Clinical trial NCT04925934
Conditions: Lupus Erythematosus, Systemic
Sponsor: Amgen
Start date: 2021-05-28; Completion date: 2023-06-09
Enrollment: 214 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of VIB7734 for the Treatment of Moderate to Severely Active Systemic Lupus Erythematosus in approximately 195 participants. The study duration will be 48 weeks, with a safety follow-up through week 56.There will be 3 parallel arms - 2 active treatment and 1 placebo.

Detailed description:

Arms: arm 1: None arm 2: None arm 3: None
Interventions: intervention 1: VIB7734 intervention 2: Placebo
Intervention descriptions: intervention 1: VIB7734 intervention 2: Placebo

Protocol documents:
Prot_000.pdf: 
Clinical Study Protocol
Viela Bio, Inc.
VIB7734.P2.S1
Version 2.0, 10 February 2022
CONFIDENTIAL AND PROPRIETARY
Page 1 of 106
A Phase 2 Randomized, Double-Blind, Placebo-
Controlled Efficacy and Safety Study of VIB7734 for 
the Treatment of Moderate to Severely Active
Systemic Lupus Erythematosus
SHORT TITLE: RECAST SLE
(A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy and 
Safety Study of VIB7734 for the Treatment of Moderate to Severely Active
Systemic Lupus Erythematosus) 
Investigational Product
VIB7734 (anti-ILT7 mAb for depletion of pDCs)
Protocol Number
VIB7734.P2.S1
Clinical Trial Registry Identifiers
clinicaltrials.gov: NCT04925934
EudraCT: 2020-005528-12
Amendment
1
Version Date
10 February 2022
IND Number
IND 127898
Lead Principal Investigator
Dr. 
Sponsor
Viela Bio, Inc.
One MedImmune Way, Gaithersburg, MD 20878 USA
Responsible Medical Officer
, MD
Executive Medical Director
Viela Bio
One MedImmune Way
Gaithersburg, MD 20878 USA
NCT Number: NCT04925934
This NCT number has been applied to the document
for purposes of posting on Clinicaltrials.gov


Clinical Study Protocol
Viela Bio, Inc.
VIB7734.P2.S1
Version 2.0, 10 February 2022
CONFIDENTIAL AND PROPRIETARY
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SPONSORS SIGNATURE PAGE
The signatures below constitute the approval of this protocol and provide the necessary 
assurances that this trial will be conducted according to this protocol, applicable local 
regulations, and ICH GCP guidelines.
Name
Title
Signature and date
(DD-MMM-YYYY)
, MD
Executive Medical Director
Viela Bio
, PhD
Sr. Director, Biostatistics, 
Biometrics
Viela Bio


Clinical Study Protocol 
 
 
 
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CONFIDENTIAL AND PROPRIETARY 
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SUMMARY OF CHANGES 
The major changes incorporated into this protocol (Version 2.0/Amendment 1) relative to the prior approved version (Version 
1.0/Original) are summarized in the table below. Editorial and formatting changes are not included in this summary. 


Clinical Study Protocol 
 
 
 
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Text 
Version 1.0, Original Protocol 
21 December 2020 
Amended Text 
Version 2.0, Amendment 1 
10 February 2022 
Rationale for Change 
Section 5.1 – Inclusion Criteria 
 
8. Women of childbearing potential must have a negative urine 
pregnancy test at Randomization.  
… 
Women of childbearing potential who are sexually active with a 
non-sterilized male partner must agree to use a highly effective 
method of contraception (Table 1) from signing of the informed 
consent, and must agree to continue using such precautions 
through the end of the study follow-up or 3 months 
(approximately 5 half-lives) following the last dose of IP in the 
case of early withdrawal from the study. 
Section 5.1 – Inclusion Criteria 
 
8. Women of childbearing potential must have a negative serum 
pregnancy test at Screening and a negative urine pregnancy test 
at Randomization.  
… 
Women of childbearing potential who are sexually active with a 
non-sterilized male partner must agree to use a highly effective 
method of contraception (Table 1) from signing of the informed 
consent, and must agree to continue using such precautions 
through the end of the study follow-up or 3 months 
(approximately 5 half-lives) following the last dose of IP in the 
case of early withdrawal from the study, and refrain from egg 
retrieval/egg donation during this period. 
Updated to clarify that 
both visits need to have 
negative serum/urine 
pregnancy tests and 
that women of 
childbearing potential 
must refrain from egg 
retrevial and donation 
while receiving IP.. 
Section 5.1 – Inclusion Criteria, Table 1  
 
Table 1 Highly Effective Methods of Contraception 
 
Section 5.1 – Inclusion Criteria; Table 1 
 
Table 1 Highly Effective Methods of Contraception 
 
a A change in birth control method is allowed during the study. 
If a change occurs, unless the patient is changing the 
method to complete abstinence, the patient must employ a 
barrier method in addition to the highly effective method of 
contraception for at least two months. 
Updated to clarify what 
should occur when 
changing hormonal 
birth control methods.  
Section 5.2.1 – General Exclusion Criteria 
 
Section 5.2.1 – General Exclusion Criteria 
 
2. Any condition that, in the opinion of the Investigator or the 
Sponsor/Central Review Committee, would interfere with 
Updated to clarify that 
the Sponsor and 
Central Review 
Committee may also 
review a participant’s 


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CONFIDENTIAL AND PROPRIETARY 
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2. Any condition that, in the opinion of the Investigator, would 
interfere with evaluation of the IP or interpretation of participant 
safety or study results.  
evaluation of the IP or interpretation of participant safety or 
study results (including borderline disease activity). 
screening data and find 
reason to not allow 
participation in the 
study.  
Section 5.2.1 – General Exclusion Criteria 
 
5. Breastfeeding or pregnant women or women who intend to 
become pregnant anytime from signing the ICF through 6 
months after receiving the last dose of IP.  
Section 5.2.1 – General Exclusion Criteria 
 
5. Breastfeeding or pregnant women or women who intend to 
become pregnant anytime from signing the ICF through 3 
months after receiving the last dose of IP. 
Updated to standardize 
the amount of time that 
breastfeeding or 
pregnant women are 
followed after receiving 
the last dose of IP 
throughout the 
protocol. 
Section 5.2.1 – General Exclusion Criteria 
 
10. At Screening, any of the following per central laboratory 
(tests may be repeated once within the same Screening period to 
confirm results prior to Randomization): 
x 
Spot UPCr > 3 mg/mg 
Section 5.2.1 – General Exclusion Criteria 
 
10. At Screening, any of the following per central laboratory 
(tests may be repeated once within the same Screening period to 
confirm results prior to Randomization): 
x 
Spot UPCr > 3 mg/mg (> 339 mg/mmol) 
Updated to add the 
mg/mmol exclusionary 
value as it is generally 
used at ex-US sites. 
Section 5.2.1 – General Exclusion Criteria 
 
13. Active TB, or positive IFN-gamma release assay (IGRA) 
test at Screening, unless documented history of appropriate 
treatment for active or latent TB. Participants with an 
indeterminated IGRA test result can repeat the test, but if the 
repeat test is also indeterminate, they are excluded.  
Section 5.2.1 – General Exclusion Criteria 
 
13. Active TB, or positive IFN-gamma release assay (IGRA) 
test at Screening, unless documented history of appropriate 
treatment for active or latent TB.  
Note that participants with an indeterminated IGRA test result 
with well-documented previous treatment do not need to repeat 
testing and are eligible for randomization. Participants with an 
indeterminate IGRA test result without previous treatment can 
repeat the test, but if the repeat test is also indeterminate, they 
are excluded.  
Updated to clarify 
actions for 
indeterminate IGRA 
test results. 
Section 5.2.1 – General Exclusion Criteria 
 
18. Any acute illness or evidence of clinically significant active 
infection, such as fever 侔 38.0˅C (侔 100.5˅F) on Day 1. 
Section 5.2.1 – General Exclusion Criteria 
 
18. Any acute illness or evidence of clinically significant active 
infection. 
Removed fever example 
as it can be a 
manifestation of lupus 
and thus possibly 
confusing.  
Section 5.2.1 – General Exclusion Criteria 
 
Section 5.2.1 – General Exclusion Criteria 
 
Updated to clarify the 
definition of clinically 


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19. History of clinically significant cardiac disease including 
unstable angina; myocardial infarction within 6 months prior to 
Randomization; congestive heart failure; arrhythmia requiring 
active therapy, except for clinically insignificant extra systoles, 
or minor conduction abnormalities; or presence of clinically 
significant abnormality on ECG if, in the opinion of the 
Investigator, it would increase the risk of study participation. 
19. Clinically significant cardiac disease including unstable 
angina and/or myocardial infarction and/or congestive heart 
failure within 6 months prior to Randomization. Or any cardiac 
condition including, but not limited to the following, if in the 
opinion of the Investigator or Medical Monitor, would increase 
the risk of study participation: 
x 
Inadequately controlled arrhythmia.  
x 
Presence of clinically significant abnormality on ECG. 
significant cardiac 
disease.  
Section 5.2.1 – General Exclusion Criteria 
 
23. Active LN OR active severe or unstable neuropsychiatric 
SLE (eg, aseptic meningitis, cerebral vasculitis, myelopathy, 
demyelination syndromes [ascending, transverse, acute 
inflammatory demyelinating polyradiculopathy], acute 
confusional state, impaired level of consciousness, psychosis, 
acute stroke or stroke syndrome, cranial neuropathy, status 
epilepticus, cerebellar ataxia, and mononeuritis multiplex) 
where, in the opinion of the Investigator or Medical Monitor, 
protocol-specified SoC is insufficient and utilization of a more 
aggressive therapeutic approach, such as IV cyclophosphamide, 
high-dose IV pulse GC therapy, MMF of > 2 gm/day (MPA of 
> 1.44 gm/day), and/or other treatments not permitted in the 
protocol, may be indicated. 
Section 5.2.1 – General Exclusion Criteria 
 
23. Active LN OR active severe or unstable neuropsychiatric 
SLE (eg, aseptic meningitis, cerebral vasculitis, myelopathy, 
demyelination syndromes [ascending, transverse, acute 
inflammatory demyelinating polyradiculopathy], acute 
confusional state, impaired level of consciousness, psychosis, 
acute stroke or stroke syndrome, cranial neuropathy, status 
epilepticus, cerebellar ataxia, and mononeuritis multiplex) 
where, in the opinion of the Investigator or Medical Monitor, 
protocol-specified SoC is insufficient and utilization of a more 
aggressive therapeutic approach, such as IV cyclophosphamide, 
high-dose IV pulse GC therapy, MMF of > 3 gm/day (MPA of 
> 2.16 gm/day), or an increase from baseline dose of 
MMF/MPA and/or other treatments not permitted in the 
protocol, may be indicated. 
Updated to include 
conventional anti-
rheumatic doses for 
treatment of SLE that 
should not be excluded 
for in the protocol.   
Section 6.2 – Tables 2, 3, 4; Section 6.3.4 – Clinical 
Laboratory Assessments 
 
Table 2 Screening Procedures 
Study Day 
-28 to -1 
Visit Number 
1 
Coombs Test 
X 
 
Table 3 Schedule of Assessments During the Treatment Period 
Section 6.2 – Tables 2, 3, 4; Section 6.3.4 – Clinical 
Laboratory Assessments 
 
Table 2 Screening Procedures 
Study Day 
-28 to -1 
Visit Number 
1 
-- 
-- 
-- removed 
 
Table 3 Schedule of Assessments During the Treatment Period 
Removed the direct 
coombs testing 
throughout the protocol 
as the specimen has 
limited stability which 
often does not allow 
testing to be performed 
by the central 
laboratory within the 
stability period due to 
courier transit time and 
is not needed on a 
routine basis.  


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Table 4 Schedule of Assessments During the Safety Follow-Up 
Period
Study Day
365
393
Visit Window (± Days)
7
7
Study Week
52
56
Visit Number
15
16
Coombs test and 
confirmatory tests of 
hemolytic anemia and 
active APS j
X
X
Table 5 Clinical Laboratory Tests
Table 4 Schedule of Assessments During the Safety Follow-Up 
Period
Study Day
365
393
Visit Window (± Days)
7
7
Study Week
52
56
Visit Number
15
16
Confirmatory tests of 
hemolytic anemia and 
active APS j
X
X
Table 5 Clinical Laboratory Tests
Section 6.2 – Table 3, Table 4; Section 6.4.3 – Withdrawal 
From Study 
Table 3 Schedule of Assessments During the Treatment Period
Table 4, Footnote – Safety Follow-Up visits will be conducted at 
4 and 8 weeks after the last dose of investigational product (IP) 
Section 6.2 – Table 3, Table 4; Section 6.4.3 – Withdrawal 
From Study 
Table 3 Schedule of Assessments During the Treatment Period
ET: Early Termination
Updated to clarify that 
the Week 48 visit is 
also considered an 
early termination (ET) 
visit as it was not 
previously defined and 
to clarify that the safety 
follow up period as is 
only for subjects that 
have completed the 48-
week treatment period 


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for participants who have been discontinued from IP or have 
completed the 48-week Treatment period. These assessments, 
however, will not be performed on participants who enter the 
long-term extension study. 
 
Section 6.4.3 – Participants are free at any time to withdraw 
from the study (IP and assessments), without prejudice to further 
treatment (withdrawal of consent). Such participants will always 
be asked about the reason(s) for withdrawal and the presence of 
any AEs. If possible, they will be seen and assessed by an 
Investigator. AEs will be followed-up. If a participant withdraws 
participation in the study, then no further study visits or data 
collection should take place. Further details concerning use of 
samples collected during the study from a participant that 
withdraws consent are provided in Section 10.6. 
 
 
Table 4, Footnote – Safety Follow-Up visits will be conducted at 
4 and 8 weeks after the last dose of investigational product (IP) 
for participants who have completed the 48-week Treatment 
period. These assessments, however, will not be performed on 
participants who enter the long-term extension study. 
Participants who permanently discontinue IP at any point in the 
study but who do not withdraw consent of study participation 
will complete all study visits through Study Week 48/ET and at 
least 12 weeks follow up after the last dose of IP.  Participants 
who permanently discontinue IP at any point in the study and 
who do withdraw consent of study participation will only 
complete the Study Week 48/ET assessments (if they agree to 
do so before withdrawing consent). 
 
Section 6.4.3 – Participants are free at any time to withdraw 
from the study (IP and assessments), without prejudice to further 
treatment (withdrawal of consent). Such participants will always 
be asked about the reason(s) for withdrawal and the presence of 
any AEs. AEs will be followed-up. 
Participants who permanently discontinue IP at any point in the 
study but who do not withdraw consent of study participation 
will complete all study visits through Study Week 48/ET and at 
least 12 weeks follow up after the last dose of IP.  Participants 
who permanently discontinue IP at any point in the study and 
who do withdraw consent of study participation will only 
complete the Study Week 48/ET assessments (if they agree to 
do so before withdrawing consent). 
If a participant withdraws consent to participation in the study, 
then no further study visits or data collection should take place. 
Further details concerning use of samples collected during the 
study from a participant that withdraws consent are provided in 
Section 10.6. 
and how participants 
who permantently 
discontinue IP should 
be followed after final 
IP administration.  
Section 6.2 – Table 3, Table 4; Section 6.3.4 – Clinical 
Laboratory Assessments  
 
Table 3, Footnote f  – Women of childbearing potential or 
women who are postmenopausal for less than 2 years. 
 
Section 6.2 – Table 3, Table 4; Section 6.3.4 – Clinical 
Laboratory Assessments  
 
Table 3, Footnote f  – Women of childbearing potential as 
defined in Inclusion Criteria #8. 
 
Updated to align the 
definition of women of 
childbearing potential 
throughout the 
protocol.  


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Table 4, Footnote e  – Women of childbearing potential or 
women who are postmenopausal for less than 2 years. 
 
Section 6.3.4 – A serum pregnancy test in postmenopausal 
women will be performed at Screening at the central laboratory. 
Urine pregnancy tests will be performed at Screening, during 
treatment, and during follow-up at the site using a dipstick. 
 
Table 4, Footnote e  – Women of childbearing potential as 
defined in Inclusion Criteria #8.  
 
Section 6.3.4 – A serum pregnancy test (in women of 
childbearing potential as defined in Inclusion Criteria #8) will be 
performed at Screening at the central laboratory. Urine 
pregnancy tests will be performed in women of childbearing 
potential during treatment and follow-up at the site using a 
dipstick. 
Section 6.2 – Table 3  
 
Table 3, Footnote g – Reflex DNA testing if isolated hepatitis B 
core positive at Baseline. 
Section 6.2 – Table 3  
 
Table 3, Footnote g – Reflex DNA testing if isolated hepatitis B 
core positive at Screening. 
Updated to reference 
the correct study visit.  
Section 6.3.3.2 – Vital Signs 
 
Prior to and after IP administration, vital signs should be 
checked as follows:  
x 
Within 15 minutes prior to administration of IP.  
Section 6.3.3.2 – Vital Signs 
 
Prior to and after IP administration, vital signs should be 
checked as follows:  
x 
Within 15 minutes prior to administration of IP (within 
30 minutes for Week 24 due to ECG requirements).  
Updated to allow for 
additional time at Week 
24 to ensure enough 
time to collect the 
vitals, labs, and ECG 
prior to dosing.  


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x 
Every 30 minutes (± 5 minutes) for 60 minutes after 
administration or until stable, whichever is later (for the 
first 2 study visits only).  
x 
Every 30 minutes (± 5 minutes) for 60 minutes after 
administration or until stable, whichever is later (for the 
first 2 study visits only). 
Section 6.3.3.6 – Tuberculosis Assessment 
 
A blood test for TB will be performed at Screening using the 
IGRA test (ie, QuantiFERON-TB Gold Plus or T-SPOT). 
Evaluation of all participants by IGRA test will be performed by 
either the local or central clinical laboratory. Results of an IGRA 
test performed within 12 weeks of the Screening visit (if 
available) are acceptable, provided there is no reason to suspect 
any re-exposure.  
Section 6.3.3.6 – Tuberculosis Assessment 
 
A blood test for TB will be performed at Screening using the 
IGRA test (ie, QuantiFERON-TB Gold Plus or T-SPOT). 
Evaluation of all participants by IGRA test will be performed by 
the central clinical laboratory. Results of an IGRA test 
performed at a local laboratory within 12 weeks of the 
Screening visit (if available) are acceptable, provided there is no 
reason to suspect any re-exposure.  
Updated to clarify that 
TB assessments at 
Screening should occur 
only at the central 
laboratory.  
Section 7.1.1.1 – Investigational Product Inspection 
 
The Sponsor’s Quality Assurance contact information for 
reporting product complaints is: 
Section 7.1.1.1 – Investigational Product Inspection 
 
The Sponsor’s Quality Assurance contact information for 
reporting product complaints is: 
Update to contact 
information 


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Section 7.1.1.3 – Investigational Product Dose Preparation 
 
A SC dose of 200 mg VIB7734 will be administered over 2 
injections. To prepare each injection, withdraw 1 mL of IP into a 
1-mL syringe using an 18-19.5G 1½-inch needle. For SC dose 
administration, a 27G ½-inch needle should be used. 
Normal saline will be used as placebo. The number and volume 
of placebo injections will match that of active drug. Saline (1 
mL) should be drawn into each of two 1-mL syringes using an 
18-19.5G 1½-inch needle. For SC dose administration, a 27G ½-
inch needle should be used.  
Section 7.1.1.3 – Investigational Product Dose Preparation 
 
A SC dose of 200 mg VIB7734 will be administered over 2 
injections. To prepare each injection, withdraw 1 mL of IP into a 
1-mL syringe using a 1½-inch needle. For SC dose 
administration, a 27G ½-inch needle should be used. 
Normal saline will be used as placebo. The number and volume 
of placebo injections will match that of active drug. Saline (1 
mL) should be drawn into each of two 1-mL syringes using a 
1½-inch needle. For SC dose administration, a 27G ½-inch 
needle should be used.  
Updated to remove the 
specific gauge size 
from the protocol, as 
these specific needles 
cannot be supplied at 
certain study sites 
where the study will be 
performed.  
Section 7.4.2.1 – Medications and Therapies That Lead to 
Immediate Discontinuation of Investigational Product 
 
Section 7.4.2.1 – Ig therapy (any).  
Section 7.4.2.1 – Medications and Therapies That Lead to 
Immediate Discontinuation of Investigational Product; 
Section 7.4.3.2.2.6 – Other  
 
Section 7.4.2.1 – Ig therapy (For Anti-COVID therapeutic 
antibodies see Permitted Medications Section 7.4.3.2.2.6). 
 
Section 7.4.3.2.2.6 – Anti-COVID therapeutic antibodies 
x 
If used during the study, the medical monitor must be 
notified immediately, and continuation of IP will be 
determined on a case by case basis.  
Updated to clarify how 
anti-COVID 
therapeutic antibody 
treatment should be 
handled within the 
study.  
Section 7.4.3.2.2.6 – Other 
 
Non-prescription NSAIDs for analgesic purposes not exceeding 
label-approved doses are permitted for pain as required based on 
Investigator judgment for up to 10 days at a time. 
Section 7.4.3.2.2.6 – Other 
 
PRN NSAIDs not exceeding label-approved doses are permitted 
for SLE or non-SLE pain as required based on Investigator 
judgment for up to 10 consecutive days at a time. Duration 
exceeding 10 consecutive days is considered chronic use. 
Updated to clarify the 
limitations for the 
permitted use of PRN 
NSAIDs.  
Section 8.1 – Definitions  
 
 
The following AESIs will be particularly 
monitored in this study: 
x 
Hypersensitivity reaction, including anaphylaxis. 
x 
Viral infection/reactivation. 
x 
Opportunistic infection. 
x 
Malignancy (except non-melanoma skin cancer). 
Section 8.1 – Definitions  
 
 
The following AESIs will be particularly 
monitored in this study: 
x 
Hypersensitivity reaction, including anaphylaxis. 
x 
Severe (Grade 3 or higher) viral 
infections/reactivations. 
x 
Opportunistic infection listed in Appendix 3 (all cases). 
Updated to clarify that 
AESI for viral infection 
and reactivation only 
includes those that are 
Grade 3 or higher and 
all cases of 
opportunistic infections 
listed in Appendix 3 


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x 
Malignancy (except non-melanoma skin cancer). 
(which includes herpes 
zoster).  
8.3 – Events Requiring Immediate Reporting 
 
All SAEs, AESIs, pregnancies, overdose, or misuse must be 
reported to the Sponsor’s designated representative, ICON, 
within 24 hours of site staff awareness by submitting a 
SAE/AESI/Pregnancy/Overdose Report Form by email to: 
ICON Patient Safety 
Email: icon-mads@iconplc.com 
Alternatively, the Report Form can be submitted by fax to: 
ICON Patient Safety 
Fax: 1-215-616-3096 
 
8.3 – Events Requiring Immediate Reporting 
 
All SAEs, AESIs (only after Randomization), pregnancies, 
overdose, or misuse must be reported to the Sponsor within 24 
hours of site staff awareness by submitting a 
SAE/AESI/Pregnancy/Overdose Report Form by email to: 
Sponsor (Horizon Therapeutics/Viela Bio) 
Email:
Alternatively, the Report Form can be submitted by fax to: 
Sponsor (Horizon Therapeutics/Viela Bio) 
Fax: 1-800-860-7836 
 
*All other references to ICON Patient Safety or ICON have 
been updated to indicated Sponsor throughout protocol 
Updated to clarify that 
AESIs only need to be 
immediately reported 
after Randomization 
and contact 
information for 
immediate reporting.  


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STATEMENT OF COMPLIANCE  
The study will be conducted in compliance with this clinical study protocol, Good Clinical 
Practice (GCP) as outlined by International Council for Harmonisation (ICH) E6(R2), and all 
applicable local and national regulatory requirements. Enrollment at any clinical study site may 
not begin prior to that site receiving approval from the ethics committee of record for the 
protocol and all materials provided to potential participants. 
Any amendments to the protocol or changes to the consent document will be approved before 
implementation of that amendment. Reconsent of previously enrolled participants may be 
necessary depending on the nature of the amendment. 
The Principal Investigator (PI) will ensure that changes to the study plan as defined by this 
protocol will not be made without prior agreement from the Sponsor and documented approval 
from the ethics committee of record, unless such a change is necessary to eliminate an immediate 
hazard to the study participants. 
All personnel involved in the conduct of this study have completed Human Subjects Protection 
and GCP Training. 
 


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TABLE OF CONTENTS 
SPONSORS SIGNATURE PAGE ................................................................................................ 2 
SUMMARY OF CHANGES ......................................................................................................... 3 
STATEMENT OF COMPLIANCE ............................................................................................. 13 
TABLE OF CONTENTS ............................................................................................................. 14 
LIST OF TABLES ....................................................................................................................... 18 
LIST OF FIGURES ..................................................................................................................... 19 
LIST OF APPENDICES .............................................................................................................. 19 
LIST OF ABBREVIATIONS ...................................................................................................... 20 
1 
SYNOPSIS ....................................................................................................................... 23 
2 
INTRODUCTION ........................................................................................................... 26 
2.1 
Background ................................................................................................................... 26 
2.1.1 
Systemic Lupus Erythematosus ................................................................................. 26 
2.1.2 
VIB7734 ..................................................................................................................... 27 
2.1.3 
Supportive Nonclinical Data ...................................................................................... 27 
2.1.4 
Risk Assessment for VIB7734 ................................................................................... 28 
2.1.4.1 
COVID-19 Risk Assessment .................................................................................. 29 
2.1.5 
Supportive Clinical Data ............................................................................................ 29 
2.1.5.1 
Phase 1 Single-Ascending Dose Study in Patients With Autoimmune Diseases ... 29 
2.1.5.2 
Phase 1b Multiple-Ascending Dose Study in Patients With Autoimmune Diseases30 
2.2 
Study Rationale ............................................................................................................. 30 
2.3 
Study Hypotheses.......................................................................................................... 31 
3 
OBJECTIVES AND OUTCOME MEASURES ............................................................. 32 
3.1 
Primary Objective and Outcome Measure .................................................................... 32 
3.2 
Secondary Objectives and Outcome Measures ............................................................. 32 
3.3 
Exploratory Objectives and Outcome Measures........................................................... 33 
4 
STUDY PLAN ................................................................................................................. 35 
4.1 
Study Design ................................................................................................................. 35 
4.2 
Dose and Treatment Rationale ...................................................................................... 37 
4.3 
Rationale for Study Population ..................................................................................... 37 
4.4 
Rationale for the Primary Outcome Measure ............................................................... 38 
5 
POPULATION ................................................................................................................ 40 


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5.1 
Inclusion Criteria .......................................................................................................... 40 
5.2 
Exclusion Criteria ......................................................................................................... 42 
5.2.1 
General Exclusion Criteria ......................................................................................... 42 
5.2.2 
Disease-Related Criteria ............................................................................................ 44 
5.2.3 
Prior and Concomitant Therapy Criteria.................................................................... 45 
5.3 
Rescreening Procedures ................................................................................................ 46 
5.4 
Replacement of Participants ......................................................................................... 46 
6 
STUDY CONDUCT ........................................................................................................ 47 
6.1 
General Instructions ...................................................................................................... 47 
6.2 
Schedule of Study Assessments .................................................................................... 47 
6.3 
Description of Study Assessments and Procedures ...................................................... 55 
6.3.1 
Screening and Randomization Procedures ................................................................. 55 
6.3.2 
Efficacy Assessments................................................................................................. 55 
6.3.2.1 
Training Provision and Requirements .................................................................... 55 
6.3.2.2 
Systemic Lupus Erythematosus Efficacy Assessments .......................................... 56 
6.3.3 
Safety Assessments .................................................................................................... 59 
6.3.3.1 
Adverse Events ....................................................................................................... 59 
6.3.3.2 
Vital Signs ............................................................................................................... 59 
6.3.3.3 
Physical Examination.............................................................................................. 59 
6.3.3.4 
Electrocardiogram ................................................................................................... 60 
6.3.3.5 
Chest X-Ray ............................................................................................................ 60 
6.3.3.6 
Tuberculosis Assessment ........................................................................................ 60 
6.3.4 
Clinical Laboratory Assessments ............................................................................... 60 
6.3.5 
Pharmacokinetic Assessments ................................................................................... 62 
6.3.6 
Immunogenicity Assessments .................................................................................... 62 
6.3.7 
Pharmacodynamic Assessments ................................................................................ 62 
6.3.8 
Exploratory Biomarker Evaluation ............................................................................ 63 


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6.4 
Discontinuation of Investigational Product, Unscheduled Visits, Withdrawal From 
Study, and Loss to Follow-up ....................................................................................... 65 
6.4.1 
Discontinuation of Investigational Product ............................................................... 65 
6.4.2 
Unscheduled Visits .................................................................................................... 66 
6.4.3 
Withdrawal From Study ............................................................................................. 66 
6.4.4 
Participants Lost to Follow-up ................................................................................... 66 
6.5 
Study Suspension or Termination ................................................................................. 67 
6.6 
End of Study ................................................................................................................. 67 
7 
STUDY INTERVENTIONS ........................................................................................... 68 
7.1 
Description of Investigational Products ........................................................................ 68 
7.1.1 
VIB7734 or Placebo ................................................................................................... 68 
7.1.1.1 
Investigational Product Inspection .......................................................................... 68 
7.1.1.2 
Investigational Product Storage .............................................................................. 68 
7.1.1.3 
Investigational Product Dose Preparation ............................................................... 68 
7.1.1.4 
Investigational Product Dosing and Administration ............................................... 69 
7.1.1.5 
Monitoring of Dose Administration........................................................................ 69 
7.1.2 
Investigational Product Accountability ...................................................................... 69 
7.1.3 
Investigational Product Handling and Disposal ......................................................... 70 
7.2 
Assessment and Verification of Compliance ................................................................ 70 
7.3 
Treatment Assignment and Bias Minimization ............................................................ 70 
7.3.1 
Randomization Strategy and Procedure ..................................................................... 70 
7.3.2 
Extent and Maintenance of Blinding ......................................................................... 70 
7.3.3 
Unblinding Procedures............................................................................................... 70 
7.3.3.1 
Unblinding in the Event of a Medical Emergency.................................................. 70 
7.3.3.2 
Unblinding for the Interim Analysis ....................................................................... 71 
7.4 
Restricted and Concomitant Medications and Treatments ........................................... 71 
7.4.1 
Medications Prohibited Prior to Screening or Randomization .................................. 71 


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7.4.3 
Permitted Medications ............................................................................................... 76 
7.4.3.1 
Concomitant Medications and Treatments ............................................................. 76 
7.4.3.2 
Concomitant Medications for Systemic Lupus Erythematosus Standard of Care 
During the Study ..................................................................................................... 76 
8 
SAFETY DATA COLLECTION AND REPORTING ................................................... 81 
8.1 
Definitions..................................................................................................................... 81 
8.2 
Documenting Adverse Events....................................................................................... 82 
8.2.1 
Causality or Relatedness ............................................................................................ 82 
8.2.2 
Severity or Intensity ................................................................................................... 82 
8.2.3 
Pregnancy ................................................................................................................... 83 
8.2.4 
Overdose or Misuse ................................................................................................... 83 
8.3 
Events Requiring Immediate Reporting ........................................................................ 83 
9 
STATISTICAL CONSIDERATIONS............................................................................. 85 
9.1 
General Considerations ................................................................................................. 85 
9.2 
Statistical Hypothesis .................................................................................................... 85 
9.3 
Determination of Sample Size ...................................................................................... 85 
9.4 
Analysis Sets ................................................................................................................. 85 
9.5 
Methods for Statistical Analyses .................................................................................. 85 
9.5.1 
Analysis of the Primary Efficacy Outcome Measure ................................................ 85 
9.5.2 
Analysis of Secondary Efficacy Outcome Measures ................................................. 86 
9.5.3 
Missing Data Handling Plan ...................................................................................... 88 
9.5.4 
Control of Type I Error .............................................................................................. 88 
9.5.5 
Safety Analysis .......................................................................................................... 88 
9.5.6 
Pharmacokinetics Analysis ........................................................................................ 88 
9.5.7 
Immunogenicity Analysis .......................................................................................... 88 
9.5.8 
Pharmacodynamics Analysis ..................................................................................... 88 
9.5.9 
Exploratory Analysis ................................................................................................. 88 
9.6 
Planned Interim Analysis .............................................................................................. 89 
9.7 
Planned Primary Analysis ............................................................................................. 89 
9.8 
Planned Final Analysis ................................................................................................. 89 


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10 
ETHICAL CONSIDERATIONS ..................................................................................... 90 
10.1 
Good Clinical Practice .................................................................................................. 90 
10.2 
Ethics Review ............................................................................................................... 90 
10.3 
Informed Consent.......................................................................................................... 90 
10.4 
Data Privacy .................................................................................................................. 90 
10.5 
Disclosure ..................................................................................................................... 91 
10.6 
Biological Specimens and Data .................................................................................... 91 
11 
OVERSIGHT ................................................................................................................... 92 
11.1 
Safety Data Monitoring Committee .............................................................................. 92 
11.2 
Quality Control and Assurance ..................................................................................... 92 
11.3 
Monitoring .................................................................................................................... 92 
11.4 
Audits/Inspections......................................................................................................... 92 
11.4.1 
Records ...................................................................................................................... 93 
11.4.2 
Data Capture and Management .................................................................................. 93 
11.4.3 
Source Documentation ............................................................................................... 93 
11.4.4 
Records Retention ...................................................................................................... 93 
12 
PUBLICATION POLICY ............................................................................................... 95 
13 
FINANCING AND INSURANCE .................................................................................. 96 
14 
REFERENCES ................................................................................................................ 97 
15 
APPENDICES ............................................................................................................... 101 
 
LIST OF TABLES  
Table 1 
Highly Effective Methods of Contraception ........................................................ 42 
Table 2 
Screening Procedures ........................................................................................... 47 
Table 3 
Schedule of Assessments During the Treatment Period ...................................... 49 
Table 4 
Schedule of Assessments During the Safety Follow-Up Period .......................... 53 
Table 5 
Clinical Laboratory Tests ..................................................................................... 61 
Table 6 
Description of Investigational Products and Dosing ........................................... 68 
Table 8 
CTCAE v5.0 General Guidelines ........................................................................ 83 
 


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LIST OF FIGURES  
Figure 1 
Study Design ........................................................................................................ 36 
 
LIST OF APPENDICES  
Appendix 1 
National Institute of Allergy and Infectious Disease and Food and Allergy 
Anaphylaxis Network Guidance for Anaphylaxis Diagnosis ............................ 102 
Appendix 2 
2019 European League Against Rheumatism/American College of Rheumatology 
Classification System for Systemic Lupus Erythematosus ................................ 103 
Appendix 3 
Study-Specified Opportunistic Infections That Meet Exclusion Criteria .......... 104 
Appendix 4 
Predisone Equivalent of Oral Glucocorticoid Dose ........................................... 105 
Appendix 5 
Oral Glucocorticoid Tapering Schedule ............................................................ 106 
 


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LIST OF ABBREVIATIONS  
Abbreviation or special term 
Definition 
ACTH 
adrenocorticotropic hormone 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase 
ANA 
antinuclear antibodies 
APS 
antiphospholipid syndrome 
AST 
aspartate aminotransferase 
AZA 
azathioprine 
BCG 
Bacille-Calmette-Guerin 
BICLA 
BILAG 2004 Index-Based Combined Lupus Assessment 
BILAG 
British Isles Lupus Assessment Group 
CD 
cluster of differentiation 
CDM 
Clinical Data Management 
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
CLASI-A 
Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity 
CLE 
cutaneous lupus erythematosus 
CMV 
cytomegalovirus 
CNS 
central nervous system 
CoV 
coronavirus 
COVID-19 
coronavirus disease 2019 
CRF 
case report form 
CRO 
contract research organization 
DC 
dendritic cell 
DMARD 
disease-modifying antirheumatic drug 
DMP 
Data Management Plan 
dsDNA 
double-stranded DNA 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
FDA 
Food and Drug Administration 
FSH 
follicle-stimulating hormone 
GC 
glucocorticoid 
GCP 
Good Clinical Practice(s) 
GLP 
Good Laboratory Practice(s) 
HBcAb 
hepatitis B core antibody 


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Abbreviation or special term 
Definition 
HBV 
hepatitis B virus 
HIV 
human immunodeficiency virus 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
IFN 
interferon 
Ig 
immunoglobulin 
IGRA 
IFN-gamma release assay 
IL 
interleukin 
ILT 
Ig-like transcript 
IP 
investigational product 
IRB 
Institutional Review Board 
IV 
intravenous(ly) 
IXRS 
interactive voice/web response system 
LLDAS 
Lupus Low Disease Activity State 
LLOQ 
lower limit of quantitation 
LN 
lupus nephritis 
LTE 
long-term extension 
mAb 
monoclonal antibody 
MAD 
multiple-ascending dose 
MCP 
metacarpophalangeal 
MMF 
mycophenolate mofetil 
6-MP 
6-mercaptopurine 
MPA 
mycophenolic acid 
MTX 
methotrexate 
NK 
natural killer 
NSAID 
nonsteroidal anti-inflammatory drug 
OGC 
oral glucocorticoid 
PD 
pharmacodynamics(s) 
pDC 
plasmacytoid DC 
PEF 
peak expiratory function 
PGA 
Physician Global Assessment 
PI 
Principal Investigator 
PIP 
proximal interphalangeal 
PK 
pharmacokinetic(s) 
PO 
oral(ly) 
Q4W 
every 4 weeks 


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Abbreviation or special term 
Definition 
Q12W 
every 12 weeks 
SAD 
single-ascending dose 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SARS 
severe acute respiratory syndrome 
SC 
subcutaneous(ly) 
SDMC 
Safety Data Monitoring Committee 
SFU 
Safety Follow-Up 
SID 
subject identification number 
SLE 
systemic lupus erythematosus 
SLEDAI-2K 
SLE Disease Activity Index 2000 
SoC 
standard of care 
SRI 
SLE Responder Index 
TB 
tuberculosis 
TLR 
toll-like receptor 
TNF 
tumor necrosis factor 
ULN 
upper limit of normal 
UPCr 
urine protein:creatinine ratio 
VAS 
visual analog scale 


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1 
SYNOPSIS  
Title 
A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy 
and Safety Study of VIB7734 for the Treatment of Moderate to 
Severely Active Systemic Lupus Erythematosus 
Short Title 
RECAST SLE 
(A Phase 2 Randomized, Double-Blind, Placebo-Controlled Efficacy 
and Safety Study of VIB7734 for the Treatment of Moderate to Severe 
Systemic Lupus Erythematosus)  
Phase 
2 
Study Design 
Randomized, double-blind, placebo-controlled, parallel-group study 
Rationale 
Data from Phase 2 and 3 studies with interferon (IFN) α-blocking 
agents and a plasmacytoid dendritic cell (pDC) antagonists have 
demonstrated improvement in systemic lupus erythematosus (SLE) or 
cutaneous lupus disease activity, supporting the rationale for blocking 
the IFN pathways and pDCs in patients with SLE. Given the lack of 
highly efficacious and safe treatments for active SLE and the 
significant impact of this disease on health-related quality of life, there 
is currently a significant unmet need for new targeted therapies. Based 
on its mechanism of action (binding to immunoglobulin-like 
transcript 7 (ILT7) on the surface of pDCs, thus inducing apoptosis and 
reduction in the number of pDCs), VIB7734 has the potential to 
decrease SLE disease activity. In addition, based on data currently 
available, VIB7734 presents an acceptable safety profile, and hence it 
is justified to evaluate its potential efficacy in patients with active SLE. 
Target Population 
Adults aged ≥ 18 to ≤ 70 years who have moderate to severely active 
(recent flares or chronic active disease) SLE as defined by the SLE 
Disease Activity Index 2000 (SLEDAI-2K), British Isles Lupus 
Assessment Group (BILAG) 2004 Index, and Physician Global 
Assessment (PGA). 
Number of Participants 
Approximately 195 participants will be randomized to 3 treatment 
groups; approximately 65 participants to each treatment group.  
Length of Participation 
On treatment: 48 weeks 
On study (including Screening and Safety Follow-Up periods): up to 
60 weeks 
Interventions 
Group 1: 
VIB7734 200 mg subcutaneous(ly) (SC) every 4 weeks (Q4W) 
Group 2:  
VIB7734 200 mg SC every 12 weeks, with an additional 200 mg SC 
dose at Week 4 
Group 3: 
Placebo SC Q4W 
Primary Objective 
Outcome Measure 
To evaluate the effect of VIB7734 
compared to placebo in reducing SLE 
disease activity at Week 48 in 
participants treated with standard of 
care therapy. 
Proportion of participants achieving a BILAG 2004 Index-based 
Combined Lupus Assessment (BICLA) response and an oral 
glucocorticoid (OGC) dose ≤ 7.5 mg/day and ≤ Baseline (Day 1) dose 
of prednisone or equivalent at Week 48. 


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Secondary Objectives  
Efficacy Objectives 
Outcome Measures 
To evaluate the effect of VIB7734 
compared with placebo to reduce 
cutaneous disease activity at Week 12. 
Proportion of participants with Cutaneous Lupus Erythematosus 
Disease Area and Severity Index (CLASI)-Activity (CLASI-A) score 
≥ 10 at Baseline (Day 1) who achieve ≥ 50% reduction from Baseline 
(Day 1) in CLASI-A score at Week 12. 
To evaluate the effect of VIB7734 
compared with placebo to reduce SLE 
disease activity at Week 48. 
Proportion of participants achieving a Systemic Lupus Responder 
Index (SRI)-4 response and an OGC dose ≤ 7.5 mg/day and ≤ Baseline 
(Day 1) dose of prednisone or equivalent at Week 48. 
To evaluate the effect of VIB7734 
compared with placebo on sustained 
OGC reduction from Week 36 to 
Week 48. 
Proportion of participants at OGC dose ≥ 10 mg prednisone or 
equivalent at Baseline (Day 1) who achieve OGC dose ≤ 7.5 mg/day 
prednisone or equivalent at Week 36 and maintained through Week 48.  
To evaluate the effect of VIB7734 
compared with placebo to achieve low 
disease activity at Week 48. 
Proportion of participants achieving Lupus Low Disease Activity State 
at Week 48. 
Pharmacokinetic/Pharmacodynamic/ 
Immunogenicity Objectives 
Outcome Measures 
To characterize the pharmacokinetics, 
pharmacodynamics, and 
immunogenicity of VIB7734. 
VIB7734 concentrations, change in pDCs, and
Safety Objectives 
Outcome Measures 
To evaluate the safety and tolerability 
of VIB7734. 
Incidence of adverse events (AEs), serious AEs, and AEs of special 
interest.  
Exploratory Objectives 
Outcome Measures 


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Number of Sites 
Approximately 88 sites 
Study Duration 
Estimated total study duration is approximately 60 weeks, including a 
Screening period of approximately 4 weeks (Days -28 to -1), treatment 
and assessments through Week 48, and a Safety Follow-Up period of 
8 weeks (through Week 56). 
Data Monitoring Committee 
An external, independent Safety Data Monitoring Committee (SDMC) 
will evaluate safety data at regular intervals throughout the study and 
make recommendations to the Sponsor as needed. The SDMC will not 
perform a futility analysis or consider early study completion for 
efficacy. 


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2 
INTRODUCTION  
2.1 
Background  
2.1.1 
Systemic Lupus Erythematosus  
Clinical Presentation 
Systemic lupus erythematosus (SLE) is an autoimmune disease that affects multiple organ 
systems and is unpredictable in disease severity, with periods of illness or flares alternating with 
periods of remission. The diverse presentation of lupus can range from rash and arthritis, to 
anemia and thrombocytopenia, to serositis, nephritis, seizures, and psychosis. At its onset, SLE 
may involve one or more organ systems, including the musculoskeletal, cutaneous, vascular, 
renal, pulmonary, hematological, and nervous systems. Additional manifestations may occur 
over time. Disease prevalence is approximately one in 1000 individuals overall but varies with 
race and ethnicity. SLE is more common in women than in men (9:1 ratio), and is more common 
in African American, African Caribbean, Hispanic, and Asian populations than Caucasians 
(Helmick et al, 2008; Feldman et al, 2013). Onset in women typically occurs during their 
childbearing years. Patients with SLE rate their health-related quality of life as significantly 
worse than patients with common chronic diseases, such as hypertension and diabetes (Jolly, 
2005), and they are chronically exposed to medication with significant side effects, such as, 
glucocorticoids (GCs) (typically prednisone or prednisolone) and immunosuppressive agents 
(King and Hahn, 2007). Fatigue, cognitive dysfunction, and depressed mood and anxiety are 
frequent debilitating comorbidities in patients with SLE and are associated with decreased 
health-related quality of life (Yurkovich et al, 2014, Schmeding and Schneider, 2013, Holloway 
et al, 2014, Lateef and Petri, 2014, Palagini et al, 2013). 
Pathogenesis and Pathology 
The pathogenesis of SLE is based on mechanisms that lead to loss of tolerance against nuclear 
autoantigens (Liu and Anders, 2014). SLE develops when autoimmunization occurs against 
nuclear autoantigens (eg, by impairing lymphocyte depletion via apoptosis, opsonization, and 
rapid phagocytic clearance). Subsequently, endogenous nucleic acids directly activate toll-like 
receptors (TLRs) on dendritic cells (DCs) or B cells that in turn drive interferon (IFN)α-driven 
immunity, antigen presentation, and the activation of autoreactive lymphocyte subsets. 
Activation of B cells and their maturation to plasma cells promotes autoantibody production. 
Complement activation and proinflammatory cytokines drive the inflammatory process that can 
cause organ injury, scarring, and chronic disease. 
The production of autoantibodies to a variety of nuclear antigens is a hallmark of SLE that 
accounts for some of the pathological findings (Rahman and Isenberg, 2008; Jimenez et al, 2003; 
Petri et al, 2009). Serologically, a series of these autoantibodies are used routinely in clinical 
practice to further characterize the disease and risk for potential manifestations. These include 


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Unmet Need 
GCs remain a therapeutic mainstay for short- and long-term control of disease activity in SLE 
and lupus nephritis (LN), and are often administered in combination with chloroquine derivatives 
(ie, antimalarials, including hydroxychloroquine sulfate) and immunosuppressants (eg, 
mycophenolate mofetil [MMF], methotrexate [MTX], azathioprine [AZA], cyclophosphamide, 
and cyclosporine) (King and Hahn, 2007; Petri, 2006). The chloroquine derivatives are of 
moderate effectiveness and may prevent flares, though breakthrough flares occur frequently, 
while the toxicity of the more aggressive drug regimens for SLE contributes significantly to 
morbidity and mortality (King and Hahn, 2007; Petri, 2006; Ruiz-Arruza et al, 2014; Doria et 
al, 2014). 
Recently, more targeted therapies (ie, monoclonal antibodies [mAbs]), have been utilized in the 
treatment of SLE. Inhibition of B lymphocyte stimulator (also known as B cell activating factor 
of the tumor necrosis factor [TNF] family) with belimumab (Benlysta®) was shown to be safe 
and effective for SLE treatment (Furie et al, 2011; Navarra et al, 2011). Belimumab was 
approved by the US Food and Drug Administration (FDA) in 2011 and in Canada and Europe for 
treatment of SLE. As the only targeted therapy approved for the treatment of SLE, belimumab 
with standard of care (SoC) demonstrated an increased rate of treatment response in SLE patients 
compared to those receiving placebo and SoC. In addition, results suggested that there was a 
reduced likelihood of severe flares and reduction in glucocorticoid (GC) doses. However, 
approximately 50% of the patients did not respond with a decrease in SLE activity when treated 
with belimumab. Therefore, there is a very high unmet medical need for novel, targeted therapies 
with improved efficacy and benefit-risk ratio. 
2.1.2 
VIB7734  
VIB7734 is a human immunoglobulin (Ig)G1κ afucosylated mAb specific for human ILT7, a cell 
surface protein expressed by plasmacytoid DCs (pDCs) (Cho et al, 2008; Rissoan et al, 2002). 
VIB7734 binding to ILT7 on the surface of pDCs leads to recruitment of macrophages and 
natural killer (NK) cells, thus inducing apoptosis and reducing the number of pDCs. The 
afucosylation of VIB7734 is designed to improve the in-life potency of the molecule and to 
enhance the capacity for antibody-dependent cellular toxicity against pDCs. 
2.1.3 
Supportive Nonclinical Data  
ILT7 is expressed only on the pDCs of humans and non-human primates; therefore, the 
cynomolgus monkey was selected as the relevant species for safety evaluation of VIB7734.  
Study 8311616 was a Good Laboratory Practice (GLP)-compliant, repeat-dose study in 
cynomolgus monkeys administered VIB7734 at 200 mg/kg intravenously (IV), 200 mg/kg 
subcutaneously (SC), and 400 mg/kg SC once weekly for 4 weeks (5 doses). No VIB7734-
related clinical observations, body weight changes, ophthalmic observations, physical 
examination observations, macroscopic observations, or changes in blood pressure or 
electrocardiograms (ECGs) were observed. VIB7734 administration had no clear or consistent 
group effects on clinical pathology parameters. VIB7734-related mild to moderate decreases of 


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the group mean, absolute, and relative values of NK cells were observed in males given 200 or 
400 mg/kg SC and in females given 200 mg/kg IV or SC and 400 mg/kg SC on Days 15 and 29 
of the dosing phase. VIB7734-related pDC depletion was observed at all dose groups starting on 
Day 2 of the dosing phase. pDC values were maintained at < 10% of mean Baseline values in the 
majority of animals on Day 29. By Day 209, mean pDC values returned to Baseline or 
approximately 50% of Baseline in animals administered 200 mg/kg IV and 200 or 400 mg/kg 
SC, respectively. No other VIB7734-related changes in peripheral blood immunophenotyping 
cells (total T cells, helper T cells, cytotoxic T cells, B cells, monocytes, and myeloid DCs) were 
observed in the blood, lymph nodes, and spleens of animals given ≥ 200 mg/kg IV or SC. 
VIB7734 had no effect on the ability to mount a T cell-dependent antibody response to primary 
or secondary administration of antigen, indicating intact humoral immunity during VIB7734 
administration. 
Study 8338846 was a GLP-compliant, 6-month, repeat-dose study in cynomolgus monkeys. 
VIB7734 was administered once weekly via SC injection for 6 months (a total of 28 doses) at 
doses of 200 and 400 mg/kg/week. There were no VIB7734-related clinical, ophthalmic, body 
weight, or physical observations; no changes were observed in cardiac measurements or 
observations, or clinical or anatomic pathology. In addition, there were no VIB7734-related 
effects on reproductive organs or assessments. No VIB7734-related changes were noted for IgG, 
IgM, IgA, IgE, or peripheral blood immunophenotyping, except pDCs as expected by 
pharmacology. VIB7734-related depletion of mean absolute and relative values for pDCs was 
noted on Day 2 of the dosing phase in animals administered 200 or 400 mg/kg/week. The only 
VIB7734-related observation was a minor increase in mononuclear cell and macrophage 
infiltrates at the injection sites of animals administered VIB7734, compared with controls. These 
increases were not dose dependent, and partial reversibility was noted in recovery animals.  
Based on these results, the no-observed-adverse-effect-level is 200 mg/kg when given via IV 
infusion and 400 mg/kg/week when given by SC injection. Additional details of these and other 
nonclinical studies are included in the Investigator’s Brochure. 
2.1.4 
Risk Assessment for VIB7734  
There are no important identified risks for VIB7734. Important potential risks for VIB7734 may 
include viral infection and viral reactivation, opportunistic infection, malignancy, and 
hypersensitivity reactions, including anaphylaxis. More detailed descriptions of these potential 
risks are included in the Investigator’s Brochure. 
Hypersensitivity reactions, including anaphylaxis, are a risk associated with administration of 
biologic drugs. Definitions for these reactions can be found in Appendix 1. Appropriate drugs 
and medical equipment to treat acute anaphylactic and serious hypersensitivity reaction must be 
immediately available at study sites, and study personnel must be competent to recognize and 
treat anaphylaxis. In addition, participants will be monitored after investigational product (IP) 
administration for immediate drug reactions. Hypersensitivity reactions and anaphylaxis have not 
been observed in Phase 1 single-ascending dose (SAD) and 1b multiple ascending dose (MAD) 
studies. 


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2.1.4.1 
COVID-19 Risk Assessment  
An additional risk of study participation includes potential exposure of the participant to severe 
acute respiratory syndrome (SARS)-coronavirus (CoV)-2, the virus that causes CoV disease 
2019 (COVID-19), by visiting the study site. Sites must have a plan in place to minimize this 
risk. Although testing for COVID-19 prior to Dose 1 is not required, the Investigator may choose 
to have this test performed locally in accordance with his/her judgment based on participant risk. 
This test is not provided through the study’s central laboratory, because the result of a test at 
Screening would not be appropriately timed to be relevant to Dose 1. Such testing is not 
required. 
To minimize risk to participants, study sites will be activated to initiate participant enrollment 
only after review of local COVID-19 disease incidence, prevalence, containment measures, 
availability of healthcare resources, ability to monitor site activities, and the presence of a site 
plan to minimize participant exposure to SARS-CoV-2 during site visits have been confirmed.  
There are no data on the effect of VIB7734 on the risk for infection with SARS-CoV-2 or on the 
severity of COVID-19 illness.  
The current available evidence does not suggest a difference in COVID-19 infection risk in 
persons with SLE compared to the general population except for what is known about the 
increased risk that may be associated with comorbid disease and use of immunosuppressive 
treatment. 
The Investigator will assess the benefit-risk for each individual participant for determination of 
suitability for enrollment based on known risk factors for COVID-19 severity and possible or 
known exposure to SARS-CoV-2.  
Because of the evolving spread and containment measures of COVID-19, ongoing risk 
assessment will be required of participating study sites and Investigators. 
2.1.5 
Supportive Clinical Data  
VIB7734 has been investigated in Phase 1 SAD and Phase 1b MAD clinical studies in patients 
with autoimmune diseases (Studies D6080C00001 and VIB7734.P1b.S1, respectively). Study 
D6080C00001 has been completed. Study VIB7734.P1b.S1 has a locked database and all clinic 
visits have been completed. 
2.1.5.1 
Phase 1 Single-Ascending Dose Study in Patients With Autoimmune Diseases  
A Phase 1 SAD study (Study D6080C00001) of VIB7734 enrolled participants with any of 
5 autoimmune diseases: dermatomyositis, polymyositis, SLE, Sjögren’s syndrome, and systemic 
sclerosis. Single SC doses of VIB7734 (1, 5, 15, 50, or 150 mg) or placebo were administered to 
36 participants. No safety, tolerability, or immunogenicity issues were identified. 
Pharmacodynamic (PD) analysis showed a dose-dependent reduction in pDC levels, which was 
observable on Day 2 (one day after dosing on Baseline [Day 1]) and maximal on Day 15. The 
duration of pDC reduction was largely dose dependent and was reversible in all cases. Median 
pDC levels returned to above 50% of Baseline at the following time points for each cohort: 
1 mg: Day 29; 5 mg: Day 57; 15 mg: Day 57; and 50 mg: Day 85. The time to return to above 
50% of Baseline could not be determined for 150 mg, since participants met protocol-defined 
minimum absolute pDC number repletion criteria and exited the study before this occurred.  


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2.1.5.2 
Phase 1b Multiple-Ascending Dose Study in Patients With Autoimmune Diseases  
In a single-blind (participants and site blinded, Sponsor unblinded), Phase 1b MAD study (Study 
VIB7734.P1b.S1), VIB7734 or placebo was administered SC every 4 weeks (Q4W) for 3 doses 
to a total of 31 participants in 3 cohorts. In the first cohort, 8 participants with any of 
6 autoimmune diseases (dermatomyositis, polymyositis, SLE, cutaneous lupus erythematosus 
(CLE), Sjögren’s syndrome, or systemic sclerosis) were randomized to VIB7734 (5 mg SC) or 
placebo in a 3:1 ratio. The second and third cohorts enrolled participants with active cutaneous 
lupus, defined as a Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI)-
Activity (CLASI-A) score ≥ 8. In the second cohort, 12 participants were randomized to 
VIB7734 50 mg SC or placebo in a 2:1 ratio. In Cohort 3, 11 participants were randomized to 
VIB7734 150 mg SC or placebo in a 2:1 ratio.  
A reduction in blood pDC level was observed at the first time point after dosing (Week 1) and 
persisted through the 3-month Treatment period. A high type I IFN signature was present at 
Baseline in 18 of 23 participants (78%) in Cohorts 2 and 3. The median change in IFN signature 
at Month 3 was -54% in the VIB7734 50 mg group, -83% in the VIB7734 150 mg group, and 
+8% in the placebo group. On the Month 3 skin biopsy, the median change in pDC density 
was -87% for the 50 mg group, -99% for the 150 mg group, and -14% for the placebo group. The 
median change in CLASI-A from Baseline to Month 3 was -5 in the 50 mg group, -9.5 in the 
150 mg group, and -5 in the placebo group. At Month 3, a ≥ 50% improvement in CLASI-A was 
observed in 38% of participants who received 50 mg VIB7734, 75% of participants who 
received 150 mg VIB7734, and 29% of participants who received placebo. The proportion of 
participants with an adverse event (AE) was similar in the VIB7734 and placebo groups (73% 
versus 67%, respectively). No serious AEs (SAEs) or other clinically important AEs occurred in 
VIB7734-treated study participants.  
2.2 
Study Rationale  
In the absence of exogenous triggers, DCs contribute to the clearance of dying cells and the 
maintenance of tolerance (Klarquist et al, 2016; Huang et al, 2015). However, during infection or 
in the context of autoimmunity, DCs play a key role in activating cluster of differentiation (CD)4 
and CD8 T cells. pDCs are also known for their capacity to produce vast amounts of IFNα via 
engagement of TLRs in response to viruses, including virus-derived nucleic acids, and in 
response to lupus-related, nucleic acid-containing immune complexes (Siegal et al, 1999). While 
pDCs from healthy donors have been shown to induce suppressive T regulatory cell features 
(Foxp3 expression) in vitro, SLE pDCs failed to do so (Jin et al, 2010). In mouse models, 
constitutive depletion of pDCs in lupus-prone mice resulted in markedly reduced type I IFN 
production, a reduced IFN signature, reduced autoantibody production, and reduction in the 
severity of kidney pathology glomerulonephritis (Rowland et al, 2014). Importantly, transient 
pDC depletion during the early stages of disease was sufficient to significantly alter the course of 
the disease, suggesting a more prominent role for pDCs in the induction of the disease than in 
disease pathogenesis at later stages of disease (Rowland et al, 2014). Recent data from Phase 2 
and Phase 3 studies with IFNα pathway-blocking agents (sifalimumab and anifrolumab) as well 
as another pDC antagonist (BIIB059) demonstrated improvement in SLE or cutaneous lupus 
disease activity, further supporting the rationale for blocking the IFN pathway and pDCs in 
patients with SLE (Furie et al, 2017; Furie et al, March 2019; Furie et al, November 2019; 
Khamashta et al, 2016; Morand et al, 2020; Werth et al, 2020). 


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Altogether, given the lack of highly efficacious and safe treatments for active SLE and the 
significant impact of this disease on health-related quality of life, in part from SLE-associated 
fatigue, cognitive dysfunction, and mood disorders, there is currently a significant unmet need 
for new targeted therapies. Based on its mechanism of action, VIB7734 has the potential to 
decrease SLE disease activity. In addition, based on data currently available, VIB7734 presents 
an acceptable safety profile, and hence, it is therefore justified to evaluate its potential efficacy in 
patients with active SLE. 
2.3 
Study Hypotheses  
Primary Hypothesis 
VIB7734 is efficacious in reducing disease activity in participants with moderate to severely 
active SLE. 
Secondary Hypothesis 
VIB7734 has an acceptable safety, tolerability, and immunogenicity profile in participants with 
moderate to severely active SLE. 


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3 
OBJECTIVES AND OUTCOME MEASURES  
3.1 
Primary Objective and Outcome Measure  
Objective 
Outcome Measure 
To evaluate the effect of VIB7734 
compared to placebo in reducing 
SLE disease activity at Week 48 in 
participants treated with SoC 
therapy. 
Proportion of participants achieving a BICLA response and an OGC dose 
≤ 7.5 mg/day and ≤ Baseline (Day 1) dose of prednisone or equivalent at 
Week 48. 
The BICLA response is defined as meeting all the following conditions as 
compared to Baseline (Day 1): 
x BILAG 2004 Index improvement (all Baseline [Day 1] BILAG A 
improving to B/C/D, all Baseline [Day 1] BILAG B to C/D, and 
≤ 1 new BILAG B and no new BILAG A). 
x No deterioration in SLEDAI-2K total score. 
x No significant worsening in PGA score (< 10% increase). 
x No use of restricted medications beyond the protocol-allowed threshold 
before assessment. 
x No discontinuation of IP.  
BICLA: BILAG 2004 Index-based Combined Lupus Assessment; BILAG: British Isles Lupus Assessment 
Group; IP: investigational product; OGC: oral glucocorticoid; PGA: Physician Global Assessment; 
SLE: systemic lupus erythematosus; SLEDAI-2K: SLE Disease Activity Index 2000; SoC: standard of care. 
3.2 
Secondary Objectives and Outcome Measures  
Efficacy Objectives 
Outcome Measures 
To evaluate the effect of VIB7734 
compared with placebo to reduce 
cutaneous disease activity at 
Week 12. 
Proportion of participants with CLASI-A score ≥ 10 at Baseline (Day 1) 
who achieve ≥ 50% reduction from Baseline (Day 1) in CLASI-A score at 
Week 12. Reduction of 50% in CLASI-A score is defined by meeting all 
the following conditions: 
x A ≥ 50% reduction of CLASI-A score at Week 12 as compared to 
Baseline (Day 1). 
x No use of restricted medications beyond the protocol-allowed threshold
before assessment.  
x No discontinuation of IP. 
To evaluate the effect of VIB7734 
compared with placebo to reduce 
SLE disease activity at Week 48. 
Proportion of participants achieving an SRI-4 response and an OGC dose 
≤ 7.5 mg/day and ≤ Baseline (Day 1) dose of prednisone or equivalent at 
Week 48. The SRI-4 response is defined as meeting all of the following 
conditions compared to Baseline (Day 1): 
x Reduction from Baseline (Day 1) of ≥ 4 points in the SLEDAI-2K. 
x No new organ system affected as defined by one or more BILAG A or 
2 or more BILAG B items. 
x No significant worsening in PGA score (< 10% increase). 
x No use of restricted medications beyond the protocol-allowed threshold 
before assessment. 
x No discontinuation of IP. 


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Efficacy Objectives 
Outcome Measures 
To evaluate the effect of VIB7734 
compared with placebo on 
sustained OGC reduction from 
Week 36 to Week 48. 
Proportion of participants at OGC dose ≥ 10 mg prednisone or equivalent at 
Baseline (Day 1) who: 
x Achieve OGC dose ≤ 7.5 mg/day prednisone or equivalent at Week 36.  
x Maintain OGC dose ≤ 7.5 mg/day from Week 36 through Week 48. 
x No use of restricted medications beyond the protocol-allowed threshold 
before assessment. 
x No discontinuation of IP. 
To evaluate the effect of VIB7734 
compared with placebo to achieve 
low disease activity at Week 48. 
Proportion of participants achieving LLDAS at Week 48. LLDAS is 
defined as meeting all the following conditions: 
x SLEDAI-2K ≤ 4, with no activity in major organ system (renal, CNS, 
cardiopulmonary, vasculitis, fever) and hemolytic anemia or 
gastrointestinal activity. 
x No new lupus disease activity as compared to the previous assessment. 
x PGA ≤ 1 (on a scale of 0 to 3). 
x Current prednisone or equivalent dose of ≤ 7.5 mg/day. 
x Well-tolerated standard maintenance doses of immunosuppressive drugs 
and approved treatments as allowed and specified in the Clinical Study 
Protocol. 
x No use of restricted medications beyond the protocol-allowed threshold. 
x No discontinuation of IP. 
PK/PD/Immunogenicity 
Objectives 
Outcome Measures 
To characterize the PK, PD, and 
immunogenicity of VIB7734. 
VIB7734 concentrations, change in pDCs, 
. 
Safety Objectives 
Outcome Measures 
To evaluate the safety and 
tolerability of VIB7734. 
Incidence of AEs, SAEs, and AESIs.  
 AE: adverse event; AESI: AE of special interest; BILAG: British Isles Lupus 
Assessment Group; CLASI-A: Cutaneous Lupus Erythematosus Disease Area and Severity Index-Activity; 
CNS: central nervous system; IP: investigational product; LLDAS: Lupus Low Disease Activity State; 
OGC: oral glucocorticoid; PD: pharmacodynamic(s); pDC: plasmacytoid dendritic cell; PGA: Physician 
Global Assessment; PK: pharmacokinetic(s); SAE: serious AE; SLEDAI-2K: Systemic Lupus Erythematosus 
Disease Activity Index 2000; SRI: Systemic Lupus Erythematosus Responder Index. 
3.3 
Exploratory Objectives and Outcome Measures  
Objectives 
Outcome Measures 


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Objectives 
Outcome Measures 
 


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4 
STUDY PLAN  
4.1 
Study Design  
This study is a Phase 2, multicenter, international, double-blind, randomized, placebo-controlled, 
parallel-group trial to assess the efficacy and safety of VIB7734 in participants with moderate to 
severely active SLE.  
In this study, approximately 195 participants will be randomized in a ratio of 1:1:1 
(65 participants per group) to receive VIB7734 200 mg Q4W SC, VIB7734 200 mg every 
12 weeks (Q12W) SC, with an additional 200 mg SC dose at Week 4, or placebo. To maintain 
blinding, participants randomized to the VIB7734 200 mg Q12W SC dosing regimen will receive 
SC placebo injections on dosing visits outside the Q12W schedule. Randomization will be 
stratified by SLE Disease Activity Index 2000 (SLEDAI-2K) total score at Screening (≥ 10 or 
< 10) and prednisone or equivalent oral GC (OGC) dose at Baseline (Day 1) (≥ 10 mg or 
< 10 mg).  
The study will comprise a Screening period of approximately 4 weeks (Days -28 to -1), 
Randomization on Day 1, treatment and assessments through Week 48, and a Safety Follow-Up 
(SFU) period of 8 weeks (through Week 56). Under exceptional circumstances such as delayed 
laboratory results, drug washout, or the impact of COVID-19, the Screening period may be 
increased by 2 weeks, upon approval by the Medical Monitor. The study will be conducted on an 
outpatient basis. For all administrations, IP will be administered by site staff in the clinic and the 
participant will be observed for at least 60 minutes after the first and second doses. Participants 
who prematurely stop dosing prior to Week 44 will be followed through Week 56. Participants 
will not automatically be removed from the study if any administration of IP is missed. 
A long-term extension (LTE) study for safety and efficacy may be offered as part of a separate 
protocol, to participants who complete the Week 48 visit. Participants who enter the LTE study 
directly after completion of the Week 48 visit will not complete the visits of the SFU period.  
The study design is summarized in Figure 1.


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Figure 1 
Study Design  
 
COVID-19: coronavirus disease 2019; OGC: oral glucocorticoid; Q4W: every 4 weeks; Q12W: every 12 weeks; SC: subcutaneous(ly); SLE: systemic lupus 
erythematosus; SLEDAI-2K: SLE Disease Activity Index 2000; W: week.  
 


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4.2 
Dose and Treatment Rationale  
The VIB7734 SAD study demonstrated that the safety profile for single SC doses of 1 to 150 mg 
is acceptable (Section 2.1.5.1). Pharmacokinetic (PK) exposure increased in an approximately 
dose-proportional manner. Increasing doses were associated with an increase in maximal pDC 
reductions and a longer duration of pDC reduction. In the VIB7734 MAD study 
(Section 2.1.5.2), up to 150 mg Q4W was demonstrated to have an acceptable safety profile in 
patients with SLE, CLE, Sjögren’s syndrome, systemic sclerosis, polymyositis, and 
dermatomyositis. Treatment with VIB7734 resulted in rapid and durable depletion of blood 
pDCs in all patients receiving a 150 mg Q4W dose. In addition, at Day 85, the median percent 
change from Baseline in CLASI-A was -59% for patients receiving the 150 mg Q4W dose 
and -33% for the 50 mg Q4W dose, compared with -38% in the placebo-dosed group. 
In this Phase 2 study, 2 dose regimens, 200 mg Q4W and 200 mg Q12W, have been selected to 
establish an exposure-response relationship. A nonclinical safety study of VIB7734 in 
cynomolgus monkeys provided sufficient PK exposure coverage (over 300-fold) for the 
proposed clinical dose regimens to be evaluated in this study. The high dose selected to be 
evaluated in participants with moderate to severely active SLE is 200 mg Q4W. Furthermore, 
given the prolonged pDC suppression observed after completion of treatment in the MAD study 
(Section 2.1.5.2), a second dose regimen of 200 mg Q12W has been selected to evaluate pDC 
response and efficacy of less frequent dosing of VIB7734.  
A 48-week treatment duration is considered sufficient to demonstrate an effect on the primary 
and secondary outcome measures selected for this study and current nonclinical safety data 
(Section 2.1.3) supports this treatment duration.  
4.3 
Rationale for Study Population  
This study is designed to assess the efficacy of VIB7734 in reducing SLE disease activity. At 
Screening, participants will be required to have moderate to severely active disease as defined by 
the SLEDAI-2K, British Isles Lupus Assessment Group (BILAG) 2004 Index, and Physician 
Global Assessment (PGA) (Bombardier et al, 1992; Gladman et al, 2000). This active disease 
can either be a recent flare or chronic active disease. Failure of the Phase 2 trial of belimumab in 
SLE patients was attributed in part to the relative lack of responsiveness in the approximately 
25% of patients with a negative ANA or anti-dsDNA at Screening compared to those with a 
positive serology (Wallace et al, 2009). The responsiveness of seropositive patients was 
corroborated by the positive efficacy results observed in the BLISS-52 and BLISS-76 belimumab 
trials that included only seropositive patients (Furie et al, 2011; Navarra et al, 2011). Hence, the 
presence of a positive ANA and/or autoantibodies with high specificity for SLE are a mandatory 
criterion for enrollment in this study. 
Stabilization of the SLE treatment regimen in SLE participants prior to Baseline (Day 1) 
decreases the confounding of the study results by the SoC (ie, changes in disease activity post-
Baseline [Day 1] are more likely to be attributable to the introduction of VIB7734, rather than a 
change in background therapy). 
Severe central nervous system (CNS) lupus and LN may be less responsive to therapy than other 
manifestations or may require different treatment regimens (eg, cyclophosphamide, IV Ig, high-
dose mycophenolate) than typically used in extrarenal SLE. Therefore, these individuals will be 


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excluded from participating in this study. Also, individuals with significantly impaired renal 
function are excluded since they may have advanced, fixed disease that will not be responsive to 
therapy, and furthermore, these individuals are at higher risk for AEs.  
A urine protein:creatinine ratio (UPCr) of up to 3 mg/mg is allowed. This limit is applied 
because higher levels of proteinuria increase the risk of AEs. 
The recent or ongoing use of systemic GCs for any comorbidities other than SLE is excluded. 
Such use would confound the analysis of the effect of VIB7734 on SLE activity. In addition, it 
would confound the analysis of the potential GC-sparing effects of VIB7734, which is a 
component of the primary objective of the study. Individuals with active or significant recent 
infection are excluded to avoid possible recurrence or worsening. Individuals with active or 
untreated latent tuberculosis (TB) infection or hepatitis B or C infection are excluded to avoid 
the risk of reactivation. A number of abnormalities or interventions known to interfere with the 
immune system are excluded to avoid possible confounding of the VIB7734 efficacy and safety 
profile. In terms of cardiac risk, individuals with an increased risk of recurrent cardiovascular 
events (those with a recent event) and/or significant arrhythmia will be excluded to decrease 
potential confounding of study outcomes. Randomization of a screened participant will require 
review to confirm that all relevant inclusion and exclusion criteria have been applied in 
consideration of the participant’s eligibility. The protocol contains specific inclusion and 
exclusion criteria; however, not every possible clinical scenario can be addressed in the protocol. 
The impetus for this requirement has been the observance in other studies that some participants 
enrolled in trials are not considered appropriate participants by those reviewing the study. The 
most common reasons for exclusion in trials are the presence of certain comorbidities as well as 
the absence of sufficient SLE activity. Participants failing to be randomized (ie, screen failures) 
may be rescreened once for participation with Medical Monitor approval. 
4.4 
Rationale for the Primary Outcome Measure  
The primary outcome measure is the proportion of participants achieving a BILAG 2004 Index-
based Combined Lupus Assessment (BICLA) response and an oral (PO) prednisone (or 
equivalent) dose of 侓 7.5 mg/day and 侓 Baseline (Day 1) dose at Week 48. The BICLA is driven 
by improvement in the BILAG 2004 Index score, which measures organ-specific activity 
(Wallace et al, 2011). The BILAG 2004 Index incorporates a comprehensive, organ-specific, 
97-question assessment, which requires the Investigator to score organ manifestations as 
improving, same, worse, or new over the previous 4 weeks. The scores (A, B, C, D) derived from 
the assessments (improving, same, worse, or new, respectively) will determine whether further 
treatment is needed to resolve disease activity. The change in treatment does not determine the 
scoring (Yee et al, 2009).  
The BICLA was used as the primary endpoint in a Phase 2b trial of epratuzumab (Wallace et al, 
2014) and in a Phase 3 trial of anifrolumab (Morand et al, 2020). Given the clinical relevance for 
the use of BICLA and its ability to discern effect as suggested in the anifrolumab Phase 3 study, 
the BICLA was selected as the clinical disease activity assessment for the primary outcome 
measure. In addition, there is a requirement to achieve and maintain an PO prednisone or 
equivalent dose of 侓 7.5 mg/day and 侓 Baseline (Day 1) dose for at least 12 weeks. A major 
potential benefit of any new therapeutic in SLE is to be GC sparing. Further, as placebo-treated 
participants on stable SoC therapy may be less likely to have their GCs tapered, but with higher 


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doses of OGC relative to the active treatment group still achieve/maintain lower levels of disease 
activity, the ability to have OGC tapered is included as a component of the primary outcome 
measure. 


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5 
POPULATION  
5.1 
Inclusion Criteria  
To be included in this study, each participant must satisfy all the following criteria: 
1. Age ≥ 18 years to ≤ 70 years at the time of signing the informed consent form (ICF). 
2. Willing and able to understand and provide written informed consent prior to any study-
related procedures and to comply with all study requirements and complete study 
assessments. 
3. Fulfill the 2019 European League Against Rheumatism/American College of 
Rheumatology Classification Criteria for SLE (Appendix 2) (Aringer et al, 2019). 
4. Disease duration of at least 6 months from the time of diagnosis at the time of signing the 
ICF. 
5. Active SLE as indicated by presence of all the following: 
x SLEDAI-2K total score ≥ 6 at Screening, excluding fever, SLE headache, or organic 
brain syndrome.  
x SLEDAI-2K total score ≥ 4, excluding points attributable to any urine or laboratory 
results, immunologic measures, fever, SLE headache, or organic brain syndrome at 
Screening and Baseline (Day 1). 
x At least one of the following BILAG 2004 Index levels of disease at Screening: 
 BILAG A disease in ≥ 1 organ system. 
 BILAG B disease in ≥ 2 organ systems. 
x PGA score ≥ 1 on a 0 to 3 visual analog scale (VAS) at Screening. 
6. Have at least one of the following at Screening per central lab: 
7. Ongoing treatment for SLE defined as (a) or (b): 
a. Treatment with one or more disease-modifying anti-rheumatic drug (DMARD) or 
immunosuppressive medication: Any of the following medications each administered 
at conventional anti-rheumatic doses for treatment of SLE for at least 12 weeks 
before Screening (unless discontinued or dose adjusted for documented drug-related 
toxicity or size/weight), and at a stable dose (including route of administration) for a 
minimum of 8 weeks prior to Screening and maintained through Baseline (Day 1): 
i. Antimalarial  
 Chloroquine  
 Hydroxychloroquine   
 Quinacrine 
ii. Azathioprine (AZA) or 6-mercaptopurine (6-MP) 
iii. Leflunomide  
iv. Mycophenolate mofetil (MMF) or mycophenolic acid (MPA) 


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v. Methotrexate (MTX) (participants must be on concomitant folic or folinic acid 
supplementation if using MTX) 
vi. Voclosporin (if approved for treatment) 
vii. GCs are permitted but not required if a participant is receiving at least one other 
medication listed above. If GCs are used in combination with allowed DMARDs 
or immunosuppressants, they must be at an average daily dose of PO prednisone 
≤ 40 mg (or prednisone equivalent) for a minimum of 2 weeks prior to Screening 
and at a stable dose for a minimum of 2 weeks prior to Screening. In addition, the 
dose of OGC must be kept stable for a minimum of 2 weeks prior to 
Randomization. Daily dosing or alternate day dosing of PO prednisone (or 
prednisone equivalent) is allowed. 
b. Treatment with OGC monotherapy (without the concomitant use of DMARDs or 
immunosuppressants): 
i. Average daily dose of PO prednisone ≥ 10 mg but ≤ 40 mg (or prednisone 
equivalent) for a minimum of 4 weeks prior to Screening and at a stable dose for a 
minimum of 2 weeks prior to Screening. In addition, the dose of OGC must be 
kept stable for a minimum of 2 weeks prior to Randomization. Daily dosing or 
alternate day dosing of PO prednisone (or prednisone equivalent) is allowed. 
8. Women of childbearing potential must have a negative serum pregnancy test at Screening 
and a negative urine pregnancy test at Randomization. Women of childbearing potential 
are defined as those who are not surgically sterile (ie, surgical sterilization includes 
bilateral tubal ligation, bilateral oophorectomy, or hysterectomy) or those who are not 
postmenopausal (defined as 12 months with no menses without an alternative medical 
cause and a follicle-stimulating hormone [FSH] within the postmenopausal range as 
established by the central laboratory, unless on postmenopausal hormone replacement 
therapy). 
 
Women of childbearing potential who are sexually active with a non-sterilized male 
partner must agree to use a highly effective method of contraception (Table 1) from 
signing of the informed consent, and must agree to continue using such precautions 
through the end of the study follow-up or 3 months (approximately 5 half-lives) 
following the last dose of IP in the case of early withdrawal from the study, and refrain 
from egg retrieval/egg donation during this period. A decision about contraception after 
this point should be made by the participant and her regular healthcare providers. 
 
Sustained abstinence is an acceptable practice; however periodic abstinence, the rhythm 
method, and the withdrawal method are not acceptable methods of contraception.  
 
Note that because mycophenolate affects the metabolism of hormonal contraceptives and 
may reduce their effectiveness in women receiving MMF or MPA who are using 
hormonal contraceptives for birth control, the participant must employ an additional 
contraceptive method (eg, barrier method). 


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Table 1 
Highly Effective Methods of Contraception  
Physical Methods 
Hormonal Methods a 
x Intrauterine device  
x Intrauterine hormone-releasing system b 
x Bilateral tubal occlusion 
x Vasectomized partner c 
x Sexual abstinence d 
Combined (estrogen and progestogen-containing 
hormonal contraception) 
x PO (combined pill) 
x Injectable 
x Transdermal (patch) 
x Progestogen-only hormonal contraception 
associated with inhibition of ovulation e 
x Injectable 
x Implantable 
x Intravaginal 
PO: oral(ly). 
a A change in birth control method is allowed during the study. If a change occurs, unless the patient is changing 
the method to complete abstinence, the patient must employ a barrier method in addition to the highly 
effective method of contraception for at least two months. 
b This is also considered to be a hormonal method. 
c A vasectomized partner is a highly effective method of birth control provided that partner is the sole sexual 
partner of the woman of childbearing potential study participant and that the vasectomized partner has 
received medical assessment of the surgical success. 
d Sexual abstinence is considered to be a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of the study and if it is the preferred and usual lifestyle of the participant. 
e Progestogen-only hormonal contraception where inhibition of ovulation is not the primary mode of action 
(minipill) is not accepted as a highly effective method. 
9. Non-sterilized male participants who are sexually active with a woman partner of 
childbearing potential must agree to use a condom with spermicide from Randomization 
and until 3 months (approximately 5 half-lives) after receipt of the last dose. Because a 
male condom with spermicide is not a highly effective contraception method, it is 
strongly recommended that male participants advise their women partners of childbearing 
potential to use a highly effective method of contraception throughout this period (refer 
to Table 1). 
5.2 
Exclusion Criteria  
If an individual meets any of the following criteria, he or she is ineligible for this study: 
5.2.1 
General Exclusion Criteria  
1. Individuals involved in the conduct of the study, their employees, or immediate family 
members of such individuals. 
2. Any condition that, in the opinion of the Investigator or the Sponsor/Central Review 
Committee, would interfere with evaluation of the IP or interpretation of participant 
safety or study results (including borderline disease activity). 
3. History of allergy, hypersensitivity reaction, or anaphylaxis to any component of the IP 
or to a previous mAb or human Ig therapy. 
4. Participation in another clinical study with an investigational drug within 4 weeks prior to 
Day 1 or within 5 published half-lives, whichever is longer (also refer to Section 5.2.3). 
5. Breastfeeding or pregnant women or women who intend to become pregnant anytime 
from signing the ICF through 3 months after receiving the last dose of IP. 


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6. History of drug or alcohol abuse that, in the opinion of the Investigator, might affect 
participant safety or compliance with visits, or interfere with other study assessments. 
7. Major surgery within 8 weeks prior to Screening or elective surgery planned from 
Screening through Day 393. 
8. Spontaneous or induced abortion, still or live birth, or pregnancy ≤ 4 weeks prior to 
Screening. 
9. Known history of a primary immunodeficiency or an underlying condition such as known 
human immunodeficiency virus (HIV) infection, a positive result for HIV infection per 
central laboratory, splenectomy, or any underlying condition that in the opinion of the 
Investigator significantly predisposes the participant to infection. 
10. At Screening, any of the following per central laboratory (tests may be repeated once 
within the same Screening period to confirm results prior to Randomization):  
x Aspartate aminotransferase (AST) > 2.5× upper limit of normal (ULN) 
x Alanine aminotransferase (ALT) > 2.5× ULN 
x Total bilirubin > 1.5× ULN (unless due to Gilbert’s syndrome) 
x Serum IgG < 600 mg/dL (or < 6 g/L) 
x Neutrophil count < 1000/μL (or < 1.0×109/L) or < 500/μL (< 0.5×109/L) if due to active 
SLE 
x Platelet count < 50,000/μL (or < 50×109/L) or < 25,000/μL (< 25×109/L) if due to active 
SLE 
x Hemoglobin < 8 g/dL (or < 80 g/L) or < 7 g/dL (< 70 g/L) if due to active SLE 
x Glycosylated hemoglobin > 8% (or > 0.08) 
x Total lymphocyte count < 200 cells/mm3 
x Glomerular filtration rate < 30 mL/min/1.73 m2  
x Spot UPCr > 3 mg/mg (> 339 mg/mmol) 
11. Confirmed positive test for hepatitis B serology defined as: 
x Hepatitis B surface antigen (HBsAg), or  
x Hepatitis B core antibody (HBcAb) AND hepatitis B virus (HBV) DNA detected above 
the lower limit of quantitation (LLOQ) by reflex testing by the central laboratory at 
Screening. 
 
Note that participants who are HBcAb positive at Screening will be tested every 3 months 
for HBV DNA. Study drug will be discontinued if the participant’s HBV DNA levels are 
confirmed to exceed the LLOQ as per the central laboratory. 
12. Positive test for hepatitis C virus antibody. 
13. Active TB, or a positive IFN-gamma release assay (IGRA) test at Screening, unless 
documented history of appropriate treatment for active or latent TB.  
 
Note that participants with an indeterminate IGRA test result with well-documented 
previous treatment do not need to repeat testing and are eligible for randomization. 
Participants with an indeterminate IGRA test result without previous treatment can repeat 
the test, but if the repeat test is also indeterminate, they are excluded. 
14. Any severe herpes virus family infection (including Epstein-Barr virus, cytomegalovirus 
[CMV]) at any time prior to Randomization, including, but not limited to, disseminated 


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herpes, herpes encephalitis, recent recurrent herpes zoster (defined as 2 episodes within 
the last 2 years), or ophthalmic herpes. 
15. Any herpes zoster, CMV, or Epstein-Barr virus infection that was not completely 
resolved 12 weeks prior to Randomization. 
16. Any of the following within 30 days prior to signing the ICF and though Randomization: 
x Clinically significant active infection in the opinion of the Investigator, including 
ongoing, and chronic infection requiring antibiotics or antiviral medication (chronic nail 
infections are allowed). 
x Any infection requiring hospitalization or treatment with IV anti-infectives. 
x A participant with a documented positive SARS-CoV-2 test may be rescreened at least 
2 weeks after a positive test if the participant is asymptomatic and at least 3 weeks after 
symptomatic COVID-19 illness. 
17. Opportunistic infection requiring hospitalization or parenteral antimicrobial treatment 
within 2 years prior to Randomization (Appendix 3). 
18. Any acute illness or evidence of clinically significant active infection,  
19. Clinically significant cardiac disease including unstable angina and/or myocardial 
infarction and/or congestive heart failure within 6 months prior to Randomization. Any 
cardiac condition including, but not limited to the following, if in the opinion of the 
Investigator or Medical Monitor, would increase the risk of study participation: 
x Inadequately controlled arrhythmia.  
x Presence of clinically significant abnormality on ECG. 
20. History of cancer within the past 5 years, except as follows: 
x In situ carcinoma of the cervix treated with apparent success with curative therapy 
> 12 months prior to Screening, or 
x Cutaneous basal cell or squamous cell carcinoma treated with apparent success with 
curative therapy. 
21. Receipt of a live-attenuated vaccine within 4 weeks prior to Day 1. Administration of 
inactivated (killed) vaccines is acceptable. 
22. Participant should be assessed for epidemiologic risk of COVID-19 (ie, recent exposure, 
high-risk housing) and for health-related risk of COVID-19 severity based on current 
understanding of risk factors for severe disease when making a decision regarding the 
individual’s risk of participation. Participants who have COVID-19 or other significant 
infection, or in the judgment of the Investigator, may be at a high risk of COVID-19 or its 
complications should not be randomized. 
5.2.2 
Disease-Related Criteria  
23. Active LN OR active severe or unstable neuropsychiatric SLE (eg, aseptic meningitis, 
cerebral vasculitis, myelopathy, demyelination syndromes [ascending, transverse, acute 
inflammatory demyelinating polyradiculopathy], acute confusional state, impaired level 
of consciousness, psychosis, acute stroke or stroke syndrome, cranial neuropathy, status 
epilepticus, cerebellar ataxia, and mononeuritis multiplex) where, in the opinion of the 
Investigator or Medical Monitor, protocol-specified SoC is insufficient and utilization of 
a more aggressive therapeutic approach, such as IV cyclophosphamide, high-dose IV 
pulse GC therapy, MMF of > 3 gm/day (MPA of > 2.16 gm/day), or an increase from 


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baseline dose of MMF/MPA and/or other treatments not permitted in the protocol, may 
be indicated. 
24. Current diagnosis of non-SLE vasculitis syndrome, mixed connective tissue disease, or 
rheumatic (overlap) syndrome that may confound clinical assessments in the study (eg, 
scleroderma/systemic sclerosis). Secondary sicca or Sjögren’s syndrome, 
antiphospholipid antibody syndrome, and overlap with myositis or rheumatoid arthritis 
without erosive joint disease (“rhupus”) are allowed provided the participant also meets 
the criteria for classification as SLE. A history of mixed connective tissue disease that 
over time has developed into a diagnosis of SLE is permitted provided diagnosis of SLE 
has been present for at least 6 months. 
25. History of antiphospholipid syndrome (APS) with thromboembolic event within 6 
months of Screening or not on an adequate anticoagulation regimen in the 6 weeks prior 
to or at Screening in the opinion of the Investigator. However, presence of 
antiphospholipid antibodies alone (without a history of thromboembolic event) is not 
exclusionary. 
26. Current inflammatory joint or skin disease other than SLE that, in the opinion of the 
Investigator, could interfere with the inflammatory arthritis or skin assessments and 
confound the disease activity assessments. 
5.2.3 
Prior and Concomitant Therapy Criteria  
27. Unstable dosing or initiation of a regularly used nonsteroidal anti-inflammatory drug 
(NSAID) within 2 weeks prior to Baseline (Day 1) other than low-dose [侓 350 mg] 
aspirin for cardiovascular prophylaxis or for APS, which is permitted. Non-regular use of 
NSAID for pain control is permitted. 
28. Receipt of any of the following treatments within the following timeframes. Refer to 
Section 7.4.1 for more details: 
x 2 Weeks prior to Screening and through Randomization: 
 Initiation of or unstable dosing of topical therapy (eg, GCs, calcineurin inhibitors) for 
cutaneous lupus (cyclosporine eye drops are permitted). 
 Opioid use above 40 mg/day morphine-equivalent, unstable dosing, or initiation of 
regular dosing. 
x 4 Weeks prior to Screening and through Randomization: 
 Intra-articular therapies, such as GCs. 
 Systemic GC doses of ≥ 100 mg prednisone or equivalent or intramuscular, IV or 
intralesional GCs. 
 Intradermal GC for alopecia. 
 IV, intramuscular, or SC Ig. 
 Other non-biologic immunosuppressive agents (eg, dapsone, danazol, calcineurin 
inhibitors, sulfasalazine, mizoribine, mechanistic target of rapamycin inhibitors, 
retinoids, thalidomide, lenalidomide, adrenocorticotropic hormone [ACTH] analogs, 
dehydroepiandrosterone), or Janus kinase inhibitors. 
 Transfusion with blood, packed red blood cells, platelets or treatment with 
plasmapheresis, plasma exchange, or Therakos® photopheresis. 


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x 12 Weeks (or 5 half-lives, whichever is longer) prior to Randomization: 
 Cyclophosphamide or alkylating agents (eg, chlorambucil). 
 Cytokine or cytokine receptor antagonists, including but not limited to interleukin 
(IL)-1, IL-6, IL-17, IL-12/23, IL-23, IFN, integrin, or TNFα antagonists (except for IFNα 
kinoid, for which receipt at any time is exclusionary). 
 Belimumab, abatacept, or eculizumab. 
 Other biologics used for immunosuppression or immunomodulation (eg, IFN therapy, 
IL-2).  
 Investigational drugs. 
 IPP-201101 (Lupuzor™). 
x 24 Weeks prior to Randomization: 
 B cell-depleting therapies (eg, rituximab, ocrelizumab, ofatumumab, inebilizumab, 
telitacicept) other than atacicept or obinutuzumab. 
 Receipt of systemic GCs for more than a total of 2 weeks for any concurrent illness, 
including asthma, inflammatory bowel disease, or drug-induced SLE. 
o Systemic is defined as PO, rectal, or any injectable route of administration. 
x 40 Weeks prior to Randomization: 
 Atacicept. 
x 1 Year prior to Randomization: 
 Bacille-Calmette-Guerin (BCG) vaccination. 
x 1.5 Years prior to Randomization: 
 Obinutuzumab. 
5.3 
Rescreening Procedures  
Participants may be rescreened once after a screen failure for inadequate disease activity or other 
reason which, in the opinion of the Investigator, may change to make the participant eligible. A 
participant who rescreens will be required to re-sign the ICF. A screen failure is a consented 
participant who has been deemed ineligible on the basis of one or more eligibility criteria or who 
has withdrawn consent prior to treatment assignment. Participants who rescreen within 8 weeks 
of signing the ICF do not have to repeat serum virology, TB assessment, or chest X-ray if 
performed within 12 weeks, or, if relevant, FSH testing. 
5.4 
Replacement of Participants  
Participants who have been randomized but not dosed will not be followed to completion of the 
study and may be replaced at the discretion of the Sponsor. 


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6 
STUDY CONDUCT  
6.1 
General Instructions  
Participants will undergo a Screening period of approximately 4 weeks (Days -28 to -1), 
Randomization on Day 1, treatment and assessments through Week 48, and a SFU period of 
8 weeks (through Week 56).  
6.2 
Schedule of Study Assessments  
Table 2, Table 3, and Table 4 summarize the Screening, treatment, and follow-up assessments 
and procedures. 
Table 2 
Screening Procedures  
Study Day 
-28 to -1 
Visit Number 
1 
General Assessments 
Informed consent 
X 
Eligibility review 
X 
Demographic data 
X 
Review of SLE and other medical history, medications, and surgery/procedures 
X 
Documentation of SLE classification criteria 
X 
Chest X-ray a 
X 
TB assessment b 
X 
12-lead ECG (after 10 minutes rest in supine position) c 
X 
Vital signs, height, and weight d 
X 
Physical examination e 
X 
BILAG 2004 assessments, SLEDAI-2K, CLASI, PGA,
f 
X 
Laboratory Assessments 
Pregnancy (serum βhCG) test (in women of childbearing potential) 
X 
FSH (to confirm postmenopausal status, as appropriate) g 
X 
Serum virology h 
X 
Routine hematology and chemistry i 
X 
HbA1c 
X 
Urinalysis and spot UPCr (aim to collect urine sample at same time of day, if possible) j 
X 
Anticardiolipin antibodies (IgG, IgA, and IgM) 
X 
Anti-β2GP1 antibody 
X 
Lupus anticoagulant 
X 
Haptoglobin k 
X 
C3 and C4 
X 
PT/INR and PTT 
X 


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Table 2 
Screening Procedures  
Study Day 
-28 to -1 
Visit Number 
1 
Serum IgG, IgA, IgM 
X 
Questionnaires l 
Safety 
Concomitant medications 
X 
AEs, SAEs, and/or AESIs 
X 
AE: adverse event; AESI: AE of special interest;
 β2GP1: β2-glycoprotein 1; BILAG: British 
Isles Lupus Assessment Group; C: complement; 
CLASI: Cutaneous Lupus Erythematosus Disease Area and Severity Index:
ECG: electrocardiogram; FSH: follicle-stimulating hormone; HbA1c: glycosylated hemoglobin;
 
Ig: immunoglobulin; INR: international normalized ratio;
 PT: prothrombin time; 
PTT: partial thromboplastin time; SAE: serious AE; SLE: systemic lupus 
erythematosus; SLEDAI-2K: SLE Disease Activity Index 2000; TB: tuberculosis; UPCr: urine protein:creatinine ratio; 
X: to be performed. 
a The results of a chest X-ray (posterior-anterior, anterior-posterior, and lateral views) performed within 12 weeks of the 
Screening visit (if available) are acceptable, provided there is no reason to suspect any clinical changes. The chest X-ray 
may be completed anytime during the Screening period as long as all results have been reviewed by the Investigator prior 
to Randomization. If the chest X-ray is performed at Screening, posterior-anterior and lateral views should be evaluated, 
unless where prohibited by local health authority. Magnetic resonance imaging or computed tomography scans of the 
chest performed within 12 weeks of the Screening visit are acceptable. 
b The results of an IFN-gamma release assay (ie, QuantiFERON-TB Gold Plus or T-SPOT) performed within 12 weeks of the 
Screening visit (if available) are acceptable, provided there is no reason to suspect any re-exposure. 
c Should be performed after vital signs are collected. 
d Vital signs include systolic and diastolic blood pressure obtained after at least 5 minutes at rest in a seated position, heart 
rate, respiratory rate (breaths/min), and body temperature. Height will be measured at Screening only. 
e A focused physical examination should be performed. A focused physical examination should always include assessment of 
head, ears, eyes, nose, throat, lungs, heart, abdomen, skin, and extremities. 
f Additional assessments, (eg, ECG or chest radiograph) should be performed as needed to fully obtain information needed for 
the BILAG 2004 Index and and/or SLEDAI-2K assessments. Assessments at Screening should be compared to previous 
lupus disease and medical history, as appropriate.  
g FSH testing does not have to be repeated if performed within 12 weeks prior to Screening (eg, re-Screening). 
h Includes human immunodeficiency virus testing, hepatitis B testing (hepatitis B surface antigen and hepatitis core antibody 
[HBcAb] with reflex DNA testing), and hepatitis C virus antibody testing. Participants who are HBcAb positive with a 
negative hepatitis B virus (HBV) DNA at Screening will be tested every 3 months for HBV DNA. To remain eligible for 
the study, the participant’s HBV DNA levels must be confirmed to remain below the lower limit of quantitation as per 
the central laboratory. Serum virology does not have to be repeated if performed within 12 weeks prior to Screening (eg, 
re-Screening). 
i Refer to Table 5 for a list of routine laboratory assessments.  
j Urine collection can be postponed for up to 14 days in women with menstrual bleeding or a urinary tract infection at the 
scheduled visit. 
k Haptoglobin will be collected during Screening but will only be tested if needed to confirm suspected hemolytic anemia. 
l Questionnaires are strongly recommended to be completed before any other procedures are performed. 


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Table 3 
Schedule of Assessments During the Treatment Period  
Study Day 
1 
29 
57 
85 
113 
141 
169 
197 
225 
253 
281 
309 
337 
Visit Window (± days) 
- 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
Study Week 
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48/ET 
Visit Number 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
General Assessments/Procedures 
12-lead ECG (after 10 minutes rest in supine position) a 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
Vital signs and weight b 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examination c 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
BILAG 2004 assessments, SLEDAI-2K, CLASI, PGA, and Joint 
Count d 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Eligibility review e 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
Laboratory Assessments  
Pregnancy (urine) test f 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Hepatitis B DNA testing g 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Routine hematology and chemistry h 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
HbA1c 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
Lipids (after an 8-hour fast; water allowed) i 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
Urinalysis and spot UPCr (aim to collect urine sample at same time 
of day, if possible) j 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Confirmatory tests for hemolytic anemia and active APS k  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Anticardiolipin antibodies (IgG, IgA, IgM) 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Anti-β2GP1 antibody  
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Lupus anticoagulant l 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
C3 and C4 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Table 3 
Schedule of Assessments During the Treatment Period  
Study Day 
1 
29 
57 
85 
113 
141 
169 
197 
225 
253 
281 
309 
337 
Visit Window (± days) 
- 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
Study Week 
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48/ET 
Visit Number 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
PT/INR and PTT 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
Serum IgA, IgG, and IgM 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
hs-CRP 
X 
 
 
X 
 
 
X 
 
 
X 
 
 
X 
pDC FACS 
X 
X 
X 
X 
 
X 
X 
 
X 
X 
 
X 
X 
Whole blood transcriptomics 
X 
X 
 
X 
 
 
X 
 
 
X 
 
 
X 
PBMC cytometry 
X 
 
 
 
 
 
X 
 
 
 
 
 
X 
VIB7734 PK (serum) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Questionnaires m 


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Table 3 
Schedule of Assessments During the Treatment Period  
Study Day 
1 
29 
57 
85 
113 
141 
169 
197 
225 
253 
281 
309 
337 
Visit Window (± days) 
- 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
Study Week 
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48/ET 
Visit Number 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
Investigational Product Administration 
IP administration 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 
Safety 
Local injection tolerability 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
AEs, SAEs, and/or AESIs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
 AE: adverse event; AESI: AE of special interest
APS: antiphospholipid syndrome; β2GP1: β2-
glycoprotein 1; BILAG: British Isles Lupus Assessment Group; C: complement;
 CLASI: Cutaneous Lupus Erythematosus Disease Area and Severity Index: ECG: electrocardiogram; ET: 
Early Termination; FACS: fluorescence-activated cell sorting; 
HbA1c: glycosylated hemoglobin; hs-CRP: high-sensitivity C-reactive protein; Ig: immunoglobulin;
INR: international 
normalized ratio; IP: investigational product;
PBMC: peripheral blood mononuclear cells; pDC: plasmacytoid dendritic 
cell; PGA: Physician Global Assessment;
 PK: pharmacokinetic(s); 
PT: prothrombin time;
PTT: partial thromboplastin time;
 SAE: serious AE;
SLEDAI-
2K: Systemic Lupus Erythematosus Disease Activity Index 2000;
UPCr: urine protein:creatinine ratio; X: to be performed. 
All collections and assessments should be performed predose on days when IP is administered, unless otherwise specified. 
a Should be performed after vital signs are collected. 
b Vital signs include systolic and diastolic blood pressure obtained after at least 5 minutes at rest in a seated position, heart rate, respiratory rate (breaths/min), 
and body temperature. 
c A focused physical examination should be performed at all visits, except during the Baseline (Day 1), Week 48, or Early Termination visits. A focused 
physical examination should always include assessment of head, ears, eyes, nose, throat, lungs, heart, abdomen, skin, and extremities. 
d Additional assessments, (eg, ECG or chest X-ray) should be performed as needed to fully obtain information needed for the BILAG and and/or SLEDAI-2K 
assessments. 
e Participant eligibility (based on Screening assessments, including non–laboratory-based assessments at Baseline [Day 1] as per the inclusion and exclusion 
criteria [Section 5]) must be checked again on Day 1 prior to Randomization. 
f Women of childbearing potential as defined in Inclusion Criteria #8.   
g Reflex DNA testing if isolated hepatitis B core positive at Screening. 


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Table 3 
Schedule of Assessments During the Treatment Period  
Study Day 
1 
29 
57 
85 
113 
141 
169 
197 
225 
253 
281 
309 
337 
Visit Window (± days) 
- 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
3 
Study Week 
0 
4 
8 
12 
16 
20 
24 
28 
32 
36 
40 
44 
48/ET 
Visit Number 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12 
13 
14 
h Refer to Table 5 for a list of routine laboratory assessments. 
i This visit recommended to occur in the morning. 
j Urine collection can be postponed for up to 14 days in women with menstrual bleeding or a urinary tract infection at the scheduled visit. 
k Serum aliquots will be used for the BILAG confirmatory tests, including haptoglobin if needed to confirm suspected hemolytic anemia, and anticardiolipin 
antibodies (IgG, IgA, and IgM) and anti-β2GP1 antibody if needed to confirm suspected APS.  
l If an active manifestation of APS is suspected, the lupus anticoagulant should be collected and tested at all relevant study days, in addition to those already 
indicated in the schedule of assessments during the Treatment period. 
m Questionnaires are strongly recommended to be completed before any other procedures are performed. 


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Table 4 
Schedule of Assessments During the Safety Follow-Up Period  
Study Day 
365 
393 
Visit Window (± Days) 
7 
7 
Study Week 
52 
56 
Visit Number 
15 
16 
General Assessments 
12-lead ECG (after 10 minutes rest in supine position) a 
 
X 
Vital signs and weight b 
X 
X 
Physical examination c 
X 
X 
BILAG 2004 Index assessments, SLEDAI-2K, CLASI, PGA,
d 
X 
X 
Laboratory Assessments 
Pregnancy (urine) test e 
X 
X 
Hepatitis B DNA testing f 
 
X 
Routine hematology and chemistry g 
X 
X 
HbA1c  
 
X 
Lipids (after an 8-hour fast; water allowed) h 
 
X 
Urinalysis and spot UPCr (aim to collect urine sample at same time of day, if 
possible) i 
X 
X 
Confirmatory tests for hemolytic anemia and active APS j  
X 
X 
Anticardiolipin antibodies (IgG, IgA, and IgM) 
 
X 
Anti-β2GP1 antibody 
 
X 
Lupus anticoagulant k 
 
X 
C3 and C4 
X 
X 
PT/INR and PTT 
 
X 
Serum IgA, IgG, and IgM 
 
X 
hs-CRP 
X 
X 
pDC FACS 
X 
X 
PBMC cytometry 
 
X 
VIB7734 PK (serum)  
X 
X 
Questionnaires l 


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Table 4 
Schedule of Assessments During the Safety Follow-Up Period  
Study Day 
365 
393 
Visit Window (± Days) 
7 
7 
Study Week 
52 
56 
Visit Number 
15 
16 
Safety 
Concomitant medications 
X 
X 
AEs, SAEs, and/or AESIs 
X 
X 
AE: adverse event; AESI: AE of special interest; 
APS: antiphospholipid syndrome; β2GP1: β2-glycoprotein 1; BILAG: British Isles Lupus Assessment 
Group; C: complement; CLASI: Cutaneous Lupus Erythematosus Disease Area and Severity Index; 
 ECG: electrocardiogram; FACS: fluorescence-activated cell sorting; 
 
HbA1c: glycosylated hemoglobin; hs-CRP: high-sensitivity C-reactive protein;
Ig: immunoglobulin; INR: international normalized ratio;
 PBMC: 
peripheral blood mononuclear cells; pDC: plasmacytoid dendritic cell; PGA: Physician Global Assessment; 
 PK: pharmacokinetic(s); PT: prothrombin time; 
 PTT: partial thromboplastin time; SAE: serious AE; SLEDAI-2K: Systemic Lupus 
Erythematosus Disease Activity Index 2000; UPCr: urine protein:creatinine ratio; X: to be performed., Safety 
Follow-Up visits will be conducted at 4 and 8 weeks after the last dose of investigational product (IP) for 
participants who have completed the 48-week Treatment period. These assessments, however, will not be 
performed on participants who enter the long-term extension study.   
Participants who permanently discontinue IP at any point in the study but who do not withdraw consent of study 
participation will complete all study visits through Study Week 48/ET and at least 12 weeks follow up after 
the last dose of IP. Participants who permanently discontinue IP at any point in the study and who do 
withdraw consent of study participation will only complete the Study Week 48/ET assessments (if they agree 
to do so before withdrawing consent). 
a Should be performed after vital signs are collected. 
b Vital signs include systolic and diastolic blood pressure obtained after at least 5 minutes at rest in a seated 
position, heart rate, respiratory rate (breaths/min), and body temperature.  
c A focused physical examination should be performed. A focused physical examination should always include 
assessment of head, ears, eyes, nose, throat, lungs, heart, abdomen, skin, and extremities.  
d Additional assessments, (eg, ECG, or chest radiograph) should be performed as needed to fully obtain 
information needed for the BILAG 2004 Index and and/or SLEDAI-2K assessments. 
e Women of childbearing potential as defined in Inclusion Critertia #8. 
f Reflex DNA testing if isolated hepatitis B core positive. 
g Refer to Table 5 for a list of routine laboratory assessments. 
h This visit recommended to occur in the morning. 
i Urine collection can be postponed for up to 14 days in women with menstrual bleeding or a urinary tract 
infection at the scheduled visit. 
j Serum aliquots will be used for the BILAG confirmatory tests, including haptoglobin if needed to confirm 
suspected hemolytic anemia, and anticardiolipin antibodies (IgG, IgA, and IgM) and anti-β2GP1 antibody if 
needed to confirm suspected APS. 
k If an active manifestation of APS is suspected, the lupus anticoagulant should be collected and tested at both 
Study Days 365 and 393. 
l Questionnaires are strongly recommended to be completed before any other procedures are performed. 


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6.3 
Description of Study Assessments and Procedures  
A laboratory manual will be provided to the sites that specifies the procedures for collection, 
processing, storage, and shipment of samples, as well as laboratory contact information, specific 
to this clinical research study.  
6.3.1 
Screening and Randomization Procedures  
All candidates for enrollment will sign an ICF prior to any protocol-related procedures, including 
Screening activities. Informed consent must be obtained by the PI or a designee, such as an 
appropriately qualified sub-Investigator. The informed consent process should be documented. 
Storage and future testing of blood samples will be conducted for participants who sign an 
additional optional consent. 
All Screening procedures listed in Table 2 will be performed within 28 days prior to IP 
treatment. The Screening period may be increased by 2 weeks, under exceptional circumstances 
such as delayed laboratory results or the impact of COVID-19, and upon approval by the 
Medical Monitor. Once Screening assessments are complete, all necessary laboratory results 
required to confirm eligibility are reported, and Medical Monitor eligibility review is complete, a 
participant may be randomized.  
After signing the ICF, each participant will be assigned a subject identification number (SID) 
that will be used on all participant documentation. SIDs will be assigned in ascending sequential 
order. Rescreened participants will receive a new SID.  
On Day 1, the Investigator will confirm that all eligibility criteria still are fulfilled prior to 
Randomization, including that the SLEDAI-2K eligibility criteria (Section 5.1; Item 5), OGC 
dose, and dose and route of other permitted immunosuppressants have been stable during the 
Screening period as defined in the eligibility criteria [Section 5]). 
Randomization will be stratified by SLEDAI-2K score at Screening (≥ 10 or < 10) and 
prednisone or equivalent OGC dose at Baseline (Day 1) (≥ 10 mg or < 10 mg). Stratification is 
implemented in order to minimize risk for Baseline imbalances across treatment groups on 
disease activity and OGC dose/use. Baseline imbalances of disease activity and OGC dose/use 
impact efficacy and/or safety assessments of VIB7734 versus placebo. 
6.3.2 
Efficacy Assessments  
Efficacy measurements will be made at the times indicated in Section 6.2; refer to Table 2, 
Table 3, and Table 4 for Screening, treatment, and follow-up assessments and procedures. 
6.3.2.1 
Training Provision and Requirements  
The Sponsor or designee will provide necessary training to instruct the Investigators, study 
coordinators, and other applicable site staff to ensure appropriate study conduct. This training 
will include information on the protocol, study procedures including completion of the lupus 
assessments, the completion of the case report forms (CRFs), and other identified training topics. 
Training will include printed training materials, online videos and formal presentations, as well 
as web-based training modules. Required trainings will be documented in the Site Training Plan. 
All assessments and certifications must be renewed prior to expiration. If there is a change in site 
personnel over the course of the study, new Investigators or physicians must complete all the 


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required training prior to performing study procedures. Documentation of completed training 
will be filed in the Investigator Site File and the Trial Master File. 
6.3.2.1.1 
Collection of Efficacy Assessments and Lupus Assessment Completion and 
Review Process  
Appropriately trained and qualified Investigators will complete the lupus assessments, including 
but not limited to, the BILAG 2004 Index, SLEDAI-2K, CLASI, 
 The 
SLEDAI-2K, BILAG 2004 Index, PGA, and CLASI must be administered by the Investigator or 
appropriately qualified physician, unless prior Sponsor approval has been obtained for any other 
clinically trained site personnel with documentation of adequate assessment experience.
 The PI retains overall responsibility for the accuracy of 
the collected data. The lupus assessments will be reviewed centrally by a team designated by the 
Sponsor to ensure appropriate disease activity level at study entry and accurate completion and 
consistency in scoring throughout the study Treatment period.  
Assessment scores will be programmatically derived and reviewed centrally. Additional 
information regarding programmatic calculation including any data imputation considerations 
will be detailed in the statistical analysis plan (SAP). 
Prior to Randomization, the Sponsor or designee Medical Monitor will confirm the Investigator’s 
assessment of participant eligibility based on specified data to be reviewed centrally. This 
confirmation must be obtained prior to Randomization. If the central review team does not agree 
on participant disease activity level for eligibility, the Sponsor and/or an external unbiased 
consultant may be consulted for input. The PI retains responsibility for final confirmation of 
participant eligibility based on all specified study entry criteria. 
6.3.2.2 
Systemic Lupus Erythematosus Efficacy Assessments  
6.3.2.2.1 
Systemic Lupus Erythematosus Disease Activity Index 2000  
The SLEDAI-2K index consists of a list of organ manifestations, each with a definition. A 
certified Investigator or designated physician will complete the SLEDAI-2K assessment and 
decide whether each manifestation is “present” or “absent” within the last 4 weeks. The 
assessment also includes the collection of blood and urine for assessment of the laboratory 
categories of the SLEDAI-2K. 
The SLEDAI-2K assessment consists of 24 lupus-related items. It is a weighted instrument, in 
which descriptors are multiplied by an organ’s “weight”. For example, renal descriptors are 
multiplied by 4 and CNS descriptors by 8; these weighted organ manifestations are totaled into 
the final score. The SLEDAI-2K scores are valid, reliable, and sensitive clinical assessments of 
lupus disease activity. The SLEDAI-2K, calculated using a timeframe of 30 days prior to a visit 
for clinical and laboratory values, has been shown to be like the SLEDAI-2K with a 10-day 
window (Touma et al, 2010). A timeframe of 28 days (± allowed visit window) will be used in 
this study. 


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6.3.2.2.2 
British Isles Lupus Assessment Group 2004 Index  
The BILAG 2004 Index is a translational index with 9 systems (General, Mucocutaneous, 
Neuropsychiatric, Musculoskeletal, Cardiorespiratory, Gastrointestinal, Ophthalmic, Renal, and 
Hematology) that can capture the changing severity of clinical manifestations. It has ordinal 
scales by design and does not have a global score; rather it captures disease activity across the 
different systems at a glance by comparing the immediate past 4 weeks to the 4 weeks preceding 
them. It is based on the principle of physicians’ intention to treat and categorizes disease activity 
into 5 different levels, from A to E: 
x Grade A represents very active disease requiring immunosuppressive drugs and/or a 
prednisone dose of > 20 mg/day or equivalent. 
x Grade B represents moderate disease activity requiring a lower dose of GCs, topical GCs, 
topical immunosuppressives, antimalarials, or NSAIDs. 
x Grade C indicates mild stable disease. 
x Grade D implies no disease activity, but the system has previously been affected. 
x Grade E indicates no current or previous disease activity. 
Although the BILAG 2004 Index was developed based on the principle of intent to treat, the 
treatment has no bearing on the scoring index. Only the presence of active manifestations 
influences the scoring. 
6.3.2.2.3 
Physician Global Assessment  
A trained and certified Investigator will complete the PGA after all laboratory tests have been 
reviewed. The PGA represents the physician’s overall assessment of average SLE disease 
severity on a VAS with 0 (no disease) to 3 (severe) disease activity over the previous 4 weeks. 
The PGA for a given participant should be completed by the same physician whenever possible. 
The PGA is a modification of the classic analog scale in that it is anchored with numbers from 0 
to 3 demarcating no, mild, moderate, and severe disease. The number 3 indicates severe disease 
and is at the end of the scale. This refers to the most severe disease possible; it does not reflect 
the most severe disease observed in a particular participant, but the most severe disease ever 
observed in all SLE participants. Therefore, the line made along this scale by the physician 
should virtually never approach this edge. Any disease rated greater than 2.5 is very severe. The 
range of moderate disease covers approximately 1.5 to 2.4. Mild disease falls below 1.5. The 
instrument is like a logarithmic scale, with greater distances or demarcations possible among 
more mild-moderate symptoms. 
When scoring the PGA, the score from the previous visit should be reviewed and the mark 
should be moved relative to the score from the previous visit. This is a global assessment, 
factoring in all aspects of the participant’s lupus disease activity. It should not reflect non-lupus 
medical conditions.  


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6.3.2.2.4 
Lupus Low Disease Activity State  
The Lupus Low Disease Activity State (LLDAS) is a composite measure of SLE disease activity 
that has been utilized in clinical trials (Franklyn et al, 2016). LLDAS is defined and measured by 
attaining all the following 5 criteria:  
1. SLEDAI-2K ≤ 4, with no activity in major organ systems (renal, CNS, cardiopulmonary, 
vasculitis, fever) and no hemolytic anemia or gastrointestinal activity,  
2. No new lupus disease activity compared with the previous assessment (SLEDAI-2K),  
3. PGA ≤ 1 (scale 0 to 3), 
4. A current prednisone (or equivalent) dose ≤ 7.5 mg daily, and 
5. Well-tolerated standard maintenance doses of immunosuppressive drugs and approved 
biological agents (Franklyn et al, 2016). 
6.3.2.2.5 
Oral Glucocorticoid Reduction  
Refer to Section 7.4.3.2.2 for all information regarding OGC tapering. 
6.3.2.2.7 
Cutaneous Lupus Erythematosus Disease Area and Severity Index  
The CLASI is a validated index used for assessing the cutaneous lesions of SLE and consists of 
2 separate scores: the first summarizes the inflammatory activity of the disease; the second is a 
measure of the damage done by the disease. The activity score considers erythema, 
scale/hypertrophy, mucus membrane lesions, recent hair loss, and non-scarring alopecia. The 
damage score represents dyspigmentation, scarring/atrophy/panniculitis, and scarring of the 
scalp. Participants are asked if their dyspigmentation lasted 12 months or longer, in which case 
the dyspigmentation score is doubled. Each of the above parameters is measured in 13 different 
anatomical locations, included specifically because they are the most often involved in CLE. The 
most severe lesion in each area is measured. 


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6.3.3 
Safety Assessments  
Key safety assessments are AEs, AEs of special interest (AESIs), vital signs, physical 
examinations, safety laboratory tests, and ECGs. Safety assessments will be performed at the 
visits specified in Section 6.2; refer to Table 2, Table 3, and Table 4 for Screening, treatment, 
and follow-up assessments and procedures. 
6.3.3.1 
Adverse Events  
AEs, SAEs, and AESIs are defined in Section 8.1. Recording of AEs is described in Section 8.2 
and reporting of SAEs and AESIs is described in Section 8.3. 
6.3.3.2 
Vital Signs  
Vital signs, blood pressure (mmHg), pulse rate (beats/min), respiratory rate (breaths/min), body 
temperature (ºC), and body weight (kg) will be obtained at Screening, treatment, and follow-up 
as outlined in Table 2, Table 3, and Table 4 using clinically acceptable methods and devices as 
defined in the schedule of assessments. Vital signs should be measured in a seated position 
having rested in this position for at least 5 minutes before each reading and, when possible, 
should be taken before any blood draws. Prior to and after IP administration, vital signs should 
be checked as follows:  
x Within 15 minutes prior to administration of IP (within 30 minutes for Week 24 due to 
the ECG requirements).  
x Every 30 minutes (± 5 minutes) for 60 minutes after administration or until stable, 
whichever is later (for the first 2 study visits only).  
If anaphylaxis or a hypersensitivity reaction occurs after the SC administration of IP, vital signs 
will be taken more frequently, based on Investigator judgment and as warranted by the severity 
of the reaction (Appendix 1). 
6.3.3.3 
Physical Examination  
Body height will be collected at Screening only. Participants will be weighed at each study visit. 
Medically significant changes from the Screening physical examination will be recorded as AEs, 
unless they are considered a manifestation of SLE and captured on the BILAG 2004 Index, 
SLEDAI-2K, or CLASI. 
A focused physical examination should be performed at all visits, except for Baseline (Day 1) 
and Week 48 (Day 337)/Early Termination visits, where a complete physical examination should 
be performed.  


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A focused physical examination should always include assessment of head, ears, eyes, nose, 
throat, lungs, heart, abdomen, skin, and extremities. A complete physical examination should 
include all organ systems; a genital, rectal, and breast examination can be omitted from the 
complete physical examination unless clinically indicated. 
6.3.3.4 
Electrocardiogram  
A computerized 12-lead ECG will be performed at the visits specified in Section 6.2; refer to 
Table 2, Table 3, and Table 4 for Screening, treatment, and follow-up assessments and 
procedures. The Investigator or a qualified designee will review and indicate if the ECG is 
normal, abnormal but not clinically significant, or abnormal and potentially clinically significant. 
The ECG should be performed after vital signs are examined and after 10 minutes at rest in a 
supine position.  
6.3.3.5 
Chest X-Ray  
A chest X-ray will be performed at Screening. Results of a chest X-ray (posterior-anterior, 
anterior-posterior, and lateral views) performed within 12 weeks of the Screening visit (if 
available) are acceptable, provided there is no reason to suspect any clinical changes. If 
performed at Screening, posterior-anterior and lateral views should be evaluated, unless where 
prohibited by local health authority. Magnetic resonance imaging or computed tomography scans 
of the chest performed within 12 weeks of the Screening visit are acceptable. 
6.3.3.6 
Tuberculosis Assessment  
A blood test for TB will be performed at Screening using the IGRA test (ie, QuantiFERON-TB 
Gold Plus or T-SPOT). Evaluation of all participants by IGRA test will be performed by the 
central clinical laboratory. Results of an IGRA test performed at a local laboratory within 12 
weeks of the Screening visit (if available) are acceptable, provided there is no reason to suspect 
any re-exposure.  
6.3.4 
Clinical Laboratory Assessments  
All clinical laboratory tests will be performed at a central laboratory at the visits specified in 
Section 6.2; refer to Table 2, Table 3, and Table 4 for Screening, treatment, and follow-up 
assessments and procedures. Urgent safety labs should be performed at the central laboratory, if 
possible. If urgent results are needed, testing can be sent to a local laboratory, but blood for the 
same tests should be sent to the central laboratory as well, if possible. 
A serum pregnancy test (in women of childbearing potential as defined in Inclusion Criteria #8) 
will be performed at Screening at the central laboratory. Urine pregnancy tests will be performed 
in women of childbearing potential during treatment and follow-up at the site using a dipstick. 
Abnormal safety laboratory results should be repeated as clinically indicated, as soon as possible 
(preferably within 24 to 48 hours). 
Additional safety samples may be collected as clinically indicated at the discretion of the 
Investigator. 
Every attempt should be made to redraw any missing safety laboratory tests, even if the 
participant has received the IP. 


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The Investigator should assess the available results with regards to clinically relevant 
abnormalities.  
For suspected hemolytic anemia, a haptoglobin level should be tested, if needed, for 
confirmation. For suspected APS, anticardiolipin antibodies (IgG, IgA, IgM), anti-β2-
glycoprotein 1 antibody, and lupus anticoagulant should be tested.  
The laboratory results should be signed and dated and retained at the site as source data for 
laboratory variables.  
Clinical laboratory tests are presented in Table 5. 
Table 5 
Clinical Laboratory Tests  
Immunology 
x Anticardiolipin antibodies (IgG, IgA and IgM) 
x Anti-β2GP1 antibody 
x C3 and C4 
x Lupus anticoagulant 
x Rheumatoid factor 
Hematology and Coagulation 
x Hemoglobin 
x Hematocrit 
x Mean corpuscular hemoglobin concentration 
x Mean corpuscular volume 
x Platelet count 
x PT/INR and PTT 
x RBC count 
x Reticulocyte count 
x WBC with differential 
Pregnancy Tests 
x Serum β-hCG a 
x Serum FSH a 
x Urine dipstick β-hCG b 
Other Laboratory Tests 
x Haptoglobin 
x HbA1c 
x Hs-CRP 
x Lipids (TC, TG, HDL-C, and LDL-C) 
x pDC 
x Serum IgG, IgA, and IgM 
Serum Chemistry 
x Albumin 
x ALT 
x ALP 
x AST 
x Bicarbonate 
x Blood urea nitrogen 
x Calcium 
x Creatinine 
x eGFR 
x GGT 
x Glucose 
x Potassium 
x Sodium 
x Total bilirubin 


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Table 5 
Clinical Laboratory Tests  
x Chloride 
x Creatine kinase 
x Total protein 
Serum Virology 
x HBcAb (reflex DNA testing if isolated hepatitis 
B core positive) 
x Hepatitis B surface antigen 
x Hepatitis C antibody 
x HIV 
Urinalysis 
x Dipstick 
 
Appearance 
 
Bilirubin 
 
Blood 
 
Color 
 
Epithelial cells 
 
Glucose 
 
Ketones 
 
Leukocyte esterase 
 
pH 
 
Protein 
 
Specific gravity 
x Microscopy, including WBC/HPF, RBC/HPF, and 
casts 
x Urine creatinine and protein; spot UPCr 
ALP: alkaline phosphatase; ALT: alanine aminotransferase;
AST: aspartate 
aminotransferase; β2GP1: β2-glycoprotein 1; β-hCG: beta-human chorionic gonadotropin; C: complement; 
 eGFR: estimated; glomerular filtration rate; FSH: follicle-stimulating 
hormone; GGT: gamma glutamyl transferase; HbA1c: glycosylated hemoglobin; HBcAb: hepatitis B core 
antibody; HDL-C: high-density lipoprotein-cholesterol; HIV: human immunodeficiency virus; HPF: high-
power field; hs-CRP: high-sensitivity C-reactive protein; Ig: immunoglobulin; INR: international normalized 
ratio; LDL-C: low-density lipoprotein-cholesterol; pDC: plasmacytoid dendritic cell; PT: prothrombin time; 
PTT: partial thromboplastin time; RBC: red blood cell;
TC: total cholesterol; TG: triglycerides; 
UPCr: urine protein:creatinine ratio; WBC: white blood cell.  
a At Screening only. 
b At every visit post-Screening. 
6.3.5 
Pharmacokinetic Assessments  
Serum for PK analysis will be collected at the visits specified in Table 3 and Table 4 and 
analyzed using a validated bioanalytical method. 
6.3.6 
Immunogenicity Assessments  
6.3.7 
Pharmacodynamic Assessments  
Whole blood will be collected for the assessment of pDC levels by flow cytometry at the visits 
specified in Table 3 and Table 4. VIB7734 binds to ILT7 on the surface of pDCs leading to 


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recruitment of macrophages and NK cells, thus inducing apoptosis and reduction in the number 
of pDCs.  
6.3.8 
Exploratory Biomarker Evaluation  


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6.4 
Discontinuation of Investigational Product, Unscheduled Visits, Withdrawal From 
Study, and Loss to Follow-up  
6.4.1 
Discontinuation of Investigational Product  
An individual participant will not receive any further IP if any of the following occur in the 
participant: 
x Receipt of any medications in Section 7.4.2.1. 
x A Grade 3 or higher allergic reaction to the IP. 
x A Grade 3 or higher infection considered related to the IP.  
x Other AE that contraindicates further dosing in the opinion of the Investigator and/or the 
Sponsor, Medical Monitor, and/or the Safety Data Monitoring Committee (SDMC). 
x Withdrawal of consent from further treatment with IP. 
x Participant is determined to have met one or more of the exclusion criteria or failed to 
meet all the inclusion criteria for study participation and there is a potential safety risk 
associated with continuation identified upon consultation with the Medical Monitor. 
x Pregnancy or a decision to become pregnant. 
x Any of the following liver function abnormalities: 
 ALT or AST 侔 8× ULN. 
 ALT or AST 侔 5× ULN for more than 2 weeks. 
 ALT or AST 侔 3× ULN and total bilirubin 侔 2× ULN or international normalized 
ratio 侔 1.5 without alternative explanation. 


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 ALT or AST ≥ 3× ULN with the appearance of fatigue, nausea, vomiting, right upper 
quadrant pain or tenderness, fever, rash, and/or eosinophilia (≥ 5%). 
Participants who are permanently discontinued from receiving IP will be followed for protocol-
specified assessments including follow-up of any AEs unless consent is withdrawn specifically 
from further study participation (as defined in Section 6.4.3), or the participant is lost to follow-
up (Section 6.4.4). 
6.4.2 
Unscheduled Visits  
An Unscheduled Visit should be performed if a participant complains of worsening SLE 
symptoms, use of OGC outside of study-permitted doses, necessity to repeat a blood 
test/evaluation, evaluation of an AE, or any situation which, in the opinion of the Investigator, 
requires an evaluation. Clinically indicated relevant and necessary assessments should be 
performed during Unscheduled Visits, including assessment of concomitant medications and 
AEs, as appropriate. 
6.4.3 
Withdrawal From Study 
Participants are free at any time to withdraw from the study (IP and assessments), without 
prejudice to further treatment (withdrawal of consent). Such participants will always be asked 
about the reason(s) for withdrawal and the presence of any AEs. AEs will be followed-up. 
Participants who permanently discontinue IP at any point in the study but who do not withdraw 
consent of study participation will complete all study visits through Study Week 48/ET and at 
least 12 weeks follow up after the last dose of IP. Participants who permanently discontinue IP at 
any point in the study and who do withdraw consent of study participation will only complete the 
Study Week 48/ET assessments (if they agree to do so before withdrawing consent). 
If a participant withdraws consent to participation in the study, then no further study visits or 
data collection should take place. Further details concerning use of samples collected during the 
study from a participant that withdraws consent are provided in Section 10.6. 
6.4.4 
Participants Lost to Follow-up  
Participants will be considered lost to follow-up only if no contact has been established by the 
time the study is completed and such that there is insufficient information to determine the 
participant’s status at Day 393/Visit 16. A participant is considered lost to follow-up when 
3 documented attempts at contact (with one documented attempt being registered letter/certified 
mail) are unsuccessful: 
x Registered letter/certified mail. 
x Phone calls, text messages, or emails. 
x Consulting publicly available sources, if allowed by local regulations, to determine the 
status of the participant. 
“Lost to follow-up” as a reason for study discontinuation must be documented by time and date 
of telephone calls, emails, text messages, numbers called, individuals spoken to if not the 
participant, documentation that a certified/registered letter was sent, and documentation of 
publicly available sources that were consulted. 


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6.5 
Study Suspension or Termination  
The Sponsor reserves the right to suspend or terminate this study at any time. The reasons for 
suspending or terminating the study may include, but are not limited to, the following: 
x The incidence or severity of AEs in this or other studies indicates a potential health 
hazard to participants. 
x Participant enrollment is unsatisfactory. 
x Noncompliance that might significantly jeopardize the validity or integrity of the study. 
x Sponsor decision to terminate development. 
If the Sponsor determines that temporary suspension or termination of the study is required, the 
Sponsor will discuss the reasons for taking such action with all participating Investigators. When 
feasible, the Sponsor will provide advance notice to all participating Investigators of the 
impending action. 
If the study is suspended or terminated for safety reasons, the Sponsor will promptly inform all 
Investigators and/or institutions conducting the study. The Sponsor will also promptly inform the 
relevant regulatory authorities of the suspension/termination along with the reasons for such 
action. Where required by applicable regulations, the Investigator must inform the Institutional 
Review Board (IRB) or Independent Ethics Committee (IEC) promptly and provide the reason(s) 
for the suspension/termination. If the study is suspended for safety reasons and it is deemed 
appropriate by the Sponsor to resume the study, approval from the relevant regulatory authorities 
(and IRBs/IECs when applicable) will be obtained prior to resuming the study. 
6.6 
End of Study  
An individual participant will be considered to have completed the study if the participant was 
followed through the last protocol-specified visit, regardless of the number of doses of IP that 
was received. 
Participants will be considered not to have completed the study if consent was withdrawn 
(Section 6.4.3) or the participant was lost to follow-up (Section 6.4.4). 
The end of the study (“study completion”) is defined as the date of the last protocol-specified 
visit/assessment for the last participant in the study. 


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7 
STUDY INTERVENTIONS  
7.1 
Description of Investigational Products  
Table 6 provides a description of the IP to be used in the study. 
Table 6 
Description of Investigational Products and Dosing  
Product 
Concentration and Formulation as Supplied 
Manufacturer 
VIB7734 
Supplied as a 2R vial with nominal 1 mL of 100 mg/mL 
VIB7734 containing
 mM L-histidine/L-histidine 
HCl,
mM sucrose,
% (w/v) PS 80, pH
Berkshire Sterile Manufacturing, 
Inc. 
Placebo 
Normal saline  
Commercially available 
PS: polysorbate; w/v: weight per volume. 
7.1.1 
VIB7734 or Placebo  
7.1.1.1 
Investigational Product Inspection  
Each VIB7734 vial selected for dose preparation should be inspected. Any defects with the IP 
must be reported immediately to the Sponsor’s Quality Assurance Department and the site 
Monitor. The Sponsor’s Quality Assurance contact information for reporting product complaints 
is:
 During the investigation of the 
product complaint, all IP must be stored at labeled conditions unless otherwise instructed.    
7.1.1.2 
Investigational Product Storage  
VIB7734 should be stored at
. Labels will be prepared in accordance 
with Good Manufacturing Practice (GMP) and local regulatory guidelines. 
Each kit has a unique number that is printed on all labels within the kit (ie, the outer carton label 
and the label on the vial within the carton). 
7.1.1.3 
Investigational Product Dose Preparation  
Preparation of VIB7734 and preparation of the syringe for SC administration are to be performed 
by an unblinded pharmacist/IP manager using aseptic technique.  
VIB7734 is supplied as a sterile liquid in a 2R glass vial at a nominal fill volume of 1.0 mL, 
stoppered with a 13-mm elastomeric stopper, and sealed with flip-off cap overseal. Allow the 
kits to equilibrate to room temperature about 30 minutes prior to dose preparation.   
No incompatibilities between VIB7734 and plastic syringes (ie, polypropylene and 
polycarbonate) have been observed. 
VIB7734 does not contain preservatives and any unused portion must be discarded. Total in-use 
storage time from needle puncture of the IP vial to start of administration should not exceed 
4 hours at room temperature or 24 hours at
 If storage time exceeds 
these limits, a new dose must be prepared from new vials. 
If syringes containing IP have been stored at
 for any length of time, 
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This one-hour equilibrium period is included in the total room temperature hold time for 
prepared syringes, which must not exceed 4 hours. DO NOT FREEZE. 
A SC dose of 200 mg VIB7734 will be administered over 2 injections. To prepare each injection, 
withdraw 1 mL of IP into a 1-mL syringe using a 1½-inch needle. For SC dose administration, a 
27G ½-inch needle should be used. 
Normal saline will be used as placebo. The number and volume of placebo injections will match 
that of active drug. Saline (1 mL) should be drawn into each of two 1-mL syringes using a 1½-
inch needle. For SC dose administration, a 27G ½-inch needle should be used.  
7.1.1.4 
Investigational Product Dosing and Administration  
The first day of dosing is considered Day 1. To reduce the risk of unblinding the study personnel 
who will be evaluating the participant, IP will be administered by an unblinded pharmacist/IP 
Manager or a study site staff member who is not otherwise involved in the participant’s 
participation in the study. The IP administrator should be experienced in performing SC 
injections. The skin surface of the anterolateral thigh, upper outer triceps area, upper buttocks, or 
abdomen (avoiding a 2-inch [5 cm] radius around the umbilicus) should be prepared with an 
alcohol wipe and allowed to air dry. The skin will be pinched to isolate SC tissue from the 
muscle. The needle will be inserted at a 90-degree angle to the skin surface approximately 
halfway into the SC tissue. The prepared IP will be slowly injected (at least 5-second duration is 
recommended per 1 mL syringe) into the SC tissue using gentle pressure. The area should not be 
massaged after injection. The SC injection site can be changed during the study as per participant 
preference. 
The IP should NOT be administered if it has been at room temperature for more than 4 hours, or 
if it has been at
for more than 24 hours. 
7.1.1.5 
Monitoring of Dose Administration  
Participants should be monitored under direct observation for at least 60 minutes after the first 
and second doses of IP administration or until the participant is stable, whichever is longer. Vital 
signs should be measured as indicated in Section 6.3.3.2. 
As with any antibody, allergic reactions to dose administration are possible. Therefore, 
appropriate drugs and medical equipment to treat acute anaphylactic reactions must be 
immediately available, and study personnel must be trained to recognize and treat anaphylaxis. 
7.1.2 
Investigational Product Accountability  
Study site staff will maintain a record of the IP received, dispensed, administered, and destroyed. 
All records will be maintained with controlled access to unblinded Site, Sponsor, and contract 
research organization (CRO) Staff only. An unblinded Study Monitor will perform IP 
accountability and compliance monitoring during the study. A qualified study site staff member 
will only administer the study product to participants included in this study and according to 
procedures established in this study protocol. There is potential of unblinding of staff members 
who administer the study product, however, they will not be involved in any other parts of the 
study. Each administration of study product will be documented and transferred to the electronic 
CRF (eCRF). 


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7.1.3 
Investigational Product Handling and Disposal  
It is preferred that unused IP be destroyed at the site after accountability and approval to destroy, 
regardless of whether the study was completed or terminated prematurely, with agreement from 
the Sponsor. 
The Investigator may return any unused vials of VIB7734 to the Sponsor or designee. At the 
time of return, the Investigator must verify and the Study Monitor must confirm that unused or 
partially used study products have been returned and that no study products remain at the site. 
7.2 
Assessment and Verification of Compliance  
Site staff will administer the IP SC at the study center. The dose and date of administration of IP 
must be recorded in the participant’s medical/study record and eCRF. Treatment compliance will 
be assessed based on this information. 
7.3 
Treatment Assignment and Bias Minimization  
7.3.1 
Randomization Strategy and Procedure  
An interactive voice/web response system (IXRS) will be used for Randomization to a treatment 
group and assignment of IP kit numbers. A participant is considered randomized into the study 
when the Investigator or appropriate designee notifies the IXRS that the participant meets 
eligibility criteria and the IXRS provides the assignment of treatment group. 
Additional details are provided in the IXRS manual. 
7.3.2 
Extent and Maintenance of Blinding  
This is a double-blind study. IP handling and administration is managed to ensure proper 
blinding for the Sponsor and investigational site staff. Since VIB7734 and the placebo can be 
distinguished at the preparation step with potential for unblinding during administration, the IP 
will be prepared by an unblinded pharmacist/IP manager at the site. Because VIB7734 and 
placebo could be distinguished during administration, the IP will be administered by either the 
unblinded pharmacist/IP manager or site personnel who will not be involved in management of 
the study participants. To maintain blinding, participants randomized to VIB7734 Q12W SC 
dosing regimen will receive SC placebo injections on study visits outside the Q12W schedule.  
Neither the participant nor any of the Investigator or Sponsor staff who are involved in the 
treatment or clinical evaluation and monitoring of the participants will be aware of the treatment 
received. If treatment allocation for a participant becomes known to the Investigator or other 
study staff in the management of study participants, the Sponsor must be notified immediately. 
7.3.3 
Unblinding Procedures  
7.3.3.1 
Unblinding in the Event of a Medical Emergency  
In the event of a medical emergency, the Investigator may unblind an individual participant’s IP 
allocation. Instructions for unblinding an individual participant’s IP allocation are contained in 
the IXRS manual. In general, unblinding should only occur if management of the medical 
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the management of a medical emergency would be the same whether or not VIB7734 was 
received by the participant. If this was the case, the IP allocation should not be unblinded. 
7.3.3.2 
Unblinding for the Interim Analysis  
The interim analysis will be conducted after all participants have completed the Week 24 visit or 
discontinued early from the study. A small pre-specified number of Sponsor staff who are not 
directly involved in the conduct of the study will be unblinded for decision making purposes. 
Study site personnel, participants, and CRO and Sponsor personnel directly associated with the 
conduct of the study will remain blinded to the treatment assignment for individual participants 
and the results of the interim analysis until the completion of the study. 
7.4 
Restricted and Concomitant Medications and Treatments  
Any additional concomitant therapy that becomes necessary during the trial and any change to 
concomitant drugs must be recorded in the corresponding section of the eCRF, noting the name, 
dose, duration, and indication of each drug. 
7.4.1 
Medications Prohibited Prior to Screening or Randomization  
The treatments and therapies listed in Table 7 are not permitted prior to Screening or 
Randomization with specific usage washout periods provided for each treatment. Additionally, 
these treatments should not be used during the trial (with exceptions as noted for those therapies 
that are potentially permitted per Section 7.4.3.2). 


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7.4.3 
Permitted Medications  
7.4.3.1 
Concomitant Medications and Treatments  
All concomitant medications, from the time of the Screening visit, taken while the participant is 
participating in the study will be recorded on the eCRF. Participants must be instructed not to 
take any medications, including over-the-counter or herbal products or ayurvedic medications 
without first consulting the Investigator. 
Permitted medications (including rescue medications) are any medications required per the 
medical history and not specifically prohibited by the protocol during the trial (ie, from 
Screening to the end of the SFU period). Any such medications prescribed or used should be 
recorded in the eCRF. 
7.4.3.2 
Concomitant Medications for Systemic Lupus Erythematosus Standard of Care 
During the Study  
The SoC medications are part of the participant’s previous SLE treatment and, thus, will not be 
provided by the Sponsor. 
7.4.3.2.1 
Immunosuppressants  
All immunomodulator therapy for SLE given prior to Screening must have been kept stable or 
discontinued according to the specifications in the inclusion and exclusion criteria (Section 5) for 
a participant to be eligible for the study. These medications must remain stable during the 
Screening and Treatment periods except for OGC and NSAIDs, which can be adjusted as long as 
doses are consistent with the parameters as indicated in Sections 7.4.3.2.2 and 7.4.3.2.2.6, 
respectively. Background therapy may only be changed for documented safety issues. The 
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(Day 1) level if the toxicity/event resolves and if clinically indicated. Initiation of any new 
immunosuppressant or immunomodulator therapy or increase in dose above the Baseline (Day 1) 
level would be considered a treatment failure and may result in withdrawal of the participant 
from the IP (per Sponsor Medical Monitor discretion).  
7.4.3.2.2 
Glucocorticoids  
OGCs are permitted but not required for participation in the study as outlined in the inclusion 
criteria [Section 5.1]). OGCs other than prednisone may be used at equivalent PO doses (refer to 
Appendix 4). Investigators are required to decrease the OGC dose as much as tolerated by the 
participant starting at Week 4 up until Week 36 of the Treatment period, within the rules for dose 
changes outlined below. 
7.4.3.2.2.1 
Oral Glucocorticoid Tapering Guidance  
OGC tapering may be started at any time prior to Week 4 but must be started within 14 days 
after the Week 4 visit. On treatment days, tapering will start after all assessments have been 
completed and IP has been administered. Tapering can be started on the scheduled study visit 
day (eg, Week 4 Visit) based on clinical manifestations and the laboratory values from the 
previous visit. If laboratory values of the current visit show SLE activity consistent with 
Exception Rule 1 or 2 below, the tapering can be reversed. OGC tapering should be attempted 
until Week 36 to achieve the lowest possible OGC dose, including discontinuation of the OGC, 
if clinically feasible. Note that there is no change in OGC dose permitted between Week 20 and 
Week 24. Beginning at Week 4 and continuing through Week 36, tapering to an OGC dose of 
≤ 7.5 mg/day MUST be attempted at all visits in all participants with OGC dose of > 7.5 mg/day, 
unless at least one of the following criteria (Exception Rules) is met: 
1. SLEDAI-2K activity which is worsened compared to Baseline (Day 1) in major organ 
systems (renal, CNS, cardiopulmonary, vasculitis, fever, thrombocytopenia), hemolytic 
anemia, or increased gastrointestinal activity. 
2. Newly affected organ system(s) based on the SLEDAI-2K, excluding serological 
abnormalities (dsDNA antibodies, hypocomplementemia). 
3. Moderate to severe skin disease as reflected by a CLASI-A score ≥ 10. 
4. Moderate to severe arthritis as reflected by ≥ 8 tender and/or swollen joints. 
If OGC tapering is not attempted in an eligible participant, the Sponsor or Sponsor’s designee 
must be contacted immediately. An example of suggested OGC tapering regimen is provided in 
Appendix 5 as guidance for Investigators. However, due to variability in participant responses to 
OGC treatment and tolerability of taper, Investigators will have flexibility in how the OGC dose 
is reduced at each visit. 
Investigators will not be required to, but are encouraged to, taper OGC dose beyond the target of 
7.5 mg/day including discontinuation of OGC up to Week 36, if clinically feasible. Tapering will 
not be permitted after Week 36. A participant experiencing an increase in disease activity 
secondary to OGC tapering may increase the OGC dose up to a maximum of the Baseline 
(Day 1) OGC therapy dose between Week 4 up to Week 36. Participants who require an OGC 
dose above their Baseline (Day 1) level may continue in the study but could be considered 
nonresponders for subsequent assessments of disease activity. 


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7.4.3.2.2.2 
Steroid Burst and Taper – Week 0 (Day 1) to Week 12  
In order to allow adequate time for the IP to achieve significant clinical benefit, Investigators 
may administer one burst and taper of OGCs between and including Baseline (Day 1) and prior 
to Week 12 for increased SLE disease activity/non-SLE activity as outlined below.  
A GC burst is defined as receipt of only one of the following: 
x An OGC increase above Baseline (Day 1) up to a maximum daily dose of 40 mg/day 
prednisone (or equivalent) for up to a total of 14 days which must be fully administered 
and tapered to less than or equal to the Baseline (Day 1) dose by the end of the 14th day. 
Any course of OGC above the Baseline (Day 1) dose must not extend beyond Week 12, 
regardless of when the course was started. 
x Intramuscular methylprednisolone (≤ 80 mg) or equivalent administered as a single dose 
between Baseline (Day 1) and Week 10. 
x A maximum of 2 intra-articular/tendon sheath/bursal injections (for a total 
methylprednisolone dose of ≤ 80 mg or equivalent) can be given between Baseline 
(Day 1) and Week 10.  
Participants who receive more than one OGC burst and taper between Baseline (Day 1) and prior 
to Week 12, or who violate any of the criteria above, may continue in the study, but will be 
considered nonresponders for subsequent assessments of disease activity, regardless of whether 
the OGC burst was administered for increased SLE activity or non-SLE causes. 
7.4.3.2.2.3 
Increase in OGC from Week 12 to Week 36  
Between Week 12 and Week 36, an increase in OGC dose above Baseline (Day 1) dose for 
increased SLE activity is NOT allowed. A participant receiving an OGC dose above his or her 
Baseline (Day 1) dose after Week 12 for SLE may continue in the study but will be considered a 
nonresponder for subsequent assessments of disease activity.  
An increase in OGC above current dose for non-SLE causes (eg, asthma or chronic obstructive 
pulmonary disease exacerbation) is allowed ONCE either between Week 12 and Week 20 ahead 
of planned interim analysis time point at Week 24 OR between Week 24 (after all assessments 
complete) and Week 36. This might include a non-SLE OGC dose up to ≤ 20 mg/day of 
prednisone or equivalent for up to a total of 10 days. This will be captured as burst and taper not 
attributable to SLE. The non-SLE indication must be clearly indicated in the source documents. 
The increase must be fully administered and tapered to less than or equal to the dose used prior 
to the implementation of the increase by the end of the 10th day after initiating the OGC burst 
and by the Week 20 Visit day (if the increase is implemented between Week 12 and Week 20) or 
by the Week 36 Visit day (if the increase is implemented between Week 24 and Week 36).  
Participants who receive an increase in OGC for non-SLE causes at a dose of > 20 mg/day 
prednisone (or equivalent) OR above Baseline (Day 1) dose for > 10 days will be considered 
nonresponders for subsequent assessments of disease activity. If a participant receives > 40 mg 
prednisone or equivalent or a dose above Baseline (Day 1) level for more than 10 days, it must 
be reported to the Medical Monitor. The Medical Monitor will determine with the Sponsor if the 
participant may continue to receive IP based on the assessment of potential risk. 


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7.4.3.2.2.4 
Oral Glucocorticoids After Week 36  
No change in OGC is allowed after Week 36. Participants who receive an increase in their OGC 
dose above 7.5 mg/day or Baseline (Day 1) dose after Week 36 will be considered nonresponders 
for the primary and secondary outcome measures at Week 48.  
7.4.3.2.2.5 
Increase in Oral Glucocorticoids for Surgery and Prevention of Adrenal 
Insufficiency  
In addition to the burst and tapers described above, participants who are taking ≤ 7.5 mg/day 
prednisone or equivalent will be allowed to receive up to an additional 7.5 mg/day to a total of 
15 mg/day prednisone or equivalent for a total of up to 14 days or a single course of IV 
hydrocortisone (≤ 100 mg hydrocortisone followed by half that dose for 2 days before returning 
to their usual dose of OGC) for surgery or symptoms of adrenal insufficiency or GC withdrawal 
if clinically warranted from Baseline (Day 1) to Week 36. The non-SLE indication must be 
clearly indicated in the source documents. 
7.4.3.2.2.6 
Other  
For all enrolled participants, additional treatments given to participants with SLE are permitted 
during the study as follows: 
x Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers 
 If used at Screening, it is recommended that they be maintained at a stable dose 
during the trial, unless dose change, discontinuation, or initiation is required for 
documented safety reasons. 
x Anti-COVID therapeutic antibodies  
 If used during the study, the medical monitor must be notified immediately, and 
continuation of IP will be determined on a case by case basis.   
x Aspirin  
 Low-dose aspirin (≤ 350 mg/day) may be used for cardiovascular prophylaxis; this is 
permitted in addition to use of NSAID as specified below. 
x Osteoporosis Prophylaxis and treatment 
 Vitamin D and calcium supplementation, and if necessary, treatment of osteoporosis 
is allowed according to local SoC guidelines. These medications will not be supplied by 
the Sponsor. 
x Herbal supplements 
 May be continued during the study. It is strongly recommended that the dosages and 
preparations remain stable unless discontinued all together. It is recommended that no 
herbal supplements be initiated, or reinitiated once discontinued, during the study. 
x Medications for the treatment of injection site reactions 
 These are allowed and may include topical or systemic antihistamines, topical GCs, 
paracetamol, or NSAIDs. 


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x NSAIDs 
 Regularly prescribed NSAIDs may not be initiated during the 48-week Treatment 
period. 
 Participants taking a NSAID (including cyclooxygenase 2 inhibitors; topical, 
prescription, or over-the-counter) on a regular schedule for SLE symptoms at 
Randomization can continue to do so throughout the trial at a stable dose. 
 NSAIDs should not be taken on visit days until all assessments are complete. 
Participants may have the dose adjusted during the trial for documented toxicity/safety 
reasons. 
 Any NSAIDs (whether prescription, over-the-counter, or topical) should not be used 
above the maximum allowable doses per local labeling, and site should perform regular 
AE monitoring of these concomitant medications.  
 PRN NSAIDs not exceeding label-approved doses are permitted for SLE or non-SLE 
pain as required based on Investigator judgment for up to 10 consecutive days  Duration 
exceeding 10 consecutive days is considered chronic use.  
x Opioids 
 Up to 40 mg/day morphine-equivalent are permitted at stable dose if present at 
Screening. Initiation of opioids and/or prn (as needed) dosing of opioids after Screening 
for SLE is not permitted. These may be titrated off as tolerated during the study. 
Analgesics, including opiates, may be used at stable doses or prn (as needed) for 
temporary relief of symptoms not due to SLE, but then are strongly recommended to be 
avoided 24 hours prior to each trial visit. 
x Acetaminophen (paracetamol) 
 Short acting acetaminophen/paracetamol may be initiated or continued for pain 
control during the study at approved doses. Pain medications should not be used within a 
minimum of 6 to 12 hours (based on known duration of effect) of a scheduled visit. 
x Topical therapy for CLE 
 Concurrent use of topical therapy for CLE (eg, GCs, pimecrolimus) is permitted. 
Topical therapy must be the same being used in the 2 weeks prior to Screening and the 
dose and frequency of application must be stable during Screening.  During the study, 
topical therapy may be reduced or discontinued based on clinical manifestations and 
Investigator discretion. Should cutaneous skin manifestations reoccur, the same topical 
therapy may be resumed up to the Baseline (Day 1) dose. It is encouraged that no new 
dermatologic preparations be used for the duration of the study. It is also recommended 
that participants use sunscreen (list as concomitant medication for SLE) and avoid sun 
exposure during the study. Topical moisturizers are also permitted. 
Any medications (other than those prohibited by the protocol) that are considered necessary for 
the participants’ welfare and will not interfere with the trial medication may be given at the 
Investigator’s discretion. 


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8 
SAFETY DATA COLLECTION AND REPORTING  
The Investigator is responsible for the detection and documentation of events meeting the criteria 
and definition of an AE or SAE, as provided in the protocol. During the study when there is a 
safety evaluation, the Investigator or site staff will be responsible for detecting, documenting, 
and reporting AEs and SAEs as detailed in this section of the protocol. 
An external, independent SDMC will perform evaluations of safety data at specified regular 
intervals throughout the study and make recommendations to the Sponsor regarding further 
conduct of the study. See Section 11.1 for details on SDMC activities. 
8.1 
Definitions  
x Adverse event (AE) – An AE is any untoward medical occurrence associated with the 
use of an intervention in humans whether or not it is considered intervention-related. 
x Serious adverse event (SAE) – An event is considered “serious” if, in the view of either 
the Investigator or Sponsor, it results in any of the following outcomes:  
 Death 
 A life-threatening AE (An event is considered nlife-threatening| if, in the view of 
either the Investigator or Sponsor, its occurrence places the participant or participant at 
immediate risk of death. It does not include an AE or suspected adverse reaction that, had 
it occurred in a more severe form, might have caused death.) 
 Inpatient hospitalization or prolongation of existing hospitalization 
 A persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
 A congenital anomaly/birth defect 
 Important medical events that may not result in death, be life-threatening, or require 
hospitalization may be considered serious when, based upon appropriate medical 
judgment, they may jeopardize the participant or participant and may require medical or 
surgical intervention to prevent one of the outcomes listed in this definition. Examples of 
such medical events include allergic bronchospasm requiring intensive treatment in an 
emergency room or at home, blood dyscrasias or convulsions that do not result in 
inpatient hospitalization, or the development of drug dependency or drug abuse. 
x Adverse reaction – An adverse reaction is any AE caused by a drug. 
x Adverse event of special interest (AESI) – An AESI is an AE of scientific and medical 
interest specific to understanding of the IP and may require close monitoring and 
collection of additional information by the Investigator. An AESI may be serious or 
nonserious. 
 
The rapid reporting of AESIs allows ongoing surveillance of these events in order to 
characterize and understand them in association with the use of this IP. 
 
The following AESIs will be particularly monitored in this study: 
 Hypersensitivity reaction, including anaphylaxis. 
 Severe (Grade 3 or higher) viral infections/reactivations. 


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 Opportunistic infection listed in Appendix 3 (all cases). 
 Malignancy (except non-melanoma skin cancer). 
8.2 
Documenting Adverse Events  
Report initiation for all AEs and SAEs will begin from the time of signing ICF and continue up 
until the final study visit. All events will be followed to resolution or until they are considered as 
a non-clinically significant event. 
AEs reported by the participant, spontaneously or in response to an open question from the study 
personnel, and AEs revealed by observation will be recorded during the study at the 
investigational site.  
Clinically significant abnormalities in vital signs, body weight, physical examination, laboratory 
parameters, and ECGs will be recorded as separate AEs or SAEs if they are not considered as 
part of pre-existing medical conditions or have already been recorded due to other AEs or SAEs. 
Worsening or new manifestations of SLE (eg, those captured by SLEDAI-2K, BILAG 2004 
Index, or CLASI) do not have to be reported as AEs, unless they meet the criteria for a SAE. All 
AEs meeting criteria must be reported immediately.  
For each AE, the Investigator will evaluate and report the onset (date and time), resolution (date 
and time), severity, causality, action taken, serious outcome (if applicable), and whether it caused 
the participant to discontinue the study. The AE term should be reported in standard medical 
terminology when possible. 
8.2.1 
Causality or Relatedness  
The Investigator is required to provide an assessment of the relationship of AEs and SAEs to the 
IP. An event will be considered “not related” to use of IP if any of the following tests are met: 
x An unreasonable temporal relationship between administration of the IP and the onset of 
the event (eg, the event occurred either before, or too long after, administration of the IP 
for it to be considered IP related). 
x A causal relationship between the IP and the event is biologically implausible (eg, death 
as a passenger in an automobile accident). 
x A clearly more likely alternative explanation for the event is present (eg, typical adverse 
reaction to a concomitant drug and/or typical disease-related event). 
Individual AE/SAE reports will be considered “related” to use of the IP if the “not related” 
criteria are not met. 
“Related” implies that the event is considered to be “associated with the use of the drug” 
meaning that there is “a reasonable possibility” that the event may have been caused by the IP 
(ie, there are facts, evidence, or arguments to suggest possible causation). 
8.2.2 
Severity or Intensity  
The guidelines outlined in CTCAE v5.0 will be used for assessing the severity or intensity of the 
event. The general guidelines for assessing the AE grade are provided in Table 8. 


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Table 8 
CTCAE v5.0 General Guidelines  
Grade 
Description 
Grade 1 
Mild; asymptomatic or mild symptoms; clinical or diagnostic observations only; intervention not 
indicated. 
Grade 2 
Moderate; minimal, local, or noninvasive intervention indicated; limiting age-appropriate 
instrumental ADL a.  
Grade 3 
Severe or medically significant but not immediately life-threatening; hospitalization or prolongation 
of hospitalization indicated; disabling; limiting self-care ADL b. 
Grade 4 
Life-threatening consequences; urgent intervention indicated. 
Grade 5 
Death related to AE. 
ADL: activities of daily living; AE: adverse event; CTCAE: Common Terminology for Adverse Events. 
The CTCAE v5.0 is dated to 27Nov2017. 
a Instrumental ADL refers to preparing meals, shopping for groceries or clothes, using the telephone, managing 
money, etc. 
b Self-care ADL refers to bathing, dressing, and undressing, feeding self, using the toilet, taking medications, and 
not bedridden. 
8.2.3 
Pregnancy  
Pregnancy in a woman who has received IP must be reported to Sponsor from time of signed ICF 
until end of study follow-up or 3 months (approximately 5 half-lives) following the last dose of 
IP in case of early withdrawal (Section 8.3). 
Participants who become pregnant during the study period must not receive additional doses of 
IP but will not be withdrawn from the study. If the participant requests to know which treatment 
she received, this information will be provided to her. The pregnancy will be followed for 
outcome of the mother and child (including any premature terminations) and should be reported 
to the Sponsor after outcome. 
Should the Investigator become aware of a pregnancy in the partner of a male study participant 
who has received IP, this should be reported to Sponsor within 24 hours of knowledge of the 
event, by fax or email using the Pregnancy Report Form (refer to Section 8.3 for contact 
information). The Sponsor will endeavor to collect follow-up information on such pregnancies, 
provided the partner of the study participant provides consent for disclosure of their information. 
8.2.4 
Overdose or Misuse  
Any instance of overdose of IP (suspected or confirmed) must be communicated to Sponsor 
(Section 8.3). Any associated AEs or SAEs must also be reported and their management should 
be recorded.  
8.3 
Events Requiring Immediate Reporting  
All AEs will be recorded from written ICF signature up to exit from the study, whether related to 
the study.  


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All SAEs, AESIs (only after Randomization), pregnancies, overdose, or misuse must be reported 
to the Sponsor within 24 hours of site staff awareness by submitting a 
SAE/AESI/Pregnancy/Overdose Report Form by email to: 
Sponsor (Horizon Therapeutics/Viela Bio) 
Email:
Alternatively, the Report Form can be submitted by fax to: 
Sponsor (Horizon Therapeutics/Viela Bio) 
Fax: 1-800-860-7836 
Additional follow-up information, if required or available, should all be reported within one 
business day of receipt, should be completed on a follow-up report form, placed with the original 
SAE information, and kept with the appropriate section of the study file.  
Sponsor will work with the Investigator to ensure that all the necessary information is provided 
within 1 calendar day of initial receipt for fatal and life-threatening events and within 5 calendar 
days of initial receipt for all other SAEs. 
Sponsor is responsible for notifying the relevant regulatory authorities of certain events. 
Notification of the IRB or IEC of all SAEs that occur at the Investigator’s site are the 
responsibility of the Investigator. Investigators will be notified of all unexpected, serious, drug-
related events (7-- and 15--Calendar Day Safety Reports) that occur at other investigative sites 
during the clinical trial. Each Investigator is responsible for notifying its IRB or IEC of these 
additional SAEs in accordance with IRB or IEC requirements. 


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9 
STATISTICAL CONSIDERATIONS  
9.1 
General Considerations  
Tabular summaries will be presented by treatment group. For continuous data, number of 
observations, mean, standard deviation, median, minimum, and maximum will be reported. For 
categorical data, percent and frequency will be reported. Data listings will be sorted by treatment 
group and participant number. Details of the statistical analysis will be specified in a separate 
SAP. 
9.2 
Statistical Hypothesis  
The following are the statistical hypotheses associated with the primary efficacy outcome 
measure (proportion of participants achieving BICLA response + OGC ≤ 7.5 mg/day and 
≤ Baseline (Day 1) prednisone or equivalent dose at Week 48).  
x Null hypothesis (H0): Difference in proportion of responders (VIB7734 versus 
placebo) = 0. 
x Alternative hypothesis (Ha): Difference in proportion of responders (VIB7734 versus 
placebo) ≠ 0. 
9.3 
Determination of Sample Size  
The sample size was calculated based on the primary efficacy outcome measure. Assuming a 
placebo response rate of 20%, 65 participants per treatment group will provide at least 80% 
power to detect an increase in response of 20% in a VIB7734 group as compared to the placebo 
group at the 2-sided alpha level of 0.10 using a Chi-square test. The minimum detectable 
difference is 13% between the 2 treatment groups. The assumption of a 20% responder rate for 
placebo is based upon published results (Furie et al, 2017). 
9.4 
Analysis Sets  
Full Analysis Set: The Full Analysis Set will include all randomized participants who receive 
any dose of IP in the study. Participants will be analyzed according to the treatment randomized. 
The efficacy analysis will be based on the Full Analysis Set. 
Safety Analysis Set: The Safety Analysis Set will include all participants who received any dose 
of IP in the study. Participants will be analyzed according to the treatment that they received. 
Safety, PD, and
analyses will be based on the Safety Analysis Set. 
PK Analysis Set: The PK Analysis Set will include all participants who receive any dose of 
VIB7734 in the study and have at least one quantifiable serum PK observation post-first dose. 
Participants will be analyzed according to the treatment that they received. The PK analysis will 
be based on the PK Analysis Set. 
9.5 
Methods for Statistical Analyses  
9.5.1 
Analysis of the Primary Efficacy Outcome Measure  
The estimand of primary interest is defined as follows, using composite variable strategy to 
address intercurrent events. 


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x Population: Participants in the Full Analysis Set with active SLE despite receiving one or 
more SoC treatments as defined by the inclusion-exclusion criteria of the study. 
x Variable (outcome measure): Response in BICLA + OGC ≤ 7.5 mg/day and ≤ Baseline 
(Day 1) dose at Week 48, where BICLA is defined by meeting the following criteria 
compared to Baseline: 
 BILAG 2004 Index improvement (all Baseline BILAG A improving to B/C/D, all 
Baseline BILAG B to C/D, and ≤ 1 new BILAG B and no new BILAG A). 
 No deterioration in SLEDAI-2K total score. 
 No significant worsening in PGA score (< 10% increase). 
 No use of restricted medications beyond the protocol-allowed threshold before 
assessment.  
 No discontinuation of IP.  
x Intercurrent event:  
 Rescue medications: Captured in the primary variable definition.  
 Treatment discontinuation: Captured in the primary variable definition.  
x Population-level summary: Difference in proportion of responders between the VIB7734 
group and placebo group. 
The proportion of participants achieving BICLA response + OGC ≤ 7.5 mg/day and ≤ Baseline 
(Day 1) dose prednisone or equivalent at Week 48 in the VIB7734 treatment group will be 
compared to that of the placebo group using a logistic regression model with treatment, 
Randomization stratification factors, and Baseline IFN inducible gene signature level included in 
the model. The difference in proportion of responders of VIB7734 versus placebo will be 
estimated together with its associated 90% CI. 
A sensitivity analysis with the same model will be performed using a treatment policy strategy to 
address intercurrent events defined above. All observed values will be used regardless of 
occurrence of an intercurrent event. 
9.5.2 
Analysis of Secondary Efficacy Outcome Measures  
All secondary outcome measures will be analyzed similarly to the primary outcome measure 
using composite variable strategy to address intercurrent events. The estimands are defined as 
follows: 
x Population:  
 CLASI: Participants in the Full Analysis Set with active SLE and CLASI-A score 
≥ 10 at Baseline despite receiving one or more SoC treatments as defined by the 
inclusion-exclusion criteria of the study. 
 OGC reduction: Participants in the Full Analysis Set with active SLE taking an OGC 
of ≥ 10 mg/day of prednisone or equivalent at Baseline despite receiving one or more 
SoC treatments as defined by the inclusion-exclusion criteria of the study. 
 SRI-4 + OGC ≤ 7.5 mg/day and ≤ Baseline (Day 1) dose and LLDAS: Participants in 
the Full Analysis Set with active SLE despite receiving one or more SoC treatments as 
defined by the inclusion-exclusion criteria of the study. 


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x Variable (outcome measure):  
 CLASI: ≥ 50% reduction in CLASI-A score at Week 12 defined by meeting the 
following criteria: 
o A ≥ 50% reduction of CLASI-A score at Week 12 as compared to Baseline. 
o No use of restricted medications beyond the protocol-allowed threshold before 
assessment.  
o No discontinuation of IP before assessment.  
 SRI-4 + OGC ≤ 7.5 mg/day and ≤ Baseline (Day 1) dose: Response in SRI-4 + OGC 
≤ 7.5 mg/day and ≤ Baseline (Day 1) dose at Week 48, where SRI-4 is defined by 
meeting the following criteria compared to Baseline: 
o Reduction from Baseline of ≥ 4 points in the SLEDAI-2K. 
o No new organ system affected as defined by one or more BILAG A or 2 or more 
BILAG B items. 
o No significant worsening in PGA score (< 10% increase). 
o No use of restricted medications beyond the protocol-allowed threshold before 
assessment. 
o No discontinuation of IP. 
 OGC reduction: Maintained OGC reduction from Week 36 to Week 48 defined by 
meeting the following criteria: 
o An OGC dose of ≤ 7.5 mg/day prednisone or equivalent at Week 36 that is 
maintained through Week 48. 
o No use of restricted medications beyond the protocol-allowed threshold before 
assessment.  
o No discontinuation of IP before assessment.  
 LLDAS: Response in LLDAS at Week 48, where LLDAS is defined by meeting the 
following criteria: 
o A SLEDAI-2K ≤ 4, with no activity in major organ systems (renal, CNS, 
cardiopulmonary, vasculitis, fever) and no hemolytic anemia or gastrointestinal 
activity. 
o No new lupus disease activity compared with the previous assessment measured 
by SLEDAI-2K. 
o A PGA ≤ 1 (on a scale of 0 to 3). 
o Current prednisone or equivalent dose of ≤ 7.5 mg/day. 
o Well-tolerated standard maintenance doses of immunosuppressive drugs and 
approved medications as allowed and specified in the Clinical Study Protocol. 
o No use of restricted medications beyond the protocol-allowed threshold before 
assessment.  
o No discontinuation of IP.  
x Intercurrent event:  
 Rescue medications: Captured in the variable definition. 
 Treatment discontinuation: Captured in the variable definition. 
x Population-level summary for all secondary outcome measures: Difference in proportions 
of responders between VIB7734 and placebo. 


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Similar sensitivity analysis to the primary outcome measure analysis will be performed using a 
treatment policy strategy to address intercurrent events defined above. All observed values will 
be used regardless of occurrence of an intercurrent event. 
9.5.3 
Missing Data Handling Plan  
Intermittent missing data will be imputed using last observation carried forward approach. 
Participants with missing primary or secondary outcome measures due to early discontinuation 
of study will be considered nonresponders. 
9.5.4 
Control of Type I Error  
No multiplicity adjustment will be planned to control Type I error. 
9.5.5 
Safety Analysis  
AEs will be coded using the Medical Dictionary for Regulatory Activities by System Organ 
Class and Preferred Term. The number and percentage of participants reporting treatment-
emergent AEs with onset on or after the start of the first administration of IP will be summarized 
for each treatment group by System Organ Class and Preferred Term, by severity, and by 
relationship to the IP. The number and percentage of participants reporting treatment-emergent 
SAEs and treatment-emergent AESIs will also be summarized.  
Clinically significant abnormalities in laboratory parameters, vital signs, ECGs, and physical 
examinations will be recorded as AEs or SAEs. Laboratory assessments, vital signs, and ECGs, 
as well as their changes from Baseline at each visit will also be summarized descriptively. 
9.5.6 
Pharmacokinetics Analysis  
The PK analysis will be based on the PK Analysis Set. Descriptive statistics of the serum 
VIB7734 concentration will be tabulated by visit and by treatment group. Individual and mean 
serum concentration-time profiles of VIB7734 by treatment group will be generated. Population 
modeling will be performed to better characterize the PK of VIB7734 given by SC injection in 
SLE participants.  
9.5.7 
Immunogenicity Analysis  
9.5.8 
Pharmacodynamics Analysis  
Absolute values and change from baseline in pDCs will be summarized descriptively by visit for 
each treatment group. 
9.5.9 
Exploratory Analysis  
The exploratory analyses will be detailed in the SAP. 


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9.6 
Planned Interim Analysis  
An interim analysis will be conducted after all participants have completed the Week 24 visit or 
are discontinued early from the study. A small prespecified number of Sponsor staff who are not 
directly involved in the conduct of the study will be unblinded to make a go/no-go decision for 
future studies.  
Sponsor personnel directly associated with the conduct of the study, study site personnel, 
participants, and CRO will remain blinded to the treatment assignment for individual participants 
and the results of the interim analysis until the completion of the study. The efficacy and safety 
data prior to the data cut-off for the interim analysis will be analyzed. No multiplicity adjustment 
is planned for the interim analysis because there is no provision to stop the trial early at the 
interim analysis to claim efficacy. Details of the interim analysis (go/no-go criteria, unblinding 
plan, and communication plan) will be specified in an interim unblinding analysis plan prior to 
unblinding. 
9.7 
Planned Primary Analysis  
The primary analysis will be conducted after the last participant has completed the Week 48 visit 
or discontinued from study early. For the primary analysis, all the efficacy and safety data 
collected prior to the data cut-off for the primary analysis will be analyzed. 
9.8 
Planned Final Analysis  
The final analysis will be conducted after all participants have completed or discontinued early 
from the study. 


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10 
ETHICAL CONSIDERATIONS  
10.1 
Good Clinical Practice  
The study will be performed in accordance with ICH/GCP, applicable regulatory requirements, 
and the Viela Bio policy on Ethical Interactions. 
10.2 
Ethics Review  
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB or IEC, as appropriate. The Investigator must submit 
written approval to the Sponsor or representative before he or she can enroll any participant into 
the study. 
The PI is responsible for informing the IRB or IEC of any amendment to the protocol in 
accordance with local requirements, and obtaining their approval prior to its implementation, 
except to avoid an immediate hazard to participants. In addition, the IRB or IEC must approve all 
advertising used to recruit participants for the study. The protocol must be re‑approved by the 
IRB or IEC upon receipt of amendments and annually, as local regulations require. The PI is also 
responsible to adhere to requirements stipulated by the respective IRB/IEC and for providing the 
IRB/IEC with reports, including those of any reportable serious adverse drug reactions from any 
other study conducted with the IP. The Sponsor will provide this information to the PI. 
10.3 
Informed Consent  
The Investigator or their designee must provide the Sponsor/designee with a copy of the 
IRB/IEC-approved informed consent document(s) prior to the start of the study at the site. It is 
the responsibility of the Investigator (or their designee, where allowed by local requirements) to 
obtain written informed consent from all study participants. All consent documentation must be 
in accordance with applicable regulations and ICH E6(R2). The participants will be informed 
that their study record and medical records/documents that identify them, that pertain directly to 
the study, will be reviewed by the Sponsor or its designee, and or a local or foreign governmental 
agency (such as FDA), and that every effort will be made to maintain participant confidentiality. 
The informed consent must allow for access to the records for at least 25 years to allow for 
possible future inspections. The participant should be given the opportunity to ask questions and 
allowed time to consider the information provided. 
The original, appropriately signed and dated ICF must be retained by the Investigator/study site 
as part of that participant’s record. A copy of the signed ICF must be given to the participant. 
The ICF must be fully approved by an IRB or an IEC prior to its use with study participants. 
The Sponsor reserves the right to delay initiation of the study at a site where the informed 
consent document(s) do not meet the standards of this section, applicable regulations, and/or ICH 
E6(R2). 
10.4 
Data Privacy  
All information generated in this study is considered highly confidential and must not be 
disclosed to any person or entity not directly involved with the study unless prior written consent 
is obtained from the Sponsor. However, authorized regulatory officials, IRB/IEC personnel, the 


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Sponsor and its authorized representatives must be allowed full access to the original source 
records.  
10.5 
Disclosure  
The Sponsor is responsible for preparing and providing the appropriate regulatory authorities 
with Clinical Study Reports, according to the applicable regulatory requirements. 
10.6 
Biological Specimens and Data  
Study data are protected by the use of a SID number, which is a number specific to the 
participant. The Investigator is in control of the information that is needed to connect a study 
sample to a participant; a participant may withdraw consent at any time by notifying the 
Investigator. If consent is withdrawn, any samples collected prior to that time may still be given 
to and used by the Sponsor, but no new data or samples will be collected unless specifically 
required to monitor the safety of the participant.  
Leftover samples stored for future research with participant consent will be labeled with a 
sample identification number. If the participant consents to have his/her samples used for future 
research, this additional research may not start immediately and may start at any time during the 
storage period. The participant’s sample(s) will be stored by the Sponsor with similar samples in 
a secure laboratory. The participant’s samples will not be kept for more than 25 years after the 
end of the study in which they were collected. If the participant chooses not to allow his/her 
study samples to be used for future research, the samples will be destroyed by the Sponsor once 
they are no longer required for the main study. If future use consent is withdrawn, the Sponsor 
and the Investigator will ensure that the participant’s sample(s) are destroyed unless the 
identification number has been removed and the participant can no longer be linked to any 
samples. However, if the participant’s sample has already been used for research, the Sponsor is 
not required to destroy the results of this research. In this case, only the remaining sample(s) will 
be destroyed. 


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11 
OVERSIGHT  
11.1 
Safety Data Monitoring Committee  
The external, independent SDMC is responsible for safeguarding the interests of study 
participants via review of accumulating safety data and for supporting study integrity and 
interpretability based on their review of ongoing study conduct. The SDMC will provide Viela 
Bio with recommendations for actions with respect to study conduct and the management of 
participants treated under the study protocol. The SDMC members are independent of Viela Bio 
and any CRO/organization collaborating with Viela Bio on the study.  
The SDMC will not be charged with any formal interim analysis, will not conduct a futility 
analysis, and will not be asked to consider early study completion for efficacy. For additional 
details, refer to the SDMC Charter. 
11.2 
Quality Control and Assurance  
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor may 
conduct a quality assurance audit. See Section 11.4 for details regarding the audit process. 
11.3 
Monitoring  
The Sponsor and any third party to whom aspects of study management or monitoring have been 
delegated, will undertake their roles in accordance with all applicable regulations and ICH 
E6(R2). 
A representative of the Sponsor and/or its designee will perform periodic monitoring of the study 
to ensure compliance with ICH GCP guidelines and regulatory requirements. The Sponsor’s 
designated representatives (the Study Monitors) will inspect the site’s study documentation 
(including qualification and training of site personnel, IRB communications, etc), study data, 
participants’ original medical records, and completed eCRFs. The Investigator agrees to allow 
unblinded Study Monitors to inspect the drug storage area, IP stocks, drug accountability 
records, subject charts, original study source documents (regardless of media), and other records 
relative to study conduct. The Study Monitors will maintain frequent contact with the 
investigational site and meet with the Investigator and site staff throughout the course of the 
study. 
The Investigator will facilitate monitoring activities and the Study Monitors’ access to required 
records. 
During scheduled monitoring visits, the Investigator and the investigational site staff must be 
available to meet with the Study Monitor in order to discuss the progress of the study, make 
necessary corrections to eCRF entries, respond to data clarification requests, and respond to any 
other study-related inquiries from the Study Monitor. 
11.4 
Audits/Inspections  
To ensure compliance with GCP and all applicable regulatory requirements, the Sponsor or its 
authorized representatives may conduct a quality assurance audit. Local or foreign regulatory 
authorities may conduct regulatory inspections. Regulatory inspections may be in response to a 
marketing application, and this may occur years after completion of the clinical study. 


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Authorized representatives of the Sponsor, a regulatory authority, an IEC, and/or an IRB may 
visit the site to perform audits or inspections, including review of original medical records. The 
purpose of a Sponsor audit or regulatory inspection is to systematically and independently 
examine all study-related activities and documents to determine whether these activities were 
conducted and data were recorded, analyzed, and accurately reported according to the protocol, 
ICH GCP guidelines, and any applicable regulatory requirements. 
Initial IRB/IEC approval, and all materials approved by the IRB/IEC for this study, including the 
ICF and recruitment materials, must be maintained by the Investigator and made available for 
inspection.  
In addition to the above, representatives of the Sponsor auditing staff or government inspectors 
may review the conduct/results of the study at the investigational site. The Investigator should 
contact the Sponsor immediately if contacted by a regulatory agency about an inspection. The 
Investigator cooperates with the auditor(s), makes available to the auditor all requested 
documentation, and ensures that issues detected during these audits are satisfactorily resolved. 
The Investigator supplies the Sponsor with copies of all documentation and correspondence 
related to regulatory agency audits as outlined in the Clinical Trial Agreement. If the results of 
the audit result in a Form FDA 483 (or similar document from another regulatory agency), the 
Investigator promptly provides a copy to a Sponsor representative and a draft response to the 
Sponsor prior to submission to the regulatory agency. 
11.4.1 
Records  
11.4.2 
Data Capture and Management  
Clinical Data Management (CDM) will be performed according to the Data Management Plan 
(DMP). The DMP will document procedures and roles and responsibilities related to CDM 
activities, including data validation, data transfer and reconciliation, CDM communications, 
medical coding and dictionaries, CDM reports, and data formats. An electronic data capture 
system compliant with 21 Code of Federal Regulations Part 11 will be used for data collection 
and query handling. The Investigator will ensure that data are recorded in the eCRFs as specified 
in the study protocol and in accordance with the eCRF Completion Guidelines provided. The 
Investigator ensures the accuracy, completeness, and timeliness of the data recorded and of the 
provision of answers to data queries. The Investigator will sign the completed eCRFs 
electronically. Upon completion of the study, a copy of the completed eCRFs will be provided to 
the study site for archival purposes. 
11.4.3 
Source Documentation  
The Investigator is responsible for maintaining adequate and accurate medical records from 
which the Investigator/designee will transcribe information in the eCRFs.  
11.4.4 
Records Retention  
Essential documents should be retained 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 


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clinical development of the IP. These documents should be retained for a longer period, 
however, if required by applicable regulatory requirement. 
The Investigator may not destroy any study records without written permission from the 
Sponsor. 
 


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12 
PUBLICATION POLICY  
The publication policy of the Sponsor is discussed in the Investigator's Clinical Research 
Agreement. 


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13 
FINANCING AND INSURANCE  
Financing and insurance for this study will be addressed in the Clinical Trial Agreement with the 
study site(s). 
 


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14 
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15 
APPENDICES  
 


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APPENDIX 1 
NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASE 
AND FOOD AND ALLERGY ANAPHYLAXIS NETWORK 
GUIDANCE FOR ANAPHYLAXIS DIAGNOSIS  
National Institute of Allergy and Infectious Disease (NIAID) and Food and Allergy Anaphylaxis 
Network (FAAN) define anaphylaxis as a serious allergic reaction that is rapid in onset and may 
cause death (Sampson et al, 2006). They recognize 3 categories of anaphylaxis, with criteria 
designated to capture from 80% of cases (Category 1) to > 95% of all cases of anaphylaxis (for 
all 3 categories). 
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 ONE OF THE FOLLOWING: 
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory function [PEF], hypoxemia). 
b. 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 patient (minutes to several hours): 
a. Involvement of the skin-mucosal tissue (eg, generalized hives, itch-flush, swollen 
lips-tongue-uvula). 
b. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced PEF, 
hypoxemia). 
c. Reduced blood pressure or associated symptoms (eg, hypotonia [collapse], syncope, 
incontinence). 
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting). 
3. Reduced blood pressure after exposure to known allergen for that patient (minutes to 
several hours): 
a. Infants and children ─ low systolic blood pressure (age specific) or greater than 30% 
decrease in systolic blood pressure. 
b. Adults ─ systolic blood pressure of less than 90 mmHg or greater than 30% decrease 
from that participant’s baseline. 


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APPENDIX 2 
2019 EUROPEAN LEAGUE AGAINST RHEUMATISM/AMERICAN 
COLLEGE OF RHEUMATOLOGY CLASSIFICATION SYSTEM FOR 
SYSTEMIC LUPUS ERYTHEMATOSUS  
 
Source: Aringer et al, 2019. 
β2GP1: β2-glycoprotein 1; C: complement; dsDNA: double-stranded DNA; Hep-2: human epithelial type 2 cells; 
SLE: systemic lupus erythematosus. 


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APPENDIX 3 
STUDY-SPECIFIED OPPORTUNISTIC INFECTIONS THAT MEET 
EXCLUSION CRITERIA  
Definite a,b Opportunistic Infection 
Probable c Opportunistic Infection 
x Pneumocystis jirovecii 
x BK virus disease, including polyomavirus-associated 
nephropathy  
x CMV disease 
x Post-transplant lymphoproliferative disorder (EBV) 
x Progressive multifocal leukoencephalopathy 
x Bartonellosis (disseminated disease only) 
x Blastomycosis 
x Toxoplasmosis 
x Coccidioidomycosis 
x Histoplasmosis 
x Aspergillosis (invasive disease only) 
x Candidiasis (invasive disease or pharyngeal) 
x Cryptococcosis 
x Other invasive fungi: Mucormycosis (zygomycosis) 
(Rhizopus, Mucor, and Lichtheimia), 
Scedosporium/Pseudallescheria boydii, Fusarium) 
x Legionellosis 
x Listeria monocytogenes (invasive disease only) 
x TB 
x Nocardiosis 
x Non-tuberculous mycobacterium disease 
x Salmonellosis (invasive disease only) 
x HBV reactivation 
x Herpes simplex (invasive disease only) 
x Herpes zoster (any form) 
x Strongyloides  
(hyperinfection syndrome and disseminated forms only) 
x Paracoccidioides infections 
x Penicillium marneffei (talaromyces) 
x Sporothrix schenckii 
x Cryptosporidium species  
(chronic disease only) 
x Microsporidiosis 
x Leishmaniasis (visceral only) 
x Trypanosoma cruzi infection  
(Chagas’s disease) (disseminated disease only) 
x Campylobacteriosis (invasive disease only) 
x Shigellosis (invasive disease only) 
x Vibriosis  
(invasive disease due to Vibrio vulnificus) 
x HCV progression 
CMV: cytomegalovirus; EBV: Epstein-Barr virus; HBV: hepatitis B virus; HCV: hepatitis C virus; TB: 
tuberculosis. 
Source: Winthrop et al, 2015. 
a Generally does not occur in the absence of immunosuppression, but whose presence indicates a potential or 
likely alteration in host immunity. 
b Can occur in patients without recognized forms of immunosuppression, but whose presence indicates a potential 
or likely alteration in host immunity. 
c Published data are currently lacking, but expert opinion believes that risk is likely elevated in the setting of 
biologic therapy. 
 
 


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APPENDIX 4 
PREDISONE EQUIVALENT OF ORAL GLUCOCORTICOID DOSE  
Glucocorticoid 
Prednisone Equivalent Dose 
PO prednisone 
5 mg 
7.5 mg 
10 mg 
20 mg 
30 mg 
40 mg 
Prednisolone 
5 mg 
7.5 mg 
10 mg 
20 mg  
30 mg 
40 mg 
Methylprednisolone 
4 mg 
6 mg 
8 mg 
16 mg 
24 mg 
32 mg 
Hydrocortisone 
20 mg 
30 mg 
40 mg 
80 mg 
120 mg 
160 mg 
Cortisone 
25 mg 
37.5 mg 
50 mg 
100 mg 
150 mg 
200 mg 
Triamcinolone 
4 mg 
6 mg 
8 mg 
16 mg 
24 mg 
32 mg 
PO: oral(ly). 
 


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APPENDIX 5 
ORAL GLUCOCORTICOID TAPERING SCHEDULE  
Visit 
Dose of Oral Prednisone or Equivalent at Start of Specified Study Visit a 
Week 0 
Investigators may initiate OGC taper as tolerated;  
target ≤ 7.5 mg/day to meet response criteria b 
Week 4 
40 mg 
30 mg 
20 mg 
10 mg 
7.5 mg 
Week 8 
30 mg 
22.5 mg 
15 mg 
7.5 mg 
5 mg c 
Week 12 
20 mg 
15 mg 
10 mg 
7.5 mg 
5 mg c 
Week 16 
12.5 mg 
10 mg 
7.5 mg 
5 mg c 
≤ 5 mg c 
Week 20 
7.5 mg 
7.5 mg 
7.5 mg 
≤ 5 mg c 
≤ 5 mg c 
No Change in OGC Permitted between Week 20 and Week 24 
Week 24 to Week 36 
It is encouraged to taper OGC dose beyond the target for response criteria of 7.5 mg/day 
including discontinuation of OGC up to Week 36, if clinically feasible. 
No change in OGC is permitted between Week 36 and Week 48. 
OGC: oral glucocorticoid. 
The doses in the table are shown for prednisone. Refer to Table 3 for equivalent doses of other OGCs. 
The OGC tapering schedule represents an example of a tapering regimen to provide guidance to Investigators in 
the approach to mandatory steroid taper starting at Week 4 with a target OGC dose of ≤ 7.5mg/day 
prednisone (or equivalent) to meet the response criteria at Week 20 and to aim for a lower daily dose at 
Week 36. 
a Specified prednisone dose is dose at the beginning of the week. 
b Due to variability in participant responses to OGC treatment and tolerability of taper, Investigators have 
flexibility in how the OGC dose is reduced at each study visit. 
c Investigators are encouraged to taper OGC dose beyond the target for response criteria of ≤ 7.5 mg/day 
including discontinuation of OGC, if clinically feasible. 
 
  

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STATISTICAL ANALYSIS PLAN
Protocol Title:
A phase 2 randomized, double-blind, placebo-controlled 
efficacy and safety study of VIB7734 for the treatment of 
moderate to severely active systemic lupus erythematosus  
(RECAST SLE)
Name of Test Drug:
Daxdilimab (HZN-7734)
Protocol Number:
VIB7734.P2.S1
Protocol Version (Date):
10-Feb-2022
Analysis Type:
All Planned Analyses 
Analysis Plan Version:
v2.0
Analysis Plan Author(s):
NCT Number: NCT04925934
This NCT number has been applied to the document
for purposes of posting on Clinicaltrials.gov


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TABLE OF CONTENTS 
1 
INTRODUCTION ......................................................................................................6 
2 
Study Overview ...........................................................................................................6 
2.1 
Study Objectives and Endpoints...........................................................................6 
2.2 
Study Design ...........................................................................................................8 
2.3 
Sample Size .............................................................................................................9 
3 
Statistical Methods ......................................................................................................9 
3.1 
General Considerations .........................................................................................9 
3.1.1 
Definition of Baseline .....................................................................................10 
3.1.2 
Analysis Windows ..........................................................................................10 
3.2 
Protocol Deviations ..............................................................................................10 
3.3 
Analysis Sets .........................................................................................................11 
3.3.1 
All participant analysis set ............................................................................11 
3.3.2 
Full analysis set ..............................................................................................11 
3.3.3 
Safety analysis set ...........................................................................................11 
3.3.4 
Pharmacokinetic analysis set ........................................................................11 
3.4 
Study Participants ................................................................................................11 
3.4.1 
Participant Disposition ..................................................................................11 
3.4.2 
Demographics, Baseline Characteristics, and Medical History .................11 
3.5 
Investigational Product Exposure ......................................................................12 
3.6 
Prior and Concomitant Medications ..................................................................13 
3.7 
Efficacy Analyses .................................................................................................15 
3.7.1 
Primary Endpoint and Analyses...................................................................15 
3.7.1.1 
Primary endpoint and estimand .............................................................15 
3.7.1.2 
Primary efficacy analysis ........................................................................15 
3.7.1.3 
Sensitivity analysis of primary endpoint................................................16 
3.7.1.4 
Handling plan for missing data ..............................................................16 
3.7.1.5 
Multiplicity adjustment ...........................................................................16 
3.7.2 
Secondary Efficacy Endpoints and Analyses ..............................................16 
3.7.2.1 
Secondary efficacy endpoints and estimands ........................................16 
3.7.2.2 
Secondary efficacy analysis .....................................................................18 
3.7.2.3 
Sensitivity analysis of secondary endpoints ...........................................18 
3.7.3 
Exploratory Efficacy Endpoints and Analyses ...........................................19 
3.7.3.1 
Exploratory efficacy endpoints ...............................................................19 
3.7.3.2 
Exploratory efficacy analyses .................................................................27 
3.7.4 
Handling Missing Items of Clinical Outcome Assessments .......................29 
3.7.5 
Subgroup Analysis .........................................................................................31 
3.8 
Safety Analysis .....................................................................................................32 
3.8.1 
Adverse Events ...............................................................................................32 
3.8.2 
Clinical Laboratory Evaluation ....................................................................32 
3.8.3 
Other Safety Evaluations ..............................................................................33 
3.8.3.1 
Overdose ...................................................................................................33 
3.8.3.2 
Vital signs ..................................................................................................33 
3.8.3.3 
Electrocardiogram ...................................................................................33 


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3.8.3.4 
Physical Examination and Weight .........................................................33 
3.9 
Pharmacokinetics .................................................................................................34 
3.10 
Immunogenicity....................................................................................................34 
3.11 
Pharmacodynamics ..............................................................................................34 
3.12 
Exploratory Analyses...........................................................................................35 
4 
Planned Analysis .......................................................................................................35 
4.1 
Planned Interim Analysis ....................................................................................35 
4.2 
Planned Primary Analysis ...................................................................................36 
4.3 
Planned Final Analysis ........................................................................................36 
5 
References ..................................................................................................................37 
6 
Appendix ....................................................................................................................39 
 
LIST OF TABLES 
Table 1 
Study Objectives and Endpoints.....................................................................6 
Table 2 
Weighted Score of Different GC Doses ........................................................22 
Table 3 
Imputation for Missing BILAG Items at Visitx ...........................................29 
LIST OF FIGURES 
Figure 1 
Study Flow Diagram ..................................................................................9 


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LIST OF ABBREVIATIONS 
Abbreviation or Specialized Term 
Definition 
AE 
adverse event 
AESI 
adverse event of special interest 
ANCOVA 
Analysis of covariance 
AUC 
area under the concentration-time curve 
BICLA 
BILAG 2004 Index-Based Combined Lupus Assessment 
BILAG 
British Isles Lupus Assessment Group 
CI 
confidence interval 
CLASI 
Cutaneous Lupus Erythematosus Disease Area and Severity Index 
CLASI-A 
Cutaneous Lupus Erythematosus Disease Area and Severity Index-
Activity 
CNS 
central nervous system 
ECG 
electrocardiogram 
GC 
glucocorticoid 
HRQoL 
health related quality of life 
IP 
Investigational product 
PGA 
physician global assessment of disease activity 
LLDAS 
Lupus Low Disease Activity State 
LLN 
lower limit of normal 
LOCF 
last observation carried forward  
mCLASI-A 
modified CLASI-A 
MCP 
metacarpophalangeal 
MDA 
minimal disease activity  
MedDRA 
Medical Dictionary for Regulatory Activities 
MMRM 
mixed model for repeated measures 
OGC 
oral glucocorticoid 


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Abbreviation or Specialized Term 
Definition 
PD 
pharmacodynamic(s) 
pDC 
plasmacytoid DC 
PK 
Pharmacokinetic(s) 
PIP 
proximal interphalangeal 
PT 
preferred term 
Q12W 
every 12 weeks 
QTc 
corrected QT interval 
RF 
rheumatoid factor 
SAE 
serious adverse event 
SC 
subcutaneous(ly) 
SE 
standard error 
SLE 
systemic lupus erythematosus 
SLEDAI-2K 
SLE Disease Activity Index 2000 
SLEDAI-2KG 
SLEDAI-2K GC 
SOC 
system organ class 
SPP 
statistical programming plan 
SRI 
SLE Responder Index 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
ULN 
upper limit of normal 
UPCR 
urine protein:creatinine ratio 
VAS 
visual analog scale 


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1 INTRODUCTION 
This document describes the statistical analysis for protocol VIB7734.P2.S1, a Phase 2, 
multicenter, international, randomized, double-blind, placebo-controlled, parallel-arm trial to 
assess the efficacy and safety of VIB7734 in participants with moderate to severely active 
systemic lupus erythematosus (SLE). 
2 STUDY OVERVIEW 
2.1 
Study Objectives and Endpoints 
The objectives and corresponding endpoints are listed in Table 1 below: 
Table 1 
Study Objectives and Endpoints 
Primary objective 
Endpoints/variables 
To evaluate the effect of VIB7734 compared to 
placebo in reducing SLE disease activity at Week 48 
in participants treated with standard of care therapy 
Proportion of participants achieving a BILAG-2004 
Index-based BICLA response and an OGC dose 
≤ 7.5 mg/day and ≤ Baseline (Day 1) dose of 
prednisone or equivalent at Week 48. 
The BICLA response is defined as meeting all the 
following conditions as compared to Baseline: 
x BILAG-2004 Index improvement (all Baseline 
[Day 1] BILAG A improving to B/C/D, all 
Baseline [Day 1] BILAG B to C/D, and ≤ 1 new 
BILAG B and no new BILAG A. 
x No deterioration in SLEDAI-2K total score. 
x No significant worsening in PGA score (< 10% 
increase (< 0.3-point increase on a 3-point VAS)). 
x No use of restricted medications beyond the 
protocol-allowed threshold before assessment. 
x No discontinuation of IP.  
Secondary objectives 
Endpoints/variables 
To evaluate the effect of VIB7734 compared with 
placebo to reduce cutaneous disease activity at 
Week 12. 
Proportion of participants with CLASI-A score ≥ 10 
at Baseline who achieve ≥ 50% reduction from 
Baseline in CLASI-A score at Week 12. Reduction 
of 50% in CLASI-A score is defined by meeting all 
the following conditions: 
x A ≥ 50% reduction of CLASI-A score at Week 12 
as compared to Baseline. 
x No use of restricted medications beyond the 
protocol-allowed threshold before assessment.  
x No discontinuation of IP. 
To evaluate the effect of VIB7734 compared with 
placebo to reduce SLE disease activity at Week 48. 
Proportion of participants achieving a SRI-4 response 
and an OGC dose ≤ 7.5 mg/day and ≤ Baseline (Day 
1) dose of prednisone or equivalent at Week 48. The 
SRI-4 response is defined as meeting all of the 
following conditions compared to Baseline: 


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Table 1 
Study Objectives and Endpoints 
x Reduction from Baseline of ≥ 4 points in the 
SLEDAI-2K. 
x No new organ system affected as defined by 1 or 
more BILAG A or 2 or more BILAG B items. 
x No significant worsening in PGA score (< 10% 
increase (< 0.3 point increase on a 3-point VAS)). 
x No use of restricted medications beyond the 
protocol-allowed threshold before assessment. 
x No discontinuation of IP. 
To evaluate the effect of VIB7734 compared with 
placebo on sustained OGC reduction from Week 36 
to Week 48. 
Proportion of participants with OGC dose ≥ 10 mg 
prednisone or equivalent at Baseline (Day 1) who: 
x Achieve OGC dose ≤ 7.5 mg/day prednisone or 
equivalent at Week 36.  
x Maintain OGC dose ≤ 7.5 mg/day from Week 36 
through Week 48. 
x No use of restricted medications beyond the 
protocol-allowed threshold before assessment. 
x No discontinuation of IP. 
To evaluate the effect of VIB7734 compared with 
placebo to achieve low disease activity at Week 48. 
Proportion of participants achieving LLDAS at Week 
48. LLDAS is defined as meeting all the following 
conditions: 
x SLEDAI-2K ≤ 4, with no activity in major organ 
system (renal, CNS, cardiopulmonary, vasculitis, 
fever) and hemolytic anemia or gastrointestinal 
activity. 
x No new lupus disease activity as compared to the 
previous assessment. 
x PGA ≤ 1 (on a 3-point VAS). 
x Current prednisone or equivalent dose of 
≤ 7.5 mg/day. 
x Well-tolerated standard maintenance doses of 
immunosuppressive drugs and approved 
treatments as allowed and specified in the 
protocol. 
x No use of restricted medications beyond the 
protocol-allowed threshold. 
x No discontinuation of IP. 
Safety objective 
Endpoints/variables 
To evaluate the safety and tolerability of VIB7734. 
Incidence of adverse events, serious adverse events, 
and adverse events of special interest.  
PK/PD/Immunogenicity Objectives 
Outcome Measures 
To characterize the PK, PD, and immunogenicity of 
VIB7734. 
VIB7734 concentrations, change in pDC,
 


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Table 1 
Study Objectives and Endpoints 
Exploratory objectives 
Endpoints/variables 
2.2 
Study Design 
This study is a Phase 2, multicenter, international, double-blind, randomized, placebo-
controlled, parallel-arm trial to assess the efficacy and safety of VIB7734 in participants with 
moderate to severely active SLE.  
In this study, approximately 195 participants will be randomized in a ratio of 1:1:1 
(65 participants per group) to receive VIB7734 200 mg every 4 weeks subcutaneously (SC), 
VIB7734 200 mg every 12 weeks (Q12W) SC, with an additional 200 mg SC dose at 
Week 4, or placebo. To maintain blinding, participants randomized to the VIB7734 200 mg 
Q12W SC dosing regimen will receive SC placebo injections on dosing visits outside the 
Q12W schedule. Randomization will be stratified by SLEDAI-2K total score at Screening 


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(≥ 10 or < 10) and prednisone or equivalent oral glucocorticoid (OGC) dose at Baseline 
(Day 1) (≥ 10 mg or < 10 mg).  
The study will comprise a Screening period of approximately 4 weeks (Days -28 to -1), 
Randomization on Day 1, treatment and assessments through Week 48, and a Safety Follow-
Up period of 8 weeks (through Week 56). 
A study schematic is presented in Figure 1. 
Figure 1 
Study Flow Diagram 
 
2.3 
Sample Size 
The sample size was calculated based on the primary efficacy outcome measure. Assuming a 
placebo response rate of 20%, 65 participants per treatment group will provide at least 80% 
power to detect an increase in response of 20% in a VIB7734 group as compared to the 
placebo group at the 2-sided alpha level of 0.10 using a Chi-square test. The minimum 
detectable difference is 13% between placebo and VIB7734 treatment groups. The 
assumption of a 20% responder rate for placebo is based upon published results (Furie R et 
al, 2017). 
3 STATISTICAL METHODS 
3.1 
General Considerations 
All statistical calculations will be primarily performed using SAS® System Version 9.4 or 
higher. Categorical data will be summarized by the frequency counts and percentage of 
participants in each category. Continuous variables will be summarized by descriptive 
statistics, including number of observations, mean, standard deviation, median, first quartile, 
third quartile, minimum, and maximum. 


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3.1.1 
Definition of Baseline 
Unless otherwise specified, baseline will be defined as the last non-missing valid observation 
prior to the first administration of investigational product (IP). In cases where baseline 
measurements are taken on the same day as IP and no times are reported, it will be assumed 
that these measurements are taken prior to IP being administered. 
3.1.2 
Analysis Windows 
Analysis visit windows will be used for all visit-based assessments to map longitudinal 
observations to scheduled visits and thereby allow for by-visit analyses, since not all 
assessments are performed on the scheduled day. Unless otherwise specified, all longitudinal 
efficacy, safety, and biomarker data analyses will be based on the analysis visit windows. The 
analysis visit windows will be calculated by bisecting the interval between adjacent 
scheduled visit days except for the first post-treatment visit. The first post-treatment visit will 
start at Day 2. The detailed analysis visit windows will be specified in the statistical 
programming plan (SPP). 
The actual assessment day will be mapped to the windows defined for each scheduled study 
visit with following rules:  
x If more than one assessment falls within a visit window, the closest non-missing 
assessment to the scheduled day will be used in the analysis. 
x If 2 non-missing assessment actual dates are equidistant from the target day, the later 
visit will be used in the analysis. 
x For retest value of laboratory data, the retest value will be chosen. 
All observations will be included in data listings.   
3.2 
Protocol Deviations 
All protocol deviations will be classified as critical protocol deviations, major protocol 
deviations, or minor protocol deviations. A critical protocol deviation is a significant 
departure from protocol requirements resulting in a life-threatening risk to an individual 
subject, or where the safety or well-being of trial subjects has been or has significant potential 
to be jeopardized, a significant portion of the clinical trial data might be unreliable, and/or a 
significant portion of critical data being jeopardized. All the protocol deviations will be 
listed, and the critical protocol deviation will be summarized. Some classifications of critical 
protocol deviations are listed below.  
x Did not meet inclusion criteria or met exclusion criteria 
x Blinding of treatment assignment was broken by site investigator  
x Received prohibited concomitant medication 
x Serious breach of good clinical practice. 
The list may be updated and will be finalized and documented prior to the database lock for 
the interim analysis. 


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3.3 
Analysis Sets 
3.3.1 
All participant analysis set 
This analysis set includes all participants screened for the study and will be used for the 
reporting of participant disposition. 
3.3.2 
Full analysis set 
The full analysis set includes all randomized participants who receive any dose of IP. 
Participants will be analyzed according to the treatment randomized. The efficacy analysis 
will be based on the full analysis set. 
3.3.3 
Safety analysis set 
The safety analysis set includes all participants who receive any dose of IP. Participants will 
be analyzed according to the treatment that they received. The safety, pharmacodynamics 
(PD), 
analyses will be based on the safety analysis set. 
3.3.4 
Pharmacokinetic analysis set 
The pharmacokinetic (PK) analysis set includes all participants who receive any dose of 
VIB7734 in the study and have at least 1 quantifiable serum PK observation post-first dose. 
Participants will be analyzed according to the treatment that they received. The PK analysis 
will be based on the PK analysis set. 
3.4 
Study Participants 
3.4.1 
Participant Disposition 
A summary of participant disposition will be presented using the categories presented below.  
x Screened 
x Screen failed with reasons 
x Randomized 
x Randomized but not treated 
x Randomized and treated 
x Completed treatment  
x Discontinued treatment with reasons 
x Completed study 
x Discontinued study with reasons 
3.4.2 
Demographics, Baseline Characteristics, and Medical History 
The demographics (age, gender, race, ethnicity, height, weight, and body mass index) will be 
summarized by treatment group and overall, for the full analysis set.  


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A summary of baseline characteristics, by treatment group and overall, for the full analysis 
set will include the following: 
x Time from initial diagnosis to randomization  
x SLE Disease Activity Index-2000 (SLEDAI-2K) total score  
x SLEDAI-2K total score category (<10 vs ≥10)  
x British Isles Lupus Assessment Group (BILAG)-2004 total score  
x BILAG-2004 organ system involvement at baseline (yes vs no for each organ system 
domain). Involvement requires a baseline BILAG-2004 scale of A or B  
x Physician global assessment (PGA) score 
x Cutaneous Lupus Erythematosus Disease Area and Severity Index (CLASI) activity 
(CLASI-A)
x CLASI-A score category (<10 vs ≥10)  
x Low C3 (below lower limit of normal (<LLN) (yes vs no) 
x Low C4 (<LLN) (yes vs no)   
x Positive rheumatoid factor (RF) (yes vs no)   
x Region (Europe, North America, Latin America, and Asia)  
American College of Rheumatology criteria will be summarized by treatment group and 
overall for the full analysis set. Significant medical history findings will be summarized by 
Medical Dictionary for Regulatory Activities (MedDRA) system organ class (SOC) and 
preferred term (PT) by treatment group and overall for the full analysis set. 
3.5 
Investigational Product Exposure 
The number of doses received, amount (mg) of the IP received, durations of the IP exposure, 
and total participant years exposure will be summarized by treatment using the full analysis 
set. The number and percentage of participants treated ≥4 weeks, ≥12 weeks, ≥24 weeks, ≥36 
weeks, and ≥48 weeks will also be provided. 
x Duration of the IP exposure is defined as (last dose date + 28 ‒ first dose date + 1) 
x The amount of IP received: if a participant received partial dose at a dosing visit, then 
the amount of IP at that dosing visit will be estimated based on the actual volume 
administered. The amount of VIB7734 is 0 mg for dosing visits with placebo 
administered. 


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x Treatment compliance for an individual patient = (Total number of doses received)/ 
(Total number of doses planned per protocol) ×100%.  
Furthermore, the time to discontinuation of IP will be presented as Kaplan-Meier plot 
including the number of participants at risk.  
3.6 
Prior and Concomitant Medications 
Number (%) of participants who receive prior medications and concomitant medications will 
be summarized by world health organization drug dictionary Anatomical Therapeutic 
Chemical category and PT based on the full analysis set and safety analysis set respectively. 
At each level of summarization, a participant is counted once if he/she reported one or more 
medications at that level. The concomitant medications will be summarized by category 
(immunomodulatory vs non- immunomodulatory medications). The prior and concomitant 
medications are defined as below.  
x Prior medications are defined as medications with a stop date occurring before the 
first IP administration date. 
x Concomitant medications are defined as medications with a stop date on or after the 
first IP administration date. 
SLE disease related immunosuppressants including glucocorticoid (GC) at Baseline are 
defined as all immunosuppressants with an intake at the date of first dose of IP (ie, start date 
on or before the date of first dose and end date on or after date of first dose or ongoing).  
Disease related immunosuppressants at Baseline will be summarized in the following 
categories for the full analysis set. 
x Baseline oral glucocorticoid (OGC) dose (≥10 mg/day vs. <10 mg/day of prednisone 
or equivalent) 
x Baseline OGC use (yes vs no)  
x Baseline OGC dose of prednisone or equivalent for participants on OGC at Baseline 
x Baseline antimalarial use (yes vs no)   
x Other immunosuppressants (mycophenolate, methotrexate, azathioprine, etc.) use at 
Baseline (yes vs no)   
x OGC only 
x Antimalarials only 
x Other immunosuppressants only 
x OGC and antimalarials only 
x OGC and other immunosuppressants only 
x Antimalarials and other immunosuppressants only 
x OGC, antimalarials, and other immunosuppressants 


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The number and percentage of participants who receive restricted medications beyond the 
protocol-allowed threshold during treatment period will also be summarized in the following 
categories for the full analysis set.  
The selection of GC and non-GC immunosuppressants will be specified in the SPP. The 
missing start/stop date of medications will be imputed as appropriate, and the details of the 
imputation will be included in the SPP. 


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3.7 
Efficacy Analyses 
3.7.1 
Primary Endpoint and Analyses 
3.7.1.1 
Primary endpoint and estimand 
The estimand of primary interest is defined as follows, using composite variable strategy to 
address intercurrent events. 
x Population: Participants in the full analysis set with active SLE despite receiving 1 or 
more standard of care treatments as defined by the inclusion-exclusion criteria of the 
study (excluding subjects from Russia and Ukraine sites) 
x Variable (endpoint): Response in BICLA + OGC ≤ 7.5 mg/day and ≤ Day 1 dose at 
Week 48, where BICLA is defined by meeting the following criteria compared to 
Baseline: 
 BILAG-2004 Index improvement (all Baseline BILAG A improving to B/C/D, all 
Baseline BILAG B to C/D, and ≤ 1 new BILAG B and no new BILAG A). 
 No deterioration in SLEDAI-2K total score, where deterioration is defined as an 
increase from baseline of > 0 points in SLEDAI-2K. 
 No significant worsening in PGA score (< 0.3 point increase). 
 No use of restricted medications beyond the protocol-allowed threshold (see 
section 3.6) before assessment.  
 No discontinuation of IP.  
x Intercurrent event:  
 Rescue medications: Captured in the primary variable definition.  
 Treatment discontinuation: Captured in the primary variable definition.  
x Population-level summary: Difference in proportions of responders between the 
VIB7734 group and placebo group. 
3.7.1.2 
Primary efficacy analysis 
Participants with no BILAG A or B at baseline and no worsening in any organ systems (≤ 1 
new BILAG B and no new BILAG A), as well as participants with a baseline PGA score > 
2.7 will be considered as having met the criteria for BILAG and PGA, respectively.
The proportion of participants achieving BICLA response + OGC ≤ 7.5 mg/day and ≤ Day 1 
dose prednisone or equivalent at Week 48 in the VIB7734 treatment group will be compared 
to that of the placebo group for the full analysis set using a logistic regression model with 
treatment, and randomization stratification factors included in the model.  
The difference in proportions of responders between each of VIB7734 groups and placebo 
group will be estimated together with its associated 2-sided 90% confidence interval (CI) and 
p-value. The significance of treatment effect will be tested by using a 2-sided test at 
significance level α of 0.1. Additionally, estimates of the response rate for each treatment 
group will be obtained, together with the associated standard error (SE). 


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Longitudinal presentations of results over time based on the same analysis will be created.  
3.7.1.3 
Supplementary analysis of primary endpoint 
A supplementary analysis with the same model as primary analysis will be performed using a 
treatment policy strategy to address intercurrent events defined in section 3.7.1.1. All 
observed values will be used regardless of occurrence of an intercurrent event. 
3.7.1.4 
Handling plan for missing data 
Intermittent missing data will be imputed using last observation carried forward approach 
(LOCF). Participants with missing primary outcome measures due to early discontinuation of 
study will be considered nonresponders. If any of the criteria cannot be evaluated at a visit, 
that criterion will be imputed using LOCF.  
Missing items in SLEDAI-2K and BILAG-2004 will be imputed according to the specific 
rules described in Section 3.7.4. 
3.7.1.5 
Multiplicity adjustment 
No multiplicity adjustment is planned since this is a phase 2 exploratory trial. 
3.7.2 
Secondary Efficacy Endpoints and Analyses 
3.7.2.1 
Secondary efficacy endpoints and estimands 
The estimands are defined as follows, using composite variable strategy to address 
intercurrent events. 
x Population:  
 CLASI: Participants in the full analysis set with active SLE and CLASI-A score 
≥ 10 at Baseline despite receiving one or more standard of care treatments as 
defined by the inclusion-exclusion criteria of the study (excluding subjects from 
Russia and Ukraine sites). 
 OGC reduction: Participants in the full analysis set with active SLE taking an 
OGC of ≥ 10 mg/day of prednisone or equivalent at Baseline despite receiving 
one or more standard of care treatments as defined by the inclusion-exclusion 
criteria of the study (excluding subjects from Russia and Ukraine sites). 
 SRI-4 + OGC ≤ 7.5 mg/day and ≤ Baseline (Day 1) dose and LLDAS: 
Participants in the full analysis set with active SLE despite receiving one or more 
standard of care treatments as defined by the inclusion-exclusion criteria of the 
study (excluding subjects from Russia and Ukraine sites). 
x Variable (endpoint):  


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 CLASI: ≥ 50% reduction in CLASI-A score at Week 12 defined by meeting the 
following criteria: 
o A ≥ 50% reduction of CLASI-A score at Week 12 as compared to Baseline. 
o No use of restricted medications beyond the protocol-allowed threshold (see 
section 3.6) before assessment.  
o No discontinuation of IP before assessment.  
 SRI-4 + OGC ≤ 7.5 mg/day and ≤ Baseline (Day 1) dose: Response in SRI-4 + 
OGC ≤ 7.5 mg/day and ≤ Baseline (Day 1) dose at Week 48, where SRI-4 is 
defined by meeting the following criteria compared to Baseline: 
o Reduction from Baseline of ≥ 4 points in the SLEDAI-2K. 
o No new organ system affected as defined by one or more BILAG A or 2 or 
more BILAG B items. 
o No significant worsening in PGA score (< 0.3 point increase). 
o No use of restricted medications beyond the protocol-allowed threshold (see 
section 3.6) before assessment. 
o No discontinuation of IP. 
 OGC reduction: Maintained OGC reduction from Week 36 to Week 48 defined by 
meeting the following criteria: 
o An OGC dose of ≤ 7.5 mg/day prednisone or equivalent at Week 36 that is 
maintained through Week 48. 
o No use of restricted medications beyond the protocol-allowed threshold (see 
section 3.6) before assessment.  
o No discontinuation of IP before assessment.  
 LLDAS: Response in LLDAS at Week 48, where LLDAS is defined by meeting 
the following criteria: 
o A SLEDAI-2K ≤ 4, with no activity in major organ systems (renal, central 
nervous system (CNS), cardiopulmonary, vasculitis, fever) and no hemolytic 
anemia or gastrointestinal activity.  
 SLEDAI-2K organ system is define in section 3.7.3.1.8. Hemolytic anemia 
and gastrointestinal activity will be assessed by BILAG-2004 (present 
evidence of active hemolysis and gastrointestinal manifestation respectively).  
o No new lupus disease activity compared with the previous assessment 
measured by SLEDAI-2K. 
 New lupus disease activity is defined as present activity (item score >0) in 
at least one new SLEDAI-2K item compared with the previous visit.  
o A PGA ≤ 1 (on a scale of 0 to 3). 
o Current prednisone or equivalent dose of ≤ 7.5 mg/day. 
o Well-tolerated standard maintenance doses of immunosuppressive drugs and 
approved medications as allowed and specified in the protocol. 


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 Any discontinuation of permitted non-GC immunosuppressants is assumed 
to be due to toxicity. 
o No use of restricted medications beyond the protocol-allowed threshold (see 
section 3.6) before assessment.  
o No discontinuation of IP.  
x Intercurrent event:  
 Rescue medications: Captured in the variable definition. 
 Treatment discontinuation: Captured in the variable definition. 
x Population-level summary for all secondary endpoints: Difference in proportions of 
responders between VIB7734 and placebo. 
3.7.2.2 
Secondary efficacy analysis 
SRI-4 + OGC ≤ 7.5 mg/day and ≤ Baseline (Day 1) dose at Week 48 and LLDAS at Week 48 
will be analyzed using the same logistic regression model as described in section 3.7.1.2 for 
the primary endpoint based on the full analysis set.   
Maintained OGC reduction from Week 36 to Week 48 will be analyzed using a similar 
logistic regression model as described in section 3.7.1.2 replacing baseline OGC category 
(≥ 10 or < 10 mg/day) with Baseline OGC dose based on subgroup of participants with OGC 
of ≥ 10 mg/day of prednisone or equivalent at Baseline.  
Achieving a ≥ 50% reduction in CLASI-A score at Week 12 will be analyzed using a similar 
logistic regression model as described in section 3.7.1.2 including Baseline CLASI-A score 
as an additional covariate based on subgroup of participants with CLASI-A score ≥ 10 at 
Baseline.  
The difference in proportions of responders of VIB7734 versus placebo will be estimated for 
all secondary endpoints together with its associated 2-sided 90% CI and p-value. In addition, 
estimates of the response rate for each treatment group will be obtained, together with the 
associated SE.  
Longitudinal presentations of results over time based on the same analysis will be created. 
3.7.2.3 
Supplementary analysis of secondary endpoints 
A supplementary analysis with the same model as described in section 3.7.2.2 for each 
secondary endpoint will be performed using a treatment policy strategy to address 
intercurrent events defined in section 3.7.2.1. All observed values will be used regardless of 
occurrence of an intercurrent event. 


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3.7.2.4 
Handling plan for missing data 
The missing data will be handled the same way as that for the primary endpoint analysis (see 
section 3.7.1.4). 
3.7.3 
Exploratory Efficacy Endpoints and Analyses 
3.7.3.1 
Exploratory efficacy endpoints 


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3.7.3.2 
Exploratory efficacy analyses 


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3.7.4 
Handling Missing Items of Clinical Outcome Assessments 
The BILAG-2004, SLEDAI-2K, CLASI, 
are clinician reported 
outcomes and will be captured electronically. There will be very few missing items expected. 
All PROs will be administered electronically too. Questions are mandatory so there will be 
very few missing items expected. But in case there are missing items, the following 
algorithms will be used to handle the missing items. 


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3.7.5 
Subgroup Analysis  
To explore the uniformity of the detected overall treatment effect, subgroup analyses on the 
primary endpoint and secondary endpoints of SRI-4 + OGC ≤ 7.5 mg/day and ≤ Baseline 
dose and LLDAS will be performed for the following factors:  
x SLEDAI-2K total score at screening (<10 points versus ≥10 points)  
x OGC dose at baseline (<10 mg/day versus ≥10 mg/day prednisone or equivalent)  
 
x Age (<55 versus ≥55 years)  
x Onset of disease (adult versus pediatric onset)  
x BMI (≤30 versus >30 kg/m2)  
x Race (white, black or African American, other) 
x Ethnicity (Hispanic/Latino versus not Hispanic/Latino) 
x Geographic region (Asia, Latin America, Europe, North America) 


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3.8 
Safety Analysis 
3.8.1 
Adverse Events 
In general, if an adverse event (AE) onset is on or after the first dose of IP administration, the 
AE will be considered as a treatment emergent AE (TEAE). Otherwise, the AE will be 
considered as a non-treatment emergent AE.  
An overall summary table will be showing the number and percentage of participants with at 
least 1 event in any of the following categories: TEAE, treatment emergent serious AE 
(TESAE), TEAE with outcome of death, TEAE leading to discontinuation of IP, grade 3 or 
higher TEAE, serious and/or grade 3 or higher TEAE, IP related TEAE, IP related TESAE.  
AEs will be coded using the most recent version of MedDRA. All TEAEs will be 
summarized overall and by MedDRA SOC and PT, by severity and by relationship to IP. 
Specific AEs will be counted once for each participant for calculating rates, but all events 
will be presented in subject listings. In addition, if the same AE occurs multiple times within 
a particular participant, the highest severity and level of causality will be reported. 
The TEAEs, TESAEs, TEAEs resulting in death, TEAEs leading to discontinuation of IP, 
Grade 3 or higher TEAEs, IP related TEAEs, and IP related TESAEs will be summarized by 
SOC and PT. TESAEs will be summarized by SAE criteria as well. In addition, a summary of 
TEAEs sorted by frequency will be presented by PT.  
An AE of special interest (AESI) is an AE of scientific and medical interest specific to 
understanding of the IP and may require close monitoring and collection of additional 
information by the Investigator. AESIs for this protocol include: 
x Hypersensitivity reaction, including anaphylaxis 
x Viral infection/reactivation 
x Opportunistic infection 
x Malignancy (except non-melanoma skin cancer) 
Treatment emergent AESIs will be summarized by SOC and PT. 
Listings will be provided for all TEAEs and non-treatment emergent AEs. 
3.8.2 
Clinical Laboratory Evaluation 
The hematology, coagulation, serum chemistry, lipid profile, urinalysis, immunoglobulins 
parameters, and high-sensitivity C-reactive protein, as well as changes from baseline, will be 
summarized with descriptive statistics at each visit. Shift from the baseline relative to the 
normal range will also be summarized. Additionally, worst toxicity grade, ≥grade 3 toxicity 
post-baseline, and shift from baseline to worst toxicity grade in hematology, coagulation, 
serum chemistry, and lipid profile parameter will be produced. 


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3.8.3 
Other Safety Evaluations 
3.8.3.1 
Overdose 
The incidence of TEAE associated with overdose will be summarized by MedDRA SOC and 
PT if applicable. 
3.8.3.2 
Vital signs 
The observed values along with the changes from baseline will be summarized for systolic 
blood pressure, diastolic blood pressure, body temperature, heart rate, and respiratory. In 
addition, a summary of participants with clinically significant vital signs values (meeting any 
of following criteria) will be provided. 
x Systolic blood pressure: <90 mmHg, >160 mmHg 
x Diastolic blood pressure: <60 mmHg, >100 mmHg 
x Heart rate: <50 beats/min, >100 beats/min 
x Respiratory rate: <12 breaths/min, >23 breaths/min 
x Temperature: <36°C, >38°C 
3.8.3.3 
Electrocardiogram 
The observed values along with the changes from baseline will be summarized for heart rate, 
RR interval, PR Interval, QRS duration, QT interval and the corrected QT interval (QTc) 
using Bazett’s and Fridericia’s corrections. The number (%) of participants meeting the 
following criteria will be summarized. 
x QTc > 450 msec 
x QTc > 480 msec 
x QTc > 500 msec 
x QTc increases from baseline > 30 msec 
x QTc increases from baseline > 60 msec 
In addition, the overall clinical evaluation of ECG results (normal, abnormal, not clinically 
significant abnormal, clinically significant abnormal) will also be summarized. 
3.8.3.4 
Physical Examination and Weight 
Significant physical examination findings will be summarized if data are available. The 
observed values and the changes from baseline in the weight and BMI will be summarized. 


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3.9 
Pharmacokinetics 
The PK analysis will be based on the PK analysis set. Descriptive statistics of the serum 
VIB7734 concentration will be tabulated by visit and by treatment group. Mean serum 
concentration-time profiles of VIB7734 by treatment group will be generated. Serum 
VIB7734 concentration data for individual participant will be presented in a listing.  
Population modeling will be performed by vendor to better characterize the PK of VIB7734 
given by SC injection in SLE participants. 
3.10 
Immunogenicity 
3.11 
Pharmacodynamics 
Absolute values and change from baseline in pDCs will be summarized descriptively by visit 
for each treatment group based on safety analysis set. 


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3.12 
Exploratory Analyses 
4 PLANNED ANALYSIS 
4.1 
Planned Interim Analysis 
An interim analysis will be conducted after all participants have completed the Week 24 visit 
or are discontinued early from the study. A small prespecified number of Sponsor staff who 
are not directly involved in the conduct of the study will be unblinded to make a go/no-go 
decision for future studies.  
Sponsor personnel directly associated with the conduct of the study, study site personnel, 
participants, and CRO will remain blinded to the treatment assignment for individual 
participants and the results of the interim analysis until the completion of the study. The 
efficacy and safety data prior to the data cut-off for the interim analysis will be analyzed. No 
multiplicity adjustment is planned for the interim analysis because there is no provision to 
stop the trial early at the interim analysis to claim efficacy. Details of the interim analysis 
(go/no-go criteria, unblinding plan, and communication plan) will be specified in an interim 
unblinding analysis plan prior to unblinding. 


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4.2 
Planned Primary Analysis 
The primary analysis will be conducted after the last participant has completed the Week 48 
visit or discontinued from study early. For the primary analysis, all the efficacy and safety 
data collected prior to the data cut-off for the primary analysis will be analyzed. 
4.3 
Planned Final Analysis 
The final analysis will be conducted after all participants have completed or discontinued 
early from the study.  
 
 


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5 REFERENCES 
Furie R, et al, 2017 
Furie R, Khamashta M, Merrill JT et al. Anifrolumab, an anti-interferon-alpha receptor 
monoclonal antibody, in moderate-to-severe systemic lupus erythematosus. Arthritis 
Rheumatology 2017; 69(2): 376-386 
Merrill JT, et al, 2018 
Merrill JT, Furie R, Werth VP et al. Anifrolumab effects on rash and arthritis: impact of the 
type I interferon gene signature in the phase IIb MUSE study in patients with systemic lupus 
erythematosus. Lupus Science & Medicine 2018; 5: e000284. doi: 10.1136/lupus-2018-
000284 
Penner IK, et al 2009 
Penner IK, Raselli C, Stöcklin M et al. The Fatigue Scale for Motor and Cognitive Functions 
(FSMC): Validation of a new instrument to assess multiple sclerosis-related fatigue. Multiple 
Sclerosis Journal 2009; 15(12): 1509–1517 
Smarr KL and Keefer AL 2011 
Smarr KL and Keefer AL. Measures of depression and depression symptoms: Beck 
Depression Inventory-II (BDI-II), Center for Epidemiologic Studies Depression Scale (CES-
D), Geriatric Depression Scale (GDS), Hospital Anxiety and Depression Scale (HADS), and 
Patient Health Questionnaire-9 (PHQ-9). Arthritis Care Research 2011; 63(Suppl 11): S454-
466 
van Vollenhoven RF, et al, 2021 
2021 DORIS definition of remission in SLE: final recommendations from an international 
task force. Lupus Science & Medicine 2021; 8:e000538. doi:10.1136/ lupus-2021-000538 
Yee CS, et al, 2010 
Yee CS, Cresswell L, Farewell V et al. Numerical scoring for the BILAG-2004 index. 
Rheumatology 2010; 49(9): 1665-1669 
 
 


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Revision History: 
Version # 
Description of Change 
1.0 
Initial version 
2.0 
 
 


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6 APPENDIX 
 
 


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APPENDIX 1. Grading Algorithm for Each Domain of BILAG-2004 
CONSTITUTIONAL 
 
Category A: 
Pyrexia recorded as 2 (same), 3 (worse) or 4 (new) AND 
 
Any 2 or more of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Weight loss 
Lymphadenopathy/sp
lenomegaly 
Anorexia 
 
Category B: 
Pyrexia recorded as 2 (same), 3 (worse) or 4 (new) OR 
 
Any 2 or more of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Weight loss 
Lymphadenopathy/sp
lenomegaly 
Anorexia 
 
BUT do not fulfil criteria for Category A 
 
Category C 
Pyrexia recorded as 1 (improving) OR 
One or more of the following recorded as > 0: 
Weight loss 
Lymphadenopathy/Splenomegaly 
Anorexia 
 
BUT does not fulfil criteria for category A or B 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 


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MUCOCUTANEOUS 
 
Category A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Skin eruption - 
severe Angio-
oedema - 
severe Mucosal 
ulceration - 
severe 
Panniculitis/Bullous lupus - severe 
Major cutaneous vasculitis/thrombosis 
 
Category B 
Any Category A features recorded as 1 (improving) OR 
Any of the following recorded as 2 (same), 3 (worse) 
or 4 (new): Skin eruption - mild 
Panniculitis/Bullous 
lupus - mild Digital 
infarcts or nodular 
vasculitis Alopecia - 
severe 
 
Category C 
Any Category B features recorded as 1 (improving) OR 
Any of the following recorded as > 0: 
Angio-oedema - mild 
Mucosal ulceration - mild 
Alopecia - mild 
Periungual erythema/chilblains 
Splinter haemorrhages 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 
 


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NEUROPSYCHIATRIC 
 
Category A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Aseptic meningitis 
Cerebral vasculitis 
Demyelinating syndrome 
Myelopathy 
Acute confusional state 
Psychosis 
Acute inflammatory demyelinating polyradiculoneuropathy 
Mononeuropathy (single/multiplex) 
Cranial neuropathy 
Plexopathy 
Polyneuropathy 
Status epilepticus 
Cerebellar ataxia 
 
Category B 
Any Category A features recorded as 1 (improving) OR 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
Seizure disorder 
Cerebrovascular disease (not due 
to vasculitis) Cognitive 
dysfunction 
Movement disorder 
Autonomic disorder 
Lupus headache - severe unremitting 
Headache due to raised intracranial hypertension 
 
Category C 
Any Category B features recorded as 1 (improving) 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 


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MUSCULOSKELETAL 
 
Category A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Severe Myositis 
Severe Arthritis 
 
Category B 
Any Category A features recorded as 1 (improving) OR 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
Mild Myositis 
Moderate Arthritis/Tendonitis/Tenosynovitis 
 
Category C 
Any Category B features recorded as 1 (improving) OR 
 
Any of the following recorded as > 0: 
Mild Arthritis/Arthralgia/Myalgia 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 


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CARDIORESPIRATORY 
 
Category A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Myocarditis/Endocarditis + Cardiac failure 
Arrhythmia 
New valvular dysfunction 
Cardiac tamponade 
Pleural effusion with dyspnoea 
Pulmonary haemorrhage/vasculitis 
Interstitial alveolitis/pneumonitis 
Shrinking lung syndrome 
Aortitis 
Coronary vasculitis 
 
Category B 
Any Category A features recorded as 1 (improving) OR 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
Pleurisy/Pericarditis 
Myocarditis - mild 
 
Category C 
Any Category B features recorded as 1 (improving) 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 


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GASTROINTESTINAL 
 
Category A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Peritonitis 
Lupus enteritis/colitis 
Intestinal pseudo-obstruction 
Acute lupus cholecystitis 
Acute lupus pancreatitis 
 
Category B 
Any Category A feature recorded as 1 (improving) OR 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
Abdominal serositis and/or ascites 
Malabsorption 
Protein losing enteropathy 
Lupus hepatitis 
 
Category C 
Any Category B features recorded as 1 (improving) 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 


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OPHTHALMIC 
 
Category A 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
 
Orbital inflammation/myositis/proptosis 
Keratitis - severe 
Posterior uveitis/retinal vasculitis - severe 
Scleritis - severe 
Retinal/choroidal vaso-occlusive disease 
Optic neuritis 
Anterior ischaemic optic neuropathy 
 
Category B 
Any Category A features recorded as 1 (improving) OR 
Any of the following recorded as 2 (same), 3 (worse) or 4 (new): 
Keratitis - mild 
Anterior uveitis 
Posterior uveitis/retinal vasculitis - mild 
Scleritis - mild 
 
Category C 
Any Category B features recorded as 1 (improving) OR 
Any of the following recorded as > 0: 
Episcleritis 
Isolated cotton-wool spots (cytoid bodies) 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 


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RENAL 
 
Category A 
Two or more of the following providing 1, 4 or 5 is included: 
 
1. Deteriorating proteinuria (severe) defined as 
 
(a) urine dipstick increased by ≥ 2 levels (used only if other methods of urine protein 
estimation not available); or 
(b) 24 hour urine protein > 1 g that has not decreased (improved) by ≥ 25%; or 
(c) urine protein-creatinine ratio > 100 mg/mmol that has not decreased (improved) by 
≥25%; or 
(d) urine albumin-creatinine ratio > 100 mg/mmol that has not decreased (improved) by 
≥25% 
 
2. Accelerated hypertension 
3. Deteriorating renal function (severe) defined as 
 
 
(a) plasma creatinine > 130 μmol/l and having risen to > 130% of previous value; or 
(b) GFR < 80 ml/min per 1.73 m2 and having fallen to < 67% of previous value; or 
(c) GFR < 50 ml/min per 1.73 m2, and last time was > 50 ml/min per 1.73 m2 or was not 
measured. 
 
4. Active urinary sediment 
5. Histological evidence of active nephritis within last 3 months 
6. Nephrotic syndrome 
 
Category B 
One of the following: 
 
1. One of the Category A feature 
 
2. Proteinuria (that has not fulfilled Category A criteria) 
(a) urine dipstick which has risen by 1 level to at least 2+ (used only if other 
methods of urine protein estimation not available); or 
(b) 24 hour urine protein ≥ 0.5 g that has not decreased (improved) by ≥ 25%; or 
(c) urine protein-creatinine ratio ≥ 50 mg/mmol that has not decreased (improved) by 
≥25%; or 
(d) urine albumin-creatinine ratio ≥ 50 mg/mmol that has not decreased (improved) by 
≥25% 
 
 
3. Plasma creatinine > 130 μmol/l and having risen to ≥ 115% but ≤ 130% of previous value 
 
Category C 
One of the following: 
 
1. Mild/Stable proteinuria defined as 


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(a) urine dipstick ≥ 1+ but has not fulfilled criteria for Category A & B (used only if 
other methods of urine protein estimation not available); or 
(b) 24 hour urine protein > 0.25 g but has not fulfilled criteria for Category A & B ; or 
(c) urine protein-creatinine ratio > 25 mg/mmol but has not fulfilled criteria for Category 
A & B; or 
(d) urine albumin-creatinine ratio > 25 mg/mmol but has not fulfilled criteria for 
Category A & B 
 
 
2. Rising blood pressure (providing the recorded values are > 140/90 mm Hg) which has 
not fulfilled criteria for Category A & B, defined as 
 
(a) systolic rise of ≥ 30 mm Hg; and 
(b) diastolic rise of ≥ 15mm Hg 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 
 
Note: although albumin-creatinine ratio and protein-creatinine ratio are different, we use 
the same cut- off values for this index 
 
 


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HAEMATOLOGICAL 
 
Category A 
TTP recorded as 2 (same), 3 (worse) or 4 (new) OR 
 
Any of the following: 
 
Evidence of haemolysis and Haemoglobin < 8 g/dl 
Platelet count 
< 25 x 109/l 
 
Category B 
TTP recorded as 1 (improving) OR 
 
Any of the following: 
 
Evidence of haemolysis and Haemoglobin 8 - 9.9 g/dl 
Haemoglobin 
< 8 g/dl (without haemolysis) 
White cell count 
< 1.0 x 109/l 
Neutrophil count 
< 0.5 x 109/l 
Platelet count 
25 - 49 x 109/l 
 
Category C 
Any of the following: 
 
Evidence of haemolysis and Haemoglobin ≥ 10g/dl 
Haemoglobin 
8 - 10.9 g/dl (without haemolysis) 
White cell count 
1 - 3.9 x 109/l 
Neutrophil count 
0.5 - 1.9 x 109/l 
Lymphocyte count 
< 1.0 x 109/L 
Platelet count 
50 - 149 x 109/l 
Isolated Coombs’ test positive 
 
Category D 
Previous involvement 
 
Category E 
No previous involvement 
 
 


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APPENDIX 2. APPROVALS
Confirmation by the study biostatistician (or designee), biostatistics management (or designee), and the 
study clinical colleague or therapeutic lead (or designee) that the review of this statistical analysis plan is 
complete, and there is agreement on the content. 
Sr Director, Biostatistics
Name, 
Title
Signature/Date
VP, Biometrics
Name, 
Title
Signature/Date
Executive Medical Director, Clinical 
Development
Name, 
Title
Signature/Date


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