 
10.1 
Anti-Dapirolizumab antibodies 
Anti-dapirolizumab antibody (anti-DZP) will be measured as specified in the schedule of 
assessments during the double-blind treatment period and the observational period at Day 1, 
Week 4, Week 8, Week12, Week 16, Week 20, Week 24, Week 28, Week 32 and Week 48. 
The Anti-drug antibody (ADA) analysis and determination of anti-DZP antibodies will occur via 
a dual assay strategy, consisting of first ADA assay (which is sensitive towards target 
interference) followed by further characterization of confirmed ADA positive samples in a 
second ADA assay that has been optimized with regards to target tolerance characteristics, which 
will generate the final ADA result. For both ADA assays a tiered analysis approach will be 
followed. 
Samples will first be evaluated in the screening assay using a false positivity rate of 5%, 
followed by analysis of screened positive samples in the confirmatory assay (which is a drug 
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depletion assay) to confirm the true positivity of the samples. Samples that are confirmed as 
positive will be evaluated in a titration assay to quantify the anti-DZP antibody level and will be 
reported as titer (= dilution factor). The titer represents the last dilution factor of the sample’s 
titration series still scoring positive in the screening ADA assay. 
The screening cut-point, the confirmatory cut-point and titration cut-point will be determined by 
the bioanalytical laboratory during assay validation. 
 
Results from the first ADA assay will be reported as  
 negative (either screening negative or negative in the confirmatory assay as 
immunodepletion negative) 
  or as a final titer result. 
Samples that are confirmed as positive (and will be reported with a titer result) from the first 
ADA assay will be further evaluated in the 2nd target tolerant ADA assay for which the screening 
result (screening positive or negative), the confirmatory result (confirmed positive or negative) 
and the titer result will be reported. 
 
Anti-DZP status should be determined for each visit where samples were taken for ADA 
analysis. At each visit 
 Values reported as negative (either screening negative or negative in the confirmatory 
assay based on the first ADA assay or screening negative or confirmed negative based on 
the 2nd ADA) are defined as anti-DZP- 
 Values reported as titers based on the 2nd ADA assay (positive titer values) are defined as 
anti-DZP+ 
The MRD will be outlined in the Data Transfer Agreement from the laboratory and 
footnoted where relevant in tables, listings and figures.  
 
In addition, subjects will receive an overall anti-DZP subject classification based on their pre-
existing antibody (pre-Ab) status at baseline and their treatment emergent ADA status, and will 
be classified as follows based on the ADA assay results (with anti-DZP+ samples being defined 
as outlined above). This analysis is done based on the results from the second ADA assay. 
This classification will be done based on the ADA results obtained 1) during the double-blind 
treatment period for the interim analysis and 2) over the entire study period (i.e. the double-blind 
treatment period and the observational period for the final analysis). 
1. Pre-Ab negative – treatment emergent ADA negative = subjects who are negative at 
baseline visit and are ADA negative at all sampling time points post-treatment (during in 
the double-blind treatment period or over the entire study period) 
2. Pre-Ab negative – treatment induced ADA positive = subjects who are negative at 
baseline visit and having a positive ADA value at any time in post-treatment. 
3. Pre-Ab positive – treatment reduced ADA = subjects who are ADA positive at 
baseline visit and are ADA negative at all times post-treatment  
4. Pre-Ab positive – treatment unaffected ADA= subjects who are ADA positive at 
baseline visit and are positive at any sampling time point post-treatment with all titer 
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values of the same or less magnitude as baseline (titers post-treatment are ≤ a predefined 
fold difference from baseline)   
5. Pre-Ab positive – treatment boosted ADA= subjects who are positive at baseline and 
are positive at any sampling time point post-treatment with at least one titer value that is 
increased compared to baseline (i.e. having post-treatment a titer value ≥ a predefined 
fold increase from the highest reported titer at baseline) 
The fold increase from baseline needed to consider a titer value reported post-treatment to be 
above the assay variation will be noted in the relevant tables, listings and figures. 
 
Based on the overall anti-DZP subject classification above, the following will be determined and 
presented: 
o Total prevalence of pre-Ab: n/N % number of subjects in category 3, 4 and 5. 
o Total incidence of treatment-emergent ADA positive: n/N % number of subjects 
in category 2 and category 5 
  
10.2 
Anti-PEG antibodies 
Anti-PEG antibody (anti-PEG) will be measured for each visit as specified in the schedule of 
assessments during the double-blind treatment period and the observational period at Day 1, 
Week 4, Week 8, Week12, Week 16, Week 20, Week 24, Week 28, Week32 and Week 48. 
Determination of anti-PEG antibodies will occur via a tiered analysis approach, where samples 
are first being evaluated in the screening assay using a false positivity rate of 5%, followed by 
analysis of screened positive samples in the confirmatory assay (which is a drug depletion assay) 
to confirm the true positivity of the samples. Samples that are confirmed as positive will be 
evaluated in a titration assay to quantify the anti-PEG antibody level and will be reported as titer 
(= dilution factor). The titer represents the last dilution factor of the sample’s titration series still 
scoring positive in the screening ADA assay. 
The screening cut-point, the confirmatory cut-point and titration cut-point will be determined by 
the bioanalytical laboratory during assay validation. 
 
The screening result (screening positive or negative), the confirmatory result (confirmed positive 
or negative) and the titer result will be reported. 
 
Anti-PEG status should be determined for each visit where samples were taken for ADA sample 
analysis. At each visit 
 Values reported as negative (either screening negative or negative in the confirmatory 
assay) are defined as anti-PEG- 
 Values reported as titers (positive titer values or reported as ≥ MRD) are defined as anti-
PEG+ 
 
In addition, subjects will receive an overall anti-PEG subject classification based on their pre-
existing antibody (pre-Ab) status and treatment emergent ADA status, and will be classified as 
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follows based on the ADA assay results (with anti-PEG+ samples being defined as outlined 
above). 
This classification will be done based on the ADA results obtained 1) during the double-blind 
treatment period for the interim analysis and 2) over the entire study period (i.e. the double-blind 
treatment period and the observational period) for the final analysis. 
 
1. Pre-Ab negative – treatment emergent ADA negative = subjects who are negative at 
baseline visit and are ADA negative at all sampling time points post-treatment (during in 
the double blind treatment period or over the entire study period) 
2. Pre-Ab negative – treatment induced ADA positive = subjects who are negative at 
baseline visit and having a positive ADA value at any time in post-treatment. 
3. Pre-Ab positive – treatment reduced ADA = subjects who are ADA positive at 
baseline visit and are ADA negative at all times post-treatment  
4. Pre-Ab positive – treatment unaffected ADA= subjects who are ADA positive at 
baseline visit and are positive at any sampling time point post-treatment with all titer 
values of the same or less magnitude as baseline (titers post-treatment are ≤ a predefined 
fold difference from baseline).   
5. Pre-Ab positive – treatment boosted ADA= subjects who are positive at baseline and 
are positive at any sampling time point post-treatment with at least one titer value that is 
increased compared to baseline (i.e. having post-treatment a titer value ≥ a predefined 
fold increase from the highest reported titer at baseline) 
The fold increase from baseline needed to consider a titer value reported post-treatment to be 
above the assay variation will be noted in the relevant tables, listings and figures. 
 
 Overall subject classification: 
o Total prevalence of pre-Ab: n/N % number of subjects in category 3, 4 and 5. 
o Total incidence of treatment-emergent ADA positive: n/N % number of subjects 
in category 2 and category 5 
  
10.3 
Analyses Done for Both Anti-DZP and Anti-PEG Antibodies 
Immunogenicity will only be summarized and analyzed for the final analysis, and results will be 
reported in the Final CSR only.   
 
Immunogenicity will be assessed through summary tables and figures, and listing of individual 
results by subject. Note that placebo subjects will not be included for analyses of anti-DZP.  
However, placebo subjects will be included for analyses of anti-PEG, as subjects may have anti-
PEG antibodies pre-existing.  
 
All analyses will be run on the safety population, unless specified otherwise. 
All ADA (anti-DZP and anti-PEG) results will be listed.  
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 The incidence of the ADA+ and ADA- (for anti-DZP+ and anti-DZP- and for anti-PEG+ 
and anti-PEG-) will be tabulated by treatment group and visit, and incidence reported as 
proportion of subjects having positive ADA samples at any time point (number and 
percentage). Missing samples will not be included in the denominator. 
 Same table as above tabulated by treatment group and visit and overall anti-DZP subject 
classification and overall anti-PEG subject classification (defined in sections 10.1 and 
10.2). 
 Boxplots of the ADA titer for subjects who are ADA+ (anti-DZP+ and anti-PEG+) will 
be presented by treatment group and visit, with the incidence (i.e., proportion) of subjects 
having ADA+ samples at each visit (number and percentage) presented in the legend 
along the X-axis. Visits will be presented along the X-axis. Each treatment group will be 
displayed on a separate page. Missing samples will not be included in the denominator.  
 The number and percentage of subjects with the first occurrence of ADA positivity (both 
anti-DZP+ and anti-PEG+) at each visit will be provided.  
 The number and percentage of subjects in the overall anti-DZP subject classification and 
overall anti-PEG subject classification (specified in sections 10.1 and 10.2) will be 
reported and tabulated per dose group and over for all Dapirolizumab treated subjects. 
 The time to achieving treatment-emergent ADA positivity, separated by treatment group 
and overall anti-DZP subject classification / overall anti-PEG subject classification 
(defined in sections 10.1 and 10.2), will be analyzed based on Kaplan-Meier approach. 
Subjects will be considered to have an event at time where treatment emergent ADA 
positive is first achieved. Subjects classified as treatment-emergent ADA negative will be 
censored at time of last available ADA result. Note subjects presenting a treatment 
emergent response are subjects classified as i) preAb negative – treatment induced ADA 
positive or as ii) pre-Ab positive – treatment emergent ADA boosted positive. 
 Spaghetti plots of ADA titer (Y-axis) against time (X-axis), separated by treatment group 
for all ADA positive subjects and for the subjects in each overall anti-DZP subject 
classification and overall anti-PEG subject classification (defined in sections 10.1 and 
10.2). 
 
For the evaluation of impact of immunogenicity on PD and efficacy, the PD and efficacy 
variables will be determined following interim analysis. The analyses described below will only 
be done if data merit, and results will be reported in the Final CSR only.  
 Spaghetti plots for DZP plasma concentration, PK, and efficacy marker per overall anti-
DZP subject classification and overall anti-PEG subject classification (defined in sections 
10.1 and 10.2) and per dose group with identification of the different subject categories 
and on individual subject level. A minimum of 3 subjects in the overall anti-DZP subject 
classification and overall anti-PEG subject classification is required for summary figures. 
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 Descriptive statistics for DZP plasma concentration, PK, and efficacy marker (geometric 
mean +/-SD of PK, PD, efficacy read-outs time profile) per overall anti-DZP subject 
classification and overall anti-PEG subject classification (defined in sections 10.1 and 
10.2) and per dose group. A minimum of 3 subjects in the overall anti-DZP subject 
classification and overall anti-PEG subject classification is required for summary tables. 
 Individual subject plots that present ADA titer, DZP plasma concentration and 
PD/efficacy marker on the same plot over time. These will be line plots with a separate 
page for each subject, time on the X axis and a line plotted for each of ADA titer, DZP 
plasma concentration and PD/efficacy marker on overlaid Y-axes. 
 Bar chart of efficacy responder, separated by dose group and overall anti-DZP subject 
classification and overall anti-PEG subject classification (defined in sections 10.1 and 
10.2), the time points of primary efficacy evaluation as a function of ADA titer will be 
presented graphically. To create this bar chart, ADA titer will be classified into groups as 
in the box plot described below.  Those groups must be determined after seeing the ADA 
data. 
 Box plots of all DZP plasma concentrations for subjects who are ADA+ (anti-DZP+) 
versus overall anti-DZP subject classification (group 1; group 2) presented on a linear 
scale. 
Immunogenicity is also evaluated as a covariate in the PK/PD modelling analysis. This analysis 
will be described in a separate PK/PD data analysis plan and results will be reported in an 
appendix to the CSR. 
 
If data merits, immunogenicity may also be correlated with possible safety findings for reporting 
in the Final CSR only.  
 A summary table of all immune related TEAEs by ADA Status. For this summary, 
subjects will be categorized by the overall anti-DZP subject classification and overall 
anti-PEG subject classification (defined in sections 10.1 and 10.2), and will be presented 
for immune related TEAEs occurring prior to becoming treatment emergent ADA 
positive, TEAEs occurring after becoming TE ADA positive, and TEAEs for subjects 
who remained TE ADA negative.  
In addition, the immunogenicity results will be correlated with thromboembolic events provided 
as an individual listing of subjects experiencing thromboembolic events with identification of the 
subject category for anti-DZP antibodies and anti-PEG antibodies and the onset of ADA (both 
anti-DZP and anti-PEG antibodies). This will only be done if data merit and results will be 
reported in the Final CSR only. 
11 
SAFETY ANALYSES 
All safety analyses will be based on the Safety Set. 
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11.1 
Extent of exposure 
11.1.1 
Presentation of dosing data 
Administration of investigational medicinal product (IMP) will be listed by subject. The listing 
will include the following information for each dose received: 
 Date of infusion 
 Start and stop time of infusion 
 Total volume of IMP given (mL) 
 Estimated fraction of dose remaining (%) 
 Compliance (%)  
 Planned dose (mg) 
 Actual dose (mg) 
 Percent of planned dose administered (%)  
 Whether or not the infusion was stopped (including the reason) 
 Whether the infusion was permanently discontinued (including the reason) 
For all subjects the planned infusion volume will be 150 mL. The planned infusion time will be 
approximately 120 min. 
For the total volume infused (mL), the duration of infusion (min), the actual dose (mg), the total 
duration of exposure (days) and the compliance (%) summary statistics will be provided.  
The duration of infusion will be calculated as follows: 
Duration of infusion (min) = Stop infusion – start infusion 
The total duration of exposure will be calculated as follows: 
Exposure (days) = (Date of last dose − Date of first dose) + 84 
11.1.2 Calculation of planned and actual dose received 
The total planned dose given at each visit will then be calculated to 1 decimal place as follows: 
Planned dose (mg) = Body weight (kg) x Randomized Dose (mg/kg). 
The actual dose (mg) received will be calculated to 1 decimal place, and is based on the infusion 
volume given (mL) and the actual concentration of DZP in the infusion bag (mg/mL): 
Actual dose (mg) = Infusion volume given (mL) x Concentration DZP in infusion (mg/mL). 
The concentration of DZP in the infusion IV bag (mg/mL) is based on the number of mL of 
reconstituted solution from vials of DZP that were included in the IV bag and the total volume of 
the IV bag. There were 100mg DZP per every 1 mL of reconstituted solution from the vials. 
Concentration DZP in infusion (mg/mL) =  
      { [Sum across all vials used (amount of reconstituted solution taken from the vial (mL)) x 
           100 mg/mL (DZP in the reconstituted solution)] / Total volume of IV bag prepared (mL) } 
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Compliance is based on the volume given (mL) compared to the 150mL that were supposed to be 
administered for each infusion, thus representing the site’s compliance with the dosing regimen, 
and will be calculated to 1 decimal place for each visit: 
Compliance (%) = (Infusion volume given (mL)/150 mL) x 100%. 
Percent of planned dose administered (%) is based on the actual dose compared to the planned 
dose, thus representing both the volume of infusion given as well as the actual contents of the IV 
bag, and will be calculated to 1 decimal place for each visit: 
 
Percent of planned dose administered (%) = [Actual dose (mg) / Planned dose (mg)] x100% 
Study drug exposure and treatment compliance will also be assessed across the duration of the 
study and tabulated by treatment group for the following parameters: 
 Percent of doses (i.e., infusions) with the correct dose administered. Correct dose is defined 
as any infusion where 80% ≤ (Percent of planned dose administered) ≤ 120%. 
 Percent of doses (i.e., infusions) with incorrect dose administered. Incorrect dose is defined 
as any infusion where (Percent of planned dose administered) <80% or (Percent of planned 
dose administered) >120%, excluding those cases where the subject may not have received 
intended dose due to that infusion being permanently discontinued. 
 Percent of doses (i.e., infusions) where the length of infusion was too short, excluding cases 
where the infusion was permanently discontinued. Too short is defined as less than 90 
minutes. 
 Percent of skipped doses (i.e., infusions) will be summarized. Skipped doses will be 
identified using missing data on CRF at regularly-scheduled dosing visits. 
11.2 
Adverse events 
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 occurring during the study (i.e., after signature of the informed consent document) will 
be recorded in the electronic case report form (eCRF). For each AE the following information 
will be recorded in the eCRF: AE term (verbatim term), date and time of onset, whether or not 
the AE was an infusion reaction, if yes, whether this infusion reaction fulfills the Sampson 
criteria (for definition of Sampson criteria, see Sampson et al, 2006), pattern of event, whether or 
not the AE was classified as a SAE, as an AE of interest or as an AE of special interest, 
intensity, relationship to IMP, action taken with IMP, other action taken, outcome, date and time 
of outcome, intensity, and whether the AE led to study drug discontinuation or to study 
discontinuation. 
Adverse events (including serious AEs) are characterized as either pretreatment or treatment-
emergent according to the following criteria: 
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 Pretreatment AEs are the events with onset date and time prior to the first administration of 
study drug (DZP or PBO). 
 Treatment-emergent AEs are those with onset date and time at or after the first 
administration of study drug, and up to 12 weeks (84 days) after last dose. The events that 
emerge after the final drug administration up to 12 weeks after last dose, will therefore also 
be considered as treatment-emergent (e.g., in the case of premature discontinuation or during 
the FU period (12 weeks after last dose)). 
Time to onset of AE (noted as “Time Since First Dose” on AE listings) is calculated as the time 
between first dose and onset of AE. Time to onset is expressed in days, hours, minutes. Time to 
onset of AE is not calculated for pretreatment AEs. 
The time to onset for each AE (relative to the first dose) will be calculated as follows for all 
TEAEs: 
 
Time to onset since first dose= (Date:time of AE onset − Date:time of first dose of IMP) 
For AEs with time of onset not provided,  
     Time to onset since first dose will be estimated by:  
(Date of AE onset - date of first dose of IMP) 
and will be shown in days only (without hours). If the date of AE onset and date of first dose of 
IMP are the same, Time to onset since first dose will be shown as <1 day. 
In addition, the time to onset since the most recent dose prior to the TEAE will be calculated: 
 
Time to onset since most recent dose=  
      (Date:time of AE onset − Date:time of most recent dose of IMP prior to the TEAE start) 
For AEs with time of onset not provided,  
     Time to onset since most recent dose will be estimated by:  
(Date of AE onset - date of most recent dose of IMP prior to the TEAE start) 
and will be shown in days only (without hours). If the date of AE onset and date of most recent 
dose of IMP prior to the TEAE start are the same, Time to onset since most recent dose will be 
shown as <1 day. 
The duration of each AE will be calculated as follows: 
 
AE Duration (days) = (Date:time of outcome − date:time of onset) 
For AEs with time of onset and/or time of outcome not provided,  
     AE duration will be estimated by:  (Date of AE outcome - date of AE onset) 
and will be shown in days only (without hours). If the date of AE onset and date of AE outcome 
are the same, AE duration will be shown as <1 day.Any AEs with incomplete onset and outcome 
(end) dates/times will be handled according to the following rules for classification as treatment-
emergent and for calculation of time to onset. Such imputations will only be performed for these 
classifications and calculations; in the listings all data will be shown as recorded on the eCRF. 
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 If only the month and year are specified and the month and year of first dose is not the same 
as the month and year of onset, then use the 1st of the month. 
 If only the month and year are specified and the month and year of first dose is the same as 
the month and year of onset, then use the date of first dose. 
 If only the year is specified, and the year of first dose is not the same as the year of onset, 
then use January 1 of the year of onset. 
 If only the year is specified, and the year of first dose is the same as the year of onset, then 
use the date of first dose. 
 If the AE onset date is completely unknown, then use the date of first dose. 
 Imputations for missing end dates/times will not be performed for classification as treatment-
emergent and for calculation of time to onset as this is not required. 
In the listings, AE duration will be presented in hours and minutes for durations of less than 24h. 
For AEs with duration longer than 24h the duration will be presented in days and hours (where 
hour will be rounded to the nearest integer). For the calculation of duration for AEs with missing 
start dates, the dates will be imputed as described above. 
In case of uncoded AEs, these AEs should be designated as “UNCODED” at all MedDRA 
levels, and such AEs will be included in summary tables and subject listings based on this 
classification. 
The listings show the data on AEs for all subjects in the Randomized Set who had at least one 
AE (pretreatment and/or treatment-emergent). Subjects who had no AEs are not presented on the 
listings. 
All AEs will be listed by subject including the information described above. In addition, all 
TEAEs will be flagged in the listing.  
Pre-treatment AEs will only be listed.  
For the AEs, 4 kinds of tables will be provided:  
For the Interim Analysis,  
 all TEAEs of the DB Treatment Period (all TEAEs through Week 24),  
and for the Final Analysis: 
 All TEAEs (all TEAEs from first dose to +84 days after last infusion)  
 All AEs of Observational period (all AEs from Week 24+1 day through end of study) 
 All AEs (all AEs from 1st dose to end of study). 
For a subject who withdraws from the study, all TEAEs of the DB Treatment Period will include 
all AEs through the day of the last DB Treatment Period visit, and all AEs of Observational 
Period will include all AEs from 1 day after the last DB Treatment Period visit through the end 
of study. 
The incidence of treatment-emergent adverse events (TEAEs) will be summarized by MedDRA 
system organ class, high level term, and preferred term. In addition the incidence of TEAEs 
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starting within 1 Day after infusion will be presented. Tables with incidences of classified 
TEAEs by maximum intensity, by relationship, and by aPL status positive/negative at any time 
during the study will be provided.  
Furthermore, a table including the exposure adjusted incidences will be presented. In detail, the 
table will include the number of events, number and proportion of subjects with the event (ie, 
incidence proportion), the exposure-adjusted incidence rate with the associated 95% confidence 
interval, and the exposure adjusted event rate.  
For incidence rate, the numerator will be the total number of subjects experiencing the AE, each 
subject counted once only even if the subject has the event multiple times. The denominator will 
be in 100 patient-years. That is, the total summation of individual patient-years at risk up to the 
first occurrence of the AE for subjects with that AE, and the total patient-years at risk for those 
subjects not experiencing that AE, divided by 100. Incidence rates will be presented with a 95% 
exact confidence interval based upon the Chi-Square distribution (Ulm, 1990). 
For exposure adjusted event rate, the numerator will be the number of AEs including repeat 
occurrences in individual subjects. The denominator will be in 100 patient-years. That is, the 
total summation of individual patient-years at risk (total sum of duration of exposure for all 
subjects) divided by 100. No confidence interval will be computed. 
Tables summarizing the incidence of TEAEs will also be provided for: 
 the number of subjects with thromboembolic TEAEs (based on the “Embolic and 
thrombotic events” SMQ plus the additional item “antiphospholipid syndrome”) (this 
incidence table will be presented by maximum intensity),  
 the number of subjects with opportunistic infection TEAEs (based on a review of 
MedDRA preferred terms by the sponsor),  
 the number of subjects with infusion reactions (as indicated by the investigator on the 
CRF)  
 the number of subjects with hypersensitivity TEAEs (based on the narrow SMQ for 
hypersensitivity) as well as the number of subjects with hypersensitivity TEAEs starting 
within 1 Day after an infusion. 
Incidence tables with the TEAEs leading to study discontinuation and/or permanent withdrawal 
of study drug, and incidence tables with the serious AEs (SAEs) will also be provided.  
Furthermore, a figure with the most frequent AEs sorted by relative risk will be provided. 
To further support public disclosure, the following summaries of TEAEs will be produced for the 
Final Analysis only for the grouping of All TEAEs (all TEAEs from first dose to +84 days after 
last infusion) only: 
 a summary of the incidence of non-serious TEAEs occurring in >5% of subjects within 
any individual treatment group (incidence is compared to the threshold prior to any 
rounding),  
 a summary of the incidence of drug-related, treatment emergent SAEs 
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 a summary of the incidence of drug related, TEAEs leading to withdrawal from 
treatment. 
11.2.1 
Adverse events of special interest and adverse events of interest 
An AE of special interest is any AE that a regulatory authority has mandated to 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 (AESI). For 
definition of Potential Hy’s law, s. Section 11.3.3. 
Any PDILI event that meets the criterion for potential Hy's Law must be reported as an AESI, 
but not all PDILI events meet Hy's Law. For details of PDILI events, s. Section 11.3.3. 
Adverse events of interest (AEOI), regardless of seriousness, as defined for this study are 
 Moderate to severe infections, including opportunistic infections and tuberculosis 
 Infusion reactions (as indicated by the investigator on the CRF, including hypersensitivity 
and anaphylaxis). Hypersensitivity AEs will be based on the narrow SMQ for 
hypersensitivity. 
 Thromboembolic events (including but not limited to cardiovascular events, stroke, 
myocardial infarction, pulmonary embolism, and deep vein thrombosis). Thromboembolic 
events will be based on the Embolic and Thrombotic Events SMQ plus the additional item 
“antiphospholipid syndrome”. 
 Prespecified neurological events: Severe and/or serious headache, positional headache, 
cranial nerve dysfunction, or signs and symptoms of meningitis (photophobia, neck stiffness) 
 Malignancies 
All AEOIs will be listed by subject. The incidence of the AEOIs will be summarized by 
MedDRA system organ class, high level term and preferred term. Subjects who meet Hy’s Law 
Criteria will be listed.  
 
There will be additional summaries of the incidence of TEAEs for these subsets of AEOIs: 
thromboembolic AEs, hypersensitivity AEs, and opportunistic infections. 
11.3 
Clinical laboratory evaluations 
11.3.1 
Routine safety laboratory evaluations 
The routine clinical laboratory evaluations are specified in Table 11‒1Table 11‒1 . 
Table 11‒1: Routine Clinical Laboratory Evaluations  
Category 
Panel 
Parameters/ Comments 
Clinical chemistry 
Electrolytes 
Sodium and potassium 
Clinical chemistry 
Minerals 
Calcium and phosphate 
Formatte
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Table 11‒1: Routine Clinical Laboratory Evaluations  
Category 
Panel 
Parameters/ Comments 
Clinical chemistry 
Metabolic 
Glucose, lipase, and creatine phosphokinase 
Clinical chemistry 
Kidney Function 
Urea nitrogen, and creatinine 
Clinical chemistry 
Proteins 
Total protein and albumin 
Clinical chemistry 
Liver Function 
ALP, ALT, AST, GGT, bilirubin and LDH 
Clinical chemistry 
Lipids 
Total cholesterol and triglycerides 
Hematology 
RBC 
RBC count, hemoglobin and hematocrit 
Hematology 
RBC Indices 
Mean corpuscular volume, mean corpuscular 
hemoglobin, mean corpuscular hemoglobin 
concentration and erythrocyte sedimentation 
rate 
Hematology 
Platelets 
Platelet count 
Hematology 
WBC 
WBC count 
Hematology 
WBC Differential 
Neutrophils, basophils, eosinophils, 
lymphocytes, atypical lymphocytes, and 
monocytes 
Hematology 
 
T cells (CD3+), B cells (CD19+) 
Urinalysis 
 
pH, protein, glucose, ketone, urobilinogen, 
bilirubin, blood, nitrite, leukocytes 
Urine sediment 
 
RBCs, WBCs, RBC casts and WBC casts 
Measurements outside the clinical reference ranges will be assessed by the Investigator. In 
addition, laboratory values will be graded (where possible) according to CTCAE Version 4.03.  
All laboratory data will be listed by subject and time point including changes from Baseline (as 
defined in Section 3.3), percentage changes from Baseline for numeric variables and flags for 
measurements outside the normal ranges. 
Values that are below the lower limit of the reference range will be flagged as ‘L’ (low) and 
values that are above the upper limit of the reference range will be flagged as ‘H’ (high). The 
flag and the CTCAE grade will be included in the listings. 
Any laboratory parameters that are given as ‘<xx’ or ‘>xx’ in the database will be imputed with 
the absolute value of the number without the sign (eg, <2.2 will be imputed as 2.2) for the 
calculation of the changes from Baseline. 
Summary tables will be provided for both absolute values and changes from Baseline. Shift 
tables for CTCAE grading category will be presented for clinical chemistry and hematology 
parameters.  For each of clinical chemistry and hematology, there will be: 
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 one table for lab parameters that have a CTCAE grading based on values that are <LLN. 
This table will show the number and percentage of subjects in their maximum CTCAE 
grading category compared to Baseline.  The maximum grading category will represent 
the maximum decrease from Baseline.  
 one table for lab parameters that have a CTCAE grading based on values that are >ULN. 
This table will show the number and percentage of subjects in their maximum CTCAE 
grading category compared to Baseline.  The maximum grading category will represent 
the maximum increase from Baseline. 
The denominator for the percentages in both types of CTCAE grading shift tables will be the 
number of subjects in the Safety Set.  
Urinalysis and urine sediment results will be listed and tabulated. Note that for RBCs and WBCs 
in urine sediment, a few samples were reported as “TNTC” which means “too numerous to 
count”.  For summary, these samples will be counted at the upper limit of quantification 
provided by the lab, 719.9/hpf. 
Furthermore, figures will be provided both for the mean value by visit and for the mean changes 
from baseline by visit for continuous laboratory parameters (as observed). 
11.3.2 
Additional laboratory evaluations 
The additional laboratory evaluations are specified in Table 11‒2Table 11‒2 . 
Table 11‒2: Additional Laboratory Evaluations 
Parameter 
Assessment Visits 
Coagulation and hemostasis tests  
(prothrombin time, activated partial 
thromboplastin time, prothrombin intl. 
normalized ratio, and fibrinogen (fibrinogen 
was optional, ordered by sites as needed)) 
Visit 1 (Screening), 7 (Week 12), and 10/EWV 
(Week 24), 12 (Week 32) predose on dosing days 
Urinary albumin:creatinine ratio (mg/mmol), 
Urinary protein:creatinine ratio (mg/mmol) 
Visit 1 (Screening), Visit 2 (Day 1), 3 (Week 2), 4 
(Week 4), 6 (Week 8), 7 (Week 12), 8 (Week 16), 9 
(Week 20), and 10/EWV (Week 24), 11 (Week 28), 
12 (Week 32), 14 (Week 40) , 16 (Week 48)  
predose on dosing days 
The urinary albumin:creatinine ratio (mg/mmol) and urinary protein:creatinine ratio (mg/mmol) 
will be calculated by the laboratory from the corresponding urinary albumin, protein and 
creatinine measurements obtained at Visit 1 (Screening) to 16/EWV (Week 28), except Visit 5 
(Week 6). A summary table showing descriptive statistics for the change from Baseline values 
by visit for urinary protein:creatinine ratio and urinary albumin:creatinine ratio will be provided 
for the subset of subjects with a urinary protein:creatinine ratio >56 mg/mmol at Baseline. 
HIV test at Screening, hepatitis test at Screening and Tuberculosis test are done as part of the 
inclusion/exclusion criteria. Therefore they are only listed, but no analysis on this will be done. 
 The other parameters defined above will be listed by subject and time point including changes 
from Baseline for numeric variables and flags for measurements outside the clinical reference 
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ranges (where applicable). Values that are below the lower limit of the reference range will be 
flagged as ‘L’ (low) and values that are above the upper limit of the reference range will be 
flagged as ‘H’ (high) and listed as well. Summary tables will be presented for both absolute 
values and changes from Baseline. 
11.3.3 
Potential drug-induced liver injury 
Evaluation of potential drug-induced liver injury (PDILI) consists of the diagnostic testing, 
continued monitoring and consult with a local hepatologist. The following testing is requested 
for PDILI: 
 If ALT and/or AST ≥3xULN and no symptoms of hepatitis or hypersensitivity then the 
subject must be discussed with the Study Physician within 24h. 
 If ALT and/or AST ≥3xULN and symptoms of hepatitis or hypersensitivity present then the 
local hepatologist should be consulted by the physician for assessment and management of 
potential hepatic disease and the subject must be discussed with the Study Physician. 
 If ALT and/or AST ≥3xULN and total bilirubin of ≥2xULN then the local hepatologist 
should be consulted by the physician for assessment and management of potential hepatic 
disease and the subject must be discussed with the Study Physician. 
Hepatitis symptoms include fatigue, nausea, vomiting, right upper quadrant pain or tenderness. 
Hypersensitivity symptoms include eosinophilia (>5%), rash and fever without clear alternative 
cause. The subjects who meet the PDILI criteria will be listed.  
A listing of subjects who possible meet the Hy’s Law criteria, 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, will be provided. 
11.4 
Vital signs, physical findings, and other observations related to 
safety 
11.4.1 
Vital signs 
The following vital signs measurements will be assessed: 
 Pulse rate (PR) (bpm) 
 Systolic blood pressure (SBP) (mmHg) 
 Diastolic blood pressure (DBP) (mmHg) 
 Body temperature (ºC) 
 Body weight (kg) 
 Body height (cm) 
Vital signs measurements (absolute values and changes from Baseline) will be summarized and 
listed by visit and timing relative to dosing including changes from Baseline, as well as changes 
from pre-infusion to post-infusion time points at infusion visits. The listing will also include 
details to abnormal values. Vital signs with values below lower limit of normal and a decrease 
greater than the limit given in the following table or vital signs with values above upper limit of 
normal and an increase greater than the given value in the table will be classified as abnormal. 
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A summary of the number and percentage of subjects with a vital sign abnormality at any post-
Baseline time point will also be provided by vital sign measurement. 
Table 11‒3: Reference ranges for vital signs 
 
 
Absolute Values 
Changes from 
Baseline 
Parameter 
Unit 
Lower 
Limit 
Upper 
Limit 
Decrease 
Increase 
Pulse rate 
bpm 
  45 
  90 
  -15 
  15 
Systolic blood pressure 
mmHg 
  90 
150 
  -15 
  15 
Diastolic blood pressure 
mmHg 
  40 
  90 
  -15 
  15 
Body temperature 
ºC 
  35.9 
  37.6 
  - 
  - 
11.4.2 
Electrocardiogram 
Abnormal ECGs will be listed by subject, visit, and timing relative to dosing. Only the 
Investigator/Cardiologist evaluation will be presented in the listing together with the details of 
any abnormalities. Only ECGs, evaluated as ‘abnormal, not clinically significant’ or ‘abnormal, 
clinically significant’ will be included.  
A summary of the number and percentage of subjects with an abnormal ECG finding observed at 
any post-Baseline time point will also be provided by each reported ECG abnormal finding. 
According to CRF quantitative ECG parameters will not be evaluated. 
11.4.3 
Physical examination 
Abnormal results of the physical examination together with details of abnormalities: abnormality 
SLE related or not, abnormality clinically significant or not, will be listed by subject and visit.  
11.4.4 
Other safety variables 
11.4.4.1 
Assessment of suicidal ideation and behavior 
Suicidal ideation and behavior will be assessed using the C-SSRS (Columbia Suicide Severity 
Rating Scale). This scale will be used to assess suicidal ideation and behavior that may occur at 
Screening, Visit 10 (Week 24) and Visit 12 (Week 32). At Screening, subjects will be asked to 
assess suicidal ideation and behavior for their lifetime and also for the past 6 months prior to 
Screening. At Visit 10 and Visit 12, subjects will be asked to assess suicidal ideation and 
behavior since the last study visit.  
The C-SSRS includes 10 categories with binary responses (yes/no): 
Category 1:  
 
Category 2:  
 
Category 3:  
  
Category 4:  
  
Category 5:  
 
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Category 6:  
 
Category 7:  
  
Category 8:  
  
Category 9:  
  
Category 10:  Completed Suicide 
Endpoints based on the above categories are defined as 
Suicidal ideation:   
A “yes” answer at any time during treatment to any one of the 5 suicidal 
ideation questions (Categories 1-5) on the C-SSRS. 
Suicidal behavior:   A “yes” answer at any time during treatment to any one of the 5 suicidal 
behavior questions (Categories 6-10) on the C-SSRS. 
Suicidal ideation or behavior:  A “yes” answer at any time during treatment to any one of the 
10 suicidal ideation and behavior questions (Categories 1-10) on the C-SSRS. 
 
A listing will be provided including all data for only those subjects who have a ‘Yes’ response in 
any category (for any timeframe) at any visit. The listing will indicate each visit at which the 
scale was administered and the timeframe upon which each C-SSRS category was evaluated.  
 
 
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12 
REFERENCES 
Albrecht J, Taylor L, Berlin JA, Dulay S, Ang G, Fakharzadeh S, et al. The CLASI (Cutaneous 
LE Disease Area and Severity Index): an outcome instrument for cutaneous lups erythematosus. 
J Invest Dermatol. 2005 November;125(5):889-894. 
Bretz F, Pinheiro JC, Branson M. Combining multiple comparisons and modeling techniques in 
dose-response studies. Biometrics. 2005;61:738-748. 
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;30:1955-1959. 
Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. 
J Rheumatol. 2002;29:288-291. 
Isenberg DA, Allen E, Farewell V, D’Cruz D, Alarcon GS, Aranow C, et al. An assessment of 
disease flare in patients with systemic lupus erythematosus: a comparison of BILAG 2004 and 
the flare version of SELENA. Ann Rheum Dis. 2011;70:54-59.  
McElhone K, Abbott J, Shelmerdine J, Bruce IN, Ahmad Y, Gordon C, et al. Development and 
validation of a disease-specific health-related quality of life measure, the LupusQol, for adults 
with systemic lupus erythematosus. Arthritis Rheum. 2007;57:972-979. 
Pinheiro J, Bornkamp B, Glimm E, Bretz F. Model-based dose finding under model uncertainty 
using general parametric models. Statist. Med. 2014;33:1646–1661. 
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson NF Jr, Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: summary report—Second 
National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
symposium. J Allergy Clin Immunol. 2006;117(2):391-397. 
Touma Z, Gladman DD, Ibañez D, Taghavi-Zadeh S, Urowitz MB. Systemic Lupus 
Erthematosus Disease Activity Index 200 Responder Index-50 enhances the ability of SLE 
Responder Index to identify responders in clinical trials. J Rheumatol. 2011;38:2395-2399. 
Tsokos GC, Gordon C, Smolen JS, editors. Systemic Lupus Erythematosus: A companion to 
Rheumatology. Pennsylvania: Mosby Elsevier; 2007. 
Yee C-S, Cresswell L, Farewell V, Rahman A, Teh L-S, Griffiths B, et al. Numerical scoring for 
the BILAG-2004 index. Rheumatology 2010;49:1665-1669. 
Yee C-S, Gordon C, Isenberg DA, Griffiths B, Teh L-S, Bruce I, et al. The BILAG-2004 systems 
tally – a novel way of representing the BILAG-2004 index scores longitudinally. Rheumatology. 
2012;51:2099-2105. 
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13 
APPENDICES 
13.1 
Schedule of study assessments 
A schedule of study assessments is presented in Table 13‒1.   
Gray-shaded visits in Table 13‒1Table 13‒1 were not covered by the Interim Analysis. 
 
Formatte
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Table 13‒1: 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 D11 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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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 
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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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 
 
X 
X c 
X 
X 
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 (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 
S2K RI-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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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=EarlyWithdrawal 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 
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Clinics/American College of Rheumatology Damage Index; S2K RI-50=Systemic Lupus Erythematosus Disease Activity Index-2K Responder Index-50; TB=tuberculosis; 
TJC=tender joint count; V=Visit; W=Week 
 
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 predose or at unspecified times during the visit. 
k Tuberculosis testing should be done using IGRA. The QFT-GIT is the preferred IGRA test (see protocol, 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 protocol, 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 (i.e., 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 predose 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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13.2 
SLEDAI-2K and SRI-50 
 
Table 13‒2: SLEDAI-2K and SRI-50 
 
 
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14 
AMENDMENT(S) TO THE STATISTICAL ANALYSIS PLAN 
(SAP) (IF APPLICABLE) 
14.1 
AMENDMENT 1 
Rationale for the amendment 
During programming of analysis datasets and analyses, it was recognized that additional detail 
for aspects of analysis including endpoint definitions, data imputations, statistical model 
implementation, and display of results were needed.  SAP Amendment 1 was written to clarify 
and document those details. 
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STATISTICAL ANALYSIS PLAN SIGNATURE PAGE 
This document has been reviewed and approved per the Review and Approval of Clinical 
Documents Standard Operating Procedures. Signatures indicate that the final version of the 
Statistical Analysis Plan (SAP) or amended SAP is released for execution. 
 
 
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