A Phase 3, Randomized, Double-blind, Multicenter, Placebo Controlled Study of Inebilizumab Efficacy and Safety in IgG4-Related Disease
Phase: PHASE3
Conditions: IgG4 Related Disease
Sponsor: Amgen

Clinical Study Protocol
Horizon Therapeutics Ireland DAC
VIB0551.P3.S2 - MITIGATE
Inebilizumab
Amendment 9.1, 08AUG2023
IgG4-Related Disease
CONFIDENTIAL AND PROPRIETARY
Page 1 of 142
A PHASE 3, RANDOMIZED, DOUBLE-BLIND, 
MULTICENTER, PLACEBO-CONTROLLED
STUDY OF INEBILIZUMAB EFFICACY AND 
SAFETY IN IGG4-RELATED DISEASE
SHORT TITLE: MITIGATE
Investigational Product
Inebilizumab
Protocol Number
VIB0551.P3.S2
Clinical Trial Registry Identifiers
EudraCT: 2020-000417-33
ClinicalTrials.gov: NCT04540497
Amendment
9.1
Version Date
08AUG2023
IND Number
IND 144957
International Coordinating 
Investigator
, MD, MPH
Harvard Medical School
Massachusetts General Hospital, Division of Rheumatology
55 Fruit Street, YAW 2C
Boston, MA, 02114, USA
Sponsor
Viela Bio, Inc. / Horizon Therapeutics
2400 Research Blvd. Suite 200
Rockville MD, 20850, USA
Responsible Medical Officer
, MD
Executive Director, Clinical Development

Clinical Study Protocol
Horizon Therapeutics Ireland DAC
VIB0551.P3.S2 - MITIGATE
Inebilizumab
Amendment 9.1, 08AUG2023
IgG4-Related Disease
CONFIDENTIAL AND PROPRIETARY
Page 2 of 142
SPONSORS SIGNATURE PAGE
Medical Representative
Name:
Title:
Signature and Date:
, MD
Executive Director, 
Clinical Development
Biostatistics Representative
Name:
Title:
Signature and Date:
 PhD
Senior Director, 
Biostatistics

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 3 of 142 
SUMMARY OF CHANGES TO THE PROTOCOL  
The following table summarizes the key changes to the protocol made in Amendment 1: 
Protocol Amendment 1 (25Feb2020) 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 1, Synopsis 
Section 9.3, 
Determination of Sample 
Size 
The maximum sample size and process for 
re-estimation were clarified. 
Clarifications were in response 
to scientific advice from the 
European Medicines Agency 
(EMA). 
Section 1, Synopsis 
Section 3.2, Secondary 
Objectives and Endpoints 
The secondary safety objective and endpoint were 
updated to clarify that adverse event data 
collected during both the 52-week randomized-
controlled period (RCP) and the open-label 
period (OLP) will be used to evaluate the safety 
and tolerability of inebilizumab. 
To clarify the objectives of the 
OLP, in response to scientific 
advice from EMA. 
Section 1, Synopsis 
Section 3.3, Exploratory 
Objectives and Endpoints 
Section 1, Synopsis 
Section 3.3, Exploratory 
Objectives and Endpoints 
Section 6.2.2, Schedule of 
RCP Assessments and 
Procedures, Table 4 
Section 1, Synopsis 
Section 3.3, Exploratory 
Objectives and Endpoints 
Section 4.1, Study Design 
Section 2.1.1, IgG4-
Related Disease 
Section 13, References 
The description of IgG4-RD pathogenesis was 
updated to include recent concepts and 
publications. 
To provide investigators with 
the most recent understanding 
of the pathophysiology of 
IgG4-RD. 
Section 2.1.5, Supportive 
Clinical Data 
Section 13, References 
References to published data from the first 
2 studies of inebilizumab were added. 
To provide investigators with 
additional data on the safety of 
inebilizumab. 
Section 4.1, Study Design 
Section 6.4.2, Withdrawal 
from Study 
In Section 4.1, the description of the RCP was 
revised to emphasize that any subject who 
withdraws from the study should be asked to 
complete a final visit (early discontinuation visit 
[EDV]). 
Similar edits were made to the text in 
Section 6.4.2. 
Clarification.  

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 4 of 142 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 4.1, Study Design 
Language added to clarify the intent to follow all 
subjects in the OLP to the end of the OLP for 
safety and efficacy; at least 6 months after the last 
dose. 
Clarification added in response 
to EMA scientific advice. 
Section 5.1, Inclusion 
Criteria 
Amended inclusion criterion 4 to clarify that both 
inclusion and exclusion criteria for the 
ACR/EULAR classification criteria must be met. 
Clarification added in response 
to EMA scientific advice. 
Section 6.2.1, Schedule of 
Screening Assessments 
and Procedures, Table 3 
The following was added to the list of laboratory 
tests at screening: B cell count in patients who 
received B cell depleting therapy in the 
6-12 months prior to screening.  
To clarify and ensure that the 
required B cell counts are 
obtained to address exclusion 
criterion 5. 
Section 6.2.1, Schedule of 
Screening Assessments 
and Procedures, Table 3 
Section 6.2.2, Schedule of 
RCP Assessments and 
Procedures, Table 4 
Section 6.1.1, Order of 
Assessments 
Section 6.2.1, Schedule of 
Screening Assessments 
and Procedures, Table 3 
Section 6.3.1.2, 
Demographics and 
Baseline Characteristics 
Section 6.2.2, Schedule of 
RCP Assessments and 
Procedures, Table 4 
Section 6.2.2, Schedule of 
RCP Assessments and 
Procedures, Table 4 
Section 6.2.3, Schedule of 
OLP Assessments and 
Procedures, Table 5 
A footnote was added to both the RCP and OLP 
schedule of assessments to emphasize that 
premedication will be administered prior to each 
IP infusion. 
To add additional guidance to 
help ensure adherence to 
required protocol procedures 
for administration of IP. 
Section 6.2.2, Schedule of 
RCP Assessments and 
Procedures, Table 4 
Added rows to the RCP assessment table for 
providing oral GCs (Day 1 [Visit 2]) and 
assessing oral GC compliance (Days 15, 29, and 
57 [Visits 3, 4, and 5]).  
Added to the assessment table 
to ensure adherence to the 
protocol procedures for the 
additional study medication. 
Section 6.2.3, Schedule of 
OLP Assessments and 
Procedures, Table 5 
The schedule of assessments during the OLP was 
revised as follows: 
x In addition to the symptom-driven physical 
exams, full physical exams will be performed 
on Days 1 and 365 (Visits 1 and 14 [or EDV]). 
x To add a full physical exam 
at the start and end of the 
OLP. 

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 5 of 142 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 6.3.1.3, Safety 
Assessments at Screening 
The description of the tuberculosis (TB) testing at 
screening was updated to remove “as per local 
standard-of-care guidelines”. 
This text was removed because 
initial TB testing will be 
performed by the central 
laboratory. 
Section 6.2.3.1, Eligibility 
for OLP 
Some specific B-cell agents that would be 
exclusionary were added to the eligibility criteria 
for the OLP. 
Additions were in response to 
EMA scientific advice. 
Section 6.4.1, 
Discontinuation of 
Investigational Product 
Amended events requiring discontinuation of 
investigational product (IP): 
x Added “Any AE of immune complex disease” 
x Replaced “Any Grade 4 SAE” and “Any 
Grade 4 infection” with “Any life-threatening 
(Grade 4) adverse event” 
x Removed “Any Grade 3 infusion-related 
reaction” 
x Added “Any Grade 3 adverse event” with 
listed exceptions 
The list of events requiring 
discontinuation of IP was 
revised in response to advice 
from the US FDA. 
Section 9.5.1, Analysis of 
the Primary Efficacy 
Endpoint 
Section 9.5.2, Analysis of 
the Secondary Efficacy 
Endpoints 
To clarify the subgroup who will be censored for 
the additional analysis. 
Similar language was removed from Section 9.5.2 
to reduce redundancy. 
Text was revised in response to 
EMA scientific advice. 
Section 9.5.4, Subgroup 
Analyses 
Specified subgroup analysis by stratification 
factors: first or subsequent treatment course for 
IgG4-RD. 
Text was revised in response to 
EMA scientific advice. 
Section 10.7, Biological 
Specimens and Data 
Added clarification that storage of leftover 
samples for future research will be with patient 
consent. 
Clarification. 
Appendix C 
Updated version of the IgG4-related disease 
Responder Index was attached and the version 
from a previous paper was deleted. 
Updated to include the correct 
scoring table. 
The following table summarizes the key changes to the protocol made in Amendment 2: 

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 6 of 142 
Protocol Amendment 2 (30Mar2020) 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 14, Appendices, 
and references to 
appendices 
x Former Appendix A (2019 ACR/EULAR 
Classification Criteria), Appendix B (Flare 
Criteria), and former Appendix C (IgG4-RD 
Responder Index) were removed from the 
protocol and will be provided via other means 
to the Investigators. 
x The remaining appendices were re-lettered to 
reflect the change. 
x References to the appendices were updated 
throughout the document to reflect the change. 
Appendices were removed that 
will be best provided to 
Investigators via means other 
than the protocol.  
Section 4.1, Study Plan 
Section 7.4.1, Treatment 
Allocation for RCP 
The description of stratification was clarified to 
be by IgG4-RD manifestation (ie, newly-
diagnosed vs recurrent). 
Further clarification following 
Amendment 1. 
Section 5.1, Inclusion 
Criteria 
Added “Females of childbearing potential must 
have a negative serum pregnancy test at 
screening” to the text of inclusion criterion no 8. 
Clarification. 
Section 5.4, Replacement 
of Subjects 
Clarified that subjects who have been randomized 
but not dosed will not be followed to completion 
of the RCP. 
Clarification. 
Section 6.3.1.3, Safety 
Assessments at Screening 
x The description of TB testing at screening was 
further updated to remove the option of “other 
interferon gamma release assay test” 
x A clarification was added that serum will be 
frozen for possible testing for JCV antibodies 
“in case of suspected PML”. 
Clarifications. 
Section 6.4.1, 
Discontinuation of 
Investigational Product 
Text revised to clarify that subjects who 
discontinue IP should remain in the study and 
complete procedures, except IP administration 
and
sampling. 
x Clarification requested by 
US FDA. 
Section 8.4, Adverse 
Events of Special Interest 
Replaced a reference to the Safety Handling Plan 
with specific instructions for adverse event of 
special interest (AESI) reporting. 
x Instructions in the protocol 
are more accessible to sites. 

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 7 of 142 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 9.5.5, Safety 
Analysis 
x The definition of the rate of AEs per 100 
person-years at risk was updated to: (total 
number of AEs)/(total person years) × 100. 
x Stratification factor was added to the list of 
subgroup analyses. 
x Corrections. 
The following table summarizes the key changes to the protocol made in Amendment 3: 
Protocol Amendment 3 (16Apr2020) 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 2.1.4, Risk 
Assessment for 
Inebilizumab 
Updated identified risks to include neutropenia, 
arthralgia, and reduced immunoglobulin levels. 
Changes reflect planned 
updates to the safety 
information in the 
Investigator’s Brochure, which 
is currently in revision. 
Protocol Amendment 4 (Japan) (06May2020) (Previously reviewed and approved in Japan 
only) 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 1, Synopsis 
Section 5.1, Inclusion 
Criteria 
Updated the age requirement to ≥ 20 years. 
In Japan, adults are defined as 
20 years of age or older.  
Section 5.1, Inclusion 
Criteria 
Revised the text describing any locally required 
authorization from the subject in inclusion 
criterion 2.  
Removed content that does not 
apply to Japan. 
 
Section 5.2, Exclusion 
Criteria 
Section 6.2.1, Schedule of 
Screening Assessments 
and Procedures, Table 3 
Section 6.3.1.3, Safety 
Assessments at Screening  
Added “(3) hepatitis B surface antibody 
(HBsAb)” to exclusion criterion 12. 
Added HBsAb to the list of tests that require 
blood collection. 
Added a third method to 
hepatitis B testing.  
 
Section 7.1.1.4, 
Investigational Product 
Dosing and 
Administration 
Added text to clarify the administration procedure 
for the initial randomized-controlled period dose 
for Japanese subjects. 
Added text specific for sites in 
Japan. 
Section 10.1, Good 
Clinical Practice 
Added applicable regulatory requirements in 
Japan. 
Added text specific for sites in 
Japan. 
Section 10.2.1, Ethics and 
Regulatory Review in 
Japan 
Added details for the ethics and regulatory review 
in Japan. 
Added text specific for sites in 
Japan.  

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 8 of 142 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 10.4, Deviation 
from the Clinical Study 
Protocol 
Added a description of the procedures required in 
the event of a protocol deviation. 
Clarification.  
Protocol Amendment 5 (Japan) (22Jun2020) (Previously reviewed and approved in Japan, 
only) 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 7.1.1.4, 
Investigational Product 
Dosing and 
Administration 
Removed text requiring inpatient administration 
of IP for the initial randomized-controlled period 
dose for Japanese subjects. 
Hospitalization for dose 
administration is not required 
but is permitted. 
Protocol Amendment 6 (China) (19Nov2020) (Previously reviewed and approved in China, 
only) 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Protocol Amendment 7 (Global) (16Aug2021) 
Amendments 4, 5, and 6 are incorporated into this global amendment but were previously only 
reviewed locally (Amendments 4 and 5 for Japan; Amendment 6 for China). 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
All sections 
“Viela Bio” changed to “Sponsor”. 
Clarification as Viela Bio, Inc. 
was acquired by Horizon 
Therapeutics. 
All sections 
Minor corrections and clarifications throughout 
the document. 
To correct typographical and 
other minor errors. 

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 9 of 142 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Cover Page 
Responsible Medical Officer was changed to 
MD FACS  
Responsible Medical Officer 
has been updated to reflect staff 
change. 
Section 1, Synopsis 
Section 5.1, Inclusion 
Criterion 1 
Updated to “Male or female adults who have 
reached the age of consent in the applicable 
region (eg, ≥ 18 years in the US, ≥ 20 years in 
Japan)”. 
As in Protocol Amendment 4 
(Japan), the age of consent is 
≥ 20 years.   
 
Incorporated the age of consent 
in all global regions. 
Section 1, Synopsis 
Section 9.3, 
Determination of Sample 
Size 
Updated to “approximately 160 subjects will be 
randomized and dosed”. 
 
To keep the number of subjects 
consistent with the number of 
subjects needed for the primary 
analysis, which is based on the 
Full Analysis Set and defined 
as “all subjects randomized and 
who received any dose of IP in 
the study”.  
Section 4.1, Study Design 
Updated to allow for remote visits in exceptional 
circumstances (due to COVID-19 restrictions or 
other reasons). 
To minimize data loss for 
subjects who cannot attend in-
person visits. 
Section 5.1, Inclusion 
Criterion 2 
Changed to “any locally required authorization 
(eg, data privacy) obtained from the subject prior 
to performing any protocol related procedures, 
including screening evaluations”. 
Changes were made in Protocol 
Amendment 4 (Japan) to 
remove content that did not 
apply to Japan.  
 
To address local requirements 
without specifying for each 
region. 
Section 5.1, Inclusion 
Criterion 5 
Added text “Total duration of GC treatment must 
be at least 3 weeks and not exceed 8 weeks prior 
to randomization”. 
Clarification. 
Section 5.1, Inclusion 
Criterion 6 
Added text “One organ must meet the 
requirements for the ACR/EULAR classification 
criteria (inclusion 4); the second organ is as 
defined by the Investigator”. 
Clarification that only one 
organ must meet ACR/EULAR 
classification organ list. 
Section 5.1, Inclusion 
Criterion 8 
Updated text to “A condom with spermicide 
(where spermicide is available)”. 
To account for country-specific 
availability of spermicide. 
Section 5.2, Exclusion 
Criteria 5 and 19 
 
Exclusion 5 is amended to delete requirement to 
have B cell counts ≥LLN in subjects who 
received a B cell depleting agent in the period 6-
12 months prior to screening.    
 
Exclusion 19 excludes subjects with CD19+ B 
cells at screen < 40 cells/μL; an exclusionary 
value may be repeated.   
 
To require a minimal detectable 
B cell count in all enrolled 
subjects to permit assessment 
of B cell decline in response to 
inebilizumab. 

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 10 of 142 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 5.2, Exclusion 
Criterion 9 
Added text specifying that required GC taper 8 
weeks post randomization is for GCs other than 
≤ 2.5 mg/day prednisone or equivalent for 
treatment of adrenal insufficiency or intolerance 
of taper. 
Clarification. 
Section 5.2, Exclusion 
Criterion 12 
Section 6.2.1, Schedule of 
Screening Assessments 
and Procedures, Table 3 
Section 6.3.1.3, Safety 
Assessments at Screening 
Added “(3) hepatitis B surface antibody 
(HBsAb)” to exclusion criterion 12 for Japan 
only. 
 
Added HBsAb to the list of tests that require 
blood collection in Japan (no additional blood 
sample required). 
Changes were made in Protocol 
Amendment 4 (Japan) to add 
HbsAb to exclusion criterion 
12. 
 
Incorporates Japanese 
requirement.  
Section 5.2, Exclusion 
Criterion 13 
Updated to clarify that HCV viral load testing 
must be completed at site or central lab.  
Clarification. 
Section 5.2, Exclusion 
Criterion 19 
Prothrombin time exclusion criteria updated to 
> 1.2 x ULN and added that subjects who are 
anticoagulated due to atrial fibrillation and who 
have aspartate aminotransferase (AST) and 
alanine aminotransferase (ALT) levels ≤ 2 x ULN 
are not excluded. 
Updated to account for 
laboratory variability and to 
permit enrollment of subjects 
whose prothrombin time 
abnormality is related to 
anticoagulation for atrial 
fibrillation but is not suggestive 
of significant hepatic disease.  
Section 5.2, Exclusion 
Criterion 19 
Section 6.2.1, Schedule of 
Screening Assessments 
and Procedures, Table 3 
Subjects are excluded for total immunoglobulins 
<600 mg/dL. 
 
For subject safety as post-dose 
immunoglobulin levels is not 
provided to site or Sponsor, 
although they are available to 
the SDMC. 
 
Section 5.2, Exclusion 
Criterion 21 
Section 6.2.1, Schedule of 
Screening Assessments 
and Procedures, Table 3 
Updated to clarify that subjects are excluded for 
known positive anti-neutrophil cytoplasmic 
antibodies (ANCA) targeted against proteinase 3 
or myeloperoxidase based on patient records   
 
ANCA is deleted from laboratory tests obtained 
at screen, and other references to ANCA testing 
are deleted.  
ANCA is not required for 
ACR/EULAR classification 
criteria, but a known positive is 
exclusionary per classification 
criteria. ANCA testing can be 
deleted at screening without 
affecting assessment of safety.  
Section 5.3, Rescreening 
Procedures 
Section 5.4, Replacement 
of Subjects 
 
Updated to “Subjects will not be replaced”. 
All randomized subjects will be 
included in the clinical database 
regardless of whether the 
subject was dosed or not.  
 
Section 6.1.2, Availability 
of Laboratory Results 

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 11 of 142 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 6.2.1, Schedule of 
Screening Assessments 
and Procedures, Table 3 
For legend c: liver functions may be repeated 
during screening if subject enrolls with 
hepatobiliary flare, changed to exclusion 20. 
Correction of typographical 
error. 
Section 6.2.3, Schedule of 
OLP Assessments and 
Procedures, Table 5 
Updated to state “All procedures and blood 
sampling must be collected before IP 
administration on days when IP is administered”. 
Clarification. 
Section 6.2.3.1, Eligibility 
for OLP, Eligibility 
Criterion 2 
Removed “non” and added “open-label 
commercial inebilizumab” for the criteria 
“Subjects eligible for the OLP must not have had 
IP discontinued for any safety reason other than 
the use of non B cell depleting 
immunosuppressive agents (eg, rituximab, 
ocrelizumab, obinutuzumab, ofatumumab, 
inebilizumab) during the RCP”. 
Correction of error.  
Section 6.2.3.1, Eligibility 
for OLP , Eligibility 
Criterion 2 
Modified to state that subjects “must not have had 
IP discontinued for any of the following reasons”. 
 
Updated to exclude subjects who were in 
“Receipt of any B cell-depleting therapy (eg, 
rituximab, ocrelizumab, obinutuzumab, 
ofatumumab, commercially available 
inebilizumab) in the 6 months prior to enrollment 
in the OLP. Receipt of such a B cell-depleting 
agent in the period 6 to 12 months prior to 
enrollment in OLP is exclusionary unless B cell 
counts have returned to ≥ 40 cells/μL by central 
laboratory”. 
Correction of error and 
clarification of eligibility for 
OLP if subject receives B cell- 
depleting therapy during RCP. 
Section 6.2.3.1, Eligibility 
for OLP, Eligibility 
Criterion 3 
Removed “specified” from the 28-day washout 
period” after discontinuation of non-B cell 
depleting, non-GC immunosuppressive therapy 
initiated during RCP. 
Correction of error. 
Section 6.2.3 Schedule of 
OLP assessments and 
Procedures, Table 5 
x Removal of Physical exam from assessment 
on V1 OLP 
Correction of errors. 
 

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 12 of 142 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
x Removal of Symptom-driven physical exam 
on V14 OLP 
Section 6.3.1.2, 
Demographics and 
Baseline Characteristics 
Updated to collect year of birth, sex, and where 
permitted, race, and ethnicity. 
In response to limitations on 
collections of these data in 
some regions. 
Section 6.3.4,. Clinical 
Laboratory Assessments  
Updated text to specify that in certain instances, 
safety laboratory tests may be run in a licensed 
local laboratory with approval of the Sponsor 
even where the exclusion criterion specifies use 
of the central laboratory. Instances of use of local 
laboratory with approval of the sponsor will not 
be considered protocol deviations. 
The effect of COVID-19 on 
availability of tubes and kits for 
central lab testing risks loss of 
data, and it is preferable to use 
local laboratories than to have 
loss of safety data; therefore, in 
some circumstances, use of 
local laboratories will be 
permitted.  
Section 6.4.1, 
Discontinuation of 
Investigational Product 
Added text “Subjects who discontinue IP during 
the RCP may be eligible to enroll in the OLP, if 
they meet criteria outlined in Section 6.2.3.1”. 
Clarification. 
Section 7.1, Description 
of Investigational 
Product, Table 7 
IP manufacture legal entity name changed from 
MedImmune Pharma, BV to AstraZeneca 
Nijmegen, B.V. 
 
Alternate placebo manufacturer Berkshire Sterile 
Manufacturing, Inc. was added. 
Change of manufacturer legal 
entity name. 
 
An alternate placebo 
manufacturer has been added. 
Section 7.5.2, Permitted 
Glucocorticoid Uses 
Updated text to “Oral GC treatment for ≤ 2 weeks 
(for any purpose)”. 
 
Updated text to “GCs at a dose of ≤ 2.5 mg of 
prednisone or equivalent for treatment of adrenal 
insufficiency (mineralocorticoids are permitted) 
or intolerance of steroid taper (in this case, 
continued tapering of steroids should be 
performed as tolerated).  GCs at any dose should 
not be continued for the purpose of prevention of 
IgG4-RD related flare”. 
 
Updated text to “Inhaled, intranasal, or topical 
corticosteroids”.  
Clarification. 
Section 8.1, Definitions  
 
Updated the Serious Adverse Event definition to 
include “A hospitalization for elective or pre-
planned treatment of a pre-existing condition that 
did not worsen from baseline will not be 
considered an SAE”. 
Clarification. 
Section 8.1, Definitions  
Updated the Severity or Intensity definition to 
include “The determination of severity for events 
not listed in the CTCAE should be made by the 
Investigator based upon medical judgment and 
the severity categories of Grade 1 to Grade 5 as 
Clarification. 

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 13 of 142 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
defined here, with the maximum severity 
recorded”. 
Section 9.1, General 
Considerations 
Replaced “after randomization” with “from Day 1 
(Dosing) 
For consistency of the 
definition of RCP 
Section 10.1, Good 
Clinical Practice 
 
Added text regarding applicable local and 
regional regulatory requirements, which includes 
Japanese-specific requirements. 
 
Changes were originally made 
in Protocol Amendment 4 
(Japan) to include text specific 
to regulatory requirements in 
Japan.   
 
Incorporates local and regional 
regulatory requirements within 
a single protocol used globally. 
Section 10.2, Ethics 
Review 
 
Updated to state “In Japan the head of the study 
site should submit a notification of 
direction/determination, as well as IRB written 
approval, to the Sponsor and the Principal 
Investigator before enrollment of any subject into 
the study”. 
Changes were originally made 
in Protocol Amendment 4 
(Japan) to Section 10.2.1, 
Ethics and Regulatory Review 
in Japan. 
 
Incorporates Japanese 
requirement. 
Section 10.4, Deviation 
from the Clinical Study 
Protocol 
Added a description of the procedures required in 
the event of a protocol deviation. 
 
Changes were originally made 
in Protocol Amendment 4 
(Japan) 
 
Includes additional changes 
applicable to all regions within 
a single protocol used globally. 
Section 10.7, Biological 
Specimens and Data 
Added “Samples collected in China will be 
destroyed upon publication of the Clinical Study 
Report”. 
Changes were originally made 
in Protocol Amendment 6 
(China). 
 
Includes changes applicable to 
all regions within a single 
protocol used globally. 
Section 11.5.3, Records 
Retention 
Updated to “Investigators must maintain all 
documentation related to the study for a period of 
25 years. Retention  may be shorter in accordance 
with local regulations, as long as records are 
maintained for a minimum of 2 years following 
the last marketing application approval, if 
marketing applications are filed.  
 
Added “Sites must obtain sponsor approval prior 
to destroying any records.”.  
Clarification. 

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Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Appendix D 
IgG4-RD Flare Evaluation and Criteria document 
added to protocol. 
To include the flare criteria as 
part of the protocol, because the 
definition of flare is an 
important component of the 
primary endpoint. 
Protocol Amendment 8 (Global) (30JUN2022) 
Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Title page 
Updated name and contact information for 
responsible medical officer 
Change in personnel 
Sponsors Signature Page 
Added sponsors signature page 
Change in signature collection 
process 
Summary of Changes, 
Amendment 6 and 
Amendment 7 
Dates of amendments updated in summary of 
change table 
Error correction 
Section 1 Synopsis: 
Length of Participation; 
Synopsis: Study Duration; 
Section 4.1 Study Design; 
Figure 1 
OLP lengthened from 365 days to 1,095 days; 
follow-up for 730 days after IP discontinuation; 
total maximum duration now is equal to 2,273 
days 
Collection of long-term safety 
and efficacy data, and data on 
B cell/immunoglobulin 
recovery after IP 
discontinuation 
Section 1 Synopsis: 
Interventions; Section 4.1 
Study Design 
OLP treatments clarified and expanded to include 
lengthened OLP 
Change of OLP duration 
Section 2.1.5 Supportive 
Clinical Data 
Deleted text indicating that Study 1155 is 
ongoing 
Study has been completed 
Section 2.1.5.3 Phase 2/3 
Efficacy and Safety Study 
in NMOSD 
Updated duration of Study 1155 OLP from 52 
weeks to 2 years. Added information on study 
closure and exposure. Removed reference to 
subjects ongoing in the study 
Error correction, updated status 
of the study 
Section 5.1 Inclusion 
Criteria 
Removed age of consent example ≥ 20 years in 
Japan for Criterion 1 
Decision to cite a single 
example of age of consent 
Section 5.2 Exclusion 
Criteria 
Added criterion allowing for patients with thyroid 
cancer for which surgery has been performed and 
there is no evidence of active disease for 
Criterion 4 
To accommodate this relatively 
common condition in study 
participants at the request of 
investigators 
Section 6.2.1, Table 3 
Screening Assessment 
and Procedures 
Removed “in patients who have received B cell 
depleting therapy in the 6-12 months prior to 
screening (see exclusion criterion no 5, Section 
5.2)” 
B cell count at screening is 
required for all participants, not 
just those who had recent/prior 
B cell depletion therapy 
Section 6.2.2 Schedule of 
RCP Assessments and 
Procedures 
Added language that Visit 9 (D183, a dosing 
visit) may be delayed in certain circumstances, 
with prior approval of sponsor, and added 
instructions for subjects who discontinue IP 
during the RCP. 
Allow subjects (particularly in 
China) with temporary 
COVID-related travel 
restrictions to continue 
receiving IP 

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Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 6.2.3.1 Eligibility 
for OLP  
Removed language allowing participants who 
received prohibited B cell-depleting therapy 
during the RCP to participate in the OLP, with 
some conditions.   
Due to potential safety risks, 
receipt of B cell depleting agent 
during the RCP is always 
exclusionary for OLP 
participation 
Section 6.2.3.1 Eligibility 
for OLP  
Removed text regarding follow-up after IP 
discontinuation, as this paragraph has been 
replaced by Section 6.2.4 and language added to 
6.4.1. 
Redundant text 
Section 6.2.3, Table 5 
Open-Label Period 
Assessments and 
Procedures  
Added columns for visits during years 2 and 3 of 
the OLP; Removed EDV designation from the 
Week 52 OLP visit and made the Week 156 OLP 
visit the EDV; changed physical exam at Week 
52 visit to symptom-driven physical exam; 
removed footnote related to 90-day follow up, as 
this has been replaced by the 2-year follow up 
described in Section 6.2.4. 
Accommodate the less-frequent 
visit schedule during years 2 
and 3 of the OLP, reflects 
desired changes to the physical 
exam assessments during this 
period, removes reference to 90 
day follow up 
Section 6.2.4 Safety 
Follow-Up Period 
Added new section to describe the assessments 
that take place during the 2-year safety follow-up 
period after IP discontinuation (was previously a 
90-day follow-up with EDV assessments taking 
place) 
Extended SFUP to 2 years 
(from 90 days) after IP 
discontinuation 
Section 6.3.1.3 Safety 
Assessments at Screening 
Added language that permits, in exceptional 
circumstances, the use of local lab results for 
screening purposes with prior approval by the 
Sponsor 
Mitigate risk of screen fails due 
to travel restrictions in the 
context of a failed central lab 
test(for example) 
Section 6.3.2.2 IgG4-RD 
Responder Index 
Provided language to clarify data entry timelines 
(up to 15 days after the visit) for the IgG4-RD RI, 
given that some results needed to complete the RI 
will not be available on the data of the study visit 
Guidance to investigator 
Section 6.3.4 Clinical 
Laboratory Assessments 
Added text that a local lab used for safety 
assessments must be qualified as well as licensed, 
and that prior approval from the sponsor is 
required. 
Conditions for the use of local 
labs 
Section 6.4.1 
Discontinuation of IP 
Added language to describe the 2-year follow-up 
for patients who discontinue IP (was previously a 
90-day follow-up), with reference to details in 
Section 6.2.4.   
Extended follow-up after IP 
discontinuation for certain labs 
and safety events 
Section 6.4.2 Withdrawal 
from Study 
Removed a redundant sentence 
Clarification 
Section 6.6 End of Study 
Removed completion of OLP as the time point 
for study completion and specified that the study 
will end when the last subject has completed all 
protocol-specified visits. 
Need to accommodate SFUP 
visits before study closure 
Section 7.4.2 Treatment 
Allocation for OLP 
Added text to clarify dosing interval after OLP 
D15 
OLP lengthened to 3 years 

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Protocol Section(s) 
Impacted by Change 
Change 
Reason for Change 
Section 7.5.1 Prohibited 
Medications 
Added “RCP” to clarify which study period was 
referenced by Week 52 
Clarification 
Section 8.4 Adverse 
Events of Special Interest 
Added text that AESIs must be reported within 24 
hours of awareness regardless of seriousness or 
relationship to IP 
Clarification to avoid protocol 
deviations and enhance safety 
reporting 
Section 9.3 Determination 
of Sample Size 
Added text to clarify the rationale for the blinded 
event rate assessment and to indicate that this 
analysis “may” take place rather that “will” take 
place  
Clarification of the purpose of 
the blinded event assessment, 
and description as optional. 
Section 9.5.5 Safety 
Analysis  
Added summary for SFUP 
To be consistent to the change 
of the safety follow up period 
 
Protocol Amendment 9 (Global) (15JUN2023) 
Protocol Section(s) Impacted by 
Change 
Change 
Reason for Change 
Title page 
Updated name and address of 
Sponsor 
Acquisition of Viela Bio by 
Horizon Therapeutics 
Synopsis; Section 3.2 Secondary 
Objectives and Endpoints; Section 
9.5.2.3 Flare-free Complete 
Remission; Section 9.5.3 Control 
of Type I Error 
Updated definition of flare-free 
complete remission to include either 
a Responder Index score of 0, or 
determination by the investigator that 
there is no active disease, at the 
Week 52 visit 
Expanded definition avoids 
subjects without active disease 
failing to meet this endpoint due to 
requirement for a Responder Index 
score of 2 in the absence of 
imaging 
Section 6.1.2. Availability of 
Laboratory Results 
Specified that serum Ig results will 
be made available beginning at OLP 
Week 26 
Numerous requests from 
investigators for access to this data 
to monitor patient safety (e.g., risk 
of infection).  At this point in the 
OLP, the risk of serum Ig results 
unmasking treatment assignment in 
the preceding RCP is very low. 
Section 6.2.2 Schedule of RCP 
Assessments and Procedures 
Footnote ‘d’ to Table 4 was updated  
Clarification due to elimination of 
90 day follow-up at the last 
protocol amendment (replaced by 
2 year Safety Follow-Up) 
Section 6.2.3 Schedule of OLP 
Assessments 
Vital sign assessments for dosing 
visits in years 2-3 of the OLP 
denoted with superscript ‘d’ 
Unintentionally omitted in 
previous amendment 
Section 6.2.4 Safety Follow-Up 
Period 
Visit windows added to Table 6 
Unintentionally omitted in 
previous amendment 
Section 6.3.3.3 Pregnancy; Section 
8.3 Reporting Adverse Events; 
Section 8.4 Adverse Events of 
Special Interest; Section 8.5.1 
Pregnancy; Section 8.5.2 Overdose 
or Misuse 
Updated “ICON” to “Sponsor”; 
updated safety reporting email and 
fax numbers 
Change from ICON to internal 
safety reporting process 

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Protocol Amendment 9.1 (Global) (08AUG2023) 
Protocol Section(s) Impacted by 
Change 
Change 
Reason for Change 
All 
Typographical and formatting 
corrections 
n/a 
Synopsis; Section 3.2 Secondary 
Objectives and Endpoints; Section 
9.5.2.3 Flare-free Complete 
Remission; Section 9.5.3 Control 
of Type I Error 
For the secondary endpoint “The 
proportion of subjects achieving 
flare-free complete remission at 
Week 52,” added the phrase 
“treatment-free.”. 
Distinguish this endpoint from the 
new key secondary (below).  
 
Synopsis; Section 3.2 Secondary 
Objectives and Endpoints 
Added a new key secondary 
endpoint, “The proportion of 
subjects achieving flare-free, 
corticosteroid-free complete 
remission at Week 52, defined as the 
lack of evident disease activity at 
Week 52, no AC-determined flare 
during the RCP, and no 
corticosteroid treatment for flare or 
disease control except the required 
8-week GC taper. Lack of evident 
disease activity is defined as either 
an IgG4-RD Responder Index 
(Wallace et al, 2018) score of 0, or a 
determination by the investigator 
that no disease activity is present 
based on physical, laboratory, 
pathology or other evidence.” 
This new key secondary endpoint 
reflects the importance of 
glucocorticoids as frontline 
treatment in many areas of the 
world where alternative treatments 
may not be readily available.   
Synopsis; Section 3.2 Secondary 
Objectives and Endpoints; 
Reordered the list of secondary 
endpoints so that the three key 
secondary endpoints are listed first. 
Clarity 
Section 9.5.2.3. 
Changed the analyses for the flare-
free complete remission related 
endpoints 
To be consistent to the updated 
flare-free complete remission 
related endpoints in Section 3.2. 
Section 9.5.3 Control of Type I 
Error 
Redesignated a key secondary 
endpoint (time to treatment for new 
or worsening disease activity by the 
Investigator regardless of AC 
determination of flare) as a non-key 
secondary. A new secondary (flare-
free, corticosteroid-free complete 
remission) was made a key 
secondary endpoint in its place. 
Study aims to have only three key 
secondary endpoints, and the 
endpoints were reordered based on 
clinical importance. 
 
 

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STATEMENT OF COMPLIANCE  
The study will be conducted in compliance with this clinical study protocol, Good Clinical 
Practices (GCP) as outlined by International Council for Harmonisation 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. 

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TABLE OF CONTENTS 
SUMMARY OF CHANGES TO THE PROTOCOL  ................................................................... 3 
STATEMENT OF COMPLIANCE ............................................................................................. 18 
LIST OF TABLES ....................................................................................................................... 24 
LIST OF FIGURES ..................................................................................................................... 24 
LIST OF APPENDICES .............................................................................................................. 24 
LIST OF ABBREVIATIONS ...................................................................................................... 25 
1 
SYNOPSIS ....................................................................................................................... 28 
2 
INTRODUCTION ........................................................................................................... 31 
2.1 
Background ................................................................................................................... 31 
2.1.1 
IgG4-Related Disease ................................................................................................ 31 
2.1.2 
Inebilizumab .............................................................................................................. 33 
2.1.3 
Supportive Nonclinical Data ...................................................................................... 33 
2.1.4 
Risk Assessment for Inebilizumab............................................................................. 33 
2.1.5 
Supportive Clinical Data ............................................................................................ 34 
2.1.5.1 
Phase 1 Dose-escalation Study in Systemic Sclerosis ............................................ 34 
2.1.5.2 
Phase 1 Dose-escalation Study in Multiple Sclerosis ............................................. 35 
2.1.5.3 
Phase 2/3 Efficacy and Safety Study in NMOSD ................................................... 35 
2.1.5.5 
Immunogenicity ...................................................................................................... 37 
2.2 
Study Rationale ............................................................................................................. 38 
2.3 
Study Hypotheses.......................................................................................................... 38 
3 
OBJECTIVES AND ENDPOINTS ................................................................................. 39 
3.1 
Primary Objectives and Endpoints................................................................................ 39 
3.2 
Secondary Objectives and Endpoints............................................................................ 39 
3.3 
Exploratory Objectives and Endpoints ......................................................................... 40 
4 
STUDY PLAN ................................................................................................................. 41 
4.1 
Study Design ................................................................................................................. 41 
4.2 
Dose and Treatment Regimen Rationale ...................................................................... 45 
4.3 
Rationale for Study Population ..................................................................................... 45 
4.4 
Rationale for the Primary Endpoint .............................................................................. 46 

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5 
POPULATION ................................................................................................................ 46 
5.1 
Inclusion Criteria .......................................................................................................... 46 
5.2 
Exclusion Criteria ......................................................................................................... 48 
5.3 
Rescreening Procedures ................................................................................................ 51 
5.4 
Replacement of Subjects ............................................................................................... 51 
6 
STUDY CONDUCT ........................................................................................................ 51 
6.1 
General Instructions ...................................................................................................... 51 
6.1.1 
Order of Assessments ................................................................................................ 51 
6.1.2 
Availability of Laboratory Results............................................................................. 52 
6.1.3 
Repeating Procedures After Randomization .............................................................. 52 
6.2 
Schedules of Study Assessments .................................................................................. 52 
6.2.1 
Schedule of Screening Assessments and Procedures ................................................. 52 
6.2.2 
Schedule of RCP Assessments and Procedures ......................................................... 54 
6.2.3 
Schedule of OLP Assessments and Procedures ......................................................... 58 
6.2.3.1 
Eligibility for OLP .................................................................................................. 58 
6.2.4 
Safety Follow-Up Period ........................................................................................... 62 
6.3 
Description of Study Assessments and Procedures ...................................................... 62 
6.3.1 
Screening Procedures ................................................................................................. 62 
6.3.1.1 
Informed Consent.................................................................................................... 62 
6.3.1.2 
Demographics and Baseline Characteristics ........................................................... 62 
6.3.1.3 
Safety Assessments at Screening ............................................................................ 63 
6.3.1.4 
Eligibility Committee.............................................................................................. 63 
6.3.2 
Efficacy Assessments................................................................................................. 64 
6.3.2.1 
Flare Assessment, Diagnosis, and Adjudication ..................................................... 64 
6.3.2.2 
IgG4-RD Responder Index ..................................................................................... 66 
6.3.2.3 
Cumulative Glucocorticoid Use .............................................................................. 66 
6.3.3 
Safety Assessments .................................................................................................... 68 
6.3.3.1 
Vital Signs, Body Weight, and Physical Examinations .......................................... 68 
6.3.3.2 
Electrocardiogram ................................................................................................... 68 

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6.3.3.3 
Pregnancy ................................................................................................................ 68 
6.3.3.4 
Assessment of Adverse Events ............................................................................... 69 
6.3.3.5 
Safety Laboratory Assessments .............................................................................. 69 
6.3.3.6 
Anti-drug Antibody Assessments ........................................................................... 69 
6.3.4 
Clinical Laboratory Assessments ............................................................................... 69 
6.3.4.1 
Hematology ............................................................................................................. 69 
6.3.4.2 
Serum Chemistry .................................................................................................... 69 
6.3.4.3 
Coagulation Parameters .......................................................................................... 70 
6.3.4.4 
Urinalysis ................................................................................................................ 70 
6.3.4.5 
Progressive Multifocal Leukoencephalopathy ........................................................ 70 
6.3.6 
Imaging ...................................................................................................................... 71 
6.3.7 
Immunogenicity Assessments .................................................................................... 71 
6.4 
Discontinuation of Investigational Product, Withdrawal from Study, and Loss to 
Follow-up ...................................................................................................................... 72 
6.4.1 
Discontinuation of Investigational Product ............................................................... 72 
6.4.2 
Withdrawal from Study.............................................................................................. 73 
6.4.3 
Subjects Lost to Follow-up ........................................................................................ 73 
6.5 
Study Suspension or Termination ................................................................................. 73 
6.6 
End of Study ................................................................................................................. 74 
7 
STUDY INTERVENTIONS ........................................................................................... 74 
7.1 
Description of Investigational Products ........................................................................ 74 
7.1.1 
Inebilizumab or Matched Placebo ............................................................................. 75 
7.1.1.1 
Investigational Product Inspection .......................................................................... 75 

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7.1.1.2 
Investigational Product Storage .............................................................................. 75 
7.1.1.3 
Investigational Product Dose Preparation ............................................................... 75 
7.1.1.4 
Investigational Product Dosing and Administration ............................................... 76 
7.1.1.5 
Monitoring of Dose Administration........................................................................ 77 
7.1.2 
Investigational Product Accountability ...................................................................... 77 
7.1.3 
Investigational Product Handling and Disposal ......................................................... 77 
7.2 
Additional Study Medication ........................................................................................ 78 
7.2.1 
Oral Glucocorticoid Taper ......................................................................................... 78 
7.3 
Assessment and Verification of Compliance ................................................................ 78 
7.4 
Treatment Assignment and Bias Minimization ............................................................ 78 
7.4.1 
Treatment Allocation for RCP ................................................................................... 78 
7.4.2 
Treatment Allocation for OLP ................................................................................... 78 
7.4.3 
Randomization Strategy and Procedure ..................................................................... 79 
7.4.4 
Extent and Maintenance of Blinding ......................................................................... 79 
7.4.5 
Unblinding Procedures............................................................................................... 79 
7.5 
Concomitant Medications and Treatments ................................................................... 79 
7.5.1 
Prohibited Medications .............................................................................................. 79 
7.5.2 
Permitted Glucocorticoid Uses .................................................................................. 80 
7.6 
Management of Flare of IgG4-RD During the Study ................................................... 80 
8 
SAFETY DATA COLLECTION AND REPORTING ................................................... 80 
8.1 
Definitions..................................................................................................................... 81 
8.2 
Documenting Adverse Events....................................................................................... 82 
8.3 
Reporting Adverse Events ............................................................................................ 83 
8.4 
Adverse Events of Special Interest ............................................................................... 83 
8.5 
Other Events Requiring Immediate Reporting ............................................................. 84 
8.5.1 
Pregnancy ................................................................................................................... 84 
8.5.2 
Overdose or Misuse ................................................................................................... 84 
9 
STATISTICAL CONSIDERATIONS............................................................................. 84 
9.1 
General Considerations ................................................................................................. 84 
9.2 
Statistical Hypotheses ................................................................................................... 85 
9.3 
Determination of Sample Size ...................................................................................... 85 
9.4 
Analysis Sets ................................................................................................................. 86 

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9.5 
Methods for Statistical Analyses .................................................................................. 86 
9.5.1 
Analysis of the Primary Efficacy Endpoint ............................................................... 86 
9.5.2 
Analysis of Secondary Efficacy Endpoints................................................................ 87 
9.5.2.1 
Annualized Flare Rate for Treated and AC-determined Flares During the 
RCP ......................................................................................................................... 87 
9.5.2.2 
Annualized Flare Rate for AC-determined Flares During the RCP, Whether 
or Not Treated ......................................................................................................... 87 
9.5.2.3 
Flare-free Complete Remission .............................................................................. 88 
9.5.2.4 
Time to Initiation of Treatment for IgG4-RD, Regardless of AC 
Determination of Flare ............................................................................................ 88 
9.5.2.5 
Glucocorticoid Use ................................................................................................. 89 
9.5.3 
Control of Type I Error .............................................................................................. 89 
9.5.4 
Subgroup Analyses .................................................................................................... 90 
9.5.5 
Safety Analysis .......................................................................................................... 90 
9.5.7 
Immunogenicity Analysis .......................................................................................... 91 
10 
ETHICAL CONSIDERATIONS ..................................................................................... 91 
10.1 
Good Clinical Practice .................................................................................................. 91 
10.2 
Ethics Review ............................................................................................................... 91 
10.3 
Informed Consent.......................................................................................................... 92 
10.4 
Deviation from the Clinical Study Protocol.................................................................. 92 
10.5 
Data Privacy .................................................................................................................. 93 
10.6 
Disclosure ..................................................................................................................... 93 
10.7 
Biological Specimens and Data .................................................................................... 94 
11 
OVERSIGHT ................................................................................................................... 94 
11.1 
Safety Data Monitoring Committee .............................................................................. 94 
11.2 
Quality Control and Assurance ..................................................................................... 94 
11.3 
Monitoring .................................................................................................................... 95 
11.4 
Audits ............................................................................................................................ 95 
11.5 
Records ......................................................................................................................... 96 

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11.5.1 
Data Capture and Management .................................................................................. 96 
11.5.2 
Source Documentation ............................................................................................... 96 
11.5.3 
Records Retention ...................................................................................................... 96 
12 
PUBLICATION POLICY ............................................................................................... 97 
13 
REFERENCES  ............................................................................................................... 97 
14 
APPENDICES ............................................................................................................... 101 
 
LIST OF TABLES 
Table 2 
Highly Effective Methods of Contraception for Females of Childbearing 
Potential ............................................................................................................... 48 
Table 3 
Screening Assessments and Procedures ............................................................... 52 
Table 4 
Randomized-Controlled Period Assessments and Procedures ............................ 55 
Table 5 
Open-Label Period Assessments and Procedures ................................................ 59 
Table 6 
Safety Follow Up Period Assessment and Procedures ........................................ 62 
Table 7 
Description of Investigational Products and RCP Dosing ................................... 74 
Table 8 
Infusion Rate for Investigational Product after Dilution in a 250 mL IV 
Bag ....................................................................................................................... 76 
Table 9 
Glucocorticoid Taper Schedule (Randomized-controlled Period) ....................... 78 
 
LIST OF FIGURES 
Figure 1 
Study Design ........................................................................................................ 44 
Figure 2 
Flare Assessment and Adjudication Process ........................................................ 64 
 
LIST OF APPENDICES 
APPENDIX A 
STUDY-SPECIFIED OPPORTUNISTIC INFECTIONS THAT MEET 
EXCLUSION CRITERIA AND REQUIRE DISCONTINUATION OF IP 
APPENDIX B 
GUIDANCE FOR ANAPHYLAXIS DIAGNOSIS 
APPENDIX C 
INVESTIGATOR’S AGREEMENT 
APPENDIX D 
IGG4-RD FLARE EVALUATION AND CRITERIA 
 

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LIST OF ABBREVIATIONS  
Abbreviation or special term 
Definition 
AC 
Adjudication Committee 
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 
ANCA 
anti-neutrophil cytoplasmic antibodies 
anti-HBc 
hepatitis B core antibody 
AST 
aspartate aminotransferase 
AQP4-IgG 
antibodies against aquaporin-4 
β-hCG 
serum human chorionic gonadotropin  
CD 
cluster of differentiation 
CDM 
Clinical Data Management 
CI 
confidence interval 
CRO 
contract research organization 
CT 
computed tomography 
CTCAE 
Common Terminology Criteria for Adverse Events 
DMARD 
disease-modifying anti-rheumatic drug 
DMP 
Data Management Plan 
EC 
Eligibility Committee 
ECG 
electrocardiogram 
eCRF 
electronic case report form 
EDV 
early discontinuation visit 
eGFR 
estimated glomerular filtration rate 
EU 
European Union 
EULAR 
European League Against Rheumatism 
FDA 
Food and Drug Administration 
GC 
glucocorticoid 
GCP 
Good Clinical Practice 
GDPR 
General Data Protection Regulation 

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Abbreviation or special term 
Definition 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HPF 
high power field 
HR 
hazard ratio 
huCD19 Tg 
human CD19 transgenic 
IB 
Investigator’s Brochure 
ICF 
informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
Ig 
immunoglobulin 
IgG4-RD 
immunoglobulin G4-related disease 
IP 
investigational product 
IRB 
Institutional Review Board 
IRR 
infusion-related reaction 
IV 
intravenous(ly) 
IXRS 
interactive voice/web response system 
JCV 
John Cunningham virus 
LLN 
lower limit of normal 
LSMEANS 
least square means 
mAb 
monoclonal antibody(ies) 
MRI 
magnetic resonance imaging 
NOAEL 
no-observed-adverse-effect level 
NMOSD 
neuromyelitis optica spectrum disorder 
OLP 
open-label period 
PET 
positron emission tomography 
PI 
Principal Investigator 
PML 
progressive multifocal leukoencephalopathy 
RCP 
randomized-controlled period 
RI 
Responder Index 
SAE 
serious adverse event 
SAP 
statistical analysis plan 
SAR 
suspected adverse reaction 
SC 
subcutaneous 
SDMC 
Safety Data Monitoring Committee 

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Abbreviation or special term 
Definition 
SID 
subject identification number 
SFUP 
Safety Follow-Up Period 
TB 
tuberculosis 
TBL 
total bilirubin 
TEAE 
treatment-emergent adverse event 
TESAE 
treatment-emergent serious adverse event 
ULN 
upper limit of normal 
US 
United States 
WBC 
white blood cell count 
 

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1 
SYNOPSIS  
Title 
A Phase 3, Randomized, Double-blind, Multicenter, Placebo-Controlled Study of 
Inebilizumab Efficacy and Safety in IgG4 Related Disease 
Short Title 
MITIGATE 
Phase 
3 
Study Design 
Randomized, double-blind, placebo-controlled, parallel-cohort study 
Rationale 
There are currently no medicinal products approved for the treatment of immunoglobulin 
G4-related disease (IgG4-RD), a rare disease. The majority of cases follow a relapsing 
course that can lead to permanent tissue damage with attendant morbidity and potential 
mortality. Glucocorticoids (GCs) are widely and effectively used for acute treatment of 
initial disease activity and of recurrent episodes (flares), but GCs do not prevent recurrence 
of active disease during their taper or after their discontinuation. Moreover, GCs are 
associated with substantial toxicity. Thus, there is a high unmet medical need for therapies 
that prevent disease recurrence and limit GC exposure. The pathogenesis of IgG4-RD 
suggests that B-cell depletion may be an effective avenue for therapeutic intervention. An 
important role for B cells, particularly plasmablasts and plasma cells, in the pathogenesis of 
the disease appears likely. The anti-CD19 B cell-depleting activity of inebilizumab suggests 
that it may provide benefit as treatment for IgG4-RD. This study aims to define the efficacy 
and safety of inebilizumab for the prevention of flare of IgG4-RD. 
Target 
Population 
Male or female adults, who have reached the age of consent in the applicable region, who 
have recently active IgG4-RD (initial diagnosis or flare) that requires new or ongoing 
treatment, are at high risk of future flare (as evidenced by multi-organ disease involvement), 
and meet the 2019 American College of Rheumatology/European League Against 
Rheumatism (ACR/EULAR) IgG4-RD classification criteria. 
Number of 
Subjects 
Approximately 160 subjects will be randomized and dosed in a 1:1 ratio to 2 treatment 
groups; approximately 80 subjects to each treatment group. Enrollment may be increased to 
a maximum of 200 subjects total based on blinded event-rate analysis. 
Length of 
Participation 
Screening period: Up to 28 days 
Randomized-control period (RCP): 365 (± 7) days 
Optional open-label period (OLP): 1,095 (+ 10) days 
Safety Follow-Up period (SFUP) after investigational product (IP) discontinuation:  730 
days 
Total maximum duration of study participation: 2,273 days 
Interventions 
RCP: Blinded treatment on Day 1, Day 15, and Week 26: 
x Inebilizumab group: Inebilizumab 300 mg intravenous (IV) 
x Placebo group: IV placebo 
Both groups: Oral prednisone (or equivalent) tablets from Day 1 to the end of Week 8 
(tapering dose regimen: 2 weeks each at 20, 15, 10, and 5 mg/day of prednisone or 
equivalent, open-label, from commercial supply).  
Optional OLP: Open-label inebilizumab 300 mg IV on Day 1, blinded inebilizumab 300 
mg or matching placebo on Day 15 (depending on assigned RCP treatment), and then a 
single inebilizumab 300 mg IV infusion every 6 months for the duration of the OLP. 
Primary 
Objectives and 
Primary 
Endpoints 
Primary objective: 
To evaluate the efficacy of inebilizumab in reducing the risk of a disease flare in patients 
with IgG4-RD. 

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Primary endpoint: 
Time to disease flare, defined as the time in days from Day 1 (dosing) to the date of the first 
treated and Adjudication Committee (AC)-determined IgG4-RD flare within the 52-week 
RCP. The date of disease flare is defined as the date of initiation of any flare treatment (new 
or increased GC treatment, other immunotherapy, or interventional procedure) deemed 
necessary by the Investigator for the flare. 
Secondary 
Objectives and 
Corresponding 
Endpoints 
Secondary objectives: 
x To evaluate the safety and tolerability of inebilizumab in patients with IgG4-RD. 
x To evaluate the effect of inebilizumab on other measures of disease activity. 
Secondary endpoints: 
x Annualized flare rate for treated and AC-determined flares during the RCP. 
x The proportion of subjects achieving flare-free, treatment-free complete remission at 
Week 52, defined as the lack of evident disease activity at Week 52, no AC-determined 
flare during the RCP, and no treatment for flare or disease control except the required 8-
week GC taper. Lack of evident disease activity is defined as either an IgG4-RD 
Responder Index (Wallace et al, 2018) score of 0, or a determination by the investigator 
that no disease activity is present based on physical, laboratory, pathology or other 
evidence. 
x The proportion of subjects achieving flare-free, corticosteroid-free complete remission at 
Week 52, defined as the lack of evident disease activity at Week 52, no AC-determined 
flare during the RCP, and no corticosteroid treatment for flare or disease control except 
the required 8-week GC taper. Lack of evident disease activity is defined as either an 
IgG4-RD Responder Index (Wallace et al, 2018) score of 0, or a determination by the 
investigator that no disease activity is present based on physical, laboratory, pathology or 
other evidence. 
x Time to initiation of first treatment (medication or procedure) for new or worsening 
disease activity by the Investigator within the RCP, regardless of AC determination of 
flare. 
x Annualized flare rate for AC-determined flares, whether or not treated, during the RCP. 
x Glucocorticoid use, calculated as the cumulative GC dose taken for the purpose of 
IgG4-RD disease control during the RCP. 
x Incidence of treatment emergent adverse events (TEAEs), serious TESAEs, and TEAEs 
of special interest (AESIs) during the 52-week RCP and during the OLP. 
x The incidence of ADAs directed against inebilizumab during the RCP. 
Exploratory 
Objectives and 
Corresponding 
Endpoints 

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Number of Sites 
Approximately 60-80 sites in approximately 20 countries 
Study Duration 
Estimated total study duration is approximately  
x 1,526 days (4.2 years) for screening, randomized controlled period, and open-label 
period 
x Up to an additional 730 days (2 years) for safety follow-up in patients who do not 
participate in the OLP or who discontinue treatment during the OLP 
 
Data Monitoring 
Committee 
An external, independent Safety Data Monitoring Committee will evaluate safety data at 
regular intervals throughout the study and make recommendations to the Sponsor as needed. 
The Committee will not perform a futility analysis or consider early study completion for 
efficacy. 
 

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2 
INTRODUCTION  
2.1 
Background  
2.1.1 
IgG4-Related Disease  
Clinical Presentation and Flares 
Immunoglobulin G4-related disease (IgG4-RD) is a recently described chronic, 
relapsing -remitting, immune-mediated fibroinflammatory disorder that can affect virtually every 
organ system, with a predilection for salivary glands, orbits, lacrimal glands, pancreas, biliary 
tree, lungs, kidneys, aorta and retroperitoneum, meninges, and thyroid gland (Stone et al, 2012; 
Kamisawa et al, 2015). Pancreato-hepatobiliary disease is present in approximately half of cases, 
and disease is present in at least 2 organs in approximately three-fourths of patients (Wallace et 
al, 2019a).  
Organ involvement generally manifests as swelling, presence of a mass, or organ-specific 
consequences of tissue damage. The clinical presentation is generally subacute, and most patients 
are neither acutely ill nor febrile; however, weight loss can be significant, particularly in the 
setting of exocrine pancreatic failure in IgG4-related autoimmune pancreatitis. Multi-organ 
involvement is common either at baseline or after progression over time (Umehara et al, 2017). 
The course depends in part on the predominant organ affected. For example, IgG4-RD-related 
cholangitis can lead to hepatic failure within months; autoimmune pancreatitis leads to diabetes 
mellitus, exocrine insufficiency, or both; tubulointerstitial nephritis can lead to renal failure; and 
aortitis can lead to aneurysms and dissections. 
Symptomatic patients with IgG4-RD require treatment. Glucocorticoids (GCs) are the 
cornerstone of therapy, and rapid GC responsiveness, particularly for the proliferative subtype, is 
a hallmark of the disease (Stone et al, 2012; Abraham and Khosroshahi 2017; Zhang and Stone, 
2019). Treatment has not been fully standardized, but international consensus guidelines 
recommend 2-4 weeks of induction with 0.6 mg/kg of prednisone equivalent (~30-40 mg/day) 
tapering over 8-12 weeks (Khosroshahi et al, 2015). Despite remission occurring in the majority 
of patients, disease flares requiring re-institution of therapy are typical. Patients with more 
fibrosis in the affected organ tend to have worse clinical responses to treatment; in contrast to 
proliferative disease, fibrotic disease tends not to improve with treatment.  
Steroid-sparing drugs such as disease-modifying anti-rheumatic drugs (DMARDs) generally are 
not used alone for the induction of remission, and their efficacy in IgG4-RD has not been 
established (Zhang and Stone, 2019). B-cell depletion with the cluster of differentiation 
(CD)20-targeted agent rituximab has demonstrated effectiveness in case series and in a small, 
open-label study in which 97% of 30 subjects had some disease response, and almost half were 
in complete remission at 6 months, with 86% of these in complete remission at one year 
(Carruthers et al, 2015). Reponses were rapid, and serum IgG4 decline was observed. 
Histopathology and Pathogenesis 
Manifestations of IgG4-RD are linked by a common histopathology: a dense lymphoplasmacytic 
infiltrate containing IgG4-positive (IgG4+) plasma cells, storiform fibrosis, and obliterative 
phlebitis, often accompanied by tissue eosinophilia (Deshpande et al, 2012). The inflammatory 

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infiltrate is a mixture of T and B lymphocytes, with B cells typically organized in germinal 
centers. Although all Ig subclasses may be present, IgG4 predominates, and the IgG4+:IgG+ 
plasma cell ratio is an important feature.  
There has been recent progress in understanding the pathophysiological mechanisms responsible 
for IgG4-RD. Limited genetic studies suggest predisposition based on human leukocyte antigen 
serotype and polymorphisms in some genes involved in immunity (Stone et al, 2012; Terao et al, 
2019). Dysregulated follicular helper T cells and cytotoxic CD4+ T cells may play a role in 
disease initiation, through secretion of profibrotic cytokines and other proteins, as well as the 
induction of IgG4 class switching and plasmablast expansion (Abraham and Khosroshahi, 2017; 
Kamekura et al, 2019; Mattoo et al, 2017; Perugino et al, 2017). In addition, B cells are 
important drivers of the disease via antibody-independent (eg, secretion of pro-inflammatory and 
pro-fibrotic factors) and antibody-dependent (eg, T cell interactions) mechanisms (Della-Torre et 
al, 2019; Pillai et al, 2020, Lanzillotta et al, 2016). A critical role for B cells in the pathogenesis 
of IgG4-RD is supported by data from small clinical trials and observational studies that show 
reduced disease flares in response to rituximab, an anti-CD20 antibody that depletes B cells 
(Carruthers et al, 2015; Lanzillotta et al, 2016). 
The IgG4 antibody produced by plasmablasts and plasma cells in IgG4-RD is probably not 
pathogenic. However, there is a general correlation between IgG4 serum concentration and 
disease severity/extent; most patients have elevated IgG4 levels that decline with clinical 
response to GC treatment (Huggett et al, 2014). Recently, IgG reactivity against self-antigens, 
including laminin 511 and galectin-3 of the extracellular matrix, were reported to be involved in 
the pathogenesis of IgG4-RD. Although these antibodies may not be specific to IgG4-RD, 
patients with IgG4 antibodies against at least 2 autoantigens were reported to have had more 
severe disease (Liu et al, 2019; Umehara et al, 2019). 
Epidemiology 
The epidemiology of IgG4-RD, given its recent categorization and variable presentation, remains 
uncertain. The majority of patients are men, and most are older than 50 years of age. In a study 
from Japan, the incidence of IgG4-RD was estimated to be 2.8-10.8/million population, with a 
median age of onset of 58 years (Umehara et al, 2012). 
Unmet Need 
To date, no randomized prospective controlled studies have been performed for this disease, and 
no approved therapy is available. IgG4-RD is associated with substantial morbidity and 
mortality, but there is no established therapy other than GCs for an acute flare (Huggett et al, 
2014; Evans et al, 2018; Zhang and Stone, 2019). Although GCs are widely and effectively used 
for treatment of initial disease and of flare, they are associated with substantial toxicity that 
limits their use as long-term therapy. Disease flares also occur in many patients either during the 
GC taper or after GC discontinuation. Patients also continue to relapse on the off-label steroid-
sparing immunosuppressive medications used by some physicians to manage patients with 
IgG4-RD (Omar et al, 2019); thus, there is a high unmet medical need for more effective 
therapies for prevention of flare in this patient population. Patients need a treatment that will 
more effectively control their disease and avoid GC toxicity (Omar et al, 2019). 

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2.1.2 
Inebilizumab  
Inebilizumab (formerly MEDI-551) is a humanized, affinity-optimized, afucosylated IgG1 kappa 
monoclonal antibody (mAb) known as 16C-aFuc that binds to the B-cell specific surface antigen 
CD19, resulting in depletion of CD19+ B cells. Inebilizumab is glycoengineered by expression 
of mAb 16C4 in a fucosyltransferase-deficient Chinese hamster ovary producer cell line (BioWa 
Potelligent® Technology), which generates a homogenously afucosylated antibody with 
enhanced antibody-dependent cellular cytotoxicity. In contrast to the anti-CD20 mAb rituximab, 
inebilizumab does not mediate complement-dependent cytotoxicity but eliminates B cells via 
antibody-dependent cellular cytotoxicity and antibody-medicated cellular phagocytosis 
mechanisms (Herbst et al, 2010). 
2.1.3 
Supportive Nonclinical Data  
As inebilizumab specifically recognizes human CD19 and has poor or no cross-reactivity to 
CD19 from nonhuman primates, rabbits, or rodents, the human CD19 transgenic (huCD19 Tg) 
mouse was selected as the relevant animal model. In huCD19 Tg mice, inebilizumab selectively 
targeted and depleted B cells (Study ONC551-0010). Also in the huCD9 Tg mouse, 2 single and 
3 repeated dose intravenous (IV) toxicology studies (one month, 3 months, and 6 months), and a 
repeated dose subcutaneous (SC) toxicology study found the highest doses tested, 50 mg/kg as a 
single dose and 30-36.6 mg/kg/week, to be the no-observed-adverse-effect level (NOAEL). 
An embryo-fetal development study (Study AAO00141) demonstrated a reduction in fertility 
index and the number of pregnant mice per cohabitating mice; however, there was no 
inebilizumab impact on embryo/fetal development. In fetal livers, the site of B-cell development 
in mice, there was a difference in huCD19+ B cells between progeny of dosed and undosed mice, 
suggesting inebilizumab crossed the placenta and depleted fetal B cells. In a pre- and post-natal 
development study (Study 62509), the NOAEL for F0 maternal, F1 systemic and reproductive, 
and F2 embryo/fetal developmental toxicity was the highest tested dose, 30 mg/kg. F1 pups had 
a diminished response to antigen challenge after B cells repopulated and the NOAEL for F1 
development and immunotoxicity could not be determined.  
For details, refer to the inebilizumab Investigator’s Brochure (IB). 
2.1.4 
Risk Assessment for Inebilizumab  
The identified risks of inebilizumab are infusion-related reaction (IRR), arthralgia, neutropenia, 
and reduced immunoglobulin levels. 
x Infusion reactions can include headache, nausea, somnolence, dyspnea, fever, myalgia, 
rash, or other symptoms. Most observed infusion reactions were mild to moderate in 
severity; however, rare, serious infusion reactions were observed. Potential risks 
associated with administration of inebilizumab are infection, redness, swelling, pain, and 
induration at the administration site. Prior to each IV infusion (inebilizumab or placebo) 
subjects will receive prophylaxis with IV methylprednisolone, oral diphenhydramine, and 
oral acetaminophen, or equivalent(s) to reduce the risk or severity of IRR. 
x The proportion of subjects with arthralgia was numerically higher in the inebilizumab 
group than the placebo group during the RCP of Study CD-IA-MEDI-551-1155. There is 

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no known biological mechanism for a potentially higher rate of arthralgia with 
inebilizumab. 
x Neutropenia was reported at low frequency and was generally transient. Neutropenia has 
been observed with other B cell depleting monoclonal antibodies (rituximab, 
ocrelizumab). 
x Immunoglobulin levels have been observed to decrease with inebilizumab use, most 
significantly for IgM. Reduction in Ig levels has been observed with other B cell 
depleting monoclonal antibodies (rituximab, ocrelizumab) and may be a class effect. 
Other important potential risks for inebilizumab are based on mechanism of action, nonclinical 
data, and clinical data. They include: 
x Serious infections 
x Progressive multifocal leukoencephalopathy (PML) 
x Cytopenia 
x Hypersensitivity (including anaphylaxis and serious skin reactions) 
x Immune complex disease 
The safety of use of inebilizumab during pregnancy is unknown; however, inebilizumab is a 
mAb, and immunoglobulins are known to cross the placental barrier. Transient peripheral B-cell 
depletion and lymphocytopenia have been reported in infants born to mothers exposed to other 
B cell-depleting antibodies during pregnancy. One uncomplicated pregnancy occurred in an 
inebilizumab-exposed subject who discontinued treatment. There were no birth defects in the 
baby. There are no data on the presence of inebilizumab in human breast milk, but lactating 
women should be advised not to breastfeed during treatment and for at least 6 months after the 
last dose.  
For a complete summary of risks for inebilizumab, refer to the IB. 
2.1.5 
Supportive Clinical Data  
Inebilizumab has been investigated in both non-oncology and oncology clinical studies. In 
non-oncology studies, inebilizumab has been investigated in subjects with systemic sclerosis 
(Study MI-CP200), multiple sclerosis (Study CD-IA-MEDI-551-1102), and neuromyelitis optica 
spectrum disorder (NMOSD; Study CD-IA-MEDI-551-1155 [Study 1155]). 
2.1.5.1 
Phase 1 Dose-escalation Study in Systemic Sclerosis  
The first clinical study of inebilizumab in subjects with systemic sclerosis was MI-CP200, a 
phase 1, randomized, double-blind, placebo-controlled study evaluating the safety and 
tolerability of escalating single IV doses of inebilizumab (0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg) in 
28 adult subjects with systemic sclerosis who had at least moderate skin thickening in an area 
suitable for repeat biopsy. This study is complete; 4 subjects received placebo and 24 subjects 
received inebilizumab (Schiopu et al, 2016). 
In Study MI-CP200, one subject in the 3.0 mg/kg inebilizumab dose group died during the 
course of the study following renal crisis; the underlying cause of the terminal renal insufficiency 
was assessed as related to progression of systemic sclerosis. The most frequent (incidence > 15% 
of subjects) treatment-emergent adverse events (TEAEs) in the total inebilizumab group were 

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nausea, arthralgia, pain in extremity, fatigue, and IRR, with the majority of TEAEs being 
Grade 1 (mild) or Grade 2 (moderate) in severity. Treatment-emergent serious adverse events 
(TESAEs) occurred in 6 of 24 subjects (25.0%) in the inebilizumab group, with no events 
occurring in more than one subject. Two TESAEs (supraventricular tachycardia and subclavian 
vein thrombosis) were assessed by the Investigator as being possibly related to inebilizumab. 
2.1.5.2 
Phase 1 Dose-escalation Study in Multiple Sclerosis  
Study CD-IA-MEDI-551-1102 was a phase 1, multicenter, multinational, randomized, masked, 
placebo-controlled, dose-escalation study evaluating the safety and tolerability of IV or SC doses 
of inebilizumab in 28 adult subjects with relapsing forms of multiple sclerosis. A total of 
28 subjects were enrolled in the study to receive 2 IV administrations of inebilizumab (30, 100, 
or 600 mg) or placebo on Day 1 and Day 15, or a single SC dose of inebilizumab (60 or 300 mg) 
or placebo over a 24-week period (Days 1-169) with long-term follow-up for all subjects for 
B-cell recovery starting after Day 169 (Agius et al, 2019). This study has been completed, with 
7 subjects receiving placebo and 21 subjects receiving inebilizumab. Dosing continued through 
the highest doses tested (600 mg IV and 300 mg SC), and inebilizumab was reasonably tolerated 
at all doses tested. The most frequent TEAEs (incidence ≥ 14% of subjects) in the total 
inebilizumab group were IRR, nasopharyngitis, upper respiratory infection, blood pressure 
increased, pyrexia, urinary tract infection, and urinary tract inflammation, with the majority of 
TEAEs being Grade 1 or Grade 2 in severity. Injection-related reactions occurred in 2 of 
5 subjects (40.0%) in the IV placebo group and 6 of 15 subjects (40.0%) in the total IV 
inebilizumab group, which all were Grade 1 or 2 in severity and assessed as related to the 
investigational product (IP). IRRs occurred in none of the subjects in the SC placebo group and 
in 1 of 6 subjects (16.7%) in the total SC inebilizumab group. One of 7 subjects (14.3%) in the 
placebo group and 3 of 21 subjects (14.3%) in the inebilizumab groups had at least one TESAE. 
One subject in the 300 mg SC cohort had a TESAE of pyrexia that was related to IP.  
The mean number of cumulative new gadolinium-enhancing magnetic resonance imaging (MRI) 
lesions by Week 24 was lower in the inebilizumab group than in the placebo group as was the 
mean number of new or newly enlarged T2 MRI lesions. 
2.1.5.3 
Phase 2/3 Efficacy and Safety Study in NMOSD  
Study 1155 is a randomized, double-masked, placebo-controlled study with an open-label 
extension, evaluating the efficacy and safety of IV inebilizumab in adult subjects with NMOSD 
who are seropositive and seronegative for autoantibodies against aquaporin-4 (AQP4-IgG) (Cree 
et al, 2019). In this study, inebilizumab (300 mg) or placebo was administered as a fixed IV dose 
on Days 1 and 15 (ie, 300 mg on Day 1 and 300 mg on Day 15) of a 28-week randomized-
controlled period (RCP). Thereafter, 300 mg IV inebilizumab was administered every 26 weeks 
in an open-label extension for at least 2 years. Enrollment into the study was stopped in 
September 2018 following a recommendation from the Independent Data Monitoring 
Committee. The Sponsor accepted the recommendation, closed study enrollment, and offered all 
remaining RCP subjects the option to enroll in the OLP. The primary endpoint of the study was 
the time (days) from Day 1 to onset of an Adjudication Committee (AC)-determined NMOSD 
attack on or before Day 197. The study was closed in November 2020, with a total of 225 

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subjects having received inebilizumab for a median duration of 3.2 years (maximum duration 5.4 
years; 730.4 person-years total exposure). 
In total, 231 subjects were randomized in Study 1155, including 18 AQP4-IgG seronegative 
subjects (7.8%) and 213 AQP4-IgG seropositive subjects (92.2%); 230 subjects overall were 
included in the intent-to-treat population. A total of 223 subjects (97.0%) completed the RCP. 
The primary endpoint of this study was met. In both the AQP4-IgG seropositive and total 
intent-to-treat populations, treatment with inebilizumab statistically significantly reduced the risk 
of an AC-determined NMOSD attack as compared to treatment with placebo. During the RCP, 
the hazard ratio (HR) of AC-determined attacks with inebilizumab treatment relative to placebo 
was 0.227 (95% confidence interval [CI]: 0.1214, 0.4232) for the AQP4-IgG seropositive 
population and was 0.272 (95% CI: 0.1496, 0.4691) for the total intent-to-treat population; 
p-value: < 0.0001 for each comparison). Additionally, a statistically significant improvement 
with inebilizumab compared with placebo was demonstrated for 3 of 4 key secondary endpoints: 
worsening from baseline in Expanded Disability Severity Scale, cumulative number of total 
active MRI lesions, and cumulative number of inpatient hospitalizations. One key secondary 
endpoint, low-contrast visual acuity, did not demonstrate a significant treatment effect with 
inebilizumab. 
In Study 1155, repeated doses of inebilizumab in the RCP and OLP were well-tolerated. The 
incidence of TEAEs was balanced across the treatment groups during randomized treatment 
(71.8% in the inebilizumab group and 73.2% in the placebo group). Among subjects treated with 
inebilizumab across both the randomized and open-label portions of the study, the most common 
TEAEs by preferred term were urinary tract infection (19.6%), nasopharyngitis (12.9%), IRRs 
(11.6%), and arthralgia (10.2%). During the RCP, arthralgia incidence was higher in the 
inebilizumab group than the placebo group (9.8% vs 3.6%) but was lower in the OLP than in the 
RCP (4.3% for inebilizumab/inebilizumab subjects and 5.9% for placebo/inebilizumab subjects). 
No events of anaphylaxis or hypersensitivity were observed. 
During the RCP, the proportion of subjects with IRR was similar in the inebilizumab and placebo 
groups (9.2% and 10.7%, respectively). All IRRs were Grade 1 or Grade 2, and the most 
common symptoms were headache and nausea. Infusion reactions were most common with the 
first infusion but were observed during subsequent infusions. 
The proportion of subjects with a TEAE in the Infections and Infestations System Organ Class 
was similar in the 2 groups during the RCP (37.9% and 41.1% in the inebilizumab and placebo 
groups, respectively); serious infections occurred in 3 subjects (1.7%) in the inebilizumab group 
and 2 subjects (3.6%) in the placebo group. The most common infections reported by 
inebilizumab-treated subjects in the RCP and OLP included urinary tract infection (19.6%), 
nasopharyngitis (12.9%), upper respiratory tract infection (7.6%), and influenza (6.2%). 
Laboratory changes observed included cytopenias: leukopenia, lymphopenia, and neutropenia 
were observed more frequently in the inebilizumab group than in the placebo group. Neutropenia 
(counts between 0.5-1.0 × 109/L) occurred in 2.3% vs 0% of subjects who received inebilizumab 
or placebo, respectively, during the RCP. Consistent with the mechanism of action of the drug, 
lymphocyte counts were lower in the inebilizumab group than the placebo group during the RCP: 
1.7% of inebilizumab-treated subjects had lymphopenia vs 0% in the placebo group. 

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Immunoglobulin levels decreased with inebilizumab use, most significantly for IgM. At the end 
of the 6.5-month randomized period, the proportions of subjects with levels < lower limit of 
normal (LLN) were greater in placebo than in inebilizumab-treated subjects for IgE (13% 
placebo and 11% inebilizumab) and IgG (9.4% placebo and 3.8% inebilizumab), and greater in 
inebilizumab than in placebo for IgA (3.1% in placebo and 9.8% in inebilizumab), and IgM 
(16% placebo and 29% inebilizumab). 
During the RCP, TESAEs were reported in 4.6% and 8.9% of subjects in the inebilizumab and 
placebo groups, respectively. There were no deaths during the RCP of the study. There were 
2 deaths during the OLP: one subject died from complications of NMOSD and another died of 
pneumonia in the context of new brain lesions considered to be probably due to PML; however, 
a definitive diagnosis was not established, and the differential diagnosis included PML, acute 
disseminated encephalomyelitis, or an atypical NMOSD attack. 
2.1.5.5 
Immunogenicity  
In Study MI-CP200, ADA to inebilizumab were detected in 4/24 subjects (16.7%) treated with 
inebilizumab (1 each in 0.3, 1.0, 3.0, and 10.0 mg/kg dose cohort). None of the subjects treated 
with placebo (N = 4) tested positive for the presence of ADA at any time throughout the study. 

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No apparent impact on B-cell depletion was observed in ADA-positive subjects following a 
single dose of inebilizumab.  
In Study 1102, none of the 28 subjects in the study (21 inebilizumab-treated and 7 placebo) 
tested positive for the presence of ADA. 
In the RCP of Study 1155, the prevalence of ADA-positive subjects (ADA positive at baseline or 
at any time during the RCP) was 9.8% of the inebilizumab group and 14.3% of the placebo 
group. Treatment-emergent ADA (post-baseline positive only) were observed in 2.9% and 7.1% 
of inebilizumab and placebo-treated subjects, respectively. Overall, there was no marked 
difference in the mean PK profiles of inebilizumab in ADA-positive and ADA-negative subjects. 
Additionally, there was no apparent effect of ADA on the efficacy of inebilizumab. 
2.2 
Study Rationale  
This study will establish the safety and tolerability of inebilizumab monotherapy in IgG4-RD 
and its ability to reduce the risk of disease flares. There are currently no medicinal products 
approved for the treatment of IgG4-RD. The majority of cases follow a relapsing course that can 
lead to permanent tissue damage with attendant morbidity and potential mortality (Huggett et al, 
2014). Glucocorticoids are widely and effectively used for treatment of initial disease and of 
flare, but they do not prevent recurrence of active disease after their discontinuation and are 
associated with substantial toxicity. Patients also continue to relapse on the off-label 
steroid-sparing immunosuppressive medications used by some physicians to manage patients 
with IgG4-RD (Omar et al, 2019); thus, there is a high unmet medical need for more effective 
therapies in this patient population.  
The pathogenesis of IgG4-RD suggests that B-cell depletion may be an effective avenue for 
therapeutic intervention. An important role for B cells, particularly plasmablasts and plasma 
cells, in the pathogenesis of the disease appears likely (Mattoo et al, 2014; Wallace et al, 2015; 
Cassione et al, 2017; Lin et al, 2017; Perugino et al, 2017; Lanzillotta et al, 2018), and 
therapeutic depletion of B cells with rituximab reduces disease-relevant biomarkers (Della-Torre 
et al, 2015) and appears to have clinical benefit in uncontrolled, retrospective and prospective 
clinical studies (Carruthers et al, 2015; Ebbo et al, 2017; Majumder et al, 2018). The anti-CD19 
B cell-depleting activity of inebilizumab suggests that it may provide benefit as treatment for 
IgG4-RD. This study aims to define the efficacy and safety of inebilizumab for the prevention of 
flares of this rare disease. 
In addition, the potential of inebilizumab for minimizing GC exposure could limit the 
well-known adverse effects of GCs on bone, skin, muscle, adrenal gland, and eyes, and GC 
association with weight gain, diabetes, hypertension, and neuropsychiatric effects (Miloslavsky 
et al, 2017). 
Existing
safety data from the development of inebilizumab in 
non-oncology indications are relevant to the IgG4-RD population, providing a pharmacologically 
active dose regimen with an acceptable safety profile for use in this phase 3 study. 
2.3 
Study Hypotheses  
Primary Hypothesis: 

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By depleting CD19+ B cells, including plasmablasts and some plasma cells, inebilizumab will 
reduce IgG4-RD activity by preventing disease flares. 
Secondary Hypotheses: 
x Inebilizumab will reduce disease activity in patients with IgG4-RD as assessed by 
additional measures of efficacy. 
x Inebilizumab will be well-tolerated and have an acceptable safety profile in patients with 
IgG4-RD. 
3 
OBJECTIVES AND ENDPOINTS  
3.1 
Primary Objectives and Endpoints  
Primary Objective 
To evaluate the efficacy of inebilizumab in reducing the risk of a disease flare in patients with 
IgG4-RD. 
Primary Endpoint 
Time to disease flare, defined as the time in days from Day 1 (dosing) to the date of the first 
treated and AC-determined IgG4 RD flare within the 52-week RCP. The date of disease flare is 
defined as the date of initiation of any flare treatment (new or increased GC treatment, other 
immunotherapy, or interventional procedure) deemed necessary by the Investigator for the flare. 
3.2 
Secondary Objectives and Endpoints  
Secondary Objectives 
x To evaluate the safety and tolerability of inebilizumab in patients with IgG4-RD. 
x To evaluate the effect of inebilizumab on other measures of disease activity. 
Secondary Endpoints 
x Annualized flare rate for treated and AC-determined flares during the RCP. 
x The proportion of subjects achieving flare-free, treatment-free complete remission at 
Week 52, defined as the lack of evident disease activity at Week 52, no AC-determined 
flare during the RCP, and no treatment for flare or disease control except the required 8-
week GC taper. Lack of evident disease activity is defined as either an IgG4-RD 
Responder Index (Wallace ) score of 0, or a determination by the investigator that no 
disease activity is present based on physical, laboratory, pathology or other evidence. 
x The proportion of subjects achieving flare-free, corticosteroid-free complete remission at 
Week 52, defined as the lack of evident disease activity at Week 52, no AC-determined 
flare during the RCP, and no corticosteroid treatment for flare or disease control except 
the required 8-week GC taper. Lack of evident disease activity is defined as either an 
IgG4-RD Responder Index (Wallace ) score of 0, or a determination by the investigator 
that no disease activity is present based on physical, laboratory, pathology or other 
evidence. 

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x Time to initiation of first treatment (medication or procedure) for new or worsening 
disease activity by the Investigator within the RCP, regardless of AC determination of 
flare. 
x Annualized flare rate for AC-determined flares, whether or not treated, during the RCP. 
x Glucocorticoid use, calculated as the cumulative GC dose taken for the purpose of 
IgG4-RD disease control during the RCP. 
x Incidence of TEAEs, TESAEs, and treatment-emergent adverse events of special interest 
(AESIs) during the 52-week RCP and during the OLP. 
x The incidence of ADAs directed against inebilizumab during the RCP. 
3.3 
Exploratory Objectives and Endpoints  

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4 
STUDY PLAN  
4.1 
Study Design  
This is a multicenter, randomized, double-blind (Investigator, subject, and Sponsor will be 
blinded to treatment assignment), placebo-controlled, parallel-cohort study to evaluate the 
efficacy and safety of inebilizumab for prevention of disease flare in adults with active IgG4-RD 
who are at high risk of recurrent flare.  
Figure 1 presents the overall study design. The study aims to enroll 160 subjects and will be 
conducted at approximately 60-80 sites in 20 countries. The expected duration of each subject’s 
participation in this study is up to 400 days (screening and RCP) or, for eligible subjects who 
enroll in the optional OLP, up to 2,273 days (screening, RCP, interval between RCP and OLP, 
OLP.  A safety follow-up of 2 years after the last IP dose will take place for subjects who do not 
enter the OLP or who discontinue IP during the OLP. 
Eligible patients must have a diagnosis of IgG4-RD and meet the 2019 American College of 
Rheumatology/European League Against Rheumatism (ACR/EULAR) IgG4-RD classification 
criteria (Wallace et al, 2019b), have recent or ongoing active disease (new onset or relapse) 
requiring GC treatment, and be at high risk of further disease flare based on a history of disease 
in at least 2 organ systems/sites (see Section 5.1). 
An Eligibility Committee (EC) will review patient data to confirm eligibility with reference to 
the 2019 ACR/EULAR IgG4-RD classification criteria prior to randomization (Section 6.3.1.4). 
During the screening period (up to 28 days), all subjects must receive at least 3 weeks of GC 
treatment for their recent flare. The exact GC dose and taper schedule prior to randomization will 
be determined by the Investigator, but subjects must be at a dose of 20 mg/day prednisone or 
equivalent on the day prior to randomization. This GC treatment can either be newly initiated or 
be increased from a prior maintenance dose of ≤ 10 mg/day of prednisone or equivalent. The GC 
treatment for recent flare must not have exceeded 60 mg/day prednisone or equivalent at any 
point. Patients who are receiving GCs for treatment of recent flare at the time of consent are not 
eligible if this treatment has exceeded 4 weeks in duration.  
Subjects will be stratified by first or subsequent IgG4-RD manifestation (ie, newly-diagnosed vs 
recurrent) and randomized 1:1 by an interactive voice/web response system (IXRS) to one of two 
blinded treatment groups:  
x Inebilizumab group: Subjects will receive an infusion of inebilizumab 300 mg IV on 
Day 1, Day 15, and at Week 26. 

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x Placebo group: Subjects will receive an infusion of placebo on Day 1, Day 15, and at 
Week 26. 
Both treatment groups will receive open-label IV methylprednisolone 100 mg (or equivalent), 
diphenhydramine 25-50 mg or equivalent, and paracetamol/acetaminophen 500-650 mg or 
equivalent, 30-60 minutes prior to each IV infusion for prophylaxis of infusion reactions.  
Both treatment groups will continue to receive open-label GCs, from local commercial supply, 
during an 8-week taper regimen (2 weeks each at 20, 15, 10, and 5 mg/day of prednisone or 
equivalent), representing completion of the GC taper regimen following treatment for their 
recent flare (Section 7.2.1). 
During the 52-week RCP, subjects will attend monthly visits for study assessments and 
procedures (Section 546.2.2. Suspicion of flare will trigger diagnostic assessments by the 
Investigator (Section 6.3.2.1). The Investigator will determine if the event meets 
protocol -defined criteria for flare, and, independent of the flare determination, will decide if the 
event requires treatment. The same data reviewed by the Investigator will also be evaluated by a 
central, independent, and blinded AC that will determine whether protocol-defined flare criteria 
are met (Section 6.3.2.1). 
The end of the RCP is defined, per subject, as the date of completion of the Week 52 RCP visit. 
All subjects should be followed through the end of the RCP. In exceptional circumstances and 
with agreement of the medical monitor, particular study visits or procedures may be performed 
remotely (via teleconference, video conference, or similar) if the subject is not able to physically 
attend the clinic for that visit or procedure (eg, due to COVID-19 restrictions or for other 
reasons).  Such instances will not be considered protocol deviations. If virtual visits must occur, 
subjects should obtain safety laboratory testing locally when feasible.  
A subject who decides to withdraw from the RCP should be asked to complete the final RCP 
visit (early discontinuation visit [EDV], Table 4) for safety follow-up whether or not they will 
permit phlebotomy. 
In an optional three-year OLP, all eligible subjects who choose to participate will receive 
inebilizumab (Section 7.4.2). Flare data collection will continue during this period, and the flare 
rate will be calculated. The OLP will also contribute to the safety database of inebilizumab in 
patients with IgG4-RD by increasing the number of patients exposed (those who originally 
received placebo and who then receive inebilizumab in the OLP) as well as the duration of 
exposure (in subjects who received inebilizumab in the RCP and then continue in the OLP). 
In the OLP, subjects who were assigned to the placebo group during the preceding RCP will 
receive inebilizumab infusions on OLP Day 1 and Day 15, while those assigned to the 
inebilizumab group in the RCP will receive IV inebilizumab on OLP Day 1 and a matching 
placebo infusion on Day 15 to maintaining blinding of sites and subjects to the RCP treatment 
assignment. Both groups will then receive inebilizumab infusions every 6 months for the 
duration of the OLP.  
Subjects who discontinue IP during the RCP will remain in the RCP for its duration and 
complete the Day 365 visit.  

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In addition, all subjects who discontinue IP during the OLP, or who do not participate in the 
OLP, will be asked to return to the clinic for a series of follow-up visits with limited 
assessments, occurring every six months for a total of two years after their last IP administration 
(see Section 6.4.1). This safety follow-up period (SFUP) will provide data on recovery of B cell 
counts and immunoglobulin levels and monitor for safety events after IP discontinuation. 
An independent Safety Data Monitoring Committee (SDMC) charged with monitoring subject 
safety and ethical conduct of the study will periodically review study data and make 
recommendations regarding continued conduct of the study. 

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Figure 1
Study Design
D = day; IV = intravenous.

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4.2 
Dose and Treatment Regimen Rationale  
The regimen of inebilizumab selected for this study, 300 mg administered as an IV infusion on 
Day 1, Day 15, and every 6 months thereafter, is supported by data from the phase 1 studies in 
multiple sclerosis and scleroderma in which B-cell depletion at lower dose levels was less 
complete and/or less durable than at the 300 mg dosage level, and is further supported by data 
from Study 1155 in which the 300 mg dose level was associated with 
 effect, efficacy, and 
acceptable safety. In Study 1155, the dosing regimen of 300 mg IV on Day 1 and Day 15, and 
then a single 300 mg infusion approximately every 6 months thereafter, was sufficient to achieve 
the rapid, profound, and durable depletion of B cells in the vast majority of subjects. The 300 mg 
dose resides at the efficacy plateau, minimizing the impact of 
 variability. The second dose of 
inebilizumab on Day 15 is timed to deplete newly circulating B cells mobilized out of lymphoid 
and other tissues. Subsequent doses administered at 6-month intervals are timed to maintain the 
 effect based on observations in Study 1155 in which CD20+ B cell counts were significantly 
reduced 8 days after the initial infusion and remained below the LLN in 100% of subjects at 
4 weeks and 94% of subjects at 28 weeks. 
Both efficacy and safety outcomes in NMOSD subjects support this dose regimen. In Study1155, 
inebilizumab reduced the risk of NMOSD attack by 77% relative to placebo in AQP4-IgG 
seropositive subjects. At the 300 mg dose level, the safety profile was acceptable for further 
development. 
The requirement for prednisone (or equivalent) treatment for 3-8 weeks prior to randomization 
and a subsequent 8-week taper of prednisone (or equivalent) during the RCP reflect the standard 
of care for the treatment of active IgG4-RD (Khosroshahi et al, 2015). 
The use of IV placebo is justified by the need to assess inebilizumab monotherapy and to 
maintain blinding (subject, site, Investigator, Sponsor) to assigned treatment during the RCP, 
limiting bias. 
4.3 
Rationale for Study Population  
The study population will be adults with a diagnosis of IgG4-RD who meet the 2019 
ACR/EULAR classification criteria (Wallace et al, 2019b); who have had recent active disease 
(initial diagnosis or flare) requiring treatment; and who are at high risk of recurrent flare. The 
classification criteria have been demonstrated to have high specificity for the disease. The 
inclusion of patients at a high risk of disease recurrence, based on the number of involved 
organs, represents the population with the greatest medical need and permits a reasonable rate of 
accrual of events contributing to the efficacy endpoints (Khosroshahi et al, 2015; Omar et al, 
2019; Abraham and Khosroshahi, 2017; Zhang and Stone, 2019). Active disease responds well 
and rapidly to GC therapy; however, recurrence of flare, with its attendant risk of progression of 
disease and of GC toxicity, requires an approach to the prevention, not just treatment, of disease 
flares. 
The inclusion of subjects with recent active disease (either due to flare or initial diagnosis), 
serves to enroll patients at risk and to partially harmonize their treatment regimen at study entry. 
Because subjects have had a recent flare, they need to be appropriately treated but also, for 
purposes of study, be able to be safely taper and discontinue GCs. Thus, the protocol provides 

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limits to their GC therapy. To permit an 8-week completion of active disease treatment after 
randomization, patients must be able to tolerate 20 mg/day of prednisone or equivalent at 
randomization.  
Patients are excluded for risks related to potential immunosuppression and for advanced renal 
disease or other serious illness that could alter the potential benefit-risk assessment. To avoid 
confounding interpretation of safety and efficacy data based on the use of prior 
immunosuppressive drugs, especially B-cell depletive agents, exclusion criteria provide 
limitations on prior therapy. Patients must have had baseline scans to permit assessment of 
disease activity and on-study comparisons.
4.4 
Rationale for the Primary Endpoint  
The primary endpoint for this study is time to a treated and AC-determined flare. Flares requiring 
medical intervention are the most clinically significant events in patients with IgG4-RD, based 
on the severity of manifestations, the potential for durable morbidity and even mortality, and the 
toxicity of the GC therapy that is the standard of care for flares. Flares that do not require 
treatment are not included in the primary endpoint.  
Although most (but not all) flares respond rapidly to GC therapy, there are medical consequences 
of flare, including debilitation during flare, adverse consequences of GC therapy, potential need 
for medical procedures such as stenting, and the potential for irreversible progression of disease 
or, less commonly, mortality (Huggett et al, 2014).  
The use of time to first flare as the primary endpoint is not affected by standard of care 
treatments for flare that may be used in enrolled patients after the first flare in accordance with 
the judgment of their treating physician(s). Such treatments may include steroid-sparing 
immunosuppressive agents or chronic GC dosing intended to prevent further flares, which would 
confound interpretation of flare risk after their initiation. 
Furthermore, the use of time to first on-study, treated, and AC-determined flare as the primary 
endpoint does not require all subjects to have achieved complete remission at the time of 
randomization. The proposed flare definitions accommodate significant worsening of disease 
activity from a low baseline level (patients must be at 20 mg of prednisone or equivalent to be 
randomized), which could meet criteria for flare (Section 6.3.2.1).  
5 
POPULATION  
5.1 
Inclusion Criteria  
To be included in the study, each individual must satisfy all of the following criteria: 

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1. Male or female adults who have reached the age of consent in the applicable region (eg, ≥ 
18 years in the US) 
2. Written informed consent and any locally required authorization (eg, data privacy) 
obtained from the subject prior to performing any protocol-related procedures, including 
screening evaluations. 
3. Clinical diagnosis of IgG4-RD. 
4. Fulfillment of the 2019 ACR/EULAR classification criteria as determined by the 
Eligibility Committee. Specifically, subjects must meet the classification criteria entry 
requirements (including involvement of one of the following organs: pancreas, bile 
ducts/biliary tree, orbits, lungs, kidneys, lacrimal glands, major salivary glands, 
retroperitoneum, aorta, pachymeninges, or thyroid gland [Riedel’s thyroiditis]), must not 
meet any of the classification criteria exclusions, and must achieve at least 20 
classification criteria inclusion points. 
5. Experiencing (or recently experienced) an IgG4-RD flare that requires initiation or 
continuation of GC treatment at the time of informed consent. This criterion may be met 
in two ways: 
 On GC therapy for recent IgG4-RD flare, having received a maximum of 4 weeks of 
treatment prior to informed consent at a dose no higher than 60 mg/day prednisone or 
equivalent, and at 20 mg/day prednisone or equivalent on the day prior to 
randomization, or 
 Experiencing active disease not currently being treated at the time of informed 
consent, with planned initiation of treatment for flare with GC at a maximum dose of 
60 mg/day prednisone (or equivalent) and with a plan to be treated at a dose of 
20 mg/day of prednisone (or equivalent) on the day prior to randomization, for a total 
duration of GC treatment during screening period of at least 3 weeks at the time of 
randomization. 
This GC therapy can either be newly initiated or be increased from a maintenance 
dose of ≤ 10 mg/day of prednisone or equivalent. 
Subjects unable to be tapered to 20 mg/day of prednisone or equivalent by Visit 2 
may not be randomized.  
Total duration of GC treatment must be at least 3 weeks and not exceed 8 weeks prior 
to randomization. 
6. IgG4-RD affecting at least 2 organs/sites at any time in the course of IgG4-RD with 
documentation to confirm. One organ must meet the requirements for the ACR/EULAR 
classification criteria (inclusion 4); the second organ is as defined by the investigator.  
7. Willing and able to comply with the protocol, complete study assessments, and complete 
the study period. 
8. Non-sterilized male subjects who are sexually active with a female partner of 
childbearing potential must use a condom with spermicide (where spermicide is 
available) from Day 1 through to the end of the study and must agree to continue using 
such precautions for at least 6 months after the final dose of IP. 
 

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Females of childbearing potential must have a negative serum pregnancy test at 
screening. Females of childbearing potential who are sexually active with a non-sterilized 
male partner must use a highly effective method of contraception (Table 2) from signing 
informed consent and must agree to continue using such precautions through the end of 
the follow-up of the study and at least 180 days after the last dose of IP; cessation of 
contraception after this point should be discussed with a responsible physician. Periodic 
abstinence, the rhythm method, and the withdrawal method are not acceptable methods of 
contraception. A recommendation will be made that the female partners (of childbearing 
potential) of male study participants should use a highly effective method of 
contraception other than a barrier method. 
 
Females of childbearing potential are defined as those who are not surgically sterile (ie, 
surgical sterilization includes bilateral tubal ligation, bilateral oophorectomy, or 
hysterectomy) or those who are not postmenopausal (defined as 12 months with no 
menses without an alternative medical cause and a follicle-stimulating hormone within 
the postmenopausal range as established by the clinical laboratory). 
Table 2 
Highly Effective Methods of Contraception for Females of Childbearing 
Potential  
Physical Methods 
Hormonal Methods 
x Intrauterine device (IUD) 
x Intrauterine hormone-releasing system (IUS) a 
x Bilateral tubal occlusion 
x Vasectomized partner b 
x Sexual abstinence c 
 
x Combined (estrogen and progestogen-containing 
hormonal contraception) 
x Oral (combined pill) 
x Injectable 
x Transdermal (patch) 
x Progestogen-only hormonal contraception 
associated with inhibition of ovulation d 
x Implantable 
x Intravaginal 
a 
This is also considered to be a hormonal method. 
b 
With appropriate post-vasectomy documentation of surgical success (absence of sperm in ejaculate). 
c 
Sexual abstinence is considered to be a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of the study and if it is the preferred and usual lifestyle of the subject. 
d 
Progestogen-only hormonal contraception, where inhibition of ovulation is not the primary mode of action 
(minipill) is not accepted as a highly effective method. 
5.2 
Exclusion Criteria  
Any of the following excludes an individual from participation in the study: 
1. 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 patient at unacceptable risk of complications, 
interfere with evaluation of the IP, or confound the interpretation of patient safety or 
study results. 
2. History of solid organ or cell-based transplantation. 
3. Known immunodeficiency disorder. 

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4. Active malignancy or history of malignancy that was active within the last 10 years, 
except as follows: 
 In situ carcinoma of the cervix following apparently curative therapy > 12 months 
prior to screening, 
 Cutaneous basal cell or squamous cell carcinoma following apparently curative 
therapy, 
 Prostate cancer treated with radical prostatectomy or radiation therapy with curative 
intent > 3 years prior to screening and without known recurrence or current treatment, 
or 
 Thyroid cancer for which surgery has been performed and there is no evidence of 
active disease. 
5. Receipt of any biologic B cell-depleting therapy (eg, rituximab, ocrelizumab, 
obinutuzumab, ofatumumab, inebilizumab) in the 6 months prior to screening.  
6. Receipt of non-depleting B-cell-directed therapy (eg, belimumab), abatacept, or other 
biologic immunomodulatory agent within 6 months prior screening. 
7. Receipt of non-biologic DMARD or immunosuppressive agent other than GCs (eg, 
azathioprine, mycophenolate mofetil, methotrexate, others) within 4 weeks prior to 
screening. 
8. Receipt of any investigational agent < 12 weeks or < 5 half-lives of the drug (whichever 
is longer) prior to screening. 
9. Inability to be tapered off of GC therapy by 8 weeks post-randomization (other than ≤ 2.5 
mg/day prednisone or equivalent for treatment of adrenal insufficiency or intolerance of 
taper) in the opinion of the Investigator. 
10. Receipt of live vaccine or live therapeutic infectious agent within the 2 weeks prior to 
screening. 
11. Pregnancy, lactation, or planning to become pregnant within 6 months of the last dose of 
IP. 
12. Positive test for, or prior treatment for, hepatitis B or HIV infection. A positive test for 
hepatitis B is detection of either (1) hepatitis B surface antigen (HBsAg); or (2) hepatitis 
B core antibody (anti-HBc); and in Japan only (3) hepatitis B surface antibody (HBsAb) 
13. History of untreated hepatitis C infection, or positive antibody test for hepatitis C virus 
(HCV) unless patient is considered to be cured following antiviral therapy and has a HCV 
viral load below the limit of detection at least 24 weeks after completion of treatment at 
site or central lab.  
14. Evidence of active tuberculosis (TB) or being at high risk for TB based on: 
 History of active TB or untreated/incompletely treated latent TB. Patients with a 
history of active or latent TB who have documentation of completion of treatment 
according to local guidelines may be enrolled. 
 History of recent (≤ 12 weeks of screening) close contact with someone with active 
TB (close contact is defined as ≥ 4 hours/week OR living in the same household OR 
in a house where a person with active TB is a frequent visitor). 
 Signs or symptoms that could represent active TB by medical history or physical 
examination. 

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 Positive, indeterminate, or invalid interferon-gamma release assay test result at 
screening, unless previously treated for TB. Patients with an indeterminate test result 
can repeat the test once, but if the repeat test is also indeterminate, the patient is 
excluded.  
 Chest radiograph, chest computed tomography (CT) or MRI scan that suggests a 
possible diagnosis of TB or suggests that a work-up for TB should be considered; all 
patients must have had lung imaging with an acceptable reading within 6 months 
prior to consent, or during screening. 
15. History of > 1 episode of herpes zoster (any grade) and/or any other definite or probable 
opportunistic infection in the 12 months prior to screening (see Appendix A) for details 
on opportunistic infections that require exclusion). 
16. Known history of allergy or reaction to any component of inebilizumab formulation or 
history of anaphylaxis to any human gamma globulin therapy. 
17. Allergy to or intolerance of protocol-required treatment, including medications for 
prophylaxis of infusion reactions (antipyretic such as paracetamol/acetaminophen or 
equivalent, diphenhydramine or equivalent, and methylprednisolone or equivalent).  
18. Estimated glomerular filtration rate < 30 mL/min/1.73 m2 by Modification of Diet in 
Renal Disease Study (MDRD) equation (NIDDK). 
19. Blood tests at screening that meet any of the following criteria: 
 Hemoglobin < 7.5 g/dL 
 Neutrophils < 1200/mm3  
 Platelets < 110 × 109/L  
 Eosinophil count > 3000/mm3  
 Prothrombin time > 1.2 x upper limit of normal (ULN); however, subjects who are 
anticoagulated due to atrial fibrillation and who have aspartate aminotransferase 
(AST) and alanine aminotransferase (ALT) levels ≤ 2 x ULN are not excluded 
 Total immunoglobulins < 600 mg/dL 
 CD19+ B cells at screen < 40 cells/PL; an exclusionary value may be repeated.  
20. Subjects with the following abnormal liver function tests in the absence of hepatobiliary 
IgG4-RD activity:  
 Aspartate aminotransferase (AST) > 2 × ULN 
 Alanine aminotransferase (ALT) > 2 × ULN 
 Total bilirubin (TBL) > 2 × ULN unless AST, ALT, and hemoglobin are within 
central laboratory normal range and the patient has a known history of Gilbert 
syndrome 
 
OR 
Subjects with the following abnormal liver function tests in the presence of hepatobiliary 
IgG4-RD activity: 
 AST > 10 × ULN 
 ALT > 10 × ULN 

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 TBL > 5 × ULN 
 Screening liver function tests may be repeated prior to randomization to permit 
abnormal values due to hepatobiliary IgG4-RD activity to respond to GC treatment. 
21. Known positive anti-neutrophil cytoplasmic antibodies (ANCA) targeted against 
proteinase 3 or myeloperoxidase based on patient records.  
22. History of alcohol or drug abuse that, in the opinion of the Investigator, might affect 
patient safety or compliance with visits or interfere with safety or other study 
assessments. 
23. Active, clinically significant infection at the time of randomization (IP administration 
may be delayed until recovery, if within screening window, otherwise subject may be 
rescreened). 
24. Participation in any clinical trial that includes use of any pharmacologic intervention. 
5.3 
Rescreening Procedures  
Patients may be rescreened once if, in the Investigator’s judgment, the reason for ineligibility is 
likely to have resolved at the time of rescreen. Subjects who rescreen within 8 weeks of their 
original screen do not have to repeat hepatitis testing, HIV testing, interferon-gamma release 
assay (IGRA) testing, IgG4 levels or, if relevant, B cells and follicle-stimulating hormone 
testing. A repeat blood sample to freeze for possible John Cunningham virus (JCV) antibody 
testing is not required. 
5.4 
Replacement of Subjects  
 Subjects will not be replaced. 
6 
STUDY CONDUCT  
6.1 
General Instructions  
6.1.1 
Order of Assessments  
Subjects should be asked to complete
prior to other procedures. 
Whenever vital signs, 12-lead electrocardiograms (ECGs), and blood draws are scheduled for the 
same nominal time, blood draws should occur after ECGs and vital signs (temperature, pulse, 
respiratory rate, and blood pressure). If these investigations did not occur in this order, at least 
15 minutes must elapse between blood draw and either ECG or vital signs. 
All laboratory sample collections and assessments that are scheduled for a dosing day must be 
performed prior to dosing, except
 Safety laboratory results from the 
day of dosing will not be available prior to dosing, because a central laboratory will perform 
those analyses. Any ECG performed on the day of dosing should be examined by the 
Investigator prior to dosing to assess the safety of dosing.  

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6.1.2 
Availability of Laboratory Results  
All safety laboratory results will be made available to Investigators by the central laboratory. 
This includes serum IgG4 levels, which will be provided to Investigators per standard 
management practices for patients with IgG4-RD.  
Due to the inebilizumab mechanism of action, results of B cell testing and serum Ig levels post 
dose could be potentially unblinding. Post-randomization B cell results will not be available to 
blinded staff or Investigators until the study is unblinded.  Serum Ig results will be made 
available to Investigators only from OLP Week 26 onwards. Research laboratory values,
 and ADA results will also not be available until the study is unblinded. 
6.1.3 
Repeating Procedures After Randomization  
Abnormal laboratory or ECG results obtained after randomization that, in the Investigator’s 
opinion, represent a clinically significant finding or clinically significant change from baseline 
should be repeated as soon as possible, preferably within 48 hours. If urgent results are needed, 
testing can be sent to a local laboratory, but blood for the same tests should be sent to the central 
laboratory as well. 
6.2 
Schedules of Study Assessments  
6.2.1 
Schedule of Screening Assessments and Procedures  
Table 3 summarizes the screening procedures for the study. All screening assessments must be 
completed within 28 days prior to randomization. In some cases, more than one screening visit 
may be required to complete all procedures. Safety laboratory tests may be repeated once during 
screening. 
Table 3 
Screening Assessments and Procedures  
Study Period 
Screening 
Visit Number 
V1  
Study Day 
Up to Day -28 a 
Written informed consent and IXRS assignment of SID number 
X 
Demographics 
X 
Medical history 
X 
Assessment of AEs and SAEs 
X 
Review of vaccination history b 
X 
Assessment of prior and concomitant medications 
X 
Vital signs (temperature, pulse, respiration rate, and blood pressure) 
X 
Height and weight 
X 
Full physical examination excluding pelvic and rectal exam   
X 
12-lead ECG 
X 

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Table 3 
Screening Assessments and Procedures  
Study Period 
Screening 
Visit Number 
V1  
Study Day 
Up to Day -28 a 
CT or MRI scan (or equivalent) of chest, abdomen and pelvis at screen or during most recent 
active disease (ie, within prior 3 months), and, if head and neck disease, MRI (or equivalent) of 
affected area at screen or within prior 3 months. If clinically indicated, repeat imaging can be 
performed prior to randomization to assess response to glucocorticoids and to ensure exclusion of 
malignancy. 
X 
IgG4-RD RI score 
X 
Blood collection for: 
x 
Safety laboratory testing (serum chemistry c , hematology, and coagulation) 
x 
Serum β-hCG pregnancy test (all females) 
x 
Follicle-stimulating hormone (potentially postmenopausal females) 
x 
Hepatitis B surface antigen, anti-HBc, and in Japan only HBsAb  
x 
Hepatitis C testing: 
a) Hepatitis C Ab in patients not known to have had HCV 
b) HCV load in patients known to have completed curative HCV treatment at least 
24 weeks prior to screening 
x 
HIV-1 and HIV-2 testing 
x 
IGRA testing for TB 
x 
IgG4 level 
x 
Serum to be frozen for possible testing for JCV antibodies or other safety testing 
X 
Urine collection for urinalysis (dipstick and, for abnormal dipstick, microscopic) and for urine 
protein/creatinine ratio 
X 
Verify preliminary eligibility based on data from Screening Visit prior to scheduling Visit 2 
X 
Ab = antibody; AE = adverse event; β-hCG = serum human chorionic gonadotropin; CT = computed tomography; 
ECG = electrocardiogram;
 HCV = 
hepatitis C virus; Ig = immunoglobulin; IgG4-RD RI = IgG4-RD Responder Index; IGRA = interferon-gamma 
release assay; IXRS = interactive voice/web response system; JCV = John Cunningham virus; MRI = magnetic 
resonance imaging;
 SAE = serious adverse 
event;
 SID = subject identification; 
TB = tuberculosis; V1 = visit 1. 
a 
Screening may be conducted over multiple visits. 
b 
Subjects should be advised to be up to date on vaccines in accordance with local recommendations prior to 
enrollment. Vaccines are optimally administered at least 4 weeks prior to dosing to permit development of 
immune response. Subjects who, on the advice of their physician, should delay Dose 1 for > 28 days to permit a 
4-week post vaccine interval to occur should be screen-failed and may be rescreened. 
c 
In patients who enroll with a hepatobiliary flare whose screening liver function test values do not meet 
eligibility criteria, liver function tests may be repeated (Exclusion 20). Subjects whose values do not fall below 
the exclusionary values upon repeat may not be randomized. 
 

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6.2.2 
Schedule of RCP Assessments and Procedures  
Table 4 summarizes the schedule of procedures for the RCP.

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Table 4 
Randomized-Controlled Period Assessments and Procedures  
Study Period 
Randomized-Controlled Period 
Visit Number 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
Week 
0 
2 
4 
8 
12 
16 
20 
26 
30 
34 
38 
42 
46 
52 or 
EDV d 
Nominal Day 
1 
15 
29 
57 
85 
113 
141 
183 
211 
239 
267 
295 
323 
365 
Window 
-- 
± 1 
day 
± 3 
days 
± 3 
days 
± 3 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 7 
days 
± 7 
days 
± 7 
days 
± 7 
days 
± 7 
days 
± 7 
days 
Assessment of 
AEs/SAEs/AESIs 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant medications  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ECG (prior to IP 
administration) 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
Vital Signs 
X b 
X b 
X 
X 
X 
X 
X 
X b 
X 
X 
X 
X 
X 
X 
Weight 
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
Full physical examination  
X 
 
 
 
 
 
 
X 
 
 
 
 
 
X 
Symptom-driven physical 
exam 
 
X 
X 
X 
X 
X 
X 
 
X 
X 
X 
X 
X 
 
IgG4-RD RI 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Urine pregnancy test in 
women capable of 
pregnancy 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Table 4 
Randomized-Controlled Period Assessments and Procedures  
Study Period 
Randomized-Controlled Period 
Visit Number 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
Week 
0 
2 
4 
8 
12 
16 
20 
26 
30 
34 
38 
42 
46 
52 or 
EDV d 
Nominal Day 
1 
15 
29 
57 
85 
113 
141 
183 
211 
239 
267 
295 
323 
365 
Window 
-- 
± 1 
day 
± 3 
days 
± 3 
days 
± 3 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 7 
days 
± 7 
days 
± 7 
days 
± 7 
days 
± 7 
days 
± 7 
days 
Urinalysis (microscopic if 
abnormal) and urine 
protein/creatinine ratio 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Safety labs (chemistry, 
hematology, coagulation) 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
ADA  
X 
 
X 
 
X 
 
 
X 
 
 
X 
 
 
X 
IgG4 
 levels 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 

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Table 4 
Randomized-Controlled Period Assessments and Procedures  
Study Period 
Randomized-Controlled Period 
Visit Number 
V2 
V3 
V4 
V5 
V6 
V7 
V8 
V9 
V10 
V11 
V12 
V13 
V14 
V15 
Week 
0 
2 
4 
8 
12 
16 
20 
26 
30 
34 
38 
42 
46 
52 or 
EDV d 
Nominal Day 
1 
15 
29 
57 
85 
113 
141 
183 
211 
239 
267 
295 
323 
365 
Window 
-- 
± 1 
day 
± 3 
days 
± 3 
days 
± 3 
days 
± 5 
days 
± 5 
days 
± 5 
days 
± 7 
days 
± 7 
days 
± 7 
days 
± 7 
days 
± 7 
days 
± 7 
days 
Verify eligibility  
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Randomization 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
IP administration e 
X 
X 
 
 
 
 
 
X 
 
 
 
 
 
 
Provide oral GCs 
X 
 
 
 
 
 
 
 
 
 
 
 
 
 
Assess GC compliance 
 
X 
X 
X 
 
 
 
 
 
 
 
 
 
 
AE = adverse event; ADA = anti-drug antibodies; AESI = adverse event of special interest; ECG = electrocardiogram; EDV = early discontinuation visit; 
 GC = glucocorticoid; Ig = 
immunoglobulin(s); IgG4-RD RI = IgG4-RD Responder Index; IP = investigational product;
 SAE = serious adverse event;
 
 
 V = visit. 
Note: On days of IP administration, all procedures and blood sampling, except for
must be collected before IP administration. 
 
b 
Vital signs obtained as per Section 7.1.1.5. 
d 
Subjects who have indicated their intent to withdraw consent during the RCP should be asked to complete an EDV visit. 
e 
Premedication will be administered approximately 30-60 minutes prior to each IP infusion (see Section 7.1.1.4).  If IP administration at Visit 9 (Day 183) is 
unavoidably delayed, for example due to COVID travel restrictions, the dosing visit may be delayed upon discussion and agreement with the Sponsor. 
Adjustment of the timing of the subsequent OLP IP doses will be discussed on a case-by-case with the Sponsor.  If a subject discontinues IP during the RCP, 
they should complete all RCP visits. If they do not subsequently enter the OLP, they should then enter the SFUP (Section 6.2.4).

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6.2.3 
Schedule of OLP Assessments and Procedures  
6.2.3.1 
Eligibility for OLP  
Subjects eligible for the OLP must: 
1. Have completed the RCP Week 52 visit (end of RCP). 
2. Must not have had IP discontinued for any of the following safety reasons:  
 
Anaphylaxis or a serious hypersensitivity reaction that occurred within 7 days after 
IV dosing and cannot be attributed to another known allergen exposure (see 
Appendix B). 
 
Any adverse event (AE) or significant laboratory abnormality that, in the opinion of 
the Investigator, Sponsor, or SDMC, warrants discontinuation of dosing. 
 
Any life-threatening (Grade 4) infection. 
 
Any event of sepsis or febrile neutropenia. 
 
Any infection listed as either a definite or probable opportunistic infection in 
Appendix A. 
 
Any Grade 3 IRR. 
 
Any Grade 4 serious adverse event (SAE). 
 
Pregnancy or a decision to become pregnant. 
 
Malignancy. 
 
Absolute neutrophil count < 800 cells/μL confirmed by repeat testing. 
 
Determination that the subject was ineligible for study participation and continuation 
of IP could pose a safety risk to the subject in the judgment of the Investigator or 
Sponsor.  
 
Significant noncompliance with the study protocol, as judged by the Investigator or 
Sponsor. 
 
Receipt of any B cell-depleting therapy (eg, rituximab, ocrelizumab, obinutuzumab, 
ofatumumab, commercially available inebilizumab). 
3. Have completed a 28-day washout period after discontinuation of non-B cell-depleting, 
non-GC immunosuppressive therapy initiated during the RCP, if relevant. 
4. Receive Dose 1 in the OLP within the window of 1-38 days after the RCP Week 52 visit 
(the final visit for the RCP and the first visit for the OLP cannot occur on the same day). 
5. Have a planned taper of GCs to discontinuation by 8 weeks after OLP Dose 1, if 
receiving GC at the time of OLP entry. 
To maintain the every-6-month dosing of IP, subjects should enroll in the OLP and be dosed as 
soon as is feasible after completion of the RCP. All SAEs and AEs that occur between the end of 
the RCP and start of the OLP must be collected at OLP Visit 1. Investigational product 
discontinuation rules apply during the OLP (Section 6.4.1).  
Table 5 summarizes the schedule of procedures for the OLP. 

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Table 5 
Open-Label Period Assessments and Procedures  
 
 
 
Study Period 
Open-Label Period 
 
 
 
OLP Visit Number 
OLP  
V1 
OLP  
V2 
OLP  
V3, V4 
OLP  
V5 
OLP  
V6, V7 
OLP  
V8 
OLP  
V9, 
V10 
OLP 
V11 
OLP  
V12, 
V13 
OLP 
V14  
OLP 
V15, 
17, 19, 
21 
OLP 
V16, 
18, 20, 
OLP 
V22/EDV 
OLP Week(s) 
0 
2 
4, 8 
12 
16, 20 
26 
30, 34 
38 
42, 46 
52  
61, 87, 
113, 
139 
78, 
104, 
130 
156 
Window 
1-38 
days 
after 
last 
RCP 
visit 
± 2 
days 
Phone 
contact 
±10 
days b 
±10 
days 
Phone 
contact 
±10 
days b 
± 10 
days 
Phone 
contact 
±10 
days b 
±10 
days 
Phone 
contact 
±10 
days b 
+10 
days 
Phone 
contact 
±20 
days b 
±20 
days 
±20 days 
Assessment of 
AEs/SAEs/AESIs 
X c 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Concomitant 
medications  
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs 
X d 
X d 
 
X 
 
X d 
 
X 
 
 X d 
 
X d  
X 
Physical exam 
 
 
 
 
 
 
 
 
 
 
 
 
X 
Symptom-driven 
physical exam 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
 
IgG4-RD RI 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Urine pregnancy test 
in women capable of 
pregnancy e 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Safety labs f 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 

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Table 5 
Open-Label Period Assessments and Procedures  
 
 
 
Study Period 
Open-Label Period 
 
 
 
OLP Visit Number 
OLP  
V1 
OLP  
V2 
OLP  
V3, V4 
OLP  
V5 
OLP  
V6, V7 
OLP  
V8 
OLP  
V9, 
V10 
OLP 
V11 
OLP  
V12, 
V13 
OLP 
V14  
OLP 
V15, 
17, 19, 
21 
OLP 
V16, 
18, 20, 
OLP 
V22/EDV 
OLP Week(s) 
0 
2 
4, 8 
12 
16, 20 
26 
30, 34 
38 
42, 46 
52  
61, 87, 
113, 
139 
78, 
104, 
130 
156 
Window 
1-38 
days 
after 
last 
RCP 
visit 
± 2 
days 
Phone 
contact 
±10 
days b 
±10 
days 
Phone 
contact 
±10 
days b 
± 10 
days 
Phone 
contact 
±10 
days b 
±10 
days 
Phone 
contact 
±10 
days b 
+10 
days 
Phone 
contact 
±20 
days b 
±20 
days 
±20 days 
Urinalysis g 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
ADA  
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
IgG4 
 
X 
X 
 
X 
 
X 
 
X 
 
X 
 
X 
X 
Assessment of 
eligibility for OLP 
X 
 
 
 
 
 
 
 
 
 
 
 
 
IP administration h 
X 
X 
 
 
 
X 
 
 
 
X 
 
X 
 

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AE = adverse event; ADA = anti-drug antibodies; AESI = adverse event of special interest; EDV = early discontinuation visit;
score; Ig = immunoglobulin; IgG4-RD RI = IgG4-RD Responder Index; IP = investigational product, OLP = open-label period; RCP = randomized-controlled 
period; SAE = serious adverse event;
 V = visit. 
Note: All procedures and blood sampling must be collected before IP administration on days when IP is administered. 
a 
Subjects who have received immunosuppressive therapy other than glucocorticoid treatments must have a washout period of at least 28 days prior to Dose 1 
of inebilizumab in the OLP. 
b 
Monthly telephone calls in months without in-person visits.  If, during the telephone contact, a safety event or possible flare that requires further follow-up is 
identified, the subject should be evaluated in the clinic as an unscheduled visit. 
c 
AEs and SAEs occurring after completion of the RCP must be collected at OLP Visit 1. 
d 
Vital signs obtained as per Section 7.1.1.5. 
e 
Perform on days of dosing; confirm negative prior to dose. 
f 
Safety labs include chemistry, hematology, and coagulation; 
 will not be performed during the OLP. 
g 
Microscopic if abnormal 
h     Premedication will be administered approximately 30-60 minutes prior to each IP infusion (see Section 7.1.1.4). If a subject discontinues IP during the OLP, 
they should enter the SFUP (Section 6.2.4). 

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6.2.4 
Safety Follow-Up Period 
Subjects who do not enter the OLP, or who discontinue IP during the OLP, will be followed for 
an additional two years from the date of last IP infusion.  During this time subjects will be seen 
every six months in-clinic for blood draws and other limited assessments.   
Assessments and procedures during the SFUP are detailed in Table 6. 
Table 6 
Safety Follow Up Period Assessment and Procedures 
Study Period 
SFUP 
Visit Number 
V1, 2, 3, 4  
SFUP Weeks 
26, 52, 78, 104 
Window 
±4 weeks 
Assessment of AEs and SAEs 
X 
Assessment of concomitant medications 
X 
AE = adverse event; SAE = serious adverse event; SFUP = safety follow-up period; V = visit 
 
6.3 
Description of Study Assessments and Procedures  
6.3.1 
Screening Procedures  
6.3.1.1 
Informed Consent  
Subjects officially enter the screening period following provision of informed consent.  
All candidates for enrollment will sign an informed consent form (ICF) prior to any 
protocol-related procedures, including screening activities. Informed consent must be obtained 
by the Principal Investigator (PI) or a designee, such as an Investigator, with Institutional Review 
Board (IRB)/Independent Ethics Committee (IEC) approved qualifications. See Section 10.3 for 
additional details. 
After signing the ICF, each subject will be assigned a subject identification (SID) number that 
will be used on all subject documentation. Numbers will be assigned in ascending, sequential 
order. This number will also correspond to the subject number entered on test materials. 
Rescreened patients will receive a new SID number. See Section 5.3 for limitations on 
rescreening. 
6.3.1.2 
Demographics and Baseline Characteristics  
Demographic information to be collected includes year of birth, sex, and where permitted, race, 
and ethnicity. Medical history information to be collected includes all ongoing conditions and 
relevant/significant medical history (including all major hospitalizations and surgeries), as 
determined by the Investigator. Prior and concomitant medications will be recorded. A complete 

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physical examination (with the exception of rectal and pelvic examinations) will be conducted at 
baseline, including vital signs, height, and weight.  
Blood will be collected for IgG4 levels. 
Examinations needed for the IgG4-RD RI score will also be performed at screening
6.3.1.3 
Safety Assessments at Screening  
Safety-related screening assessments will include AEs, safety laboratory tests (serum chemistry, 
hematology, and urinalysis), coagulation parameters, ECG, and serum human chorionic 
gonadotropin (β-hCG) pregnancy test for females.  
All screening labs should be performed by the central lab. In exceptional circumstances, for 
example travel restrictions due to COVID or failure of a central lab test during the screening 
period without sufficient time for central lab repeat, a local lab with appropriate qualifications 
and certifications may be used with prior approval by the Sponsor. 
Baseline imaging will be performed unless recent readings are available from within the prior 
3 months: CT or MRI scan (or equivalent) of chest, abdomen, and pelvis; and if subject has head 
or neck disease, an MRI (or equivalent) of the affected area. If clinically indicated, repeat 
imaging can be performed prior to randomization to assess response to GCs and confirm 
eligibility. 
Blood will be collected at screening for the following tests: 
x Hepatitis B testing: HBsAg, anti-HBc, and in Japan only HBsAb 
x Hepatitis C antibody (HCV load in patients at least 24 weeks after curative treatment for 
HCV) 
x HIV testing: HIV-1 antibody, HIV-2 antibody 
x TB testing (eg, QuantiFERON®-TB Gold Test) 
x Serum will be frozen for possible testing for JCV antibodies in case of suspected PML 
For additional details on safety assessments, see Sections 6.3.3 and 8. 
6.3.1.4 
Eligibility Committee  
Data related to subjects’ IgG4-RD disease history and current disease manifestations will be 
provided to an EC composed of physicians with expertise in the diagnosis and care of patients 
with IgG4-RD. EC members will independently review these data, including any available 
biopsy reports, to determine whether a subject fulfills the ACR/EULAR IgG4-RD classification 
criteria (Wallace et al, 2019b) per Inclusion Criteria 4. These classification criteria were 
developed to ensure that studies in IgG4-RD avoid enrollment of subjects who do not have a 
clear diagnosis of IgG4-RD. Accordingly, these criteria are highly specific (99.2% in the first 
validation cohort and 97.8% in the second) and appropriately sensitive (85.5% in the first 
validation cohort and 82.0% in the second). 

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6.3.2
Efficacy Assessments
Over the course of the study, Investigator assessments for a given subject should be completed 
by the same Investigator, designated physician, or qualified site personnel whenever possible.
6.3.2.1
Flare Assessment, Diagnosis, and Adjudication
The Investigator is responsible for identifying, diagnosing, and treating IgG4-RD flares during 
the RCP and OLP. As outlined in Figure 2, this process and the Investigator’s specific 
responsibilities are as follows:
x
Investigator suspects flare based on symptoms or clinical findings
x
Investigator assesses the appropriate sites/organs
x
Investigator determines whether protocol-defined flare criteria are met
x
Investigator decides whether flare treatment is warranted and initiates treatment
Data collected by the Investigator in this process will be sent to the AC for independent, blinded
determination of whether the event meets protocol-defined flare criteria.
These processes are each described in detail in the following sections.
Figure 2
Flare Assessment and Adjudication Process

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AC = Adjudication committee; IgG4-RD = immunoglobulin G4-related disease. 
Note: This diagram outlines the assessment and adjudication process for suspected flares and highlights the events 
that contribute to the primary endpoint. 
Investigator Assessment of Flare 
If a subject’s symptoms, physical examination, laboratory parameters, or other clinical finding 
suggests the possibility that a disease flare may be occurring, the Investigator should evaluate the 
subject, conduct any medically indicated assessments, and review any relevant data collected at 
facilities other than the investigational site. Assessments should be per local standard of care and 
at the discretion of the Investigator. Flare assessments should be conducted prior to the initiation 
of treatment for flare, if possible.  
Data to be evaluated when considering a potential flare may include: 
x Symptoms 
x Physical examination findings 
x Laboratory results 
x Imaging results 
x Biopsy results 
Flare Diagnosis 
To promote uniformity and objectivity in the diagnosis of flare, the Investigator will use the flare 
criteria to determine whether the event meets the definition of flare for this study. 
Flare Treatment 
For detailed information on flare management, and which flare treatments require 
discontinuation of IP, refer to Section 7.6. 
Briefly, flare treatment is at the discretion of the Investigator and should be initiated after 
completion of assessments and flare diagnosis, if possible. Flare treatment is not dependent on 
protocol-specified flare criteria being met. 
Investigators will record on the electronic case report form (eCRF) when a subject starts 
treatment or interventional procedure for IgG4-RD disease activity. Treatment start date for flare 
will be recorded whether or not the treatment is a prohibited concomitant medication 
(Section 7.5.1). The indication for use of medications and procedures will be collected to 
document if the intervention was to control disease activity.  
Treatment initiated by a facility or provider other than the Investigator may be used when 
determining the start of treatment for the purposes of this study, provided that the Investigator 
reviews all subject data and agrees that initiation of treatment at that time was warranted. 
Flare Adjudication 
An independent AC, composed of experts in the field, will review the data available to the 
Investigator or used by the Investigator for decision-making (including any available and 
relevant imaging reports, laboratory testing, biopsy reports, description of patient symptoms, and 
a narrative) and will use the same study-specific definition of flare that will be used by the 

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Investigator. The AC will be blinded and independent, and will be composed of physicians with 
expertise in the care of patients with IgG4-RD. AC members will review and adjudicate cases 
individually but will be permitted to discuss cases as a committee as needed. A majority vote is 
required for AC decisions. Additional details of the process will be provided in the AC Charter. 
The AC, in a similar process, is also charged with determining whether sequential IgG4-RD 
activity events represent a single or more than one flare for the purpose of secondary efficacy 
endpoints. In general, for treated flares, disease manifestations present prior to flare diagnosis or 
treatment initiation represent a single flare. New or worsening disease activity that presents 
during treatment for a flare represents a separate flare. If the flare was not treated, new or 
worsening of IgG4-RD activity occurring prior to resolution of the presenting flare 
manifestations does not constitute a new flare. 
6.3.2.2 
IgG4-RD Responder Index  
The IgG4-RD RI is a validated instrument for longitudinal assessment of IgG4-RD disease 
activity, developed and refined by an international team of IgG4-RD experts specifically to 
permit structured assessment of response to treatment by clinical investigators (Carruthers et al, 
2012; Wallace et al, 2018). The RI captures disease activity and damage in 25 domains, with 
higher weights for disease manifestations that require urgent treatment or that worsen despite 
treatment. The RI incorporates an activity score for each organ/site of disease, a score for 
symptomatic disease at each of these sites, and a score amendment for a need for urgent 
treatment. Serum IgG4 concentration and presence of organ-specific damage are collected but 
are not part of the overall RI. Because visit-to-visit consistency is important, whenever possible, 
the same Investigator should complete the IgG4-RD RI for the same subject across all visits. 
Not all results needed to complete the IgG4-RD RI (in particular, labs and imaging) will be 
available at the time of the subject’s visit. Therefore, the investigator may delay completion of 
the IgG4-RD RI for up to 15 business days of the visit date to permit all results to be considered. 
All other assessments related to the IgG4-RD RI should be completed on the day of the visit. 
6.3.2.3 
Cumulative Glucocorticoid Use  
Cumulative GC use will be calculated as the total GC dose in mg of prednisone or prednisone 
equivalent taken for the purpose of IgG4-RD disease control during the RCP. 

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6.3.3 
Safety Assessments  
Clinically important abnormalities in vital signs, body weight, physical examination, laboratory 
parameters, and ECGs will be recorded as AEs or SAEs. 
6.3.3.1 
Vital Signs, Body Weight, and Physical Examinations  
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 schedules of assessments and 
the IP Administration Manual. Subjects should be seated or supine when vital signs are obtained.  
Depending on the visit, physical examinations will be either a full examination (excluding rectal 
and pelvic examinations) or a symptom-driven examination. Examination of the head and neck, 
including orbits, salivary glands, and lymph nodes, are to be included in both the complete and 
the symptom-driven physical examinations. 
6.3.3.2 
Electrocardiogram  
A 12-lead ECG will be performed according to the schedule of assessments and procedures. All 
ECG recordings will be made with the subject in a supine position, having rested in this position 
for at least 5 minutes before the start of the ECG. 
Each ECG will include ventricular heart rate and intervals (PR, RR, QRS, QT, QTc). The 
Investigator will be responsible for providing an interpretation of the ECG. Clinically significant 
abnormalities will be recorded as AEs.  
6.3.3.3 
Pregnancy  
Serum β-hCG pregnancy test(s) will be completed for all females during the screening period 
and urine pregnancy tests will be completed in females of childbearing potential at all subsequent 
study visits. At visits where an IP infusion will be administered, a negative urine pregnancy test 
result must be obtained prior to administration of IV IP in female patients capable of pregnancy. 
Urine pregnancy tests will be performed at the site. Pregnancy in a female subject who has 
received IP must be reported to the Sponsor within 24 hours of Investigator awareness (Section 
8.5.1). 

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6.3.3.4 
Assessment of Adverse Events  
For instructions on collecting and reporting AEs, refer to Section 8. 
6.3.3.5 
Safety Laboratory Assessments  
For descriptions of all laboratory assessments, refer to Section 6.3.4. 
6.3.3.6 
Anti-drug Antibody Assessments  
For descriptions of ADA assessments, refer to Section 6.3.7. 
6.3.4 
Clinical Laboratory Assessments  
Blood and urine samples will be collected for laboratory safety tests as specified in the schedules 
of assessments (Section 6.2). Laboratory testing is described below. For further details regarding 
laboratory assessments, see the Study Laboratory Manual. 
In certain instances, safety laboratory tests may be run in a qualified and licensed local 
laboratory with prior approval of the sponsor, even where the exclusion criterion specifies use of 
the central laboratory. Such instances will not be considered protocol deviations. 
6.3.4.1 
Hematology  
The hematology panel will include a complete blood count, with white blood cell count (WBC) 
and differential (basophils, eosinophils, lymphocytes, monocytes, and neutrophils), hemoglobin, 
hematocrit, and platelet count. 
6.3.4.2 
Serum Chemistry  
Serum chemistry assessments will include: 
x 
Albumin 
x 
Alkaline phosphatase (ALP) 
x 
Alanine transaminase (ALT) 
x 
Amylase 
x 
Aspartate transaminase (AST) 
x 
Bicarbonate 
x 
Blood urea nitrogen (BUN) 
x 
Calcium 
x 
Chloride 
x 
Creatinine 
x 
Gamma-glutamyl transferase 
(GGT) 
x 
Glucose (random) 
x 
Hemoglobin A1C (HbA1C) 
x 
Lipase 
x 
Magnesium 
x 
Phosphorus 
x 
Potassium 
x 
Serum to be frozen for possible future safety 
testing 
x 
Sodium 
x 
Total bilirubin (TBL): (if > 1.5 ULN, indirect 
and direct bilirubin will be measured) 
x 
Total protein 
x 
Uric acid 
Tests for AST, ALT, ALP, and TBL must be conducted concurrently and assessed concurrently. 

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6.3.4.3 
Coagulation Parameters  
Coagulation parameters will include prothrombin time, international normalized ratio, and 
activated partial thromboplastin time. 
6.3.4.4 
Urinalysis  
Urinalysis will evaluate color, appearance, and specific gravity. Standard dipstick analysis, 
including pH, protein, glucose, blood, and bilirubin, will be performed. Samples with abnormal 
dipstick will have microscopy performed. Microscopy will include WBC/high power field (HPF) 
and red blood cell count/HPF. 
Urine protein/creatinine ratio calculates the protein/creatinine ratio from a random urine sample 
to estimate the 24-hour protein excretion as a marker of renal disease. 
6.3.4.5 
Progressive Multifocal Leukoencephalopathy  
PML is a rare, life-threatening CNS infection caused by the JCV (Berger et al, 2013). Although 
no confirmed cases of PML have been reported following inebilizumab exposure, PML remains 
a potential risk based on the inebilizumab mechanism of action. In a case of suspected PML, a 
cerebrospinal fluid sample should be collected to test for JCV by polymerase chain reaction 
testing using a validated assay in a clinical testing laboratory.  

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6.3.6 
Imaging  
All subjects will have had chest, abdomen, and pelvis imaging (CT scans, unless a CT scan is 
contraindicated) at baseline unless a CT scan or other appropriate imaging (such as, but not 
limited to, positron emission tomography [PET] scan or MRI) had been performed within the 3 
months prior to screening visit and the reading is available. If clinically indicated, imaging (PET 
scan excluded) may be repeated prior to randomization, to clarify illness, to assess response to 
GCs, or to ensure exclusion of malignancy. Other imaging is at the discretion of the Investigator. 
6.3.7 
Immunogenicity Assessments  
Blood samples for immunogenicity (ADA to inebilizumab) will be obtained prior to IP 
administration according to the visits specified in Section 6.2 and will be assessed using a 
validated immunoassay. 

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6.4 
Discontinuation of Investigational Product, Withdrawal from Study, and Loss to 
Follow-up  
6.4.1 
Discontinuation of Investigational Product  
IP must be discontinued if the Investigator determines that continuing it would result in a 
significant safety risk for that subject. The following events require discontinuation of IP: 
1. Anaphylaxis or a serious hypersensitivity reaction that occurred within 7 days after IV 
dosing and cannot be attributed to another known allergen exposure (see Appendix B). 
2. Any AE or significant laboratory abnormality that, in the opinion of the Investigator, 
Sponsor, or SDMC, warrants discontinuation of dosing. 
3. Any AE of immune complex disease. 
4. Any life-threatening (Grade 4) AE. 
5. Any event of sepsis or febrile neutropenia. 
6. Any infection listed as either a definite or probable opportunistic infection in Appendix 
A. 
7. Any Grade 3 AE with the following exceptions: 
 A Grade 3 AE of flare or exacerbation of IgG4-RD (per protocol, these events are not 
reported as SAEs as they may represent the primary endpoint of the study) 
 A Grade 3 event that is not an IRR or infection, does not meet any other 
discontinuation criterion, and for which the SDMC has agreed that IP dosing can 
continue 
8. Pregnancy or a decision to become pregnant. 
9. Malignancy. 
10. Absolute neutrophil count < 800 cells/μL confirmed by repeat testing. 
11. Withdrawal of consent for further study participation or for further receipt of IP. 
12. Receipt of prohibited medication(s) (see Section 7.5.1). 
13. Determination that the subject was ineligible for study participation and continuation of 
IP could pose a safety risk to the subject in the judgment of the Investigator or Sponsor.  
14. Significant noncompliance with the study protocol, as judged by the Investigator or 
Sponsor. 
Severity of AEs will be graded according to the National Cancer Institute Common Terminology 
Criteria for Adverse Events (CTCAE) (Section 8.1) 
Subjects with Grade 3 SAEs should have their AE data reviewed by the Investigator to 
specifically address whether or not IP should be discontinued or delayed to ensure patient safety, 
particularly for Grade 3 SAEs of infection (Section 7.1.1.4). The medical monitor(s) and the 
SDMC are available for discussions regarding suitability of repeat dosing in a subject who has 
had a Grade 3 SAE. 

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The reason(s) for discontinuing IP must be recorded on the appropriate page of the eCRF. If 
subjects choose to discontinue IP, the reason, such as an AE, lack of efficacy, or other reason, 
must be recorded in the eCRF.  
Subjects who discontinue IP during the RCP should remain in the study and complete all RCP 
study visits, assessments, and procedures (with the exception of IP administration and associated 
 unless they have withdrawn consent for study participation or 
withdrawn consent for specific assessments (if subjects will not agree to return for visits, safety 
data can be collected by telephone call if subjects agree).  
Subjects who discontinue IP during the RCP may be eligible to enroll in the OLP, if they meet 
criteria outlined in Section 6.2.3.1. Site Investigators will be trained about the importance of 
retention of subjects through the completion of the RCP, and patients will be informed about the 
continued scientific importance of their data even if they discontinue study treatment early.  
Subjects who do not participate in the OLP, and subjects who discontinue IP during the OLP, 
will be asked to return to the clinic for a series of visits occurring every six months for a total of 
two years after their last dose of IP.  These post-discontinuation follow-up visits will include a 
limited set of assessments including CD20+ B cell counts, immunoglobulins levels, concomitant 
medications, and adverse events. These visits are described in detail in Section 6.2.4, Safety 
Follow-Up Period. 
6.4.2 
Withdrawal from Study  
Subjects who wish to withdraw from the study will be invited to return, if willing, for a single 
additional EDV, unless all study procedures to be completed at the EDV had been completed 
within the past 30 days.  
6.4.3 
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 the steps taken to contact the 
subject, eg, dates of telephone calls, registered letters, etc. 
Efforts to ensure complete subject follow-up include proactive site contact of subjects who have 
missed visits (at least 3 documented attempts to reach by telephone and at least 3 documented 
attempts to reach by letter) or through emergency/other contact if subjects have provided such 
contacts. Email can be used for contact and scheduling of visits as long as subjects have given 
permission for email contact.  
6.5 
Study Suspension or Termination  
The Sponsor reserves the right to temporarily suspend or terminate this study at any time. The 
reasons for temporary suspension or termination of 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. 

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x Noncompliance that might significantly jeopardize the validity or integrity of the study.  
x Sponsor decision to terminate development. 
If Sponsor determines that temporary suspension or termination of the study is required, Sponsor 
will communicate the reasons for taking such action to 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/IEC 
promptly and provide the reason(s) for the suspension/termination. If the study is suspended for 
safety reasons and it is deemed appropriate by the Sponsor to resume the study, approval from 
the relevant regulatory authorities (and IRBs/IECs, when applicable) will be obtained prior to 
resuming the study. 
6.6 
End of Study  
The primary analysis of the study data will be conducted when the last subject completes the 
Day 365 visit of the RCP or discontinues the RCP. The study will be complete when the last 
active subject completes all protocol-specified visits. 
7 
STUDY INTERVENTIONS  
7.1 
Description of Investigational Products  
Table 7 provides a description of the IPs to be used in the study. 
Table 7 
Description of Investigational Products and RCP Dosing  
Investigational 
Product 
Concentration and Formulation as Supplied 
Route 
Dose 
RCP 
Dosing 
Regimen 
Manufacturer 
Inebilizumab 
(100 mg per 
vial, nominal) 
Inebilizumab for IV administration is supplied as a 
sterile liquid filled at a nominal volume of 10 mL in 
10R vials. Each vial contains inebilizumab 
formulated at 10 mg/mL, in 20 mM 
histidine/histidine hydrochloride, 70 mM NaCl, 
106 mM (4% [w/v]) trehalose dihydrate, and 0.01% 
(w/v) polysorbate 80, pH 6.0 
IV 
300 mg 
Day 1, 
Day 15, 
and 
Week 26 
AstraZeneca 
Nijmegen, 
B.V. (formerly 
MedImmune 
Pharma, BV) 
Placebo 
Placebo for IV administration is supplied in 10R 
vials filled with 10 mL (nominal) solution containing 
10 mM histidine/histidine hydrochloride, 75 mM 
NaCl, 106 mM (4% [w/v]) trehalose dihydrate, and 
0.02% (w/v) polysorbate 80, pH 6.0 
IV 
Day 1, 
Day 15, 
and 
Week 26 
AstraZeneca 
Nijmegen, 
B.V. (formerly 
MedImmune 
Pharma, BV) 
 

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Table 7 
Description of Investigational Products and RCP Dosing  
Investigational 
Product 
Concentration and Formulation as Supplied 
Route 
Dose 
RCP 
Dosing 
Regimen 
Manufacturer 
Berkshire 
Sterile 
Manufacturing, 
Inc. 
IV = intravenous; NaCl = sodium chloride; RCP = randomized-controlled period; w/v = weight/volume. 
7.1.1 
Inebilizumab or Matched Placebo  
7.1.1.1 
Investigational Product Inspection  
Each vial selected for dose preparation should be inspected. Both inebilizumab and placebo are 
supplied as a clear to slightly opalescent, colorless to slightly yellow solution, free from or 
practically free from visible particles. Inebilizumab is a sterile liquid drug product (100 mg 
inebilizumab per vial, nominal) intended for IV infusion following dilution in normal saline. 
Placebo is a sterile liquid product intended for IV infusion following dilution in normal saline. 
Any defects with the IP must be reported immediately to the Sponsor’s Quality Assurance 
Department and the site monitor. The Sponsor’s Quality Assurance contact information for 
reporting product complaints is: ClinicalProductComplaints@horizontherapeutics.com . During 
the investigation of the product complaint, all IP must be stored at labeled conditions unless 
otherwise instructed. 
7.1.1.2 
Investigational Product Storage  
Investigational product to be diluted for IV use will be appropriately labeled in accordance with 
national laws and regulations, including required translations. Investigational product is provided 
as 3 vials per blinded kit. 
This IP should not be shaken and requires no special biohazard handling. It must be stored at 2ºC 
to 8ºC (36ºF to 46ºF) in a refrigerator with adequate temperature monitoring. The IP must not be 
frozen. It should be stored in the original outer package in a location with limited access. 
7.1.1.3 
Investigational Product Dose Preparation  
Inebilizumab for IV administration and placebo for IV administration are supplied as a sterile 
liquid in a 10R glass vial at a nominal fill volume of 10 mL with 20-mm stopper and flip-off cap 
overseal. 
No incompatibility has been observed between inebilizumab or placebo and IV infusion bags 
made of polyolefin or polyvinyl chloride. Inebilizumab and placebo do not contain preservatives 
and any unused portions must be discarded. Preparation of IP and IV bags is to be performed 
aseptically. 
To prepare each inebilizumab or placebo dose, 3 vials of IP, one 250 mL IV bag containing 0.9% 
(weight/volume) saline, and one IV infusion pump are required. Each vial should be used only 
one time to prepare a single dose. With approval of the Sponsor (and using additional 

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administration instructions), 100 mL or 500 mL saline bags may be used if 250 mL bags are not 
available or not appropriate.  
The dose preparation steps are as follows: 
x The tab portion of the vial cap should be removed and the rubber stopper cleaned with 
70% ethyl alcohol or equivalent. 
x For each dose, 30 mL of blinded IP will be obtained from 3 vials by withdrawing 10 mL 
from each vial. Use a new needle for each withdrawal. 
x Add 30 mL of blinded IP to the saline bag using aseptic technique. 
x Gently mix the contents of the IV bag by inversion. Do not shake the solution. The saline 
bag should then be inspected to ensure the solution is clear. 
Total in-use storage time from needle puncture of the IP vials to start of administration should 
not exceed 4 hours at room temperature or 24 hours at 2°C to 8°C (36°F to 46°F). Although 
prepared IP is stable for 24 hours at 2°C to 8°C (36°F to 46°F), the dose of IP must be mixed on 
the day of administration. 
The prepared infusion solution should be at room temperature prior to the start of the IV 
infusion.  
7.1.1.4 
Investigational Product Dosing and Administration  
Prior to each infusion in the RCP and OLP, the Investigator or other qualified medical personnel 
must confirm that none of the conditions requiring delay or discontinuation of IP administration 
are met (Section 6.4.1). 
Premedication (from commercial supplies) with a corticosteroid (eg, methylprednisolone 100 mg 
IV or equivalent), an antihistamine (eg, diphenhydramine 25-50 mg orally or equivalent), and an 
anti-pyretic (eg, acetaminophen 500-650 mg orally or equivalent) will be administered 
approximately 30-60 minutes prior to each IP infusion. 
Vital signs will be obtained prior to the start of each IP infusion. An experienced and qualified 
staff member will place the IV access. 
The prepared solution will be administered IV via an infusion pump at an incrementally 
increasing rate through an IV line containing a sterile, low-protein binding 0.2 or 0.22 micron 
in-line filter according to the schedule in Table 8. 
Table 8 
Infusion Rate for Investigational Product after Dilution in a 250 mL IV 
Bag  
Elapsed Time (minutes) 
Infusion Rate (mL/hour) 
0-30 
42 
31-60 
125 
61 to end of infusion 
333 
IV = intravenous. 

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Unless an infusion reaction occurs resulting in discontinuation of infusion, the entire infusion 
bag contents must be administered and the tubing must be flushed with a volume of saline at 
least as large as that of the tubing to ensure complete delivery of the IP infused at a rate not to 
exceed 333 mL/hour. 
After completion of the infusion, subjects will be observed for at least one hour. 
Medically qualified personnel must be immediately available to respond to emergencies during 
administration of IP. Appropriate drugs and medical equipment to treat acute hypotensive, 
bronchoconstrictive, or anaphylactic reactions must be immediately available, and study 
personnel must be trained to recognize and treat these reactions. Additionally, appropriate drugs 
and medical equipment to treat IRRs must be immediately available, and study personnel must 
be trained to recognize and treat IRRs. 
If an infusion reaction occurs, the site may stop or slow the infusion. Resumption of the infusion 
is at the discretion of the site. Management of infusion reactions will depend on the type and 
severity of the reaction and is at the discretion of the Investigator. For life-threatening infusion 
reactions, IP should be immediately and permanently stopped and appropriate supportive 
treatment administered. For less severe infusion reactions, management may involve temporarily 
stopping the infusion, reducing the infusion rate, and/or administering symptomatic treatment.  
7.1.1.5 
Monitoring of Dose Administration  
Vital signs (body temperature, blood pressure, pulse rate, and respiratory rate) must be obtained: 
x Within 60 minutes prior to IP administration 
x 15 (± 5) minutes after the start of the infusion and then every 30 (± 10) minutes until 
completion of infusion 
x At the completion of infusion (+ 10 minutes) 
x 60 (± 10) minutes after dosing (repeated as needed until stable) 
7.1.2 
Investigational Product Accountability  
Study site staff will maintain a record of the IP doses received, dispensed, administered, and 
destroyed. All records will be maintained with controlled access. The Investigator will 
administer the IP only to subjects included in this study and according to the procedures 
established in this study protocol. Each administration of IP will be documented and transferred 
to the eCRF. 
7.1.3 
Investigational Product Handling and Disposal  
The Investigator or designee must either destroy unused IP on site or return any unused IP to the 
Sponsor or designee, regardless of whether the study was completed or terminated prematurely. 
Destruction or return of IP must be appropriately documented. 

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7.2 
Additional Study Medication  
7.2.1 
Oral Glucocorticoid Taper  
All subjects will receive daily oral prednisone (or equivalent) from Day 1 through Week 8, 
according to a tapering dose schedule (Table 9). The open-label GCs will be local, commercial 
products supplied to subjects by the investigational sites. 
Table 9 
Glucocorticoid Taper Schedule (Randomized-controlled Period)  
RCP Week 
Oral Prednisone Dose (or Equivalent) 
Weeks 1-2 
20 mg/day 
Weeks 3-4 
15 mg/day 
Weeks 5-6 
10 mg/day 
Weeks 7-8 
5 mg/day 
RCP = randomized-controlled period. 
7.3 
Assessment and Verification of Compliance  
Site staff will administer the infusion IPs at the study center. The dose and date of administration 
of IP must be recorded in the subject eCRF. Treatment compliance for IV inebilizumab and IV 
placebo will be assessed based on this information. 
Patients are to bring their prednisone (or equivalent) tablets with them each visit until the end of 
the 8-week GC taper so that a compliance check (pill count) can be performed. An assessment of 
compliance will be recorded by the study staff in source documentation. 
7.4 
Treatment Assignment and Bias Minimization  
7.4.1 
Treatment Allocation for RCP  
Subjects will be randomized 1:1 within each stratum (by first or subsequent IgG4-RD 
manifestation, ie, newly-diagnosed vs recurrent) by the IXRS to either the inebilizumab group or 
the placebo group. 
x Inebilizumab group: Inebilizumab 300 mg IV on Day 1, Day 15, and at Week 26 
x Placebo group: Matching IV placebo on Day 1, Day 15, and at Week 26 
7.4.2 
Treatment Allocation for OLP  
All subjects in the OLP will receive open-label inebilizumab 300 mg IV on Day 1 and at 
Week 26. On Day 15, subjects who were randomized to receive inebilizumab in the RCP will 
receive a blinded dose of IV placebo, while subjects who were randomized to receive placebo in 
the RCP will receive a blinded 300 mg dose of inebilizumab. This allocation will be managed by 
the IXRS to maintain the blinding of sites and subjects to treatment assignment during the 
preceding RCP. Subsequent administrations of 300 mg IV inebilizumab will occur every six 
months for the remainder of the OLP. 

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7.4.3 
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 are provided in the IXRS manual. 
7.4.4 
Extent and Maintenance of Blinding  
This is a double-blind study in which inebilizumab and placebo are matched in appearance.  
The Sponsor will remain blinded until after the database lock for primary efficacy analysis, 
which will occur after all subjects have completed the Day 365 visit (Visit 15) or discontinued 
early from the RCP. Subjects, site staff, and contract research organization (CRO) personnel will 
remain blinded to individual subject treatment assignment until final database lock at the 
conclusion of the study. Potentially unblinding laboratory data will not be available to 
investigative site personnel until after final database lock. 
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. 
7.4.5 
Unblinding Procedures  
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. 
7.5 
Concomitant Medications and Treatments  
Subjects should receive all medications, including treatments for IgG4-RD, that are considered 
by their physician to be necessary for their health and well-being. 
The Sponsor recommends that Investigators ensure that all patients are up to date with 
required vaccinations prior to entry into the study. 
7.5.1 
Prohibited Medications  
Patients must receive all treatments that are considered necessary for their health in the judgment 
of their physician(s). The following prohibited medications will require the discontinuation of IP, 
but subjects who receive prohibited medications must remain in the study through the final 
Week 52 RCP visit.  
Generally, GC treatment for reasons other than new or worsening IgG4-RD activity is 
prohibited, but exceptions are described in Section 7.5.2 (GCs for uses other than IgG4-RD). The 
per-protocol limitations on dose and duration of GC treatment for IgG4-RD flare are described in 
Section 7.6. The Investigator must provide the indication for each use of GC or other 
immunosuppressive therapy. 

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Additional prohibited medications in the RCP and OLP include: 
x Biologic or non-biologic immunosuppressive agents other than GCs, including but not 
limited to, azathioprine, mycophenolate mofetil, cyclosporine, methotrexate, leflunomide, 
cyclophosphamide, rituximab, etanercept, adalimumab, infliximab, certolizumab pegol, 
golimumab, abatacept, and tocilizumab.  
x Live viral vaccines or live therapeutic infectious agents. 
Receipt of prohibited medication requires discontinuation of IP as described in Section 6.4.1. 
7.5.2 
Permitted Glucocorticoid Uses  
Aside from the required 8-week GC taper (Section 7.2.1), GCs are generally only permitted in 
this study to treat IgG4-RD flares (see Section 7.6). However, the following are permitted GC 
use for indications other than IgG4-RD flare: 
x Oral GC treatment for ≤ 2 weeks (for any purpose). 
x GCs at a dose of ≤ 2.5 mg of prednisone or equivalent for treatment of adrenal 
insufficiency (mineralocorticoids are permitted) or intolerance of steroid taper (in this 
case, continued tapering of steroids should be performed as tolerated). GCs at any dose 
should not be continued for the purpose of prevention of IgG4-RD related flare. 
x Inhaled, intranasal or topical corticosteroids. 
x Up to 2 intra-articular steroid injections that do not exceed 40 mg methylprednisolone or 
equivalent per injection. 
7.6 
Management of Flare of IgG4-RD During the Study  
Treatment of flares is at the discretion of the Investigator. Subjects should be managed in 
accordance with best medical practice for their condition regardless of whether protocol-defined 
flare criteria are met. Stenting or other procedures are permitted as medically warranted per the 
judgment of the Investigator. Unless treatment is urgent, in which case medically appropriate 
therapy should be instituted without delay, Investigators should conduct flare assessments 
according to the organ(s) affected prior to initiation of treatment, if possible. 
Choice of flare treatment is at the discretion of the Investigator. The use of GCs at a dose 
exceeding 40 mg/day of prednisone or equivalent, or for a duration exceeding 8 weeks including 
taper to discontinuation, requires discontinuation of IP. Use of any prohibited 
immunosuppressive treatment for flares requires discontinuation of IP (Section 7.5.1). 
8 
SAFETY DATA COLLECTION AND REPORTING  
An external, independent SDMC will perform evaluations of safety data at specified regular 
intervals throughout the study and make recommendations to the Sponsor regarding further 
conduct of the study. See Section 11.1 for details on SDMC activities.  

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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 – A 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 
 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. 
For the purposes of this protocol, IgG4-RD disease activity or flare that meets any of the 
above SAE criteria, including hospitalization for a procedure required to manage an 
IgG4-RD flare, will not be reported as an SAE unless it results in death or occurs during 
the screening period. Clinically significant events of IgG4-RD disease activity, as 
determined by the Investigator, should be reported as AEs. 
A hospitalization for elective or pre-planned treatment of a pre-existing condition that did 
not worsen from baseline will not be considered an SAE. 
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 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.  

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“Related” implies that the event is considered to be “associated with the use of the drug” 
meaning that there is “a reasonable possibility” that the event may have been caused by the IP 
(ie, there are facts, evidence, or arguments to suggest possible causation). 
x Adverse reaction – An adverse reaction is any AE caused by a drug. 
x Suspected adverse reaction – A SAR is any AE for which there is a reasonable 
possibility that the drug caused the AE. For the purposes of safety reporting to regulatory 
agencies, “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 an adverse reaction. 
x Unexpected – An event is considered unexpected if it is not listed in the 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. 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 graded according to the CTCAE, version 5.0. 
The determination of severity for events not listed in the CTCAE should be made by the 
Investigator based upon medical judgment and the severity categories of Grade 1 to 
Grade 5 as defined here, with the maximum severity recorded: 
 Grade 1 (mild): 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. 
 Grade 2 (moderate): 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. 
 Grade 3 (severe): 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. 
 Grade 4 (life-threatening): 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). 
 Grade 5 (fatal): Death (loss of life) as a result of an event. 
8.2 
Documenting Adverse Events  
AEs reported by the subject, spontaneously or in response to an open question from the study 
personnel, and AEs revealed by observation will be recorded during the study at the 
investigational site. 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 

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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 exit from the 
study, whether or not related to the study.  
In addition to eCRF entry, all SAEs must be reported to the Sponsor within 24 hours of site staff 
awareness by submitting a SAE Report Form by email to: 
Email: Clinicalsafety@horizontherapeutics.com 
Alternatively, the SAE Report Form can be submitted by fax to: 
US-Only Fax Number: 1-800-860-7836 
EX-US Fax Number: 1-224-855-5055 
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 Sponsor will work with the Investigator to ensure that all the necessary information is 
provided within one 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. Notification of the IRB or IEC of all SAEs that occur at the Investigator’s site are the 
responsibility of the Investigator. Investigators will be notified of all unexpected, serious, 
drug -related events (7 and 15 Day Safety Reports) that occur at other investigative sites during 
the clinical trial. Each Investigator is responsible for notifying its IRB or IEC of these additional 
SAEs. 
8.4 
Adverse Events of Special Interest  
An AESI is an AE of scientific and medical interest specific to understanding of the IP and may 
require close monitoring and collection of additional information by the Investigator. An AESI 
may be serious or nonserious.  
The rapid reporting of AESIs allows ongoing surveillance of these events in order to characterize 
and understand them in association with the use of this IP. All AESIs, regardless of seriousness 
or investigator-determined relationship to IP, must be reported to the Sponsor within 24 hours of 
site staff awareness by submitting an AESI Report Form by email to: 
Email: Clinicalsafety@horizontherapeutics.com 
Alternatively, the AESI Report Form can be submitted by fax to: 
US-Only Fax Number: 1-800-860-7836 
EX-US Fax Number: 1-224-855-5055 

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The following AESIs will be particularly monitored in this study: 
x Anaphylaxis and serious hypersensitivity reactions 
x Infusion-related reactions 
x Immune complex disease 
x Cytopenia 
x Serious and/or opportunistic infections, including PML (see Appendix A for list of 
opportunistic infections). 
8.5 
Other Events Requiring Immediate Reporting  
8.5.1 
Pregnancy  
Pregnancy in a female subject who has received IP must be reported to the Sponsor (Section 8.3) 
within 24 hours of Investigator awareness of the event, by email or fax using the Pregnancy 
Report Form. 
Subjects who become pregnant during the study period must not receive additional doses of IP 
but will not be withdrawn from the study. If the subject requests to know which treatment she 
received, this information will be provided to her. The pregnancy will be followed for outcome 
of the mother and child (including any premature terminations) and should be reported to the 
Sponsor’s Patient Safety group after outcome. 
Should the Investigator become aware of a pregnancy in the partner of a male study subject who 
has received IP, this should be reported to the Sponsor within 24 hours of knowledge of the 
event, by fax or email using the Pregnancy Report Form (see Section 8.3 for contact 
information). The Sponsor will endeavor to collect follow-up information on such pregnancies, 
provided the partner of the study subject provides consent. 
8.5.2 
Overdose or Misuse  
Any instance of overdose of IP (suspected or confirmed) must be communicated to the Sponsor 
(Section 8.3) within 24 hours of Investigator awareness. Any associated AEs or SAEs must also 
be reported and their management should be recorded. 
9 
STATISTICAL CONSIDERATIONS  
9.1 
General Considerations  
The analyses with a treatment policy strategy will include all data captured during the 52-week 
RCP, defined as the period from Day 1 (Dosing) at Visit 2 to the conclusion of the scheduled last 
RCP visit at Visit 15 (Week 52), inclusive. 
The analyses applying the while-on-treatment strategy will include all data captured while 
subjects are on treatment, defined as the period from Day 1 (Dosing) at Visit 2 and 6 months 
after the last treatment during the RCP, inclusive. 

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Summary data will be presented in tabular format 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, including N, mean, standard deviation, median, and 
range. Data listings will be sorted by treatment group and patient number. Additional details of 
statistical analyses will be described in the statistical analysis plan (SAP). 
9.2 
Statistical Hypotheses  
The following is the null and alternative hypotheses associated with the primary endpoint: 
H0: HR = 1 vs H1: HR ≠ 1, 
where HR indicates the hazard ratio of treated and AC-determined IgG4-RD flares relative to 
placebo. The hypothesized treatment effect of a relative reduction of 65% in risk implies a HR of 
0.35. 
9.3 
Determination of Sample Size  
A total of 39 flares are required to detect a relative reduction of 65% in risk for time from Day 1 
(dosing) to onset of flare during the RCP with at least 90% power, two-sided α = 0.05, and a 
1:1 randomization ratio based on log-rank test for comparison. Assuming the probability of 
having a treated and AC-determined IgG4-RD flare during the RCP in the placebo group is 0.35 
(Yunyun et al, 2017; Yunyun et al, 2019; Wang et al, 2018), a total of 160 subjects (80 subjects 
per treatment group) are expected to be randomized and dosed  using the following formula: 
 
where 
Pr(Fail) = 0.5P0 + 0.5P1 
is the weighted average of the failure probabilities P0 and P1 and in the placebo and inebilizumab 
groups, respectively. Assuming the probability of having a treated and AC-determined IgG4-RD 
flare during the RCP in the placebo group is 0.35 and an exponential survival distribution, the 
hazard rate for the placebo group is -log(1-0.35) = 0.4308. With the hypothesized treatment 
effect of a relative reduction of 65% in risk, the hazard rate for the inebilizumab group during the 
RCP is -0.35 log(1-0.35) = 0.1508. Pr(Fail) = (0.35 + [1 - exp(-0.1508)])/2 = 0.245. 
The hypothesized 65% reduction in risk is an estimate based on the observed treatment effect for 
attack reduction with inebilizumab in the phase 3 NMOSD trial (77% reduction in risk), and 
limited published clinical data on the efficacy of the B cell-depleting agent rituximab in 
IgG4-RD.  
To mitigate uncertainties in the flare event rate in the study population, a blinded event rate 
assessment may take place after the 50th dosed subject competes the RCP or has a positively 
treated adjudicated flare or early discontinued from the study during the RCP. This assessment 
will be performed on all available data and will not take into account treatment information. 
These first 50 dosed subjects who complete the RCP or have a positively treated adjudicated 
flare or early discontinued from the study will be randomly sampled and used to simulate 

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different sample sizes between 160 and 200 in increments of 10. For each of the sample sizes, 
this simulation process will be repeated 10,000 times to give a distribution of the number of 
flares. The target sample size is the one that achieves 39 flares 90% of the time. 
If the blinded assessment from these first 50 dosed subjects indicates that the number of flares 
expected with 160 subjects is less than 39, then the sample size may be adjusted based on the 
above exercise to the number of subjects anticipated to achieve 39 flares with a maximum of 
200 subjects (100 subjects per treatment group). 
9.4 
Analysis Sets  
Full Analysis Set: The Full Analysis Set will include all subjects randomized and who receive 
any dose of IP in the study. Subjects will be analyzed according to the treatment randomized. 
The efficacy analysis will be based on the Full Analysis Set. 
Safety Analysis Set: The Safety Analysis Set will include all subjects who received any dose of 
IP during the RCP. Subjects will be analyzed according to the treatment that they actually 
received. Specifically, subjects randomized to inebilizumab who received all placebo doses will 
be included in the placebo group; conversely, subjects randomized to the placebo group who 
received at least one dose of inebilizumab will be included in the inebilizumab group. Safety, 
and ADA analyses will be based on Safety Analysis Set. 
The Open-label Analysis Set: The Open-Label Analysis Set will include all subjects who 
receive any dose of inebilizumab during the OLP. 
The Any Inebilizumab Analysis Set: The Any Inebilizumab Analysis Set will include all 
subjects who receive any dose of inebilizumab. 
9.5 
Methods for Statistical Analyses  
9.5.1 
Analysis of the Primary Efficacy Endpoint  
The primary efficacy analysis will use the treatment policy strategy, which includes all data 
captured during the 52-week RCP.  
The primary efficacy variable is the time in days from Day 1 (dosing) to the date of the first 
treated and AC-determined IgG4-RD flare within the 52-week RCP. The date of disease flare is 
defined as the date of initiation of any flare treatment (new or increased GC treatment, other 
immunotherapy, or interventional procedure) deemed necessary by the Investigator for the flare. 
The hazard rate in the inebilizumab group will be compared to that in the placebo group using 
the Cox proportional hazards model with the treatment indicator (inebilizumab or placebo) and 
the stratification factor as the explanatory variables. The HR of inebilizumab versus placebo will 
be estimated together with its associated 95% CI. SAS PROC PHREG will be used for fitting 
this model. The data cutoff for the primary analysis will be when all subjects have completed or 
discontinued from the RCP. 

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Subjects who discontinue prematurely from the RCP without a treated and AC-determined flare 
will be censored in this model at the time of discontinuation. 
Additional analysis with the same model will be performed with data from subjects who meet the 
following criteria, censored at the time the relevant treatment was first received:  
x Received any treatment for IgG4-RD, including GC or immunosuppressive treatment, 
prior to experiencing a treated and AC-determined flare; or 
x Received any prohibited GC or immunosuppressive treatment prior to experiencing a 
treated and AC-determined flare. 
9.5.2 
Analysis of Secondary Efficacy Endpoints  
9.5.2.1 
Annualized Flare Rate for Treated and AC-determined Flares During the RCP  
The annualized flare rate for treated and AC-determined flares during the RCP will be analyzed 
with a treatment policy strategy, which includes all data captured during the 52-week RCP. The 
efficacy variable is annualized flare rate, which will be compared between the inebilizumab 
group and the placebo group using a negative binomial model. The response variable in the 
model will be the number of treated AC-determined flares experienced by a subject over the 
52-week RCP. The model will include covariates of treatment group (inebilizumab or placebo) 
and stratification factor. The logarithm of the subject’s corresponding follow-up time will be 
used as an offset variable in the model to adjust for patients having different exposure times 
during which the events occur. 
The estimated treatment effect (ie, the rate ratio of inebilizumab versus placebo), corresponding 
95% CI, and two-sided p-value for the rate ratio will be presented. In addition, the annual flare 
rate and the corresponding 95% CI within each treatment group, and the absolute difference 
between treatment groups with the corresponding 95% CI, will be presented. 
9.5.2.2 
Annualized Flare Rate for AC-determined Flares During the RCP, Whether or 
Not Treated  
The annualized flare rate for AC-determined flares, whether or not treated, during the RCP will 
be analyzed with a treatment policy strategy, which includes all data captured during the 
52-week RCP. The efficacy variable is the annualized flare rate, which will be compared 
between the inebilizumab group and the placebo group using a negative binomial model. The 
response variable in the model will be the number of AC-determined flares, regardless of 
treatment experienced by a subject, over the 52-week RCP. The model will include covariates of 
treatment group (inebilizumab or placebo) and stratification factor. The logarithm of the 
subject’s corresponding follow-up time will be used as an offset variable in the model to adjust 
for patients having different exposure times during which the events occur. 
The estimated treatment effect (ie, the rate ratio of inebilizumab versus placebo), corresponding 
95% CI, and two-sided p-value for the rate ratio will be presented. In addition, the annual flare 
rate and the corresponding 95% CI within each treatment group, and the absolute difference 
between treatment groups with the corresponding 95% CI, will be presented. 

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9.5.2.3 
Flare-free Treatment-free Complete Remission  
Two types of flare-free complete remission will be analyzed: flare-free treatment-free complete 
remission and flare-free corticosteroid-free complete remission.   
Flare-free treatment-free complete remission is defined as the lack of evident disease activity at 
Week 52, no AC-determined flare during the RCP, and no treatment for flare or disease control 
during the RCP except the required 8-week GC taper. Lack of evident disease activity is defined 
as either an IgG4-RD Responder Index (Wallace ) score of 0, or a determination by the 
investigator that no disease activity is present based on physical, laboratory, pathology or other 
evidence. 
Flare-free corticosteroid-free complete remission is defined as the lack of evident disease activity 
at Week 52, no AC-determined flare during the RCP, and no corticosteroid treatment for flare or 
disease control during the RCP except the required 8-week GC taper. Lack of evident disease 
activity is defined as either an IgG4-RD Responder Index (Wallace ) score of 0, or a 
determination by the investigator that no disease activity is present based on physical, laboratory, 
pathology or other evidence. 
The analysis of the proportion of subjects achieving each flare-free complete remission defined 
above for the composite estimand will include all data captured during the 52-week RCP. For 
both of these endpoints, the efficacy variable for each flare-free complete remission is the 
proportion of subjects achieving the corresponding flare-free complete remission at Week 52, 
which will be assessed using a logistic regression model respectively. The response variable in 
the model will be whether or not a subject achieves the corresponding flare-free complete 
remission at Week 52. The model will have treatment indicator (inebilizumab or placebo) and 
stratification factor as the explanatory variables.  
Subjects who discontinue prematurely from the RCP will be treated as not achieving complete 
remission at Week 52. The results of the analyses will be presented using odds ratios, together 
with associated 95% CI and two-sided p-value for inebilizumab versus placebo. 
An additional analysis under a treatment policy strategy with the same model will be conducted, 
with complete remission defined as the lack of evident disease activity at Week 52 and no 
AC-determined flare during the RCP. 
9.5.2.4 
Time to Initiation of Treatment for IgG4-RD, Regardless of AC Determination of 
Flare  
The analysis of time to initiation of treatment for IgG4-RD activity by the Investigator within the 
RCP, regardless of AC determination of flare, will use a treatment policy strategy, which 
includes all data captured during the 52-week RCP. The date of disease flare is defined as the 
date of initiation of any flare treatment (new or increased GC treatment, other immunotherapy, or 
interventional procedure) deemed necessary by the Investigator for the flare. 
The efficacy variable is the time in days from Day 1 (dosing) to the date of the first treatment for 
disease activity by the Investigator within the RCP, regardless of AC determination of flare 
within the 52-week RCP. 

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The hazard rate in the inebilizumab group will be compared to that in the placebo group using 
the Cox proportional hazards model with the treatment indicator (inebilizumab or placebo) and 
the stratification factor as the explanatory variables. The HR of inebilizumab versus placebo will 
be estimated together with its associated 95% CI. SAS PROC PHREG will be used for fitting 
this model.  
Subjects who discontinue prematurely from the RCP without receiving treatment for 
management of flare, as defined above, will be censored in this model at the time of 
discontinuation. 
9.5.2.5 
Glucocorticoid Use  
The analysis of GC use will include all data captured during the 52-week RCP. For each subject, 
GC use will be calculated as the cumulative GC dose taken for the purpose of disease control 
during the RCP. 
An analysis of covariance model with treatment indicator (inebilizumab or placebo) and 
stratification factor as the explanatory variables will be used. 
GC use for a purpose other than controlling IgG4-RD will not be included in the analysis. For 
subjects who discontinue prematurely from the RCP, further GC use will be imputed as 0.  
Results will be presented in terms of least square means (LSMEANS), treatment differences in 
LSMEANS, 95% CIs, and p-values. 
9.5.3 
Control of Type I Error  
The primary null hypothesis will be tested at two-sided α = 0.05. If, and only if, the treatment 
group comparison is statistically significant, the secondary hypotheses will be tested.  
The 3 key secondary endpoints to be considered for study-wise type I error control are: 
x Annualized flare rate for treated, AC-determined flares during the RCP. 
x The proportion of subjects achieving flare-free, treatment-free complete remission at 
Week 52, defined as the lack of evident disease activity at Week 52, no AC-determined 
flare during the RCP, and no treatment for flare or IgG4-RD disease control except the 
required 8-week GC taper. Lack of evident disease activity is defined as either an IgG4-
RD Responder Index (Wallace ) score of 0, or a determination by the investigator that no 
disease activity is present based on physical, laboratory, pathology or other evidence. 
x The proportion of subjects achieving flare-free, corticosteroid-free complete remission at 
Week 52, defined as the lack of evident disease activity at Week 52, no AC-determined 
flare during the RCP, and no corticosteroid treatment for flare or disease control except 
the required 8-week GC taper.  
Null hypotheses for the three key secondary endpoints will be tested using Hochberg procedure 
(Hochberg, 1988). If the largest p-value is < 0.05, the null hypotheses for all three secondary 
endpoints will be rejected. If the largest p-value is ≥ 0.05 and the second largest one is < 0.025, 
the null hypotheses corresponding to the two endpoints with smaller p-values will be rejected. If 
the largest p-value is ≥ 0.05, the second largest one is ≥ 0.025, and the smallest p-value is 

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< 0.0167, only the null hypothesis corresponding to the endpoint with the smallest p-value will 
be rejected. Otherwise, no null hypothesis will be rejected. 
9.5.4 
Subgroup Analyses  
Consistency of treatment effect measured by primary and 3 key secondary endpoints in the 
following subgroups will be investigated for the Full Analysis Set: 
x Age (< 65 vs ≥ 65) 
x Sex (male vs female) 
x Region (US vs non-US; EU vs non-EU; and Asia vs non-Asia) 
x Serum IgG4 concentrations at baseline 
x Racial/ethnic subgroups as needed for national/regional regulatory filings 
x First or subsequent treatment course for IgG4-RD 
The nominal p-value and 95% CIs of treatment effect will be provided for each subgroup 
analysis. Forest plots will be generated to visually present the consistency of treatment effect in 
different subgroups with overall treatment effect. 
9.5.5 
Safety Analysis  
Safety endpoints will be summarized separately for the RCP, OLP and SFUP. Safety data from 
the RCP and OLP will be presented based on the Safety Analysis Set and on the Open-label 
Analysis Set, respectively. Data after subjects receive inebilizumab will be analyzed based on the 
Any Inebilizumab Analysis Set.  
AE and SAE collection begins after the subject signs the informed consent document and lasts 
until the end of study visit. AESI identification will be based on MedDRA coding. The search 
criteria for the AESIs will be established prior to database lock for the primary analysis. 
The number and percentage of subjects reporting TEAEs and TESAEs will be summarized for 
each treatment group by system organ class and preferred terms, by severity, and by relationship 
to the IP. The rate of AEs per 100 person-years at risk, calculated as (total number of AEs)/(total 
person years) × 100, will also be reported.  
AEs and SAEs collected during the RCP will be analyzed using a treatment policy strategy, 
(which includes all data captured during the RCP) and a while-on-treatment strategy (which 
includes all data captured while subjects are on treatment). The risk difference and corresponding 
95% CI will be presented. In addition, the time to first instance of an AESI and duration of the 
AESI will summarized by treatment group when appropriate.  
Clinically important abnormalities in vital signs, laboratory parameters, ECGs, and physical 
examinations will be recorded as AEs or SAEs. Laboratory measurements, as well as their 
changes from baseline at each collection time point and shift from baseline, if applicable, will be 
summarized descriptively. 
Safety subgroup analyses will be investigated when appropriate and may include analyses by age 
(< 65 vs ≥ 65), sex (male vs female), region (US vs non-US; EU vs non-EU; and Asia vs 

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non-Asia), serum IgG4 concentrations at baseline, stratification factor, and subgroups as needed 
for national/regional regulatory submissions. 
9.5.7 
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 potential impact of ADA on the safety and efficacy of inebilizumab may be explored if data 
allow. 
10 
ETHICAL CONSIDERATIONS  
10.1 
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 Council for Harmonisation 
(ICH)/Good Clinical Practice (GCP), the European Union (EU) Clinical Trials Regulation No 
536/2014 and applicable local and regional regulatory requirements.   
10.2 
Ethics Review  
The final study protocol, including the final version of the ICF, must be approved or given a 
favorable opinion in writing by an IRB or IEC, as appropriate. The Investigator must submit 
written approval to 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 

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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’s representative. 
In Japan the head of the study site should submit a notification of direction/determination, as 
well as IRB written approval, to the Sponsor and the Principal Investigator before enrollment of 
any subject into the study.  
10.3 
Informed Consent  
The Investigator or other study site designee with IRB/IEC-approved qualifications will ensure 
that the patient is given full and adequate oral and written information about the nature, purpose, 
possible risk, and benefit of the study. Patients must also be notified that they are free to 
discontinue from the study at any time. The patients 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 Food and Drug 
Administration [FDA]), and that every effort will be made to maintain patient confidentiality. 
The patient 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 PI or his/her designee, and the original retained by 
the Investigator/study site as part of that subject’s record. 
The Investigator must maintain the original, signed ICF. A copy of the signed ICF must be given 
to the patient. 
Patients 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. 
10.4 
Deviation from the Clinical Study Protocol  
The Investigator(s) must not deviate from or make any changes to the protocol without 
documented agreement between the Principal Investigator and the Sponsor or IRB/IEC approval, 
based on deliberations. This shall not apply to cases where the deviation or change is necessary 
to avoid an immediate hazard to the subjects, for other compelling medical reasons, or where the 
changes involve only logistical or administrative aspects of the clinical study (eg, changes to the 
organization/structure of Sponsor, the name/department of the study site, the address or phone 
number of the study site or Sponsor, or the job title of the Investigator or Medical Monitor). In 
such cases, the Principal Investigator must notify Sponsor, the head of the study site, and the IRB 
as soon as possible about the details of the deviation or change, the reason for the deviation, and 
a proposed revision in the protocol, if required, to obtain their approval.  

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For study sites in Japan, a certificate of approval by the head of the study site should be obtained 
via the head of the study site.  
The Investigator(s) should document all deviations from the protocol regardless of the reason(s) 
or justification. 
10.5 
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 CRFs shall be by subject ID numbers only. If required, the 
subject’s full name may be made known to an authorized regulatory agency or other authorized 
official. 
The conduct of this study and the processing of any personal data collected from each subject (or 
from a subject’s healthcare professional or other relevant third-party sources) by the Sponsor or 
its designee, the site, or the Investigator for use in the study will fully adhere to the requirements 
set out in applicable data protection and medical privacy laws or regulations, including, without 
limitation, the General Data Protection Regulation (GDPR) EU 2016/679 and EU 
Directive 95/46/EEC. The Sponsor or its designee shall ensure that, at all times, it has an 
appropriate legal basis for processing personal data under applicable data protection laws. Site-
based organizational and technical arrangements to avoid unauthorized access vary by site but all 
include access-controlled/access-limited document control and technical solutions, including 
passwords and security control measures to protect study-specific data, both in paper and 
electronic format. 
The Investigators shall provide coded data to the Sponsor or its designee, which do not reveal the 
patient’s name, full date of birth, or any other information that can identify the patient. All 
personal information shall be replaced with a SID number before any information leaves the 
investigative sites.  
The Investigator shall report any data breaches that occur to the Sponsor or its designee, without 
undue delay and in line with GDPR requirements. The Sponsor shall address data breaches in 
compliance with the requirements of applicable laws and regulations, including the GDPR. Any 
data breach procedures implemented by Sponsor shall provide specific responses to actual or 
potential threats and involve investigation, containment, and mitigation. If applicable, the 
authorities and the data subjects shall be notified of a data breach within the required timeframes 
of the applicable laws and regulations, including those of the GDPR. 
10.6 
Disclosure  
Sponsor is responsible for preparing and providing the appropriate regulatory authorities with 
Clinical Study Reports, according to the applicable regulatory requirements. 

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10.7 
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 samples will be collected unless specifically required to monitor the safety of the subject. 
Leftover samples stored for future research (not obtained in China) with patient consent 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. Samples 
collected in China will be destroyed upon publication of the Clinical Study Report. 
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. 
11 
OVERSIGHT  
11.1 
Safety Data Monitoring Committee  
The external, independent SDMC is responsible for safeguarding the interests of study 
participants via review of accumulating safety data and for supporting study integrity and 
interpretability based on their review of ongoing study conduct. The SDMC will provide Sponsor 
with recommendations for actions with respect to study conduct and the management of subjects 
treated under the study protocol. The SDMC members are independent of Sponsor and any 
CRO/organization collaborating with Sponsor on the study.  
The SDMC will not be charged with any formal interim analysis, will not conduct a futility 
analysis, and will not be asked to consider early study completion for efficacy.  
For additional details, refer to the SDMC Charter. 
11.2 
Quality Control and Assurance  
To ensure compliance with GCP and all applicable regulatory requirements, Sponsor may 
conduct a quality assurance audit. See Section 11.4 for details regarding the audit process. 

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11.3 
Monitoring  
Before an investigational site can enter a subject into the study, a representative of Sponsor or of 
the CRO 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 or the CRO will have regular contact 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 CRFs 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 study-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, confirm that any 
SAEs have been forwarded to Sponsor or representative, and confirm those SAEs that 
met criteria for reporting have been forwarded to the IRB/IEC. 
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. 
11.4 
Audits  
To ensure compliance with GCP and all applicable regulatory requirements, Sponsor or its 
authorized representatives 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. 

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Initial IRB/IEC approval, and all materials approved by the IRB/IEC for this study, including the 
ICF and recruitment materials, must be maintained by the Investigator and made available for 
inspection. 
In addition to the above, representatives of 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 
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. 
11.5 
Records  
11.5.1 
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. 
An electronic data capture system compliant with 21 CFR Part 11 will be used for data collection 
and query handling. The Investigator will ensure that data are recorded on the eCRFs as specified 
in the study protocol and in accordance with the eCRF Completion Guidelines provided. 
The Investigator ensures the accuracy, completeness, and timeliness of the data recorded and of 
the provision of answers to data queries 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. 
11.5.2 
Source Documentation  
Sponsor or its authorized representative 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, IP stocks, drug accountability records, subject 
charts, study source documents, and other records relative to study conduct. 
11.5.3 
Records Retention  
Investigators must maintain all documentation related to the study for a period of 25 years. 
Retention may be shorter in accordance with local regulations, as long as records are maintained 
for a minimum of 2 years following the last marketing application approval, if marketing 
applications are filed. Sites must obtain sponsor approval prior to destroying any records.  
If it becomes necessary for the Sponsor or a regulatory authority to review any documentation 
relating to the study, the Investigator must permit access to such records.  

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12 
PUBLICATION POLICY  
The publication policy of Sponsor is discussed in the Investigator's Clinical Research 
Agreement. 
13 
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information/communication-programs/nkdep/laboratory-evaluation/glomerular-filtration-rate-
calculators/mdrd-adults-si-units. 
Orbai AM, Bingham CO. Patient reported outcomes in rheumatoid arthritis clinical trials. Curr 
Rheumatol Rep. 2015;17(4):28. 
Omar D, Chen Y, Cong Y, Dong L. Glucocorticoids and steroid sparing medications 
monotherapies or in combination for IgG4-RD: a systematic review and network meta-analysis. 
Rheumatology (Oxford). 2019 Sep 11. pii: kez380. doi: 10.1093/rheumatology/kez380. [Epub 
ahead of print] 
Perugino CA, Mattoo H, Mahajan VS, Maehara T, Wallace ZS, Pillai S, et al. Emerging 
Treatment Models in Rheumatology: IgG4-Related Disease: Insights Into Human Immunology 
and Targeted Therapies. Arthritis Rheumatol. 2017;69(9):1722-32. 
Pillai S, Perugino C, Kaneko N. Immune mechanisms of fibrosis and inflammation in IgG4-
related disease. Curr Opin Rheumatol. 2020;32(2):146-51. 
Rohekar G, Pope J. Test-retest reliability of patient global assessment and physician global 
assessment in rheumatoid arthritis. J Rheumatol. 2009;36(10):2178-82. 
Schiopu E, Chatterjee S, Hsu V, Flor A, Cimbora D, Patra K, et al. Safety and tolerability of an 
anti-CD19 monoclonal antibody, MEDI-551, in subjects with systemic sclerosis: a phase I, 
randomized, placebo-controlled, escalating single-dose study. Arthritis Res Ther. 
2016;18(1):131. 
Stone JH, Zen Y, Deshpande V. IgG4-related disease. N Engl J Med 2012;366:539-51. 
Streicher K, Morehouse CA, Groves CJ, Rajan B, Pilataxi F, Lehmann KP, et al. The plasma cell 
signature in autoimmune disease. Arthritis Rheumatol. 2014;66(1):173-84. 
Terao C; Ota M; Iwasaki T, Shiokawa M, Kawaguchi S, Kuriyama K, et al. IgG4-related disease 
in the Japanese population: a genome-wide association study. Lancet Rheumatol. 
2019;1(1):pe14-22. E-publication 06 August 2019. 

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Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T, et al. Comprehensive 
diagnostic criteria for IgG4-related disease (IgG4-RD), 2011. Mod Rheumatol. 
2012;22(1):21-30. 
Umehara H, Okazaki K, Nakamura T, Satoh-Nakamura T, Nakajima A, Kawano M, et al. 
Current approach to the diagnosis of IgG4-related disease - Combination of comprehensive 
diagnostic and organ-specific criteria. Mod Rheumatol. 2017;27(3):381-91. 
Umehara H, Okazaki K, Kawano M, Tanaka Y. The front line of research into immunoglobin 
G4-related disease - Do autoantibodies cause immunoglobin G4-related disease? Mod 
Rheumatol. 2019;29(2):214-18. 
Wallace ZS, Mattoo H, Carruthers M, Mahajan VS, Della Torre E, Lee H, et al. Plasmablasts as 
a biomarker for IgG4-related disease, independent of serum IgG4 concentrations. Ann Rheum 
Dis. 2015;74(1):190-5. 
Wallace ZS, Khosroshahi A, Carruthers MD, Perugino CA, Choi H, Campochiaro C, et al. An 
international multispecialty validation study of the IgG4-related disease responder index. 
Arthritis Care Res (Hoboken). 2018;70(11):1671-78. 
Wallace ZS, Zhang Y, Perugino CA, Naden R, Choi HK, Stone JH, ACR/EULAR IgG4-RD 
Classification Criteria Committee. Clinical phenotypes of IgG4-related disease: an analysis of 
two international cross-sectional cohorts. Ann Rheum Dis. 2019a;78(3):406-12.  
Wallace ZS, Naden RP, Chari S, Choi H, Dellatorre E, Dicaire J-F, et al. The 2019 American 
College of Rheumatology/European League Against Rheumatism Classification Criteria for 
IgG4-Related Disease. Arthritis Rheumatol. 2019b. doi: 10.1002/art.41120. [Epub 2019 Dec 2 
ahead of print]. 
Wang L, Zhang P, Wang M, Feng R, Lai Y, Peng L, et al. Failure of remission induction by 
glucocorticoids alone or in combination with immunosuppressive agents in IgG4-related disease: 
a prospective study of 215 patients. Arthritis Res Ther. 2018 Apr 10;20(1):65. 
Yunyun F, Yu C, Panpan Z, Hua C, Di W, Lidan Z, et al. Efficacy of Cyclophosphamide 
treatment for immunoglobulin G4-related disease with addition of glucocorticoids. Sci Rep. 
2017;7(1):6195. doi: 10.1038/s41598-017-06520-5. Epub 2017 Jul 21. 
Yunyun F, Yu P, Panpan Z, Xia Z, Linyi P, Jiaxin Z, et al. Efficacy and safety of low dose 
Mycophenolate mofetil treatment for immunoglobulin G4-related disease: a randomized clinical 
trial. Rheumatology (Oxford). 2019;58(1):52-60. 
Zhang W, Stone JH. Management of IgG4-related disease. Lancet Rheumatol in press (Sept 
2019).  

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14 
APPENDICES  
 

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APPENDIX A 
STUDY-SPECIFIED OPPORTUNISTIC INFECTIONS THAT MEET 
EXCLUSION CRITERIA AND REQUIRE DISCONTINUATION OF IP  
Definite a,b Opportunistic Infection 
Probable c Opportunistic Infection 
Pneumocystis jirovecii 
Paracoccidioides infections 
BK virus disease including polyomavirus-associated 
nephropathy  
Penicillium marneffei (Talaromyces) 
Cytomegalovirus disease 
Sporothrix schenckii 
Post-transplant lymphoproliferative disorder (EBV) 
Cryptosporidium species (chronic disease only) 
Progressive multifocal leukoencephalopathy 
Microsporidiosis 
Bartonellosis (disseminated disease only) 
Leishmaniasis (visceral only) 
Blastomycosis 
Trypanosoma cruzi infection (Chagas’s disease) 
(disseminated disease only) 
Toxoplasmosis 
Campylobacteriosis (invasive disease only) 
Coccidioidomycosis 
Shigellosis (invasive disease only) 
Histoplasmosis 
Vibriosis (invasive disease due to Vibrio vulnificus) 
Aspergillosis (invasive disease only) 
HCV progression 
Candidiasis (invasive disease or pharyngeal) 
 
Cryptococcosis 
 
Other invasive fungi: Mucormycosis (zygomycosis) 
(Rhizopus, Mucor and Lichtheimia), 
Scedosporium/Pseudallescheria boydii, Fusarium) 
 
Legionellosis 
 
Listeria monocytogenes (invasive disease only) 
 
Tuberculosis 
 
Nocardiosis 
 
Non-tuberculous mycobacterium disease 
 
Salmonellosis (invasive disease only) 
 
HBV reactivation 
 
Herpes simplex (invasive disease only) 
 
Herpes zoster (any form) 
 
Strongyloides (hyperinfection syndrome and 
disseminated forms only) 
 
EBV = Epstein-Barr visu; HBV = hepatitis B virus; HCV = hepatitis C virus. 
a 
Generally does not occur in the absence of immunosuppression and whose presence suggests a severe alteration 
in host immunity. 
b 
Can occur in patients without recognized forms of immunosuppression, but whose presence indicates a potential 
or likely alteration in host immunity. 
c 
Published data are currently lacking, but expert opinion believes that risk is likely elevated in the setting of 
biologic therapy. 
Source: Winthrop KL, Novosad SA, Baddley JW, Calabrese L, Chiller T, Polgreen P, et al. Opportunistic infections 
and biologic therapies in immune-mediated inflammatory diseases: consensus recommendations for infection 
reporting during clinical trials and postmarketing surveillance. Ann Rheum Dis. 2015;74(12):2107-16. 

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Additional infections may be considered to be exclusionary and to require discontinuation of IP 
according to the judgment of the Investigator. Investigators can also exercise discretion in 
recording opportunistic infections as AESIs that are not specified in Appendix A. 
 
 

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APPENDIX B 
GUIDANCE FOR ANAPHYLAXIS DIAGNOSIS  
The National Institute of Allergy and Infectious Disease (NIAID) and Food and Allergy 
Anaphylaxis Network (FAAN) define anaphylaxis as a serious allergic reaction that is rapid in 
onset and may cause death. 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). Their clinical criteria for diagnosing anaphylaxis are: 
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 
lipstongueuvula) 
AND AT LEAST ONE OF THE FOLLOWING 
a. Respiratory compromise (eg, dyspnea, wheeze-bronchospasm, stridor, reduced peak 
expiratory flow (PEF), hypoxemia) 
b. Reduced blood pressure (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 mmHg or greater than 30% decrease from that 
person’s baseline. 
Reference 
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(2):391-7. 

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APPENDIX C 
INVESTIGATOR’S AGREEMENT  
INVESTIGATOR’S AGREEMENT  
I have read the protocol, appendices, and accessory materials related to Study VIB0551.P3.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 International Council for Harmonisation 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 
 
 
 
Signature 
Date 
 
 
 
 
 

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APPENDIX D 
IGG4-RD FLARE EVALUATION AND CRITERIA  
IGG4-RD FLARE EVALUATION AND CRITERIA 
Investigational Product 
Inebilizumab 
Protocol Number 
VIB0551.P3.S2 
Version 
1.0 
Version Date 
2-Oct-2020 

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TABLE OF CONTENTS 
1 
PURPOSE ...................................................................................................................... 108 
2 
FLARE DEFINITION ................................................................................................... 109 
3 
COLLECTION OF DATA RELATED TO FLARE EVALUATION .......................... 110 
4 
ORGAN-SPECIFIC FLARE CRITERIA ...................................................................... 112 
4.1 
Pachymeninges ........................................................................................................... 113 
4.2 
Pituitary Gland ............................................................................................................ 115 
4.3 
Orbits........................................................................................................................... 117 
4.4 
Lacrimal Glands .......................................................................................................... 119 
4.5 
Salivary Glands ........................................................................................................... 121 
4.6 
Lymph node(s) ............................................................................................................ 123 
4.7 
Lungs, Including Pleura and Parenchyma .................................................................. 125 
4.8 
Aorta & large blood vessels ........................................................................................ 127 
4.9 
Retroperitoneum, Mediastinum, & Mesentery ........................................................... 129 
4.10 
Pancreas and Common Bile Duct ............................................................................... 132 
4.11 
Biliary tree (IgG4-RD sclerosing cholangitis) ............................................................ 134 
4.12 
Kidney ......................................................................................................................... 136 
4.13 
Skin ............................................................................................................................. 138 
4.14 
Other sclerosis/mass formation in thyroid (Riedel’s thyroiditis), liver, breast, 
prostate, maxillary sinus, nasal septum, pericardium, peripheral nerves, other ......... 140 
5 
SELECTED REFERENCES ......................................................................................... 142 

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1 
PURPOSE 
This document serves two purposes: 
x Provide guidance to the investigator regarding information to be entered into the 
electronic case report form(s) (eCRFs) related to flare assessments. This guidance is also 
anticipated to be useful to members of the study Adjudication Committee, who will 
review the information provided by the investigator when evaluating potential flares. 
x Establish clear and objective criteria, for each organ or site affected by IgG4-RD, for 
diagnosis of an IgG4-RD flare for the purpose of this clinical study.  The same criteria 
are used by investigators and AC members for diagnosis of flares. 
This document is not intended to specify or limit which assessments should be conducted by the 
investigator and which results should be considered when evaluating a potential flare. Rather, 
this document specifies the flare-related data that will be entered into the eCRFs and how that 
data contributes to the diagnosis of flare. 

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2 
FLARE DEFINITION 
An IgG4-RD flare is defined as new or worsening signs and symptoms of IgG4-RD disease 
activity that meet one or more organ-specific flare criteria, and for which there is no clear 
alternative diagnosis or conflicting biopsy findings. 

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3 
COLLECTION OF DATA RELATED TO FLARE EVALUATION 
For each potential flare event, the investigator will provide the following information. 
1. Observation that led to initiation of evaluation for flare 
x Patient-reported new/worsening symptoms 
x New/worsening physical exam (PE) finding 
x New/worsening laboratory finding 
x Incidental finding on imaging (not imaging triggered by symptom, PE or laboratory 
finding) 
x Other (describe) 
2. Organ-specific findings 
Findings are to be recorded separately for every affected organ, even if flare criteria for 
that organ are not met.  Data to be provided include symptoms, physical exam findings, 
laboratory findings, imaging findings, and biopsy results.  In addition, the investigator’s 
opinion whether the organ-specific criteria have been met will be documented, and a 
narrative providing the rationale for this organ-specific decision will be recorded. See 
Section 4 for complete organ-specific details. 
3. Investigator Narrative for the Entire Event 
This free-text narrative should be a complete medical account of the event. The narrative 
should include a description of any symptoms, physical examination findings, laboratory 
abnormalities, imaging findings, or biopsy results (including fine needle biopsy) collected 
for the evaluation of this event and should refer to historical data to establish the 
new/worsening nature of the disease manifestations. The descriptions must be detailed 
enough to understand the findings and the investigator’s interpretation of them. The 
narrative must describe findings in every involved organ (for which data are also 
recorded on the organ-specific criteria pages, above). 
The narrative must NOT include any information regarding treatment of the event, 
response to treatment, or the investigator’s decision whether the event met protocol-
defined flare criteria. 
4. Treatment 
If the event was treated, the details of the medical treatment(s) or procedure(s) will be 
recorded. Categories of treatment to be recorded include: 
x Glucocorticoids 
x Supportive therapy eg, pancreatic enzyme replacement, bile acid sequestrant, 
artificial saliva/lubricant 
x Immunosuppression other than glucocorticoids 
x Surgical intervention or other procedural intervention (eg, stenting) 

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5. Outcome of treatment 
Outcome of treatment for the event will be recorded as follows: 
 Returned to pre-flare baseline 
 Improved but not completely returned to pre-flare baseline 
 Neither worsened nor improved over pre-flare baseline 
 Flare activity worsened compared to pre-flare baseline 
 
Flare activity resolved with sequela (resultant organ damage compared to pre-
flare baseline) 
 
 
 

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4 
ORGAN-SPECIFIC FLARE CRITERIA 
The following sections describe information to be collected from the investigator regarding 
organ-specific symptoms and findings, flare criteria, and opinion and decisions regarding the 
event. This information is presented in the form of a questionnaire which will be recapitulated in 
a similar manner for entry of data in the eCRFs. The investigator will be required to complete 
assessments and data entry for those organs(s)/site(s) that are suspected of being involved in the 
event (ie, those with symptoms or other findings that lead to suspicion of flare), regardless 
whether flare criteria are deemed to have been met.  The investigator is not required to perform 
assessments or enter data for organs/sites for which no suspicion of involvement exists. 
 
 
 

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4.1 
Pachymeninges 
Symptoms and Findings 
Symptom(s) 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with 
pachymeningeal flare 
 
 
Describe (1) Each finding and (2) Why worsened 
from recent baseline (or new onset) 
Headache 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent 
with pachymeningeal 
flare 
 
 
Describe (1) Each finding and (2) Why worsened 
from recent baseline (or new onset) 
CN palsy, neurologic 
abnormalities consistent 
with radiculomyelopathy 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Laboratory findings 
consistent with 
pachymeningeal flare 
 
 
Describe (1) Each finding and (2) Why worsened 
from recent baseline (or new onset) 
CSF pleocytosis 
 
 
 
CSF increased protein 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Imaging of 
pachymeninges 
 
 
Describe (1) Each finding and (2) Why worsened 
from recent baseline (or new onset) 
Meningeal enhancement 
or thickening 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Biopsy results consistent 
with pachymeningeal 
flare 
 
 
Describe tissue and reading 
Biopsy not done, 
unreadable, or report 
unavailable  
 
 
 

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Symptom(s) 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Biopsy consistent with 
pachymeningeal flare 
 
 
 
Biopsy not consistent 
with pachymeningeal 
flare 
 
 
 
Criteria for Pachymeningitis Flare 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: 1 and either 2a OR 2b 
 
 
1. New or worsening symptom or PE finding consistent with 
IgG4-RD pachymeningitis 
 
 
2. EITHER: 
a. CSF lab finding consistent with IgG4-RD pachymeningitis 
OR 
 
 
b. Imaging finding confirming new or worsening meningeal 
involvement 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy finding 
 
 
Investigator Conclusion – Pachymeningitis Flare 
F Yes 
F No 
Why do you believe this patient is or is not having a pachymeningitis disease flare? 
 
 
 
 
 
 
 

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4.2 
 Pituitary Gland 
Symptoms and Findings 
Symptom(s) 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Descriptions 
Symptoms consistent with 
pituitary flare 
 
 
Describe (1) Each finding and (2) Why worsened 
from recent baseline (or new onset) 
Visual field 
abnormalities, headache, 
symptoms consistent with 
anterior or posterior 
pituitary endocrine failure 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent 
with pituitary flare 
 
 
Describe (1) Each finding and (2) Why worsened 
from recent baseline (or new onset) 
CN palsy, visual field 
abnormalities  
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Laboratory findings 
consistent with pituitary 
flare 
 
 
Describe (1) Each finding and (2) Why worsened 
from recent baseline (or new onset) 
Pituitary endocrine 
dysfunction 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Imaging of pituitary 
gland 
 
 
Describe (1) Each finding and (2) Why worsened 
from recent baseline (or new onset) 
Pituitary mass or 
enhancement 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Biopsy results consistent 
with pituitary flare 
 
 
Describe tissue and reading 
Biopsy not done, 
unreadable, or report 
unavailable  
 
 
 

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Symptom(s) 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Descriptions 
Biopsy consistent with 
pituitary gland flare 
 
 
 
Biopsy not consistent 
with pituitary gland flare 
 
 
 
Criterion for Pituitary Gland Flare 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: at least one of the following 
 
 
EITHER New or worsening anterior/posterior pituitary endocrine 
dysfunction in patient with known pituitary disease OR 
 
 
Imaging finding confirming new or worsening pituitary involvement 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 
Investigator Conclusion – Flare in Pituitary Gland 
F Yes 
F No 
Why do you believe this patient is or is not having a pituitary gland disease flare? 
 
 
 
 
 

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4.3 
Orbits 
Symptoms and Findings 
Symptom(s) or Finding(s) 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with flare in 
orbits: 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Diplopia, proptosis, foreign body 
sensation, eye or retrobulbar 
discomfort or pain, or other visual 
symptoms including vision blurring or 
loss, symptoms consistent with 
scleritis, symptoms from compression 
of peripheral nerves in the area of the 
orbit, such as trigeminal and infra-
orbital nerves (pain or numbness) 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with orbital 
flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Proptosis, supra-orbital swelling or 
other peri-orbital swelling consistent 
with enlargement of extra-ocular 
muscles, field cuts, cranial nerve 
palsies, extraocular movement 
abnormality, infra-orbital/supra-
orbital nerve enlargement   
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Imaging of orbits   
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Compatible with orbital disease 
(enlargement of extra-ocular muscles, 
enlargement of optic nerve including 
abnormalities of retrobulbar space or 
within cavernous sinus) 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 

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Symptom(s) or Finding(s) 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Biopsy results consistent with orbital 
flare 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or report 
unavailable  
 
 
 
Biopsy consistent with orbital flare 
 
 
 
Biopsy not consistent with orbital 
flare 
 
 
 
Criterion for Orbital Flare 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: at least one of the following 
 
 
EITHER New or worsening symptom or PE finding consistent with 
orbital flare OR 
 
 
New or worsening orbital abnormality on imaging consistent with 
orbital flare 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 
Investigator Conclusion – Flare in the Orbit 
F Yes 
F No 
Why do you believe this patient is or is not having an orbital disease flare? 
 
 
 
 
 
 

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4.4 
Lacrimal Glands  
Symptoms and Findings 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with flare in 
lacrimal glands  
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Lacrimal gland discomfort, pain or 
swelling; redness of the eye, 
excessive tearing; eyelid crusting; 
blurred vision 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with 
lacrimal gland flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Lacrimal gland swelling/mass 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Imaging of lacrimal gland  
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Consistent with lacrimal gland 
swelling 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Biopsy results consistent with 
lacrimal gland flare 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or 
report unavailable  
 
 
 
Biopsy consistent with lacrimal 
gland flare     
 
 
 
Biopsy not consistent with 
lacrimal gland flare     
 
 
 
 
 
 

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Criterion for Lacrimal Glands Flare  
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: 
 
 
New or worsening lacrimal gland enlargement/mass on PE or 
observed on imaging 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 
Investigator Conclusion – Lacrimal Gland Flare 
F Yes 
F No 
Why do you believe this patient is or is not having a lacrimal gland disease flare? 
 
 
 
 
 
 

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4.5 
Salivary Glands 
Specific salivary gland(s) involved:  
F Parotid 
F Submandibular 
F Sublingual 
Symptoms and Findings 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with salivary 
gland flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
 Pain orswelling of gland(s) 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with 
salivary gland flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Salivary gland swelling or 
tenderness 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Imaging of salivary gland  
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Compatible with salivary gland 
swelling 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Biopsy results consistent with 
salivary gland flare 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or 
report unavailable  
 
 
 
Biopsy consistent with salivary 
gland flare    
 
 
 
 

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Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Biopsy not consistent with salivary 
gland flare    
 
 
 
Criterion for Salivary Gland Flare 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: 
 
 
New or worsening salivary gland enlargement or tenderness on PE  
or new or worsening enlargement on imaging 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 
Investigator Conclusion – Flare in Salivary Gland(s) 
F Yes 
F No 
Why do you believe this patient is or is not having a salivary gland disease flare? 
 
 
 
 
  
 

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4.6 
Lymph node(s) 
Symptoms and Findings 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with flare in 
lymph node(s) 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Subject reported swelling    
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with flare 
in lymph node(s) 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Lymphadenopathy (specify 
localized or diffuse 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Imaging of lymphadenopathy 
(localized or diffuse) 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Consistent with lymphadenopathy   
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Biopsy results consistent with 
lymph node flare 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or 
report unavailable  
 
 
 
Biopsy consistent with lymph node 
flare  
 
 
 
Biopsy not consistent with lymph 
node flare 
 
 
 

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Criterion for Lymph Node Flare 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: at least one of the following 
 
 
In a patient with concurrent IgG4 disease in another organ:  Multiple enlarged nodes 
(primarily nontender) by PE or imaging in an area separate from other current organ 
with flare OR 
 
 
In a patient with no other organ with concurrent flare: Multiple enlarged lymph nodes 
(primarily nontender) by PE or imaging AND lymph node biopsy to exclude other 
diagnosis, such as malignancy 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 
 
Investigator Conclusion – Flare in Lymph Node(s) 
F Yes 
F No 
Why do you believe this patient is or is not having a lymph node disease flare? 
 
 
 
 

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4.7 
Lungs, Including Pleura and Parenchyma 
Symptoms and Findings 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with lung 
flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Dyspnea at rest or with exertion, 
cough 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with lung 
flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Increased respiratory rate, findings 
suggestive of pleural effusion, dry 
crackles compatible with 
pulmonary fibrosis, localized 
diminished breath sounds, findings 
consistent with infiltrate 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Laboratory findings consistent 
with lung flare  
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
New or worsening pulmonary 
function test abnormalities 
consistent with lung flare 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Imaging of lungs 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 

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Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Pulmonary nodules or mass and/or 
pulmonary infiltrate/ground glass 
opacities consistent with interstitial 
pneumonia and/or pulmonary 
fibrosis and/or pleural effusion or 
pleural thickening and/or 
peribronchovascular and septal 
thickening and/or paravertebral 
mass, paravertebral band-like soft 
tissue in thorax 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Biopsy results consistent with lung 
flare 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or 
report unavailable  
 
 
 
Biopsy consistent with lung flare  
 
 
 
Biopsy not consistent with lung 
flare 
 
 
 
Criterion for Parenchymal or Pleural Lung Flare 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: 
 
 
New or worsening imaging finding confirming pleuropulmonary involvement 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 
Investigator Conclusion – Lung Flare 
F Yes 
F No 
Why do you believe this patient is or is not having a lung disease flare? 
 
 
 

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4.8 
 Aorta & large blood vessels 
Symptoms and Findings 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with aorta & 
large blood vessels flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Pain, palpable mass 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with aorta 
& large blood vessels flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Palpable arterial mass, especially if 
pulsatile, or bruit 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Imaging of aorta & large blood 
vessels 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Consistent with aneurysm, 
dissection, 
thickening/enhancement of vessel 
wall or other vessel abnormality 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Biopsy results consistent with 
aorta/large blood vessel flare 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or 
report unavailable  
 
 
 
Biopsy consistent with aorta/large 
blood vessel flare 
 
 
 
 
Biopsy not consistent with 
aorta/large blood vessel flare 
 
 
 
 

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Criterion for Aorta & Large Blood Vessel Flare 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: At least one of the following 
 
 
Either New or worsening aortic or other vessel wall thickening or 
other evidence of aortitis (dissection, aneurysm) by imaging OR 
 
 
Demonstration of new or worsening aortitis, dissection or aneurysm or 
similar findings for other large artery at surgery or intervention 
(stenting) of an aneurysm, dissection or other vascular anomaly 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 
Investigator Conclusion – Aorta & Large Blood Vessel Flare 
F Yes 
F No 
Why do you believe this patient is or is not having an aorta/large blood vessel disease flare? 
 
 
 
 

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4.9 
Retroperitoneum, Mediastinum, & Mesentery 
Symptoms and Findings 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with 
retroperitoneum, mediastinum & 
mesentery flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Pain (eg, flank, back, thighs, 
abdominal, other including chronic 
pain), leg edema, dyspnea, cough 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with 
retroperitoneum, mediastinum & 
mesentery flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Palpable mass or findings 
consistent with superior vena cava 
syndrome, leg edema, or fibrosing 
mediastinitis 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Laboratory findings consistent 
with retroperitoneum, 
mediastinum & mesentery flare 
 
 
 
For retroperitoneal involvement of 
ureters: elevated creatinine, 
decreased estimated glomerular 
filtration rate (eGFR) 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 

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Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Imaging of retroperitoneum, 
mediastinum & mesentery 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Finding of mass lesion, ureteral 
stenosis or hydronephrosis, 
findings consistent with superior 
vena cava syndrome, other 
evidence of inflammation in 
retroperitoneum typically with 
enhancement (often infra-renal, 
peri-aortic distribution extending 
down to iliac vessels but may 
involve root of mesentery), 
circumferential/antero-lateral soft 
tissue around infrarenal aorta or 
iliac arteries, other radiologic 
evidence of inflammation in 
mesentery or mediastinum 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Biopsy results consistent with 
retroperitoneum, mediastinum & 
mesentery flare 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or 
report unavailable  
 
 
 
Biopsy consistent with 
retroperitoneum, mediastinum & 
mesentery flare 
 
 
 
Biopsy not consistent with 
retroperitoneum, mediastinum & 
mesentery flare 
 
 
 
Criterion for Flare in Retroperitoneum, Mediastinum & Mesentery Vessels 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: At least one of the following 
 
 
EITHER New or worsening imaging evidence of involvement of 
retroperitoneum, mediastinum and/or mesentery OR 
 
 
Tissue confirmation at time of surgery or intervention (stenting) that 
confirms new or worsening involvement of retroperitoneum, 
mediastinum and/or mesentery 
 
 
Required to be absent: 
 
 

Clinical Study Protocol 
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Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Alternative diagnosis or inconsistent biopsy findings 
 
 
Investigator Conclusion – Flare in Retroperitoneum, Mediastinum & Mesentery Vessels 
F Yes 
F No 
Why do you believe this patient is or is not having a retroperitoneum/mediastinum/mesentery 
vessel disease flare? 
 
 
 
 
 
 

Clinical Study Protocol 
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4.10 
Pancreas and Common Bile Duct 
Symptoms and Findings 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with flare of 
pancreas/common bile duct 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Pain (eg, flank, back, abdominal), 
weight loss  
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with flare of 
pancreas/common bile duct 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Abdominal tenderness, jaundice, 
palpable mass, weight loss 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Laboratory findings consistent with 
flare of pancreas/common bile duct 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Elevated bilirubin, alk phos, GGT, 
amylase and/or lipase 
 
 
 
Other, including low fecal elastase, 
high glucose/HbA1C (describe) 
 
 
 
None 
 
 
 
Imaging of pancreas/common bile 
duct 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Consistent with pancreatic mass or 
diffuse pancreatic enlargement with 
loss of lobulations, diffuse 
pancreatic enlargement, 
pseudocapsule, pancreatic duct 
stricture, common bile duct 
abnormality   
 
 
 
Other (describe) 
 
 
 
None 
 
 
 

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Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Biopsy results consistent flare of 
pancreas/common bile duct 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or 
report unavailable 
 
 
 
Biopsy consistent with 
pancreatic/common bile duct flare 
 
 
 
Biopsy not consistent with 
pancreatic/common bile duct flare 
 
 
 
Criterion for Pancreatic Flare 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: 
 
 
In a patient with a prior history of IgG4-related autoimmune pancreatitis 
EITHER:  
 
 
New or worsening symptom and/or PE finding AND new or worsening 
laboratory finding consistent with flare in disease of pancreas/common bile 
duct OR 
 
 
Imaging or endoscopic finding that confirms new or worsening involvement 
of pancreas/common bile duct 
 
 
In a patient with no prior history of IgG4-related autoimmune pancreatitis: 
 
 
New symptom, PE finding and/or laboratory finding consistent with 
involvement of the pancreas/common bile duct, AND EITHER 
 
 
New imaging or endoscopic finding that confirms involvement of the 
pancreas/common bile duct, OR 
 
 
Biopsy evidence of involvement of the pancreas 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 
Investigator Conclusion – Pancreatic Flare 
F Yes 
F No 
Why do you believe this patient is or is not having a pancreas/common bile duct disease flare? 
 
 
 

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4.11 
Biliary tree (IgG4-RD sclerosing cholangitis) 
Symptoms and Findings 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with flare of 
bile ducts/biliary tree 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Itching, abdominal pain, right upper 
quadrant pain 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with flare of 
bile ducts/biliary tree 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Abdominal tenderness, jaundice, 
right upper quadrant fullness 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Laboratory findings consistent with 
flare of bile ducts/biliary tree 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Elevated bilirubin, ALT/AST, 
alkaline phosphatase, GGT 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Imaging of bile ducts/biliary tree 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Thickening, mass, strictures, 
dilatation of extra-hepatic and/or 
intrahepatic bile ducts 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Biopsy results consistent with bile 
ducts/biliary tree flare 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or 
report unavailable 
 
 
 

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Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Biopsy of liver or biliary tree 
consistent with bile duct/biliary tree 
flare 
 
 
 
Biopsy not consistent with bile 
duct/biliary tree flare 
 
 
 
Criterion for Flare in Bile Ducts/Biliary Tree 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: 
 
 
In a patient with a prior history of IgG4-related sclerosing cholangitis, 
EITHER: 
 
 
New or worsening laboratory finding consistent with biliary tree flare OR 
 
 
New or worsening imaging or endoscopic finding that confirms worsening 
involvement of bile ducts/biliary tree    
 
 
In a patient with no prior history of IgG4-related sclerosing cholangitis: 
 
 
New laboratory finding consistent with biliary tree flare, AND 
 
 
Imaging or endoscopic finding that confirms involvement of the bile 
ducts/biliary tree 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 
Investigator Conclusion – Flare in Bile Ducts/Biliary Tree 
F Yes 
F No 
Why do you believe this patient is or is not having a biliary tree disease flare? 
 
 
 
 
 
 

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4.12 
Kidney 
Kidney flare is specifically intrinsic renal disease or ureteropelvic junction (UPJ) obstruction. 
Disease caused by ureteral obstruction below the UPJ should be entered under retroperitoneum. 
Symptoms and Findings 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with kidney 
flare   
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Fatigue, mental status changes 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with kidney 
flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Edema 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Laboratory findings consistent with 
kidney flare 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Elevated creatinine, decreased 
eGFR, hematuria or proteinuria 
 
 
 
Other, including 
hypocomplementemia (describe) 
 
 
 
None 
 
 
 
Imaging of kidneys   
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Diffuse kidney enlargement, renal 
abnormality including, hypodense 
lesions in the renal cortex,renal 
atrophy, and/or pelvis thickening 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 

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Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Biopsy results consistent with 
kidney disease flare 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or 
report unavailable 
 
 
 
Biopsy consistent with kidney 
disease flare 
 
 
 
Biopsy not consistent with kidney 
disease flare 
 
 
 
Criterion for Kidney Flare 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: 
 
 
In a patient with a prior history of IgG4-related renal disease EITHER: 
 
 
Worsening renal function or proteinuria, OR 
 
 
Any imaging finding or biopsy that confirms worsened involvement of the 
kidney 
 
 
In a patient with no prior history of IgG4-related renal disease EITHER: 
 
 
Worsening renal function, or proteinuria AND either biopsy or imaging 
finding consistent with renal flare, OR 
 
 
Worsening renal function in the setting of active IgG4-RD in other organs 
with worsened hypocomplementemia and increased IgG4 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 
Investigator Conclusion – Kidney Flare 
F Yes 
F No 
Why do you believe this patient is or is not having a kidney disease flare? 
 
 
 
 
 
 

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4.13 
Skin 
Symptoms and Findings 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with flare of 
skin disease 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Rash 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with flare of 
skin disease 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Erythematous papules or nodules, 
hyperpigmented lesions or other 
skin lesions 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Biopsy results consistent with skin 
disease flare 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or 
report unavailable 
 
 
 
Biopsy consistent with skin disease 
flare 
 
 
 
Biopsy not consistent with skin 
disease flare 
 
 
 
Criterion for Skin Flare 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: 
 
 
New or worsening IgG4-RD skin lesions from symptoms or PE AND 
EITHER 
 
 
Prior biopsy proven IgG4-related skin disease, OR 
 
 
Current biopsy consistent with diagnosis 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 

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Investigator Conclusion – Skin Flare 
F Yes 
F No 
Why do you believe this patient is or is not having a skin disease flare? 
 
 
 

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4.14 
Other sclerosis/mass formation in thyroid (Riedel’s thyroiditis), liver, breast, 
prostate, maxillary sinus, nasal septum, pericardium, peripheral nerves, other 
Specify site of sclerosis/mass formation: (pulldown menu) 
Symptoms and Findings 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Symptoms consistent with flare of 
other sclerotic/mass forming disease 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Site dependent, describe 
 
 
 
Systemic/constitutional 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
PE findings consistent with flare of 
sclerotic/mass forming disease 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Site dependent, describe 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Laboratory findings consistent with 
flare of sclerotic/mass forming 
disease 
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Site dependent, describe 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Imaging  
 
 
Describe (1) Each finding and (2) Why 
worsened from recent baseline (or new 
onset) 
Consistent with sclerotic/mass-
forming disease 
 
 
 
Other (describe) 
 
 
 
None 
 
 
 
Biopsy results consistent with 
sclerotic/mass forming disease 
 
 
Describe tissue and reading 
Biopsy not done, unreadable, or 
report unavailable 
 
 
 
Biopsy consistent with 
sclerotic/mass forming disease flare 
 
 
 

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 141 of 142 
Symptom(s) or Findings 
Observed 
(✓) 
New onset 
or 
worsening 
(N/W) 
Description 
Biopsy not consistent with 
sclerotic/mass forming disease flare 
 
 
 
Criterion for Sclerotic/Mass Forming Flare 
Criteria for Flare 
Present 
(✓) 
Absent 
(✓) 
Required to be present: At least one of the following 
 
 
EITHER New or worsening imaging result that confirms involvement 
(specify) OR 
 
 
Any new biopsy evidence of new or worsening involvement 
 
 
Required to be absent: 
 
 
Alternative diagnosis or inconsistent biopsy findings 
 
 
Investigator Conclusion – Sclerotic/Mass Forming Flare 
F Yes 
F No 
Why do you believe this patient is or is not having an “other” organ-specific disease flare? 
 
 
 
 
 
 

Clinical Study Protocol 
Horizon Therapeutics Ireland DAC 
VIB0551.P3.S2 - MITIGATE 
Inebilizumab 
Amendment 9.1, 08AUG2023 
IgG4-Related Disease 
CONFIDENTIAL AND PROPRIETARY 
Page 142 of 142 
5 
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