A Phase II, Multicenter Induction Study With an Active Treatment Extension to Evaluate the Efficacy, Safety, and Pharmacokinetics of Vixarelimab in Patients With Moderate to Severe Ulcerative Colitis
Phase: PHASE2
Conditions: Ulcerative Colitis
Sponsor: Genentech, Inc.

 
Official Title: 
A Phase II, Multicenter Induction Study with an Active Treatment 
Extension to Evaluate the Efficacy, Safety, and Pharmacokinetics of 
Vixarelimab in Patients with Moderate to Severe Ulcerative Colitis 
NCT Number: 
NCT06137183 
Document Date: 
Protocol Amendment Version 2: 29-Oct-2024 
 
 
 
 

CONFIDENTIAL 
The information contained in this document, especially any unpublished data, is the property of 
Genentech, Inc. (or under its control) and therefore is provided to you in confidence as an investigator, 
potential investigator, or consultant, for review by you, your staff, and an applicable Ethics Committee 
or Institutional Review Board.  It is understood that this information will not be disclosed to others 
without written authorization from Genentech except to the extent necessary to obtain informed 
consent from persons to whom the drug may be administered. 
Vixarelimab—Genentech, Inc. 
Protocol GA44839, Version 2 
PROTOCOL 
TITLE: 
A PHASE II, MULTICENTER INDUCTION STUDY WITH 
AN ACTIVE TREATMENT EXTENSION TO EVALUATE 
THE EFFICACY, SAFETY, AND PHARMACOKINETICS 
OF VIXARELIMAB IN PATIENTS WITH MODERATE TO 
SEVERE ULCERATIVE COLITIS 
PROTOCOL NUMBER: 
GA44839 
VERSION NUMBER: 
2 
REGULATORY AGENCY 
IDENTIFIER NUMBERS: 
IND Number:  167385 
EU CT Number:  2023-506655-19-00 
TEST PRODUCT: 
Vixarelimab (RO7622888; KPL-716) 
SPONSOR NAME AND 
ADDRESS: 
Genentech, Inc. 
1 DNA Way 
South San Francisco, CA 94080 
APPROVAL: 
See electronic signature and date stamp on the final page 
of this document. 

Vixarelimab—Genentech, Inc. 
2/Protocol GA44839, Version 2 
PROTOCOL HISTORY 
 
Protocol 
Associated Region-Specific Protocols 
Version 
Date Final 
Region 
Version 
Date Final 
2 
See electronic date 
stamp on final page. 
 
 
 
1 
11 October 2023 
European 
Economic Area 
2 
12 April 2024 
China 
1 
26 January 2024  
European 
Economic Area 
1 
24 October 2023 
 

Vixarelimab—Genentech, Inc. 
3/Protocol GA44839, Version 2 
PROTOCOL AMENDMENT, VERSION 2: 
RATIONALE 
Protocol GA44839 has been amended primarily to incorporate changes made in the 
latest European Economic Area (EEA)-specific and China-specific versions of the 
protocol, as well as to incorporate additional new changes.  Changes to the protocol, 
along with a rationale for each change, are summarized below. 
Changes Incorporated from Version 1 (China)  
The following changes were previously implemented in Version 1 (China) to enhance 
suitability of the study for the patient population in China and to clarify laboratory 
assessments specific to China. These changes have been included in this amended 
global version of the protocol: 
 
The retesting period for patients with cytomegalovirus or Clostridium difficile at 
screening has been reduced from 60 days to 30 days to enable easier enrollment of 
patients with resolved infections (Sections 3.1.1 and 4.1.2). 
 
The exclusion criteria regarding tuberculosis (TB) testing has been expanded to 
enable patients with latent TB to be included in the study if they are on treatment to 
enable enrollment of patients with TB infection with minimal risk of reactivation.  The 
concomitant medications section reflects this change, and additional frequency of 
chemistry testing has been implemented to enable safe usage of these medications 
(Sections 4.1.2, 4.4.2.1, and 4.5.8; Appendices 1 and 2). 
 
Because of the operational complexity of sample shipment and processing, certain 
laboratory assessments for exploratory biomarker research and genomic analyses 
will not be collected or analyzed in China (Section 4.5.8; Appendices 1 and 2).  The 
description of central laboratories for testing, analysis, and sample destruction in 
China has been added, as well as a summary of laboratory samples which will not 
be collected in China (Appendix 9). 
 
The monitoring parameters and discontinuation parameters have been expanded to 
clarify how patients on latent TB treatment or patients who develop active TB should 
be managed (Section 4.6.1). 
 
Serum chemistry testing has been included at the Week
and Week 
 timepoints 
and hematology testing at the Week 
 timepoint for the monitoring of patients while 
on TB medications (Appendix 1).  
  
Changes Incorporated from Version 2 (EEA)  
The following changes were previously implemented in Version 2 (EEA) primarily to 
address requests from the European Medicines Agency.  These changes have been 
included in this amended global version of the protocol: 
 
Text has been added to indicate that the selected dosing regimens are based on the 
developed population PK model outlined in the Vixarelimab Investigator's Brochure 
(Section 3.4.1). 

Vixarelimab—Genentech, Inc. 
4/Protocol GA44839, Version 2 
 
An exclusion criterion has been modified to clarify that patients will be excluded if 
they have a history of known or suspected allergic reaction or anaphylactic reaction 
to vixarelimab or its excipients (Section 4.1.2). 
 
Text has been added to specify the timing for blinding of study site personnel, 
patients, and the Sponsor and to clarify that unblinded Sponsor personnel will 
consist of a limited set of individuals who are not directly involved with study conduct 
and require access to patient treatment assignments to fulfill their jobs during the 
study (Section 4.2.2). 
 
Text has been added to describe the statistical methods for multiplicity adjustment 
and subgroup (advanced failure) analysis for the primary efficacy endpoint 
(Sections 6.4 and 6.4.1). 
 
 
 
The schedule of activities has been revised to include additional chemistry tests 
(including ALT, AST, and ALP) at Week
(Appendix 1). 
 
Text has been added to clarify that serum pregnancy tests will be performed at a 
central laboratory (Section 4.5.8). 
 
For consistency with the schedule of activities, text has been modified to clarify that 
all patients will undergo urine drug screening, regardless of history of drug abuse 
(Section 4.5.8). 
Additionally, the open-label treatment part of the study and all associated text in 
Version 2 (EEA) of the protocol (originally added in Version 1 [EEA]) have now been 
removed.  The Sponsor has determined that the rate of global enrollment into the 
randomized part of the study is sufficient to enable initial proof of activity within a 
reasonable timeframe.  
 
Additional New Changes in Version 2  
The following changes have been newly implemented in this version of the protocol: 
 
The list of approved interleukin agents and sphingosine-1-phosphate receptor 
modulators for the treatment of ulcerative colitis (UC) has been updated to reflect 
recent health authority approvals (Section 1.1). 
 
Descriptions of a Phase II trial of vixarelimab and adverse events have been 
updated to align with the most recently available data (Section 1.2.2). 
 
Language in the Summary of Clinical Studies has been reduced, as the updated 
Vixarelimab Investigator’s Brochure provides the most up-to-date and detailed 
information on vixarelimab (Section 1.2.2). 
 
Additional citations have been included to provide further evidence supporting the 
role of OSMR in the intestinal mucosa and in IBD (Sections 1.3 and 10). 

Vixarelimab—Genentech, Inc. 
5/Protocol GA44839, Version 2 
 
The partial Mayo Score (pMS) will not be collected for this study.  All text regarding 
the pMS has been removed (Sections 3.1.1 and 4.5.7.2 and Appendix 3).  All 
components of the Mayo Score, including the Physician’s Global Assessment 
(PGA), will still be collected. 
 
The re-screen criteria have been revised to allow forin exceptional casesre-
screening for screen failure due to an ineligible modified Mayo Score if driven by the 
endoscopy subscore  2 and not by the average stool frequency or rectal bleeding 
score (Section 3.1). 
 
Additional guidance has been provided on the re-screening process and required 
retesting (Section 3.1). 
 
In consultation with the Medical Monitor, an additional 7 days maximum may be 
added to the 35-day screening period for unforeseen events such as administrative 
or other logistical delays (Section 3.1). 
 
The exclusion criterion regarding previous treatment with JAK inhibitors has been 
revised to only exclude patients who have experienced inadequate response or loss 
of response to a JAK inhibitor for the treatment of UC (Sections 3.4.2 and 4.1.2). 
 
The inclusion criterion for permitted and prohibited UC therapies were revised to 
anchor to screening endoscopy date rather than screening date to reduce patient 
burden (Sections 4.1.1.1 and 4.4.2.2 and Table 2). 
 
Instruction has been added that women of childbearing potential must agree to 
refrain from donating eggs during the treatment period and for 
 after the 
final dose of study treatment (Section 4.1.1.1). 
 
Clarification has been provided regarding the definition of history of intolerance to 
AZA, 6-MP, or MTX (Section 4.1.1.3). 
 
The definition of corticosteroid dependence has been revised to align with global 
guidelines 1 (Section 4.1.1.3). 
 
CMV testing has been modified to be required only if clinical suspicion of infection is 
high during endoscopy, which aligns with clinical practice (Section 4.5.8). 
 
The language regarding single-patient emergency and non-emergency unblinding 
requested by the investigator has been updated to align with internal procedures 
(Section 4.2.2). 
 
Text has been modified to align with updates to the Roche Global Policy on 
Continued Access to Investigational Medicinal Products (Section 4.3.4). 
 
Short-term, intermittent use of topical (rectally administered) 5-ASA is now allowed 
during the optional active treatment extension (ATE) period up to 
 to reduce 
potential patient burden (Section 4.4.1 and Table 2). 
 
 
1 Stange EF, Travis SPL, Vermeire S, et al. European evidence-based Consensus on the 
diagnosis and management of ulcerative colitis: definitions and diagnosis. J Crohns Colitis 
2008;2:123.  

Vixarelimab—Genentech, Inc. 
6/Protocol GA44839, Version 2 
 
The visit windows for the Week 1 and Week 2 timepoints have been expanded to 
reduce site and patient burden (Appendix 1). 
 
Additional guidance has been provided regarding the order of study assessments 
prior to performing ECG (Study 4.5.5, Appendix 1, and Appendix 2). 
 
 
Additional minor changes have been made to improve clarity and consistency.  
Substantive new information appears in italics.  This amendment represents cumulative 
changes to the original protocol. 
 

 
Vixarelimab—Genentech, Inc. 
7/Protocol GA44839, Version 2 
 
 
TABLE OF CONTENTS 
PROTOCOL AMENDMENT ACCEPTANCE FORM .......................................... 13 
PROTOCOL SYNOPSIS .................................................................................... 14 
1. 
BACKGROUND ............................................................................ 19 
1.1 
Background on Ulcerative Colitis ............................................. 19 
1.2 
Background on Vixarelimab ..................................................... 20 
1.2.1 
Summary of Nonclinical Safety ................................................ 20 
1.2.2 
Summary of Clinical Studies .................................................... 21 
1.3 
Study Rationale and BenefitRisk Assessment ....................... 22 
2. 
OBJECTIVES AND ENDPOINTS ................................................. 23 
3. 
STUDY DESIGN ........................................................................... 26 
3.1 
Description of the Study ........................................................... 26 
3.1.1 
Overview of Study Design........................................................ 26 
3.1.2 
Patient Input into Study Design ................................................ 30 
3.2 
End of Study Definition ............................................................ 30 
3.3 
Duration of Participation .......................................................... 30 
3.4 
Rationale for Study Design ...................................................... 30 
3.4.1 
Rationale for Vixarelimab Dose and Schedule......................... 30 
3.4.2 
Rationale for Patient Population .............................................. 31 
3.4.3 
Rationale for Placebo Control Group ....................................... 32 
3.4.4 
Rationale for Biomarker Assessments ..................................... 33 
3.4.5 
Rationale for Optional Active Treatment Extension ................. 33 
4. 
MATERIALS AND METHODS ...................................................... 33 
4.1 
Patients .................................................................................... 33 
4.1.1 
Inclusion Criteria ...................................................................... 33 
4.1.1.1 
General Inclusion Criteria for All Patients ................................ 33 
4.1.1.2 
Inclusion Criteria for Advanced Failures .................................. 35 
4.1.1.3 
Inclusion Criteria for Conventional Failures ............................. 36 
4.1.2 
Exclusion Criteria ..................................................................... 37 
4.2 
Method of Treatment Assignment and Blinding ....................... 40 

 
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8/Protocol GA44839, Version 2 
4.2.1 
Treatment Assignment ............................................................. 40 
4.2.2 
Blinding  ................................................................................... 40 
4.3 
Study Treatment and Other Treatments Relevant to the 
Study Design ........................................................................... 41 
4.3.1 
Study Treatment Formulation and Packaging .......................... 41 
4.3.1.1 
Vixarelimab and Placebo ......................................................... 41 
4.3.2 
Study Treatment Dosage, Administration, and Compliance .... 42 
4.3.2.1 
Vixarelimab and Placebo ......................................................... 42 
4.3.3 
Investigational Medicinal Product Handling and 
Accountability ........................................................................... 43 
4.3.4 
Continued Access to Vixarelimab ............................................ 43 
4.4 
Concomitant Therapy .............................................................. 44 
4.4.1 
Permitted and Prohibited Therapy for Ulcerative Colitis 
(Including Background and Rescue Therapy) .......................... 44 
4.4.2 
Other Concomitant Therapy..................................................... 48 
4.4.2.1 
Other Permitted Concomitant Therapy .................................... 48 
4.4.2.2 
Other Prohibited Concomitant Therapy ................................... 48 
4.5 
Study Assessments ................................................................. 49 
4.5.1 
Informed Consent Forms and Screening Records ................... 49 
4.5.2 
Medical History, Baseline Conditions, Concomitant 
Medication, and Demographic Data ......................................... 49 
4.5.3 
Physical Examinations ............................................................. 50 
4.5.4 
Vital Signs ................................................................................ 50 
4.5.5 
Electrocardiograms .................................................................. 50 
4.5.6 
Colonoscopy or Flexible Sigmoidoscopy with Colonic 
Biopsies ................................................................................... 51 
4.5.7 
Clinical Outcome Assessments ............................................... 52 
4.5.7.1 
Data Collection Methods for Clinical Outcome 
Assessments ........................................................................... 52 
4.5.7.2 
Description of Clinical Outcome Assessment Instruments ....... 53 
4.5.8 
Laboratory, Biomarker, and Other Biological Samples ............ 55 
4.5.9 
Use of Screen-Fail Samples (Patients at Participating 
Sites) ....................................................................................... 58 
4.5.10 
Blood Samples for Whole Genome Sequencing or Whole 
Exome Sequencing (Patients at Participating Sites) ................ 58 

 
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9/Protocol GA44839, Version 2 
4.5.11 
Optional Samples for Research Biosample Repository ........... 59 
4.5.11.1 
Overview of the Research Biosample Repository .................... 59 
4.5.11.2 
Approval by the Institutional Review Board or Ethics 
Committee ............................................................................... 59 
4.5.11.3 
Sample Collection .................................................................... 60 
4.5.11.4 
Data Protection, Use, and Sharing .......................................... 60 
4.5.11.5 
Consent to Participate in the Research Biosample 
Repository................................................................................ 61 
4.5.11.6 
Withdrawal from the Research Biosample Repository ............. 62 
4.5.11.7 
Monitoring and Oversight ......................................................... 62 
4.6 
Treatment, Patient, Study, and Site Discontinuation ................ 62 
4.6.1 
Study Treatment Discontinuation ............................................. 62 
4.6.2 
Patient Discontinuation from the Study .................................... 63 
4.6.3 
Study Discontinuation .............................................................. 64 
4.6.4 
Site Discontinuation ................................................................. 64 
5. 
ASSESSMENT OF SAFETY ......................................................... 64 
5.1 
Safety Plan .............................................................................. 64 
5.1.1 
Potential Risks Associated with Vixarelimab ........................... 64 
5.1.2 
Management of Patients Who Experience Adverse Events ..... 65 
5.1.2.1 
Dose Modifications .................................................................. 66 
5.1.2.2 
Treatment Interruption ............................................................. 66 
5.2 
Safety Parameters and Definitions .......................................... 66 
5.2.1 
Adverse Events ........................................................................ 67 
5.2.2 
Serious Adverse Events (Immediately Reportable to the 
Sponsor) .................................................................................. 67 
5.2.3 
Adverse Events of Special Interest (Immediately 
Reportable to the Sponsor) ...................................................... 68 
5.3 
Methods and Timing for Capturing and Assessing 
Safety Parameters ................................................................... 68 
5.3.1 
Adverse Event Reporting Period .............................................. 69 
5.3.2 
Eliciting Adverse Event Information ......................................... 69 
5.3.3 
Assessment of Severity of Adverse Events ............................. 69 
5.3.4 
Assessment of Causality of Adverse Events............................ 70 
5.3.5 
Procedures for Recording Adverse Events .............................. 71 

 
Vixarelimab—Genentech, Inc. 
10/Protocol GA44839, Version 2 
5.3.5.1 
Injection Reactions and Anaphylactic Reactions ..................... 71 
5.3.5.2 
Diagnosis versus Signs and Symptoms ................................... 71 
5.3.5.3 
Adverse Events That Are Secondary to Other Events ............. 72 
5.3.5.4 
Persistent or Recurrent Adverse Events .................................. 72 
5.3.5.5 
Abnormal Laboratory Values ................................................... 73 
5.3.5.6 
Abnormal Vital Sign Values ..................................................... 73 
5.3.5.7 
Abnormal Liver Function Tests ................................................ 74 
5.3.5.8 
Deaths ..................................................................................... 74 
5.3.5.9 
Preexisting Medical Conditions ................................................ 75 
5.3.5.10 
Lack of Efficacy or Worsening of Ulcerative Colitis .................. 75 
5.3.5.11 
Hospitalization or Prolonged Hospitalization ............................ 75 
5.3.5.12 
Patient-Reported Outcome Data .............................................. 76 
5.3.6 
Special Situations (Accidental Overdose and/or Medication 
Error) ....................................................................................... 76 
5.4 
Immediate Reporting Requirements from Investigator to 
Sponsor ................................................................................... 76 
5.4.1 
Emergency Medical Contacts .................................................. 77 
5.4.2 
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest .......................................... 77 
5.4.2.1 
Events That Occur prior to Study Treatment Initiation ............. 77 
5.4.2.2 
Events That Occur after Study Treatment Initiation ................. 77 
5.4.3 
Reporting Requirements for Pregnancies ................................ 78 
5.4.3.1 
Pregnancies in Female Patients .............................................. 78 
5.4.3.2 
Pregnancies in Female Partners of Male Patients ................... 78 
5.4.3.3 
Abortions.................................................................................. 79 
5.4.3.4 
Congenital Anomalies/Birth Defects ........................................ 80 
5.5 
Follow-Up of Patients after Adverse Events............................. 80 
5.5.1 
Investigator Follow-Up ............................................................. 80 
5.5.2 
Sponsor Follow-Up .................................................................. 80 
5.6 
Adverse Events That Occur after the Adverse Event 
Reporting Period ...................................................................... 80 
5.7 
Expedited Reporting to Health Authorities, Investigators, 
Institutional Review Boards, and Ethics Committees ............... 81 
6. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN ......... 81 

 
Vixarelimab—Genentech, Inc. 
11/Protocol GA44839, Version 2 
6.1 
Determination of Sample Size ................................................. 81 
6.2 
Summaries of Conduct of Study .............................................. 82 
6.3 
Summaries of Demographic and Baseline Characteristics ...... 82 
6.4 
Efficacy Analyses ..................................................................... 82 
6.4.1 
Primary Efficacy Endpoint ........................................................ 82 
6.4.2 
Secondary Efficacy Endpoints ................................................. 83 
6.4.3 
Exploratory Efficacy Endpoints ................................................ 83 
6.5 
Safety Analyses ....................................................................... 83 
6.6 
Pharmacokinetic Analyses ....................................................... 84 
6.7 
Immunogenicity Analyses ........................................................ 84 
6.8 
Biomarker Analyses ................................................................. 85 
..................................................................... 85 
7. 
DATA COLLECTION AND MANAGEMENT ................................. 85 
7.1 
Data Quality Assurance ........................................................... 85 
7.2 
Electronic Case Report Forms ................................................. 86 
7.3 
Electronic Patient- and Clinician-Reported Outcome Data ...... 86 
7.4 
Source Data Documentation .................................................... 87 
7.5 
Use of Computerized Systems ................................................ 87 
7.6 
Retention of Records ............................................................... 87 
8. 
ETHICAL CONSIDERATIONS ...................................................... 88 
8.1 
Compliance with Laws and Regulations .................................. 88 
8.2 
Informed Consent .................................................................... 88 
8.3 
Institutional Review Board or Ethics Committee ...................... 89 
8.4 
Confidentiality .......................................................................... 90 
8.5 
Financial Disclosure ................................................................. 91 
9. 
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION ....................................................................... 91 
9.1 
Study Documentation .............................................................. 91 
9.2 
Protocol Deviations .................................................................. 91 
9.3 
Management of Study Quality .................................................. 91 
9.4 
Site Inspections ....................................................................... 92 
9.5 
Administrative Structure ........................................................... 92 

 
Vixarelimab—Genentech, Inc. 
12/Protocol GA44839, Version 2 
9.6 
Dissemination of Data and Protection of Trade Secrets .......... 92 
9.7 
Protocol Amendments ............................................................. 93 
10. 
REFERENCES.............................................................................. 94 
 
 
LIST OF TABLES 
Table 1 
Objectives and Corresponding Endpoints ................................... 24 
Table 2 
Permitted and Prohibited Therapies for Ulcerative Colitis ........... 45 
Table 3 
Guidelines for Management of Patients Who Experience 
Specific Adverse Events ............................................................. 66 
Table 4 
Adverse Event Severity Grading Scale for Events Not 
Specifically Listed in DAIDS Toxicity Grading Scale ................... 70 
Table 5 
Causal Attribution Guidance ....................................................... 71 
 
 
LIST OF FIGURES 
Figure 1 
Study Schema ............................................................................. 29 
 
 
LIST OF APPENDICES 
Appendix 1 
Schedule of Activities:  Induction ................................................ 98 
Appendix 2 
Schedule of Activities:  Optional Active Treatment Extension ... 102 
Appendix 3 
Mayo Score ............................................................................... 105 
Appendix 4 
Ulcerative Colitis Patient-Reported Outcome Signs and 
Symptoms (UC-PRO/SS) .......................................................... 106 
Appendix 5 
Anaphylaxis Precautions ........................................................... 108 
Appendix 6 
Investigational and Non-Investigational Medicinal Product 
Designations (for Use in European Economic Area and 
United Kingdom) ....................................................................... 109 
Appendix 7 
Division of AIDS (DAIDS) Table for Grading the Severity of 
Adult and Pediatric Adverse Events .......................................... 111 
Appendix 8 
Sampson Criteria for Diagnosing Potential Cases of 
Anaphylaxis ............................................................................... 142 
Appendix 9 
Laboratory Sampling in China .................................................. 143 
 

 
Vixarelimab—Genentech, Inc. 
13/Protocol GA44839, Version 2 
PROTOCOL AMENDMENT ACCEPTANCE FORM 
TITLE: 
A PHASE II, MULTICENTER INDUCTION STUDY 
WITH AN ACTIVE TREATMENT EXTENSION TO 
EVALUATE THE EFFICACY, SAFETY, AND 
PHARMACOKINETICS OF VIXARELIMAB IN 
PATIENTS WITH MODERATE TO SEVERE 
ULCERATIVE COLITIS 
PROTOCOL NUMBER: 
GA44839 
VERSION NUMBER: 
2 
REGULATORY AGENCY 
IDENTIFIER NUMBERS: 
IND Number:  167385  
EU CT Number:  2023-506655-19-00  
TEST PRODUCT: 
Vixarelimab (RO7622888; KPL-716) 
SPONSOR: 
Genentech, Inc. 
 
I agree to conduct the study in accordance with the current protocol. 
 
 
 
Principal Investigator's Name  (print) 
 
 
 
 
 
Principal Investigator's Signature 
 
Date 
 
Please retain the signed original of this form for your study files.  Please return a copy of 
the signed form as instructed by your Contract Research Associate.. 

 
Vixarelimab—Genentech, Inc. 
14/Protocol GA44839, Version 2 
 
PROTOCOL SYNOPSIS 
TITLE: 
A PHASE II, MULTICENTER INDUCTION STUDY WITH AN 
ACTIVE TREATMENT EXTENSION TO EVALUATE THE 
EFFICACY, SAFETY, AND PHARMACOKINETICS OF 
VIXARELIMAB IN PATIENTS WITH MODERATE TO SEVERE 
ULCERATIVE COLITIS 
PROTOCOL NUMBER: 
GA44839 
VERSION NUMBER: 
2 
REGULATORY AGENCY 
IDENTIFIER NUMBERS: 
IND Number:  167385  
EU CT Number:  2023-506655-19-00 
SPONSOR: 
Genentech, Inc. 
 
 
PRIMARY AND SECONDARY OBJECTIVES AND ENDPOINTS 
This study will evaluate the efficacy, safety, and pharmacokinetics of vixarelimab compared with 
placebo in patients with moderate to severe ulcerative colitis (UC) who have demonstrated 
inadequate response to, loss of response to, or intolerance to prior conventional or advanced 
therapy.  Specific objectives and corresponding endpoints for the study are outlined below. 
 
Primary Objective 
Corresponding Endpoint 
 To evaluate the induction efficacy of 
vixarelimab compared with placebo 
 To evaluate the induction efficacy of 
vixarelimab compared with placebo in 
advanced failures 
 Clinical remission at Week 12, with clinical 
remission defined as mMS a of  2, including: 
o 
Stool frequency subscore  1 
o 
Rectal bleeding subscore  0 
o 
Endoscopy subscore  1 (score of 1 modified 
to exclude friability) b 
mMS  modified Mayo Score.  
a Modified Mayo Score is the composite of three Mayo Score assessments: stool frequency, 
rectal bleeding, and centrally read endoscopy. 
b Endoscopy scores will be based on interpretation by a blinded central reader. 
 
 
 

 
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15/Protocol GA44839, Version 2 
Secondary Objectives 
Corresponding Endpoints 
 To evaluate the induction efficacy of 
vixarelimab compared with placebo 
 To evaluate the induction efficacy of 
vixarelimab compared with placebo in 
advanced failures 
 
 Clinical response at Week 12, with clinical 
response defined as meeting both of the following 
criteria: 
o 
Decrease from baseline in the mMS a of  2 
and  30% reduction from baseline 
o 
Decrease in rectal bleeding subscore of  1 or 
absolute rectal bleeding subscore of  1  
 Endoscopic improvement at Week 12, with 
endoscopic improvement defined as a Mayo 
endoscopy subscore of  1 (score of 1 modified to 
exclude friability) b 
 Endoscopic remission at Week 12, with 
endoscopic remission defined as a Mayo 
endoscopy subscore of 0 b 
 To evaluate the safety of vixarelimab 
compared with placebo 
 Incidence and severity of adverse events, with 
severity determined according to the DAIDS 
toxicity grading scale c  
 Change from baseline in selected vital signs 
 Change from baseline in selected clinical 
laboratory test results 
 To characterize the pharmacokinetics 
of vixarelimab 
 Serum concentration of vixarelimab at specified 
timepoints  
 To evaluate the immune response to 
vixarelimab 
 Prevalence of ADAs at baseline and incidence of 
ADAs during the study 
ADA  anti-drug antibody; DAIDS  Division of AIDS; mMS  modified Mayo Score.  
a Modified Mayo Score is the composite of three Mayo Score assessments: stool frequency, 
rectal bleeding, and centrally read endoscopy. 
b Endoscopy scores will be based on interpretation by a blinded central reader. 
c Adverse events will be graded according to the DAIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events, with slight modifications for clarity and for alignment with 
internal practices. 
 
OVERALL DESIGN AND STUDY POPULATION 
This is a Phase II, multicenter, randomized, parallel-group, double-blind, placebo-controlled, 
dose-ranging study to evaluate the efficacy, safety, and pharmacokinetics of vixarelimab 
compared with placebo in patients with active moderate to severe UC, including 1) patients who 
have demonstrated inadequate response to, loss of response to, or intolerance to prior 
advanced therapy which includes biologics and targeted small molecules (advanced failures), 
and 2) patients who have demonstrated inadequate response to, loss of response to, or 
intolerance to prior conventional therapies (corticosteroids and/or immunosuppressants) but 
have not failed advanced therapy (conventional failures).  

 
Vixarelimab—Genentech, Inc. 
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Several key aspects of the study design and study population are summarized below. 
 
Phase: 
Phase II 
Population Type: 
Adult patients 
Control Method: 
Placebo 
Population Diagnosis 
or Condition: 
Ulcerative colitis 
Interventional 
Model: 
Parallel group 
Population Age: 
 18 years 
Test Compound: 
Vixarelimab 
Site Distribution: 
Multi-site and multi-
region 
Active Comparator: Not applicable 
Study Intervention 
Assignment Method: 
Randomized 
Number of Arms: 
3 
Number of Participants 
to Be Enrolled: 
Approximately 210 
 
STUDY TREATMENT 
Patients will be randomized to receive SC injections of either vixarelimab 
, vixarelimab 
 
, or placebo
) during the induction period 
; all patients will receive 
SC injections of vixarelimab 
 during the optional active treatment 
extension (ATE) period (
). 
 
DURATION OF PARTICIPATION 
The total duration of study participation for each patient is expected to be approximately 
who complete the optional ATE. 
 
COMMITTEES 
Independent Committees: Not applicable 
Other Committees: 
Internal Monitoring Committee 
 

 
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LIST OF ABBREVIATIONS AND DEFINITIONS OF TERMS 
Abbreviation 
Definition 
5-ASA 
5-aminosalicylic acid 
6-MP 
6-mercaptopurine 
AD 
atopic dermatitis 
ADA 
anti-drug antibody 
ATE 
active treatment extension 
AUC 
area under the concentration–time curve 
AxMP 
auxiliary medicinal product 
AZA 
azathioprine 
BCG 
Bacillus Calmette-Guérin 
BEN 
benign ethnic neutropenia 
C. difficile 
Clostridium difficile 
ClinRO 
clinician-reported outcome 
Cmax 
maximum serum concentration 
CMV 
cytomegalovirus 
CRO 
contract research organization 
CRP 
C-reactive protein 
DAIDS  
Division of AIDS (Table for Grading the Severity of Adult and 
Pediatric Adverse Events) 
DAP 
Data Analysis Plan 
EC 
Ethics Committee 
eCRF 
electronic Case Report Form 
EDC 
electronic data capture 
e-diary 
electronic diary 
EMA 
European Medicines Agency 
FDA 
U.S. Food and Drug Administration 
FeCal 
fecal calprotectin 
GLP 
Good Laboratory Practice 
gp130 
glycoprotein 130 
HBcAb 
hepatitis B core antibody 
HBsAb 
hepatitis B surface antibody 
HBsAg 
hepatitis B surface antigen 
HCV 
hepatitis C virus 
HIPAA 
Health Insurance Portability and Accountability Act 
IBD 
inflammatory bowel disease 
ICH 
International Council for Harmonisation 
IGRA 
interferon- release assay 

 
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Abbreviation 
Definition 
IL 
interleukin 
IMC 
Internal Monitoring Committee 
IMP 
investigational medicinal product 
IND 
Investigational New Drug (Application) 
IRB 
Institutional Review Board 
IxRS 
interactive voice or web-based response system 
JAK 
Janus kinase 
LIFR 
leukemia inhibitory factor receptor 
mMS 
modified Mayo Score 
MTX 
methotrexate 
NOAEL 
no-observed-adverse-effect level 
NSAID 
nonsteroidal anti-inflammatory drug 
OSM 
oncostatin M 
OSMR 
oncostatin M receptor 
OSMR 
oncostatin M receptor-beta 
PD 
pharmacodynamic 
PGA 
Physician’s Global Assessment 
PK 
pharmacokinetic 
PN 
prurigo nodularis 
PPD 
purified protein derivative 
PRO 
patient-reported outcome 
QTcF 
QT interval corrected through use of Fridericia's formula 
QTL 
quality tolerance limit 
QW 
weekly 
RBR 
Research Biosample Repository 
SAE 
serious adverse event 
TB 
tuberculosis 
TNF 
tumor necrosis factor 
UC 
ulcerative colitis 
UC-PRO/SS 
Ulcerative Colitis Patient-Reported Outcome Signs and 
Symptoms  
ULN 
upper limit of normal 
WES 
whole exome sequencing 
WGS 
whole genome sequencing 

 
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1. 
BACKGROUND 
1.1 
BACKGROUND ON ULCERATIVE COLITIS  
Ulcerative colitis (UC) is a chronic inflammatory condition that affects the rectum and 
extends proximally to the colon in a diffuse, continuous, superficial pattern.  UC is 
characterized by mucosal ulceration, rectal bleeding, diarrhea, and abdominal pain and 
may be complicated by severe bloody diarrhea and toxic megacolon, requiring major 
and sometimes urgent surgery.  One-third of patients with UC can also experience 
extra-intestinal complications affecting the skin, joints, eyes, mouth, liver, and lungs 
(Ungaro et al. 2017; Kobayashi et al. 2020).  Although there are many risk factors 
associated with the development of UC, the disease fundamentally represents 
dysregulation of the mucosal immune system in a genetically susceptible individual in 
response to commensal microbiota and other environmental triggers.  
The burden of UC is rising, with increasing worldwide incidence and prevalence over 
time (Unagaro et al. 2017).  The highest incidence rates have been reported in Europe 
(0.6 to 24.3 per 100,000), North America (8.8 to 23.1 per 100,000), and Oceania (7.3 to 
17.41 per 100,000) (Du and Ha 2020).  While the incidence of UC is stabilizing in 
Western countries, the prevalence continues to rise, and incidence is increasing in many 
newly industrialized countries in South America, Asia, Africa, and the Middle East (Ng 
et al. 2017; Du and Ha 2020; Mak et al. 2020).  This rise may be due in part to better 
detection and diagnosis as well as environmental factors such as improved hygiene and 
a Western diet.  The disease can affect any age group, but onset peaks between the 
ages of 15 and 35 years. 
Current pharmacologic management of UC includes conventional therapies: 
anti-inflammatory drugs (corticosteroids and aminosalicylates such as 5-aminosalicylic 
acid [5-ASA]), immunosuppressants (such as azathioprine [AZA], 6-mercaptopurine 
[6-MP], and methotrexate [MTX]); and advanced therapies: tumor necrosis factor 
(TNF) inhibitors, anti-integrin agents (e.g., vedolizumab), anti-interleukin agents 
(e.g., ustekinumab, mirikizumab, risankizumab, guselkumab), Janus kinase (JAK) 
inhibitors (e.g., tofacitinib, upadacitinib, filgotinib), and sphingosine-1-phosphate receptor 
modulators (e.g., ozanimod, etrasimod) (Ungaro et al. 2017; Aslam et al. 2022).  Current 
treatment strategies are focused on disease modification via induction of mucosal 
healing, decreased dependence on corticosteroids, and reduction in the probability of 
progression to surgery, without significant compromise of immune competence (Danese 
et al. 2020; Cai et al. 2021; Le Berre et al. 2022).  
Despite the availability of advanced therapies, a therapeutic ceiling remains in patients 
with moderate to severe UC, with remission rates of only 20%30% in induction trials 
(Alsoud et al. 2021).  Recent estimates of remission rates from an international survey 
are 37%55% with current treatments; however, 22%29% of patients have experienced 
a loss of response to current medications (i.e., anti-TNF therapy, anti-integrin, JAK 
inhibitor, or anti-IL-12/23) (Rubin et al. 2021), highlighting the need for more durable 

 
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treatment options for patients with UC.  Additionally, available advanced therapies have 
been associated with serious infections, infusion reactions, cardiovascular events, 
thrombosis, and malignancies (Gordon et al. 2015; XELJANZ [tofacitinib] U.S. 
Prescribing Information; RINVOQ [upadacitinib] U.S. Prescribing Information; 
STELARA [ustekinumab] U.S. Prescribing Information; HUMIRA [adalimumab] U.S. 
Prescribing Information).  Therefore, there remains an unmet need for additional safe 
UC treatments that are both well tolerated and have durable efficacy. 
1.2 
BACKGROUND ON VIXARELIMAB 
Vixarelimab (also known as KPL-716 and RO7622888) is a first-in-class, fully human, 
monoclonal antibody that targets oncostatin M receptor-beta (OSMR).  OSMR is a 
cytokine receptor subunit that heterodimerizes with interleukin (IL)-31 receptor-alpha or 
glycoprotein 130 (gp130) to form two distinct cytokine receptors, IL-31 and oncostatin M 
(OSM) receptors, which mediate signaling of the cytokines IL-31 and OSM, respectively.  
Both cytokines mediate signaling pathways implicated in inflammation and fibrosis 
(Mozaffarian et al. 2008; Marden et al. 2020; Yaseen et al. 2020; Kuzumi et al. 2021).  
Vixarelimab binds to the human and cynomolgus monkey cytokine-binding domain of 
OSMR with an equilibrium dissociation constant of 
, respectively, 
and does not bind to 
 OSMR.  Vixarelimab does not inhibit signaling of 
OSM via the leukemia inhibitory factor receptor (LIFR) pathway, which is implicated in 
hematopoiesis and the synthesis of platelets (Qadi et al. 2016), therefore leaving this 
pathway unaltered. 
1.2.1 
Summary of Nonclinical Safety 
The nonclinical toxicology program for vixarelimab was designed to support IV and SC 
administration in clinical studies and included a Good Laboratory Practice (GLP) in vitro 
study of hemolytic potential (Study WIL-793060), an ex vivo tissue cross-reactivity study 
in a full panel of human and cynomolgus monkey tissues (Study 20080123), and 7-week 
(Study WIL-793057) and 26-week (Study CRL-082322) repeat-dose toxicology studies in 
cynomolgus monkeys.   
Vixarelimab did not cause hemolysis in vitro when tested at concentrations up to 
in human blood. 
In an ex vivo tissue cross-reactivity study, vixarelimab staining was observed 
 
  
 
 
 
 
 
There were no vixarelimab-related effects in male and female cynomolgus monkeys 
following weekly IV or SC administration of doses up to
 (the highest dose 

 
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tested) for up to 26 weeks.  Thus, the no-observed-adverse-effect level (NOAEL) was 
considered to be 
 IV/SC when administered weekly.  The corresponding mean 
Day 176 area under the concentration–time curve from time 0 to the end of the dosing 
interval (AUC0–168h) for both sexes was 
for IV administration and 
for SC administration; the corresponding mean last-dose maximum 
serum concentration (Cmax) for both sexes was
 for IV administration and 
for SC administration. 
In summary, the vixarelimab toxicology program supports the clinical program.  Refer to 
the Vixarelimab Investigator's Brochure for additional details on nonclinical studies. 
1.2.2 
Summary of Clinical Studies  
Results from previous Phase I and Phase II studies have produced robust safety and 
efficacy data in inflammatory, hyperkeratotic skin disorders.  In completed studies as of 
15 July 2024, a total of 327 healthy volunteers and patients were exposed to 
vixarelimab across all studies.  Thirty-seven healthy volunteers (Phase Ib Study KPL-
716-C001, Part 3), 41 patients with atopic dermatitis (AD) (Phase Ib Study KPL-716-
C001, Parts 1 and 4), 23 patients with prurigo nodularis (PN) (Phase IIa portion of Study 
KPL-716-C201), 187 patients with PN (Phase IIb portion of Study KPL-716-C201), 14 
patients with plaque psoriasis, 14 patients with chronic idiopathic pruritis, 4 patients with 
chronic idiopathic urticaria, 3 patients with lichen planus, and 4 patients with lichen 
simplex chronicus (Phase II Study KPL-716-C202) have been exposed to at least one 
dose of vixarelimab.  Evidence of clinical activity (i.e., significant improvements in 
pruritus, sleep loss, and skin lesions) have been demonstrated with varying doses of 
vixarelimab in patients with AD, PN, or other chronic pruritic conditions across the 
completed Phase I and Phase II trials.  
 
 
 
 
 
 
 
 
 
  
The ongoing Phase II clinical trial (GB44496) is evaluating the efficacy, safety, and 
pharmacokinetics of vixarelimab at 
 versus placebo in 
patients with idiopathic pulmonary fibrosis and in patients with systemic 
sclerosisassociated interstitial lung disease.  

 
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Overall, vixarelimab has been well tolerated with an acceptable safety profile in healthy 
volunteers and in patients with AD, PN, and other chronic pruritic conditions.  Refer to 
the Vixarelimab Investigator's Brochure for additional details on clinical studies. 
1.3 
STUDY RATIONALE AND BENEFITRISK ASSESSMENT 
Despite the emergence of new agents to treat patients with UC, additional treatment 
options are needed to improve disease control and outcomes, particularly targeting 
novel mechanisms in the pathophysiology of UC.  Vixarelimab is a first-in-class 
oncostatin M receptor (OSMR) inhibitor, blocking signaling via the OSM and IL-31 
pathways implicated in fibrosis, inflammation, hyperplasia, and pruritis; while sparing 
OSM signaling via gp130/LIFR, which is involved in hematopoiesis (Hermanns 2015; 
West et al. 2018; Stawski and Trojanowska 2019).  Study GA44839 is the first study of 
vixarelimab in patients with UC. 
Genome-wide association studies have identified polymorphisms in both OSM and 
OSMR associated with UC and Crohn’s disease (Jostins et al. 2012; Liu et al. 2015).  
Further, OSM and OSMR mRNA and protein are increased in patients with inflammatory 
bowel disease (IBD).  OSMR protein expression was higher in colonic biopsies from 
patients with active UC compared with those from patients in remission, with the highest 
expression observed in the epithelial and lamina propria cells (Beigel et al. 2014).  Both 
mRNA and protein expression of OSM and OSMR were upregulated in the intestinal 
mucosa of patients with IBD and active disease relative to healthy controls (West et al. 
2017; Bondensgaard et al. 2021; Verstockt et al. 2021).   
In the intestinal mucosa, OSMR is expressed in nonhematopoietic and nonepithelial 
stromal cells (West et al. 2017; Bondensgaard et al. 2021), notably in inflammatory 
fibroblasts.  Emerging evidence suggests that intestinal stromal cells play a key role in 
IBD pathogenesis (Barnhoorn et al. 2020).  Inflammatory fibroblasts are greatly 
expanded in areas of active disease in the colon of patients with UC compared with 
healthy individuals, indicating that increased expression of OSMR may be driven by cell 
population numbers rather than upregulation of OSMR (Smillie et al. 2019).  Additional 
data have shown a higher abundance of inflammatory fibroblasts in IBD lesions 
compared with other fibroblast types (Kokkotis et al. 2024; Toghi Eshghi et al. 2024).  
OSM is expressed by hematopoietic cells of the intestinal mucosa, including CD4 
T cells and myeloid cells (West et al. 2017).  
 

 
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Of note, increased mucosal OSM and OSMR expression is correlated with worse 
disease prognosis, and increased levels were predictive of the absence of response to 
anti-TNF therapy in patients with IBD (West et al. 2017; Verstockt et al. 2021).  Similar 
findings have been observed with serum/plasma OSM and response to anti-TNF therapy 
(Minar et al. 2019; Bertani et al. 2020; Guo et al. 2022).  Further, an anti-TNF drug 
resistance signature was identified in OSMR-expressing inflammatory fibroblasts and 
OSM-expressing inflammatory monocytes and myeloid cells from inflamed colon 
biopsies of patients with UC (Smillie et al. 2019).  This suggests that inhibition of OSM 
signaling may be of particular benefit in patients with UC who fail anti-TNF therapy.  
As a selective inhibitor of OSMR, vixarelimab is anticipated to confer clinical benefit in 
UC patients.  Vixarelimab has already been evaluated in healthy volunteers and patients 
with inflammatory skin disorders, including AD and PN, in Phase I and Phase II trials 
(see Section 1.2.2).  Results from these trials to date demonstrate that vixarelimab is 
well tolerated with no identified safety risks. 
As with all protein therapies, there is a possibility that administration of vixarelimab may 
lead to the development of anti-vixarelimab antibodies, which could lead to adverse 
events and/or decreased vixarelimab exposure.  However, the immunogenicity rates 
observed with vixarelimab in clinical studies thus far have generally been low and with 
no apparent relationship between anti-drug antibody (ADA) positivity and exposure or 
safety in these studies.  Monoclonal antibodies also carry a potential risk of 
hypersensitivity reactions and anaphylaxis, or hypersensitivity-like reactions.  
Hypersensitivity reactions are less frequent with SC administration in comparison with IV 
use (Pintea et al. 2021).  Nevertheless, several measures, including implementation of 
stringent inclusion and exclusion criteria, and close monitoring of hypersensitivity 
reactions, have been implemented in this protocol to ensure the safety of patients 
participating in this study (see Section 5.1).  
In summary, given the well-tolerated safety profile demonstrated by nonclinical and 
clinical results, the risk mitigation measures for the study, and the scientific rationale 
supporting the potential benefit of vixarelimab in patients with IBD, there is strong 
support for conducting this Phase II study in patients with UC. 
2. 
OBJECTIVES AND ENDPOINTS 
This study will evaluate the efficacy, safety, and pharmacokinetics of vixarelimab 
compared with placebo in patients with moderate to severe UC who have demonstrated 
inadequate response to, loss of response to, or intolerance to prior conventional or 
advanced therapy.  Specific objectives and corresponding endpoints for the study are 
outlined in Table 1. 

 
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Table 1 
Objectives and Corresponding Endpoints 
Primary Objective 
Corresponding Endpoint 
 To evaluate the induction efficacy of 
vixarelimab compared with placebo  
 To evaluate the induction efficacy of 
vixarelimab compared with placebo in 
advanced failures  
 
 Clinical remission at Week 12, with clinical 
remission defined as mMS a of  2, including: 
o 
Stool frequency subscore  1 
o 
Rectal bleeding subscore  0   
o 
Endoscopy subscore  1 (score of 1 modified 
to exclude friability) b 
Secondary Objectives 
Corresponding Endpoints 
 To evaluate the induction efficacy of 
vixarelimab compared with placebo  
 To evaluate the induction efficacy of 
vixarelimab compared with placebo in 
advanced failures  
 
 Clinical response at Week 12, with clinical 
response defined as meeting both of the 
following criteria: 
o 
Decrease from baseline in the mMS a of  2 
and  30% reduction from baseline 
o 
Decrease in rectal bleeding subscore of  1 
or absolute rectal bleeding subscore of  1  
 Endoscopic improvement at Week 12, with 
endoscopic improvement defined as a Mayo 
endoscopy subscore of  1 (score of 1 modified 
to exclude friability) b 
 Endoscopic remission at Week 12, with 
endoscopic remission defined as a Mayo 
endoscopy subscore of 0 b 
 To evaluate the safety of vixarelimab 
compared with placebo  
 Incidence and severity of adverse events, with 
severity determined according to the DAIDS 
toxicity grading scale c  
 Change from baseline in selected vital signs 
 Change from baseline in selected clinical 
laboratory test results 
 To characterize the pharmacokinetics of 
vixarelimab  
 Serum concentration of vixarelimab at specified 
timepoints  
 To evaluate the immune response to 
vixarelimab  
 Prevalence of ADAs at baseline and incidence of 
ADAs during the study 
ADA  anti-drug antibody; DAIDS  Division of AIDS; mMS  modified Mayo Score.  
a Modified Mayo Score is the composite of three Mayo Score assessments: stool frequency, 
rectal bleeding, and centrally read endoscopy (see Appendix 3). 
b Endoscopy scores will be based on interpretation by a blinded central reader. 
c Adverse events will be graded according to the DAIDS Table for Grading the Severity of Adult 
and Pediatric Adverse Events (HHS 2017), with slight modifications for clarity and for 
alignment with internal practices (see Section 5.3.3 and Appendix 7). 

 
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Table 1 
Objectives and Corresponding Endpoints (cont.) 
Exploratory Objectives 
Corresponding Endpoints 
 To evaluate the long-term efficacy of 
vixarelimab 
 Sustained remission, defined as clinical 
remission at 
 Week 12 
 
 Clinical remission at 
 
 Clinical response at 
 
 Endoscopic improvement at 
 
 Endoscopic remission at 
 
 Change from baseline in UC bowel movement 
signs and symptoms at Week 12 and 
, 
as assessed by UC-PRO/SS score 
 Improvement in UC bowel movement signs and 
symptoms at Week 12 
, as defined 
by the proportion of patients with a   6-point 
decrease in the UC-PRO/SS bowel domain score  
 Change from baseline in UC functional signs and 
symptoms at Week 12 and 
, as 
assessed by UC-PRO/SS score 
 Improvement in UC functional symptoms at 
Week 12 and 
, as defined by the 
proportion of patients with a   2-point decrease 
in the UC-PRO/SS functional domain score  
 To evaluate potential relationships 
between vixarelimab exposure and the 
efficacy and safety of vixarelimab  
 Relationship between PK parameters for 
vixarelimab and efficacy endpoints 
 Relationship between PK parameters for 
vixarelimab and safety endpoints 
 To evaluate potential relationships 
between selected covariates and 
exposure to vixarelimab  
 Relationship between selected covariates and 
PK parameters for vixarelimab 
 To evaluate potential effects of ADAs  
 Relationship between ADA status and efficacy, 
safety, or PK endpoints 
ADA  anti-drug antibody; PK  pharmacokinetic; UC  ulcerative colitis; UC-PRO/SS  Ulcerative 
Colitis Patient-Reported Outcomes Signs and Symptoms. 
 
 

 
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extension (ATE) period
  During the ATE period, all patients will receive 
vixarelimab, including patients who received placebo during the induction period, and the 
durability of clinical response and remission will be explored. 
Approximately 210 patients, including advanced failures and conventional failures, will 
be enrolled across global investigational sites.  
 
 Randomization will be stratified by 
previous advanced or conventional therapy failure and baseline modified Mayo Score 
(mMS)
  Restrictions regarding concomitant therapy are outlined in 
Section 4.4.1. 
Eligible patients will be randomized in a 
 ratio to one of the following treatment arms 
for the induction period (
:  
 
Vixarelimab
 arm 
 
 
Vixarelimab 
 arm 
 
 
 
Placebo 
 arm 
 
 
All patients who complete the induction period can receive SC injections of vixarelimab 
 during the optional ATE period 
.  Patients assigned to the 
vixarelimab 
 arm or vixarelimab
arm during the induction 
period will continue on their randomized treatment assignment during the optional ATE 
period:  
 
Patients in the vixarelimab 
 arm will receive vixarelimab 
. 
 
Patients in the vixarelimab 
arm will receive vixarelimab 
 
 and placebo 
 
.   
 
Patients  in the placebo arm during the induction period will receive vixarelimab 
 during the optional ATE period.   
 
Patients will undergo an endoscopy with biopsy and a full Mayo Score assessment (see 
Appendix 3) at screening (baseline), 
.  Efficacy will be assessed 
using the modified Mayo Score (mMS; see Appendix 3), with the Mayo endoscopic 
subscore calculated on the basis of centrally read endoscopy.  The mMS (see 
Appendix 3) will be derived from the Mayo Score (see Section 4.5.7).   
Patients who complete the treatment period (induction and optional ATE) will enter the 
safety follow-up period and undergo assessments at 
  Patients 
who discontinue study treatment without entering the optional ATE period will enter the 
safety follow-up period and undergo assessments at 
 following 
the final dose of study treatment.  Patients who discontinue study treatment prematurely 
for the reasons listed in Section 4.6.1 should return to the clinic for a treatment 

 
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discontinuation visit within 14 days of the event and will then enter the safety follow-up 
period. 
Patients who do not meet the criteria for participation in this study (screen failure) may 
qualify for one re-screening opportunity (for a total of two screenings per patient) at the 
investigator's discretion.  In exceptional cases and in consultation with the Medical 
Monitor, a patient who screen fails because of an ineligible mMS may be re-screened if 
the screen fail is due to an ineligible endoscopy subscore (i.e., < 2) and not due to the 
average stool frequency and rectal bleeding score.  Patients who are classified as screen 
failures due to the presence of Clostridium difficile (C. difficile), cytomegalovirus (CMV), 
or other intestinal pathogen infection may be re-screened 30 days after successful 
treatment, per local practice.   
Patients are not required to re-sign the consent form if they are re-screened within 6 
weeks after previously signing the consent form.  The investigator will maintain a record 
of reasons for screen failure (see Section 4.5.1).  
In the event the individual is re-screened, screening assessments should be repeated as 
follows: 
 
If the individual is re-screened  6 weeks after the initial consent form is signed, 
only the assessments that triggered screen failure need to be repeated. 
– 
Screening endoscopy does not need to be repeated if the initial endoscopy was 
performed within 35 days prior to dosing on Day 1, and  
– 
Colonic biopsies as specified by the protocol have been obtained. 
 
If the individual is re-screened  6 weeks after the initial consent form is signed, all 
screening assessments must be repeated, with the following exceptions: 
– 
HIV and hepatitis B and C testing do not need to be repeated if re-screening 
occurs within 3 months after the initial consent form was signed. 
– 
The chest X-ray does not need to be repeated if results are available from a 
chest X-ray or chest CT scan performed within 3 months prior to re-screening. 
 
If a second ECG is required for re-screening purposes, it must be performed at least 
30 minutes after the first ECG. 
 
The screening period is up to 35 days; however, if required because of unforeseen 
circumstances, the screening period may be extended up to 7 additional days, in 
consultation with the Medical Monitor. 
An overview of the study design is presented in Figure 1.  Schedules of activities are 
provided in Appendix 1 (induction period) and Appendix 2 (optional ATE period). 

 
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3.1.2 
Patient Input into Study Design  
This protocol was developed considering the perspective of individuals living with IBD 
and IBD patient organization representatives.  Insights, lessons learned from prior 
studies, and examples of what individuals living with IBD consider to be a patient-friendly 
trial were previously generated through multiple interactions and collaborations with 
individuals in the IBD community (Roche IBD Patient Council).  
3.2 
END OF STUDY DEFINITION 
The end of this study is defined as the date when the last patient has completed his or 
her last visit or the date at which the last data point required for statistical analysis or 
safety follow-up is received from the last patient, whichever occurs later.  The end of the 
study is expected to occur 
 after the last patient is enrolled.   
In addition, the Sponsor may decide to terminate the study at any time. 
3.3 
DURATION OF PARTICIPATION 
The total duration of study participation for each patient is expected to be approximately 
 
who complete the optional ATE. 
3.4 
RATIONALE FOR STUDY DESIGN 
3.4.1 
Rationale for Vixarelimab Dose and Schedule 
 
 
 
: 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
   

 
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 
 
 
 
 
 
 
 
 
 
 
 
  
 
 
 
 
 
 
 
 
 
 
  
3.4.2 
Rationale for Patient Population 
There is an ongoing high unmet medical need in the treatment of patients with moderate 
to severe UC.  Despite advances in the range of therapeutic options from biologics to 
targeted small molecules, many patients have an inadequate response to therapy, lose 
response over time, or cannot tolerate available treatments.  In addition to inadequate 
disease control, available treatments are associated with at least one or more risks such 

 
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as serious infections and thromboembolic, cardiovascular, and malignancy.  Because of 
the limitations of currently available therapies, there exists a need for new safe and 
effective UC treatment options, especially in patients for whom prior therapies have 
failed.  Vixarelimab is being developed as a novel therapeutic agent to achieve clinical 
remission in patients with moderate to severe UC who have demonstrated inadequate 
response to, loss of response to, or intolerance to prior conventional or advanced 
therapy.  
.  All patients considered for participation will have a 
diagnosis of moderate to severe UC established at least 3 months prior to screening, 
with active disease confirmed by clinical and endoscopic evidence during 
screening.  Patients must have demonstrated an inadequate response, loss of response, 
or intolerance to prior conventional UC therapies and/or to 
 
approved advanced therapies (as defined in Section 4.1.1).  
 
 
   
Because OSMR mediates signal transduction of OSM via a signaling pathway involving 
JAKs, patients with inadequate response or loss of response to JAK inhibitors are less 
likely to benefit from treatment with vixarelimab, and therefore patients who have 
experienced inadequate response or loss of response to a JAK inhibitor for treatment of 
UC will be excluded.  Additionally, patients who may be at increased risk and those who 
require intervention other than the standard-of-care therapies as defined in this protocol 
will be excluded (see Section 4.1.2). 
3.4.3 
Rationale for Placebo Control Group  
In accordance with the International Council for Harmonisation (ICH) E10 guideline, the 
European Medicines Agency (EMA) “Guideline on the Development of New Medicinal 
Products for the Treatment of Ulcerative Colitis” (EMA 2018), and the FDA draft 
“Ulcerative Colitis: Developing Drugs for Treatment” Guidance for Industry (FDA 2022), 
a placebo-treated control group will be used to provide optimal evaluation of the efficacy 
and safety of vixarelimab.  Because observed placebo response and remission rates 
have been highly variable across prior UC clinical trials (Jairath et al. 2017), a placebo 
group controls for the variability in outcome measures associated with subjective 
assessments such as patient-reported outcomes and disease factors such as 
spontaneous remission and the inherent variability in disease flares.  Patients in the 
placebo arm who complete the induction period at 
 will be provided the option to 
receive active treatment with vixarelimab in the optional ATE period of the study.  

 
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3.4.4 
Rationale for Biomarker Assessments  
Target engagement and pharmacodynamic biomarkers will be assessed in serum, stool, 
and colon biopsy tissue to demonstrate evidence of biologic activity of vixarelimab in 
patients to support interpretation of clinical endpoints and selection of recommended 
dose and dosing regimen. 
Disease biomarkers, including fecal calprotectin and serum CRP, are associated with 
active disease and are commonly used for disease monitoring.  Therefore, levels of 
these biomarkers will be assessed for change to support the interpretation of clinical 
endpoints and selection of recommended dosing regimen. 
UC is a heterogenous disease, with treatment response varying among patients due to 
factors that are not fully understood, highlighting the need for biomarkers that may 
predict treatment response and guide treatment decisions.  Baseline biomarkers in 
serum, blood, tissue, and fecal samples will be assessed for any prognostic association 
with disease projection or trajectory and potential value in predicting response.  
3.4.5 
Rationale for Optional Active Treatment Extension 
The optional ATE period will explore the durability of clinical response and remission and 
the long-term safety of vixarelimab over an extended treatment period of 
.  The 
design of the optional ATE period will allow all eligible patients who have completed the 
induction period to be treated with vixarelimab, regardless of initial treatment 
assignment. 
4. 
MATERIALS AND METHODS  
4.1 
PATIENTS 
Approximately 210 patients with moderate to severe UC will be enrolled in this study.  
4.1.1 
Inclusion Criteria 
4.1.1.1 
General Inclusion Criteria for All Patients 
All patients must meet the following criteria for study entry, as well as additional criteria 
for advanced failures (Section 4.1.1.2) or conventional failures (Section 4.1.1.3): 
 
Signed Informed Consent Form 
 
Adults ( 18 years of age or per local standards) at time of signing Informed Consent 
Form 
 
Ability to comply with the study protocol 
 
Diagnosis of UC established at least 3 months prior to screening, confirmed by 
clinical and endoscopic evidence during screening  

 
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The diagnosis of UC should be corroborated by histopathology and 
documented by a histopathology report.  A histopathologic examination should 
be performed at screening if no prior report is readily available. 
 
 
 
 
 
Any permitted background UC therapy must be at stable doses, as outlined below: 
– 
May be receiving oral 5-ASA compounds at a dose that has been stable for 
 2 weeks immediately prior to screening endoscopy. 
– 
May be receiving oral corticosteroid therapy at a dose of  20 mg/day of 
prednisone (or equivalent) that has been stable for  2 weeks immediately prior 
to screening endoscopy. 
– 
May be receiving oral probiotic (e.g., Culturelle, Saccharomyces boulardii), at a 
dose has been stable for  2 weeks immediately prior to screening endoscopy. 
– 
May be receiving AZA, 6-MP, or MTX at a dose that has been stable for 
 12 weeks immediately prior to screening endoscopy. 
 
Must have received a colonoscopy within 2 years prior to screening or be willing to 
undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening.  This 
colonoscopy must: 
– 
Confirm disease extent, defined as 1) left-sided colitis (inflammation up to the 
splenic flexure), 2) extensive colitis (inflammation beyond the splenic flexure but 
not involving the entire colon), or 3) pancolitis (inflammation of the entire colon) 
– 
Include removal of any adenomatous polyps 
– 
Include surveillance to detect dysplasia per local standard of care for all 
patients with left-sided colitis of  12 years’ duration or extensive colitis or 
pancolitis of  8 years’ duration 
 
For women of childbearing potential: agreement to remain abstinent (refrain from 
heterosexual intercourse) or use contraception, and agreement to refrain from 
donating eggs, as defined below: 
Women must remain abstinent or use two methods of contraception, including 
at least one method with a failure rate of  1% per year, during the treatment 
period and for 
 after the final dose of study treatment.  Women must 
refrain from donating eggs during this same period. 
A woman is considered to be of childbearing potential if she is postmenarchal, 
has not reached a postmenopausal state ( 12 continuous months of 
amenorrhea with no identified cause other than menopause), and is not 
permanently infertile due to surgery (i.e., removal of ovaries, fallopian tubes, 
and/or uterus) or another cause as determined by the investigator 

 
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(e.g., Müllerian agenesis).  Per this definition, a woman with a tubal ligation is 
considered to be of childbearing potential.  The definition of childbearing 
potential may be adapted for alignment with local guidelines or regulations. 
Examples of contraceptive methods with a failure rate of  1% per year include 
bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit 
ovulation, hormone-releasing intrauterine devices, and copper intrauterine 
devices. 
A barrier method may be used as the second contraceptive method. 
The reliability of sexual abstinence should be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the patient.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not adequate methods of contraception.  
If required per local guidelines or regulations, locally recognized adequate 
methods of contraception and information about the reliability of abstinence will 
be described in the local Informed Consent Form. 
 
For men: agreement to remain abstinent (refrain from heterosexual intercourse) or 
use a condom, and agreement to refrain from donating sperm, as defined below: 
With a female partner of childbearing potential or pregnant female partner, men 
must remain abstinent or use a condom during the treatment period and for 
 after the final dose of study treatment to avoid exposing the embryo.  
Men must refrain from donating sperm during this same period. 
The reliability of sexual abstinence should be evaluated in relation to the 
duration of the clinical trial and the preferred and usual lifestyle of the patient.  
Periodic abstinence (e.g., calendar, ovulation, symptothermal, or postovulation 
methods) and withdrawal are not adequate methods of preventing drug 
exposure.  If required per local guidelines or regulations, information about the 
reliability of abstinence will be described in the local Informed Consent Form. 
 
4.1.1.2 
Inclusion Criteria for Advanced Failures  
Advanced failure patients must meet the following criteria for study entry: 
 
Inadequate response, loss of response to, or intolerance to 
 of 
approved advanced therapies, which include biologics and targeted small 
molecules, as defined by the following: 
– 
Inadequate response is defined by persistent signs and symptoms of active 
disease despite at least one induction regimen of advanced therapy.  
– 
Loss of response is defined by the recurrence of symptoms during maintenance 
dosing of advanced therapy following prior clinical benefit (discontinuation 
despite clinical benefit or discontinuation due to loss of access does not 
qualify). 
– 
Intolerance is defined by history of adverse effect necessitating treatment 
discontinuation of advanced therapy (including, but not limited to infusion-
related reaction, demyelination, congestive heart failure, infection). 
 

 
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4.1.1.3 
Inclusion Criteria for Conventional Failures   
Conventional failure patients must meet the following criteria for study entry: 
 
Inadequate response, loss of response to, or intolerance to prior conventional UC 
therapies (immunosuppressant and/or corticosteroid treatment)  
Failure to only 5-ASA treatment is not sufficient.  
Inadequate response to, loss of response to, or intolerance to prior 
immunosuppressant treatment (i.e., AZA, 6-MP, or MTX), is defined as one or 
more of the following:  
– 
Persistent signs and symptoms of active disease despite treatment with at 
least one 12-week regimen of AZA ( 1.5 mg/kg/day) or 6-MP 
( 0.75 mg/kg/day) and/or MTX   15 mg/week)  
– 
Persistent signs and symptoms of active disease despite a 6-thioguanine 
nucleotide level of  230 pmol/8  108 RBCs (as measured by quantitative 
high-performance liquid chromatography or liquid chromatography/tandem 
mass spectrometry) during at least one 12-week regimen of oral AZA or 
6-MP at a stable or increasing dose  
– 
History of intolerance to, or inability to titrate doses to levels listed above 
for, AZA, 6-MP, or MTX because of the risk of adverse effects (including, but 
not limited to, nausea/vomiting, abdominal pain, pancreatitis, liver function 
test abnormalities, lymphopenia, TPMT genetic mutation, or infection)  
Inadequate response, loss of response, or intolerance to corticosteroid 
treatment is defined as one or more of the following: 
– 
Steroid refractory: persistent symptoms of active disease despite treatment 
with at least one 4-week induction regimen that included  30 mg/day of 
oral prednisone (or equivalent) for at least 2 weeks or  30 mg/day of IV 
prednisone (or equivalent) for at least 1 week  
– 
Steroid dependent: one failed attempt to taper corticosteroids below a dose 
equivalent to 10 mg/day of oral prednisone (or equivalent) within 3 
months, or disease relapse within 3 months after corticosteroid 
discontinuation 
– 
Steroid intolerant: history of intolerance to corticosteroids (including, but not 
limited to, Cushing’s syndrome, osteopenia/osteoporosis, hyperglycemia, 
insomnia, or infection)  
 
Conventional failures who have received a prior advanced therapy but do not meet 
inclusion criteria for advanced failures (Section 4.1.1.2) may be enrolled, in 
consultation with the Medical Monitor  
Patients must have discontinued the biologic for reasons other than inadequate 
response, loss of response, or intolerance (e.g., change of insurance, well 
controlled disease), and must meet the criteria for inadequate response, loss of 
response, or intolerance to immunosuppressants and/or corticosteroids defined 
above.  
 

 
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4.1.2 
Exclusion Criteria 
Patients who meet any of the following criteria will be excluded from study entry: 
 
Pregnancy or breastfeeding or intention to become pregnant during the study or 
within 
 after the final dose of study treatment 
Women of childbearing potential must have a negative serum pregnancy test 
result at screening and a negative urine pregnancy test on Day 1 prior to 
initiation of study treatment. 
 
History of alcohol, drug, or chemical abuse  2 years prior to screening 
 
Prior extensive colonic resection, subtotal or total colectomy, or planned surgery for 
UC 
 
Past or present ileostomy or colostomy 
 
Diagnosis of Crohn’s disease or indeterminate colitis 
 
Suspicion of ischemic colitis, radiation colitis, or microscopic colitis 
 
Diagnosis of toxic megacolon within 12 months of initial screening visit 
 
Past or present fistula or abdominal abscess 
 
History or current evidence of unresected adenomatous colonic polyps or colonic 
mucosal dysplasia 
 
Any stricture (stenosis) of the colon that precludes endoscopic evaluation 
 
Diagnosis or suspicion of primary sclerosing cholangitis 
 
History of known or suspected allergic reaction or anaphylactic reaction to a biologic 
agent, including vixarelimab or its excipients 
 
Previous treatment with vixarelimab or current participation in Study GB44496 
 
Inadequate response or loss of response to previous treatment of UC with tofacitinib, 
upadacitinib, or other systemic JAK inhibitor  
 
Treatment of UC with approved biologic agents within 8 weeks or 5 half-lives prior to 
screening endoscopy, whichever is longer 
If there is proper documentation of undetectable drug level measured by a 
commercially available assay for any of the approved biologics, there is no 
minimum washout prior to screening endoscopy. 
 
Treatment of UC with approved non-biologic therapies other than those specifically 
listed as permitted medications (Section 4.4) within 2 weeks or 5 half-lives prior to 
screening endoscopy, whichever is longer 
 
Use of IV corticosteroids within 2 weeks prior to screening endoscopy 
 
Treatment with corticosteroid enemas or suppositories and/or topical (rectal) 5-ASA 
preparations within 2 weeks prior to screening endoscopy 
 
Apheresis (e.g., Adacolumn apheresis) within 2 weeks prior to screening 
endoscopy or intent to receive during the study 
 
Chronic nonsteroidal anti-inflammatory drug (NSAID) use 

 
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Occasional use of NSAIDs [e.g., headache, arthritis, myalgias, or menstrual 
cramps] and aspirin (up to 325 mg/day) is permitted. 
 
Participation in an investigational study involving non-biologic therapy within 4 weeks 
or 5 half-lives of the investigational product (whichever is greater) prior to screening, 
or biologic therapy (including vaccines) within 8 weeks or 5 half-lives of the 
investigational product (whichever is greater) prior to screening 
 
Treatment with any live-attenuated vaccine within 4 weeks prior to screening or 
intended to receive such during the study.  
Uses of non-live (inactivated) vaccines are allowed. 
 
Treatment with immunoglobulin or blood products within 4 weeks prior to screening, 
or any condition that is likely to require such treatment during the course of the 
study, unless the treatment is deemed acceptable by the investigator, in 
consultation with the Medical Monitor 
 
Conditions other than UC that could require treatment with  20 mg/day of 
prednisone (or equivalent) during the course of the study, per the investigator’s 
assessment 
 
Significant uncontrolled medical condition or comorbidity, such as cardiac 
(e.g., moderate to severe heart failure New York Heart Association Class III/IV or 
historical evidence of left ventricular ejection fraction  35%), pulmonary, renal, 
hepatic, endocrine, or gastrointestinal disorders (excluding UC) that in the opinion of 
the investigator, would confound the study results or compromise patient safety 
 
Hospitalized (other than for elective reasons) during the screening period 
 
History of malignancy within the 5 years prior to screening, with the exception of 
basal cell or squamous cell skin neoplasms  
In addition, a malignant diagnosis or condition that occurred more than 5 years 
prior to screening, and any basal cell or squamous cell neoplasm must be 
considered cured, inactive, and not under treatment.  
 
History or presence of complete left bundle branch block, second- or third-degree 
atrioventricular heart block, or other abnormal ECG finding during screening that is 
deemed clinically significant by the investigator 
 
QT interval corrected through use of Fridericia’s formula (QTcF)  450 ms if patient 
is male or QTcF  470 if patient is female 
For male or female patients with QRS  120:  QTcF  480 ms 
 
Acquired or congenital immunodeficiency  
 
Positive HIV antibody test at screening 
 
Positive hepatitis C virus (HCV) antibody test result accompanied by a positive HCV 
RNA test at screening 
 
Positive test results for hepatitis B infection at screening, defined as meeting either 
of the following criteria:  
– 
Positive hepatitis B surface antigen (HBsAg) test at screening 

 
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– 
Quantitative HBV DNA  20 IU/mL in patients with a negative hepatitis B 
surface antibody (HBsAb) test and positive total hepatitis B core antibody 
(HBcAb) test  
 
Positive for tuberculosis (TB) during screening or within 3 months prior to screening, 
defined as a positive interferon- release assay (IGRA; e.g., QuantiFERON-TB 
Gold or T-SPOT.TB), or if not available, a positive purified protein derivative (PPD) 
skin test according to Centers for Disease Control and Prevention guidelines, with 
the following exceptions: 
– 
Patients with a history of Bacillus Calmette-Guérin (BCG) vaccination who have 
a positive PPD skin test will not be excluded if they have a negative IGRA at 
screening 
– 
Patients who have a positive or indeterminate IGRA and patients with no 
history of BCG vaccination who have a positive PPD skin test will not be 
excluded if they meet all of the following criteria: 
No symptoms consistent with TB 
Documented history of a completed course of adequate prophylaxis 
(completed treatment for latent TB) per local standard of care prior to 
screening, or initiation of treatment for latent TB per local standard of 
care at least 3 weeks prior to randomization with intention to complete 
treatment while on study 
For patients not currently on latent TB treatment, no known exposure to 
a case of active TB after most recent completed prophylaxis, if applicable 
No evidence of active TB on chest X-ray performed during screening or 
within 3 months prior to screening 
 
Evidence of C. difficile (as assessed by C. difficile toxin testing) or other intestinal 
pathogens (as assessed by stool culture and ova and parasite evaluation) at 
screening or within 30 days prior to screening 
 
Colonic biopsy positive for CMV, as determined by histologic examination or 
immunohistochemistry per local standards, at screening or within 30 days prior to 
screening  
Laboratory confirmation of CMV from a colon biopsy sample is required 
during screening evaluation only if clinical suspicion is high and to determine 
the need for CMV treatment. 
 
Clinically significant abnormality on laboratory tests during screening (hematology, 
serum chemistry, and urinalysis) that, in the opinion of the investigator, may pose an 
additional risk in administering study treatment to the patient  
 
ALT, AST, or ALP  2.5  upper limit of normal (ULN), total bilirubin  2  ULN, or 
presence of abnormalities in synthetic liver function tests judged to be clinically 
significant by the investigator 
Patients with known Gilbert syndrome who have unconjugated 
hyperbilirubinemia will not be excluded. 

 
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 
ANC  1.5  109/L (1500/L), with one exception:  
Patients with benign ethnic neutropenia (BEN):  ANC  1.3  109/L (1300/L)  
BEN (also known as constitutional neutropenia) is an inherited cause of mild 
or moderate neutropenia that is not associated with any increased risk for 
infections or other clinical manifestations (Atallah-Yunes et al. 2019).  BEN is 
referred to as ethnic neutropenia because of its increased prevalence in 
people of African descent and other specific ethnic groups. 
 
Absolute lymphocyte count  0.5  109/L (500/L) 
  
4.2 
METHOD OF TREATMENT ASSIGNMENT AND BLINDING  
4.2.1 
Treatment Assignment  
This is a three-arm randomized study.  After initial written informed consent has been 
obtained, all screening procedures and assessments have been completed, and 
eligibility has been established for a patient, the study site will obtain the patient's 
treatment assignment from an interactive voice or web-based response system (IxRS). 
Patients will be randomly assigned to one of three treatment arms:  the vixarelimab 
 arm, vixarelimab 
 arm, or placebo arm in a 
 ratio.  
Randomization will occur through use of a permuted-block randomization method to 
ensure a 
.  Randomization will be stratified 
by advanced or conventional failure and baseline mMS
  During the optional 
ATE period, patients assigned to the vixarelimab 
 arm or the vixarelimab 
 arm during the induction period will continue on the randomized treatment 
assignment; patients treated with placebo during the induction period will receive 
vixarelimab 
 (see Section 3.1.1 for further details). 
4.2.2 
Blinding  
Study site personnel and patients will be blinded to treatment assignment until database 
lock.  The Sponsor and its agents will also be blinded to treatment assignment until the 
execution of the primary analyses, with the exception of a limited set of individuals who 
are not directly involved with study conduct and require access to patient treatment 
assignments to fulfill their job roles during a clinical trial.  These roles include the 
unblinding group responsible, clinical supply chain managers, sample handling staff, 
operational assay group personnel, IxRS service provider, and IMC members. 
While PK and immunogenicity samples must be collected from patients assigned to the 
placebo arm to maintain the blinding of treatment assignment, PK and ADA assay 
results for these patients are generally not needed for the safe conduct or proper 
interpretation of the study data.  Laboratories responsible for performing study drug PK 
and ADA assays will be unblinded to patient treatment assignments to identify 
appropriate samples for analysis.  PK samples from patients assigned to the placebo 
arm will not be analyzed for study drug PK concentration except by request (e.g., to 

 
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evaluate a possible error in dosing).  Baseline immunogenicity samples will be analyzed 
for all patients.  Postbaseline immunogenicity samples from patients assigned to the 
placebo arm will not be analyzed for ADAs except by request. 
If unblinding becomes necessary because of a medical emergency (e.g., serious adverse 
event for which management might be affected by knowledge of the participant's 
treatment assignment), the investigator will be able to break the treatment code via the 
IxRS.  The investigator is not required to contact the Medical Monitor prior to breaking 
the treatment code in an emergency situation.  However, the Medical Monitor should be 
informed that the treatment code has been broken. 
The investigator will also be able to break the treatment code to determine the 
suitability of subsequent medical care for a participant.  However, approval must be 
obtained from the Sponsor Medical Monitor if the investigator wants to break the 
treatment code to determine a participant's eligibility for a subsequent clinical trial 
testing investigational medicinal products or procedures.  The investigator must 
contact the Sponsor Medical Monitor prior to breaking the treatment code for any 
reason other than a medical emergency.  The investigator should document and provide 
an explanation for any non-emergency unblinding. 
As per health authority reporting requirements, the Sponsor's Drug Safety representative 
will break the treatment code for all serious, unexpected suspected adverse reactions  
that are considered by the investigator or Sponsor to be related to drugs listed in 
Section 5.7).  The investigator, patient, and Sponsor personnel, with the exception of the 
Drug Safety representative and personnel who must have access to patient treatment 
assignments to fulfill their roles (as defined above), will remain blinded to treatment 
assignment. 
4.3 
STUDY TREATMENT AND OTHER TREATMENTS RELEVANT 
TO THE STUDY DESIGN 
The investigational medicinal product (IMP) for this study is vixarelimab.  
Appendix 6 identifies all investigational and non-investigational medicinal products for 
this study. 
4.3.1 
Study Treatment Formulation and Packaging 
4.3.1.1 
Vixarelimab and Placebo 
Vixarelimab will be supplied by the Sponsor as sterile liquid in glass vials.  For 
information on the vixarelimab formulation, see the pharmacy manual and 
Vixarelimab Investigator's Brochure. 
Placebo will be supplied by the Sponsor as sterile liquid in glass vials indistinguishable 
from vials of blinded vixarelimab.  For information on the placebo formulation, see the 
pharmacy manual. 

 
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4.3.2 
Study Treatment Dosage, Administration, and Compliance 
The treatment regimens are summarized in Section 3.1.1. 
Refer to the pharmacy manual for detailed instructions on drug preparation. 
Details on treatment administration (e.g., dose and timing) should be noted on the 
Study Drug Administration electronic Case Report Form (eCRF).  Cases of accidental 
overdose or medication error, along with any associated adverse events, should be 
reported as described in Section 5.3.6. 
Guidelines for treatment interruption or discontinuation for patients who experience 
adverse events are provided in Section 5.1.2. 
4.3.2.1 
Vixarelimab and Placebo 
Vixarelimab and matching placebo will be administered by SC injection.  
Patients assigned to vixarelimab 
 arm will receive 
 vixarelimab at 
 throughout the induction period and optional ATE 
period.  Patients assigned to vixarelimab 
 will receive 
 vixarelimab 
 throughout the induction period and optional ATE 
period.  
, patients assigned to vixarelimab 
 will also 
receive 
 through the induction period and 
optional ATE period.  Patients assigned to placebo 
 
 in the induction period and 
 vixarelimab 
 
in the optional ATE period.  Study treatment should be administered after all other 
procedures have been completed at each visit, unless specifically indicated otherwise.   
Administration of study treatment will be performed at the clinical site by trained 
personnel in a monitored setting where there is immediate access to adequate 
equipment and medications (e.g., IV solutions, epinephrine, antihistamines, 
corticosteroids) to manage potentially serious reactions.  
Patients should be monitored during study treatment 
 
 
  
Investigators and healthcare professionals administering study treatment should 
recognize and manage the signs and symptoms of anaphylactic reactions according to 
2006 National Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis 
Network guidelines (Sampson et al. 2006; Appendix 8).  Healthcare professionals should 
also instruct patients on how to recognize the symptoms of any such events and to 
contact a healthcare provider or seek emergency care in case of any such symptoms.  
All cases of suspected allergic or anaphylactic reactions will be documented through the 

 
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Anaphylaxis, Anaphylactoid, and Hypersensitivity Reaction eCRF.  For anaphylaxis 
precautions, see Appendix 5.  
Rules for treatment interruption are provided in Section 5.1.2.2.  Dose modifications are 
not permitted.  
4.3.3 
Investigational Medicinal Product Handling and Accountability 
All IMPs required for completion of this study will be provided by the Sponsor.  The study 
site (i.e., investigator or other authorized personnel [e.g., pharmacist]) is responsible for 
maintaining records of IMP delivery to the site, IMP inventory at the site, IMP use by 
each patient, and disposition or return of unused IMP, thus enabling reconciliation of all 
IMP received, and for ensuring that patients are provided with doses specified by the 
protocol. 
The study site should follow all instructions included with each shipment of IMP.  The 
study site will acknowledge receipt of IMPs supplied by the Sponsor, using the IxRS to 
confirm the shipment condition and content.  Any damaged shipments will be replaced.  
The investigator or designee must confirm that appropriate temperature conditions have 
been maintained during transit, either by time monitoring (shipment arrival date and 
time) or temperature monitoring, for all IMPs received and that any discrepancies have 
been reported and resolved before use of the IMPs.  All IMPs must be stored in a 
secure, environmentally controlled, and monitored (manual or automated) area in 
accordance with the labeled storage conditions, with access limited to the investigator 
and authorized staff. 
Only patients enrolled in the study may receive IMPs, and only authorized staff may 
supply or administer IMPs. 
IMPs will either be disposed of at the study site according to the study site's institutional 
standard operating procedure or be returned to the Sponsor with the appropriate 
documentation.  The site's method of destroying Sponsor-supplied IMPs must be agreed 
to by the Sponsor.  The site must obtain written authorization from the Sponsor before 
any Sponsor-supplied IMP is destroyed, and IMP destruction must be documented on 
the appropriate form. 
Accurate records of all IMPs received at, dispensed from, returned to, and disposed of by 
the study site should be recorded on the drug accountability log. 
Refer to the pharmacy manual and/or the Vixarelimab Investigator's Brochure for 
information on IMP handling, including preparation and storage, and accountability. 
4.3.4 
Continued Access to Vixarelimab 
Currently, the Sponsor (Genentech, a member of the Roche Group) does not have any 
plans to provide Genentech IMP (vixarelimab) or any other study treatments to patients 

 
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who have completed the study.  The Sponsor may evaluate whether to continue 
providing vixarelimab in accordance with the Roche Global Policy on Continued Access 
to Investigational Medicinal Product, available at the following website: 
https://assets.cwp.roche.com/f/176343/x/92d6b13ee6/policy_continued_access_to_invest
igational_medicines.pdf 
4.4 
CONCOMITANT THERAPY 
Concomitant therapy consists of any medication (e.g., prescription drugs, over-the-
counter drugs, vaccines, herbal or homeopathic remedies, nutritional supplements) used 
by a patient in addition to protocol-mandated treatment from the start of the screening 
period to the study completion or discontinuation visit.  All such medications should be 
reported to the investigator and recorded on the Concomitant Medication eCRF. 
Patients requiring a prohibited therapy (refer to Section 4.4.1 [Table 2] and 
Section 4.4.2.2) will be discontinued from study treatment (see Section 4.6.1) and will 
undergo follow-up assessments as described in Appendix 1 and Appendix 2. 
4.4.1 
Permitted and Prohibited Therapy for Ulcerative Colitis 
(Including Background and Rescue Therapy) 
Permitted and prohibited concomitant therapies for UC, including background and 
rescue therapies, are outlined in Table 2. 

 
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Table 2 
Permitted and Prohibited Therapies for Ulcerative Colitis 
Therapy 
Prior to Screening Endoscopy a 
During Screening and 
Induction  
During Optional ATE and 
Safety Follow-Up 
Rescue Therapy  
Anti-Inflammatories 
Topical (rectal) 5-ASA  
 Must not have received topical 
(rectal) 5-ASA within 2 weeks 
prior to screening endoscopy 
 Treatment with topical 
(rectal) 5-ASA is prohibited 
 Intermittent use of 
topical (rectal) 5-ASA is 
permitted up to 2 weeks 
of daily use; must be 
discontinued by 
 
 Initiation of topical 
(rectal) 5-ASA is 
considered rescue 
therapy and is 
permitted only during 
the optional ATE 
period 
Oral 5-ASA  
 May be receiving oral 5-ASA if 
dose has been stable for at 
least 2 weeks prior to 
screening endoscopy 
 Baseline level of oral 5-ASA 
must be maintained  
 Initiation or increase in 
dose of oral 5-ASA is 
prohibited 
 For patients on oral 
5-ASA at baseline, the 
dose may be tapered 
until discontinuation, 
starting at 
  
 Initiation or increase in 
dose of oral 5-ASA is 
prohibited  
 Initiation of oral 5-ASA 
or increase in dose of 
oral 5-ASA compared 
with baseline is 
considered rescue 
therapy and is 
prohibited 
IV corticosteroids and 
rectal corticosteroids (i.e., 
enemas or suppositories) 
 Must not have received IV 
corticosteroids within 2 weeks 
prior to screening endoscopy 
 Must not have received rectal 
corticosteroids within 2 weeks 
prior to screening endoscopy 
 Treatment with IV or rectal 
corticosteroids is prohibited 
 Treatment with IV or 
rectal corticosteroids is 
prohibited 
 Initiation of IV or rectal 
corticosteroids is 
considered rescue 
therapy and is 
prohibited 
5-ASA  5-aminosalicylic acid; ATE  active treatment extension. 
a See inclusion and exclusion criteria in Section 4.1.1 and Section 4.1.2 for additional details. 
 
 
 

 
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Table 2 
Permitted and Prohibited Therapies for Ulcerative Colitis (cont.) 
Therapy 
Prior to Screening 
Endoscopy a 
During Screening 
and Induction 
During Optional ATE and Safety Follow-Up 
Rescue Therapy 
Anti-Inflammatories (cont.) 
Oral 
corticosteroids  
 May be receiving oral 
corticosteroids at doses 
 20 mg/day prednisone (or 
equivalent) if dose has been 
stable for at least 2 weeks 
prior to screening endoscopy 
(baseline steroid level) b, c 
 Baseline level of oral 
corticosteroids must 
be maintained 
( 20 mg/day 
prednisone or 
equivalent) 
 Initiation or increase 
in dose of oral 
corticosteroids is 
prohibited 
 For patients on oral corticosteroids at baseline, 
corticosteroid dose may be tapered until 
discontinuation, starting at 
 
 For patients who cannot tolerate the 
corticosteroid taper without recurrence of UC 
symptoms or experience symptoms of 
corticosteroid withdrawal, the corticosteroid 
dose can be increased d 
 Initiation or increase in dose of oral 
corticosteroids above baseline steroid level is 
prohibited 
 Initiation of oral 
corticosteroids or 
increase in dose of 
oral corticosteroids 
above baseline 
steroid level is 
considered rescue 
therapy and is 
prohibited 
Immunosuppressants 
AZA, 6-MP, or 
MTX 
 May be receiving AZA, 
6-MP, or MTX if the dose 
has been stable for at least 
12 weeks prior to screening 
endoscopy 
 Discontinuation of AZA, 6-
MP, or MTX must be for at 
least 2 weeks prior to 
screening endoscopy 
 Baseline level of 
AZA, 6-MP, or MTX 
must be maintained  
 Initiation or increase 
in dose of AZA, 6-
MP, or MTX is 
prohibited 
 For patients on AZA, 6-MP, or MTX at 
baseline, the dose may be tapered until 
discontinuation, starting at 
  
 Initiation or increase in dose of AZA, 6-MP, or 
MTX is prohibited  
 Initiation or 
increase in dose of 
AZA, 6-MP, or 
MTX is considered 
rescue therapy and 
is prohibited 
6-MP  6-mercaptopurine; ATE  active treatment extension; AZA  azathioprine; MTX  methotrexate. 
a See inclusion and exclusion criteria in Section 4.1.1 and Section 4.1.2 for additional details. 
b The equivalent dose of budesonide to prednisone has not been fully characterized; however,  6 mg/day budesonide is permitted . 
c There is limited/no data on beclomethasone dipropionate equivalency in inflammatory bowel disease.  Beclomethasone dipropionate should not 
be used for more than 4 weeks based on the Clipper Summary of Product Characteristics. 
d If the corticosteroid dose has not been increased above the baseline level, these patients can re-initiate corticosteroid dose tapering.  Treatment 
with corticosteroids above the baseline dose will be considered rescue therapy. 

 
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Table 2 
Permitted and Prohibited Therapies for Ulcerative Colitis (cont.) 
Therapy 
Prior to Screening Endoscopy a 
During Screening and 
Induction 
During Optional ATE 
and Safety Follow-Up 
Rescue Therapy 
Advanced Therapies 
Biologics: 
 Anti-TNFs  
 Anti-integrin  
 Anti-interleukins  
Small molecules: 
 S1P receptor modulators  
 Must not have received an 
advanced therapy within 
8 weeks for biologic therapy, 2 
weeks for non-biologic therapy, 
or 5-half-lives prior to screening 
endoscopy, whichever is longer 
 Treatment with advanced 
therapy is prohibited 
 Treatment with 
advanced therapy is 
prohibited 
 Advanced therapies are 
prohibited as rescue 
therapy 
JAK inhibitors  
 Inadequate response or loss of 
response to prior treatment with 
JAK inhibitor is exclusionary 
 Discontinuation of JAK 
inhibitor must be for at least 2 
weeks prior to screening 
endoscopy  
 Treatment with JAK 
inhibitors is prohibited 
 Treatment with JAK 
inhibitors is prohibited  
 JAK inhibitors are 
prohibited as rescue 
therapy 
Other Therapies 
Oral probiotics 
 May be receiving oral probiotics 
(e.g., Culturelle, S. boulardii) if 
dose has been stable for at 
least 2 weeks at the time of 
screening endoscopy 
 Initiation of oral probiotics 
is not permitted 
 Baseline usage of oral 
probiotics must remain 
stable during the study 
 
 
ATE  active treatment extension; JAK  Janus kinase; TNF  tumor necrosis factor. 
a See inclusion and exclusion criteria in Section 4.1.1 and Section 4.1.2 for additional details. 
 
 

 
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4.4.2 
Other Concomitant Therapy 
4.4.2.1 
Other Permitted Concomitant Therapy 
Patients are permitted to use the following therapies during the study: 
 
Oral contraceptives with a failure rate of  1% per year (see Section 4.1.1) 
 
Hormone-replacement therapy 
 
Latent TB treatment per local standard of care, as described in Section 4.1.2 
 
In general, investigators should manage a patient's care with supportive therapies as 
clinically indicated, per local standard practice.  Premedication with antihistamines, anti-
pyretics, and/or analgesics may be administered at the discretion of the investigator. 
Patients may continue on stable regimens of drugs they are receiving as treatment for 
coexistent stable diseases (e.g., antihypertensives, cholesterol-lowering drugs, or 
bronchodilators). 
Over-the-counter preparations deemed necessary after taking into consideration 
prohibited concomitant therapies, as described in Section 4.4.2.2 and not expected to 
interfere with the study drug, will be allowed during the study.  Initiation of over-the-
counter medications during the study will need to be approved by the investigator in 
consultation with the Medical Monitor, if necessary. 
4.4.2.2 
Other Prohibited Concomitant Therapy 
Use of the following concomitant therapies during the study is prohibited as described 
below: 
 
Any treatment for UC other than those listed in Section 4.4.1  
 
Chronic use of NSAIDs is prohibited prior to and during the study. 
Occasional use of NSAIDs(e.g., headache, arthritis, myalgias, or menstrual 
cramps), and aspirin (up to 325 mg daily) is permitted. 
 
Apheresis (e.g., Adacolumn apheresis) is prohibited within 2 weeks prior to 
screening endoscopy and during the study. 
 
Chronic use of anti-diarrheals (e.g., loperamide, diphenoxylate with atropine) is 
prohibited prior to and during the study. 
 
Investigational biologic and non-biologic therapy use is prohibited within 8 weeks 
or 4 weeks, respectively, or 5 half-lives (whichever is greater) prior to screening 
and during the study. 
 
Live-attenuated vaccines are prohibited within 4 weeks prior to screening and 
during the study.  
 
Treatment with immunoglobulin or blood products within 4 weeks prior to 
screening and during the study.  
 

 
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4.5 
STUDY ASSESSMENTS  
The schedule of activities to be performed during the study is provided in Appendix 1 
and Appendix 2.  All activities should be performed and documented for each patient.   
Patients will be closely monitored for safety and tolerability throughout the study.  
Patients should be assessed for toxicity prior to each dose; dosing will occur only if the 
clinical assessment and recent laboratory test values, if available, are acceptable. 
4.5.1 
Informed Consent Forms and Screening Records 
Written informed consent for participation in the study must be obtained before 
performing any study-related procedures (including screening evaluations).  Informed 
Consent Forms for enrolled patients and for patients who are not subsequently enrolled 
will be maintained at the study site. 
All screening evaluations must be completed and reviewed to confirm that patients meet 
all eligibility criteria before enrollment.  The investigator will maintain a detailed record of 
all patients screened, to document eligibility or record reasons for screening failure, as 
applicable. 
4.5.2 
Medical History, Baseline Conditions, Concomitant Medication, 
and Demographic Data 
Medical history and baseline conditions, including clinically significant diseases, 
surgeries, cancer history (including prior cancer therapies and procedures), reproductive 
status, smoking history, and use of alcohol and drugs of abuse, will be recorded at 
screening.  In addition, all concomitant therapy (see Section 4.4) used by the patient 
from the start of the screening period will be recorded.  Demographic data, including 
age, sex, and self-reported race or ethnicity, will also be recorded. 
A UC-specific history including complications and surgeries related to UC, and a detailed 
history of UC medications used by the patient within 1 year prior to the screening visit 
will be recorded.  In addition, a detailed history of advanced therapies used by the 
patient within 5 years prior to the screening visit (e.g., name and duration of previous 
biologic therapies and reason for discontinuation) will be recorded. 
The extent and duration of the patient’s disease, as recorded in the patient's medical 
record, will be captured in the eCRF.  The extent of disease should be identified as one 
of the following: 
 
Left-sided colitis (inflammation up to the splenic flexure) 
 
Extensive colitis (inflammation beyond the splenic flexure but not involving the 
entire colon) 
 
Pancolitis (inflammation of the entire colon) 
 

 
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An interval medical history should be obtained at subsequent clinic visits, and any 
changes in medications and allergies should be recorded. 
4.5.3 
Physical Examinations 
A complete physical examination, performed at screening and other specified visits, 
should include an evaluation of the head, eyes, ears, nose, and throat, and the 
cardiovascular, dermatologic, musculoskeletal, respiratory, gastrointestinal, 
genitourinary, and neurologic systems. 
Limited, symptom-directed physical examinations, including an abdominal examination, 
should be performed at specified visits and as clinically indicated.  Changes from 
abnormalities identified at screening should be recorded in patient notes. 
Any abnormality identified at screening or prior to initiation of study treatment should be 
recorded on the General Medical History and Baseline Conditions eCRF (unless 
considered related to a protocol-mandated intervention; see Section 5.3.1).  After 
initiation of study treatment, any new or worsened clinically significant abnormalities 
should be recorded as adverse events on the Adverse Event eCRF. 
4.5.4 
Vital Signs  
Vital signs will include measurements of respiratory rate, pulse rate, and systolic and 
diastolic blood pressure while the patient is in a seated position, and temperature. 
Any abnormality identified at screening or prior to initiation of study treatment should be 
recorded on the General Medical History and Baseline Conditions eCRF (unless 
considered related to a protocol-mandated intervention).  After initiation of study 
treatment, any new or worsened clinically significant abnormalities should be recorded 
as adverse events on the Adverse Event eCRF. 
4.5.5 
Electrocardiograms 
Single 12-lead ECG recordings will be obtained at specified timepoints (see Appendix 1 
and Appendix 2) and may be obtained at unscheduled timepoints as indicated.  
All ECG recordings must be performed on a device that is equipped with reliable, 
automated algorithms for measuring heart rate and ECG intervals and capable of local 
printing.  Paper copies of ECG tracings will be kept as part of the patient's permanent 
study file at the site. 
Lead placement should be as consistent as possible.  ECG recordings should be 
performed after the patient has been resting in a supine or semi-supine position for at 
least 10 minutes, and the patient should remain in a supine or semi-supine position 
during recording.  The same positioning should be maintained for each patient 
throughout the study.  ECG recordings should be performed prior to invasive procedures 
scheduled at that same time (e.g., blood draws) and should not be performed within 

 
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2.5 hours after any meal.  Vital sign measurements, physical examinations, and diary 
training may be conducted prior to performing the ECG.  Circumstances that may 
induce changes in heart rate, including environmental distractions (e.g., television, radio, 
conversation), should be avoided during the pre-ECG resting period and during ECG 
recording. 
Paper copies of all ECG tracings must be reviewed, annotated to indicate any clinical 
findings, signed, and dated by a medically qualified member of the site staff.  For each 
timepoint, heart rate, RR interval, PR interval, QRS interval, uncorrected QT interval, 
and QTcF based on machine readings of ECG tracings should be recorded on the 
appropriate eCRF.  Any morphologic waveform changes or other ECG abnormalities 
must be documented on the eCRF. 
If at a particular postdose timepoint the mean QTcF is  500 ms or  60 ms longer than 
the baseline value (i.e., last value prior to initiation of study treatment), another ECG 
must be recorded, ideally within the next 5 minutes, and ECGs should be repeated at 
least hourly until two successive ECGs show resolution of the findings.  A PK sample 
should be obtained if not already scheduled for that timepoint.  The Medical Monitor 
should be notified, and standard-of-care treatment may be instituted at the discretion of 
the investigator.  A decision on study treatment discontinuation should be made, as 
described in Section 5.1.2.2.  The investigator should also evaluate the patient for 
potential concurrent risk factors (e.g., electrolyte abnormalities, concomitant medications 
known to prolong the QT interval, severe bradycardia). 
4.5.6 
Colonoscopy or Flexible Sigmoidoscopy with Colonic Biopsies 
All patients will undergo either a colonoscopy or flexible sigmoidoscopy with collection of 
colonic biopsies at baseline/screening, at 
 or the treatment 
discontinuation visit.  Patients without documentation of a colonoscopy within 2 years 
prior to screening must have a colonoscopy in lieu of a flexible sigmoidoscopy at 
screening.  Every effort should be made to schedule on-treatment endoscopies on the 
same day as the protocol-specified study visit.   
Bowel preparation prior to the colonoscopy and flexible sigmoidoscopy procedures 
should be done per local practice.  Medications used for bowel preparation should be 
reported on the Concomitant Medications eCRF.  Scheduled stool samples should be 
taken prior to bowel preparation. 
For each patient, a video recording will be performed during the colonoscopy or flexible 
sigmoidoscopy procedure through use of high-definition video recording per the 
endoscopy manual.  
Video recordings should be taken of the entire endoscopic procedure, starting from 
insertion into the bowel.  Biopsies should be performed upon withdrawal of the 

 
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endoscope from the bowel.  Technical instructions for video recording and biopsy 
collection will be provided in the endoscopy and/or laboratory manual.  
The clinician who performs the endoscopy may take into account endoscopy findings 
when completing the Physician’s Global Assessment (PGA) subscore of the Mayo Score 
(see Section 4.5.7.2). 
All video recordings will be submitted to a central reading facility to be centrally reviewed 
for mucosal lesions and endoscopic severity by an independent gastroenterologist 
experienced in UC who is blinded to the patient’s clinical activity, study visit, and 
treatment allocation.  Endoscopic videos will be assessed to determine if patients meet 
the endoscopic inclusion criterion as well as to objectively document subsequent 
disease activity.  For efficacy assessment of primary, secondary, and exploratory 
endpoints, Mayo endoscopy subscore will be calculated on the basis of centrally read 
patient videos.  Locally read endoscopic videos will be used to inform investigator-
determined clinical or treatment decisions.  
 
4.5.7 
Clinical Outcome Assessments  
Clinical outcome assessments of treatment benefit will be primarily collected through the 
Mayo Score, a composite endpoint incorporating both patient-reported outcome (PRO) 
and clinician-reported outcome (ClinRO) measures (Appendix 3).   
PRO data will be collected through use of the following instruments: Mayo Score (Stool 
Frequency and Rectal Bleeding items; Appendix 3) and Ulcerative Colitis Patient-
Reported Outcomes Signs and Symptoms (UC-PRO/SS; Appendix 4).  PRO instruments 
will capture each patient's direct experience with vixarelimab. 
ClinRO data will be collected using the Mayo Score Physician’s Global Assessment item 
(PGA; Appendix 3). 
4.5.7.1 
Data Collection Methods for Clinical Outcome Assessments 
PRO instruments will be self-administered at home at specified timepoints during the 
study (see schedule of activities in Appendix 1 and Appendix 2).   
PRO instruments (Rectal Bleeding/Stool Frequency Mayo Score items and UC-
PRO/SS), translated into the local language as appropriate, will be completed through 
use of an electronic device, either the patient's own device or one provided by the 
Sponsor.  The device will be preprogrammed to enable the appropriate instruments to be 
administered in the correct order at each specified timepoint.  The electronic device and 
instructions for completing the instruments electronically will be provided by the site staff.  
The data will be transmitted to a centralized database maintained by the electronic 
device vendor.  The data will be available for access by appropriate study personnel. 

 
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Patients should be given the following instructions for completing instruments at home: 
 
Patients should complete the instruments in a quiet area with minimal distractions 
and disruptions. 
 
Patients should answer questions to the best of their ability; there are no right or 
wrong answers. 
 
Patients should not obtain advice or help from others (e.g., family members or 
friends) when completing the instruments. 
 
The ClinRO instrument (the PGA component of the Mayo Score) will be completed at the 
clinic at specified timepoints during the study (see schedule of activities in Appendix 1 
and Appendix 2).  The PGA will be completed prior to the administration of study 
treatment and entered into the Mayo Clinic Score - Revised eCRF.   
4.5.7.2 
Description of Clinical Outcome Assessment Instruments 
Mayo Score and Modified Mayo Score  
The Mayo Score (including mMS) will be assessed during the study at specified 
timepoints. 
The Mayo Score is a composite of four assessments, each having a scoring range of 
03: stool frequency, rectal bleeding, endoscopy (score of 1 modified to exclude 
friability), and PGA.  The Mayo Score is the sum of these assessment subscores and 
has a range of 012, with higher scores indicating more severe disease (see 
Appendix 3). 
The mMS is a composite of three assessments from the Mayo Score, each having a 
scoring range of 03: stool frequency, rectal bleeding, and centrally read endoscopy.  
The mMS has a range of 09, with higher scores indicating more severe disease (see 
Appendix 3). 
Patients are to report their stool frequency and rectal bleeding, as described below. 
Stool Frequency and Rectal Bleeding 
Stool frequency and rectal bleeding are components of the Mayo Score and mMS. 
At screening, the patient’s normal number of stools, defined as the number of stools 
passed when a patient is in remission (i.e., not in flare), or prior to the onset of UC if a 
patient has never been in remission, will be documented.  
Patients are to record stool frequency and rectal bleeding daily in their electronic diary 
(e-diary) during screening and induction, beginning with the first screening visit, and at 
specified timepoints throughout the study (see Appendix 1 and Appendix 2).  The 
average stool frequency and rectal bleeding scores from the daily e-diary entries within 
the 
 will be used as 
efficacy baseline and for inclusion.  
 

 
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  If the average stool frequency and rectal bleeding scores are not 
available from the 
 
the average stool frequency and rectal bleeding scores from the 
 
 will be used as the baseline for efficacy 
assessment and for inclusion.  
Because the endoscopy and associated bowel preparation can interfere with the 
assessment of PROs, e-diary entries on days of bowel preparation, endoscopy, and the 
day after endoscopy will not be used to calculate any stool frequency or rectal bleeding 
scores. 
Physician's Global Assessment 
PGA data will be collected through use of the Mayo Clinic Score - Revised eCRF.  The 
PGA is a component of the Mayo Score.  The PGA should reflect the clinician's 
assessment of the patient's current overall status, taking into account stool frequency 
and rectal bleeding scores, clinician endoscopy findings, patient-reported symptoms, 
clinician observations, physical examination findings, and other pertinent findings.  If 
possible, the clinician who completes the PGA should not be the same clinician who 
assesses adverse events.  If possible, the same clinician should complete the PGA at 
each timepoint. 
Ulcerative Colitis Patient-Reported Outcome Signs and Symptoms 
Patients are to complete the UC-PRO/SS in the e-diary at specified timepoints 
throughout the study (see Appendix 1 and Appendix 2). 
The UC-PRO/SS is a 9-item daily diary to quantify the effects of treatment on patient-
reported signs and symptoms of UC.  The UC-PRO/SS assesses the presence of UC 
symptoms and, in some cases, the severity or frequency of the symptoms (Higgins et al. 
2017; Pulley et al. 2021).  The UC-PRO/SS includes two domains, Bowel Signs and 
Symptoms (6 items) and Functional Symptoms (3 items), and yields two separate 
weekly average scores.  Each scale is scored separately; there is no total score.  
Patients are instructed to complete the diary each evening, reflecting back on their 
experiences during the past 24 hours.  The UC-PRO/SS takes approximately 3 minutes 
to complete.  The UC-PRO/SS will be collected daily during screening and daily over at 
least a 7-day period before each specified study visit. 
Because the endoscopy and associated bowel preparation can interfere with the 
assessment of PROs, e-diary entries on days of bowel preparation, endoscopy, and the 
day after endoscopy will not be used to calculate any stool frequency or rectal bleeding 
scores.  
A copy of the UC-PRO/SS instrument is provided in Appendix 4. 

 
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4.5.8 
Laboratory, Biomarker, and Other Biological Samples 
Samples for Local Laboratory Tests 
Samples for the following laboratory tests will be sent to the study site's local laboratory 
for analysis: 
 
Urine pregnancy test 
All women of childbearing potential will have urine pregnancy tests performed 
at specified visits during the study.  Urine pregnancy tests will be reviewed prior 
to each study drug administration for confirmation of a negative result.  
If a urine pregnancy test is positive, it must be confirmed by a serum pregnancy 
test, which will be sent to a central laboratory for analysis. 
 
Analysis of colonic tissue obtained by biopsy performed during screening 
endoscopic procedure (flexible sigmoidoscopy or colonoscopy) 
– 
Patients with clinical suspicion of CMV colitis:  CMV, as determined by 
histologic examination or immunohistochemistry per local standards 
– 
Patients without a prior histopathology report corroborating UC diagnosis:  
histopathologic examination 
– 
Patients with left-sided colitis of  12 years’ duration or extensive colitis or 
pancolitis of  8 years’ duration with no documentation of colonic cancer 
surveillance within 2 years prior to screening:  evaluation for dysplasia per local 
standards  
 
Samples for Local Laboratory Tests or Option for Analysis at Central 
Laboratory 
Samples for the following laboratory tests will be sent to the study site's local laboratory 
for analysis, but may be sent to a central laboratory for analysis if local analysis is not 
available: 
 
Stool analysis:  culture and sensitivity, ova and parasites, and C. difficile toxin 
 
Urinalysis:  pH, specific gravity, glucose, protein, ketones, blood by dipstick 
Abnormalities should be confirmed by microscopic examination (sediment, 
RBCs, WBCs, casts, crystals, epithelial cells, bacteria). 
 
Samples for Central Laboratory Tests 
Samples for the following laboratory tests will be sent to one or several central 
laboratories for analysis: 
 
Urine drug screening 
 
Hematology:  WBC count, RBC count, hemoglobin, hematocrit, platelet count, and 
differential count (neutrophils, eosinophils, basophils, monocytes, lymphocytes, 
other cells) 
 
Chemistry panel (serum or plasma):  bicarbonate or total carbon dioxide (if 
considered standard of care for the region), sodium, potassium, chloride, glucose, 
BUN or urea, creatinine, total protein, albumin, phosphate, calcium, total and direct 
bilirubin, ALP, ALT, AST, urate, and lactate dehydrogenase 

 
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 
Coagulation:  INR, aPTT, and PT 
 
HIV serology:  HIV-1/2 antibody 
 
HBV serology:  HBsAg, HBsAb, and total HBcAb for all patients 
If a patient has a negative HBsAg and HBsAb tests and a positive total HBcAb 
test at screening, an HBV DNA test must also be performed to determine if the 
patient has an HBV infection. 
 
HCV serology:  HCV antibody for all patients 
If a patient has a positive HCV antibody test at screening, an HCV RNA test 
must also be performed to determine if the patient has an HCV infection. 
 
TB test:  IGRA or, if IGRA is unavailable, PPD skin test 
Test may be performed locally. 
 
Serum pregnancy test 
All women of childbearing potential (defined in Section 4.1.1) will have a serum 
pregnancy test performed at screening.  Urine pregnancy tests will be 
performed at specified subsequent visits at the site’s local laboratory.  If a urine 
pregnancy test is positive, it must be confirmed by a serum pregnancy test. 
Test for follicle-stimulating hormone may be performed at screening to confirm 
postmenopausal state, if required per local guidelines.  
 
Serum CRP 
 
Fecal calprotectin 
 
The following PK and biomarker samples will be sent to the Sponsor or a designee for 
analysis: 
 
Serum samples for PK analysis 
 
Serum samples for immunogenicity analysis 
 
Serum samples for exploratory biomarker research and PK/PD analyses 
 
Stool samples for exploratory biomarker research that may include, but will not be 
limited to, microbiota analyses and inflammatory proteins 
Note:  These samples will not be collected or analyzed in China (see 
Appendix 9). 
 
Colonic tissue samples obtained by biopsy performed during screening and 
subsequent endoscopic procedures (flexible sigmoidoscopy or colonoscopy) for 
histological assessment and exploratory biomarker research that may include, but 
will not be limited to, 
 and 
, and other molecular assessments 
Note:  These samples will not be collected or analyzed in China (see 
Appendix 9). 
 
Exploratory biomarker research may include, but will not be limited to, 
 
 gene signatures associated with IBD severity, treatment response, and 

 
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non-response; and analysis of immune response in blood and colonic tissue.  Research 
may involve extraction of cells, DNA, cell-free DNA, or RNA; analysis of mutations, 
single nucleotide polymorphisms, and other genomic variants; and genomic profiling.  
Genomic research may include exploration of germline variants.  Genomic profiling may 
include whole genome sequencing (WGS) or whole exome sequencing (WES) of blood 
samples, but only at participating sites (see Section 4.5.10).  These samples, 
 
, will not be collected or analyzed in 
China (see Appendix 9).   
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual. 
Unless the patient gives specific consent for his or her leftover samples to be stored for 
optional exploratory research (see Section 4.5.11), biological samples will be destroyed 
no later than the time of completion of the final Clinical Study Report, with the following 
exceptions: 
 
Residual serum samples collected for PK or immunogenicity analysis may be 
needed for additional immunogenicity characterization and for PK or immunogenicity 
assay development and validation, or may be used for exploratory biomarker 
research as described above; therefore, these samples will be destroyed no later than 
5 years after the final Clinical Study Report has been completed.  Samples collected 
in China will not be used for exploratory research. 
 
Serum, plasma, stool, and colonic tissue samples collected for exploratory 
biomarker research, including biomarker assay development, will be destroyed no 
later than 15 years after the final Clinical Study Report has been completed.  
However, the storage period will be in accordance with applicable laws (e.g., health 
authority requirements) and the Informed Consent Form approved by the 
Institutional Review Board or Ethics Committee (IRB/EC). 
 
When a patient withdraws from the study, samples collected prior to the date of 
withdrawal may still be analyzed, unless the patient specifically requests that the 
samples be destroyed or local laws require destruction of the samples.  However, if 
samples have been tested prior to withdrawal, results from those tests will remain as 
part of the overall research data. 
Data arising from sample analysis, including data on genomic variants, will be subject to 
the confidentiality standards described in Section 8.4. 
Given the complexity and exploratory nature of exploratory biomarker analyses, data 
derived from these analyses will generally not be provided to investigators or patients 
unless required by law.  The aggregate results of any conducted research will be 
available in accordance with the effective Sponsor policy on study data publication. 

 
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4.5.9 
Use of Screen-Fail Samples (Patients at Participating Sites)  
At participating sites, screening blood and tissue from colon biopsy samples collected 
from patients who do not enroll in the study (screen-fail samples) may be used for 
research related to the disease under study and the development of disease-related 
tests or tools. 
If a site does not permit research on screen-fail samples, this section of the protocol 
(Section 4.5.9) will not be applicable at that site. 
4.5.10 
Blood Samples for Whole Genome Sequencing or Whole 
Exome Sequencing (Patients at Participating Sites) 
At participating sites, blood samples will be collected for DNA extraction to enable WGS 
or WES to identify variants that are predictive of response to study drug, are associated 
with progression to a more severe disease state, are associated with susceptibility to 
developing adverse events, can lead to improved adverse event monitoring or 
investigation, or can increase the knowledge and understanding of disease biology and 
drug safety.  Research will include exploration of germline variants.  The samples may 
be sent to one or more laboratories for analysis. 
Collection and submission of blood samples for WGS or WES is contingent upon the 
review and approval of the exploratory research by each site's IRB/EC and, if applicable, 
an appropriate regulatory body.  If a site has not been granted approval for WGS or 
WES, this section of the protocol (Section 4.5.10) will not be applicable at that site. 
Genomics is increasingly informing researchers' understanding of disease pathobiology.  
WGS and WES provide a comprehensive characterization of the genome and exome, 
respectively, and, along with clinical data collected in this study, may increase the 
opportunity for developing new therapeutic approaches or new methods for monitoring 
efficacy and safety or predicting which patients are more likely to respond to a drug or 
develop adverse events.  Data will be analyzed in the context of this study but may also 
be explored in aggregate with data from other studies.  The availability of a larger 
dataset will assist in identification and characterization of important biomarkers and 
pathways to support future drug development. 
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual.   
Blood samples collected for WGS or WES are to be stored until they are no longer 
needed or until they are exhausted.  However, the storage period will be in accordance 
with the IRB/EC-approved Informed Consent Form and applicable laws (e.g., health 
authority requirements). 
Refer to Section 4.5.8 for details on use of samples after patient withdrawal and 
confidentiality standards for data. 

 
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Data generated from blood samples collected for WGS or WES will be analyzed in 
aggregate rather than on an individual patient basis.  Thus, there will be no identification 
and reporting of incidental findings to investigators or patients.   
If permitted by local law, a patient may request access to uninterpreted WGS or WES 
data derived from analysis of his or her blood sample.  If a patient wishes to access 
these data, the investigator must inform the Sponsor, using the following email address:  
global.return-genomics-results@roche.com.  The Sponsor will provide available data to 
the investigator in the form of a raw genomic sequencing data file, but will not provide 
any interpretation of the data.  The investigator should not include the data file in the 
patient's medical record.  Samples may be stored and analyzed in the future, and some 
samples may never be analyzed.  Thus, data may not be available at the time of the 
request or may never be available. 
The aggregate results of any conducted research will be available in accordance with 
the effective Sponsor policy on study data publication. 
4.5.11 
Optional Samples for Research Biosample Repository  
4.5.11.1 
Overview of the Research Biosample Repository 
The Research Biosample Repository (RBR) is a centrally administered group of facilities 
used for the long-term storage of human biological specimens, including body fluids, 
solid tissues, and derivatives thereof (e.g., DNA, RNA, proteins, peptides).  The 
collection, storage, and analysis of RBR samples will facilitate the rational design of new 
pharmaceutical agents and the development of diagnostic tests, which may allow for 
individualized drug therapy for patients in the future. 
Samples for the RBR will be collected from patients who give specific consent to 
participate in this optional research.  RBR samples will be analyzed to achieve one or 
more of the following objectives: 
 
To study the association of biomarkers with efficacy or disease progression 
 
To identify safety biomarkers that are associated with susceptibility to developing 
adverse events or can lead to improved adverse event monitoring or investigation 
 
To increase knowledge and understanding of disease biology and drug safety 
 
To study drug response, including drug effects and the processes of drug absorption 
and disposition 
 
To develop biomarker or diagnostic assays and establish the performance 
characteristics of these assays 
 
4.5.11.2 
Approval by the Institutional Review Board or Ethics 
Committee 
Collection, storage, and analysis of RBR samples is contingent upon the review and 
approval of the exploratory research and the RBR portion of the Informed Consent Form 
by each site's IRB/EC and, if applicable, an appropriate regulatory body.  If a site has not 

 
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been granted approval for RBR sampling, this section of the protocol (Section 4.5.11) 
will not be applicable at that site. 
4.5.11.3 
Sample Collection 
The following samples will be stored in the RBR and used for research purposes, 
including, but not limited to, research on biomarkers related to vixarelimab, diseases, or 
drug safety: 
 
Leftover blood, serum, stool, and colon biopsy tissue samples and any derivatives 
thereof (e.g., DNA, RNA, proteins, peptides), including leftover tissue samples from 
medically indicated procedures (e.g., bronchoscopy, esophagogastroduodenoscopy, 
colonoscopy) performed at the investigator's discretion during the course of the 
study 
 
The above samples may be sent to one or more laboratories for analysis of germline or 
somatic variants via WGS, WES, or other genomic analysis methods.  Genomics is 
increasingly informing researchers' understanding of disease pathobiology.  WGS and 
WES provide a comprehensive characterization of the genome and exome, respectively, 
and, along with clinical data collected in this study, may increase the opportunity for 
developing new therapeutic approaches or new methods for monitoring efficacy and 
safety or predicting which patients are more likely to respond to a drug or develop 
adverse events. 
Data generated from RBR samples will be analyzed in the context of this study but may 
also be explored in aggregate with data from other studies.  The availability of a larger 
dataset will assist in identification and characterization of important biomarkers and 
pathways to support future drug development. 
For sampling procedures, storage conditions, and shipment instructions, see the 
laboratory manual.   
RBR samples are to be stored until they are no longer needed or until they are 
exhausted.  However, the RBR storage period will be in accordance with the IRB/EC-
approved Informed Consent Form and applicable laws (e.g., health authority 
requirements). 
4.5.11.4 
Data Protection, Use, and Sharing 
RBR samples and associated data will be labeled with a unique patient identification 
number. 
Patient medical information associated with RBR samples is confidential and may be 
disclosed to third parties only as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the 
patient, unless permitted or required by law. 

 
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Data generated from RBR samples will be analyzed in aggregate rather than on an 
individual patient basis.  Thus, there will be no identification and reporting of incidental 
findings to investigators or patients.  In addition, given the complexity and exploratory 
nature of the analyses of RBR samples, data derived from these analyses will generally 
not be provided to study investigators or patients, unless required by law, with the 
exception of data generated from blood samples collected for WGS or WES as 
described below. 
If permitted by local law, a patient may request access to uninterpreted WGS or WES 
data derived from analysis of his or her blood sample.  If a patient wishes to access 
these data, the investigator must inform the Sponsor, using the following email address:  
global.return-genomics-results@roche.com.  The Sponsor will provide available data to 
the investigator in the form of a raw genomic sequencing data file, but will not provide 
any interpretation of the data.  The investigator should not include the data file in the 
patient's medical record.  Samples may be stored and analyzed in the future, and some 
samples may never be analyzed.  Thus, data may not be available at the time of the 
request or may never be available.  
The aggregate results of any conducted research will be available in accordance with 
the effective Sponsor policy on study data publication. 
Data generated from RBR samples must be available for inspection upon request by 
representatives of national and local health authorities, and Sponsor monitors, 
representatives, and collaborators, as appropriate. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of the RBR data will become and remain the exclusive and unburdened property 
of the Sponsor, except where agreed otherwise. 
4.5.11.5 
Consent to Participate in the Research Biosample Repository 
The Informed Consent Form will contain a separate section that addresses participation 
in the RBR.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential hazards of participation in the RBR.  Patients will be 
told that they are free to refuse to participate and may withdraw their consent at any time 
and for any reason during the storage period.  A separate, specific signature will be 
required to document a patient's agreement to provide optional RBR samples.  Patients 
who decline to participate will not provide a separate signature.  The investigator should 
document whether or not the patient has given consent to participate and (if applicable) 
the date of consent, by completing the Sample Informed Consent/Withdrawal eCRF. 
In the event of an RBR participant's death or loss of competence, the participant's 
samples and data will continue to be used as part of the RBR research. 

 
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4.5.11.6 
Withdrawal from the Research Biosample Repository 
Patients who give consent to provide RBR samples have the right to withdraw their 
consent at any time for any reason.  After withdrawal of consent, any remaining samples 
will be destroyed.  However, if RBR samples have been tested prior to withdrawal of 
consent, results from those tests will remain as part of the overall research data.  If a 
patient wishes to withdraw consent to the testing of his or her RBR samples during the 
study, the investigator must inform the Medical Monitor in writing of the patient's wishes 
through use of the appropriate RBR Subject Withdrawal Form and must enter the date of 
withdrawal on the Sample Informed Consent/Withdrawal eCRF.  If a patient wishes to 
withdraw consent to the testing of his or her RBR samples after closure of the site, the 
investigator must inform the Sponsor by emailing the study number and patient number 
to the following email address: 
global.rcr-withdrawal@roche.com 
A patient's withdrawal from this study does not, by itself, constitute withdrawal of consent 
for testing of RBR samples.  Likewise, a patient's withdrawal of consent for testing of 
RBR samples does not constitute withdrawal from this study. 
4.5.11.7 
Monitoring and Oversight 
RBR samples will be tracked in a manner consistent with Good Clinical Practice by a 
quality-controlled, auditable, and appropriately validated laboratory information 
management system, to ensure compliance with data confidentiality as well as 
adherence to authorized use of samples as specified in this protocol and in the Informed 
Consent Form.  Sponsor monitors and auditors will have direct access to appropriate 
parts of records relating to patient participation in the RBR for the purposes of verifying 
the data provided to the Sponsor.  The site will permit monitoring, audits, IRB/EC review, 
and health authority inspections by providing direct access to source data and 
documents related to the RBR samples. 
4.6 
TREATMENT, PATIENT, STUDY, AND SITE DISCONTINUATION 
4.6.1 
Study Treatment Discontinuation 
Patients must permanently discontinue study treatment if any of the following criteria are 
met: 
 
Any medical condition that the investigator or Sponsor determines may jeopardize 
the patient's safety if he or she continues to receive study treatment 
 
Investigator or Sponsor determination that treatment discontinuation is in the best 
interest of the patient 
 
Confirmed anaphylaxis related to study treatment 
 
Pregnancy 
 
Use of a prohibited therapy, including rescue therapy for worsening UC (see 
Section 4.4.1 and Section 4.4.2) 

 
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 
Significant laboratory abnormalities, confirmed on repeat laboratory collection and, 
if applicable, confirmed after holding or discontinuation of concomitant 
medications with known relevant toxicities (e.g., latent TB infection treatments), 
and determined to be related to study drug: 
– 
ALT, AST, or ALP  2.5  ULN, total bilirubin  2  ULN, or presence of 
abnormalities in synthetic liver function tests judged to be clinically significant 
by the investigator  
– 
ANC  1.5  109/L (1500/L), with one exception:  
Patients with BEN:  ANC  1.3  109/L (1300/L)  
– 
Absolute lymphocyte count  0.5  109/L (500/L) 
 
For cases of active TB or reactivation of TB, permanent discontinuation should be 
considered. 
The primary reason for study treatment discontinuation should be documented on the 
appropriate eCRF.  Patients who discontinue study treatment will not be replaced. 
Patients will return to the clinic for a treatment discontinuation visit within 
14 ( 3) days after the final dose of study treatment. 
Refer to the schedule of activities (see Appendix 1 and Appendix 2) for details on follow-
up assessments to be performed for patients who permanently discontinue study 
treatment.  If a patient requests to be withdrawn from treatment or follow-up 
assessments, this request must be documented in the source documents and signed by 
the investigator. 
4.6.2 
Patient Discontinuation from the Study 
Patients have the right to voluntarily withdraw from the study at any time for any reason.  
In addition, the investigator has the right to withdraw a patient from the study at any time. 
Reasons for patient discontinuation from the study may include, but are not limited to, 
the following: 
 
Patient withdrawal of consent 
 
Study termination or site closure 
 
Adverse event 
 
Loss to follow-up 
 
Patient non-compliance, defined as failure to comply with protocol requirements as 
determined by the investigator or Sponsor 
 
Every effort should be made to obtain a reason for patient discontinuation from the 
study.  The primary reason for discontinuation from the study should be documented on 
the appropriate eCRF.  If a patient requests to be withdrawn from the study, this request 

 
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must be documented in the source documents and signed by the investigator.  Patients 
who withdraw from the study will not be replaced. 
4.6.3 
Study Discontinuation 
The Sponsor has the right to terminate this study at any time.  Reasons for terminating 
the study may include, but are not limited to, the following: 
 
The incidence or severity of adverse events in this or other studies indicates a 
potential health hazard to patients 
 
Patient enrollment is unsatisfactory 
 
The Sponsor will notify the investigator if the Sponsor decides to discontinue the study.   
4.6.4 
Site Discontinuation 
The Sponsor has the right to close a site at any time.  Reasons for closing a site may 
include, but are not limited to, the following: 
 
Excessively slow recruitment 
 
Poor protocol adherence 
 
Inaccurate or incomplete data recording 
 
Non-compliance with the International Council for Harmonisation (ICH) guideline for 
Good Clinical Practice 
 
No study activity (i.e., all patients have completed the study and all obligations have 
been fulfilled) 
 
5. 
ASSESSMENT OF SAFETY  
5.1 
SAFETY PLAN 
Vixarelimab is not approved by health authorities, and clinical development is ongoing.  
The safety plan for patients in this study is based on clinical experience with vixarelimab 
in completed and ongoing studies.  There are currently no identified risks.  The potential 
risks associated with vixarelimab are outlined below.  Please refer to the Vixarelimab 
Investigator's Brochure for a complete summary of safety information.  
Several measures will be taken to ensure the safety of patients participating in this 
study.  Eligibility criteria have been designed to exclude patients at higher risk for 
adverse events.  Patients will undergo safety monitoring during the study, including 
assessment of the nature, frequency, and severity of adverse events.  In addition, 
guidelines for managing specific adverse events, including criteria for treatment 
interruption or discontinuation, are provided below. 
5.1.1 
Potential Risks Associated with Vixarelimab 
Hypersensitivity Reactions 
Monoclonal antibodies carry a potential risk of hypersensitivity reactions and anaphylaxis 
(allergic reactions), or hypersensitivity-like reactions (pseudoallergic reactions).  In 

 
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  Differentiating allergic reactions from 
pseudoallergic reactions is important because it may impact the understanding of the 
risk profile of the drug.  In instances where the reaction occurs with the first study drug 
administration without any suspicion of prior sensitization, it is less likely to be an allergic 
reaction.  When a new reaction is seen with the second or subsequent injections, or if 
there is an atypical presentation (e.g., rapid onset or increase in severity when 
compared with previous reactions), there is a higher likelihood that the reaction is 
allergic. 
Patients with a history of severe allergic reaction or anaphylactic reaction to a biologic 
agent are excluded from this study. 
Hypersensitivity reactions, including injection-site reactions, will be closely monitored 
during the study. 
 
 
 
Investigators and healthcare professionals administering study treatment should 
recognize and manage the signs and symptoms of such reactions and should be familiar 
with Sampson’s criteria for defining anaphylaxis events (Sampson et al. 2006; 
Appendix 8).  All potential cases of anaphylaxis should be captured on the Adverse 
Event eCRF as instructed in Section 5.2 and Section 5.3.  Investigators and healthcare 
professionals should accurately report these events immediately to the Sponsor as 
serious adverse events if appropriate.  Healthcare professionals should also instruct 
patients on how to recognize the symptoms of any such events and to contact a 
healthcare provider or seek emergency care in case of any such symptoms. 
5.1.2 
Management of Patients Who Experience Adverse Events 
Guidelines for management of patients who experience specific adverse events are 
outlined in Table 3. 

 
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Table 3 
Guidelines for Management of Patients Who Experience Specific 
Adverse Events  
Event 
Action to Be Taken  
Acute allergic reaction or ISR,  
Grade 1  
 Observe. 
 Capture signs and symptoms per appropriate eCRF. 
 Administer non-systemic symptomatic treatment (topical 
corticosteroids, antihistamines). 
Acute allergic reaction or ISR, 
Grades 2 and 3 
 Capture signs and symptoms per appropriate eCRF. 
 Administer symptomatic treatment (e.g., oral or IV 
antihistamine, anti-pyretic medication, glucocorticoids, 
epinephrine, bronchodilators, oxygen, IV fluids). 
 For subsequent doses, consider administration of oral 
premedication with antihistamines, anti-pyretics, and/or 
analgesics and monitor closely for ISRs or systemic 
symptoms. 
Acute allergic reaction or ISR,  
Grade 4 
 Capture signs and symptoms per appropriate eCRF.  
 Administer aggressive symptomatic treatment (e.g., oral 
or IV antihistamine, anti-pyretic medication, 
glucocorticoids, epinephrine, bronchodilators, oxygen, 
IV fluids). 
 Permanently discontinue study treatment and contact 
Medical Monitor. 
eCRF  electronic Case Report Form; ISR  injection-site reaction. 
 
5.1.2.1 
Dose Modifications 
Dose modifications are not permitted.  
5.1.2.2 
Treatment Interruption 
Study treatment may be interrupted (withheld) for patients who experience a treatment-
emergent adverse event considered to be related to study treatment.  If study treatment 
has been withheld for  2 consecutive doses because of an ongoing adverse event 
related to study treatment, the patient should be permanently discontinued from study 
treatment, unless resumption of treatment is approved by the investigator following 
consultation with the Medical Monitor.  Study treatment may be withheld for reasons 
other than a treatment-emergent adverse event (e.g., surgical procedures) at the 
investigator's discretion following consultation with the Medical Monitor.  The investigator 
should consult with the Medical Monitor to determine the acceptable length of treatment 
interruption. 
5.2 
SAFETY PARAMETERS AND DEFINITIONS 
Safety assessments will consist of monitoring and recording adverse events, including 
serious adverse events and adverse events of special interest, performing protocol-
specified safety laboratory assessments, measuring protocol-specified vital signs, and 

 
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conducting other protocol-specified tests that are deemed critical to the safety evaluation 
of the study. 
Certain types of events require immediate reporting to the Sponsor, as outlined in 
Section 5.4. 
5.2.1 
Adverse Events 
According to the ICH guideline for Good Clinical Practice, an adverse event is any 
untoward medical occurrence in a clinical investigation subject administered a 
pharmaceutical product, regardless of causal attribution.  An adverse event can 
therefore be any of the following: 
 
Any unfavorable and unintended sign (including an abnormal laboratory finding), 
symptom, or disease temporally associated with the use of a medicinal product, 
whether or not considered related to the medicinal product 
 
Any new disease or exacerbation of an existing disease (a worsening in the 
character, frequency, or severity of a known condition) (see Sections 5.3.5.9 and 
5.3.5.10 for more information) 
 
Recurrence of an intermittent medical condition (e.g., headache) not present at 
baseline 
 
Any deterioration in a laboratory value or other clinical test (e.g., ECG, X-ray) that is 
associated with symptoms or leads to a change in study treatment or concomitant 
treatment or discontinuation from study treatment 
 
Adverse events that are related to a protocol-mandated intervention, including those 
that occur prior to assignment of study treatment (e.g., screening invasive 
procedures such as biopsies) 
 
5.2.2 
Serious Adverse Events (Immediately Reportable to the 
Sponsor) 
A serious adverse event is any adverse event that meets any of the following criteria: 
 
Is fatal (i.e., the adverse event actually causes or leads to death) 
 
Is life threatening (i.e., the adverse event, in the view of the investigator, places the 
patient at immediate risk of death) 
This does not include any adverse event that, had it occurred in a more severe 
form or was allowed to continue, might have caused death. 
 
Requires or prolongs inpatient hospitalization (see Section 5.3.5.11) 
 
Results in persistent or significant disability/incapacity (i.e., the adverse event 
results in substantial disruption of the patient's ability to conduct normal life 
functions) 
 
Is a congenital anomaly/birth defect in a neonate/infant born to a mother exposed to 
study treatment 

 
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 
Is a significant medical event in the investigator's judgment (e.g., may jeopardize the 
patient or may require medical/surgical intervention to prevent one of the outcomes 
listed above) 
 
The terms "severe" and "serious" are not synonymous.  Severity refers to the intensity of 
an adverse event (e.g., rated mild, moderate, severe, life-threatening, or according or 
according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and 
Pediatric Adverse Events; see Section 5.3.3); the event itself may be of relatively minor 
medical significance (such as severe headache without any further findings). 
Severity and seriousness need to be independently assessed for each adverse event 
recorded on the eCRF. 
Serious adverse events are required to be reported by the investigator to the Sponsor 
immediately (i.e., no more than 24 hours after the investigator becomes aware of the 
event; see Section 5.4.2 for reporting instructions). 
5.2.3 
Adverse Events of Special Interest (Immediately Reportable to 
the Sponsor) 
Adverse events of special interest are required to be reported by the investigator to the 
Sponsor immediately (i.e., no more than 24 hours after the investigator becomes aware 
of the event; see Section 5.4.2 for reporting instructions).  Adverse events of special 
interest for this study are as follows: 
 
Cases of potential drug-induced liver injury that include an elevated ALT or AST in 
combination with either an elevated bilirubin or clinical jaundice, as defined by 
Hy's Law (see Section 5.3.5.7) 
 
Suspected transmission of an infectious agent by the study treatment, as defined 
below 
Any organism, virus, or infectious particle (e.g., prion protein transmitting 
transmissible spongiform encephalopathy), pathogenic or non-pathogenic, is 
considered an infectious agent.  A transmission of an infectious agent may be 
suspected from clinical symptoms or laboratory findings that indicate an 
infection in a patient exposed to a medicinal product.  This term applies only 
when a contamination of the study treatment is suspected. 
 
Suspected angioedema, anaphylactic, or hypersensitivity reactions (DAIDS Grade 3 
or greater) 
  
5.3 
METHODS AND TIMING FOR CAPTURING AND ASSESSING 
SAFETY PARAMETERS 
The investigator is responsible for ensuring that all adverse events (see Section 5.2.1 for 
definition) are recorded on the Adverse Event eCRF and reported to the Sponsor in 
accordance with instructions provided in this section and in Sections 5.45.6. 

 
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For each adverse event recorded on the Adverse Event eCRF, the investigator will make 
an assessment of seriousness (see Section 5.2.2 for seriousness criteria), severity (see 
Section 5.3.3), and causality (see Section 5.3.4).   
5.3.1 
Adverse Event Reporting Period 
Investigators will seek information on adverse events at each patient contact.  All 
adverse events, whether reported by the patient or noted by study personnel, will be 
recorded in the patient's medical record and on the Adverse Event eCRF. 
After informed consent has been obtained but prior to initiation of study treatment, only 
serious adverse events caused by a protocol-mandated intervention (e.g., invasive 
procedures such as biopsies, discontinuation of medications) should be reported 
(see Section 5.4.2 for instructions for reporting serious adverse events). 
After initiation of study treatment, all adverse events will be reported until 
 after 
the final dose of study treatment. 
Instructions for reporting adverse events that occur after the adverse event reporting 
period are provided in Section 5.6. 
5.3.2 
Eliciting Adverse Event Information 
A consistent methodology of non-directive questioning should be adopted for eliciting 
adverse event information at all patient evaluation timepoints.  Examples of non-directive 
questions include the following: 
"How have you felt since your last clinic visit?" 
"Have you had any new or changed health problems since you were last here?"  
 
5.3.3 
Assessment of Severity of Adverse Events 
The investigator will use the DAIDS toxicity grading scale (HHS 2017), with slight 
modifications for clarity and for alignment with internal practices (see Appendix 7), 
for assessing the severity of each adverse event reported during the study.  The 
investigator will use the grading scale in Table 4 for assessing the severity of adverse 
events that are not specifically listed in the DAIDS toxicity grading scale. 

 
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Table 4 
Adverse Event Severity Grading Scale for Events Not Specifically 
Listed in DAIDS Toxicity Grading Scale 
Grade 
Severity 
1 
Mild; transient or mild discomfort ( 48 hours); no medical intervention or 
therapy required 
2 
Moderate; mild to moderate limitation in activity; some assistance may be 
needed; no or minimal medical intervention or therapy required 
3 
Severe; marked limitation in activity; some assistance usually required; 
medical intervention or therapy required; hospitalization possible 
4 
Life-threatening; extreme limitation in activity; significant assistance required; 
significant medical intervention or therapy required, hospitalization or hospice 
care probable 
DAIDS  Division of AIDS. 
Notes:  Developed by the Division of AIDS, National Institute of Allergy and Infectious Diseases, 
National Institutes of Health, US Department of Health and Human Services. 
Regardless of severity, some events may also meet seriousness criteria.  Refer to definition of a 
serious adverse event (see Section 5.2.2). 
 
5.3.4 
Assessment of Causality of Adverse Events 
Investigators should use their knowledge of the patient, the circumstances surrounding 
the event, and an evaluation of any potential alternative causes to determine whether an 
adverse event is considered to be related to the study treatment, indicating "yes" or "no" 
accordingly.  The following guidance should be taken into consideration (see also 
Table 5): 
 
Temporal relationship of event onset to the initiation of study treatment 
 
Course of the event, with special consideration of the effects of dose reduction, 
discontinuation of study treatment, or reintroduction of study treatment (as 
applicable) 
 
Known association of the event with the study treatment or with similar treatments 
 
Known association of the event with the disease under study 
 
Presence of risk factors in the patient or use of concomitant medications known to 
increase the occurrence of the event 
 
Presence of non-treatment-related factors that are known to be associated with the 
occurrence of the event 
 

 
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Table 5 
Causal Attribution Guidance 
Is the adverse event suspected to be caused by the study drug on the basis of facts, evidence, 
science-based rationales, and clinical judgment? 
YES 
There is a plausible temporal relationship between the onset of the adverse event and 
administration of the study drug, and the adverse event cannot be readily explained by 
the patient's clinical state, intercurrent illness, or concomitant therapies; and/or the 
adverse event follows a known pattern of response to the study drug; and/or the 
adverse event abates or resolves upon discontinuation of the study drug or dose 
reduction and, if applicable, reappears upon re-challenge. 
NO 
An adverse event will be considered related, unless it fulfills the criteria specified below.   
Evidence exists that the adverse event has an etiology other than the study drug 
(e.g., preexisting medical condition, underlying disease, intercurrent illness, 
or concomitant medication); and/or the adverse event has no plausible temporal 
relationship to administration of the study drug (e.g., cancer diagnosed 2 days after 
first dose of study drug). 
 
5.3.5 
Procedures for Recording Adverse Events 
Investigators should use correct medical terminology/concepts when recording adverse 
events on the Adverse Event eCRF.  Avoid colloquialisms and abbreviations. 
Only one adverse event term should be recorded in the event field on the Adverse Event 
eCRF. 
5.3.5.1 
Injection Reactions and Anaphylactic Reactions 
Adverse events that occur during or within 24 hours after study treatment administration 
and are judged to be related to study treatment injection should be captured as a 
diagnosis (e.g., "injection-related reaction", "injection-site reaction," or "anaphylactic 
reaction”) on the Adverse Event eCRF.  If possible, avoid ambiguous terms such as 
"systemic reaction."  Associated signs and symptoms should be recorded on the 
dedicated Injection Reaction eCRF or Anaphylaxis, Anaphylactoid, and Hypersensitivity 
Reaction eCRF, as appropriate.  If a patient experiences both a local and systemic 
reaction to a single administration of study treatment, each reaction should be recorded 
as a separate diagnosis on the Adverse Event eCRF, with associated signs and 
symptoms also recorded separately on the Injection Reaction and Anaphylaxis, 
Anaphylactoid and Hypersensitivity Reaction eCRFs.  Investigators may use the 
Sampson criteria as a guideline to identify and report anaphylaxis events (see 
Appendix 8). 
5.3.5.2 
Diagnosis versus Signs and Symptoms 
For all adverse events, a diagnosis (if known) should be recorded on the Adverse Event 
eCRF rather than individual signs and symptoms (e.g., record only liver failure or 
hepatitis rather than jaundice, asterixis, and elevated transaminases).  However, if a 
constellation of signs and/or symptoms cannot be medically characterized as a single 
diagnosis or syndrome at the time of reporting, each individual event should be recorded 

 
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on the Adverse Event eCRF.  If a diagnosis is subsequently established, all previously 
reported adverse events based on signs and symptoms should be nullified and replaced 
by one adverse event report based on the single diagnosis, with a starting date that 
corresponds to the starting date of the first symptom of the eventual diagnosis. 
5.3.5.3 
Adverse Events That Are Secondary to Other Events 
In general, adverse events that are secondary to other events (e.g., cascade events or 
clinical sequelae) should be identified by their primary cause, with the exception of 
severe or serious secondary events.  A medically significant secondary adverse event 
that is separated in time from the initiating event should be recorded as an independent 
event on the Adverse Event eCRF.  For example: 
 
If vomiting results in mild dehydration with no additional treatment in a healthy adult, 
only vomiting should be reported on the eCRF. 
 
If vomiting results in severe dehydration, both events should be reported separately 
on the eCRF. 
 
If a severe gastrointestinal hemorrhage leads to renal failure, both events should be 
reported separately on the eCRF. 
 
If dizziness leads to a fall and consequent fracture, all three events should be 
reported separately on the eCRF. 
 
If neutropenia is accompanied by an infection, both events should be reported 
separately on the eCRF. 
 
All adverse events should be recorded separately on the Adverse Event eCRF if it is 
unclear as to whether the events are associated. 
5.3.5.4 
Persistent or Recurrent Adverse Events 
A persistent adverse event is one that extends continuously, without resolution, between 
patient evaluation timepoints.  Such events should only be recorded once on the 
Adverse Event eCRF.  The initial severity (intensity or grade) of the event will be 
recorded at the time the event is first reported.  If a persistent adverse event becomes 
more severe, the most extreme severity should also be recorded on the Adverse Event 
eCRF.  Details regarding any increases or decreases in severity will be captured on the 
Adverse Event Intensity or Grade Changes eCRF.  If the event becomes serious, it 
should be reported to the Sponsor immediately (i.e., no more than 24 hours after the 
investigator becomes aware that the event became serious; see Section 5.4.2 for 
reporting instructions).  The Adverse Event eCRF should be updated by changing the 
event from "non-serious" to "serious," providing the date that the event became serious, 
and completing all data fields related to serious adverse events. 
A recurrent adverse event is one that resolves between patient evaluation timepoints 
and subsequently recurs.  Each recurrence of an adverse event should be recorded as a 
separate event on the Adverse Event eCRF. 

 
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5.3.5.5 
Abnormal Laboratory Values 
Not every laboratory abnormality qualifies as an adverse event.  A laboratory test result 
must be reported as an adverse event if it meets any of the following criteria: 
 
Is accompanied by clinical symptoms 
 
Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation) 
 
Results in a medical intervention (e.g., potassium supplementation for hypokalemia) 
or a change in concomitant therapy 
 
Is clinically significant in the investigator's judgment  
 
It is the investigator's responsibility to review all laboratory findings.  Medical and 
scientific judgment should be exercised in deciding whether an isolated laboratory 
abnormality should be classified as an adverse event. 
If a clinically significant laboratory abnormality is a sign of a disease or syndrome 
(e.g., ALP and bilirubin 5  ULN associated with cholestasis), only the diagnosis 
(i.e., cholestasis) should be recorded on the Adverse Event eCRF. 
If a clinically significant laboratory abnormality is not a sign of a disease or syndrome, 
the abnormality itself should be recorded on the Adverse Event eCRF, along with a 
descriptor indicating whether the test result is above or below the normal range 
(e.g., "elevated potassium," as opposed to "abnormal potassium").  If the laboratory 
abnormality can be characterized by a precise clinical term per standard definitions, the 
clinical term should be recorded as the adverse event.  For example, an elevated serum 
potassium level of 7.0 mEq/L should be recorded as "hyperkalemia." 
Observations of the same clinically significant laboratory abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section 5.3.5.4 for 
details on recording persistent adverse events). 
5.3.5.6 
Abnormal Vital Sign Values 
Not every vital sign abnormality qualifies as an adverse event.  A vital sign result must 
be reported as an adverse event if it meets any of the following criteria: 
 
Is accompanied by clinical symptoms 
 
Results in a change in study treatment (e.g., dosage modification, treatment 
interruption, or treatment discontinuation) 
 
Results in a medical intervention or a change in concomitant therapy 
 
Is clinically significant in the investigator's judgment  
 
It is the investigator's responsibility to review all vital sign findings.  Medical and scientific 
judgment should be exercised in deciding whether an isolated vital sign abnormality 
should be classified as an adverse event. 

 
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If a clinically significant vital sign abnormality is a sign of a disease or syndrome 
(e.g., high blood pressure), only the diagnosis (e.g., hypertension) should be recorded 
on the Adverse Event eCRF. 
Observations of the same clinically significant vital sign abnormality from visit to visit 
should only be recorded once on the Adverse Event eCRF (see Section 5.3.5.4 for 
details on recording persistent adverse events). 
5.3.5.7 
Abnormal Liver Function Tests 
The finding of an elevated ALT or AST (  3   ULN) in combination with either an 
elevated total bilirubin (  2  ULN) or clinical jaundice in the absence of cholestasis or 
other causes of hyperbilirubinemia is considered to be an indicator of severe liver injury 
(as defined by Hy's Law).  Therefore, investigators must report as an adverse event the 
occurrence of either of the following: 
 
Treatment-emergent ALT or AST   3  ULN in combination with total bilirubin 
  2   ULN 
 
Treatment-emergent ALT or AST   3  ULN in combination with clinical jaundice 
 
The most appropriate diagnosis or (if a diagnosis cannot be established) the abnormal 
laboratory values should be recorded on the Adverse Event eCRF (see  Section 5.3.5.2) 
and reported to the Sponsor immediately (i.e., no more than 24 hours after the 
investigator becomes aware of the event), either as a serious adverse event or an 
adverse event of special interest (see Section 5.4.2). 
5.3.5.8 
Deaths 
All deaths that occur during the protocol-specified adverse event reporting period (see 
Section 5.3.1), regardless of relationship to study treatment, must be recorded on the 
Adverse Event eCRF and immediately reported to the Sponsor (see Section 5.4.2). 
Death should be considered an outcome and not a distinct event.  The event or condition 
that caused or contributed to the fatal outcome should be recorded as the single medical 
concept on the Adverse Event eCRF.  Generally, only one such event should be 
reported.  If the cause of death is unknown and cannot be ascertained at the time of 
reporting, "unexplained death" should be recorded on the Adverse Event eCRF.  If the 
cause of death later becomes available (e.g., after autopsy), "unexplained death" should 
be replaced by the established cause of death.  The term "sudden death" should not be 
used unless combined with the presumed cause of death (e.g., "sudden cardiac death"). 
Deaths that occur after the adverse event reporting period should be reported as 
described in Section 5.6. 

 
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5.3.5.9 
Preexisting Medical Conditions 
A preexisting medical condition is one that is present at the screening visit for this study.  
Such conditions should be recorded on the General Medical History and Baseline 
Conditions eCRF. 
A preexisting medical condition should be recorded as an adverse event only if the 
frequency, severity, or character of the condition worsens during the study.  When 
recording such events on the Adverse Event eCRF, it is important to convey the concept 
that the preexisting condition has changed by including applicable descriptors 
(e.g., "more frequent headaches"). 
5.3.5.10 
Lack of Efficacy or Worsening of Ulcerative Colitis 
Deterioration that is judged by the investigator to have unexpectedly worsened in 
severity or frequency or changed in nature (i.e., deterioration beyond the expected 
pattern of progression of the underlying disease) should be recorded as an adverse 
event.  When recording an unanticipated worsening of ulcerative colitis on the Adverse 
Event eCRF, it is important to convey the concept that the condition has changed by 
including applicable descriptors (e.g., "accelerated worsening of ulcerative colitis”).  
Events that are clearly consistent with the expected pattern of progression of the 
underlying disease should not be recorded as adverse events.  These data will be 
captured as efficacy assessment data only.  In most cases, the expected pattern of 
progression will be based on the Mayo Score, which includes endoscopic disease 
evaluation.  In rare cases, the determination of clinical progression will be based on 
symptomatic deterioration.  However, every effort should be made to document 
progression through use of objective criteria.  If there is any uncertainty as to whether an 
event is due to disease progression, it should be reported as an adverse event. 
5.3.5.11 
Hospitalization or Prolonged Hospitalization 
Any adverse event that results in hospitalization (i.e., inpatient admission to a hospital) 
or prolonged hospitalization should be documented and reported as a serious adverse 
event (per the definition of serious adverse event in Section 5.2.2), except as outlined 
below.   
An event that leads to hospitalization under the following circumstances should not be 
reported as an adverse event or a serious adverse event: 
 
Hospitalization for respite care 
 
Hospitalization for a preexisting condition, provided that all of the following criteria 
are met: 
The hospitalization was planned prior to the study or was scheduled during the 
study when elective surgery became necessary because of the expected 
normal progression of the disease 
The patient has not experienced an adverse event 
 

 
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An event that leads to hospitalization under the following circumstances is not 
considered to be a serious adverse event, but should be reported as an adverse event 
instead: 
 
Hospitalization that was necessary because of patient requirement for outpatient 
care outside of normal outpatient clinic operating hours 
 
5.3.5.12 
Patient-Reported Outcome Data 
Adverse event reports will not be derived from PRO data by the Sponsor.  Sites are not 
expected to review the PRO data for adverse events. 
5.3.6 
Special Situations (Accidental Overdose and/or Medication 
Error) 
Accidental overdose and medication error (hereafter collectively referred to as 
"special situations"), are defined as follows: 
 
Accidental overdose:  accidental administration of a drug in a quantity that is higher 
than the assigned dose 
 
Medication error:  accidental deviation in the administration of a drug (e.g., wrong 
drug, expired drug, accidental overdose, underdose, wrong dosing schedule, 
incorrect route of administration) 
 
After initiation of study treatment, special situations associated with vixarelimab or 
matching placebo and any associated adverse events will be reported until 
 
after the final dose of study treatment. 
Special situations, regardless of whether they result in an adverse event, should be 
recorded on the Special Situations eCRF.  If there are any associated adverse events, 
each event should be recorded separately on the Adverse Event eCRF. 
Special situations and any associated adverse events should be reported within 30 days 
after the investigator becomes aware of the situation.  However, if an associated 
adverse event fulfills seriousness criteria or qualifies as an adverse event of special 
interest, both the event and the special situation should be reported to the Sponsor 
immediately (i.e., no more than 24 hours after the investigator becomes aware of the 
event), as described in Section 5.4.2.2. 
5.4 
IMMEDIATE REPORTING REQUIREMENTS FROM 
INVESTIGATOR TO SPONSOR 
Certain events require immediate reporting to allow the Sponsor to take appropriate 
measures to address potential new risks in a clinical trial.  The investigator must report 
such events to the Sponsor immediately; under no circumstances should reporting take 
place more than 24 hours after the investigator becomes aware of the event.  The 
following is a list of events that the investigator must report to the Sponsor within 

 
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24 hours after the investigator becomes aware of the event, regardless of relationship to 
study treatment: 
 
Serious adverse events (defined in Section 5.2.2; see Section 5.4.2 for details on 
reporting requirements) 
 
Adverse events of special interest (defined in Section 5.2.3; see Section 5.4.2 for 
details on reporting requirements) 
 
Pregnancies (see Section 5.4.3 for details on reporting requirements) 
 
For serious adverse events and adverse events of special interest, the investigator must 
report new significant follow-up information to the Sponsor immediately (i.e., no more 
than 24 hours after the investigator becomes aware of the information).  New significant 
information includes the following: 
 
New signs or symptoms or a change in the diagnosis 
 
Significant new diagnostic test results 
 
Change in causality based on new information 
 
Change in the event's outcome, including recovery 
 
Additional narrative information on the clinical course of the event 
 
Investigators must also comply with local requirements for reporting serious adverse 
events to the local health authority and IRB/EC. 
5.4.1 
Emergency Medical Contacts 
To ensure the safety of study participants, access to the Medical Monitors is available 
24 hours per day, 7 days per week.  Details will be provided separately. 
5.4.2 
Reporting Requirements for Serious Adverse Events and 
Adverse Events of Special Interest 
5.4.2.1 
Events That Occur prior to Study Treatment Initiation 
After informed consent has been obtained but prior to initiation of study treatment, only 
serious adverse events caused by a protocol-mandated intervention should be reported.  
The paper Clinical Trial Adverse Event/Special Situations Form provided to investigators 
should be completed and submitted to the Sponsor or its designee immediately (i.e., no 
more than 24 hours after the investigator becomes aware of the event), either by faxing 
or by scanning and emailing the form using the fax number or email address provided to 
investigators. 
5.4.2.2 
Events That Occur after Study Treatment Initiation 
After initiation of study treatment, serious adverse events and adverse events of special 
interest will be reported until 
 after the final dose of study treatment.  
Investigators should record all case details that can be gathered immediately (i.e., within 
24 hours after the investigator becomes aware of the event) on the Adverse Event eCRF 

 
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and submit the report via the electronic data capture (EDC) system.  A report will be 
generated and sent to Safety Risk Management by the EDC system. 
In the event that the EDC system is unavailable, the paper Clinical Trial Adverse 
Event/Special Situations Form provided to investigators should be completed and 
submitted to the Sponsor or its designee immediately (i.e., no more than 24 hours after 
the investigator becomes aware of the event), either by faxing or by scanning and 
emailing the form using the fax number or email address provided to investigators.  
Once the EDC system is available, all information will need to be entered and submitted 
via the EDC system.   
Instructions for reporting serious adverse events that occur
after the final 
dose of study treatment are provided in Section 5.6. 
5.4.3 
Reporting Requirements for Pregnancies 
5.4.3.1 
Pregnancies in Female Patients 
Female patients will be instructed through the Informed Consent Form to immediately 
inform the investigator if they become pregnant during the study or within 
 after 
the final dose of study treatment.  A paper Clinical Trial Pregnancy Reporting Form 
should be completed and submitted to the Sponsor or its designee immediately (i.e., no 
more than 24 hours after learning of the pregnancy), either by faxing or by scanning and 
emailing the form using the fax number or email address provided to investigators.  
Pregnancy should not be recorded on the Adverse Event eCRF.  The investigator should 
discontinue study treatment and counsel the patient, discussing the risks of the 
pregnancy and the possible effects on the fetus.  Monitoring of the patient should 
continue until conclusion of the pregnancy.  Any serious adverse events associated with 
the pregnancy (e.g., an event in the fetus, an event in the mother during or after the 
pregnancy, or a congenital anomaly/birth defect in the child) should be reported on the 
Adverse Event eCRF.  In addition, the investigator will submit a Clinical Trial Pregnancy 
Reporting Form when updated information on the course and outcome of the pregnancy 
becomes available.   
Attempts should be made to collect and report infant health information.  When permitted 
by the site, an Authorization for the Use and Disclosure of Infant Health Information 
would need to be signed by one or both parents (as per local regulations) to allow for 
follow-up on the infant.  If the authorization has been signed, the infant's health status at 
birth should be recorded on the Clinical Trial Pregnancy Reporting Form.  In addition, the 
Sponsor may collect follow-up information on the infant's health status at 6 and 
12 months after birth. 
5.4.3.2 
Pregnancies in Female Partners of Male Patients  
Male patients will be instructed through the Informed Consent Form to immediately 
inform the investigator if their partner becomes pregnant during the study or within 
 after the final dose of study treatment.  The investigator should report the 

 
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pregnancy on the paper Clinical Trial Pregnancy Reporting Form and submit the form to 
the Sponsor or its designee immediately (i.e., no more than 24 hours after learning of the 
pregnancy), either by faxing or by scanning and emailing the form using the fax number 
or email address provided to investigators.  Attempts should be made to collect and 
report details of the course and outcome of any pregnancy in the partner of a male 
patient exposed to study treatment.  When permitted by the site, the pregnant partner 
would need to sign an Authorization for the Use and Disclosure of Pregnancy Health 
Information to allow for follow-up on her pregnancy.  If the authorization has been 
signed, the investigator should submit a Clinical Trial Pregnancy Reporting Form with 
additional information on the pregnant partner and the course and outcome of the 
pregnancy as it becomes available.   
Attempts should be made to collect and report infant health information.  When permitted 
by the site, an Authorization for the Use and Disclosure of Infant Health Information 
would need to be signed by one or both parents (as per local regulations) to allow for 
follow-up on the infant.  If the authorization has been signed, the infant's health status at 
birth should be recorded on the Clinical Trial Pregnancy Reporting Form.  In addition, the 
Sponsor may collect follow-up information on the infant's health status at 6 and 
12 months after birth. 
An investigator who is contacted by the male patient or his pregnant partner may provide 
information on the risks of the pregnancy and the possible effects on the fetus, to 
support an informed decision in cooperation with the treating physician and/or 
obstetrician. 
5.4.3.3 
Abortions 
A spontaneous abortion in a female patient exposed to study treatment or the female 
partner of a male patient exposed to study treatment should be classified as a serious 
adverse event (as the Sponsor considers abortions to be medically significant), recorded 
on the Adverse Event eCRF, and reported to the Sponsor immediately (i.e., no more 
than 24 hours after the investigator becomes aware of the event; see Section 5.4.2). 
If a therapeutic or elective abortion was performed because of an underlying maternal or 
embryofetal toxicity, the toxicity should be classified as a serious adverse event, 
recorded on the Adverse Event eCRF, and reported to the Sponsor immediately (i.e., no 
more than 24 hours after the investigator becomes aware of the event; see 
Section 5.4.2).  A therapeutic or elective abortion performed for reasons other than an 
underlying maternal or embryofetal toxicity is not considered an adverse event. 
All abortions should be reported as pregnancy outcomes on the paper Clinical Trial 
Pregnancy Reporting Form.  

 
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5.4.3.4 
Congenital Anomalies/Birth Defects 
Any congenital anomaly/birth defect in a child born to a female patient exposed to study 
treatment or the female partner of a male patient exposed to study treatment should be 
classified as a serious adverse event, recorded on the Adverse Event eCRF, and 
reported to the Sponsor immediately (i.e., no more than 24 hours after the investigator 
becomes aware of the event; see Section 5.4.2). 
5.5 
FOLLOW-UP OF PATIENTS AFTER ADVERSE EVENTS 
5.5.1 
Investigator Follow-Up 
The investigator should follow each adverse event until the event has resolved to 
baseline grade or better, the event is assessed as stable by the investigator, the patient 
is lost to follow-up, or the patient withdraws consent.  Every effort should be made to 
follow all serious adverse events considered to be related to study treatment or trial-
related procedures until a final outcome can be reported. 
During the adverse event reporting period (defined in Section 5.3.1), resolution of 
adverse events (with dates) should be documented on the Adverse Event eCRF and in 
the patient's medical record to facilitate source data verification. 
All pregnancies reported during the study should be followed until pregnancy outcome, 
with follow-up information on the infant collected according to procedures outlined in 
Section 5.4.3. 
5.5.2 
Sponsor Follow-Up 
For serious adverse events, adverse events of special interest, and pregnancies, the 
Sponsor or a designee may follow up by telephone, fax, email, and/or a monitoring visit 
to obtain additional case details and outcome information (e.g., from hospital discharge 
summaries, consultant reports, autopsy reports) in order to perform an independent 
medical assessment of the reported case. 
5.6 
ADVERSE EVENTS THAT OCCUR AFTER THE ADVERSE 
EVENT REPORTING PERIOD 
The Sponsor should be notified if the investigator becomes aware of any serious 
adverse event that occurs after the end of the adverse event reporting period (defined as 
 after the final dose of study treatment), if the event is believed to be related to 
prior exposure to study treatment.  These events should be reported through use of the 
Adverse Event eCRF.  However, if the EDC system is not available, the investigator 
should report these events directly to the Sponsor or its designee, either by faxing or by 
scanning and emailing the paper Clinical Trial Adverse Event/Special Situations Form 
using the fax number or email address provided to investigators. 

 
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5.7 
EXPEDITED REPORTING TO HEALTH AUTHORITIES, 
INVESTIGATORS, INSTITUTIONAL REVIEW BOARDS, 
AND ETHICS COMMITTEES 
The Sponsor will promptly evaluate all serious adverse events and adverse events of 
special interest against cumulative product experience to identify and expeditiously 
communicate possible new safety findings to investigators, IRBs, ECs, and applicable 
health authorities based on applicable legislation. 
To determine reporting requirements for single adverse event cases, the Sponsor will 
assess the expectedness of these events through use of the reference safety 
information in the document listed below: 
Drug 
Document 
Vixarelimab 
 Vixarelimab Investigator's Brochure  
 
The Sponsor will compare the severity of each event and the cumulative event 
frequency reported for the study with the severity and frequency reported in the 
applicable reference document. 
Reporting requirements will also be based on the investigator's assessment of causality 
and seriousness, with allowance for upgrading by the Sponsor as needed. 
An Internal Monitoring Committee (IMC) will monitor the incidence of the above-listed 
anticipated events during the study.  An aggregate report of any clinically relevant 
imbalances that do not favor the test product will be submitted to health authorities. 
6. 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN 
The primary analyses of efficacy and safety data will be performed after all enrolled 
patients have either completed the 
 visit or have discontinued from the study 
prior to 
, and all data from this period are in the database and have been 
cleaned and verified.  The final analyses of complete data for the study will be performed 
when all enrolled patients have either completed the safety follow-up period or 
discontinued early from the study, all data from the study are in the database, and the 
database is locked.  Detailed specifications of the statistical methods will be described in 
the Data Analysis Plan (DAP). 
6.1 
DETERMINATION OF SAMPLE SIZE 
Approximately 210 patients will be enrolled in this study.  
 
  Eligible patients will be randomized in a 
 
to vixarelimab 
 arm, vixarelimab 
 arm, or placebo
arm 
during the induction period
  
 
 

 
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6.2 
SUMMARIES OF CONDUCT OF STUDY 
The number of patients who enroll, discontinue (early discontinuation of treatment or 
early termination from the study), or complete the study will be summarized.  Reasons 
for premature treatment discontinuation or early termination from the study will be listed 
and summarized.  Enrollment and major protocol deviations will be listed and evaluated 
for their potential effects on the interpretation of study results. 
6.3 
SUMMARIES OF DEMOGRAPHIC AND BASELINE 
CHARACTERISTICS 
Demographic and baseline characteristics (including, but not limited to, age, sex, 
race/ethnicity) will be summarized using means, standard deviations, medians, and 
ranges for continuous variables and proportions for categorical variables, as appropriate.  
Summaries will be presented overall and by treatment group. 
6.4 
EFFICACY ANALYSES 
The analysis population for the efficacy analyses will be the modified intent-to-treat 
population defined as all patients who received at least one dose of study treatment and 
have at least one postbaseline efficacy measurement, with patients grouped according 
to their assigned treatment. 
Because the study is hypothesis-generating in nature, hypothesis testing will be carried 
out in an exploratory fashion, at a two-sided 0.20 significance level.  
 
.  A 
separate DAP will contain more details on the statistical analyses. 
6.4.1 
Primary Efficacy Endpoint 
The primary efficacy endpoint is clinical remission at Week 12 (see definition of clinical 
remission in Section 2).  A comparison between the vixarelimab arms and the placebo 
arm will be carried out.  The difference between vixarelimab arms versus placebo arm in 
the proportion of patients with clinical remission at Week 12 will be evaluated by the 
Cochran-Mantel-Haenszel test, stratified by advanced or conventional failure and 
baseline mMS
  The non-responder imputation method, where subjects with 
missing data at scheduled assessment visits will be considered as “not achieved” for the 
clinical remission, will be used for primary analysis.  A subgroup (advanced failure) 
analysis for the primary efficacy endpoint will be conducted using the same methods 
outlined above, except that the Cochran-Mantel-Haenszel test will be stratified by 
baseline mMS 
.  

 
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6.4.2 
Secondary Efficacy Endpoints 
The secondary efficacy endpoints are defined in Section 2.  The secondary efficacy 
endpoints will be summarized by descriptive statistics based on the following 
calculations: 
 
Proportion of patients with clinical response at Week 12 
 
Proportion of patients with endoscopic improvement at Week 12 
 
Proportion of patients with endoscopic remission at Week 12 
 
Data will be summarized by treatment arms.  In addition, the secondary endpoints will be 
analyzed in the advanced failure subgroup. 
6.4.3 
Exploratory Efficacy Endpoints 
The exploratory efficacy endpoints are defined in Section 2.  The exploratory efficacy 
endpoints will be summarized by descriptive statistics based on the following 
calculations: 
 
Proportion of patients with sustained remission at 
 Week 12 
 
 
Proportion of patients with clinical remission 
 
 
Proportion of patients with clinical response 
 
 
Proportion of patients with endoscopic improvement 
 
 
Proportion of patients with endoscopic remission 
 
 
Change from baseline in UC bowel movement signs and symptoms at Week 12 
 
 as assessed by UC-PRO/SS score 
 
Improvement in UC bowel movement signs and symptoms at Week 12 
 
 as defined by the proportion of patients with a  6-point decrease in the 
UC-PRO/SS bowel domain score  
 
Change from baseline in UC functional signs and symptoms at Week 12 
 
, as assessed by UC-PRO/SS score 
 
Improvement in UC functional symptoms at Week 12 
, as defined by 
the proportion of patients with a  2-point decrease in the UC-PRO/SS functional 
domain score  
 
Data will be summarized by treatment arms. 
6.5 
SAFETY ANALYSES 
The safety analysis population will consist of all randomized patients who received at 
least one dose of study treatment, with patients grouped according to treatment 
received.  
Safety will be assessed by adverse events, clinical laboratory evaluations, vital signs, 
and ECGs.  

 
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Separate summaries of adverse events will be provided for the screening period, the 
induction period, and optional ATE period.  Adverse events will be summarized by 
treatment arms. 
All verbatim adverse event terms will be mapped to Medical Dictionary for Regulatory 
Activities thesaurus terms, and adverse event severity will be graded according to 
DAIDS toxicity grading scale.  
Relevant laboratory, vital sign (e.g., pulse rate), and ECG data will be displayed by time, 
with grades identified where appropriate.   
6.6 
PHARMACOKINETIC ANALYSES 
The PK analysis population will consist of patients with at least one postdose serum PK 
sample in which vixarelimab concentration is evaluable, unless major protocol deviations 
or unavailability of information (e.g., exact blood sampling time) occurred which may 
interfere with PK evaluation, with patients grouped according to treatment arm. 
Serum vixarelimab concentration data will be tabulated and summarized (mean, 
standard deviation, coefficient of variation, median, minimum, and maximum) at relevant 
timepoints.  Inter-participant variability and drug accumulation will be evaluated.  
Exploratory analyses may be conducted to evaluate potential relationships between drug 
exposure and efficacy/safety endpoints and to evaluate potential relationships between 
selected covariates and exposure to vixarelimab.  Additional exploratory PK analyses 
(e.g., using PK data from this study in a population PK analysis) may be conducted as 
appropriate, and the results may be reported separately from this study report. 
6.7 
IMMUNOGENICITY ANALYSES  
The immunogenicity analysis population will consist of all patients with at least one 
postdose ADA assessment.  Patients will be grouped according to treatment received or, 
if no treatment is received prior to study discontinuation, according to treatment 
assigned. 
The numbers and proportions of ADA-positive patients and ADA-negative patients at 
baseline (baseline prevalence) and after drug administration (postbaseline incidence) 
will be summarized by treatment group.  When determining postbaseline incidence, 
patients are considered to be ADA positive if they are ADA negative or have missing 
data at baseline but develop an ADA response following study drug exposure 
(treatment-induced ADA response), or if they are ADA positive at baseline and the titer 
of one or more postbaseline samples is at least 0.60 titer unit greater than the titer of the 
baseline sample (treatment-enhanced ADA response).  Patients are considered to be 
ADA negative if they are ADA negative or have missing data at baseline and all 
postbaseline samples are negative, or if they are ADA positive at baseline but do not 

 
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have any postbaseline samples with a titer that is at least 0.60 titer unit greater than the 
titer of the baseline sample (treatment unaffected). 
The relationship between ADA status and safety, efficacy, PK, and biomarker endpoints 
may be analyzed and reported via descriptive statistics. 
6.8 
BIOMARKER ANALYSES  
The PD biomarker analyses will include all patients with one pretreatment and at least 
one post-treatment biomarker assessment, with patients grouped according to the 
treatment received.  PD biomarker analyses will include examination of changes from 
baseline (pretreatment) with post-treatment timepoints.  PD biomarkers will be assessed 
as an absolute increase over time, and/or as a percent change relative to original 
baseline for each patient.  In addition, efforts will be made to perform PK/PD analyses 
based on PD and PK exposure data.  Results will be summarized through use of 
summary statistics and or other graphs as required.  Descriptive statistics will be listed 
by dose, treatment arm, and response status.  Additional PD analyses will be conducted 
as appropriate. 
Additional (e.g., predictive, prognostic, pathway) biomarker analyses will include all 
patients with one pretreatment biomarker assessment, with patients grouped according 
to the treatment received, provided there are sufficient data in each biomarker arm to 
facilitate a meaningful analysis.  Baseline values may be used to evaluate predictive 
biomarkers in the context of activity (clinical and/or pharmacological), drug levels, safety, 
and/or immunogenicity endpoints.  Results will be summarized descriptively. 
7. 
DATA COLLECTION AND MANAGEMENT 
7.1 
DATA QUALITY ASSURANCE 
The Sponsor will be responsible for data management of this study, including quality 
checking of the data.  Data entered manually will be collected via EDC through use of 
eCRFs.  Sites will be responsible for data entry into the EDC system.  In the event of 
discrepant data, the Sponsor will request data clarification from the sites, which the sites 
will resolve electronically in the EDC system. 
The Sponsor will produce an EDC Study Specification document that describes the 
quality checking to be performed on the data.  Central laboratory data, endoscopy 
scores, electronic diary data, and some ClinRO and PRO data will be sent directly to the 
Sponsor, using the Sponsor's standard procedures to handle and process the electronic 
transfer of these data. 

 
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eCRFs and correction documentation will be maintained in the EDC system's audit trail.  
System backups for data stored by the Sponsor and records retention for the study data 
will be consistent with the Sponsor's standard procedures. 
PRO and ClinRO data will be collected through the use of an electronic device/portal 
provided by a vendor (see Section 7.3 for details). 
ClinRO data may be collected on paper questionnaires.  The data from the 
questionnaires will be entered into the EDC system by site staff.  
7.2 
ELECTRONIC CASE REPORT FORMS  
eCRFs are to be completed through use of a Sponsor-designated EDC system.  Sites 
will receive training and have access to a manual for appropriate eCRF completion.  
eCRFs will be submitted electronically to the Sponsor and should be handled in 
accordance with instructions from the Sponsor. 
All eCRFs should be completed by designated, trained site staff.  eCRFs should be 
reviewed and electronically signed and dated by the investigator or a designee. 
At the end of the study, the investigator will receive patient data for his or her site in a 
readable format that must be kept with the study records.  Acknowledgement of receipt 
of the data is required. 
7.3 
ELECTRONIC PATIENT- AND CLINICIAN-REPORTED 
OUTCOME DATA 
An electronic device/portal will be used to capture PRO and ClinRO data.  The 
device/portal is designed for entry of data in a way that is attributable, secure, and 
accurate, in compliance with FDA regulations for electronic records (21 CFR Part 11).  
The data will be transmitted to a centralized database maintained by the electronic 
device vendor. 
The electronic data will be available for view access only, via a secure method.  Only 
identified and trained users may view the data, and their actions will become part of the 
audit trail.  The Sponsor will have view access only.  System backups for data stored by 
the Sponsor and records retention for the study data will be consistent with the 
Sponsor's standard procedures. 
Once the study is complete, the data, audit trail, and trial and system documentation will 
be archived.  The investigator will receive patient data for the site in both human- and 
machine-readable formats that must be kept with the study records as source data.  
Acknowledgement of receipt of the data is required.  In addition, the Sponsor will receive 
all data in a machine-readable format. 

 
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7.4 
SOURCE DATA DOCUMENTATION 
Study monitors will perform ongoing source data verification and review to confirm that 
critical protocol data (i.e., source data) entered into the eCRFs by authorized site 
personnel are accurate, complete, and verifiable from source documents.  
Source documents (paper or electronic) are those in which patient data are recorded 
and documented for the first time.  They include, but are not limited to, hospital records, 
clinical and office charts, laboratory notes, memoranda, patient-reported outcomes, 
evaluation checklists, pharmacy dispensing records, recorded data from automated 
instruments, copies of transcriptions that are certified after verification as being accurate 
and complete, microfiche, photographic negatives, microfilm or magnetic media, X-rays, 
patient files, and records kept at pharmacies, laboratories, and medico-technical 
departments involved in a clinical trial. 
Before study initiation, the types of source documents that are to be generated will be 
clearly defined in the Trial Monitoring Plan.  This includes any protocol data to be 
entered directly into the eCRFs (i.e., no prior written or electronic record of the data) and 
considered source data. 
Source documents that are required to verify the validity and completeness of data 
entered into the eCRFs must not be obliterated or destroyed and must be retained per 
the policy for retention of records described in Section 7.6. 
To facilitate source data verification and review, the investigators and institutions must 
provide the Sponsor direct access to applicable source documents and reports for 
trial-related monitoring, Sponsor audits, and IRB/EC review.  The study site must also 
allow inspection by applicable health authorities. 
7.5 
USE OF COMPUTERIZED SYSTEMS 
When clinical observations are entered directly into a study site's computerized medical 
record system (i.e., in lieu of original hardcopy records), the electronic record can serve 
as the source document if the system has been validated in accordance with health 
authority requirements pertaining to computerized systems used in clinical research.  An 
acceptable computerized data collection system allows preservation of the original entry 
of data.  If original data are modified, the system should maintain a viewable audit trail 
that shows the original data as well as the reason for the change, name of the person 
making the change, and date of the change. 
7.6 
RETENTION OF RECORDS 
Records and documents pertaining to the conduct of this study and the distribution of 
IMP, including eCRFs, electronic or paper PRO and ClinRO data (if applicable), 
Informed Consent Forms, laboratory test results, medication inventory records, and 
images, must be retained by the investigator for 15 years after completion or 

 
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discontinuation of the study or for the length of time required by relevant national or local 
health authorities, whichever is longer.  After that period of time, the documents may be 
destroyed, subject to local regulations.   
No records may be disposed of without the written approval of the Sponsor.  Written 
notification should be provided to the Sponsor prior to transferring any records to 
another party or moving them to another location. 
The Sponsor will retain study data for 25 years after the final study results have been 
reported or for the length of time required by relevant national or local health authorities, 
whichever is longer. 
8. 
ETHICAL CONSIDERATIONS 
8.1 
COMPLIANCE WITH LAWS AND REGULATIONS 
This study will be conducted in full conformance with the ICH E6 guideline for Good 
Clinical Practice and the principles of the Declaration of Helsinki, or the applicable laws 
and regulations of the country in which the research is conducted, whichever affords the 
greater protection to the individual.  The study will comply with the requirements of the 
ICH E2A guideline (Clinical Safety Data Management:  Definitions and Standards for 
Expedited Reporting).  Studies conducted in the United States or under a U.S. 
Investigational New Drug (IND) Application will comply with U.S. FDA regulations and 
applicable local, state, and federal laws.  Studies conducted in the European Union or 
European Economic Area will comply with the E.U. Clinical Trials Directive (2001/20/EC) 
or Clinical Trials Regulation (536/2014) and applicable local, regional, and national laws. 
8.2 
INFORMED CONSENT 
The Sponsor's sample Informed Consent Form (and ancillary sample Informed Consent 
Forms such as an Assent Form or Mobile Nursing Informed Consent Form, if applicable) 
will be provided to each site.  If applicable, it will be provided in a certified translation of 
the local language.  The Sponsor or its designee must review and approve any proposed 
deviations from the Sponsor's sample Informed Consent Forms or any alternate consent 
forms proposed by the site (collectively, the "Consent Forms") before IRB/EC 
submission.  The final IRB/EC-approved Consent Forms must be provided to the 
Sponsor for health authority submission purposes according to local requirements. 
If applicable, the Informed Consent Form will contain separate sections for any optional 
procedures.  The investigator or authorized designee will explain to each patient the 
objectives, methods, and potential risks associated with each optional procedure.  
Patients will be told that they are free to refuse to participate and may withdraw their 
consent at any time for any reason.  A separate, specific signature will be required to 
document a patient's agreement to participate in optional procedures.  Patients who 
decline to participate will not provide a separate signature. 

 
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The Consent Forms must be signed and dated by the patient or the patient's legally 
authorized representative before his or her participation in the study.  The case history or 
clinical records for each patient shall document the informed consent process and that 
written informed consent was obtained prior to participation in the study. 
The Consent Forms should be revised whenever there are changes to study procedures 
or when new information becomes available that may affect the willingness of the patient 
to participate.  The final revised IRB/EC-approved Consent Forms must be provided to 
the Sponsor for health authority submission purposes. 
If the Consent Forms are revised (through an amendment or an addendum) to 
communicate information that might affect a patient's willingness to continue in the 
study, the patient or a legally authorized representative must re-consent by signing the 
most current version of the Consent Forms or the addendum, in accordance with 
applicable laws and IRB/EC policy.  For any updated or revised Consent Forms, the 
case history or clinical records for each patient shall document the informed consent 
process and that written informed consent was obtained using the updated/revised 
Consent Forms for continued participation in the study. 
A copy of each signed Consent Form must be provided to the patient or the patient's 
legally authorized representative.  All signed and dated Consent Forms must remain in 
each patient's study file or in the site file and must be available for verification by study 
monitors at any time. 
For sites in the United States, each Consent Form may also include patient authorization 
to allow use and disclosure of personal health information in compliance with the U.S. 
Health Insurance Portability and Accountability Act (HIPAA) of 1996.  If the site utilizes a 
separate Authorization Form for patient authorization for use and disclosure of personal 
health information under the HIPAA regulations, the review, approval, and other 
processes outlined above apply except that IRB review and approval may not be 
required per study site policies. 
8.3 
INSTITUTIONAL REVIEW BOARD OR ETHICS COMMITTEE 
This protocol, the Informed Consent Forms, any information to be given to the patient, 
and relevant supporting information must be submitted to the IRB/EC by the investigator 
and reviewed and approved by the IRB/EC before the study is initiated.  In addition, any 
patient recruitment materials must be approved by the IRB/EC.  
The investigator is responsible for providing written summaries of the status of the study 
to the IRB/EC annually or more frequently in accordance with the requirements, policies, 
and procedures established by the IRB/EC.  Investigators are also responsible for 
promptly informing the IRB/EC of any protocol amendments (see Section 9.6). 

 
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In addition to the requirements for reporting all adverse events to the Sponsor, 
investigators must comply with requirements for reporting serious adverse events to the 
local health authority and IRB/EC.  Investigators may receive written IND safety reports 
or other safety-related communications from the Sponsor.  Investigators are responsible 
for ensuring that such reports are reviewed and processed in accordance with health 
authority requirements and the policies and procedures established by their IRB/EC, and 
archived in the site's study file.  
8.4 
CONFIDENTIALITY 
Information technology systems used to collect, process, and store study-related data 
are secured by technical and organizational security measures designed to protect such 
data against accidental or unlawful loss, alteration, or unauthorized disclosure or access.  
In the event of a data security breach, appropriate mitigation measures will be 
implemented. 
The Sponsor maintains confidentiality standards by coding each patient enrolled in the 
study through assignment of a unique patient identification number.  This means that 
patient names are not included in data sets that are transmitted to any Sponsor location. 
Patient medical information obtained by this study is confidential and may be disclosed 
to third parties only as permitted by the Informed Consent Form (or separate 
authorization for use and disclosure of personal health information) signed by the 
patient, unless permitted or required by law. 
Medical information may be given to a patient's personal physician or other appropriate 
medical personnel responsible for the patient's welfare, for treatment purposes. 
Given the complexity and exploratory nature of exploratory biomarker analyses, data 
derived from these analyses will generally not be provided to study investigators or 
patients unless required by law.  The aggregate results of any conducted research will 
be available in accordance with the effective Sponsor policy on study data publication 
(see Section 9.6). 
Data generated by this study must be available for inspection upon request by 
representatives of national and local health authorities, Sponsor monitors, 
representatives, and collaborators, and the IRB/EC for each study site, as appropriate. 
Study data, which may include imaging data and data on genomic variants, may be 
submitted to government or other health research databases or shared with researchers, 
government agencies, companies, or other groups that are not participating in this study.  
These data may be combined with or linked to other data and used for research 
purposes, to advance science and public health, or for analysis, development, and 
commercialization of products to treat and diagnose disease.  In addition, data may be 
disseminated as described in Section 9.6. 

 
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8.5 
FINANCIAL DISCLOSURE 
Investigators will provide the Sponsor with sufficient, accurate financial information in 
accordance with local regulations to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate health authorities.  
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study (see definition of end of 
study in Section 3.2). 
9. 
STUDY DOCUMENTATION, MONITORING, AND 
ADMINISTRATION 
9.1 
STUDY DOCUMENTATION 
The investigator must maintain adequate and accurate records to enable the conduct of 
the study to be fully documented, including, but not limited to, the protocol, protocol 
amendments, Informed Consent Forms, and documentation of IRB/EC and 
governmental approval.  In addition, at the end of the study, the investigator will receive 
the patient data, including an audit trail containing a complete record of all changes to 
data. 
9.2 
PROTOCOL DEVIATIONS 
The investigator should document and explain any protocol deviations.  The investigator 
should promptly report any deviations that might have an impact on patient safety and 
data integrity to the Sponsor and to the IRB/EC in accordance with established IRB/EC 
policies and procedures.  The Sponsor will review all protocol deviations and assess 
whether any represent a serious breach of Good Clinical Practice guidelines and require 
reporting to health authorities.  As per the Sponsor's standard operating procedures, 
prospective requests to deviate from the protocol, including requests to waive protocol 
eligibility criteria, are not allowed. 
9.3 
MANAGEMENT OF STUDY QUALITY 
The Sponsor will implement a risk-based quality management approach to ensure the 
quality of the study, focusing on processes and data that are critical to ensuring patient 
safety and data integrity.  Prior to study initiation, the Sponsor will identify and evaluate 
potential risks associated with critical study processes and data, and will implement 
appropriate mitigation plans for evaluating and controlling these risks.  Details regarding 
the applied approach for the study will be provided in an Integrated Quality Risk 
Strategy. 
Risk control will include the selection of risk-based parameters and an evaluation for 
quality tolerance limits (QTLs).  For studies applying QTLs, details on the management 
and review of QTLs will be provided in a separate Quality Tolerance Limit Plan. 

 
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9.4 
SITE INSPECTIONS 
Site visits will be conducted by the Sponsor or an authorized representative for 
inspection of study data, patients' medical records, and eCRFs.  The investigator will 
permit national and local health authorities; Sponsor monitors, representatives, and 
collaborators; and the IRBs/ECs to inspect facilities and records relevant to this study. 
9.5 
ADMINISTRATIVE STRUCTURE 
This trial will be sponsored and managed by Genentech, Inc.  The Sponsor will provide 
clinical operations management, data management, and medical monitoring. 
Approximately
will participate to enroll approximately 210 patients.  
Enrollment will occur through an IxRS.   
Central facilities will be used for certain study assessments throughout the study 
(e.g., specified laboratory tests, biomarker and PK analyses), as specified in Section 4.5.  
Accredited local laboratories will be used for routine monitoring; local laboratory ranges 
will be collected. 
9.6 
DISSEMINATION OF DATA AND PROTECTION OF TRADE 
SECRETS 
Regardless of the outcome of a trial, the Sponsor is dedicated to openly providing 
information on the trial to health care professionals and to the public, at scientific 
congresses, in clinical trial registries, and in peer-reviewed journals.  The Sponsor will 
comply with all requirements for publication of study results.  Study data may be shared 
with others who are not participating in this study (see Section 8.4 for details), and 
redacted Clinical Study Reports and/or other summaries of clinical study results may be 
available in health authority databases for public access, as required by local regulation, 
and will be made available upon request.  For more information, refer to the Roche 
Global Policy on Sharing of Clinical Study Information at the following website: 
https://www.roche.com/innovation/process/clinical-trials/data-sharing/ 
The results of this study may be published or presented at scientific congresses.  For all 
clinical trials in patients involving an IMP for which a marketing authorization application 
has been filed or approved in any country, the Sponsor aims to submit a journal 
manuscript reporting primary clinical trial results within 6 months after the availability of 
the respective Clinical Study Report.  In addition, for all clinical trials in patients involving 
an IMP for which a marketing authorization application has been filed or approved in any 
country, the Sponsor aims to publish results from analyses of additional endpoints and 
exploratory data that are clinically meaningful and statistically sound. 
The investigator must agree to submit all manuscripts or abstracts to the Sponsor prior 
to submission for publication or presentation.  This allows the Sponsor to protect 

 
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proprietary information and to provide comments based on information from other 
studies that may not yet be available to the investigator. 
In accordance with standard editorial and ethical practice, the Sponsor will generally 
support publication of multicenter trials only in their entirety and not as individual center 
data.  In this case, a coordinating investigator will be designated by mutual agreement. 
Authorship will be determined by mutual agreement and in line with International 
Committee of Medical Journal Editors authorship requirements.  Any formal publication 
of the study in which contribution of Sponsor personnel exceeded that of conventional 
monitoring will be considered as a joint publication by the investigator and the 
appropriate Sponsor personnel. 
Any inventions and resulting patents, improvements, and/or know-how originating from 
the use of data from this study will become and remain the exclusive and unburdened 
property of the Sponsor, except where agreed otherwise. 
9.7 
PROTOCOL AMENDMENTS 
Any protocol amendments will be prepared by the Sponsor.  Protocol amendments will 
be submitted to the IRB/EC and to regulatory authorities in accordance with local 
regulatory requirements. 
Approval must be obtained from the IRB/EC and regulatory authorities (as locally 
required) before implementation of any changes, except for changes necessary to 
eliminate an immediate hazard to patients or changes that involve logistical or 
administrative aspects only (e.g., change in Medical Monitor or contact information). 

 
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10. 
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definition and management of anaphylaxis: summary report: Second National 
Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
Symposium. J Allergy Clin Immunol 2006;117:3917. 
Sedano R, Hogan M, Nguyen TM, et al. Systematic review and meta-analysis: clinical, 
endoscopic, histological and safety placebo rates in induction and maintenance 
trials of ulcerative colitis. J Crohns Colitis 2022;16:22443. 
Smillie CS, Biton M, Ordovas-Montanes J, et al. Intra- and inter-cellular rewiring of the 
human colon during ulcerative colitis. Cell 2019;178:714730.e22. 
Stawski L, Trojanowska M. Oncostatin M and its role in fibrosis. Connect Tissue Res 
2019;60:409. 

 
Vixarelimab—Genentech, Inc. 
97/Protocol GA44839, Version 2 
Toghi Eshghi S, Gubatan JM, Mazrooei P, et al. Molecular characterization of response 
to etrolizumab and anti-TNF reveals treatment resistance in ulcerative colitis is 
associated with the abundance of residual neutrophil subsets and inflammatory 
fibroblast populations. bioRxiv 2024.07.02.601267. 
Ungaro R, Mehandru S, Allen PB, et al. Ulcerative colitis. Lancet 2017;389:175670. 
Verstockt S, Verstockt B, Machiels K, et al. Oncostatin M is a biomarker of diagnosis, 
worse disease prognosis, and therapeutic nonresponse in inflammatory bowel 
disease. Inflamm Bowel Dis 2021;27:156475. 
West NR, Hegazy AN, Owens BMJ, et al. Oncostatin M drives intestinal inflammation 
and predicts response to tumor necrosis factor-neutralizing therapy in patients with 
inflammatory bowel disease. Nat Med 2017;23:57989. 
West NR, Owens BMJ, Hegazy AN. The oncostatin M-stromal cell axis in health and 
disease. Scand J Immunol 2018;88:e12694. 
Yaseen B, Lopez H, Taki Z, et al. Interleukin-31 promotes pathogenic mechanisms 
underlying skin and lung fibrosis in scleroderma. Rheumatology (Oxford) 
2020;59:262536. 
 

 
Vixarelimab—Genentech, Inc. 
98/Protocol GA44839, Version 2 
Appendix 1  
Schedule of Activities:  Induction 

Appendix 1: Schedule of Activities for Induction 
  
Vixarelimab—Genentech, Inc. 
99/Protocol GA44839, Version 2 
ADA  anti-drug antibody; ATE  active treatment extension; CMV  cytomegalovirus; CRP  C-reactive protein; FeCal  fecal calprotectin; 
IxRS  interactive voice or web-based response system; PK  pharmacokinetic; PRO  patient-reported outcome;
 
 TB  tuberculosis; TD  treatment discontinuation; UC-PRO/SS  Ulcerative Colitis Patient-Reported Outcomes Signs and 
Symptoms; UV  unscheduled visit; WES  whole exome sequencing; WGS  whole genome sequencing. 
Notes:  On treatment days, all assessments should be performed prior to study treatment administration, unless otherwise specified. 
Assessments shaded in gray are not applicable for sites in China. 

Appendix 1: Schedule of Activities for Induction 
  
Vixarelimab—Genentech, Inc. 
101/Protocol GA44839, Version 2 
p All women of childbearing potential will have a serum pregnancy test performed at screening.  Urine pregnancy tests will be performed at 
specified subsequent visits during treatment, at the treatment discontinuation visit, and at 
 after the final dose of study 
treatment.  Urine pregnancy tests will be reviewed prior to each study drug administration for confirmation of a negative result.  If a urine 
pregnancy test is positive, it must be confirmed by a serum pregnancy test. 
q All patients will undergo either a colonoscopy or a flexible sigmoidoscopy at specified timepoints.  Patients without documentation of a 
colonoscopy within 2 years prior to screening must undergo a colonoscopy in lieu of a flexible sigmoidoscopy at screening.  The screening 
endoscopy will be used as efficacy baseline and for inclusion.  Video recordings should be taken of the entire endoscopic procedure 
(colonoscopy or flexible sigmoidoscopy), starting from insertion into the bowel.  Biopsies should be performed upon withdrawal of the endoscope 
from the bowel.  Technical instructions for video recording and biopsy collection will be provided in the endoscopy and/or laboratory manual. 
r Tissue collected at screening will be analyzed for CMV, if required (see Section 4.1.2), as determined by histologic examination or 
immunohistochemistry per local standards, and will undergo histopathologic examination for patients without a prior histopathology report.  
Tissue collected at screening and subsequent timepoints will also be used for histologic assessments and exploratory biomarker research at 
participating sites, excluding China (see Appendix 9).  For endoscopy assessments after screening for sites located in China, endoscopy will 
be performed but no biopsy will be collected. 
s See Appendix 3.  The Mayo Score will be calculated by the Sponsor. 
t Clinician-reported outcome instruments will be completed after the physical examination, prior to the administration of study treatment. 
u An electronic diary will be used to collect PRO data, including stool frequency/rectal bleeding and the UC-PRO/SS instrument (see 
Section 4.5.7.2).  Stool frequency and rectal bleeding will be recorded daily; UC-PRO/SS will be collected daily during screening and daily over 
at least a 7-day period before each specified study visit. 
v On treatment days, all samples should be collected prior to dosing.    
w Additional ADA samples should be collected in patients with signs and symptoms of injection-related reactions. 
x Not applicable for a site that has not been granted approval for WGS/WES.  If a sample is not collected at the randomization visit (Day 1), it may 
be collected at any subsequent visit. 
 
 
 
 

 
Vixarelimab—Genentech, Inc. 
102/Protocol GA44839, Version 2 
Appendix 2  
Schedule of Activities:  Optional Active Treatment Extension 

Appendix 2: Schedule of Activities for Optional Active Treatment Extension 
  
Vixarelimab—Genentech, Inc. 
103/Protocol GA44839, Version 2 
ADA  anti-drug antibody; ATE  active treatment extension; CRP  C-reactive protein; FeCal  fecal calprotectin; NA  not applicable; 
PK  pharmacokinetic; PRO  patient-reported outcome;
 SC  study completion; TD  treatment 
discontinuation; UC-PRO/SS  Ulcerative Colitis Patient-Reported Outcomes Signs and Symptoms; UV  unscheduled visit. 
Notes:  On treatment days, all assessments should be performed prior to study treatment administration, unless otherwise specified. 
Patients must complete induction treatment and assessments through 
 to continue into active treatment extension. 
Assessments shaded in gray are not applicable for sites in China. 
a Patients who complete the active treatment extension period will return to the clinic for a study completion visit at 
 
b Patients who discontinue study treatment prematurely will return to the clinic for a treatment discontinuation visit within 14 days after their final 
dose of study treatment and will then enter the safety follow-up period.  
c Patients who complete the active treatment extension period and patients who discontinue study treatment prior to 
 will undergo 
follow-up assessments at 
 after their final dose of study treatment. 
d Unscheduled visits may be performed if clinically indicated (e.g., for evaluation of an adverse event).  The specified assessments are required at 
each unscheduled visit, unless otherwise specified.  Assessments listed in parentheses are not required, but may be performed for patients who 
receive rescue therapy or experience persistent or worsening disease for which rescue therapy is indicated, as determined by the investigator.  
Additional assessments may be performed if clinically indicated, as determined by the investigator. 
e Samples will be analyzed for culture and sensitivity, ova and parasites, and C. difficile. 
f Stool samples should be obtained prior to bowel preparation for endoscopy (colonoscopy or sigmoidoscopy), if applicable. 

 
Vixarelimab—Genentech, Inc. 
105/Protocol GA44839, Version 2 
Appendix 3  
Mayo Score 
The Mayo Score is a composite endpoint consisting of patient-reported outcomes (stool 
frequency, rectal bleeding), endoscopy, and clinician-reported outcome (Physician's 
Global Assessment) components.  Each component is scored on a scale from 0 to 3, 
and totaled for a maximum score of 12. 
The modified Mayo Score (mMS) is a composite of stool frequency, rectal bleeding, and 
centrally read endoscopy.  Maximum total score of 9. 
1. Stool frequency a 
0 = Normal number of stools for this patient 
1 = 12 more stools than normal 
2 = 34 more stools than normal 
3 = 5 or more stools than normal 
 
2. Rectal bleeding b 
0 = No blood seen or no bowel movement 
1 = Stool with streaks of blood 
2 = Stool with more than streaks of blood 
3 = Blood alone passed 
 
3. Endoscopy 
0 = Normal appearance of mucosa 
1 = Mild disease (erythema, decreased vascular pattern), no friability 
2 = Moderate disease (marked erythema, absent vascular pattern, friability, 
erosions) 
3 = Severe disease (spontaneous bleeding, ulceration) 
 
4. Physician's Global Assessment 
0 = Normal 
1 = Mild 
2 = Moderate 
3 = Severe 
 
a Each patient provides own baseline against which to compare the degree of abnormality in 
stool frequency. 
b Represents the worst bleeding score for that day.

 
Vixarelimab—Genentech, Inc. 
108/Protocol GA44839, Version 2 
Appendix 5  
Anaphylaxis Precautions 
These guidelines are intended as a reference and should not supersede pertinent local 
or institutional standard operating procedures. 
REQUIRED EQUIPMENT AND MEDICATION 
The following equipment and medication are needed in the event of a suspected 
anaphylactic reaction during study treatment administration in a clinical setting: 
 
Monitoring devices:  ECG monitor, blood pressure monitor, oxygen saturation 
monitor, and thermometer 
 
Oxygen 
 
Epinephrine for intramuscular (preferred route), SC, IV, or endotracheal 
administration in accordance with institutional guidelines 
 
Antihistamines 
 
Corticosteroids 
 
IV infusion solutions, tubing, catheters, and tape 
 
PROCEDURES 
In the event of a suspected anaphylactic reaction during study treatment administration, 
the following procedures should be performed: 
 
Stop the study treatment administration, if possible.  
 
Call for additional medical assistance. 
 
Maintain an adequate airway. 
 
Ensure that appropriate monitoring is in place, with continuous ECG and pulse 
oximetry monitoring if possible. 
 
Administer antihistamines, epinephrine, or other medications and IV fluids as 
required by patient status and as directed by the physician in charge. 
 
Continue to observe the patient and document observations. 
 
Collect serum samples for immunogenicity testing. 
 
Ask the patient to return for immunogenicity sample collection at the time of 
washout, if appropriate. 

 
Vixarelimab—Genentech, Inc. 
109/Protocol GA44839, Version 2 
Appendix 6  
Investigational and Non-Investigational Medicinal Product 
Designations (for Use in European Economic Area and United 
Kingdom) 
Table 1 
Investigational, Authorized Auxiliary, and Unauthorized Auxiliary 
Medicinal Product Designations for European Economic Area  
Product Name 
IMP/AxMP  
Designation 
Marketing 
Authorization Status 
in EEA 
Used within 
Marketing 
Authorization 
Vixarelimab (RO7622888) 
IMP (test product) 
Not approved 
Not applicable 
Vixarelimab placebo 
IMP (placebo) 
Not approved 
Not applicable 
Topical 5-ASA 
AxMP (rescue 
therapy) 
Approved 
Yes 
Oral 5-ASA 
AxMP (other a) 
Approved 
Yes 
IV corticosteroids and rectal 
corticosteroids (i.e., enemas 
or suppositories) 
AxMP (rescue 
therapy) 
Approved 
Yes 
Oral corticosteroids 
AxMP (other a) 
Approved 
Yes 
AZA 
AxMP (other a) 
Approved 
Yes 
6-MP 
AxMP (other a) 
Approved 
Yes 
MTX 
AxMP (other a) 
Approved 
Yes 
5-ASA  5-aminosalicylic acid; 6-MP  6-mercaptopurine; AxMP  auxiliary medicinal product; 
AZA  azathioprine; EEA  European Economic Area; IMP  investigational medicinal product; 
MTX  methotrexate. 
a Used as a background or rescue therapy; will differ patient to patient. 
 
 
 

Appendix 6: Investigational Medicinal Product and Non-Investigational Medicinal Product 
Designations (for Use in European Economic Area and United Kingdom) 
  
Vixarelimab—Genentech, Inc. 
110/Protocol GA44839, Version 2 
Table 2 
Investigational and Non-Investigational Medicinal Product 
Designations for United Kingdom 
Product Name 
IMP/NIMP  
Designation 
Marketing 
Authorization Status 
in U.K. 
Used within 
Marketing 
Authorization 
Vixarelimab (RO7622888) 
IMP (test product) 
Not Approved 
Not applicable 
Vixarelimab placebo 
IMP (placebo) 
Not Approved 
Not applicable 
Topical 5-ASA 
NIMP (rescue 
therapy) 
Approved 
Yes 
Oral 5-ASA 
NIMP (other a) 
Approved 
Yes 
IV corticosteroids and 
rectal corticosteroids (i.e. 
enemas or suppositories) 
NIMP (rescue 
therapy) 
Approved 
Yes 
Oral corticosteroids 
NIMP (other a) 
Approved 
Yes 
AZA 
NIMP (other a) 
Approved 
Yes 
6-MP 
NIMP (other a) 
Approved 
Yes 
MTX 
NIMP (other a) 
Approved 
Yes 
5-ASA  5-aminosalicylic acid; 6-MP  6-mercaptopurine; AZA  azathioprine; EEA  European 
Economic Area; IMP  investigational medicinal product; MTX  methotrexate; 
NIMP  non-investigational medicinal product. 
a Used as a background or rescue therapy; will differ patient to patient. 
 
 

 
Vixarelimab—Genentech, Inc. 
111/Protocol GA44839, Version 2 
Appendix 7  
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
The investigator will use the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
(HHS 2017), with slight modifications for clarity and for alignment with internal practices, for assessing the severity of each adverse 
event reported during the study. 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Cardiovascular 
Arrhythmia (by ECG or 
physical examination) 
(Specify type if applicable) 
No symptoms and 
no intervention indicated 
No symptoms and 
non-urgent intervention 
indicated 
Nonlife-threatening 
symptoms and non-urgent 
intervention indicated 
Life-threatening arrhythmia or 
urgent intervention indicated 
Hypertension (with the 
lowest reading taken after 
repeat testing during a visit): 
 18 years of age  
140 to  160 mmHg systolic 
or  
90 to  100 mmHg diastolic a 
 160 to  180 mmHg 
systolic or  
 100 to  110 mmHg 
diastolic a 
 180 mmHg systolic or 
 110 mmHg diastolic a 
Life-threatening consequences in 
a participant not previously 
diagnosed with hypertension 
(e.g., malignant hypertension) or 
hospitalization indicated 
Hypertension (with the 
lowest reading taken after 
repeat testing during a visit): 
 18 years of age b 
 120 mmHg systolic or  
 80 mmHg diastolic, but 
systolic and diastolic  
 95th percentile adjusted 
for age, height, and sex 
 95th to  5 mmHg above 
the 99th percentile 
adjusted for age, height, 
and sex (systolic and/or 
diastolic) a 
 5 mmHg above the 
99th percentile adjusted 
for age, height, and sex 
(systolic and/or diastolic) a 
Life-threatening consequences in 
a participant not previously 
diagnosed with hypertension 
(e.g., malignant hypertension) or 
hospitalization indicated 
Hypotension 
No symptoms 
Symptoms corrected with 
oral fluid replacement 
Symptoms and IV fluids 
indicated 
Shock requiring use of 
vasopressors or mechanical 
assistance to maintain blood 
pressure 
a When systolic and diastolic blood pressures meet criteria for different grades, the higher grade should be used. 
b Blood pressure norms for children  18 years of age can be found in: Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk 
Reduction in Children and Adolescents; National Heart, Lung, and Blood Institute. Expert panel on integrated guidelines for cardiovascular health 
and risk reduction in children and adolescents: summary report. Pediatrics 2011;128(Suppl 5):S21356.   
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
112/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Cardiovascular (cont.) 
Cardiac ischemia or 
infarction 
(Report the most 
appropriate term) 
 
 
New symptoms with 
ischemia (stable angina) 
or new testing consistent 
with ischemia 
Unstable angina or acute 
myocardial infarction 
Heart failure 
No symptoms and laboratory 
or cardiac imaging 
abnormalities 
Symptoms with mild to 
moderate activity or 
exertion 
Symptoms at rest or with 
minimal activity or exertion 
(e.g., hypoxemia) or 
intervention indicated 
(e.g., oxygen) 
Life-threatening consequences 
or urgent intervention indicated 
(e.g., vasoactive medications, 
ventricular assist device, 
heart transplant) 
Hemorrhage (with 
significant acute blood loss) 
 
Symptoms and no 
transfusion indicated 
Symptoms and transfusion 
of  2 units packed RBCs 
(for children, packed RBCs 
 10 cc/kg) indicated 
Life-threatening hypotension or 
transfusion of  2 units packed 
RBCs (for children, packed RBCs 
 10 cc/kg) indicated 
Prolonged PR interval or 
AV block:   16 years of age 
(Report the most 
appropriate term) 
PR interval 0.21 to 
 0.25 seconds 
PR interval 
 0.25 seconds or Type I 
second-degree AV block 
Type II second-degree AV 
block or ventricular pause 
 3.0 seconds 
Complete AV block 
Prolonged PR interval or 
AV block:   16 years of age 
(Report the most 
appropriate term) 
First-degree AV block 
(PR interval  normal for 
age and rate) 
Type I second-degree AV 
block 
Type II second-degree AV 
block or ventricular pause 
 3.0 seconds 
Complete AV block 
Prolonged QTc interval 
(corrected per Bazett's 
formula) 
0.45 to 0.47 seconds 
 0.47 to 0.50 seconds 
 0.50 seconds or 
 0.06 seconds above 
baseline 
Life-threatening consequences 
(e.g., torsade de pointes, other 
associated serious ventricular 
dysrhythmia) 
AV  atrioventricular. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
113/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Cardiovascular (cont.) 
Thrombosis or embolism 
(Report the most 
appropriate term) 
 
Symptoms and no 
intervention indicated 
Symptoms and 
intervention indicated 
Life-threatening embolic event 
(e.g., pulmonary embolism, 
thrombus) 
Dermatologic 
Alopecia (scalp only) 
Detectable by study 
participant, caregiver, or 
physician and causing 
no or minimal interference 
with usual social and 
functional activities 
Obvious on visual 
inspection and causing 
greater than minimal 
interference with usual 
social and functional 
activities 
 
 
Bruising 
Localized to one area 
Localized to more than 
one area 
Generalized 
 
Cellulitis 
 
Non-parenteral treatment 
indicated (e.g., oral 
antibiotics, antifungals, 
antivirals) 
IV treatment indicated 
(e.g., IV antibiotics, 
antifungals, antivirals) 
Life-threatening consequences 
(e.g., sepsis, tissue necrosis) 
Hyperpigmentation 
Slight or localized causing 
no or minimal interference 
with usual social and 
functional activities 
Marked or generalized 
causing greater than 
minimal interference 
with usual social and 
functional activities 
 
 
Hypopigmentation 
Slight or localized causing 
no or minimal interference 
with usual social and 
functional activities 
Marked or generalized 
causing greater than 
minimal interference 
with usual social and 
functional activities 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
114/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Dermatologic (cont.) 
Petechiae 
Localized to one area 
Localized to more than 
one area 
Generalized 
 
Pruritus c 
(without skin lesions) 
Itching causing no or 
minimal interference with 
usual social and 
functional activities 
Itching causing greater 
than minimal interference 
with usual social and 
functional activities 
Itching causing inability to 
perform usual social and 
functional activities 
 
Rash 
(Specify type, if applicable) 
Localized rash 
Diffuse rash or target 
lesions 
Diffuse rash and vesicles 
or limited number of bullae 
or superficial ulcerations 
of mucous membrane 
limited to one site 
Extensive or generalized bullous 
lesions or ulceration of mucous 
membrane involving two or more 
distinct mucosal sites or 
Stevens-Johnson syndrome or 
toxic epidermal necrolysis 
Endocrine and Metabolic 
Diabetes mellitus 
Controlled without 
medication 
Controlled with 
medication or 
modification of current 
medication regimen 
Uncontrolled despite 
treatment modification or 
hospitalization for 
immediate glucose 
control indicated 
Life-threatening consequences 
(e.g., ketoacidosis, hyperosmolar 
non-ketotic coma, end organ 
failure) 
Gynecomastia 
Detectable by study 
participant, caregiver, or 
physician and causing no or 
minimal interference with 
usual social and 
functional activities 
Obvious on visual 
inspection and causing 
pain with greater than 
minimal interference with 
usual social and 
functional activities 
Disfiguring changes and 
symptoms requiring 
intervention or causing 
inability to perform usual 
social and functional 
activities 
 
c For pruritus associated with injections or infusions, see "Site Reactions to Injections and Infusions." 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
115/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Endocrine and Metabolic (cont.) 
Hyperthyroidism 
No symptoms and abnormal 
laboratory value 
Symptoms causing 
greater than minimal 
interference with usual 
social and functional 
activities or thyroid 
suppression therapy 
indicated 
Symptoms causing inability 
to perform usual social 
and functional activities 
or uncontrolled despite 
treatment modification 
Life-threatening consequences 
(e.g., thyroid storm) 
Hypothyroidism 
No symptoms and abnormal 
laboratory value 
Symptoms causing 
greater than minimal 
interference with usual 
social and functional 
activities or thyroid 
replacement therapy 
indicated 
Symptoms causing inability 
to perform usual social 
and functional activities 
or uncontrolled despite 
treatment modification 
Life-threatening consequences 
(e.g., myxedema coma) 
Lipoatrophy (disorder 
characterized by fat loss in 
the face, extremities, and 
buttocks) 
Detectable by study 
participant, caregiver, or 
physician and causing 
no or minimal interference 
with usual social and 
functional activities 
Obvious on visual 
inspection and causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Disfiguring changes 
 
Lipohypertrophy (disorder 
characterized by abnormal 
fat accumulation on the 
back of the neck, breasts, 
and abdomen) 
Detectable by study 
participant, caregiver, or 
physician and causing 
no or minimal interference 
with usual social and 
functional activities 
Obvious on visual 
inspection and causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Disfiguring changes 
 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
116/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Gastrointestinal 
Anorexia 
Loss of appetite without 
decreased oral intake 
Loss of appetite 
associated with 
decreased oral intake 
without significant 
weight loss 
Loss of appetite  
associated with 
significant weight loss 
Life-threatening consequences or 
aggressive intervention 
indicated (e.g., tube feeding, 
total parenteral nutrition) 
Ascites 
No symptoms 
Symptoms and 
intervention indicated 
(e.g., diuretics, 
therapeutic paracentesis) 
Symptoms recur or persist 
despite intervention 
Life-threatening consequences 
Bloating or distension 
(Report the most 
appropriate term) 
Symptoms causing 
no or minimal interference 
with usual social and 
functional activities 
Symptoms causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Symptoms causing inability 
to perform usual social and 
functional activities 
 
Cholecystitis 
 
Symptoms and medical 
intervention indicated 
Radiologic, endoscopic, 
or operative intervention 
indicated 
Life-threatening consequences 
(e.g., sepsis, perforation) 
Constipation 
 
Persistent constipation 
requiring regular use of 
dietary modifications, 
laxatives, or enemas 
Obstipation with manual 
evacuation indicated 
Life-threatening consequences 
(e.g., obstruction) 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
117/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Gastrointestinal (cont.) 
Diarrhea:   1 year of age 
Transient or intermittent 
episodes of unformed stools 
or increase of  3 stools 
over baseline per 
24-hour period 
Persistent episodes of 
unformed to watery stools 
or increase of 4 to 
6 stools over baseline 
per 24-hour period 
Increase of  7 stools over 
baseline per 24-hour 
period or IV fluid 
replacement indicated 
Life-threatening consequences 
(e.g., hypotensive shock) 
Diarrhea:   1 year of age 
Liquid stools (more 
unformed than usual) but 
usual number of stools 
Liquid stools with 
increased number of 
stools or mild dehydration 
Liquid stools with 
moderate dehydration 
Life-threatening consequences 
(e.g., liquid stools resulting in 
severe dehydration, 
hypotensive shock) 
Dysphagia or odynophagia 
(Report the most 
appropriate term and 
specify location) 
Symptoms but able to eat 
usual diet 
Symptoms causing 
altered dietary intake with 
no intervention indicated 
Symptoms causing 
severely altered dietary 
intake with intervention 
indicated 
Life-threatening reduction in 
oral intake 
Gastrointestinal bleeding 
Not requiring intervention 
other than iron supplement 
Endoscopic intervention 
indicated 
Transfusion indicated 
Life-threatening consequences 
(e.g., hypotensive shock) 
Mucositis or stomatitis 
(Report the most 
appropriate term and 
specify location) 
Mucosal erythema 
Patchy 
pseudomembranes 
or ulcerations 
Confluent 
pseudomembranes or 
ulcerations or mucosal 
bleeding with minor trauma 
Life-threatening consequences 
(e.g., aspiration, choking) or 
tissue necrosis or diffuse 
spontaneous mucosal bleeding 
Nausea 
Transient ( 24 hours) or 
intermittent nausea and 
no or minimal interference 
with oral intake 
Persistent nausea 
resulting in decreased 
oral intake for 
2448 hours 
Persistent nausea resulting 
in minimal oral intake for 
 48 hours or rehydration 
indicated (e.g., IV fluids) 
Life-threatening consequences 
(e.g., hypotensive shock) 
Pancreatitis 
 
Symptoms with 
hospitalization not 
indicated 
Symptoms with 
hospitalization indicated 
Life-threatening consequences 
(e.g., circulatory failure, 
hemorrhage, sepsis) 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
118/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Gastrointestinal (cont.) 
Perforation 
(colon or rectum) 
 
 
Intervention indicated 
Life-threatening consequences 
Proctitis 
Rectal discomfort with no 
intervention indicated 
Symptoms causing 
greater than minimal 
interference with usual 
social and functional 
activities or medical 
intervention indicated 
Symptoms causing inability 
to perform usual social 
and functional activities 
or operative intervention 
indicated 
Life-threatening consequences 
(e.g., perforation) 
Rectal discharge 
Visible discharge 
Discharge requiring the 
use of pads 
 
 
Vomiting 
Transient or intermittent 
vomiting and no or minimal 
interference with oral intake 
Frequent vomiting 
episodes and no or mild 
dehydration 
Persistent vomiting 
resulting in orthostatic 
hypotension or aggressive 
rehydration indicated 
(e.g., IV fluids) 
Life-threatening consequences 
(e.g., hypotensive shock) 
Musculoskeletal 
Arthralgia 
Joint pain causing no or 
minimal interference with 
usual social and functional 
activities 
Joint pain causing greater 
than minimal interference 
with usual social and 
functional activities 
Joint pain causing inability 
to perform usual social 
and functional activities 
Disabling joint pain causing 
inability to perform basic 
self-care functions 
Arthritis 
Joint stiffness or swelling 
causing no or minimal 
interference with usual 
social and functional 
activities 
Joint stiffness or swelling 
causing greater than 
minimal interference with 
usual social and 
functional activities 
Joint stiffness or swelling 
causing inability to 
perform usual social and 
functional activities 
Disabling joint stiffness or 
swelling causing inability to 
perform basic self-care functions 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
119/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Musculoskeletal (cont.) 
Myalgia (generalized) 
Muscle pain causing no or 
minimal interference with 
usual social and functional 
activities 
Muscle pain causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Muscle pain causing 
inability to perform usual 
social and functional 
activities 
Disabling muscle pain causing 
inability to perform basic self-care 
functions 
Osteonecrosis 
 
No symptoms but with 
radiographic findings 
and no operative 
intervention indicated 
Bone pain with 
radiographic findings 
or operative intervention 
indicated 
Disabling bone pain with 
radiographic findings causing 
inability to perform basic 
self-care functions 
Osteopenia:   
 30 years of age 
BMD t-score 2.5 to 1 
 
 
 
Osteopenia:   
 30 years of age 
BMD z-score 2 to 1 
 
 
 
Osteoporosis:   
 30 years of age 
 
BMD t-score   2.5 
Pathologic fracture 
(e.g., compression 
fracture causing loss 
of vertebral height) 
Pathologic fracture causing 
life-threatening consequences 
Osteoporosis:   
 30 years of age 
 
BMD z-score  2 
Pathologic fracture 
(e.g., compression 
fracture causing loss 
of vertebral height) 
Pathologic fracture causing 
life-threatening consequences 
BMD  bone mineral density. 
 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
120/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Neurologic 
Acute CNS ischemia 
 
 
Transient ischemic attack 
Cerebral vascular accident (e.g., 
stroke with neurological deficit) 
Altered mental status 
(for dementia, see cognitive, 
behavioral, or attentional 
disturbance below) 
Changes causing no or 
minimal interference with 
usual social and functional 
activities 
Mild lethargy or 
somnolence causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Confusion, memory 
impairment, lethargy, or 
somnolence causing 
inability to perform usual 
social and functional 
activities 
Delirium or obtundation or coma 
Ataxia 
Symptoms causing no or 
minimal interference with 
usual social and functional 
activities or no symptoms 
with ataxia detected on 
examination 
Symptoms causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Symptoms causing 
inability to perform usual 
social and functional 
activities 
Disabling symptoms causing 
inability to perform basic 
self-care functions 
Cognitive, behavioral, or 
attentional disturbance 
(includes dementia and 
attention deficit disorder) 
(Specify type, if applicable) 
Disability causing no or 
minimal interference with 
usual social and functional 
activities or specialized 
resources not indicated 
Disability causing greater 
than minimal interference 
with usual social and 
functional activities or 
specialized resources on 
part-time basis indicated 
Disability causing inability 
to perform usual social and 
functional activities or 
specialized resources on 
a full-time basis indicated 
Disability causing inability to 
perform basic self-care functions 
or institutionalization indicated 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
121/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Neurologic (cont.) 
Developmental delay 
 18 years of age  
(Specify type, if applicable) 
Mild developmental delay, 
either motor or cognitive, 
as determined by 
comparison with a 
developmental screening 
tool appropriate for the 
setting 
Moderate developmental 
delay, either motor or 
cognitive, as determined 
by comparison with a 
developmental screening 
tool appropriate for the 
setting 
Severe developmental 
delay, either motor or 
cognitive, as determined 
by comparison with a 
developmental screening 
tool appropriate for the 
setting 
Developmental regression, either 
motor or cognitive, as determined 
by comparison with a 
developmental screening tool 
appropriate for the setting 
Headache 
Symptoms causing no 
or minimal interference 
with usual social and 
functional activities 
Symptoms causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Symptoms causing 
inability to perform usual 
social and functional 
activities 
Symptoms causing inability to 
perform basic self-care functions 
or hospitalization indicated 
or headache with significant 
impairment of alertness or other 
neurologic function 
Neuromuscular weakness 
(includes myopathy and 
neuropathy) 
(Specify type, if applicable) 
Minimal muscle weakness 
causing no or minimal 
interference with usual 
social and functional 
activities or no symptoms 
with decreased strength on 
examination 
Muscle weakness 
causing greater than 
minimal interference with 
usual social and 
functional activities 
Muscle weakness 
causing inability to 
perform usual social and 
functional activities 
Disabling muscle weakness 
causing inability to perform basic 
self-care functions or respiratory 
muscle weakness impairing 
ventilation 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
122/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Neurologic (cont.) 
Neurosensory alteration 
(includes paresthesia and 
painful neuropathy) 
(Specify type, if applicable) 
Minimal paresthesia 
causing no or minimal 
interference with usual 
social and functional 
activities or no symptoms 
with sensory alteration 
on examination 
Sensory alteration or 
paresthesia causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Sensory alteration or 
paresthesia causing 
inability to perform usual 
social and functional 
activities 
Disabling sensory alteration or 
paresthesia causing inability to 
perform basic self-care functions 
Seizure, new onset:  
 18 years of age 
 
 
13 seizures 
Prolonged and repetitive seizures 
(e.g., status epilepticus) or difficult 
to control (e.g., refractory epilepsy) 
Seizure, new onset:  
 18 years of age (includes 
new or preexisting febrile 
seizures) 
Seizure lasting  5 minutes 
with  24 hours postictal 
state 
Seizure lasting 5 to 
 20 minutes with 
 24 hours postictal state 
Seizure lasting 
 20 minutes or  24 hours 
postictal state 
Prolonged and repetitive seizures 
(e.g., status epilepticus) 
or difficult to control 
(e.g., refractory epilepsy) 
Seizure, preexisting 
(excludes preexisting febrile 
seizures) 
 
Increased frequency 
from previous level of 
control without change 
in seizure character 
Change in seizure 
character either in 
duration or quality 
(e.g., severity or focality) 
Prolonged and repetitive seizures 
(e.g., status epilepticus) or 
difficult to control 
(e.g., refractory epilepsy) 
Syncope 
Near syncope without loss 
of consciousness 
(e.g., pre-syncope) 
Loss of consciousness 
with no intervention 
indicated 
Loss of consciousness 
and hospitalization or 
intervention required 
 
Pregnancy, Puerperium, and Perinatal 
Stillbirth 
 
 
Fetal death occurring at 
 20 weeks gestational age 
 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
123/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Pregnancy, Puerperium, and Perinatal (cont.) 
Preterm birth 
Live birth at 
34 to  37 weeks 
gestational age 
Live birth at 
28 to  34 weeks 
gestational age 
Live birth at 
24 to  28 weeks 
gestational age 
Live birth at  24 weeks 
gestational age 
Spontaneous abortion (a 
pregnancy loss occurring at 
 20 weeks gestational age; 
also known as miscarriage) 
Chemical pregnancy 
Uncomplicated 
spontaneous abortion 
Complicated 
spontaneous abortion 
 
Psychiatric 
Insomnia 
Mild difficulty falling asleep 
or staying asleep or 
mild difficulty caused by 
early morning awakening, 
causing no or minimal 
interference with usual 
social and functional 
activities 
Moderate difficulty falling 
asleep or staying asleep, 
or moderate difficulty 
caused by early morning 
awakening, causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Severe difficulty falling 
asleep or staying asleep or 
severe difficulty caused by 
early morning awakening, 
causing inability to perform 
usual social and functional 
activities and requiring 
intervention or 
hospitalization 
 
Psychiatric disorder (includes 
anxiety, depression, mania, 
and psychosis) 
(Specify disorder) 
Symptoms with 
intervention not indicated 
or behavior causing 
no or minimal interference 
with usual social and 
functional activities 
Symptoms with 
intervention indicated or 
behavior causing greater 
than minimal interference 
with usual social and 
functional activities 
Symptoms with 
hospitalization indicated 
or behavior causing 
inability to perform 
usual social and 
functional activities 
Threatens harm to self or others 
or acute psychosis or behavior 
causing inability to perform basic 
self-care functions 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
124/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Psychiatric (cont.) 
Suicidal ideation or suicide 
attempt 
(Report the most appropriate 
term) 
Preoccupied with thoughts 
of death and no wish to 
kill oneself 
Preoccupied with 
thoughts of death and 
wish to kill oneself with 
no specific plan or intent 
Thoughts of killing oneself 
with partial or complete 
plans but no attempt to do 
so or hospitalization 
indicated 
Suicide attempted 
Respiratory 
Acute bronchospasm 
Forced expiratory volume in 
1 second or peak flow 
reduced to  70 to  80% of 
predicted or mild symptoms 
with intervention not 
indicated 
Forced expiratory volume 
in 1 second or peak flow 
50% to  70% of 
predicted or symptoms 
with intervention indicated 
or symptoms causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Forced expiratory 
volume in 1 second or 
peak flow 25% to  50% of 
predicted or symptoms 
causing inability to perform 
usual social and functional 
activities 
Forced expiratory 
volume in 1 second or 
peak flow  25% of predicted or 
life-threatening respiratory or 
hemodynamic compromise or 
intubation 
Dyspnea or respiratory 
distress 
(Report the most appropriate 
term) 
Dyspnea on exertion with 
no or minimal interference 
with usual social and 
functional activities 
or wheezing 
or minimal increase in 
respiratory rate for age 
Dyspnea on exertion 
causing greater than 
minimal interference 
with usual social and 
functional activities or 
nasal flaring or intercostal 
retractions or pulse 
oximetry 90% to  95% 
Dyspnea at rest causing 
inability to perform usual 
social and functional 
activities or pulse 
oximetry  90% 
Respiratory failure with ventilator 
support indicated (e.g., CPAP, 
BPAP, intubation) 
BPAP  bilevel positive airway pressure; CPAP  continuous positive airway pressure. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
125/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Sensory 
Hearing loss (based on a 1, 
2, 3, 4, 6 and 8 kHz 
audiogram):   
 12 years of age 
 
Hearing aid or 
intervention not indicated 
Hearing aid or 
intervention indicated 
Profound bilateral hearing loss 
( 80 dB at 2 kHz and above) or 
non-serviceable hearing 
(i.e.,  50 dB audiogram and 
 50% speech discrimination) 
Hearing loss (based on a 1, 
2, 3, 4, 6 and 8 kHz 
audiogram):   
 12 years of age 
 20 dB hearing loss at 
 4 kHz 
 20 dB hearing loss at 
 4 kHz 
 20 dB hearing loss at 
 3 kHz in one ear with 
additional speech 
language related services 
indicated (where available) 
or hearing loss sufficient 
to indicate therapeutic 
intervention, including 
hearing aids 
Audiologic indication for 
cochlear implant and additional 
speech-languagerelated 
services indicated 
(where available) 
Tinnitus 
Symptoms causing no or 
minimal interference with 
usual social and functional 
activities and intervention 
not indicated 
Symptoms causing 
greater than minimal 
interference with usual 
social and functional 
activities or intervention 
indicated 
Symptoms causing inability 
to perform usual social and 
functional activities 
 
Uveitis 
No symptoms and 
detectable uveitis on 
examination 
Anterior uveitis with 
symptoms or medical 
intervention indicated 
Posterior uveitis or 
panuveitis or operative 
intervention indicated 
Uveitis with disabling visual loss 
in affected eye(s) 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
126/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Sensory (cont.) 
Vertigo 
Vertigo causing no 
or minimal interference 
with usual social and 
functional activities 
Vertigo causing greater 
than minimal interference 
with usual social and 
functional activities 
Vertigo causing inability 
to perform usual social 
and functional activities 
Disabling vertigo causing 
inability to perform basic  
self-care functions 
Visual changes (assessed 
from baseline) 
Visual changes causing no 
or minimal interference 
with usual social and 
functional activities 
Visual changes causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Visual changes causing 
inability to perform usual 
social and functional 
activities 
Visual changes with disabling 
visual loss in affected eye(s) 
Systemic 
Acute allergic reaction 
Localized urticaria (wheals) 
with no intervention 
indicated 
Localized urticaria with 
intervention indicated or 
mild angioedema with no 
intervention indicated 
Generalized urticaria 
or angioedema with 
intervention indicated 
or symptoms of mild 
bronchospasm 
Acute anaphylaxis or 
life-threatening bronchospasm 
or laryngeal edema 
Chills 
Symptoms causing no 
or minimal interference 
with usual social and 
functional activities 
Symptoms causing 
greater than minimal 
interference with usual 
social and functional 
activities 
Symptoms causing inability 
to perform usual social 
and functional activities 
 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
127/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Systemic (cont.) 
Cytokine-release syndrome 
(disorder characterized by 
nausea, headache, 
tachycardia, hypotension, 
rash, and/or shortness of 
breath) 
Mild signs and symptoms 
and therapy (i.e., antibody 
infusion) interruption not 
indicated 
Therapy (i.e., antibody 
infusion) interruption 
indicated and responds 
promptly to symptomatic 
treatment or prophylactic 
medications indicated 
for  24 hours 
Prolonged severe signs 
and symptoms or 
recurrence of symptoms 
following initial 
improvement 
Life-threatening consequences 
(e.g., requiring pressor or 
ventilator support) 
Fatigue or malaise 
(Report the most appropriate 
term) 
Symptoms of fatigue or 
malaise causing no or 
minimal interference 
with usual social and 
functional activities 
Symptoms of fatigue or 
malaise causing greater 
than minimal interference 
with usual social and 
functional activities 
Symptoms of fatigue or 
malaise causing inability 
to perform usual social 
and functional activities 
Incapacitating symptoms of 
fatigue or malaise causing 
inability to perform basic 
self-care functions 
Fever (non-axillary 
temperatures only) 
38.0 to  38.6C or 
100.4 to  101.5°F 
 38.6 to  39.3C or 
 101.5 to  102.7F 
 39.3 to  40.0C or 
 102.7 to  104.0F 
 40.0C or  104.0F 
Pain (not associated with 
study agent injections and 
not specified elsewhere) 
(Specify location) 
Pain causing no or 
minimal interference 
with usual social and 
functional activities 
Pain causing greater than 
minimal interference 
with usual social and 
functional activities 
Pain causing inability to 
perform usual social and 
functional activities 
Disabling pain causing inability to 
perform basic self-care functions 
or hospitalization indicated 
Serum sickness (disorder 
characterized by fever, 
arthralgia, myalgia, skin 
eruptions, lymphadenopathy, 
marked discomfort, and/or 
dyspnea) 
Mild signs and symptoms 
Moderate signs and 
symptoms and 
intervention indicated 
(e.g., antihistamines) 
Severe signs and 
symptoms and higher level 
intervention indicated 
(e.g., corticosteroids 
or IV fluids) 
Life-threatening consequences 
(e.g., requiring pressor or 
ventilator support) 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
128/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Systemic (cont.) 
Underweight:   
 5 to 19 years of age 
WHO BMI z-score d 
 1 to 2 
WHO BMI z-score d 
 2 to 3 
WHO BMI z-score d  3 
WHO BMI z-score d  3 with 
life-threatening consequences 
Underweight:   
2 to 5 years of age 
WHO weight-for-height 
z-score e  1 to 2 
WHO weight-for-height 
z-score e  2 to 3 
WHO weight-for-height 
z-score e  3 
WHO weight-for-height 
z-score e  3 with  
life-threatening consequences 
Underweight:   
 2 years of age 
WHO weight-for-length 
z-score e  1 to 2 
WHO weight-for-length 
z-score e  2 to 3 
WHO weight-for-length 
z-score e  3 
WHO weight-for-length 
z-score e  3 with  
life-threatening consequences 
Unintentional weight loss 
(excludes postpartum weight 
loss) 
 
5% to  9% loss in body 
weight from baseline 
 9% to  20% loss in body 
weight from baseline 
 20% loss in body weight from 
baseline or aggressive intervention 
indicated (e.g., tube feeding, 
total parenteral nutrition) 
Urinary 
Urinary tract obstruction 
 
Signs or symptoms of 
urinary tract obstruction 
without hydronephrosis or 
renal dysfunction 
Signs or symptoms of 
urinary tract obstruction 
with hydronephrosis or 
renal dysfunction 
Obstruction causing 
life-threatening consequences 
BMI  body mass index; WHO  World Health Organization. 
d WHO reference tables for participants  5 to 19 years of age:  http://www.who.int/growthref/who2007_bmi_for_age/en/. 
e WHO reference tables for participants  5 years of age:  http://www.who.int/childgrowth/standards/chart_catalogue/en/. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
129/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Site Reactions to Injections and Infusions f 
Injection-site pain or 
tenderness f 
Pain or tenderness 
causing no or minimal 
limitation of use of limb 
Pain or tenderness 
causing greater than 
minimal limitation of 
use of limb 
Pain or tenderness 
causing inability to 
perform usual social 
and functional activities 
Pain or tenderness causing 
inability to perform basic 
self-care function or 
hospitalization indicated 
Injection-site erythema, 
redness, induration, or 
swelling: f   15 years of age 
(Report the most appropriate 
term; report multiple events 
if appropriate) 
2.5 to  5 cm in diameter 
or 6.25 to  25 cm2 
surface area g and 
symptoms causing no 
or minimal interference 
with usual social and 
functional activities 
 5 to  10 cm in diameter 
or  25 to  100 cm2 
surface area g or 
symptoms causing 
greater than minimal 
interference with usual 
social and functional 
activities 
 10 cm in diameter or 
 100 cm2 surface area g 
or ulceration or secondary 
infection or phlebitis or 
sterile abscess or drainage 
or symptoms causing 
inability to perform usual 
social and functional 
activities 
Potentially life-threatening 
consequences (e.g., abscess, 
exfoliative dermatitis, necrosis 
involving dermis or deeper tissue) 
Injection-site erythema, 
redness, induration, or 
swelling: f   15 years of age 
(Report the most appropriate 
term; report multiple events 
if appropriate) 
 2.5 cm in diameter g 
 2.5 cm in diameter 
with  50% surface 
area g of the extremity 
segment involved 
(e.g., upper arm or thigh) 
 50% surface area g of 
the extremity segment 
involved (e.g., upper arm 
or thigh) or ulceration or 
secondary infection or 
phlebitis or sterile abscess 
or drainage 
Potentially life-threatening 
consequences (e.g., abscess, 
exfoliative dermatitis, necrosis 
involving dermis or deeper tissue) 
f Refer to Section 5.3.5.1 for instructions on reporting injection-site reactions to study treatment (if applicable).  For reactions to drugs other than 
study treatment, report the most appropriate term and report multiple events, if applicable. 
g Grading should be based on the greatest single diameter or measured surface area. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
130/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Site Reactions to Injections and Infusions (cont.) f 
Injection-site pruritus f 
Itching localized to the 
injection site that is 
relieved spontaneously 
or requires treatment 
for  48 hours 
Itching beyond the 
injection site that is not 
generalized or itching 
localized to the injection 
site that requires 
treatment for  48 hours 
Generalized itching 
causing inability to 
perform usual social 
and functional activities 
 
Chemistries 
Acidosis 
 
pH  7.3 to  LLN 
pH  7.3 without 
life-threatening 
consequences 
pH  7.3 with  
life-threatening  
consequences 
Albumin, low 
3.0 g/dL to  LLN 
(30 g/L to  LLN) 
 2.0 to  3.0 g/dL 
( 20 to  30 g/L) 
 2.0 g/dL 
( 20 g/L) 
 
Alkaline phosphatase, high 
1.25 to  2.5  ULN 
2.5 to  5.0  ULN 
5.0 to  10.0  ULN 
 10.0  ULN 
Alkalosis 
 
pH  ULN to  7.5 
pH  7.5 without 
life-threatening 
consequences 
pH  7.5 with  
life-threatening 
consequences 
ALT or SGPT, high 
(Report the most 
appropriate term) 
1.25 to  2.5  ULN 
2.5 to  5.0  ULN 
5.0 to  10.0  ULN 
 10.0  ULN 
Amylase (pancreatic) or 
amylase (total), high 
(Report the most 
appropriate term) 
1.1 to  1.5  ULN 
1.5 to  3.0  ULN 
3.0 to  5.0  ULN 
 5.0  ULN 
LLN  lower limit of normal; ULN  upper limit of normal. 
f Refer to Section 5.3.5.1 for instructions on reporting injection-site reactions to study treatment (if applicable).  For reactions to drugs other than 
study treatment, report the most appropriate term and report multiple events, if applicable. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
131/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Chemistries (cont.) 
AST or SGOT, high 
(Report the most 
appropriate term) 
1.25 to  2.5  ULN 
2.5 to  5.0  ULN 
5.0 to  10.0  ULN 
 10.0  ULN 
Bicarbonate, low 
16.0 mEq/L to  LLN 
(16.0 mmol/L to  LLN) 
11.0 to  16.0 mEq/L 
(11.0 to  16.0 mmol/L) 
8.0 to  11.0 mEq/L 
(8.0 to  11.0 mmol/L) 
 8.0 mEq/L 
( 8.0 mmol/L) 
Bilirubin (direct), high: 
 28 days of age 
 
 
 ULN with other signs 
and symptoms of 
hepatotoxicity 
 ULN with life-threatening 
consequences (e.g., signs and 
symptoms of liver failure) 
Bilirubin (direct), high:  
 28 days of age 
ULN to  1 mg/dL 
 1 to  1.5 mg/dL 
 1.5 to  2 mg/dL h 
 2 mg/dL h 
Bilirubin (total), high:  
 28 days of age 
1.1 to  1.6  ULN 
1.6 to  2.6  ULN 
2.6 to  5.0  ULN 
 5.0  ULN 
Bilirubin (total), high:  
 28 days of age 
See Table 2 
Calcium, high:   
 7 days of age  
10.6 to  11.5 mg/dL 
(2.65 to  2.88 mmol/L) 
11.5 to  12.5 mg/dL 
(2.88 to  3.13 mmol/L) 
12.5 to  13.5 mg/dL 
(3.13 to  3.38 mmol/L) 
 13.5 mg/dL 
( 3.38 mmol/L) 
Calcium, high:   
 7 days of age  
11.5 to  12.4 mg/dL 
(2.88 to  3.10 mmol/L) 
12.4 to  12.9 mg/dL 
(3.10 to  3.23 mmol/L) 
12.9 to  13.5 mg/dL 
(3.23 to  3.38 mmol/L) 
 13.5 mg/dL 
( 3.38 mmol/L) 
Calcium (ionized), high 
 ULN to  6.0 mg/dL 
( ULN to  1.5 mmol/L) 
6.0 to  6.4 mg/dL 
(1.5 to  1.6 mmol/L) 
6.4 to  7.2 mg/dL 
(1.6 to  1.8 mmol/L) 
 7.2 mg/dL 
( 1.8 mmol/L) 
LLN  lower limit of normal; ULN  upper limit of normal. 
h Direct bilirubin  1.5 mg/dL in a participant  28 days of age should be graded as Grade 2, if  10% of the total bilirubin. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
132/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Chemistries (cont.) 
Calcium, low:   
 7 days of age  
7.8 to  8.4 mg/dL 
(1.95 to  2.10 mmol/L) 
7.0 to  7.8 mg/dL 
(1.75 to  1.95 mmol/L) 
6.1 to  7.0 mg/dL 
(1.53 to  1.75 mmol/L) 
 6.1 mg/dL 
( 1.53 mmol/L) 
Calcium, low:   
 7 days of age  
6.5 to  7.5 mg/dL 
(1.63 to  1.88 mmol/L) 
6.0 to  6.5 mg/dL 
(1.50 to  1.63 mmol/L) 
5.50 to  6.0 mg/dL 
(1.38 to  1.50 mmol/L) 
 5.50 mg/dL 
( 1.38 mmol/L) 
Calcium (ionized), low  
 LLN to 4.0 mg/dL 
( LLN to 1.0 mmol/L) 
3.6 to  4.0 mg/dL 
(0.9 to  1.0 mmol/L) 
3.2 to  3.6 mg/dL 
(0.8 to  0.9 mmol/L) 
 3.2 mg/dL 
( 0.8 mmol/L) 
Cardiac troponin I, high  
 
 
 
Levels consistent with myocardial 
infarction or unstable angina as 
defined by the local laboratory  
Creatine kinase, high  
3 to  6  ULN 
6 to  10  ULN 
10 to  20  ULN 
 20  ULN 
Creatinine, high 
1.1 to 1.3  ULN 
 1.3 to 1.8  ULN 
or increase to 
1.3 to  1.5  baseline i 
 1.8 to  3.5  ULN 
or increase to 
1.5 to  2.0  baseline i 
 3.5  ULN or increase to 
 2.0  baseline i 
Creatinine clearance or 
eGFR, low 
(Report the most 
appropriate term) 
 
 90 to 60 mL/min or 
mL/min/1.73 m2 or 
10% to  30% decrease 
from baseline j 
 60 to 30 mL/min or 
mL/min/1.73 m2 or 
30% to  50% decrease 
from baseline j 
 30 mL/min or mL/min/1.73 m2 or 
 50% decrease from baseline j 
or dialysis needed  
eGFR  estimated glomerular filtration rate; LLN  lower limit of normal; ULN  upper limit of normal. 
i For participant with normal baseline value, grade should be based on current value relative to ULN.  For participant with elevated baseline 
value, grade should be based on current value relative to baseline value. 
j For participant with normal baseline value, grade should be based on current value.  For participant with elevated baseline value, grade should 
be based on current value relative to baseline value. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
133/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Chemistries (cont.) 
Glucose (fasting), high 
110 to 125 mg/dL 
(6.11 to  6.95 mmol/L) 
 125 to 250 mg/dL 
(6.95 to  13.89 mmol/L) 
 250 to 500 mg/dL 
(13.89 to  27.75 mmol/L) 
 500 mg/dL 
( 27.75 mmol/L) 
Glucose (non-fasting), high  
116 to 160 mg/dL 
(6.44 to  8.89 mmol/L) 
 160 to 250 mg/dL 
(8.89 to  13.89 mmol/L) 
 250 to 500 mg/dL 
(13.89 to  27.75 mmol/L) 
 500 mg/dL 
( 27.75 mmol/L) 
Glucose, low:   
28 days of age 
55 to 64 mg/dL 
(3.05 to  3.55 mmol/L) 
40 to  55 mg/dL 
(2.22 to  3.05 mmol/L) 
30 to  40 mg/dL 
(1.67 to  2.22 mmol/L) 
 30 mg/dL 
( 1.67 mmol/L) 
Glucose, low:   
 28 days of age 
50 to 54 mg/dL 
(2.78 to  3.00 mmol/L) 
40 to  50 mg/dL 
(2.22 to  2.78 mmol/L) 
30 to  40 mg/dL 
(1.67 to  2.22 mmol/L) 
 30 mg/dL 
( 1.67 mmol/L) 
Lactate, high 
ULN to  2.0  ULN 
without acidosis 
 2.0  ULN 
without acidosis 
Increased lactate with 
pH  7.3 without 
life-threatening 
consequences 
Increased lactate with pH  7.3 
with life-threatening  
consequences 
Lipase, high 
1.1 to  1.5  ULN 
1.5 to  3.0  ULN 
3.0 to  5.0  ULN 
 5.0  ULN 
Lipid disorder:   
cholesterol (fasting), high:  
 18 years of age 
200 to  240 mg/dL 
(5.18 to  6.19 mmol/L) 
240 to  300 mg/dL 
(6.19 to  7.77 mmol/L) 
 300 mg/dL 
( 7.77 mmol/L) 
 
Lipid disorder:   
cholesterol (fasting), high:  
 18 years of age 
170 to  200 mg/dL 
(4.40 to  5.15 mmol/L) 
200 to  300 mg/dL 
(5.15 to  7.77 mmol/L) 
 300 mg/dL 
( 7.77 mmol/L) 
 
Lipid disorder:   
LDL (fasting), high:  
 18 years of age 
130  to  160 mg/dL 
(3.37 to  4.12 mmol/L) 
160 to  190 mg/dL 
(4.12 to  4.90 mmol/L) 
 190 mg/dL 
( 4.90 mmol/L) 
 
ULN  upper limit of normal. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
134/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Chemistries (cont.) 
Lipid disorder:   
LDL (fasting), high:  
 2 to  18 years of age 
110 to  130 mg/dL 
(2.85 to  3.34 mmol/L) 
130 to  190 mg/dL 
(3.34 to  4.90 mmol/L) 
 190 mg/dL 
( 4.90 mmol/L) 
 
Lipid disorder:   
triglycerides (fasting), high 
150 to 300 mg/dL 
(1.71 to 3.42 mmol/L) 
 300 to 500 mg/dL 
( 3.42 to 5.7 mmol/L) 
 500 to  1,000 mg/dL 
( 5.7 to 11.4 mmol/L) 
 1,000 mg/dL 
( 11.4 mmol/L) 
Magnesium, low 
1.2 to  1.4 mEq/L 
(0.60 to  0.70 mmol/L) 
0.9 to  1.2 mEq/L 
(0.45 to  0.60 mmol/L) 
0.6 to  0.9 mEq/L 
(0.30 to  0.45 mmol/L) 
 0.6 mEq/L 
( 0.30 mmol/L) 
Phosphate, low:   
 14 years of age 
2.0 mg/dL to  LLN 
(0.65 mmol/L to  LLN) 
1.4 to  2.0 mg/dL 
(0.45 to  0.65 mmol/L) 
1.0 to  1.4 mg/dL 
(0.32 to  0.45 mmol/L) 
 1.0 mg/dL 
( 0.32 mmol/L) 
Phosphate, low:   
1 to 14 years of age 
3.0 to  3.5 mg/dL 
(0.97 to  1.13 mmol/L) 
2.5 to  3.0 mg/dL 
(0.81 to  0.97 mmol/L) 
1.5 to  2.5 mg/dL 
(0.48 to  0.81 mmol/L) 
 1.5 mg/dL 
( 0.48 mmol/L) 
Phosphate, low:   
 1 year of age 
3.5 to  4.5 mg/dL 
(1.13 to  1.45 mmol/L) 
2.5 to  3.5 mg/dL 
(0.81 to  1.13 mmol/L) 
1.5 to  2.5 mg/dL 
(0.48 to  0.81 mmol/L) 
 1.5 mg/dL 
( 0.48 mmol/L) 
Potassium, high 
5.6 to  6.0 mEq/L or 
mmol/L 
6.0 to  6.5 mEq/L or 
mmol/L 
6.5 to  7.0 mEq/L or 
mmol/L 
 7.0 mEq/L or mmol/L 
Potassium, low 
3.0 to  3.4 mEq/L or 
mmol/L 
2.5 to  3.0 mEq/L or 
mmol/L 
2.0 to  2.5 mEq/L or 
mmol/L 
 2.0 mEq/L or mmol/L 
Sodium, high 
146 to  150 mEq/L or 
mmol/L 
150 to  154 mEq/L or 
mmol/L 
154 to  160 mEq/L or 
mmol/L 
 160 mEq/L or mmol/L 
Sodium, low 
130 to  135 mEq/L or 
mmol/L 
125 to  130 mEq/L or 
mmol/L 
121 to  125 mEq/L or 
mmol/L 
 121 mEq/L or mmol/L 
Uric acid, high 
7.5 to  10.0 mg/dL 
(0.45 to  0.59 mmol/L) 
10.0 to  12.0 mg/dL 
(0.59 to  0.71 mmol/L) 
12.0 to  15.0 mg/dL 
(0.71 to  0.89 mmol/L) 
 15.0 mg/dL 
( 0.89 mmol/L) 
LLN  lower limit of normal. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
135/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Hematology 
Absolute CD4+ count, low 
(not HIV infected):   
 5 years of age 
300 to  400 cells/mm3 
(0.300  109 to 
 0.400  109 cells/L) 
200 to  300 cells/mm3 
(0.200  109 to 
 0.300  109 cells/L) 
100 to  200 cells/mm3 
(0.100  109 to 
 0.200  109 cells/L) 
 100 cells/mm3 
(0.100  109 cells/L) 
Absolute lymphocyte count, 
low (not HIV infected):   
 5 years of age 
600 to  650 cells/mm3 
(0.600  109 to 
 0.650  109 cells/L) 
500 to  600 cells/mm3 
(0.500  109 to 
 0.600  109 cells/L) 
350 to  500 cells/mm3 
(0.350  109 to 
 0.500  109 cells/L) 
 350 cells/mm3 
( 0.350  109 cells/L) 
Absolute neutrophil count, 
low:   7 days of age 
800 to 1000 cells/mm3 
(0.800  109 to 
1.000  109 cells/L) 
600 to 799 cells/mm3 
(0.600  109 to 
0.799  109 cells/L) 
400 to 599 cells/mm3 
(0.400  109 to  
0.599  109 cells/L) 
 400 cells/mm3 
( 0.400  109 cells/L) 
Absolute neutrophil count, 
low:  2 to 7 days of age 
1250 to 1500 cells/mm3 
(1.250  109 to 
1.500  109 cells/L) 
1000 to 1249 cells/mm3 
(1.000  109 to 
1.249  109 cells/L) 
750 to 999 cells/mm3 
(0.750  109 to  
0.999  109 cells/L) 
 750 cells/mm3 
( 0.750  109 cells/L) 
Absolute neutrophil count, 
low:   1 day of age 
4000 to 5000 cells/mm3 
(4.000  109 to 
5.000  109 cells/L) 
3000 to 3999 cells/mm3 
(3.000  109 to 
3.999  109 cells/L) 
1500 to 2999 cells/mm3 
(1.500  109 to  
2.999  109 cells/L) 
 1500 cells/mm3 
( 1.500  109 cells/L) 
Fibrinogen, decreased 
100 to  200 mg/dL 
(1.00 to  2.00 g/L) 
or 
0.75 to  1.00  LLN 
75 to  100 mg/dL 
(0.75 to  1.00 g/L) 
or 
 0.50 to  0.75  LLN 
50 to  75 mg/dL 
(0.50 to  0.75 g/L) 
or 
0.25 to  0.50  LLN 
 50 mg/dL 
( 0.50 g/L) 
or 
 0.25  LLN 
or associated with gross bleeding 
LLN  lower limit of normal. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
136/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Hematology (cont.) 
Hemoglobin, low: 
 13 years of age  
(male only) k 
10.0 to 10.9 g/dL 
(6.19 to 6.76 mmol/L) 
9.0 to  10.0 g/dL 
(5.57 to  6.19 mmol/L) 
7.0 to  9.0 g/dL 
(4.34 to  5.57 mmol/L) 
 7.0 g/dL 
( 4.34 mmol/L) 
Hemoglobin, low: 
 13 years of age 
(female only) k 
9.5 to 10.4 g/dL 
(5.88 to 6.48 mmol/L) 
8.5 to  9.5 g/dL 
(5.25 to  5.88 mmol/L) 
6.5 to  8.5 g/dL 
(4.03 to  5.25 mmol/L) 
 6.5 g/dL 
( 4.03 mmol/L) 
Hemoglobin, low: 
57 days to  13 years of age 
(male and female) k 
9.5 to 10.4 g/dL 
(5.88 to 6.48 mmol/L) 
8.5 to  9.5 g/dL 
(5.25 to  5.88 mmol/L) 
6.5 to  8.5 g/dL 
(4.03 to  5.25 mmol/L) 
 6.5 g/dL 
( 4.03 mmol/L) 
Hemoglobin, low: 
36 to 56 days of age 
(male and female) k 
8.5 to 9.6 g/dL 
(5.26 to 5.99 mmol/L) 
7.0 to  8.5 g/dL 
(4.32 to  5.26 mmol/L) 
6.0 to  7.0 g/dL 
(3.72 to  4.32 mmol/L) 
 6.0 g/dL 
( 3.72 mmol/L) 
Hemoglobin, low: 
22 to 35 days of age 
(male and female) k 
9.5 to 11.0 g/dL 
(5.88 to 6.86 mmol/L) 
8.0 to  9.5 g/dL 
(4.94 to  5.88 mmol/L) 
6.7 to  8.0 g/dL 
(4.15 to  4.94 mmol/L) 
 6.7 g/dL 
( 4.15 mmol/L) 
Hemoglobin, low: 
8 to 21 days of age (male and 
female) k 
11.0 to 13.0 g/dL 
(6.81 to 8.10 mmol/L) 
9.0 to  11.0 g/dL 
(5.57 to  6.81 mmol/L) 
8.0 to  9.0 g/dL 
(4.96 to  5.57 mmol/L) 
 8.0 g/dL 
( 4.96 mmol/L) 
Hemoglobin, low: 
 7 days of age 
(male and female) k 
13.0 to 14.0 g/dL 
(8.05 to 8.72 mmol/L) 
10.0 to  13.0 g/dL 
(6.19 to  8.05 mmol/L) 
9.0 to  10.0 g/dL 
(5.59 to  6.19 mmol/L) 
 9.0 g/dL 
( 5.59 mmol/L) 
k Male and female sex are defined as sex at birth.  For transgender participants  13 years of age who have been on hormone therapy for more 
than 6 consecutive months, hemoglobin grade should be based on values for the gender with which they identify (e.g., grade for a transgender 
female should be based on hemoglobin laboratory values for females). 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
137/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Hematology (cont.) 
INR, high (not on 
anticoagulation therapy) 
1.1 to  1.5  ULN 
1.5 to  2.0  ULN 
2.0 to  3.0  ULN 
 3.0  ULN 
Methemoglobin 
(% hemoglobin) 
5.0% to  10.0% 
10.0% to  15.0% 
15.0% to  20.0% 
 20.0% 
PTT, high (not on 
anticoagulation therapy) 
1.1 to  1.66  ULN 
1.66 to  2.33  ULN 
2.33 to  3.00  ULN 
 3.00  ULN 
Platelets, decreased 
100,000 to  
 125,000 cells/mm3 
(100.000  109 to 
 125.000  109 cells/L) 
50,000 to  
 100,000 cells/mm3 
(50.000  109 to 
 100.000  109 cells/L) 
25,000 to  
 50,000 cells/mm3 
(25.000  109 to  
 50.000  109 cells/L) 
 25,000 cells/mm3 
( 25.000  109 cells/L) 
PT, high (not on 
anticoagulation therapy) 
1.1 to  1.25  ULN 
1.25 to  1.50  ULN 
1.50 to  3.00  ULN 
 3.00  ULN 
WBC, decreased:   
 7 days of age 
2000 to 2499 cells/mm3 
(2.000  109 to  
2.499  109 cells/L) 
1500 to 1999 cells/mm3 
(1.500  109 to  
1.999  109 cells/L) 
1000 to 1499 cells/mm3 
(1.000  109 to  
1.499  109 cells/L) 
 1000 cells/mm3 
( 1.000  109 cells/L) 
WBC, decreased:   
 7 days of age 
5500 to 6999 
(5.500  109 to  
6.999  109 cells/L) 
4000 to 5499 
(4.000  109 to  
5.499  109 cells/L) 
2500 to 3999 
(2.500  109 to  
3.999  109 cells/L) 
 2500 
( 2.500  109 cells/L) 
ULN  upper limit of normal. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 1 
Severity Grading for Adult and Pediatric Adverse Events (cont.) 
Vixarelimab—Genentech, Inc. 
138/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Urinalysis 
Glycosuria (random collection 
tested by dipstick) 
Trace to 1+ or 
 250 mg 
2+ or  250 to 
 500 mg 
 2+ or  500 mg 
 
Hematuria (not to be reported 
based on dipstick findings or 
on blood believed to be of 
menstrual origin) 
6 to  10 RBCs per high 
power field 
 10 RBCs per high 
power field 
Gross, with or without clots 
or with RBC casts 
or intervention indicated 
Life-threatening consequences 
Proteinuria (random 
collection tested by dipstick) 
1+ 
2+ 
3+ or higher 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Vixarelimab—Genentech, Inc. 
139/Protocol GA44839, Version 2 
Table 2 
Severity Grading for Elevated Total Bilirubin in Neonates 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Neonates  35 Weeks Gestational Age 
 24 hours of age  
4 to  7 mg/dL 
(68.4 to  119.7 mol/L) 
7 to  10 mg/dL 
(119.7 to  171 mol/L) 
10 to  17 mg/dL 
(171 to  290.7 mol/L) 
 17 mg/dL 
( 290.7 mol/L) 
24 to  48 hours of age  
5 to  8 mg/dL 
(85.5 to  136.8 mol/L) 
8 to  12 mg/dL 
(136.8 to  205.2 mol/L) 
12 to  19 mg/dL 
(205.2 to  324.9 mol/L) 
 19 mg/dL 
( 324.9 mol/L) 
48 to  72 hours of age  
8.5 to  13 mg/dL 
(145.35 to  222.3 mol/L) 
13 to  15 mg/dL 
(222.3 to  256.5 mol/L) 
15 to  22 mg/dL 
(256.5 to  376.2 mol/L) 
 22 mg/dL 
( 376.2 mol/L) 
72 hours to  7 days of age  
11 to  16 mg/dL 
(188.1 to  273.6 mol/L) 
16 to  18 mg/dL 
(273.6 to  307.8 mol/L) 
18 to  24 mg/dL 
(307.8 to  410.4 mol/L) 
 24 mg/dL 
( 410.4 mol/L) 
7 to 28 days of age (breast 
feeding)  
5 to  10 mg/dL 
(85.5 to  171 mol/L) 
10 to  20 mg/dL 
(171 to  342 mol/L) 
20 to  25 mg/dL 
(342 to  427.5 mol/L) 
 25 mg/dL 
( 427.5 mol/L) 
7 to 28 days of age (not 
breast feeding)  
1.1 to  1.6 ULN 
1.6 to  2.6 ULN 
2.6 to  5.0 ULN 
 5.0 ULN 
ULN  upper limit of normal. 
 
 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Table 2 
Severity Grading for Elevated Total Bilirubin in Neonates (cont.) 
 
 
Vixarelimab—Genentech, Inc. 
140/Protocol GA44839, Version 2 
Parameter 
Grade 1 
(Mild) 
Grade 2 
(Moderate) 
Grade 3 
(Severe) 
Grade 4 
(Potentially Life-Threatening) 
Neonates  35 Weeks Gestational Age 
32 to  35 weeks gestational 
age and  7 days of age  
 
 
10 to  14 mg/dL 
(171 to  239.4 mol/L) 
 14 mg/dL 
( 239.4 mol/L) 
28 to  32 weeks gestational 
age and  7 days of age  
 
 
6 to  10 mg/dL 
(102.6 to  171 mol/L) 
 10 mg/dL 
( 171 mol/L) 
 28 weeks gestational age 
and  7 days of age  
 
 
5 to  8 mg/dL 
(85.5 to  136.8 mol/L) 
 8 mg/dL 
( 136.8 mol/L) 
7 to 28 days of age 
(breast feeding)  
5 to  10 mg/dL 
(85.5 to  171 mol/L) 
10 to  20 mg/dL 
(171 to  342 mol/L) 
20 to  25 mg/dL 
(342 to  427.5 mol/L) 
 25 mg/dL 
( 427.5 mol/L) 
7 to 28 days of age 
(not breast feeding)  
1.1 to  1.6  ULN 
1.6 to  2.6 ULN 
2.6 to  5.0 ULN 
 5.0 ULN 
ULN  upper limit of normal. 

Appendix 7: 
Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events 
 
Vixarelimab—Genentech, Inc. 
141/Protocol GA44839, Version 2 
Table 3 
Severity Grading for Events Not Specifically Listed in Tables 1 and 2 
Grade 
Severity 
1 
Mild; transient or mild discomfort ( 48 hours); no medical intervention or 
therapy required 
2 
Moderate; mild to moderate limitation in activity; some assistance may be 
needed; no or minimal medical intervention or therapy required 
3 
Severe; marked limitation in activity; some assistance usually required; 
medical intervention or therapy required; hospitalization possible 
4 
Life-threatening; extreme limitation in activity; significant assistance required; 
significant medical intervention or therapy required, hospitalization or hospice 
care probable 
  
REFERENCE 
[HHS] U.S. Department of Health and Human Services, National Institutes of Health, National Institute of Allergy and Infectious 
Diseases, Division of AIDS. Division of AIDS (DAIDS) table for grading the severity of adult and pediatric adverse events, 
corrected version 2.1 [resource on the Internet]. 2017 [cited: 16 May 2023]. Available from: 
https://rsc.niaid.nih.gov/sites/default/files/daidsgradingcorrectedv21.pdf. 
 

 
Vixarelimab—Genentech, Inc. 
142/Protocol GA44839, Version 2 
Appendix 8  
Sampson Criteria for Diagnosing Potential Cases of Anaphylaxis 
Anaphylaxis is highly likely when any one of the following three criteria is fulfilled: 
1. 
Acute onset of an illness (minutes to several hours) with involvement of the skin, 
mucosal tissue, or both (e.g., generalized hives, pruritus or flushing, swollen lips-
tongue-uvula) 
AND AT LEAST ONE OF THE FOLLOWING: 
a) Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, 
reduced peak expiratory flow [PEF], hypoxemia) 
b) Reduced blood pressure (BP) or associated symptoms of end organ 
dysfunction (e.g., 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 (e.g., generalized hives, itch-flush, 
swollen lips-tongue-uvula) 
b) Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, 
reduced PEF, hypoxemia) 
c) 
Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, 
incontinence) 
d) Persistent gastrointestinal symptoms (e.g., crampy abdominal pain, vomiting) 
 
3. 
Reduced BP after exposure to known allergen for that patient (minutes to several 
hours): 
a) Adults:  Systolic BP of less than 90 mmHg or greater than 30% decrease from 
that person's baseline 
 
REFERENCE 
Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the 
definition and management of anaphylaxis: summary report: Second National 
Institute of Allergy and Infectious Disease/Food Allergy and Anaphylaxis Network 
Symposium. J Allergy Clin Immunol 2006;117:3917. 
 
 
 

 
Vixarelimab—Genentech, Inc. 
143/Protocol GA44839, Version 2 
Appendix 9  
Laboratory Sampling in China 
Testing, Analysis, and Biosample Destruction in China 
The Sponsor delegates the testing, analysis, and destruction of samples for 
Study GA44839 from China sites to the following China domestic companies: 
 
Testing Items 
Central Laboratory for 
Testing and Analysis 
Biosample Destruction 
Provider 
Hematology:  WBC count, 
RBC count, hemoglobin, 
hematocrit, platelet count, 
and differential count 
(neutrophils, eosinophils, 
basophils, monocytes, 
lymphocytes, other cells) 
Labcorp Pharmaceutical 
Research & Development 
(Shanghai)Co, Ltd.  
Shanghai Solid Waste 
Disposal, Co., Ltd. 
 
Clarification of Laboratory Sample Collection in China 
The following table describes laboratory samples that will not be collected in China: 
 
Samples that will not be collected in China: 
 Colonic tissue samples for histologic biomarker assessment and for exploratory biomarker 
research 
 Genomic research (analysis or mutations, single nucleotide polymorphisms, or other 
genomic variants) or genomic profiling (WGS or WES) samples 
 Stool sample for exploratory biomarker research 
 Samples for Research Biosample Repository 
WES  whole exome sequencing; WGS   whole genome sequencing. 
 
 

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