Conditions: Sjögren's Syndrome
Keywords: Sjögren's Syndrome SS VIB4920 MEDI4920
Allocation: RANDOMIZED | Intervention model: PARALLEL
Enrollment: 183
Healthy volunteers: no

Brief summary:
The purpose of the study is to evaluate the efficacy, safety, and tolerability of VIB4920 (formerly MEDI4920) in adult participants with Sjögren's Syndrome (SS).

Detailed description:
The study will enrol 2 SS populations: Population 1 will include participants with moderate to high systemic disease activity defined by European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) \>= 5; Population 2 will include participants with moderate to severe subjective symptoms defined by EULAR Sjögren's Syndrome Patient Reported Index (ESSPRI) score \>= 5 and residual stimulated salivary flow but with mild systemic disease activity defined by ESSDAI score \< 5. This study will include 3 periods: screening (4 weeks), treatment period (40 Weeks) and follow-up period (12 weeks). In the treatment period, participants from each of the populations will be randomized at 1:1 ratio to receive intravenous (IV) dose of VIB4920 or placebo (Stage I). After completion of Stage I, participants randomized to VIB4920 in Stage I will receive placebo and participants randomized to placebo in Stage I will receive VIB4920 (Stage II). Participants who had study drug discontinuation will not be eligible for treatment during Stage II. All participants will be followed for at least 12 weeks after their last dose of study drug administration.

Study acquired from Horizon in 2024.

Arms:
arm 1: Participants in population 1 will receive IV VIB4920 Dose 1 in Stage I and placebo matched to VIB4920 in Stage II. arm 2: Participants in population 1 will receive IV placebo matched to VIB4920 in Stage I and IV VIB4920 Dose 1 in Stage II. arm 3: Participants in population 2 will receive IV VIB4920 Dose 1 in Stage I and placebo matched to VIB4920 in Stage II. arm 4: Participants in population 2 will receive IV placebo matched to VIB4920 in Stage I and IV VIB4920 Dose 1 in Stage II.

Interventions: intervention 1: VIB4920 intervention 2: Placebo
Intervention descriptions: intervention 1: Intravenous Dose 1. intervention 2: Intravenous dose matched to VIB4920.

Protocol document:
Prot_000.pdf: 
Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
Page 1 of 2 
HORIZON THERAPEUTICS IRELAND DAC 
(FORMERLY VIELA BIO, INC.) 
A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO-
CONTROLLED, PROOF OF CONCEPT STUDY TO EVALUATE THE 
EFFICACY AND SAFETY OF VIB4920 IN SUBJECTS WITH SJÖGREN’S 
SYNDROME (SS) 
 
Investigational Product(s) 
VIB4920 
Protocol Number 
VIB4920.P2.S2  
Clinical Trial Registry Identifiers 
ClinicalTrials.gov: NCT04129164 
EudraCT: 2019-002713-19 
Version Number 
3.0 
Version Date 
8 Nov 2022 
Amendment 
2 
Administrative Change 
1 
IND Number 
IND 128905 
Principal Investigator 
, MD 
Duke University Medical Center 
Durham, North Carolina, USA 
Sponsor 
Horizon Therapeutics Ireland DAC (formerly Viela Bio, Inc.) 
Responsible Medical Officer: 
, MD  
Associate Medical Director, Clinical Development  
Phone: 
  
2400 Research Blvd., Suite 200, Rockville, MD 20850, USA㻌


Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
Page 2 of 3 
SUMMARY OF CHANGES TO THE PROTOCOL 
Protocol Amendment 1;   21 July 2020 
The Amendment 1changes to the protocol included the following:  
Protocol Section(s) 
Impacted by Change 
(Section Title) 
Change 
Reason for Change 
Title page (Clinical Trial 
Registry Identifiers) 
Clinical Trial Registry Identifiers added. 
Clarification.  
Title page (Responsible 
Medical Officer) 
Responsible Medical Officer changed from 
“
” to “
”. 
(Corresponding details regarding qualifications, 
role, and contact details updated to align with 
change.) 
Correction. 
List of Abbreviations 
Synopsis 
Section 3.3.3 (Exploratory 
Endpoints for Population #1) 
Section 3.4.3 (Exploratory 
Endpoints for Population #2) 
Section 6.4.1.14 
(ClinESSDAI) 
 
Correction 
List of Abbreviations 
The term “serum human chorionic 
gonadotrophin” was changed to “beta-human 
chorionic gonadotrophin”. 
Correction. 
List of Abbreviations 
Synopsis 
Section 6.7 (Study 
Suspension or Termination) 
Section 8 (Safety 
Assessment) 
Section 12.1 (Safety and 
Data Monitoring Committee) 
The terms “Data and Safety Monitoring Board” 
and “DSMB” were changed to “Safety and Data 
Monitoring Committee” and “SDMC”, 
respectively. 
Clarification and consistency 
in nomenclature. 
Section 1 (Synopsis) 
Section 3.3.3 (Exploratory 
Endpoints for Population #1) 
Section 3.4.3 (Exploratory 
Endpoints for Population #2) 
Section 6 (Study Conduct), 
Table 1 and Table 3 
Section 6.2.4 (
 
(optional)) 
The term “(optional)” was added to end of 
items/statements/headings describing 
 
Clarification. 
Section 1 (Synopsis) 
Section 4.1 (Study Design) 
The number of sites was revised from 
approximately “50” to “70”. 
Correction. 
Section 2.1.5.1 (Benefit-Risk 
Assessment) 
Text describing the benefit-risk assessment of 
VIB4920 was inserted. 
Clarification. 


Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
Page 3 of 4 
Section 2.1.5.2 (Anaphylaxis, 
Serious Allergic Reactions, 
and Infusion-Related 
Reactions) 
Text inserted describing premedication options 
in the event of Grade  2 infusion-related 
reactions being observed was added. 
Clarification. 
Section 2.1.5.7 (Risks related 
to the COVID-19 pandemic) 
Section providing update on how COVID-19 
affected the study to date, and overview of 
COVID-19 risk factors associated with study 
participation was added. 
Clarification. 
Section 2.2 (Study 
Rationale), Table 1 
Text addressing COVID-19 risk, and steps to 
minimize COVID-19 risk was added. This 
includes the requirement for a negative SARS-
CoV-2 test within 2 weeks prior to 
randomization. SARS-CoV-2 testing added to 
screening procedures (Table 1). 
Clarifies the benefit-risk 
assessment is reasonable for 
a phase 2 study. 
Section 4.1 (Study Design), 
Figure 1 
Figure replacing previous figure was added.  
Correction. Day 309 arrows 
denoting administration of 
study treatment during safety 
follow-up period in 
Population #2 replaced by 
tick marks. 
Section 5.1.1 (Inclusion 
Criteria for Population #1) 
Section 5.1.3 (Inclusion 
Criteria for Population #2) 
The phrase “(the minimum age for adult 
participants can be higher than 18 years in 
countries with different regulations)” was added. 
Clarifies potential country-
specific differences in the 
study population. 
Section 5.1.1 (Inclusion 
Criteria for Population #1) 
Text inserted clarifying that, in subjects with 
(66'$,VFRUHRI 5 at screening, all ESSDAI 
domains will be scored; however, not all will 
contribute to the minimum ESSDAI score of 5 
that is required for inclusion. 
Clarification. 
Section 5.1.1 (Inclusion 
Criteria for Population #1) 
Section 5.1.3 (Inclusion 
Criteria for Population #2) 
Text providing additional details regarding 
appropriate contraception methods that must be 
adhered to in order to meet eligibility criteria 
was added. 
Clarification. 
Section 5.1.2 (Exclusion 
Criteria for Population #1) 
Section 5.1.4 (Exclusion 
Criteria for Population #2) 
The term “enrollment” was revised to “signing 
the ICF”. 
Clarification of medical 
history timeframe applicable 
to patients’ eligibility 
(confirmed deep venous 
thrombosis or arterial 
thromboembolism). 
Section 5.1.2 (Exclusion 
Criteria for Population #1) 
Section 5.1.4 (Exclusion 
Criteria for Population #2) 
Text clarifying additional exclusion criteria 
relating to infections (bacterial/viral/other), 
including COVID-19 risk was added. 
Clarification. 
Section 5.1.2 (Exclusion 
Criteria for Population #1) 
The phrase “indications other than SS” was 
changed to “indications other than SS, RA, and 
SLE”. 
Clarification of additional 
autoimmune diseases 
excluded from systemic 
corticosteroid treatment 
timeframe applicable to 
patients’ eligibility. 


Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
Page 4 of 5 
Section 5.1.2 (Exclusion 
Criteria for Population #1) 
The term “ICF signature” was revised to 
“screening visit”. 
Clarification of systemic 
corticosteroid treatment 
timeframe applicable to 
patients’ eligibility. 
Section 5.1.2 (Exclusion 
Criteria for Population #1) 
Text inserted providing timeframe applicable to 
use of “other DMARDs, immunosuppressant, or 
antiproliferative agents” and patients’ eligibility. 
Clarification. 
Section 5.1.4 (Exclusion 
Criteria for Population #2) 
Text inserted providing timeframe applicable to 
use of “MTX, AZA, leflunomide any other 
DMARDs, immunosuppressant, or 
antiproliferative agents” and patients’ eligibility. 
Clarification. 
Section 6 (Study Conduct) 
Sentence “More than one visit might be needed 
to complete screening” was added. 
Clarification. 
Section 6 (Study Conduct), 
Table 1 and Table 2. 
Section 6.4.3.1 
(Autoantibody Panel). 
The term “cryoglobulins” removed from 
autoantibody panel. 
Correction. 
Section 6 (Study Conduct), 
Table 1. 
The term “cryoglobulins” added as part of 
ESSDAI-required blood tests. 
Correction. 
Section 6 (Study Conduct), 
Table 1. 
 
 
Correction. 
Section 6 (Study Conduct), 
Table 2 and Table 3. 
Footnote “If no symptoms are present, the exam 
can be limited to assess ESSDAI” added as part 
of symptom-driven physical exam. 
Clarification. 
Section 6 (Study Conduct), 
Table 2. 
Number of visits when an autoantibody panel 
needs to be conducted has been revised. 
Clarification that 
autoantibody panel to be 
conducted at Visits 6 and 9 
only. 
Section 6 (Study Conduct), 
Table 2. 
Correction. 
Section 6 (Study Conduct), 
Table 2 and Table 3 
 
 
 
Assessments no longer 
required. 
Section 6 (Study Conduct), 
Table 2 and Table 3 
Clarification. 
Section 6 (Study Conduct), 
Table 3 
Inserted requirement for additional urine 
pregnancy test(s) at Visit 15 and EDV. 
Clarification. 
Section 6 (Study Conduct), 
Table 3 
The procedures “Autoantibody panel” and 
“Cryoglobulins” deleted. 
Correction. These procedures 
are no longer required during 
the off-treatment period or at 
any unscheduled visits. 
Section 6.2.1 (Informed 
Consent) 
The phrase “by the interactive voice/web 
response system (IXRS)” was inserted. 
Clarification on how the 
subject identification (SID) 
number will be assigned. 


Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
Page 5 of 6 
Section 6.4.1.10 
 
) 
 
. 
Clarification. 
Section 6.4.3.2 
(Inflammatory Markers) 
Section 8.5.3 
(Immunoglobulins) 
Section 6.4.3.3 (Exploratory 
 
 
Correction. 
Section 6.6.1 
(Discontinuation of 
Treatment) 
Reason for study drug discontinuation 
(withdrawal of consent) expanded to incorporate 
additional text addressing “noncompliance with 
study procedures”. 
Clarification. 
Section 6.6.1 
(Discontinuation of 
Treatment) 
Three additional reasons for study drug 
discontinuation provided (relating to receipt of 
restricted medication, receipt of rescue 
medication, and “any other reason” in the 
opinion of the Investigator). 
Clarification. 
Section 6.8 (End of Study) 
Phrase “or if a subject withdraws and completes 
the EDV (Table 2)” deleted. 
Correction. 
Section 7.1.1.4 (Peri- and 
Post-Administration 
Observations) 
Text describing the monitoring of vital signs on 
dosing days (from Section 8.6) was repositioned 
to here. 
Clarification. 
Section 7.1.1.5 
(Investigational Product 
Accountability) 
The sentences “The study IXRS system will be 
used by clinical sites to acknowledge receipt of 
study drug. Damaged shipments will be 
replaced” were inserted. 
Clarification. 
Section 7.4 (Prohibited and 
Restricted Therapies) 
Text inserted explaining Investigator discretion 
to give “medications that are considered 
necessary for the safety and well-being of 
subjects”. 
Clarification. 
Section 7.4.3 (Rescue 
Medications for Population 
#1) 
New section stating, “The initiation or increase 
in dose of the restricted medications in 
Section 7.4.2 are also considered as rescue 
medications for Population #1” was inserted. 
Clarification. 
Section 7.4.5 (Rescue 
Medications for Population 
#2) 
New section stating, “The initiation or increase 
in dose of the restricted medications in 
Section 7.4.4 are also considered as rescue 
medications for Population #2” was inserted. 
Clarification. 
Section 8.5.2 (Serum 
Chemistry) 
The parameter “creatine kinase” was added to 
the components that will be measured as part of 
the Chemistry and Renal Profile. 
Clarification. 
Section 8.5.6 (Testing for 
SARS-CoV-2) 
Section added explaining requirement for 
negative SARS-CoV-2 test. 
Clarification. 
Section 8.6 (Vital Signs) 
Sentence regarding frequency of vital sign 
observations prior, during, and post infusion 
(including cross-reference to Section 7.1.1.4) 
was inserted. 
Clarification. 


Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
Page 6 of 7 
Section 8.10 (Contacting 
Sponsor Regarding Urgent 
Protocol-related Medical 
Questions) 
Section added providing 24-7 contact details in 
the event of a study-related health emergency. 
Clarification. 
Section 9 (Other 
Assessments), Section 9.1 
(Qualitative Patient 
Interviews) and Table 2. 
Section added describing qualitative patient 
interviews and corresponding details added to 
table of scheduled study assessments. 
To gain insights into the 
overall study experience of 
participants and to generate 
patient-level qualitative 
evidence to support the 
suitability of currently 
utilized clinician-reported 
outcome and patient-reported 
outcome instruments. 
 
Protocol Amendment 2: 7 Oct 2022 
The Amendment 2 changes to the protocol included the following: 
Protocol Section(s) Impacted 
by Change (Section Title) 
Change 
Reason for Change 
Page 1 
Updated company name from Viela Bio, Inc to 
Viela Bio, Inc.(acquired by Horizon 
Therapeutics) 
Update 
Section 6.1 Sjögren’s 
Syndrome Data Medical 
Review Team 
Text clarifying the MR team will remain blinded 
to the treatment assignment for individual 
subjects until the completion of the study. 
Clarification 
Section 7.2.4.2 Unblinding 
for Interim Analysis and 
Primary Analysis 
Text clarifying any communication of unblinded 
results will be documented in an unblinding 
memo.  Population-based treatment group level 
results may be released after completion of 
primary analysis.  
Clarification 
 
Administrative Change 1: 8 Nov 2022 
The administrative change to the protocol includes the following 
Protocol Section(s) Impacted 
by Change (Section Title) 
Change 
Reason for Change 
Title Page 
Updated company name from Viela Bio, Inc. 
(acquired by Horizon Therapeutics) to Horizon 
Therapeutics Ireland DAC (formerly known as 
Viela Bio, Inc.) 
This administrative change 
includes Sponsor entity and 
company name change 
All Sections 
Viela Bio, Inc. name is removed throughout 
protocol and is replaced with Sponsor 


Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
Page 7 of 8 
 
STATEMENT OF COMPLIANCE 
The study will be conducted in compliance with this clinical study protocol, Good Clinical 
Practices (GCP) as outlined by International Conference on 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 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 as outlined by their governing institution. 


Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
Page 8 of 9 
TABLE OF CONTENTS 
1 
SYNOPSIS ....................................................................................................................... 18 
2 
INTRODUCTION ........................................................................................................... 22 
2.1 
Background ................................................................................................................... 22 
2.1.1 
Target Indication and Population ............................................................................... 23 
2.1.2 
Description of VIB4920 ............................................................................................. 24 
2.1.3 
Supportive Nonclinical Data ...................................................................................... 24 
2.1.3.1 
Pharmacology ......................................................................................................... 24 
2.1.4 
Supportive Clinical Data ............................................................................................ 25 
2.1.4.1 
Phase 1 Single-ascending Dose Study in Healthy Volunteers ................................ 25 
2.1.4.2 
Phase 1b Multiple-ascending Dose Study in Rheumatoid Arthritis ....................... 26 
2.1.5 
Risk Assessment ........................................................................................................ 27 
2.1.5.6 
Exposure In Utero ................................................................................................... 29 
2.1.5.7 
Risks related to the COVID-19 pandemic .............................................................. 29 
2.2 
Study Rationale ............................................................................................................. 29 
2.3 
Study Hypotheses.......................................................................................................... 31 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 31 
3.1 
Objectives in Population #1 .......................................................................................... 31 
3.1.1 
Primary Objective in Population #1 ........................................................................... 31 
3.1.2 
Secondary Objectives in Population #1 ..................................................................... 31 
3.1.3 
Exploratory Objectives in Population #1 ................................................................... 32 
3.2 
Objectives in Population #2 .......................................................................................... 32 
3.2.1 
Primary Objective in Population #2 ........................................................................... 32 
3.2.2 
Secondary Objectives in Population #2 ..................................................................... 32 
3.2.3 
Exploratory Objectives in Population #2 ................................................................... 32 
3.3 
Endpoints for Population #1 ......................................................................................... 32 


Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
Page 9 of 10 
3.3.1 
Primary Endpoint for Population #1 .......................................................................... 32 
3.3.2 
Secondary Endpoints for Population #1 .................................................................... 32 
3.3.3 
Exploratory Endpoints for Population #1 .................................................................. 33 
3.4 
Endpoints for Population #2 ......................................................................................... 34 
3.4.1 
Primary Endpoint for Population #2 .......................................................................... 34 
3.4.2 
Secondary Endpoints for Population #2 .................................................................... 34 
3.4.3 
Exploratory Endpoints for Population #2 .................................................................. 34 
4 
STUDY PLAN ................................................................................................................. 35 
4.1 
Study Design ................................................................................................................. 35 
4.2 
Dose and Treatment Regimen Rationale ...................................................................... 38 
4.3 
Rationale for 2 Study Populations ................................................................................ 38 
4.4 
Rationale for Primary Endpoint Selection .................................................................... 39 
5 
POPULATION ................................................................................................................ 39 
5.1 
Inclusion and Exclusion Criteria ................................................................................... 39 
5.1.1 
Inclusion Criteria for Population #1 .......................................................................... 39 
5.1.2 
Exclusion Criteria for Population #1 ......................................................................... 41 
5.1.3 
Inclusion Criteria for Population #2 .......................................................................... 43 
5.1.4 
Exclusion Criteria for Population #2 ......................................................................... 45 
6 
STUDY CONDUCT ........................................................................................................ 47 
6.1 
Sjögren’s Syndrome Data Medical Review Team ........................................................ 56 
6.2 
Screening Procedures .................................................................................................... 56 
6.2.1 
Informed Consent....................................................................................................... 56 
6.2.2 
Demographics and Baseline Characteristics .............................................................. 56 
6.2.3 
Re-screening Procedures ............................................................................................ 57 
6.3 
Randomization .............................................................................................................. 57 
6.4 
Treatment Period ........................................................................................................... 58 
6.4.1 
Efficacy Assessments................................................................................................. 58 
6.4.1.1 
ESSDAI................................................................................................................... 58 
6.4.1.2 
ESSPRI ................................................................................................................... 59 
6.4.1.3 
36-Item Short Form Survey version 2 (acute recall) Questionnaire ....................... 59 
6.4.1.4 
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue ................... 59 


Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
Page 10 of 11 
6.4.1.7 
Ocular Surface Disease Index (OSDI) .................................................................... 60 
6.4.1.8 
Patient Global Impression of Change ..................................................................... 60 
6.4.1.9 
Patient Global Impression of Severity .................................................................... 60 
6.4.1.14 
ClinESSDAI ............................................................................................................ 61 
6.4.2 
Safety Assessments .................................................................................................... 61 
6.4.3 
Additional Disease-related Assessments ................................................................... 62 
6.4.3.1 
Autoantibody Panel ................................................................................................. 62 
6.4.3.2 
Inflammatory Markers ............................................................................................ 62 
6.4.4 
Immunogenicity Assessments .................................................................................... 63 
6.4.5 
Pharmacokinetic Assessments ................................................................................... 63 
6.5 
Off-treatment Period ..................................................................................................... 63 
6.6 
Discontinuation or Withdrawal ..................................................................................... 63 
6.6.1 
Discontinuation of Treatment .................................................................................... 63 
6.6.2 
Withdrawal from Study.............................................................................................. 64 
6.6.3 
Replacement of Subjects ............................................................................................ 65 
6.6.4 
Subjects Lost to Follow-up ........................................................................................ 65 
6.7 
Study Suspension or Termination ................................................................................. 65 
6.8 
End of Study ................................................................................................................. 65 
7 
STUDY INTERVENTIONS ........................................................................................... 66 
7.1 
Description of Products................................................................................................. 66 
7.1.1 
VIB4920 ..................................................................................................................... 66 


Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
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7.1.1.1 
Formulation, Storage, Preparation, and Handling .................................................. 66 
7.1.1.2 
Dose Preparation ..................................................................................................... 66 
7.1.1.3 
Dosing and Administration ..................................................................................... 67 
7.1.1.4 
Peri- and Post-Administration Observations .......................................................... 68 
7.1.1.5 
Investigational Product Accountability ................................................................... 68 
7.1.1.6 
VIB4920 Handling and Disposal ............................................................................ 68 
7.1.2 
Placebo ....................................................................................................................... 68 
7.1.2.1 
Formulation, Storage, Preparation and Handling ................................................... 68 
7.1.2.2 
Dosing and Administration ..................................................................................... 69 
7.2 
Treatment Assignment and Bias Minimization ............................................................ 69 
7.2.1 
Treatment Allocation ................................................................................................. 69 
7.2.2 
Randomization Strategy and Procedure ..................................................................... 69 
7.2.3 
Extent and Maintenance of Blinding ......................................................................... 69 
7.2.4 
Unblinding Procedures............................................................................................... 69 
7.2.4.1 
Unblinding in the Event of a Medical Emergency.................................................. 69 
7.2.4.2 
Unblinding for Interim Analysis and Primary Analysis ......................................... 69 
7.3 
Assessment and Verification of Compliance ................................................................ 70 
7.4 
Prohibited and Restricted Therapies ............................................................................. 70 
7.4.1 
Medications Leading to Immediate Discontinuation of Investigational Product for 
Both Populations ........................................................................................................ 70 
7.4.2 
Restricted Medications in Population #1 ................................................................... 70 
7.4.3 
Rescue Medications for Population #1 ...................................................................... 71 
7.4.4 
Restricted Medications in Population #2 ................................................................... 71 
7.4.5 
Rescue Medications for Population #2 ...................................................................... 71 
8 
SAFETY ASSESSMENT ................................................................................................ 71 
8.1 
Definitions..................................................................................................................... 71 
8.2 
Documenting Adverse Events....................................................................................... 73 
8.3 
Reporting Adverse Events ............................................................................................ 73 
8.4 
Adverse Events of Special Interest ............................................................................... 74 
8.5 
Clinical Laboratory Findings ........................................................................................ 74 
8.5.1 
Hematology ................................................................................................................ 75 
8.5.2 
Serum Chemistry ....................................................................................................... 75 


Module 5.3.5.1 Clinical Study Protocol  
VIB4920 
VIB4920.P2.S2 - VIB4920 in Subjects with Sjögren’s Syndrome 
Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
Page 12 of 13 
8.5.3 
Immunoglobulins ....................................................................................................... 75 
8.5.4 
Coagulation Parameters ............................................................................................. 75 
8.5.5 
Urinalysis ................................................................................................................... 75 
8.5.6 
Testing for SARS-CoV-2 ........................................................................................... 75 
8.6 
Vital Signs ..................................................................................................................... 75 
8.7 
Electrocardiogram ......................................................................................................... 75 
8.8 
Pregnancy ...................................................................................................................... 76 
8.9 
Overdose or Misuse ...................................................................................................... 76 
8.10 
Contacting Sponsor Regarding Urgent Protocol-related Medical Questions ............... 76 
9 
OTHER ASSESSMENTS ............................................................................................... 77 
9.1 
Qualitative Patient Interviews (optional) ...................................................................... 77 
10 
STATISTICAL CONSIDERATIONS............................................................................. 78 
10.1 
General Considerations ................................................................................................. 78 
10.2 
Statistical Hypotheses ................................................................................................... 78 
10.3 
Determination of Sample Size ...................................................................................... 78 
10.4 
Analysis Sets ................................................................................................................. 78 
10.4.1 
Full Analysis Set ........................................................................................................ 78 
10.4.2 
Safety Analysis Set .................................................................................................... 79 
10.4.3 
Pharmacokinetic Analysis Set.................................................................................... 79 
10.5 
Methods for Statistical Analyses .................................................................................. 79 
10.5.1 
Analysis of the Primary Efficacy Endpoint ............................................................... 79 
10.5.2 
Analysis of Secondary Efficacy Endpoints................................................................ 79 
10.5.3 
Explore Clinically Meaningful Within-subject Change Score of Clinical Outcome 
Assessments (COAs) ................................................................................................. 80 
10.5.4 
Handling Missing Items of COAs.............................................................................. 80 
10.5.4.1 
ESSDAI and ESSPRI .............................................................................................. 80 
10.5.4.2 
FACIT-Fatigue ........................................................................................................ 80 
10.5.5 
Safety Analysis .......................................................................................................... 80 
10.5.5.1 
Adverse Events ....................................................................................................... 80 
10.5.5.2 
Clinical Laboratory ................................................................................................. 81 


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10.5.5.3 
Vital Signs ............................................................................................................... 81 
10.5.5.4 
Electrocardiogram ................................................................................................... 81 
10.5.6 
Pharmacokinetics Analysis ........................................................................................ 81 
10.5.7 
Immunogenicity Analysis .......................................................................................... 81 
10.5.8 
Pharmacodynamics and Biomarker Analysis ............................................................ 81 
10.5.9 
Exploratory Analysis ................................................................................................. 81 
10.6 
Planned Analysis ........................................................................................................... 81 
11 
ETHICAL CONSIDERATIONS ..................................................................................... 82 
11.1 
Good Clinical Practice .................................................................................................. 82 
11.2 
Ethics Review ............................................................................................................... 82 
11.3 
Informed Consent.......................................................................................................... 82 
11.4 
Data Privacy .................................................................................................................. 83 
11.5 
Disclosure ..................................................................................................................... 83 
11.6 
Biological Specimens and Data .................................................................................... 83 
12 
OVERSIGHT ................................................................................................................... 84 
12.1 
Safety and Data Monitoring Committee ....................................................................... 84 
12.2 
Training of Site Personnel ............................................................................................ 84 
12.3 
Quality Control and Assurance ..................................................................................... 84 
12.4 
Monitoring .................................................................................................................... 85 
12.5 
Audits ............................................................................................................................ 85 
12.6 
Records ......................................................................................................................... 86 
12.6.1 
Data Capture and Management .................................................................................. 86 
12.6.2 
Source Documentation ............................................................................................... 86 
12.6.3 
Records Retention ...................................................................................................... 86 
13 
PUBLICATION POLICY ............................................................................................... 86 
14 
REFERENCES ................................................................................................................ 87 
15 
APPENDICES ................................................................................................................. 92 
 
LIST OF TABLES 
Table 1 ............ Screening Procedures ........................................................................................... 48 
Table 2 ............ Schedule of Study Assessments During the Treatment Period ............................ 50 


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Table 3 ............ Schedule of Assessments During the Off-treatment Period and Any Unscheduled 
Visits .................................................................................................................... 54 
Table 4 ............ Description of Investigational Products ............................................................... 66 
 
LIST OF FIGURES 
Figure 1 ........... Study Flow Diagram ............................................................................................ 37 
LIST OF APPENDICES 
Appendix 1 ..... ACR-EULAR CLASSIFICATION CRITERIA FOR PRIMARY SJÖGREN’S 
SYNDROME ....................................................................................................... 93 
Appendix 2 ..... GUIDANCE FOR ANAPHYLAXIS DIAGNOSIS ............................................ 95 
Appendix 3 ..... ACTIONS REQUIRED IN CASES OF INCREASES IN LIVER 
BIOCHEMISTRY AND EVALUATION OF HY’S LAW ................................ 96 
Appendix 4 ..... INVESTIGATOR’S AGREEMENT ................................................................... 99 
 


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LIST OF ABBREVIATIONS 
Abbreviation 
Definition 
ACR 
American College of Rheumatology 
ADA 
anti-drug antibody(ies) 
AE 
adverse event 
AESI 
adverse event of special interest 
ALP 
alkaline phosphatase 
ALT 
alanine aminotransferase 
AR 
adverse reaction 
AST 
aspartate aminotransferase 
AZA 
azathioprine  
ȕ-hCG 
beta-human chorionic gonadotrophin 
HBc 
hepatitis B core  
HBsAg 
hepatitis B surface antigen 
CD 
cluster of differentiation 
CD40L 
CD40 ligand 
CDM 
Clinical Data Management 
cDMARD 
conventional disease-modifying anti-rheumatic drug 
CI 
confidence interval 
ClinESSDAI 
Clinical EULAR Sjögren’s Syndrome Disease Activity Index 
COA 
clinical outcome assessment 
CRP 
C-reactive protein 
CSR 
clinical study report 
CTCAE 
Common Terminology Criteria for Adverse Events 
DAS28-CRP  
Disease Activity Score in 28 Joints Using C-reactive Protein 
DMARD 
disease-modifying anti-rheumatic drug 
DMP 
Data Management Plan 
ECG 
electrocardiogram 
eCRF 
electronic Case Report Form 
EDV 
early discontinuation visit 
Emax 
maximum effect 
ESSDAI 
EULAR Sjögren’s Syndrome Disease Activity Index  
ESSPRI 
EULAR Sjögren’s Syndrome Patient Reported Index 
EU 
European Union 
EULAR 
European League Against Rheumatism 
FACIT-Fatigue 
Functional Assessment of Chronic Illness Therapy -Fatigue 
FAS 
full analysis set 
FDA 
Food and Drug Administration 
Fn3 
fibronectin type III 


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Abbreviation 
Definition 
GCP 
Good Clinical Practice 
HSA 
human serum albumin 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Conference on Harmonisation 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IGRA 
Interferon Gamma Release Assay 
IL 
interleukin 
IP 
investigational product 
IRB 
Institutional Review Board 
IV 
intravenous(ly) 
IXRS 
interactive voice/web response system 
KLH 
keyhole limpet hemocyanin 
mAb 
monoclonal antibody 
MAD 
multiple-ascending dose 
MCP 
metacarpophalangeal 
MMF 
mycophenolate mofetil 
MMRM 
mixed-effect model for repeated measures 
MR 
Medical Review 
MTX 
methotrexate 
NOAEL 
no-observed-adverse-effect level 
OSDI 
Ocular Surface Disease Index  
PD 
pharmacodynamic(s) 
PGIS 
Patient’s Global Impression of Severity 
PIP 
proximal interphalangeal 
PK 
pharmacokinetic(s) 
PRO 
patient-reported outcome 
pSS 
primary Sjögren’s syndrome 
PT 
preferred term 
PTT 
partial thromboplastin time 
Q2W 
once every 2 weeks 
Q4W 
once every 4 weeks 
QoL 
quality of life 
RA 
rheumatoid arthritis 
RF 
rheumatoid factor 


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Abbreviation 
Definition 
SAE 
serious adverse event 
SAR 
suspected adverse reaction 
SAP 
statistical analysis plan 
SC 
subcutaneous 
sCD40L 
soluble CD40 ligand 
SDMC 
Safety and Data Monitoring Committee 
SID 
subject identification number 
SLE 
systemic lupus erythematosus 
SNP 
single nucleotide polymorphism 
SOC 
system organ class 
SS 
Sjögren’s syndrome 
sSS 
secondary Sjögren’s syndrome 
TB 
tuberculosis 
TBL 
total bilirubin 
TDAR 
T-cell dependent antibody response 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
TK 
toxicokinetic(s) 
TNF 
tumor necrosis factor 
ULN 
upper limit of normal 
w/v 
weight/volume 


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1 
SYNOPSIS 
Title 
A Phase 2 Randomized, Double-Blind, Placebo-Controlled, Proof of Concept Study 
to Evaluate the Efficacy and Safety of VIB4920 in Subjects with Sjögren’s 
Syndrome (SS) 
Phase 
2 
Study Design 
Randomized, double-blind, placebo-controlled, parallel-arm study 
Rationale 
Activation of cluster of differentiation (CD40) has been shown to be critical in 
germinal center formation, immunoglobulin (Ig)-class switching and expression of 
cytokines, such as interferon-Įtumor necrosis factor-Į, and interleukin-6, all of 
which have been previously associated with the pathophysiology of SS. 
Dysregulation of the CD40/ CD40 ligand (CD40L) has been observed in patients 
with SS in both the circulating cells and in the epithelial salivary cells. 
Downregulation of T- and B-cell activation, inhibition of CD40-mediated epithelial 
activation, and reduction in the local inflammatory factors contributing to salivary 
gland inflammation would be expected to improve glandular function in SS. 
Target Population 
The study will enroll 2 SS populations:  
Population #1: subjects with moderate to high systemic disease activity defined by 
European League Against Rheumatism (EULAR) Sjögren’s Syndrome Disease 
Activity Index (ESSDAI)  5.  
Population #2: subjects with moderate to severe subjective symptoms defined by 
EULAR Sjögren’s Syndrome Patient 5HSRUWHG,QGH[(6635,VFRUH 5 and 
residual 
 but with mild systemic disease activity defined by 
ESSDAI score < 5.  
Number of Subjects 
Total: Population #1: 72 subjects; Population #2: 102 subjects 
Per treatment:  
Population #1: n = 36 per treatment group 
Population #2: n = 51 per treatment group 
Length of Participation 
On treatment: 40 weeks. 
Subjects will receive randomized treatment (VIB4920 or placebo) 24 weeks 
(Stage I). After completion of Stage I, subjects initially randomized to VIB4920 will 
initiate placebo treatment and subjects initially randomized to placebo will initiate 
VIB4920 treatment for 16 weeks (Stage II). 
On study (including screening and follow-up): 56 weeks (393 days). 
Intervention 
Stage I: VIB4920, 1500 mg intravenously (IV) once every 2 weeks x 3, then once 
every 4 weeks (Q4W) or placebo 
Stage II: VIB4920 Q4W x 5 or placebo 
Primary Objective and 
Primary Endpoint 
Objective:  
Population #1: To evaluate the clinical efficacy of multiple doses of VIB4920 in 
glandular and extraglandular manifestations of SS patients with moderate to high 
systemic disease activity. 
Population #2: To evaluate the clinical efficacy of multiple doses of VIB4920 in the 
key subjective complaints of SS (dryness, fatigue, and pain). 
Endpoint: 
Population #1: Change from baseline in ESSDAI at Day 169. 
Population #2: Change from baseline in ESSPRI at Day 169. 


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Secondary Objective(s) 
and Corresponding 
Endpoint(s) 
Objectives: 
Population #1: 
1. To evaluate the effect of VIB4920 on systemic activity and patient-reported 
outcomes in subjects with SS 
2. To evaluate the safety and tolerability of multiple doses of VIB4920 in subjects 
with SS 
3. To characterize the pharmacokinetics (PK) of VIB4920 in subjects with SS 
4. To assess the immunogenicity of VIB4920 in subjects with SS 
Population #2: 
1. To evaluate the effect of VIB4920 on patient-reported outcomes in subjects with 
SS 
2. To evaluate the safety and tolerability of multiple doses of VIB4920 in subjects 
with SS 
3. To characterize the PK of VIB4920 in subjects with SS 
4. To assess the immunogenicity of VIB4920 in subjects with SS 
Endpoints: 
Population #1: 
1. Change from baseline in ESSPRI at Day 169. 
2. Proportion of subjects achieving ESSDAI[3] and ESSDAI[4] response, defined as 
a decrease of at least 3[4] points from baseline in the ESSDAI at Day 169 without 
premature discontinuation from the study and without receiving rescue therapy 
3. Change from baseline in Functional Assessment of Chronic Illness Therapy 
(FACIT)-Fatigue score at Day 169. 
4. Change from baseline in Ocular Surface Disease Index (OSDI©) at Day 169.  
5. Patient’s Global Impression of Severity (PGIS) at Day 169 
6. Safety and tolerability of multiple IV doses of VIB4920 as measured by the 
incidence of treatment-emergent adverse events (TEAEs), treatment-emergent 
serious adverse events (TESAEs), adverse events of special interest (AESIs), and 
laboratory, vital sign, and electrocardiogram (ECG) abnormalities. 
7. PK during the study. 
8. Proportion of subjects with positive immunogenic response measured by anti-
VIB4920 antibodies until the completion of the study. 
Population #2: 
1. PrRSRUWLRQRIVXEMHFWVDFKLHYLQJ(6635,UHVSRQVHGHILQHGDV 1 point or 15% 
reduction from baseline in ESSPRI score at Day 169 without premature 
discontinuation from the study and without receiving rescue therapy. 
2. Change from baseline in FACIT-Fatigue at Day 169. 
3. Change from baseline in OSDI at Day 169.  
4. PGIS at Day 169 
5. Safety and tolerability of multiple IV doses of VIB4920 as measured by the 
incidence of TEAEs, TESAEs, AESIs, and laboratory, vital sign, and ECG 
abnormalities. 
6. PK during the study. 
7. Proportion of subjects with positive immunogenic response measured by 
anti-VIB4920 antibodies until the completion of the study. 


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Exploratory 
Objective(s) and 
Corresponding 
Endpoint(s) 
Objectives: 
Endpoints: 


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Number of Sites 
Approximately 70 international sites. 
Study Duration 
Estimated duration: 25 months 
Safety and Data 
Monitoring Committee 
An independent Safety and Data Monitoring Committee 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.  


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2 
INTRODUCTION 
2.1 
Background 
Sjögren's syndrome (SS) is a systemic autoimmune disease characterized by chronic lymphocytic 
inflammation of the exocrine glands, mainly the salivary and lacrimal glands, leading to loss of 
function manifesting as excessive dryness (Mavragani, 2017). Additionally, extraglandular 
manifestations are described as multi-organ involvement affecting musculoskeletal, pulmonary, 
renal, nervous, dermatological, gastrointestinal, hematological, hepatobiliary, or vascular 
systems, while fatigue is one of the most prominent comorbidities (Leone et al, 2017; Manuel et 
al, 2017; McCoy and Baer, 2017). The joints, lung, skin, and peripheral nerves are the most 
frequent organ systems involved, while cytopenia, hypocomplementemia, and cryoglobulinemia 
at diagnosis are strongly associated with greater systemic activity. SS may also present in 
association with other autoimmune diseases and historically it has been characterized as 
secondary Sjögren’s syndrome (sSS) when co-existing with selected other autoimmune diseases 
such as rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), or scleroderma 
(Hernandez-Molina et al, 2010). 
The subjective aspects of SS, which include the patient’s perception of dryness, musculoskeletal 
pain, and fatigue can be debilitating and have been shown to have a substantial negative impact 
on quality of life (QoL) (Hammit et al, 2017). QoL is also affected by psychological and 
emotional challenges and impaired social life with dependency on relatives in daily life and 
difficulties at work, as well as with other tasks (Lackner et al, 2017). 
Demographic data for SS vary largely. A meta-analysis of epidemiological studies in primary 
Sjögren’s syndrome (pSS) published in 2014 estimated a worldwide prevalence of pSS of 60.82 
per 100,000 inhabitants, or one person in 1644 (Qin et al, 2015). Even more recently, a French 
group estimated the prevalence of pSS in Europe of being lower, using exclusively studies with 
good methodology (population-based study, effective case-finding methods, ascertainment of 
cases using the initially developed diagnostic criteria, large background population) and that 
have been performed exclusively in European countries. Only 3 studies have been identified 
fulfilling all the above criteria and combining these results, the estimated prevalence of SS in 
Europe was calculated to be 38.95/100,000, or one person in 2567 (Cornec and Chiche 2015). 
Until recently, the most commonly used classification criteria for SS were developed in 2002 
(Vitali et al, 2002). As of 2016, an international set of classification criteria for pSS based on 
guidelines from the American College of Rheumatology (ACR) and the European League 
Against Rheumatism (EULAR) was developed and validated (Shiboski et al, 2017). Although 
these criteria were developed for classification of pSS and not for sSS, the International SS 
Criteria Working Group suggested that these criteria could also be applicable for sSS, and 
recommended confirmatory studies (Shiboski et al, 2017; Tsuboi et al, 2017).  
Two disease activity indices suitable for use as SS endpoints have recently been developed by 
EULAR through an international collaborative project: the EULAR Sjögren’s Syndrome Disease 
Activity Index (ESSDAI) to assess the systemic manifestations, and the EULAR Sjögren’s 
Syndrome Patient Reported Index (ESSPRI) for patients’ symptoms (Seror et al, 2010; Seror et 
al, 2011).  


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Standard of care for SS focuses on controlling sicca symptoms using pharmaceutical and 
nonpharmaceutical approaches and managing extraglandular manifestations with glucocorticoids 
and immunosuppressive drugs (Ramos-Casals et al, 2010). Sialogogues, such as pilocarpine or 
cevimeline, can be used to stimulate residual saliva production, but they have limited efficacy 
and systemic side effects. Cyclosporine eye drops are effective in improving dry eye symptoms 
in a subset of SS patients. Currently, there are no approved immunomodulating agents or 
evidence-based therapeutic guidelines available for treatment of the extraglandular 
manifestations of SS. Therefore, standard of care for extraglandular manifestations varies widely 
and is based on local practices, expert opinion, and personal experience of the treating physicians 
(Ramos-Casals et al, 2010). Disease-modifying anti-rheumatic drugs (DMARDs) approved for 
other rheumatic diseases are frequently used for the treatment of extraglandular manifestation 
based on clinical similarities but without direct evidence of efficacy in SS. Hydroxychloroquine 
is also used often for improvement of fatigue and joint pain despite a negative clinical trial 
(Gottenberg et al, 2014).  
A number of biological treatments have been evaluated for efficacy in controlled and 
uncontrolled clinical studies. Tumor necrosis factor inhibitors were shown to be ineffective and 
are not recommended in SS (Ramos-Casals et al, 2010). Several studies evaluated B-cell 
depletion with rituximab with mixed results with the 2 larger trials failing to reach their primary 
endpoints (Dass et al, 2008; Meijer et al, 2010; Devauchelle-Pensec et al, 2014; Bowman et al, 
2017). An open label study with abatacept showed encouraging results (Meiners et al, 2014) that 
need further exploration in controlled studies. In fact, abatacept recently completed enrollment in 
a large phase 3 trial (NCT02915159). A trial targeting the costimulatory molecule CD40 
(NCT02291029) was recently completed and showed a statistically significant decrease in 
disease activity (ESSDAI score) in 12 weeks in pSS (Fisher et al, 2017).  
2.1.1 
Target Indication and Population 
It is possible to use the ESSDAI and ESSPRI indices to define SS population subsets with 
distinct disease manifestations, both of which have significant unmet medical needs. For this 
clinical study, these have been termed Population #1 and Population #2. 
Population #1, which includes SS patients with moderate to high systemic activity defined by 
ESSDAI  5, has been the focus of many recent SS trials. About 15-20% of SS patients present 
with systemic manifestations beyond the commonly affected exocrine glands (salivary and 
ocular). These manifestations most commonly include arthritis, lung disease, renal disease, 
vasculitis, neuropathies, and autonomic nervous system dysfunction, which accompany glandular 
involvement. Moderate to high disease activity is not only debilitating but can also lead to 
dysfunction of the affected organ(s), or to hematologic pathologies, including thrombocytopenia 
and lymphoma, that have been associated with increased risk of mortality (Brito-Zeron et al, 
2016). Despite the increased number of trials, no biologics or DMARDs have been shown to be 
efficacious in significantly reducing SS systemic disease activity. 
Population #2 includes SS patients with exocrine dysfunction, severe subjective symptoms 
defined by an ESSPRI score of  5, considered as the cut-off point for “unsatisfactory symptom 
state” (Seror et al, 2016a) but with lower systemic disease activity (with ESSDAI score < 5). 
This population represents a large subset of SS patients who have been excluded from recent 
trials despite the substantial disease burden and overall unacceptable health status. 


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Based on patient surveys and assessments supported by the SS Foundation, SS makes every day 
a challenge for 86% of patients, interfering with their everyday activities and also adding a 
significant emotional and financial burden. The major contributors to the decreased QoL are 
dryness and fatigue. When asked how important it would be to have a new systemic therapy 
created to address a list of symptoms, 82% of the “patients were most likely to say it is 
absolutely essential/extremely important to have a therapy created to address dryness” (Sjögren’s 
Syndrome Foundation, 2017). The inclusion of Population #2 in the proposed study is intended 
to address this clear unmet clinical need.  
2.1.2 
Description of VIB4920 
VIB4920 (formerly known as MEDI4920) is a cluster of differentiation (CD) 40 ligand (CD40L) 
antagonist that comprises 2 identical Tn3 modules fused to human serum albumin (HSA). Each 
Tn3 is an engineered form of the third fibronectin type III (Fn3) protein domain of human 
Tenascin C. Polyglycine linkers join the 2 Tn3 domains, and the second Tn3 domain to the HSA 
protein. Each Tn3 binds specifically to human CD40L and inhibits its interaction with human 
CD40. The CD40/CD40L interaction plays a critical role in the activation of B cells, which 
produce autoantibodies and inflammatory mediators that contribute to autoimmune disease 
pathology. By blocking the CD40/CD40L interaction, VIB4920 may act as an immune 
modulator with potential therapeutic activity in a range of autoimmune diseases, including SS 
(Jobling and Ng, 2018; Karnell et al, 2018; Wieczorek et al, 2019). 
2.1.3 
Supportive Nonclinical Data 
2.1.3.1 
Pharmacology 
Nonclinical pharmacology studies demonstrated that VIB4920 binds human CD40L specifically 
and with high affinity. In addition, in vitro and in vivo studies have demonstrated the mechanism 
of action of VIB4920. Lastly, VIB4920 demonstrated an acceptable safety profile in in vivo and 
in in vitro functional platelet assessment systems, compared with anti-CD40L monoclonal 
antibodies (mAbs), which have been tested in both nonclinical and clinical studies. These results 
highlight the potential for VIB4920 to be a key modulator in treating autoimmune disease. 


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2.1.4 
Supportive Clinical Data 
2.1.4.1 
Phase 1 Single-ascending Dose Study in Healthy Volunteers 
Study D5100C00001 was a single-center, first-time-in-human single-ascending dose study that 
evaluated the safety and tolerability of IV doses of VIB4920 in healthy adult male subjects and 
healthy adult female subjects of non-childbearing potential. The study also characterized the PK 
of VIB4920, assessed ADA to VIB4920, and evaluated the effect of VIB4920 on TDAR after 
administration of KLH antigen. VIB4920 was administered as a single IV infusion at dose levels 
of 3, 10, 30, 100, 300, 1000, and 3000 mg. A total of 59 male subjects were randomized, 56 
subjects were treated, and 53 subjects completed the study. In this study, VIB4920 demonstrated 


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an acceptable safety and tolerability profile. There were no reports of thromboembolic events or 
clinically significant abnormalities related to hemostasis. The PK of VIB4920 was linear 
following a single IV dose ranging from 3 to 3000 mg. TDAR was inhibited in a dose-dependent 
manner, showing statistically significant differences with the higher VIB4920 doses (300, 1000, 
and 3000 mg) compared with placebo. There was a dose-dependent increase in total sCD40L 
after VIB4920 administration, indicating binding of VIB4920 to sCD40L and target engagement. 
There was a decrease in ADA incidence and titers observed with increasing doses of VIB4920 
that is consistent with the immunosuppressive mechanism of action of VIB4920. There was no 
identified association of ADA with any treatment-emergent adverse events (TEAEs) reported in 
this study. A dose-response model was generated for TDAR inhibition and showed that the 1000 
mg dose achieved approximately 78% inhibition and the 3000 mg approximately 86% inhibition 
compared with placebo, indicating adequate inhibition for the 2 highest doses tested. 
2.1.4.2 
Phase 1b Multiple-ascending Dose Study in Rheumatoid Arthritis 
A phase1b, multiple-ascending dose (MAD) study (D5100C00002) recruited 57 subjects with 
RA. This multicenter, randomized, double-blind (Investigator, subject, and Sponsor blinded to 
treatment assignment), placebo-controlled study evaluated the safety and tolerability of MADs of 
VIB4920 in subjects with adult-onset RA (moderate to severe, as defined by Disease Activity 
Score in 28 Joints Using C-reactive Protein (DAS28-CRP)  3.2 at screening) with an inadequate 
response to methotrexate (MTX) or other conventional DMARDs (cDMARDs) or to a biologic 
anti-tumor necrosis factor (TNF)-ĮDJHQW6XEMHFWVZHUHUDQGRPL]HGDQGWUHDWHGDFURVV
4 sequential cohorts; the VIB4920 doses used were 75, 500, 1000, and 1500 mg. Treatment with 
investigational product (IP) (VIB4920 or placebo) was administered by IV infusion once every 
2 weeks (Q2W) up to Day 85/Week 12 for a total of 7 doses, followed by a 12-week follow-up 
period.  
VIB4920 significantly reduced disease activity, quantified by DAS28-CRP score, in RA patients 
at higher doses at Day 85 (VIB4920 1500 mg and VIB4920 1000 mg). The effect of VIB4920 on 
DAS28-CRP was rapid, with reductions evident as early as Day 15, after only a single dose of 
drug. The reduction of disease activity as compared with placebo was both clinically and 
statistically meaningful in the groups receiving the highest 2 doses of VIB4920: the adjusted 
mean (standard error) difference compared to placebo at Week 12 for VIB4920 1500 mg and 
1000 mg groups were -1.4 (0.4) and -1.2 (0.4) with p-values of 0.002 and 0.006, respectively.  
The statistically significant response over placebo observed in DAS28-CRP at Day 85 with the 
VIB4920 1000 mg and VIB4920 1500 mg doses was maintained for 3 months after the last dose 
until the end of the study at Day 169. 
In terms of individual clinical response, 75% of subjects in the 1500 mg group and 50% of 
subjects in 1000 mg dose group achieved a DAS28-CRP score  3.2 at Day 85, indicating they 
were in low disease activity or clinical remission. 
RF exhibited a statistically significant Emax dose response (Emax = maximum effect attributable to 
VIB4920) for change from baseline in RF at Day 85 (p < 0.001). The estimated percent reduction 
over placebo at Day 85 was 47% (90% confidence interval [CI]: 38%, 55%) for the 1000 mg 
dose, and 52% (90% CI: 43%, 60%) for the 1500 mg dose. Vectra® DA score was also reduced 
by VIB4920 1500 and 1000 mg dose levels. The adjusted mean difference vs placebo at Day 85 
was -14.4 (90% CI: -21.5, -7.2), p = 0.001 and -10.3 (90% CI: -17.4, -3.3), p = 0.018 for the 


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1500 and 1000 mg dose, respectively. Other endpoints (eg, Clinical Disease Activity Index, 
tender joint count, swollen joint count, Patient’s Global Assessment, Physician’s Global 
Assessment, C-reactive protein [CRP], and erythrocyte sedimentation rate) generally supported 
the result for 1000 and 1500 mg not only at Day 85, but to the end of the study. 
Based on clinical data from Study D5100C00001 and Study D5100C00002, there are no 
identified risks for humans associated with VIB4920. 
2.1.5 
Risk Assessment 


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2.1.5.6 
Exposure In Utero 
No embryo-fetal studies have been conducted to date. 
2.1.5.7 
Risks related to the COVID-19 pandemic 
After the start of this study, the COVID-19 pandemic resulted in temporary study closure after 
6 subjects had been dosed. All 6 participants continued on the study after discussing with the site 
Investigators the potential risks from SARS-CoV-2. None of the 6 subjects is known to have had 
COVID-19. There are limited data on the excess risks from COVID-19 in patients with SS or 
receiving the protocol allowed concomitant treatments for SS, such as steroids (Gianfrancesco et 
al, 2020). There are no data on the effect of VIB4920 on the risk for infection with SARS-CoV-2 
or on the severity of COVID-19 illness. 
Risk factors for severe or life-threatening COVID-19 illness continue to be assessed; currently, 
risk factors are thought to include older age, male sex, obesity (especially body mass index 
> 40), comorbidities such as hypertension, diabetes, heart disease (especially heart failure), 
chronic kidney disease, lung disease, and malignancy (Docherty et al, 2020; Petrilli et al, 2020; 
Zhou et al, 2020). Subjects also have individual epidemiologic risk related to local rates of 
infection and infection transmission, and also to their individual exposure or potential exposure 
to infected individuals; for example, transmission risks have been very high in care facilities 
such as nursing homes. 
It is possible that, based on its mechanism of action, VIB4920 will interfere with mounting an 
optimal vaccine response. It is possible that a vaccine may not provide optimal or even any 
protection if administered during the effect of VIB4920 on the immune system. For this reason, 
Investigators should ensure that all patients are up to date with required vaccinations prior to 
entry into the study. There is currently no vaccine against COVID-19, but there is a risk that 
VIB4920 could impair a response to any/all COVID-19 vaccines that might become available. 
An additional risk of study participation includes exposure of the subject to SARS-CoV-2, the 
virus that causes COVID-19, by visiting the study site. Sites must have a plan in place to 
minimize this risk. 
2.2 
Study Rationale 
The CD40/CD40L pathway has been extensively studied for its role in immunity and 
autoimmunity, especially in its role in B- and T-cell activation and B- and T-cell costimulation 


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(Jobling and Ng, 2018; Karnell et al, 2018). Specifically, activation of CD40 has been shown to 
be critical in germinal center formation, Ig-class switching and expression of cytokines such as 
interferon-Į71)-ĮDQGinterleukin (IL)-6, all of which have been previously associated with the 
pathophysiology of SS (Jobling and Ng, 2018; Wieczorek et al, 2019).  
CD40L on circulating CD4+ T cells has also been shown to be increased in women with SS 
(Belkhir et al, 2014). Ectopic lymphoid follicles are commonly found in SS salivary glands and 
are believed to be involved in tissue destruction and the local production of autoantibodies 
(Karnell et al, 2018). Additionally, in SS salivary glands, 30-50% of the infiltrating lymphocytes 
have been shown to express CD40L (Dimitriou et al, 2002).  
Importantly, the dysregulation of the CD40/CD40L is not only seen in the circulating cells but 
also in the epithelial salivary cells. Immunocytochemistry and flow cytometry have identified 
significantly higher, constitutively expressed CD40 on long term primary epithelial salivary cell 
cultures from SS patients compared to controls, suggesting pathologic intrinsic activation 
(Dimitriou et al, 2002). Epithelial activation, an important component of the pathophysiologic 
process in SS, results in the secretion of proinflammatory cytokines and other mediators, which 
in turn may contribute to the initiation and/or propagation of the chronic inflammatory response. 
The importance of the CD40/CD40L pathway in SS is central to autoimmunity in general and 
this conceptual framework has led to a number of clinical trials of novel therapies targeting this 
pathway in autoimmune diseases such as lupus nephritis, psoriatic arthritis, SLE, and RA, among 
others. A phase 2a trial in SS with an anti-CD40 agent showed efficacy in decreasing ESSDAI in 
subjects with moderate to high disease activity (Fisher et al, 2017) which supports the rationale 
for the proposed study of VIB4920 in this disease.  
Although they preferentially target different tissues, SS and RA share common underlying 
autoimmune pathologic mechanisms likely to involve activation of the CD40/CD40L pathway. 
For example, the target tissues, namely the salivary glands and synovium, respectively, are 
populated by hyperactivated B cells that often contain ectopic lymphoid organelles thought to 
contribute to the disease progression. The clinical and biomarker improvements observed in 
subjects with RA following treatment with VIB4920 in the phase 1b study provide further 
rationale for targeting the CD40-CD40L pathway in SS. Downregulation of T- and B-cell 
activation, inhibition of CD40-mediated epithelial activation, and reduction in the local 
inflammatory factors contributing to salivary gland inflammation would be expected to improve 
glandular function in SS (Dimitriou et al, 2002). Moreover, CD40-CD40L pathway blockade 
may also favorably impact the diverse systemic manifestations of SS that are dependent on this 
pathway, as observed in patients with RA showing improvement in joint inflammation and in 
other organ systems, such as the lung and kidney, where epithelial cells may play key roles in 
driving the inflammatory response. 
After this study was opened to enrollment in November 2019, the onset of the pandemic caused 
by SARS-CoV-2 resulted in temporary halt of the study to enrollment. The decision to re-open 
the study was based on an overall assessment of potential benefit-risk for subjects in the study 
during what is likely to be continued circulation of COVID-19. There are no clear data on the 
possible potentiation of COVID-19 risk by active SS on- or off-treatment and there are no data 
on the effect of VIB4920 on this risk. A potential risk of VIB4920 is infection, based on its 
mechanism of action. The subjects in this study, however, have the health risk of active SS 
despite standard of care treatment. 


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The following are included in this study to minimize risk to subjects: 
x Opening a site only after review of local COVID-19 epidemiology, availability of 
healthcare resources, ability to monitor site activities, and the presence of a site plan to 
minimize patient exposure to SARS-CoV-2 during site visits. Each of these factors is likely 
to differ over time in ways that are difficult to predict, so ongoing risk assessment is required 
and will be implemented. 
x Assessment of the benefit-risk for each individual subject for determination of suitability 
for enrollment based on known risk factors for COVID-19 severity and possible or known 
exposure to SARS-CoV-2. 
x Requiring a negative SARS-CoV-2 test within 2 weeks prior to randomization. 
Considering the measures taken to minimize risk to subjects participating in this study and the 
benefit that may be afforded to study subjects, the benefit-risk assessment is reasonable for a 
phase 2 study. 
2.3 
Study Hypotheses 
Primary Hypothesis for Population #1:  
x VIB4920 reduces clinical activity in subjects with SS with moderate to high systemic 
disease activity  
Primary Hypothesis for Population #2:  
x VIB4920 reduces clinical activity in subjects with SS with moderate to severe subjective 
complaints 
Secondary Hypothesis for Populations #1 and #2:  
x VIB4920 has an acceptable safety profile and is well tolerated in subjects with SS  
3 
OBJECTIVES AND ENDPOINTS 
This study will be conducted in 2 SS subpopulations, as discussed in Section 2.1.1, 
Population #1 and Population #2. There will be a different set of objectives and endpoints in 
each population. 
3.1 
Objectives in Population #1 
3.1.1 
Primary Objective in Population #1 
To evaluate the clinical efficacy of multiple doses of VIB4920 in glandular and extraglandular 
manifestations of SS patients with moderate to high systemic disease activity. 
3.1.2 
Secondary Objectives in Population #1 
1. To evaluate the effect of VIB4920 on systemic activity and patient-reported outcomes in 
subjects with SS. 
2. To evaluate the safety and tolerability of multiple doses of VIB4920 in subjects with SS. 
3. To characterize the PK of VIB4920 in subjects with SS. 


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4. To assess the immunogenicity of VIB4920 in subjects with SS. 
3.1.3 
Exploratory Objectives in Population #1 
3.2 
Objectives in Population #2 
3.2.1 
Primary Objective in Population #2 
To evaluate the clinical efficacy of multiple doses of VIB4920 in the key subjective complaints 
of SS (dryness, fatigue, and pain). 
3.2.2 
Secondary Objectives in Population #2 
1. To evaluate the effect of VIB4920 on patient-reported outcomes in subjects with SS. 
2. To evaluate the safety and tolerability of multiple doses of VIB4920 in subjects with SS. 
3. To characterize the PK of VIB4920 in subjects with SS. 
4. To assess the immunogenicity of VIB4920 in subjects with SS. 
3.2.3 
Exploratory Objectives in Population #2 
3.3 
Endpoints for Population #1 
3.3.1 
Primary Endpoint for Population #1 
Change from baseline in ESSDAI at Day 169. 
3.3.2 
Secondary Endpoints for Population #1 
1. Change from baseline in ESSPRI at Day 169. 


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2. Proportion of subjects achieving ESSDAI[3] and ESSDAI[4] response, defined as a 
decrease of at least 3[4] points from baseline in the ESSDAI at Day 169 without 
premature discontinuation from the study and without receiving rescue therapy. 
3. Change from baseline in Functional Assessment of Chronic Illness Therapy (FACIT)-
Fatigue score at Day 169. 
4. Change from baseline in Ocular Surface Disease Index (OSDI©) at Day 169.  
5. Patient’s Global Impression of Severity (PGIS) at Day 169. 
6. Safety and tolerability of multiple IV doses of VIB4920 as measured by the incidence of 
TEAEs, treatment-emergent serious adverse events (TESAEs), adverse events of special 
interest (AESIs), and laboratory, vital sign, and electrocardiogram (ECG) abnormalities. 
7. PK during the study. 
8. Proportion of subjects with positive immunogenic response measured by anti-VIB4920 
antibodies until the completion of the study. 
3.3.3 
Exploratory Endpoints for Population #1 


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3.4 
Endpoints for Population #2 
3.4.1 
Primary Endpoint for Population #2 
Change from baseline in ESSPRI at Day 169. 
3.4.2 
Secondary Endpoints for Population #2 
1. 3URSRUWLRQRIVXEMHFWVDFKLHYLQJ(6635,UHVSRQVHGHILQHGDVSRLQWRUUHGXFWLRQ
from baseline in ESSPRI score at Day 169 without premature discontinuation from the 
study and without receiving rescue therapy. 
2. Change from baseline in FACIT-Fatigue score at Day 169. 
3. Change from baseline in OSDI at Day 169.  
4. Patient’s Global Impression of Severity at Day 169 
5. Safety and tolerability of multiple IV doses of VIB4920 as measured by the incidence of 
TEAEs, TESAEs, AESIs, and laboratory, vital sign, and ECG abnormalities. 
6. PK during the study. 
7. Proportion of subjects with positive immunogenic response measured by anti-VIB4920 
antibodies until the completion of the study. 
3.4.3 
Exploratory Endpoints for Population #2 


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4 
STUDY PLAN 
4.1 
Study Design 
This is a randomized, double-blind, placebo-controlled, parallel-arm study to evaluate the 
efficacy, safety, and tolerability of VIB4920 in adult subjects with SS diagnosed according to the 
2016 ACR/EULAR Criteria (see Appendix 1). The study will enroll 2 SS populations. 
Population #1 will be composed of subjects with moderate to severe systemic disease activity 
defined by ESSDAI  5. Population #2 will be composed of subjects with mild systemic disease 
activity defined by ESSDAI score < 5 but with moderate to severe subjective symptoms defined 
by ESSPRI score  5 and residual stimulated salivary flow. Approximately 70 international sites 
may be involved in this study.  
SS patients meeting the 2016 ACR/EULAR classification criteria and the rest of the 
inclusion/exclusion criteria will be accordingly assigned to Population #1 or Population #2. Each 
of the populations will then be randomized at 1:1 ratio to receive either placebo (n = 36 for 
Population #1, n = 51 for Population #2) or 1500 mg VIB4920 (n = 36 for Population #1, n = 51 
for Population #2). Randomization will be stratified by ESSDAI score at screening (< 10 points 
YVSRLQWVIRU3RSXODWLRQDQGE\(6635,VFRUHDWVFUHHQLQJSRLQWVYV 7.5 points) 
for Population #2. To ensure balanced rates of enrollment of the 2 populations throughout the 
study, the Sponsor will implement a procedure where enrollment of subjects in Population #2 at 
each site is linked to enrollment of Population #1 subjects at the site with a progressively 
increasing ratio of Population #2:Population #1 subjects. At least 1 subject of the first 
2 randomized at each site must be from Population #1. 
The primary objective for Population #1 is to evaluate the clinical efficacy of multiple doses of 
VIB4920 in glandular and extraglandular manifestations of SS subjects with moderate to high 
systemic disease activity. The primary objective for Population #2 is to evaluate the clinical 


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efficacy of VIB4920 in the key subjective complaints of SS. Full lists of the objectives for 
Populations #1 and #2 are presented in Sections 3.1 and 3.2, respectively. 
The primary endpoint for Population #1 will be change from baseline in ESSDAI at Day 169. 
The primary endpoint for Population #2 will be change from baseline in ESSPRI at Day 169. 
Full lists of the endpoints for Populations #1 and #2 are presented in Section 3.3 and 3.4, 
respectively. 
Within each population, eligible subjects will be randomized to receive VIB4920 1500 mg IV or 
placebo Q2W x 3 doses, then once every 4 weeks (Q4W) for 4 additional doses (Stage I). 
Starting on Day 169, subjects randomized to VIB4920 will receive placebo Q4W for 5 doses and 
subjects randomized to placebo will receive VIB4920 Q4W for 5 doses (Stage II). Subjects who 
had IP discontinuation will not be eligible for treatment during Stage II. All subjects will be 
followed for at least 12 weeks after their last dose of IP administration. 
A study schematic is presented in Figure 1. 


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Figure 1
Study Flow Diagram
ǻ GHOWD' GD\V(R6 (QGRI6WXG\EP = endpoint; ESSDAI = European League Against Rheumatism Sjögren’s Syndrome Disease Activity Index; 
ESSPRI = in EULAR Sjögren’s Syndrome Patient Reported Index; IA = interim analysis; mos = months; PE = primary endpoint.


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4.2 
Dose and Treatment Regimen Rationale 
The safety, tolerability, and PD effects of multiple IV doses of 1500 mg VIB4920 have been 
evaluated in RA patients with moderate to severe disease activity. 
VIB4920 1500 mg Q2W proved to be efficacious in significantly decreasing disease activity, and 
clinical improvement lasted through the final visit at 12 weeks after the last dose. Based on 
PK/PD modeling and biomarker changes observed in the RA patients, the selected dose for this 
trial is 1500 mg IV Q2W for 3 doses as an induction dose, followed by 1500 mg IV 
administrations Q4W for an additional 4 doses. Starting at Day 169 of treatment, assignment of 
subjects will be crossed: subjects randomized to placebo will receive VIB4920 and subjects 
randomized to VIB4920 will receive placebo in a blinded fashion Q4W for 5 doses. This design 
has several advantages. First, it provides exposure to VIB4920 to all randomized subjects. 
Second, omitting the Day 15 induction dose in Stage II allows assessment of the effect of such an 
induction dose on the rate and magnitude of biologic response and may help optimize the dosing 
regimen. Third, the longer follow-up of the VIB4920 arms provides an opportunity to better 
assess the duration of clinical and biologic responses. 
No dose-limiting toxicities were identified in the human trials. 
4.3 
Rationale for 2 Study Populations 
The 2 SS populations, which distinguish patients with predominantly glandular dysfunction and 
those with both glandular dysfunction and systemic manifestations, represent subsets with 
significant unmet need that require different endpoints to assess efficacy. The ESSDAI is a 
validated instrument to assess systemic disease activity (Seror et al, 2010). The ESSPRI uses a 
0-10 numerical analog scale, one for the assessment of each of the 3 domains of SS symptoms: 
dryness, fatigue, and pain (articular and/or muscular). 
3RSXODWLRQZLWKPRGHUDWHWRKLJKV\VWHPLFDFWLYLW\GHILQHGE\(66'$,ௗ 5, has been the 
focus of many recent SS trials. About 15-20% of SS patients present with systemic 
manifestations beyond the commonly affected exocrine glands (salivary and ocular). These 
manifestations most commonly include arthritis, lung disease, renal disease, vasculitis, and 
peripheral neuropathies, as well as autonomic nervous system dysfunctions that accompany 
glandular involvement. Moderate to high disease activity may lead to physical dysfunction and 
poor QoL, as well as dysfunction of the affected organ(s). In addition, patients with pSS who 
have moderate to high disease activity are more prone to developing B-cell lymphoma, which in 
turn, has been associated with an increased risk of death (Brito-Zeron et al, 2016). Despite the 
increased number of trials, no biologics or DMARDs have been shown to be efficacious in 
significantly reducing SS systemic disease activity. 
Population #2 comprises SS patients with exocrine dysfunction and severe subjective symptoms 
GHILQHGE\DQ(6635,VFRUHRI 5, considered as the cut-off point for “unsatisfactory symptom 
state” (Seror et al, 2016a) but lower systemic disease activity. This population represents a large 
subset of SS patients who have been excluded from recent trials despite the substantial disease 
burden and overall unacceptable health status. 
The Eligibility Criteria related to the 2016 ACR/EULAR Classification Criteria for SS for both 
Population #1 and Population #2 and the disease activity data for the ESSDAI score for 


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Population #1 will be reviewed by the Sponsor/designee prior to enrollment to confirm subject 
eligibility. 
4.4 
Rationale for Primary Endpoint Selection 
VIB4920 targets B cell-mediated autoimmune diseases and has been shown in the phase 1b RA 
trial to significantly decrease inflammatory markers and inflammatory cytokines (eg, CRP, IL-6) 
that are known to be associated with systemic, glandular, and subjective manifestations of SS, 
including pain, fatigue, and dryness. Thus, VIB4920 has the potential to improve inflammatory 
manifestations of SS and also to alleviate the most prominent features that lead to the 
unsatisfactory symptom state observed in SS. 
The primary endpoints have been selected for each of the 2 SS Populations in this study: Change 
from baseline in ESSDAI for Population #1 and Change from baseline in ESSPRI for Population 
#2. Both are validated measures of objective (ESSDAI) and subjective (ESSPRI) disease activity 
in SS and have been used widely in SS clinical trials. 
5 
POPULATION 
5.1 
Inclusion and Exclusion Criteria 
The study medical review (MR) team will review the Eligibility Criteria related to the 2016 
ACR/EULAR Classification Criteria for SS and ESSDAI score to confirm patient eligibility for 
Population #1 and will review items related to the 2016 ACR/EULAR Classification Criteria for 
SS for Population #2 (see Section 6.1 for details). 
5.1.1 
Inclusion Criteria for Population #1 
To be included in Population #1 of this study, each individual must satisfy all the following 
criteria: 
1. Adults, 18 years or older at time of informed consent (the minimum age for adult 
participants can be higher than 18 years in countries with different regulations). 
2. Diagnosed with SS by meeting the 2016 ACR/EULAR Classification Criteria. 
3. +DYHDQ(66'$,VFRUHRI 5 at screening; the following domains will be scored but they 
will not contribute to the minimum ESSDAI score of 5 required for inclusion: Peripheral 
nervous system, Central nervous system, and Pulmonary. 
4. Positive for either anti-Ro autoantibodies or RF, or both at screening, as per the definition 
of the standard central laboratory test. 
5. Written informed consent and any locally required authorization (eg, Health Insurance 
Portability and Accountability Act in the United States, European Union [EU] Data 
Privacy Directive in the EU) obtained from the subject/legal representative prior to 
performing any protocol-related procedures, including screening evaluations. 
6. Females of childbearing potential who are sexually active with a nonsterilized male 
partner must use a highly effective method of contraception from signing the informed 
consent form (ICF), and must agree to continue using such precautions through the end of 


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the study follow-up; cessation of contraception after this point should be discussed with a 
responsible physician. Highly effective methods of contraception include: 
x combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation: 
 oral 
 intravaginal 
 transdermal 
x progestogen-only hormonal contraception associated with inhibition of ovulation:  
 oral 
 injectable 
 implantable 
x intrauterine device (IUD)  
x intrauterine hormone-releasing system (IUS) 
x bilateral tubal occlusion  
x vasectomized partner 
x sexual abstinence 
Sexual abstinence is considered a highly effective method only if it is the preferred 
and usual lifestyle of the subject and the subject agrees to refrain from heterosexual 
intercourse from signing the ICF through the end of the study follow-up. Periodic 
abstinence, the rhythm method, and the withdrawal method are not acceptable 
methods of contraception. A recommendation that the female partners (of 
childbearing potential) of male study participants should use a highly effective 
method of contraception other than a barrier method is made. 
 Females of childbearing potential are defined as those who are not surgically 
sterile (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). 
 Vasectomized partner is a highly effective birth control method provided that 
partner is the sole sexual partner of the woman of childbearing potential trial 
participant and that the vasectomized partner has received medical assessment of 
the surgical success. 
7. Nonsterilized male subjects who are sexually active with a female partner of childbearing 
potential must use a condom with spermicide from Day 1 through the end of the study. 
8. Meets all of the following tuberculosis (TB) criteria: 
a. No history of latent or active TB prior to screening, with the exception of latent TB 
with documented completion of appropriate treatment.  
b. No signs or symptoms suggestive of active TB from medical history or physical 
examination. 


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c. No recent ZHHNVRIVFUHHQLQJclose contact with a person with active TB (close 
FRQWDFWLVGHILQHGDVKRXUVZHHN25OLYLQJLQWKHVDPHKRXVHKROG25LQDKRXVH
where a person with active TB is a frequent visitor). 
d. Negative Interferon Gamma Release Assay (IGRA) test result for TB obtained within 
12 weeks prior to randomization. Subjects with an indeterminate test result can repeat 
the test, but if the repeat test is also indeterminate, they are excluded. 
e. A chest radiograph (obtained during the screening period or any time within 12 weeks 
prior to signing of the ICF) with no evidence of current active TB or other infection, 
or old active TB, malignancy, or clinically significant abnormalities suggesting an 
active process (unless due to SS). 
5.1.2 
Exclusion Criteria for Population #1 
If an individual for Population #1 meets any of the following criteria, he or she is ineligible for 
this study: 
1. Patients with medical history of confirmed deep venous thrombosis or arterial 
thromboembolism within 2 years of signing the ICF. 
2. Patients with risk factors for venous thromboembolism or arterial thrombosis (eg, 
immobilization or major surgery within 12 weeks before screening), prothrombotic status 
(including, but not limited to, congenital or inherited deficiency of antithrombin III, 
protein C, protein S, or confirmed diagnosis of catastrophic antiphospholipid syndrome). 
3. Patients requiring treatment with anticoagulant drugs (clopidogrel, prasugrel, warfarin, 
low molecular weight heparin, others). Low-dose aspirin treatment (up to 325 mg/day) is 
allowed.  
4. Concomitant polymyositis or dermatomyositis or systemic sclerosis. 
5. Active malignancy or history of malignancy, except as follows: 
a. In situ carcinoma of the cervix treated with apparent success with curative therapy 
> 12 months prior to screening; or  
b. Cutaneous basal cell carcinoma following apparently curative therapy.  
6. Subjects who are pregnant or lactating or planning to become pregnant during the 
duration of the study. 
7. Subjects who have a positive test for, or have been treated for hepatitis B, hepatitis C, or 
HIV infection. 
Regarding hepatitis B, positive test for chronic hepatitis B infection at screening, defined 
as either (1) positive hepatitis B surface antigen (HBsAg) or (2) a positive hepatitis B 
core antibody (anti-HBc). 
8. Subjects with: 
a. A history of more than one episode of herpes zoster and/or opportunistic infections in 
the last 12 months, with the exception of oral candidiasis, vaginal candidiasis, and 
cutaneous fungal infections. 


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b. Active viral, bacterial or other infections requiring systemic treatment at the time of 
screening or through randomization, or history of more than 2 infections requiring IV 
antibiotics within 12 months prior to signing the ICF. 
c. Epidemiologic risk of COVID-19 (recent exposures, 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 subject’s 
risk of participation. Subjects who have active COVID-19 infection or disease or 
other significant infection, or, in the judgment of the investigator, who may be at 
unacceptable risk of COVID-19 or its complications should not be randomized. 
d. A documented positive SARS-CoV-2 test within 2 weeks prior to randomization. 
Subjects with a positive test for SARS-CoV-2 may be rescreened at least 2 weeks 
after a positive test if asymptomatic and at least 3 weeks after symptomatic COVID-
19 illness. 
9. Subjects with known history of severe allergy or reaction to any component of the IP 
formulation or to any other biologic therapy. 
10. Subjects with any severe cardiovascular, respiratory, endocrine, gastrointestinal, 
hematological, neurological, psychiatric, or systemic disorder or any other condition that 
in the opinion of the Investigator, would place the subject at unacceptable risk of 
complications, interfere with evaluation of the IP or confound the interpretation of 
subject safety or study results. 
11. Subjects who are unable or unwilling to comply with protocol requirements (eg, active 
drug or alcohol abuse). 
12. Subjects who have received live (attenuated) vaccine within the 4 weeks prior to ICF 
signature.  
13. Last administration of experimental biologic (other than those listed in Point 14) or oral 
agents < 3 months or 5 half-lives before randomization.  
14. Subjects who have had previous treatment with any biologic B-cell-depleting therapy (eg, 
rituximab, ocrelizumab, or ofatumumab) within 12 months or other B-cell targeting 
therapy (eg, belimumab) < 3 months before randomization. 
15. Injectable corticosteroids (including intra-articular) or treatment with > 10 mg/day dose 
oral prednisone or equivalent within 6 weeks prior to randomization. Concomitant 
WUHDWPHQWZLWKRUDOFRUWLFRVWHURLGV 10 mg/day prednisone or equivalent is permitted 
SURYLGHGWKDWWKHGRVHLVVWDEOH 2 weeks prior to screening through randomization 
(Day 1) and is expected to remain stable for the duration of the treatment period. Inhaled 
or topical corticosteroids given for asthma, chronic obstructive pulmonary disease or 
dermatological conditions are allowed provided doses are expected to be stable during the 
study. 
16. Subjects treated with systemic corticosteroids for indications other than SS, RA, and SLE 
for more than a total of 2 weeks within 24 weeks prior to screening visit. 
17. Use of the following medications:  


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a. Antimalarials (eg, chloroquine, hydroxychloroquine, quinacrine) if they have been 
initiated or if the dose has changed within 8 weeks prior to signing the ICF or during 
the screening period.  
b. MTX, if the dose is > 20 mg/week; or if there is any change or initiation of new dose 
within 4 weeks prior to signing the ICF through randomization (Day 1), or if there has 
been any change in route of administration. 
c. Azathioprine (AZA), if the dose is > 150 mg/day and there is any change or initiation 
of new dose within 4 weeks prior to signing the ICF through randomization (Day 1) 
and any change in route of administration. 
d. Leflunomide, if the dose is >20 mg/day; or if there is any change or initiation of new 
dose within 4 weeks prior to signing the ICF through randomization (Day 1).  
e. Mycophenolate mofetil (MMF), if the dose is >2g/day; or if there is any change or 
initiation of new dose within 4 weeks prior to signing the ICF through randomization 
(Day 1). 
f. Any other DMARD, immunosuppressant, or antiproliferative agents, if last dose was 
taken within: 
 4 weeks prior to signing ICF or 
 Drug-specific 5 half-lives elimination period (if longer than 4 weeks). 
g. Any medication that, in the opinion of the Investigator, would interfere with 
evaluation of the IP or interpretation of subject safety or study results. 
h. Any increase or initiation of new doses of cevimeline or pilocarpine and cyclosporine 
eye drops (Restasis®) within 2 weeks prior to signing the ICF through randomization 
'D\ௗ 
18. Subjects who have received previous treatment with anti-CD40L compounds at any time 
before screening. 
19. Subjects with blood tests, at screening, of any of the following: 
x Aspartate aminotransferase (AST) > 2 x upper limit of normal (ULN) 
x Alanine aminotransferase (ALT) > 2 x ULN 
x Total bilirubin (TBL) > 2 x ULN 
x Hemoglobin < 75 g/L 
x Neutrophils < 1.0 x 109/L 
x Platelets < 100 x 109/L 
x Prothrombin or partial thromboplastin time (PTT) > ULN 
5.1.3 
Inclusion Criteria for Population #2 
To be included in Population #2 of this study, each individual must satisfy all the following 
criteria. 
1. Adults, 18 years or older at time of informed consent (the minimum age for adult 
participants can be higher than 18 years in countries with different regulations). 


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2. Diagnosed with SS by meeting the 2016 ACR/EULAR Classification Criteria.  
3. +DYHDQ(6635,VFRUHRIDWVFUHHQLQJ 
4. Have an ESSDAI score of < 5 at screening. 
5. Positive for either anti-Ro autoantibodies or RF, or both at screening, as per the definition 
of the standard central laboratory test available.  
6. Residual salivary gland function as defined by whole stimulated salivary flow 
> 0.1 mL/min. 
7. Written informed consent and any locally required authorization (eg, Health Insurance 
Portability and Accountability Act in the United States, EU Data Privacy Directive in the 
EU) obtained from the subject/legal representative prior to performing any protocol-
related procedures, including screening evaluations. 
8. Females of childbearing potential who are sexually active with a nonsterilized male 
partner must use a highly effective method of contraception from signing the ICF, and 
must agree to continue using such precautions through the end of the study follow-up; 
cessation of contraception after this point should be discussed with a responsible 
physician. Highly effective methods of contraception include: 
x combined (estrogen and progestogen containing) hormonal contraception 
associated with inhibition of ovulation: 
 oral 
 intravaginal 
 transdermal 
x progestogen-only hormonal contraception associated with inhibition of ovulation:  
 oral 
 injectable 
 implantable 
x intrauterine device (IUD)  
x intrauterine hormone-releasing system (IUS) 
x bilateral tubal occlusion  
x vasectomized partner 
x sexual abstinence 
Sexual abstinence is considered a highly effective method only if it is the preferred 
and usual lifestyle of the subject and the subject agrees to refrain from heterosexual 
intercourse from signing the ICF through the end of the study follow-up. Periodic 
abstinence, the rhythm method, and the withdrawal method are not acceptable 
methods of contraception. A recommendation that the female partners (of 
childbearing potential) of male study participants should use a highly effective 
method of contraception other than a barrier method is made. 
 Females of childbearing potential are defined as those who are not surgically 
sterile (surgical sterilization includes bilateral tubal ligation, bilateral 


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oophorectomy, or hysterectomy) or those who are not postmenopausal (defined as 
12 months with no menses without an alternative medical cause). 
 Vasectomized partner is a highly effective birth control method provided that 
partner is the sole sexual partner of the woman of childbearing potential trial 
participant and that the vasectomized partner has received medical assessment of 
the surgical success. 
9. Nonsterilized male subjects who are sexually active with a female partner of childbearing 
potential must use a condom with spermicide from Day 1 through to the end of the study. 
10. Meets all of the following TB criteria: 
a. No history of latent or active TB prior to screening, with the exception of latent TB 
with documented completion of appropriate treatment.  
b. No signs or symptoms suggestive of active TB from medical history or physical 
examination. 
c. No recent ZHHNVRIVFUHHQLQJclose contact with a person with active TB (close 
FRQWDFWLVGHILQHGDVKRXUVZHHN25OLYLQJLQWKHVDPHKRXVHKROG25LQDKRXVH
where a person with active TB is a frequent visitor). 
d. Negative IGRA test result for TB obtained within 12 weeks prior to randomization. 
Subjects with an indeterminate test result can repeat the test, but if the repeat test is 
also indeterminate, they are excluded. 
e. A chest radiograph (obtained during the screening period or anytime within 12 weeks 
prior to signing of the ICF) with no evidence of current active TB or other infection, 
or old active TB, malignancy, or clinically significant abnormalities suggesting an 
active process (unless due to SS). 
5.1.4 
Exclusion Criteria for Population #2 
If an individual for Population #2 meets any of the following criteria, he or she is ineligible for 
this study: 
1. Patients with medical history of confirmed deep venous thrombosis or arterial 
thromboembolism within 2 years of signing the ICF. 
2. Patients with risk factors for venous thromboembolism or arterial thrombosis (eg, 
immobilization or major surgery within 12 weeks before screening), prothrombotic status 
(including, but not limited to, congenital or inherited deficiency of antithrombin III, 
protein C, protein S, or confirmed diagnosis of catastrophic antiphospholipid syndrome). 
3. Patients requiring treatment with anticoagulant drugs (clopidogrel, prasugrel, warfarin, 
low molecular weight heparin, etc). Low-dose aspirin treatment (up to 325 mg/day) is 
allowed. 
4. Concomitant polymyositis or dermatomyositis or systemic sclerosis. 
5. Active malignancy or history of malignancy, except as follows:  


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a. In situ carcinoma of the cervix treated with apparent success with curative therapy 
> 12 months prior to screening; or  
b. Cutaneous basal cell carcinoma treated with apparent success with curative therapy  
6. Subjects who are pregnant or lactating or planning to get pregnant during the duration of 
the study. 
7. Subjects who have a positive test for, or have been treated for, hepatitis B, hepatitis C, or 
HIV infection.  
Regarding hepatitis B, a positive test for chronic hepatitis B infection at screening is 
defined as detection of either (1) hepatitis B surface antigen (HBsAg); or (2) hepatitis B 
core antibody (anti-HBc). 
8. Subjects with: 
a. A history of more than one episode of herpes zoster and/or opportunistic infections in 
the last 12 months, with the exception of oral candidiasis, vaginal candidiasis, and 
cutaneous fungal infections. 
b. Active viral, bacterial or other infections requiring systemic treatment at the time of 
screening or through randomization, or history of more than 2 infections requiring IV 
antibiotics within 12 months prior to signing the ICF. 
c. Epidemiologic risk of COVID-19 (recent exposures, 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 subject’s 
risk of participation. Subjects who have active COVID-19 infection or disease or 
other significant infection, or, in the judgment of the investigator, who may be at 
unacceptable risk of COVID-19 or its complications should not be randomized. 
d. A documented positive SARS-CoV-2 test within 2 weeks prior to randomization. 
Subjects with a positive test for SARS-CoV-2 may be rescreened at least 2 weeks 
after a positive test if asymptomatic and at least 3 weeks after symptomatic COVID-
19 illness. 
9. Subjects with known history of severe allergy or reaction to any component of the IP 
formulation or to any other biologic therapy. 
10. Subjects with any severe cardiovascular, respiratory, endocrine, gastrointestinal, 
hematological, neurological, psychiatric, or systemic disorder or any other condition that, 
in the opinion of the Investigator would interfere with evaluation of the IP or 
interpretation of subject safety or study results. 
11. Subjects who are unable or unwilling to comply with protocol requirements (eg, active 
drug or alcohol abuse). 
12. Subjects who have received live (attenuated) vaccine within the 4 weeks before ICF 
signature. 
13. Last administration of experimental biologic (other than those listed in Point 14) or oral 
agents < 3 months or 5 half-lives before randomization.  


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14. Subjects who have had previous treatment with any biologic B cell-depleting therapy (eg, 
rituximab, ocrelizumab, ofatumumab) within 12 months or other B-cell targeting therapy 
(eg, belimumab) < 3 months before randomization. 
15. Use of the following medications:  
a. $QWLPDODULDOVHJௗFKORURTXLQHK\GUR[\FKORURTXLQHTXLQDFULQHLIWKH\KDYHEHHQ
initiated or if the dose has changed within 8 weeks prior to signing the ICF or during 
the screening period.  
b. Oral, intramuscular, IV, or intra-articular corticosteroids within 4 weeks prior to 
signing the ICF through randomization (Day 1). 
c. MTX, AZA, leflunomide, other cDMARD, or immunosuppressive or antiproliferative 
medications, if last dose was taken within: 
 4 weeks prior to signing ICF or 
 Drug-specific 5 half-lives elimination period (if longer than 4 weeks). 
d. Any medication that in the opinion of the Investigator would interfere with evaluation 
of the IP or interpretation of subject safety or study results 
e. Any increase or initiation of a new dose of regularly scheduled nonsteroidal anti-
inflammatory drugs within 2 weeks prior to signing the ICF through randomization 
(Day 1).  
f. Any increase or initiation of new doses of cevimeline or pilocarpine and cyclosporine 
eye drops (Restasis) within 2 weeks prior to signing the ICF through randomization 
'D\ௗ 
16. Subjects who have received previous treatment with anti-CD40L compounds at any time 
before screening. 
17. Subjects with blood tests, at screening, of any of the following: 
x AST > 2 x ULN 
x ALT > 2 x ULN 
x TBL > 2 x ULN 
x Hemoglobin < 75 g/L 
x Neutrophils < 1.0 x 109/L 
x Platelets < 100 x 109/L 
x Prothrombin or PTT > ULN 
6 
STUDY CONDUCT 
Subjects will undergo a screening period of up to 4 weeks followed by randomization and 
treatment for 40 weeks (24 weeks [169 days] for Stage I and 16 weeks [112 days] for Stage II). 
Subjects will be followed for an additional 12 weeks [84 days] for safety and for assessment of 
duration of efficacy. The expected full duration of each subject’s participation in this study is up 
to 393 days. 


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Table 1 summarizes the screening procedures for the study. More than one visit might be needed 
to complete screening. 
The 2016 ACR/EULAR Criteria for Classification of SS are provided in Appendix 1. 
Table 1 
Screening Procedures 
Study Period 
Screening 
Visit Number 
V1 
Procedure / Study Day 
Day -28 to Day -1 
Written informed consent 
X 
SID number assignment 
X 
Medical history 
X 
2016 ACR/EULAR Criteria for classification of SS 
X 
ESSDAI 
X 
ESSPRI 
X 
Assessment of prior and concomitant medications 
X 
Verify eligibility criteria 
X 
Complete physical examination (including weight and height) 
X 
ECG 
X 
Vital signs 
X 
Assessment of AEs/SAEs 
X 
Virology: Hepatitis B, C; HIV-1; HIV-2, SARS-CoV-2b 
X 
TB test (IGRA)c 
X 
Safety Lab Tests: Serum Chemistry, Hematology, Urinalysis 
X 
Baseline coagulation panel (prothrombin time, PTT) 
X 
Autoantibody panel (anti-SSA [Ro], anti-SSB [La], ANA) 
X 
RF 
X 
Chest X-rayd 
X 
Thyroid Function Tests (TSH, T3, T4, free T4) 
X 
3UHJQDQF\WHVWVHUXPȕ-hCG; females of childbearing potential only) 
X 
ActiGraph provided to subject (optional) 
X 
AE = adverse event; ANA = antinuclear antibodies; APL = antiphospholipid; EhCG = beta-human chorionic 
gonadotropin; C = complement; ECG = electrocardiogram; ESSDAI = European League Against Rheumatism 
(EULAR) Sjögren’s Syndrome Disease Activity Index; ESSPRI = EULAR Sjögren’s Syndrome Patient Reported 


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Index; HIV = human immunodeficiency virus; IGRA = Interferon Gamma Release Assay; PTT = partial 
thromboplastin time; RF = rheumatoid factor; SAE = serious adverse event; SID = subject identification; SS = 
Sjögren’s syndrome; TB = tuberculosis; TSH = thyroid stimulating hormone.  
b 
To participate in study, subjects required a negative SARS-CoV-2 test within 2 weeks prior to 
randomization. 
c 
IGRA not required during screening if performed within 12 weeks prior to screening visit with a 
documented negative result. 
d 
Chest X-ray not required during screening if performed within 12 weeks prior to screening visit. 
The schedules of study assessments for the active treatment period and for the off-treatment 
period are presented in Table 2 and Table 3, respectively. 
Table 3 also summarizes all assessments that could be conducted at any unscheduled visit during 
the study. 
 


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Table 2 
Schedule of Study Assessments During the Treatment Period 
Visit number 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
 
Stage I 
Stage I/ 
Stage IIa 
Stage II 
Study day 
Procedure 
1 
Baseline 
15 ± 
1d 
29 ± 3d 
57 ± 3d 
85 ± 3d 
113 ± 
3d 
141 ± 
3d 
EP:169 
± 3d 
197 ± 
3d 
225 ± 3d 
253 ± 3d 
281 ± 3d 
Verify eligibility 
criteria 
X 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
ESSPRI 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FACIT-Fatigue 
Questionnaire  
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
OSDI 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
PGIS 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ESSDAI  
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Assessment of 
AEs/SAEs 
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 


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Table 2 
Schedule of Study Assessments During the Treatment Period 
Visit number 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
 
Stage I 
Stage I/ 
Stage IIa 
Stage II 
Study day 
Procedure 
1 
Baseline 
15 ± 
1d 
29 ± 3d 
57 ± 3d 
85 ± 3d 
113 ± 
3d 
141 ± 
3d 
EP:169 
± 3d 
197 ± 
3d 
225 ± 3d 
253 ± 3d 
281 ± 3d 
Full physical 
examination 
X 
 
 
 
 
 
 
X 
 
 
 
X 
Symptom-driven 
physical examb 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
 
Vital Signs (BP, 
HR, RR and 
temp) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG 
X 
 
 
 
 
 
 
X 
 
 
 
 
Weight 
X 
 
 
 
 
 
 
X 
 
 
 
X 
Safety lab testsc 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy 
test in women of 
childbearing 
potential 
X 
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Coagulation tests 
(prothrombin 
time, PTT) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Autoantibody 
paneld 
 
 
 
 
X 
 
 
X 
 
 
 
 
RF 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 


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Table 2 
Schedule of Study Assessments During the Treatment Period 
Visit number 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
 
Stage I 
Stage I/ 
Stage IIa 
Stage II 
Study day 
Procedure 
1 
Baseline 
15 ± 
1d 
29 ± 3d 
57 ± 3d 
85 ± 3d 
113 ± 
3d 
141 ± 
3d 
EP:169 
± 3d 
197 ± 
3d 
225 ± 3d 
253 ± 3d 
281 ± 3d 
Inflammatory 
markerse 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ADA (plasma)  
X 
 
X 
 
X 
 
 
X 
X 
 
X 
 
PK (plasma) 
Xg 
X 
X 
X 
X 
X 
Xg 
Xg 
X 
X 
X 
X 


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Table 2 
Schedule of Study Assessments During the Treatment Period 
Visit number 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
 
Stage I 
Stage I/ 
Stage IIa 
Stage II 
Study day 
Procedure 
1 
Baseline 
15 ± 
1d 
29 ± 3d 
57 ± 3d 
85 ± 3d 
113 ± 
3d 
141 ± 
3d 
EP:169 
± 3d 
197 ± 
3d 
225 ± 3d 
253 ± 3d 
281 ± 3d 
Qualitative 
Patient Interview 
(optional)h 
 
 
 
 
 
 
 
X 
 
 
 
 
Administration 
of IP 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ADA = anti-drug antibodies; AE = adverse event; ANA = antinuclear antibody; BP = blood pressure; C = complement; d = day(s); ECG = electrocardiogram; 
EP = endpoint; ESSDAI = EULAR Sjögren’s Syndrome Disease Activity Index; ESSPRI = EULAR Sjögren’s Syndrome Patient Reported Index; FACIT-
Fatigue =  Functional Assessment of Chronic Illness Therapy -Fatigue; HR = heart rate; IP = investigational product; OSDI = Ocular Surface Disease Index; 
; PGIS = Patient Global Impression of Severity; PK = pharmacokinetic;
 PTT = partial thromboplastin time; RF = rheumatoid factor; RR = respiratory rate; SAE = serious 
adverse event;
; V = Visit; 
. 
Note: All laboratory sample collections and assessments on dosing day must be performed at pre-dose, unless specified otherwise. 
a 
Day 169 is primary endpoint for Stage I and first day of IP administration for Stage II. 
b 
If no symptoms are present, the exam can be limited to assess ESSDAI. 
c 
Safety laboratory tests: Serum chemistry, hematology and urinalysis.  
d 
Autoantibody panel: anti-SSA (Ro), anti-SSB (La), and ANA. 
3 
g 
Plasma sample for PK to be collected pre- and postdose (at the end of infusion). 
h 
Telephone-based interview applicable to English-speaking subjects in the USA and UK only, and can be conducted anytime from Day 169 onwards. 
 
 


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Table 3 
Schedule of Assessments During the Off-treatment Period and Any Unscheduled Visits 
Visit number 
V14 
V15 and EDV 
Unscheduled Visita 
 
Off-treatment Period 
Study day Procedure 
D309 ± 7d 
D365 ± 7d 
 
ESSPRI 
X 
X 
 
FACIT-Fatigue questionnaires 
X 
X 
 
OSDI 
X 
X 
 
PGIS 
X 
X 
 
ESSDAI 
X 
X 
 
Assessment of AEs/SAEs 
X 
X 
X 
Concomitant medications  
X 
X 
X 
Full physical examination 
X 
X 
 
Symptom-driven physical examb 
 
 
X 
Vital Signs (BP, HR, RR and temp) 
X 
X 
X 
ECG 
 
X 
 
Weight 
X 
X 
  
Safety lab tests 
X 
X 
X 
Urine pregnancy test 
X 
X 
X 


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Table 3 
Schedule of Assessments During the Off-treatment Period and Any Unscheduled Visits 
Visit number 
V14 
V15 and EDV 
Unscheduled Visita 
 
Off-treatment Period 
Study day Procedure 
D309 ± 7d 
D365 ± 7d 
 
Coagulation tests 
X 
X 
X 
RF 
X 
X 
 
Inflammatory markers 
X 
X 
 
ADA 
X 
X 
 
PK (plasma) 
X 
X  
 
ActiGraph collected from subject (optional) 
 
X 
 
ADA = anti-drug antibodies; AE = adverse event; BP = blood pressure; C = complement; D = Day; d = days; ECG = electrocardiogram; EDV = early 
discontinuation visit; ESSDAI = EULAR Sjögren’s Syndrome Disease Activity Index; ESSPRI = EULAR Sjögren’s Syndrome Patient Reported Index; FACIT-
Fatigue =  Functional Assessment of Chronic Illness Therapy -Fatigue; HR = heart rate; OSDI = Ocular Surface Disease Index;
 
; PGIS = Patient Global Impression of Severity; PK = pharmacokinetic; RF = rheumatoid factor; RR = respiratory rate; SAE = serious 
adverse event; 
 V = Visit;
 
a 
The assessments at any unscheduled visits may be adjusted as clinically indicated. 
b 
If no symptoms are present, the exam can be limited to assess ESSDAI. 
c 
Will not be collected in China. 
 


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The study assessments are described by study period in the following sections, with reference to 
the study schedules of assessment for details by study visit. 
6.1 
Sjögren’s Syndrome Data Medical Review Team  
The SS Data MR team members are medically qualified individuals who will review all SS data 
in conjunction with any other relevant data (including medical history, adverse event [AE], 
laboratory data, and concomitant medications as appropriate) that is necessary to characterize the 
subject’s SS. The MR team members will have access to an expert on SS disease activity for 
unanticipated issues with regard to interpretation of these indices. 
A separate procedure will outline the review and escalation details. The MR team will be utilized 
throughout the study to confirm classification of SS and ESSDAI scoring. The purpose of the 
review is to ensure medical plausibility, coherence, consistency, and clarity of data. The MR 
team will query any inconsistent scoring and follow for resolution of any discrepancy. The MR 
team will monitor trends in issues encountered during their review and liaise with the study team 
for additional training to be provided for the site staff or study monitoring team as appropriate. 
The MR team will remain blinded to the treatment assignment for individual subjects until the  
completion of the study. 
6.2 
Screening Procedures 
6.2.1 
Informed Consent 
All screening procedures listed in Table 1 will be performed within 28 days prior to 
randomization.  
Subjects officially enter the screening period following provision of informed consent either 
directly or via a legally authorized representative. 
A screen failure is a consented subject who has been deemed ineligible on the basis of one or 
more eligibility criteria or who has withdrawn consent prior to treatment assignment. Screen 
failures may be rescreened with Medical Monitor approval. 
A randomized subject is one who has been deemed eligible and has been assigned to a treatment 
group. 
All candidates for enrollment or legally authorized representative will sign an ICF prior to any 
protocol-related procedures, including screening activities. Informed consent must be obtained 
by the Principal Investigator or a designee, such as an Investigator, with Institutional Review 
Board (IRB)-approved qualifications. 
After signing the ICF, each subject will be assigned a subject identification (SID) number by the 
interactive voice/web response system (IXRS) that will be used on all subject documentation. 
Numbers will be assigned in ascending sequential order. Rescreened patients will receive a new 
SID number. This number will also correspond to the subject number entered on test materials. 
6.2.2 
Demographics and Baseline Characteristics  
Demographic information to be collected includes date of birth, sex, race and ethnicity. Medical 
history information to be collected includes all ongoing conditions and relevant/significant 


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medical history (including all major hospitalizations and surgeries), as determined by the 
Investigator. Prior and concomitant medications will be recorded. A complete physical 
examination, including weight, height, and 
 will be conducted. 
The 2016 ACR/EULAR Criteria will be used for classification of SS for both Population #1 and 
Population #2, as confirmed by the MR team (Section 6.1). The classification of SS will apply to 
any individual who meets the inclusion criteria, does not have any condition listed as an 
H[FOXVLRQFULWHULRQDQGZKRKDVDVFRUH 4 when summing the weights from the items listed in 
Appendix 1. Eligibility related to ESSDAI scores for Population #1 will also be confirmed by the 
MR team. 
Whole 
 will be conducted at screening to 
determine study eligibility. See Section 6.4.1 (Efficacy Assessments) for details on these 
assessments. ESSDAI-required blood tests will be conducted. 
Additionally, an autoantibody panel, which includes RF will be collected. See Section 6.4.3.1 for 
details. 
Safety-related screening assessments will include AEs, safety laboratory tests (serum chemistry, 
hematology, and urinalysis), coagulation parameters, chest X-ray, thyroid function tests, and 
serum beta-human chorionic gonadotropin (ȕ-hCG) pregnancy test for females of childbearing 
potential. For details on safety assessments, see Section 6.4.2 and 8. 
6.2.3 
Re-screening Procedures 
Abnormal laboratory values meeting exclusion criteria may be re-tested during the screening 
period without this being considered re-screening. Subjects may be rescreened once if, in the 
Investigator’s judgment, the reason for ineligibility is likely to have resolved at the time of 
rescreen. 
6.3 
Randomization 
Prior to randomization, subject eligibility must be confirmed by the MR team (see Section 6.1). 
Subjects who meet all eligibility criteria, including confirmation of eligibility by the study MR 
review team, will be randomized. A subject is considered randomized into the study when the 
Investigator notifies the IXRS that the subject meets eligibility criteria and the IXRS provides the 
assignment of treatment group and allocates treatment, including IP kit number (Day 1, Baseline 
[Table 2]). To ensure balanced rates of enrollment for the 2 populations, the Sponsor will 
implement a procedure where enrollment of subjects in Population #2 at each site is linked to 
enrollment of Population #1 subjects at the site with a progressively increasing ratio of 


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Population #2:Population #1 subjects. At least one subject of the first 2 randomized at each site 
must be from Population #1. 
For details on the MR procedure, see Section 6.1. 
6.4 
Treatment Period 
All assessments that will be conducted during Stage I and Stage II of the treatment period are 
summarized by study visit in Table 2. Efficacy assessments are described in Section 6.4.1 and 
safety assessments are described in Section 6.4.2. 
The primary endpoint assessments will be conducted on Day 169 (Visit 9) of Stage I of the 
active treatment period. 
6.4.1 
Efficacy Assessments 
Some of the efficacy assessments are patient-reported outcomes (PRO) instruments. PRO 
instruments will be administered electronically and will be completed at the site.  
To ensure data integrity the following best practice guidelines should be followed: 
x Always administer PRO instruments before other study procedures.  
x Provide the subject with a quiet and private location to complete the instrument. 
x Remind subjects that there are no right or wrong answers and the reason they are being 
asked to complete these questionnaires is because we are interested in hearing directly from 
them as to how they feel. 
Assist subjects only with procedural questions, such as what it means to “tick a box” and do not 
clarify the meaning of questions to avoid bias. Subjects should be told to select the response that 
best answers the question as they understand it. 
Subject should be given as much time as is needed to complete the questionnaires. 
Promptly review the questionnaires for completeness and provide an opportunity for the subject 
to answer if an item is left blank. 
6.4.1.1 
ESSDAI 
The ESSDAI is a systemic disease activity index that includes organ-by-organ definitions of 
disease activity (Seror et al, 2010). The ESSDAI grades disease activity in 12 domains 
(cutaneous, respiratory, renal, articular, muscular, peripheral nervous system, central nervous 
system, hematological, glandular, constitutional, lymphadenopathic, and biological). The weights 
of each domain were obtained by multiple regression modeling, using the Physician’s Global 
Assessment of Activity as gold standard. 
Each domain is weighted from 1 (Biologic domain) to 6 (Muscular domain) and has 3 or 4 levels 
of activity per domain, ranging from 0 (no activity) to 3 (high activity). 
The theoretical range of values for the ESSDAI is 0 to 123, with the final score being calculated 
as follows: 
Final Score = Sum of all 12 domain scores 
Domain score = Activity level × Domain weight 


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Low activity status is defined as ESSDAI < 5, moderate activity as 5  ESSDAI  13 and high 
activity as ESSDAI  14 (Seror et al, 2016a). The MR team described in Section 6.1 will confirm 
disease activity based on ESSDAI at key time points during the study. 
6.4.1.2 
ESSPRI 
ESSPRI is a self-evaluation tool that was developed in a multicenter international cohort of 230 
patients (Seror et al, 2011). The ESSPRI uses a 0 to 10 numerical analog scale (ranging from 0 
[no symptoms] to 10 [maximal imaginable severity]), one for the assessment of each of the 
3 domains: dryness, fatigue, and pain (articular and/or muscular). The weights of the domains are 
identical, and the mean of the scores of the 3 domains represents the final score. The recall 
period is stated in each question as “the last 2 weeks.” The instrument can be completed in 
approximately 1 minute. 
6.4.1.4 
Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue   
The FACIT-Fatigue is a 13-item questionnaire, subject-completed, used to assess the impact of 
fatigue. Its recall period is 7 days. The responses range from 0 (Not at all) to 4 (Very Much). To 
calculate the total score, the negatively stated items are reversed by subtracting the response 
from “4”. Final scores are the sum of the responses and range from 0 to 52. Higher scores 
indicate better QoL. It takes 5-10 minutes to complete. 


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6.4.1.7 
Ocular Surface Disease Index (OSDI) 
OSDI is a valid and reliable instrument for assessing effect on vision-related function and dry 
eye disease severity (normal, mild, moderate, and severe). Its recall period is 1 week. It is 
composed of 12 questions that the physician asks the subject and circles the number that best 
represents each question. The responses for each question range from 0 (None of the time) to 4 
(All of the time). The OSDI score is calculated as (sum of scores for questions 
answered)/(number of questions answered)×25, which ranges from 0 to 100 with higher scores 
signifying greater disability. The assessment can be completed in 5 minutes. 
6.4.1.9 
Patient Global Impression of Severity 
The PGIS is a single item designed to capture the subject’s perception of overall symptom 
severity over the past week on a 5-point categorical response scale (none, mild, moderate, severe, 
or very severe). 


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6.4.1.14 
ClinESSDAI 
ClinESSDAI is a validated SS disease activity index, based on ESSDAI that excludes the 
biological domain and assigns different weights assigned to each domain. ClinESSDAI was 
developed in an effort to diminish possible associations between the B-cell biomarkers measured 
by the ESSDAI biological domain and clinical activity measures (Seror et al, 2016b). The 
theoretical range of values for the ClinESSDAI is 0 to 135, and similar to ESSDAI, low-activity 
status is defined as < 5, moderate-DFWLYLW\DV&OLQ(66'$,DQGKLJK-DFWLYLW\DV
(Seror et al, 2016a). ClinESSDAI has been validated and shown to correlate well with ESSDAI 
and is considered a useful tool to detect change independent of biological effect of the drug 
(Seror et al, 2016b; Dumusc et al, 2018; Quartuccio et al, 2017). 
6.4.2 
Safety Assessments 
Safety assessments will be conducted during the active treatment period according to the 
assessments shown in Table 2 and will consist of: 
x Monitoring and recording all AEs (including AESIs) and SAEs (see Section 8.1 through 
8.4 for details) 
x Safety laboratory tests (serum chemistry, hematology, and urinalysis [see Section 8.5 for 
details]) 
x Concomitant medications 
x Vital signs, physical examination (full or symptom-driven depending on the visit), and 
weight 
x ECG 
x Urine pregnancy test (for females of childbearing potential) 
x Coagulation tests  


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6.4.3 
Additional Disease-related Assessments 
The assessments related to SS described in the following sections will be conducted according to 
the schedules shown in Table 2 (treatment period) and Table 3 (off-treatment period). 
6.4.3.1 
Autoantibody Panel 
Serum will be collected to assess the presence of anti-SSA (Ro), anti-SSB (La), antinuclear 
antibodies, and RF. 
6.4.3.2 
Inflammatory Markers 
Whole blood, plasma, serum, and urine will be collected to assess levels of plasma 
immunoglobulins (IgM, IgG, and IgA), beta-2 microglobulin, high sensitivity CRP, C3, C4, 
serum free light chains, cryoglobulins, and serum and urine immunofixation. 


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6.4.4 
Immunogenicity Assessments 
Plasma samples for immunogenicity (ADA to VIB4920) will be taken prior to drug 
administration according to the visits specified in Table 2 (treatment period) and Table 3 
(off-treatment period) and assessed using a validated immunoassay. 
6.4.5 
Pharmacokinetic Assessments 
Plasma samples to determine the concentration of VIB4920 will be taken according to the visits 
specified in Table 2 (treatment period) and (Table 3) (off-treatment period) using a validated 
assay. 
6.5 
Off-treatment Period 
The off-treatment period will comprise 12 weeks following the last dose of IP and includes Visit 
14 and Visit 15 (or EDV in the event of premature discontinuation from the study). All 
procedures to be conducted at the Off-treatment visits are listed in Table 3. 
Efficacy assessments to be conducted at the off-treatment visits will include: Patient Global 
Impression of Severity, Patient Global Impression of Change, ESSPRI, 
 
FACIT-Fatigue,
, OSDI, 
 
, and 
. Details on these assessments 
are presented in Section 6.4.1. 
Safety assessments will include: AEs/SAEs, concomitant medications, full or symptom-driven 
physical examination, vital signs, ECG, weight, and safety laboratory tests. For details of these 
assessments, see Section 8. 
Additional disease-related assessments will be conducted as shown in Table 3 and are described 
in Section 6.4.3.  
The 
 device will be collected at the last patient visit or the EDV, whichever is later 
(Table 3). 
6.6 
Discontinuation or Withdrawal 
6.6.1 
Discontinuation of Treatment 
IP must be discontinued if the Investigator determines that continuing it would result in a 
significant safety risk for that subject. Reasons for study drug discontinuation are or can be: 
1. Withdrawal from the study (due to withdrawal of consent or noncompliance with study 
procedures), as described in Section 6.6.2. 


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2. Withdrawal of consent from further treatment with IP. 
3. Receipt of restricted medication, as described in Section 7.4.2 for Population #1 and 
Section 7.4.4 for Population #2. 
4. Receipt of rescue medication for increased disease activity may lead to discontinuation of 
IP, as described in Section 7.4.3 for Population #1 and Section 7.4.5 for Population #2. 
5. AE or significant laboratory abnormality that, in the opinion of the Investigator and/or the 
Sponsor, warrants discontinuation of further dosing. 
6. Pregnancy or a decision to become pregnant. 
7. $Q\*UDGH7($(WKDWLVFRQVLGHUHGWREHUHODWHGWRIP by the Investigator, unless in 
the opinion of the Investigator, the event(s) are manifestations of SS (eg, within the 
definitions included in the (66'$,,VRODWHG*UDGHODERUDWRU\DEQRUPDOLWLHVZLWKRXW
a clinical event meeting the above criteria will not automatically lead to discontinuation 
of IP. 
8. Any of the following liver function abnormalities: 
a. ALT or AST > 8 × ULN; 
b. ALT or AST > 5 × ULN for more than 2 weeks; 
c. ALT or AST > 3 × ULN and bilirubin > 2 × ULN or international normalized ratio 
(INR) > 1.5; see Appendix 3 for additional details regarding reporting of subjects 
with ALT or AST > 3 × ULN and bilirubin > 2 × ULN with unknown etiology (ie, 
Hy’s law [HL] cases). 
9. Anaphylaxis or a serious hypersensitivity reaction attributed to VIB4920. 
10. Any life-threatening or serious infection or opportunistic infection.  
11. Malignancy. 
12. Any other reason when the Investigator determines that continuing IP would result in a 
significant safety risk for that subject. 
Subjects who prematurely discontinue IP before Day 169 will undergo scheduled evaluations 
until Day 169 visit and at least 3 months of off-treatment follow-up after the last IP 
administration, at which time they will undergo an EDV. They will not be eligible for treatment 
during Stage II. 
Subjects who prematurely discontinue IP after Day 169, while in Stage II, will undergo 
scheduled evaluations until the end of the off-treatment period (Day 365) or complete at least 
3 months of off-treatment follow-up after the last IP administration, at which time they will have 
an EDV. An IP discontinuation form should be completed, giving the date and primary reason 
for stopping study treatment. 
6.6.2 
Withdrawal from Study 
For subjects who withdraw prematurely from the study (eg, due to withdrawal of consent or 
noncompliance with study procedures), the reason(s) for withdrawal must be recorded on the 
appropriate page of the electronic case report form (eCRF). If possible, any subject who is 


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withdrawn from the study will have, at the time of withdrawal, all exit procedures performed (ie, 
Day 365 safety and efficacy assessments). All clinically significant abnormalities will be 
followed-up, if possible, until resolved to the satisfaction of the Investigator. 
6.6.3 
Replacement of Subjects 
Subjects will not be replaced after randomization. 
6.6.4 
Subjects Lost to Follow-up 
For subjects who are lost to follow-up (ie, those subjects whose status is unclear because they 
fail to appear for study visits without stating an intention to withdraw), the Investigator should 
show “due diligence” by documenting in the source documents steps taken to contact the subject, 
eg, dates of telephone calls, registered letters, etc. 
6.7 
Study Suspension or Termination 
The Sponsor reserves the right to temporarily suspend or terminate this study at any time. The 
reasons for temporarily suspending or terminating the study may include but are not limited to 
the following:  
x The incidence or severity of AEs indicates a potential health hazard to subjects.  
x Subject enrollment is unsatisfactory. 
x Noncompliance that might significantly jeopardize the validity or integrity of the study.  
x Sponsor decision to terminate development. 
Additional guidance is provided in the Safety and Data Monitoring Committee (SDMC) Charter. 
If Sponsor determines that temporary suspension or termination of the study is required, Sponsor 
will communicate the reasons for taking such action with all participating Investigators (or head 
of the medical institution, where applicable). When feasible, Sponsor will provide advance 
notice to all participating Investigators (or head of the medical institution, where applicable) of 
the impending action. 
If the study is suspended or terminated for safety reasons, Sponsor will promptly inform all 
Investigators, heads of the medical institutions (where applicable), and/or institutions conducting 
the study. Sponsor or designee 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 or head of the medical institution must inform the IRB/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. 
6.8 
End of Study 
Once a subject has completed all assessments listed for Visit 15 (Day 365 ± 7 days), the subject 
will be considered to have completed the study. The study will be completed once the last 
subject out has completed all Visit 15 or EDV assessments (Day 365 ±7 days; shown in Table 3). 


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7 
STUDY INTERVENTIONS 
7.1 
Description of Products 
Table 4 provides a description of IP to be used in the study. Details are presented in the 
following sections. 
Table 4 
Description of Investigational Products 
Product 
Dose 
Frequency 
Route 
Duration 
Manufacturer 
VIB4920 
1500 mg 
Stage I: 
Q2W x 3 
Q4W x 4 
Stage II: 
Q4W x 5 
IV 
Up to 169 days 
MedImmune, 
LLC 
VIB4920 Placebo 
0.9% (w/v) 
saline 
Stage I: 
Q2W x 3 
Q4W x 4 
Stage II: 
Q4W x 5 
IV 
Up to 169 days 
Provided by site 
IV = intravenous; Q2W = once every 2 weeks; Q4W = once every 4 weeks; w/v = weight/volume. 
7.1.1 
VIB4920 
7.1.1.1 
Formulation, Storage, Preparation, and Handling 
VIB4920 is formulated at 100 mg/mL VIB4920 in 
 mM sodium phosphate buffer, 
 mM 
sucrose,
% (weight/volume [w/v]) poloxamer 188, pH 
. The nominal volume in each vial 
is 5.0 mL. VIB4920 is a sterile liquid Drug Product (500 mg VIB4920 per vial, nominal) 
intended for IV infusion following dilution in normal saline. 
The IP will be appropriately labeled in accordance with national laws and regulations. VIB4920 
is provided with 3 vials per kit. 
VIB4920 should not be shaken and requires no special biohazard handling. It must be stored at 
 in refrigerator with adequate temperature monitoring. VIB4920 must 
not be frozen. It should be stored in the original outer package in a location with limited access. 
Each vial selected for dose preparation should be inspected. If there are any defects noted with 
the VIB4920, the Investigator and site monitor should be notified immediately.  
7.1.1.2 
Dose Preparation 
VIB4920 is supplied as a sterile liquid in a 6R glass vial at a nominal fill volume of 5.0 mL, 
stoppered with 20 mm Teflon-coated elastomeric stopper, and sealed with flip-off cap overseal. 
No incompatibilities between VIB4920 and the components recommended for IV infusion (ie, 
polyolefin IV bags for IV infusion, non-diethylhexyl phthalate infusion lines, and syringes used 
for dose preparation) have been observed. 
VIB4920 does not contain preservatives and any unused portions must be discarded. Preparation 
of IP and IV bags is to be performed aseptically.  


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Prepared VIB4920 IV Bags may be stored refrigerated at 2-8°C for up to 24 hours and/or at 
room temperature for up to 4 hours. The total allowable in-use storage time from the time of the 
first vial puncture of VIB4920 to IV bag administration is 24 hours.  
DO NOT FREEZE. If storage time exceeds these limits, a new dose must be prepared from new 
vials. 
Three vials, one 250 mL IV bag containing 0.9% (w/v) saline (weight/volume [w/v]), and one IV 
infusion pump is required for administration of each 1500 mg dose of VIB4920.  
The dose preparation steps are as follows: 
x For each 1500 mg IV dose, 15.0 mL of 0.9% (w/v) saline should be removed from a 
prefilled 250 mL IV bag. 
x 15.0 mL of VIB4920 will be obtained from three (3) 500 mg vials by withdrawing 
5.0 mL from each vial. Use a new needle for each withdrawal. 
x IP should be added to the saline bag. 
x Gently mix the contents of the IV bag. The saline bag should then be inspected to ensure 
the solution is clear. 
x Prepared bags will be covered to protect blinding. 
During preparation of the IP for infusion, the capacity of the tubing should be calculated in order 
to adjust the volume of IP solution needed to prime the IV tubing. This step is also necessary 
because the same volume of saline will be needed to flush the IV tubing at the completion of the 
infusion in order to deliver the complete volume of IP solution. Because the IV tubing contains 
IP solution, the saline flush must be infused using the same infusion rate as that used for the IP 
solution in the infusion bag. 
For example, if the IV tubing capacity is 15 mL, the IV tubing should be primed with 15 mL of 
IP solution from the infusion bag before initiating the infusion. Once the infusion bag is empty, 
the IV tubing should be flushed with at least 15 mL of 0.9% (w/v) saline via the infusion pump at 
the same rate as dosing. The start time of the infusion will be the time when infusion of the IP 
solution from the infusion bag (with IV tubing primed with IP solution) is started. The stop time 
of the infusion will be the time when the IV tubing has been flushed with a volume of 0.9% 
(w/v) normal saline equivalent to IV tubing capacity (eg, 15 mL for the example above) to 
administer the residual IP solution. 
7.1.1.3 
Dosing and Administration 
Both Populations #1 and #2 will receive the following treatment regimen: 
x Treatment group 1 will receive 1500 mg VIB4920 as an IV infusion, Q2W x 3, then 
Q4W for 4 additional doses (Stage I). Starting on Day 169 subjects will receive placebo 
Q4W for 5 doses (Stage II).   
x Treatment group 2 will receive placebo as an IV infusion Q2W x3, then Q4W for 4 
additional doses (Stage I). Starting on Day 169 subjects will receive VIB4910 1500 mg Q4W 
for 5 doses (Stage II). 
An experienced and qualified staff member will place the IV access. 


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IP will be infused using an IV infusion pump. During Stage I each subject must receive the entire 
volume of IP solution in the IV bag over at least 90 minutes (approximately 2.8 mL/min). IP 
must be infused through a low-protein binding 0.2- or 0.22-line filter. Vital signs will be 
obtained prior to the start of each IP infusion. For Stage II, infusions can be administered over at 
least 60 minutes (approximately 4.2 mL/min). 
A physician must be present at the site or immediately available to respond to emergencies 
during administration of IP. Fully functional resuscitation facilities should be available. 
Further information on IP preparation and administration is provided in the IP Manual. 
7.1.1.4 
Peri- and Post-Administration Observations 
On the first 2 dosing days of both Stage I (Day 1 and Day 15) and Stage II (Day 169 and 
Day 197) vital signs will be measured within 30 minutes prior to the start of infusion, every 
30 minutes (± 5 minutes) during the infusion, at the end of the infusion (+ 5 minutes), then at 
1 hour and 2 hours after the end of infusion (± 10 minutes). On subsequent dosing days, vital 
signs will be measured within 30 minutes prior to the start of infusion, every 30 minutes 
(± 5 minutes), at the end of the infusion (+ 5 minutes) and 30 minutes after the end of the 
infusion (± 5 minutes). At the end of these observation periods, subjects can be discharged if 
they are stable. 
7.1.1.5 
Investigational Product Accountability 
The study IXRS system will be used by clinical sites to acknowledge receipt of study drug. 
Damaged shipments will be replaced. Study site staff will maintain a record of the IP received, 
dispensed, administered, and destroyed. All records will be maintained with controlled access. 
An unblinded study monitor will perform drug accountability and compliance monitoring during 
the study. The Investigator will administer the study product only to subjects included in this 
study and according to the procedures established in this clinical study protocol. Each 
administration of study product will be documented and transferred to the eCRF. 
7.1.1.6 
VIB4920 Handling and Disposal 
The Investigator or designee must return any unused vials of VIB4920 to Sponsor or designee 
regardless of whether the study was completed or terminated prematurely. At the time of return, 
the Investigator must verify that unused or partially used study products have been returned and 
that no study products remain at the site. As an alternative to returning unused study product at 
the end of the study, the Investigator may destroy unused study medication on site with 
agreement from Sponsor. 
7.1.2 
Placebo 
7.1.2.1 
Formulation, Storage, Preparation and Handling 
Placebo will be 0.9% (w/v) saline provided by the site as 250 mL prefilled IV bags.  


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7.1.2.2 
Dosing and Administration 
For each dose of placebo, one 250 mL IV bag containing 0.9% (w/v) saline (weight/volume 
[w/v]) and one IV infusion pump is required for administration. 
7.2 
Treatment Assignment and Bias Minimization 
7.2.1 
Treatment Allocation 
Subjects will be randomized in a 1:1 ratio to receive either VIB4920 or placebo. 
IP (VIB4920 or placebo) must be administered the same day the IP is assigned. If there is a delay 
in the administration of IP such that it will not be administered within the specified timeframe, 
the study monitor must be notified immediately. 
7.2.2 
Randomization Strategy and Procedure 
An IXRS will be used for randomization to a treatment group and assignment of IP kit numbers. 
A subject is considered randomized into the study when the Investigator notifies the IXRS that 
the subject meets eligibility criteria and the IXRS provides the assignment of treatment group. 
Additional details will be provided in the IXRS Manual. 
7.2.3 
Extent and Maintenance of Blinding 
This is a double-blind study in which VIB4920 and the saline placebo are not identical in 
appearance. For maintaining the blinding of the subjects, Investigator, site staff, Sponsor, 
Contract Research Organization and staff, a local unblinded pharmacy staff member will be 
nominated by each site and will have the responsibility of allocating, dispensing and preparing 
the IP, and covering the IV bags. In addition, a separate unblinded monitor will be used for the 
oversight of IP management. If treatment allocation for a subject becomes known to the 
Investigator or other study staff involved in the management of study subjects, the Sponsor must 
be notified immediately. 
7.2.4 
Unblinding Procedures 
7.2.4.1 
Unblinding in the Event of a Medical Emergency 
In the event of a medical emergency, the Investigator may unblind an individual subject’s IP 
allocation. Instructions for unblinding an individual subject’s IP allocation are contained in the 
IXRS manual. In general, unblinding should only occur if management of the medical 
emergency would be different based on the subject having received IP. In the majority of cases, 
the management of a medical emergency would be the same whether or not IP was received by 
the subject. If this was the case, the IP allocation should not be unblinded.  
7.2.4.2 
Unblinding for Interim Analysis and Primary Analysis 
An interim analysis will be conducted for each population after all subjects have completed the 
Day 85 visit for that population, and the primary analysis will be conducted for each population 
after all subjects have completed the Day 169 visit for that population (see Section 10.6). To 
ensure the blinding of each subject’s treatment assignment throughout the study, both the interim 


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analysis and the primary analysis will be performed by a limited number of Sponsor personnel 
who are not involved in the conduct of the study. Study site personnel, subjects, and Sponsor 
personnel directly associated with the conduct of the study will remain blinded to the treatment 
assignment for individual subjects until the completion of the study.  Any communications of 
unblinded results will be documented in an unblinding memo.  Population-based treatment group 
level results may be released after completion of primary analysis. 
7.3 
Assessment and Verification of Compliance 
Site staff will administer all IPs IV at the study center. The dose and date of administration of IP 
must be recorded in the subject eCRF. Treatment compliance will be assessed based on this 
information. 
7.4 
Prohibited and Restricted Therapies 
Medications that are considered necessary for the safety and well-being of subjects may be given 
at the discretion of the Investigator, and recorded in the appropriate section of the eCRF. Use of 
treatments listed below may lead to IP discontinuation. Subjects should not start taking any of 
the following without discussing with the Investigator: 
1. Naturopathic, herbal, or ayurvedic remedies. 
2. Nutritional or dietary supplements 
3. Vitamins and/or minerals. 
7.4.1 
Medications Leading to Immediate Discontinuation of Investigational Product 
for Both Populations 
Receipt of any of these medications leads to immediate discontinuation of IP: 
x Investigational agents 
x Immunosuppressants with the exceptions listed below 
x Biologic immunomodulators (including belimumab, abatacept, rituximab) 
x Live or attenuated vaccines (the Sponsor recommends that Investigators ensure all 
subjects are up-to-date with required vaccinations prior to entry into the study) 
x Plasmapheresis/Plasma exchange 
x Any Ig therapy 
x Corticosteroids > 0.5 mg/kg/day or > 40 mg/day prednisone-equivalent 
7.4.2 
Restricted Medications in Population #1 
If a subject receives any of the following after randomization, the Investigator must notify the 
Sponsor/Designee Medical Monitor immediately. The Medical Monitor will determine with the 
Sponsor if the subject may continue to receive IP, however, the subject would be considered a 
non-responder for binary assessments. 
x AZA > 150 mg/day, MTX > 20 mg/week, leflunomide >40 mg/day, MMF > 2gm/day, 
hydroxychloroquine > 400 mg/day OR any increase from baseline (including initiation of 
treatment) 
x Prednisone > 10 mg/day OR any increase from baseline (including initiation of treatment) 


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x Initiation of any new cDMARD 
x Corticosteroids with a long biologic half-life (eg, dexamethasone, betamethasone) 
7.4.3 
Rescue Medications for Population #1 
The initiation or increase in dose of the restricted medications in Section 7.4.2 are also 
considered as rescue medications for Population #1. 
7.4.4 
Restricted Medications in Population #2 
If a subject receives any of the following after randomization, the Investigator must notify the 
Sponsor/Designee Medical Monitor immediately. The Medical Monitor will determine with the 
Sponsor if the subject may continue to receive IP, however, the subject would be considered a 
non-responder for binary assessments. 
x Oral, intramuscular, IV, or intra-articular corticosteroids 
x MTX, AZA, leflunomide MMF, and other cDMARD or immunosuppressive or 
antiproliferative medications. 
x Any medication that in the opinion of the Investigator would interfere with evaluation of 
the IP or interpretation of subject safety or study results 
x Any increase or initiation of new doses of cevimeline or pilocarpine and cyclosporine eye 
drops (Restasis). 
7.4.5 
Rescue Medications for Population #2 
The initiation or increase in dose of the restricted medications in Section 7.4.4 are also 
considered as rescue medications for Population #2. 
8 
SAFETY ASSESSMENT 
An 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 12.1 for details on SDMC activities.  
8.1 
Definitions 
x Adverse event – 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 – An SAE 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 “life-threatening” if, in the view of 
either the Investigator or Sponsor, its occurrence places the patient or subject at 
immediate risk of death. It does not include an AE or suspected adverse reaction 
(SAR) 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 


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 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 patient or subject 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 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: 
 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) 
 A causal relationship between the IP and the event is biologically implausible (eg, 
death as a passenger in an automobile accident) 
 A clearly more likely alternative explanation for the event is present (eg, typical 
adverse reaction [AR] 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 
product under investigation (ie, there are facts, evidence, or arguments to suggest possible 
causation). 
x Adverse reaction – An AR is any AE caused by a drug. 
x Suspected adverse reaction (SAR) – An SAR is any AE for which there is a reasonable 
possibility that the drug caused the AE. For the purposes of Investigational New Drug safety 
reporting, “reasonable possibility” means there is evidence to suggest a causal relationship 
between the drug and the AE. SAR implies a lesser degree of certainty about causality than 
AR. 
x Unexpected – An event is considered unexpected if it is not listed in the Investigator’s 
Brochure (IB), is not listed at the specificity or severity that has been observed, or, if an IB is 
not required or available, is not consistent with the risk information described in the General 
Investigational Plan or elsewhere in the IND. Unexpected also refers to events that are 
mentioned in the IB as occurring with a class of drugs or as anticipated from the 
pharmacological properties of the drug but are not specifically mentioned as occurring with 
the particular IP. 
x Severity or intensity: 
Severity will be assessed according to the following scale: 


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x Grade 1: An event of mild intensity that is usually transient and may require only 
minimal treatment or therapeutic intervention. The event does not generally interfere with 
usual activities of daily living. 
x Grade 2: An event of moderate intensity that is usually alleviated with additional, specific 
therapeutic intervention. The event interferes with usual activities of daily living, causing 
discomfort but poses no significant or permanent risk of harm to the subject. 
x Grade 3: A severe event that requires intensive therapeutic intervention. The event 
interrupts usual activities of daily living, or significantly affects the clinical status of the 
subject. 
x Grade 4: An event, and/or its immediate sequelae, that is associated with an imminent 
risk of death or with physical or mental disabilities that affect or limit the ability of the 
subject to perform activities of daily living (eating, ambulation, toileting, etc). 
x Grade 5: Death (loss of life) as a result of an event. 
8.2 
Documenting Adverse Events 
AEs spontaneously reported by the subject and/or in response to an open question from the study 
personnel or revealed by observation will be recorded during the study at the investigational site. 
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 or not it 
caused the subject to discontinue the study. The AE term should be reported in standard medical 
terminology when possible. 
8.3 
Reporting Adverse Events 
All AEs (related and unrelated) will be recorded from written ICF signature up to the end of the 
off-treatment period, whether or not they are related to the study. Any SAEs considered related 
to the IP and discovered by the Investigator at any time after the study should be reported. 
All SAEs must be reported within 24 hours by submitting a SAE Report Form by email to: 
ICON Patient Safety 
Email: icon-mads@iconplc.com 
Alternatively, the SAE Report Form can be submitted by fax to: 
ICON Patient Safety 
Fax: 1-215-616-3096 
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 SAE form, placed with the original 
SAE information and kept with the appropriate section of the eCRF and/or study file. 
The designated Sponsor representative (ICON) 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 or designee is responsible for notifying the relevant regulatory authorities of certain 
events. It is the Principal Investigator’s responsibility to notify the IRB or IEC of all SAEs that 


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occur at his or her site. Investigators will also be notified of all unexpected, serious, drug-related 
events (7/15 Day Safety Reports) that occur during the clinical trial. Each site is responsible for 
notifying its IRB or IEC of these additional SAEs. 
8.4 
Adverse Events of Special Interest  
An AESI is one 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 (see the Safety Handling Plan 
for instructions and timing on completing any additional information required for specific types 
of events related to the categories noted below): 
x Thrombotic and embolic events 
x Hepatic function abnormality (meeting the definition of HL) (see Appendix 3) for details) 
x Anaphylaxis and clinically significant (Grade 3 or higher) hypersensitivity reactions 
(see Appendix 2 for guidance on diagnosis of anaphylaxis reactions) 
x Severe Infusion-related reactions (Common Terminology Criteria for Adverse Events 
(CTCAE) Grade 3 or higher). 
Severity will be assessed according to CTCAE v5 
 Grade 1: Mild transient reaction; infusion interruption not indicated; intervention not 
indicated. 
 Grade 2: Therapy or infusion interruption indicated but responds promptly to 
symptomatic treatment (eg, antihistamines, NSAIDS, narcotics, IV fluids); 
prophylactic medications indicated for  24 hours 
 Grade 3: Prolonged (eg, not rapidly responsive to symptomatic medication and/or 
brief interruption of infusion); recurrence of symptoms following initial 
improvement; hospitalization indicated for clinical sequelae 
 Grade 4: Life-threatening consequences; urgent intervention indicated 
x Malignant neoplasm 
x Immune complex disease 
x Infections: 
 Clinically significant (Grade 3 or higher) 
 Opportunistic infections including but not limited to reactivation of latent viral 
infection, invasive fungal infections, and TB 
8.5 
Clinical Laboratory Findings 
Blood and urine samples will be collected for laboratory safety tests as specified in the Schedule 
of Assessments shown in Table 1 (screening), Table 2 (during the treatment period [Stages I and 
II]), and Table 3 (off-treatment period). Laboratory testing is described below. For further details 
regarding laboratory assessments see the Study Laboratory Manual. 


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8.5.1 
Hematology 
The hematology panel will include a complete blood count, with differential (including 
basophils, eosinophils, lymphocytes, monocytes, and neutrophils), hemoglobin, hematocrit, 
platelets and white blood cell count. 
8.5.2 
Serum Chemistry 
Chemistry and Renal Profile: 
x Creatinine, blood urea nitrogen, fasting glucose, total protein, creatine kinase and 
electrolytes (including sodium, potassium, chloride, calcium, bicarbonate, and phosphorus) 
Hepatic Profile: 
x Albumin, TBL, indirect bilirubin, AST, ALT, alkaline phosphatase (ALP), and gamma-
glutamyltransferase. 
8.5.3 
Immunoglobulins 
x Total immunoglobulins, IgA, IgG, and IgM. 
8.5.4 
Coagulation Parameters 
Subjects will be evaluated for prothrombin time and PTT during screening and at all study visits 
during the treatment and off-treatment periods (Table 2 and Table 3, respectively). 
8.5.5 
Urinalysis 
The urinalysis will include protein, glucose, blood, ketones, leukocytes, and pH by dipstick 
analysis. Microscopy (crystals, casts, white blood cells, red blood cells) will also be performed if 
any abnormalities are observed. 
8.5.6 
Testing for SARS-CoV-2 
The investigator must ensure that the subject has a documented negative SARS-CoV-2 viral test 
within 2 weeks prior to randomization. Testing for antibodies to SARS-CoV-2 will not meet the 
testing requirement. 
8.6 
Vital Signs  
Vital signs including systolic and diastolic blood pressure (mmHg), pulse rate (beats/min), 
respiratory rate (breaths/min), body temperature (ºC) and body weight (kg) will be measured 
using clinically acceptable methods and devices as defined in the schedule of assessments in 
Table 1 (screening), Table 2 (treatment period), and Table 3 (off-treatment period) and the IP 
Administration manual. 
Section 7.1.1.4 describes the frequency of vital sign observations prior, during and post infusion. 
8.7 
Electrocardiogram 
A 12-lead ECG will be performed according to the schedule of assessments in Table 1 
(screening), Table 2 (treatment period), and Table 3 (off-treatment period). Each ECG will 


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include ventricular heart rate and intervals (PR, QRS, QT, QTc). The Investigator will be 
responsible for providing an interpretation of the ECGs in terms of clinical significance to the 
subject (ie, normal, abnormal but not clinically significant, abnormal and clinically significant.). 
Any abnormalities and clinical significance will be entered on the eCRF. 
8.8 
Pregnancy 
6HUXPȕ-hCG pregnancy test(s) will be completed for all females of childbearing potential 
during the screening period (before Day 0) and by urine pregnancy test at the visits in the 
Schedule of Assessments in Table 2 (treatment period) and Table 3 (off-treatment period). 
8.9 
Overdose or Misuse 
Any instance of overdose (suspected or confirmed and irrespective of whether or not it involved 
VIB4920) must be communicated to Sponsor or a specified designee within 24 hours and be 
fully documented as an SAE. Details of any signs or symptoms and their management should be 
recorded including details of any antidote(s) administered. 
8.10 
Contacting Sponsor Regarding Urgent Protocol-related Medical Questions 
In the event of a study-related health emergency (when assigned Medical Monitors for a study 
cannot be reached by a caller for discussion of urgent protocol-related medical questions), an 
on-call physician can be reached 24 hours per day, 7 days per week via an ICON Call-Center:  
x Telephone: +1 857 957 5013 (global reachable number) 
x https://icophone.iconplc.com/24-7-Medical.pdf 
On this internet page, a list of country-specific contact numbers is provided. Countries not listed 
here need to dial the global reachable number as indicated above. Furthermore, there may be 
restrictions when dialing a country-specific number from a mobile phone. 
 


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9 
OTHER ASSESSMENTS 
9.1 
Qualitative Patient Interviews (optional) 
In the USA and UK, a subset of English-speaking patients will be asked to participate in a 
telephone-based qualitative interview after completing protocol Day 169. The overall objective 
of these interviews is to gather additional information about patients’ experiences with SS and its 
treatment. Although not intended as a formal study assessment, the qualitative interviews aim to 
collect additional contextual information from the patient perspective that can further inform the 
formal efficacy and safety assessments detailed in Sections 6.4.1 and 6.4.2. Specific details 
regarding the methods used to conduct these qualitative patient interviews will be provided to the 
IRBs/IECs of the participating countries (USA and UK) as a separate appendix to the protocol. 
Participation in the qualitative patient interview is optional and will only be conducted after 
obtaining specific consent from interested subjects. 


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10 
STATISTICAL CONSIDERATIONS 
10.1 
General Considerations 
Tabular summaries will be presented by treatment group. Categorical data will be summarized 
by the number and percentage of subjects in each category. Continuous variables will be 
summarized by descriptive statistics. Additional details of statistical analyses will be described in 
the statistical analysis plan (SAP). 
10.2 
Statistical Hypotheses 
Population #1:  
x Null hypothesis: the mean change from baseline in ESSDAI score at Day 169 for the 
VIB4920 group is equal to that for the placebo group. 
x Alternative hypothesis: the mean change from baseline in ESSDAI score at Day 169 for 
the VIB4920 group is not equal to that for the placebo group. 
Population #2:  
x Null hypothesis: the mean change from baseline in ESSPRI score at Day 169 for the 
VIB4920 group is equal to that for the placebo group. 
x Alternative hypothesis: the mean change from baseline in ESSPRI score at Day 169 for 
the VIB4920 group is not equal to that for the placebo group. 
10.3 
Determination of Sample Size  
Population #1: The planned sample size of 72 subjects (36 subjects in the VIB4920 group and 
36 subjects in the placebo group) will provide 80% power to detect a difference in mean change 
from baseline to Day 169 in ESSDAI of 3.0 (assumed standard deviation of 5) between the 
VIB4920 and placebo treatment groups at a 2-sided alpha level of 0.10 using 2-sample t-test. The 
minimum detectable difference is 2.0 between the 2 treatment groups. The estimated standard 
deviation of 5 is based on the published results (Mariette et al, 2015; Fisher et al, 2017) and 
internal data.  
Population #2: The planned sample size of 102 subjects (51 subjects in the VIB4920 group and 
51 subjects in the placebo group) will provide 80% power to detect a difference in mean change 
from baseline to Day 169 in ESSPRI of 1.0 (assumed standard deviation of 2) between the 
VIB4920 and placebo treatment groups at a two-sided alpha level of 0.10 using 2-sample t-test. 
The minimum detectable difference is 0.66 between the 2 treatment groups. The estimated 
standard deviation of 2 is based on the published results (Mariette et al, 2015; Fisher et al, 2017) 
and internal data. 
10.4 
Analysis Sets 
10.4.1 
Full Analysis Set 
The full analysis set (FAS) includes all randomized subjects who received any dose of IP in the 
study. Subjects will be analyzed according to the treatment randomized. The efficacy analysis 
will be based on the FAS. 


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10.4.2 
Safety Analysis Set 
The safety analysis set includes all subjects who received any dose of IP. Subjects will be 
analyzed according to the treatment that they actually received. The safety and ADA analysis 
will be based on the safety analysis set. 
10.4.3 
Pharmacokinetic Analysis Set 
The PK analysis set includes all subjects who receive IP and have at least 1 quantifiable serum 
PK observation post-first dose. Subjects will be analyzed according to the treatment that they 
actually received. The PK analysis will be based on the PK analysis set. 
10.5 
Methods for Statistical Analyses 
10.5.1 
Analysis of the Primary Efficacy Endpoint 
Primary efficacy analyses: 
Population #1: The primary efficacy endpoint of change from baseline to Day 169 in ESSDAI 
score will be analyzed using the mixed-effect model for repeated measures (MMRM) approach 
based on the FAS. 
Population #2: The primary efficacy endpoint of change from baseline to Day 169 in ESSPRI 
score will be analyzed using the MMRM approach based on the FAS. 
Handling plan for rescue medication use:  
For subjects who take rescue medications before Day 169, the data collected after administration 
of the rescue medications will not be included in the primary analysis. This approach attempts to 
reduce the confounding effects of rescue medications. 
Handling plan for treatment discontinuation: 
Subjects who discontinue IP before Day 169 will be asked to come to scheduled evaluations until 
Day 169 visit and at least 3 months of off-treatment follow-up after the last IP administration. 
The data collected after discontinuation of study treatment will be included in the analysis. 
Handling plan for missing data: 
Missing data will be handled using the MMRM approach based on missing at random 
assumption. 
Supplementary analysis with a different handling plan for rescue medication use and missing 
data due to dropouts will be detailed in the SAP. 
Multiplicity adjustment: 
There is no multiplicity issue for the primary endpoint analysis for each population because there 
is only one primary comparison (VIB4920 1500mg vs placebo) for each population. 
10.5.2 
Analysis of Secondary Efficacy Endpoints 
The categorical secondary efficacy endpoints of Population #1 and Population #2 will be 
analyzed using a logistic regression model based on the FAS. The continuous secondary efficacy 


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endpoints of Population #1 and Population #2 will be analyzed using the MMRM approach 
based on the FAS.  
10.5.3 
Explore Clinically Meaningful Within-subject Change Score of Clinical 
Outcome Assessments (COAs) 
The anchor-based methods supplemented with both empirical cumulative distribution function 
(eCDF) and probability density function will be used to explore the clinically meaningful within-
subject change score of COAs. The detailed plan will be specified in the SAP. 
10.5.4 
Handling Missing Items of COAs 
The ESSDAI is a clinician reported outcome. There will be very few missing items expected. All 
PROs will be administered by ePRO. Questions are mandatory so there will be no skipped items. 
But in case there are missing items, the following algorithms will be used to handle the missing 
items. 
10.5.4.1 
ESSDAI and ESSPRI 
If less than 50% of items are missing, the missing individual items are imputed using last 
observation carry forward approach before calculation of total score. The total score will not be 
calculated and will be treated as missing if 50% or more of items are missing. 
10.5.4.2 
FACIT-Fatigue  
The missing items will be handled according to FACIT scoring guidelines. If less than 50% of 
items are missing, the total scores will be calculated as follows:  
Total score = (Sum of scores for items answered)/(N of items answered)u13 
The total score will not be calculated and will be treated as missing if 50% or more of items are 
missing. 
10.5.5 
Safety Analysis 
10.5.5.1 
Adverse Events 
The AEs will be summarized descriptively for each population. AEs will be coded using the 
Medical Dictionary for Regulatory Activities by system organ class (SOC) and preferred term 
(PT). The number and percentage of subjects reporting TEAEs with onset on or after the start of 
the first infusion of IP will be summarized for each treatment group by SOC and PTs, by 
severity, and by relationship to the IP. The number and percentage of subjects reporting TESAEs 
and AESIs will also be summarized.  


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10.5.5.2 
Clinical Laboratory 
Laboratory results, as well as changes from baseline, at each visit and shift from baseline, if 
applicable, will be summarized descriptively by treatment group for each population. 
10.5.5.3 
Vital Signs 
Vital signs results, as well as changes from baseline, at each visit will be summarized 
descriptively by treatment group for each population. 
10.5.5.4 
Electrocardiogram 
ECG results, as well as their changes from baseline, at each visit will be summarized 
descriptively by treatment group for each population. The overall clinical evaluation of ECG 
results (normal, abnormal, not clinically significant abnormal, clinically significant abnormal) 
will also be summarized. 
10.5.6 
Pharmacokinetics Analysis 
Plasma VIB4920 concentration data at each time point will be tabulated by dose cohort together 
with descriptive statistics. Individual and mean plasma concentration-time profiles of VIB4920 
by population and treatment will be generated. If the data allow, population PK analysis will be 
performed and reported separately from the clinical study report (CSR). 
10.5.7 
Immunogenicity Analysis 
ADA will be summarized using descriptive statistics for each population. Number and 
percentage of subjects who developed positive ADA will be summarized by treatment group. 
The impact of ADA on PK endpoint will be assessed. The potential association of ADA with 
safety and efficacy may be explored if data allow. 
10.5.9 
Exploratory Analysis 
10.6 
Planned Analysis 
An interim analysis will be conducted for each population after all subjects have completed the 
Day 85 visit for that population. 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. The 
final assessment of efficacy will be determined at the primary analysis. Details of the interim 
analysis will be specified in the interim unblinding analysis plan prior to unblinding. 


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The primary analysis will be conducted for each population after all subjects have completed the 
Day 169 visit for that population. The efficacy and safety data prior to the data cut-off for the 
interim analysis will be analyzed. 
The final analysis will be conducted for each population after all subjects have completed study 
for that population. 
11 
ETHICAL CONSIDERATIONS 
11.1 
Good Clinical Practice 
The study will be performed in accordance with ethical principles that have their origin in the 
Declaration of Helsinki and are consistent with International Conference on Harmonisation 
(ICH) / Good Clinical Practice (GCP), applicable regulatory requirements and the Sponsor 
policy on Ethical Interactions. 
11.2 
Ethics Review  
The final clinical 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 Sponsor or representative before he or she can enroll any patient into 
the study. 
The PI is responsible for informing the IRB or IEC of any amendment to the protocol in 
accordance with local requirements. In addition, the IRB or IEC must approve all advertising 
used to recruit subjects 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 of any reportable serious adverse drug reactions from any other study conducted with the 
IP. Sponsor will provide this information to the PI. 
Progress reports and notifications of serious adverse drug reactions will be provided to the IRB 
or IEC according to local regulations and guidelines. Copies of all correspondence between the 
Investigator and the IRB/IEC is provided to Sponsor representative. 
11.3 
Informed Consent 
The PI(s) or other members of the study site’s treatment team will ensure that the subject or 
legally authorized representative is given full and adequate oral and written information about 
the nature, purpose, possible risk and benefit of the study. Subjects or legally authorized 
representative must also be notified that they are free to discontinue from the study at any time. 
The subjects or legally authorized representatives will be informed that their study record and 
medical records/documents that pertain directly to the study will be reviewed and possibly 
copied by Sponsor or its designee, or a governmental agency (such as the FDA), and that every 
effort will be made to maintain patient confidentiality. The patient or legally authorized 
representative should be given the opportunity to ask questions and allowed time to consider the 
information provided. 
The ICF must be witnessed and dated by the Investigator or his/her designee, and the original 
retained by the Investigator/study site as part of that subject’s record. 


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The PI(s) must maintain the original, signed ICF. A copy of the signed ICF must be given to the 
patient or legally authorized representative. 
Subjects may be rescreened within 30 days under the current and signed ICF. 
The ICF must be fully approved by an IRB or an IEC prior to its use with study participants. 
11.4 
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 Sponsor. However, authorized regulatory officials, IRB/IEC personnel, Sponsor 
and its authorized representatives are allowed full access to the records. 
Identification of subjects and eCRFs shall be by initials, screening, and treatment numbers only. 
If required, the subject's full name may be made known to an authorized regulatory agency or 
other authorized official. 
11.5 
Disclosure 
Sponsor is responsible for preparing and providing the appropriate regulatory authorities with 
CSRs, according to the applicable regulatory requirements. 
11.6 
Biological Specimens and Data 
Study data are protected by the use of a SID number, which is a number specific to the subject. 
The Investigator is in control of the information that is needed to connect a study sample to a 
subject. A subject’s consent to the use of data does not have a specific expiration date, but the 
subject 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 
subject. 
Samples obtained for future research will be labeled with a sample identification number. If the 
subject withdraws consent for participating in future research, the Sponsor will locate the 
subject’s sample and destroy it. 
If the subject 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 subject’s 
sample(s) will be stored by the Sponsor with similar samples in a secure central laboratory. The 
subject’s samples will not be kept for more than 25 years after the end of the study in which they 
were collected. If the subject 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 consent is withdrawn, the Sponsor and the Investigator will ensure that the subject’s sample(s) 
are destroyed unless the identification number has been removed and the subject can no longer 
be linked to any samples. However, if the subject’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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12 
OVERSIGHT 
12.1 
Safety and Data Monitoring Committee 
An 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. The SDMC will not routinely review efficacy data (blinded or unblinded).  
At any time during the study, as well as on an ad hoc basis, the SDMC will also review any 
safety data assessed by the Sponsor/Designee Medical Monitor as medically relevant. Additional 
information, including frequency of SDMC review, can be found in the SDMC charter.  
If any event(s) occur that, in the opinion of the SDMC, contraindicates further dosing of 
additional subjects, the Sponsor will conduct a prompt cumulative review of safety data and the 
circumstances of the event in question to determine whether dosing and study randomization 
should be stopped, whether the protocol will be modified, or whether the study will be 
discontinued permanently. In the event that the study is interrupted, review by the SDMC and 
Sponsor decision to resume (with or without modifications) is required for resumption of the 
study. Where applicable, the regulatory authorities and IRBs/IECs will be notified of any actions 
taken with the study. 
12.2 
Training of Site Personnel 
To maintain consistent evaluation of SS disease activity within and across study sites, Sponsor 
will provide training or access to training tools to Principal Investigators and any designated site 
personnel who will be completing the following disease evaluation assessments: 
The ESSDAI and joint count must be administered by the Investigator or another qualified site 
personnel who, as per Investigator discretion, are qualified to perform the assessments. Training 
will include printed training materials and formal presentations, as well as web-based training 
modules.  
Over the course of the study, Investigator assessments for a given subject should be completed 
by the same trained Investigator, designated physician, or qualified site personnel whenever 
possible. If there is a change in site personnel over the course of the study, new Principal 
Investigators or site physicians/personnel must be trained prior to performing the ESSDAI and 
joint count assessments. 
It is expected that the Investigator will ensure their site personnel have adequate experience and 
training qualifications to perform disease assessments. Documentation of all training will be 
maintained in the site’s study file. 
12.3 
Quality Control and Assurance 
To ensure compliance with GCP and all applicable regulatory requirements, Sponsor may 
conduct a quality assurance audit. See Section 12.5 for details regarding the audit process. 


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12.4 
Monitoring 
Before an investigational site can enter a subject into the study, a representative of Sponsor or of 
the Contract Research Organization will visit the investigational study site to: 
x Determine the adequacy of the facilities. 
x Discuss with the Investigator(s) and other personnel their responsibilities with regard to 
protocol adherence, and the responsibilities of Sponsor or its representatives. This will be 
documented in a Clinical Study Agreement between Sponsor and the Investigator. 
During the study, a representative from Sponsor will have regular contacts with the 
investigational site, for the following: 
x Provide information and support to the Investigator(s). 
x Confirm that facilities remain acceptable. 
x Confirm compliance with the principles of GCP and regulatory requirements. 
x Review of written ICFs for subjects screened/enrolled 
x Confirm that the investigational team is adhering to the protocol, that data are being 
accurately recorded in the eCRFs, and that IP accountability checks are being performed. 
x Perform source data verification. This includes a comparison of the data in the case report 
forms with the subject medical records at the hospital or practice, and other records relevant 
to the study for accuracy and completeness. This will require direct access to all original 
medical and other trial related records for each subject (eg, clinic charts). 
x Record and report any protocol deviations not previously sent to Sponsor 
x Confirm AEs and SAEs have been properly documented on eCRFs and confirm that any 
SAEs have been forwarded to Sponsor or representative and those SAEs that met criteria for 
reporting have been forwarded to the IRB. 
x 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 monitor. 
12.5 
Audits 
To ensure compliance with GCP and all applicable regulatory requirements, Sponsor may 
conduct a quality assurance audit.  
Authorized representatives of Sponsor, a regulatory authority, an IEC and/or an IRB may visit 
the site to perform audits or inspections, including source data verification. The purpose of a 
Sponsor audit or 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, GCP guidelines of the 
ICH, and any applicable regulatory requirements. 
Initial IRB approval, and all materials approved by the IRB 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 Sponsor auditing staff or government inspectors may 
review the conduct/results of the study at the investigational site. The Investigator should contact 
Sponsor immediately if contacted by a regulatory agency about an inspection. The Investigator 


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cooperates with the auditor(s), makes available to the auditor all requested documentation, and 
ensures that issues detected during the course of these audits are satisfactorily resolved. The 
Investigator supplies 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 
Sponsor prior to submission to the regulatory agency. 
12.6 
Records  
12.6.1 
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. 
A 21 CFR Part 11 compliant electronic data capture system will be used for data collection and 
query handling. The Investigator will ensure that data are recorded on the eCRFs as specified in 
the clinical 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 according to the Clinical Study Agreement. 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. 
12.6.2 
Source Documentation 
Sponsor will be allowed to conduct site visits to the investigation facilities for the purpose of 
monitoring any aspect of the study. The Investigator agrees to allow the monitor to inspect the 
drug storage area, study drug stocks, drug accountability records, subject charts and study source 
documents, and other records relative to study conduct. 
12.6.3 
Records Retention 
The PI must maintain all documentation relating to the study for a period of 2 years after the last 
marketing application approval, or if not approved 2 years following the discontinuance of the 
test article for investigation. If it becomes necessary for Sponsor or the regulatory authority to 
review any documentation relating to the study, the Investigator must permit access to such 
records. 
13 
PUBLICATION POLICY 
The publication policy of Sponsor is discussed in the Investigator's Clinical Research 
Agreement. 


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14 
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2020;395:1054-62. 


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15 
APPENDICES 
 


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APPENDIX 1 
ACR-EULAR CLASSIFICATION CRITERIA FOR PRIMARY 
SJÖGREN’S SYNDROME  
The classification of SS applies to any individual who meets the inclusion criteria,1 does not have 
any condition listed as exclusion criteria,2 and who KDVDVFRUHZKHQVXPPLQJWKHZHLJKWV
from the following items: 
Item 
Weight / Score 
/DELDOVDOLYDU\JODQGZLWKIRFDOO\PSKRF\WLFVLDODGHQLWLVDQGIRFXVVFRUH3 
3 
Anti-SSA (Ro) + 
3 
Ocular staLQLQJVFRUHRUYDQ%LMVWHUYeld VFRUHRQDWOHDVWRQHH\H4 
1 
6FKLUPHUPPPLQRQDWOHDVWRQHH\H 
1 
8QVWLPXODWHGZKROHVDOLYDIORZUDWHPOPLQ5 
1 
1  Inclusion criteria: these criteria are applicable to any patient with at least one symptom of ocular or oral dryness 
(defined as a positive response to at least one of the following questions: 1) Have you had daily, persistent, 
troublesome dry eyes for more than 3 months? 2) Do you have a recurrent sensation of sand or gravel in the 
eyes? 3) Do you use tear substitutes more than 3 times a day? 4) Have you had a daily feeling of dry mouth for 
more than 3 months? 5) Do you frequently drink liquids to aid in swallowing dry food?); or suspicion of SS 
from ESSDAI questionnaire (at least one domain with positive item) 
2  Exclusion criteria: Prior diagnosis of any of the following conditions would exclude diagnosis of SS and 
participation in SS studies or therapeutic trials because of overlapping clinical features or interference with 
criteria tests: 
x 
History of head and neck radiation treatment 
x 
Active Hepatitis C infection (with positive PCR) 
x 
Acquired immunodeficiency syndrome 
x 
Sarcoidosis 
x 
Amyloidosis 
x 
Graft versus host disease 
x 
IgG4-related disease 
Note: Patients who are normally taking anticholinergic drugs should be evaluated for objective signs of salivary 
hypofunction and ocular dryness after a sufficient interval off these medications for these components to be a 
valid measure of oral and ocular dryness 
3  The histopathologic examination should be performed by a pathologist with expertise in the diagnosis of focal 
lymphocytic sialadenitis, and focus score count (based on number of foci per 4 mm2) following a protocol 
described in Daniels et al, 2011. 
4  
Ocular staining score described in Whitcher et al, 2009; van Bijsterfeld score described in van Bijsterveld, 
1969. 
5  
Unstimulated whole saliva described Navazesh and Kumar, 2008. 
 
References (cited in Appendix 1) 
Daniels et al, 2011 
Daniels TE, Cox D, Shiboski CH, Schiodt M, Wu A, Lanfranchi H, et al. Associations between 
salivary gland histopathologic diagnoses and phenotypic features of Sjögren's syndrome among 
1,726 registry participants. Arthritis Rheum. 2011;63(7):2021–30. 


Module 5.3.5.1 Clinical Study Protocol  
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Navazesh and Kumar, 2008 
Navazesh M, Kumar SK Measuring salivary flow: challenges and opportunities. J Am Dent 
Assoc. 2008;139(Suppl):35S–40S. 
van Bijsterveld, 1969 
van Bijsterveld OP. Diagnostic tests in the Sicca syndrome. Arch Ophthalmol. 1969;82(1):10–4. 
Whitcher et al, 2009 
Whitcher JP, Shiboski CH, Shiboski SC, Heidenreich AM, Kitagawa K, Zhang S, et al. A 
simplified quantitative method for assessing keratoconjunctivitis sicca from the Sjögren's 
Syndrome International Registry. Am J Ophthalmol. 2009;149(3):405–15.  
 


Module 5.3.5.1 Clinical Study Protocol  
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Version 3.0 (8Nov2022) 
 
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APPENDIX 2 
GUIDANCE FOR ANAPHYLAXIS DIAGNOSIS 
National Institute of Allergy and Infectious Disease (NIAID) and Food and Allergy Anaphylaxis 
Network (FAAN) Guidance for Anaphylaxis Diagnosis 
Sampson HA, Muñoz-Furlong A, Campbell RL, Adkinson FN Jr, Bock SA, Branum A, et al. 
Second symposium on the definition and management of anaphylaxis: Summary report -- Second 
National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
symposium. J Allergy Clin Immunol. 2006;117:391-7. 
NIAID and FAAN define anaphylaxis as a serious allergic reaction that is rapid in onset and may 
cause death. 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 flow (PEF), hypoxemia) 
b. Reduced BP 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 BP or associated symptoms (eg, hypotonia [collapse], syncope, 
incontinence) 
d. Persistent gastrointestinal symptoms (eg, crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
a. Infants and children: low systolic BP (age specific) or greater than 30% decrease in 
systolic BP 
b. Adults: systolic BP of less than 90 mm Hg or greater than 30% decrease from that 
person’s baseline. 
 


Module 5.3.5.1 Clinical Study Protocol  
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CONFIDENTIAL AND PROPRIETARY 
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APPENDIX 3 
ACTIONS REQUIRED IN CASES OF INCREASES IN LIVER 
BIOCHEMISTRY AND EVALUATION OF HY’S LAW 
Introduction 
This Appendix describes the process to be followed in order to identify and appropriately report 
cases of Hy’s Law (HL). It is not intended to be a comprehensive guide to the management of 
elevated liver biochemistries.  
During the course of the study the Investigator will remain vigilant for increases in liver 
biochemistry. The Investigator is responsible for determining whether a subject meets potential 
Hy’s Law (PHL) criteria at any point during the study. 
The Investigator participates, together with Sponsor clinical project representatives, in review 
and assessment of cases meeting PHL criteria to agree whether HL criteria are met. HL criteria 
are met if there is no alternative explanation for the elevations in liver biochemistry other than 
Drug-Induced Liver Injury (DILI) caused by the IP.  
The Investigator is responsible for recording data pertaining to PHL/HL cases and for reporting 
AE and SAE according to the outcome of the review and assessment in line with standard safety 
reporting processes. 
Definitions 
Potential Hy’s Law 
$67RU$/7î8/1WRJHWKHUZLWKWRWDOELOLUXELQ7%/î8/1 at any point during the 
study following the start of IP irrespective of an increase in ALP. 
Hy’s Law 
$67RU$/7î8/1WRJHWKHUZLWK7%/î8/1ZKHUHQRRWKHUUHDVRQRWKHUWKDQWKHIP, 
can be found to explain the combination of increases; eg, elevated ALP indicating cholestasis, 
viral hepatitis, another drug.   
For PHL and HL the elevation in transaminases must precede or be coincident with (ie, on the 
same day) the elevation in TBL, but there is no specified timeframe within which the elevations 
in transaminases and TBL must occur. 
Identification of Potential Hy’s Law Cases 
In order to identify cases of PHL it is important to perform a comprehensive review of laboratory 
data for any subject who meets any of the following identification criteria in isolation or in 
combination: 
$/7î8/1 
$67î8/1 
7%/î8/1 
The Investigator will without delay review each new laboratory report and if the identification 
criteria are met will: 
Notify the Sponsor study representative 


Module 5.3.5.1 Clinical Study Protocol  
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CONFIDENTIAL AND PROPRIETARY 
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Determine whether the subject meets PHL criteria by reviewing laboratory reports from all 
previous visits 
Promptly enter the laboratory data into the laboratory eCRF. 
Follow-up 
Potential Hy’s Law Criteria Are Not Met 
If the subject does not meet PHL criteria the Investigator will: 
Inform the Sponsor representative that the subject has not met PHL criteria 
Perform follow-up on subsequent laboratory results according to the guidance provided in the 
clinical study protocol. 
Potential Hy’s Law Criteria Are Met 
If the subject does meet PHL criteria the Investigator will notify the Sponsor study representative 
who will then inform the central study team. The Medical Monitor contacts the Investigator, to 
provide guidance, discuss and agree an approach for the study subject’s follow-up and the 
continuous review of data. Subsequent to this contact the Investigator will: 
Monitor the subject until liver biochemistry parameters and appropriate clinical symptoms and 
signs return to normal or baseline levels, or as long as medically indicated  
Investigate the etiology of the event and perform diagnostic investigations as discussed with the 
Study Physician.  
If at any time (in consultation with the Medical Monitor) the PHL case meets serious criteria, 
report it as an SAE using standard reporting procedures. 
Review and Assessment of Potential Hy’s Law Cases 
The instructions in this section should be followed for all cases where PHL criteria are met. 
No later than 3 weeks after the biochemistry abnormality was initially detected, the Medical 
Monitor will contact the Investigator in order to review available data and agree on whether there 
is an alternative explanation for meeting PHL criteria other than DILI caused by the IP. The 
Medical Monitor and safety physician will also be involved in this review together with other 
subject matter experts as appropriate.   
According to the outcome of the review and assessment, the Investigator will follow the 
instructions below. 
If there is an agreed alternative explanation for the ALT or AST and TBL elevations, a 
determination of whether the alternative explanation is an AE will be made and subsequently 
whether the AE meets the criteria for a SAE: 
If the alternative explanation is not an AE, record the alternative explanation on the appropriate 
eCRF. 
If the alternative explanation is an AE/SAE, record the AE/SAE in the eCRF accordingly and 
follow the sponsor standard processes. 


Module 5.3.5.1 Clinical Study Protocol  
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If it is agreed that there is no explanation that would explain the ALT or AST and TBL 
elevations other than the IP: 
Report an SAE (report term ‘Hy’s Law’) according to Sponsor standard processes.  
x The ‘Medically Important’ serious criterion should be used if no other serious criteria 
apply 
x As there is no alternative explanation for the HL case, a causality assessment of ‘related’ 
should be assigned 
If there is an unavoidable delay, of over 3 weeks, in obtaining the information necessary to 
assess whether or not the case meets the criteria for HL, then it is assumed that there is no 
alternative explanation until such time as an informed decision can be made: 
Report an SAE (report term ‘Potential Hy’s Law’) applying serious criteria and causality 
assessment as per above 
Continue follow-up and review according to agreed plan. Once the necessary supplementary 
information is obtained, repeat the review and assessment to determine whether HL criteria are 
met. Update the SAE report according to the outcome of the review 
FDA Guidance for Industry (issued July 2009) ‘Drug-induced liver injury: premarketing clinical 
evaluation’: 
https://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/
UCM174090.pdf 
 


Module 5.3.5.1 Clinical Study Protocol  
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Version 3.0 (8Nov2022) 
 
CONFIDENTIAL AND PROPRIETARY 
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APPENDIX 4 
INVESTIGATOR’S AGREEMENT  
I have read the protocol, appendices, and accessory materials related to Study VIB4920.P2.S2 
and agree to the following: 
x To conduct this study as described by the protocol and any accessory materials 
x To protect the rights, safety, and welfare of the participants under my care 
x To provide oversight to all personnel to whom study activities have been delegated 
x To control all investigational products provided by the Sponsor and maintain records of 
the disposition of those products 
x To conduct the study in accordance with all applicable local and national regulations, the 
requirements of the ethics committee of record for my clinical site, and Good Clinical 
Practices as outlined by ICH E6(R2) 
x To obtain approval for the protocol and all written materials provided to participants prior 
to initiating the study at my site 
x To obtain informed consent – and updated consent in the event of new information or 
amendments – from all participants enrolled at my study site prior to initiating any study-
specific procedures or administering investigational products to those participants 
x To maintain records of each subject’s participation and all data required by the protocol 
 
Name 
Title 
Institution 
[Insert last name, first name] 
[Insert title (at institution)] 
[Insert address] 
 
 
Signature 
 
Date 
 
[DD Month YYYY] 
 
 
 


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SPONSOR SIGNATURE PAGE
 
 
 

SAP_001.pdf: 
Statistical Analysis Plan 
VIB4920 
VIB4920.P2.S2 
02NOV2021, Version 2.0 
 
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Internal Use Only Medical and Scientific Affairs
 
VIELA BIO, INC. 
 
STATISTICAL ANALYSIS PLAN 
Investigational Product: 
VIB4920 
Protocol Number: 
VIB4920.P2.S2 
 
A PHASE 2 RANDOMIZED, DOUBLE-BLIND, PLACEBO 
CONTROLLED, PROOF OF CONCEPT STUDY TO 
EVALUATE THE EFFICACY AND SAFETY OF VIB4920 IN 
SUBJECTS WITH SJÖGREN’S SYNDROME (SS)  
 
 


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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 ...........................................................................................................7 
2.2.1 
Overview ...........................................................................................................7 
2.3 
Sample Size .............................................................................................................8 
3 
Statistical Methods ......................................................................................................9 
3.1 
General Considerations .........................................................................................9 
3.1.1 
Definition of Baseline .......................................................................................9 
3.1.2 
Analysis Windows ............................................................................................9 
3.2 
Protocol Deviations ................................................................................................9 
3.3 
Analysis Sets .........................................................................................................10 
3.3.1 
Full analysis set ..............................................................................................10 
3.3.2 
Safety analysis set ...........................................................................................10 
3.3.3 
Pharmacokinetics analysis set .......................................................................10 
3.3.4 
Cross-over analysis set ...................................................................................10 
3.3.5 
Any VIB4920 analysis set ..............................................................................10 
3.4 
Study Subjects ......................................................................................................10 
3.4.1 
Subject Disposition.........................................................................................10 
3.4.2 
Demographics, Baseline Characteristics, and Medical History .................11 
3.4.3 
Investigational product Exposure ................................................................12 
3.4.4 
Prior and Concomitant Medications ............................................................12 
3.5 
Efficacy Analyses .................................................................................................13 
3.5.1 
Primary Efficacy Endpoint(s) and Analyses ...............................................13 
3.5.1.1 
Primary efficacy endpoint .......................................................................13 
3.5.1.2 
Primary efficacy analysis ........................................................................14 
3.5.1.3 
Handling plan for Intercurrent Events ..................................................15 
3.5.1.4 
Handling plan for missing data ..............................................................15 
3.5.1.5 
Sensitivity analysis of primary efficacy endpoint .................................15 
3.5.1.6 
Subgroup analyses of primary endpoint ................................................16 
3.5.1.7 
Multiplicity adjustment ...........................................................................16 
3.5.1.8 
Additional analysis ...................................................................................16 
3.5.2 
Secondary Efficacy Endpoints and Analyses ..............................................17 
3.5.2.1 
Secondary efficacy endpoints ..................................................................17 
3.5.2.2 
Secondary efficacy analysis .....................................................................18 
3.5.3 
Exploratory Efficacy Endpoints and Analyses............................................18 
3.5.3.1 
Exploratory efficacy endpoints ...............................................................18 
3.5.3.2 
Exploratory efficacy analyses .................................................................20 
3.5.4 
Handling missing items of clinical outcome assessments (COAs) .............20 
3.5.4.1 
ESSDAI and ESSPRI ...............................................................................20 
3.5.4.2 
FACIT-Fatigue .........................................................................................20 
3.5.5 
Explore clinically meaningful within-subject change score of COAs .......21 
3.5.5.1 
ESSDAI .....................................................................................................21 
3.5.5.2 
ESSPRI......................................................................................................22 
3.6 
Safety Analysis .....................................................................................................22 


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3.6.1 
Adverse Events ...............................................................................................22 
3.6.2 
Clinical Laboratory Evaluation ....................................................................23 
3.6.3 
Other Safety Evaluations ..............................................................................23 
3.6.3.1 
Overdose ...................................................................................................23 
3.6.3.2 
Vital signs ..................................................................................................24 
3.6.3.3 
Electrocardiogram ...................................................................................24 
3.6.3.4 
Weight .......................................................................................................24 
3.7 
Pharmacokinetics .................................................................................................25 
3.8 
Immunogenicity....................................................................................................25 
3.9 
Exploratory Analyses...........................................................................................26 
3.9.4 
Other exploratory endpoints .........................................................................26 
4 
Planned Analysis .......................................................................................................26 
4.1 
Interim Analysis ...................................................................................................26 
4.2 
Primary Efficacy Analysis ...................................................................................27 
4.3 
Final Analysis .......................................................................................................27 
5 
References ..................................................................................................................27 
 
LIST OF TABLES 
Table 1 
Study Objectives and Endpoints.....................................................................6 
Table 2  
ESSDAI Domains, Weights and Activity Levels .........................................14 
Table 3  
TEAEs for different study periods ...............................................................22 
Table 4  
Definition of ADA Status ...............................................................................25 
LIST OF FIGURES 
Figure 1 
Study Flow Diagram ..................................................................................8 


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LIST OF ABBREVIATIONS  
Abbreviation or Specialized Term 
Definition 
ACR 
American College of Rheumatology 
ADA 
anti-drug antibodies 
ATC 
Anatomical Therapeutic Chemical 
AUC 
area under the curve 
AZA 
azathioprine  
CI 
confidence interval 
cDMARD 
conventional disease-modifying anti-rheumatic drug 
COA 
clinical outcome assessment 
CTCAE 
common terminology criteria for adverse event 
eCDF 
empirical cumulative distribution function 
ECG 
electrocardiogram 
ESSDAI 
EULAR Sjögren’s Syndrome Disease Activity Index  
ESSPRI 
EULAR Sjögren’s Syndrome Patient Reported Index 
EULAR 
European League Against Rheumatism 
FACIT-Fatigue 
Functional Assessment of Chronic Illness Therapy -Fatigue 
IP 
Investigational product 
IV 
Intravenously 
 
 
MedDRA 
Medical Dictionary for Regulatory Activities 
MMF 
mycophenolate mofetil 
MMRM 
mixed-effect model for repeated measures 
MTX 
methotrexate 
OSDI 
Ocular Surface Disease Index  
PDF 
probability density function 
 
 
PGIS 
Patient’s Global Impression of Severity 
PK 
Pharmacokinetic(s) 
 
  
PT 
preferred term 
Q4W 
once every 4 weeks 
Q-Q 
quartile-quartile 
QTc 
corrected QT interval 
RF 
rheumatoid factor 
ROC 
receiver operating characteristic 
SE 
standard error 


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Abbreviation or Specialized Term 
Definition 
 
 
SOC 
system organ class 
SPP 
statistical programming plan 
SS 
Sjögren’s Syndrome 
TEAE 
treatment-emergent adverse event 
TEAESI 
treatment-emergent adverse event of special interest 
TESAE 
treatment-emergent serious adverse event 
 
 
WHO 
world health organization 


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1 INTRODUCTION  
This document describes the statistical analysis for protocol VIB4920.P2.S2, a Phase 2 
randomized, double-blind, placebo controlled, proof of concept study to evaluate the efficacy 
and safety of VIB4920 in subjects with Sjögren’s Syndrome (SS). The study will enroll 2 SS 
populations. Population #1 will be composed of subjects with moderate to severe systemic 
disease activity defined by European League Against Rheumatism (EULAR) Sjögren’s 
Syndrome Disease Activity Index (ESSDAI) ≥ 5. Population #2 will be composed of subjects 
with moderate to severe subjective symptoms defined by EULAR Sjögren’s Syndrome 
Patient Reported Index (ESSPRI) score ≥ 5 and residual stimulated salivary flow but with 
mild systemic disease activity defined by ESSDAI score < 5. 
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 
• Population #1: To evaluate the clinical efficacy of 
multiple doses of VIB4920 in glandular and 
extraglandular manifestations of SS patients with 
moderate to high systemic disease activity 
• Population #1: Change from baseline in ESSDAI 
at Day 169 
• Population #2: To evaluate the clinical efficacy of 
multiple doses of VIB4920 in the key subjective 
complaints of SS (dryness, fatigue, pain) 
• Population #2: Change from baseline in ESSPRI 
at Day 169 
Secondary objectives 
Endpoints/variables 
• Population #1: To evaluate the effect of VIB4920 
on systemic activity and patient-reported 
outcomes in subjects with SS 
• ESSPRI 
• ESSDAI[3] and ESSDAI[4] response 
• Functional Assessment of Chronic Illness 
Therapy (FACIT)-Fatigue 
• Ocular Surface Disease Index (OSDI)  
• Patient’s Global Impression of Severity (PGIS)  
• Population #2: To evaluate the effect of VIB4920 
on patient-reported outcomes in subjects with SS 
• ESSPRI response 
• FACIT-Fatigue 
• OSDI 
• PGIS 
• Population #1 & #2: To evaluate the safety and 
tolerability of multiple doses of VIB4920 in 
subjects with SS 
• Incidence of treatment emergent adverse events 
(TEAEs), TE serious adverse events (TESAEs), 
TE adverse events of special interest (TEAESIs), 
and laboratory, vital sign, and electrocardiogram 
(ECG) abnormalities 


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Table 1 
Study Objectives and Endpoints  
• Population #1 & #2: To characterize the 
pharmacokinetics (PK) of VIB4920 in subjects 
with SS 
• Drug concentration and PK parameters 
• Population #1 & #2: To assess the 
immunogenicity of VIB4920 in subjects with SS 
• Anti-drug antibodies (ADA) 
Exploratory objectives (Population #1 & #2) 
Endpoints/variables 
2.2 
Study Design  
2.2.1 
Overview  
This is a randomized, double-blind, placebo-controlled, parallel-arm study to evaluate the 
efficacy, safety, and tolerability of VIB4920 in adult subjects with SS, diagnosed according 
to the 2016 American College of Rheumatology (ACR)/EULAR Criteria. The study will 
enroll 2 SS populations as defined in section 1 INTRODUCTION. Within each population, 


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eligible subjects will be randomized to receive VIB4920 1500 mg or placebo intravenously 
(IV) once every 2 weeks x 3 doses, then once every 4 weeks (Q4W) for 4 additional doses 
(Stage I). Randomization will be stratified by ESSDAI score at screening (< 10 points vs ≥ 10 
points) for Population #1 and by ESSPRI score at screening (< 7.5 points vs ≥ 7.5 points) for 
Population #2. Starting on Day 169, subjects randomized to VIB4920 will receive placebo 
Q4W for 5 doses and subjects randomized to placebo will receive VIB4920 Q4W for 5 doses 
(Stage II). Subjects who had investigational product (IP) discontinuation will not be eligible 
for treatment during Stage II. All subjects will be followed for at least 12 weeks after their 
last dose of IP administration. 
A study schematic is presented in Figure 1. 
Figure 1 
Study Flow Diagram  
 
2.3 
Sample Size  
Population #1: The planned sample size of 72 subjects (36 subjects in the VIB4920 group and 
36 subjects in the Placebo group) will provide 80% power to detect a difference in mean 
change from baseline to Day 169 in ESSDAI of 3.0 (assumed standard deviation of 5) 
between the VIB4920 and placebo treatment groups at a two-sided alpha level of 0.10 using 
2-sample t-test. The minimum detectable difference is 2.0 between the 2 treatment groups. 
The estimated standard deviation of 5 is based on the published results (Mariette et al, 2015; 
Fisher et al, 2017) and internal data.  
Population #2: The planned sample size of 102 subjects (51 subjects in the VIB4920 group 
and 51 subjects in the Placebo group) will provide 80% power to detect a difference in mean 
change from baseline to Day 169 in ESSPRI of 1.0 (assumed standard deviation of 2) 
between the VIB4920 and placebo treatment groups at a two-sided alpha level of 0.10 using 
2-sample t-test. The minimum detectable difference is 0.66 between the 2 treatment groups. 
The estimated standard deviation of 2 is based on the published results (Mariette et al, 2015; 
Fisher et al, 2017) and internal data. 


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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 
subjects 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. 
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 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 and safety 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 and Day 169 visit. The first post-treatment visit 
will start at Day 2. When slotting visits to the Day 169 window, this should only occur for 
assessments on or before the date of the nominal Day 169 dose. Assessments after this date 
should be slotted to the following visit window. 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:  
• 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. 
• If 2 non-missing assessment actual dates are equidistant from the target day, the later 
visit will be used in the analysis. 
• For retest values of laboratory data, the retest value (the last valid observation 
assessed on the same visit day) will be chosen. 
3.2 
Protocol Deviations  
All protocol deviations will be classified as either major protocol deviations or minor 
protocol deviations. The major protocol deviations are considered as the important protocol 
deviations, which may significantly impact the completeness, accuracy, and/or reliability of 
the study data, and may significantly affect a subject’s rights, safety, or well-being. All the 
protocol deviations will be listed, and the major protocol deviation will be summarized. Some 
classifications of major protocol deviations are listed below. 


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• Did not meet inclusion criteria or met exclusion criteria. 
• Blindness of treatment assignment was broken by site investigator before Day 169 
• Received prohibited concomitant medication 
• 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. 
3.3 
Analysis Sets  
3.3.1 
Full analysis set  
The full analysis set includes all randomized subjects who received any dose of IP. Subjects 
will be analyzed according to the treatment randomized. The efficacy analysis will be based 
on the full analysis set. 
3.3.2 
Safety analysis set  
The safety analysis set includes all subjects who received any dose of IP. Subjects will be 
analyzed according to the treatment that they actually received. The safety and ADA analyses 
will be based on the safety analysis set. 
If subjects who are randomized to placebo receive any dose of VIB4920 in Stage I of the 
study, the treatment actually received will be VIB4920 for the subjects. 
3.3.3 
Pharmacokinetics analysis set  
The PK analysis set includes all subjects who received IP and have at least one quantifiable 
plasma PK observation post-first dose. Subjects will be analyzed according to the treatment 
that they actually received. PK analyses will be based on the PK analysis set. 
3.3.4 
Cross-over analysis set  
The cross-over analysis set includes all subjects who received any dose of IP during Stage II 
of the study. 
3.3.5 
Any VIB4920 analysis set  
The any VIB4920 analysis set includes all subjects who received at least one dose of 
VIB4920 during the study. 
3.4 
Study Subjects  
3.4.1 
Subject Disposition  
A summary of subject disposition will be presented using the categories presented below. 
• Screened 


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• Screen failed with reasons 
• Randomized 
• Randomized but not treated 
• Randomized and treated 
• Completed Stage I treatment 
• Completed treatment  
• Discontinued treatment with reasons 
• Completed Stage I 
• Completed study 
• 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.  
A summary of baseline disease characteristics, by treatment group and overall for the full 
analysis set will include 
• Baseline ESSDAI total score - descriptive statistics 
• Baseline ESSDAI total score (< 10 points vs ≥ 10 points) - n (%)  
• Baseline ESSPRI total and component score - descriptive statistics 
• Baseline ESSPRI total score (< 7.5 points vs ≥ 7.5 points) - n (%)  
• Baseline OSDI - descriptive statistics - descriptive statistics 
• Schirmer’s test ≤5 mm in at least 1 eye - n (%) 
• Time (years) from initial diagnosis to randomization - descriptive statistics 
• Positive SS-A/SS-B at baseline - n (%) 
• Baseline RF auto-antibody levels: - descriptive statistics 
• Stimulated salivary flow at baseline - descriptive statistics 
• Concomitant RA or SLE - n (%) 


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Significant medical history finding will be summarized by MedDRA system organ class 
(SOC) and preferred term (PT) by treatment group and overall for the full analysis set. 
3.4.3 
Investigational Product Exposure  
The number of doses received, amount (mg) of the IP received, durations of the IP exposure, 
and total subject years exposure will be summarized by treatment. This summary will be 
produced for the Stage I and Stage II separately using the safety analysis set and cross-over 
analysis set respectively, and for the overall study using any VIB4920 analysis set. 
• Duration of the IP exposure is defined as follows 
- 
Stage I: minimum of (date of last dose before Day 169 + 28 ‒ first dose date) and 
(Day 169 date - first dose date) 
- 
Stage II: last dose date + 28 ‒ Day 169 date + 1 
- 
Overall study using any VIB4920 analysis set: duration of exposure to VIB4920 
in the study 
• The amount (mg) of IP: if a subject 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. 
• Treatment compliance for an individual subject = (Total number of doses received)/ 
(Total number of doses planned per protocol) ×100%.  
3.4.4 
Prior and Concomitant Medications  
Number (%) of subjects who receive prior medications and concomitant medications during 
Stage I and during Stage II + Off-treatment follow-up period will be summarized by world 
health organization (WHO) Drug dictionary Anatomical Therapeutic Chemical (ATC) 
category and PT. At each level of summarization, a subject is counted once if he/she reported 
one or more medications at that level. The summary of prior medications and concomitant 
medications during Stage I will be based on the safety analysis set. The summary of 
concomitant medications during Stage II + Off-treatment follow-up period will be based on 
the cross-over analysis set. 
The prior and concomitant medications are defined as below. 
• Prior medications are defined as medications with a stop date occurring before the 
first IP administration date. 
• Concomitant medications during Stage I are defined as follows: 
- 
Medications with a start date before the Day 169 IP administration date and stop 
date on or after the first IP administration date for subjects entering Stage II. 
- 
Medications with a stop date on or after the first IP administration date for 
subjects not entering Stage II. 


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• Concomitant medications during Stage II + Off-treatment follow-up period are 
defined as medications with a stop date on or after the Day 169 IP administration date. 
Use of disease-related medications at baseline, defined as all disease-related medications 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) will be summarized for the full analysis set. 
The number and percentage of subjects who receive rescue medication during Stage I and 
during Stage II + Off-treatment follow-up period will also be summarized for the full analysis 
set and cross-over analysis set respectively.  
Rescue medications for population #1 are listed below: 
• Azathioprine (AZA) > 150 mg/day, methotrexate (MTX) > 20 mg/week, leflunomide 
>20 mg/day, mycophenolate mofetil (MMF) > 2gm/day OR any increase from baseline 
(including initiation of treatment) 
• Any increase from baseline in anti-malarial (including initiation of treatment) 
• Initiation of any new conventional disease-modifying anti-rheumatic drug 
(cDMARD) 
• Oral prednisone > 10 mg/day OR any increase from baseline (including initiation of 
treatment) 
• Intramuscular, IV, or intraarticular corticosteroids 
• Corticosteroids with a long biologic half-life (eg, dexamethasone, betamethasone) 
Rescue medications for population #2 are listed below: 
• Oral, intramuscular, IV, or intraarticular corticosteroids 
• MTX, AZA, leflunomide, MMF, and other cDMARD or immunosuppressive or 
antiproliferative medications 
• Any increase from baseline in anti-malarial (including initiation of treatment) 
• Any increase or initiation of new doses of cevimeline or pilocarpine and cyclosporine 
eye drops (Restasis)  
The missing start/stop date of medications will be imputed as appropriate and the details of 
the imputation will be included in the SPP. 
3.5 
Efficacy Analyses  
3.5.1 
Primary Efficacy Endpoint(s) and Analyses  
3.5.1.1 
Primary efficacy endpoint  
Population #1: The primary efficacy endpoint is change from baseline in ESSDAI at Day 
169.  


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Population #2: The primary efficacy endpoint is change from baseline in ESSPRI at Day 169.  
ESSDAI: 
The ESSDAI is a validated consensus disease activity index that is able to capture changes in 
the severity of systemic manifestations of SS, with 12 domains, with associated weights as 
shown in Table 2.  
Table 2  
ESSDAI Domains, Weights and Activity Levels  
Domain 
Weight 
Activity Levels 
Constitutional 
3 
0-2 
Lymphadenopathy 
4 
0-3 
Glandular 
2 
0-2 
Articular 
2 
0-3 
Cutaneous 
3 
0-3 
Pulmonary 
5 
0-3 
Renal 
5 
0-3 
Muscular 
6 
0-3 
Peripheral Nervous System 
5 
0-3 
Central Nervous System 
5 
0,2,3 
Hematological 
2 
0-3 
Biological 
1 
0-2 
The final score is calculated as follows: 
Total Score = Sum of all 12 domain scores 
Domain score = Activity level × Domain weight 
The theoretical range of values for the ESSDAI is 0 to 123, with higher ESSDAI scores 
indicate more severe disease. 
ESSPRI: 
The ESSPRI is a 3-item, subject-completed assessment of SS symptoms. The instrument 
captures subject-rated severity of dryness, fatigue, and pain using 0-10 numeric rating scales 
anchored as no symptom (0) and maximal imaginable symptom (10). The recall period is 
stated in each question as “the last 2 weeks.” The ESSPRI total score is the mean of the 3 
items and is calculated as follows: 
ESSPRI Total Score = (Dryness + Fatigue + Pain) / 3 
3.5.1.2 
Primary efficacy analysis  
Population #1: The primary efficacy endpoint will be analyzed using the mixed-effect model 
for repeated measures (MMRM) approach based on Stage I data for the full analysis set. The 


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model will include fixed effects for treatment, visit, visit by treatment interaction, and 
baseline ESSDAI score. 
Population #2: The primary efficacy endpoint will be analyzed using the MMRM approach 
based on Stage I data for the full analysis set. The model will include fixed effects for 
treatment, visit, visit by treatment interaction, and baseline ESSPRI score. 
From the model, the estimated treatment effect (ie the difference (VIB4920 – placebo) in 
LSMeans) at Day 169 will be obtained, together with a two-sided 90% confidence interval 
(CI), standard error (SE) and p-value. The significance of treatment effect will be tested by 
using a two-sided test at significance level α of 0.1. Additionally, estimates of the LSMeans 
for each treatment group will be obtained, together with the associated SE. 
Longitudinal presentations of results over time up to Day 169 based on the same analysis will 
be created.  
Model assumptions for MMRM will be checked with graphical displays (residual plots and a 
quartile-quartile (Q-Q) plot). If the model assumptions are not met, appropriate data 
transformations or the non-parametric approaches will be used. 
3.5.1.3 
Handling plan for Intercurrent Events  
Rescue medication use:  
For subjects who take rescue medications defined in section 3.4.4 before Day 169, the data 
collected after administration of the rescue medications will not be included in the primary 
analysis. This approach attempts to reduce the confounding effects of rescue medications. 
Treatment discontinuation: 
Subjects who discontinue IP before Day 169 will be asked to come to scheduled evaluations 
until Day 169 visit and at least 3 months of off-treatment follow-up after the last IP 
administration. The data collected after discontinuation of study treatment will be included in 
the analysis. 
3.5.1.4 
Handling plan for missing data  
Missing data will be handled using the MMRM approach. 
3.5.1.5 
Sensitivity analysis of primary efficacy endpoint  
The sensitivity analysis will be performed for the primary efficacy endpoint using the same 
model as the primary analysis with the following handling plan for the rescue medication use 
and treatment discontinuation. 
• Impute result after rescue medications using the worst score on or before Day 169 
including baseline. Include data collected after discontinuation of study treatment. 
• Include data collected after rescue medications and data collected after 
discontinuation of study treatment. 


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In addition, the primary efficacy endpoint will be analyzed based on the time adjusted area 
under the curve (AUC) of change from baseline. First, the AUC of the ESSDAI and ESSPRI 
score from baseline to Day 169 will be calculated using the trapezoidal rule. Second, the time 
adjusted AUC will be obtained by dividing the AUC by the total time for baseline. Third, 
time adjusted AUC of change from baseline will be calculated by subtracting the baseline 
score from the time adjusted AUC. All observed data including data collected after rescue 
medications will be used to calculate the time adjusted AUC. The time adjusted AUC of 
change from baseline will be analyzed using MMRM approach including fixed effects for 
treatment, visit, visit by treatment interaction, and corresponding baseline score. 
3.5.1.6 
Subgroup analyses of primary endpoint  
3.5.1.7 
Multiplicity adjustment  
There is no multiplicity issue for the primary endpoint analysis for each population because 
there is only one primary comparison (VIB4920 1500mg vs placebo) for each population. 
3.5.1.8 
Additional analysis  
The change from baseline in ESSDAI for population #1 and change from baseline in ESSPRI 
for population #2 will be analyzed for Stage II + Off-treatment follow-up period based on the 
cross-over analysis set using the same MMRM model as the primary analysis. Data collected 
after rescue medications and after discontinuation of study treatment will be included. 
The change from baseline in modified ESSDAI excluding peripheral nervous system, central 
nervous system, and pulmonary domains for population #1 will be analyzed using MMRM 
approach for Stage I and Stage II + Off-treatment follow-up period based on the full analysis 
set and cross-over analysis set respectively. The model will include fixed effects for 
treatment, visit, visit by treatment interaction, and baseline modified ESSDAI score. The 
handling plan for rescue medication use and treatment discontinuation for Stage I analysis is 
the same as those for the primary (section 3.5.1.3) and sensitivity (section 3.5.1.5) analyses of 
the primary efficacy endpoint. Data collected after rescue medications and after 
discontinuation of study treatment will be included for the Stage II + Off-treatment follow-up 
period analysis. 


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3.5.2 
Secondary Efficacy Endpoints and Analyses  
3.5.2.1 
Secondary efficacy endpoints  
The secondary efficacy endpoints are as follows: 
• Change from baseline in ESSPRI at Day 169 (population #1) 
• Proportion of subjects achieving ESSDAI[3] and ESSDAI[4] response, defined as a 
decrease of at least 3[4] points from baseline in the ESSDAI at Day 169 without 
premature discontinuation from the study and without receiving rescue medications 
(population #1) 
• Proportion of subjects achieving ESSPRI response, defined as ≥ 1 point or 15% 
reduction from baseline in ESSPRI score at Day 169 without premature discontinuation 
from the study and without receiving rescue medications (population #2) 
• Change from baseline in FACIT-Fatigue score at Day 169 (population #1 and #2) 
• Change from baseline in OSDI at Day 169 (population #1 and #2) 
• Change from baseline in PGIS at Day 169 (population #1 and #2) 
FACIT-Fatigue: 
The FACIT-Fatigue is a 13-item questionnaire, subject-completed, used to assess the impact 
of fatigue. Its recall period is 7 days. The responses range from 0 (Not at all) to 4 (Very 
Much). To calculate the total score, the negatively stated items are reversed by subtracting the 
response from “4”. Final scores are the sum of the responses and range from 0 to 52. Higher 
scores indicate better quality of life. 
OSDI: 
OSDI is a valid and reliable instrument for assessing effect on vision-related function and dry 
eye disease severity (normal, mild, moderate, and severe). Its recall period is 1 week. It is 
composed of 12 questions that the physician asks the subject and circles the number that best 
represents each question. The responses for each question range from 0 (None of the time) to 
4 (All of the time). The OSDI score is calculated as follows: 
OSDI score = (sum of scores for questions answered) / (number of questions answered) × 25 
The OSDI score ranges from 0 to 100 with higher scores signifying greater disability. 
PGIS: 
The PGIS is a single item designed to capture the subject’s perception of overall symptom 
severity over the past week on a 5-point categorical response scale (none, mild, moderate, 
severe, very severe). 


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3.5.2.2 
Secondary efficacy analysis  
The continuous secondary efficacy endpoints of population #1 and population #2 will be 
analyzed based on Stage I data for the full analysis set using the MMRM approach, with 
treatment, visit, visit by treatment interaction, randomization stratification factor, and 
corresponding baseline value. Handling plan for the rescue medication use and treatment 
discontinuation will be the same as those described for the primary endpoints in sections 
3.5.1.3 and 3.5.1.5. 
The details of these analyses and presentations of results will be the same as those described 
for the primary endpoints in section 3.5.1.2. 
The analysis for Stage II + Off-treatment follow-up period will be performed using the same 
MMRM approach based on the cross-over analysis set. Data collected after rescue 
medications and after discontinuation of study treatment will be included. 
The binary secondary efficacy endpoints of population #1 and population #2 will be analyzed 
for the full analysis set using a logistic regression model, with treatment and corresponding 
baseline score included in the model.  
The estimated treatment effect (ie, the odds ratio for VIB4920 versus placebo), corresponding 
90% CI, and 2-sided p-value will be presented. In addition, the response rate and the 
corresponding 90% CI within each treatment group will be presented. Longitudinal 
presentations of results over time up to Day 169 will be created using full analysis set. In 
addition, the analysis will be produced for Stage II + Off-treatment follow-up period 
separately using the cross-over analysis set. 
3.5.3 
Exploratory Efficacy Endpoints and Analyses  
3.5.3.1 
Exploratory efficacy endpoints  
The exploratory efficacy endpoints are as follows: 


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3.5.4 
Handling missing items of clinical outcome assessments (COAs)  
The ESSDAI is a clinician reported outcome. There will be very few missing items expected. 
All PROs will be administered by ePRO. Questions are mandatory so there will be no 
skipped items. But in case there are missing items, the following algorithms will be used to 
handle the missing items. 
3.5.4.1 
ESSDAI and ESSPRI  
If less than 50% of items are missing, the missing individual items are imputed using last 
observation carry forward (LOCF) approach before calculation of total score. The total score 
will not be calculated and will be treated as missing if 50% or more of items are missing. 
3.5.4.2 
FACIT-Fatigue  
The missing items will be handled according to FACIT scoring guidelines. If less than 50% 
of items are missing, the total scores will be calculated as follows:  


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Total score = (Sum of scores for items answered) / (N of items answered) × 13 
The total score will not be calculated and will be treated as missing if 50% or more of items 
are missing. 
3.5.5 
Explore clinically meaningful within-subject change score of COAs  
The anchor-based methods supplemented with both empirical cumulative distribution 
function (eCDF) and probability density function (PDF) will be used to explore the clinically 
meaningful within-subject change score of COAs. The eCDFs display a continuous view of 
the score change (both positive and negative) in the COA endpoint from baseline to the 
proposed time point on the X-axis (horizontal axis), with the Y-axis (vertical axis) 
representing the cumulative proportion of subjects experiencing up to that level of score 
change.  
The receiver operating characteristic (ROC) curve analysis will be used as supportive 
approach to explore the clinically meaningful within-subject change score. 
Spearman’s correlation analyses will be used to examine the strength and magnitude of 
relationship between the COA measures and potential anchors. The threshold for 
consideration as an anchor will be a correlation coefficient > 0.30. 
3.5.5.1 
ESSDAI  
The clinically meaningful within-subject change score of ESSDAI will be explored for 
population #1 based on the pooled data across treatment groups. The anchor measures for 
ESSDAI are PGIS, 
. The eCDF curve of change from baseline to Day 169 
in ESSDAI will be plotted for each distinct anchor category as defined and identified by the 
anchor measures. A potential range for the meaningful change can be derived from eCDF 
plots (e.g., using median change, 25th percentile change, 75th percentile change). 
• 
 
• PGIS and 
 ≥2 category decrease, 1 category decrease, no change, 1 category 
increase, and ≥2 category increase 
The PDF curves of change from baseline to Day 169 in ESSDAI will also be plotted for each 
distinct anchor category to aid the interpretation of eCDF curves. 
The eCDF curve of change from baseline to Day 169 in ESSDAI will also be plotted by each 
treatment group without separating into distinct anchor category. 


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The ROC curve analysis will be performed using logistic regression model with anchor as 
binary outcome and change from baseline to Day 169 in ESSDAI score as quantitative 
predictor. The score that best distinguishes levels of the anchor as listed below (based on 
sensitivity and specificity) will be identified. 
• 
 
• PGIS and 
 ≥2 category decrease, ≥1 category decrease 
3.5.5.2 
ESSPRI  
The clinically meaningful within-subject change score of ESSPRI will be explored for 
population #1 and population #2 based on the pooled data across treatment groups within 
each population. The anchor measures for ESSPRI are PGIS and 
 The eCDF and PDF 
curves of change from baseline to Day 169 in ESSPRI will be plotted the same way as that 
for ESSDAI. The ROC curve analysis will be performed as well. 
3.6 
Safety Analysis  
3.6.1 
Adverse Events  
In general, if an AE onset is on or after the first dose of IP administration, the AE will be 
considered as a TEAE. Otherwise, the AE will be considered as a non-treatment emergent 
AE.  
The AEs will be summarized for different study periods as defined in the Table 3. 
Table 3  
TEAEs for different study periods  
Study Period 
Inclusion of AEs for Summary 
Stage I (Safety analysis set) 
Include AEs with an onset on or after the first dose of IP in Stage I up to the 
time prior to the first dose of IP in Stage II (Day 169) for subjects entering 
Stage II, and AEs with an onset on or after the first dose of IP in Stage I for 
subjects not entering Stage II. 
Stage II + Off-treatment 
follow-up (Cross-over 
analysis set) 
Include AEs with an onset on or after the first dose of IP in Stage II (Day 169).  
Any VIB4920 exposure 
(Any VIB4920 analysis set) 
Include AEs with onset on or after the first VIB4920 dose (either Stage I or 
Stage II) 
An overall summary table will be showing the number and percentage of subjects with at 
least 1 event in any of the following categories: TEAE, 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 subject for calculating rates, but all events will be 
presented in subject listings. In addition, if the same AE occurs multiple times within a 
particular subject, the highest severity and level of causality will be reported. 


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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 AESI is one of scientific and medical interest specific to understanding of the IP. AESIs 
for this protocol include: 
• Thrombotic and embolic events 
• Hepatic function abnormality (meeting the definition of Hy’s Law) 
• Anaphylaxis and clinically significant (Grade 3 or higher) hypersensitivity reactions 
• Severe Infusion-related reactions (common terminology criteria for adverse event 
(CTCAE) Grade 3 or higher) 
• Malignant neoplasm 
• Immune complex disease 
• Infections: 
− Clinically significant (Grade 3 or higher) 
− Opportunistic infections including but not limited to reactivation of latent viral 
infection, invasive fungal infections, and TB 
TEAESIs will be summarized by SOC and PT. 
Listings will be provided for all TEAEs and non-treatment emergent AEs. 
3.6.2 
Clinical Laboratory Evaluation  
The hematology, coagulation, serum chemistry, urinalysis, and immunoglobulins parameters, 
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 and serum chemistry parameter will be produced. The 
summary of clinical laboratory data will be generated for Stage I and Stage II + Off-treatment 
follow-up period separately based on the safety analysis set and cross-over analysis set 
respectively. 
3.6.3 
Other Safety Evaluations  
3.6.3.1 
Overdose  
The incidence of TEAE associated with overdose will be summarized by MedDRA SOC and 
PT if applicable. 


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3.6.3.2 
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 subjects with clinically significant vital signs values (meeting any of 
following criteria) will be provided. 
• Systolic blood pressure: <90 mmHg, >160 mmHg 
• Diastolic blood pressure: <60 mmHg, >100 mmHg 
• Heart rate: <50 Beats/min, >100 beats/min 
• Respiratory rate: <12 breaths/min, >23 breaths/min 
• Temperature: <36°C, >38°C 
The summary of vital sign data will be generated for Stage I and Stage II + Off-treatment 
follow-up period separately based on the safety analysis set and cross-over analysis set 
respectively. 
3.6.3.3 
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 subjects meeting the 
following criteria will be summarized. 
• QTc > 450 msec 
• QTc > 480 msec 
• QTc > 500 msec 
• QTc increases from baseline > 30 msec 
• 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. 
The summary of ECG data will be generated for Stage I and Stage II + Off-treatment follow-
up period separately based on the safety analysis set and cross-over analysis set respectively. 
3.6.3.4 
Weight  
The observed values and the changes from baseline in the weight will be summarized for 
Stage I and Stage II + Off-treatment follow-up period separately based on the safety analysis 
set and cross-over analysis set respectively. 


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3.7 
Pharmacokinetics  
VIB4920 plasma concentration will be summarized descriptively by visits for PK analysis 
set. VIB4920 concentration-time profiles will be generated. Noncompartmental analysis will 
be performed for VIB4920-treated subject. Descriptive statistics for PK parameters will be 
provided.  
Plasma concentration of VIB4920, summary statistics, PK profile and the additional PK-
related analyses will be reported in a clinical PK report (an addendum to the clinical study 
report) by PK group. 
3.8 
Immunogenicity  
The ADA status will be summarized by the categories defined in Table 4. The ADA 
incidence rate may also be summarized, where the incidence is the proportion of the subjects 
with ADA positive post-baseline only or boosted their pre-existing ADA during the study 
period. The cutoff for the boosted ADA will be determined before the database lock for the 
interim analysis. If data allow, the ADA titer for the ADA positive subjects will be 
summarized and the impact of ADA on efficacy and safety will be evaluated. 
The ADA summary will be produced for Stage I using safety analysis set and for the whole 
study period using any VIB4920 analysis set. For the summary for the whole study period 
using any VIB4920 analysis set, the baseline positive is defined as any positive ADA prior to 
the first administration of VIB4920.  


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3.9 
Exploratory Analyses  
4 PLANNED ANALYSIS  
4.1 
Interim Analysis  
An interim analysis will be conducted for each population after all subjects have completed 
the Day 85 visit or withdrawn prior to Day 85 for that population. The efficacy and safety 
data prior to the data cut-off for the interim analysis will be analyzed. No multiplicity 


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adjustment is planned for the interim analysis because there is no provision to stop the trial 
early at the interim analysis to claim efficacy. The final assessment of efficacy will be 
determined at the primary analysis. Details of the interim analysis will be specified in the 
interim unblinding analysis plan prior to unblinding. 
4.2 
Primary Efficacy Analysis  
The primary analysis will be conducted for each population after all subjects have completed 
the Day 169 visit or withdrawn prior to Day 169 for that population. The efficacy and safety 
data prior to the data cut-off for the primary analysis will be analyzed.  
4.3 
Final Analysis  
The final analysis will be conducted for each population after all subjects have completed 
study for that population.  
5 REFERENCES  
Fisher et al, 2017 
Fisher B, Zeher M, Ng WF, Bombardieri M, Posch M, Farag AM, et al. The Novel Anti-
CD40 Monoclonal Antibody CFZ533 Shows Beneficial Effects in Patients with Primary 
Sjögren’s Syndrome: A Phase IIa Double-Blind, Placebo-Controlled Randomized Trial 
[abstract]. Arthritis Rheumatol. 2017; 69. Available at: https://acrabstracts.org/abstract/the-
novel-anti-cd40-monoclonal-antibody-cfz533-shows-beneficial-effects-in-patients-with-
primary-sjogrens-syndrome-a-phase-iia-double-blind-placebo-controlled-randomized-trial/. 
Mariette et al, 2015 
Mariette X, Seror R, Quartuccio L, Baron G, Salvin S, Fabris M, et al. Efficacy and safety of 
belimumab in primary Sjögren's syndrome: results of the BELISS open-label phase II study. 
Ann Rheum Dis. 2015; 74(3):526-31. 
 
Revision History: 
Version # 
Description of Change 
2 
1. Change IgA, IgG and IgM RF to total RF 
2. Added “If subjects who are randomized to placebo receive any dose of VIB4920 in 
Stage I of the study, the treatment actually received will be VIB4920 for the 
subjects.” to section 3.3.2