A Three-year, Multi-center, Double-blind, Extension Study to Evaluate the Long-term Safety and Efficacy of Ligelizumab in Patients Who Completed Ligelizumab's Phase III Studies in Food Allergy
Phase: PHASE3
Conditions: Food Allergy
Sponsor: Novartis Pharmaceuticals

Novartis Research and Development 
Clinical Trial Protocol Title
A three-year, multi-center, double-blind, extension study to 
evaluate the long-term safety and efficacy of ligelizumab in 
patients who completed ligelizumab’s Phase III studies in 
food allergy 
Clinical Trial Protocol Number: CQGE031G12303B 1&7
Version Number: V02 (Amended Protocol) (Clean) 
Compound: QGE031 (ligelizumab) 
Brief Title: Long term extension study of ligelizumab in food allergy 
Study Phase: III
Sponsor Name: Novartis Pharma AG
Sponsor Address in the EEA: Novartis Pharma AG, Lichtstrasse 35, 4056, Basel 
Town, Switzerland 
Regulatory Agency Identifier Number(s): 2022-502366-25-00 (EU trial number) 
Approval Date: 14-Aug-2023 (content final) 
Property of Novartis 
Confidential 
May not be used, divulged, published, or otherwise disclosed 
without the consent of Novartis 
Clinical Trial Protocol Template Version 5.0 dated 14-Jan-2022 

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Table of contents
Table of contents .................................................................................................................2 
List of tables ........................................................................................................................7 
List of figures ......................................................................................................................8 
Amendment 2 (14-Aug-2023).............................................................................................9 
Amendment 1 (25-Jul-2023) .............................................................................................10 
1 
Protocol summary..............................................................................................................11 
1.1 
Summary................................................................................................................11 
1.2 
Schema...................................................................................................................14 
1.3 
Schedule of activities (SoA) ..................................................................................15 
2 
Introduction .......................................................................................................................24 
2.1 
Study rationale.......................................................................................................25 
2.2 
Background............................................................................................................25 
2.3 
Benefit/Risk assessment ........................................................................................27 
3 
Objectives, endpoints, and estimands................................................................................32 
3.1 
Primary estimands .................................................................................................33 
3.2 
Secondary estimands .............................................................................................33 
4 
Study design ......................................................................................................................33 
4.1 
Overall design........................................................................................................33 
4.1.1 
Transition from the core study..............................................................33 
4.1.2 
Conditional discontinuation of study treatment in Maximum 
Responder Participants..........................................................................34 
4.1.3 
Administration of study treatment at home...........................................40 
4.2 
Scientific rationale for study design ......................................................................51 
4.2.1 
Participant input into design..................................................................52 
4.3 
Justification for dose..............................................................................................52 
4.3.1 
Rationale for choice of background therapy .........................................52 
4.4 
Rationale for choice of control drugs (comparator/placebo) or combination 
drugs ......................................................................................................................52 
4.5 
Rationale for public health emergency mitigation procedures..............................52 
4.6 
Purpose and timing of interim analyses/design adaptations..................................52 
4.7 
End of study definition ..........................................................................................53 
5 
Study population................................................................................................................53 
5.1 
Inclusion criteria ....................................................................................................53 
5.2 
Exclusion criteria...................................................................................................53 
5.3 
Screen failures .......................................................................................................55 
5.3.1 
Participant numbering ...........................................................................55 

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6 
Study treatment(s) and concomitant therapy.....................................................................55 
6.1 
Study treatment(s)..................................................................................................55 
6.1.1 
Bio-batch retention samples..................................................................56 
6.1.2 
Additional study treatments ..................................................................56 
6.1.3 
Treatment arms/group ...........................................................................56 
6.1.4 
Treatment duration................................................................................56 
6.1.5 
Medical devices.....................................................................................56 
6.2 
Preparation, handling, storage, and accountability................................................57 
6.2.1 
Handling of study treatment..................................................................57 
6.2.2 
Handling of other treatment ..................................................................58 
6.2.3 
Instruction for prescribing and taking study treatment .........................58 
6.3 
Measures to minimize bias: randomization and blinding......................................61 
6.3.1 
Treatment assignment, randomization ..................................................61 
6.3.2 
Treatment blinding................................................................................62 
6.3.3 
Emergency breaking of assigned treatment code..................................63 
6.4 
Study treatment compliance ..................................................................................64 
6.4.1 
Recommended treatment of adverse events..........................................64 
6.5 
Dose modification..................................................................................................64 
6.5.1 
Definitions of dose limiting toxicities (DLTs)......................................64 
6.5.2 
Dose modifications................................................................................64 
6.5.3 
Follow-up for toxicities.........................................................................65 
6.5.4 
Retreatment criteria...............................................................................66 
6.6 
Continued access to study treatment after the end of the study.............................66 
6.6.1 
Post trial access .....................................................................................66 
6.7 
Treatment of overdose ...........................................................................................67 
6.7.1 
Reporting of study treatment errors including misuse/abuse................67 
6.8 
Concomitant and other therapy..............................................................................67 
6.8.1 
Concomitant therapy .............................................................................67 
6.8.2 
Prohibited medication ...........................................................................68 
6.8.3 
Rescue medicine....................................................................................69 
7 
Discontinuation of study treatment and participant discontinuation/withdrawal..............70 
7.1 
Discontinuation of study treatment........................................................................70 
7.2 
Participant discontinuation from the study............................................................71 
7.3 
Withdrawal of informed consent and exercise of participants’ data privacy 
rights ......................................................................................................................71 
7.4 
Lost to follow-up ...................................................................................................71 

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7.5 
Early study termination by the Sponsor.................................................................72 
8 
Study Assessments and Procedures...................................................................................72 
8.1 
Screening ...............................................................................................................72 
8.2 
Participant demographics/other baseline characteristics .......................................73 
8.3 
Efficacy assessments .............................................................................................73 
8.3.1 
Oral Food Challenge (OFC)..................................................................73 
8.3.2 
Skin Prick Test (SPT)............................................................................74 
8.3.3 
Appropriateness of efficacy assessments..............................................75 
8.4 
Safety assessments.................................................................................................75 
8.4.1 
Physical examinations...........................................................................75 
8.4.2 
Vital signs..............................................................................................76 
8.4.3 
Electrocardiograms ...............................................................................76 
8.4.4 
Clinical safety laboratory tests..............................................................77 
8.4.5 
Pregnancy testing ..................................................................................78 
8.4.6 
Other safety evaluations........................................................................79 
8.4.7 
Appropriateness of safety measurements..............................................80 
8.5 
Additional assessments..........................................................................................80 
8.5.1 
Clinical Outcome Assessments (COAs) ...............................................80 
8.6 
Adverse events (AEs), serious adverse events (SAEs), and other safety 
reporting.................................................................................................................82 
8.6.1 
Adverse events ......................................................................................82 
8.6.2 
Serious adverse events ..........................................................................84 
8.6.3 
SAE reporting........................................................................................85 
8.6.4 
Pregnancy..............................................................................................85 
8.6.5 
Disease-related events and/or disease-related outcomes not 
qualifying as AEs or SAEs....................................................................86 
8.6.6 
Adverse events of special interest.........................................................86 
8.6.7 
Medical device deficiencies ..................................................................86 
8.7 
86 
8.8 
87 
8.8.1 
.87 
8.8.2 
.87 
8.9 
88 
8.9.1 
88 
8.9.2 
88 
8.10 
Health economics OR Medical resource utilization and health economics ..........88 
9 
Statistical considerations ...................................................................................................88 
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9.1 
Analysis sets ..........................................................................................................88 
9.2 
Statistical analyses.................................................................................................88 
9.2.1 
General considerations..........................................................................88 
9.2.2 
Participant demographics and other baseline characteristics................89 
9.2.3 
Treatments.............................................................................................89 
9.3 
Primary endpoint(s)/estimand(s) analysis..............................................................89 
9.3.1 
Definition of primary endpoint(s).........................................................89 
9.3.2 
Statistical model, hypothesis, and method of analysis..........................89 
9.3.3 
Handling of intercurrent events of primary estimand (if applicable)....90 
9.3.4 
Handling of missing values...................................................................90 
9.3.5 
Multiplicity adjustment (if applicable)..................................................90 
9.3.6 
Sensitivity analyses...............................................................................90 
9.3.7 
Supplementary analysis.........................................................................90 
9.4 
Secondary endpoint(s)/estimand(s) analysis..........................................................91 
9.4.1 
Efficacy and/or pharmacodynamic endpoint(s) ....................................91 
9.4.2 
Safety endpoints....................................................................................91 
9.4.3 
Patient reported outcomes.....................................................................91 
9.5 
Exploratory endpoint(s)/estimand(s) analysis .......................................................92 
9.5.1 
.92 
9.5.2 
.92 
9.5.3 
.92 
9.5.4 
.92 
9.6 
(Other) Safety analyses..........................................................................................93 
9.7 
Other analyses........................................................................................................93 
9.8 
Interim analysis......................................................................................................93 
9.9 
Sample size determination.....................................................................................93 
9.9.1 
Primary endpoint(s)...............................................................................93 
9.9.2 
Secondary Endpoints.............................................................................93 
10 Supporting documentation and operational considerations...............................................94 
10.1 
Appendix 1: Regulatory, ethical, and study oversight considerations...................94 
10.1.1 
Regulatory and ethical considerations ..................................................94 
10.1.2 
Informed consent process......................................................................95 
10.1.3 
Data protection......................................................................................96 
10.1.4 
Committees structure ............................................................................96 
10.1.5 
Data quality assurance...........................................................................97 
10.1.6 
Source documents .................................................................................98 
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10.1.7 
Publication policy..................................................................................99 
10.1.8 
Protocol adherence and protocol amendments......................................99 
10.2 
Appendix 2: Abbreviations and definitions.........................................................100 
10.2.1 
List of abbreviations............................................................................100 
10.2.2 
Definitions...........................................................................................103 
10.3 
Appendix 3: Clinical laboratory tests ..................................................................106 
10.3.1 
Clinically notable laboratory values and vital signs ...........................106 
10.4 
Appendix 4: Participant Engagement ..................................................................107 
10.5 
Appendix 5: Liver safety monitoring ..................................................................108 
10.5.1 
Liver event and laboratory trigger definitions & follow-up
requirements........................................................................................108 
10.6 
Appendix 6: Renal safety monitoring..................................................................110 
10.6.1 
Specific Renal Alert Criteria and Actions and Event Follow-up........111 
10.7 
Appendix 7: Oral Food Challenge.......................................................................112 
10.7.1 
Background .........................................................................................112 
10.7.2 
Dosing Schedule..................................................................................112 
10.7.3 
Peanut OFC material...........................................................................113 
10.7.4 
Preparing for the food challenge.........................................................114 
10.7.5 
Evaluation parameters of the OFC......................................................114 
10.7.6 
OFC completion..................................................................................115 
10.8 
Appendix 8: Guidance for Skin Prick Test..........................................................116 
10.8.1 
Background of Skin Prick Test ...........................................................116 
10.8.2 
Material ...............................................................................................116 
10.8.3 
Starting the Skin Prick Test.................................................................117 
10.8.4 
Completion of the Skin Prick Test......................................................118 
10.9 
Appendix 9: PRO Measures ................................................................................119 
10.9.1 
FAQLQ-CF: Food Allergy Quality of Life Questionnaire Child 
Form....................................................................................................119 
10.9.2 
FAIM-CF: Food Allergy Independent Measure Child Form..............121 
10.9.3 
FAQLQ-TF: Food Allergy Quality of Life Questionnaire Teenager 
Form....................................................................................................122 
10.9.4 
FAIM-TF: Food Allergy Independent Measure Teenager Form ........124 
10.9.5 
FAQLQ-AF: Food Allergy Quality of Life Questionnaire Adult 
Form....................................................................................................125 
10.9.6 
FAIM-AF: Food Allergy Independent Measure Adult Form .............128 
10.9.7 
FAQLQ-PF: Food Allergy Quality of Life Questionnaire Parental 
Form....................................................................................................129 

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10.9.8 
FAQL-PB: Food Allergy Quality of Life - Parental Burden 
Questionnaire ......................................................................................133 
10.9.9 
SF-36v2 Acute Version Short Form 36-Health Survey 
Questionnaire v2 .................................................................................136 
10.9.10 
Home Administration Study Drug Diary (example)...........................139 
10.9.11 
140 
11 References .......................................................................................................................142 
List of tables
Table 1-1 
Study objectives and endpoints.............................................................11 
Table 1-2 
Study Treatment and Treatment Form:.................................................12 
Table 1-3 
Definition of Maximum Responder based on the DBPCFC/OL-
OFC.......................................................................................................15 
Table 1-4 
Assessment Schedule ............................................................................17 
Table 3-1 
Objectives and related endpoints ..........................................................32 
Table 4-1 
Maximum Responder during the DBPCFC/OL-OFC...........................35 
Table 4-2 
Home Administration Assessment Schedule ........................................42 
Table 4-3 
Rationale for study design.....................................................................51 
Table 6-1 
Investigational and control drug............................................................56 
Table 6-2 
Blinding level........................................................................................63 
Table 6-3 
Guidance to rule-out possible alternative causes of LFT 
abnormalities.........................................................................................66 
Table 6-4 
Medications allowed under certain conditions......................................68 
Table 6-5 
Prohibited medication ...........................................................................68 
Table 8-1 
Laboratory evaluations..........................................................................77 
Table 8-2 
PROs based on participant’s age...........................................................80 
Table 9-1 
Precision Levels (95%) for sensitivity of safety incidence rate............93 
Table 10-1 
Notable values for Heart Rate (HR) and Blood Pressure in children 
and adolescents....................................................................................107 
Table 10-2 
Liver event and laboratory trigger definitions ....................................108 
Table 10-3 
Follow-up requirements for liver laboratory triggers..........................109 
Table 10-4 
Follow-up requirements for liver laboratory triggers..........................109 
Table 10-5 
Base Renal Monitoring .......................................................................110 
Table 10-6 
Specific renal alert criteria and actions ...............................................111 
Table 10-7 
Renal event follow-up.........................................................................111 
Table 10-8 
Allergen Dosing Table (active ingredient dry weight) .......................113 
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Table 10-9 
Definition of Dose-Limiting Symptoms (per the CoFAR* grading 
scale, Chinthrajah et al 2022 ).............................................................114 
Table 10-10 
Medications to be washed out prior to SPT ........................................117 
List of figures
Figure 1-1 
Study design including transition from the core study..........................14 
Figure 4-1 
Study design including transition from the core study..........................34 
Figure 4-2 
Conditional discontinuation for the MR participants who transition 
from Study CQGE031G12301..............................................................38 
Figure 4-3 
Conditional discontinuation for the MR participants who transition 
from other studies..................................................................................40 
Figure 10-1 
Measurement of skin reaction .............................................................118 

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Protocol No. CQGE031G12303B
Amendment 2 (14-Aug-2023)
Amendment rationale 
The protocol is being amended to clarify that the present protocol is dedicated to include only 
peanut allergic patients from the CQGE031G12301 study. It also clarifies that the duration of 
the period elapsed since end of treatment in the core study until Day 1 of study 
CQGE031G12303B will be derived from collected CRF data.
At the time of this amendment, participants have already started transitioning to the extension 
study in countries with all required approvals in place. These protocol changes are expected to 
have minimal impact on the study population or results.
Changes to the protocol
IRBs/IECs
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities.
The changes described in this amended protocol are non-substantial and do not require IRB/IEC 
approval prior to implementation.
The changes herein do NOT affect the Informed Consent.
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Protocol No. CQGE031G12303B
Amendment 1 (25-Jul-2023)
Amendment rationale 
The protocol is being amended to emphasize that future protocol amendments will be submitted 
for approval to update study features, if needed, to account for new study populations from 
other core studies, for the results of the CQGE031G12301 study once available, and to clarify 
that there is no placebo arm in the study. Clarification has also been included about the transition 
of participants from core to extension study in the case of operational delays. 
At the time of this amendment, participants have already started transitioning to the extension 
study in countries with all required approvals in place. These protocol changes are expected to 
have minimal impact on the study population or results.
Changes to the protocol
IRBs/IECs
A copy of this amended protocol will be sent to the Institutional Review Board 
(IRBs)/Independent Ethics Committee (IECs) and Health Authorities.
The changes described in this amended protocol are non-substantial and do not require IRB/IEC 
approval prior to implementation.
The changes herein do NOT affect the Informed Consent.
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Protocol No. CQGE031G12303B
1
Protocol summary
1.1
Summary
Protocol Title:
A three-year, multi-center, double-blind, extension study to evaluate the long-term safety and 
efficacy of ligelizumab in patients who completed ligelizumab’s Phase III studies in food 
allergy
Brief Title:
Long-term extension study of ligelizumab in food allergy
Purpose
Long-term safety and efficacy
Study Indication /Medical Condition:
Food allergy
Treatment type
Biological (monoclonal antibody)
Study type
Interventional
Objectives and Endpoints:
Table 1-1
Study objectives and endpoints
Objectives
Endpoints
Primary
To evaluate the long-term safety and tolerability of 
ligelizumab in participants with food allergy
Overall incidence and exposure-adjusted occurrence 
rates of treatment-emergent AEs and SAEs
Secondary
To describe the long-term efficacy of ligelizumab as 
measured by the tolerance of an allergen food protein 
during an open-label OFC at scheduled timepoints.
To assess the safety and tolerability of ligelizumab in 
all participants who are administered study treatment 
at home by self-administration or parent/caregiver
To assess the long-term impact of ligelizumab on the 
health related quality of life (HRQoL) of patients with 
food allergy
Proportion of participants tolerating a single dose of ≥ 
600 mg of peanut protein without dose limiting 
symptoms during an open label OFC at scheduled 
timepoints
Overall incidence and exposure-adjusted occurrence 
rates of treatment-emergent AEs and SAEs
Summaries of total scores in the FAQLQ, FAIM and 
SF-36v2 by age and responder (participants and/or 
caregiver) at scheduled timepoints
Trial Design:
This is a multi-center, double-blind, 3-year, extension study to evaluate the long-term safety 
and efficacy of ligelizumab in participants who completed ligelizumab Phase III studies in food 
allergy. Novartis conducts this study as a basket extension study which enables the participants 

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from planned multiple Phase III “core” studies to roll over to this extension study 
(CQGE031G12303B) once the participants have completed a “core” study and agreed to 
consent to participate in Study CQGE031G12303B.
A subset of participants will also be offered administration of study treatment at home either by 
the participant him/herself (self-administration) or by parent/caregiver following training at a 
number of clinic visits.
Brief Summary:
This is an extension study to evaluate the long-term safety and efficacy of ligelizumab in 
participants who have completed a ligelizumab Phase III study in food allergy. Participants will 
receive up to 3 years treatment with ligelizumab after which they will enter a follow-up period 
for 16 weeks. During the study, participants will undergo allergy testing by a Skin Prick Test 
and Oral Food challenge to test if the treatment is working or not. Accordingly, this study will 
generate data that should provide guidance relative to the long-term (chronic) use of ligelizumab 
in food allergic patients in terms of safety, efficacy, pharmaco-dynamics, biomarkers and 
Quality of Life, and potential discontinuation from treatment.
During the study, treatment will be administered every 4 weeks and while this can take place in 
the hospital clinic, some participants will be trained to administer study treatment at home by 
either the participant or parent/caregiver. Participants at home will record administration of the 
study treatment on a dosing log and return this to the clinic for review.
Table 1-2
Study Treatment and Treatment Form:
Investigational/ 
Control Drug
(Name and 
Strength)
Treatment Form or 
Pharmaceutical 
Dosage Form
Route of 
Administration
Presentation
Sponsor (global or 
local)
QGE031 120mg/1ml
Solution for injection
SC
Double-blind
Sponsor (global)
QGE031 
Placebo/1ml*
Solution for injection
SC
Double Blind
Sponsor (global)
* Placebo will only be administered alongside the 120mg/1ml dose to protect the dose blinding. There is no 
placebo arm
Study Duration:
3 years (172 weeks including 16 weeks follow-up)
Treatment Duration:
3 years (Up to 156 weeks)
Visit Frequency:
The visit frequency will be every 4 weeks for those who are administered study treatment in the 
clinic, and every 12 to 16 weeks for home administration participants, with a phone call every 
4 weeks. At week 156, when the study treatment period is complete, all participants will have 
visits every 4 weeks for follow-up for a period of 16 weeks.

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Treatment of interest
Participants will receive ligelizumab treatment allocated in the core study. There is a possibility 
to discontinue the study treatment in the Maximum Responder (MR) participants who 
successfully continue “conditional discontinuation of study treatment” (Section 4.1.1). Please 
refer to the detailed definition of responder status in Table 1-3 (or Table 4-1).
Number of Participants
This study population will consist of participants who have successfully completed ligelizumab 
Phase III studies in food allergy including (but not limited to) Study CQGE031G12301 (peanut 
allergy). The expectation is that approximately 550 participants will enroll in this extension 
study. This extension study will be opened for participants joining from additional QGE031 
food allergy trials.
In line with each core study, this extension will involve male and female participants who have 
successfully completed a core study and are eligible to continue to extension study.
Key Inclusion criteria
Participants eligible for inclusion in this study must meet all of the following criteria:
x
Signed informed consent form (ICF) and assent form (where applicable) obtained from the 
participant/legal representative before study participation. If a minor participant reaches the 
age of legal majority (as defined by local law), they must be re-consented at the next study 
visit
x
Participants have completed the treatment period in any ligelizumab Phase III studies in 
food allergy (e.g., Study CQGE031G12301). Please refer to the Section 4.1 for the timing 
of transition.
x
Participants who are willing to adhere to the study visits and procedures, including receiving 
injections (study treatment) and participating in the OL-OFC (open label oral food 
challenge)
x
Participants who agree to continue avoiding exposure to allergens (per core study) and any 
other foods they are allergic to throughout this study
x
Participants who are able to safely continue into the study as judged by the investigator
Key Exclusion criteria
x
Development of a severe or life-threatening episode of an allergic reaction that required 
intubation and/or ICU admission during the core studies
x
Development of a serious adverse event which is suspected to be related to the study 
treatment judged by the investigator during the core study
x
Development of uncontrolled asthma during the core study that could compromise the safety 
of the participants judged by the investigator
x
Development of clinically significant cardiovascular, neurological, and or psychiatric 
conditions during the core study that could interfere with or compromise the safety of the 
participants, interfere with evaluation or interpretation of the study results or preclude 
completion of the study judged by the investigator

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x
Participants who failed to comply with the protocol requirements and procedures during the 
core study, and in the Investigator's opinion they should not participate in this extension 
study
x
Platelets <75,000/ul at EoT of the core study
Treatment Groups:
Ligelizumab 120 mg SC q4w
Ligelizumab 240 mg SC q4w
There is a possibility to discontinue the study treatment in participants who successfully 
continue “conditional discontinuation of study treatment” (Section 4.1.2).
Data Monitoring/Other Committee:
Yes, Section 10.1.4
Key words
Food allergy, peanut allergy, oral food challenge, IgE, ligelizumab
1.2
Schema
Participants from Study CQGE031G12301 will enter the extension study after completing the 
follow-up period of the core study. The participants from other future study(ies) may then enter 
the extension study immediately after completion of the treatment period of a core study, hence 
without treatment interruption (Figure 1-1).
Figure 1-1
Study design including transition from the core study
DBPCFC: Double Blind Placebo Controlled OFC, OL-OFC: Open Label Oral Food Challenge, MR: Maximum 
Responder, EOT: End of Treatment, EOFu: End of Follow-Up.

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Transition from Study CQGE031G12301 at the end of the post treatment follow-
up period of the core study:
The participants from Study CQGE031G12301 will transition into the extension study after 
completion of the follow-up period (washout) in the core study. The end of follow-up visit of 
the core study will become the first visit of this extension study (Screening/Day 1) for these 
participants. Some of the assessments at EOFu of the core study will form the baseline at 
Screening/Day 1 in the extension study. The informed consent must be obtained before 
initiating any study related activities of the extension study at Screening/Day 1.
Transition from other future study(ies) at the end of treatment period of the 
core study:
The participants from other future study(ies) who complete the study treatment period of the 
core study and are willing to participate in the extension study will consent to the extension 
study. The first visit of the extension study (Screening/Day 1) will be scheduled four weeks 
after the end of the treatment visit of the core study and participants will consent on 
Screening/Day 1 of the extension study.
Conditional discontinuation of study treatment in the Maximum Responder 
Participants (See Figure 1-1):
Interruption of treatment until the next OL-OFC to explore the long-term objective of achieving 
discontinuation of ligelizumab treatment. The detailed process will be described in 
Section 4.1.2.
Table 1-3
Definition of Maximum Responder based on the DBPCFC/OL-OFC
Responder status
Dose of allergen (food)
Maximum Responder (MR)
Maximum Tolerated Dose (MTD) of 
.
● Participant WITHOUT Dose Limiting Symptom (DLS) at any dose 
including the maximum dose, 
DBPCFC will be conducted at the end of treatment period of a core study
OL-OFC will be conducted during the extension study
1.3
Schedule of activities (SoA)
The Schedule of Assessments (Table 1-4) lists all of the assessments and when they are 
performed. All data obtained from these assessments must be supported in the participant’s 
source documentation. The “X” in the table denotes the assessments to be recorded in the 
clinical database or received electronically from a vendor. The “S” in the table denotes the 
assessments that are only in the participant’s source documentation and do not need to be 
recorded in the clinical database.
Participants should be seen for all visits/assessments as outlined in the SoA or as close to the 
designated day/time as possible. Missed or rescheduled visits should not lead to automatic 
discontinuation. The only remote procedures for this study are the ePRO questionnaires and for 
a subset of participants the safety phone calls, "at home study drug administration", completion 
of "Study Drug Dosing Log" and 
 "urine pregnancy test".
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Participants who permanently discontinue from study treatment are to complete the end of 
treatment visit as soon as possible, and attend the follow-up visits as indicated in the SoA. The 
participants performing conditional discontinuation of study treatment need to visit the clinic 
for the necessary on site activities such as SPT & OFC, blood collection and safety assessments. 
Otherwise they will be contacted by the site via phone call every 4 weeks according to the study 
schedule to monitor safety.
Participants who discontinue from study should be scheduled for a final evaluation visit if they 
agree, as soon as possible, at which time all of the assessments listed for the final visit will be 
performed. At this final visit, all dispensed investigational product should be reconciled, and 
the adverse events and concomitant medications not previously reported must be recorded on 
the case report form (CRF).
Patient Reported Outcomes (PRO) measure(s) must be completed before any assessments are 
performed at any given visit.
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e., pandemic, epidemic or natural disaster that limits or prevents on-site study visits, alternative 
methods of providing continuing care may be implemented by the Investigator as the situation 
dictates. If allowable by a local health authority, national and local regulations and depending 
on operational capabilities, phone calls, virtual contacts (e.g., tele consultation) or visits by site 
staff/ off-site healthcare professional(s) staff to the participant´s home, can replace certain 
protocol assessments, for the duration of the disruption until it is safe for the participant to visit 
the site again. If the Investigator delegates tasks to an off-site healthcare professional, the 
Investigator must ensure the individual(s) is/are qualified and appropriately trained to perform 
assigned duties. The Investigator must oversee their conduct and remain responsible for the 
evaluation of the data collected.
Please refer to the assessment schedule Table 1-4 to understand which assessments have to be 
carried out in what order. This is especially critical for days on when the OFC is carried out: 
(e.g., Cellular biomarker blood draw has to be done before SPT). Please refer to Table 4-2 for 
the assessment schedule specific to the participants administering study treatment at home.
Administration of study drug has to be done before the OFC. There must be a minimum of 1
hour between study drug administration and OFC.
Please make sure the order of assessments is respected consistently.

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Table 1-4
Assessment Schedule
Period
Extension-Treatment1 Treatment
Visit Name
SCRN/Day 1
WK
4
WK
8
WK
12
WK
16
WK
20
WK
24
WK
28
WK
32
WK
36
WK
40
WK
44
WK
48
WK 52-OFC
WK
56
WK
60
WK
64
WK
68
WK
72
WK
76
Weeks
1
4
8
12
16
20
24
28
32
36
40
44
48
52
56
60
64
68
72
76
Days
1
28
56
84
112 140 168 196 224 252 280 308 336 364
392 420 448 476 504 532
Informed consent
X
Inclusion / Exclusion criteria
X
Demography/Medical history X
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications, 
therapies, procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PRO Completion Reminder
S
Patient reported outcomes 
(PROs)
X
approx. 10 days 
before and 3 
days after the 
OFC
Physical Examination
S
S
S
S
Electrocardiogram (ECG)
*
X
Body Weight
X
X
Body Height 
*
S
Vital Signs
*
X
X
X
X
X
X
X
X
Spirometry in co-morbid 
asthma only
X
X
Urine pregnancy test
*
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
Serum Pregnancy test 
X2
Chemistry & Hematology
*
X
X
X
Urinalysis dipstick
*
S
S
Stool Sample (ova & 
parasitic test) by local lab 
*

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Period
Extension-Treatment1 Treatment
Visit Name
SCRN/Day 1
WK
4
WK
8
WK
12
WK
16
WK
20
WK
24
WK
28
WK
32
WK
36
WK
40
WK
44
WK
48
WK 52-OFC
WK
56
WK
60
WK
64
WK
68
WK
72
WK
76
Weeks
1
4
8
12
16
20
24
28
32
36
40
44
48
52
56
60
64
68
72
76
Days
1
28
56
84
112 140 168 196 224 252 280 308 336 364
392 420 448 476 504 532
Safety Phone Call3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Skin Prick Test4
*
X
X
X
Contact IRT (on-site visit)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Treatment 
Administration5,6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Treatment 
Accountability
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
Providing rescue 
medication, counseling, 
training & accountability
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
OL-OFC
X7
X8
X
X9
X8
Study disposition 
X
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Period
Treatment
Visit Name
WK
80
WK
84
WK
88
WK
92
WK
96
WK
100
WK 104-OFC
WK
108
WK
112
WK
116
WK
120
WK
124
WK
128
WK
132
WK
136
WK140 WK
144
WK
148
WK
152
WK 156-OFC
Weeks
80
84
88
92
96
100
104
108
112
116
120
124
128
132
136
140
144
148
152
156
Days
560 588 616 644 672 700
728
756
784
812
840
868
896
924
952
980
1008 1036 1064 1092
Informed consent
Inclusion / Exclusion criteria
Demography/ Medical 
history
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant medications, 
therapies, procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
PRO Completion Reminder
S
S
Patient reported outcomes 
(PROs)
approx. 10 
days before 
and 3 days 
after the OFC
approx. 10 
days before 
and 3 days 
after the OFC
Physical Examination
S
S
S
Electrocardiogram (ECG)
X
X
Body Weight
X
X
Body Height 
S
S
Vital Signs
X
X
X
Spirometry in co-morbid 
asthma only
X
X
Urine pregnancy test
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
Serum Pregnancy test 
Clinical Chemistry & 
Hematology
X
X
X
Urinalysis dipstick
S
S
Stool Sample (ova & 
parasitic test) by local lab 

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Period
Treatment
Visit Name
WK
80
WK
84
WK
88
WK
92
WK
96
WK
100
WK 104-OFC
WK
108
WK
112
WK
116
WK
120
WK
124
WK
128
WK
132
WK
136
WK140 WK
144
WK
148
WK
152
WK 156-OFC
Weeks
80
84
88
92
96
100
104
108
112
116
120
124
128
132
136
140
144
148
152
156
Days
560 588 616 644 672 700
728
756
784
812
840
868
896
924
952
980
1008 1036 1064 1092
Safety Phone Call3
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Skin Prick Test4
X
X
X
Contact IRT (on-site visit)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Treatment 
Administration5,6
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Treatment 
Accountability
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
Providing rescue medication, 
counseling, training & 
accountability
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
OL-OFC
X
X9
X8
X
Study disposition 
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Period
Follow-up
Visit Name
WK 160
WK 164
WK 168
EoS/PSD
Weeks
160
164
168
172
Days
1120
1148
1176
1204
Informed consent
Inclusion / Exclusion criteria
Demography/ Medical history
Adverse Events
X
X
X
X
Concomitant medications, 
therapies, procedures
X
X
X
X
PRO Completion Reminder
Patient reported outcomes 
(PROs)
Physical Examination
S
Electrocardiogram (ECG)
X
Body Weight
Body Height 
Vital Signs
X
Spirometry in co-morbid 
asthma only
Urine pregnancy test
Serum Pregnancy test 
Clinical Chemistry & 
Hematology
X
Urinalysis dipstick
S
Stool Sample (ova & parasitic 
test) by local lab 
S
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Period
Follow-up
Visit Name
WK 160
WK 164
WK 168
EoS/PSD
Weeks
160
164
168
172
Days
1120
1148
1176
1204
Safety Phone Call3
Skin Prick Test4
X
Contact IRT (on-site visit)
Study Treatment 
Administration5,6
Study Treatment 
Accountability
Providing rescue medication, 
counseling, training & 
accountability
S
S
S
S
OL-OFC
Study disposition 
X
X Assessment to be recorded in the clinical database or received electronically from a vendor
S Assessment to be recorded in the source documentation only
1 * Assessments collected at last visit of core study
2 Serum pregnancy test to be done at day 1 visit and thereafter, only in case the Urine pregnancy test is positive, then this assessment must be performed at site.
3 Only for MR participants when not attending site for SPT, OFC or blood collection
4 Please check the medications prior to skin prick test. 
5 Depending on the responder status, participants may not receive study treatment at every visit. If participant is a Maximum Responder, they will conditionally 
discontinue treatment until the next scheduled OFC for Maximum Responders.
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Period
Follow-up
Visit Name
WK 160
WK 164
WK 168
EoS/PSD
Weeks
160
164
168
172
Days
1120
1148
1176
1204
6 For MR participants defined by previous OFC which have changed responder status (no longer MR), the study treatment should be administered at least 24-hours after 
OFC.
7 Only for participants transitioning from Study CQGE031G12301 who were MR at DBPCFC at EoT
8 Ad hoc OL-OFC visits based on the SPT at Weeks 24, 76, 128 (scheduled time points) or prior to Week 104 and/or 156 (unscheduled time points) to allow the 
Investigator to check the level of desensitization. Investigator may conduct ad hoc OL-OFC in case of positive (or shift from prior assessment) SPT. The same (SPT 
followed by OL-OFC) is allowed in case of suspected allergic event during the extended wash out. The results of the ad hoc OL-OFC might lead to the resumption of 
study treatment (same dose as in the core study or in the previous year) for patients currently undergoing conditional discontinuation.
9 Ad hoc OL-OFC visit for patients who meet the definition of MR at weeks 52 and 104 and have completed a 16-week wash-out period to determine if the study 
treatment should be restarted.

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2
Introduction
In the last years, food allergy is rising worldwide affecting people of all ages and nations, with 
an increase in prevalence and costs associated with the disease making it an emerging 
population health priority (Gupta et al 2013, Gupta et al 2019, Warren et al 2020). Recent data 
demonstrate that between one-third and one-half of food allergy patients, including adults, are 
likely to be allergic to more than one food (Gupta et al 2019). Among food types, peanut, milk 
and egg represent a high prevalence of food allergens and the ingestion of even small quantities 
of the these allergens may lead to a severe and potentially life-threatening allergic reaction 
(Savage et al 2003, Fair Health White Paper 2017).
The National Institute of Health (NIH) Food Allergy Expert Panel defines food allergy as a 
specific IgE-mediated adverse reaction to a given food (Boyce et al 2011). A slightly broader 
definition by the European Academy of Allergy and Clinical Immunology (EAACI) regards 
food allergy as an immune mediated adverse reaction to food involving specific IgE-mediated, 
cell-mediated, or combined IgE and cellular mechanisms (Muraro et al 2014).
The underlying pathogenesis of food allergy involves an immunologic mechanism in which IgE 
is synthesized in response to allergen exposure and binds to high affinity receptors for IgE 
(FcεRI receptors) via its Fc region on the surface membranes of mast cells and basophils 
(Sampson et al 2006). Cross-linking of receptor-bound IgE molecules occurs on re-exposure to 
the allergen and results in cell activation and mediator release (Peavy, Metcalfe 2008). IgE also 
contributes to the intensity of the reaction by enhancing the expression of FcεRI on mast cells 
and basophils. Mast cells and basophils play an important role in initiating and amplifying the 
acute allergic response through the release of preformed chemical mediators of inflammation, 
as well as newly generated mediators leading to the characteristic symptoms of allergic reaction 
and anaphylaxis (Vadas et al 2008).
The diagnosis of food allergy begins with the clinical history of immediate allergic symptom(s) 
after intake of food allergen(s) together with either a combination of skin prick tests (SPT) 
and/or specific IgE (sIgE). However the predictive rate of this varies ranging from 50% to 
100%. Therefore oral food challenge (OFC) which is the current gold standard is required to 
confirm the diagnosis of food allergy. Because of the potential of outgrowing a food allergy, 
re-evaluation of tolerance to the food by OFC might be needed and the interval of OFC is 
dependent on the food allergen, e.g., every 6 – 12 months in milk and egg and every 2 years in 
peanut (Muraro et al 2014).
Currently the standard of care for food allergy is limited to strict avoidance of the inciting 
food(s), rescue medication in case of unintentional exposure, and community wide interventions 
for schools (i.e., peanut free classrooms) and restaurants (i.e., ingredient alerts) 
(Jones, Burks 2017). Nevertheless, accidental exposures of food-sensitive individuals to the 
very antigen they are striving to avoid are frequent. For example, 58% of young children with 
clinical peanut hypersensitivity followed for up to 5 years experienced adverse reactions from 
accidental peanut exposure despite best efforts at allergen avoidance (Vander Leek et al 2000).
Recently, a peanut oral immunotherapy (OIT) (Vickery et al 2018) was approved by Food and 
Drug Administration (FDA) to mitigate allergic reactions during accidental exposure to peanuts 

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(Jan-2020) and by European Medicines Agency (EMA) for the treatment of peanut allergy 
(Dec-2020). However, this treatment is not fundamentally changing the unmet medical need in 
this space, as it is only targeting one allergen; it is indicated only for a subset of age groups and 
might not be suitable for all peanut allergic patients.
2.1
Study rationale
This is a multi-center, double-blind, 3-year, extension study with a 16 week follow-up period 
which is designed to establish ligelizumab’s long-term safety, and explore its long-term 
efficacy, in participants with food allergy who have completed the Phase III studies with 
ligelizumab in food allergy including (but not limited to) Study CQGE031G12301 (peanut 
allergy). This protocol is designed as a basket extension study, open to the participants from 
multiple planned Phase III “core” studies in addition to the Study CQGE031G12301. Of note, 
the present protocol is dedicated to include only peanut allergic patients from study 
CQGE031G12301. Future amendments will be submitted for approval to update study 
features, if needed, before the extension study CQGE031G12303B is opened to 
participants from future core studies other than study CQGE031G12301.
This study will generate data that should provide guidance relative to the long-term (chronic) 
use of ligelizumab in food allergic patients in terms of safety, efficacy, pharmacodynamics 
(PD), biomarkers, quality of life (QoL), and potential discontinuation from treatment. Indeed 
some of the important clinical points that this study will explore focus on:
x
Longer-term (>1y) sustainability of ligelizumab efficacy
x
x
Alignment with international guidelines (Muraro et al 2014) that recommend regular 
assessment of the underlying phenotype including the option to discontinue treatment 
(further supported by the analysis of the operating characteristics of several biomarkers that 
strengthen the decision making)
x
A subset of participants will also be offered administration of study treatment at home either 
by the participant him/herself (self-administration) or by parent/caregiver following 
appropriate training at three visits in the clinic.
In addition, the 3-year treatment period of this study will also fulfill the Novartis commitment 
to provide post trial access (PTA) to the participants who have completed ligelizumab Phase III 
studies in food allergy. In case ligelizumab is not commercially available in some countries at 
completion of this study, every effort will be made to continue provision of ligelizumab for the 
participants in those countries that in the opinion of the investigator might still benefit from 
longer treatment with ligelizumab.
2.2
Background
A recognized medical need in developing novel therapies for food allergy is forthcoming due 
to
rising 
prevalence 
of 
food 
allergy 
(including 
allergy 
to 
multiple 
foods) 
(Sicherer, Sampson 2018), and the limited therapeutic options leading to potentially lifelong 
disease burden in many patients. Following the identification of IgE as a principal player in 
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allergic diseases and the advent of monoclonal antibody (mAb) technology in the 1970s, mAbs 
to IgE have been developed that recognized the IgE binding site that binds the FcεRI receptor 
(Baniyash et al 1988).
These antibodies were identified based on their ability to inhibit the IgE–FcεRI interaction and 
to block the activation of IgE sensitized cells. It was recognized that these antibodies would 
thereby prevent the initiation of the allergic cascade through both the FcεRI and FcεRII (CD23) 
pathways. Such antibodies are termed “non-triggering” in contrast to conventional anti-IgE 
antibodies that cross-link cell bound IgE thus precipitating degranulation and even systemic 
anaphylaxis. Based on this strategy, the development of monoclonal anti-IgE treatment (TNX-
901) was shown to be able to significantly increase the threshold of sensitivity to peanut antigen, 
as assessed by an oral food challenge (OFC), in a dose dependent manner, to levels that should 
translate into at least partial protection against most unintended ingestions of peanut 
(Leung et al 2003).
Ligelizumab (QGE031) is a humanized IgG-type mAb that binds to human IgE ([Investigator 
Brochure, 18 Ed.]).
 
Ligelizumab does not mediate IgE receptor cross-linking and 
consequent histamine release (i.e., is non-activating). The rationale for its development reflects 
the evidence that a more efficient suppression of IgE than that achieved by omalizumab may be 
associated with improved clinical outcomes in IgE mediated diseases (Lowe et al 2009,
Ankerst et al 2010).
During the treatment with ligelizumab, circulating IgE is rapidly bound by the anti-IgE antibody 
and becomes inaccessible to IgE receptors on mast cells and basophils. Ligelizumab has 
demonstrated dose and time-dependent suppression of free IgE, reduction in basophil FcεRI 
expression and thus basophil surface IgE, and inhibition of skin prick test (SPT) responses to 
allergens, superior in extent and duration to those observed with omalizumab (Arm et al 2014,
Gauvreau et al 2016). Omalizumab is the only humanized anti-IgE antibody currently 
commercially available. Multiple studies suggest it has efficacy in food allergy in reducing the 
risk of peanut-induced allergic reactions in a double-blind-placebo-controlled food challenge 
(Sampson et al 2011, Savage et al 2012, Schneider et al 2013).
IgE is necessary for the enhanced expression of the FcεRI seen in atopic participants 
(MacGlashan et al 1997, MacGlashan et al 1998), and thus a decrease in FcεRI expression on 
circulating basophils accompanies ligelizumab treatment. Other potentially beneficial effects 
from anti-IgE therapy include decreased IgE production (Lowe, Renard 2011), reduced IgE and 
B cell numbers (Ota et al 2009) and reduced cytokine production by T cells (Coyle et al 1996).
Consequently, in the ongoing Study CQGE031G12301 (peanut allergy) and planned other food 
allergy study(ies), it is hypothesized that the very high level of suppression elicited by 
ligelizumab will result in a very efficient desensitization against the food allergens hence 
ensuring protection against food allergic reactions by decreasing the sensitivity to those 
allergens.
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2.3
Benefit/Risk assessment
The risks to participants in this study will be minimized by compliance with all of the eligibility 
criteria including completion of the core study and by close clinical monitoring including 
periodic review of data by an independent Data Monitoring Committee (DMC). To further 
minimize risk the study will be conducted in selected highly specialized centers involved in the 
phase III studies with ligelizumab in food allergy, who have great experience in the treatment 
of food allergies and in conducting oral food challenges.
Mechanism of action
The key mechanism underlying IgE mediated food allergy is the cross-linking of allergen 
specific IgE molecules bound to the high affinity receptor (FcεRI) on effector cells like 
basophils and mast cells, which triggers the release of inflammatory mediators responsible for 
the final clinical presentation. Therefore, IgE suppression is expected to decrease the probability 
of food allergens to initiate such an acute inflammatory response. Multiple studies have 
supported 
this 
therapeutic 
approach 
(Leung et al 2003,
Savage et al 2012,
Schneider et al 2013).
 hence supporting 
its use in food allergy and anticipating a therapeutic benefit (basophil/ mast cell desensitization).
Available safety data
As of the cut-off date of 22-Jan-2022, approximately 2976 participants have been exposed to 
ligelizumab across completed, prematurely terminated and ongoing studies, covering the 
indications of Chronic Spontaneous Urticaria (CSU), asthma, atopic dermatitis, and bullous 
pemphigoid. The longest exposure to ligelizumab is approximately 17 months. The following 
doses have been tested in the clinical programs: 12 mg, 24 mg, 36 mg, 72 mg, 120 mg, 180 mg 
and 240 mg subcutaneous (SC) q2w/q4w, 280 mg SC q2w and 240 mg and 420 mg SC single 
dose.
In the CSU Phase II program, 291 participants have been exposed to ligelizumab at doses up to 
72 mg, 120 mg and 240 mg SC q4w ([Investigator Brochure, 18 Ed.]). In addition, in the most 
recent CSU Phase III program (Studies CQGE031C2302 and CQGE031C2303), a total of 2150 
patients (including 93 adolescent patients) received ligelizumab 72 mg, 120 mg, omalizumab 
300 mg and placebo. Overall, no apparent dose-dependent safety signals (except for a trend in 
injection site reactions, which can be managed in the clinic) have been observed to date, 
although the number of participants studied is relatively small, in line with the development 
phase of the CSU program. In the asthma clinical study CQGE031B2201, there appeared to be 
a dose dependency of injection site reactions between ligelizumab high dose group (28.6% of 
199 participants, pooled from ligelizumab 240 mg SC q2w, 240 mg SC q4w, 180 mg SC q2w, 
and 120 mg SC q2w treatment arms) and ligelizumab low dose group (12.5% of 40 participants, 
pooled from ligelizumab 36 mg SC q2w and 12 mg SC q2w treatment arms), which was 
comparable to omalizumab (14.5% of 131 participants). The incidence of injection site 
reactions was higher among all the active treatment groups compared to that of placebo (5.2% 
of 96 participants). Similarly, in the CSU dose-finding study (CQGE031C2201), the overall 
safety profile was comparable between different doses of ligelizumab (24 mg, 72 mg and 240 
mg SC q4w or 120 mg single dose), omalizumab and placebo. The exceptions were adverse 
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events (AEs) related to injection site reactions, where a possible trend of dose dependency for 
ligelizumab was observed. All cases of injection site reactions (except 1 case of medical 
significance), regardless of treatment group or doses, were non-serious, mild to moderate in 
severity, reversible, and did not lead to discontinuation of study treatment.
Regarding serious adverse events (SAEs), the incidence of SAEs was comparable between 
participants treated with ligelizumab and those receiving placebo in both asthma and CSU 
studies. There has been no dose dependency in SAEs observed among participants treated with 
different doses of ligelizumab (Study CQGE031B2201 in asthma and Study CQGE031C2201 
in CSU).
Biologics can cause hypersensitivity reactions. Ligelizumab is in the same drug class as 
omalizumab, for which the risk and characteristics of anaphylaxis are well-characterized and 
are theoretically applicable to the study treatment. 
 In all completed studies to date, four cases have 
been positively adjudicated as anaphylaxis: three in asthma studies and one in a CSU study. 
Two out of four cases occurred after restart of ligelizumab. Investigators should therefore be 
alert to the occurrence of hypersensitivity events, including anaphylaxis, following the 
administration of ligelizumab and be familiar with the information and guidance provided.
IgE is an antibody that may have an adaptive role in immunity to parasitosis, particularly 
helminthic infections. Blocking the interaction of IgE and its receptors with ligelizumab may 
therefore alter immunologic responsiveness to parasites. For this reason, monitoring for the 
occurrence of infection and response to therapy is recommended for participants who receive 
ligelizumab and are at high risk of geohelminth infection. There is insufficient data to determine 
the length of monitoring required for geohelminth infections after stopping ligelizumab. 
However, it is expected that ligelizumab will not interfere with a polyclonal reaction triggered 
by exposure to parasites. The resulting increase of IgE production would decrease, through 
target-mediated disposition, the half-life of ligelizumab hence restoring normal IgE levels more 
rapidly. 
In the most recent CSU Phase III program (Studies CQGE031C2302 and CQGE031C2303), a 
total of 2150 patients (including 93 adolescent patients) received ligelizumab 72 mg, 120 mg, 
omalizumab 300 mg and placebo. Ligelizumab was well-tolerated, consistent with previous 
studies.
Therefore, based on the cumulative data available across all clinical studies in different 
populations for ligelizumab, the current evidence suggests that ligelizumab is safe and well 
tolerated and thus appropriate for further development.
The non-clinical safety evaluation for ligelizumab supports the clinical treatment of children 
down to the age of 2 years. In a juvenile toxicity study that was conducted in 6-month-old
cynomolgus monkeys there was no evidence to suggest that ligelizumab will have a different 
mode of action or will be cleared differently in pediatric versus adult participants. No new or 
unexpected safety signals were identified in the Study CQGE031C2201 (CSU dose-ranging) 
study in adults and in the Study CQGE031C2202 (CSU) in adolescents
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Study treatments
Transition from the core study:
There are two groups of core study participants that will be enrolled in the extension study:
x
from the Study CQGE031G12301, after completion of post treatment follow-up period of 
the core study (Figure 1-1)
x
from other future study(ies) after completion of the treatment period of a core study 
(Figure 1-1).
For both groups, participants have to maintain strict avoidance of the inciting food(s) and 
symptomatic (rescue) treatment of allergic symptoms (e.g., epinephrine, antihistamines, 
corticosteroids and saline bolus) should be available to reduce the risk to the participants.
As the risk of anaphylaxis related to the reintroduction of treatment after the interruption has 
not yet been characterized in this population, participants who transition to the extension study 
at the end of the follow-up period of core Study CQGE031G12301 must remain on-site for 
observation for a period of 2 hour (h) post-dose for the first three visits after drug administration 
following the reintroduction of study treatment.
Conditional discontinuation of study treatment in Maximum Responder Participants
This study is exploring long-term treatment strategies based on the efficacy levels (responder 
status) achieved by the participants at the end of the core study and during the extension study.
For the participants who meet the definition of Maximum Responder (MR, see below), the 
interruption of the study drug will be commenced, and participants will remain off-treatment 
unless the sensitivity to the food returns based on the results of the OFC (no longer MR). The 
rest of the participants continue the study treatment throughout the extension study.
x
Definition of Maximum Responder (MR)
x
No dose limiting symptom (DLS) at any dose including the maximum dose of OFC, 
of peanut protein.
A maximum responder (MR) status might reflect either an optimal effect of the investigational 
drug and/or a change in the underlying phenotype (loss of disease either following natural 
history or through potential disease modification by the study treatment). In this case, 
conditional termination will be carried out to assess whether further treatment is still required, 
as determined by the following OL-OFC. In case of sustained un-responsiveness, the 
participants will remain in the study without treatment to keep monitoring his/her condition 
through selected biomarkers. In case of resurgence of the phenotype, participants will be 
brought back to the study drug dose that led to MR status
x
Conditional discontinuation of study treatment is only for the participants who showed 
maximum response by DBPCFC (EOT of the core study)/OL-OFC (the extension study). 
Conditional discontinuation will be allowed only once in any given participant through the 
entire study. After start of the interruption of study treatment, participants will be allowed 
to re-start treatment in case of clinical (allergic reactions to food) or other findings (e.g., 
SPT) suggesting of resurgence of the allergic phenotype. Following these indications, the 
investigator proposes an optional OL-OFC to more formally re-assess the level of reactivity 
of the participants and decide on reintroduction of study treatment. As the risk of 
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anaphylaxis related to the reintroduction of treatment after the washout period has not yet 
been characterized in this population, participants who will restart study treatment must 
remain on-site for observation for a period of 2 h post-dose for the first three drug 
administrations.
Study treatment administration at home:
Ligelizumab will be administered using a single-use, disposable combination product, intended 
for the subcutaneous (SC) application of a fixed dose of ligelizumab. The combination product 
consists of a pre-filled syringe (PFS) pre-assembled within a needle safety device (NSD) from 
the Becton Dickinson UltraSafe Passive™NSD X100L Plus series (hereinafter called QGE031 
PFS in X100L Plus). The design and technical features of the QGE031 PFS in X100L Plus 
combination product are based on well-established technology and are in line with the current 
common treatment technology for self-injection drugs. It is permitted for adult participants to 
do self-administration with QGE031 PFS in X100L Plus while children and adolescent 
participants must be administered QGE031 PFS in X100L Plus by parent/caregiver. 
Parent/caregiver can also administer QGE031 PFS in X100L Plus to adult participants, if 
necessary.
Eligibility criteria
The participants in this basket extension study should have successfully completed a core study. 
Therefore, the participants who developed any condition meeting discontinuation criteria during 
a core study, AND/OR participants who developed any clinically significant medical condition 
listed in the exclusion criteria of a core study judged by the investigator, must not be rolled over 
into this study.
Oral food challenge (OFC)
In this extension study, open-label OFC will be conducted.
OFC is a standard procedure to diagnose the food allergy. OFC has inherent risks including 
acute allergic reactions with potentially life-threatening anaphylaxis, exacerbation of atopic 
dermatitis, and emotional distress; particularly in older children, teenagers, and adults who may 
become more anxious about their food allergy (Feng, Kim 2019). To further limit the risks 
associated with this procedure the following measures have been applied:
x
Only highly trained experts representing experienced facilities that are equipped and have 
the expertise to handle potentially life-threatening hypersensitivity events can participate in 
this study.
x
A Data Monitoring Committee (DMC) will monitor the safety in this study including events 
incurred during OFC. The DMC will review the data generated externally and 
independently of Novartis according to the DMC charter. Based on the safety implications 
of the data, the DMC may recommend modification or termination of the study.
Female participants
Female participants of childbearing potential (defined as all females physiologically capable of 
becoming pregnant which includes female pediatric participants who are menarchal or who 

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become menarchal during the study) must be informed that taking the study treatment may 
involve unknown risks to the fetus, if pregnancy were to occur during the study, they must agree 
that in order to participate in the study they are required to adhere to the basic (acceptable 
effective) contraception requirements outlined in the exclusion criteria. If there is any question 
that the participant will not reliably comply, they should not be entered or continue in the study. 
Female children participants who became older than 12 years during the core studies should be 
reassessed in regards to contraception requirements established in the respective exclusion 
criterion.
It is important to be sensitive in introducing this issue, as understanding and comprehension of 
puberty, sexual activity, pregnancy and contraception is influenced by age, as well as factors 
such as precocity, socio(educational) economic and familial background. These discussions 
with the patient and her parents/caregivers are therefore best performed by investigators familiar 
with the pediatric subject and her family and should be guided by requirements of the local 
regulatory authorities. These discussions should take into account the socio-economic, cultural 
factors and religious beliefs of the adolescent participant and her family. The investigator should 
also discuss the management of the pregnancy test results with the patient and her 
parents/caregivers. The privacy of the patient should be considered in accordance with the local 
law and ethics.
COVID-19
With respect to the ongoing COVID-19 pandemic, IgE suppression is not expected to increase 
the risk of infection. (Teach et al 2015). For participants, vaccination against COVID-19 
(inactivated, non-live vaccine) is permitted during the study but not administered within 48 h 
prior to the study visit (Table 6-5).
Risk and benefit evaluation for adolescents (12-17 yrs) and children (6-11 yrs)
IgE mediated food allergy affects all ages and upon exposure to the allergen(s) it can result in 
considerable morbidity and life-threatening anaphylaxis.
The standard of care consists of allergen avoidance and the treatment for allergic reaction. There 
is an unmet medical need for therapeutic interventions. As the pathophysiology of IgE mediated 
food allergy is not affected by the age, IgE suppression is expected to provide a benefit in 
younger patients as well.
The evaluations specified in this study (including SPT and OL-OFC) are clinically accepted 
and widely used in clinical research that investigates food allergy in adults, adolescents and 
children. The experience with the OFC is very much established in children where most 
publications have developed (Nowak-Wegrzyn et al 2009). Blood volume for laboratory 
evaluations for children 6-11 years is in line with The Hospital for Sick Children (SickKids) 
Research Ethics Board Blood Sampling Guidelines (Howie 2011), (Section 8.4.4).
In conclusion, IgE mediated food allergy is a potentially life-threatening condition affecting all 
age groups for which current standard of care still mainly consists of allergen avoidance and 
epinephrine use upon accidental exposure. IgE suppression directly addresses the underlying 
pathophysiology and data from other anti-IgE monoclonal antibodies support this mechanism. 
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generating exposures that have been well characterized clinically and that accordingly have not 
been associated with dose-related safety concerns. Residual risks due to hypersensitivity 
reactions related to the investigational drug or to the oral food challenge have been addressed 
by a series of measures that include (but are not limited to) clear eligibility criteria, study 
treatment discontinuation rules, limitations of key risk factors (uncontrolled asthma, selected 
medications), a highly standardized food challenge protocol (and material), adjudication 
committees for events of special interests, and the implementation of a DMC.
3
Objectives, endpoints, and estimands
Table 3-1
Objectives and related endpoints
Objective(s)
Endpoint(s)
Primary objective(s)
Endpoint(s) for primary objective(s)
● To evaluate the long-term safety and tolerability of 
ligelizumab in participants with food allergy
● Overall incidence and exposure-adjusted 
occurrence rates of treatment-emergent AEs and 
SAEs
Secondary objective(s)
Endpoint(s) for secondary objective(s)
● To describe the long-term efficacy of ligelizumab as 
measured by the tolerance of an allergen food protein 
during an open-label OFC at scheduled timepoints
● Proportion of participants tolerating a single dose 
of ≥ 600 mg of peanut protein without dose-limiting 
symptoms during an open label OFC at scheduled 
timepoints
● To assess the safety and tolerability of ligelizumab in 
all participants who administered study treatment at 
home by self-administration or parent/caregiver
● Overall incidence and exposure-adjusted 
occurrence rates of treatment emergent-AEs and 
SAEs
● To assess the long-term impact of ligelizumab on the 
health-related quality of life (HRQoL) of patients with 
food allergy
● Summaries of total scores in the FAQLQ, FAIM, 
and SF-36v2 by age and responder (participants 
and/or parent/caregiver) at scheduled timepoints
Exploratory objective(s)
Endpoint(s) for exploratory objective(s)
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Objective(s)
Endpoint(s)
3.1
Primary estimands
Not Applicable.
3.2
Secondary estimands
Not Applicable.
4
Study design
4.1
Overall design
This is a multi-center, double-blind, 3-year, extension study with a 16 week follow-up period, 
which is designed to establish ligelizumab’s long-term safety and tolerability, and to explore its 
long-term efficacy in participants with food allergy who have completed Phase III studies with 
ligelizumab in food allergy. Novartis conducts this study as a basket extension study, which 
enables the participants from planned multiple Phase III “core” studies to roll over to this 
extension study once the participants have completed predefined minimal requirements 
(completion of a treatment or a follow-up period, see Section 4.1.1) of a “core” study and agreed 
to consent to participate in this study.
Participants will receive ligelizumab treatment allocated in the core study, except for MR 
participants performing conditional discontinuation of study treatment. 
A subset of participants will also be offered administration of study treatment at home either by 
the participant him/herself (self-administration) or by parent/caregiver following training at 
three visits at the clinic (Section 4.1.3).
4.1.1
Transition from the core study
Transition from Study CQGE031G12301 at the end of follow-up period:
The participants will transition into the extension study after completion of the follow-up period 
(washout) in the core study (see Figure 4-1).
 The end of follow-up
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visit of the core study will also become the first visit of this extension study (Screening/Day 1). 
Some of the assessments at EOFu of the core study will form the baseline at Screening/Day 1 
of the extension study. The informed consent must be obtained before initiating any study 
related activities of the extension study at Screening/Day 1.
Transition from other study(ies) at end of treatment period of core study (no 
post treatment follow-up period):
The participants will transition into the extension study after completion of the study treatment 
period of the core study. The first visit of the extension study (Screening/Day 1) will be 
scheduled four weeks after the end of the treatment visit of the core study and participants will 
consent on Day 1 of the extension study.
Figure 4-1
Study design including transition from the core study
DBPCFC: Double Blind Placebo Controlled OFC, OL-OFC: Open Label Oral Food Challenge, MR: Maximum 
Responder, EOT: End of Treatment, EOFu: End of Follow-Up.
Should operational reasons prevent timely scheduling of Day 1 during transition from any core 
study, participants may still be eligible to be included in the extension study based on a case by 
case assessment as long as all inclusion and exclusion criteria are fulfilled at the time of the 
assessment.
The duration of period elapsed since the end of treatment in the core study until Day 1 of study 
CQGE031G12303B will be derived from collected CRF data.
4.1.2
Conditional discontinuation of study treatment in Maximum 
Responder Participants
In some participants the study treatment might no longer be required because of disease 
modification by ligelizumab and/or by simply outgrowing the allergy (Savage, Johns 2015). 
Therefore, conditional discontinuation of study drug is started in all participants whose 
responder status is MR (maximum responder) as shown in Figure 4-2 (for the participants from 

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Study CQGE031G12301 who transition at EOFu of the core study and Figure 4-3 for the 
participants from other study(ies) who transition at End of Treatment (EoT) of the core study).
For the participants who meet the definition of Maximum Responder (MR, see below), the 
interruption of the study drug will be commenced and participants will continue off-treatment, 
unless the sensitivity to the food returns based on the OFC (no longer MR).
The detailed process of the treatment for the MR participants is summarized in the 
Section 4.1.2.1.
This conditional discontinuation of study drug will be controlled by Interactive Response 
Technology (IRT) which informs the investigator about the treatment/off-treatment in each 
participant based on the outcome from DBPCFC (at EoT of a core study) / OL-OFC (in the 
extension study).
Table 4-1
Maximum Responder during the DBPCFC/OL-OFC
Responder status
Dose of allergen (food)
Maximum Responder (MR)
Maximum Tolerated Dose (MTD) of 
● Participant WITHOUT Dose Limiting Symptom (DLS) at any dose 
including the maximum dose, 
DBPCFC will be conducted at the end of treatment period of the core study
OL-OFC will be conducted during the extension study
4.1.2.1
Detailed process for study treatment and conditional discontinuation 
of study treatment in MR participants
The conditional discontinuation of study treatment can only be performed once. In other words, 
if following study treatment interruption, the MR responder status is not confirmed at the next 
OFC, the study treatment should be restarted and continue until the end of treatment (Week 
156), (unless participants are permanently discontinued from study treatment earlier see 
Section 7.1).
The processes of study treatment and conditional discontinuation of study treatment in the first, 
second and third year of the extension study are summarized below.
The participants who transition from Study CQGE031G12301 (Figure 4-2)
First year
x
Participants who meet the definition of MR by DBPCFC at EoT of the core study and 
transition from the core study at EOFu will perform an OL-OFC at Screening/Day 1:
x
If the participants still meet the definition of MR by OL-OFC on Day 1, the off-
treatment period will be continued until Week 52.
x
If the participants are no longer MR by OL-OFC on Day 1, the study treatment will be 
started (same dose as in the core study) after at least 24 h from completion of the OL-
OFC on Day 1. If participants become MR again at a later timepoint, no interruption of 
treatment is commenced. The study treatment will continue until the EoT of the 
extension study (Week 156).
x
NOTE: The Investigator is able to check the level of desensitization by SPT at Week 24 
(scheduled time point) and can decide to conduct ad hoc OL-OFC in case of positive (or 
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shift from prior assessment) SPT. The same (SPT followed by OL-OFC) is allowed in case 
of suspected allergic event during the off-treatment period. The results of the ad hoc OL-
OFC may lead to the resumption of study treatment (same dose as in the core study) after at 
least 24 h from completion of the OL-OFC and treatment will continue until the EoT of the 
extension study (Week 156).
x
Participants who did not meet the definition of MR by DBPCFC at EoT of the core study 
and transition from the core study at EOFu will not perform an OL-OFC at Screening/Day 
1. Study treatment will be started (same dose as in the core study) until week 52.
Second year:
x
For participants who have been off-treatment in the first year until Week 52 (i.e., MR 
participants since Day 1):
1. If the participants still meet the definition of MR by OL-OFC at Week 52, the off-
treatment period will continue up to Week 104 of the extension study.
2. If the participants are no longer MR by OL-OFC at Week 52, the study treatment will 
be re-started (same dose as in the core study) after at least 24 h from completion of the 
OL-OFC. If the participants become MR again at a later timepoint, no interruption of
treatment is commenced. The study treatment will continue until the EoT of the 
extension study (Week 156).
x
NOTE: The Investigator is able to check the level of desensitization by SPT at Week 76 
(scheduled time point) and can decide to conduct an ad hoc OL-OFC in case of positive (or 
shift from prior assessment) SPT. The same (SPT followed by OL-OFC) is allowed in case 
of a suspected allergic event during the off-treatment period. The results of the ad hoc OL-
OFC may lead to the resumption of study treatment (at the same dose as in the core study) 
after at least 24 h from completion of the OL-OFC, and treatment will continue until the 
EoT of the extension study (Week 156).
x
For participants who have received the study treatment in the first year until Week 52 (i.e., 
participants who did not have OL-OFC at Screening/Day 1):
1. If the participants meet the definition of MR by OL-OFC at Week 52, the interruption 
of study treatment (off-treatment) will be initiated.
x
If the participants still meet the definition of MR by OL-OFC after 16 weeks of 
study treatment interruption (at Week 68), the interruption (off-treatment) period 
will be extended up to Week 104.
x
If the participants are no longer MR by OL-OFC after 16 weeks of study treatment 
interruption (at Week 68), the study treatment will be re-started (same dose as in 
previous year) after at least 24 h from completion of the OL-OFC. If the 
participants become MR again at a later timepoint, no interruption of treatment is 
commenced. The study treatment will continue until the EoT of the extension study 
(Week 156).
x
NOTE: The investigator is able to check the level of desensitization by SPT at an 
unscheduled time point prior to Week 104, and the results of the ad hoc OL-OFC may lead 
to the resumption of study treatment (same dose as taken previously) after at least 24 h from 
completion of the OL-OFC and treatment will continue until the EoT of the extension study 
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x
If the participants do not meet the definition of MR by OL-OFC at Week 52, the study 
treatment will be continued (same dose as in the previous year) until Week 104.
Third year:
x
For participants who have been off-treatment in the second year until Week 104:
1. If the participants meet the definition of MR by OL-OFC at Week 104, the off-treatment 
period will continue up to Week 156.
2. If the participants are no longer MR by OL-OFC at Week 104, the study treatment will 
be re-started (same dose as in previous year) after at least 24 h from completion of the 
OL-OFC. The study treatment will continue until the EoT of the extension study (Week 
156).
x
NOTE: The Investigator is able to check the level of desensitization by SPT at Week 128 
(scheduled time point) and can decide to conduct an ad hoc OL-OFC in case of positive (or 
shift from prior assessment) SPT. The same (SPT followed by OL-OFC) is allowed in case 
of suspected allergic event during the off-treatment period. The results of the ad hoc OL-
OFC may lead to the resumption of study treatment (same dose as in core or previous year) 
after at least 24 h from completion of the OL-OFC, and treatment will continue until the 
EoT of the extension study (Week 156).
x
For participants who have received the study treatment continuously until Week 104:
x
If the participants meet the definition of MR by OL-OFC at Week 104, the off-treatment 
period will be initiated (unless the participants met MR earlier and already had 
treatment interruption, in which case treatment continues with the same dose).
1. If the participants still meet the definition of MR by OL-OFC after 16 weeks of 
study treatment interruption (at Week 120), the off-treatment period will be 
extended up to Week 156.
2. If the participants are no longer MR by OL-OFC after 16 weeks of study treatment 
interruption (at Week 120), the study treatment will be re-started (same dose as in 
previous year) after at least 24 h from completion of the OL-OFC. The study 
treatment will continue until the EoT of the extension study (Week 156).
x
NOTE: The investigator is able to check the level of desensitization by SPT at an 
unscheduled time point prior to Week 104, and the results of the ad hoc OL-OFC may lead 
to the resumption of study treatment (same dose as previously) after at least 24 h from
completion of the OL-OFC, and treatment will continue until the EoT of the extension study 
(Week 156).
x
If the participants do not meet the definition of MR by OL-OFC at Week 104, the study 
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Figure 4-2
Conditional discontinuation for the MR participants who transition 
from Study CQGE031G12301
The participants who transition from other study(ies) (Figure 4-3)
First year:
No conditional discontinuation is allowed even if the participants meet the definition of MR by 
DBPCFC at EoT of the core study. The first visit of the extension study (Screening/Day 1) will 
be scheduled 4 weeks after EoT of the core study, and the study treatment will be continued 
(same dose as in the core study) for the first year of extension study.
Second year:
x
If the participants meet the definition of MR by OL-OFC at Week 52 of the extension study, 
the interruption of study treatment (off-treatment) will be initiated:
1. If the participants still meet the definition of MR by OL-OFC after 16 weeks of study 
treatment interruption (at Week 68), the interruption (off-treatment period) will be 
extended up to Week 104.
2. If the participants are no longer MR by OL-OFC after 16 weeks of interruption (at 
Week 68), the study treatment will be re-started (same dose as in previous year) after 
at least 24 h from completion of the OL-OFC. If the participants become MR again at 
a later timepoint, no interruption is commenced. The study treatment will continue until 
the EoT of the extension study (Week 156).
x
NOTE: The Investigator is able to check the level of desensitization by SPT at an 
unscheduled time point prior to Week 104 and can decide to conduct ad hoc OL-OFC in 
case of positive (or shift from prior assessment) SPT. The same (SPT followed by OL-OFC) 
is allowed in case of suspected allergic event during the off-treatment period. The results of 
the ad hoc OL-OFC may lead to the resumption of study treatment (same dose as in the core 

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study) after at least 24 h from completion of the OL-OFC, and treatment will continue until 
the EoT of the extension study (Week 156).
x
If the participants do not meet the definition of MR by OL-OFC at Week 52, the study 
treatment will be continued (same dose as in previous year) until Week 104.
Third year:
x
For participants who have been off-treatment in the second year until Week 104
1. If the participants meet the definition of MR by OL-OFC at Week 104, the off-treatment 
period will continue up to Week 156.
2. If the participants are no longer MR by OL-OFC at Week 104, the study treatment will 
be re-started (same dose as in previous year) after at least 24 h from completion of the 
OL-OFC. The study treatment will continue until the EoT of the extension study (Week 
156).
x
NOTE: The Investigator is able to check the level of desensitization by SPT at an 
unscheduled time point prior to Week 156 and can decide to conduct ad hoc OL-OFC in 
case of positive (or shift from prior assessment) SPT. The same (SPT followed by OL-OFC) 
is allowed in case of suspected allergic event during the off-treatment period. The results of 
the ad hoc OL-OFC may lead to the resumption of study treatment (same dose as in previous 
year) after at least 24 h from completion of the OL-OFC. The study treatment will continue 
until the EoT of the extension study (Week 156).
x
For participants who have received the study treatment continuously until Week 104
x
If the participants meet the definition of MR by OL-OFC at Week 104, the interruption 
of study treatment (off-treatment period) will be initiated.
1. If the participants still meet the definition of MR by OL-OFC after 16 weeks of the 
study treatment interruption (at Week 120), the interruption (off-treatment period) 
will be extended up to Week 156.
2. If the participants are no longer MR by OL-OFC after 16 weeks of interruption (at 
Week 120), the study treatment will be re-started (same dose as in previous year) 
after at least 24 h from completion of the OL-OFC. The study treatment will 
continue until the EoT of the extension study (Week 156).
x
NOTE: The Investigator is able to check the level of desensitization by SPT at an 
unscheduled time point prior to Week 156 and can decide to conduct ad hoc OL-OFC in 
case of positive (or shift from prior assessment) SPT. The same (SPT followed by OL-OFC) 
is allowed in case of suspected allergic event during the extended washout. The results of 
the ad hoc OL-OFC may lead to the resumption of study treatment (same dose as in previous 
year) after at least 24 h from completion of the OL-OFC. The study treatment will continue 
until the EoT of the extension study (Week 156).
x
If the participants do not meet the definition of MR by OL-OFC at Week 104, the study 
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Figure 4-3
Conditional discontinuation for the MR participants who transition 
from other studies
4.1.3
Administration of study treatment at home
This study will also assess the safety of ligelizumab administered in the home setting by either 
the adult participant (self-administration) or parent/caregiver (in case of adolescent and 
children) during the extension study.
There are several potential benefits associated with home administration of medication 
(including self-administration) (Richardson et al 2014):
x
it reduces the burden and cost on patients, caregivers, healthcare professionals and the 
overall health care systems
x
it improves patients’ knowledge about the disease and medication, and increases sense of 
responsibility and independence of managing their condition
x
the sense of ownership may decrease the chance of medication errors
x
a better compliance leading to improved effectiveness of disease management
Participants or parents/caregivers are asked if they are interested in administration in the home 
setting. Participants or parents/caregivers will undergo required training at three clinic visits 
under supervision of the site personnel. After undergoing 3 consecutive training visits at the 
site, participants will then be provided with medication kits to permit their first administration 
at home. The administration of study treatment at home may take any of the following forms 
(see Section 6.2.3):
x
adult participant: appropriately trained and aware of the responsibility relating to the 
injection procedure of the study treatment;
x
adult participant's parent/caregiver: in case an adult participant is not able to perform the 
procedure, an adult participant's parent/caregiver appropriately trained by the site can take 
responsibility for the injection procedure of the study treatment to the adult participant;
x
adolescent (12 - 17 years)/child (6 - 11 years) participant: adult parent/caregiver 
appropriately trained by site, takes complete responsibility for the injection procedure of the 
study treatment to the adolescent/child participant.

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The importance of study treatment administration at home in this Phase III extension study in 
addition to the benefits detailed above, will:
x
allow evaluation of the safety of administration at home of ligelizumab in the treatment for 
food allergy over a long period of time
x
reduce the burden required for participants to make on-site visits, with all the associated 
benefits described above.
Administration at home will be commenced in the first year of the study in the non MR 
participants who transition at the end of follow-up period of the core study as well as non MR 
participants who transition at the end of treatment period of other studies. For those participants, 
who started the home-administration in year 1 and continue the treatment in years 2 and 3, they 
will be able to continue the administration at home for the remainder of the study.
It will be possible to start the administration at home also in the second/third year for 
participants no longer MR at the end of first/second year or in participants who express the 
interest in administration at home after the first/second year of treatment.
The detailed process of administration at home is written in Section 6.2.3.
Rationale for starting points of administration at home
To allow sufficient training to participant or parent/caregiver on the use of pre-filled syringe 
(PFS), training will commence at Week 16 and thereafter take place at Weeks 20 and 24. The 
first self-administration outside the clinic could start at Week 28 of the extension treatment 
period. However, if the investigator feels it is in the best interest of the participant, they can 
defer the training until a suitable timepoint, in agreement with the site staff and participant. In 
addition, before start of training, the clinical data of the participants who will be administered 
at home should be frozen in the electronic data capture (EDC) system (confirmed by Novartis 
Data Management) so that the blinded data of the core study can be protected despite potential 
un-blinding occurring during the administration at home without "unblinded" administrator.
For participants starting the administration at home after the first/second year the training visits 
will be:
x
after first year: training at weeks 56, 60 and 64 with the first administration at home on 
week 68
x
after second year: training at weeks 108, 112 and 116 with the first administration at home 
on week 120

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Table 4-2
Home Administration Assessment Schedule
Period
Screening-
Treatment
Treatment
Visit Name
SCRN/Day 
1
WK
4
WK
8
WK
12
WK
16
WK
20
WK
24
WK
28
WK
32
WK
36
WK
40
WK
44
WK
48
WK 52-
OFC
WK
56
WK
60
WK
64
WK
68
WK
72
WK
76
Week
1
4
8
12
16
20
24
28
32
36
40
44
48
52
56
60
64
68
72
76
Days
1
28
56
84
112
140
168
196
224
252
280
308
336
364
392
420
448
476
504
532
Informed consent 
X
Inclusion / Exclusion 
criteria
X
Demography/ 
Medical history
X
Adverse Events
*
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant 
medications, 
therapies, 
procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient reported 
outcomes (PROs)
X
approx. 
10 days 
before / 
3 days 
after 
OFC
Physical Examination
S
S
S
S
ECG
*
X
Body Weight
X
X
Body Height
*
S
Vital Signs
*
X
X
X
X
X
X
X
X
Spirometry in co-
morbid asthma only
X
X
Urine pregnancy test2
*
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S

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Period
Screening-
Treatment
Treatment
Visit Name
SCRN/Day 
1
WK
4
WK
8
WK
12
WK
16
WK
20
WK
24
WK
28
WK
32
WK
36
WK
40
WK
44
WK
48
WK 52-
OFC
WK
56
WK
60
WK
64
WK
68
WK
72
WK
76
Week
1
4
8
12
16
20
24
28
32
36
40
44
48
52
56
60
64
68
72
76
Days
1
28
56
84
112
140
168
196
224
252
280
308
336
364
392
420
448
476
504
532
Serum Pregnancy 
test 
X3
Chemistry & 
Hematology
*
X
X
X
Urinalysis dipstick
*
S
S
Stool Sample (ova & 
parasitic test) by local 
lab
*
Skin Prick Test4
*
X
X
X
Contact IRT 
X
X
X
X
X
Home Administration 
Training
X
X
X
X5
X5
X5
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Period
Screening-
Treatment
Treatment
Visit Name
SCRN/Day 
1
WK
4
WK
8
WK
12
WK
16
WK
20
WK
24
WK
28
WK
32
WK
36
WK
40
WK
44
WK
48
WK 52-
OFC
WK
56
WK
60
WK
64
WK
68
WK
72
WK
76
Week
1
4
8
12
16
20
24
28
32
36
40
44
48
52
56
60
64
68
72
76
Days
1
28
56
84
112
140
168
196
224
252
280
308
336
364
392
420
448
476
504
532
Study Drug 
Administration (on-
site)
X
X
X
X
X
X
X
X
X6
X
X
Dispense Home 
Administration 
Dosing Log
S
Study Drug 
Administration (at 
home)
X
X
X
X
X
X
X
X
X
Safety Phone Call (at 
home)
X
X
X
X
X
X
X
X
X
Study Drug 
Accountability
S
S
S
S
S
S
S
S
S
S
S
Review Home 
Administration 
Dosing Log
X
X
X
X
Providing rescue 
medication, 
counseling, training & 
accountability
S
S
S
S
S
S
S
S
S
S
S
OL-OFC
X7
X
Study disposition
X
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Period
Treatment Period
Visit Name
WK
80
WK
84
WK
88
WK
92
WK
96
WK
100
WK
104-
OFC
WK
108
WK
112
WK
116
WK
120
WK
124
WK
128
WK
132
WK
136
WK140
WK
144
WK
148
WK
152
WK
156-
OFC
Weeks
80
84
88
92
96
100
104
108
112
116
120
124
128
132
136
140
144
148
152
156
Days
560
588
616
644
672
700
728
756
784
812
840
868
896
924
952
980
1008
1036
1064
1092
Informed consent 
Inclusion / 
Exclusion criteria
Demography/ 
Medical history
Adverse Events
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Concomitant 
medications, 
therapies, 
procedures
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Patient reported 
outcomes (PROs)
approx. 
10
days 
before 
and 3 
days 
after 
the 
OFC
approx. 
10 days 
before 
and 3 
days 
after the 
OFC
Physical 
Examination
S
S
S
Electrocardiogram 
(ECG)
X
X
Body Weight
X
X
Body Height
S
S
Vital Signs
X
X
X

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Period
Treatment Period
Visit Name
WK
80
WK
84
WK
88
WK
92
WK
96
WK
100
WK
104-
OFC
WK
108
WK
112
WK
116
WK
120
WK
124
WK
128
WK
132
WK
136
WK140
WK
144
WK
148
WK
152
WK
156-
OFC
Weeks
80
84
88
92
96
100
104
108
112
116
120
124
128
132
136
140
144
148
152
156
Days
560
588
616
644
672
700
728
756
784
812
840
868
896
924
952
980
1008
1036
1064
1092
Spirometry in co-
morbid asthma 
only
X
X
Urine pregnancy 
test2
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
S
Serum Pregnancy 
test
Clinical Chemistry 
& Hematology
X
X
X
Urinalysis dipstick
S
S
Stool Sample (ova 
& parasitic test) 
by local lab
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Period
Treatment Period
Visit Name
WK
80
WK
84
WK
88
WK
92
WK
96
WK
100
WK
104-
OFC
WK
108
WK
112
WK
116
WK
120
WK
124
WK
128
WK
132
WK
136
WK140
WK
144
WK
148
WK
152
WK
156-
OFC
Weeks
80
84
88
92
96
100
104
108
112
116
120
124
128
132
136
140
144
148
152
156
Days
560
588
616
644
672
700
728
756
784
812
840
868
896
924
952
980
1008
1036
1064
1092
Skin Prick Test4
X
X
X
Contact IRT 
X
X
X
X
X
X
Home 
Administration 
Training
X5
X5
X5
Study Treatment 
Administration
(on-site)
X
X6
X
X
X
X6
Dispense Home 
Administration 
Dosing Log
Study Treatment 
Administration (at 
home)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Safety Phone Call 
(at home)
X
X
X
X
X
X
X
X
X
X
X
X
X
X
Study Treatment 
Accountability
S
S
S
S
S
S
Review Home 
Administration 
Dosing Log
X
X
X
X
X
X
Providing rescue 
medication, 
counseling, 
training & 
accountability
S
S
S
S
S
S
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Period
Treatment Period
Visit Name
WK
80
WK
84
WK
88
WK
92
WK
96
WK
100
WK
104-
OFC
WK
108
WK
112
WK
116
WK
120
WK
124
WK
128
WK
132
WK
136
WK140
WK
144
WK
148
WK
152
WK
156-
OFC
Weeks
80
84
88
92
96
100
104
108
112
116
120
124
128
132
136
140
144
148
152
156
Days
560
588
616
644
672
700
728
756
784
812
840
868
896
924
952
980
1008
1036
1064
1092
OL-OFC
X
X
Study disposition
Period
Follow-up
Visit Name
WK 160
WK 164
WK 168
EOS/PSD
Weeks
160
164
168
172
Days
1120
1148
1176
1204
Informed consent 
Inclusion / Exclusion criteria
Demography/ Medical history
Adverse Events
X
X
X
X
Concomitant medications, 
therapies, procedures
X
X
X
X
Patient reported outcomes (PROs)
Physical Examination
S
Electrocardiogram (ECG)
X
Body Weight
Body Height
Vital Signs
X
Spirometry in co-morbid asthma 
only
Urine pregnancy test2
CCI

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Period
Follow-up
Visit Name
WK 160
WK 164
WK 168
EOS/PSD
Weeks
160
164
168
172
Days
1120
1148
1176
1204
Serum Pregnancy test
Clinical Chemistry & Hematology
X
Urinalysis dipstick
S
Stool Sample (ova & parasitic test) 
by local lab
S
Skin Prick Test4
X
Contact IRT 
Home Administration Training
Study Treatment Administration
(on-site)
Dispense Home Administration 
Dosing Log
Study Treatment Administration (at 
home)
Safety Phone Call (at home)
X
X
CCI

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Period
Follow-up
Visit Name
WK 160
WK 164
WK 168
EOS/PSD
Weeks
160
164
168
172
Days
1120
1148
1176
1204
Study Treatment Accountability
Review Home Administration 
Dosing Log
Providing rescue medication, 
counseling, training & 
accountability
S
S
S
S
OL-OFC
Study disposition
X
X Assessment to be recorded in the clinical database or received electronically from a vendor.
S Assessment to be recorded in the source documentation only.
1 * Assessments collected at last visit of Core Study.
2 Urine pregnancy tests will be provided to all self-administration patients who are women of child-bearing age, for home use. In the event that the home test is positive, 
the patient must call site and arrange for an immediate visit to perform a serum pregnancy test.
3 Serum pregnancy test to be done at day 1 visit and thereafter, only in case the Urine pregnancy test is positive, then this assessment must be performed at site.
4 Please check the medications prior to skin prick test.
5 This training only applies to patients who started treatment after the first/second year of treatment.
6 Study drug must be administered on site at least one hour before OFC.
7 Only for participants transitioning from CORE Study QGE031G12301 who were MR at DBPCFC at EoT.
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4.2
Scientific rationale for study design
The current standard of care for the patients with food allergy is strict avoidance of the inciting 
food(s) and symptomatic treatment of allergic symptoms (e.g., epinephrine and antihistamines). 
Anti-IgE medication is not currently indicated for the prevention of allergic events in patients 
with food allergy and there is limited knowledge and experience in the clinical research setting.
Ligelizumab is an investigational treatment aimed at the protection of patients against allergic 
reactions due to an accidental exposure to the allergen(s). Therefore it is important to understand 
the long-term safety and efficacy of ligelizumab in food allergy.
Table 4-3
Rationale for study design
Study Design Aspect
Rationale
Overall
This Phase III extension study of ligelizumab is designed to build on ongoing study 
data by further evaluating long-term (3 years) safety and efficacy in the participants 
who have completed the treatment period of the ligelizumab food allergy Phase III 
studies.
Randomization
No randomization for the study treatment will occur.
The participants in this extension study will receive the same dose as in the core 
studies.
Blinding
The purpose of double-blind design in this extension study is to protect the blinding 
of data in the core studies.
The participants from the core studies will not be unblinded in order to enter this 
extension study.
Population
The participants who have completed the treatment period of the core studies are 
considered suitable to continue the study treatment in this extension study from an 
ethical and safety perspective.
Duration of study 
periods
Long-term safety data of ligelizumab is critical in food allergy patients and to assess 
the sustainability of the effect of the clinical response.
As described in the earlier section, the exploration of efficacy in ligelizumab based 
on the “response driven approach” is planned in this study (e.g., conditional 
discontinuation of study treatment in the maximum responder participants).
The long-term safety and efficacy data of ligelizumab could support the practicing 
physician's treatment plan for the management of food allergy patients with 
ligelizumab.
In addition, the extended duration of treatment in this study will support Novartis' 
commitment to Post Trial Access (PTA) for participants completing Phase III studies.
Administration at home
There are several potential benefits associated with home self-administration of 
medication (Richardson et al 2014):
In this study protocol, the term "administration at home" refers to the process by 
which the study treatment is administered to the participants in the home setting 
outside of the clinic.
Self-administration is allowed only for adult participants. If adult participants do not 
want to self-administer, the parent/caregiver of adult participants can administer the 
study treatment to the adult participants.
In the participants aged 6 to 17 years, self-administration is NOT allowed, and 
trained parent/caregiver will administer study treatment to the participants aged 6 to 
17 years.
The data collected will be used to evaluate the safety of ligelizumab in the 
participants who express interest in the administration of the study treatment at 
home and fulfill the suitability requirements.

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4.2.1
Participant input into design
There was engagement with a Food Allergy Advocacy group composed of parents and 
parents/caregivers.
They provided some feedback on study design. They welcomed the opportunity for the 
administration of the study treatment at home. In addition they welcomed frequent contact at 
home by their study doctor or study site personnel during administration at home in case they 
had questions or anything to report. Participants and parents/caregivers also expressed interest 
in having a dosing log to record their medication.
4.3
Justification for dose
The same ligelizumab doses and regimen used in the core studies will be evaluated in this 
extension study. 
4.3.1
Rationale for choice of background therapy
Strict avoidance of the inciting food(s) and symptomatic treatment of allergic symptoms with 
epinephrine, anti-histamines and corticosteroids represent the current standard of care. No other 
anti-IgE medication is currently indicated for the prevention of allergic events in food allergy 
patients. In addition, oral immunotherapy is currently only approved for peanut, in a limited age 
group and in few geographies.
4.4
Rationale for choice of control drugs (comparator/placebo) or 
combination drugs
Not applicable.
4.5
Rationale for public health emergency mitigation procedures
In the event of a public health emergency as declared by local or regional authorities (i.e., 
pandemic, epidemic or natural disaster), mitigation procedures may be required to ensure 
participant safety and trial integrity and are listed in relevant sections of the study protocol. At 
the investigator’s direction based on benefit-risk considerations of the participant’s clinical 
condition, qualifying participants may be offered the option to have certain clinical trial 
procedures according to SoA performed at a remote location such as the patient’s home, in the 
event that the patient cannot attend site during a public health emergency. Notification of the 
public health emergency should be discussed with Novartis prior to implementation of 
mitigation procedures, and permitted/approved by local or regional health authorities and ethics 
committees as appropriate.
4.6
Purpose and timing of interim analyses/design adaptations
One or more interim analyses may be conducted to support decision-making in relation to the 
current clinical study, the future of the sponsor's clinical development plan, or the long-term 
safety and efficacy of ligelizumab. Additional details will be provided in the Statistical Analysis 
Plan (SAP).
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4.7
End of study definition
The end of the study is defined as the date of the last visit (end of follow-up period) of the last 
participant according to the Section 1.3 Schedule of Activities globally.
Study completion in each participant is defined as when the participant finishes their last study 
visit (end of follow-up period) and any repeat assessments associated with this visit have been 
documented and followed-up appropriately by the Investigator.
5
Study population
This study population will consist of participants who have successfully completed ligelizumab 
Phase III studies in food allergy including (but not limited to) Study CQGE031G12301 (peanut 
allergy). Considering the estimated drop out rate of the core study (15%) and a limited 
alternative standard of care in the patients with food allergy, the expectation is that 
approximately 550 participants will enroll in this extension study. This extension study will be 
opened for participants joining from additional ligelizumab food allergy studies.
In line with each core study this extension study will involve male and female participants who 
have successfully completed a core study and are eligible to continue to the extension study.
5.1
Inclusion criteria
Participants eligible for inclusion in this study must meet all of the following criteria:
1. Signed informed consent form (ICF) and assent form (where applicable) obtained from the 
participant/legal representative before study participation. If a minor participant reaches the 
age of legal majority (as defined by local law), they must be re-consented at the next study 
visit.
2. Participants have completed the treatment period in any ligelizumab’s Phase III studies in 
food allergy (e.g., CQGE031G12301). Please refer to the Section 4.1 for the timing of
transition.
3. Participants who are willing to adhere to the study visits and procedures, including receiving 
injections (study treatment) and participating in the OL-OFC.
4. Participants who are willing to continue avoiding exposure to allergens (per core study) and 
any other foods they are allergic to throughout this study.
5. Participants who are able to safely continue into the study as judged by the investigator
5.2
Exclusion criteria
Participants meeting any of the following criteria are not eligible for inclusion in this study.
1. Development of a severe or life-threatening episode of an allergic reaction that requires 
intubation and/or Intensive Care Unit (ICU) admission during a core study.
2. Development of a serious adverse event which is suspected to be related to the study 
treatment judged by the investigator during a core study.
3. Development of uncontrolled asthma during a core study that could compromise the safety 
of the participants as judged by the investigator.

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4. Development of clinically significant cardiovascular, neurological, and/or psychiatric 
conditions during a core study that could interfere with or compromise the safety of the 
participants, interfere with evaluation or interpretation of the study results or preclude 
completion of the study as judged by the investigator.
5. Development of malignancy of any organ system during a core study (except for basal cell 
carcinoma; actinic keratoses; Bowen disease (carcinoma in situ) that has been treated, with 
no evidence of recurrence in the past 12 weeks and carcinoma in situ of the cervix or non-
invasive malignant colon polyps that have been removed).
6. Development of clinically significant abnormality in laboratory testing, ECG, and/or vital 
signs during a core study that could interfere with or compromise the safety of the 
participants, interfere with evaluation or interpretation of the study results or preclude 
completion of the study as judged by the investigator.
7. Use of prohibited medications (Table 6-5) or medication that is not allowed under certain 
conditions (Table 6-4).
8. Participants who discontinued from a core study, irrespective of the reason.
9. Participants who failed to comply with the protocol requirements and procedures during a 
core study, and in the Investigator’s opinion should not participate in this extension study.
10. Platelets <75,000/uL at EoT of core study.
11. Pregnant or nursing (lactating) females.
12. Sexually active children below the age of 12 years.
13. Female participants, incl. adolescent females of 12 to less than 18 years of age at the entry 
of the extension study, of childbearing potential, defined as all women physiologically 
capable of becoming pregnant, unless they are using basic (acceptable effective) methods 
of contraception for the duration of the study (appr. 4 months, e.g., 5 half-lives, after the 
last dose of ligelizumab). Basic (acceptable and effective) contraception methods include:
x
Total abstinence (when this is in line with the preferred and usual lifestyle of the 
participant). Periodic abstinence (e.g., calendar, ovulation, symptothermal, post-ovulation 
methods) and withdrawal are not acceptable effective methods of contraception.
x
Female sterilization (surgical bilateral oophorectomy with or without hysterectomy), total 
hysterectomy or bilateral tubal ligation at least six weeks before taking Investigational 
Medicinal Product (IMP). In the case of oophorectomy alone, only when the reproductive 
status of the woman has been confirmed by follow-up hormone level assessment.
x
Male sterilization (at least 6 months prior to screening). For female participants, the 
vasectomized male partner should be confirmed as their sole partner.
x
Barrier methods of contraception: condom or occlusive cap (e.g., diaphragm or 
cervical/vault caps). For UK: with spermicidal foam/gel/film/cream/vaginal suppository.
x
Use of oral (estrogen and progesterone) injected or implanted hormonal methods of 
contraception or other forms of hormonal contraception that have comparable efficacy 
(failure rate <1%), for example, hormone vaginal ring or transdermal hormone 
contraception or placement of an intrauterine device (IUD) or intrauterine system (IUS)
Female participants using oral contraception should be on a stable dose for a minimum of 3 
months prior to taking study treatment. Female participants are considered post-menopausal 
and not of child-bearing potential if they have had 12 months of natural (spontaneous) 

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amenorrhea with an appropriate clinical profile (e.g., age-appropriate history of vasomotor 
symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total 
hysterectomy, or bilateral tubal ligation at least six weeks ago. In the case of oophorectomy 
alone, only when the reproductive status of the female has been confirmed by follow-up 
hormone level assessment is she considered not of child-bearing potential. If local regulations 
deviate from the contraception methods listed above to prevent pregnancy, local regulations 
apply and will be described in the ICF/assent.
5.3
Screen failures
A screen failure occurs when a participant who consents to participate in the clinical study is 
subsequently found to be ineligible and therefore will not receive the study treatment. A 
minimal set of screen failure information is required to ensure transparent reporting of screen 
failure participants to meet the Consolidated Standards of Reporting Trials (CONSORT) 
publishing requirements and to respond to queries from regulatory authorities. Minimal 
information includes demography, screen failure details, eligibility criteria, and any serious 
adverse event (SAE).
5.3.1
Participant numbering
Each participant is identified in the study by a Participant Number (Participant No.), that is 
assigned when the participant is enrolled for screening and is retained for the participant 
throughout his/her participation in the trial. The participant number will be different to the core 
study participant number. The Participant No. consists of the Site Number (Site No.) (as 
assigned by Novartis to the investigative site) with a sequential participant number suffixed to 
it, so that each participant’s participation is numbered uniquely across the entire database. Upon 
signing the informed consent form, the participant is assigned to the next sequential Participant 
No. available. In order to link between the core study and the extension study, the participants 
No. of the core study will be recorded in the respective CRF in the extension study.
6
Study treatment(s) and concomitant therapy
6.1
Study treatment(s)
During the extension study, participants will be receiving the same dose of ligelizumab as 
assigned at randomization in the core studies. There is a possibility to discontinue the study 
treatment in the MR participants who successfully continue “conditional discontinuation of 
study treatment” (Section 4.1.2).
Study treatment includes investigational drug ligelizumab (120 mg/ml) and placebo, all 
participants will receive 2 injections, so participants on 120mg/ml will also receive a matching 
placebo injection to protect the study blinding. Study treatment must be administered by an 
independent drug administrator or unblinded pharmacist at the study site who is not involved 
in any of the study assessments. The procedure for the administration at home is summarized 
in the Section 6.2.3.1. The administration will be performed by the participant and/or 
parent/caregiver in the case of a child/adolescent at home.

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Novartis will supply ligelizumab (QGE031) 120 mg per 1 mL as prefilled syringe (PFS) pre-
assembled within a needle safety device (NSD) from the Becton Dickinson UltraSafe Passive™
NSD X100L Plus series and placebo.
Table 6-1
Investigational and control drug
Investigational/ 
Control Drug
(Name and 
Strength)
Treatment Form or 
Pharmaceutical 
Dosage Form
Route of 
Administration
Presentation
Sponsor (global or 
local)
QGE031 120mg/1ml
Solution for injection
SC
Double-blind
Sponsor (global)
QGE031 
Placebo/1ml*
Solution for injection
SC
Double Blind
Sponsor (global)
* Placebo will only be administered alongside the 120mg/1ml dose to protect the dose blinding. There is no 
placebo arm
6.1.1
Bio-batch retention samples
Not applicable.
6.1.2
Additional study treatments
No other treatment beyond investigational drug and control drug are included in this trial.
6.1.3
Treatment arms/group
Participants will be assigned to one of the following two treatment arms depending on responder 
status in the previous study/ies) as per Section 4.1.1 and Section 4.1.2.
Each participant (except the MR participants undergoing conditional discontinuation) will 
receive two (2) SC injections every four weeks starting at Day 1.
1. ligelizumab 240 mg arm: 2 injections of 1.0 mL ligelizumab
2. ligelizumab 120 mg arm: 1 injection of 1.0 mL ligelizumab and 1 injection of 1.0 mL 
placebo
The assignment to receive 120 mg or 240 mg ligelizumab will be determined by treatment 
received during the previous study(ies). All participants (except the MR participants undergoing 
conditional discontinuation (Section 4.1.2)) will receive study drug (ligelizumab). There is no 
placebo arm. 
Of note, based on CQGE031G12301 core study results, Novartis will assess the need to switch 
participants in CQGE031G12303B to a different dose than the one they were receiving in 
CQGE031G12301.
6.1.4
Treatment duration
The planned duration of treatment is up to 156 weeks (three years). There is a possibility of a 
shorter treatment period than three years in the MR participants who successfully continue 
“conditional discontinuation of study treatment” (Section 4.1.2).
6.1.5
Medical devices
Not applicable.

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6.2
Preparation, handling, storage, and accountability
Each study site will be supplied with study treatment in packaging as described under Table 6-1
Investigational and control drugs section.
A unique medication number is printed on the study medication label.
An independent unblinded administrator will identify the study treatment kits to dispense to the 
participant by contacting the Interactive Response Technology (IRT) and obtaining the 
medication number(s). The study treatment has a 2-part label (base plus peel-off label). 
Immediately before preparing study treatment, the unblinded pharmacist (or authorized 
delegate) will detach the outer part of the label from the packaging and affix it to the source 
document.
The guidelines for the storage, preparation and administration of study treatment are described 
in the pharmacy manual (provided separately).
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e., pandemic, epidemic or natural disaster, that limits or prevents on-site study visits, delivery 
of IMP directly to a participant's home may be permitted for the participants or 
parents/caregivers who have completed the training of injection (if allowed by local or regional 
health authorities and ethics committees, as appropriate) or in the event the Investigator has 
decided that an on-site visit by the participant is no longer appropriate or possible. The dispatch 
of IMP from the site to the participant’s home remains under the accountability of the 
Investigator. Each shipment/provisioning will be for either 12 or 16 weeks as per IRT supply. 
In this case, regular phone calls or virtual contacts (every 4 weeks or more frequently if needed) 
will occur between the site and the participant for instructional purposes, safety monitoring, 
investigation of any adverse events, ensuring participant continues to benefit from treatment, 
and discussion of the participant's health status until the participant can resume visits at the 
study site.
6.2.1
Handling of study treatment
Study treatment must be received by a designated person at the study site, handled and stored 
safely and properly and kept in a secured location to which only the Investigator and designated 
site personnel have access. Upon receipt, all study treatment must be stored according to the 
instructions specified on the labels and in the Investigator's Brochure.
Clinical supplies are to be dispensed only in accordance with the protocol. Technical complaints 
are to be reported to the respective Novartis Country Organization Quality Assurance.
Medication labels will be in the local language and comply with the legal requirements of each 
country. They will include storage conditions for the study treatment but no information about 
the participant except for the medication number.
The Investigator or designated site staff (blinded or unblinded, as applicable) must maintain an 
accurate record of the shipment and dispensing of study treatment in a drug accountability log. 
Monitoring of drug accountability will be performed by field monitors during site or remote 
monitoring visits, and at the completion of the trial. The Investigator must provide 
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At the conclusion of the study, and as appropriate during the course of the study, the investigator 
will return all unused study treatment, packaging, drug labels, and a copy of the completed drug 
accountability log to the Novartis monitor or to the Novartis address provided in the investigator 
folder at each site. If study treatment is administered at home, participants will be asked to 
return all unused study treatment and packaging at the end of the study, and as appropriate 
during the course of the study or at the time of discontinuation of study treatment.
6.2.2
Handling of other treatment
All rescue medication regardless of dispensation method, must be documented in source and 
closely monitored. Participants should be reminded to bring rescue medication to all study 
visits. This applies to the following:
x
Short-acting Beta-agonist (SABA) (for participants with a documented diagnosis of 
asthma)
x
Epinephrine (e.g., EpiPen)
If rescue medication is provided at the study site it must be handled and stored according to the 
package label, kept in a secured location and dispensed only in accordance with the protocol.
The investigator must maintain an accurate record of dispensing of the above-mentioned
treatment in a drug accountability log/inventory log, and source documents. Monitoring of drug 
accountability will be performed by monitors during site visits and at the completion of the 
study. Participants will be asked to return all unused SABA and epinephrine treatments and 
packaging at the end of the study or at the time of discontinuation from the study.
Any unused epinephrine and SABA stored at the site will be disposed of according to local 
regulation.
6.2.3
Instruction for prescribing and taking study treatment
The independent study treatment administrator or unblinded pharmacist will administer the 
study treatment to the participant during the study visit without engaging in any unnecessary 
interactions that may have the potential to un-blind the participant or any of the study site 
personnel.
The subcutaneous injections can be administered in the deltoid region on the upper right and/or 
left arm, the lower stomach area (but not the area 5 cm around the belly button) and/or into the 
front of the right and/or left thigh, or the abdomen as preferred by the participant and/or site. 
Do not inject into skin that is tender, bruised, red, scaly, hard or into areas with scars or stretch 
marks. Each injection must be administered at a different site (e.g., right arm and left thigh). 
The guidelines for the preparation and administration of study treatment are described in the 
pharmacy manual (provided separately).
Participants who join the study after the follow-up period of the core study will remain on site 
for observation for a period of 2 h post-dose for the first three drug administration visits, this 
equates to week 0, 4 and 8. Thereafter a 30 minute wait will suffice. Participants who join the 
extension study from continuous treatment will only require a 30 minute wait at the site. The 2-
hour observation period for the first three drug administrations must be observed in all instances 
where study treatment is reintroduced after a washout/interruption period (e.g., restart of the 

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study treatment after the conditional discontinuation of study treatment because of no longer 
MR).
At Week 52, 104, and 156 there must be a minimum of 1 hour between administration of 
study treatment and performing the OFC (Section 8.3.1). Study treatment must be given 
before the OFC.
In case the study treatment should be started based on the responder driven approach (Previous 
MR is no longer MR after off-treatment, Section 4.1.2), the time interval between OFC and 
restart of study treatment must be a minimum of 24 h.
These observation periods follow the recommendation suggested by the National Heart, Lung, 
and Blood Institute and by the American Academy of Allergy, Asthma & Immunology and the 
American College of Allergy, Asthma and Immunology Executive Committees Joint Task 
Force (Cox et al 2007) for the anti-IgE therapy currently available (omalizumab). As described 
in the Investigator Brochure, the site needs to ensure readiness to react to anaphylactic events 
(e.g., immediate availability of qualified staff, available injectable epinephrine, antihistamine, 
corticosteroids, intravenous supplies, oxygen, an oral airway, Ambu bag and the ability to 
transport a participant rapidly to an emergency department/hospital).
The dose for individual participants will be the same within a treatment arm and will be 
managed by the IRT.
All study treatment dosages prescribed and dispensed to the participant and all dosing errors or 
missed administrations during the study must be recorded on the appropriate electronic case 
report form (eCRF).
All kits of study treatment assigned by the IRT will be recorded in the IRT system. The 
investigator must promote compliance by instructing the participant to take the study treatment 
exactly as prescribed and by stating that compliance is necessary for the participant's safety and 
validity of the study. The participant must also be instructed to contact the investigator if he/she 
is unable, for any reason, to take the study treatment as prescribed.
6.2.3.1
Administration at home by participant or parent/caregiver
The study treatment should only be administered via PFS by adults. In other words, if the 
participant is below 18 years (< 18), the administration should be done by his/her 
parent/caregiver. Even an adult participant who is willing to be part of the administration at 
home BUT not comfortable with self administration, in this instance the parent/caregiver can 
be an administrator.
The participant will be given the option to start administration at home once their training is 
completed. The participants doing conditional discontinuation of study treatment won't be 
offered the opportunity of drug administration at home.
Before initiation of training visit, participants who are willing to take part in administration at 
home should be evaluated according to the below criteria. If the criteria are satisfied, then the 
Instruction For Use (IFU) Guide will be provided to the participants or caregiver who will then 
undergo training in administration of the study treatment.
The clinical eligibility criteria for administration at home of ligelizumab are below:

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x
participant/caregiver should be capable and willing to self-administer ligelizumab.
x
participant/caregiver should know how to recognize symptoms/signs of severe 
hypersensitivity reactions
For the first and second use of PFS, the injection will take place as a site staff assisted injection 
i.e., with the help of the site staff performing the injection steps. At the third use of PFS, the 
self-injection will take place under supervision however without the help of the site staff, i.e., 
the site staff only observes and does not help in performing the injection steps. The training of 
each injection, be it assisted or under supervision, will be provided individually by the site staff 
to the participant/caregiver.
Participants who administered ligelizumab at home in the first year of the extension study and 
continue into the second/third year of the study, will continue the home-administration. 
However, those participants who are unable to adhere to administration at home in the first year 
of study can then revert to clinic visits, they will subsequently be supported by the clinic to do 
home administration and training during the second/third year.
First dose of PFS: Assisted administration of study treatment
x
The site staff will show the participant how to use the PFS based on the instructions provided 
in the IFU, with emphasis on specific checks for device use evaluation.
x
Participant will be given the opportunity to raise questions if any.
x
Participant will perform the injection into an appropriate injection site of the body with the 
site staff actively assisting him/her during the injection. If the site staff observes that the 
participant is performing an action that may jeopardize the participant's safety, site staff will 
intervene to prevent any potential harm and guide/correct the participant.
Second dose of PFS: Assisted supervision of study treatment
x
Study staff should ask the participant whether they wish to be retrained prior to injection. If 
needed, site staff will retrain the participant.
x
Participant will perform the injection into the appropriate injection site of the body with the 
site staff actively assisting him/her during the injection. If the site staff observes that the 
participant is performing an action that may jeopardize the participant's safety, site staff will 
intervene to prevent any potential harm and guide/correct the participant.
Third dose of PFS: Supervised administration of study treatment
x
Participant will perform the injection into the appropriate injection site of the body 
mimicking an outside of clinic administration i.e., without the active assistance of the site 
staff but under their supervision.
x
If the site staff observes that the participant is performing an action that may jeopardize the 
participant's safety, site staff intervene to prevent any potential harm and guide/correct the 
participant.
x
The site staff will observe that the dose is administered in accordance to the steps indicated 
in the self-injection assessment list and the potential hazard assessment list as described in 
the pharmacist manual. The site staff will observe the participant actions as per the lists to 
evaluate if the participant is capable of self-administration outside of clinic.

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Thereafter, outside of clinic administrations should be done at pre-defined time points as per 
assessment schedule (Table 1-4). If self-administration is performed by a parent/caregiver, 
the parent/caregiver will then be trained as outlined above.
All participants self-administering study treatment at home should remain under observation by 
a family member or colleague, for symptoms and signals of hypersensitivity in a quiet 
environment for 30 minutes after each administration.
Participants carrying out administration outside the clinic setting will:
x
have in-clinic safety and efficacy assessments done at least at Weeks 24, 52, 76, 104, 128 
and 156 intervals
x
on site visits will take place every 12-16 weeks, to collect study treatment (2 or 3 kits), 
review dosing log and safety check
x
At the site visits, participant or parent/caregiver will be offered the opportunity to perform 
a self administration under the supervision of the study staff and to be retrained on the 
injection technique upon request or if whenever required.
x
be assessed remotely (i.e., outside of clinic) by safety phone call from the site every 4 weeks 
either on the day of study treatment administration or 1 to 3 days after, unless there is an in-
clinic visit scheduled (at Weeks 24, 52, 76, 104, 128 and 156 as per protocol).
During outside of clinic administrations, participants are expected to contact the 
investigator/site staff in case they are experiencing any AE/SAEs or have any concerns 
immediately.
At any time during the study, should a participant or parent/caregiver or investigator decide not 
to continue with administration of study treatment at home, the participant must contact the site, 
or the site staff must contact the participant, to arrange for all subsequent visits and treatments 
to be administered at the site.
6.3
Measures to minimize bias: randomization and blinding
6.3.1
Treatment assignment, randomization
No randomization will be performed in this study. Clinical trial treatment randomization codes 
are generated in the core studies and the same will be used in the extension study. The 
assignment of treatment will depend on the previous study treatment assignment during the core 
study, as well as a response driven approach.
At screening, all eligible participants will be allocated via Interactive Response Technology 
(IRT) to the treatment dose that the participant was assigned to in the core study, except in some 
scenarios described in Section 4.1.2. The Investigator or his/her delegate will contact the IRT 
after confirming that the participant fulfills all the inclusion/exclusion criteria. The IRT will 
assign the participant to a treatment and will specify a unique medication number for the 
package of investigational treatment to be dispensed to the participant. All kits of study 
treatment assigned by the IRT will be recorded in the IRT system.
MR participants will continue off-treatment or re-start study treatment (if no longer MR) during 
the study as part of "conditional discontinuation" which will be controlled by IRT.

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6.3.2
Treatment blinding
The purpose of the double-blind design in this extension study is to protect the blinding of data 
in the core studies.
Participants, investigator, study staff and the Novartis Clinical Trial Team will remain blinded 
to the identity of the treatment assignment from the time of enrollment until clinical database 
lock. Randomization data are kept strictly confidential until the time of unblinding, and will not 
be accessible by anyone else involved in the study with the following exceptions:
x
Bioanalyst
 to enable identification of samples from the ligelizumab treatment 
arms of the study to facilitate bioanalysis;
x
Specific vendors whose role in trial conduct requires their unblinding (e.g., IRT)
x
Global Clinical Supply (GCS)
x
An independent Data Monitoring Committee (DMC) if required, and the independent 
statistician & programmer supporting the DMC activities.
x
Novartis associates who are involved the analysis before final Database lock (DBL) 
described in Section 4.6
The following measures must be applied by the study site to keep the data integrity of the core 
studies in terms of the identity of the treatment:
x
As per Section 6.1, two completely identical syringes will be supplied for the ligelizumab 
120 mg (120mg and placebo) or 240 mg (120 mg x 2).
x
The study treatment must be administered by an independent drug administrator or 
unblinded pharmacist who is not involved in the performance of any of the study 
assessments.
x
Apart from the independent drug administrator or unblinded pharmacist, study site staff 
should NOT handle the Investigational Medicinal Product (IMP) and no information 
regarding the IMP should be discussed with the blinded site staff
x
An independent administrator or unblinded pharmacist will not be involved for the 
participants who are part of study treatment administration at home. Although the 
appearance of syringes (ligelizumab 120 mg, placebo) is the same, there is a potential risk 
to be unblinded by the speculation of participant or parent/caregiver. Therefore before 
start of training for the study treatment administration at home, the clinical data of the 
participants who will be administered at home should be frozen in the EDC system
(confirmed by Novartis Data Management).
For any interim analysis before final database lock (Section 9.8) a limited number of pre-
specified members of the program team from Novartis will be unblinded in a phasic manner. 
The study will be under the management of a separate blinded team, replacing pre-specified 
unblinded team members, who will be responsible for study conduct. To maintain the integrity 
of the study data, the blinded team members will not have access to any of the unblinded data.
Un-blinding will occur in the case of participant emergencies and at the conclusion of the study. 
Health authorities will be granted access to unblinded data if needed. Any participant whose 
treatment code has been broken inadvertently or for any non-emergency reason will be 
discontinued from study treatment. These participants will transition into the follow-up period 
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of the study. The investigator must maintain an accurate record of the shipment and dispensing 
of investigational treatment in a drug accountability log.
Table 6-2
Blinding level
Role
Time or Event
Treatment 
assignment 
list generated
Treatment 
allocation 
& dosing
Safety event 
(single participant 
unblinded)
Interim 
analysis
Participants
B
B
B
B
Investigator and site staff
B
B
B
B
Site staff: Pharmacy staff and IMP 
administrator
B
UI
B
B
Global Clinical Supply and Randomization 
Office
UI
UI
UI
UI
sponsor staff: CRA
B
B
B
B
Sponsor staff: Pharmacovigilance staff
B
B
UI
B
Sponsor staff: Bioanalysis 
B
UI
B
B
DMC independent statistician and 
programmer
B
UI
UI
UI
Data monitoring committee
B
UI
UI
UI
Adjudication committee
B
B
B
B
All other sponsor staff not identified above 
but defined in the charter
B
B
B
UI
B Remains blinded UI Allowed to be unblinded on individual participant level *DMC will review unblinded data.
6.3.3
Emergency breaking of assigned treatment code
Emergency code breaks must only be undertaken when it is required to in order to treat the 
participant safely.
Most often, discontinuation from study treatment and knowledge of the possible treatment 
assignments are sufficient to treat a study participant who presents with an emergency 
condition. Emergency treatment code breaks are performed using the IRT. When the
Investigator contacts the system to break a treatment code for a participant, he/she must provide 
the requested participant identifying information and confirm the necessity to break the 
treatment code for the participant. The Investigator will then receive details of the 
investigational drug treatment for the specified participant and a fax or email confirming this 
information. The system will automatically inform the Novartis monitor for the site and the 
study team that the code has been broken.
It is the Investigator’s responsibility to ensure that there is a dependable procedure in place to 
allow access to the IRT/code break cards at any time in case of emergency. The Investigator 
will provide:
x
protocol number
x
participant number
In addition, oral and written information to the participant must be provided on how to contact 
his/her backup in cases of emergency, or when he/she is unavailable, to ensure that un-blinding 
can be performed at any time.
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6.4
Study treatment compliance
Participants will receive two injections SC q4w during the treatment period. Compliance is 
assured as long as the participant attends all study visits according to the Schedule of 
Assessments (Table 1-4). For participants receiving study treatment at the site, compliance is 
assured, as study treatment must be administered by study personnel (independent study 
treatment administrator or unblinded pharmacist) via SC injection.
For administration at home by participant or parent/caregiver: The Investigator must promote 
compliance by instructing the participant to take the study treatment exactly as prescribed and 
by stating that compliance is necessary for the participant’s safety and the validity of the study. 
The participant must also be instructed to contact the Investigator if he/she is unable for any 
reason to take the study treatment as prescribed. In addition compliance will be measured by a 
dosing log for those undergoing administration at home. The administration of study treatment 
must be recorded in the dosing log and compliance should be monitored by the Investigator 
and/or study personnel. All study treatment dispensed and returned must be recorded in the 
Drug Accountability Log.
6.4.1
Recommended treatment of adverse events
Any treatment deemed necessary by the investigator for the safety of the participant is allowed.
For treatment of severe allergic reactions including anaphylaxis, epinephrine and short-acting 
beta2-agonist (SABA) are typically used.
Treatments of adverse events should align with medications allowed under certain conditions 
(Section 6.8.1.1) and prohibited medication (Table 6-5) where possible. Medication used to 
treat AEs must be recorded on the appropriate CRF.
For adverse events associated with the OFC, please see the Appendix 7 (Section 10.7).
6.5
Dose modification
6.5.1
Definitions of dose limiting toxicities (DLTs)
Not applicable.
6.5.2
Dose modifications
Study treatment dose adjustments are not permitted.
Any interruption of study treatment administration should be discussed with Novartis or 
delegate regarding the participant’s eligibility to continue study treatment except for the cases 
based on the response driven approach (Section 4.1.2).
Any missed or altered study treatment administration must be recorded on the appropriate eCRF 
in order to reconstruct an accurate dosing history for each participant.

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6.5.3
Follow-up for toxicities
6.5.3.1
Follow-up on potential drug-induced liver injury (DILI) cases
Participants with transaminase increase combined with total bilirubin increase may be 
indicative of potentially severe DILI and should be considered as clinically important events 
and assessed appropriately to establish the diagnosis. The required clinical information, as 
detailed below, should be sought to obtain the medical diagnosis of the most likely cause of the 
observed laboratory abnormalities.
The threshold for potential DILI may depend on the participant’s baseline AST/ALT and total 
bilirubin value; participants meeting any of the following criteria will require further follow-up 
as outlined below:
x
For participants with normal ALT and AST and total bilirubin value at baseline: AST or 
ALT > 3.0 x ULN combined with total bilirubin > 2.0 x ULN
x
For participants with elevated AST or ALT or total bilirubin value at baseline: [AST or 
ALT > 2 x baseline] OR [AST or ALT >300 U/L], whichever occurs first combined with 
[total bilirubin > 2 x baseline AND > 2.0 x ULN]
As DILI is essentially a diagnosis of exclusion, other causes of abnormal liver tests should be 
considered and their role clarified before DILI is assumed to be the cause of liver injury.
A detailed history, including relevant information such as review of ethanol consumption, 
concomitant medications, herbal remedies, supplement consumption, history of any pre-
existing liver conditions or risk factors, should be collected.
Laboratory tests should include ALT, AST, total bilirubin, direct and indirect bilirubin, GGT, 
prothrombin time (PT)/INR, alkaline phosphatase, albumin, and creatine kinase. If available, 
testing of Glutamate Dehydrogenase (GLDH) is additionally recommended.
Perform 
relevant 
examinations 
(Ultrasound 
or 
MRI, 
Endoscopic 
retrograde 
cholangiopancreatography (ERCP)) as appropriate to rule-out an extrahepatic cause of 
cholestasis. Cholestasis (is defined as an ALP elevation > 2.0 x ULN with R value < 2 in 
participants without bone metastasis, or elevation of the liver-specific ALP isoenzyme in 
participants with bone metastasis).
Note: The R value is calculated by dividing the ALT by the ALP, using multiples of the ULN 
for both values. It denotes whether the relative pattern of ALT and/or ALP elevation is due to 
cholestatic (R ≤ 2), hepatocellular (R ≥ 5), or mixed (R >2 and < 5) liver injury. For children, 
there are caveats to calculating the R-ratio as normal levels of ALP are higher than in adults 
with standard ranges varying by developmental age. In clinical situations where it is suspected 
that ALP elevations are from an extrahepatic source, the GGT can be used if available. GGT 
may be less specific than ALP as a marker of cholestatic injury, since GGT can also be elevated 
by enzyme induction or by ethanol consumption. It is more sensitive than ALP for detecting 
bile duct injury.
Table 6-3 provides guidance on specific clinical and diagnostic assessments which can be 
performed to rule-out possible alternative causes of observed Liver function test (LFT) 
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Table 6-3
Guidance to rule-out possible alternative causes of LFT abnormalities
Disease
Assessment
Hepatitis A, B, C, E
● IgM anti-HAV; HBsAg, IgM & IgG anti-HBc, HBV DNA; anti-HCV, HCV 
RNA, IgM & IgG anti-HEV, HEV RNA
CMV, HSV, EBV infection
● IgM & IgG anti-CMV, IgM & IgG anti-HSV; IgM & IgG anti-EBV
Autoimmune hepatitis
● Antinuclear Antibodies (ANA) & Anti-Smooth Muscle Antibody (ASMA) 
titers, total IgM, IgG, IgE, IgA
Alcoholic hepatitis
● Ethanol history, GGT, MCV, CD-transferrin
Nonalcoholic steatohepatitis
● Ultrasound or MRI
Hypoxic/ischemic hepatopathy
● Medical history: acute or chronic congestive heart failure, hypotension, 
hypoxia, hepatic venous occlusion. Ultrasound or MRI.
Biliary tract disease
● Ultrasound or MRI, ERCP as appropriate.
Wilson disease (if <40 yrs old)
● Caeruloplasmin
Hemochromatosis
● Ferritin, transferrin
Alpha-1-antitrypsin deficiency
● Alpha-1-antitrypsin
Other causes should also be considered based upon participants’ medical history 
(hyperthyroidism / thyrotoxic hepatitis – T3, T4, TSH; cardiovascular disease / ischemic 
hepatitis – ECG, prior hypotensive episodes; Type 1 diabetes mellitus / glycogenic hepatitis).
Following appropriate causality assessments, as outlined above, the causality of the treatment 
is estimated as “probable” (i.e.,>50% likely), if it appears greater than all other possible causes 
of liver injury combined. The term “treatment-induced” indicates probably caused by the 
treatment, not by something else, and only such a case can be considered a DILI case and should 
be reported as an SAE.
All cases confirmed on repeat testing meeting the laboratory criteria defined above, with no 
other alternative cause for LFT abnormalities identified, should be considered as “medically 
significant” and thus, meet the definition of SAE and should be reported as a SAE using the 
term “potential treatment-induced liver injury.” All events should be followed up with the 
outcome clearly documented.
6.5.4
Retreatment criteria
Restart of study treatment is only possible for the participants undergoing conditional 
discontinuation of study treatment, but becoming sensitive to the food allergen, as defined by 
the OFC (no longer MR) after being off-treatment.
6.6
Continued access to study treatment after the end of the study
6.6.1
Post trial access
This is an extension study to the core studies of ligelizumab Food Allergy Program which will 
provide access to ligelizumab to those participants who decide to join the study until it is 
commercially available or accessible in the participating countries (up to 3 years in some 
regions). The 3-year treatment period of this study will also fulfill the Novartis commitment to 
provide post trial access (PTA) to the participants who have completed ligelizumab Phase III 
studies in food allergy. For the participants who complete this extension study prior to the 
ligelizumab becoming available in the country of the participant and is, in the opinion of the 

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investigator still deriving clinical benefit from ligelizumab, every effort will be made to 
continue provision of ligelizumab.
6.7
Treatment of overdose
In the event of an overdose for participants administering study treatment at home, e.g., when 
more than 2 doses were given to the participant, the participant or parent/caregiver should:
x
Contact the study site staff immediately.
x
Site should then contact the medical monitor
x
Advise the participant or parent/caregiver to report any untoward events to the study site 
staff and continue to closely monitor the participant
x
Evaluate the participant to determine, in consultation with the medical monitor, whether 
study treatment should be interrupted
x
Document the quantity of the excess dose as well as the duration of the overdose.
6.7.1
Reporting of study treatment errors including misuse/abuse
Medication errors are unintentional errors in the prescribing, dispensing, administration or 
monitoring of a medicine while under the control of a healthcare professional, participant or 
consumer (EMA definition).
Misuse refers to situations where the medicinal product is intentionally and inappropriately used 
not in accordance with the protocol.
Abuse corresponds to the persistent or sporadic, intentional excessive use of a medicinal 
product, which is accompanied by harmful physical or psychological effects.
Study treatment errors and uses outside of what is foreseen in the protocol will be recorded on 
the appropriate CRF irrespective of whether or not associated with an AE/SAE. Study treatment 
errors and uses outside of what is foreseen in the protocol, misuse or abuse will be collected 
and reported in the safety database irrespective of it being associated with an AE/SAE within 
24 hours of Investigator’s awareness. For more information on AE and SAE definition and 
reporting requirements, please see the respective sections.
6.8
Concomitant and other therapy
6.8.1
Concomitant therapy
All medications, procedures, and significant non-drug therapies (including physical therapy and 
blood transfusions) administered after the participant was enrolled on the study must be 
recorded on the appropriate eCRF.
Each concomitant drug must be individually assessed against all exclusion criteria and against 
the medication allowed under certain conditions (listed in Table 6-4) and prohibited medication 
listed in Table 6-5. If in doubt, the Investigator should contact the Novartis medical monitor 
before starting Screening/Day 1 visit or allowing a new medication to be started. If the 
participant is already enrolled, contact Novartis to determine if the participant should continue 
participating in the study.

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It is recommended that participants with asthma who are eligible for study participation 
maintain a stable regimen of controller treatment throughout the study.
6.8.1.1
Permitted concomitant therapy requiring caution and/or action
The following medications below are allowed under certain conditions:
Table 6-4
Medications allowed under certain conditions
Medication
Condition under which medication is permitted
Topical corticosteroids and other topical 
immunosuppressants
In recommended doses and dosage regimens
Immunotherapy in the maintenance phase for the 
treatment of allergies (except food allergies)
SC (subcutaneous) immunotherapy: time window of 1 
week between OFC or study treatment administration 
and immunotherapy shot.
SLIT (sublingual immunotherapy): Hold SLIT dose on 
the day of OFC
Inactivated, non-live vaccines (including Covid19 
vaccine)
Not administered within 48 hours prior to a study visit
Short acting and long acting anti-histamines (e.g., 
chlorpheniramine, promethazine, diphenhydramine, 
loratidine, cetirizine)
Not administered within 5 half-lives prior to SPT (skin 
prick test) and OFC
Short Acting Beta Agonist (SABA)
Not used within 6h of all spirometry assessments for 
asthma participants and within 6h prior to start of OFC
Short-term burst of systemic corticosteroids for the 
treatment of acute signs and symptoms
Not administered within 5 half-lives prior to SPT and 
OFC.
Oral H2 receptor antagonists (e.g., cimetidine, 
ranitidine, famotidine, nizatidine)
Not administered within 24 hours prior to SPT and 
OFC
Corticosteroids nasal spray
In recommended doses and dosage regimens
Anti-Histamine nasal spray
6.8.2
Prohibited medication
Use of the treatments displayed below is not allowed after the start of the study treatment.
If a participant develops a medical condition that requires use of prohibited treatment or if 
participant exhibits a behavior of non-compliance regarding prohibited medications at any 
timepoint from Screening/Day 1 to the end of the study, investigational treatment and OL-OFC 
must be discontinued.
Table 6-5
Prohibited medication 
Medication
Prohibition period
Action taken
Any monoclonal antibody treatment (including any 
Fab fragments); e.g., omalizumab (Xolair®),
dupilumab (Dupixent®), benralizumab (Fasenra™),
mepolizumab (Nucala®), reslizumab (Cinqair®)
Any time
Discontinue investigational 
treatment
Immunotherapy for the treatment of food allergies
Any time
Discontinue investigational 
treatment
Other systemic immunosuppressive medications 
including but not limited to methotrexate, 
cyclosporine A, cyclophosphamide, tacrolimus and 
mycophenolate mofetil, Janus Kinase inhibitors
Any time
Discontinue investigational 
treatment

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Medication
Prohibition period
Action taken
Chronic use of systemic corticosteroids
Any time (See 
Table 6-4 above for 
short-term burst)
Discontinue investigational 
treatment
Beta blockers
Any time
Discontinue investigational 
treatment
ACE inhibitors
Any time
Discontinue investigational 
treatment
Tricyclic antidepressants
Any time
Discontinue investigational 
treatment
Other investigational drugs
Any time
Discontinue investigational 
treatment
Live attenuated vaccines
Any time
Discontinue investigational 
treatment
6.8.3
Rescue medicine
Any treatment deemed necessary by the investigator can be used to treat adverse events, 
including allergic reactions. Typically, this includes epinephrine, SABA, anti-histamines and 
saline bolus. Any use of rescue medication must be captured on the designated CRF.
Rescue medication can either be provided directly at the study center or prescribed to the 
participant.
The counseling of participants/caregivers on the identification of allergic reactions and 
symptoms of anaphylaxis, as well as proper instruction for the use of rescue medication must 
be documented in the source.
Repeat counseling should be provided as needed to ensure complete understanding. Additional 
supplies of rescue medication should be provided as needed throughout the study.
These two rescue medications are to be provided to the participant locally at the transition to 
this extension study (or continuously carrying the rescue med from the core study). Participants 
should be instructed to bring them to each visit.
Epinephrine:
In alignment with treatment guidelines for food allergy, all study participants will be provided 
with rescue medication epinephrine (e.g., EpiPen® 150 μg, 300 μg, 500 μg, Jext® 150 μg or 300 
μg) to be used to treat any allergic reactions and potential anaphylactic events that occur 
throughout the study as needed. This qualifies as authorized auxiliary medicinal product 
(AxMP) under the European Clinical Trial Regulation 536/2014. If the participant is treated 
with epinepherine (e.g., EpiPen®, Jext®) outside of a study visit, the participant or 
parent/caregiver should contact the study site staff immediately.
SABA (salbutamol/albuterol):
Participants with a documented diagnosis of asthma will additionally be provided with SABA 
rescue medication. This qualifies as authorized auxiliary medicinal product (AxMP) under the 
European Clinical Trial Regulation 536/2014. As listed in Table 6-4, the participant should not 
use SABA rescue medication within 6 hours of a spirometry assessment and/or OFC.

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7
Discontinuation of study treatment and participant 
discontinuation/withdrawal
7.1
Discontinuation of study treatment
Discontinuation of study treatment for a participant occurs when study treatment is permanently 
stopped for any reason (prior to the planned completion of study treatment administration, if 
any) and can be initiated by either the participant or the Investigator.
The Investigator must discontinue study treatment for a given participant if, he/she believes that 
continuation would negatively impact the participant's well-being.
Discontinuation from study treatment is required under the following circumstances:
x
Participant/guardian decision
x
Pregnancy
x
AEs for which continued exposure to the study drug would be detrimental
x
Abnormal liver and/or renal laboratory results requiring discontinuation
x
Platelets <75000 /uL
x
Participant experiences a life-threatening hypersensitivity event due to any reason needing 
an ICU admission or intubation
x
Participant experiences a serious hypersensitivity event suspected to be related to study 
treatment
x
Use of prohibited treatment as per recommendations in the prohibited treatment section
x
Any situation in which continued study participation might result in a safety risk to the 
participant
x
Following emergency unblinding
If discontinuation from study treatment occurs, the Investigator should make a reasonable effort 
to understand the primary reason for the participant’s discontinuation from study treatment and 
record this information.
Participants who discontinue from study treatment agree to return for the end of treatment and 
follow-up visits indicated in Section 1.3 Schedule of Activities.
If the participant cannot or is unwilling to attend any visit(s), the site staff should maintain 
regular telephone contact with the participant, or with a person pre-designated by the 
participant. This telephone contact should preferably be done according to the study visit 
schedule. Participants who discontinue study treatment will no longer undergo any OFC that 
may be planned on the remaining visit(s). After discontinuation from study treatment, at a 
minimum, in abbreviated visits, the following data should be collected at clinic visits or via 
telephone/email contact:
x
New / concomitant treatments
x
Adverse Events / Serious Adverse Events
The Investigator must also contact the IRT to register the participant’s discontinuation from 
study treatment.

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7.2
Participant discontinuation from the study
Discontinuation from study is when the participant permanently stops receiving the study 
treatment, and further protocol-required assessments or follow-up, for any reason.
If the participant agrees, a final evaluation at the time of the participant’s study discontinuation 
should be made as detailed in Section 1.3 Schedule of Activities.
7.3
Withdrawal of informed consent and exercise of participants’ 
data privacy rights
Withdrawal of consent/opposition to use of data and/or biological samples occurs in countries 
where the legal justification to collect and process the data is consent and when a participant:
x
Explicitly requests to stop use of their data
and
x
No longer wishes to receive study treatment
and
x
Does not want any further visits or assessments (including further study-related contacts)
This request should be as per local regulations (e.g., in writing) and recorded in the source 
documentation.
Withdrawal of consent impacts ability to further contact the participant, collect follow-up data 
(e.g., to respond to data queries) and potentially other country-specific restrictions. It is 
therefore very important to ensure accurate recording of withdrawal vs. discontinuation based 
on the protocol definitions of these terms.
In this situation, the Investigator should make a reasonable effort (e.g., telephone, e-mail, letter) 
to understand the primary reason for the participant’s decision to withdraw their 
consent/exercise data privacy rights and record this information. The Investigator shall clearly 
document if the participant has withdrawn his/her consent for the use of data in addition to a 
study discontinuation.
Study treatment must be discontinued and no further assessments conducted, and the data that 
would have been collected at subsequent visits will be considered missing.
Further attempts to contact the participant are not allowed unless safety findings require 
communicating or follow-up.
If the participant agrees, a final evaluation at the time of the participant’s withdrawal of 
consent/exercise data privacy rights should be made as detailed in Section 1.3 Schedule of 
Activities.
Further details on withdrawal of consent or the exercise of participants' data privacy rights are 
included in the corresponding informed consent form.
7.4
Lost to follow-up
For participants whose status is unclear because they fail to appear for study visits or fail to 
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study treatment or discontinue from study or withdraw consent (or exercise other participants’ 
data privacy rights), the Investigator must show "due diligence" by documenting in the source 
documents steps taken to contact the participant, e.g., dates of telephone calls, registered letters, 
etc. A participant should not be considered as lost to follow-up until due diligence has been 
completed.
7.5
Early study termination by the Sponsor
The study can be terminated by Novartis at any time.
Reasons for early termination (but not limited to):
x
Unexpected, significant, or unacceptable safety risk to participants enrolled in the study
x
Decision based on recommendations from applicable board(s) after review of safety and 
efficacy data
x
Discontinuation of study treatment development
In taking the decision to terminate, Novartis will always consider participant welfare and safety. 
Should early termination be necessary, participants must be seen as soon as possible and treated 
as a participant who discontinued from study treatment. The Investigator may be informed of 
additional procedures to be followed in order to ensure that adequate consideration is given to 
the protection of the participant’s interests. The Investigator or Novartis depending on local 
regulation will be responsible for informing IRBs/IECs of the early termination of the trial.
8
Study Assessments and Procedures
x
Study procedures and their timing are summarized in Section 1.3 Schedule of Activities. 
Protocol waivers or exemptions are not allowed.
x
Immediate safety concerns should be discussed with Novartis upon occurrence or awareness 
to determine if the participant should continue or discontinue study treatment.
x
Adherence to the study design requirements, including those specified in Section 1.3
Schedule of Activities, is essential and required for study conduct.
x
Safety/laboratory/analyte results that could un-blind the study will not be reported to 
investigative sites or other blinded personnel until the study has been unblinded.
x
Repeat or unscheduled samples may be taken for safety reasons or for technical issues with 
the samples.
8.1
Screening
In this extension study, Screening and Day 1 with the first administration of study treatment 
will occur on the same day, except the MR participants who transition at the end of the follow-
up period of the core study, when the first administration of study treatment will be given on a 
different day (Section 4.1.2).
Each participant must have completed the treatment period in the Phase III studies with 
ligelizumab in food allergy including (but not limited to) Study CQGE031G12301 (peanut 
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Participants who are from Study CQGE031G12301 will transition into the extension study after 
completion of the follow-up period (washout) of the core study. The end of follow-up visit of 
the core study will also become the first visit of this extension study (Screening/Day 1). The 
informed consent must be obtained before initiating any study related activities in the extension 
study at Screening/Day 1 (Figure 4-1).
Participants from other study(ies) who complete the study treatment period of a core study and 
are willing to participate in the extension study will consent to the extension study. Four weeks 
after the end of the final treatment visit of a core study, the first visit of this extension study will 
be scheduled (Screening/Day 1) (Figure 4-1).
Participants who sign an informed consent form (and assent form if applicable) for this 
extension study and are subsequently found to be ineligible prior to the first dose of study 
treatment administration (Day 1) will be considered as a screen failure. The reason for screen 
failure should be recorded on the appropriate CRF.
8.2
Participant demographics/other baseline characteristics
Participant demographics and baseline characteristics will be collected at Screening, as 
specified in Section 1.3 Schedule of Activities.
Data collected will include age; sex; race; ethnicity; height and weight; relevant medical history, 
and prior and concomitant medications. A detailed medical history (including family medical 
history) and current medical conditions present before entering the extension study will be 
recorded, including any ongoing adverse events from the core study. Clinically relevant 
abnormal test findings should also be captured in medical history once it occurred prior to the 
informed consent signature. Participant race and ethnicity are collected and analyzed to identify 
variations in safety or efficacy due to these factors as well as to assess the diversity of the study 
population as required by Health Authorities.
8.3
Efficacy assessments
8.3.1
Oral Food Challenge (OFC)
In this extension study, the open-label OFC will be conducted to evaluate the level of 
desensitization to the food(s) every year as well as for MR to extend the off-treatment (washout) 
period. Details of this procedure are outlined in the Appendix 7 (Section 10.7) and preparation 
of the allergen is outlined in the Pharmacy Manual.
Although OL-OFC will be conducted in this study, it is recommended that same site personnel 
(unblinded and independent) as in the core study continues the preparation of the challenge 
material. However it is not necessary to keep blinding because the participants will receive 
allergen food protein (and not placebo).
Conducting the food challenge requires the physical facility to store and prepare material, as 
well as the assessment itself conducted under medical supervision. Sites should be equipped 
with supplies to treat allergic reactions (including severe anaphylaxis) (Section 10.7), as well 
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To ensure participant safety, on study visits where the OFC is conducted, it is critical to follow 
the order of assessments as outlined in Table 1-4. i.e., concomitant medication check, physical 
examination, ECG, vital signs, spirometry (for asthma participants only), urine pregnancy (if 
applicable), laboratory evaluations, skin prick test (SPT) and study treatment administration 
must be performed prior to the start of the OFC. 
The site should be prepared to react to immediate and late hypersensitivity reactions, including 
anaphylaxis. At the completion of the OFC participants must remain under observation at the 
site for a minimum of 2 hours after the last OFC dose (or for a positive challenge at least for 1 
hour after all allergic symptoms have improved). After the observation period, discharge from 
the study site is at the discretion of the investigator. Prior to discharge, all participants should 
be briefed about the signs and symptoms of anaphylaxis and in possession of an epinephrine 
auto-injector consistent with local guideline.
OFC data will be captured on a designated page of the electronic case report form (eCRF).
8.3.1.1
Spirometry before OFC
For participants with a documented diagnosis of asthma, spirometry is performed prior to the 
OFC and if the Forced Expiratory Volume during the 1st second (FEV1) % predicted normal 
value is below 80% (< 80%), the OFC should not be performed and rescheduled as appropriate.
For each spirometry measurement, the accurate participant data (e.g., age, gender and height) 
should be used for the calculation of FEV1 predicted normal value at the site.
The spirometry assessment should be performed in accordance with the standard practice at the 
site including the quality check. It is recommended to follow the American Thoracic Society / 
European Respiratory Society (ATS/ERS) standard (ATS/ERS Task Force: Standardization of 
Lung Function Testing, Graham et al 2019) if possible.
8.3.2
Skin Prick Test (SPT)
An allergen specific SPT is a commonly used diagnostic tool (Heinzerling et al 2013). In this 
study, a titration SPT using peanut allergen will provide additional information on the impact 
of IgE suppression on skin mast cells. Milk and/or egg allergens will also be tested based on 
the participant's medical history.
SPT is scheduled every 6 months during the extension study Table 1-4. At the visit where 
dosing of study treatment, SPT and OFC are scheduled, SPT should be performed before dosing 
of study treatment followed by OFC.
The SPT procedure is summarized separately in Appendix 8 (Section 10.8).
The SPT may rarely cause serious allergic reactions, including anaphylaxis, and the site should 
be prepared to provide immediate treatment should that occur. If the participant experiences a 
systemic allergic reaction and/or an event which is judged by the investigator as an adverse 
reaction, it should be reported on the designated CRF.
CCI

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8.3.3
Appropriateness of efficacy assessments
OFC
The Oral Food Challenge (OFC) represents the gold standard for diagnosing food allergies. It 
is also the most objective method to clinically estimate threshold doses for allergenic foods in 
highly sensitive individuals. In this study, the OFC is based upon several available guidelines, 
PRACTALL (Cox, Nowak-Wegrzyn 2018) and the CoFAR Grading Definition of Dose-
Limiting Symptoms. The test itself corresponds most closely to the natural ingestion of food.
Although the average amount of peanut consumed in an accidental exposure has not been 
accurately quantified, it is generally believed to be no more than one or two peanuts, or the 
equivalent of approximately 160 to 325 mg of peanut protein. Therefore, as proposed in this 
study, an increase in the threshold of peanut flour required to provoke symptoms should serve 
as a proxy to estimate the level of protection against unintended ingestion
SPT assessment
Skin prick Test is used in clinical practice as a diagnostic modality to detect the presence of 
sIgE antibodies to the food source. The size of the SPT wheal correlates with an increased 
likelihood of clinical food allergy. However, a positive result alone indicates sensitization and 
does not equate to food allergy (Foong et al 2021)
8.4
Safety assessments
Safety assessments are specified below with Table 1-4 Assessment Schedule detailing when 
each assessment is to be performed.
For details on AE collection and reporting, refer to Section 8.6:
AEs and SAEs, including AEs leading to treatment discontinuation and events of interest, such 
as injection site reactions, anaphylaxis, pre-malignancy/malignancy, cardio-cerebrovascular 
events
Physical examination
Vital signs
Laboratory evaluations
Spirometry (asthma patients only) refer to Section 8.3.1.1
Electrocardiogram (ECG)
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e. pandemic, epidemic or natural disaster, that limits or prevents on-site study visits, regular 
phone or virtual calls can occur (every 4 weeks or more frequently if needed) for safety 
monitoring and discussion of the participant´s health status until it is safe for the participant to 
visit the site again.
8.4.1
Physical examinations
A complete physical examination will be performed as specified in the schedule of activities 
table (Table 1-4) and will include the examination of general appearance, skin, neck (including 

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thyroid), eyes, ears, nose, throat, lungs, heart, abdomen, back, lymph nodes, extremities, 
vascular and neurological. If indicated based on medical history and/or symptoms, rectal, 
external genitalia, breast, and pelvic exams will be performed.
Height in centimeters (cm) and body weight (to the nearest 0.1 kilogram (kg) in indoor clothing, 
but without shoes) will be measured.
Investigators should pay special attention to clinical signs related to previous serious illnesses.
Information on all physical examinations must be included in the source documentation at the 
study site. Clinically relevant findings that are present prior to signing informed consent must 
be recorded on the appropriate CRF that captures medical history. Significant findings made 
after signing informed consent which meet the definition of an Adverse Event must be recorded 
as an adverse event.
8.4.2
Vital signs
Vital signs include blood pressure and pulse measurements will be measured as specified in the 
schedule of assessments Table 1-4. After the participant has been sitting for five minutes, with 
the back supported and both feet placed on the floor, systolic and diastolic blood pressure will 
be measured three times using an automated validated device, e.g., OMRON, with an 
appropriately sized cuff. The repeat sitting measurements will be made at 1 - 2 minute intervals 
and the mean of the three measurements will be used. In case the cuff sizes available are not 
large enough for the participant's arm circumference, a sphygmomanometer with an 
appropriately sized cuff may be used.
During and up to at least one hour after the completion of the OL-OFC, vital signs should be 
monitored approximately every 15 minutes and documented in source.
Clinically notable vital signs are defined in Appendix 3 (Section 10.3.1).
8.4.3
Electrocardiograms
ECGs will be measured once a year as specified in the schedule of assessments in Table 1-4.
Single 12 lead ECGs are collected, and the original trace should be printed on non-heat sensitive 
paper. Each ECG will be sent electronically for central review directly from the ECG machine. 
One print-out will be generated and kept at the investigator site as source documentation and 
will be dated and signed. The participant's number, the date, actual time of the tracing, and 
Study Code must appear on each page.
ECGs must be recorded after 10 minutes rest in the supine position to ensure a stable 
baseline/according to the ECG investigator manual. The preferred sequence of cardiovascular 
data collection during study visits is ECG collection first, followed by vital signs, and blood 
sampling. The Fridericia QT correction formula (QTcF) should be used for clinical decisions.
Additional, unscheduled, safety ECGs may be repeated at the discretion of the investigator at 
any time during the study as clinically indicated. For any ECGs with participant safety concerns, 
two additional ECGs must be performed to confirm the safety finding. ECG safety monitoring 
or a review process should be in place for clinically significant ECG findings at baseline before 
administration of study treatment and during the study.

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Clinically significant abnormalities must be recorded on the CRF as either medical 
history/current medical conditions or adverse events as appropriate.
8.4.4
Clinical safety laboratory tests
A central laboratory will be used for analysis of all specimens detailed in this section unless 
noted otherwise. Details on the collections, shipment of samples and reporting of results by the 
central laboratory are provided to investigators in the laboratory manual. The blood volume 
collected for pediatric participants aligns with The Hospital for Sick Children (SickKids) 
Research Ethics Board Blood Sampling Guidelines (Howie 2011) and is outlined in detail in 
the QGE031G12303B Laboratory Manual. If local regulatory requirements stipulate more 
stringent limits for blood volumes for pediatric participants, the Novartis Clinical Team should 
be consulted for implementation of prioritization of lab evaluations.
Where health authorities require additional testing on biological samples, such tests will be 
done, wherever possible.
Clinically notable laboratory findings are defined in Appendix 3 (Section 10.3.1). In case of lab 
abnormalities, an additional re-draw for central laboratory assessment is allowed during the 
screening period to confirm eligibility criteria.
Clinically significant abnormalities must be recorded on the relevant section of the CRFs 
capturing medical history/current medical conditions/AEs.
A serum β-hCG will be collected at Screening/Visit 1 as specified in the schedule of 
assessments in Table 1-4 for all after menarche and pre-menopausal women who are not 
surgically sterile.
As per Section 4.5, during a public health emergency as declared by local or regional 
authorities, i.e., pandemic, epidemic or natural disaster, that limits or prevents on-site study 
visits, if participants cannot visit the site for protocol-specified safety lab assessments, an 
alternative lab (local) collection site may be used.
Table 8-1
Laboratory evaluations
Test category
Test name
Hematology
Hemoglobin, hematocrit, red blood cell count, white blood cell count with differential and 
platelet count
Chemistry
Albumin, Alkaline phosphatase (ALP), ALT, Amylase, AST, Calcium, Chloride, Creatinine, 
Direct Bilirubin, Gamma-glutamyl-transferase (GGT), Glucose, Lactate dehydrogenase 
(LDH), Lipase, Magnesium, Phosphate, Potassium, Sodium, Total Bilirubin (If the total 
bilirubin concentration is increased above 1.5 times the upper limit of normal, direct and 
indirect reacting bilirubin should be differentiated), Urea/BUN, Uric Acid
Urinalysis
A midstream urine sample (approximately 30 mL) will be obtained, in order to avoid 
contamination with epithelial cells and sediments and allow proper assessments. Semi-
quantitative “dipstick” evaluation for specific gravity, glucose, protein, bilirubin, ketones, 
leukocyte esterase and blood will be performed at site. When a dipstick evaluation is 
abnormal, e.g., positive for WBC and/or blood, a urine sample must be sent to the Central 
Lab for microscopic examination including RBC and WBC. (Details on collection of urine 
for analysis by central laboratory are provided to investigators in the laboratory manual.)
Parasite screening
Assessment of stool samples for parasitic infections is done by the local laboratory (refer 
to Assessment of parasitic infections Section 8.4.6.1.

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Test category
Test name
Pregnancy Test and 
Assessments of 
Fertility
Serum / Urine pregnancy test (refer to Pregnancy and assessments of fertility 
Section 8.4.5).
Confirmatory serum pregnancy required in case of positive urine pregnancy test
8.4.5
Pregnancy testing
All pre-menopausal female participants, including female pediatric participants who are 
menarchal or who become menarchal during the study, who are not surgically sterile will have 
pregnancy testing. Post-menopausal status should be recorded in the Medical History CRF.
Continuing from the core studies and up to the EOS, all pre-menopausal female participants 
who are not surgically sterile will have urine pregnancy testing performed BEFORE 
administration of the study treatment. Females participating in the home administration will 
receive urine pregnancy kits to test prior to study treatment injection.
A positive urine test requires the participant to contact the site staff and they will then need to 
confirm the result with a central lab serum test, prior to further study treatment administration, 
in the interim, they should withhold study medication. If positive after serum test, the participant 
must be discontinued from study treatment.
Additional pregnancy testing might be performed if requested by local regulatory/ethics 
committee requirements.
Assessments of fertility
Medical documentation of oophorectomy, hysterectomy, or tubal ligation must be retained as 
source documents. Subsequent hormone level assessment to confirm the female participants not 
of child-bearing potential must also be available as source documentation in the following 
cases:
1. Surgical bilateral oophorectomy without a hysterectomy
2. Reported 12 months of natural (spontaneous) amenorrhea with an appropriate clinical 
profile.
In the absence of the above medical documentation, Follicle Stimulating Hormone (FSH) 
testing is required of any female participant regardless of reported reproductive/menopausal 
status at screening.
As per Section 4.5, during a public health emergency as declared by local or regional 
authorities, i.e., pandemic, epidemic or natural disaster, that limits or prevents on-site study 
visits, if participants cannot visit the site to have serum pregnancy tests, urine pregnancy test 
kits may be used. Relevant participants can perform the urine pregnancy test at home and report 
the result to the site. It is important that participants are instructed to perform the urine 
pregnancy test first and only if the test result is negative proceed with the administration of the 
study treatment. A communication process should be established with the participant so that the 
site is informed and can verify the pregnancy test results, following any local country 
procedures.

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8.4.6
Other safety evaluations
8.4.6.1
Assessment of parasitic infection
Reduction in IgE levels may confer increased susceptibility to parasitic infections. The risk of 
acquiring or activating infections with helminthes during or after treatment with anti-IgE 
therapy such as ligelizumab is suspected to be low.
Stool sampling for the assessment of parasitic infection is scheduled:
x
Beginning of the study:
x
No stool sample for the extension study is required (results from the Core study(ies) 
will be used)
x
End of the study:
x
All participants: Single stool sample is required and sample kit will be given at the visit 
before the end of study visit
x
Participants who report diarrhoea, or any other symptoms suggestive of parasitic infection 
at any time during the study will be given three stool sample collection kits. These 
participants have to collect stool samples ideally on three different days, and then to return 
the samples to the clinic or local lab as soon as possible after collection. For home 
administration participants, they need to arrange to collect kits and return them to the clinic 
as agreed with the clinic staff.
Stool samples for parasitic disease will be examined for ova and parasites by the local 
laboratory. The identification of organisms in positive stools will be made by local laboratory. 
If stool testing is positive for pathogenic organisms (pathogenic as defined by the local 
laboratory), the result must be recorded in the source data as well as eCRF as an AE. Stool 
samples negative for pathogenic organisms must be recorded in the source data.
Subjects who develop stools positive for pathogenic helminthic infections during the study 
should have their infection treated according to current local practice and can continue the study 
as per schedule.
8.4.6.2
Independent data review by adjudication committee
An adjudication committee (AC) will be put in place to determine whether cases of 
hypersensitivity identified through a search algorithm based on the Standardized Medical 
Dictionary for Regulatory Activities (MedDRA) Queries may represent cases of:
x
anaphylactic events
x
cardio-cerebrovascular events
x
neoplastic events
The clinical presentation and association of these events with pre-existing risk factors will be 
part of the assessment.
Further details regarding the AC will be documented in an AC charter.

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8.4.7
Appropriateness of safety measurements
The safety assessments of this extension study are in line with that of each core study and are 
standard in this population, in addition they are based on the available ligelizumab safety data. 
Participants have completed a core study before entering to this extension study, therefore it is 
important to monitor the participants' safety continuously in the same manner.
Also, study treatment will be discontinued if the participant experiences a life-threatening 
hypersensitivity event needing an Intensive Care Unit (ICU) admission or intubation OR a 
serious hypersensitivity event suspected to be related to study treatment.
8.5
Additional assessments
8.5.1
Clinical Outcome Assessments (COAs)
Patient reported outcomes (PRO)
The impact of ligelizumab on the health-related quality of life (HRQoL) of participants with a 
food allergy will be assessed by the following measures based on age group and responder type:
FAQLQ-CF: Food Allergy Quality of Life Questionnaire – Child Form
FAIM-CF: Food Allergy Independent Measure – Child Form
FAQLQ-TF: Food Allergy Quality of Life Questionnaire – Adolescent Form
FAIM-TF: Food Allergy Independent Measure – Adolescent Form
FAQLQ-AF: Food Allergy Quality of Life Questionnaire – Adult Form
FAIM-AF: Food Allergy Independent Measure – Adult Form
FAQLQ-PF: Food Allergy Quality of Life Questionnaire – Parental Form
FAQL-PB: Food Allergy Quality of Life - Parental Burden Questionnaire
SF-36v2 Acute Version – Medical Outcomes Study 36-Item Short Form Version 2 Acute 
Version (recall period is past week)
Table 8-2
PROs based on participant’s age
Age Group/ 
Respondent 
Type
Day 1 
Screening
Week 52
10 days 
Before 
OFC
Week 52
3 days 
After OFC
Week 104
10 days 
Before 
OFC
Week 104
3 days 
After OFC
Week 156
10 days 
Before 
OFC
Week 156
3 days 
After OFC
Children 
aged 6-7
Children aged 6-7 will NOT be completing any PRO measures.
Parents/Caregivers of children aged 6-17 will complete specific PROs designed for 
Parents/Caregivers.
Note: Children aged 8-12 will self-complete PROs (next row) and their parents/caregivers will 
also complete PROs.
Children 
aged 8-12
FAQLQ-
CF
FAIM-CF
FAQLQ-
CF
FAIM-CF
FAQLQ-
CF
FAIM-CF
FAQLQ-
CF
FAIM-CF
FAQLQ-
CF
FAIM-CF
FAQLQ-
CF
FAIM-CF
FAQLQ-
CF
FAIM-CF
Adolescent
s aged 13-
17
FAQLQ-TF
FAIM-TF
FAQLQ-TF
FAIM-TF
FAQLQ-TF
FAIM-TF
FAQLQ-TF
FAIM-TF
FAQLQ-TF
FAIM-TF
FAQLQ-TF
FAIM-TF
FAQLQ-TF
FAIM-TF
Adults aged 
18+
FAQLQ-
AF
FAIM-AF
SF-36v2
FAQLQ-
AF
FAIM-AF
FAQLQ-
AF
FAIM-AF
SF-36v2
FAQLQ-
AF
FAIM-AF
FAQLQ-
AF
FAIM-AF
SF-36v2
FAQLQ-
AF
FAIM-AF
FAQLQ-
AF
FAIM-AF
SF-36v2

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Age Group/ 
Respondent 
Type
Day 1 
Screening
Week 52
10 days 
Before 
OFC
Week 52
3 days 
After OFC
Week 104
10 days 
Before 
OFC
Week 104
3 days 
After OFC
Week 156
10 days 
Before 
OFC
Week 156
3 days 
After OFC
Parents/Car
egivers of 
Children 6-
12
FAQLQ-
PF
FAQL-PB
FAQLQ-
PF
FAQLQ-
PF
FAQL-PB
FAQLQ-
PF
FAQLQ-
PF
FAQL-PB
FAQLQ-
PF
FAQLQ-
PF
FAQL-PB
Parents/Car
egivers of 
Adolescent
s13-17
FAQL-PB
FAQL-PB
FAQL-PB
FAQL-PB
The Food Allergy Quality of Life Questionnaire (FAQLQ) is a self-reported instrument 
intended to assess the effect of food allergy on the participant’s HRQoL (i.e., domains consist 
of risk of accidental exposure, emotional impact, allergen avoidance and dietary restrictions). 
The FAQLQ- Child Form (aged 8-12) (Flokstra-de Blok et al 2009a), FAQLQ-Teenager Form 
(aged 13-17) Flokstra-de Blok et al 2008) and FAQLQ-Adult Form (≥18 years of age) 
(Flokstra-de Blok et al 2009b), are self-administered, validated, food allergy-specific HRQoL 
questionnaires. The FAQLQ-parental form (FAQLQ-PF) is completed by parents of children 
aged 0-12 with food allergy (DunnGalvin et al 2008).
The number of items and domains varies by FAQLQ instrument administered. Each question is 
scored on a seven-point scale from 1 to 7 (i.e., from ‘no’ to ‘maximal’ impairment in HRQoL, 
respectively). The total score is the arithmetic average of all non-missing items. Domain scores 
are calculated similarly.
The Food Allergy Independent Measure (FAIM) reflects the participant’s perceived food 
allergy severity and food allergy-related risk. The total score for the FAIM ranges from 1 to 7 
(i.e., from ‘limited’ to ‘the greatest’ severity perception). If less than 80% of the items are 
complete, then the total score will not be calculated. Similarly, if less than 80% of the items 
within a domain are complete, then the domain score will not be calculated. 
(van der Velde et al 2010)
The Food Allergy Quality of Life-Parental Burden (FAQL-PB) Questionnaire is a self-
administered, disease-specific instrument developed to measure the effect of pediatric food 
allergy on HRQoL among caregivers. The instrument includes 17 items investigating the effect 
of having a child with food allergy on family/social activities, school, meal preparation, health 
concerns and emotional issues, using a 7-point Likert scale (Cohen et al 2004).
The SF-36v2® Health Survey is a 36-item instrument for measuring health status and outcomes 
via participant self-report. It is designed for use in surveys of general and specific populations, 
health policy evaluations, and clinical practice and research. The SF-6Dv2 (Brazier et al 2020)
will be derived from the SF-36v2 (Maruish 2011) for health economic evaluations. The SF-
6Dv2 captures the impacts of food allergy on social activities and depression/nervousness.
All questionnaires will be completed in the language most familiar to the respondent. The same 
parent/caregiver should complete the assessments throughout the study.
The participant should be given sufficient instruction, space, time and privacy to complete the 
questionnaire during the Screening visit. The study coordinator should encourage the 
participants to complete all of the available questionnaires.

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All participants will complete the PRO questions via a handheld electronic device (note: 
children aged 6-7 will NOT be completing any PRO measures). Participants will take the device 
home and should complete them 10 days before the OFC and 3 days after the OFC at Week 52, 
104 and 156. If participants experience any difficulties with submission after completing the 
PROs, they should contact the study staff for assistance. Available training materials related to 
the administrative procedures of the questionnaires will be provided to the sites.
Participant refusal to complete study PROs is not a protocol deviation. The participant should 
be made aware that completed measures are not reviewed by the investigator/study personnel.
8.6
Adverse events (AEs), serious adverse events (SAEs), and other 
safety reporting
The definitions of adverse events (AEs) and serious adverse events (SAEs) can be found in 
Section 8.6.
AEs will be reported by the participant (or, when appropriate, by a caregiver, surrogate, or the 
participant’s legally authorized representative).
The Investigator and any qualified designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for following 
up (see Section 7).
The method of recording, evaluating, and assessing causality of AEs and SAEs and the 
procedures for completing and transmitting SAE reports are provided in Section 8.6.3.
8.6.1
Adverse events
An adverse event (AE) is any untoward medical occurrence (e.g., any unfavorable and 
unintended sign [including abnormal laboratory findings], symptom or disease) in a clinical 
investigation participant after providing written informed consent for participation in the study. 
Therefore, an AE may or may not be temporally or causally associated with the use of a 
medicinal (investigational) product.
The Investigator has the responsibility for managing the safety of individual participant and 
identifying adverse events.
Novartis qualified medical personnel will be readily available to advise on trial-related medical 
questions or problems.
The occurrence of adverse events must be sought by non-directive questioning of the participant 
at each visit during the study. Additionally, the investigator should proactively query the 
participants about the occurrence of specific adverse events suggestive of hypersensitivity 
reactions during and after the OFC, the administration of study drug, and in the event of 
accidental food ingestion. Adverse events also may be detected when they are volunteered by 
the participant during or between visits or through physical examination findings, laboratory 
test findings, or other assessments.
Adverse events must be recorded under the signs, symptoms, or diagnosis associated with them, 
accompanied by the following information (as far as possible) (if the event is serious refer to 
Section 8.6.2):

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1. The severity grade
x
mild: usually transient in nature and generally not interfering with normal activities
x
moderate: sufficiently discomforting to interfere with normal activities
x
severe: prevents normal activities
2. Its relationship to the study treatment. If the event is due to lack of efficacy or progression 
of underlying illness (i.e., progression of the study indication) the assessment of causality 
will usually be ‘Not suspected.’ The rationale for this guidance is that the symptoms of a 
lack of efficacy or progression of underlying illness are not caused by the trial drug, they 
happen in spite of its administration and/or both lack of efficacy and progression of 
underlying disease can only be evaluated meaningfully by an analysis of cohorts, not on a 
single participant
3. Its duration (start and end dates or ongoing) and the outcome must be reported
4. Whether it constitutes a SAE (see Section 8.6.2 for definition of SAE) and which 
seriousness criteria have been met
5. Action taken with study treatment.
All adverse events must be treated appropriately. Treatment may include one or more of 
the following:
x
Dose not changed
x
Drug interrupted/permanently discontinued
6. Its outcome
Conditions that were already present at the time of informed consent should be recorded in 
medical history of the participant.
Adverse events (including lab abnormalities that constitute AEs) should be described using a 
diagnosis whenever possible, rather than individual underlying signs and symptoms.
Adverse event monitoring should be continued for at least 30 days or 5 half-lives following the 
last dose of study treatment.
Once an adverse event is detected, it must be followed until its resolution or until it is judged to 
be not recovered/not resolved (e.g., continuing at the end of the study), and assessment must be 
made at each visit (or more frequently, if necessary) of any changes in severity, the suspected 
relationship to the interventions required to treat it, and the outcome.
Information about adverse drug reactions for the investigational drug can be found in the 
Investigator's Brochure (IB).
Abnormal laboratory values or test results constitute adverse events only if they fulfill at least 
one of the following criteria:
x
they induce clinical signs or symptoms
x
they are considered clinically significant
x
they require therapy
Clinically significant abnormal laboratory values or test results must be identified through a 
review of values outside of normal ranges/clinically notable ranges, significant changes from 
baseline or the previous visit, or values which are considered to be non-typical in participants 

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with the underlying disease. Alert ranges for laboratory and other test abnormalities are included 
in Section 10.3.1.
Please refer to Section 10.7 for the assessment, reporting and management of hypersensitivity 
reactions observed during the OFC and the post-OFC observation period.
8.6.2
Serious adverse events
An SAE is defined as any adverse event [appearance of (or worsening of any pre-existing)] 
undesirable sign(s), symptom(s), or medical conditions(s) which meets any one of the following 
criteria:
x
fatal
x
life-threatening
Life-threatening in the context of a SAE refers to a reaction in which the participant was at risk 
of death at the time of the reaction; it does not refer to a reaction that hypothetically might have 
caused death if it were more severe (please refer to the ICH-E2D Guidelines).
x
results in persistent or significant disability/incapacity
x
constitutes a congenital anomaly/birth defect, fetal death or a congenital abnormality or 
birth defect
x
requires inpatient hospitalization or prolongation of existing hospitalization, unless 
hospitalization is for:
x
routine treatment or monitoring of the studied indication, not associated with any 
deterioration in condition
x
elective or pre-planned treatment for a pre-existing condition that is unrelated to the 
indication under study and has not worsened since signing the informed consent
x
social reasons and respite care in the absence of any deterioration in the participant’s 
general condition
x
treatment on an emergency outpatient basis for an event not fulfilling any of the 
definitions of a SAE given above and not resulting in hospital admission
x
is medically significant, e.g., defined as an event that jeopardizes the participant or may 
require medical or surgical intervention to prevent one of the outcomes listed above
Medical and scientific judgment should be exercised in deciding whether other situations should 
be considered serious reactions, such as important medical events that might not be immediately 
life-threatening or result in death or hospitalization but might jeopardize the participant or might 
require intervention to prevent one of the other outcomes listed above. Such events should be 
considered as “medically significant.” Examples of such events are intensive treatment in an 
emergency room or at home for allergic bronchospasm, blood dyscrasias, or convulsions that 
do not result in hospitalization or development of dependency or abuse (please refer to the ICH-
E2D Guidelines).
All new malignant neoplasms will be assessed as serious under “medically significant” if other 
seriousness criteria are not met.
All reports of intentional misuse and abuse of the product are also considered serious adverse 
events irrespective of whether a clinical event has occurred.

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Any suspected transmission via a medicinal product of an infectious agent is also considered a 
serious adverse reaction.
8.6.3
SAE reporting
To ensure participant safety, every SAE, regardless of causality, occurring after the participant 
has provided informed consent and until 30 days after the last study visit must be reported to 
Novartis safety immediately, without undue delay, but under no circumstances later than within 
24 hours of obtaining knowledge of the events (Note: If more stringent, local regulations 
regarding reporting timelines prevail). Any SAEs experienced after the 30 day period should 
only be reported to Novartis Safety if the investigator suspects a causal relationship to study 
treatment, unless otherwise specified in local regulations. Any SAEs reported up to the last 
study visit will be reported in the eCRF. SAEs beyond that date will only be recorded in the 
Novartis Safety database. Detailed instructions regarding the submission process and 
requirements are to be found in the Investigator folder provided to each site.
Information about all SAEs is collected and recorded on the electronic Serious Adverse Event 
Report Form; all applicable sections of the form must be completed in order to provide a 
clinically thorough report.
All follow-up information for the SAE including information on complications, progression of 
the initial SAE and recurrent episodes must be reported as follow-up to the original episode 
immediately, without undue delay, but under no circumstances later than within 24 hours of the 
Investigator receiving the follow-up information (Note: If more stringent, local regulations 
regarding reporting timelines prevail). An SAE occurring at a different time interval or 
otherwise considered completely unrelated to a previously reported one must be reported 
separately as a new event.
If the SAE is not previously documented in the Investigator’s Brochure or Package Insert (new 
occurrence) and is thought to be related to the study treatment, a CMO & PS Department 
associate may urgently require further information from the Investigator for health authority 
reporting. Novartis may need to issue an Investigator Notification (IN) to inform all 
Investigators involved in any study with the same study treatment that this SAE has been 
reported.
Suspected Unexpected Serious Adverse Reactions (SUSARs) will be collected and reported to 
the competent authorities and relevant ethics committees in accordance with European Union 
(EU) Clinical Trial Regulation 536/2014 or as per national regulatory requirements in 
participating countries.
8.6.4
Pregnancy
Details of all pregnancies in female participants will be collected after the start of study 
treatment and until 5 half-lives after the last dose of ligelizumab.
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or 
elective termination of a pregnancy for medical reasons will be reported as an AE or SAE.
Abnormal pregnancy outcomes (e.g., spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) are considered SAEs and will be reported as such.

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Any post study pregnancy-related SAE considered reasonably related to the study treatment by 
the Investigator will be reported to Novartis as described in Section 8.6.3. While the 
Investigator is not obligated to actively seek this information in former study participants, he or 
she may learn of an SAE through spontaneous reporting.
Pregnancies
If a female trial participant becomes pregnant, the study treatment should be stopped, and the 
pregnancy consent form should be presented to the trial participant. The participant must be 
given adequate time to read, review and sign the pregnancy consent form. This consent form is 
necessary to allow the Investigator to collect and report information regarding the pregnancy. 
To ensure participant safety, each pregnancy occurring after signing the informed consent must 
be reported to Novartis within 24 hours of learning of its occurrence. The pregnancy should be 
followed up to determine outcome, including spontaneous or voluntary termination, details of 
the birth, and the presence or absence of any birth defects, congenital abnormalities, or maternal 
and/or newborn complications.
Pregnancy should be recorded and reported by the Investigator to the Novartis Chief Medical 
Office and Patient Safety (CMO&PS). Pregnancy follow-up should be recorded on the same 
form and should include an assessment of the possible relationship to the study treatment any 
pregnancy outcome. Any SAE experienced during pregnancy must be reported.
After consent is provided, the pregnancy reporting will occur up to one year after the estimated 
date of delivery.
8.6.5
Disease-related events and/or disease-related outcomes not qualifying 
as AEs or SAEs
Not applicable.
8.6.6
Adverse events of special interest
The following safety topics of interest are described in the Investigators Brochure edition 18 
“Section 7: Summary of the data and guidance for the investigator”: Injection site reactions, 
Hypersensitivity reactions (including anaphylaxis), 
Thrombocytopenia, Parasitic (Helminthic) infection, and Reduction in vaccine efficacy.
8.6.7
Medical device deficiencies
Not applicable.
8.7
CCI
CCI
CCI

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8.8
8.8.1
8.8.2
CCI
CCI
CCI
CCI
CCI
CCI

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8.9
8.9.1
8.9.2
8.10
Health economics OR Medical resource utilization and health 
economics
Not applicable.
9
Statistical considerations
9.1
9.2
Statistical analyses
9.2.1
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

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9.2.2
9.2.3
9.3
Primary endpoint(s)/estimand(s) analysis
9.3.1
Definition of primary endpoint(s)
The primary objective of the study is to assess the long-term safety and tolerability of 
ligelizumab in participants with food allergy for an additional three year period after a core 
study.
Primary endpoints are overall incidence and exposure-adjusted occurrence rates of treatment-
emergent adverse events (TEAEs) and serious adverse events (TESAEs).
TEAEs are defined as events that either: 1) started after the first dose of study treatment and 
within 16 weeks after the last study treatment; or 2) began prior to the first dose of study 
treatment but increased in severity (based on preferred term) within 16 weeks after the last study 
treatment.
For all safety analyses, the safety sets defined in Section 9.1 will be used. All participants 
enrolled into the extension study, regardless of which preceding studies they came from, will 
be included in the safety analysis. All listings and tables will be presented by treatment dose. 
All data will be included in the analysis, regardless of rescue medication use.
9.3.2
Statistical model, hypothesis, and method of analysis
There is no pre-specified hypothesis for the primary endpoints, and no inferential analysis will 
be done for the primary endpoints.
CCI
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Summary statistics will be provided.
Summaries will include: 1) the number and percentages of participants with at least one event 
(incidence rates); and 2) exposure-adjusted occurrence rates (the number of events per 
participant year of exposure). The following treatment-emergent AE summaries will be 
provided for the Safety Set 1 (SAF-1), presented by dose and cumulative duration of exposure:
x
Overall, by primary system organ class and preferred term,
x
Overall, by primary Standardized MedDRA Query (SMQ) and preferred term,
x
Overall, by primary system organ class, preferred term and maximum severity,
x
Suspected drug-related AEs by primary system organ class and preferred term,
x
SAEs by primary system organ class and preferred term,
x
AEs leading to permanent discontinuation of study-drug by primary system organ class 
and preferred term,
x
Adverse events of special interest (AESI).
Other tables will be generated to summarize safety data for participants in SAF-1 who restarted 
study treatment after a protocol mandated interruption period (> 16weeks). Details will be 
provided in the SAP.
Summaries will be performed as well for non-TEAEs for participants who did not receive any 
study treatment doses during the extension study (SAF-2).
Separate summaries will be provided for study treatment-related adverse events, death, serious 
adverse events, and other significant adverse events leading to discontinuation. If a participant 
reported more than one AE with the same preferred term, the AE with the greatest severity will 
be presented. If a participant reported more than one AE within the same primary system organ 
class, the participant will be counted only once with the greatest severity at the system organ 
class level, where applicable.
Other safety analyses (laboratory data, vital signs, ECG) are described in Section 9.4.2.
9.3.3
Handling of intercurrent events of primary estimand (if applicable)
Not Applicable
9.3.4
Handling of missing values
Missing data will not be replaced.
9.3.5
Multiplicity adjustment (if applicable)
Not Applicable
9.3.6
Sensitivity analyses
Not Applicable
9.3.7
Supplementary analysis
Supplementary analyses will be described in the SAP

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9.4
Secondary endpoint(s)/estimand(s) analysis
No multiplicity adjustment will be carried out for secondary analyses described below.
9.4.1
Efficacy and/or pharmacodynamic endpoint(s)
In order to describe the long-term efficacy of ligelizumab, as measured by the tolerance of an 
allergen food protein, summaries will be provided for the proportion of participants tolerating 
a single dose of ≥ 600 mg of peanut protein without dose-limiting symptoms during an open-
label OFC at scheduled timepoints. Additional analysis methods may be specified in the SAP.
9.4.2
Safety endpoints
Safety analyses will be conducted on SAF-1 and may be conducted on other safety analysis sets 
as well. All listings and tables will be presented by treatment group.
Adverse events
Analysis of adverse events has been described in Section 9.3: Analysis of the Primary Endpoint.
Vital signs
Change from baseline in vital sign measurements for each post-baseline visit will be analyzed 
using summary statistics, for each vital sign and treatment group.
Change from baseline will only be summarized for subjects with both baseline and post-baseline 
values. Missing values will not be imputed. Subjects with notable vital signs, as defined in 
Section 10.3, will be listed.
12-lead ECG
All ECG data will be listed by treatment group, participant, and visit/time. Any abnormalities 
will be flagged. Summary statistics will be provided by treatment and visit/time.
Clinical laboratory evaluations
The summary of laboratory evaluations will be presented for two groups of laboratory tests 
(hematology and serum chemistry). Descriptive summary statistics for the change from baseline 
to each study visit will be presented. These descriptive summaries will be presented by 
laboratory test and treatment group. Change from baseline will only be summarized for subjects 
with both baseline and post baseline values. Shift tables using the low/normal/high/ (low and 
high) classification will be used to compare baseline to the worst on-treatment value.
9.4.3
Patient reported outcomes
As described in Section 8.5.1, the impact of ligelizumab on the HRQoL of participants with a 
food allergy will be assessed by several measures based on age group and responder type.
Summaries of domain and total scores in the FAQLQ, FAIM and SF-36v2 will be reported by 
age and responder (participants and/or caregiver) at scheduled timepoints.
Further details will be provided in the SAP.

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9.5
Exploratory endpoint(s)/estimand(s) analysis
9.5.1
9.5.2
9.5.3
9.5.4
DNA
CCI
CCI
CCI
CCI
CCI
CCI
CCI
CCI

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9.6
(Other) Safety analyses
Refer to the SAP for details
9.7
Other analyses
Not applicable.
9.8
Interim analysis
One or more interim analyses may be conducted to support decision-making in relation to the 
current clinical study, the future of the sponsor's clinical development plan, or the long-term 
safety and efficacy of ligelizumab. Additional details will be provided in the SAP.
9.9
Sample size determination
9.9.1
Primary endpoint(s)
The expectation is that approximately 550 participants from the Study CQGE01G12301 and 
other QGE031 Phase III studies will enroll in this extension study, after accounting for an 
estimated drop-out rate of 15% during the core phase of the studies.
No hypothesis testing is planned in the extension study.
9.9.2
Secondary Endpoints
All participants will have the opportunity to receive ligelizumab during the study. This sample 
size is sufficient to yield adequate precision in estimating AE rates in this study. For example, 
if one percent of 200 participants has an AE, the exact 95% Clopper-Pearson confidence interval 
for the proportion of participants would be 0.12% to 3.6%. The table below gives the 95% 
confidence intervals for varying sample sizes and incidence rates, assuming approximately 200 
or 300 subjects are in each treatment dose group.
Table 9-1
Precision Levels (95%) for sensitivity of safety incidence rate
Number of Participants
Event Rate (%)
95% Confidence Interval
200
1
(0.12%, 3.6%)
2
(0.55%, 5%)
3
(1.10%, 6.4%)
300
1
(0.21%, 2.9%)
2
(0.74%, 4.3%)
3
(1.40%, 5.6%)
550
1
(0.35%, 2.2%)
2
(1.00%, 3.6%)
3
(1.70%, 4.8%)
Confidence intervals generated using the exact Clopper-Pearson method.

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10
Supporting documentation and operational considerations
10.1
Appendix 1: Regulatory, ethical, and study oversight 
considerations
10.1.1
Regulatory and ethical considerations
This study will be conducted in accordance with the protocol and with the following:
x
Consensus ethical principles derived from international guidelines including the Declaration 
of Helsinki and Council for International Organizations of Medical Sciences (CIOMS) 
international ethical guidelines
x
Applicable ICH Good Clinical Practice (GCP) guidelines
x
Applicable laws and regulations
The protocol, protocol amendments, ICF, Investigator’s Brochure, and other relevant 
documents (e.g., advertisements) must be submitted to an Institutional Review 
Board/Independent Ethics Committee (IRB/IEC) by the Investigator and reviewed and 
approved by the IRB/IEC before the study is initiated.
Any amendments to the protocol will require IRB/IEC approval before implementation of 
changes made to the study design, except for changes necessary to eliminate an immediate 
hazard to study participants.
Protocols and any substantial amendments/modifications to the protocol will require health 
authority approval prior to initiation except for changes necessary to eliminate an immediate 
hazard to study participants.
The Investigator will be responsible for the following:
Signing a protocol signature page confirming his/her agreement to conduct the study in 
accordance with these documents and all of the instructions and procedures found in this 
protocol and to give access to all relevant data and records to Novartis monitors, auditors, 
Novartis Quality Assurance representatives, designated agents of Novartis, IRBs/IECs, and 
regulatory authorities as required
Providing written summaries of the status of the study to the IRB/IEC annually or more 
frequently in accordance with the requirements, policies, and procedures established by the 
IRB/IEC
Notifying the IRB/IEC of SAEs or other significant safety findings as required by IRB/IEC 
procedures
Providing oversight of the conduct of the study at the site and adherence to requirements of 21 
CFR, ICH guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), European Medical Device Regulation 2017/745 for clinical device research (if 
applicable), and all other applicable local regulations
Inform Novartis immediately if an inspection of the clinical site is requested by a regulatory 
authority

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This clinical study was designed and shall be implemented, executed and reported in accordance 
with the ICH Harmonized Tripartite Guidelines for Good Clinical Practice, with applicable 
local regulations (including European Clinical Trial Regulation 536/2014, US CFR 21), and 
with the ethical principles laid down in the Declaration of Helsinki.
10.1.2
Informed consent process
The Investigator or his/her representative will explain the nature of the study, including the risks 
and benefits, to the participant or their legally authorized representative (defined as 
parent/caregiver) and answer all questions regarding the study.
Participants must be informed that their participation is voluntary. Participants or their legally 
authorized representatives will be required to sign a statement of informed consent that meets 
the requirements of 21 CFR 50, local regulations, ICH guidelines, privacy and data protection 
requirements, where applicable, and the IRB/IEC or study center.
Informed consent must be obtained before conducting any study-specific procedures (e.g., all 
of the procedures described in the protocol). The process of obtaining informed consent must 
be documented in the participant source documents.
The medical record must include a statement that written informed consent was obtained before 
the participant was enrolled in the study and the date the written consent was obtained. The 
authorized person obtaining the informed consent must also sign the ICF.
A copy of the ICF(s) must be provided to the participant or their legally authorized 
representative.
The ICF will contain a separate section that addresses the use of remaining mandatory samples 
for optional additional research. The Investigator or authorized designee will explain to each 
participant the objectives of the additional research. Participants 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 signature will be required to document a participant’s agreement 
to allow any remaining specimens to be used for additional research. Participants who decline 
to participate in this optional additional research will document this.
Eligible participants may only be included in the study after providing (witnessed, where 
required by law or regulation), IRB/IEC-approved informed consent.
If applicable, in cases where the participant's representative(s) gives consent (if allowed 
according to local requirements), the participant must be informed about the study to the extent 
possible given his/her level of understanding. If the participant is capable of doing so, he/she 
must indicate agreement by personally signing and dating the written informed consent 
document.
Information about common side effects already known about the investigational treatment can 
be found in the Investigator's Brochure (IB). This information will be included in the participant 
informed consent and should be discussed with the participant upon obtaining consent and also 
during the study as needed. Any new information regarding the safety profile of the 
investigational drug that is identified between IB updates will be communicated as appropriate, 
for example, via an Investigator notification or an aggregate safety finding. New information 
might require an update to the informed consent and then must be discussed with the participant.

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The following informed consents are included in this study:
x
Main study consent, which also includes:
x
A subsection that requires a separate signature for the ‘Optional Consent for 
Additional Research’ to allow future research on data/samples collected during this 
study
x
Parent/Guardian study consent
x
Child Assent for ages 6-11 years
x
Adolescent Assent for ages 12-17 years
x
As applicable, Pregnancy Outcomes Reporting Consent for female participants
If a minor participant reaches the age of legal majority in the course of the study, he/she/they 
must be re-consented as an adult.
A copy of the approved version of all consent/assent forms must be provided to Novartis after 
IRB/IEC approval.
As per Section 4.5, during a public health emergency as declared by local or regional authorities 
i.e., pandemic, epidemic or natural disaster, that may challenge the ability to obtain a standard 
written informed consent due to limits that prevent an on-site visit, Investigator may conduct 
the informed consent discussion remotely (e.g., telephone, videoconference) if allowable by a 
local health authority.
Guidance issued by local regulatory bodies on this aspect prevail and must be implemented and 
appropriately documented (e.g., the presence of an impartial witness, sign/dating separate ICFs 
by trial participant and person obtaining informed consent, etc.).
10.1.3
Data protection
Participants will be assigned a unique identifier by Novartis. Any participant records or datasets 
that are transferred to Novartis will contain the identifier only; participant names or any 
information which would make the participant identifiable will not be transferred.
The participant must be informed that his/her personal study-related data will be used by 
Novartis in accordance with local data protection law. The level of disclosure must also be 
explained to the participant who will be required to give consent for their data to be used as 
described in the informed consent
The participant must be informed that his/her medical records may be examined by Clinical 
Quality Assurance auditors or other authorized personnel appointed by Novartis, by appropriate 
IRB/IEC members, and by inspectors from regulatory authorities.
Novartis has appropriate processes and policies in place to handle personal data breaches 
according to applicable privacy laws.
10.1.4
Committees structure
10.1.4.1 Data Monitoring Committee
This study will include a data monitoring committee (DMC) which will function independently 
of all other individuals associated with the conduct of this clinical trial, including the site 

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Investigators participating in the study. The DMC will monitor the safety in this study including 
events incurred during OFC at defined intervals the progress of a clinical trial and recommend 
to Novartis whether to continue, modify, or terminate a trial.
Specific details regarding composition, responsibilities, data monitoring, and meeting 
frequency, and documentation of DMC reports, minutes, and recommendations will be 
described in a separate charter that is established between Novartis and the DMC.
10.1.4.2 Adjudication committee
The role of the Adjudication Committee (AC) is to ensure that all treatment outcomes are judged 
uniformly, using standard criteria and processes. The AC will be composed of clinical experts 
to evaluate disease progression and harmonize endpoint assessment criteria using data provided 
by Novartis.
There are three ACs in this study: anaphylactic events, cardio-cerebrovascular events and 
neoplastic events.
An AC will be put in place to review all cases identified through a search algorithm based on 
the Standardized MedDRA Queries of above three events. The clinical presentation and 
association of these events with pre-existing risk factors will be part of the assessment.
All personnel involved in the adjudication process will remain blinded to treatment allocation 
throughout the trial. Specific details regarding endpoint definitions can be found in the 
adjudication charter.
10.1.5
Data quality assurance
Monitoring details describing strategy, including definition of study critical data items and 
processes (e.g., risk-based initiatives in operations and quality such as risk management and 
mitigation strategies and analytical risk-based monitoring), methods, responsibilities, and 
requirements, including handling of noncompliance issues and monitoring techniques (central, 
remote, or on-site monitoring) are provided in the monitoring plan, contracts.
Records and documents, including signed ICFs, pertaining to the conduct of this study must be 
retained by the Investigator for 15 years after study completion unless local regulations or 
institutional policies require a longer retention period. No records may be destroyed during the 
retention period without the written approval of Novartis. No records may be transferred to 
another location or party without written notification to Novartis.
10.1.5.1 Data collection
Designated Investigator staff will enter the data required by the protocol into the Electronic 
Case Report Forms (eCRF). The eCRFs have been built using fully validated secure web-
enabled software that conforms to 21 CFR Part 11 requirements, Investigator site staff will not 
be given access to the EDC system until they have been trained. Automatic validation programs 
check for data discrepancies in the eCRFs, allow modification and/or verification of the entered 
data by the Investigator staff.

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The Investigator/designee is responsible for assuring that the data (recorded on CRFs) (entered 
into eCRF) is complete, accurate, and that entry and updates are performed in a timely manner. 
The Investigator must certify that the data entered are complete and accurate.
After final database lock, the Investigator will receive copies of the participant data for 
archiving at the investigational site.
All data should be recorded, handled, and stored in a way that allows its accurate reporting, 
interpretation, and verification.
10.1.5.2 Database management and quality control
Novartis personnel (or designated CRO) will review the data entered by investigational staff 
for completeness and accuracy. Electronic data queries stating the nature of the problem and 
requesting clarification will be created for discrepancies and missing values and sent to the 
investigational site via the EDC system. Designated Investigator site staff are required to 
respond promptly to queries and to make any necessary changes to the data.
Concomitant treatments and prior medications entered into the database will be coded using the 
World Health Organization (WHO) Drug Reference List, which employs the Anatomical 
Therapeutic Chemical classification system. Medical history/current medical conditions and 
adverse events will be coded using the Medical Dictionary for Regulatory Activities (MedDRA) 
terminology.
Dates of screenings, randomizations, screen failures and study completion, as well as 
randomization codes and data about all study treatment (s) dispensed to the participant and all 
dosage changes will be tracked using an Interactive Response Technology (IRT). The system 
will be supplied by a vendor, who will also manage the database. The data will be sent 
electronically to Novartis (or a designated CRO) at specific timelines.
Each occurrence of a code break via IRT will be reported to the clinical team and monitor. The 
code break functionality will remain available until study shut down or upon request of 
Novartis.
Once all the necessary actions have been completed and the database has been declared to be 
complete and accurate, it will be locked and the treatment codes will be unblinded and made 
available for data analysis. Any changes to the database after that time can only be made after 
written agreement by Novartis development management.
10.1.6
Source documents
Source documents provide evidence for the existence of the participant and substantiate the 
integrity of the data collected. Source documents are filed at the Investigator’s site.
Data reported on the CRF or entered in the eCRF that are transcribed from source documents 
must be consistent with the source documents or the discrepancies must be explained. The 
Investigator may need to request previous medical records or transfer records, depending on the 
study. Also, current medical records must be available.
The Investigator must give the monitor access to all relevant source documents to confirm their 
consistency with the data capture and/or data entry. The Investigator must also keep the original 

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informed consent form signed by the participant (a signed copy is given to the participant). 
Definition of what constitutes source data and its origin can be found in, e.g., source data 
acknowledgment and/or monitoring guidelines.
The Investigator must maintain accurate documentation (source data) that supports the 
information entered in the CRF. Study monitors will perform ongoing source data verification 
to confirm that data entered into the CRF by authorized site personnel are accurate, complete, 
and verifiable from source documents; that the safety and rights of participants are being 
protected; and that the study is being conducted in accordance with the currently approved 
protocol and any other study agreements, ICH GCP, and all applicable regulatory requirements.
Key study personnel must be available to assist the field monitor during these visits. Continuous 
remote monitoring of each site’s data may be performed by a centralized Novartis / delegated 
CRO /CRA organization. Additionally, a central analytics organization may analyze data & 
identify risks & trends for site operational parameters, and provide reports to Novartis clinical 
teams to assist with trial oversight.
10.1.7
Publication policy
The protocol will be registered in a publicly accessible database such as clinicaltrials.gov and 
as required in CTIS public website. In addition, after study completion (defined as last 
participant last visit) and finalization of the study report the results of this trial will be submitted 
for publication and posted in a publicly accessible database of clinical trial results, such as the 
Novartis clinical trial results website and all required health authority websites (e.g., 
Clinicaltrials.gov, CTIS public website etc.).
For details on the Novartis publication policy including authorship criteria, please refer to the 
Novartis publication policy training materials that were provided to you at the trial Investigator 
meetings.
Any data analysis carried out independently by the Investigator should be submitted to Novartis 
before publication or presentation.
Summary results of primary and secondary endpoints will be disclosed based upon the global 
Last Participant Last Visit (LPLV) date, since multinational studies are locked and reported 
based upon the global LPLV.
10.1.8
Protocol adherence and protocol amendments
This protocol defines the study objectives, the study procedures and the data to be collected on 
study participants. Additional assessments required to ensure safety of participants should be 
administered as deemed necessary on a case by case basis. Under no circumstances including 
incidental collection is an Investigator allowed to collect additional data or conduct any 
additional procedures for any purpose involving any investigational drugs under the protocol, 
other than the purpose of the study. If despite this interdiction prohibition, data, information, 
observation would be incidentally collected, the Investigator shall immediately disclose it to 
Novartis and not use it for any purpose other than the study, except for the appropriate 
monitoring on study participants.

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Investigators ascertain they will apply due diligence to avoid protocol deviations. If an 
Investigator feels a protocol deviation would improve the conduct of the study this must be 
considered a protocol amendment, and unless such an amendment is agreed upon by Novartis 
and approved by the IRB/IEC and health authorities, where required, it cannot be implemented.
10.1.8.1 Protocol amendments
Any change or addition to the protocol can only be made in a written protocol amendment that 
must be approved by Novartis, health authorities where required, and the IRB/IEC prior to 
implementation.
Only amendments that are required for participant safety may be implemented immediately 
provided the health authorities are subsequently notified by protocol amendment and the 
reviewing IRB/IEC is notified.
Notwithstanding the need for approval of formal protocol amendments, the Investigator is 
expected to take any immediate action required for the safety of any participant included in this 
study, even if this action represents a deviation from the protocol. In such cases, Novartis should 
be notified of this action and the IRB/IEC at the study site should be informed according to 
local regulations.
10.2
Appendix 2: Abbreviations and definitions
10.2.1
List of abbreviations
AC
Adjudication Committee
ACE
Angiotensin-converting-enzyme
AE
Adverse Event
AESI
Adverse Events of Special Interest
AF
Adult form
ALP
Alkaline Phosphatase
ALT
Alanine Aminotransferase
ANA
Antinuclear Antibodies
ASMA
Anti-smooth muscle antibody
AST
Aspartate Aminotransferase
ATC
Anatomical Therapeutic Chemical
ATS/ERS
American Thoracic Society / European Respiratory Society
AUC
Area under the Curve
AxMP
Auxiliary Medicinal Product
bpm
Beats per minute
BUN
Blood Urea Nitrogen
CD23
IgE (low affinity) receptor
CF
Child form
CIOMS
Council for International Organizations of Medical Sciences
CK
Creatine Kinase
cm
centimetre
CMO&PS
Chief Medical Office and Patient Safety
CCI
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CMV
Cytomegalovirus
COA
Clinical Outcome Assessment
CoFAR
Consortium of Food Allergy Research
CONSORT
Consolidated Standards of Reporting Trials
COVID-19
Coronavirus pandemic 2019
CRF
Case Report/Record Form (paper or electronic)
CRO
Contract Research Organization
CSR
Clinical study report
CSU
Chronic Spontaneous Urticaria
CV
coefficient of variation
DBL
Database lock
DBPCFC
Double Blind Placebo Controlled Food Challenge
DILI
Drug-Induced Liver Injury
DIN
Drug Inducted Nephrotoxicity
DLS
Dose Limiting Symptoms
DLT
Dose Limiting Toxicity
DMC
Data Monitoring Committee
DNA
Deoxyribonucleic acid
EAACI
European Academy of Allergy and Clinical Immunology
EBV
Epstein-Barr virus
ECG
Electrocardiogram
eCRF
electronic Case Report Form
EDC
Electronic Data Capture
EEA
European Economic Area
EMA
European Medicines Agency
EOFu
End of Follow-up
EoT
End of Treatment
ERCP
Endoscopic Retrograde Cholangiopancreatography
eSource
Electronic Source
EU
European Union
FAIM
Food Allergy Independent Measure
FAQL
Food allergy quality of life
FAQLQ
Food Allergy Quality of Life Questionnaire
FAS
Full Analysis Set
FDA
Food and Drug Administration
FEV1
Forced Expiratory Volume during the 1st second
FSH
Follicle Stimulating Hormone
GCP
Good Clinical Practice
GCS
Global Clinical Supply
GGT
Gamma-glutamyl transferase
GLDH
Glutamate Dehydrogenase
h
Hour
HBsAg
Hepatitis B virus surface antigen
HBV
Hepatitis B Virus
HCV
Hepatitis C Virus
HEV
High endothelial venules
HRQoL
Health-Related Quality of Life

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HSV
Herpes simplex virus
IB
Investigator’s Brochure
ICF
Informed Consent Form
ICH
International Council for Harmonization of Technical Requirements for Pharmaceuticals for 
Human Use
ICU
Intensive Care Unit
IEC
Independent Ethics Committee
IFU
Instructions for Use
IgE
Immunoglobulin E
IMP
Investigational Medicinal Product
IN
Investigator Notification
INR
International Normalized Ratio
IRB
Institutional Review Board
IRT
Interactive Response Technology
IUD
Intrauterine device
IUS
Intrauterine system
L
Litre
LDH
lactate dehydrogenase
LFT
Liver function test
LLOQ
lower limit of quantification
LPLV
Last patient last visit
mAb
Monoclonal Antibody
MCV
Mean corpuscular volume
MedDRA
Medical dictionary for regulatory activities
mg
milligram(s)
mL
milliliter(s)
mm
millimeter
mmHg
millimeters of mercury, blood pressure measurement
MR
Maximum Responder
MRI
Magnetic Resonance Imaging
MTD
Maximum Tolerated Dose
NIH
National Institute of Health
No.
Number
NSD
Needle safety device
OFC
Oral Food Challenge
OHP
Off-site Healthcare Professional
OIT
Oral Immunotherapy
OL-OFC
Open label oral food challenge
PB
Parental burden
PCM
Peanut Challenge Meal
PD
Pharmacodynamic(s)
PF
Parental form
PFS
Pre-filled syringe
PRACTALL
Practical Allergy
PRO
Patient Reported Outcomes
CCI
CCI

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PSD
Premature Subject Discontinuation
PT
prothrombin time
PTA
Post trial access
q2w
every two weeks
QoL
Quality of Life
QTcF
QT interval corrected by Fridericia’s formula
RBC
Red Blood Cells
RNA
Ribonucleic acid
SABA
short-acting ß-agonist
SAE
Serious Adverse Event
SAF
Safety analysis set
SAP
Statistical Analysis Plan
SC
subcutaneous
SCRN
Screening
SD
standard deviation
SF-36v2
Acute Version – Medical Outcomes Study 36-Item Short Form Version 2 Acute Version (recall 
period is past week)
SLIT
Sublingual immunotherapy
SMQ
Standardized MedDRA Query
SoA
Schedule of Activities
SPT
Skin Prick Test
SUSAR
Suspected Unexpected Serious Adverse Reaction
TBL
Total Bilirubin
TEAEs
Treatment Emergent Adverse events
TESAEs
Treatment Emergent Serious Adverse Events
TF
Adolescent form
TSH
Thyroid stimulating hormone
TSPT
Titration skin prick test
ULN
upper limit of normal
ULQ
Upper limit of quantification
WBC
White blood cells
WHO
World Health Organization
WK
Week
β-hCG
Beta-Human Chorionic Gonadotropin
μL
microlitre
10.2.2
Definitions
Additional 
treatment
Medicinal products that may be used during the clinical trial as described in the protocol, 
but not as an investigational medicinal product (e.g., any background therapy)
Assessment
A procedure used to generate data required by the study
Auxiliary medicinal 
product
As per EU CTR Auxiliary Medicinal Product is:
Medicinal product used for the needs of a clinical trial as described in the protocol, but 
not as an investigational medicinal product (e.g., rescue medication, challenge agents, 
background treatment or medicinal products used to assess end-points in the clinical 
CCI
CCI
CCI

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trial).
Concomitant therapy is not considered as AMP.
Biologic Samples
A biological specimen including, for example, blood (plasma, serum), saliva, tissue, 
urine, stool, etc. taken from a study participant
CE marking
A marking by which a manufacturer indicates that a device is in conformity with the 
applicable requirements set out in European Union legislation providing for its affixing.
CE marking of medical devices is required prior to lawfully placing them on the 
European Union market.
Clinical Outcome 
Assessment (COA)
A measure that describes or reflects how a participant feels, functions, or survives
Clinical Trial Team
A group of people responsible for the planning, execution and reporting of all clinical trial 
activities. Examples of team members include the Study Lead, Medical Monitor, Trial 
Statistician etc.
Cohort
A group of individuals who share a common exposure, experience or characteristic, or a 
group of individuals followed-up or traced over time
Control drug
A study intervention (active or placebo) used as a comparator to reduce assessment 
bias, preserve blinding of investigational drug, assess internal study validity, and/or 
evaluate comparative effects of the investigational drug
Cycles
Number and timing or recommended repetitions of therapy are usually expressed as 
number of days (e.g., q28 days)
Discontinuation 
from study
Point/time when the participant permanently stops receiving the study treatment and 
further protocol required assessments or follow-up, for any reason. No specific request 
is made to stop the use of their samples or data.
Discontinuation 
from study 
treatment
Point/time when the participant permanently stops receiving the study treatment for any 
reason (prior to the planned completion of study intervention administration, if any). 
Participant agrees to the other protocol required assessments including follow-up. No 
specific request is made to stop the use of their samples or data.
Dosage
Dose of the study treatment given to the participant in a time unit (e.g., 100 mg once a 
day, 75 mg twice a day)
Electronic Data 
Capture (EDC)
Electronic data capture (EDC) is the electronic acquisition of clinical study data using 
data collection systems, such as Web-based applications, interactive voice response 
systems and clinical laboratory interfaces. EDC includes the use of Electronic Case
Report Forms (eCRFs) which are used to capture data transcribed from source 
data/documents used at the point of care
End of the clinical 
trial
The end of the clinical trial is defined as the last visit of the last participant.
Enrollment
Point/time of participant entry into the study at which informed consent must be 
obtained. The action of enrolling one or more participants
eSource (DDE)
eSource Direct Data Entry (DDE) refers to the capture of clinical study data 
electronically, at the point of care. eSource Platform/Applications combines source 
documents and case report forms (eCRFs) into one application, allowing for the real 
time collection of clinical trial information to Novartis and other oversight authorities, as 
appropriate
Estimand
As defined in the ICH E9(R1) addendum, estimand is a precise description of the 
treatment effect reflecting the clinical question posed by the trial objective. It summarizes 
at a population-level what the outcomes would be in the same participants under 
different treatment conditions being compared. Attributes of an estimand include the 
population, variable (or endpoint) and treatment of interest, as well as the specification 
of how the remaining intercurrent events are addressed and a population-level summary 
for the variable.
Healthy volunteer
A person with no known significant health problems who volunteers to be a study 
participant 
Intercurrent events
Events occurring after treatment initiation that affect either the interpretation or the 
existence of the measurements associated with the clinical question of interest.

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Investigational 
drug/ treatment
The drug whose properties are being tested in the study
Investigational 
Medical Device
Medical Device being assessed for safety or performance in a clinical investigation. This 
includes devices already on the market and being evaluated for new intended uses, new 
populations, new materials, or design changes
Medication number
A unique identifier on the label of medication kits
Mis-randomized 
participants
Mis-randomized participants are those who were not qualified for randomization and 
who did not take study treatment, but have been inadvertently randomized into the study 
or the participant allocated to an invalid stratification factor
Off-site
Describes trial activities that are performed at remote location by an off-site healthcare 
professional, such as procedures performed at the participant's home.
Off-site healthcare 
Professional (OHP)
A qualified healthcare professional, who performs certain protocol procedures for the 
participant in an off-site location such as a participant's home.
Other treatment
Treatment that may be needed/allowed during the conduct of the study (i.e., concomitant 
or rescue therapy)
Part
A sub-division of a study used to evaluate specific objectives or contain different 
populations. For example, one study could contain a single dose part and a multiple 
dose part, or a part in participants with established disease and in those with newly-
diagnosed disease
Participant
A trial participant (can be a healthy volunteer or a patient). "Participant" terminology is 
used in the protocol whereas term "Subject" is used in data collection
Participant number
A unique number assigned to each participant upon signing the informed consent. This 
number is the definitive, unique identifier for the participant and should be used to 
identify the participant throughout the study for all data collected, sample labels, etc.
Patient-Reported 
Outcome (PRO)
A measurement based on a report that comes directly from the participant about the 
status of a participant's health condition without amendment or interpretation of the 
participant's report by a clinician or anyone else
Period
The subdivisions of the trial design (e.g., Screening, Treatment, Follow-up) which are 
described in the Protocol. Periods define the study phases and will be used in clinical 
trial database setup and eventually in analysis
Personal data
Participant information collected by the Investigator that is coded and transferred to 
Novartis for the purpose of the clinical trial. This data includes participant identifier 
information, study information and biological samples.
Premature 
participant 
withdrawal
Point/time when the participant exits from the study prior to the planned completion of all 
study drug administration and/or assessments: at this time all study drug administration 
is discontinued and no further assessments are planned.
Randomization
The process of assigning trial participants to investigational drug or control/comparator 
drug using an element of chance to determine the assignments in order to reduce bias.
Randomization 
number
A unique identifier assigned to each randomized participant
Remote
Describes any trial activities performed at a location that is not the investigative site.
Rescreening
If a participant fails the initial screening and is considered as a Screen Failure, he/she 
can be invited once for a new Screening visit after medical judgment and as specified by 
the protocol
Run-in Failure
A participant who is screened but not randomized/treated after the run-in period (where 
run-in period requires adjustment to participant's intervention or other treatment)
Screen Failure
A participant who did not meet one or more criteria that were required for participation in 
the study
Source 
Data/Document
Source data refers to the initial record, document, or primary location from where data 
comes. The data source can be a database, a dataset, a spreadsheet or even hard-
coded data, such as paper or eSource

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Stage in cancer
The extent of a cancer in the body. Staging is usually based on the size of the tumor, 
whether lymph nodes contain cancer, and whether the cancer has spread from the 
original site to other parts of the body
Start of the clinical 
trial
The start of the clinical trial is defined as the signature of the informed consent by the 
first participant
Study device
Study device is a medical device (marketed or investigational) that is used in a 
circumstance that makes it part of the investigation.
Study treatment
Any drug or combination of drugs or intervention administered to the study participants 
as part of the required study procedures; includes investigational drug(s), control(s) or 
background therapy
Tele-visit
Procedures or communications conducted using technology such as telephone or video-
conference, whereby the participant is not at the investigative site where the Investigator 
will conduct the trial.
Treatment 
arm/group
A treatment arm/group defines the dose and regimen or the combination, and may 
consist of 1 or more cohorts.
Treatment of 
interest
The treatment of interest and, as appropriate, the alternative treatment to which 
comparison will be made. These might be individual interventions, combinations of 
interventions administered concurrently, e.g., as add-on to standard of care, or might 
consist of an overall regimen involving a complex sequence of interventions. This is the 
treatment of interest used in describing the related clinical question of interest, which 
might or might not be the same as the study treatment.
Variable (or 
endpoint)
The variable (or endpoint) to be obtained for each participant that is required to address 
the clinical question. The specification of the variable might include whether the 
participant experiences an intercurrent event.
Withdrawal of 
consent
Withdrawal of consent from the study occurs when the participant explicitly requests to 
stop use of their data and/or biological samples AND no longer wishes to receive study 
treatment, AND does not agree to further protocol required assessments. This request 
should be in writing (depending on local regulations) and recorded in the source 
documentation.
This request should be distinguished from a request to discontinue the study. Other 
study participant's privacy rights are described in the corresponding informed consent 
form.
10.3
Appendix 3: Clinical laboratory tests
10.3.1
Clinically notable laboratory values and vital signs
Laboratory assessments
Refer to Section 10.5 for clinically notable laboratory values for liver safety monitoring.
Refer to Section 10.6 for clinically notable laboratory values for renal safety monitoring
The following other specific criteria have been identified for this study:
x
Platelets < 75 000/μL
x
Any participant who has platelets < 75 000/μL after first study drug administration should 
discontinue study treatment.
For all other laboratory assessments, the Central Laboratory will flag laboratory values falling 
outside of the normal ranges on the Central Laboratory Report (which the investigator should 
review and sign-off) and the investigator will report any values considered clinically significant 
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Vital signs
Notable values for vital signs for adults are:
x
heart rate of < 60 and > 100 bpm
x
systolic blood pressure of < 90 and ≥ 140 mmHg
x
diastolic blood pressure of < 60 and ≥ 90 mmHg
For children (6-11 years) and adolescents, the notable values are described in Table 10-1:
Table 10-1
Notable values for Heart Rate (HR) and Blood Pressure in children and 
adolescents
Age range
HR (bpm)
Low
High
6-8 years
<74
>111
8-12 years
<67
>103
12-15 years
<62
>96
≥ 15 years
<58
>92
Age (years)
Blood pressure (mmHg)
Boys
Girls
6
105
66
105
67
7
106
68
106
68
8
107
69
107
69
9
107
70
108
71
10
108
72
109
72
11
110
74
111
74
12
113
75
114
75
13
120
80
120
80
Heart Rate (HR) Adapted from Fleming et al 2011; Blood Pressure (BP) adapted from Flynn et al 2017
ECG
For adults, a notable QTc value is defined as a QTcF (Fridericia’s) interval of greater than 450 
ms for males or greater than 460 ms for females – all such ECGs will be flagged by the Central 
CRO’s cardiologist and require assessment for clinical relevance by the investigator.
For children, a QTc ≤450 ms is recommended as the upper limit of normal for children up to 
12 years of age. In children older than 12 years, the same thresholds apply as for adults i.e.,QTc 
<450 ms in males and QTc <460 ms in females (Novartis ECG and QTc Clinical Development 
Safety Guideline, 2017)
10.4
Appendix 4: Participant Engagement
The following participant engagement initiatives are included in this study and will be provided, 
as available, for distribution to study participants at the time points indicated. If compliance is 
impacted by cultural norms or local laws and regulations, sites may discuss modifications to 
these requirements with Novartis.
x
Thank You letter
x
Plain language trial summary - after CSR publication

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10.5
Appendix 5: Liver safety monitoring
To ensure participant safety and enhance reliability in determining the hepatotoxic potential of 
an investigational drug, a standardized process for identification, monitoring and evaluation of 
liver events has to be followed.
Please refer to Table 10-2 in Appendix 5 for complete definitions of liver laboratory triggers.
Once a participant is exposed to study treatment, every liver event defined in Table 10-3 should 
be followed up by the Investigator or designated personnel at the trial site, as summarized 
below. Additional details on actions required in case of liver events are outlined in Table 10-4.
Repeat liver chemistry tests (i.e., ALT, AST, TBL, PT/INR, ALP and G-GT) to confirm 
elevation.
x
These liver chemistry repeats will be performed using the central laboratory. If results will 
not be available from the central laboratory, then the repeats can also be performed at a local 
laboratory to monitor the safety of the participant. If a liver event is subsequently reported, 
any local liver chemistry tests previously conducted that are associated with this event 
should have results recorded on the appropriate CRF.
x
If the initial elevation is confirmed, close observation of the participant will be initiated, 
including consideration of treatment interruption if deemed appropriate.
x
Discontinuation of the investigational drug (refer to the Discontinuation of study treatment 
section), if appropriate
x
Hospitalization of the participant if appropriate
x
Causality assessment of the liver event
x
Thorough follow-up of the liver event should include
x
These investigations can include based on Investigator’s discretion: serology tests, 
imaging and pathology assessments, hepatologist’s consultancy; obtaining more 
detailed history of symptoms and prior or concurrent diseases, history of concomitant 
drug use, exclusion of underlying liver disease
All follow-up information and procedures performed must be recorded as appropriate in the 
CRF.
10.5.1
Liver event and laboratory trigger definitions & follow-up requirements
Table 10-2
Liver event and laboratory trigger definitions
Definition/ threshold
Liver laboratory triggers
If ALT, AST and total bilirubin normal at 
baseline:
● ALT or AST > 5 × ULN
● ALP > 2 × ULN (in the absence of known bone pathology)
● Total bilirubin > 3 × ULN (in the absence of known Gilbert 
syndrome)
● ALT or AST > 3 × ULN and INR > 1.5
● Potential Hy’s Law cases (defined as ALT or AST > 3 × ULN and 
Total bilirubin > 2 × ULN [mainly conjugated fraction] without notable 
increase in ALP to > 2 × ULN)
● Any clinical event of jaundice (or equivalent term)
● ALT or AST > 3 × ULN accompanied by (general) malaise, fatigue, 
abdominal pain, nausea, or vomiting, or rash with eosinophilia
● Any adverse event potentially indicative of a liver toxicity*

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Definition/ threshold
If ALT or AST abnormal at baseline:
● ALT or AST > 3x baseline or > 300 U/L (whichever occurs first)
*These events cover the following: hepatic failure, fibrosis and cirrhosis, and other liver damage-related 
conditions; non-infectious hepatitis; benign, malignant and unspecified liver neoplasms ULN: upper limit of 
normal
Table 10-3
Follow-up requirements for liver laboratory triggers 
ALT
TBL
Liver 
Symptoms
Action
ALT increase without bilirubin increase:
If normal at baseline:
ALT > 3 x ULN
Normal
For participants 
with Gilbert’s 
syndrome: No 
change in baseline 
TBL
None
● No change to study 
treatment
● Measure ALT, AST, ALP, 
GGT, TBIL, INR, albumin, 
CK, and GLDH in 48-72
hours.
● Follow-up for symptoms.
If elevated at baseline:
ALT > 2 x baseline
or > 300 U/L (whichever occurs ﬁrst)
If normal at baseline:
ALT > 5 x ULN for more than two 
weeks
Normal
For participants 
with Gilbert’s 
syndrome: No 
change in baseline 
TBL
None
● Interrupt study 
treatment
● Measure ALT, AST, ALP, 
GGT, TBIL, INR, albumin, 
CK, and GLDH in 48-72
hours.
● Follow-up for symptoms.
● Initiate close monitoring 
and workup for competing 
etiologies.
● Study treatment can be 
restarted only if another 
etiology is identiﬁed and 
liver enzymes return to 
baseline.
If elevated at baseline:
ALT > 3 x baseline
AND > 5 x ULN for more than two 
weeks
If normal at baseline:
ALT > 8 x ULN
Normal
None
ALT increase with bilirubin increase:
If normal at baseline:
ALT > 3 x ULN
TBL > 2 x ULN (or 
INR > 1.5)
For participants 
with Gilbert’s 
syndrome: Doubling 
of direct bilirubin
None
If elevated at baseline:
ALT > 2 x baseline
or > 300 U/L (whichever occurs ﬁrst)
If normal at baseline:
ALT > 3 x ULN
Normal or elevated
Severe 
fatigue, 
nausea, 
vomiting, 
right upper 
quadrant 
pain
If elevated at baseline:
ALT > 2 x baseline
or > 300 U/L (whichever occurs ﬁrst)
Table 10-4
Follow-up requirements for liver laboratory triggers
Criteria
Actions required
Follow-up monitoring
Total Bilirubin 
(isolated)
>1.5 – 3.0 ULN
● Maintain treatment
● Repeat LFTs within 48-72 hours
Monitor LFTs weekly until 
resolutionc to ≤ Grade 1 or to 
baseline

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Criteria
Actions required
Follow-up monitoring
> 3 - 10 × ULN (in 
the absence of 
known Gilbert 
syndrome)
● Interrupt treatment
● Repeat LFT within 48-72 hours
● Hospitalize if clinically appropriate
● Establish causality
● Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF
Monitor LFTs weekly until resolution 
to ≤ Grade 1 or to baseline (ALT, 
AST, total bilirubin, Alb, PT/INR, 
ALP and GGT)
Test for hemolysis (e.g., 
reticulocytes, haptoglobin, 
unconjugated [indirect] bilirubin)
> 10 x ULN
● Discontinue the study treatment immediately
● Hospitalize the participant
● Establish causality
● Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF
ALT, AST, total bilirubin, Alb, 
PT/INR, ALP and GGT until 
resolution (frequency at Investigator 
discretion)
Any AE potentially 
indicative of a liver 
toxicity*
● Consider study treatment interruption or 
discontinuation
● Hospitalization if clinically appropriate
● Establish causality
● Record the AE and contributing factors (e.g., 
conmeds, med hx, lab) in the appropriate CRF
Investigator discretion
c Resolution is defined as an outcome of one of the following: (1) return to baseline values, (2) stable values at 
three subsequent monitoring visits at least 2 weeks apart, (3) remain at an elevated level after a maximum of 6 
months, (6) liver transplantation, and (5) death.
*These events cover the following: hepatic failure, fibrosis and cirrhosis, and other liver damage-related 
conditions; non-infectious hepatitis; the benign, malignant and unspecified liver neoplasms.
Based on Investigator’s discretion investigation(s) for contributing factors for the liver event 
can include: Serology tests, imaging and pathology assessments, hepatologist’s consultancy; 
obtaining more detailed history of symptoms and prior or concurrent diseases, history of 
concomitant drug use, exclusion of underlying liver disease.
10.6
Appendix 6: Renal safety monitoring
The following base monitoring for renal laboratory values, as per the Novartis Drug-Induced 
Nephrotoxicity Guidelines (Nov 2017; Table 10-5 below) of abnormal renal laboratory values 
will be carried out as part of the assessment schedule (Table 1-4) during the course of the study.
Table 10-5
Base Renal Monitoring
Assessment
Assessment Frequency
Serum
1. Single baseline
Creatinine, Electrolytes (Na, Ca, K)
2. Steady State assessment
Urine
3. 6-monthly during the study
Dipstick (Spot urine sample)
4. Final visit >= 48h after the last dose
Every renal laboratory trigger or renal event as defined in Table 10-6 should be followed up by 
the investigator or designated personnel at the trial site as summarized in Table 10-7.

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10.6.1
Specific Renal Alert Criteria and Actions and Event Follow-up
Table 10-6
Specific renal alert criteria and actions
Renal Event
Actions
Confirmed serum creatinine increase 25% –
49%
• Consider causes and possible interventions
• Follow-up within 2-5 days
Serum creatinine increase ≥ 50% + OR if <18 
years old, eGFR ≤ 35mL/min/1.73 m2
• Consider causes and possible interventions
• Repeat assessment within 24-48h if possible
• Consider drug interruption or discontinuation unless other 
causes are diagnosed and corrected
• Consider participant hospitalization and specialized 
treatment
New onset dipstick proteinuria ≥ 3+
OR
Protein-creatinine ratio (PCR) ≥ 1g/g
Cr (or mg/mmol equivalent as converted by the
measuring laboratory)
• Consider causes and possible interventions
• Assess serum albumin & serum protein
• Repeat assessment to confirm
• Consider drug interruption or discontinuation unless other 
causes are diagnosed and corrected
New onset hematuria ≥ 3+ on urine dipstick
Assess & document
• Repeat assessment to confirm
• Distinguish hemoglobinuria from hematuria
• Urine sediment microscopy
• Assess sCr
• Exclude infection, trauma, bleeding from the distal urinary 
tract/bladder, menstruation
• Consider bleeding disorder
+ Corresponds to KDIGO criteria for Acute Kidney Injury (Kidney Disease: Improving Global Outcomes 
(KDIGO) CKD Work 2013)
Whenever a renal event is identified, a detailed participant history and examination are indicated to identify and 
potentially eliminate risk factors that may have initiated or contributed to the event: 
· Blood pressure assessment (after 5-minute rest, with an appropriate cuff size) 
· Signs and symptoms like fever, headache, shortness of breath, back or abdominal pain, dysuria or hematuria, 
dependent or periorbital edema 
· Changes in blood pressure, body weight, fluid intake, voiding pattern, or urine output 
· Concomitant events or procedures such as trauma, surgical procedures, cardiac or hepatic failure, contrast 
media or other known nephrotoxin administration, or other diseases or causes, e.g., dehydration due to 
delirium, tumor lysis
Table 10-7
Renal event follow-up
FOLLOW-UP OF RENAL EVENTS
Assess+, document and record in CRF • Urine dipstick and sediment microscopy evidence of DIN: crystals, red 
blood cells (dysmorphic/glomerular vs. non-dysmorphic/non-glomerular), white blood cells, tubular epithelial 
cells • Blood pressure and body weight • Serum creatinine, BUN, electrolytes (sodium, potassium, phosphate, 
calcium), bicarbonate and uric acid • Urine output
Review and record possible contributing factors to the renal event (co-medications, other co-morbid conditions) 
and additional diagnostic procedures (MRI etc) in the CRF
Monitor participant regularly (frequency at investigator’s discretion) until - • Event resolution: (sCr within 10% of 
baseline or protein-creatinine ratio < 1 g/g Cr, or ACR <300 mg/g Cr of baseline) or • Event stabilization: sCr 
level with ±10% variability over last 6 months or protein-creatinine ratio stabilization at a new level with ±50% 
variability over last 6 months
Analysis of urine markers in samples collected over the course of the DIN event

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10.7
Appendix 7: Oral Food Challenge
10.7.1
Background
The Oral Food Challenge (OFC) represents the gold standard for diagnosing food allergies. It 
is also the most objective method to clinically estimate threshold doses for allergenic foods in 
highly sensitive individuals (Taylor et al 2004). In this study, the OFC is based upon several 
available guidelines, PRACTALL (Sampson et al 2012) and the CoFAR Grading Definition of 
Dose-Limiting Symptoms. The test itself corresponds most closely to the natural ingestion of 
food.
In general, the OFC is to be strictly performed under medical supervision to document the dose 
of allergen that provokes a reaction and, if needed, to administer symptomatic treatment which 
could potentially require the management of anaphylaxis. Participants must be in good health 
before proceeding with the food challenge and should be advised to avoid physical exercise at 
least one hour prior to the start of the procedure. A light breakfast is optional on the day of the 
OFC, in line with local practice. Additionally, participants should be on minimal or no 
symptomatic medication before starting the OFC (Table 6-4 and Table 6-5).
Intravenous access may be set up before the OFC at the investigator’s discretion (e.g., 
participant at high risk of reaction or severe reaction based upon prior history and medical 
history).
At the start of the OFC, a small dose of allergen is administered. This dose is intentionally lower 
than any dose expected to induce a reaction (Niggemann and Beyer 2007). While monitoring 
the participant for any allergic symptoms, the allergen dose is gradually increased until a 
cumulative dose at least equivalent to the portion of allergen as defined in the objectives 
(Section 3) is ingested (refer to the QGE031G12303B Pharmacy Manual)
10.7.2
Dosing Schedule
This study includes OFC as per the Assessment Schedule (Table 1-4). Each OFC consists of an 
active allergen peanut challenge meal.
Study treatment must be administered at least 1 hour before the OFC. If study treatment 
is started based on the responder-driven approach (Previous MR is no longer MR after 
being off-treatment (Section 4.1.2) the time interval between the OFC and restart of study 
treatment must be a minimum of 24 h.
10.7.2.1 Maximum dose
Within the OFC, incremental allergen dose increases continue until the highest dose for the 
challenge has been reached or until the participant displays (a) dose-limiting symptom(s) 
(Section 10.7.5).
For the OFC, three hundred (300) mg of food protein is estimated to correspond to the amount 
of allergen generally associated with accidental exposure, while 
 corresponds to the 
highest food protein dose used within this protocol.
The OFC allergen doses are indicated by dry weight (mg) in Table 10-8. The allergen granules 
are to be reconstituted for administration and given to the participant in portions measured by 
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volume (mL) starting from the lowest dose. Refer to the Pharmacy Manual for complete 
preparation and administration instruction.
10.7.2.2 OFC allergen dose administration instruction
Table 10-8
Allergen Dosing Table (active ingredient dry weight)
Allergen dose No.
Food allergen protein (mg)
Cumulative dose (mg)
1
1
1
2
3
4
3
10
14
4
30
44
5
100
144
6
300
444
7
600
1044
8
1000
2044
9
After each administered dose of reconstituted allergen, participants are to be monitored for any 
reaction. In the presence of an allergic reaction, and at the investigator's discretion, the interval 
between escalating doses can be increased or the challenge can be stopped. (Section 10.7.5)
The minimum observation time between doses is 15 minutes; the maximum observation time 
is 30 minutes. If needed, an additional 30 minutes of observation is permitted for further 
evaluation of symptoms. If the continuation of the OFC is still in question after 1 hour of 
observation, the challenge should be considered positive and should be stopped.
During and up to at least one hour after the completion of the OFC, vital signs should be 
monitored approximately every 15 minutes and documented in source.
In the event of an allergen dosing error, the site should contact Novartis.
10.7.3
Peanut OFC material
Novartis will supply the Oral Food Allergen Peanut Flour Chocolate Meal Base globally in an 
open-label fashion.
x
high dose: 20%w/w Peanut Flour Chocolate Flavour Challenge Meal Base (20%w/w 
Peanut Choc)
x
low dose: 0.67%w/w Peanut Flour Chocolate Flavour Challenge Meal Base (0.67%w/w 
Peanut Choc)
Pharmaceutical Dosage Form: Granules for oral suspension
Route of Administration: Oral
The Peanut Challenge Meal (PCM001) will be used for the open-label OFC. This Auxiliary 
Medicinal Product (AxMP) is currently not approved for marketing in any country worldwide. 
It is important to conduct OFC by using standardized material in this study, however, there is 
currently no authorized AxMP available appropriate for this trial, therefore PCM001 will be 
used.
CCI
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The food challenge material and preparation instructions are described in detail in the 
QGE031G12301B Pharmacy Manual provided separately.
10.7.4
Preparing for the food challenge
Prior to OFC material preparation, study site personnel need to access the IRT system to obtain 
the allergen kit number to be used.
10.7.5
Evaluation parameters of the OFC
Objective symptoms exhibited by participants should be evaluated through physical 
examination. Complaints arising from the participant without observable changes will be 
classified as subjective.
The OFC will be considered positive with the occurrence of any dose-limiting symptom(s). 
Dose-limiting symptoms indicate a true allergic reaction occurring during the administration of 
a single dose that should preclude the administration of any further doses. Investigators should 
refer to Table 10-9 (CoFAR grading scale) for the definition of dose-limiting symptoms. 
Symptoms can be mild, moderate or severe. Mild symptoms are not usually considered dose-
limiting, although a combination of mild symptoms during a single dose might lead to the 
cessation of the OFC at the discretion of the investigator. All moderate and severe symptoms 
as defined in Table 10-9 are considered dose-limiting.
Symptoms requiring administration of any rescue medication (e.g., SABA, epinephrine or 
other) are considered dose-limiting. In this case, the challenge has to be stopped, and the 
challenge is considered positive.
All findings that the investigator classifies as reactions to the OFC should be recorded in source 
documentation and on a designated eCRF. These events should not be reported on the Adverse 
Event eCRF unless they constitute an SAE according to the investigator’s judgement.
The details and start time of any treatment and/or medication provided to treat OFC-related 
allergic reactions should be recorded on the respective eCRF. The OFC will be considered 
negative if a participant does not exhibit (a) dose-limiting symptom(s) (= positive challenge) 
at the end of the challenge.
Table 10-9
Definition of Dose-Limiting Symptoms (per the CoFAR* grading scale, 
Chinthrajah et al 2022 )
MILD (not typically dose 
limiting)
MODERATE (dose limiting)
SEVERE (dose limiting)
● Skin – limited (few) or localized 
hives, swelling (e.g., mild lip 
edema), skin flushing (e.g., few 
areas of faint erythema) or mild 
pruritus (e.g., occasional 
scratching)
● Respiratory – rhinorrhea (e.g., 
occasional sniffling or sneezing), 
nasal congestion, occasional 
cough, throat discomfort
● GI – mild abdominal discomfort 
(including mild nausea with or 
● Skin – systemic hives (e.g., 
numerous or widespread hives), 
swelling (e.g., significant lip or face 
edema), pruritus causing 
protracted scratching, more than a 
few areas of erythema or 
pronounced erythema
● Respiratory – throat tightness 
without hoarseness, persistent 
cough, wheezing without dyspnea
● Skin – severe generalized 
urticaria/angioedema/erythema
● Respiratory – laryngeal edema, 
throat tightness with hoarseness, 
wheezing with dyspnea, stridor
● GI – severe abdominal 
pain/cramping/repetitive vomiting
● Neurological – change in mental 
status
● Circulatory – clinically significant 
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without decreased activity), 
isolated emesis thought to be 
secondary to gag
● GI – persistent moderate 
abdominal pain/cramping/nausea 
with decreased activity, vomiting
10.7.6
OFC completion
At the completion of the OFC (post-administration of the last dose of allergen), participants 
must remain under observation at the study site for a minimum of 2 hours to confirm a negative 
challenge. In the event of a positive challenge, participants must remain under observation at 
the study site for a minimum of 1 hour after allergic symptoms have improved to a level 
compatible with safe discharge. Observation beyond this timepoint remains at the Investigator's 
discretion and could potentially include hospital overnight observation.
Treatment of positive reactions
Epinephrine, SABA, anti-histamines and saline bolus are typically used to treat allergic 
reactions. Treatment in line with local clinic provisions/ guidelines is at the investigator's 
discretion. All treatment must be documented in the corresponding eCRF.
Discharge procedures
Upon discharge from the study site, post-OFC participants should be provided with a 24-hour 
emergency telephone contact. Furthermore, participants should be advised to avoid physical 
exercise within 2 hours after receiving the last dose of the OFC.
Delayed or late-onset reactions to the OFC are defined as reactions occurring after the 
participant was discharged from the clinic. Since a delayed reaction to the OFC cannot be 
predicted prior to discharge, all participants should be briefed about the signs and symptoms of 
anaphylaxis and provided with rescue medication (epinephrine auto-injector and short acting 
beta-agonists [asthma participants only]). Participants should also receive specific information 
on how to recognize a late reaction and on how and when to use rescue medication. Delayed or 
late-onset reactions will not be considered dose-limiting and will be captured on a designated 
CRF.
Post-discharge, participants who need to use epinephrine due to a suspected reaction should 
immediately go to the closest emergency room for additional assessment and contact the 
investigative site.
Adverse event reporting
If the participant experiences an allergic reaction associated with the OFC (immediate, delayed 
or late-onset) that meets the criteria for a serious adverse event in the investigator's judgment, 
it should be captured on the designated CRF and reported as described in Section 8.6.3 SAE 
Reporting.
The administration of study medication will precede the OFC. Investigators should apply their 
medical judgement when assessing if reactions occurring during the OFC or during the post-
OFC observation period are symptoms caused by the food challenge or whether they are adverse 
events suspected to be related to the study treatment. Both adverse events suspected to be related 
to study treatment and allergic reactions due to the OFC should be captured on the designated 
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a causality assessment to either study treatment or OFC must be provided and documented 
together with its medical rationale.
10.8
Appendix 8: Guidance for Skin Prick Test
10.8.1
Background of Skin Prick Test
This study includes a Skin Prick Test (SPT) targeting peanut allergen as well as milk and/or 
egg allergens (if indicated by medical history). These diagnostic agents to test for allergic 
diseases (ATC code: V04CL) qualify as auxiliary medicinal products (AxMP) under the 
European Clinical Trial Regulation 536/2014. The products used in European Economic Area 
(EEA) countries are authorized at least in one EEA member state. SPT assessments are 
performed before study drug dosing as per the Assessment Schedule Table 1-4.
This study specifies the use of BOTH a titration SPT (TSPT) and non-TSPT. All participants 
will receive the TSPT to peanut. In addition, all participants should receive the non-titration 
SPT (undiluted) to milk and/or egg based on medical history.
The TSPT will be conducted to the peanut allergen; undiluted extract, five 10-fold dilutions 
(1:10, 1:100, 1:1’000, 1:10’000, and 1:100’000).
In addition to peanut, milk stock and egg stock has to be tested (if indicated by medical history).
Positive and negative controls should be tested together.
10.8.2
Material
Preparation for the reagent of titration SPT.
x
~ 5ml Vials (can be purchased from any supplier)
x
Diluent (saline) (also purchased from any supplier)
x
Pipette with disposable pipette tip or syringe (able to measure 0.1 to 0.9 ml)
x
Add 0.9 mL of diluent to each of 5 vials (~ 5 mL in size). Label them from 1:10, 1:100, 
1:1’000, 1:10’000, 1:100’000; and include the name of the allergen, the lot number, and 
the date on which the dilutions were made.
x
Take 0.1 mL of the undiluted peanut stock and add to vial 1:10. Mix well.
x
Take 0.1 mL from the 1:10 vial and add to vial 1:100. Mix well.
x
Take 0.1 mL from the 1:100 vial and add to vial 1:1’000. Mix well.
x
Take 0.1 mL from the 1:1,000 vial and add to vial 1:10’000. Mix well.
x
Take 0.1 mL from the 1:10,000 vial and add to vial 1:100’000. Mix well.
Only a very small volume of allergen is needed per test – one “drop”.
The prepared dilutions should not be used for more than one week after 
reconstitution.
The non-TSPT will be conducted using the stock (undiluted) of peanut and milk and/or egg (if 
indicated in the medical history).
Positive and negative control always need to be tested together.

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EXAMPLE:
TSPT: if the participant had a positive medical history of milk and egg in addition to peanut, 
total 10 pricks are needed; positive control, negative control, peanut stock (-undiluted), peanut 
(1:10), peanut (1:100), peanut (1:1’000), peanut (1:10’000), peanut (1:100’000), milk 
(undiluted), and egg (undiluted).
10.8.3
Starting the Skin Prick Test
x
Location of SPT: The skin of the participant's back is the preferred site of testing; 
alternatively the forearm may be used. For consistency purposes, it is important for 
individual participants to perform the SPT at the same site during the study.
x
Test time: Skin reactions should be recorded after 15 minutes of dropping the allergen to 
the pricked location.
x
Positive/negative control: The SPT must be repeated if the results for the positive control 
(≥ 3 mm average wheal diameter) and/or negative control (0 mm wheal diameter) were 
not obtained.
x
Medications to be washed out prior to the SPT are listed in Table 10-10.
Table 10-10
Medications to be washed out prior to SPT
Medication
Prohibited 
period
Short acting and long acting anti histamines (e.g., chlorpheniramine, prometazine, 
diphenhydramine, loratadine, cetirizine)
≥5 half-lives
Antihistamine nose spray
12 hours
Oral H2-receptor antagonist (e.g., cimetidine, ranitidine, famotidine, roxatidine, lafutidine)
24 hours
Systemic corticosteroids (including short-term burst of OCS)
≥5 half-lives
10.8.3.1 Performing the Skin Prick Test
Clean the area of the skin with 70% alcohol and allow it to dry
1. Use a pen (which can be washed off with an alcohol wipe) to mark the skin with the sites 
where SPT will be performed. Put a mark beside the area where a particular solution will 
be placed, or draw boxes on the skin 
x
Label allergen: peanut stock, milk stock (if positive Medical History), egg stock (if positive 
Medical History), and diluted peanut stock for TSPT (from 1:10 to 100’000)
x
Label histamine (positive control) and diluent-saline (negative control)
2. Place one drop of the test solution at the appropriate labelled site as above and “prick” the 
skin with an appropriate SPT device: 1) Start from saline, positive control, then allergen 
(for TSPT, from the lowest concentration), 2) Use different lancet for other allergen
3. Start a time (record it)
4. After pricking the skin, immediately blot the skin with tissue paper to absorb excess liquid; 
avoid letting the liquid run from one site to another
5. After 15 minutes measure the size of the wheal at each site: 1) Start with the site you first 
pricked and then work your way in the same order in which the pricks were applied. The 
time taken to do this will be approximately the time it took to apply the solutions and prick 

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them, 2) Measure and record the longest diameter at each site (record in eCRF), 3) Measure 
and record the midpoint orthogonal diameter (record in eCRF).
Figure 10-1
Measurement of skin reaction
10.8.4
Completion of the Skin Prick Test
After measurement of skin reaction and recording them in the source document, clean the skin 
with alcohol to remove the ink from the marker pen on the skin.
Rarely, SPT can cause a generalized allergic reaction (e.g., hives itchy, runny nose, asthma) or 
even anaphylaxis. Therefore, at the completion of SPT, the participants should remain under 
observation at the site as per the investigator's discretion.
Adverse event reporting
If the participant experiences a systemic allergic reaction suspected to be triggered by the SPT, 
the event should be captured in the designated CRF. Adverse events meeting the criteria for a 
SAE should be reported as described in Section 8.6.3.

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10.9
Appendix 9: PRO Measures
10.9.1
FAQLQ-CF: Food Allergy Quality of Life Questionnaire Child Form

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10.9.2
FAIM-CF: Food Allergy Independent Measure Child Form

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10.9.3
FAQLQ-TF: Food Allergy Quality of Life Questionnaire Teenager Form

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10.9.4
FAIM-TF: Food Allergy Independent Measure Teenager Form

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10.9.5
FAQLQ-AF: Food Allergy Quality of Life Questionnaire Adult Form

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10.9.6
FAIM-AF: Food Allergy Independent Measure Adult Form

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10.9.7
FAQLQ-PF: Food Allergy Quality of Life Questionnaire Parental Form

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10.9.8
FAQL-PB: Food Allergy Quality of Life - Parental Burden 
Questionnaire

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10.9.9
SF-36v2 Acute Version Short Form 36-Health Survey Questionnaire v2

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10.9.10
Home Administration Study Drug Diary (example)
CQGE031G12303B – Home Administration Study Drug Diary
Questions/answers
Triggers
Q1
If you /participant are a female who can get pregnant, 
please perform a pregnancy test prior to injecting the 
study treatment. If the result is positive DO NOT inject 
the study treatment and inform the site personnel.
Only show to female participants
Instruction 
screen
Study treatment pre-filled syringe injections
Reminder:
The dose includes 2 injections.
At each site visit, please return unused/used kit 
packaging.
Q2
Has the study drug been injected?
Yes / No
If Yes, go to Q3.
If No, skip Q3, go to Q4 and end of 
the diary.
Q3
How many injections did you have?
1 / 2
If 1, go to Q5, Q6, Q7, and Q9.
If 2, skip Q4 and go to Q5, Q6, Q7, 
Q8, and Q9.
Q4
You had 0 or 1 injection, select the reason:
Participant decision
Parent/Caregiver decision
Adverse Event
Technical Problems
Pregnancy
Q5
Please enter the date of injection(s):
Date picker
Q6
Please enter the time of injections:
Time picker (Hour: minutes)
Q7
Select the site of the 1st injection.
Left Thigh
Right Thigh
Left Abdomen
Right Abdomen
Left Upper Arm
Right Upper Arm
Q8
Select the site of the 2nd injection.
Left Thigh
Right Thigh
Left Abdomen
Right Abdomen
Left Upper Arm
Right Upper Arm
Q9
Who performed the injections?
Myself
Parent/Caregiver
Study site personnel

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10.9.11
10.9.11.1
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11
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