Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen Oral Immunotherapy (OIT) in Food Allergic Children and Adults (CoFAR-11)
Phase: PHASE3
Conditions: Peanut Allergy, Multi-food Allergy
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

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PROTOCOL CoFAR-11 
Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen OIT in  
Food Allergic Children and Adults 
OUtMATCH 
IND # 140847 
National Clinical Trial (NCT) # NCT03881696 
Version 10.0 / 07Jun2024 
IND Sponsor 
The Division of Allergy, Immunology, and Transplantation (DAIT), The 
National Institute of Allergy and Infectious Diseases (NIAID) 
NIAID Funding Mechanism 
Grants UM2AI130836-01 and UM2AI117870 
Investigational Agents 
Manufacturers/Providers 
Omalizumab: Genentech/Novartis 
Multi-Allergen Oral Immunotherapy: Stanford University 
 
 
 
 
PROTOCOL CHAIR – ROBERT WOOD, MD 
Professor of Pediatrics and International Health 
Johns Hopkins University School of Medicine 
 
 
 
 
PROTOCOL CO-CHAIR – SHARON CHINTHRAJAH, MD 
Associate Professor Allergy and Clinical Immunology 
Pulmonary and Critical Care  
Stanford University, Biomedical Innovations Building 
 
 
 
 
MEDICAL MONITOR – 
  
Division of Allergy, Immunology, and Transplantation  
National Institute of Allergy and Infectious Diseases 
 
 
PROJECT MANAGER – 
 
Division of Allergy, Immunology, and Transplantation 
National Institute of Allergy and Infectious Diseases 
  
 
  
PHARMACEUTICAL SPECIALIST – 
 
Division of Allergy, Immunology, and Transplantation  
National Institute of Allergy and Infectious Diseases 
  
 
 
 
REGULATORY OFFICER – 
 
Office of Regulatory Affairs 
Division of Allergy, Immunology, and Transplantation 
National Institute of Allergy and Infectious Diseases 
 
 
 
 

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SCCC LEAD SCIENTIST – 
 
Principal Research Scientist 
Rho Federal Systems Division, Inc. 
 
 
 
 
 
 
 
Confidentiality Statement 
The information contained within this document is not to be disclosed in any way without the prior permission of the 
Division of Allergy, Immunology, and Transplantation, National Insitututes of Allergy and Infectious Diseases, National 
Institutes of Health. 
 
 
 
 
 

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Protocol Synopsis 
Title 
Omalizumab as Monotherapy and as Adjunct Therapy to Multi-Allergen 
OIT in Food Allergic Children and Adults 
Short Title 
OUtMATCH 
Clinical Phase 
Phase III 
Number of Sites 
10 Clinical Research Units (CRUs) in the United States 
IND Sponsor/Number 
IND Sponsor: DAIT/NIAID 
IND#: 140847 
Study Objectives 
The primary objective is to compare the ability to consume foods without 
dose-limiting symptoms during a double-blind placebo-controlled food 
challenge (DBPCFC) after treatment with either omalizumab or placebo 
for omalizumab. 
 
Secondary objectives are:  
Stage 1 
1. To evaluate safety during treatment with either omalizumab or 
placebo for omalizumab. 
Stage 2 
2. To compare the ability to consume foods without dose-limiting 
symptoms during a DBPCFC after treatment with either 
omalizumab-facilitated Oral Immunotherapy (OIT) or omalizumab + 
placebo OIT. This is the primary objective for Stage 2. 
3. To evaluate safety during treatment with either omalizumab-
facilitated OIT or omalizumab + placebo OIT. 
Stage 3 
4. To compare dietary consumption of foods after the conclusion of 
treatment with either omalizumab-facilitated OIT or omalizumab + 
placebo OIT during a follow-up period in which participants either 
received guided dietary instructions and/or rescue OIT for up to 
three foods.  
5. To evaluate safety after the conclusion of treatment with either 
omalizumab-facilitated OIT or omalizumab + placebo OIT during a 
follow-up period in which participants either received guided 
dietary instructions and/or rescue OIT for up to three foods. 
 

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Exploratory objectives are: 
Stage 1 
1. To compare quality of life after treatment with either omalizumab 
or placebo for omalizumab. 
Stage 1 Open Label Extension (OLE) 
2. To assess the safety and efficacy of either 24 or 40 weeks of 
treatment with omalizumab. 
3. To assess quality of life at the end of either 24 or 40 weeks of 
treatment with omalizumab. 
Stage 2 
4. Among participants who do not respond to treatment with 
omalizumab alone, compare the ability to consume foods without 
dose-limiting symptoms during a DBPCFC after treatment with 
omalizumab-facilitated OIT or omalizumab + placebo OIT. 
5. Among participants who respond to treatment with omalizumab 
alone, compare the ability to consume foods without dose-limiting 
symptoms during a DBPCFC after treatment with omalizumab-
facilitated OIT or omalizumab + placebo OIT. 
6. To compare the change in the dose of each food that is consumed 
without dose-limiting symptoms during a DBPCFC at the end of 
Stage 1 and during a DBPCFC at the end of Stage 2 between 
treatment with either omalizumab-facilitated OIT or omalizumab + 
placebo OIT. 
7. To compare quality of life after treatment with either omalizumab-
facilitated OIT or omalizumab + placebo OIT. 
Stage 3 
8. To compare quality of life after the conclusion of treatment with 
either omalizumab-facilitated OIT or omalizumab + placebo OIT 
during a follow-up period in which participants either receive 
guided dietary instructions and/or rescue OIT for up to three foods. 
9. To describe dietary consumption of foods after the conclusion of 
either 24 or 40 weeks of treatment with omalizumab during a 
follow-up period in which participants either received guided 
dietary instructions and/or rescue OIT for up to three foods. 
10. To assess safety after the conclusion of either 24 or 40 weeks of 
treatment with omalizumab during a follow-up period in which 

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participants either received guided dietary instructions and/or 
rescue OIT for up to three foods. 
11. To measure quality of life after the conclusion of either 24 or 40 
weeks of treatment with omalizumab during a follow-up period in 
which participants either received guided dietary instructions 
and/or rescue OIT for up to three foods. 
Pharmacokinetic (PK) objectives are: 
Stage 1 
12. To evaluate serum omalizumab concentrations during treatment 
with omalizumab. 
Stage 1 OLE 
13. To assess serum omalizumab concentrations at the end of either 24 
or 40 weeks of treatment with omalizumab. 
Stage 2 
14. To evaluate serum omalizumab concentrations during treatment 
with either omalizumab-facilitated OIT or omalizumab + placebo 
OIT. 
Biomarker objectives are: 
Stage 1 
15. To compare immunological responses after treatment with either 
omalizumab or placebo for omalizumab. 
16. To determine whether immunological responses can be used to 
predict the ability to consume foods without dose-limiting 
symptoms during a DBPCFC after treatment with either omalizumab 
or placebo for omalizumab. 
Stage 1 OLE 
17. To assess immunological responses at the end of either 24 or 40 
weeks of treatment with omalizumab. 
Stage 2 
18. To compare immunological responses during and after treatment 
with either omalizumab-facilitated OIT or omalizumab + placebo 
OIT. 
19. To determine whether immunological responses can be used to 
predict the ability to consume foods without dose-limiting 
symptoms during a DBPCFC after treatment with either 
omalizumab-facilitated OIT or omalizumab + placebo OIT. 

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Stage 3 
20. To compare immunological responses after the conclusion of 
treatment with either omalizumab-facilitated OIT or omalizumab + 
placebo OIT during a follow-up period in which participants either 
received guided dietary instructions and/or rescue OIT for up to 
three foods. 
21. To assess immunological responses after the conclusion of either 24 
or 40 weeks of treatment with omalizumab during a follow-up 
period in which participants either received guided dietary 
instructions and/or rescue OIT for up to three foods. 
Study Design 
This study is a multi-center, randomized, double-blind, placebo-controlled 
study in participants 1 year to less than 56 years of age who are allergic to 
peanut and at least two other foods (including milk, egg, wheat, cashew, 
hazelnut, or walnut). While each participant may be allergic to more than 
two other foods, the primary endpoint in this study will only be assessed 
in peanut and two other foods for each participant. 
There are three stages: Stage 1, Stage 2, and Stage 3. Stage 1 includes 
Stage 1 OLE.  
Stage 1: Participants who experience dose-limiting symptoms to a single 
dose of ≤100 mg of peanut protein, ≤300 mg protein for each of the other 
two foods, and no dose-limiting symptoms to placebo at any single dose 
up to 300 mg protein during the Screening DBPCFC will be randomized 2:1 
to 16-20 weeks of treatment with omalizumab or placebo for omalizumab 
per a standard omalizumab dosing table. After 16 weeks of treatment, 
each participant will complete a DBPCFC consisting of placebo and each of 
their three specific foods to a cumulative dose of 6044 mg protein of each 
food. 
The first 60 participants who complete Stage 1 will participate in the 
Stage 1 OLE. All other participants who complete Stage 1 will move to 
Stage 2 of the study. 
Stage 1 OLE: Each participant will receive 24-28 weeks of open label 
omalizumab. After 24 weeks of treatment, each participant will complete 
a DBPCFC consisting of placebo and each of their three specific foods to a 
cumulative dose of 8044 mg protein of each food. Each participant who 
completes Stage 1 OLE will move on to Stage 3 of the study. 
Stage 2: Each participant will receive eight weeks of treatment with open 
label omalizumab. One week after beginning Stage 2, participants will be 
randomized 1:1 to: 

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• 
Omalizumab-facilitated OIT: Open label omalizumab + Multi-
allergen OIT for eight weeks, followed by placebo for omalizumab + 
Multi-allergen OIT for 44 weeks. 
• 
Omalizumab + placebo OIT: Open label omalizumab + placebo for 
Multi-allergen OIT for eight weeks, followed by omalizumab + 
placebo for Multi-allergen OIT for 44 weeks. 
After completion of eight weeks of treatment with open label 
omalizumab, each participant will receive an additional eight weeks of 
open label omalizumab followed by either 44 weeks of omalizumab or 
placebo for omalizumab (depending on the arm). While receiving 
omalizumab or placebo for omalizumab injections, each participant will 
complete 52 weeks of Multi-allergen OIT or placebo for Multi-allergen 
OIT. Each participant who tolerates at least 9 mg protein of Multi-allergen 
OIT or placebo for Multi-allergen OIT during an Initial Dose Escalation 
(IDE) Visit will enter a Build-Up Phase for up to 24 weeks to reach a 
maximum maintenance dose of 1000 mg protein of each of their three 
specific foods (i.e., a total maximum dose of 3000 mg protein or 3000 mg 
placebo for Multi-allergen OIT, depending on arm). Each participant who 
reaches a minimum total maintenance dose of 750 mg protein 
(equivalent to 250 mg protein of each of their three specific foods or 750 
mg of placebo) within 24 weeks of completing the IDE will remain on this 
dose during the Maintenance Phase until 52 weeks after the IDE is 
completed, at which time each participant will complete a DBPCFC 
consisting of placebo and each of their three specific foods to a 
cumulative dose of 8044 mg protein of each food. Each participant who 
completes Stage 2 will move to Stage 3 of the study. 
Stage 3: Upon completion of Stage 1 OLE or Stage 2, each participant will 
receive a separate treatment plan for peanut and each of the two other 
participant-specific foods based on the results of the DBPCFC. A 
treatment plan will include instructions for one of the following: 
• 
Long-term follow-up with dietary consumption of a food; 
• 
Long-term follow-up with avoidance of a food; or 
• 
Rescue OIT for a food. 
The treatment plan for each food may change throughout Stage 3 
depending on a participant’s response to treatment. Once a participant 
enters Stage 3, the participant will have a minimum of 12 months of 
follow-up in Stage 3. 
Long-term follow-up with dietary consumption of a food: For each food 
the participant receives long-term follow-up with dietary consumption of 
a food, there will be an initial open feeding of the food in the CRU. 
Following completion of each open feeding, the participant will be 
provided individualized guided dietary food instructions that will include a 

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minimum and maximum quantity deemed to be safe for the participant. 
After the last open feeding, the participant will receive a follow-up call or 
email weekly for the first four weeks, every other week between six and 
sixteen weeks, and every two months thereafter during follow-up. During 
long-term follow-up, each participant will also complete a CRU visit every 
six months. A participant who does not tolerate ≥300 mg protein of the 
food during the first six months of long-term follow-up will either receive 
long-term follow-up with avoidance of that food or be referred to an 
allergist, as appropriate.  
Long-term follow-up with avoidance of a food: For each food the 
participant receives long-term follow-up with avoidance of a food, the 
participant will avoid eating the food and will return to the CRU every six 
months for follow-up. 
Rescue OIT for a food: If the participant receives rescue OIT for the food 
immediately after completing Stage 1 OLE or Stage 2, the participant may 
skip the IDE Visit and enter the Build-Up Phase (depending on the results 
of the DBPCFC). Otherwise, the participant will attend an IDE Visit. The 
participant must tolerate at least 3 mg protein of the food during the IDE 
Visit to enter the Build-Up Phase. Participants will remain in the Build-Up 
Phase for up to 16 weeks to reach a maximum maintenance dose of 1000 
mg protein of the food. Each participant who reaches a maintenance dose 
of 375 mg, 560 mg, 800 mg, or 1000 mg protein of the food within 16 
weeks of entering rescue OIT and tolerates this dose for 4 weeks after 
starting the Maintenance Phase will complete an open feeding in CRU to 
determine if they will transition to Long-Term Follow-Up with Dietary 
consumption of the food, will receive Long-Term Follow- Up with 
Avoidance of the food, or be withdrawn from the study and referred to an 
allergist, as appropriate.  
 
Primary Endpoint 
The primary endpoint is consumption of a single dose of ≥600 mg of 
peanut protein without dose-limiting symptoms during the DBPCFC at the 
end of Stage 1. Dose-limiting symptoms are defined in Appendix 1. A 
participant who meets this endpoint will be considered a ‘success’ while a 
participant who does not meet this endpoint will be considered a ‘failure’.  
Secondary Endpoints  
Key secondary endpoints: 
Stage 1 
1. Consumption of a single dose of ≥1000 mg of cashew protein 
without dose-limiting symptoms during the DBPCFC at the end of 
Stage 1. 

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2. Consumption of a single dose of ≥1000 mg of milk protein without 
dose-limiting symptoms during the DBPCFC at the end of Stage 1. 
3. Consumption of a single dose of ≥1000 mg of egg protein without 
dose-limiting symptoms during the DBPCFC at the end of Stage 1. 
Stage 2 
4. Consumption of ≥1 dose of 2000 mg protein of all three foods 
without dose-limiting symptoms during the DBPCFC at the end of 
Stage 2. This is the primary endpoint for Stage 2. 
Other secondary endpoints: 
5. Consumption of a single dose of ≥600 mg, ≥1000 mg, ≥1 dose of 
2000 mg, or 2 doses of 2000 mg protein of each food, at least two 
foods, or all three foods without dose-limiting symptoms during the 
DBPCFC at the end of Stage 1 (except those endpoints already 
defined by the primary and key secondary endpoints in Stage 1). 
6. Number of foods consumed at a single dose of ≥600 mg, ≥1000 mg, 
≥1 dose of 2000 mg, or 2 doses of 2000 mg protein of each food 
without dose-limiting symptoms during the DBPCFC at the end of 
Stage 1. 
7. Consumption of a single dose of ≥600 mg, ≥1000 mg, ≥1 dose of 
2000 mg, ≥2 doses of 2000 mg, or 3 doses of 2000 mg protein of 
each food, at least two foods, or all three foods without dose-
limiting symptoms during the DBPCFC at the end of Stage 2 (except 
the endpoint already defined by the primary endpoint for Stage 2). 
8. Number of foods consumed at a single dose of ≥600 mg, ≥1000 mg, 
≥1 dose of 2000 mg, ≥2 doses of 2000 mg, or 3 doses of 2000 mg 
protein of each food without dose-limiting symptoms during the 
DBPCFC at the end of Stage 2. 
9. For each food, at 3, 6, 9 and 12 months following the first Stage 3 
visit, consuming a daily median of 300 mg on the dietary 
consumption treatment plan where participants received guided 
dietary instructions.  
Safety endpoints include: 
10. An AE related to study therapy regimen received during Stage 1. 
11. An AE related to study therapy regimen received during Stage 1 
OLE. 
12. An AE related to study therapy regimen received during Stage 2. 
13. An AE related to oral food intake received during Stage 3. 
Exploratory Endpoints 
Exploratory endpoints: 

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1. Percent change in the maximum dose of food protein consumed 
without dose-limiting symptoms during the DBPCFC at the end of 
Stage 1 and during the DBPCFC at the end of Stage 2. 
2. Consumption of a single dose of ≥600 mg, ≥1000 mg, ≥1 dose of 
2000 mg, ≥2 doses of 2000 mg, or 3 doses of 2000 mg protein of 
each food, at least two foods, or all three foods without dose-
limiting symptoms during the DBPCFC at the end of Stage 1 OLE. 
3. Number of foods consumed at a single dose of ≥600 mg, ≥1000 mg, 
≥1 dose of 2000 mg, ≥2 doses of 2000 mg, or 3 doses of 2000 mg 
protein of each food without dose-limiting symptoms during the 
DBPCFC at the end of Stage 1 OLE. 
4. Change in quality of life between Week 0 in Stage 1 and the 
following times: 
• 
First DBPCFC Visit at the end of Stage 1; 
• 
For those participants who move to Stage 1 OLE: 
o First omalizumab injection visit in Stage 1 OLE;  
o First DBPCFC Visit at the end of Stage 1 OLE;  
o Last DBPCFC Visit at the end of Stage 1 OLE. 
• 
For those participants who move to Stage 2: 
o First omalizumab injection visit in Stage 2;  
o First DBPCFC Visit at the end of Stage 2;  
o Last DBPCFC Visit at the end of Stage 2. 
• 
Six months after beginning Stage 3. 
Quality of life is measured by the Food Allergy Quality of Life 
Questionnaire – Parent Form (FAQLQ-PF) for participants aged 0-12 
years, Food Allergy Quality of Life Questionnaire – Child Form 
(FAQLQ-CF) for children/adolescents aged 8-12 years, Food Allergy 
Quality of Life Questionnaire – Teenager Form (FAQLQ-TF) for 
participants aged 13-17 years, and Food Allergy Quality of Life 
Questionnaire – Adult Form (FAQLQ-AF) for participants aged 18 
years and older. 
PK exploratory endpoints: 
5. Omalizumab trough concentration, measured at the following 
times: 
• 
First Screening DBPCFC Visit; 
• 
First DBPCFC Visit at the end of Stage 1; 
• 
First DBPCFC Visit at the end of Stage 1 OLE (for those 
participants who move to Stage 1 OLE); 
• 
IDE Visit during Stage 2 (for those participants who move to 
Stage 2); and 
• 
First DBPCFC Visit at the end of Stage 2 (for those 
participants who move to Stage 2). 

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Biomarkers include the following: 
6. Total immunoglobulin E (IgE) 
7. Total free IgE 
8. Allergen-specific IgE 
9. Allergen-specific immunoglobulin G4 (IgG4) 
10. Allergen-specific immunoglobulin A (IgA) 
11. IgG4/IgE ratio 
12. Basophil activation 
13. Skin prick tests (SPTs) 
Allergen-specific immune biomarkers (allergen-specific IgE, allergen-
specific IgG4, allergen-specific IgA, basophil activation, and SPTs) will be 
evaluated using peanut and the two other participant-specific foods. 
Immune biomarkers will be measured at the following times: 
• 
First Screening DBPCFC Visit; 
• 
First DBPCFC Visit at the end of Stage 1; 
• 
First DBPCFC Visit at the end of Stage 1 OLE (for those participants 
who move to Stage 1 OLE); 
• 
IDE Visit during Stage 2, except the SPTs, total IgE, and allergen-
specific IgE (for those participants who move to Stage 2); 
• 
Initial Maintenance Dose Visit during Stage 2, except the SPTs, total 
IgE, and allergen-specific IgE (for those participants who move to 
Stage 2); 
• 
First DBPCFC Visit at the end of Stage 2 (for those participants who 
move to Stage 2); and 
• 
Six months after beginning Stage 3. 
Mechanistic endpoints will be measured at the following times: 
• 
First Screening DBPCFC Visit; 
• 
First DBPCFC Visit at the end of Stage 1; 
• 
IDE Visit during Stage 2 (for those participants who move to Stage 
2); 
• 
Initial Maintenance Dose Visit during Stage 2 (for those participants 
who move to Stage 2); and 
• 
First DBPCFC Visit at the end of Stage 2 (for those participants who 
move to Stage 2). 
Accrual Objective 
210 pediatric participants and up to 225 total participants (≥50 
participants aged 1 year to less than 6 years, approximately 160 
participants aged 6 years to less than 18 years, and approximately 15 
participants aged 18 years to less than 56 years).  

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Participant accrual was stopped on March 23, 2023, after the Interim 
Analysis was performed, with a final total of 182 participants randomized 
(180 participants in Stage 1 and 2 participants directly into Stage 2).  
Study Duration 
Individual study participation will consist of a maximum of 84 weeks for 
treatment and a minimum of 12 months of follow-up. 
Treatment Description  
Multi-allergen OIT: peanut, milk, egg, wheat, cashew, hazelnut, walnut 
flour or powder.  
Placebo for Multi-allergen OIT: oat flour. 
Multi-allergen OIT and placebo for Multi-allergen OIT will be 
manufactured by the Sean N. Parker Center for Allergy & Asthma 
Research with Stanford University (Mountain View, CA). 
The dosing schedule for IDE for Multi-allergen OIT or placebo for Multi-
allergen OIT in Stage 2 is as follows: 
Dose # 
Food Allergen Dose  
(mg protein of each 
allergen) 
Total Food Allergen 
Dose (mg protein) 
1 
3 
9 
2 
30 
90 
3 
60 
180 
4 
125 
375 
5 
250 
750 
6 
375 
1125 
 
The dosing schedule for Stage 3 IDE per allergen for rescue OIT in Stage 3 
is as follows: 
Dose # 
Food Allergen Dose  
(mg protein of each 
allergen) 
1 
3 
2 
10 
3 
30 
4 
60 
5 
125 
6 
250 
7 
375 
 
All Multi-allergen OIT or placebo for Multi-allergen OIT dose build-ups for 
Stage 2 will occur under observation in the CRU per the dosing schedule 
below: 

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Dose #1 
Food Allergen Dose  
(mg protein of each 
allergen) 
Total Food Allergen 
Dose (mg protein) 
Interval 
(weeks) 
1 
3 
9 
2 
2 
30 
90 
2 
3 
60 
180 
2 
4 
125 
375 
2 
5 
250 
750 
2 
6 
375 
1125 
2 
7 
560 
1680 
2 
8 
800 
2400 
2 
9 
1000 
3000 
2 
1. Dose build-up will begin at the last dose the participant was able to tolerate 
on the IDE Visit. 
 
All rescue OIT dose build-ups per allergen for Stage 3 will occur under 
observation in the CRU per the dosing schedule below: 
Dose #1 
Food Allergen Dose  
(mg protein of each 
allergen) 
Interval 
(weeks) 
1 
3 
2 
2 
10 
2 
3 
30 
2 
4 
60 
2 
5 
125 
2 
6 
250 
2 
7 
375 
2 
8 
560 
2 
92 
800 
2 
102 
1000 
2 
1. Dose build-up will begin at the last dose the participant was able to tolerate 
on the IDE Visit. If a participant does not require an IDE visit, the starting 
dose of build-up will be determined by the results of their last end of stage 
DBPCFC, outlined in Table 3.1.5.3 C. 
2. Participants will have 16 weeks to build up to their maximum maintenance 
dose. Doses 9 and 10 may only be achieved for participants starting at 
higher doses based on their IDE visit and end of Stage 2 DBPCFC results.  
Omalizumab: Omalizumab is a recombinant humanized immunoglobulin 
G1 monoclonal antibody that binds to the FcεR1 binding epitope of 
human IgE, preventing human IgE from binding to its specific high-affinity 
receptors on mast cells and basophils. Omalizumab is approved by the 
European Commission and US FDA for patients with moderate-severe 
asthma ≥6 years of age for patients with chronic spontaneous urticaria 
≥12 years of age and for patients with nasal polyps ≥ 18 years of age. As 
of 16Feb2024, Omalizumab has also been approved for IgE-mediated 
food allergy in adult and pediatric patients aged 1 year and older for the 
reduction of allergic reactions (Type I), including anaphylaxis, that may 

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occur with accidental exposure to one or more foods. Omalizumab is to 
be used in conjunction with food allergen avoidance. 
Placebo for omalizumab: The composition of the placebo for omalizumab 
is the same as the active study drug without the omalizumab. 
Omalizumab and placebo for omalizumab will be administered as a 
subcutaneous injection and will be dosed according to the omalizumab 
dosing table given in Appendix 2. Omalizumab and placebo for 
omalizumab will be provided by Genentech Inc. 
Throughout Stage 1, Stage 1 OLE, and Stage 2, each participant will be 
instructed to strictly avoid all foods to which they are allergic. Each 
participant will also be instructed to strictly avoid a food if they receive 
rescue OIT for the food during Stage 3. 
Inclusion Criteria 
Individuals who meet all of the following criteria are eligible for study 
randomization: 
1. Participant and/or parent/legal guardian must be able to 
understand and provide informed consent and/or assent, as 
applicable 
2. Male or female, 1 year to less than 56 years of age at Screening 
3. Peanut allergic; participant must meet all of the following criteria to 
minimize the chance that the participant will develop natural 
tolerance to peanut over the course of the study: 
a. Positive SPT (≥4 mm wheal greater than saline control) to 
peanut 
b. Positive peanut IgE (≥6 kUA/L) at Screening or within three 
months of Screening, determined by ImmunoCap 
c. Positive blinded OFC to peanut during the Screening 
DBPCFC, defined as experiencing dose-limiting symptoms at 
a single dose of ≤100 mg of peanut protein 
4. Allergic to at least two of the six other foods (milk, egg, wheat, 
cashew, hazelnut, walnut); allergy to milk and egg is defined as 
unable to tolerate both cooked and uncooked forms; each 
participant must meet all of the following criteria for at least two of 
the six other foods to minimize the chance that the participant will 
develop natural tolerance to at least two of the six other foods over 
the course of the study: 
a. Milk, egg, or wheat: 
i. 
Positive SPT (≥4 mm wheal greater than saline control) 
to food  
ii. 
Positive food specific IgE (≥6 kUA/L) at Screening or 
within three months of Screening, determined by 
ImmunoCap 

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iii. 
Positive blinded OFC to food during the Screening 
DBPCFC, defined as experiencing dose-limiting 
symptoms at a single dose of ≤300 mg of food protein 
b. Cashew, hazelnut, or walnut: 
i. 
Positive SPT (≥4 mm wheal greater than saline control) 
to food or positive food specific IgE (≥6 kUA/L) at 
Screening or within three months of Screening, 
determined by ImmunoCap 
ii. 
Positive blinded OFC to food during the Screening 
DBPCFC, defined as experiencing dose-limiting 
symptoms at a single dose of ≤300 mg of food protein 
5. With body weight (as measured at Screening) and total serum IgE 
level (as measured within three months of Screening) suitable for 
omalizumab dosing 
6. If female of child-bearing potential, must have a negative urine or 
serum pregnancy test 
7. For women of childbearing potential, must agree to remain 
abstinent (refrain from heterosexual intercourse) or use acceptable 
contraceptive methods (barrier methods or oral, injected, or 
implanted hormonal methods of contraception or other forms of 
hormonal contraception that have comparable efficacy) during the 
treatment period and for 60 days after the last dose of study drug. 
8. Plan to remain in the study area of an OUtMATCH CRU during the 
trial 
9. Be willing to be trained on the proper use of an epinephrine 
autoinjector and be willing to provide an epinephrine autoinjector 
for the duration of the study 
Exclusion Criteria 
Individuals who meet any of the following criteria are not eligible for 
study randomization: 
1. Inability or unwillingness of a participant and/or parent/legal 
guardian to give written informed consent and/or assent or comply 
with the study protocol 
2. Clinically significant laboratory abnormalities at Screening 
3. Dose-limiting symptoms to the blinded OFC to placebo during the 
Screening DBPCFC  
4. Sensitivity or suspected/known allergy to any ingredients (including 
excipients) of the active or placebo OFC material, Multi-allergen 
OIT, or drugs related to omalizumab (e.g., monoclonal antibodies, 
polyclonal gamma globulin). Guidance for determination of 
sensitivity to excipients will be detailed in the Manual of Procedures 
(MOP). 
5. Poorly controlled atopic dermatitis (AD) at Screening, per the PI’s 
discretion 

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6. Poorly controlled or severe asthma/wheezing at Screening, defined 
by at least one of the following criteria: 
a. Global Initiative for Asthma (GINA) criteria regarding 
asthma control latest guidelines; see Appendix 3); 
b. History of two or more systemic corticosteroid courses 
within six months of Screening or one course of systemic 
corticosteroids within three months of Screening to treat 
asthma/wheezing; 
c. Prior intubation/mechanical ventilation for 
asthma/wheezing; 
d. One hospitalization or ED visit for asthma/wheezing within 
six months of Screening; 
e. Forced expiratory volume in one second (FEV1) <80% of 
predicted or FEV1/forced vital capacity (FVC) <75%, with or 
without controller medications (only for participants who 
are aged seven years or older and are able to perform 
spirometry); 
f. Inhaled corticosteroid (ICS) dosing of >500 mcg daily 
fluticasone (or equivalent ICS based on the CoFAR Inhaled 
Corticosteroid Equivalency Tables MOP). 
7. History of severe anaphylaxis to participant-specific foods that will 
be used in this study, defined as neurological compromise or 
requiring intubation 
8. Treatment with a burst of oral, intramuscular (IM), or intravenous 
(IV) steroids of more than two days for an indication other than 
asthma/wheezing within 30 days of Screening 
9. Currently receiving oral, IM, or IV corticosteroids, tricyclic 
antidepressants, or β-blockers (oral or topical) 
10. Past or current history of eosinophilic gastrointestinal (GI) disease 
within three years of Screening 
11. Past or current history of cancer, or currently being investigated for 
possible cancer 
12. Previous adverse reaction to omalizumab 
13. Past or current history of any immunotherapy to any of the foods 
being treated in this study (e.g., OIT, sublingual immunotherapy 
[SLIT], epicutaneous immunotherapy [EPIT]) within 6 months of 
Screening 
14. Treatment with monoclonal antibody therapy, such as omalizumab 
(Xolair®), dupilumab (Dupixent®), benralizumab (Fasenra™), 
mepolizumab (Nucala®), reslizumab (Cinqair®), or other 
immunomodulatory therapy within six months of Screening  
15. Currently on “build-up phase” of inhalant allergen immunotherapy 
(i.e., has not reached maintenance dosing). Individuals tolerating 
maintenance allergen immunotherapy can be enrolled 

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16. Inability to discontinue antihistamines for the minimum wash-out 
periods required for SPTs or OFCs 
17. Current participation in another therapeutic or interventional 
clinical trial or participation within 90 days of Screening 
18. Use of investigational drugs within 24 weeks of Screening 
19. Pregnant or breastfeeding, or intending to become pregnant during 
the study or within 60 days after the last dose of omalizumab or 
placebo for omalizumab 
20. Has a first-degree relative presently enrolled in Stage 1 or Stage 2 of 
the study 
21. Past or current medical problems (e.g., severe latex allergy), history 
of other chronic diseases (other than asthma/wheezing, AD, or 
rhinitis) requiring therapy (e.g., heart disease, diabetes), findings 
from physical assessment, or abnormalities in clinical laboratory 
testing that are not listed above, which, in the opinion of the PI, 
may pose additional risks from participation in the study, may 
interfere with the participant’s ability to comply with study 
requirements, or that may impact the quality or interpretation of 
the data obtained from the study 
Study Stopping Rules 
If any of the stopping rules listed below are met, study enrollment will be 
suspended, IDE Visits will be suspended, and dose escalation of OIT during 
Stage 2 and 3 will be stopped pending expedited review of all pertinent 
data by the NIAID Allergy and Asthma Data and Safety Monitoring Board 
(DSMB). Depending on the stopping rule, additional study procedures (as 
outlined below) will also be suspended pending expedited review of all 
pertinent data. 
• 
Any death related to OIT dosing, an OFC, omalizumab, or placebo 
for omalizumab: If this stopping rule is met, all OIT maintenance 
visits, all OFCs, all open feedings, and all omalizumab or placebo for 
omalizumab injections will be suspended. 
• 
More than three participants requiring more than two injections of 
epinephrine during a single OIT dosing: If this stopping rule is met, 
no additional study procedures aside from those outlined above will 
be suspended and all omalizumab or placebo for omalizumab 
injections will continue to be received. 
• 
More than one participant requiring more than two injections of 
epinephrine during a single omalizumab/placebo for omalizumab 
injection: If this stopping rule is met, all omalizumab or placebo for 
omalizumab injections will be suspended. 
• 
More than one participant with more than one CoFAR Grade 4 AE 
related to OIT dosing (see Table 12.4.1.2): If this stopping rule is 
met, all OFCs and all open feedings will be suspended but all OIT 

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maintenance visits and all omalizumab or placebo for omalizumab 
injections will continue to be received. 
• 
More than three CoFAR Grade 4 AEs related to an OFC (see Table 
12.4.1.2): If this stopping rule is met, all OFCs and all open feedings 
will be suspended but all OIT maintenance visits and all omalizumab 
or placebo for omalizumab injections will continue to be received. 
• 
5% or more of the randomized participants have been diagnosed 
with biopsy-proven eosinophilic esophagitis (EoE), as assessed on a 
rolling basis during regular AE reviews, and the total number of 
cases of EoE is at least five: If this stopping rule is met, no additional 
study procedures aside from those outlined above will be 
suspended and all omalizumab or placebo for omalizumab 
injections will continue to be received. 
Interim Analysis 
An interim analysis (IA) for efficacy was conducted on all pediatric 
subjects (ages 1 year to less than 18 years) randomized into Stage 1 on or 
before 08JUL2022. (N=165). The analysis was conducted after all these 
participants have either completed or discontinued from Stage 1. Efficacy 
would be declared only if the two-sided p-value for the peanut is 
significant at p< 0.0001 and the two-sided p-values for all secondary foods 
(cashew, milk, and egg) are significant at p< 0.005, with the direction of all 
treatment group difference favoring omalizumab. 
The DSMB reviewed the IA results and recommended that the trial should 
be curtailed for efficacy, which NIAID agreed. Enrollment into the trial and 
randomization into Stage 1 was discontinued on March 23, 2023.   
 
 
 

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Table of Contents 
Protocol Synopsis .................................................................................................................................................................... 4 
Glossary of Abbreviations ..................................................................................................................................................... 26 
1 
Background and Rationale ............................................................................................................................................ 29 
 
Background and Scientific Rationale ..................................................................................................................... 29 
 
Rationale for Selection of Investigational Product or Intervention ...................................................................... 30 
1.2.1 
Omalizumab .................................................................................................................................................. 30 
1.2.2 
Oral Immunotherapy..................................................................................................................................... 31 
 
Preclinical Experience ........................................................................................................................................... 31 
 
Prior Clinical Studies .............................................................................................................................................. 31 
2 
Study Hypotheses/Objectives ....................................................................................................................................... 33 
 
Hypotheses............................................................................................................................................................ 33 
 
Primary Objective .................................................................................................................................................. 33 
 
Secondary Objectives ............................................................................................................................................ 33 
 
Exploratory Objectives .......................................................................................................................................... 34 
3 
Study Design .................................................................................................................................................................. 36 
 
Description of Study Design .................................................................................................................................. 36 
3.1.1 
Screening ....................................................................................................................................................... 40 
3.1.2 
Stage 1 – Omalizumab as Monotherapy ....................................................................................................... 41 
3.1.3 
Stage 1 Open Label Extension – Long-Term Treatment with Omalizumab .................................................. 42 
3.1.4 
Stage 2 – Omalizumab as Adjunct Therapy to Multi-Allergen Oral Immunotherapy Compared to 
Omalizumab Monotherapy ........................................................................................................................................... 43 
3.1.5 
Stage 3 – Long-Term Follow-Up and Rescue Oral Immunotherapy .............................................................. 46 
 
Primary Endpoint .................................................................................................................................................. 51 
 
Secondary Endpoints ............................................................................................................................................ 51 
 
Exploratory Endpoints ........................................................................................................................................... 52 
 
Stratification, Randomization, Blinding, and Stage-specific Unblinding ............................................................... 54 
3.5.1 
Procedure for Unblinding .............................................................................................................................. 56 
4 
Selection of Participants ............................................................................................................................................... 56 
 
Rationale for Study Population ............................................................................................................................. 56 
 
Inclusion Criteria ................................................................................................................................................... 57 
 
Exclusion Criteria ................................................................................................................................................... 58 
5 
Known and Potential Risks and Benefits to Participants .............................................................................................. 59 
 
Risks of Investigational Product ............................................................................................................................ 59 

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5.1.1 
Omalizumab .................................................................................................................................................. 59 
5.1.2 
Multi-Allergen Oral Immunotherapy ............................................................................................................ 61 
5.1.3 
Multi-Allergen Oral Immunotherapy plus Omalizumab ............................................................................... 62 
 
Risks of Other Protocol Specified Medications ..................................................................................................... 62 
 
Risks of Study Procedures ..................................................................................................................................... 62 
5.3.1 
Oral Food Challenges .................................................................................................................................... 62 
5.3.2 
Open Feedings............................................................................................................................................... 63 
5.3.3 
Skin Prick Tests .............................................................................................................................................. 63 
5.3.4 
Blood Draw .................................................................................................................................................... 63 
5.3.5 
Intravenous Insertion .................................................................................................................................... 63 
5.3.6 
Spirometry and Peak Expiratory Flow Measurements ................................................................................. 64 
5.3.7 
Stool, Urine, and Saliva Sample Collection ................................................................................................... 64 
5.3.8 
Questionnaires .............................................................................................................................................. 64 
 
Potential Benefits .................................................................................................................................................. 64 
6 
Investigational Agent/Intervention ............................................................................................................................... 64 
 
Investigational Agents/Interventions.................................................................................................................... 64 
6.1.1 
Investigational Agent #1: Omalizumab and Placebo for Omalizumab ......................................................... 64 
6.1.2 
Investigational Agent #2: Multi-allergen Oral Immunotherapy and Placebo for Multi-allergen Oral 
Immunotherapy ............................................................................................................................................................ 65 
 
Drug Accountability ............................................................................................................................................... 66 
 
Assessment of Participant Compliance with Investigational Agent ..................................................................... 66 
 
Toxicity Prevention and Management .................................................................................................................. 66 
6.4.1 
Omalizumab .................................................................................................................................................. 66 
6.4.2 
Multi-allergen Oral Immunotherapy ............................................................................................................. 68 
 
Premature Discontinuation of Investigational Agent ........................................................................................... 70 
7 
Other Medications ........................................................................................................................................................ 70 
 
Concomitant Medications ..................................................................................................................................... 70 
7.1.1 
Protocol-Mandated ....................................................................................................................................... 70 
7.1.2 
Other Permitted Concomitant Medications ................................................................................................. 70 
 
Prophylactic Medications ...................................................................................................................................... 70 
 
Prohibited Medications ......................................................................................................................................... 70 
 
Rescue Medications .............................................................................................................................................. 71 
8 
Study Procedures .......................................................................................................................................................... 71 
 
Study Assessments ................................................................................................................................................ 71 

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8.1.1 
Vital Signs and Growth Parameters .............................................................................................................. 71 
8.1.2 
Medical History and Physical Examination ................................................................................................... 71 
8.1.3 
Spirometry and Peak Expiratory Flow ........................................................................................................... 72 
8.1.4 
SCORAD ......................................................................................................................................................... 72 
8.1.5 
FAQLQ ........................................................................................................................................................... 72 
8.1.6 
Questionnaires .............................................................................................................................................. 72 
8.1.7 
Diaries ........................................................................................................................................................... 73 
8.1.8 
Skin Prick Tests .............................................................................................................................................. 73 
8.1.9 
Oral Food Challenges: Double-Blind Placebo-Controlled Food Challenges and Open Oral Food Challenges
 
73 
8.1.10 
Open Feedings............................................................................................................................................... 74 
 
Sample Collections ................................................................................................................................................ 74 
8.2.1 
Blood Collection ............................................................................................................................................ 74 
8.2.2 
Stool Collection ............................................................................................................................................. 75 
8.2.3 
Urine Collection ............................................................................................................................................. 75 
8.2.4 
Saliva Collection ............................................................................................................................................ 75 
 
Screening Visit ....................................................................................................................................................... 75 
8.3.1 
Screening Double-Blind Placebo-Controlled Food Challenge Visits .............................................................. 76 
 
Stage 1 ................................................................................................................................................................... 77 
8.4.1 
Randomization Visit (Day 0) .......................................................................................................................... 77 
8.4.2 
Omalizumab Injection Visits (Week 2 – Week 14) ........................................................................................ 78 
8.4.3 
Double-Blind Placebo-Controlled Food Challenge Visits (Week 16 – Week 20) ........................................... 78 
 
Stage 1 Open Label Extension ............................................................................................................................... 79 
8.5.1 
Omalizumab Injection Visits (Stage 1 Open Label Extension Week 0 – Week 22) ....................................... 80 
8.5.2 
Double-Blind Placebo-Controlled Food Challenge Visits (Stage 1 Open Label Extension Week 24 – Week 
28) 
80 
 
Stage 2 ................................................................................................................................................................... 81 
8.6.1 
Omalizumab Injection Visits (Stage 2 Week 0 – 6) ....................................................................................... 82 
8.6.2 
Randomization Stage 2 ................................................................................................................................. 82 
8.6.3 
Initial Dose Escalation Visit (Stage 2 Week 8) ............................................................................................... 82 
8.6.4 
Initial Dose Build-Up Visit (Stage 2 Week 8 + 1 day) ..................................................................................... 83 
8.6.5 
Dose Build-Up (Stage 2 Week 10 to Week 14 – Week 32) ............................................................................ 83 
8.6.6 
Initial Maintenance Dose Visit (Stage 2 Week 16 – Week 34) ...................................................................... 84 
8.6.7 
Follow-Up Maintenance Dose Visits (Stage 2 Week 24 – Week 58) ............................................................. 85 
8.6.8 
Double-Blind Placebo-Controlled Food Challenge Visits (Stage 2 Week 60 – Week 64) .............................. 85 

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Stage 3 – Long-Term Follow-Up and Rescue Oral Immunotherapy ...................................................................... 86 
8.7.1 
Long-Term Follow-Up with Dietary Consumption ........................................................................................ 86 
8.7.2 
Long-Term Follow-Up with Avoidance .......................................................................................................... 89 
8.7.3 
Rescue Oral Immunotherapy ........................................................................................................................ 89 
8.7.4 
End of Study visit for Participants in Stage 3 ................................................................................................ 90 
 
Unscheduled Visits ................................................................................................................................................ 90 
 
Early Discontinuation Visit .................................................................................................................................... 91 
 
Re-contact of Participants after End of Study or Early Discontinuation ............................................................... 92 
 
Visit Windows ....................................................................................................................................................... 92 
9 
Laboratory Research Assays.......................................................................................................................................... 94 
 
Biomarker Assays .................................................................................................................................................. 94 
9.1.1 
Measurement of Food-Specific IgE, IgG4, and IgA ........................................................................................ 94 
9.1.2 
Basophil Activation Test ................................................................................................................................ 95 
 
Mechanistic Studies .............................................................................................................................................. 95 
9.2.1 
Predicting the Response to Omalizumab through High Dimensional Profiling of Basophil Activation (Stage 
1 and Stage 2, Peanut Response) .................................................................................................................................. 95 
9.2.2 
Assessment of the Impact of Omalizumab Treatment in Stages 1 and 2 on Dendritic Cells and Peanut-
Specific CD4+T Cells ...................................................................................................................................................... 96 
 
Other Biosamples/Assays ...................................................................................................................................... 97 
10 Biospecimen Storage..................................................................................................................................................... 97 
11 Criteria for Participant and Study Completion and Premature Study Termination...................................................... 97 
 
Participant Completion ......................................................................................................................................... 97 
 
Participant Stopping Rules and Withdrawal Criteria ............................................................................................ 98 
11.2.1 
Automatic Stopping Rules ............................................................................................................................. 98 
11.2.2 
Discretionary Stopping Rules Requiring DSMB Review ................................................................................ 98 
11.2.3 
Discretionary Stopping Rules ........................................................................................................................ 98 
 
Participant Replacement ....................................................................................................................................... 99 
 
Follow-up after Early Study Withdrawal ............................................................................................................... 99 
 
Study Stopping Rules............................................................................................................................................. 99 
12 Safety Monitoring and Reporting ............................................................................................................................... 100 
 
Overview ............................................................................................................................................................. 100 
 
Definitions ........................................................................................................................................................... 100 
12.2.1 
Adverse Event ............................................................................................................................................. 100 
12.2.2 
Adverse Event of Special Interest ............................................................................................................... 101 
12.2.3 
Suspected Adverse Reaction ....................................................................................................................... 102 

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12.2.4 
Unexpected Adverse Event ......................................................................................................................... 102 
12.2.5 
Serious Adverse Event ................................................................................................................................. 102 
 
Pregnancy Reporting ........................................................................................................................................... 103 
 
Grading and Attribution of Adverse Events ........................................................................................................ 103 
12.4.1 
Grading Criteria ........................................................................................................................................... 104 
12.4.2 
Attribution Definitions ................................................................................................................................ 106 
 
Collection and Recording of Adverse Events ...................................................................................................... 106 
12.5.1 
Collection Period ......................................................................................................................................... 106 
12.5.2 
Collecting Adverse Events ........................................................................................................................... 106 
12.5.3 
Recording Adverse Events ........................................................................................................................... 107 
 
Reporting of Adverse Events, Serious Adverse Events, and Pregnancies ........................................................... 107 
12.6.1 
Reporting of Serious Adverse Events, Adverse Events of Special Interest, and Pregnancies to the IND 
Sponsor 107 
12.6.2 
Reporting to the FDA .................................................................................................................................. 107 
12.6.3 
Reporting of Adverse Events to IRBs ........................................................................................................... 108 
12.6.4 
Reporting of Other Safety Information ....................................................................................................... 108 
 
Review of Safety Information ............................................................................................................................. 108 
12.7.1 
Medical Monitor Review ............................................................................................................................. 108 
12.7.2 
DSMB Review .............................................................................................................................................. 109 
13 Statistical Considerations and Analytical Plan ............................................................................................................ 109 
 
Overview ............................................................................................................................................................. 109 
 
Endpoints ............................................................................................................................................................ 110 
 
Missing Data ........................................................................................................................................................ 110 
 
Measures to Minimize Bias ................................................................................................................................. 110 
 
Analysis Plan ........................................................................................................................................................ 111 
13.5.1 
Analysis Populations ................................................................................................................................... 111 
13.5.2 
Timing of Analyses ...................................................................................................................................... 113 
13.5.3 
Type I Error Control ..................................................................................................................................... 114 
13.5.4 
Primary Analysis of Primary Endpoint ......................................................................................................... 114 
13.5.5 
Supportive Analyses of the Primary Endpoint ............................................................................................ 115 
13.5.6 
Analyses of Secondary Endpoints ............................................................................................................... 116 
13.5.7 
Analyses of Exploratory Endpoints ............................................................................................................. 119 
13.5.8 
Descriptive Analyses ................................................................................................................................... 120 
 
Interim Analysis ................................................................................................................................................... 120 

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Statistical Hypotheses ......................................................................................................................................... 121 
 
Sample Size Considerations ................................................................................................................................ 121 
13.8.1 
Stage 1 ......................................................................................................................................................... 121 
13.8.2 
Stage 2 ......................................................................................................................................................... 122 
14 Identification and Access to Source Data ................................................................................................................... 123 
 
Source Data ......................................................................................................................................................... 123 
 
Access to Source Data ......................................................................................................................................... 123 
15 Protocol Deviations ..................................................................................................................................................... 123 
 
Protocol Deviation Definitions ............................................................................................................................ 123 
 
Reporting and Managing Protocol Deviations .................................................................................................... 124 
16 Ethical Considerations and Compliance with Good Clinical Practice .......................................................................... 124 
 
Quality Control and Quality Assurance ............................................................................................................... 124 
 
Statement of Compliance ................................................................................................................................... 125 
 
Informed Consent/Assent Process ...................................................................................................................... 125 
 
Privacy and Confidentiality ................................................................................................................................. 125 
17 Publication Policy ........................................................................................................................................................ 125 
18 References .................................................................................................................................................................. 125 
Appendix 1: Definition of Dose-Limiting Symptoms ........................................................................................................... 128 
Appendix 2: Omalizumab Dosing Table .............................................................................................................................. 129 
Appendix 3: Evaluation of Asthma Control ......................................................................................................................... 130 
Appendix 4: Schedule of Events for Screening and Stage 1 ................................................................................................ 131 
Appendix 5: Schedule of Events for Stage 1 Open Label Extension .................................................................................... 133 
Appendix 6: Schedule of Events for Stage 2 ....................................................................................................................... 134 
Appendix 7: Schedule of Events for Stage 3 – Long-Term Follow-Up with Dietary Consumption of a Food ..................... 136 
Appendix 8: Schedule of Events for Stage 3 – Long-Term Follow-Up with Avoidance of a Food ....................................... 138 
Appendix 9: Schedule of Events for Stage 3 – Rescue Oral Immunotherapy for a Food With Long-Term Follow-Up with 
Dietary Consumption1 ......................................................................................................................................................... 139 
Appendix 10: Sampson's Criteria for Diagnosing Potential Cases of Anaphylaxis .............................................................. 141 
Appendix 11: Grading Table for Non-Allergic Adverse Events Version 2.0 ........................................................................ 142 
Appendix 12: Objective and Endpoint Mapping ................................................................................................................. 153 
 
 
 

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Glossary of Abbreviations 
Abs 
antibodies 
AD 
atopic dermatitis 
ADAs 
anti-drug antibodies 
AE 
adverse event 
AESI 
adverse event of special interest 
ALT 
alanine aminotransferase  
AST 
aspartate aminotransferase 
ATEs 
arterial thrombotic events 
BAT 
basophil activation test 
BP 
blood pressure 
CBC 
complete blood count 
CDSMC 
Clinical Data and Safety Monitoring Center 
CFR 
Code of Federal Regulations 
CIU 
chronic idiopathic urticaria 
CMP 
comprehensive metabolic panel 
CoFAR 
Consortium for Food Allergy Research 
CRU 
clinical research unit 
CTCAE 
Common Terminology Criteria for Adverse Events 
CyTOF 
cytometry by time of flight 
DAIT 
Division of Allergy, Immunology, and Transplantation 
DBPCFC 
double-blind placebo-controlled food challenge 
DC 
dendritic cell 
DSMB 
Data and Safety Monitoring Board 
eCRF 
electronic case report form 
EDC 
electronic data capture 
EGPA 
Eosinophilic Granulomatosis with Polyangiitis 
EoE 
eosinophilic esophagitis 
EPIT 
epicutaneous immunotherapy 
FA-S1 
full analysis set-Stage 1 
FA-S1OLE 
full analysis set-Stage 1 OLE 
FA-S2 
pediatric full analysis set-Stage 2 
FA-S3 
pediatric full analysis set-Stage 3 
FAQLQ 
Food Allergy Quality of Life Questionnaire 

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FAQLQ-PF 
Food Allergy Quality of Life Questionnaire – Parent Form 
FAQLQ-CF 
Food Allergy Quality of Life Questionnaire – Child Form 
FAQLQ-TF 
Food Allergy Quality of Life Questionnaire – Teenager Form 
FAQLQ-AF 
Food Allergy Quality of Life Questionnaire – Adult Form 
FDA 
Food and Drug Administration 
FEV1 
forced expiratory volume in one second 
FVC 
forced vital capacity 
GCP 
Good Clinical Practice 
GI 
gastrointestinal 
GINA 
Global Initiative for Asthma 
GMP 
Good Manufacturing Practice 
HEENT 
head, eyes, ears, nose, and throat 
ICH 
International Conference on Harmonisation 
ICS 
inhaled corticosteroid 
IDE 
initial dose escalation 
IgA 
immunoglobulin A 
IgE 
immunoglobulin E 
IgG1 
immunoglobulin G1 
IgG4 
immunoglobulin G4 
IM 
intramuscular  
IND 
Investigational New Drug 
IP 
investigational product 
IRB 
Institutional Review Board 
IV 
intravenous 
MOP 
Manual of Procedures 
NIAID 
National Institute of Allergy and Infectious Diseases 
NCI 
National Cancer Institute 
NIH 
National Institutes of Health 
OFC 
oral food challenge 
OLE 
open label extension 
OIT 
oral immunotherapy 
PEF 
peak expiratory flow 
PBMCs 
peripheral blood mononuclear cells 
PFA-S1 
pediatric full analysis set – Stage 1 

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PFA-S1OLE 
pediatric full analysis set – Stage 1 OLE 
PFS 
pre-filled syringes 
PK 
pharmacokinetic 
PI 
(CRU) Principal Investigator 
PPP-S1 
pediatric per-protocol set-Stage 1 
PP-S2 
pediatric per-protocol set-Stage 2 
PP-S3 
pediatric per-protocol set-Stage 3 
PSS-PRERAND-S1 
pediatric pre-randomization safety set-Stage 1 
PSS-S1OLE 
pediatric safety set-Stage 1 OLE 
PSS-S1 
pediatric safety set-Stage 1 
PSS-OFC-S1OLE 
pediatric safety set for OFCs- Stage 1 OLE 
PSS-PRERAND-OFC-S1 
pediatric pre-randomization safety set for screening OFCs- 
Stage 1  
PSS-OFC-S1 
pediatric safety set of OFCs- Stage 1  
SCCC 
Statistical Clinical Coordinating Center 
SAE 
Serious Adverse Event 
SAP 
Statistical Analysis Plan 
SAR 
Suspected Adverse Reaction 
SCORAD 
SCORing Atopic Dermatitis 
SLIT 
sublingual immunotherapy 
SPT 
skin prick test 
SS-S1 
safety set- Stage 1 
SS-S1OLE 
safety Set- Stage 1 OLE 
SS-PRERAND-S1 
pre-randomization safety set 
SS-PREREAND-OFC-S1 
pre-randomization safety set for screening OFCs- Stage 1  
SS-S2 
safety set-Stage 2 
SS-S3 
safety set-Stage 3 
SUSAR 
Serious and Unexpected Suspected Adverse Reaction 
ULN 
upper limit of normal 
UNC-CH 
University of North Carolina at Chapel Hill 
 
 
 

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1 Background and Rationale 
 Background and Scientific Rationale 
Food allergy affects approximately 15 million patients in the US, including six million children. It causes substantial 
morbidity and mortality, and is the most common cause of anaphylaxis in pediatric patients seen in emergency 
departments across the US. Importantly, because accidental exposures to offending foods can be extremely difficult to 
avoid, particularly for multiple-foods (herein “multi-foods”), food allergy has a major negative impact on a patient’s 
quality of life and is a significant burden on our health care system, estimated to cost approximately $25 billion 
annually.1 The burden of food allergy in adults is less often recognized, but in reality most peanut and tree nut allergies 
persist into adulthood, as do a substantial subset of milk, egg, and wheat allergies.2 
Since its initiation in 2005, the Consortium for Food Allergy Research (CoFAR) has worked to develop potential 
treatments for food allergy, with studies focused on both peanut and egg. While substantial progress has been made in 
the development of treatment of peanut allergy, even with the potential of US Food and Drug Administration (FDA) 
approved treatments in the next few years, substantial gaps remain in many areas. Most important among these include 
treatment for foods other than peanut, treatment of patients who are allergic to multi-foods, and maximizing safety. 
The overarching goal of this study is to address each of these substantial gaps, especially in patients who are highly 
allergic to multi-foods. This is clearly an unmet need, and a perfect opportunity for CoFAR to take the lead, as 30% to 
70% of children and adults with peanut allergy are indeed allergic to other foods.3,4 
As described in detail below, this study is designed to study three major questions for the patient with multi-food 
allergies. First, Stage 1 will study the potential value of omalizumab for the treatment of patients who are allergic to 
peanut as well as at least two other common food allergens. If successful, this could lead to a major advance in the 
treatment of those patients with multi-food allergies, with the potential to provide effective treatment without the need 
for a food specific treatment such as oral immunotherapy (OIT). Second, Stage 2 will directly compare the treatment of 
patients with multi-food allergies using omalizumab as monotherapy versus treatment with Multi-allergen OIT using 
omalizumab as an adjunctive treatment that may improve the safety and/or efficacy of the OIT. Third, Stage 3 will 
address the potential longer-term outcomes of these treatment approaches, including the introduction of dietary forms 
of these allergenic foods into the diets of these multi-allergic patients. 
Substantial preliminary data exist to support these study objectives. With regard to omalizumab as potential 
monotherapy for the treatment of food allergy, multiple studies have shown that omalizumab may increase the 
threshold dose for inducing allergic symptoms following food exposure, reduces allergic symptoms that occur during an 
OFC, and facilitates food OIT, resulting in faster yet safe dose escalation (see Table 1.4). Most importantly, the effects of 
omalizumab do not appear limited to any particular food; omalizumab is unique in being effective for multi-food 
allergies in patients with single or multi-food allergies.  
There are also numerous studies demonstrating the likely benefit of omalizumab in conjunction with OIT to peanut and 
other foods. A pilot study was the first of its kind to show that milk desensitization can occur relatively rapidly when 
combined with omalizumab treatment in patients with severe milk allergy.5 In other food allergy studies, omalizumab 
has been shown to be efficacious and safe even in patients with severe food allergy: patients with a history of 
anaphylaxis, those who have failed prior OIT, and patients with multi-food allergies. These studies demonstrate that the 
majority of omalizumab-treated patients tolerated acute exposures of at least 400-2000 mg of the offending foods with 
minimal or no symptoms within 8-12 weeks of starting treatment.5-11 Several pilot studies have also addressed the 
possibility that omalizumab may also be useful as an adjunctive treatment with Multi-allergen OIT.7,12 

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 Rationale for Selection of Investigational Product or Intervention 
The rationale for the proposed study interventions in this protocol is based on substantial preliminary data regarding 
both approaches, omalizumab as monotherapy and as an adjunct to Multi-allergen OIT (see Table 1.4). In Stage 1, 
monotherapy with omalizumab will be compared to placebo for omalizumab to study the hypothesis that omalizumab 
can increase oral food challenge (OFC) thresholds in a clinically significant manner. In Stage 2, longer term treatment 
with omalizumab, now combined with placebo for Multi-allergen OIT, will be compared to active Multi-allergen OIT 
initiated under the protection of open label omalizumab. Study participants will then proceed into Stage 3, where the 
possibility that these treatments will allow for the introduction of the allergenic foods into the diet will be studied. 
Whatever the outcomes, the study will provide groundbreaking data that will impact the future of treatment for both 
peanut allergy and multi-food allergy. Further, as described below, the safety and efficacy of these treatments down to 
the age of one year will be studied, another groundbreaking advance in the study of potential treatments for food 
allergy. 
1.2.1 
Omalizumab 
Omalizumab is a recombinant humanized immunoglobulin G1 (IgG1) monoclonal antibody that binds to the FcεR1 
binding epitope of human immunoglobulin E (IgE), preventing human IgE from binding to its specific high-affinity 
receptors on mast cells and basophils. Omalizumab is produced by a mammalian cell (Chinese hamster ovary cell) 
suspension culture under Good Manufacturing Practice conditions using standard processes. 
Omalizumab is approved by the European Commission and US FDA for patients six years of age or older with allergic 
asthma for patients 12 years of age or older with chronic spontaneous urticaria (CSU) and for patients 18 years of age 
or older with nasal polyps. Although the drug carries warnings about a risk of anaphylaxis as well as other potential 
adverse effects, its overall safety profile has been well established (see current Investigator Brochure for Omalizumab 
(Xolair®)). Further, use in children two years of age and older is being evaluated in other protocols, including, for food 
allergy, in a protocol conducted under IND #14831 (IND Sponsor, A. Long, Pharm.D., Stanford University) and for 
possible effects on the natural course of asthma in children down to two years of age in a study (Protocol # U01-BCH-
03, PARK) conducted under NIAID-sponsored IND#134003 (Protocol Chair: W. Phipatanakul, MD, Children’s Hospital, 
Boston, MA). While this will be the first study to expand down to one year of age, this is an important population to 
study given the prevalence of food allergy in young children, as well as data suggesting that treatment of food allergy 
may be most effective if initiated early in childhood.13  
The approach for the use of omalizumab proposed in this study is based on the rationale that this medication may be 
effective as monotherapy and/or as an adjunct to Multi-allergen OIT. As monotherapy, data from the clinical studies 
described below suggest the effects on OFCs are seen early in the course of treatment, leading to the proposal for a 
16-week course of treatment in Stage 1. Fewer data are available regarding the effects of longer treatment with 
omalizumab for food allergy, and this question will be addressed by including an open label extension (OLE) for a 
subset of participants in Stage 1. This extension will be used to assess if the effects of omalizumab on OFC outcomes 
persist, or even increase, with a longer duration of treatment. For Stage 2, data suggest that pretreatment with 
omalizumab, prior to the initiation of OIT, significantly augments safety, and that ongoing treatment through the OIT 
build-up provides additional benefit, leading to the proposal to use open label omalizumab for eight weeks prior to 
the initiation of OIT, and then continued for the first eight weeks of OIT.5,7,8,11,12,14 Most importantly, however, Stage 2 
will provide the unique opportunity to directly compare these two potential treatment approaches, with one 
treatment arm receiving omalizumab with placebo OIT and the other receiving omalizumab-facilitated OIT. 
The analyzed data from Stage 1 and OLE were reviewed by the Food and Drug Administration (FDA), and as of 16 
February 2024, Xolair® (omalizumab) is approved for IgE-mediated food allergy in adult and pediatric patients aged 

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Reference 
Study Design 
Food 
Study Population 
(actual) 
Relevant Objectives 
Results 
29 patients received 
omalizumab 
8 patients received 
placebo 
desensitization in highly 
allergic patients. 
Placebo: 13% of patients reached the 
maximum 490 mg dose of peanut 
protein 
 
After 8-12 Weeks Additional OIT 
Omalizumab: 81% of patients 
reached the maximum 4000 mg dose 
of peanut protein 
Placebo: 13% of patients reached the 
maximum 4000 mg dose of peanut 
protein 
Andorf et al. 
201712 
Omalizumab + 
OIT 
RCT, DBPCFC 
Multiple 
foods 
48 patients (median age 
8 years) with allergy to 2-
5 foods (mean 3.3 foods): 
36 patients received 
omalizumab 
12 patients received 
placebo 
To evaluate whether 
omalizumab facilitated 
desensitization in patients 
with multi-food allergies. 
After completing 8 weeks of 
omalizumab monotherapy, treated 
patients tolerated a median dose of 
mixed food of 2380 mg (max dose 
2380 mg) compared to 55 mg in the 
placebo group. 
2 Study Hypotheses/Objectives 
 Hypotheses 
The primary null hypothesis for this study is that in children and adults aged 1 year to less than 56 years who are allergic 
to peanut and at least two other foods (milk, egg, wheat, cashew, hazelnut, or walnut), the dose of oral food protein 
that is consumed without dose-limiting symptoms (defined in Appendix 1) during a DBPCFC after treatment with either 
omalizumab or placebo for omalizumab is the same. 
Secondary null hypotheses related to the use of omalizumab as monotherapy as well as adjunct therapy to Multi-
allergen OIT for the treatment of food allergy include: 
1. The effects of omalizumab will be maintained with 24 weeks of additional treatment. 
2. The dose of oral food protein that is consumed without dose-limiting symptoms during a DBPCFC after 
treatment with either omalizumab-facilitated OIT or omalizumab + placebo OIT is the same. 
3. Dietary consumption of food after the conclusion of treatment with either omalizumab-facilitated OIT or 
omalizumab + placebo OIT is the same. 
4. Treatment of food allergy with either omalizumab as monotherapy or as adjunct therapy to Multi-allergen OIT is 
safe. 
 Primary Objective 
To compare the ability to consume foods without dose-limiting symptoms during a DBPCFC after treatment with either 
omalizumab or placebo for omalizumab. 
 Secondary Objectives 
Stage 1 
 
1. To evaluate safety during treatment with either omalizumab or placebo for omalizumab. 
Stage 2 
2. To compare the ability to consume foods without dose-limiting symptoms during a DBPCFC after treatment with 
either omalizumab-facilitated OIT or omalizumab + placebo OIT. This is the primary objective for Stage 2. 

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3. To evaluate safety during treatment with either omalizumab-facilitated OIT or omalizumab + placebo OIT. 
Stage 3 
4. To compare dietary consumption of foods after the conclusion of treatment with either omalizumab-facilitated 
OIT or omalizumab + placebo OIT during a follow-up period in which participants either received guided dietary 
instructions and/or rescue OIT for up to three foods.  
5. To evaluate safety after the conclusion of treatment with either omalizumab-facilitated OIT or omalizumab + 
placebo OIT during a follow-up period in which participants either received guided dietary instructions and/or 
rescue OIT for up to three foods. 
 Exploratory Objectives 
Exploratory objectives are: 
Stage 1 
1. To compare quality of life after treatment with either omalizumab or placebo for omalizumab. 
Stage 1 OLE 
2. To assess the safety and efficacy of either 24 or 40 weeks of treatment with omalizumab.  
3. To assess quality of life at the end of either 24 or 40 weeks of treatment with omalizumab. 
Stage 2 
 
4. Among participants who do not respond to treatment with omalizumab alone, compare the ability to consume 
foods without dose-limiting symptoms during a DBPCFC after treatment with either omalizumab-facilitated OIT 
or omalizumab + placebo OIT. 
5. Among participants who respond to treatment with omalizumab alone, compare the ability to consume foods 
without dose-limiting symptoms during a DBPCFC after treatment with either omalizumab-facilitated OIT or 
omalizumab + placebo OIT. 
6. To compare the change in the dose of each food that is consumed without dose-limiting symptoms during a 
DBPCFC at the end of Stage 1 and during a DBPCFC at the end of Stage 2 between treatment with either 
omalizumab-facilitated OIT or omalizumab + placebo OIT. 
7. To compare quality of life after treatment with either omalizumab-facilitated OIT or omalizumab + placebo OIT. 
Stage 3 
8. To compare quality of life after the conclusion of treatment with either omalizumab-facilitated OIT or 
omalizumab + placebo OIT during a follow-up period in which participants either receive guided dietary 
instructions and/or rescue OIT for up to three foods. 
9. To describe dietary consumption of foods after the conclusion of either 24 or 40 weeks of treatment with 
omalizumab during a follow-up period in which participants either received guided dietary instructions and/or 
rescue OIT for up to three foods. 
10. To assess safety after the conclusion of either 24 or 40 weeks of treatment with omalizumab during a follow-up 
period in which participants either received guided dietary instructions and/or rescue OIT for up to three foods. 

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11. To measure quality of life after the conclusion of either 24 or 40 weeks of treatment with omalizumab during a 
follow-up period in which participants either received guided dietary instructions and/or rescue OIT for up to 
three foods. 
Pharmacokinetic (PK) objectives are: 
Stage 1 
12. To evaluate serum omalizumab concentrations during treatment with omalizumab. 
Stage 1 OLE 
13. To assess serum omalizumab concentrations at the end of either 24 or 40 weeks of treatment with omalizumab. 
Stage 2 
14. To evaluate serum omalizumab concentrations during treatment with either omalizumab-facilitated OIT or 
omalizumab + placebo OIT. 
Biomarker objectives are: 
Stage 1 
15. To compare immunological responses after treatment with either omalizumab or placebo for omalizumab. 
16. To determine whether immunological responses can be used to predict the ability to consume foods without 
dose-limiting symptoms during a DBPCFC after treatment with either omalizumab or placebo for omalizumab. 
Stage 1 OLE 
17. To assess immunological responses at the end of either 24 or 40 weeks of treatment with omalizumab. 
Stage 2 
 
18. To compare immunological responses during and after treatment with either omalizumab-facilitated OIT or 
omalizumab + placebo OIT. 
19. To determine whether immunological responses can be used to predict the ability to consume foods without 
dose-limiting symptoms during a DBPCFC after treatment with either omalizumab-facilitated OIT or omalizumab 
+ placebo OIT. 
Stage 3 
20. To compare immunological responses after the conclusion of treatment with either omalizumab-facilitated OIT 
or omalizumab + placebo OIT during a follow-up period in which participants either received guided dietary 
instructions and/or rescue OIT for up to three foods. 
21. To assess immunological responses after the conclusion of either 24 or 40 weeks of treatment with omalizumab 
during a follow-up period in which participants either received guided dietary instructions and/or rescue OIT for 
up to three foods. 

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3 Study Design 
 Description of Study Design  
This study is a multi-center, randomized, double-blind, placebo-controlled study in participants 1 year to less than 56 
years of age at the Screening Visit who are allergic to peanut and at least two other foods (including milk [i.e., cow’s 
milk], egg [i.e., egg white], wheat, cashew, hazelnut, or walnut [i.e., English walnut]). While each participant may be 
allergic to more than two other foods, the primary endpoint in this study will only be assessed in peanut and two other 
foods for each participant. The choice of which foods are treated is described in Section 3.1.1.  
There are three stages (see Figure 3.1). The study planned to randomize 225 participants at the beginning of Stage 1 
(≥50 participants aged 1 year to less than 6 years, approximately 160 participants aged 6 to less than 18 years, and 
approximately 15 participants aged 18 to less than 56 years). Individual study participation will consist of a maximum of 
84 weeks for treatment and a minimum of 12 months of follow-up. Throughout Stage 1, Stage 1 OLE, and Stage 2, each 
participant will be instructed to strictly avoid all foods to which they are allergic. Each participant will also be instructed 
to strictly avoid a food for which they receive rescue OIT during Stage 3. 
An interim analysis for efficacy would be conducted on all pediatric subjects (ages 1 year to less than 18 years) 
randomized into Stage 1 on or before 08JUL2022 (N=165). The analysis would be conducted after all of these 
participants have either completed or discontinued from Stage 1. Efficacy would be declared only if the two-sided p-
value for the peanut is significant at p< 0.0001 and the two-sided p-values for all secondary foods (cashew, milk, and 
egg) are significant at p< 0.005, with the direction of all treatment group difference favoring omalizumab. If the study is 
curtailed for efficacy, enrollment into the trial and randomization into Stage 1 will be immediately discontinued.  
Otherwise, if the study is not curtailed for efficacy, accrual into Stage 1 will continue to the planned 210 pediatric 
participants and up to 225 total participants. 
DAIT NIAID conducted the interim analysis for efficacy on 165 pediatric participants randomized into Stage 1 and the 
results derived from the primary and key secondary outcomes interim analysis and supportive sensitivity analyses were 
reviewed by the NIAID Allergy and Asthma Data and Safety Monitoring Board (DSMB). The data reviewed demonstrated 
benefit of omalizumab over placebo, meeting the pre-specified stopping guideline of a p-value less than 0.0001 for 
peanut and p-value less than 0.005 for secondary foods (cashew, milk and egg).  Study enrollment was stopped on 
March 23, 2023, with the final number of 182 randomized participants. 
The analyzed data from Stage 1 and OLE were reviewed by the Food and Drug Administration (FDA), and as of 16 
February 2024, Xolair® (omalizumab) is approved for IgE-mediated food allergy in adult and pediatric patients aged 1 
year and older for the reduction of allergic reactions (Type I), including anaphylaxis, that may occur with accidental 
exposure to one or more foods.  Omalizumab is to be used in conjunction with food allergen avoidance. 

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Figure 3.1 Study Design 
 
 
 
 

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3.1.1 
Screening 
During an initial Screening Visit, a participant and/or parent/legal guardian will provide informed consent and/or 
assent for study participation. A consented participant will then be assessed for study eligibility through the 
collection of medical, diet and allergy histories; a physical exam, including an assessment of atopic dermatitis (AD) 
severity; skin prick tests (SPTs); and blood sample collection to measure complete blood count (CBC), comprehensive 
metabolic panel (CMP), and IgE (total IgE and allergen-specific IgE). 
A participant who is eligible up to this point will complete a DBPCFC (see Table 3.1.1). The DBPCFC will consist of four 
blinded OFCs: three active OFCs (peanut and two additional foods) and one placebo OFC (oat). The DBPCFC may be 
conducted over four separate visits. The PI and the participant and/or parent/legal guardian will make an 
individualized decision regarding the selection of the two additional foods, as defined in the OUtMATCH OFC MOP. 
Completion of a blinded OFC is defined as ingesting any amount of protein/placebo during that blinded OFC. 
Participants who begin a blinded OFC at Screening but refuse to continue OFC dosing to the end of the OFC despite 
not experiencing dose-limiting symptoms will be allowed to repeat the blinded OFC one time on a different day. 
Participants who do not experience dose-limiting symptoms to two non-peanut foods but who may be allergic to 
additional foods will receive an additional DBPCFC consisting of up to two active OFCs for other non-peanut foods 
and one placebo OFC. 
The maximum cumulative dose for each blinded OFC during the Screening DBPCFC is 444 mg of protein. For the 
blinded OFC to peanut during the Screening DBPCFC, the maximum single dose given will be 100 mg of peanut 
protein with the final single 300 mg dose consisting of placebo. For the additional blinded OFCs to two foods and the 
blinded OFC to placebo during the Screening DBPCFC, the maximum single dose given will be 300 mg of the 
respective food protein/placebo. 
After the participant completes each blinded OFC during the Screening DBPCFC, the CRU dietitian/pharmacist (as 
applicable) will review the results of the blinded OFC to confirm that the participant still meets those inclusion 
criteria and does not meet those exclusion criteria that are based on the blinded OFCs. If the participant is no longer 
eligible for the trial, the participant will not undergo any further blinded OFCs as part of the Screening DBPCFC, will 
be considered a screen failure, and will be referred to an allergist for further evaluation. 
After completing the Screening DBPCFC, participants who experience dose-limiting symptoms to a single dose of 
≤100 mg of peanut protein, ≤300 mg protein for each of the other two foods, and no dose-limiting symptoms during 
the blinded OFC to placebo will move to Stage 1. A participant who does not experience dose-limiting symptoms to 
peanut and two other foods or reacts to the blinded OFC to placebo during the Screening DBPCFC will be considered 
a screen failure and will be referred to an allergist for further evaluation. 
Table 3.1.1 Dosing Schedule for the Screening DBPCFC 
Dose # 
Food Protein/Placebo (mg protein) 
Cumulative Dose (mg protein) 
1 
1 
1 
2 
3 
4 
3 
10 
14 
4 
30 
44 
5 
100 
144 
61 
300 
444 
1. During the blinded OFC to peanut, the 300 mg dose will be placebo so as not to surpass 
a maximum dose of 100 mg of peanut protein during the Screening DBPCFC and to 
preserve blinding. 

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3.1.2 
Stage 1 – Omalizumab as Monotherapy 
Stage 1 of the study will test whether 16-20 weeks of treatment with omalizumab versus placebo for omalizumab 
increases the proportion of participants who consume each of the foods under study without dose-limiting 
symptoms, as assessed by a DBPCFC.  
Participants who meet eligibility criteria will be randomized 2:1 to 16-20 weeks of treatment with omalizumab or 
placebo for omalizumab per a standard omalizumab dosing table (see Appendix 2). During Stage 1, all participants, 
PIs, and clinical research unit (CRU) staff will be blinded to treatment assignments, except for an unblinded CRU 
pharmacist/pharmacy staff and a CRU staff member who will administer omalizumab or placebo for omalizumab 
injections. The CRU staff member administering injections will not be involved in any other aspect of the study that 
would threaten blinding and/or that could be influenced by an unblinded CRU staff member performing the 
procedure. 
During Stage 1, each randomized participant will be instructed to strictly avoid all foods to which they are allergic. 
Each randomized participant will visit the CRU every two or four weeks (depending on omalizumab dosing frequency) 
for an injection of omalizumab or placebo for omalizumab. Each participant must be observed for at least two hours 
after the first three injections and at least 30 minutes after all subsequent injections to assess adverse events (AEs). 
After 16 weeks of treatment, each participant will complete a DBPCFC (see Table 3.1.2) consisting of placebo and 
each of their three specific foods to a cumulative dose of 6044 mg protein of each food. The DBPCFC may occur over 
four separate visits to accommodate blinded OFCs for three foods and placebo. Each participant will continue to 
receive omalizumab or placebo for omalizumab injections while these blinded OFCs are completed. All blinded OFCs 
comprising the DBPCFC must occur within a maximum period of 28 days; therefore, Stage 1 may last between 16 and 
20 weeks. 
Table 3.1.2 Dosing Schedule for a DBPCFC at the End of Stage 1, Stage 1 OLE, and Stage 2 
Dose # 
Food Protein/Placebo (mg protein) 
Cumulative Dose (mg protein) 
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 
2000 
4044 
10 
2000 
6044 
111 
2000 
8044 
1. Dose #11 will only be performed for the DBPCFC at the end of Stage 1 OLE and Stage 2. 
Each participant who does not complete Stage 1 (i.e., does not complete all four blinded OFCs comprising the 
DBPCFC at the end of Stage 1) will be withdrawn from the study and will attend an Early Discontinuation Visit (see 
Section 8.9). Each participant who completes Stage 1 will move on to either Stage 1 OLE or Stage 2 of the study. The 
first 60 participants will participate in the Stage 1 OLE. 
In the event that Stage 1 of the trial is curtailed on the basis of the interim analysis (see section 3.1), enrollment for 
the trial will stop, and all participants will be informed of the outcome. Participants in Stage 1 at the time efficacy is 

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declared will fall in 1 of 2 categories: 1)those who have randomized and begun omalizumab/placebo for omalizumab 
injections, and 2)those who are still in screening and are deemed eligible but have not started injection therapy. 
Participants will have the following options for study continuation based on their category:  
Options for Participants that have randomized into Stage 1 and are receiving omalizumab/placebo for omalizumab 
injection therapy, if Stage 1 is curtailed on basis of the interim analysis: 
1. Stop Stage 1 immediately, randomize into Stage 2 and continue on study. 
2. Continue receiving Stage 1 injection therapy for 16 total weeks, decline Stage 1 DBPCFCs, randomize into Stage 2 
and continue on Study. 
3. Continue receiving Stage 1 injection therapy for 16 total weeks, complete Stage 1 DBPCFCs, randomize into Stage 
2 and continue on Study. 
4. Withdraw from Study.    
 
 
Options for Participants that are in screening and are determined eligible, or those who have randomized into 
Stage 1 but have not begun Stage 1 injection therapy if Stage 1 is curtailed on basis of the interim analysis: 
1. Randomize into Stage 2. 
2. Withdraw from study. 
 
3.1.3 
Stage 1 Open Label Extension – Long-Term Treatment with Omalizumab 
During the OLE, each participant will receive 24-28 weeks of treatment with open label omalizumab followed by a 
DBPCFC to test the durability of long-term treatment with omalizumab. A blinded CRU staff member can administer 

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injections during this stage of the study. 
During the OLE, each participant will be instructed to strictly avoid all foods to which they are allergic. Each 
participant will visit the CRU every two or four weeks (depending on omalizumab dosing frequency) for an injection 
of omalizumab. To maintain blinding to Stage 1 treatment arm, each participant must be observed for at least two 
hours after the first three injections and at least 30 minutes after all subsequent injections given in the OLE to assess 
AEs. 
After 24 weeks of treatment, each participant will complete a DBPCFC (see Table 3.1.2) consisting of placebo and 
each of their three specific foods to a cumulative dose of 8044 mg protein of each food. The DBPCFC may occur over 
four separate visits to accommodate blinded OFCs to the three foods and placebo. Each participant will continue to 
receive omalizumab injections while these blinded OFCs are completed. All blinded OFCs comprising the DBPCFC 
must occur within a maximum period of 28 days; therefore, the OLE may last between 24 and 28 weeks. 
Each participant who does not complete Stage 1 OLE (i.e., does not complete all four blinded OFCs comprising the 
DBPCFC at the end of the OLE) will be withdrawn from the study and will attend an Early Discontinuation Visit (see 
Section 8.9). Each participant who completes Stage 1 OLE will move on to Stage 3 of the study.  
As of protocol version 9.0, Stage 1 and Stage 1 OLE have been completed. Stages 2 and 3 are ongoing.  
3.1.4 
Stage 2 – Omalizumab as Adjunct Therapy to Multi-Allergen Oral Immunotherapy Compared to Omalizumab 
Monotherapy 
Stage 2 of the study will test if eight weeks of treatment with open label omalizumab followed by 52-56 weeks of 
treatment with omalizumab-facilitated OIT or omalizumab + placebo OIT increases the proportion of participants 
who consume each of the foods under study without dose-limiting symptoms, as assessed by a DBPCFC. 
During Stage 2, each participant will be instructed to strictly avoid all foods to which they are allergic. Each 
participant will receive eight weeks of treatment with open label omalizumab. To maintain blinding to Stage 1 
treatment arm, each participant must be observed for at least two hours after the first three injections and at least 
30 minutes after all subsequent injections given in Stage 2 to assess AEs. 
One week after beginning Stage 2, participants will be randomized 1:1 to: 
• 
Omalizumab-facilitated OIT: Open label omalizumab + Multi-allergen OIT for eight weeks, followed by 
placebo for omalizumab + Multi-allergen OIT for 44 weeks. 
• 
Omalizumab + placebo OIT: Open label omalizumab + placebo for Multi-allergen OIT for eight weeks, 
followed by omalizumab + placebo for Multi-allergen OIT for 44 weeks. 
During Stage 2, all participants, PIs, and CRU staff will be blinded to randomized treatment assignments, except for 
an unblinded CRU pharmacist/pharmacy staff and a CRU staff member who will administer omalizumab or placebo 
for omalizumab injections only. The CRU staff member administering injections during the blinded portion of Stage 2 
will not be involved in any other aspect of the study that would threaten blinding and/or that could be influenced by 
an unblinded CRU staff member performing the procedure. However, a blinded CRU staff member can administer 
injections during the open label portion of Stage 2. 
After completion of eight weeks of open label omalizumab, each participant will receive an additional eight weeks of 
open label omalizumab followed by either 44 weeks of omalizumab or placebo for omalizumab (depending on the 

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arm). While receiving omalizumab or placebo for omalizumab injections, each participant will also complete 52 
weeks of Multi-allergen OIT or placebo for Multi-allergen OIT as follows: 
Initial Dose Escalation (IDE): IDE will occur on a single day in which multiple doses of Multi-allergen OIT or placebo for 
Multi-allergen OIT will be given to the participant. 
If the participant chooses to receive their injection of open label omalizumab during the IDE Visit, the injection will be 
performed prior to the initiation of IDE to ensure that sufficient time (at least two hours or at least 30 minutes, 
depending on participant’s omalizumab dosing frequency) is given to assess AEs related to the injection. Otherwise, 
the participant will receive their injection of open label omalizumab either the day after the IDE Visit (i.e., Initial Dose 
Build-Up Visit) or at a separately scheduled visit. 
Multi-allergen OIT or placebo for Multi-allergen OIT IDE doses will be administered incrementally and increased every 
15 minutes up to a total dose of 1125 mg protein of Multi-allergen OIT or equivalent placebo for Multi-allergen OIT 
(see Table 3.1.4a). The participant must tolerate a dose of at least 9 mg protein of Multi-allergen OIT or equivalent 
placebo for Multi-allergen OIT. A participant who does not tolerate at least 9 mg protein of Multi-allergen OIT or 
equivalent placebo for Multi-allergen OIT will be considered an IDE failure and be referred to an allergist for standard 
clinical care. Each participant defined as an IDE failure will not complete any additional study visits and/or sample 
collections. 
Table 3.1.4a Dosing Schedule for Initial Dose Escalation in Stage 2 
Dose # 
Multi-Allergen 
OIT/Placebo for Multi-
Allergen OIT Food 
Allergen Dose 
(mg protein of each 
allergen) 
Multi-Allergen 
OIT/Placebo for Multi-
Allergen OIT Total Food 
Allergen Dose (mg 
protein) 
1 
3 
9 
2 
30 
90 
3 
60 
180 
4 
125 
375 
5 
250 
750 
6 
375 
1125 
 
Build-Up Phase: The day after the IDE Visit, the participant will return to the CRU for an observed administration of 
the last tolerated dose of Multi-allergen OIT or placebo for Multi-allergen OIT. The participant will then continue 
Multi-allergen OIT or placebo for Multi-allergen OIT daily at home, as prescribed. The participant will return to the 
CRU every two weeks for a dose build-up (see Table 3.1.4b) to reach a maximum maintenance dose of 1000 mg 
protein of each of their three specific foods (i.e., a total maximum dose of 3000 mg food protein or 3000 mg placebo 
for Multi-allergen OIT, depending on the arm). A participant who does not tolerate OIT dosing during a Dose Build-Up 
Visit will remain at the previously tolerated dose until the next Dose Build-Up Visit. Each participant must reach a 
dose of at least 750 mg food protein (equivalent to 250 mg protein of each of their three specific foods or 750 mg of 
placebo) within 24 weeks of IDE to enter the Maintenance Phase; otherwise, the participant will be considered a 
treatment failure and referred to an allergist for standard clinical care. A participant who has met this definition of a 
treatment failure will attend an Early Discontinuation Visit (see Section 8.9). 

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Table 3.1.4b Dosing Schedule for Multi-allergen OIT/Placebo for Multi-allergen OIT Dose Build-Up in Stage 2 
Dose #1 
Multi-allergen OIT/Placebo for Multi-
allergen OIT Food Allergen Dose  
(mg protein of each allergen) 
Multi-allergen OIT/Placebo for 
Multi-allergen OIT Total Food 
Allergen Dose (mg protein) 
Interval 
(weeks) 
1 
3 
9 
2 
2 
30 
90 
2 
3 
60 
180 
2 
4 
125 
375 
2 
5 
250 
750 
2 
6 
375 
1125 
2 
7 
560 
1680 
2 
8 
800 
2400 
2 
9 
1000 
3000 
2 
1. Dose build-up will begin at the last tolerated dose from the IDE Visit. 
Omalizumab or placebo for omalizumab injections during the Build-Up Phase may be performed on the same day as 
a Dose Build-Up Visit, with the injection occurring at least 30 minutes prior to the build-up dose to assess AEs. 
Maintenance Phase: Once each participant reaches the maintenance dose, the participant will continue daily home 
OIT dosing until 52 weeks after the IDE is completed. Each participant will return to the CRU two weeks after the end 
of the Build-Up Phase for their Initial Maintenance Dose Visit and every eight weeks thereafter for Follow-Up 
Maintenance Dose Visits. Each participant will also return to the CRU for injections of omalizumab or placebo for 
omalizumab according to their omalizumab dosing frequency; these visits may also occur on the Initial or Follow-Up 
Maintenance Dose Visits, with an observation period of at least 30 minutes prior to the maintenance dose to assess 
AEs. Depending on when a participant reaches the maintenance dose during the Build-Up Phase, the number and 
timing of Follow-Up Maintenance Dose Visits may vary among participants. 
If a participant does not tolerate a dose during the Maintenance Phase, the dose may be adjusted (see Section 6.4.2). 
In the event a participant, undergoing dose adjustments, does not tolerate at least 750 mg of Multi-allergen OIT or 
equivalent placebo for Multi-allergen OIT by two weeks before the first DBPCFC Visit at the end of Stage 2, the 
participant will be considered a treatment failure and will be referred to an allergist for standard clinical care. A 
participant defined as a treatment failure will attend an Early Discontinuation Visit (see Section 8.9). 
At the end of the Maintenance Phase, each participant will complete a DBPCFC (see Table 3.1.2) consisting of placebo 
and each of their three specific foods to a cumulative dose of 8044 mg protein of each food. The DBPCFC may occur 
over four separate visits to accommodate blinded OFCs to the three foods and placebo. Each participant will continue 
on OIT while all these blinded OFCs are completed. All blinded OFCs comprising the DBPCFC must occur within a 
maximum period of 28 days; therefore, Stage 2 may last between 60 and 64 weeks. 
Each participant who does not complete Stage 2 (i.e., does not complete all four blinded OFCs comprising the 
DBPCFC at the end of Stage 2) will be withdrawn from the study and will attend an Early Discontinuation Visit (see 
Section 8.9). Each participant who completes Stage 2 will move on to Stage 3 of the study. 

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3.1.5 
Stage 3 – Long-Term Follow-Up and Rescue Oral Immunotherapy 
During Stage 3, a participant will be offered a separate treatment plan for peanut and each of the two other 
participant-specific foods. A treatment plan will include instructions for one of the following: 
• 
Long-term follow-up with dietary consumption of a food; or 
• 
Long-term follow-up with avoidance of a food; or 
• 
Rescue OIT for a food.  
The treatment plan for each food may change throughout Stage 3 depending on a participant’s response to 
treatment. Because the visit schedule for each treatment plan differs, a participant’s visits during Stage 3 will be 
combined accordingly to minimize the number of visits a participant attends. 
Once a participant enters Stage 3, the participant will have a minimum of 12 months of follow-up in Stage 3.  
3.1.5.1 
Long-Term Follow-Up with Dietary Consumption of a Food 
A participant will undergo long-term follow-up with dietary consumption of a specified food(s) if the 
participant meets the following requirements: 
• 
Completed Stage 1 OLE or Stage 2 within the last fourteen days and consumed a single dose of 
≥600 mg protein of the food without dose-limiting symptoms. 
Long-term follow-up with dietary consumption of a food will begin with the participant being given an 
observed initial open feeding of the dietary food during a CRU visit. Open feedings to more than one dietary 
food may occur on the same day with a two-hour waiting period between each food. An open feeding may 
occur on the day of the last blinded OFC at the end of Stage 1 OLE or Stage 2 if the blinded OFC to placebo 
is performed on that day. The amount of dietary food eaten at the open feeding will be based on the 
maximum quantity deemed to be safe, as determined by the participant’s most recent OFC (see Table 
3.1.5.1). 
Participants who undergo long-term follow-up with dietary consumption of a food immediately after 
completing Stage 1 OLE or Stage 2 will remain on the treatment they were receiving until all open feedings 
are completed. 
Following completion of the open feeding(s), the participant will be provided with individualized 
instructions for inclusion of the food into their diet. For participants undergoing long-term follow-up with 
dietary consumption of a food immediately after completing Stage 2, all open feedings must be completed 
prior the participant’s receipt of the individualized instructions for the inclusion of the food into the diet.  
After the open feeding(s), the participant will be called or emailed weekly for the first four weeks, every 
other week between six and sixteen weeks, and then every two months for safety follow-up. In addition, 
the participant will be required to return to the CRU for a long-term follow-up visit every six months. 
Starting at seven months of follow-up, the participant will be called or emailed every month to complete 
monthly long-term follow-up phone calls/emails. These phone calls/emails may be combined with other 
study visits in Stage 3.  

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Table 3.1.5.1 Minimum and Maximum Amounts of Protein Contained in a Single Food That Should Be 
Consumed by Participants at Open Feeding 
Minimum 
Amount  
(mg protein of 
food) 
Cumulative Dose Consumed Without 
Dose-Limiting Symptoms  
During Most Recent OFC  
(mg protein) 
Dose Consumed Without Dose-
Limiting Symptoms  
During Most Recent OFC  
(mg protein) 
Maximum 
Amount  
(mg protein of 
food) 
300 
1044 
600 
600 
300 
2044 
1000 
1000 
300 
4044 
1st dose of 2000 
2000 
300 
6044 
2nd dose of 2000 
4000 
300 
8044 
3rd dose of 2000 
6000 
 
If the participant does not tolerate ≥300 mg protein of the food during the first six months of long-term 
follow-up with dietary consumption, the participant will be considered a treatment failure for that food and 
will either: 
• 
Receive long-term follow-up with avoidance of that food; or 
• 
Be referred to an allergist.  
If the participant tolerates ≥300 mg protein of the food for the first six months but does not tolerate ≥300 
mg protein of the food after the first six months of long-term follow-up with dietary consumption, the 
participant will be considered a treatment failure for that food and will receive long-term follow-up with 
avoidance of that food.  
3.1.5.2 
Long-Term Follow-Up with Avoidance of a Food 
A participant will undergo long-term follow-up with avoidance of a food if the participant: 
• 
Does not tolerate ≥300 mg protein of the food during the first six months of long-term follow-up 
with dietary consumption of the food; or 
• 
Does not tolerate ≥300 mg protein of the food after the first six months of long-term follow-up with 
dietary consumption; or  
• 
Was an IDE failure or treatment failure during rescue OIT for the food; or 
• 
The participant chooses to avoid that food. 
During long-term follow-up with avoidance of a food, the participant will avoid eating the food. The 
participant will return to the CRU for a long-term follow-up visit every six months for follow-up. Starting at 
seven months of follow-up, the participant will be called or emailed every month to complete monthly 
long-term follow-up phone calls/emails. These phone calls/emails may be combined with other study visits 
in Stage 3.  

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3.1.5.3 
Rescue Oral Immunotherapy for a Food 
A participant will be offered rescue OIT for a food if the participant: 
• 
Completed Stage 1 OLE or Stage 2 within the last 14 days and had dose-limiting symptoms at a 
single dose of ≤600 mg protein of the food; or 
• 
Completed the DBPCFC at the end of Stage 1 OLE or Stage 2 within the last 14 days but refused to 
continue the blinded OFC to a single dose of 600 mg protein of the food, despite not experiencing 
dose-limiting symptoms at a single dose less than 600 mg protein of the food. 
Participants who enter rescue OIT for a food will have 12 months of follow-up from the start of the rescue 
OIT for that food.  
IDE Visit during Rescue OIT: A participant will have an IDE Visit during rescue OIT if the participant: 
• 
Has dose-limiting symptoms at a single dose of ≤100 mg protein of the food during the DBPCFC at 
the end of Stage 1 OLE or Stage 2; or  
• 
Completed the DBPCFC at the end of Stage 1 OLE or Stage 2 but refused to continue the blinded 
OFC to a single dose of 100 mg protein of the food, despite not experiencing dose-limiting 
symptoms at a single dose less than 100 mg protein of the food. 
A participant who attends an IDE Visit immediately after completing Stage 1 OLE or Stage 2 will remain on 
the treatment they received in the previous stage until the IDE Visit and any needed Open Feedings (if 
needed immediately after completing Stage 1 OLE, Stage 2) are completed. 
Rescue OIT IDE doses for a food will be administered incrementally and increased every 15 minutes up to a 
dose of 375 mg protein of rescue OIT (see Table 3.1.5.3a). The participant must tolerate a dose of at least 3 
mg protein of rescue OIT for the food. A participant who does not tolerate 3 mg protein of the food during 
the IDE Visit will be considered an IDE failure, will be removed from rescue OIT for that food, and will 
receive long-term follow-up with avoidance of that food.  
Alternatively, a participant will skip the IDE Visit during rescue OIT if the participant consumed a dose of 
≥100 mg protein of the food without dose-limiting symptoms during the participant’s DBPCFC at the end of 
Stage 1 OLE or Stage 2. Participants who do not require an  IDE visit when entering Stage 3 Rescue OIT will 
begin in the build-up phase without further doses of omalizumab/placebo for omalizumab or open label  
omalizumab from the previous stage.  
 
Table 3.1.5.3a Dosing Schedule for Initial Dose Escalation in Stage 3 
 
 
Dose # 
Food Allergen Dose  
(mg protein of each 
allergen) 
1 
3 
2 
10 
3 
30 
4 
60 
5 
125 

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Dose # 
Food Allergen Dose  
(mg protein of each 
allergen) 
6 
250 
7 
375 
 
Dose Build-Up during Rescue OIT: A participant who attended an IDE Visit during rescue OIT will return to 
the CRU the next day for an observed administration of the last tolerated dose of OIT and continue with 
build-up based on doses given in Table 3.1.5.3b.  
Table 3.1.5.3b Dosing Schedule for rescue OIT dose build-up in Stage 3 
Dose #1 
Food Allergen Dose  
(mg protein of each 
allergen) 
Interval 
(weeks) 
1 
3 
2 
2 
10 
2 
3 
30 
2 
4 
60 
2 
5 
125 
2 
6 
250 
2 
7 
375 
2 
8 
560 
2 
92 
800 
2 
102 
1000 
2 
1. Dose build-up will begin at the last dose the participant was able to tolerate on the IDE Visit. 
2. Participants will have 16 weeks to build up to their maximum maintenance dose. Doses 9 and 10 may only be 
achieved for participants starting at higher doses based on their IDE visit and end of Stage 2 DBPCFC results.  
 
A participant who skipped the IDE Visit will return to the CRU for an observed administration of OIT based 
on the starting dose given in Table 3.1.5.3c. 
Table 3.1.5.3c Starting dose of OIT 
Cumulative Dose Consumed Without 
Dose-Limiting Symptoms  
During Most Recent DBPCFC  
(mg protein) 
Dose Consumed Without  
Dose-Limiting Symptoms  
During Most Recent DBPCFC  
(mg protein) 
Starting Dose of OIT  
During Build-Up Phase  
(mg protein) 
144 
100 
60 
444 
300  
250 

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The participant will return to the CRU every two weeks for a dose build-up to reach a maintenance dose for 
each food. The target maintenance dose for each individual participant may be any dose ≥375 mg protein 
for each food, as determined by the investigator and participant, the maximum being 1000 mg protein of 
the food. A participant who does not tolerate OIT dosing during a Dose Build-Up Visit will remain at the 
previously tolerated dose until the next Dose Build-Up Visit. Each participant must reach a dose of at least 
375 mg of protein of the food within 16 weeks after beginning rescue OIT to enter the Maintenance Phase; 
otherwise, the participant will be considered a treatment failure, will be removed from rescue OIT for that 
food, and will receive long-term follow-up with avoidance of that food or be referred to an allergist. 
Maintenance Phase during Rescue OIT:  
A participant who reaches a Rescue OIT target maintenance dose of 375 mg, 560 mg, 800 mg, or 1000 mg 
of the food will return to the CRU two weeks after the end of the Build-Up Phase for their Initial 
Maintenance Dose Visit. The participant will be called or emailed two weeks after the Initial Maintenance 
Dose Visit and will return to the CRU four weeks after the Initial Maintenance Dose Visit for a Follow-Up 
Maintenance Dose Visit.  
• 
If a participant does not tolerate the minimum target maintenance dose of 375 mg during this four 
week period, the participant will be considered a treatment failure for the food and will either be 
assigned to long-term follow-up with avoidance for the food or be referred to an allergist as 
appropriate. Dose adjustments during this four- week period should be discussed with the Protocol 
Chairs and Medical Monitor.  
• 
If a participant tolerates the target maintenance dose during this four week period, the participant 
will have an observed initial open feeding of the dietary food during a CRU visit. Open feedings to 
more than one dietary food may occur on the same day with a two-hour waiting period between 
each food. The amount of dietary food eaten at the open feeding will be based on the maximum 
quantity deemed to be safe, as determined by the participant’s target maintenance dose (see Table 
3.1.5.3e).  
Table 3.1.5.3e Minimum and Maximum Amounts of Protein Contained in a Single Food That Should Be 
Consumed by Participants at Open Feeding 
Minimum 
Amount  
(mg 
protein 
of food) 
Target 
Maintenance 
Dose 
(mg protein of 
food) 
Maximum 
Amount  
(mg protein 
of food) 
300 
375 
300 
300 
560 
300 
300 
800 
600 
300 
1000 
1000 
 
If the participant tolerates ≥300 mg protein of the food during the open feeding(s), the participant will 
transition to dietary consumption of the food and will be provided with individualized instructions for 
inclusion of the food into their diet. Thereafter, the participant will be called or emailed weekly for the first 
four weeks, every other week between six and sixteen weeks, and then every two months for safety follow-

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up. Starting at seven months of follow-up after the transition to Long term follow-up with dietary 
consumption, the participant will be called or emailed every month to complete monthly long-term follow-
up phone calls/emails.  In addition, the participant will be required to return to the CRU for a long-term 
follow-up visit every six months. Required phone calls/emails may be combined with other study visits in 
Stage 3.    
 Primary Endpoint 
The primary endpoint is consumption of a single dose of ≥600 mg of peanut protein without dose-limiting symptoms 
during the DBPCFC at the end of Stage 1. Dose-limiting symptoms are defined in Appendix 1. A participant who meets 
this endpoint will be considered a ‘success’ while a participant who does not meet this endpoint will be considered a 
‘failure’.  
 Secondary Endpoints 
Key secondary endpoints include: 
Stage 1 
1. Consumption of a single dose of ≥1000 mg of cashew protein without dose-limiting symptoms during the 
DBPCFC at the end of Stage 1. 
2. Consumption of a single dose of ≥1000 mg of milk protein without dose-limiting symptoms during the DBPCFC 
at the end of Stage 1. 
3. Consumption of a single dose of ≥1000 mg of egg protein without dose-limiting symptoms during the DBPCFC at 
the end of Stage 1. 
Stage 2 
4. Consumption of ≥1 dose of 2000 mg protein of all three foods without dose-limiting symptoms during the 
DBPCFC at the end of Stage 2. This is the primary endpoint for Stage 2. 
Other secondary endpoints include: 
5. Consumption of a single dose of ≥600 mg, ≥1000 mg, ≥1 dose of 2000 mg, or 2 doses of 2000 mg protein of each 
food, at least two foods, or all three foods without dose-limiting symptoms during the DBPCFC at the end of 
Stage 1 (except those endpoints already defined by the primary and key secondary endpoints in Stage 1). 
6. Number of foods consumed at a single dose of ≥600 mg, ≥1000 mg, ≥1 dose of 2000 mg, or 2 doses of 2000 mg 
protein of each food without dose-limiting symptoms during the DBPCFC at the end of Stage 1. 
7. Consumption of a single dose of ≥600 mg, ≥1000 mg, ≥1 dose of 2000 mg, ≥2 doses of 2000 mg, or 3 doses of 
2000 mg protein of each food, at least two foods, or all three foods without dose-limiting symptoms during the 
DBPCFC at the end of Stage 2 (except the endpoint already defined by the primary endpoint for Stage 2). 
8. Number of foods consumed at a single dose of ≥600 mg, ≥1000 mg, ≥1 dose of 2000 mg, ≥2 doses of 2000 mg, 
or 3 doses of 2000 mg protein of each food without dose-limiting symptoms during the DBPCFC at the end of 
Stage 2. 
9. Number of weeks in each eight-week period during Stage 3 where ≥300 mg protein of each food is consumed at 
least twice per week. 

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10. Number of weeks in each eight-week period during Stage 3 where each food is not consumed.  
Safety endpoints include: 
11. An AE related to study therapy regimen received during Stage 1. 
12. An AE related to study therapy regimen received during Stage 1 OLE. 
13. An AE related to study therapy regimen received during Stage 2. 
14. An AE related to oral food intake received during Stage 3. 
 Exploratory Endpoints 
Exploratory endpoints include: 
1. Percent change in the maximum dose of food protein consumed without dose-limiting symptoms during the 
DBPCFC at the end of Stage 1 and during the DBPCFC at the end of Stage 2. 
2. Consumption of a single dose of ≥600 mg, ≥1000 mg, ≥1 dose of 2000 mg, ≥2 doses of 2000 mg, or 3 doses of 
2000 mg protein of each food, at least two foods, or all three foods without dose-limiting symptoms during the 
DBPCFC at the end of Stage 1 OLE. 
3. Number of foods consumed at a single dose of ≥600 mg, ≥1000 mg, ≥1 dose of 2000 mg, ≥2 doses of 2000 mg, 
or 3 doses of 2000 mg protein of each food without dose-limiting symptoms during the DBPCFC at the end of 
Stage 1 OLE. 
4. Change in quality of life between Week 0 in Stage 1 and the following times: 
• 
First DBPCFC Visit at the end of Stage 1; 
• 
For those participants who move to Stage 1 OLE: 
o First omalizumab injection visit in Stage 1 OLE; 
o First DBPCFC Visit at the end of Stage 1 OLE; 
o Last DBPCFC Visit at the end of Stage 1 OLE. 
• 
For those participants who move to Stage 2: 
o First omalizumab injection visit in Stage 2; 
o First DBPCFC Visit at the end of Stage 2; 
o Last DBPCFC Visit at the end of Stage 2. 
• 
Six months after beginning Stage 3. 
Quality of life is measured by the Food Allergy Quality of Life Questionnaire – Parent Form (FAQLQ-PF) for 
participants aged 0-12 years, Food Allergy Quality of Life Questionnaire – Child Form (FAQLQ-CF) for 
children/adolescents aged 8-12 years, Food Allergy Quality of Life Questionnaire – Teenager Form (FAQLQ-TF) 

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for participants aged 13-17 years, and Food Allergy Quality of Life Questionnaire – Adult Form (FAQLQ-AF) for 
participants aged ≥18 years. 
PK endpoints include: 
5. Omalizumab trough concentration, measured at the following times: 
• 
First Screening DBPCFC Visit; 
• 
First DBPCFC Visit at the end of Stage 1;  
• 
First DBPCFC Visit at the end of Stage 1 OLE (for those participants who move to Stage 1 OLE); 
• 
IDE Visit during Stage 2 (for those participants who move to Stage 2); and 
• 
First DBPCFC Visit at the end of Stage 2 (for those participants who move to Stage 2). 
Biomarkers include the following: 
6. Total IgE 
7. Total free IgE 
8. Allergen-specific IgE 
9. Allergen-specific immunoglobulin G4 (IgG4) 
10. Allergen-specific immunoglobulin A (IgA) 
11. IgG4/IgE ratio 
12. Basophil activation 
13. SPTs  
Immune biomarkers will be measured at the following times: 
• 
First Screening DBPCFC Visit; 
• 
First DBPCFC Visit at the end of Stage 1; 
• 
First DBPCFC Visit at the end of Stage 1 OLE (for those participants who move to Stage 1 OLE); 
• 
IDE Visit during Stage 2, except the SPTs, total IgE, and allergen-specific IgE (for those participants who move to 
Stage 2); 
• 
Initial Maintenance Dose Visit during Stage 2, except the SPTs, total IgE, and allergen-specific IgE (for those 
participants who move to Stage 2); 
• 
First DBPCFC Visit at the end of Stage 2 (for those participants who move to Stage 2); and 
• 
Six months after beginning Stage 3. 

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Mechanistic endpoints will be measured at the following times: 
• 
First Screening DBPCFC Visit; 
• 
First DBPCFC Visit at the end of Stage 1; 
• 
IDE Visit during Stage 2 (for those participants who move to Stage 2); 
• 
Initial Maintenance Dose Visit during Stage 2 (for those participants who move to Stage 2); and 
• 
First DBPCFC Visit at the end of Stage 2 (for those participants who move to Stage 2). 
 Stratification, Randomization, Blinding, and Stage-specific Unblinding  
Randomization will be accomplished through a password-protected, web-based, randomization system maintained by 
the Statistical Clinical Coordinating Center (SCCC). The randomization schemes used in Screening DBPCFCs and Stages 1 
and 2 of the study are as follows: 
Screening DBPCFCs: A participant and/or parent/legal guardian who provides informed consent and/or assent and who 
meet initial eligibility criteria will undergo a Screening DBPCFC. The order of the blinded OFC to peanut in relation to the 
three other blinded OFCs during the Screening DBPCFC (i.e., first, second, third, or fourth) will be randomized using a 
1:1:1:1 allocation ratio. Participants who do not experience dose-limiting symptoms to two non-peanut foods but who 
may be allergic to additional foods will receive an additional Screening DBPCFC consisting of up to two blinded OFCs to 
other non-peanut foods and one blinded OFC to placebo; the order of these blinded OFCs will be left to the discretion of 
the CRU dietitian/pharmacist. 
Unblinding of Screening results:  
• 
Prior to randomization in Stage 1, the results of the Screening DBPCFC will be unblinded to determine eligibility. 
Stage 1: Participants who meet the eligibility criteria will be randomized to receive omalizumab or placebo to 
omalizumab using a 2:1 allocation ratio and a permuted block randomization scheme stratified by <6 years of age at 
randomization and milk as a participant-specific food (yes/no). Additionally, the order of the blinded OFC to peanut in 
relation to the three other blinded OFCs during the DBPCFC (i.e., first, second, third, or fourth) at the end of Stage 1 will 
also be randomized using a 1:1:1:1 allocation ratio and a permuted block randomization scheme stratified by Stage 1 
treatment arm. Randomization to treatment arm as well as the order of the blinded OFC to peanut during the DBPCFC 
will be conducted on the same day for each participant.  
Unblinding of Stage 1 results: 
• 
Each participant and/or parent/legal guardian will remain blinded to the participant’s treatment assignment in 
Stage 1 from the time of randomization to the time when all participants have completed Stage 2, the database 
for Stages 1 and 2 are frozen, and the study has been unblinded. For those participants who move to Stage 1 
OLE, the order of the blinded OFC to peanut in relation to the three other blinded OFCs during the DBPCFC at 
the end of the OLE will also be randomized using a 1:1:1:1 allocation ratio. 
Stage 2: Participants who move to Stage 2 will be randomized to omalizumab-facilitated OIT or omalizumab + placebo 
OIT using a 1:1 allocation ratio and a permuted block randomization scheme stratified by Stage 1 treatment arm. 
Additionally, the order of the blinded OFC to peanut in relation to the three other blinded OFCs during the DBPCFC (i.e., 
first, second, third, or fourth) at the end of Stage 2 will also be randomized using a 1:1:1:1 allocation ratio and a 

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permuted block randomization scheme stratified by Stage 2 treatment arm. Randomization to treatment arm as well as 
the order of the blinded OFC to peanut during the DBPCFC will be conducted on the same day for each participant.  
Unblinding of Stage 2 results: 
• 
For participants that completed Stage 2 prior to implementation of protocol version 10.0: Each participant 
and/or parent/legal guardian will remain blinded to the participant’s treatment assignment in Stage 2 from the 
time of randomization to the time when all participants have completed Stage 2, the database for Stage 2 has 
been frozen, and the protocol has been unblinded.  
• 
For participants that completed Stage 2 after implementation of protocol version 10.0: Each participant and/or 
parent/legal guardian will be unblinded to the assigned Stage 2 treatment arm if the participant does not 
tolerate or refuses to reach ≤600 mg of food protein during the Stage 2 DPBCFC for any of the three foods. This 
unblinding will allow shared decision making regarding participant treatment options in Stage 3 or outside of the 
study. For the remainder of the participants, they will remain blinded to the participant’s treatment assignment 
in Stage 2 from the time of randomization to the time when all participants have completed Stage 2, the 
database for Stage 2 has been frozen, and the protocol has been unblinded.  
All investigational product (IP) will be distributed to the unblinded CRU pharmacist/pharmacy staff. The unblinded CRU 
pharmacist/pharmacy staff will dispense omalizumab and placebo for omalizumab to CRU staff who will administer 
injections. As it is expected that the CRU staff administering omalizumab and placebo for omalizumab will become 
unblinded because of differences (e.g., viscosity) between omalizumab and placebo for omalizumab, such staff will be 
considered unblinded and will not be involved in any other aspect of the study that would threaten blinding and/or that 
could be influenced by an unblinded CRU staff member performing the procedure. However, open label omalizumab 
may be administered by a blinded CRU staff member. The unblinded CRU pharmacist/pharmacy staff will dispense 
Multi-allergen OIT and placebo for Multi-allergen OIT to blinded CRU staff for OIT dosing. During all DBPCFCs, the 
participant and/or parent/legal guardian, as well as the CRU staff administering the blinded OFC, will not know which 
blinded OFC contains food protein or placebo. 
Unblinding for blinded CRU staff, Laboratory Staff, Sponsor, and SCCC Statisticians:  
• 
Blinded CRU staff will be unblinded to participants’ treatment assignments in Stage 1 and 2 at the same time as 
outlined for unblinding of participants and/or parents/legal guardians.  
• 
For each stage, laboratory staff will be blinded to participant treatment assignments until all participants have 
completed the stage, the database is frozen (Stage 1 or Stage 2) or locked (Stage 3), and processing and assaying 
of samples collected during the stage are completed. 
• 
The Sponsor will be responsible for approving unblinding of individual participants as well as unblinding of 
results from Stage 1 and Stage 2 as outlined in the Randomization Plan and the OUtMATCH unblinding flow. 
Upon unblinding of a stage, the Sponsor will be unblinded to all results from that stage.   
• 
SCCC statisticians will be unblinded to DBPCFC results at the end of Stage 1 when all participants have 
completed Stage 1, and the database is frozen. Participants, blinded CRU staff, and SCCC statisticians will be 
unblinded to DBPCFC results at the end of Stage 1 OLE and Stage 2 when each participant has completed each 
stage.  

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Stage 1 and Stage 1 OLE analyses will be conducted after all participants have completed Stage 1 and Stage 1 OLE (as 
appropriate), the database is frozen, and all SCCC statisticians are unblinded to Stage 1 treatment arm. Stage 2 analyses 
will be conducted after all participants have completed Stage 2 (as appropriate), the database is frozen, and all SCCC 
statisticians are unblinded to Stage 2 treatment arm. Stage 3 analyses will be conducted after all participants have 
completed Stage 3 and the database is locked.  
Additional detail regarding the timing of the analyses, protection of the blind, and data sharing for each stage is given in 
Section 13.5.2 and in the Randomization Plan. 
3.5.1 
Procedure for Unblinding 
Unblinding of treatment assignment or early unblinding of a DBPCFC result must be approved by the Division of 
Allergy, Immunology, and Transplantation, National Institute of Allergy and Infectious Diseases (DAIT/NIAID) Medical 
Monitor unless an immediate life-threatening condition has developed and the DAIT/NIAID Medical Monitor is not 
accessible. The process for notifications of any unblinding event to study personnel is specified in the Manual of 
Procedures (MOP). Unblinding events will also be reported to the NIAID Allergy and Asthma Data and Safety 
Monitoring Board (DSMB). 
A full account of the event will be recorded, including the date and time of the unblinding, the reason for the decision 
to unblind, the name of the individual who made the decision, and the names of the DAIT/NIAID Medical Monitor 
and others who were notified. The reasons for unblinding will be included in the final study report. 
Unblinding due to an interim analysis (planned or unplanned) of each stage, final analysis of each stage, or study 
termination will require written approval from the DAIT/NIAID Medical Monitor. After unblinding for a stage, all 
subsequent Investigational New Drug (IND) Safety Reports for that stage will be reported to the FDA, NIAID Allergy 
and Asthma DSMB, and single Institutional Review Board (IRB) in an unblinded fashion. 
For scheduled Stage-specific unblinding, refer to section 3.5. 
4 Selection of Participants 
 Rationale for Study Population 
This study will enroll children and adults from 1 year to less than 56 years of age at the Screening Visit with multi-food 
allergies. The rationale for choosing this study population is three-fold. First, the value of other treatment approaches 
that focus on a single food, such as OIT for peanut, are limited by the fact that many children and adults have multi-food 
allergies. In fact, between 30% and 70% of children and adults with peanut allergy have allergies to other foods.3,4 
Therefore, treatments that could provide relief for multiple foods are highly desirable and, if successful, would represent 
a major advance in the management of food allergy. 
The second major rationale for this study population relates to age, with studies suggesting that treatment of peanut 
allergy with oral and/or epicutaneous immunotherapy (EPIT) may be more efficacious, and equally safe, when initiated 
in younger children.13,19 This was clearly demonstrated in the DEVIL study of peanut OIT, which demonstrated high rates 
of both desensitization and sustained unresponsiveness in children 9 to 36 months of age, including dietary introduction 
of peanut after the OIT. This study will therefore expand our knowledge regarding the effects of OIT in children as young 
as age one, but this time focusing on patients with allergy to multiple other foods in addition to peanut. Further, it will 
provide a unique opportunity to study the effects of omalizumab, both as monotherapy and as an adjunct to OIT, which 
to date has only been studied down to four years of age.13 

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Third, while most treatment studies for food allergy are currently focused on children, there is a high burden of food 
allergy in adults as well.2 This is especially the case for peanut and tree nut allergies, which persist into adulthood in 80-
90% of patients, but is also highly relevant for the subset of approximately 20% of patients with severe milk, egg, and/or 
wheat allergies that persist into adulthood.2 
 Inclusion Criteria 
Individuals who meet all of the following criteria are eligible for study randomization: 
1. Participant and/or parent/legal guardian must be able to understand and provide informed consent and/or 
assent, as applicable  
2. Male or female, 1 year to less than 56 years of age at Screening 
3. Peanut allergic; participant must meet all of the following criteria to minimize the chance that the participant 
will develop natural tolerance to peanut over the course of the study: 
a. Positive SPT (≥4 mm wheal greater than saline control) to peanut 
b. Positive peanut IgE (≥6 kUA/L) at Screening or within three months of Screening, determined by 
ImmunoCap 
c. Positive blinded OFC to peanut during the Screening DBPCFC, defined as experiencing dose-limiting 
symptoms at a single dose of ≤100 mg of peanut protein 
4. Allergic to at least two of the six other foods (milk, egg, wheat, cashew, hazelnut, walnut); allergy to milk and 
egg is defined as unable to tolerate both cooked and uncooked forms; each participant must meet all of the 
following criteria for at least two of the six other foods to minimize the chance that the participant will develop 
natural tolerance to at least two of the six other foods over the course of the study: 
a. Milk, egg, or wheat:  
i. Positive SPT (≥4 mm wheal greater than saline control) to food  
ii. Positive food specific IgE (≥6 kUA/L) at Screening or within three months of Screening, 
determined by ImmunoCap 
iii. Positive blinded OFC to food during the Screening DBPCFC, defined as experiencing dose-
limiting symptoms at a single dose of ≤300 mg of food protein 
b. Cashew, hazelnut, or walnut:  
i. Positive SPT (≥4 mm wheal greater than saline control) to food or positive food specific IgE (≥6 
kUA/L) at Screening or within three months of Screening, determined by ImmunoCap 
ii. Positive blinded OFC to food during the Screening DBPCFC, defined as experiencing dose-
limiting symptoms at a single dose of ≤300 mg of food protein 
5. With body weight (as measured at Screening) and total serum IgE level (as measured within three months of 
Screening) suitable for omalizumab dosing 
6. If female of child-bearing potential, must have a negative urine or serum pregnancy test 
7. For women of childbearing potential, must agree to remain abstinent (refrain from heterosexual intercourse) or 
use acceptable contraceptive methods (barrier methods or oral, injected, or implanted hormonal methods of 
contraception or other forms of hormonal contraception that have comparable efficacy) during the treatment 
period and for 60 days after the last dose of study drug.  
8. Plan to remain in the study area of an OUtMATCH CRU during the trial 
9. Be willing to be trained on the proper use of an epinephrine autoinjector and be willing to provide an 
epinephrine autoinjector for the duration of the study 

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 Exclusion Criteria 
Individuals who meet any of the following criteria are not eligible for study randomization: 
1. Inability or unwillingness of a participant and/or parent/legal guardian to give written informed consent and/or 
assent or comply with the study protocol 
2. Clinically significant laboratory abnormalities at Screening 
3. Dose-limiting symptoms during the blinded OFC to placebo during the Screening DBPCFC  
4. Sensitivity or suspected/known allergy to any ingredients (including excipients) of the active or placebo OFC 
material, Multi-allergen OIT, or drugs related to omalizumab (e.g., monoclonal antibodies, polyclonal gamma 
globulin). Guidance for determination of sensitivity to excipients will be detailed in the MOP. 
5. Poorly controlled AD at Screening, per the PI’s discretion 
6. Poorly controlled or severe asthma/wheezing at Screening, defined by at least one of the following criteria: 
a. Global Initiative for Asthma (GINA) criteria regarding asthma control latest guidelines (see Appendix 3); 
b. History of two or more systemic corticosteroid courses within six months of Screening or one course of 
systemic corticosteroids within three months of Screening to treat asthma/wheezing; 
c. Prior intubation/mechanical ventilation for asthma/wheezing; 
d. One hospitalization or ED visit for asthma/wheezing within six months of Screening; 
e. Forced expiratory volume in one second (FEV1) <80% of predicted or FEV1/forced vital capacity (FVC) 
<75%, with or without controller medications (only for participants who are aged seven years or older 
and are able to perform spirometry); 
f. Inhaled corticosteroid (ICS) dosing of >500 mcg daily fluticasone (or equivalent ICS based on the CoFAR 
Inhaled Corticosteroid Equivalency Tables MOP). 
7. History of severe anaphylaxis to participant-specific foods that will be used in this study, defined as neurological 
compromise or requiring intubation 
8. Treatment with a burst of oral, intramuscular (IM), or intravenous (IV) steroids of more than two days for an 
indication other than asthma/wheezing within 30 days of Screening 
9. Currently receiving oral, IM, or IV corticosteroids, tricyclic antidepressants, or β-blockers (oral or topical) 
10. Past or current history of eosinophilic gastrointestinal (GI) disease within three years of Screening 
11. Past or current history of cancer, or currently being investigated for possible cancer 
12. Previous adverse reaction to omalizumab 
13. Past or current history of any immunotherapy to any of the foods being treated in this study (e.g., OIT, 
sublingual immunotherapy [SLIT], EPIT) within 6 months of Screening 
14. Treatment with monoclonal antibody therapy, such as omalizumab (Xolair®), dupilumab (Dupixent®), 
benralizumab (Fasenra™), mepolizumab (Nucala®), reslizumab (Cinqair®), or other immunomodulatory therapy 
within six months of Screening  
15. Currently on “build-up phase” of inhalant allergen immunotherapy (i.e., has not reached maintenance dosing). 
Individuals tolerating maintenance allergen immunotherapy can be enrolled 
16. Inability to discontinue antihistamines for the minimum wash-out periods required for SPTs or OFCs 
17. Current participation in another therapeutic or interventional clinical trial or participation within 90 days of 
Screening 
18. Use of investigational drugs within 24 weeks of Screening 
19. Pregnant or breastfeeding, or intending to become pregnant during the study or within 60 days after the last 
dose of omalizumab or placebo for omalizumab 
20. Has a first-degree relative presently  enrolled in Stage 1 or Stage 2 of the study  

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21. Past or current medical problems (e.g., severe latex allergy), history of other chronic diseases (other than 
asthma/wheezing, AD, or rhinitis) requiring therapy (e.g., heart disease, diabetes), findings from physical 
assessment, or abnormalities in clinical laboratory testing that are not listed above, which, in the opinion of the 
PI, may pose additional risks from participation in the study, may interfere with the participant’s ability to 
comply with study requirements, or that may impact the quality or interpretation of the data obtained from the 
study. 
5 Known and Potential Risks and Benefits to Participants 
 Risks of Investigational Product 
5.1.1 
Omalizumab 
As outlined in the current Investigator Brochure for Omalizumab (Xolair®), identified risks of omalizumab (causality 
has been established with omalizumab) include injection site reactions, pyrexia, anaphylaxis, serum sickness, 
Eosinophilic Granulomatosis with Polyangiitis (EGPA aka Churg-Strauss Syndrome), hypereosinophilic syndrome, and 
thrombocytopenia; potential risks of omalizumab include malignancies, arterial thrombotic events (ATEs), and 
antibody formation to omalizumab.  
5.1.1.1 
Anaphylaxis 
Anaphylaxis has been reported to occur after administration of omalizumab in clinical trials and in post-
marketing spontaneous reports. Anaphylactic reactions were rare in clinical trials (0.1%) and estimated as 
0.2% from post-marketing reporting. The reported signs and symptoms included, but were not limited to, 
bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the throat or tongue. Some of these 
events have been reported as life threatening. 
5.1.1.2 
Serum Sickness 
Serum sickness and serum sickness−like reactions, which are delayed allergic type III reactions, have rarely 
been seen in patients treated with humanized monoclonal antibodies including omalizumab in the post-
approval use. The onset has typically been one to five days after administration of the first or subsequent 
injections, also after long duration of treatment. Symptoms suggestive of serum sickness include 
arthritis/arthralgia, rash (urticaria or other forms), fever, and lymphadenopathy. 
5.1.1.3 
EGPA (aka Churg-Strauss Syndrome) and Hypereosinophilic Syndrome 
Patients with severe asthma may rarely present with systemic hypereosinophilic syndrome or EGPA (aka 
Churg-Strauss Syndrome). In rare cases, patients on therapy with anti-asthma medicinal products, including 
omalizumab, may present or develop systemic eosinophilia and vasculitis. These events are commonly 
associated with the reduction of oral corticosteroid therapy and alerted to the development of marked 

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eosinophilia, vasculitic rash, worsening pulmonary symptoms, paranasal sinus abnormalities, cardiac 
complications, and/or neuropathy. 
5.1.1.4 
Thrombocytopenia 
In nonclinical studies, a dose-dependent and reversible circulating platelet reduction was observed. In 
clinical studies, few patients experienced platelet counts below the lower limit of the normal laboratory 
range. None of these changes was associated with bleeding episodes or a decrease in hemoglobin. 
5.1.1.5 
Malignancies 
During initial clinical trials in adults and adolescents 12 years of age and older with allergic asthma, there 
was a numerical imbalance in cancers arising in the active treatment group compared with the control 
group. The number of observed cases was uncommon (<1/100) in both the active and the control group. In 
a subsequent observational study (EXCELS) comparing 5007 omalizumab-treated patients and 2829 non 
omalizumab-treated patients followed for up to five years, the incidence rates of primary malignancies per 
1000 patient years were 16.01 (295/18,426 patient years) and 19.07 (190/9963 patient years), respectively, 
which does not indicate an increased malignancy risk (rate ratio 0.84, 95% CI: 0.62-1.13). In a further 
analysis of randomized double-blind placebo-controlled clinical trials, including 4254 patients on 
omalizumab and 3178 patients on placebo, omalizumab treatment was not associated with an increased 
malignancy risk based on incidence rates per 1000 patient years of 4.14 for omalizumab-treated patients 
and 4.45 for placebo patients (rate ratio 0.93, 95% CI: 0.39-2.27). The overall observed incidence rate of 
malignancy in the omalizumab clinical trial program was comparable to that reported in the general 
population. There were no cases of malignancy in clinical trials in allergic asthma in the 6 to <12 years of 
age group with omalizumab; there were two cases of malignancy in the control group (medulloblastoma 
and nephroblastoma). 
In the Phase III CIU program (733 patients enrolled and receiving at least one dose of omalizumab), there 
was one case of malignancy in the placebo group and one case in the omalizumab 300 mg group in a 
patient with a preexisting history. 
5.1.1.6 
Arterial Thrombotic Events 
In controlled clinical trials in allergic asthma and during interim analyses of EXCELS (an observational study), 
a numerical imbalance of ATEs was observed. ATEs included stroke, transient ischemic attack, myocardial 
infarction, unstable angina, and cardiovascular death (including death from unknown cause). The results 
from EXCELS revealed the rate of ATEs per 1,000 patient years was 7.52 (115/15,286 patient years) for 
omalizumab treated patients and 5.12 (51/9,963 patient years) for control patients. Although there was no 
consistent evidence of an association between omalizumab use and risk of ATEs, the 95% CIs were wide and 
could not definitively exclude an elevated risk. 
5.1.1.7 
Antibody Formation to Omalizumab 
Omalizumab is a humanized monoclonal anti-IgE antibody. The formation of anti-drug antibodies (also 
called ADAs) after omalizumab administration is a rare event. There were three ADA-positive cases out of 
23,375 serum samples tested in the Allergic Asthma and CIU programs following omalizumab 
administration. These cases were not associated with any severe AEs. 
There was no case of drug-induced ADAs recorded across the entire CIU development program. 

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5.1.2 
Multi-Allergen Oral Immunotherapy 
Multi-allergen OIT in this study will consist of any of the following foods: peanut, milk, egg, wheat, cashew, hazelnut, 
and walnut. The major expected risks of Multi-allergen OIT are similar to the risks of single allergen OIT. Additionally, 
the risks are similar across each of the seven food allergens and can occur during build-up or maintenance. 
Specifically, the build-up and daily maintenance doses of OIT may cause allergic symptoms including sneezing, 
rhinorrhea, urticaria, angioedema, flushing, ocular, nasal, oral and/or throat pruritus, throat tightness without or 
with hoarseness, nausea, vomiting, abdominal pain and discomfort, stridor/laryngeal edema, cough, wheezing 
and/or shortness of breath, including symptoms of severe anaphylaxis such as severe stridor/laryngeal edema, 
bronchospasm/wheezing, hypotension, and altered mental status. Other allergy-associated AEs are flares of eczema 
and eosinophilic esophagitis (EoE). 
In patients with food allergy, there have been many OIT studies performed using procedures and OIT dosing similar 
to those proposed in this study. The safety profile for OIT has been evaluated across the studies, and, approximately 
80%, 15% and <1% of the participants are expected to have mild, moderate or severe symptoms, respectively, at 
some point in their dosing with the immunotherapy.7 Most AEs have been allergy-related, predictable, and 
reversible. Of note, oral pruritus is a common local AE with single- or Multi-allergen OIT that is typically mild and 
resolves without treatment.6,13,20 
The most common AE related to single and Multi-allergen OIT is abdominal pain.6,21 OIT-related abdominal pain is 
most common during the Build-Up Phase, however, it could occur at any point during OIT therapy.22 Often, 
abdominal pain ceases with treatment with antacids and/or antihistamines, or with a temporary reduction in dose. 
However, persistent GI symptoms (such as abdominal pain, nausea, heart-burn, and vomiting) might be symptoms of 
EoE. 
EoE is a chronic immune disorder mediated by antigen exposure and is defined by clinical and histopathological 
criteria, in the absence of other causes. Clinical symptoms may include the following: reflux-like symptoms, 
abdominal pain and/or vomiting that is refractory to reflux treatment, dysphagia and/or food impaction. These 
symptoms occur in conjunction with histological evidence of dense eosinophilic infiltration of the mucosa [>15 
eosinophils per high-power field (eos/hpf)]. A meta-analysis23 and a recent retrospective review24 estimated the 
incidence of EoE during OIT at rates of 2.7% and 5.1%, respectively. However, OIT-induced EoE-like symptoms resolve 
with discontinuation of OIT in most affected patients, so that individuals do not undergo an 
esophagogastroduodenoscopy with esophageal biopsies. A definitive diagnosis of EoE cannot be made without 
histologic evidence.25,26 
Symptoms related to severe anaphylaxis include: 
• 
respiratory — stridor/laryngeal edema, throat tightness with hoarseness, wheezing with dyspnea 
• 
GI — significant severe abdominal pain/cramping/repetitive vomiting 
• 
neurological — change in mental status 
• 
circulatory — hypotension 
5.1.2.1 
Initial Dose Escalation and Dose Build-Up 
The IDE Visit followed by the Build-Up Phase was developed based on published studies and the CoFAR CRU 
Investigators’ previous experience with Multi-allergen OIT. Although there are few in number, previous 
Multi-allergen OIT studies have not reported significant clinical reactions during the Build-Up Phase of 

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treatment.6,7 The build-up and daily maintenance doses of Multi-allergen OIT may cause allergic symptoms 
including sneezing, rhinorrhea, urticaria, angioedema, flushing, flares of eczema, nausea, vomiting, 
abdominal discomfort, cough, wheezing, shortness of breath, ocular, nasal, oral, or throat pruritus, in 
addition to severe anaphylaxis. While a severe outcome of death is theoretically possible, this has not 
occurred during other dose escalations supervised by the PIs’ participating in this study. The likelihood of a 
participant experiencing any allergic symptoms or severe reactions will be lessened by initiating OIT dosing 
at extremely small amounts of Multi-allergen OIT and by increasing doses during the Build-Up Phase under 
observation in a clinical setting until the maintenance dose is achieved. If a participant has an allergic 
reaction, they may need oral, IM, or IV medications. CRU staff trained in the diagnosis and treatment of 
allergic reactions and anaphylaxis, including a trained physician available within 60 seconds, as well as 
emergency medications and resuscitation equipment, will be available to treat any allergic reactions. 
5.1.3 
Multi-Allergen Oral Immunotherapy plus Omalizumab 
In Phase 1 Multi-allergen OIT studies, participants who received omalizumab had similar symptoms to those 
participants who did not receive omalizumab; the frequency of the symptoms was less in the group who received 
omalizumab.7 These results were validated in a recent Phase 2 pilot study of 48 children undergoing Multi-allergen 
OIT with or without omalizumab; those who received omalizumab-facilitated Multi-allergen desensitization had 
significantly fewer doses associated with an AE than those who had placebo for omalizumab (27% vs 68% when 
administered with Multi-allergen OIT) during build-up.6 In particular, 22% of OIT doses in omalizumab participants 
and 54% of doses for placebo participants caused GI side effects; 0 and 1 percent of doses caused respiratory side 
effects in the omalizumab and placebo arms, respectively. 
 Risks of Other Protocol Specified Medications 
Treatment of individual acute allergic reactions during Multi-allergen OIT therapy, OFCs, and open feedings should be 
with either an antihistamine and/or epinephrine, along with IV fluids, β-adrenergic agonist (e.g., albuterol), oxygen, 
and/or oral or topical steroids, as indicated. Risks of these common medications are summarized below: 
• 
Antihistamines: drowsiness, dizziness, constipation, stomach upset, blurred vision, or dry mouth/nose/throat. 
• 
Epinephrine: tachycardia, palpitations, nervousness, sweating, nausea, vomiting, trouble breathing, headache, 
dizziness, anxiety, tremors, or pale skin. 
• 
β-adrenergic agonist: nervousness, shaking (tremor), headache, or dizziness. 
• 
Oral steroids: nausea, vomiting, loss of appetite, heartburn, trouble sleeping, increased sweating, or acne. 
• 
Topical steroids: itching, burning, erythema, skin hypopigmentation, skin thinning, striae, bruising, 
telangiectasias. 
 Risks of Study Procedures  
5.3.1 
Oral Food Challenges 
OFCs (including DBPCFCs and open OFCs) may induce an allergic response regardless of the stage of the study during 
which they are conducted. Allergic reactions range from mild to severe and include life-threatening anaphylactic 
reactions and death; however, the risk of a severe allergic reaction is reduced by initiating the OFC with a very small 
amount of the food, gradually increasing the dose over a prolonged time period, and stopping the OFC at the first 
sign of a reaction. Symptoms usually are short-lived (less than two hours) and may include an itchy skin rash, nausea, 
abdominal discomfort, vomiting and/or diarrhea, stuffy “runny” nose, and sneezing and/or wheezing. Anaphylaxis, 

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the most severe allergic reactions, may include respiratory symptoms (both laryngeal edema and 
bronchospasm/wheezing), circulatory symptoms (hypotension), and neurologic symptoms (altered mental status). 
While there has been one documented death of a child undergoing an OFC in a clinical setting, this has not occurred 
to date during medically supervised OFCs in highly trained research settings.27 If a participant has an allergic reaction 
during an OFC, they may need oral, IM, or IV medications. CRU staff trained in the diagnosis and treatment of allergic 
reactions and anaphylaxis, including a trained physician available within 60 seconds, as well as emergency 
medications and resuscitation equipment, will be available throughout the OFC to treat any allergic reactions. 
5.3.2 
Open Feedings 
While the amount of food given during an open feeding will be determined based on the amount consumed in the 
last OFC without dose-limiting symptoms, an open feeding still may induce an allergic response to food eaten. 
Allergic reactions range from mild to severe and include life-threatening anaphylactic reactions and death. Mild and 
moderate symptoms are usually short lived (less than two hours) and may include an itchy skin rash, nausea, 
abdominal discomfort, vomiting and/or diarrhea, stuffy “runny” nose, and sneezing and/or wheezing. Anaphylaxis, 
the most severe allergic reactions, may include respiratory symptoms (both laryngeal edema and 
bronchospasm/wheezing), circulatory symptoms (hypotension), and neurologic symptoms (altered mental status). If 
a participant has an allergic reaction during the open feeding, they may need oral, IM, or IV medications. CRU staff 
trained in the diagnosis and treatment of allergic reactions and anaphylaxis, including a trained physician available 
within 60 seconds, as well as emergency medications and resuscitation equipment, will be available throughout the 
open feeding to treat any allergic reactions. 
5.3.3 
Skin Prick Tests 
Participants may experience mild to moderate pruritus or local discomfort at the sites of skin pricks with allergen and 
the positive control. Usually, the allergen-induced wheal and flare responses resolve within one to two hours, but 
rarely a participant may have local swelling that takes two to three days to clear entirely. Rarely skin testing will 
cause the participant being tested to have systemic allergic symptoms. These symptoms may include sneezing, ocular 
pruritus and tearing, rhinorrhea and/or generalized pruritus or urticaria. Treatment with oral antihistamines is 
available and is effective. Very rarely, some individuals with these types of symptoms may develop a serious, 
systemic allergic reaction, but no deaths from prick skin testing using standard dosing techniques have been reported 
in 50 years. During the testing, a trained physician will be available within 60 seconds, along with the appropriate 
drugs and equipment, to provide treatment of anaphylactic reactions. 
5.3.4 
Blood Draw 
The risks associated with drawing blood include discomfort, bleeding, bruising or swelling where the needle is 
inserted, local infection, and, in rare cases, syncope. A local skin anesthetic (i.e., topical lidocaine/prilocaine cream) 
may be placed on the skin before the blood draw to reduce the pain of the stick. Side effects from this agent (mainly 
skin rash) may occur, including allergic reactions. The National Institutes of Health (NIH) guidelines for blood 
collection (amount and frequency based on age and weight) will be followed. 
5.3.5 
Intravenous Insertion 
Heparin/saline lock or IV may be inserted during an OFC, dose escalation, IDE, or dose build-up at the PI’s discretion 
(e.g., participant at high risk of reaction or severe reaction based upon prior history and medical history). The risks 
associated with IV insertion include discomfort, bleeding, bruising or swelling where the IV is inserted, local infection, 
and, in rare cases, syncope. A local skin anesthetic (i.e., topical lidocaine/prilocaine cream) may be placed on the skin 

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before the IV insertion to reduce the pain of the placement. Side effects from this agent (mainly skin rash) may occur, 
including allergic reactions. 
5.3.6 
Spirometry and Peak Expiratory Flow Measurements 
Spirometry and Peak Expiratory Flow (PEF) measurements will be performed by trained and certified CRU staff 
according to American Thoracic Society standards as performed routinely in usual care as part of subspecialist 
management of asthma. 
Spirometry and PEF measurements can cause coughing or presyncope, which will go away shortly after the test is 
finished. 
For spirometry, participants may be asked to withhold their asthma medications for 8-24 hours before the 
procedures depending on the medication. Withholding of asthma medications before testing may cause a worsening 
of asthma symptoms. These medications and withholding instructions are specified in the MOP. Participants will be 
informed that they can take their asthma medications if needed. If participants do take their medications, the 
procedure will only be rescheduled, as described in the MOP. 
5.3.7 
Stool, Urine, and Saliva Sample Collection 
There are no significant risks associated with stool, urine, and saliva sample collection. 
5.3.8 
Questionnaires 
There is a possibility that the participant and/or parent/legal guardian may find questions too personal. A participant 
and/or parent/legal guardian may refuse to answer any questions that make them feel uncomfortable. There is also a 
possibility that answers may be read by others; however, participants’ records are carefully protected so this is very 
unlikely. See Section 16.4 for more information on confidentiality. 
 Potential Benefits 
The potential benefits of this study include the possibility that the treatments will: 
• 
reduce sensitivity to peanut and other foods a study participant is allergic to; 
• 
diminish allergic reactions following an accidental ingestion of foods a study participant is allergic to; and 
• 
allow introduction of allergenic foods into the diet. 
6 Investigational Agent/Intervention  
 Investigational Agents/Interventions 
6.1.1 
Investigational Agent #1: Omalizumab and Placebo for Omalizumab 
6.1.1.1 
Formulation, Packaging, and Labeling 
Xolair® (omalizumab) is a recombinant humanized IgG1 monoclonal antibody that binds to the FcεR1 
binding epitope of human IgE, preventing human IgE from binding to its specific high-affinity receptors on 
mast cells and basophils. 
Fully blinded, packaged, and labeled Xolair® (omalizumab) liquid in pre-filled syringes (PFS) and placebo for 
omalizumab PFS will be provided to DAIT/NIAID by Genentech Inc.  

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PFS of omalizumab and placebo for omalizumab will be provided to each CRU as 75 mg and 150 mg dosage 
forms. 
6.1.1.2 
Dosage, Preparation, and Administration 
Each participant’s dose (for the duration of the study) will be calculated using the participant’s weight at 
the Screening Visit and total IgE level (as measured at the Screening Visit or within three months of the 
Screening Visit and not the total IgE level that is drawn immediately before the first Screening DBPCFC 
Visit), according to the omalizumab dosing table (see Appendix 2). The proposed omalizumab dosing table 
in Appendix 2 differs from the dosing of omalizumab recommended in the current Investigator Brochure for 
Omalizumab (Xolair®) because of the differences in study population. The omalizumab dosing table 
presented in the current Investigator Brochure for Omalizumab (Xolair®) is intended for patients with 
asthma down to the age of 6 years. The target patient population for this study is younger and is 
anticipated to have body weight and baseline IgE combinations that are not covered in the current 
Investigator Brochure for Omalizumab (Xolair®). The proposed omalizumab dosing table is informed by an 
algorithm that targets 0.016 mg/kg/IgE/4 weeks while not exceeding a 20 mg/kg dose in a single 
administration and represents an extension of the asthma algorithm. 
Omalizumab and placebo for omalizumab PFS will be blinded and identical in liquid content color, PFS type, 
and labeling; however, due to the different liquid viscosity between omalizumab and placebo for 
omalizumab, administration will be performed by CRU staff whom will not be involved in any other aspect 
of the study that would threaten blinding and/or that could be influenced by an unblinded CRU staff 
member performing the procedure. 
A full description of the PFS for both omalizumab and placebo for omalizumab is provided in the 
OUtMATCH Pharmacy Manual – Omalizumab & Placebo for Omalizumab Pre-Filled Syringes (PFS) 
Investigational Product(s) Storage, Preparation, and Dispensing. If any abnormalities are noted with the PFS 
(either in appearance or in administration), such abnormalities should be reported to DAIT/NIAID as per the 
current OUtMATCH Pharmacy Manual – Omalizumab & Placebo for Omalizumab Pre-Filled Syringes (PFS) 
Investigational Product(s) Storage, Preparation, and Dispensing. 
6.1.2 
Investigational Agent #2: Multi-allergen Oral Immunotherapy and Placebo for Multi-allergen Oral 
Immunotherapy 
6.1.2.1 
Formulation, Packaging, and Labeling 
Multi-allergen OIT will be any of the following drug products: peanut, milk, egg, wheat, cashew, hazelnut, 
and walnut (all food protein flours). Oat flour will be used for placebo for Multi-allergen OIT. Each dosage of 
each active drug product will be supplied to CRUs as measured flour packaged in one-ounce open label 
soufflé portion cups for the conduct of Protocol CoFAR-11. Each dosage of the placebo drug product will be 
supplied to CRUs as measured flour packaged in two-ounce open label soufflé portion cups. OIT products 
will be manufactured by the Sean N. Parker Center for Allergy & Asthma Research with Stanford University 
(Mountain View, CA) and provided to DAIT/NIAID for use in Protocol CoFAR-11. Each dosage of the final 
blinded OIT product (active/placebo) will be dispensed in a two-ounce blind labeled soufflé portion cup. 
6.1.2.2 
Dosage, Preparation, and Administration 
CRU staff will prepare a prescription for each participant for the appropriate dose of each of the allergens. 
The unblinded CRU pharmacist/pharmacy staff or Sponsor-approved designated staff will compound the 
appropriate allergens and the unblinded CRU pharmacist/pharmacy staff will dispense the Multi-allergen 

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OIT dose or placebo for Multi-allergen OIT dose in a blinded fashion (using the provided blinded labels for 
the study) to the PI (or designated CRU staff). OIT will be administered to the participant orally in an age-
appropriate food vehicle, as described in the associated MOP. Dosage will be administered according to the 
protocol. 
A full description of the Multi-allergen OIT/placebo for Multi-allergen OIT will be provided in the associated 
pharmacy manual. If any abnormalities are noted with these products (either in appearance or in 
administration), such abnormalities should be reported to DAIT/NIAID as per the associated pharmacy 
manual. 
 Drug Accountability 
Under Title 21 of the Code of Federal Regulations (CFR) (21CFR §312.62), the PI will maintain adequate records in a 
chronological order of the disposition of the IP, including the date and quantity of the drug received, to whom the drug 
was dispensed (participant-by-participant accounting), and a detailed accounting of any drug accidentally or deliberately 
destroyed. 
The unblinded CRU pharmacist/pharmacy staff is to maintain records for receipt, storage, use, and disposition. An IP 
accountability log will be kept current for each participant. Additionally, an overall CRU inventory and accountability of 
the IP is to be maintained. This log will contain the identification of each participant and the date and quantity of drug 
dispensed. 
All records regarding the disposition of the IP will be available for inspection by the study monitor. 
 Assessment of Participant Compliance with Investigational Agent 
Omalizumab and placebo for omalizumab will be administered subcutaneously by CRU staff and adherence will be 
determined by the number of injections received over the expected number of injections based on the protocol. 
Throughout Stage 2 and 3, each participant and/or parent/legal guardian will maintain diary logs to document daily OIT 
dosing (see Section 8.1.7). Additionally, each participant and/or parent/legal guardian will be instructed to return all 
used (empty packages) and unused Multi-allergen OIT/placebo for Multi-allergen OIT at each visit. Records of return, 
including open and unused product, will be recorded by the unblinded CRU pharmacist/pharmacy staff and CRU staff. 
Assessment of participant compliance with administration of IP will be reviewed regularly. 
 Toxicity Prevention and Management 
6.4.1 
Omalizumab 
6.4.1.1 
Anaphylaxis 
Anaphylaxis presenting as bronchospasm, hypotension, syncope, urticaria, and/or angioedema of the 
throat or tongue, has been reported to occur after administration of omalizumab. Anaphylaxis has occurred 
as early as after the first dose of omalizumab, but also has occurred beyond one year after beginning 
regularly administered treatment. The events were reported to occur predominantly within the first two 
hours post-dose, with few reports occurring as far as >36 hours post-dose. 
The PI will be prepared to manage anaphylaxis that can be life-threatening; medications for the treatment 
of anaphylactic reactions will be available at the bedside. The American College of Allergy, Asthma, and 
Immunology guideline on the observation period after omalizumab administration28 recommends two 
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agreed upon by the individual patient and healthcare professional for subsequent injections. However, a 
delayed onset of symptoms and protracted progression of anaphylaxis should be taken into account when 
administering omalizumab.29 Based on this guideline, participants will be observed for at least two hours 
after the first three doses and at least 30 minutes after subsequent doses in Stage 1, Stage 1 OLE as well as 
in Stage 2. Taking into account the time to onset of anaphylaxis seen in clinical trials and post-marketing 
spontaneous reports, some participants may require longer observation periods, depending on the PI’s 
judgment. Participants will also be informed of the signs and symptoms of anaphylaxis and they will be 
instructed to seek immediate medical care should signs or symptoms occur. 
6.4.1.2 
Serum Sickness 
Although rare, onset of serum sickness and serum sickness-like reactions, which are delayed allergic type III 
reactions, has been seen one to five days after administration of the first or subsequent injections, as well 
as after long duration of treatment. Symptoms suggestive of serum sickness include arthritis/arthralgia, 
rash (urticaria or other forms), fever, and lymphadenopathy. Antihistamines and corticosteroids may be 
useful for treating this disorder. 
Participants will be informed and advised to report any suspected symptoms of serum sickness-like 
reactions. The PI may consider stopping omalizumab or placebo for omalizumab if a participant develops 
this constellation of signs and symptoms. 
6.4.1.3 
EPGA (Churg-Strauss Syndrome) and Hypereosinophilic Syndrome  
Patients with severe asthma may rarely present systemic hypereosinophilic syndrome or EGPA (Churg-
Strauss Syndrome). In rare cases, patients on therapy with anti-asthma medicinal products, including 
omalizumab, may present or develop systemic eosinophilia and vasculitis. These events are commonly 
associated with the reduction of oral corticosteroid therapy and alerted to the development of marked 
eosinophilia, vasculitic rash, worsening pulmonary symptoms, paranasal sinus abnormalities, cardiac 
complications, and/or neuropathy. 
Abrupt discontinuation of systemic or ICS after initiation of omalizumab therapy is not recommended. 
Decreases in corticosteroids should be performed under the direct supervision of the PI and may need to be 
performed gradually. 
6.4.1.4 
Management of Drug Induced Liver Injuries 
Large clinical trial and post marketing data did not reveal any hepatotoxic potential for omalizumab. Liver 
injury has not been described/listed as a risk associated with omalizumab. However, as a general 
precautionary measure 1) if the participant’s aspartate aminotransferase (AST) or alanine aminotransferase 
(ALT) is >8 times the upper limit of normal (ULN), or 2) if the participant’s AST or ALT is >3 times the ULN 
and total bilirubin >2 times the ULN, or clinical jaundice occurs, omalizumab or placebo for omalizumab will 
be held while liver tests are repeated. If the liver function test abnormality is confirmed, a referral for 
further evaluation for causes for the liver test abnormality will be initiated. During this evaluation, the 
participant’s involvement in the study will be put on hold (no study drugs will be given or study procedures 
performed). If the abnormality is found to be unrelated to study drug or study procedure, has fully 
resolved, and is not expected to recur, the participant may restart the stage they were in when the event 
occurred. Otherwise, the participant will be withdrawn from the study. Guidelines for restarting the stage 
are provided in the OUtMATCH MOP. 

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6.4.1.5 
Thrombocytopenia 
Rare cases of thrombocytopenia have been reported in clinical studies and in post-marketing studies. As a 
general precautionary measure since the trial involves young children, a CBC will be obtained every three 
months to evaluate the platelet count. If clinically significant thrombocytopenia is observed, then 
omalizumab or placebo for omalizumab will be held while the platelet count is repeated. If clinically 
significant thrombocytopenia is confirmed, the participant will be withdrawn and a referral for further 
evaluation for thrombocytopenia will be initiated. 
6.4.2 
Multi-allergen Oral Immunotherapy 
6.4.2.1 
Reactions during Initial Dose Escalation 
Participants may develop symptoms during IDE.  
For oropharyngeal pruritus, the action should be to continue the normal IDE dosing in 15-30 minutes. 
For mild symptoms, defined as: 
• 
skin — limited or localized hives or swelling, skin flushing or pruritus; 
• 
respiratory — rhinorrhea or sneezing, nasal congestion, occasional cough, throat discomfort; 
• 
GI — mild abdominal discomfort or minor episode of vomiting; 
the action should be either to continue the normal IDE dosing in 30-60 minutes or to discontinue IDE, 
depending on the PI’s discretion. 
For moderate symptoms, defined as: 
• 
skin — systemic hives or swelling; 
• 
respiratory — throat tightness without hoarseness, persistent cough, wheezing without dyspnea; 
• 
GI — persistent moderate abdominal pain/cramping/nausea, increased vomiting; 
the IDE should be discontinued and the appropriate rescue medications (see Section 7.4) administered. 
For severe symptoms, defined as: 
• 
respiratory —stridor/laryngeal edema, throat tightness with hoarseness, wheezing with dyspnea; 
• 
GI — significant severe abdominal pain/cramping/repetitive vomiting; 
• 
neurological — change in mental status; 
• 
circulatory — hypotension; 
the IDE should be discontinued and the appropriate rescue medications (see Section 7.4) administered. 
If the participant requires treatment for symptoms with antihistamines on one occasion during IDE, then 
the rest of the IDE protocol may be followed. If the participant requires more than one medication (e.g., 
albuterol, diphenhydramine, epinephrine, or others) or multiple doses of antihistamines, the IDE should be 
discontinued and the participant will be considered an IDE failure if they did not tolerate the minimum total 

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dose of 9 mg protein during the IDE in Stage 2 or the minimum dose of 3 mg protein of the food during the 
IDE in Stage 3.  
The PI will be available for questions and decision making for any questions related to IDE dosing at all 
times. 
All participants will be observed for a minimum of two hours following administration of the final dose and 
will be discharged only when deemed clinically stable by the PI. 
6.4.2.2 
Reactions during Build-Up or Maintenance Phase 
To be eligible for a Dose Build-Up Visit, a participant cannot have active wheezing, peak flow <80% 
predicted, or a current flare of AD that contraindicates dose build-up in the clinical judgment of the PI. As 
needed, a participant will be maintained on their current dose until their flare of asthma or AD is resolved. 
If a participant has a build-up dose in the CRU without symptoms, the action should be to continue per 
protocol with daily home OIT dosing at the tolerated dose with the next build-up visit two weeks later. 
On the day of the Initial or Follow-Up Maintenance Dose Visit in the CRU, the participant may have the daily 
dose at home or in the CRU. If a participant has no symptoms, the action should be to continue per 
protocol with daily home OIT dosing at the tolerated dose with the next Follow-Up Maintenance Dose Visit 
eight weeks later. If the participant only experiences oropharyngeal pruritus during the administration of 
the daily dose, then the same dose can be repeated the next day at home and continued throughout the 
dose build-up or maintenance interval unless other symptoms begin to develop. 
If the participant experiences mild symptoms (see Section 6.4.2.1) for 3-4 consecutive days, then the 
participant should return to the CRU for a 1-2 step dose reduction. If the dose is tolerated, the participant 
will remain on that dose for two weeks and then return to the CRU for dose build-up. If the dose is not 
tolerated, consultation with the PI is indicated. 
If moderate symptoms (see Section 6.4.2.1) occur, the action should be to have the participant return to 
the CRU the next day (day 2) for OIT dosing with the same dose or a 1-2 step dose reduction, per PI 
discretion, under observation. If the dose on day 2 is tolerated in the CRU, the participant will continue on 
that daily home dose for the normal time interval per protocol. If the dose on day 2 is not tolerated in the 
CRU, the participant should receive a 1-2 step dose reduction the next day (day 3) in the CRU. If the dose on 
day 3 is tolerated in the CRU, the participant will remain on that dose for two weeks and then return to the 
CRU for dose build-up. If the dose on day 3 is not tolerated in the CRU, the participant should receive a 1-2 
step reduction the next day (day 4) in the CRU. If the dose of day 4 is tolerated in the CRU, the participant 
will remain on that dose for two weeks and then return to the CRU for dose build-up. If the dose on day 4 is 
not tolerated in the CRU, then a discussion with the PI will ensue to make a decision about whether to 
continue the participant on OIT in the study. If the participant is unable to return to the CRU for an 
observed dose on day 2 or 3 or 4, the PI will recommend that doses be skipped until the participant can be 
seen in the CRU. 
If severe symptoms (see Section 6.4.2.1) occur, the action should be to treat the participant, and at the PI’s 
discretion, either: 1) have them return to the CRU the next day (day 2) for OIT dosing with a 2-step dose 
reduction, or 2) discontinue OIT. If the participant tolerates the dose reduction, the participant will remain 
on that dose for two weeks and then return to the CRU for dose build-up. If the participant is unable to 
return to the CRU for an observed dose on day 2, the PI will recommend that doses be skipped until the 

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participant can be seen in the CRU. A discussion with the PI may ensue to make a decision about whether 
to continue the participant on OIT in the study. 
If a participant fails dose build-up after three consecutive (with 2-4 weeks between) attempts by Week 24, 
he/she will be considered a treatment failure.  
For a completed dose build-up with no symptoms, participants should be observed for 30 minutes. For mild 
symptoms, participants should be observed for at least 30 minutes. For moderate to severe symptoms, the 
observation period should be based on symptoms and the treatment regimen needed to stabilize the 
participant, but at least 2 hours in length. Length of the observation period may be longer than the stated 
minimum times, per PI discretion. 
If a participant has a severe allergic reaction to OIT, including hypoxia, hypotension or change in mental 
status and receives aggressive therapy (e.g., IV fluid resuscitation, mechanical ventilation, repeated doses 
of epinephrine for a life-threatening reaction) at any time, the participant will be withdrawn from the study 
(see Section 11.2). 
For specific questions related to dose build-up or maintenance OIT dosing, the DAIT/NIAID Medical Monitor 
and the Protocol Chair(s) will be consulted. 
 Premature Discontinuation of Investigational Agent 
Study therapy regimen may be prematurely discontinued for any participant for any of the reasons identified in Section 
11.2. A participant who prematurely discontinues any of the investigational agents will follow end of study procedures 
as described in Section 11.4.  
7 Other Medications 
 Concomitant Medications 
7.1.1 
Protocol-Mandated 
Not applicable. 
7.1.2 
Other Permitted Concomitant Medications 
Each participant may continue their usual medications, including those taken for asthma, allergic rhinitis and AD, 
during the study. However, each participant must be able to discontinue antihistamines prior to the SPTs and all 
OFCs. Regular topical steroid use is permitted at the time of a SPT. 
 Prophylactic Medications 
No prophylactic medications are required; however, the investigator may choose to instruct the participant to take 
antihistamines prior to a dose of Multi-allergen OIT during study participation. 
 Prohibited Medications 
Use of the following medications is prohibited during study participation: 
1. Monoclonal antibodies except omalizumab, such as dupilumab (Dupixent®), benralizumab (Fasenra™), 
mepolizumab (Nucala®), reslizumab (Cinqair®), or other immunomodulatory therapy 
2. Initiation of any immunotherapy such as OIT, SLIT, or EPIT (outside of that given to the participant for this study) 
3. Oral β-blockers 

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4. Tricyclic antidepressants 
5. Use of systemic cyclosporine, methotrexate, azathioprine, or mycophenolate and chronic use of systemic 
corticosteroids 
6. Changes in aspirin desensitization therapy or initiation of new aspirin desensitization therapy 
7. Investigational therapy other than study drug 
A participant who uses prohibited medications during study participation will be withdrawn and will attend an Early 
Discontinuation Visit (see Section 8.9). 
 Rescue Medications  
Participants must have epinephrine autoinjectors to use in the event of a severe reaction to one of the investigational 
agents because both Multi-allergen OIT and omalizumab (albeit rarely) may induce severe allergic reactions/anaphylaxis.  
Life-threatening allergic reactions to food allergen may occur during OIT dosing, OFCs, and open feedings; epinephrine is 
used to treat these reactions. In addition, epinephrine has a unique use in food allergic reactions that are not life 
threatening. That is, injectable epinephrine is used early during allergic reactions to food allergens in order to prevent 
the progression of these allergic reactions (see Section 12.2.5). 
A participant and/or parent/legal guardian must sign the Epinephrine Autoinjector Training Form and understand its use 
before the participant can receive the investigational agent. 
Treatment of individual allergic reactions during Multi-allergen OIT therapy, SPT, and/or to local skin anesthetic (as 
applicable) used during the blood draw, will be with either an antihistamine and/or epinephrine, along with IV fluids, 
albuterol, and corticosteroids (including topicals), as indicated. All participants will be given a food allergy action plan to 
follow while in this study. 
8 Study Procedures 
 Study Assessments 
8.1.1 
Vital Signs and Growth Parameters 
The following vital signs and growth parameters will be collected at study visits prior to all study drug administrations 
unless otherwise noted: 
• 
Weight 
• 
Height 
• 
Temperature 
• 
Pulse Rate 
• 
Respiratory Rate 
• 
Blood Pressure (BP) – BP will only be collected for participants aged 2 years or older unless clinically 
indicated. 
8.1.2 
Medical History and Physical Examination 
The participant’s medical history will be obtained at the Screening Visit. Updates to the medical history (i.e., interim 
medical history) will be obtained at all subsequent visits. 

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The PI or licensed clinician on the CRU staff will perform a comprehensive physical examination at the Screening Visit, 
at the IDE Visit, and at each visit with an OFC or open feeding. The comprehensive exam will include skin, head, eyes, 
ears, nose, and throat (HEENT), respiratory, cardiovascular, GI, endocrine/metabolic, neurological, blood/lymphatic, 
and musculoskeletal evaluation. At all other visits, the PI or licensed clinician on the CRU staff will perform a limited 
physical examination, which will include skin, HEENT, respiratory, cardiovascular, GI evaluation, and a symptom 
assessment. A comprehensive or limited physical examination may be performed at an unscheduled visit as needed. 
Additional examinations may be completed at the PI’s discretion. 
Significant findings that are present prior to the start of the study must be included on the appropriate electronic 
case report form (eCRF). Significant findings that meet the definition of an AE must also be recorded on the AE eCRF. 
8.1.3 
Spirometry and Peak Expiratory Flow 
Spirometry will be performed at the Screening Visit for participants who are age seven years or older and are able to 
perform spirometry. Spirometry will not be performed at any other visit. PEF will be performed at the Screening Visit 
for participants who are unable to perform spirometry, and at all OIT dosing visits, OFC visits, and unscheduled visits 
as needed. PEF will be attempted for participants aged four to six, but is not required if the participant is unable. PEF 
does not need to be attempted for participants younger than four and is not required. 
8.1.4 
SCORAD 
The PI or certified CRU staff will assess the disease severity for participants with AD, as determined by the PI or 
licensed clinician on the CRU staff based on the current medical history and/or the physical exam, using SCORing 
Atopic Dermatitis (SCORAD), a standardized tool for assessing the extent or areas of the body affected by AD, disease 
intensity, and subjective symptoms of pruritus and sleep loss. 
8.1.5 
FAQLQ 
The PI or CRU staff will assess quality of life using FAQLQ, a standardized and validated tool for assessing emotional 
impact, food anxiety, and social and dietary limitations in people with food allergy. 
8.1.5.1 
FAQLQ-PF 
The PI or certified CRU staff will administer the FAQLQ-PF to parents/legal guardians of participants aged 0-
12 years. 
8.1.5.2 
FAQLQ-CF 
The PI or certified CRU staff will administer the FAQLQ-CF to children/adolescents aged 8-12 years with 
food allergy. 
8.1.5.3 
FAQLQ-TF 
The PI or certified CRU staff will administer the FAQLQ-TF to adolescents aged 13-17 years. 
8.1.5.4 
FAQLQ-AF 
The PI or certified CRU staff will administer the FAQLQ-AF to adults aged ≥18 years. 
8.1.6 
Questionnaires 
The PI or certified CRU staff will administer questionnaires for the PI’s assessment of inclusion/exclusion criteria and 
to collect participant information regarding: 
1. Contact information 
2. Demographics 
3. Diet and food allergy history 

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4. GI symptoms30 
5. Family history 
6. Medication use 
7. AEs 
8. Stool Specimen Information 
9. Monthly long-term follow-up questionnaires  
8.1.7 
 Diaries 
Each participant and/or parent/legal guardian will maintain electronic and/or paper diary logs throughout Stage 2, 
Stage 3 Rescue OIT, and for the first six months in Stage 3 Long-term follow-up with dietary consumption to collect 
OIT dosing, any reaction from at-home OIT dosing, use of concomitant medications, and  food intake. CRU staff will 
have the capability to monitor participant compliance with diary completion.  
8.1.8 
Skin Prick Tests 
Each participant will have SPTs performed to food and environmental allergens according to the MOP. Each 
participant will be required to withhold antihistamines for an appropriate length of time (five half-lives of the 
antihistamine being used) to limit interference with the results of the SPT. Positive (histamine) and negative (saline 
glycerin) controls will be placed to determine the validity of the test. 
The following allergens will be tested: 
• 
Food allergens: peanut, egg white, cow’s milk, soy, wheat, sesame, tree nuts (cashew, English walnut, 
hazelnut, almond, pecan, pistachio, and Brazil nut) 
• 
Environmental allergens: dust mite, cat, dog, Timothy grass, ragweed, oak, birch, Alternaria sp. 
Oat will be tested by SPT for participants who have a suspected clinical reaction to oat since oat is used in the OFC 
material. 
8.1.9 
Oral Food Challenges: Double-Blind Placebo-Controlled Food Challenges and Open Oral Food Challenges 
OFCs will be performed under direct medical supervision in the CRU or in an OFC area with emergency medications 
and CRU staff immediately available. OFCs will follow established study procedures. A dietitian will be available at 
each CRU to consult in providing an age-appropriate vehicle for the OFCs; OFC vehicles are not to be brought to the 
CRU by the participant and/or parent/legal guardian for use in the OFC. 
OFC material consists of food protein flours (active) and oat flour (placebo) and will be prepared by the 
Manufacturing Facility for the Sean N. Parker Center for Allergy & Asthma Research with Stanford University and 
provided to DAIT/NIAID for use in Protocol CoFAR-11.  
Prior to an OFC, each participant will withhold antihistamines for an appropriate length of time (five half-lives of the 
antihistamine being used) and each participant will be assessed as outlined in the CoFAR OFC Overview MOP to 
reduce risks and ensure a safe setting for conducting the OFC. 
All OFCs at Screening and in Stages 1-2, including the OLE, will be DBPCFCs. In a DBPCFC, the participant and/or 
parent/legal guardian, as well as the CRU staff administering the OFC, will not know which OFC contains the food 
protein or the placebo. The blinded OFCs to food and placebo will be split and conducted on separate days. The 
Screening DBPCFC as well as all end of stage DBPCFCs may be conducted over four visits to accommodate OFCs to 
three foods and placebo; all blinded OFCs comprising each DBPCFC must occur within a maximum period of 28 days. 
If an additional Screening DBPCFC to other allergens is needed to identify one or two participant-specific foods, all 

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blinded OFCs comprising the additional Screening DBPCFC must occur within a maximum period of 21 days after the 
fourth blinded OFC in the original Screening DBPCFC. Each participant will remain on the treatment assigned in a 
stage while completing the end of stage DBPCFC. A participant will not take a dose of Multi-allergen OIT/placebo for 
Multi-allergen OIT on the OFC days. Omalizumab or placebo for omalizumab injections may occur on the same day as 
an OFC as long as the injection occurs at least 30 minutes prior to the OFC to assess AEs. 
Prior to randomization in Stage 1, the results of the Screening DBPCFC will be unblinded to determine eligibility. 
8.1.10 Open Feedings 
Open feedings in Stage 3 will be performed under direct medical supervision in the CRU or in an OFC area with 
emergency medications and CRU staff immediately available. An open feeding will be performed if: 
• 
a participant consumes a single dose of ≥600 mg protein of each food without dose-limiting symptoms 
during the participant’s last OFC; or  
• 
a participant has tolerated a minimum target maintenance dose of ≥375 mg of protein for a food for four  
weeks during the Maintenance Phase in rescue OIT.  
The amount of food eaten at the open feeding will be based on the maximum quantity deemed to be safe, as 
determined by the participant’s last OFC (see Table 3.1.5.1) or maintenance dose in rescue OIT (see Table 3.1.5.3e). 
During an open feeding, the participant will consume a portion of the food in a dietary form (e.g., two tablespoons of 
peanut butter) in an open setting in which all involved parties are aware of the identity of the food. The participant 
will be observed for a minimum of two hours after completing eating the food to assess if the food is tolerated. Open 
feedings to more than one food may occur on the same day with a two-hour waiting period between each food.  
Participants who undergo long-term follow-up with dietary consumption of a food following completion of Stage 1 
OLE or Stage 2 will remain on the treatment they were receiving until all open feedings are completed. Omalizumab 
or placebo for omalizumab injections may occur on the same day as an open feeding as long as the injection occurs at 
least 30 minutes prior to the open feeding to assess AEs. A participant will not take a dose of Multi-allergen 
OIT/placebo for Multi-allergen OIT/rescue OIT on the days the participant’s open feedings are conducted. 
 Sample Collections 
8.2.1 
Blood Collection 
Blood will be collected by peripheral venipuncture as per the schedule of events (Appendices 4-9) for: 
1. Biomarkers assays 
a. Total IgE 
b. Total free IgE 
c. Allergen-specific IgE, IgG4, and IgA 
d. Basophil activation 
2. PK sampling 
3. Samples for mechanistic studies (see Section 9.2) 
The blood collection should occur prior to initiating an OFC or IDE/updosing.  

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8.2.1.1 
Blood Collection for Safety 
Blood will be collected by peripheral venipuncture for safety at the Screening Visit and every three months 
during Stage 1, the OLE, Stage 2, and Stage 3 (only for participants still receiving omalizumab, placebo for 
omalizumab, or open label omalizumab from the previous stage) to assess: 
1. CBC with differential 
2. CMP 
 
Additional safety lab testing may be performed per PI discretion. 
8.2.2 
Stool Collection 
Stool samples will be collected and stored for potential microbiome studies, specifically assessing the effects of the 
microbiome on OIT responses and/or the effects of OIT on the microbiome. Studies may also be conducted to assess 
other biologic outcomes that may be related to food allergy and the effects of the study’s intervention. 
A stool collection kit and specimen information questionnaire will be provided to the participant and/or parent/legal 
guardian at pre-specified visits. Instructions for sample collection, storage, and transportation will be provided in the 
MOP. 
8.2.3 
Urine Collection 
Urine will be collected and stored for potential metabolomic studies to evaluate changes related to treatment with 
omalizumab and omalizumab-facilitated OIT. Instructions for the collection of urine samples will be provided in the 
MOP. 
8.2.3.1 
Urine Collection for Safety 
8.2.3.1.1 Urinalysis 
Urine for urinalysis will be collected at the Screening Visit and every three months during Stage 1, the OLE, 
Stage 2, and Stage 3 (only for participants still receiving omalizumab, placebo for omalizumab, or open label 
omalizumab from the previous stage). Additional Urinalysis testing may be performed at the PI’s discretion.  
8.2.3.1.2 Urine Pregnancy Testing 
All females who have undergone menarche (or who undergo menarche during the study) will be required 
to have a urine pregnancy test at the Screening Visit and then routinely at study visits, as specified in the 
schedule of events for each stage of the study. If the result is positive, the participant will either not be 
eligible for study randomization or will be discontinued from the study. Additional urine pregnancy testing 
may be performed at the PI’s discretion. Results of all pregnancy tests will be given to the caretaker (or 
participant if specified by IRB guidelines). 
8.2.4 
Saliva Collection 
Saliva will be collected and stored for the possible assessment of food-specific IgA changes in relation to OIT. 
Instructions for the collection of saliva samples will be provided in the MOP. 
 Screening Visit 
The research study will be explained in lay terms to the participant and/or parent/legal guardian of each potential 
participant. The participant or parent/legal guardian will sign an informed consent form before any study procedures are 
initiated; assent will be obtained as applicable. When the informed consent (and assent, if applicable) has been signed, 
the participant will be assigned a unique participant number. 

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The purpose of the Screening Visit is to confirm eligibility to enroll in the study. 
The Screening Visit may occur over several days and the following procedures, assessments, and laboratory measures 
will be conducted to determine participant eligibility: 
1. Informed Consent and assent, if applicable 
2. Demographics 
3. Vital Signs and Growth Parameters 
4. Medical History 
5. Comprehensive Physical Exam, including spirometry and PEF as applicable 
6. Diet and Allergy Questionnaires 
7. Concomitant Medications 
8. SPT to food and environmental allergens 
9. AEs 
10. Blood Collection 
a. CBC with differential 
b. Total and allergen-specific IgE 
c. CMP 
11. Urine Collection 
a. Urinalysis 
b. Urine Pregnancy Test (female participants of child-bearing potential) 
A potential participant may rescreen at any time. Guidelines for rescreening participants are provided in the OUtMATCH 
MOP. 
8.3.1 
Screening Double-Blind Placebo-Controlled Food Challenge Visits 
The Screening DBPCFC will be split and conducted on separate days. The Screening DBPCFC may be conducted over 
four visits to accommodate blinded OFCs to three foods and placebo; all blinded OFCs comprising the DBPCFC must 
occur within a maximum period of 28 days. The following procedures, assessments, and laboratory measures will be 
conducted to determine participant eligibility: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Comprehensive Physical Exam, including PEF 
4. SCORAD for participants with AD (assessed on the first DBPCFC visit only) 
5. Diet & Allergy Questionnaires 
6. GI Symptoms Questionnaire 
7. Concomitant Medications 
8. Blinded OFC (see Table 3.1.1) 
9. AEs 
The following specimens will be collected prior to initiating the blinded OFC at the first Screening DBPCFC Visit. 
10. Blood 
a. Total IgE 
b. Total free IgE 
c. Allergen-specific IgE, IgG4, and IgA 

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d. Basophil activation 
e. PK sampling 
f. Samples for mechanistic studies 
A stool collection kit and specimen information questionnaire will be given to the participant at the first Screening 
DBPCFC Visit. Participants will be instructed to return the stool collection kit and specimen information questionnaire 
no later than the Randomization Visit (Day 0). 
In the event that a participant does not experience dose-limiting symptoms to two non-peanut foods and may be 
allergic to additional foods, such a participant may receive an additional DBPCFC consisting of up to two blinded OFCs 
to other non-peanut foods and one blinded OFC to placebo. The additional DBPCFC is only an option if the participant 
experienced dose-limiting symptoms to peanut and did not experience dose-limiting symptoms to placebo during the 
initial Screening DBPCFC. All blinded OFCs comprising this additional DBPCFC must occur within 21 days of the fourth 
blinded OFC in the original Screening DBPCFC. 
A participant may be randomized once the assessment for all inclusion and exclusion criteria is complete and the 
participant is deemed eligible.  
 Stage 1 
Appendix 4 provides the schedule of events for Stage 1. 
Because the screening period may vary for each participant, the timing of blood and urine collections for safety during 
Stage 1 will be based on the prior collection. Females who have undergone menarche (or who undergo menarche during 
the study) will have a urine pregnancy test monthly. 
The following safety samples will be collected every three months: 
1. Blood for Safety 
a. CBC with differential 
b. CMP 
2. Urine for Safety 
a. Urinalysis 
8.4.1 
Randomization Visit (Day 0) 
Each participant who demonstrates dose-limiting symptoms at a single dose of ≤100 mg of peanut protein and ≤300 
mg protein of each of the two other foods during the Screening DBPCFC will be randomized 2:1 to receive 
omalizumab or placebo for omalizumab for 16-20 weeks. 
The following procedures and assessments will be conducted at this visit: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Limited Physical Exam 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. Family History Questionnaire 
7. FAQLQ 
8. Concomitant Medications 

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9. AEs 
10. Randomization 
11. Omalizumab or placebo for omalizumab administration 
The following specimens will be collected: 
12. Stool collection kit and specimen information questionnaire (if it has not been returned during the screening 
period) 
13. Urine 
14. Saliva 
Participants will be observed in clinic for at least two hours after the first injection of omalizumab or placebo for 
omalizumab. 
8.4.2 
Omalizumab Injection Visits (Week 2 – Week 14) 
Each participant will return to the CRU for omalizumab or placebo for omalizumab injections. Omalizumab injection 
visits may occur every two or four weeks, determined by the body weight in kilograms and total serum IgE level at 
the Screening Visit. Participants will be observed in clinic for at least two hours after the first three injections of 
omalizumab and at least 30 minutes for all subsequent injections in Stage 1. 
The following procedures and assessments will be conducted at these visits: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Limited Physical Exam 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. Concomitant Medications 
7. AEs 
8. Omalizumab or placebo for omalizumab administration 
8.4.3 
Double-Blind Placebo-Controlled Food Challenge Visits (Week 16 – Week 20) 
At Week 16, each participant will complete a DBPCFC consisting of placebo and each of their three specific foods to a 
cumulative dose of 6044 mg protein of each food using the DBPCFC dosing schedule provided in Table 3.1.2. The 
DBPCFC may occur over four separate visits to accommodate OFCs to three foods and placebo; all blinded OFCs 
comprising the DBPCFC must occur within a maximum period of 28 days. Each participant will continue to receive 
omalizumab or placebo for omalizumab injections while all these blinded OFCs are completed. Omalizumab or 
placebo for omalizumab injections may occur on the same day as a blinded OFC as long as the injection occurs at 
least 30 minutes prior to the blinded OFC to assess AEs. 
8.4.3.1 
Initial Double-Blind Placebo-Controlled Food Challenge Visit (Week 16) 
The following procedures and assessments will be conducted at the first DBPCFC Visit: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Comprehensive Physical Exam, including PEF 
4. SCORAD for participants with AD 
5. Diet & Allergy Questionnaires 

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6. GI Symptoms Questionnaire 
7. FAQLQ 
8. Concomitant Medications 
9. SPT to peanut and two other food allergens 
10. Blinded OFC (see Table 3.1.2) 
11. AEs 
12. Omalizumab or placebo for omalizumab administration (if needed) 
13. Saliva Collection 
14. Urine Collection 
15. Blood Collection 
a. Total IgE 
b. Total free IgE 
c. Allergen-specific IgE, IgG4, and IgA 
d. Basophil activation 
e. PK sampling 
f. Samples for mechanistic studies 
The blood and sample collection should occur prior to initiating the blinded OFC. If the blood collection for 
the safety labs coincides with the Week 16 blood collection, the priority, in terms of blood volume, is the 
safety labs. 
8.4.3.2 
Double-Blind Placebo-Controlled Food Challenge Visits (Week 17 – Week 20) 
The following procedures and assessments will be conducted at the subsequent DBPCFC Visits: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Comprehensive Physical Exam, including PEF 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. Concomitant Medications 
7. Blinded OFC (see Table 3.1.2) 
8. AEs 
9. Omalizumab or placebo for omalizumab administration (if needed) 
After the last DBPCFC Visit at Week 16-20, each participant will then continue to Stage 1 OLE or Stage 2 of 
the study. 
 Stage 1 Open Label Extension 
Appendix 5 provides the schedule of events for Stage 1 OLE. 
The timing of blood and urine collections for safety during Stage 1 OLE will be based on the prior collection. Females 
who have undergone menarche (or who undergo menarche during the study) will have a urine pregnancy test monthly. 
The following safety samples will be collected every three months: 
1. Blood for Safety 
a. CBC with differential 
b. CMP 

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2. Urine for Safety 
a. Urinalysis 
8.5.1 
Omalizumab Injection Visits (Stage 1 Open Label Extension Week 0 – Week 22) 
Each participant will receive 24-28 weeks of treatment with open label omalizumab. The participant will continue to 
use the same omalizumab dosing frequency in the OLE as was used in Stage 1, which was determined by the body 
weight in kilograms and total serum IgE level at the Screening Visit. The first open label omalizumab injection visit in 
the OLE will be scheduled two or four weeks after the last omalizumab or placebo for omalizumab injection in Stage 
1. Each participant will be observed in clinic for at least two hours after the first three injections of open label 
omalizumab in the OLE, and at least 30 minutes for all subsequent injections. 
The following procedures and assessments will be conducted at each of the open label omalizumab injection visits: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Limited Physical Exam 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. Interim Family History Questionnaire (Week 0 only) 
7. FAQLQ (Week 0 only) 
8. Concomitant Medications 
9. AEs 
10. Open label omalizumab administration 
8.5.2 
Double-Blind Placebo-Controlled Food Challenge Visits (Stage 1 Open Label Extension Week 24 – Week 28) 
At Week 24, each participant will complete a DBPCFC consisting of placebo and each of their three specific foods to a 
cumulative dose of 8044 mg protein of each food using the DBPCFC dosing schedule provided in Table 3.1.2. The 
DBPCFC may occur over four separate visits to accommodate blinded OFCs to three foods and placebo; all blinded 
OFCs comprising the DBPCFC must occur within a maximum period of 28 days. Each participant will continue to 
receive open label omalizumab injections while all these blinded OFCs are completed. Omalizumab injections may 
occur on the same day as a blinded OFC with the injection occurring at least 30 minutes prior to the blinded OFC to 
assess AEs. 
8.5.2.1 
Initial Double-Blind Placebo-Controlled Food Challenge Visit (Stage 1 Open Label Extension Week 24) 
The following procedures and assessments will be conducted at the first DBPCFC Visit: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Comprehensive Physical Exam, including PEF 
4. SCORAD for participants with AD 
5. Diet & Allergy Questionnaires 
6. GI Symptoms Questionnaire 
7. FAQLQ 
8. Concomitant Medications 
9. SPT to peanut and two other food allergens 
10. Blinded OFC (see Table 3.1.2) 
11. AEs 

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12. Open label omalizumab administration (if needed) 
13. Blood Collection 
a. Total IgE 
b. Total free IgE 
c. Allergen-specific IgE, IgG4, and IgA 
d. Basophil activation 
e. PK sampling 
The blood collection should occur prior to initiating the blinded OFC. 
8.5.2.2 
Double-Blind Placebo-Controlled Food Challenge Visits (Stage 1 Open Label Extension Week 25 – 28) 
The following procedures and assessments will be conducted at the subsequent DBPCFC Visits: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Comprehensive Physical Exam, including PEF 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. FAQLQ (conducted on the last DBPCFC Visit only) 
7. Concomitant Medications 
8. Blinded OFC (see Table 3.1.2) 
9. AEs 
10. Open label omalizumab administration (if needed) 
Upon completion of the last DBPCFC Visit, each participant will be unblinded to the results of the DBPCFC at 
the end of Stage 1 OLE and will move to Stage 3 of the study. 
 Stage 2 
Appendix 6 provides the schedule of events for Stage 2. 
Open label omalizumab injections and omalizumab or placebo for omalizumab injections may occur on the same day as 
the IDE, Dose Build-Up, and Initial or Follow-Up Maintenance Dose Visits with an observation period between the 
injection and OIT dosing. The observation period will be at least two hours if the injection is one of the first three 
injections in Stage 2, and at least 30 minutes for all subsequent injections. 
The timing of blood and urine collections for safety during Stage 2 will be based on the prior collection. Females who 
have undergone menarche (or who undergo menarche during the study) will have a urine pregnancy test monthly. 
The following safety samples will be collected every three months: 
1. Blood Collection for Safety 
a. CBC with differential 
b. CMP 
2. Urine Collection for Safety 
a. Urinalysis 

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8.6.1 
Omalizumab Injection Visits (Stage 2 Week 0 – 6) 
Each participant will receive eight weeks of treatment with open label omalizumab. The participant will continue to 
use the same omalizumab dosing frequency in Stage 2 as was used in Stage 1, which was determined by the body 
weight in kilograms and total serum IgE level at the Screening Visit. The first open label omalizumab injection visit will 
be scheduled two or four weeks after the last omalizumab or placebo for omalizumab injection in Stage 1. Each 
participant will be observed in clinic for at least two hours after the first three injections of open label omalizumab in 
Stage 2, and at least 30 minutes for all subsequent injections. 
The following procedures and assessments will be conducted at these visits: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Limited Physical Exam 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. Interim Family History Questionnaire (Week 0 only) 
7. FAQLQ (Week 0 only) 
8. Concomitant Medications 
9. Open label omalizumab administration 
10. AEs 
A stool collection kit and specimen information questionnaire will be given to the participant at the last open label 
omalizumab injection visit before the IDE Visit. Participants will be instructed to return the stool collection kit and 
specimen information questionnaire no later than the IDE Visit. 
8.6.2 
Randomization Stage 2 
One week after starting Stage 2, participants will be randomized 1:1 to: 
• 
Omalizumab-facilitated OIT: Open label omalizumab + Multi-allergen OIT for eight weeks, followed by 
placebo for omalizumab + Multi-allergen OIT for 44 weeks. 
• 
Omalizumab + placebo OIT: Open label omalizumab + placebo for Multi-allergen OIT for eight weeks, 
followed by omalizumab + placebo for Multi-allergen OIT for 44 weeks. 
8.6.3 
Initial Dose Escalation Visit (Stage 2 Week 8) 
Each participant randomized will receive daily oral therapy with Multi-allergen OIT or placebo for Multi-allergen OIT. 
During the IDE Visit, each randomized participant will be given Multi-allergen OIT or placebo for Multi-allergen OIT in 
incremental doses, increasing every 15 minutes, until a dose of 375 mg protein of Multi-allergen OIT for each allergen 
(1125 mg protein total food allergen dose) or placebo for Multi-allergen OIT is given (see Table 3.1.4a). 
The following procedures and assessments will be conducted at this visit: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Comprehensive Physical Exam, including PEF 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. Review  Diaries 

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7. Concomitant Medications 
8. Open label omalizumab administration (if needed) 
9. Multi-allergen OIT or placebo for Multi-allergen OIT Dose Escalation (see Table 3.1.4a) 
10. AEs 
11. Collect stool collection kit and specimen information questionnaire (if it has not been returned before the IDE 
Visit) 
12. Urine Collection 
13. Saliva Collection 
14. Blood Collection 
a. Total free IgE 
b. Allergen-specific IgG4 and IgA 
c. Basophil activation 
d. PK sampling 
e. Samples for mechanistic studies 
The blood collection should occur prior to initiating the IDE. If the blood collection for the safety lab coincides with 
the Week 8 blood collection, the priority, in terms of blood volume, is the safety labs. 
Each participant who tolerates a dose of at least 9 mg protein of Multi-allergen OIT or placebo for Multi-allergen OIT 
will remain in the study. 
8.6.4 
Initial Dose Build-Up Visit (Stage 2 Week 8 + 1 day) 
The day after the IDE Visit, each participant will return to the CRU for an observed administration of Multi-allergen 
OIT or placebo for Multi-allergen OIT at the last dose the participant was able to tolerate on the IDE Visit. 
The following procedures and assessments will be conducted at this visit: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Limited Physical Exam, including PEF 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. Review  Diaries 
7. Concomitant Medications 
8. Open label omalizumab administration (if needed only in Stage 2) 
9. Multi-allergen OIT or placebo for Multi-allergen OIT administration  
10. AEs 
If a participant cannot complete the Initial Dose Build-Up Visit within two days of the planned visit, he/she will be 
asked to repeat the IDE Visit. After completion of the Initial Dose Build-Up Visit, each participant will continue their 
daily OIT dosing at home over the next two weeks. 
8.6.5 
Dose Build-Up (Stage 2 Week 10 to Week 14 – Week 32) 
Each participant will return to the CRU every two weeks for a dose escalation to a daily dose of 1000 mg protein of 
Multi-allergen OIT for each allergen (3000 mg protein total food dose) or equivalent placebo for Multi-allergen OIT 
(see Table 3.1.4b). 
The following procedures and assessments will be conducted at each Dose Build-Up Visit: 

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1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Limited Physical Exam, including PEF 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. Review  Diaries 
7. Concomitant Medications 
8. Open label omalizumab or omalizumab/placebo for omalizumab administration (if needed, only in Stage 2) 
9. Multi-allergen OIT or placebo for Multi-allergen OIT administration (see Table 3.1.4b) 
10. AEs 
A participant who does not tolerate a dose will be assessed for dose escalation (see Section 6.4.2). A participant who 
reaches a maximum tolerated daily dose of 1000 mg protein of Multi-allergen OIT for each allergen (3000 mg protein 
total food dose) or equivalent placebo for Multi-allergen OIT will take the same maintenance dose through Week 64. 
A participant who does not reach a maintenance dose of 250 mg protein of Multi-allergen OIT for each allergen (750 
mg protein total food dose) during the Build-Up Phase will be considered a treatment failure and will be referred to 
an allergist for standard clinical care. A participant defined as a treatment failure will attend an Early Discontinuation 
Visit (see Section 8.9). 
Each participant will complete a Build-Up Phase 8-24 weeks in length. 
8.6.6 
Initial Maintenance Dose Visit (Stage 2 Week 16 – Week 34) 
Each participant will complete their Initial Maintenance Dose Visit two weeks after starting the maintenance dose 
during the Build-Up Phase. 
The following procedures and assessments will be conducted at the Initial Maintenance Dose Visit: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Limited Physical Exam 
4. PEF (only if OIT dosing occurs in clinic) 
5. Diet & Allergy Questionnaires 
6. GI Symptoms Questionnaire 
7. Review Diaries 
8. Concomitant Medications 
9. Omalizumab or placebo for omalizumab administration (if needed) 
10. Multi-allergen OIT or placebo for Multi-allergen OIT administration 
11. AEs 
12. Blood Collection 
a. Total free IgE 
b. Allergen-specific IgG4 and IgA 
c. Basophil activation 
d. Samples for mechanistic studies 
If the blood collection for the safety lab coincides with the Initial Maintenance Dose Visit collection, the priority, in 
terms of blood volume, is the safety labs. 

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8.6.7 
Follow-Up Maintenance Dose Visits (Stage 2 Week 24 – Week 58) 
After the Initial Maintenance Dose Visit, the participant will return to the CRU every eight weeks for Follow-Up 
Maintenance Dose Visits. Because each participant will complete a Build-Up Phase 8-24 weeks in length, the number 
and timing of Follow-Up Maintenance Dose Visits may vary among participants. 
The following procedures and assessments will be conducted at each Follow-Up Maintenance Dose Visit: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Limited Physical Exam 
4. PEF (only if OIT dosing occurs in clinic) 
5. Diet & Allergy Questionnaires 
6. GI Symptoms Questionnaire 
7. Review Diaries 
8. Concomitant Medications 
9. Omalizumab or placebo for omalizumab administration (if needed) 
10. AEs 
Multi-allergen OIT or placebo for Multi-allergen OIT administration may occur at a Follow-Up Maintenance Dose Visit, 
per PI discretion.  
A stool collection kit and specimen information questionnaire will be given to the participant at the last visit before 
the first DBPCFC Visit at Week 60. Participants will be instructed to return the stool collection kit and specimen 
information questionnaire no later than the first DBPCFC Visit at Week 60. 
The entire Maintenance Phase will comprise 26 to 44 weeks per participant. 
8.6.8 
Double-Blind Placebo-Controlled Food Challenge Visits (Stage 2 Week 60 – Week 64) 
At Week 60, each participant will complete a DBPCFC consisting of placebo and each of their three specific foods to a 
cumulative dose of 8044 mg protein of each food using the DBPCFC dosing schedule provided in Table 3.1.2. The 
DBPCFC may occur over four separate visits to accommodate OFCs to three foods and placebo; all blinded OFCs 
comprising the DBPCFC must occur within a maximum period of 28 days. Each participant will continue to receive 
treatment as needed while all these blinded OFCs are completed. Omalizumab or placebo for omalizumab injections 
may occur on the same day as a blinded OFC as long as the injection occurs at least 30 minutes prior to the blinded 
OFC to assess AEs. Participants will be instructed to avoid taking their OIT dose on the same day as a blinded OFC. 
8.6.8.1 
First Double-Blind Placebo-Controlled Food Challenge Visit (Stage 2 Week 60) 
The following procedures and assessments will be conducted at the first DBPCFC Visit: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Comprehensive Physical Exam, including PEF 
4. SCORAD for participants with AD 
5. Diet & Allergy Questionnaires 
6. GI Symptoms Questionnaire 
7. FAQLQ 
8. Review Diaries 
9. Concomitant Medications 

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10. Omalizumab or placebo for omalizumab administration (if needed) 
11. SPT to peanut and two other food allergens 
12. Blinded OFC (see Table 3.1.2) 
13. AEs 
14. Collect stool collection kit and specimen information questionnaire (if it has not been returned 
before the first DBPCFC Visit) 
15. Saliva Collection 
16. Urine Collection 
17. Blood Collection 
a. Total IgE 
b. Total free IgE 
c. Allergen-specific IgE, IgG4, and IgA 
d. Basophil activation 
e. PK sampling 
f. Samples for mechanistic studies 
The blood and sample collection should occur prior to initiating the blinded OFC. If the blood collection for 
the safety lab coincides with the Week 60 blood collection, the priority, in terms of blood volume, is the 
safety labs. 
8.6.8.2 
Double-Blind Placebo-Controlled Food Challenge Visits (Stage 2 Week 61 – Week 64) 
The following procedures and assessments will be conducted at the subsequent DBPCFC Visits: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Comprehensive Physical Exam, including PEF 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. FAQLQ (conducted on the last DBPCFC Visit only) 
7. Review Diaries 
8. Concomitant Medications 
9. Omalizumab or placebo for omalizumab administration (if needed) 
10. Blinded OFC (see Table 3.1.2) 
11. AEs 
Upon completion of the last DBPCFC Visit, each participant will be unblinded to the results of the DBPCFC at 
the end of Stage 2 and will move to Stage 3 of the study. 
 Stage 3 – Long-Term Follow-Up and Rescue Oral Immunotherapy  
8.7.1 
Long-Term Follow-Up with Dietary Consumption 
Appendix 7 provides the schedule of events for long-term follow-up with dietary consumption of a food during Stage 
3. 
The timing of blood and urine collections for safety during Long-Term Follow-Up with Dietary Consumption will be 
based on the prior collection and is only needed for participants still receiving omalizumab, placebo for omalizumab, 
or open label omalizumab from the previous stage. 

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The following safety samples will be collected: 
1. Blood for Safety 
a. CBC with differential 
b. CMP 
2. Urine for Safety 
a. Urinalysis 
Females who have undergone menarche (or who undergo menarche during the study) will have a monthly urine 
pregnancy test based on the prior collection until all open feedings are completed.  
8.7.1.1 
Open Feedings 
Participants who start dietary consumption of a food in Stage 3 will undergo an open feeding of that food. Such 
participants will remain on the treatment they were receiving in Stage 1 OLE or Stage 2 until all open feedings are 
completed. If a participant is transitioning to dietary consumption from Stage 3 rescue OIT for more than one food 
allergen, refer to the OUtMATCH MOP for guidance on continuing the rescue OIT for the other rescue OIT food 
allergens. Open label omalizumab injections or omalizumab or placebo for omalizumab injections may occur on the 
same day as an open feeding as long as the injection occurs at least 30 minutes prior to the open feeding to assess 
AEs. A participant will not take a dose of Multi-allergen OIT/placebo for Multi-allergen OIT/rescue OIT on the days 
the participant’s open feedings are conducted.  
The following procedures and assessments will be completed during each open feeding: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Comprehensive Physical Exam (if there is more than one open feeding on a given day, a Limited 
Physical Exam will be performed prior to initiating each subsequent open feeding). 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. Interim Family History Questionnaire (first open feeding only; do not collect if given on any other 
visit in Stage 3) 
7. Review Diaries  
8. Concomitant Medications 
9. Open label omalizumab administration (if needed and participant was in Stage 1 OLE prior to the 
open feeding) 
10. Omalizumab or placebo for omalizumab administration (if needed and participant was in Stage 2 
prior to the open feeding) 
11. Open Feeding 
12. AEs 
8.7.1.2 
Safety Phone Calls or Emails During Long Term Follow-up with Dietary Consumption 
All phone calls or emails may be combined with other study visits in Stage 3.  
8.7.1.2.1 First 6 months in Long Term Follow-up with Dietary Consumption: 
Following an observed initial open feeding of dietary food in the CRU, the participant will be called or 
emailed weekly for the first four weeks, every other week from six to sixteen weeks, and every two months 
until 6 months of Long-Term Follow-Up with Dietary Consumption has been completed. Additionally, if a 

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participant is undergoing Rescue OIT and reaches the planned target maintenance dose allowing the 
transition to dietary consumption for the food, the participant will be called or emailed two weeks 
following the completion of the rescue OIT Initial Maintenance Dose Visit. The following procedures and 
assessments will be completed during each phone call or email: 
1. Interim Medical History 
2. Diet & Allergy Questionnaires 
3. GI Symptoms Questionnaire 
4. Review Diaries  
5. Concomitant Medications 
6. AEs 
      
    8.7.1.2.2 Month 7 and beyond of Long Term Follow-up with Dietary Consumption : 
If a participant is receiving long-term follow-up with dietary consumption for a food after completing six 
months of follow-up in Stage 3, the participant will be contacted monthly by phone call or email. The 
following procedures and assessments will be completed during each monthly long-term follow-up phone 
call/email: 
1. Interim Medical History 
2. Monthly Long Term Follow-up Questionnaire 
3. Diet & Allergy Questionnaires  
4. GI Symptoms Questionnaire  
5. Concomitant Medications 
6. AEs 
 
8.7.1.3 
Long-Term Follow-Up Visits 
The participant will return to the CRU, or have a telehealth visit if in person assessments are not required,  
every six months until they have a minimum of 12 months of follow-up in Stage 3. The following procedures 
and assessments will be completed during each long-term follow-up visit: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Limited Physical Exam 
4. SCORAD for participants with AD (first six-month visit only) 
5. Diet & Allergy Questionnaires 
6. GI Symptoms Questionnaire 
7. FAQLQ (first six-month visit only) 
8. Review Diaries (if needed) 
9. Concomitant Medications 
10. SPT to peanut and two other food allergens (first six-month visit and every 12 months thereafter) 
11. AEs 
12. Blood Collection (first six-month visit only) 
a. Total IgE 
b. Total free IgE 
c. Allergen-specific IgE, IgG4, and IgA 

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d. Basophil activation 
8.7.2 
Long-Term Follow-Up with Avoidance 
Appendix 8 provides the schedule of events for long-term follow-up with avoidance of a food during Stage 3. 
Each participant who receives long-term follow-up with avoidance for a food will complete long-term follow-up visits 
every six months until the participant has completed a minimum of 12 months of follow-up in Stage 3. Procedures 
and assessments that will be completed during each visit are the same as those given in Section 8.7.1.3. An interim 
family history questionnaire will be given on the first long-term follow-up visit if it has not been collected on any 
other visit in Stage 3.  
If a participant is receiving long-term follow-up with avoidance for a food after completing six months of follow-up in 
Stage 3, the participant will be contacted monthly by phone call or email. Procedures and assessments that will be 
completed during each phone call/email are the same as those given in Section 8.7.1.2.2. These phone calls/emails 
may be combined with other study visits in Stage 3. 
8.7.3 
Rescue Oral Immunotherapy 
Appendix 9 provides the schedule of events for rescue OIT for a food during Stage 3. 
The timing of blood and urine collections for safety during rescue OIT will be based on the prior collection and is only 
needed for participants still receiving omalizumab, placebo for omalizumab, or open label omalizumab from the 
previous stage. The following safety samples will be collected: 
1. Blood for Safety 
a. CBC with differential 
b. CMP 
2. Urine for Safety 
a. Urinalysis 
Females who have undergone menarche (or who undergo menarche during the study) will have a urine pregnancy 
test routinely during rescue OIT (see Appendix 9 for scheduling details); the timing of the urine pregnancy test will be 
based on the prior collection. 
8.7.3.1 
Stage 3 Initial Dose Escalation, Dose Build-Up, and Initial and Follow-Up Maintenance Dose Visits 
Participants who undergo an IDE Visit during Stage 3 rescue OIT for a food within 14 days of completing 
Stage 1 OLE or Stage 2 will remain on the treatment they were receiving until the IDE Visit is completed. 
Open label omalizumab injections or omalizumab or placebo for omalizumab injections may occur on the 
same day as the IDE Visit as long as the injection occurs at least 30 minutes prior to the IDE Visit to assess 
AEs. Participants from Stage 2 will be instructed to avoid taking their Multi-allergen OIT dose on the same 
day as the IDE Visit. 
For the IDE Visit (if applicable in Stage 3 rescue OIT), Initial Dose Build-Up Visit, Dose Build-Up, Initial 
Maintenance Dose Visit and Follow-Up Maintenance Dose Visits, each participant will complete procedures 
and assessments as outlined in Sections 8.6.3, 8.6.4, 8.6.5, 8.6.6, and 8.6.7, excluding stool, saliva, urine and 
blood sample collections. Also exclude Multi-allergen OIT/placebo as Stage 3 rescue OIT is open label only 
and may be one, two, or three allergens. Participants who do not require an IDE visit in Stage 3 rescue OIT  
based on their End of Stage 1 OLE or Stage 2 DBPCFC,  are to begin Stage 3 rescue OIT in the build-up phase. 
They will not receive any further doses of omalizumab/placebo for omalizumab, or open label omalizumab 

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treatment from their previous Stage. Additionally, an interim family history questionnaire will be asked at 
the IDE Visit (if it has not been collected on any other visit in Stage 3) and FAQLQ and blood will be 
collected at six months after the start of rescue OIT. Urine will be collected monthly during the IDE Visit and 
Dose Build-Up Visits, at the Initial Maintenance Dose Visit, and at each Follow-Up Maintenance Dose Visit.  
If a participant cannot complete the Initial Dose Build-Up Visit within two days of the planned visit, he/she 
will be asked to repeat the IDE Visit. 
Participants who reach a planned target maintenance dose of at least 375 mg protein of the food will 
complete the visits described above; however after the Initial Maintenance Dose Visit, the participant will 
be called or emailed at two weeks  as described in Section 8.7.1.2. After the Follow-Up Maintenance Visit, 
the participant will return to CRU to complete an open feeding for the food(s) as described in Section 
8.7.1.1. If the participant tolerates ≥300 mg protein of the food during the open feeding(s), the participant 
will transition to dietary consumption of the food. Each participant will complete the procedures and 
assessments for the Safety Phone Calls or Emails and Long-Term Follow-Up Visits as described in Sections, 
8.7.1.2 and 8.7.1.3.  
If a participant is receiving rescue OIT doses for a food, the participant will complete daily diaries for that 
food.  
8.7.4 
End of Study visit for Participants in Stage 3 
A telehealth or in person visit will be conducted when participants have completed a minimum of 12 months on the 
assigned treatment plans for all three foods in Stage 3. The following procedures and assessments will be conducted 
during this visit:  
1. Interim Medical History 
2. Monthly Long Term Follow-up Questionnaire 
3. Diet & Allergy Questionnaires  
4. GI Symptoms Questionnaire  
5. Concomitant Medications 
6. AEs 
 
 Unscheduled Visits  
Unscheduled visits may be performed at any time during the study to address study related issues or assess safety. The 
PI and CRU staff may determine if unscheduled visits are required for, but not limited to, the following reasons: 
• 
Dose observation, if the participant has had symptoms with home OIT doses, missed consecutive OIT doses as a 
result of concurrent illnesses, or has had symptoms outside of the two-hour OIT dosing window.  
• 
Receive an injection of omalizumab or placebo for omalizumab that could not be scheduled on the same day as 
another study visit. 
• 
Provide additional samples for further biomarker or mechanistic studies, if samples are lost or destroyed, or if 
insufficient yields were obtained at a previous study visit. 
• 
To assess a potential AE or clinically significant laboratory result. 

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The following procedures and assessments may be completed during this visit, per PI discretion: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Comprehensive or Limited Physical Exam with or without PEF 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. Review Diaries (as applicable) 
7. Monthly Long-Term Follow-Up Questionnaires (as applicable for the Stage) 
8. Concomitant Medications 
9. AEs 
10. Omalizumab or placebo for omalizumab administration 
11. Blood Collection for Safety 
a. CBC with differential 
b. CMP 
12. Urine Collection for Safety 
a. Urine Pregnancy Test (female participants of child-bearing potential) 
b. Urinalysis 
13. Additional sample collection, as appropriate 
 Early Discontinuation Visit 
A participant who prematurely terminates the study due to withdrawal of consent or at the PI’s discretion will attend an 
Early Discontinuation Visit. 
The following procedures and assessments will be completed during this visit: 
1. Vitals & Growth Parameters 
2. Interim Medical History 
3. Limited Physical Exam 
4. Diet & Allergy Questionnaires 
5. GI Symptoms Questionnaire 
6. Review Diaries (as applicable for the Stage) 
7. Monthly Long-Term Follow-Up Questionnaires (as applicable for the Stage) 
8. Concomitant Medications 
9. Urine Pregnancy Test (female participants of child-bearing potential) 
10. AEs 
If the participant is currently in Stage 1, Stage 2, or the first 6 months of Stage 3, and the following procedures and 
assessments have not been completed within the eight weeks preceding the Early Discontinuation Visit, they will be 
completed in addition to the procedures noted above: 
11. SPT to peanut and two other food allergens 
12. Blood Collection 
a. Total IgE 
b. Total free IgE 
c. Allergen-specific IgE, IgG4, and IgA 
d. Basophil activation 

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e. CBC with differential 
f. CMP 
13. Urinalysis 
 Re-contact of Participants after End of Study or Early Discontinuation  
The participant and/or parent/legal guardian is asked during the informed consent process to indicate contact for future 
research studies is permissible.  
 Visit Windows 
Study visits must occur within the time limits specified below. 
• 
Screening 
o The first Screening DBPCFC must be completed no later than 8 weeks after the Screening Visit. For this 
Screening DBPCFC, the last DBPCFC Visit must occur no later than 28 days after the first DBPCFC Visit. 
o If an additional Screening DBPCFC to other allergens is needed, it must be completed no later than 21 
days after the fourth blinded OFC in the original Screening DBPCFC. 
o The Screening Visit and Screening DBPCFC must be completed during a 15-week period. 
 
• 
Stage 1 
o The first omalizumab injection visit (regardless of omalizumab dosing frequency) must occur between 1 
and 21 days from the last Screening DBPCFC Visit. 
o Omalizumab injection visits for 2 week omalizumab dosing must occur between 4 days before and 7 
days after the planned visit.  
o Omalizumab injection visits for 4 week omalizumab dosing must occur between 7 days before and 7 
days after the planned visit.  
o The first DBPCFC Visit at the end of Stage 1 must occur no later than 2 weeks after the planned visit. 
o The last DBPCFC Visit at the end of Stage 1 must occur no later than 28 days after the first DBPCFC Visit 
at the end of Stage 1. 
• 
Stage 1 OLE 
o Omalizumab injection visits for 2 week omalizumab dosing must occur between 4 days before and 7 
days after the planned visit.  
o Omalizumab injection visits for 4 week omalizumab dosing must occur between 7 days before and 7 
days after the planned visit.  
o The first DBPCFC Visit at the end of Stage 1 OLE must occur no later than 2 weeks after the planned visit. 
o The last DBPCFC Visit at the end of Stage 1 OLE must occur no later than 28 days after the first DBPCFC 
Visit at the end of Stage 1 OLE. 
• 
Stage 2 
o The IDE Visit must occur no later than 14 days after the planned visit. 
o The Initial Dose Build-Up Visit must occur no later than 2 days after the planned visit. 
o Dose Build-Up Visits must occur between 4 days before and 7 days after the planned visit. 
o Initial Maintenance Dose Visit must occur between 4 days before and 7 days after the planned visit. 

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o Follow-Up Maintenance Dose Visits must occur between 14 days before and 14 days after the planned 
visit. 
o Omalizumab injection visits for 2 week omalizumab dosing must occur between 4 days before and 7 
days after the planned visit.  
o Omalizumab injection visits for 4 week omalizumab dosing must occur between 7 days before and 7 
days after the planned visit.  
o The first DBPCFC Visit at the end of Stage 2 must occur no later than 2 weeks after the planned visit. 
o The last DBPCFC Visit at the end of Stage 2 must occur no later than 28 days after the first DBPCFC Visit 
at the end of Stage 2. 
• 
Stage 3 – Long-term follow-up with dietary consumption of a food 
o Omalizumab injection visits for 2 week omalizumab dosing must occur between 4 days before and 7 
days after the planned visit.  
o Omalizumab injection visits for 4 week omalizumab dosing must occur between 7 days before and 7 
days after the planned visit.  
o The first open feeding must occur no later than 14 days after the last DBPCFC visit in Stage 1 OLE or 
Stage 2. 
o The last open feeding must occur no later than 21 days after the last DBPCFC visit in Stage 1 OLE or 
Stage 2. 
o For participants who transition from rescue OIT, the open feeding for a food must occur no later than 14 
days after the first Follow-Up Maintenance Dose Visit.. 
o Weekly and every two-week phone calls/emails must occur between 3 days before and 7 days after the 
planned phone call/email. 
o Two-month phone calls/emails must occur between 2 weeks before and 2 weeks after the planned 
phone call/email. 
o Monthly long-term follow-up phone calls/emails must occur between 7 days before and 7 days after the 
planned phone call/email. 
o Long-term follow-up visits must occur between 1 month before and 1 month after the planned visit.  
o End of study visits must occur after the participant has completed a minimum of 12 months on all three 
of the assigned treatment plans, and within 1 month of the planned visit.  
 
• 
Stage 3 – Long-term follow-up with avoidance of a food 
o Monthly long-term follow-up phone calls/emails must occur between 7 days before and 7 days after the 
planned phone call/email. 
o Long-term follow-up visits must occur between 1 month before and 1 month after the planned visit. 
o End of study visits must occur after the participant has completed a minimum of 12 months on all three 
of the assigned treatment plans, and within 1 month of the planned visit.  
 
• 
Stage 3 – Rescue OIT for a food 
o For participants transitioning from Stage 1 OLE or Stage 2 who require an IDE Visit: 
 
The IDE Visit must occur no later than 14 days after the last DBPCFC Visit in Stage 1 OLE or Stage 
2. 

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 
Omalizumab/placebo for omalizumab or open label omalizumab injection visits for every 2-week 
dosing frequency must occur between 4 days before and 7 days after the planned visit.  
 
Omalizumab/placebo for omalizumab or open label omalizumab injection visits for every 4- 
week dosing frequency must occur between 7 days before and 7 days after the planned visit. 
 
The Initial Dose Build-Up Visit must occur no later than 2 days after the planned visit. 
o For participants transitioning from Stage 1 OLE or Stage 2 who do not require an IDE Visit and will enter 
directly in the build-phase of Stage 3 rescue OIT: 
 
The Initial Dose Build-Up Visit must occur no later than 14 days after the last DBPCFC Visit in 
Stage 1 OLE or Stage 2. 
o Dose Build-Up Visits must occur between 4 days before and 7 days after the planned visit. 
o Initial Maintenance Dose Visit must occur between 4 days before and 7 days after the planned visit. 
o For participants who reach a planned target dose of ≥375 mg of food protein allowing transition to 
dietary consumption, phone calls/emails at two weeks after the Initial Maintenance Dose Visit must 
occur between 3 days before and 7 days after the planned phone call/email. 
o Follow-Up Maintenance Dose Visits must occur between 7 days before and 7 days after the planned 
visit. 
o For participants transitioning to dietary consumption for a food(s) after the first Follow-Up Maintenance 
Dose Visit, refer to the Visit Windows for Long-Term Follow-Up with Dietary Consumption of a Food. 
o End of study visits must occur after the participant has completed a minimum of 12 months on all three 
of the assigned treatment plans, and within 1 month of the planned visit.  
 
• 
Safety Labs 
o For Stage 1/Stage 1 OLE and Stage 2, safety labs every 3 months must be obtained between 14 days 
before and 14 days after the planned visit. 
o For Stage 1/Stage 1 OLE, Stage 2, and Stage 3 – Rescue OIT (IDE Visit and Dose Build-Up Visits), urine 
pregnancy tests every month must be taken between 7 days before and 7 days after the planned visit. 
9 Laboratory Research Assays 
 Biomarker Assays 
9.1.1 
Measurement of Food-Specific IgE, IgG4, and IgA 
Food-specific IgE is a pre-requisite for food allergy. However, the presence of circulating food-specific IgE is not 
always a reliable marker of true food allergy and IgE antibodies (Abs) to specific allergen components are likely a 
more reliable indicator of food allergy.31,32 In contrast to IgE, IgG4, and IgA Abs specific for food allergens may be 
protective. Food- and component-specific IgG, especially IgG4, Abs have been consistently shown to increase with 
OIT and there is evidence that the ratio of food allergen-specific IgG4:IgE may be a useful predictor of therapy 
outcome.33-35 Food-specific IgA may also be a potentially useful biomarker of OIT success and is worthy of further 
investigation.36 While the mechanisms of protection of IgG4 and IgA are incompletely understood, IgG inhibits 
basophil responses in vitro and may function as a protective “blocking antibody” in vivo.37 Levels of food-specific IgE, 
IgG4, and IgA and, where relevant, component-specific Abs will be measured to determine their correlation with 
clinical and mechanistic outcomes following treatment with omalizumab or omalizumab-facilitated OIT. 

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The Central Biomarker Facility at the University of North Carolina at Chapel Hill (UNC-CH) will conduct the following 
assays on participants at specified timepoints for each stage of the protocol (the total free IgE assay will be 
conducted by Genentech): 
• 
Total IgE 
• 
Total free IgE 
• 
Food allergen-specific IgE 
• 
Food allergen-specific IgG4 
• 
Food allergen-specific IgA 
• 
IgG4/IgE ratios 
9.1.2 
Basophil Activation Test 
Basophils are circulating CD203c+ CD123+ lineage marker (CD3, CD19, CD14, and CD41) negative granulocytes that 
can release histamine and other mediators of allergic inflammation. IgE binds to basophils via the FcεRI receptor and 
cross-linking of the IgE/FcεRI complex by allergen causes the basophil to degranulate. Several groups have used the 
basophil activation test (BAT) assay to show that basophil reactivity to allergen decreases during the course of 
OIT33,34,38,39 and therefore may be a useful biomarker of responsiveness to OIT. Also, in a small study of omalizumab 
treatment for peanut allergy, basophil activation and high peanut to total IgE ratio were associated with treatment 
success.10,40 BAT assays capture functional information about the level of IgE and the activation potential of these 
circulating effector cells. BAT assays are predictive of clinical reactivity to peanut (allergic versus sensitized)41 and are 
predictive of various features of clinical response such as threshold, severity, and response to baked egg or milk.42-45  
Basophil activation is typically studied in whole blood BAT assays with several doses of allergen (1000 ng/mL, 100 
ng/mL, 10 ng/mL, and 1 ng/mL) and positive and negative controls and is quantitated by measuring the increased 
surface expression of CD63 and CD203c. For BAT assays, blood will be shipped overnight from the CRUs to the 
designated laboratory. Results of the BAT assays will be correlated with clinical and mechanistic study outcomes, 
where appropriate. 
 Mechanistic Studies 
9.2.1 
Predicting the Response to Omalizumab through High Dimensional Profiling of Basophil Activation (Stage 1 
and Stage 2, Peanut Response) 
Rationale: As described above, BAT assays are typically performed using flow cytometry with two markers of 
activation, CD63 and CD203c. However, basophils are heterogeneous46,47 and it is hypothesized that a higher 
resolution analysis of their activation will be more predictive/informative of clinical response in the context of food 
allergy. Mass cytometry by time of flight (CyTOF) has been used to profile the peripheral blood response to peanut.48 
A combination of surface markers (CD63, CD203c, CD164, and HLA-DR) and intracellular signaling molecules (MAP 
kinases, CREB, mTOR, and STAT signaling pathways) can identify cells activated in peripheral blood in response to 
allergen or IgE cross-linking. Basophils demonstrate a range of activation, including signaling in the absence of surface 
degranulation. Studies will be performed using samples from Stage 1 and Stage 2 participants to test the hypothesis 
that high dimensional analysis of peanut-specific and IgE-induced basophil activation will be predictive of the clinical 
response to omalizumab or omalizumab-facilitated OIT. 

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Approach: Heparinized peripheral blood will be used for CyTOF analysis of basophils. Whole blood will be collected at 
the following times: 
• 
First Screening DBPCFC Visit; 
• 
First DBPCFC Visit at the end of Stage 1; 
• 
IDE Visit during Stage 2; 
• 
Initial Maintenance Dose Visit during Stage 2; and 
• 
First DBPCFC Visit at the end of Stage 2. 
For each stage and at each CRU, lyophilized tubes containing a range of peanut antigen doses (a combination of 
purified Ara h 1, Ara h 2, and Ara h 3 at 100, 10, or 1 ng/mL) or anti-IgE doses (1, 0.2 µg) together with anti-CD63, -
CD203c, and -CD164 Abs will be used to do novel two-step BAT assays. Details can be found in the MOP. 
9.2.2 
Assessment of the Impact of Omalizumab Treatment in Stages 1 and 2 on Dendritic Cells and Peanut-Specific 
CD4+T Cells 
Rationale: Preliminary studies using high dimensional mass cytometry to assess immune response suggest a 
dampening of the Th2 response in successfully desensitized study participants. While the effects of OIT on allergen-
specific CD4+ T cells have been studied extensively and while it is known that omalizumab reduces the number of 
FcεRI on dendritic cells (DCs),49 relatively little is known about the effects of omalizumab therapy alone or 
omalizumab-facilitated OIT on DC subsets and their interactions with CD4+ T cells. The hypothesis to be tested in this 
study is that omalizumab treatment will downregulate additional Th2-polarizing molecules, including OX40L and TIM-
4, on DC subsets and increase expression of FcγRIIb, which in turn will result in a dampened Th2 response, as 
assessed through downregulation of interleukin-4 and interleukin-9 production and an increased allergen-specific 
IgG4:IgE ratio. DC subset-T cell cross talk will be compared in participants treated with omalizumab versus placebo 
(Stage 1) and omalizumab-facilitated OIT vs omalizumab monotherapy (Stage 2).  
Approach: High dimensional mass cytometry and functional assays with a focus on the response to peanut will be 
performed. Whole blood from participants will be collected at the following times:  
• 
First Screening DBPCFC Visit; 
• 
First DBPCFC Visit at the end of Stage 1; 
• 
IDE Visit during Stage 2; 
• 
Initial Maintenance Dose Visit during Stage 2; and 
• 
First DBPCFC Visit at the end of Stage 2. 
Peripheral blood mononuclear cells (PBMCs) and plasma will be isolated and stored frozen. Thawed PBMCs will be 
analyzed to assess any changes in frequency and/or function of DC and T cell subsets over the course of therapy. 
Statistically significant findings from mass cytometry will be validated through functional assays involving DC-T 
effector cell-Treg coculture. 

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 Other Biosamples/Assays 
Blood for PK sampling will be collected to evaluate serum omalizumab concentrations during treatment with 
omalizumab and omalizumab-facilitated OIT. 
Stool samples will be collected and stored for future analysis aiming at, but not limited to, assessing the effects of the 
gut microbiome on OIT responses and/or the effects of OIT on the microbiome. Studies may also be conducted to assess 
other biologic outcomes that may be related to food allergy and the effects of the study’s interventions. 
Urine samples will be collected and stored for future analysis aiming at, but not limited to, assessing metabolomic 
changes related to treatment with omalizumab and omalizumab-facilitated OIT. 
Saliva will be collected and stored for future analysis aiming at, but not limited to, assessing food-specific IgA changes in 
relation to OIT.  
SPT will be performed in order to assess changes in wheal size related to treatment with omalizumab and omalizumab-
facilitated OIT.  
10 Biospecimen Storage 
During the consent process, a participant and/or parent/legal guardian will be asked to give permission for long-term 
storage and future use of samples. All samples will be stored at the Central Biomarker Facility at UNC-CH. The following 
specimens will be stored: 
• 
Serum 
• 
Plasma 
• 
PBMCs 
• 
Stool 
• 
Urine 
• 
Saliva 
Plasma and PBMCs will also be stored at Stanford University. 
Instructions for sample preparation, handling, storage, and shipping will be defined in the MOP. The PI will be 
responsible for knowing about and observing all the regulations for classification, packaging and labeling, permits and 
authorizations, personnel training for shipment of biological and hazardous materials required for the conduct of this 
study. 
11 Criteria for Participant and Study Completion and Premature Study Termination 
 Participant Completion 
A participant will be considered to have completed: 
• 
Stage 1 when the participant has completed all four blinded OFCs comprising the DBPCFC at the end of Stage 1. 

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• 
Stage 1 OLE when the participant has completed all four blinded OFCs comprising the DBPCFC at the end of 
Stage 1 OLE. 
• 
Stage 2 when the participant has completed all four blinded OFCs comprising the DBPCFC at the end of Stage 2. 
• 
Stage 3 when the participant has completed the first six-month visit in Stage 3. 
 Participant Stopping Rules and Withdrawal Criteria 
11.2.1 Automatic Stopping Rules 
A participant will be prematurely terminated from the study for the following reasons: 
1. The participant and/or parent/legal guardian elects to withdraw consent/assent from all future study activities, 
including follow-up. 
2. The participant is “lost to follow-up” as defined in the MOP (i.e., no further follow-up is possible because 
attempts to reestablish contact with the participant have failed). 
3. The participant dies. 
4. The participant becomes pregnant. 
5. The participant experiences one CoFAR Grade 4 allergic reaction related to omalizumab/placebo for omalizumab 
or Multi-allergen OIT/placebo for Multi-allergen OIT (see Table 12.4.1.2). 
6. The participant develops biopsy-documented EoE. 
7. The participant is an IDE failure or treatment failure in Stage 2. 
8. The participant does not complete all four blinded OFCs comprising the DBPCFC at the end of Stage 1. 
9. The participant does not complete all four blinded OFCs comprising the DBPCFC at the end of Stage 1 OLE. 
10. The participant does not complete all four blinded OFCs comprising the DBPCFC at the end of Stage 2. 
11. The participant develops a confirmed clinically significant laboratory abnormality (i.e., transaminitis [see Section 
6.4.1.4], thrombocytopenia [see Section 6.4.1.5]) related to study drug or study procedure.  
12. The participant’s continued participation in the study is assessed by the PI to no longer be in the best interest of 
the participant or to jeopardize the safe conduct of the study. 
11.2.2 Discretionary Stopping Rules Requiring DSMB Review 
Per the PI’s discretion and in conjunction with the Protocol Chair(s) and DAIT/NIAID Medical Monitor, a participant may 
be prematurely terminated from the study if: 
1. The participant experiences a CoFAR Grade 4 AE (see Table 12.4.1.2) related to an OFC. 
However, in the circumstance that the PI, Protocol Chair(s), and DAIT/NIAID Medical Monitor deem it appropriate for 
the affected participant to continue in the study, the CoFAR Grade 4 AE will be reviewed by the NIAID Allergy and 
Asthma DSMB prior to the final participant disposition determination. 
11.2.3 Discretionary Stopping Rules 
Per the PI’s discretion and in conjunction with the Protocol Chair(s) and DAIT/NIAID Medical Monitor, a participant may 
be prematurely terminated from the study for the following reasons: 
1. One occasion in which the participant experiences a Grade 4 AE (see Section 12.4.1.1 or Table 12.4.1.2). 
2. The participant experiences recurrent symptoms that may or may not require medical intervention but prevent 
the participant from tolerating the study therapy regimen. 
3. The participant develops poor control or persistent activation of secondary atopic disease (e.g., AD, asthma). 

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4. The participant starts taking a prohibited medication (see Section 7.3), with no alternative medications available 
per the prescribing doctor. 
5. The participant misses more than two consecutive doses of omalizumab or placebo for omalizumab in any stage 
of the study. 
6. Non-adherence (non-compliance) with home OIT dosing, as indicated by missing >8 consecutive days of OIT 
dosing on any one occasion, or three consecutive days of OIT dosing on five or more occasions that was not 
directed by the PI for clinically indicated reasons. 
7. Medically indicated circumstances (e.g., as part of the treatment for intercurrent AEs) that require the 
participant to miss OIT dosing for >8 consecutive days. 
 Participant Replacement 
Participants will not be replaced.  
 Follow-up after Early Study Withdrawal 
A participant who withdraws or is withdrawn at any time in the study will attend an Early Discontinuation Visit (see 
Section 8.9). If a participant refuses to come to the CRU for an Early Discontinuation Visit, assessments that do not 
require in-person evaluation may be conducted by phone. To the extent possible, a participant will be monitored for 
safety until they come back for their Early Discontinuation Visit and for at least 30 days after the Early Discontinuation 
Visit. 
 Study Stopping Rules 
If any of the stopping rules listed below are met, study enrollment will be suspended, IDE Visits will be suspended, and 
dose escalation of OIT during Stage 2 and 3 will be stopped pending expedited review of all pertinent data by the NIAID 
Allergy and Asthma DSMB. Depending on the stopping rule, additional study procedures (as outlined below) will also be 
suspended pending expedited review of all pertinent data. 
• 
Any death related to OIT dosing, an OFC, omalizumab, or placebo for omalizumab: If this stopping rule is met, 
all OIT maintenance visits, all OFCs, all open feedings, and all omalizumab or placebo for omalizumab injections 
will be suspended. 
• 
More than three participants requiring more than two injections of epinephrine during a single OIT dosing: If 
this stopping rule is met, no additional study procedures aside from those outlined above will be suspended 
and all omalizumab or placebo for omalizumab injections will continue to be received. 
• 
More than one participant requiring more than two injections of epinephrine during a single 
omalizumab/placebo for omalizumab injection: If this stopping rule is met, all omalizumab or placebo for 
omalizumab injections will be suspended. 
• 
More than one participant with more than one CoFAR Grade 4 AE related to OIT dosing (see Table 12.4.1.2): If 
this stopping rule is met, all OFCs and all open feedings will be suspended but all OIT maintenance visits and all 
omalizumab or placebo for omalizumab injections will continue to be received. 
• 
More than three CoFAR Grade 4 AEs related to an OFC (see Table 12.4.1.2): If this stopping rule is met, all OFCs 
and all open feedings will be suspended but all OIT maintenance visits and all omalizumab or placebo for 
omalizumab injections will continue to be received. 
• 
5% or more of the randomized participants have been diagnosed with biopsy-proven EoE, as assessed on a 
rolling basis during regular AE reviews, and the total number of cases of EoE is at least five: If this stopping rule 

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is met, no additional study procedures aside from those outlined above will be suspended and all omalizumab 
or placebo for omalizumab injections will continue to be received. 
12 Safety Monitoring and Reporting 
 Overview 
This section defines the types of safety data that will be collected under this protocol and outlines the procedures for 
appropriately collecting, grading, recording, and reporting those data. AEs that are classified as serious according to the 
definition of health authorities must be reported promptly (see Section 12.6.1) to the IND Sponsor, DAIT/NIAID. 
Appropriate notifications will also be made to PIs, IRB, and health authorities, as needed.  
Information in this section complies with International Conference on Harmonisation (ICH) Guideline E2A: Clinical Safety 
Data Management: Definitions and Standards for Expedited Reporting, ICH Guideline E-6: Guideline for Good Clinical 
Practice (GCP), 21CFR Parts 312 and 320, and applies the standards set forth in the National Cancer Institute (NCI), 
Common Terminology Criteria for Adverse Events (CTCAE), Version 5.0. 
 Definitions 
12.2.1 Adverse Event 
Any untoward or unfavorable medical occurrence associated with the use of an intervention in humans, whether or 
not considered intervention related (see 21 CFR 312.32(a)).  
An AE can be any unfavorable and unintended sign, symptom, or disease temporally associated with the use of a 
drug, and does not imply any judgment about causality. An AE can arise with any use of the drug (e.g., off-label use or 
in combination with another drug) and with any route of administration, formulation, or dose, including an overdose. 
Pre-existing diseases or conditions present or detected during the first time an assessment or laboratory 
measurement is done during the Screening Visit will be considered AEs only if they change in severity of grade from 
that timepoint. Vitals or laboratory measurements repeated for confirmation of the pre-existing disease or condition 
are not considered a different timepoint. 
All symptoms or events, with the exception of oropharyngeal pruritus, that occur within two hours and that are 
expected according to the Protocol and related to administration of Multi-allergen OIT/placebo for Multi-allergen OIT 
will be recorded as an AE and will also be identified as an OIT dosing reaction on the AE eCRF. Any symptom or event, 
with the exception of oropharyngeal pruritus, that occurs more than two hours after Multi-allergen OIT/placebo for 
Multi-allergen OIT dosing will be recorded as an AE but will not be identified as an OIT dosing reaction on the AE 
eCRF. Since oropharyngeal pruritus (including lip pruritus) is expected in many participants and is not considered 
clinically significant, it will not be captured as an AE unless it is bothersome enough to require treatment with more 
than antihistamines; however, oropharyngeal pruritus will be documented on the eCRF as an OIT dosing reaction if it 
occurs within two hours of administration of Multi-allergen OIT/placebo for Multi-allergen OIT. 
For the study-mandated procedures/requirements below, only the signs and symptoms listed under each procedure 
will be considered outside normal range and will be recorded as an AE. For all other study-mandated 
procedures/requirements, all AEs will be recorded. 
Skin Prick Test 
The following events related to SPT will be considered AEs if they occur within 48 hours of the SPT: 

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• 
Prolonged (>24 hours) pruritus at the SPT site 
• 
Induration/swelling at the SPT site larger than 10 mm in diameter and lasting more than 24 hours 
• 
Allergic or anaphylactic reaction that requires the use of rescue medications, detailed in Section 7.4 
Blood Draw 
The following events related to a blood draw procedure will be considered AEs: 
• 
Syncope/vasovagal events 
• 
Bruising at the puncture site larger than 2 cm diameter 
• 
Bleeding from the puncture site lasting more than 30 minutes 
• 
Induration/swelling at the puncture site larger than 2 cm diameter 
• 
Allergic reaction to local skin anesthetic that requires rescue medications 
• 
Infection at the puncture site 
Laboratory Results 
An abnormal laboratory value will only be considered an AE if the value is clinically significant (i.e., changes in 
therapy or monitoring are implemented as a result of the event).  
Oral Food Challenge 
The following events related to an OFC will be considered AEs: 
• 
Severe dose-limiting symptoms as defined by Appendix 1 
As moderate dose-limiting symptoms as defined by Appendix 1 is the usual threshold at which an OFC will be 
considered positive to the food, almost every positive OFC will be recorded as an AE, which will dilute the true 
incidence of AEs for this trial. To avoid artificially increasing the AE incidence from OFCs, only severe dose-limiting 
symptoms as defined by Appendix 1 will be considered AEs. However, all reactions that occur during an OFC will be 
captured in the appropriate eCRF. 
Stage 3 Dosing with Dietary Food Equivalents 
The following events related to reactions following ingestion of food equivalents will be considered AEs: 
• 
Symptoms or events, with the exception of oropharyngeal pruritus, that are bothersome enough to require 
treatment with more than antihistamines. Oropharyngeal pruritus will not be considered an AE. 
12.2.2 Adverse Event of Special Interest 
Adverse Event of Special Interest (AESI) is an AE (serious or nonserious) that is one of scientific and medical concern 
specific to the IND Sponsor’s product or program, for which ongoing monitoring and rapid communication by the PI 
to the IND Sponsor can be appropriate. Such an event might warrant further investigation in order to characterize 
and understand it. Depending on the nature of the event, rapid communication by the trial Sponsor to other parties 
(e.g., regulators) might also be warranted (based on CIOMS VI and ICH E2F). 

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For Xolair® (omalizumab), AESIs have been identified and will be recorded by the CRUs and reported to the IND 
Sponsor, DAIT/NIAID. PIs should use their clinical judgment to identify the following events: 
• 
Suspected anaphylactic reactions to Xolair® (omalizumab), identified based on Sampson’s criteria (see 
Appendix 10) 
• 
Cases of potential drug-induced liver injury that include an elevated ALT or AST in combination with either 
an elevated bilirubin or clinical jaundice, as defined by Hy’s Law or Section 6.4.1.4 
• 
Suspected transmission of an infectious agent by the study drug, as defined below: 
o Any organism, virus, or infectious particle (e.g., prion protein transmitting transmissible spongiform 
encephalopathy), pathogenic or non-pathogenic, is considered an infectious agent. A transmission 
of an infectious agent may be suspected from clinical symptoms or laboratory findings that indicate 
an infection in a patient exposed to a medicinal product. This term applies only when a 
contamination of the study drug is suspected. 
• 
Any occurrences of overdose, medication errors, drug abuse and drug misuse related to IP administration. 
12.2.3 Suspected Adverse Reaction 
Any AE for which there is a reasonable possibility that the investigational drugs (Xolair® (omalizumab) and/or Multi-
allergen OIT) or investigational study therapy regimen caused the AE. For the purposes of safety reporting, 
‘reasonable possibility’ means there is evidence to suggest a causal relationship between the drug and the AE. A 
Suspected Adverse Reaction (SAR) implies a lesser degree of certainty about causality than adverse reaction, which 
means any AE caused by a drug (21 CFR 312.32(a)). 
12.2.4 Unexpected Adverse Event  
An “Unexpected AE” or “Unexpected SAR” means an AE or SAR which is considered “unexpected” because it is not 
listed in the Reference Safety Information or in the Investigator Brochure or is not listed at the specificity or severity 
that has been observed or is not consistent with the risk information described in the general investigational plan, 
protocol, or elsewhere in the current application. Unexpected AEs or Unexpected SARs are further defined in 21 CFR 
312.32.  
12.2.5 Serious Adverse Event 
An AE or SAR is considered “serious” if, in the view of the PI or Sponsor, DAIT/NIAID, it results in any of the following 
outcomes (see 21 CFR 312.32(a)): 
• 
Death. 
• 
A life-threatening event: An AE or SAR is considered “life-threatening” if, in the view of either the PI or 
Sponsor, DAIT/NIAID, its occurrence places the participant at immediate risk of death. It does not include an 
AE or SAR that, had it occurred in a more severe form, might have caused death.  
• 
Inpatient hospitalization or prolongation of existing hospitalization. 
• 
Persistent or significant incapacity or substantial disruption of the ability to conduct normal life functions. 
• 
Congenital anomaly or birth defect.  

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• 
Important medical events that may not result in death, be life threatening, or require hospitalization may be 
considered serious when, based upon appropriate medical judgment, they may jeopardize the participant 
and may require medical or surgical intervention to prevent one of the outcomes listed above. 
Elective or pre-planned hospitalizations for a pre-existing condition or hospital admissions for the purposes of 
conducting protocol mandated procedures are not considered to be a Serious Adverse Event (SAE) unless prolonged 
due to complications. 
Injectable epinephrine may be used for both life threatening and non-life threatening allergic reactions. The use of 
epinephrine will not be considered an SAE if it is used to prevent the progression of non-life-threatening allergic 
reactions that occur during OFCs (see Section 7.4). The use of epinephrine will be considered an SAE if used for an 
allergic reaction that occurs during OIT dosing, omalizumab dosing, or an open feeding.  
 Pregnancy Reporting 
The PI shall be informed immediately of any pregnancy in a study participant or a partner of a study participant during 
the study. A pregnant participant shall be instructed to stop taking all study products. The PI shall counsel the participant 
and discuss the risks of continuing with the pregnancy and the possible effects on the fetus. Monitoring of the pregnant 
participant shall continue until the conclusion of the pregnancy. 
The PI shall report to the IND Sponsor, DAIT/NIAID, all pregnancies within 24 hours of becoming aware of the event 
using the Pregnancy eCRF. The pregnancy should not be reported on the Adverse Event eCRF. All pregnancies identified 
during the study shall be followed to conclusion. Follow-up information detailing the outcome of the pregnancy should 
be entered into the electronic data capture (EDC) system, reported to the IND Sponsor, DAIT/NIAID, it becomes 
available. When possible, similar information shall be obtained for a pregnancy occurring in a partner of a study 
participant. 
• 
Information requested about the delivery shall include: 
• 
Gestational age at delivery 
• 
Birth weight, length, and head circumference 
• 
Gender 
• 
Appearance, pulse, grimace, activity, and respiration (APGAR) score at 1 minute, 5 minutes, and 24 hours after 
birth, if available 
• 
Any abnormalities 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy complication or elective termination of a 
pregnancy for medical reasons must be reported as an SAE to the IND Sponsor as described in Section 12.6.1. In 
addition, if the pregnancy results in a congenital abnormality or birth defect, a separate SAE report must be submitted 
to the IND Sponsor, DAIT/NIAID, using the SAE reporting procedures described above. 
 Grading and Attribution of Adverse Events 
Baseline-emergent and treatment-emergent AEs for each stage of the study will be defined in the Statistical Analysis 
Plan (SAP).  

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12.4.1 Grading Criteria 
12.4.1.1 Grading of Non-Allergic Adverse Events 
The PI will grade the severity of all non-allergic AEs experienced by the study participants according to the 
Grading Table for Non-Allergic Adverse Events Version 2.0 (see Appendix 11). This grading table was based 
on the Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials and adapted to make it applicable for the population under study. The modifications were 
drawn from grading scales from NIAID’s Division of AIDS and Division of Microbiology and Infectious 
Diseases, the CTCAE Version 5.0, and the 2017 AAP updated Clinical Practice Guideline for Screening and 
Management of High Blood pressure in Children and Adolescents.50-55 
AEs will be graded on a scale from 1 to 5 according to the Grading Table for Non-Allergic Adverse Events 
Version 2.0: 
Grade 1 = Mild 
Grade 2 = Moderate 
Grade 3 = Severe 
Grade 4 = Life-Threatening 
Grade 5 = Death 
Abnormal laboratory evaluations should only be captured as an AE if the abnormal result is considered 
clinically significant (i.e., changes in therapy or monitoring are implemented as a result of the abnormal 
result).  
For clinically significant abnormal laboratory values, use the Grading Table for Non-Allergic Adverse Events 
Version 2.0. If a specific abnormal value is not listed in the table, the events should be graded using the 
general grading scale at the end of the table in Appendix 11. 
12.4.1.2 Grading of Systemic Allergic Reactions other than Local Reactions to Skin Prick Testing 
The PI will grade severity of systemic allergic reactions, other than local reactions to SPT, experienced by 
the study participants according to the criteria set forth in the CoFAR Grading Scale for Systemic Allergic 
Reactions Version 3.0 defined in Table 12.4.1.2. 
Table 12.4.1.2 CoFAR Grading Scale for Systemic Allergic Reactions Version 3.0 
Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Reaction involving one 
of the following organ 
systems in which the 
symptoms are mild: 
 
Cutaneous 
Generalized pruritus, 
generalized urticaria, 
flushing, angioedema 
 
Reaction involving two 
or more of the 
following organ 
systems in which the 
symptoms are mild: 
 
Cutaneous 
Generalized pruritus, 
generalized urticaria, 
flushing, angioedema 
 
Reaction involving one 
or more of the 
following organ 
systems: 
 
Lower respiratory 
Throat tightness, 
wheezing, chest 
tightness, dyspnea, 
cough that respond to 
short-acting 
Life-threatening 
reaction involving one 
or more of the 
following organ 
systems with or 
without other 
symptoms listed in 
Grades 1 to 3: 
 
 
Lower respiratory 
 Death 

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Grade 1 
Grade 2 
Grade 3 
Grade 4 
Grade 5 
Upper respiratory 
Rhinitis, cough 
unrelated to laryngeal 
edema or 
bronchospasm 
 
Conjunctival 
Injection/redness, 
itching, tearing 
 
GI  
Nausea, abdominal 
pain (no change in 
activity level), single 
episode of vomiting 
and/or single episode 
of diarrhea 
Upper respiratory 
Rhinitis, cough 
unrelated to laryngeal 
edema or 
bronchospasm 
 
Conjunctival 
Injection/redness, 
itching, tearing 
 
GI 
Nausea, abdominal 
pain (no change in 
activity level), single 
episode of vomiting, 
and/or single episode 
of diarrhea 
 
OR 
 
Reaction involving at 
least one of the 
following organ 
systems in which the 
symptoms are 
moderate: 
 
Cutaneous 
Generalized pruritus, 
generalized urticaria, 
flushing, angioedema 
 
Upper respiratory 
Rhinitis, cough 
unrelated to laryngeal 
edema or 
bronchospasm 
 
Conjunctival 
Injection/redness, 
itching, tearing 
 
GI 
Nausea, abdominal 
pain (with change in 
activity level), two 
episodes of vomiting 
and/or diarrhea 
 
bronchodilator 
treatment (including 
IM epinephrine) with 
or without 
supplemental oxygen 
GI 
Severe abdominal 
pain, more than two 
episodes of vomiting 
and/or diarrhea 
Throat tightness with 
stridor, wheezing, 
chest tightness, 
dyspnea, or cough 
associated with a 
requirement for 
supplemental oxygen 
and refractoriness to 
short-acting 
bronchodilator 
treatment (including 
IM epinephrine)1 
 
OR 
 
Respiratory 
compromise requiring 
mechanical support 
Cardiovascular 
Reduced BP with 
associated symptoms 
of end-organ 
dysfunction (e.g., 
hypotonia [collapse], 
syncope) defined as: 
• Children: low 
systolic BP (age 
specific2) or >30% 
decrease in systolic 
BP 
• Adults: systolic BP of 
less than 90 mmHg 
or >30% decrease 
from baseline 
1. Examples of refractoriness could include continuous albuterol nebulizer or epinephrine IV infusion or more than three IM epinephrine 
injections. 
2. Low systolic BP for children is defined as: less than 70 mmHg from 1 month to 1 year of age, less than (70 mmHg + [2 x age]) from 1 to 
10 years of age, and less than 90 mmHg from 11 to 17 years of age. 

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12.4.1.3 Grading of Local Reactions to Skin Prick Testing 
Local reactions to skin prick testing will be graded by the criteria set forth in the Grading Scale for Local 
Reactions to Skin Prick Testing Version 1.0 defined in Table 12.4.1.3. 
Table 12.4.1.3 Grading Scale for Local Reactions to Skin Prick Testing Version 1.01 
Grade 1 
Grade 2 
Grade 3 
Meets the minimum criteria listed 
in Section 12.2.1, but requiring no 
medication other than topical 
corticosteroids or antihistamines. 
Interfering with usual daily 
activities or sleep and requiring 
oral steroids. 
 
Requiring a visit to a health care 
provider for treatment 
 
1. All systemic reactions due to skin prick testing that meet the minimum criteria outlined in Section 12.2.1 should be graded 
according to Table 12.4.1.2 CoFAR Grading Scale for Systemic Allergic Reactions Version 3.0. 
12.4.2 Attribution Definitions 
The relationship, or attribution, of an AE to the study therapy regimen or study procedures will initially be 
determined by the PI and recorded on the appropriate AE/SAE eCRF. Final determination of attribution for safety 
reporting will be determined by Sponsor, DAIT/NIAID. The relationship of an AE to study therapy regimen or 
procedures will be determined using the descriptors and definitions provided in Table 12.4.2.  
Table 12.4.2 Attribution of Adverse Events 
Code 
Descriptor 
Relationship (to primary investigational product and/or 
other concurrent mandated study therapy or study 
procedure) 
UNRELATED CATEGORY 
1 
Not Related 
The AE is clearly not related; there is insufficient evidence to 
suggest a causal relationship. 
RELATED CATEGORIES 
2 
Possibly 
Related 
The AE has a reasonable possibility to be related; there is 
evidence to suggest a causal relationship. 
3 
Related 
The AE is clearly related. 
 Collection and Recording of Adverse Events 
12.5.1 Collection Period 
AEs will be collected from the time of consent until a participant completes study participation or until at least 30 
days after he/she prematurely withdraws (without withdrawing consent) or is withdrawn from the study. 
12.5.2 Collecting Adverse Events 
AEs (including SAEs) may be discovered through any of these methods: 
• 
Observing the participant 
• 
Interviewing the participant (e.g., using a checklist, structured questioning, diary, etc.) 
• 
Receiving an unsolicited complaint from the participant 
• 
In addition, an abnormal value or result from a clinical or laboratory evaluation can also indicate an AE, as 
defined in Section 12.4 

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12.5.3 Recording Adverse Events 
Throughout the study, the PI will record all AEs and SAEs as described previously (Section 12.2) on the appropriate 
AE/SAE eCRF regardless of the relationship to study therapy regimen or study procedure. 
Once recorded, an AE/SAE will be followed until it resolves with or without sequelae, or until the end of study 
participation, or until at least 30 days after the participant prematurely withdraws (without withdrawing consent)/or 
is withdrawn from the study, whichever is clinically appropriate. 
 Reporting of Adverse Events, Serious Adverse Events, and Pregnancies 
12.6.1 Reporting of Serious Adverse Events, Adverse Events of Special Interest, and Pregnancies to the IND Sponsor 
This section describes the responsibilities of the PI to report SAEs, AESIs, and pregnancies to the IND Sponsor, 
DAIT/NIAID. Timely reporting of AEs is required by 21 CFR and ICH E6 guidelines. 
The PI shall report all pregnancies within 24 hours of becoming aware of the event as per the reporting process 
described in Section 12.3. 
PIs will report all SAEs and/or AESIs (see Sections 12.2), regardless of relationship or expectedness, within 24 hours of 
discovering the event. 
For SAEs and AESIs, all requested information on the AESI/SAE eCRF will be provided. However, unavailable details of 
the event will not delay submission of the known information. Initial AESI/SAE eCRFs should include as much 
information as possible, but at a minimum must include the following: 
• 
AE term 
• 
Relationship to IP and whether “OIT dosing reaction.” 
• 
Relationship to study procedure  
• 
Reason why the event is serious or AESI  
• 
Supplementary eCRF pages that are current at the time of AESI/SAE reporting: medical history, concomitant 
medications, demographics, IP administration 
As additional details become available, the AESI/SAE eCRF will be updated and submitted. During the course of the 
study, the site PI will apply an e-signature to SAEs, AESIs, and major protocol deviations within the RAVE EDC system 
on an ongoing basis. For any SAE that meets criteria for expedited reporting, the PI is to sign off electronically within 
the RAVE EDC system within 24 hours of awareness.  
12.6.2 Reporting to the FDA 
After an AE requiring 24-hour reporting (see Section 12.6.1) or pregnancy is submitted by the PI and assessed by the 
IND Sponsor, DAIT/NIAID, the IND Sponsor must report the event to the FDA using one of two categories. 
12.6.2.1 Expedited Safety Reporting  
This category applies if the safety event is classified as one of the following: 
• 
Serious and Unexpected Suspected Adverse Reaction [SUSAR] (see Sections 12.2.3 and 12.2.4 and 21 
CFR 312.32I(1)).  

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The IND Sponsor, DAIT/NIAID, shall report any SAR that is both serious and unexpected. The 
IND Sponsor, DAIT/NIAID, shall report an AE as a SAR only if there is evidence to suggest a 
causal relationship between the study drug and the AE, such as: 
1. A single occurrence of an event that is uncommon and known to be strongly 
associated with drug exposure  
2. One or more occurrences of an event that is not commonly associated with drug 
exposure, but is otherwise uncommon in the population exposed to the drug  
3. An aggregate analysis of specific events observed in a clinical trial (such as known 
consequences of the underlying disease or condition under investigation or other 
events that commonly occur in the study population independent of drug therapy) 
that indicates those events occur more frequently in the drug treatment group than 
in a concurrent or historical control group 
• 
Any findings from studies that suggests a significant human risk  
The IND Sponsor, DAIT/NIAID, shall report any findings from other clinical, epidemiological 
studies, pooled analysis of multiple studies, or any finding from animal or in vitro testing (e.g. 
mutagenicity, teratogenicity, carcinogenicity) that suggest a significant risk in humans exposed 
to the drug that would result in a safety-related change in the protocol, informed consent, 
investigator brochure, package insert, or other aspects of the overall conduct of the study. 
 
• 
AESI of anaphylaxis associated with Xolair® (omalizumab)  
The IND Sponsor, DAIT/NIAID, shall report any suspected reactions to Xolair® (omalizumab). 
The IND Sponsor, DAIT/NIAID, shall notify the FDA of the fatal or life-threatening SUSAR(s) and IND Safety 
Reports within 7 and 15 calendar days of IND Sponsor awareness, respectively. The IND Sponsor will 
provide the IND Safety Reports to the Investigational Drug Product Manufacturers and all participating PIs. 
12.6.2.2 Standard Reporting (report in the IND Annual Report) 
All AEs as per 21 CFR 312.33, as well as all pregnancies and use of epinephrine for both life-threatening and 
non-life threatening reactions, will be recorded by the CRUs, reported to the IND Sponsor, and included in 
the IND Annual Report submitted to the FDA by the IND Sponsor. 
12.6.3 Reporting of Adverse Events to IRBs 
All investigators shall report AEs and SAEs in a timely fashion to their local and single IRB in accordance with applicable 
regulations and guidelines. 
12.6.4 Reporting of Other Safety Information 
A PI shall promptly notify the IND Sponsor, DAIT/NIAID, and the SCCC via email when an “unanticipated problem 
involving risks to participants or others” is identified, which is not otherwise reportable as an AE. 
 Review of Safety Information 
12.7.1 Medical Monitor Review 
The DAIT/NIAID Medical Monitor shall receive monthly reports from the SCCC and the Clinical Data and Safety 
Monitoring Center (CDSMC), compiling new and accumulating information on AEs, SAEs, and pregnancies recorded 
by the CRUs on appropriate eCRFs. 

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In addition, the DAIT/NIAID Medical Monitor shall review and make decisions on the disposition of the SAE and 
pregnancy reports received by the SCCC (see Sections 12.6.1 and 12.3). 
12.7.2 DSMB Review 
12.7.2.1 Planned DSMB Reviews 
12.7.2.1.1 Regular Reviews of Study Progress and Safety  
The NIAID Allergy and Asthma DSMB shall review safety data twice per year during planned DSMB 
Meetings. Data for the planned safety reviews will include, at a minimum, a listing of all reported AEs 
and SAEs that is created by the SCCC with support from the CDSMC. 
12.7.2.1.2 Interim Analysis to Determine whether Stage 1 will be Curtailed due to Efficacy of Omalizumab over 
Placebo for Omalizumab for the primary and key secondary outcomes 
The independent DSMB will review the results of the interim analysis (see Sections 3.1, 13.5.3,  13.5.4, , 
and 13.6 for details) and make a recommendation to the DAIT/NIAID about whether or not to stop stage 
1 of the study for efficacy.  The DAIT/NIAID will evaluate this recommendation and communicate a final 
decision to the study team.   
12.7.2.2 Ad hoc DSMB Reviews  
In addition to the pre-scheduled data reviews and planned safety monitoring, the NIAID Allergy and 
Asthma DSMB may be called upon for ad hoc reviews when an event occurs that is of sufficient concern 
to the DAIT/NIAID Medical Monitor and/or Protocol Chair or Co-Chair to warrant a DSMB review. The 
DSMB will be notified within 24-48 hours by the DAIT/NIAID Medical Monitor and will promptly review 
any event that potentially impacts safety at the request of the Protocol Chair or Co-Chair or DAIT/NIAID 
Medical Monitor or any occurrence that meets the definition of the participant stopping rules requiring 
DSMB review defined in Section 11.2 or study stopping rules defined in Section 11.5. After review of the 
data, the DSMB will make recommendations regarding study conduct and/or continuation. 
The DSMB will also review each Xolair® (omalizumab)-associated anaphylactic reaction as identified by 
the PIs to confirm that the event: a) satisfies the criteria for anaphylactic reaction, and b) is associated 
with Xolair® (omalizumab). 
12.7.2.2.1 Temporary Suspension of Trial for Ad hoc DSMB Review for Reasons Other than a Stopping Rule  
The DAIT/NIAID Medical Monitor may temporarily suspend the trial at any time at his/her discretion. 
The DAIT/NIAID Medical Monitor will determine if a temporary halt in screening, enrollment and/or 
drug dosing/updosing should be implemented pending the review.  
13 Statistical Considerations and Analytical Plan 
 Overview  
The efficacy and safety of omalizumab as monotherapy and as an adjunct therapy to Multi-allergen OIT will be studied 
using a Phase III, randomized, double-blind, placebo-controlled, multi-site, and multi-stage trial of omalizumab and 
Multi-allergen OIT in children and adults, ages 1 year to less than 56 years, with multi-food allergy. All analyses specified 
in this document will be performed for participants aged less than 18 years and repeated in all participants aged 1 year 
to less than 56 years. Detailed specifications of the statistical methods will be described in the SAP. The SAP will be 

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reviewed by health authorities and finalized prior to database lock. To allow for incorporation of health authority input, 
the statistical methods in the SAP may differ from and will supersede those described in this document. 
 Endpoints 
Please refer to Section 3.2, 3.3, and 3.4 which provide definitions of the primary, secondary, and exploratory endpoints. 
For endpoints based on the results of DBPCFCs, if a participant has dose-limiting symptoms to any dose during the 
blinded OFC to placebo, the participant will be considered a ‘failure’ at every dose of the blinded OFCs to peanut and 
two other participant-specific foods comprising the rest of the DBPCFC. 
Appendix 12 provides a mapping of the endpoints that will be used to address each of the objectives given in Section 
2.2, 2.3, and 2.4 as well. 
 Missing Data 
If a participant does not complete a DBPCFC at the end of Stage 1, Stage 1 OLE, or Stage 2 because the participant is 
withdrawn from the study prior to the DBPCFC (see Section 11.2) or the participant misses the visit where a blinded OFC 
would be performed, the participant will be considered a ‘failure’ for all efficacy endpoints based on the blinded OFCs 
that were missed. For these participants, the maximum tolerated dose without dose-limiting symptoms will also be set 
to 0 mg. 
If a participant stops an OFC before consuming the final dose and does not have dose-limiting symptoms on the last 
dose consumed, the participant will be considered a: 
• 
‘Success’ if the participant consumed the dose that is used to define the efficacy endpoint; or 
• 
‘Failure’ if the participant did not consume the dose that is used to define the efficacy endpoint. 
For example, a participant consumes a single dose of 600 mg of peanut protein without dose-limiting symptoms during 
the blinded OFC to peanut at the end of Stage 1, but then refuses to continue with the rest of the blinded OFC to 
peanut. In this case, the participant will be assumed to have met the primary endpoint but will be marked as a failure for 
efficacy endpoints defined by consumption of a single dose of ≥1000 mg, ≥1 dose of 2000 mg, or 2 doses of 2000 mg 
peanut protein without dose-limiting symptoms during the DBPCFC at the end of Stage 1.  
Imputation of missing DBPCFC data in this way assumes that the data is missing-not-at-random (MNAR). To assess the 
impact of the MNAR assumption, a sensitivity analysis of the primary endpoint will be performed (see Section 13.5.4).  
For FAQLQ and immune biomarker endpoints, any missing data will be assumed MAR and no explicit imputation will be 
performed.  
A participant will only be included in analyses of OFC endpoints for peanut and the two other participant-specific foods.  
 Measures to Minimize Bias 
Bias will be minimized in the following ways: 
• 
The randomization scheme used for treatment arms in Stage 1 (see Section 3.5) will be stratified to ensure that 
the distribution of <6 years of age and milk as a participant-specific food (yes/no) is balanced across the 
treatment arms in Stage 1. 
• 
The randomization scheme used for treatment arms in Stage 2 (see Section 3.5) will be stratified to ensure that 
the distribution of treatment arms in Stage 1 is balanced across the treatment arms in Stage 2. 

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• 
The randomization scheme used for the order of the blinded OFC to peanut in relation to the other three 
blinded OFCs during the DBPCFC (first, second, third, or fourth) at the end of Stage 1 will be stratified to ensure 
that the distribution of the Stage 1 treatment arm is balanced across the four orderings in Stage 1. A similar 
stratified randomization scheme will be used for the order of the blinded OFC to peanut during the DBPCFC at 
the end of Stage 2 to ensure that the distribution of the Stage 2 treatment arm is balanced across the four 
orderings in Stage 2. The order of the blinded OFC to peanut in relation to the other three blinded OFCs during 
the Screening DBPCFC as well as the DBPCFC at the end of Stage 1 OLE will also be randomized. 
• 
For each participant, randomization of the order of the blinded OFC to peanut during the DBPCFC at the end of 
Stage 1, Stage 2, or Stage 1 OLE will be performed immediately after randomization of the Stage 1 or Stage 2 
treatment arm or immediately after entering Stage 1 OLE respectively. 
• 
Each participant, CRU staff (excluding the unblinded CRU pharmacist/pharmacy staff and a CRU staff member 
who will administer omalizumab or placebo for omalizumab injections), and laboratory staff will be blinded to 
treatment assignments until unblinding occurs (see Section 3.5). 
• 
During all DBPCFCs, the participant and/or parent/legal guardian, as well as the CRU staff administering the 
blinded OFC, will not know which OFC contains food protein or placebo. 
 Analysis Plan 
13.5.1 Analysis Populations  
13.5.1.1 Stage 1 Analysis Populations 
Pediatric Full Analysis Set - Stage 1 (PFA-S1): All participants aged less than 18 years at randomization who 
have been randomized to receive either omalizumab or placebo for omalizumab in Stage 1. Participants will 
be analyzed according to the treatment arm to which they were randomized in Stage 1, regardless of the 
treatment actually received in Stage 1. (For the interim analysis of efficacy and for the associated study 
report if Stage 1 is curtailed for efficacy, this analysis population will be subset on all pediatric participants  
randomized into Stage 1 by 08JUL2022 (N=165)) 
Full Analysis Set - Stage 1 (FA-S1): All participants who have been randomized to receive either 
omalizumab or placebo for omalizumab in Stage 1. Participants will be analyzed according to the treatment 
arm to which they were randomized in Stage 1, regardless of the treatment actually received in Stage 1. 
Pediatric Per-Protocol Set - Stage 1 (PPP-S1): All participants in the PFA-S1 population who have completed 
at least 75% of scheduled injections with either omalizumab or placebo for omalizumab in Stage 1 and have 
completed the blinded OFC to peanut during the DBPCFC at the end of Stage 1. The PPP-S1 population will 
only include participants who receive the correct treatment according to their randomization assignment 
and correct omalizumab dosing frequency in Stage 1. Participants with major protocol deviations that could 
be expected to materially affect efficacy during Stage 1 will also be excluded from PPP-S1. 
Pediatric Pre-Randomization Safety Set - Stage 1 (PSS-PRERAND-S1): All randomized participants aged less 
than 18 years at randomization and all participants who are enrolled but never randomized aged less than 
18 years at Screening.  
Pediatric Safety Set - Stage 1 (PSS-S1): All randomized participants aged less than 18 years at 
randomization who have received at least one dose of omalizumab or placebo for omalizumab in Stage 1 . 

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Participants will be analyzed according to the treatment they actually received in Stage 1, defined as 
“omalizumab” if a participant received any dose (including a partial single dose) of omalizumab during 
Stage 1 and “placebo for omalizumab” otherwise, regardless of the treatment arm to which they were 
randomized in Stage 1. 
Pediatric Pre-Randomization Safety Set for Screening OFCs - Stage 1 (PSS-PRERAND-OFC-S1): All  PSS-
PRERAND-S1 participants who have had at least one blinded OFC during the Screening DBPCFC. 
Pediatric Safety Set for OFCs- Stage 1 (PSS-OFC-S1): All PSS-S1 participants who have had at least one 
blinded OFC during the DBPCFC at the end of Stage 1. Participants will be analyzed according to the 
treatment they actually received in Stage 1, defined as “omalizumab” if a participant received any dose 
(including a partial single dose) of omalizumab during Stage 1 and “placebo for omalizumab” otherwise, 
regardless of the treatment arm to which they were randomized in Stage 1. 
Safety Set - Stage 1 (SS-S1): All participants who have received at least one dose of omalizumab or placebo 
for omalizumab in Stage 1. Participants will be analyzed according to the treatment they actually received 
in Stage 1, defined as “omalizumab” if a participant received any dose (including a partial single dose) of 
omalizumab during Stage 1 and “placebo for omalizumab” otherwise, regardless of the treatment arm to 
which they were randomized in Stage 1.  
Pre-Randomization Safety Set - Stage 1 (SS-PRERAND-S1): All randomized participants and all participants 
who are enrolled but never randomized (this is all enrolled (ie, consented) subjects).  
Pre-Randomization Safety Set for Screening OFCs - Stage 1 (SS-PRERAND-OFC-S1): All SS-PRERAND-S1 
participants who have had at least one blinded OFC during the Screening DBPCFC. 
Safety Set for OFCs - Stage 1 (SS-OFC-S1): All SS-S1 participants who have had at least one blinded OFC 
during the DBPCFC at the end of Stage 1. Participants will be analyzed according to the treatment they 
actually received in Stage 1, defined as “omalizumab” if a participant received any dose (including a partial 
single dose) of omalizumab during Stage 1 and “placebo for omalizumab” otherwise, regardless of the 
treatment arm to which they were randomized in Stage 1. 
13.5.1.2 Stage 1 Open Label Extension Analysis Populations 
Pediatric Full Analysis Set - Stage 1 OLE (PFA-S1OLE): All participants aged less than 18 years at 
randomization in Stage 1 who have moved to Stage 1 OLE, grouped according to treatment arm to which 
they were randomized in Stage 1.  
Full Analysis Set- Stage 1 OLE (FA-S1OLE): All participants who have moved to Stage 1 OLE, grouped 
according to treatment arm to which they were randomized in Stage 1. 
Pediatric Safety Set - Stage 1 OLE (PSS-S1OLE): All participants in the PFA-S1OLE population who have 
received any dose (including a partial single dose) of open label omalizumab during Stage 1 OLE, grouped 
according to the treatment received in Stage 1 defined as “omalizumab” if a participant received any dose 
(including a partial single dose) of omalizumab during Stage 1 and “placebo for omalizumab” otherwise.  
Pediatric Safety Set for OFCs - Stage 1 OLE (PSS-OFC-S1OLE): All PSS-S1OLE participants who have had at 
least one blinded OFC during the DBPCFC at the end of Stage 1 OLE, grouped according to treatment arm 

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received in Stage 1 defined as “omalizumab” if a participant received any dose (including a partial single 
dose) of omalizumab during Stage 1 and “placebo for omalizumab” otherwise. 
Safety Set - Stage 1 OLE (SS-S1OLE): All participants who have moved to Stage 1 OLE and received any dose 
(including a partial single dose) of open label omalizumab during Stage 1 OLE, grouped according to the 
treatment received in Stage 1 defined as “omalizumab” if a participant received any dose (including a 
partial single dose) of omalizumab during Stage 1 and “placebo for omalizumab” otherwise.  
Safety Set for OFCs - Stage 1 OLE (SS-OFC-S1OLE): All SS-S1OLE participants who have had at least one 
blinded OFC during the DBPCFC at the end of Stage 1 OLE, grouped according to treatment arm received in 
Stage 1 defined as “omalizumab” if a participant received any dose (including a partial single dose) of 
omalizumab during Stage 1 and “placebo for omalizumab” otherwise. 
13.5.1.3 Stage 2 Analysis Populations 
Full Analysis Set – Stage 2 (FA-S2): All participants who have been randomized in Stage 2 and have received 
at least one open label omalizumab injection as a part of their randomized Stage 2 treatment arm or 
attempted an OIT dose as a part of their randomized Stage 2 treatment arm. Participants who have only 
received treatment during the first 8 weeks of open-label omalizumab will not be included in this set. 
Participants will be analyzed according to the treatment arm to which they were randomized in Stage 2, 
regardless of the treatment actually received in Stage 2. 
Safety Set – Stage 2 (SS-S2): All participants who have received at least one open label omalizumab 
injection as a part of their randomized Stage 2 treatment arm or attempted an OIT dose as a part of their 
randomized Stage 2 treatment arm. Participants who have only received treatment during the first 8 weeks 
of open-label omalizumab will not be included in this set. Participants will be analyzed according to the 
treatment they actually received in Stage 2, regardless of the treatment arm to which they were 
randomized in Stage 2. Treatment will be defined as omalizumab-facilitated OIT if the participant 
attempted a partial or single dose of Multi-allergen OIT during Stage 2 or omalizumab + placebo OIT 
otherwise. 
13.5.1.4 Stage 3 Analysis Populations 
Full Analysis Set – Stage 3 (FA-S3): All participants who completed Stage 2 (see Section 11.1) and moved to 
Stage 3. Participants will be analyzed according to the treatment arm to which they were randomized in 
Stage 2, regardless of the treatment actually received in Stage 2. 
Safety Set – Stage 3 (SS-S3): All FA-S3 participants. Participants will be analyzed according to the treatment 
actually received in Stage 2, defined as omalizumab-facilitated OIT if the participant received any dose 
(including a partial single dose) of OIT during Stage 2 and omalizumab + placebo OIT otherwise, regardless 
of the treatment arm to which they were assigned in Stage 2.  
13.5.2 Timing of Analyses 
Due to the multi-stage nature of the study design, analyses of the primary, secondary, and selected exploratory 
endpoints measured in each stage of the study may be conducted before all Stages of the study have been 
completed and the corresponding data have been locked.  
An interim analysis for efficacy was conducted on all pediatric subjects (ages 1 year to less than 18 years) randomized 
into Stage 1 on or before 08JUL2022. (N=165). The analysis was conducted after all these participants have either 
completed or discontinued from Stage 1. Efficacy was declared as the two-sided p-value for the peanut is significant 

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at p< 0.0001 and the two-sided p-values for all secondary foods (cashew, milk, and egg) are significant at p< 0.005, 
with the direction of all treatment group difference favoring omalizumab. The DSMB reviewed the IA results and 
recommended that the trial should be curtailed for efficacy, which NIAID agreed. Enrollment into the trial and 
randomization into Stage 1 was discontinued on March 23, 2023.   
The analyzed data from Stage 1 and OLE were reviewed by the Food and Drug Administration, and as of 16 February 
2024, Xolair® (omalizumab) is approved for IgE-mediated food allergy in adult and pediatric patients aged 1 year and 
older for the reduction of allergic reactions (Type I), including anaphylaxis, that may occur with accidental exposure 
to one or more foods.  Omalizumab is to be used in conjunction with food allergen avoidance. 
Appendix 12 provides a mapping of the endpoints in each stage that will be used to address each of the objectives in 
each stage. 
13.5.3 Type I Error Control 
To control the inflation of Type I error that arises when multiple tests of comparison are performed within and across 
multiple families of endpoints (i.e., the primary endpoint as well as Stage 1 key secondary endpoints), both 
gatekeeping will be performed to ensure the overall family-wise error rate is ≤ 5%. All hypotheses testing under Type 
I error control will be performed in the PFA-S1 population. 
Interim Analysis 
At interim (N=165 pediatric participants), efficacy would be declared only if the two-sided p-value for the peanut is 
significant at p< 0.0001 and the two-sided p-values for all secondary foods (cashew, milk, and egg) are significant at 
p< 0.005, with all p-values being significant in the right direction (i.e., favoring omalizumab).   
Final Analysis 
If the interim analysis is unsuccessful, the final analysis will be performed (planned N=210).  At the final analysis, the 
primary endpoint will be tested using the full α of 0.05, considering the α of 0.0001 from the interim analysis to be 
trivial. Key secondary endpoints will be tested at an α of 0.0497 after using 0.005 at interim with 79% of information 
(165/210).  A gatekeeping approach will be followed that incorporates looking back to interim analysis for p-values of 
specific foods to determine if the next gate will be open or closed. The hierarchy for testing is as follows: I) peanut, II) 
cashew, III) egg, and IV) milk. For testing a specific allergen, all previous allergen(s) must be successful where success 
criteria are defined below: 
I. 
Peanut:  successful if peanut significant at interim (p<0.0001) OR at final (p<0.05)  
II. 
Cashew: successful if peanut is successful AND cashew is significant at either the interim (p<0.005) OR 
final (p<0.0497)     
III. 
Egg: successful if peanut and cashew are successful AND egg is significant at either the interim (p<0.005) 
OR final (p<0.0497)     
IV. 
Milk: successful if peanut, cashew, and egg are successful AND milk is significant at either the interim 
(p<0.005) OR final (p<0.0497)     
13.5.4 Primary Analysis of Primary Endpoint  
Using participants included in the PFA-S1 set, the primary analysis of the primary endpoint will use Fisher’s exact test 
to compare the omalizumab and placebo for omalizumab arms with respect to the proportion of participants that 

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successfully consume a single dose of ≥600 mg of peanut protein without dose-limiting symptoms during the DBPCFC 
at the end of Stage 1.  A two-sided significance level of p<0.0001 will be used at the interim analysis and, if Stage 1 is 
not curtailed at the interim analysis, a two-sided significance level of p<0.05 will be used at the final analysis. Further 
details of this analysis will be provided in the SAP.  
13.5.5 Supportive Analyses of the Primary Endpoint 
Sensitivity analyses of the primary endpoint will include: 
• 
A tipping point analysis of the primary endpoint will also be performed to assess sensitivity of results to the 
MNAR assumption (see SAP for more details). 
• 
If more than 2 participants have an imputed primary endpoint due to not having the blinded OFC to placebo, 
a sensitivity analysis of the primary endpoint will be performed using the observed outcome of the blinded 
OFC to peanut. 
Supplementary analyses of the primary endpoint will include: 
• 
The primary endpoint will also be analyzed using exact logistic regression to model the log odds a participant 
consumes a single dose of ≥600 mg of peanut protein without dose-limiting symptoms during the DBPCFC at 
the end of Stage 1. The model will include the following fixed effects based on randomization: treatment 
arm, age at randomization (<6 years versus ≥6 years), milk as a participant-specific food (yes/no), and the 
order of the blinded OFC to peanut during the DBPCFC at the end of Stage 1. The adjusted proportion (and 
associated standard error and 95% confidence interval) in each treatment arm will be reported. The odds 
ratio (and associated 95% exact confidence interval) comparing consumption of a single dose of ≥600 mg of 
peanut protein without dose-limiting symptoms between the omalizumab and placebo for omalizumab arms 
will be reported.  
• 
Separate analysis excluding participants who restarted Stage 1 from the PFA-S1 population. This analysis will 
fit a logistic regression similar to that described above.  
• 
Separate analysis excluding participants who had dose-limiting symptoms to the 300 mg dose of placebo 
used in the blinded OFC to peanut during the Screening DBPCFC from the PFA-S1 population. This analysis 
will fit a logistic regression model similar to that described above.  
• 
Analysis of the primary endpoint will be replicated using both the PPP-S1 population and the FA-S1 
population. 
• 
Separate subgroup analyses of the primary analysis for the primary endpoint will be conducted. Subgroups 
will be defined by: 1) age at Stage 1 randomization (<6, 6 to <12, 12 to <18); 2) order of blinded OFC to 
peanut during the DBPCFC at the end of Stage 1; 3) race; 4) ethnicity; 5) sex; 6) CRU; 7) dose consumed 
during the Screening DBPCFC with dose-limiting symptoms (≤30 mg or 100 mg of peanut protein); and 8) 
omalizumab dosing frequency (2 or 4 weeks).  
• 
A predictive model will also be developed to predict the probability of consuming a single dose of ≥600 mg 
of peanut protein without dose-limiting symptoms during the DBPCFC at the end of Stage 1 using each 
immune biomarker measured at the first Screening DBPCFC Visit. Only Stage 1 treatment arm, age at 
randomization (<6 years versus ≥6 years), milk as a participant-specific food (yes/no), and the order of the 
blinded OFC to peanut during the DBPCFC at the end of Stage 1 will be forced into the model as covariates. 
All immune biomarker levels measured at the first Screening DBPCFC Visit as well as the interaction between 
each immune biomarker and Stage 1 treatment arm will be included as possible covariates. Covariates will 
be log transformed, as appropriate. 

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13.5.6 Analyses of Secondary Endpoints 
13.5.6.1 Key Secondary Endpoints 
Using participants in the PFA-S1 population who have cashew, milk, or egg as a participant-specific food and the 
results of the DBPCFCs at the end of Stage 1, consumption of a single dose of ≥1000 mg protein of cashew, milk, or 
egg without dose-limiting symptoms will be evaluated using Fisher’s exact test (similar to Section 13.5.4) to each 
Stage 1 key secondary endpoint. The significance level used for each of these analyses will be adjusted to ensure that 
the overall family-wise error rate of the primary and Stage 1 key secondary endpoints is below 5% (see Section 
13.5.3). 
Using the PFA-S1  and FA-S2 populations and the results of the DBPCFCs at the end of Stage 2, consumption of ≥1 
dose of 2000 mg protein of all three foods without dose-limiting symptoms (Key Secondary Endpoint 4) will be 
evaluated by applying a logistic regression model to estimate the odds ratio (and associated 95% confidence interval) 
between the omalizumab-facilitated OIT and omalizumab + placebo OIT arms. Fixed effects will only include Stage 1 
treatment arm, Stage 2 treatment arm, an interaction between Stage 1 and Stage 2 treatment arm, age at Stage 1 
randomization (<6 years versus ≥6 years), milk as a participant-specific food, and the order of the blinded OFC to 
peanut during the DBPCFC at the end of Stage 2. A two-sided significance level of 0.05 will be used without any 
further Type I error control.  
13.5.6.2 Other Secondary Endpoints 
The analyses of all secondary endpoints that are not key secondary endpoints are summarized in Table 13.5.6.2. 
Ninety-five percent (95%) confidence intervals will also be reported of all applicable endpoint estimates. A two-sided 
significance level of 0.05 will be used for superiority tests and a one-sided significance level of 0.025 will be used for 
the non-inferiority test. Endpoints will be log-transformed, as appropriate. 
Table 13.5.6.2 Other Secondary Endpoints 
Stage 
Secondary Endpoint 
Analysis 
Population 
Type of Test 
Model 
Fixed Effects 
Endpoint Estimate 
(95% CI reported) 
1 
5 
Consumption of a single dose 
of ≥600 mg, ≥1000 mg, ≥1 
dose of 2000 mg, or 2 doses 
of 2000 mg protein of each 
food, at least two foods, or 
all three foods without dose-
limiting symptoms during the 
DBPCFC at the end of Stage 1 
(except those endpoints 
already defined by the 
primary and key secondary 
endpoints) 
PFA-S1 
Superiority 
Fisher’s 
Exact  
N/A 
 
Odds ratio between 
omalizumab and placebo for 
omalizumab arms 
6 
Number of foods consumed 
at a single dose of ≥600 mg, 
≥1000 mg, ≥1 dose of 2000 
mg, or 2 doses of 2000 mg 
protein of each food without 
dose-limiting symptoms 
during the DBPCFC at the end 
of Stage 1 
Ordinal 
Logistic 
Regression 
Model 
Stage 1 treatment 
arm, age (<6 years 
versus ≥6 years), 
milk as a 
participant-
specific food 
(yes/no), and the 
order of the 
blinded OFC to 
peanut during the 
DBPCFC at the end 
of Stage 1 
 
Odds ratio comparing 
consumption of a higher 
number of foods without 
dose-limiting symptoms 
between the omalizumab 
and placebo for omalizumab 
arms 

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Stage 
Secondary Endpoint 
Analysis 
Population 
Type of Test 
Model 
Fixed Effects 
Endpoint Estimate 
(95% CI reported) 
2 
4 
Consumption of ≥1 dose of 
2000 mg protein of all three 
foods without dose-limiting 
symptoms during the 
DBPCFC at the end of Stage 
2. This is the primary 
endpoint for Stage 2. 
FA-S2 
Superiority 
Logistic 
Regression 
Model 
Stage 1 treatment 
arm, Stage 2 
treatment arm, 
interaction 
between Stage 1 
and Stage 2 
treatment arm, 
age at Stage 1 
randomization (<6 
years versus ≥6 
years), milk as a 
participant-
specific food, and 
the order of the 
blinded OFC to 
peanut during the 
DBPCFC at the end 
of Stage 2 
Odds ratio between the 
omalizumab-facilitated OIT 
and omalizumab + placebo 
OIT arms 
7 
Consumption of a single dose 
of ≥600 mg, ≥1000 mg, ≥1 
dose of 2000 mg, ≥2 doses of 
2000 mg, or 3 doses of 2000 
mg protein of each food, at 
least two foods, or all three 
foods without dose-limiting 
symptoms during the DBPCFC 
at the end of Stage 2 (except 
the endpoint already defined 
by the primary endpoint for 
Stage 2) 
Superiority 
Logistic 
Regression 
Model 
Odds ratio between the 
omalizumab-facilitated OIT 
and omalizumab + placebo 
OIT arms 
7* 
Consumption of a single dose 
of ≥600 mg protein of all 
three foods without dose-
limiting symptoms during the 
DBPCFC at the end of Stage 2 
Non-
Inferiority 
 
Odds ratio between the 
omalizumab-facilitated OIT 
and omalizumab + placebo 
OIT arms 
8 
Number of foods consumed 
at a single dose of ≥600 mg, 
≥1000 mg, ≥1 dose of 2000 
mg, ≥2 doses of 2000 mg, or 
3 doses of 2000 mg protein 
of each food without dose-
limiting symptoms during the 
DBPCFC at the end of Stage 2 
Superiority 
Ordinal 
Logistic 
Regression 
Model 
Odds ratio comparing 
consumption of a higher 
number of foods without 
dose-limiting symptoms 
between the omalizumab-
facilitated OIT and 
omalizumab + placebo OIT 
arms  
3 
9 
For each food, at 3, 6, 9 and 
12 months following the first 
Stage 3 visit, consuming a 
daily median of 300 mg on 
the dietary consumption 
treatment plan where 
participants received guided 
dietary instructions.  
 
FA-S3 
Superiority 
Fisher’s 
Exact  
N/A 
 
Odds ratio between the 
omalizumab-facilitated OIT 
and omalizumab + placebo 
OIT arms  in Stage 2 
FA-S1OLE 
population 
who enter 
Stage 3 
N/A 
 
N/A 
 
N/A 
 
Percent and exact CI 
1. For each individual food endpoint other than peanut, participants in the PFA-S1, FA-S2, or FA-S3 population with the food designated as a 
participant-specific food will be included in the analysis. 
2. These endpoints will also be summarized in participants in the PFA-S1OLE population who enter Stage 3. 
To test that omalizumab + placebo OIT is not inferior to omalizumab-facilitated OIT, a non-inferiority test based on a 
one-sided significance level of 0.025 and a non-inferiority margin for the odds ratio of 0.35 will be performed when 
estimating the odds ratio of a participant consuming a single dose of ≥600 mg protein of all three foods without dose-
limiting symptoms during the DBPCFC at the end of Stage 2 between the omalizumab-facilitated OIT and omalizumab 
+ placebo OIT arms in the FA-S2 population (i.e., Secondary Endpoint 7*). A non-inferiority margin for the odds ratio of 
0.35 was selected because: 
1. Any difference in the proportion of participants meeting this endpoint between the arms smaller than 18% is 
not clinically significant. 
2. Unpublished data from MAP-X56, a previous Phase 2 study, showed that approximately 85% of participants in 
an arm similar to omalizumab-facilitated OIT consumed a single dose of ≥600 mg protein of all three foods 

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without dose-limiting symptoms. Assuming 10% of participants on a non-active placebo would be expected to 
meet this endpoint, a non-inferiority margin of 18% would be equivalent to 24% of an expected 75% effect 
size between omalizumab-facilitated OIT and non-active placebo. Under this scenario, a 18% non-inferiority 
margin in the difference in proportion equates to a non-inferiority margin for the odds ratio of 0.35. 
In the case that participants in the omalizumab + placebo OIT arm have significantly higher odds of 
consuming a single dose of ≥600 mg protein of all three foods without dose-limiting symptoms than 
participants in the omalizumab-facilitated OIT arm, superiority will be concluded. 
13.5.6.3 Supportive Analyses of Secondary Endpoints  
Supportive analyses of secondary endpoints will include: 
• 
For each food other than peanut, a predictive model will be developed to predict the probability of consuming a 
single dose of ≥1000 mg protein of the food without dose-limiting symptoms during the DBPCFC at the end of 
Stage 1 using each immune biomarker measured at the first Screening DBPCFC Visit. Only Stage 1 treatment 
arm, age (<6 years versus ≥6 years), milk as a participant-specific food (yes/no), and the order of the blinded OFC 
to peanut during the DBPCFC at the end of Stage 1 will be forced into the model as covariates. All immune 
biomarker levels measured at the first Screening DBPCFC Visit as well as the interaction between each immune 
biomarker and Stage 1 treatment arm will be included as possible covariates. Covariates will be log transformed, 
as appropriate.  
• 
A separate analysis of each secondary endpoint measured in Stage 2 will be performed in each of the following 
two subgroups: participants who do not respond to 16-20 weeks of treatment with omalizumab in Stage 1 and 
participants who respond to 16-20 weeks of treatment with omalizumab in Stage 1. A responder will be defined 
as a participant who consumes a single dose of ≥600 mg of peanut protein without dose-limiting symptoms 
during the DBPCFC at the end of Stage 1. These analyses will be based on a logistic regression model and will 
estimate the odds ratio comparing consumption of each food protein without dose-limiting symptoms during 
the DBPCFC at the end of Stage 2 between omalizumab-facilitated OIT and omalizumab + placebo OIT arms. 
• 
A predictive model will be developed to predict the probability of consuming ≥1 dose of 2000 mg protein of all 
three foods without dose-limiting symptoms during the DBPCFC at the end of Stage 2 using each immune 
biomarker measured at the first DBPCFC Visit at the end of Stage 1. Only Stage 1 treatment arm, Stage 2 
treatment arm, and the order of the blinded OFC to peanut during the DBPCFC at the end of Stage 2 will be 
forced into the model as covariates. All immune biomarker levels measured at the first DBPCFC Visit at the end 
of Stage 1 and the interaction between each immune biomarker and Stage 2 treatment arm will be included as 
possible covariates. Covariates will be log transformed, as appropriate.  
• 
Using the FA-S3 population and each sub-group defined by Stage 1 treatment arm, a generalized estimating 
equation will also be used to estimate the rate ratio comparing the mean rate each food is consumed at least 
twice per week in each eight-week period during Stage 3 between the two arms in Stage 2. 
13.5.6.4 Safety Endpoints 
Using the pediatric safety sets in Stage 1 and Stage 1 OLE, and safety sets in Stages 2 and 3 (see Section 13.5.1), the 
number of AEs related to the study therapy regimen will be summarized by treatment arm, AE grade, and AE severity. 
The number and proportion of participants experiencing at least one AE related to the study therapy regimen will 
also be summarized by treatment arm, AE grade, and AE severity. Separate summaries will be generated for SAEs, 
deaths, AESIs (defined in Section 12.2.2), and AEs leading to discontinuation of study drug.  

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Descriptive summaries of laboratory values at baseline and throughout the study will be generated for selected 
parameters. For these selected parameters, changes from baseline and the proportion of participants experiencing 
clinically significant changes relative to baseline will be compared between randomized treatment arms. 
Similar analyses for Stage 3 AEs will be conducted for SS-S1OLE participants who enter Stage 3.  
13.5.7 Analyses of Exploratory Endpoints 
Exploratory endpoints measured in Stage 1, Stage 1 OLE, Stage 2, and Stage 3 will be analyzed using the participants 
included in the PFA-S1, PFA-S1OLE, FA-S2, and FA-S3 sets respectively. For each individual food endpoint other than 
peanut, participants in the PFA-S1, PFA-S1OLE, FA-S2, or FA-S3 population with the food designated as a participant-
specific food will be included in the analysis. All analyses will be based on a two-sided significance level of 0.05; 95% 
confidence intervals of the appropriate endpoint estimate will also be reported. 
Exploratory Endpoint 1: For each food, an ordinal logistic regression model will be used to analyze the percent 
change in the maximum dose of food protein consumed without dose-limiting symptoms during the DBPCFC at the 
end of Stage 1 and during the DBPCFC at the end of Stage 2. Fixed effects will only include Stage 1 treatment arm, 
Stage 2 treatment arm, age (<6 years versus ≥6 years), an interaction between Stage 1 and Stage 2 treatment arms, 
milk as a participant-specific food (yes/no), and the order of the blinded OFC to peanut during the DBPCFC at the end 
of Stage 1 and Stage 2. This model will estimate the ratio of the odds that a higher maximum dose of food protein 
was consumed without dose-limiting symptoms during the DBPCFC at the end of Stage 2 compared to the DBPCFC at 
the end of Stage 1 between the omalizumab-facilitated OIT and omalizumab + placebo OIT arms. Should the 
distribution of this endpoint not meet the assumptions of an ordinal logistic regression model, other models may be 
considered, as further specified in the SAP. 
Exploratory Endpoint 2: The proportion of participants consuming a single dose of ≥600 mg, ≥1000 mg, ≥1 dose of 
2000 mg, ≥2 doses of 2000 mg, or 3 doses of 2000 mg protein of each food, at least two foods, or all three foods 
without dose-limiting symptoms during the DBPCFC at the end of Stage 1 OLE will be summarized.  
Exploratory Endpoint 3: The proportion of participants consuming 0, 1, 2, or 3 foods at a single dose of ≥600 mg, 
≥1000 mg, ≥1 dose of 2000 mg, ≥2 doses of 2000 mg, or 3 doses of 2000 mg protein of each food without dose-
limiting symptoms during the DBPCFC at the end of Stage 1 OLE will be summarized. 
Exploratory Endpoint 4: Linear mixed models will be used to estimate the change over time (relative to Week 0 in 
Stage 1) in quality of life (total score as well as each sub-domain). For Stage 1 analyses, the change over time in 
quality of life measured in Stage 1 will be compared between treatment arms in Stage 1 using a model that includes a 
random intercept and fixed effects for treatment arms in Stage 1, age (<6 years versus ≥6 years), milk as a 
participant-specific food (yes/no), time of measurement, and an interaction term between treatment arms in Stage 1 
and time of measurement. For Stage 2 analyses, the change over time in quality of life measured in Stage 1 and Stage 
2 will be compared between treatment arms in Stage 2 using a linear mixed model that includes a random intercept 
and fixed effects for Stage 1 treatment arm, Stage 2 treatment arm, an interaction between Stage 1 and Stage 2 
treatment arms, age (<6 years versus ≥6 years), milk as a participant-specific food, time of measurement, and an 
interaction term between Stage 1 treatment arm, Stage 2 treatment arm, and time of measurement. For Stage 3 
analyses, a similar model will be used to compare the change over time in quality of life measured in Stage 1, Stage 2, 
and Stage 3 between treatment arms in Stage 2. 
The mean difference in quality of life between Week 0 in Stage 1 and the first DBPCFC Visit at the end of Stage 1, the 
first omalizumab injection visit in Stage 1 OLE, and the first and last DBPCFC Visit at the end of Stage 1 OLE will be 

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summarized in PFA-S1OLE participants. The mean difference in quality of life between Week 0 in Stage 1 and the first 
DBPCFC Visit at the end of Stage 1, the first omalizumab injection visit in Stage 1 OLE, the first and last DBPCFC Visit 
at the end of Stage 1 OLE, and six months after the beginning of Stage 3 will be summarized in PFA-S1OLE 
participants who enter Stage 3.  
Exploratory Endpoint 5: Omalizumab trough concentration measured at the first Screening DBPCFC Visit and in Stage 
1, Stage 1 OLE, and Stage 2 will be summarized at each time point and each omalizumab dosing regimen, as 
appropriate.  
Exploratory Endpoints 6-12: Linear (or nonlinear, if appropriate) mixed models will be used to estimate the geometric 
mean ratio over time (relative to the first Screening DBPCFC Visit) of each immune biomarker. Models will be similar 
to that described for Exploratory Endpoint 4. 
The change in the immune biomarkers between the first Screening DBPCFC Visit, the first DBPCFC Visit at the end of 
Stage 1, and the first DBPCFC Visit at the end of Stage 1 OLE will be summarized in PFA-S1OLE participants. The 
change in the immune biomarkers between the first Screening DBPCFC Visit, the first DBPCFC Visit at the end of Stage 
1, the first DBPCFC Visit at the end of Stage 1 OLE, and six months after beginning Stage 3 will be summarized in PFA-
S1OLE participants who enter Stage 3. 
Ratios between immune biomarkers (other than IgG4/IgE) may be evaluated by applying similar approaches to that 
described above.  
Exploratory Endpoint 13: Linear mixed models will be used to estimate the mean difference in the SPT wheal size to 
each food over time (relative to the SPT wheal size at the Screening Visit). Models will be similar to that described for 
Exploratory Endpoints 4. 
The mean difference in SPT wheal size between the Screening Visit, the first DBPCFC Visit at the end of Stage 1, and 
the first DBPCFC Visit at the end of Stage 1 OLE will be summarized in PFA-S1OLE participants. The mean difference in 
SPT wheal size between the Screening Visit, the first DBPCFC Visit at the end of Stage 1, the first DBPCFC Visit at the 
end of Stage 1 OLE, and six months after the beginning of Stage 3 will be summarized in FA-S1OLE participants who 
enter Stage 3.  
13.5.8 Descriptive Analyses  
Descriptive analyses will be reported separately for randomized study therapy regimens in each stage separately. 
Continuous variables will be reported using the mean, standard deviation, minimum, maximum, median, first and 
third quartiles, and sample size. Categorical variables will be reported as frequencies and percentages. 
 Interim Analysis  
An interim analysis for efficacy will be conducted on all pediatric participants randomized into Stage 1 by 08JUL2022 
(N=165) and after all of these participants have completed or discontinued from Stage 1.  Efficacy can only be 
declared at the interim if the two-sided p-value for the peanut at interim is less than 0.0001 and the two-sided p-
values for all secondary foods (cashew, milk, and egg) are significant at 0.005 significance level.   See Section 13.5.3 
for details on the approach for Type I error control. See Section 3.1 for continuation of the study if efficacy is not 
declared at the Interim Analysis.  Additional details of the interim analysis are described in the SAP and the process 
for determining whether Stage 1 will be discontinued in protocol Section 12.7.2.1.2).  
 This interim analysis was conducted and efficacy was declared as the two-sided p-value for the peanut is significant 
at p< 0.0001 and the two-sided p-values for all secondary foods (cashew, milk, and egg) are significant at p< 0.005, 

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with the direction of all treatment group difference favoring omalizumab. The DSMB reviewed the IA results and 
recommended that the trial should be curtailed for efficacy, which NIAID agreed. Enrollment into the trial and 
randomization into Stage 1 was discontinued on March 23, 2023.   
 Statistical Hypotheses  
Most analyses of primary and secondary endpoints will be based on two-sided superiority tests. For example, the null 
and alternative hypotheses for the primary endpoint are: 
Null hypothesis: The odds of a participant consuming a single dose of ≥600 mg of peanut protein without dose-
limiting symptoms during the DBPCFC at the end of Stage 1 in omalizumab and placebo for omalizumab arms are 
equal.  
Alternate hypothesis: The odds of a participant consuming a single dose of ≥600 mg of peanut protein without dose-
limiting symptoms during the DBPCFC at the end of Stage 1 in omalizumab and placebo for omalizumab arms are not 
equal. 
The endpoint measuring consumption of a single dose of ≥600 mg protein of all three foods without dose-limiting 
symptoms during the DBPCFC at the end of Stage 2 will be based on a one-sided non-inferiority test. The null and 
alternative hypotheses for this endpoint are: 
Null hypothesis: The odds ratio of a participant consuming a single dose of ≥600 mg protein of all three foods 
without dose-limiting symptoms during the DBPCFC at the end of Stage 2 between the omalizumab + placebo OIT 
arm and omalizumab-facilitated OIT arm is less than 0.35. This hypothesis implies that omalizumab + placebo OIT is 
inferior to omalizumab-facilitated OIT. 
Alternative hypothesis: The odds ratio of a participant consuming a single dose of ≥600 mg protein of all three foods 
without dose-limiting symptoms during the DBPCFC at the end of Stage 2 between the omalizumab + placebo OIT 
arm and omalizumab-facilitated OIT arm is greater than 0.35. This hypothesis implies that omalizumab + placebo OIT 
is not inferior to omalizumab-facilitated OIT within the 0.35 non-inferiority margin. 
 Sample Size Considerations  
All power calculations were performed using SAS version 9.4. 
13.8.1 Stage 1 
A total of 225 participants (150 omalizumab and 75 placebo for omalizumab) were planned to be randomized in 
Stage 1 of this study. 210 of those participants are expected to be younger than 18 years of age, with at least 50 aged 
1 year to less than 6 years. However, based on the results of the performed interim analysis, enrollment was 
curtailed and a total of 180 participants randomized into Stage 1. 
Primary Endpoint: Table 13.8.1a provides the estimated power to detect an odds ratio of consuming a single dose of 
≥600 mg of peanut protein without dose-limiting symptoms during the DBPCFC at the end of Stage 1 between the 
omalizumab and placebo for omalizumab arms. Power calculations for this endpoint were performed using Fisher’s 
exact tests with a two-sided Type I error rate of 5%. For example, assuming 10% of participants randomized to 
placebo for omalizumab in Stage 1 and 70% of participants randomized to omalizumab in Stage 1 consume a single 
dose of ≥600 mg of peanut protein without dose-limiting symptoms during the DBPCFC at the end of Stage 1, a 
sample size of 210 participants (140 omalizumab and 70 placebo) will provide more than 99% power to detect the 
odds ratio of 21.0. Alternatively, this sample size will allow us to detect an odds ratio of 3.3-3.8 between the two 
arms in Stage 1 with 80%-90% power if 10% of participants randomized to placebo for omalizumab in Stage 1 and 

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27%-30% of participants randomized to omalizumab in Stage 1 consume a single dose of ≥600 mg of peanut protein 
without dose-limiting symptoms during the DBPCFC at the end of Stage 1. 
Table 13.8.1a Power Justification of the Primary Endpoint 
 
Stage 1 Key Secondary Endpoints: For Secondary Endpoint 1-3, it is assumed that cashew, milk, and egg allergies will 
have a prevalence of 59%, 30%, and 27% respectively (based on unpublished data obtained from M-TAX57 and MAP-
X56). Power calculations are based on a Fisher’s exact test and a significance level of 0.05 (i.e., no correction for Type I 
error control). Under this assumption, Table 13.8.1b provides the minimum odds ratio of consuming a single dose of 
≥1000 mg protein of each food without dose-limiting symptoms between omalizumab versus placebo for 
omalizumab arms that can be detected to achieve 80% and 90% power under the assumption that 10% of 
participants randomized to placebo for omalizumab consume a single dose of ≥1000 mg protein of each food without 
dose-limiting symptoms. For example, if 59% of participants have an allergy to cashew and 10% of participants in the 
placebo arm consume a single dose of ≥1000 mg of cashew protein without dose-limiting symptoms during the 
DBPCFC at the end of Stage 1, this study will be able to detect an odds ratio of consuming a single dose of ≥1000 mg 
cashew protein without dose-limiting symptoms of 5.3 between omalizumab and placebo for omalizumab arms with 
90% power and a 5% Type I error rate.  
 
Table 13.8.1b Minimum Odds Ratio to Achieve 80% and 90% Power in Consumption of a Single Dose of ≥1000 mg 
protein of Cashew, Milk, and Egg without Dose-Limiting Symptoms during the DBPCFC at the End of Stage 1 
between Arms  
Food 
Prevalence of Food 
Allergy 
Total Expected  
Sample Size 
(Omalizumab:Placebo) 
Minimum  
 Odds Ratio to 
Achieve  
80% Power1 
Minimum  
Odds Ratio to 
Achieve  
 90% Power1 
Cashew 
59% 
123 (82:41) 
4.5 
 5.3 
Egg 
30% 
63 (42:21) 
7.5 
9.5 
Milk 
27% 
57 (38:19) 
8.3 
10.6 
1. Assuming 10% of participants randomized to placebo for omalizumab consume a single dose of ≥1000 mg protein of each 
food without dose-limiting symptoms. 
13.8.2 Stage 2 
Participants must complete Stage 1 (see Section 11.1) to move to Stage 2, unless efficacy is shown at an interim 
analysis and Stage 1 is curtailed at which point participants can forgo Stage 1 and directly enter Stage 2 (see section 
3.1). Assuming approximately 10% of the 210 participants aged less than 18 years do not complete Stage 1 and 60 
Sample Size 
Per Arm 
(Omalizumab:Placebo) 
Proportion of Participants who Consume a 
Single Dose of ≥600 mg of Peanut Protein 
without Dose-Limiting Symptoms During the 
DBPCFC at the End of Stage 1 
Odds Ratio 
Power 
Omalizumab 
Placebo for 
omalizumab 
210 
140:70 
70% 
10% 
21.0 
>99% 
210 
140:70 
60% 
10% 
13.5 
>99% 
210 
140:70 
50% 
10% 
9.0 
>99% 
210 
140:70 
30% 
10% 
3.8 
90% 
210 
140:70 
27% 
10% 
3.3 
80% 

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participants aged less than 18 years move into Stage 1 OLE, it is expected that 128 participants aged less than 18 
years will be randomized in Stage 2. The assumption that all 60 participants in Stage 1 OLE would be aged less than 
18 years provides the minimum possible sample size for Stage 2. The justification for this expected sample size is 
provided using the following two endpoints measured in Stage 2. 
• 
Stage 2 Primary Endpoint (Key Secondary Endpoint 4): Consumption of ≥1 dose of 2000 mg protein of all 
three foods without dose-limiting symptoms during the DBPCFC at the end of Stage 2: Using a two-sided 
Fisher’s exact test with a Type I error rate of 5% and assuming 60% of participants randomized to 
omalizumab + placebo OIT and 85% of participants randomized to omalizumab-facilitated OIT consume a 
dose of ≥1 dose of 2000 mg protein of all three foods without dose-limiting symptoms during the DBPCFC at 
the end of Stage 2 (resulting in an odds ratio of 3.8), a sample size of 128 (64 per arm) will provide 86% 
power to detect this odds ratio. 
• 
Stage 2 Secondary Endpoint: Consumption of a single dose of ≥600 mg protein of all three foods without 
dose-limiting symptoms during the DBPCFC at the end of Stage 2: Using a binomial non-inferiority test with a 
one-sided Type I error rate of 2.5%, a non-inferiority margin for the odds ratio of 0.35, and assuming that 
86% of participants in both the omalizumab-facilitated OIT and omalizumab + placebo OIT arms consume a 
single dose of ≥600 mg protein of all three foods without dose-limiting symptoms during the DBPCFC at the 
end of Stage 2, a sample size 128 (64 per arm) will provide 84% power to detect non-inferiority of 
omalizumab + placebo OIT to omalizumab-facilitated OIT. 
14 Identification and Access to Source Data 
 Source Data 
Source documents and source data are considered to be the original documentation where participant information, 
visits consultations, examinations and other information are recorded. Documentation of source data is necessary for 
the reconstruction, evaluation and validation of clinical findings, observations and other activities during a clinical trial. 
 Access to Source Data 
The PI and CRU staff will make all source data available to the Sponsor (DAIT/NIAID), Genentech, Novartis, as well as to 
relevant health authorities. Authorized representatives as noted above are bound to maintain the strict confidentiality 
of medical and research information that may be linked to identified individuals. 
15 Protocol Deviations 
 Protocol Deviation Definitions 
Protocol Deviation – The PIs and CRU staff will conduct the study in accordance to the protocol; no deviations from the 
protocol are permitted. Any change, divergence, or departure from the study design or procedures constitutes a 
protocol deviation. As a result of any deviation, corrective actions will be developed by the CRU and implemented 
promptly where appropriate. 
Major Protocol Deviation (Protocol Violation) – A Protocol Violation is a deviation from the IRB approved protocol that 
may affect the participant’s rights, safety, or well-being and/or the completeness, accuracy and reliability of the study 
data. In addition, protocol violations include willful or knowing breaches of human participant protection regulations, or 
policies, any action that is inconsistent with the NIH Human Research Protection Program’s research, medical, and 

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ethical principles, and a serious or continuing noncompliance with federal, state, local or institutional human subject 
protection regulations, policies, or procedures. Examples of Major Protocol Deviations will be defined in the MOP. 
Non-Major Protocol Deviation – A non-major protocol deviation is any change, divergence, or departure from the study 
design or procedures of a research protocol that does not have a major impact on the participant’s rights, safety or well-
being, or the completeness, accuracy and reliability of the study data. 
 Reporting and Managing Protocol Deviations 
The PI has the responsibility to identify, document and report protocol deviations as directed by the study Sponsor, 
DAIT/NIAID. However, protocol deviations may also be identified during CRU monitoring visits or during other forms of 
study conduct review. 
Upon determination that a protocol deviation has occurred, CRU staff will: a) notify the PI, b) notify the SCCC, and c) 
complete a Protocol Deviation form. The Protocol Deviation form will document at minimum the date the deviation 
occurred, the date it was identified, a description of the event, whether the deviation resulted in an SAE/AE, PI 
signature, single IRB reporting requirement, and documentation of a corrective action plan. The Sponsor, DAIT/NIAID, 
may request discussion with the PI to determine the effect of the protocol deviation on the overall study and corrective 
actions. The PI will sign the paper source Protocol Deviation CRF, electronically sign Major Deviations in the EDC system, 
and submit the deviation to the single IRB and local IRB/ethics committee per IRB regulations. Major protocol deviations 
will be reported to the NIAID Allergy and Asthma DSMB by the DAIT/NIAID Medical Monitor at the medical monitor’s 
discretion. 
16 Ethical Considerations and Compliance with Good Clinical Practice 
 Quality Control and Quality Assurance 
The PI is required to keep accurate records to ensure that the conduct of the study is fully documented. The PI is 
required to ensure that all CRFs are completed for every participant entered in the trial. 
The Sponsor, DAIT/NIAID, is responsible for regular inspection of the conduct of the trial, for verifying adherence to the 
protocol, and for confirming the completeness, consistency, and accuracy of all documented data. 
The eCRFs will be completed online via a web-based EDC system that has been validated and is compliant with Part 11 
Title 21 of the CFR. CRU staff at the CRU will enter information into the eCRFs, and the data will be stored remotely at a 
central database. Data quality will be ensured through the EDC system’s continuous monitoring of data and real-time 
detection and correction of errors. All elements of data entry (i.e., time, date, verbatim text, and the name of the person 
performing the data entry) will be recorded in an electronic audit trail to allow all changes in the database to be 
monitored and maintained in accordance with federal regulations. 
Per 21CFR 312.62(c), the clinical research records must be retained for a minimum of two years after the marketing 
application is approved for the drug for the indication for which it was being investigated. Alternatively, if no application 
will be filed or if the application is not approved for the requested indication, the records must be retained for a 
minimum of two years after the investigation is discontinued and FDA is notified. Documents may also be retained for a 
longer period, if required by the applicable regulatory, the institution’s requirements or by an agreement with the 
Sponsor. 

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 Statement of Compliance 
This clinical study will be conducted using GCP, as delineated in Guidance for Industry: E6 Good Clinical Practice 
Consolidated Guidance, and according to the criteria specified in this study protocol. Before study initiation, the 
protocol, informed consent/assent materials, and any information given to the participant will be reviewed and 
approved by the single IRB. Any amendments to the protocol, informed consent/assent materials, or any information 
given to the participant will also be approved by the single IRB before they are implemented. 
 Informed Consent/Assent Process 
The consent process will provide information about the study to each prospective participant and/or parent/legal 
guardian and will allow adequate time for review and discussion prior to his/her decision. The PI or designee listed on 
the FDA 1572 will review the consent and answer questions as needed. Consent designees must be listed on the CRU 
delegation of responsibilities log and have demonstrated knowledge of the protocol and study procedures. The 
participant and/or parent/legal guardian will be told that being in the trial is voluntary and that the participant may 
withdraw from the study at any time, for any reason. All participants and/or parents/legal guardians will be asked to 
read, sign, and date a consent form before the participant enters the study, takes study drug, or undergoes any study-
specific procedures. Each participant will also sign an assent, as appropriate. Consent materials will be presented in the 
participant’s and/or parent’s/legal guardian’s primary language. A copy of the signed consent form will be given to the 
participant or parent/legal guardian as well. 
The consent process will be ongoing. The consent form will be revised when important new safety information is 
available, the protocol is amended, and/or new information becomes available that may affect participation in the 
study. 
 Privacy and Confidentiality 
A participant’s privacy and confidentiality will be respected throughout the study. Each participant will be assigned a 
unique identification number and these numbers rather than names will be used to collect, store, and report all 
participant information. CRU staff will not transmit documents containing protected health information to the Sponsor, 
DAIT/NIAID, or their representatives. 
17 Publication Policy 
The CoFAR policy on the publication of study results will apply to this trial. 
18 References 
1. 
Gupta R, Holdford D, Bilaver L, Dyer A, Holl JL, Meltzer D. The economic impact of childhood food allergy in the 
United States. JAMA Pediatr 2013;167:1026-31. 
2. 
Savage J, Sicherer S, Wood R. The Natural History of Food Allergy. J Allergy Clin Immunol Pract 2016;4:196-203. 
3. 
Neuman-Sunshine DL, Eckman JA, Keet CA, et al. The natural history of persistent peanut allergy. Ann Allergy 
Asthma Immunol 2012;108:326-31. 
4. 
Sicherer SH, Sampson HA. Food allergy: Epidemiology, pathogenesis, diagnosis, and treatment. J Allergy Clin 
Immunol 2014;133:291-307. 
5. 
Nadeau KC, Schneider LC, Hoyte L, Borras I, Umetsu DT. Rapid oral desensitization in combination with 
omalizumab therapy in patients with cow's milk allergy. J Allergy Clin Immunol 2011;127:1622-4. 
6. 
Andorf S, Purington N, Block WM, et al. Anti-IgE treatment with oral immunotherapy in multifood allergic 
participants: a double-blind, randomised, controlled trial. Lancet Gastroenterol Hepatol 2018;3:85-94. 
7. 
Begin P, Dominguez T, Wilson SP, et al. Phase 1 results of safety and tolerability in a rush oral immunotherapy 
protocol to multiple foods using Omalizumab. Allergy Asthma Clin Immunol 2014;10:7. 

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8. 
MacGinnitie AJ, Rachid R, Gragg H, et al. Omalizumab facilitates rapid oral desensitization for peanut allergy. J 
Allergy Clin Immunol 2017;139:873-81. 
9. 
Sampson HA, Leung DY, Burks AW, et al. A phase II, randomized, double-blind, parallel-group, placebo-controlled 
oral food challenge trial of Xolair (omalizumab) in peanut allergy. J Allergy Clin Immunol 2011;127:1309-10. 
10. 
Savage JH, Courneya JP, Sterba PM, Macglashan DW, Saini SS, Wood RA. Kinetics of mast cell, basophil, and oral 
food challenge responses in omalizumab-treated adults with peanut allergy. J Allergy Clin Immunol 2012;130:1123-9. 
11. 
Schneider LC, Rachid R, LeBovidge J, Blood E, Mittal M, Umetsu DT. A pilot study of omalizumab to facilitate 
rapid oral desensitization in high-risk peanut-allergic patients. J Allergy Clin Immunol 2013;132:1368-74. 
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Jones SM, Sicherer SH, Burks AW, et al. Epicutaneous immunotherapy for the treatment of peanut allergy in 
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Investigators PGoC, Vickery BP, Vereda A, et al. AR101 Oral Immunotherapy for Peanut Allergy. N Engl J Med 
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threshold of allergic reactions to peanut. J Allergy Clin Immunol 2015;135:179-86. 
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Wanich N, Nowak-Wegrzyn A, Sampson HA, Shreffler WG. Allergen-specific basophil suppression associated with 
clinical tolerance in patients with milk allergy. J Allergy Clin Immunol 2009;123:789-94. 
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Berin MC, Grishin A, Masilamani M, et al. Egg-specific IgE and basophil activation but not egg-specific T-cell 
counts correlate with phenotypes of clinical egg allergy. J Allergy Clin Immunol 2018;142:149-58. 
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47. 
Siracusa MC, Wojno ED, Artis D. Functional heterogeneity in the basophil cell lineage. Advances in immunology 
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48. 
Tordesillas L, Rahman AH, Hartmann BM, Sampson HA, Berin MC. Mass cytometry profiling the response of 
basophils and the complete peripheral blood compartment to peanut. J Allergy Clin Immunol 2016;138:1741-4. 
49. 
Prussin C, Griffith DT, Boesel KM, Lin H, Foster B, Casale TB. Omalizumab treatment downregulates dendritic cell 
FcepsilonRI expression. J Allergy Clin Immunol 2003;112:1147-54. 
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Andorf S, Purington N, Kumar D, et al. A Phase 2 randomized controlled multisite study using omalizumab-
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Sampson HA, Munoz-Furlong A, Campbell RL, et al. Second symposium on the definition and management of 
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Appendix 1: Definition of Dose-Limiting Symptoms 
 
OFCs will be considered positive with the occurrence of any dose-limiting symptoms during a single dose, which in the 
view of the PI indicate a true allergic reaction which should preclude the administration of any further doses. As defined 
below, mild symptoms are not usually considered dose-limiting, although a combination of mild symptoms during a 
single dose might lead to the cessation of an OFC at the discretion of the PI. All moderate and severe symptoms as 
defined below are considered dose-limiting. 
Mild: 
• 
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 without decreased activity), isolated emesis 
thought to be secondary to gag 
Moderate: 
• 
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 
• 
GI – persistent moderate abdominal pain/cramping/nausea with decreased activity, vomiting 
Severe: 
• 
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 hypotension 

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18. Samples will be collected prior to initiating the blinded OFC at the first Screening DBPCFC Visit. 
19. Provide stool collection kit and specimen information questionnaire at the first Screening DBPCFC Visit. 
20. Collect stool collection kit and specimen information questionnaire at any time prior to the first injection visit in Stage 1  
21. Only needed for female participants of child-bearing potential 
22. Monthly questionnaires only completed when participants have completed six months of follow up in Stage 3 and are assigned to avoidance or dietary 
consumption regardless of duration of time on that treatment arm.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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11. Open label omalizumab and omalizumab or placebo for omalizumab may occur at Dose Build-Up Visits or may be a separate 
visit. 
12. Randomization will occur one week after beginning Stage 2. 
13. Unblind each participant to OFC results after completing the last blinded OFC during the DBPCFC at the end of Stage 2. 
14. If safety labs coincide with the bioassay/mechanistic blood collection, the priority, in terms of blood volume, is the safety labs. 
15. Initial Maintenance Dose Visit only. 
16. Provide stool collection kit and specimen information questionnaire at the last visit before the IDE Visit. 
17. Provide stool collection kit and specimen information questionnaire at the last visit before the first DBPCFC Visit. 
18. Sample will only be collected at this visit for participants that enter Stage 2 directly if Stage 1 is curtailed (section 3.1) 
19. Only needed for female participants of child-bearing potential. 
20. PEF is not required if an OIT dose is not given during an in clinic Initial or Follow-Up Maintenance Dose Visit. 

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17. Completed once a participant has completed 12 months in Stage 3 and are on Long-Term Follow-Up with Dietary consumption of a Food at 
that time. Visit may be combined with other follow up visits in Stage 3.  
 

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4. 
Each participant will be called or emailed at two weeks after the Initial Maintenance Dose Visit. The Open Feeding will be followed by weekly 
phone visits for the first four weeks, every other week from 6 to 16 weeks, and then every two months for safety follow-up until they have 
completed 6 months of Stage 3 Long-Term Follow-Up with Dietary Consumption. 
5. 
The participant will return to the CRU every six months for up to one year. 
6. 
A limited physical exam will be performed. 
7. 
A comprehensive physical exam will be performed prior to initiating the open feeding. If there is more than one open feeding on a given day, a 
limited physical exam will be performed prior to initiating each subsequent open feeding. 
8. 
SCORAD will be performed for participants with AD. AD is determined by the PI or licensed clinician based on the current medical history and/or 
the physical exam. 
9. 
SCORAD will be collected at the first six-month visit  
10. An interim family history questionnaire will only be collected once at the beginning of Stage 3. 
11. FAQLQ will be collected at six months after the start of rescue OIT. 
12. A SPT to peanut and two other foods will be completed at the at the first six-month visit. 
13. A participant who receives rescue OIT within 14 days of completing Stage 1 OLE will receive open label omalizumab until the IDE Visit is 
completed. 
14. A participant who receives rescue OIT within 14 days of completing Stage 2 will receive the treatment they were assigned to in Stage 2 until the 
IDE Visit is completed.  
15. A venous blood sample will be collected at six months after the start of rescue OIT. If the participant has reached dietary consumption and does 
not have clinic visits scheduled, bring the participant in for an Unscheduled Visit to collect the blood. 
16. Only perform safety sample collection if it has been more than three months since the last safety sample collection and the participant is still 
receiving omalizumab, placebo for omalizumab, or open label omalizumab from the previous stage. 
17. Only needed for female participants of child-bearing potential. 
18. Urine pregnancy tests will be performed monthly during the IDE Visit and Dose Build-Up Visits. If a pregnancy test has not been performed in the 
last month, urine pregnancy tests will also be performed at the Initial Maintenance Dose Visit, at the Follow-Up Maintenance Dose Visit, at the 
Open Feeding(s).    
19. PEF is not required if an OIT dose is not given during an in clinic Initial or Follow-Up Maintenance Dose Visit.  
20. Diaries are only required during the first six months of follow-up in Stage 3 Long-term follow-up with dietary consumption.  
21. Monthly Long-Term Follow-Up Questionnaires are collected after the participant has completed six months of follow-up in Stage 3 Long term 
follow-up with dietary consumption regardless of duration of time on the treatment arm. 
22. Completed once a participant has completed 12 months in Stage 3, are on Dietary Consumption of a Food at that time after transitioning from 
Rescue OIT for a food, Visit may be combined with other follow up visits in Stage 3.  
 
 
 

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Appendix 10: Sampson's Criteria for Diagnosing Potential Cases of Anaphylaxis 
 
Anaphylaxis is highly likely when any one of the following three criteria58 is fulfilled: 
1. Acute onset of an illness (minutes to several hours) with involvement of the skin, mucosal tissue, or both (e.g., 
generalized hives, pruritus or flushing, swollen lips tongue-uvula) 
AND AT LEAST ONE OF THE FOLLOWING: 
a. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
b. Reduced BP or associated symptoms of end-organ dysfunction (e.g., hypotonia [collapse], syncope, 
incontinence) 
2. Two or more of the following that occur rapidly after exposure to a likely allergen for that patient (minutes to 
several hours): 
a. Involvement of the skin-mucosal tissue (e.g., generalized hives, itch-flush, swollen lips-tongue-uvula) 
b. Respiratory compromise (e.g., dyspnea, wheeze-bronchospasm, stridor, reduced PEF, hypoxemia) 
c. Reduced BP or associated symptoms (e.g., hypotonia [collapse], syncope, incontinence) 
d. Persistent GI symptoms (e.g., crampy abdominal pain, vomiting) 
3. Reduced BP after exposure to known allergen for that patient (minutes to several hours): 
a. Infants and children: low systolic BP (age specific) or greater than 30% decrease in systolic BP∗ 
b. Adults: systolic BP of less than 90 mmHg or greater than 30% decrease from that person's baseline 
* Low systolic BP for children is defined as less than 70 mmHg from 1 month to 1 year, less than (70 mmHg + [2 × age]) 
from 1 to 10 years, and less than 90 mmHg from 11 to 17 years