Real-World AR101 Market-Supporting Experience Study in Peanut-Allergic Children Ages 4 to 17 Years (RAMSES)
Phase: PHASE3
Conditions: Peanut Allergy
Sponsor: Aimmune Therapeutics, Inc.

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
Page 1 of 93 
 
 
 
ARC007 
Real-World AR101 Market-Supporting 
Experience Study in Peanut-Allergic Children 
Ages 4 to 17 Years (RAMSES) 
 
Clinical Study Protocol 
Version 
Date 
Original Protocol 
21 October 2016 
Amendment 1.0 
28 February 2017 
Amendment 2.0 
27 September 2017 
 
 
Aimmune Therapeutics, Inc. 
8000 Marina Blvd. 
Suite 200 
Brisbane, CA 94005 
United States 
 
 
Confidentiality Statement 
This document and its contents are the property of Aimmune Therapeutics, Inc. and are confidential. 
Unauthorized copying or use is prohibited. 

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
Page 2 of 93 
 
CLINICAL STUDY PROTOCOL ARC007 
Sponsor Personnel 
Clinical Lead, Clinical 
Operations 
Freddy Byrth 
Aimmune Therapeutics, Inc. 
 
Chief Medical Officer 
Daniel C. Adelman, MD 
Aimmune Therapeutics, Inc.  
 
Sponsor Medical 
Monitor 
Kari Brown, MD 
Aimmune Therapeutics, Inc. 
 

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
Page 3 of 93 
Sponsor Protocol Approval 
Protocol ARC007 
 
Version: Amendment 2.0 
Date:    27 September 2017 
Sponsor: Aimmune Therapeutics, Inc. 
Title: Real-World AR101 Market-Supporting Experience Study in Peanut-Allergic 
Children Ages 4 to 17 Years (RAMSES)   
I have read protocol ARC007, Amendment 2.0, and I approve it. I agree to meet all 
obligations of the Sponsor as detailed in all applicable regulations and guidelines. In 
addition, I will inform the Principal Investigators and all other Investigators of all 
relevant information that becomes available during the conduct of this study. 
 
 
Daniel C. Adelman, MD 
Date 
Chief Medical Officer 
 

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
Page 4 of 93 
Principal Investigator Protocol Acknowledgement 
Protocol ARC007 
 
 
Version: Amendment 2.0 
 
Date:    27 September 2017 
IND: 15463 
 
Title: Real-World AR101 Market-Supporting Experience Study in Peanut-Allergic 
Children Ages 4 to 17 Years (RAMSES)   
I have read Clinical Study Protocol ARC007, Amendment 2.0. As the Principal 
Investigator, I agree to conduct this protocol according to Good Clinical Practice, as 
delineated in the United States Code of Federal Regulations (CFR) – 21 CFR Parts 50, 
54, and 312 (Subpart D) and in the International Council for Harmonisation of 
Technical Requirements for Pharmaceuticals for Human Use Guideline for Good 
Clinical Practice E6(R1) 10 June 1996, and according to the criteria specified in this 
protocol. Furthermore, I will conduct this protocol in keeping with local, state, and 
federal requirements. 
 
  
Principal Investigator (Print) 
 
 
Principal Investigator (Signature) 
Date 

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
Page 5 of 93 
Protocol ARC007 Amendment 2.0 Synopsis 
Title 
REAL-WORLD AR101 MARKET-SUPPORTING EXPERIENCE 
STUDY IN PEANUT-ALLERGIC CHILDREN AGES 4 TO 17 YEARS  
Short Title 
RAMSES 
Clinical Phase 
3 
IND 
15463 
IND Sponsor 
Aimmune Therapeutics, Inc.  
Number of Subjects 
Up to 500 peanut-allergic children will be randomized in a 2:1 ratio to AR101, 
a pharmaceutical-grade peanut allergen formulation, or placebo. The study 
population will consist of children aged 4 to 17 years, inclusive. 
Randomization will be stratified by age group (4 to 11 years and 12 to 17 years 
of age). 
Objectives 
The primary objective is to assess the safety and tolerability of AR101 when 
used in a characterized oral desensitization immunotherapy (CODIT)TM 
regimen for approximately 6 months in peanut-allergic children. 
The secondary objectives are to characterize the frequency of all 
treatment-related adverse events (AEs) by study period, especially those of 
interest (defined in Section 7.3.4 of the protocol), and AR101’s effect on 
asthma control and immune parameters.  
Study Design 
This is a multicenter, randomized, double-blind, placebo-controlled safety 
study of AR101 using the CODIT regimen in peanut-allergic children. The 
study will consist of a screening phase and a double-blind treatment phase that 
includes an initial 2-day escalation period and an up-dosing period. Subjects 
will be approached at the time of enrollment about donating saliva and 
additional blood samples to support exploratory biomarker analyses in a 
sub-study. Participation in this sub-study is voluntary and requires signing 
separate consent and assent documents.  
After completion of the up-dosing period, all study exit procedures, and 
treatment unblinding, subjects who received AR101 may participate in an 
open-label maintenance trial, known as Study ARC011; subjects who received 
placebo will be offered up-dosing and maintenance treatments with AR101 in 
Study ARC008.  For subjects participating in follow-on studies, both follow-on 
protocols must be activated at the study site before subjects can complete all of 
the required ARC007 study exit procedures.  Certain procedures (specifically, 
completion of questionnaires) and treatment unblinding will be completed at a 
later unscheduled visit if necessary to accommodate institutional review board 
(IRB) review of the follow-on protocols and shipment of open-label AR101.  
Additionally, all major data queries must be resolved before subjects complete 
exit procedures and proceed to a follow-on study.  Subjects will remain on 
blinded study treatment and have an unscheduled visit every 4 weeks or sooner 
until all exit requirements are met.   
The Screening/Baseline Period is up to 21 days. Eligible subjects will be 
randomized in a 2:1 ratio to receive escalating doses of either AR101 or 
placebo, in 2 phases. Following a 2-day initial escalation phase, up-dosing will 
be a minimum of 20 weeks to a maximum of 40 weeks in duration in order to 
achieve the 300 mg/d dose level. Subjects reaching this dose will continue in 
the study for an additional 2 weeks to ensure tolerability of the 300 mg/d dose 
before proceeding to the exit visit.  If the subject is unable to tolerate the 
300 mg dose for the 2-week period, dosing may continue up to a maximum of 
48 weeks after Day 1 to ensure tolerability prior to exiting the study.  

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
Page 6 of 93 
Protocol ARC007 Amendment 2.0 Synopsis 
Title 
REAL-WORLD AR101 MARKET-SUPPORTING EXPERIENCE 
STUDY IN PEANUT-ALLERGIC CHILDREN AGES 4 TO 17 YEARS  
For subjects terminating early for related and GI AEs, additional observational 
follow-up will occur monthly in clinic or by phone for up to 6 months or until 
the symptoms have resolved or stabilized, or the Investigator deems them to be 
irreversible, according to details described further in Section 6.5 of the 
protocol. 
Beginning at signed informed consent and assent as age-appropriate, all AEs 
will be evaluated from the onset of the event until the time the event is resolved 
or medically stable, or until 30 days after the Exit or Early Discontinuation 
Visit, whichever comes first, with the exception of gastrointestinal (GI) AEs, 
detailed further below. Adverse events ongoing at the time that study treatment 
is discontinued may not be determined to be medically stable until 30 days 
after the Exit or Early Discontinuation Visit has been conducted, in which case 
additional visits after the Exit or Early Discontinuation Visit may be required. 
Subjects who discontinue dosing prematurely due to chronic/recurrent GI AEs 
will complete the Pediatric Eosinophilic Esophagitis Symptom Score 
(PEESS)TM version 2.0 questionnaire and return to the clinic for evaluation 
monthly for at least 6 months (if the subject is asymptomatic, telephone 
follow-up with an Investigator may substitute for in-clinic visit, at the 
Investigator’s discretion). If chronic/ recurrent GI AEs persist beyond 
6 months, subjects are to continue to be followed with monthly clinic visits 
(telephone follow-up with an Investigator may substitute for in-clinic visit, at 
the Investigator’s discretion) until the symptoms have resolved or are assessed 
to have stabilized with optimal medical management or the Investigator deems 
them to be irreversible. The protocol provides additional specific guidance 
about symptomatic medical management and referrals to a gastroenterologist, 
as necessary, in Section 7.3.4.2 of the protocol.  
A Data Safety Monitoring Committee has been established to monitor the 
study for safety. 
Subjects who received AR101 and completed ARC007 will have the option to 
participate in the ARC011 study.  The ARC011 study is an open-label safety 
extension study of ARC007 to evaluate the safety and tolerability of 300 mg/d 
maintenance dosing for up to 6 months. After completing Study ARC011, 
subjects will be able to proceed to ARC008 for further maintenance dosing. 
Subjects who received active treatment but did not reach 300 mg/d within 
40 weeks or were unable to tolerate 300 mg daily for 2 weeks by 48 weeks 
after Day 1 will not be eligible for enrollment in ARC011 or ARC008. 
Subjects who received placebo and completed ARC007 will be offered 
up-dosing and maintenance treatment with AR101 in the ARC008 study. In 
ARC008, these subjects will undergo an escalation schedule identical to that 
for active subjects in the ARC007 study and then continue on maintenance 
dosing at 300 mg/d.  
All subjects who enter ARC008 will be allowed to continue receiving AR101 
until it becomes commercially available or the development program is 
terminated. 
Study Duration 
Screening/baseline for up to 21 days. 
Dosing typically for 22 to 48 weeks, unless double-blind treatment is extended 
for subjects waiting for activation of follow-on protocols. 
Up to 6 months (or more) additional observational follow-up for subjects 
terminating early for GI AEs. 

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
Page 7 of 93 
Protocol ARC007 Amendment 2.0 Synopsis 
Title 
REAL-WORLD AR101 MARKET-SUPPORTING EXPERIENCE 
STUDY IN PEANUT-ALLERGIC CHILDREN AGES 4 TO 17 YEARS  
Primary Endpoint 
The primary endpoint of this study is the frequency of treatment-emergent 
AEs, including serious AEs, during the overall study period. 
Secondary 
Endpoints 
Secondary Endpoints  
• Frequency of premature discontinuation of dosing due to AEs 
• Frequency of premature discontinuation of dosing due to 
chronic/recurrent GI AEs  
• Proportion of chronic / recurrent GI AEs resolving at 2, 4, and ≥ 12 weeks 
following cessation of dosing 
• Frequency of allergic reaction (hypersensitivity) AEs occurring during 
up-dosing, normalized for duration of treatment 
• Frequency of anaphylaxis as defined in the protocol  
• Frequency of use of epinephrine as a rescue medication  
• Frequency of accidental ingestions of peanut and other allergenic foods 
and severity of any resultant reactions  
• Assessment of asthma control using the Asthma Control Test (ACT) 
questionnaire and frequency of use of asthma rescue medication (short 
acting beta-agonists) in subjects with asthma 
Exploratory 
Endpoints 
Exploratory Endpoints 
• Changes in peanut-specific and peanut component-specific serum 
immunoglobulin E (IgE) and immunoglobulin G subclass 4 (IgG4) levels 
• Changes in peanut skin prick test (SPT) mean wheal diameter 
• Changes in Total Nasal Symptom Score in subjects with allergic rhinitis 
• Changes in scores of the food allergy related quality of life questionnaire 
(FAQLQ) and food allergy independent measure (FAIM) questionnaire 
Investigational 
Product and 
Dispensing 
AR101 or Placebo 
AR101 is a characterized, oral biological drug product containing the protein 
profile found in peanuts.  AR101 doses will ascend per the dosing regimen 
outlined below. Investigational product (IP) will be provided in pull-apart 
capsules formulated to contain 0.5, 1, 10, 20, and 100 mg of peanut protein. 
Matching placebo capsules identical to the active capsules will be used to 
maintain the blind. Trained investigational site personnel will dispense the IP 
to the subject or the subject’s parent or guardian in a manner consistent with 
the assigned dose level. Investigational product will be dispensed in a 
double-blinded fashion according to subject randomization number, using an 
interactive voice/web response system. 
All IP will be stored at the site in a secure location and kept refrigerated 
between 2°C and 8°C. 
Inclusion Criteria 
1. Age 4 to 17 years, inclusive 
2. A history of physician-diagnosed IgE-mediated peanut allergy that 
includes the onset of characteristic allergic signs and symptoms within 
two hours of known oral exposure to peanut or a peanut-containing food. 
While IgE-mediated reactions have varied presentations, in general, 
characteristic allergic signs and symptoms are objective and affect the 
target organs of the skin, GI tract, upper and/or lower respiratory tract, 
cardiovascular system, or a combination (Appendix 2 of the protocol). 

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
Page 8 of 93 
Protocol ARC007 Amendment 2.0 Synopsis 
Title 
REAL-WORLD AR101 MARKET-SUPPORTING EXPERIENCE 
STUDY IN PEANUT-ALLERGIC CHILDREN AGES 4 TO 17 YEARS  
3. Mean peanut wheal diameter on SPT of ≥ 8 mm greater than the negative 
saline control at Screening 
4. Serum IgE to peanut of ≥ 14 kUA/L at Screening 
5. Written informed consent from the subject’s parent/guardian  
6. Written assent from the subject as appropriate (eg, above the age of 
7 years or the applicable age per local regulatory requirements) 
7. Use of effective birth control by sexually active female subjects of 
childbearing potential 
Exclusion Criteria 
1. Subjects in whom the clinical diagnosis of peanut allergy is uncertain 
2. History of cardiovascular disease, including uncontrolled or inadequately 
controlled hypertension (see Section 5.10 of the protocol) 
3. Use of beta-blockers, angiotensin-converting enzyme inhibitors, 
angiotensin-receptor blockers, calcium channel blockers, or tricyclic 
antidepressants (see Section 5.10 of the protocol)  
4. History of severe or life-threatening episode of anaphylaxis or 
anaphylactic shock within 60 days of screening 
5. History of eosinophilic esophagitis (EoE), other eosinophilic GI disease, 
chronic, recurrent, or severe gastroesophageal reflux disease, symptoms 
of dysphagia (eg, difficulty swallowing, food “getting stuck”), or 
recurrent GI symptoms of undiagnosed etiology  
6. History of a mast cell disorder, including mastocytosis, urticaria 
pigmentosa, chronic idiopathic or chronic physical urticaria beyond 
simple dermatographism (eg, cold urticaria, cholinergic urticaria), and 
hereditary or idiopathic angioedema 
7. Severe persistent asthma (2007 National Heart, Lung, and Blood Institute 
[NHLBI] Criteria Steps 5 or 6, see Appendix 3 of the protocol)  
8. Mild or moderate persistent asthma (2007 NHLBI Criteria Steps 1 to 4), if 
uncontrolled or difficult to control as defined by any of the following: 
a. Forced expiratory volume in 1 second (FEV1) < 80% of predicted, 
with or without controller medications (only for age 6 years or 
greater and able to do spirometry); or  
b. Inhaled corticosteroid (ICS) dosing of > 500 mcg daily fluticasone 
(or equivalent ICSs based on NHLBI dosing chart); or  
c. One hospitalization in the past year prior to screening for asthma; or  
d. Emergency room visit for asthma within 6 months prior to screening 
9. History of high-dose corticosteroid use (eg, 1 to 2 mg/kg of prednisone or 
the equivalent for > 3 days) by any route of administration in any of the 
following manners:  
a. History of daily steroid dosing for > 1 month during the past year; or 
b. 1 steroid course in the past 3 months; or  
c. > 2 steroid courses in the past year ≥ 1 week in duration  
10. History of chronic disease (other than asthma, atopic dermatitis, or 
allergic rhinitis) that is, or is at significant risk of becoming, unstable or 
requiring a change in chronic therapeutic regimen 
11. Inability to discontinue antihistamines 5 half-lives before the screening 
SPT and initial day of escalation 

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
Page 9 of 93 
Protocol ARC007 Amendment 2.0 Synopsis 
Title 
REAL-WORLD AR101 MARKET-SUPPORTING EXPERIENCE 
STUDY IN PEANUT-ALLERGIC CHILDREN AGES 4 TO 17 YEARS  
12. Lack of an available palatable vehicle food to which the subject is not 
additionally allergic  
13. Hypersensitivity to epinephrine or any of the excipients in the epinephrine 
auto-injector 
14. Use of omalizumab or any other monoclonal antibody therapy within the 
6 months prior to screening or any current immunomodulatory therapy 
besides aeroallergen or venom immunotherapy or corticosteroids (see also 
Section 5.10 of the protocol) 
15. Having received at least one dose of AR101 in a previous Aimmune or 
Allergen Research Corporation study 
16. Use of other forms of peanut immunotherapy (eg, oral, sublingual, 
epicutaneous) within 6 months prior to screening 
17. Participation in another clinical trial within 30 days or 5 half-lives of the 
IP, whichever is longer, prior to randomization 
18. Concurrent administration of “build-up phase” of immunotherapy to 
another allergen (ie, subject has not reached maintenance dosing)  
19. Pregnancy or lactation 
20. Having the same place of residence as another subject in any AR101 
study 
Treatment 
Description 
Screening/Baseline: All subjects will undergo the screening procedure outlined 
in Section 6.2 of the protocol and eligible subjects will be randomized 2:1 to 
active treatment with AR101 or placebo.  
Initial Escalation (2 days): Eligible subjects will be randomized and initiate 
CODIT starting at a dose of 0.5 mg of IP, and then increase the dose 
incrementally at 20- to 30-minute intervals over the course of a single day to a 
maximum dose of 6 mg. Subjects who fail to tolerate ≥ 3 mg dose on Day 1 
will be considered escalation failures and will be discontinued. Subjects who 
tolerate ≥ 3 mg dose on Day 1 will undergo confirmatory dosing of a single 
3 mg dose on the following day, Day 2. Subjects who tolerate this confirmatory 
dose will enter the Up-Dosing Period. Subjects who do not tolerate this 
confirmatory dose will be discontinued. Initial escalation failures, either on 
Day 1 or Day 2, will be asked to return to the clinical research center (CRC) 
14 days following the last dose of IP to undergo an Early Discontinuation Visit. 
Up-dosing: Subjects will receive IP starting at a dose of 3 mg once daily and 
will gradually escalate every 2 weeks to a maximum of 300 mg once daily, 
according to the Up-Dosing Schedule (see Table 2 of the protocol). Subjects 
who are unable to escalate to 300 mg within 40 weeks or who are unable to 
tolerate 300 mg daily for 2 weeks by 48 weeks after Day 1 will be considered 
escalation failures.   
Subjects able to escalate to 300 mg/d will continue taking the 300 mg dose for 
an additional 2 weeks and then exit the study, providing all exit requirements 
are met.  If the subject is unable to tolerate the 300 mg dose for the 2-week 
period, dosing may continue up to a maximum of 48 total weeks since Day 1 to 
ensure tolerability prior to exiting the study. 
Unblinding of each subject’s treatment assignment will occur at study 
completion per the conditions stated previously, and the subjects will have the 
option to enter a rollover study depending on their ARC007 treatment 

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
Page 10 of 93 
Protocol ARC007 Amendment 2.0 Synopsis 
Title 
REAL-WORLD AR101 MARKET-SUPPORTING EXPERIENCE 
STUDY IN PEANUT-ALLERGIC CHILDREN AGES 4 TO 17 YEARS  
assignment: ARC011 for AR101-treated subjects, and ARC008 for those 
receiving placebo.  
The first dose at each new dose level for up-dosing will be administered in a 
CRC or other monitored setting (unless required by a specific institution, no 
distinction will be drawn between an investigational site, study center office, 
clinic, or CRC, provided the capability requirements for monitoring and 
emergency intervention are met by the facility). Subsequent doses will be 
dispensed to the subject or parent/guardian and administered at home. 
All up-dosing activities will be performed under direct observation. Doses may 
be adjusted for tolerability or inter-current illness by the Investigator, except no 
down-dosing below 3 mg/day is allowed.  Up-dosing period may thereby be 
extended to a maximum of 40 weeks in order to reach 300 mg and should not 
exceed this period. Those subjects who reach the target dose of 300 mg/d of IP 
will take this dose for an additional 2 weeks.  Subjects unable to escalate to 
300 mg within 40 weeks will be considered escalation failures. Subjects able to 
escalate to 300 mg will continue taking the 300 mg dose for an additional 
2 weeks to ensure tolerability prior to exiting ARC007. Non-responder subjects 
will be asked to return to the CRC 14 days following the last dose of IP to 
undergo an Early Discontinuation Visit. 
Once all conditions are met for enrollment in the appropriate follow-on study, 
treatment assignments will then be unblinded, and subjects will have the option 
to enroll in ARC011 or ARC008. Subjects who fail to reach the 300 mg/d dose 
of IP within 40 weeks will be discontinued from ARC007 and will be ineligible 
to enroll in ARC011 or ARC008.  
Further details can be found in Section 6 of the protocol. 
Study Procedures 
The following procedures will be performed according to the scheduled visits 
tabulated in the Schedule of Events for ARC007 (Appendix 1 of the protocol): 
• Informed consent (and assent, as age appropriate) 
• Inclusion/exclusion criteria 
• Medical/allergy history  
• Diet history 
• Concomitant medications 
• Physical examination, including height and weight 
• Vital signs (blood pressure, pulse rate, temperature) 
• Spirometry (FEV1) in children ≥ 6 years  
• Peak expiratory flow rate   
• Pregnancy test for sexually active females of childbearing potential 
• Blood draw for peanut-specific IgE and IgG4 
• Complete blood cell count, obtained with the same venipuncture as the 
blood draw for the immunoglobulin assays 
• Additional blood samples for optional exploratory immunologic studies. 
These can be obtained with the same venipuncture as the blood draw for 
the immunoglobulin assays (separate informed consent required). 
• Optional blood sample(s) 
• Optional collection of saliva sample for exploratory biomarker 
development (separate informed consent required) 
• SPT 
• Randomization and IP administration 
• Dispensing of IP for home-dosing/return of unused IP 

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
Page 11 of 93 
Protocol ARC007 Amendment 2.0 Synopsis 
Title 
REAL-WORLD AR101 MARKET-SUPPORTING EXPERIENCE 
STUDY IN PEANUT-ALLERGIC CHILDREN AGES 4 TO 17 YEARS  
• AE monitoring 
• Monitoring for dosing compliance 
• Assessment of asthma control using the ACT questionnaire and frequency 
of asthma rescue medication use in subjects with asthma  
• PEESS v2.0 questionnaire (for subjects with GI AEs that interrupt dosing) 
• Peanut allergy teaching 
• Telephone follow-up 
• Completion of the FAQLQ and the FAIM questionnaire. 
• Completion of the Total Nasal Symptom Score in subjects with allergic 
rhinitis 
Statistical 
Considerations 
ARC007 is a safety study that will add critical placebo-controlled observations 
to the ongoing safety database of AR101. As such, there are no efficacy 
endpoints in the study, no specific efficacy-related hypotheses to be tested, and 
thus no prospective sample size calculations performed related to the clinical 
effectiveness of AR101 treatment versus placebo.  
A sample size of up to 500 subjects, randomized in a 2:1 ratio to AR101 or 
placebo, along with subjects enrolled in other studies in the clinical program 
will provide a sufficient number of subjects to fulfill the regulatory requirement 
for data on at least 600 subjects dosed for 6 months at 300 mg/d. 
Data will be summarized using descriptive statistics and will be displayed by 
treatment group. No specific hypothesis testing or comparisons between the 
treatment groups is planned for this study. Further details on the analytical 
approach and any exploratory comparisons between treatments will be 
provided in the statistical analysis plan. See Section 9 of the protocol for 
further information. 
 

Aimmune Therapeutics, Inc. 
AR101 (Characterized Peanut Allergen) 
ARC007 (Amendment 2.0) 
Clinical Study Protocol – 27 September 2017 
 
AIMMUNE CONFIDENTIAL 
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Table of Contents 
1. 
BACKGROUND AND RATIONALE ................................................................................. 19 
1.1 
Background ................................................................................................................... 19 
1.2 
Clinical Trials of AR101 ............................................................................................... 20 
1.2.1 
ARC001 Trial........................................................................................................ 20 
1.2.2 
ARC002 Trial........................................................................................................ 21 
1.2.3 
ARC003 Trial........................................................................................................ 21 
1.3 
Rationale for the Current Study .................................................................................... 22 
1.4 
Known and Potential Risks and Benefits of AR101 ..................................................... 23 
1.4.1 
Risks ...................................................................................................................... 23 
1.4.2 
Benefits ................................................................................................................. 23 
2. 
OBJECTIVES ....................................................................................................................... 24 
2.1 
Primary Objective ......................................................................................................... 24 
2.2 
Secondary Objectives.................................................................................................... 24 
3. 
STUDY DESIGN.................................................................................................................. 24 
3.1 
Study Periods ................................................................................................................ 25 
3.2 
Initial Escalation ........................................................................................................... 26 
3.3 
Up-Dosing ..................................................................................................................... 26 
3.4 
Treatment Unblinding and Rollover to Studies ARC011 and ARC008 ....................... 27 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS ........................................................ 28 
4.1 
Inclusion Criteria .......................................................................................................... 28 
4.2 
Exclusion Criteria ......................................................................................................... 28 
4.3 
Early Termination ......................................................................................................... 30 
4.3.1 
Criteria for Early Termination .............................................................................. 30 
4.3.2 
Follow-up of Subjects Who Discontinue Treatment ............................................ 31 
4.3.3 
Subject Replacement ............................................................................................. 31 
5. 
STUDY TREATMENT ........................................................................................................ 31 
5.1 
Formulation, Packaging, and Labeling ......................................................................... 31 
5.2 
Preparation, Administration, and Dosage ..................................................................... 32 
5.3 
Drug Accountability...................................................................................................... 33 
5.4 
Assessment of Compliance with Study Treatment and Monitoring ............................. 33 
5.5 
Modification of Study Treatment.................................................................................. 33 

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5.6 
Concomitant Medications ............................................................................................. 33 
5.7 
Prophylactic Medications.............................................................................................. 34 
5.8 
Rescue Medications ...................................................................................................... 34 
5.9 
Symptomatic Treatment for Chronic and/or Recurrent Adverse Events ...................... 34 
5.10 
Prohibited Medications ................................................................................................. 34 
6. 
STUDY PROCEDURES ...................................................................................................... 35 
6.1 
Enrollment and Randomization .................................................................................... 35 
6.2 
Screening and Baseline ................................................................................................. 35 
6.3 
Study Visits ................................................................................................................... 37 
6.3.1 
Initial Escalation: Day 1........................................................................................ 37 
6.3.2 
Initial Escalation: Day 2........................................................................................ 38 
6.3.3 
Up-Dosing (Also Referred to as Build-up) Visits ................................................. 40 
6.3.4 
Up-Dosing Interim (80 mg) Visit ......................................................................... 42 
6.3.5 
End-Up-Dosing Phase Visit .................................................................................. 42 
6.3.6 
Exit Visit/Early Discontinuation Visit .................................................................. 42 
6.4 
Unscheduled Visits / Unscheduled Blood Draws ......................................................... 44 
6.5 
Assessment and Treatment of Allergic Reactions to Peanut ........................................ 44 
6.5.1 
Definitions of Symptom Severity ......................................................................... 44 
6.5.2 
Assessment of the Tolerability of an Individual Dose of Investigational Product 45 
6.5.3 
Assessment of the Tolerability of a Dose Level ................................................... 46 
6.5.4 
Treatment of Acute Reactions to Peanut OIT During Initial Escalation .............. 48 
6.5.5 
Treatment for Reactions During the Up-dosing Period: Dose Adjustment .......... 50 
6.5.6 
Treatment for Reactions During the Up-dosing Period: Pharmacological and 
Supportive Treatments .......................................................................................... 55 
6.6 
Missed OIT (Investigational Product) Doses during Up-dosing .................................. 56 
6.7 
Skin Prick Test .............................................................................................................. 58 
6.8 
Visit Windows .............................................................................................................. 58 
7. 
SAFETY MONITORING ..................................................................................................... 58 
7.1 
Reporting of Safety Events ........................................................................................... 58 
7.2 
Dosing Symptoms as Adverse Events .......................................................................... 59 
7.3 
Definitions..................................................................................................................... 59 
7.3.1 
Adverse Event ....................................................................................................... 59 
7.3.2 
Adverse Reaction .................................................................................................. 59 

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7.3.3 
Serious Adverse Event .......................................................................................... 59 
7.3.4 
Adverse Event of Interest...................................................................................... 60 
7.4 
Severity Grading ........................................................................................................... 63 
7.4.1 
Guidelines for Determining Causality of an Adverse Event ................................ 64 
7.5 
Data Safety Monitoring Committee .............................................................................. 64 
7.6 
Adverse Event Collection Procedures .......................................................................... 64 
7.6.1 
Recording and Reporting Procedures ................................................................... 64 
7.6.2 
Serious Adverse Event Recording and Reporting Procedures .............................. 65 
7.7 
Serious Adverse Event Notification.............................................................................. 66 
7.7.1 
Notifying the Sponsor ........................................................................................... 66 
7.7.2 
Expedited SAEs Reporting to Regulatory Health Authorities .............................. 66 
7.7.3 
Notifying the DSMC ............................................................................................. 67 
7.7.4 
Notifying the Institutional Review Board and Ethics Committee ........................ 67 
7.8 
Other Safety Assessments and Precautions .................................................................. 67 
7.8.1 
Physical Examination and Vital Signs .................................................................. 67 
7.8.2 
Prior and Concomitant Medications ..................................................................... 67 
7.8.3 
Pregnancy Testing and Contraception .................................................................. 68 
7.9 
Stopping Rules .............................................................................................................. 68 
7.9.1 
Overall Stopping Rules ......................................................................................... 68 
7.9.2 
Individual Stopping Rules..................................................................................... 69 
8. 
OPTIONAL MECHANISTIC SUBSTUDIES ..................................................................... 69 
9. 
STATISTICAL CONSIDERATIONS.................................................................................. 69 
9.1 
Analysis Populations ..................................................................................................... 70 
9.2 
Study Endpoints ............................................................................................................ 70 
9.2.1 
Primary Endpoint .................................................................................................. 70 
9.2.2 
Secondary Endpoints ............................................................................................ 70 
9.2.3 
Exploratory Endpoints .......................................................................................... 71 
9.3 
Subject and Demographic Data .................................................................................... 71 
9.3.1 
Baseline Characteristics and Demographics ......................................................... 71 
9.3.2 
Use of Medications ............................................................................................... 71 
9.3.3 
Study Disposition .................................................................................................. 71 
9.3.4 
Adverse Events ..................................................................................................... 71 
9.4 
Sample Size and Power Calculations ............................................................................ 71 

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9.5 
Web-Based Data Collection and Management System ................................................ 72 
9.6 
Certification in the Use of Electronic Data Entry System ............................................ 72 
9.7 
Data Management ......................................................................................................... 72 
9.8 
Access to Data............................................................................................................... 72 
10. QUALITY CONTROL AND QUALITY ASSURANCE .................................................... 72 
10.1 
Statement of Compliance .............................................................................................. 72 
10.2 
Informed Consent and Assent ....................................................................................... 73 
10.3 
Privacy and Confidentiality .......................................................................................... 73 
11. RESOURCE SHARING ....................................................................................................... 73 
12. PROTOCOL DEVIATIONS ................................................................................................ 73 
12.1 
Reporting and Managing Protocol Deviations .............................................................. 74 
13. REFERENCE LIST .............................................................................................................. 75 
 
List of Tables 
Table 1: 
Initial Escalation Schedule .................................................................................... 26 
Table 2: 
Up-Dosing Schedule ............................................................................................. 27 
Table 3: 
Allergy Symptom Severity and Investigational Product Dose Tolerability ......... 45 
 
List of Figures 
Figure 1: 
Schematic for Initial Escalation Day 1 ................................................................. 50 
Figure 2: 
Schematic for Up-dosing Period Dose Adjustment .............................................. 54 
Figure 3: 
Reporting Decisions for Adverse Events .............................................................. 66 
 
List of Appendices 
Appendix 1: 
Schedule of Events for ARC007 ........................................................................... 78 
Appendix 2: 
Systems and Examples of Symptoms Involved in Acute IgE-mediated Reactions 
to Foods (Sampson et al, 2014)............................................................................. 80 
Appendix 3: 
Evaluation of Asthma ........................................................................................... 81 
Appendix 4: 
Criteria for Suspected Diagnosis, and Severity Grading, of Anaphylaxis ............ 82 
Appendix 5: 
Allergic Reaction Severity Grading ...................................................................... 83 
Appendix 6: 
Guidance for Determining When an Episode of Anaphylaxis Should Be Reported 
as a Serious Adverse Event ................................................................................... 84 

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Appendix 7: 
Exploratory Biochemical and Molecular Sub-study of Peanut-Allergic Children 
with Oral Immunotherapy-Related Gastrointestinal Symptoms ........................... 85 
Appendix 8: 
Total Nasal Symptom Score Sheet (Example)...................................................... 93 
 

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List of Abbreviations 
AAAAI 
American Academy of Allergy, Asthma & Immunology 
ACE 
angiotensin-converting enzyme  
ACT 
Asthma Control Test 
AE 
adverse event 
AEI 
adverse event of interest 
AR101 
characterized peanut allergen 
ARB 
angiotensin-receptor blocker 
BP 
blood pressure 
CBC 
complete blood cell count 
CFR 
US Code of Federal Regulations 
CODIT 
characterized oral desensitization immunotherapy 
CoFAR 
Consortium of Food Allergy Research 
CRC 
clinical research center 
CRF 
case report form 
DBPCFC 
double-blind, placebo-controlled food challenge 
DSMC 
Data Safety Monitoring Committee 
EAACI 
European Academy of Allergy and Clinical Immunology 
EC 
ethics committee 
EDC 
electronic data capture 
EGD 
esophagogastroduodenoscopy 
ELISA 
enzyme-linked immunosorbent assay 
EoE 
eosinophilic esophagitis 
ER 
emergency room 
FAIM 
food allergy independent measure (questionnaire) 
FAQLQ 
food allergy quality of life questionnaire 
FDA 
US Food and Drug Administration 
FEV1 
forced expiratory volume in 1 second  
GCP  
Good Clinical Practice  
GERD 
gastroesophageal reflux disease 
GI 
gastrointestinal 

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ICH 
International Council for Harmonisation 
ICF 
informed consent form 
ICS 
inhaled corticosteroid 
lgE 
immunoglobulin E 
lgG4 
immunoglobulin G subclass 4 
IND 
Investigational New Drug  
IP 
investigational product 
IRB 
institutional review board 
ITT 
intent-to-treat 
IV 
intravenous 
IXRS 
interactive voice/web response system  
NCI-CTCAE 
National Cancer Institute Common Terminology Criteria for Adverse Events 
NHLBI 
National Heart, Lung, and Blood Institute 
OIT 
oral immunotherapy 
PEESS 
Pediatric Eosinophilic Esophagitis Symptom Scores 
PEFR 
peak expiratory flow rate 
PR 
pulse rate 
PRACTALL 
PRACTical issues in ALLergology Joint United States/European Union 
qPCR 
quantitative polymerase chain reaction 
RNA 
ribonucleic acid 
SAE 
serious adverse event 
SAP  
Statistical Analysis Plan 
SOE 
schedule of events 
SPT 
skin prick test 
SVM 
support vector machine 
TEAE 
treatment-emergent adverse event 
 

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1. 
BACKGROUND AND RATIONALE 
1.1 
Background 
Peanut allergy is a common and serious condition that disproportionately affects children and is 
associated with severe reactions, including life-threatening anaphylaxis. The prevalence of 
peanut allergy, like other food allergies, has been rising, and is now at high levels, affecting up to 
2% of the population (Sicherer and Sampson 2014). The current standard of care in management 
of peanut allergy is a peanut-avoidant diet, along with education of the patient and family in the 
acute management of an allergic reaction, including ready access to self-injectable epinephrine. 
The burden of avoidance and the constant fear of accidental exposure negatively affect the 
health-related quality of life for patients and their families (Primeau et al, 2000; Avery et al, 
2003; Sicherer et al, 2010; Anagnostou et al, 2014). 
In addition, peanut-avoidant diets are complicated by the difficulty of interpreting food labels 
and the presence of undeclared or hidden allergens in commercially-prepared foods (Joshi et al, 
2002; Altschul et al, 2001; Vierk et al, 2002). Accidental exposures are common, with 55 percent 
of food-allergic patients having at least 1 allergic reaction in a 5-year period (Sicherer et al, 
1998). 
In early clinical trials, oral immunotherapy (OIT) for peanut allergy has demonstrated 
encouraging safety and efficacy results in creating a change in clinical reactivity that would 
protect recipients from these accidental exposures (Jones et al, 2009; Hofmann et al, 2009; 
Blumchen et al, 2010; Yu et al, 2012; Varshney et al, 2011; Anagnostou, et al 2014). All of these 
studies involved a period of up-dosing with increasing amounts of peanut protein, a period of 
maintenance therapy, and then an oral food challenge to assess desensitization. Dosing 
symptoms observed in these studies included rash, wheezing, rhinorrhea, sneezing, itching, 
abdominal pain, nausea, vomiting, and diarrhea. Most symptoms were mild, consistent with a 
transient, low-grade allergic reaction, and tended to diminish in frequency with increasing 
duration of treatment.  
There is evidence that OIT induces a clinically meaningful level of desensitization in most 
patients and may also induce favorable immunologic changes over time. Though these studies 
used different doses and regimens, they collectively provide supportive evidence for the efficacy 
and safety of peanut OIT and were the basis for the initiation of clinical development of AR101, 
a standardized OIT product manufactured to pharmaceutical-grade standards and previously 
tested in Aimmune’s Phase 2 program and ongoing Phase 3 programs. 
The goal of OIT with AR101 is to induce and maintain a state of desensitization to peanut 
protein, defined as the ability to consume a specific dose of peanut protein with no or mild 
symptoms. This state of desensitization, in conjunction with a peanut-avoidant diet, should be 
sufficient to protect a peanut-allergic individual from an accidental exposure to peanuts or 
peanut-containing foods.  

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1.2 
Clinical Trials of AR101 
1.2.1 
ARC001 Trial 
ARC001 was a multicenter, randomized, double-blind, placebo-controlled study of the efficacy 
and safety of AR101 in peanut-allergic children and adults 4 to 26 years of age. ARC001 
consisted of a screening period, including a screening double-blind placebo-controlled food 
challenge (DBPCFC), an initial escalation period, an up-dosing period, and a maintenance 
period, followed by an exit DBPCFC. The primary endpoint of ARC001 was the percentage of 
desensitization responders, defined as subjects tolerating 300 mg (443 mg cumulative) at the Exit 
DBPCFC. 
A total of 56 subjects were randomized: 29 subjects to AR101 and 27 subjects to placebo. One 
subject in the placebo group withdrew consent after randomization and before treatment. The 
intent-to-treat (ITT) population thus comprised 55 subjects: 29 in the AR101 and 26 in the 
placebo arm. The 2 groups were overall well matched for baseline characteristics including 
baseline sensitivity in the Screening DBPCFC. Six subjects in the AR101 arm withdrew prior to 
the Exit DBPCFC.  
In the ITT population, AR101 was statistically significantly superior to placebo, with 23 of 
29 (79%) desensitization responders in the AR101 group as compared to 5 of 26 (19%) 
desensitization responders in the placebo group, resulting in a treatment difference of 60% 
(P < 0.0001 by Fisher’s exact test). In the completer population (those subjects completing the 
Exit DBPCFC), 23 of 23 AR101 completers were desensitization responders, resulting in a 
treatment difference of 81% (P < 0.0001 by Fisher’s exact test). At the time of the exit visit, the 
geometric mean for peanut-specific IgE levels were lower for the AR101 group compared with 
the placebo group; higher for the AR101 group compared with the placebo group for 
peanut-specific IgG4; and lower for the AR101 group compared with the placebo group for 
peanut-specific IgE/IgG4 ratio. 
AR101 was generally well tolerated. The overall incidence of treatment-emergent adverse 
events (TEAEs) was 97% for the AR101 treatment group and 85% for the placebo group. One 
subject (3%) in the AR101 group experienced a treatment-emergent serious adverse event 
(SAE) of hypersensitivity (verbatim:  anaphylaxis) related to treatment. One subject (4%) in the 
placebo group experienced an SAE of presyncope/hypersensitivity (verbatim:  vaso-vagal 
reaction/anaphylaxis) related to the peanut protein in the Exit DBPCFC, not investigational 
product (IP). An additional subject experienced a prerandomization, non-treatment-emergent 
SAE of hypersensitivity (verbatim:  slow developing anaphylaxis or biphasic reaction) 
following the Screening DBPCFC.  No placebo-treated subject had an adverse event leading to 
discontinuation. A total of 4 AR101-treated subjects (14%) experienced an adverse event that 
led to permanent discontinuation of study treatment. One subject discontinued due to a 
treatment-related adverse event of eosinophilic esophagitis (EoE), 2 subjects each discontinued 
treatment due to a treatment-related adverse event of vomiting and 1 subject discontinued due 
to an adverse event of stomach pain. Two additional AR101-treated subjects withdrew from the 
study prematurely due to withdrawal of consent or investigator decision. Both subjects also 
experienced gastrointestinal (GI) adverse events that likely contributed to their withdrawal from 
the study.   

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In summary, AR101 appeared to be generally well tolerated, and significantly superior to 
placebo for reducing clinical reactivity to peanut allergen in peanut-allergic children and 
adolescents to young adults. AR101 treatment significantly increased the probability of 
tolerating peanut allergen doses ≥ 300 mg and resulted in favorable changes in clinical markers 
of peanut allergen immunoreactivity compared with placebo. 
1.2.2 
ARC002 Trial 
All ARC001 placebo subjects who completed the ARC001 study were eligible for rollover into 
the open-label ARC002 protocol. All subjects on AR101 who passed the ARC001 Exit 
DBPCFC by tolerating > 443 mg cumulative of peanut protein with no more than mild 
symptoms were also eligible to enter ARC002.  
Group 1 included subjects who completed the placebo arm of ARC001 and consented to enroll in 
ARC002, crossing over to active treatment using the same dosing regimen used in ARC001, but 
in open-label fashion. After completion of the Up-dosing Phase, Group 1 subjects underwent a 
DBPCFC (to a maximum single dose of 600 mg of peanut protein, or 1043 mg of cumulative 
peanut protein). Subjects who did not tolerate the post-low-dose build-up phase DBPCFC at 
≥ 443 mg cumulative were considered escalation failures and were discontinued from the study 
due to safety concerns. Those subjects who tolerated the DBPCFC at ≥ 443 mg cumulative of 
peanut protein entered an approximately 3-month (12- to 24-week) Plateau Phase of 
continued dosing at 300 mg/d.  
Group 2 subjects who completed the active AR101 arm of ARC001 and consented to enroll 
into ARC002 went directly into the 300 mg/d, 3-month Plateau Phase of ARC002. Following 
completion of the 3-month Plateau Phase, all ARC002 subjects underwent a post-Plateau 
Phase DBPCFC (to a maximum single dose of 1000 mg of peanut protein, or 2043 mg 
cumulative).  
Based on the total population of 26 Group 1 subjects receiving ≥ 1 dose of AR101, 76.9% of 
subjects tolerated 300 mg and 65.4% tolerated 600 mg. At the post-Plateau DBPCFC in 
40 subjects in Groups 1 and 2, 100%, 90%, and 60% of the subjects tolerated a cumulative 
peanut protein dose of 443 mg, 1043 mg, and 2043 mg, respectively. These findings demonstrate 
the persistence of desensitization during daily maintenance treatment with AR101 at 300 mg/d, 
further supporting the primary endpoint selection in the Phase 3 trial ARC003. The findings also 
indicate that treatment with AR101 may achieve a maximum tolerated dose of food allergen 
substantially higher than the dose used for maintenance itself. 
The overall profile of AEs observed in ARC002 is consistent with what was observed in 
ARC001 and with what has been reported in the literature for academic peanut oral OIT clinical 
trials. These findings continue to support the ongoing clinical development of AR101, and in 
particular, the safety and tolerability of low-dose maintenance treatment at 300 mg/d. 
1.2.3 
ARC003 Trial 
ARC003 is an ongoing international, multicenter, randomized, double-blind, placebo-controlled 
study of the efficacy and safety of AR101 in a characterized desensitization OIT regimen in 
peanut-allergic individuals. The study consists of a screening phase that includes a Screening 

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phase (including a DBPCFC), and a double-blind OIT treatment phase that includes an initial 
escalation period, an up-dosing period, and a maintenance period, followed by an Exit DBPCFC.  
All eligible subjects receive escalating doses of either AR101 or placebo, randomized in a 3:1 
ratio. A DBPCFC will be performed for those subjects achieving the target dose of 300 mg/d and 
continuing to receive that dose throughout the maintenance period (approximately 24 weeks). 
Subjects who do not reach 300 mg/d will be considered escalation failures and non-responders 
for the primary analysis. Each subject will be unblinded when he/she completes the DBPCFC at 
the end of the approximately 24-week maintenance period and all major data queries for the 
subject have been resolved. Those who do not pass the DBPCFC at ≥ 443-mg cumulative 
challenge dose level will be considered endpoint failures and non-responders for the primary 
analysis. The study is being monitored by an independent Data Safety Monitoring Committee 
(DSMC) that meets regularly at defined intervals. 
1.3 
Rationale for the Current Study 
The rationale for the ARC007 study is to characterize the safety of AR101 in a broader 
population of children who are highly likely to have been diagnosed as being peanut allergic 
based on clinical features alone. To date, Aimmune’s Phase 2 and Phase 3 randomized controlled 
trials have included a screening DBPCFC that is used to select a highly sensitive study 
population (those reacting at or before 100 mg of peanut protein during that challenge). This, in 
turn, has allowed recruitment of subjects with any value of skin prick test (SPT) or 
immunoglobulin E (IgE), since the DBPCFC establishes their baseline sensitivity. However, 
DBPCFCs are associated with a substantial risk of anaphylaxis both at screening and again at 
exit, especially in the placebo group. During North American screening for ARC003, 240 doses 
of epinephrine were administered to 457 subjects who reacted to the DBPCFC, 54 (12%) of 
whom had at least one severe symptom. Three subjects experienced anaphylaxis to the DBPCFC 
that met seriousness criteria (Vickery et al, 2017). In addition, mechanistic data suggest that the 
pre-randomization exposure to peanut required by the DBPCFC procedure may induce 
peanut-specific T cell activation and potentiate allergic inflammation detectable after the 
DBPCFC (Rust et al, 2017). This residual inflammation related to the screening food challenge 
may have unintended consequences affecting the safety and tolerability of the initial stages of the 
desensitization procedure.  
Moreover, in the anticipated post-marketing clinical use of AR101, subjects would not be 
selected for treatment on the basis of a DBPCFC, which is a research tool that is not used in 
routine clinical practice. The diagnosis and management of peanut allergy in daily practice relies 
upon a clinical history (by which the clinician establishes the pre-test probability of the 
diagnosis), and then measuring allergen sensitization with SPT and/or IgE to arrive at a post-test 
probability of peanut allergy (Roberts and Lack, 2005; Sicherer and Wood, 2013). These 
assessments are therefore dependent on the predictive power of such tests to confirm the clinical 
history, and nomograms incorporating the likelihood ratio have been established based on 
observational studies. In clinical practice, if the post-test probability of peanut allergy remains 
uncertain because the combination of the test result and the clinical history are indeterminate, 
then a food challenge may be necessary as an additional procedure to definitively establish 
known allergy. However, eliciting a convincing history of a recent allergic reaction to peanut 
establishes a pre-test probability of > 90%, such that a positive test result of any kind effectively 

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clinches the diagnosis. This obviates the need for a risky food challenge procedure for 
confirmation, and is the way most food-allergic subjects are diagnosed in practice (Gupta et al, 
2013). In addition, supportive clinical decision points (eg, a peanut IgE of ≥14 kUA/L) for 
diagnosis have been derived from allergen-specific IgE cutoff levels that are 95% predictive 
(Sampson, 2001), and these decision points have been widely adopted clinically. The objective 
of the current study is to expand the AR101 safety experience by testing it in a placebo-
controlled fashion in this clinical population, which may be more representative of the kinds of 
subjects likely to be offered therapy, as compared to those reacting at or before 100 mg of peanut 
protein in a screening DBPCFC conducted during a rigorously controlled pivotal trial.  
1.4 
Known and Potential Risks and Benefits of AR101 
1.4.1 
Risks 
Peanut is a commonly-consumed food and as such has a well-understood safety profile. Except 
for allergic reactions in subjects with peanut allergy, it does not cause discernible side effects in 
humans. 
In subjects with peanut allergy, many OIT studies have been performed using procedures and 
dosing similar to those proposed in this study. In general, the safety profile has been very good 
across the studies, and based on those studies, approximately 80%, 15%, and < l% of the subjects 
are expected to have mild, moderate, or severe symptoms, respectively, during some point in 
their dosing with peanut OIT. It is important to note that essentially all AEs have been allergy 
related, predictable, and reversible. The major atypical AE from OIT that has been reported in 
the literature is EoE, affecting an estimated 3% of OIT recipients (Lucendo et al, 2014), which is 
thought to be reversible upon dosing cessation. 
The up-dosing and daily maintenance doses of peanut OIT may cause allergic symptoms 
including sneezing, rhinorrhea, urticaria, angioedema, flushing, flares of eczema, ocular, nasal, 
oral and/or throat pruritus, nausea, vomiting, abdominal discomfort, cough, wheezing, and/or 
shortness of breath in addition to severe anaphylaxis. The likelihood of a subject experiencing a 
severe allergic symptom is expected to be lessened by initiating dosing at extremely small 
amounts of AR101 and by up-dosing under observation in a clinical setting until the maintenance 
dose is achieved. 
There may be a risk that during participation in the trial subjects may decrease their vigilance 
against accidental peanut ingestion because they believe they are protected from it. This 
phenomenon has been reported in previous trials; subjects in the trial and their participating 
families will be warned that they should continue to practice their usual vigilance against 
accidental ingestion of peanuts or peanut-containing foods. 
1.4.2 
Benefits 
There is no guarantee that participation in this study will help the subject. Information from this 
study may help researchers to better understand peanut allergy or to develop future tests or 
treatments to help patients with this condition. 
Please refer to the current edition of the AR101 Investigator Brochure for further information 
regarding the safety profile, risks, and benefits of AR101.  

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2. 
OBJECTIVES 
2.1 
Primary Objective 
The primary objective is to assess the safety and tolerability of AR101 when used in a 
characterized oral desensitization immunotherapy (CODIT)TM regimen for approximately 
6 months in peanut-allergic children.  
2.2 
Secondary Objectives 
The secondary objectives are to characterize the frequency of all treatment-related AEs by study 
period, especially those of interest (defined in Section 7.3.4), and AR101’s effect on asthma 
control and immune parameters.  
3. 
STUDY DESIGN 
This is a multicenter, randomized, double-blind, placebo-controlled safety study of AR101 using 
the CODIT regimen in peanut-allergic children.  Up to 500 peanut-allergic children ages 4 to 
17 years will be randomized in a 2:1 ratio to AR101, a pharmaceutical-grade peanut allergen 
formulation, or placebo. The study will consist of a screening phase and a double-blind treatment 
phase that includes an initial 2-day escalation period and an up-dosing period. Subjects will be 
approached at the time of enrollment about donating saliva and additional blood samples to 
support exploratory biomarker analyses in a sub-study (Appendix 7). Participation in this 
sub-study is voluntary and requires signing separate consent and assent documents.  
After completion of the up-dosing period, all study exit procedures, and treatment unblinding, 
subjects who received AR101 may participate in an open-label maintenance trial, known as 
Study ARC011; subjects who received placebo will be offered up-dosing and maintenance 
treatments with AR101 in Study ARC008.  For subjects participating in follow-on studies, both 
follow-on protocols must be activated at the study site before subjects can complete all of the 
required ARC007 study exit procedures.  Certain procedures (specifically, completion of 
questionnaires) and treatment unblinding will be completed at a later unscheduled visit if 
necessary to accommodate institutional review board (IRB) review of the follow-on protocols 
and shipment of open-label AR101.  Additionally, all major data queries must be resolved before 
subjects complete exit procedures and proceed to a follow-on study.  Subjects will remain on 
blinded study treatment and have an unscheduled visit every 4 weeks or sooner until all exit 
requirements are met.   
The primary endpoint of the study is the frequency of TEAEs, including SAEs, during the 
overall study period. Secondary endpoints are frequency of premature discontinuation of dosing 
due to AEs; frequency of premature discontinuation of dosing due to chronic / recurrent GI AEs; 
proportion of chronic / recurrent GI AEs resolving at 2, 4, and ≥ 12 weeks following cessation of 
dosing; frequency of allergic reaction (hypersensitivity) AEs occurring during up-dosing, 
normalized for duration of treatment; frequency of anaphylaxis as defined in the protocol; 
frequency of use of epinephrine as a rescue medication; frequency of accidental ingestions of 
peanut and other allergenic foods and severity of any resultant reactions; and assessment of 
asthma control using the Asthma Control Test (ACT) questionnaire and frequency of use of 
asthma rescue medication (short acting beta-agonists) in subjects with asthma.  

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Exploratory endpoints include changes in peanut- and peanut component-specific serum IgE and 
IgG4 levels, changes in peanut SPT wheal diameter, changes in Total Nasal Symptom Score in 
subjects with allergic rhinitis, and changes in scores of the food allergy related quality of life 
questionnaire (FAQLQ) and food allergy independent measure (FAIM) questionnaire. 
The Screening/Baseline Period is up to 21 days. Eligible subjects will be randomized in a 2:1 
ratio to receive escalating doses of either AR101 or placebo, in 2 phases. Randomization will be 
stratified by age group (4 to 11 years and 12 to 17 years). Following a 2-day initial escalation 
phase, the up-dosing phase will be a minimum of 20 to a maximum of 40 weeks in duration in 
order to achieve the 300 mg/d dose level. Subjects reaching this dose of 300 mg/d will continue 
for an additional 2 weeks to ensure tolerability of the 300 mg/d dose. If the subject is unable to 
tolerate the 300 mg dose for the 2-week period, dosing may continue up to a maximum of 
48 weeks after Day 1 to ensure tolerability prior to exiting the study. For subjects terminating 
early for GI AEs, additional observational follow-up will occur monthly in clinic or by phone for 
up to 6 months or until the symptoms have resolved or stabilized, or the Investigator deems them 
to be irreversible, according to details described further in Section 6.5.  
Beginning at signed informed consent and assent as age-appropriate, all AEs will be evaluated 
from the onset of the event until the time the event is resolved or medically stable, or until 
30 days after the Exit or Early Discontinuation Visit, whichever comes first, with the exception 
of GI AEs, detailed further below. Adverse events ongoing at the time that study treatment is 
discontinued may not be determined to be medically stable until 30 days after the Exit or Early 
Discontinuation Visit has been conducted, in which case additional visits after the Exit or Early 
Discontinuation Visit may be required. Subjects who discontinue dosing prematurely due to 
chronic/recurrent GI AEs will complete the Pediatric Eosinophilic Esophagitis Symptom Score 
(PEESS™ version 2.0) questionnaire and return to the clinic for evaluation monthly for at least 
6 months (if the subject is asymptomatic, telephone follow-up with an Investigator may 
substitute for in-clinic visit, at the Investigator’s discretion). If chronic/recurrent GI AEs persist 
beyond 6 months, subjects are to continue to be followed with monthly clinic visits (telephone 
follow-up with an Investigator may substitute for in-clinic visit, at the Investigator’s discretion) 
until the symptoms have resolved or are assessed to have stabilized with optimal medical 
management or the Investigator deems them to be irreversible. The protocol provides additional 
specific guidance about symptomatic medical management and referrals to a gastroenterologist, 
as necessary, in Section 7.3.4.2. Treatment will be administered in a double-blind fashion. 
A DSMC has been established to monitor the study for safety. 
3.1 
Study Periods 
The study consists of a screening period after which eligible subjects will proceed through 
2 study periods, as tolerated: 
• Initial Escalation 
• Up-Dosing 

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3.2 
Initial Escalation 
All Initial Escalation doses will be administered by investigational site personnel to the subjects 
under direct supervision. Eligible subjects will be randomized and receive treatment with IP on 
Day 1, starting at a dose of 0.5 mg, increasing the dose at 20- to 30-minute intervals to a 
maximum dose of 6 mg (Table 1), according to the Schedule of Events (SOE) in Appendix 1. 
Subjects who fail to tolerate ≥ 3 mg dose on Day 1 will be considered escalation failures and will 
be discontinued. Subjects who tolerate ≥ 3 mg dose on Day 1 will undergo confirmatory dosing 
of a single 3 mg dose on the following day, Day 2. Subjects who do not tolerate this 
confirmatory dose will be discontinued. Subjects who tolerate this confirmatory dose will enter 
the Up-Dosing Period.  
Table 1: 
Initial Escalation Schedule 
Initial Escalation Schedule 
Day 1 Dose Number 
Investigational Product Dose, mga 
Cumulative Dose, mg 
1 
0.5 
0.5 
2 
1 
1.5 
3 
1.5 
3 
4 
3 
6 
5 
6 
12 
Day 2 Dose Number  
Investigational Product Dose, mg 
Cumulative Dose, mg 
1 
3 
3 
a All mg doses shown refer to milligrams of peanut protein or the equivalent placebo dose.  
Doses will be delivered at 20 to 30 minute intervals under direct observation. 
Capsules are to be opened, contents sprinkled over an age-appropriate food, and mixed thoroughly and 
consumed. 
Day 1: Subjects who are unable to tolerate at least a single dose of 3 mg at the end of Day 1 will be considered 
escalation failures. Subjects who tolerate ≥ 3 mg on Day 1 will return on Day 2 to receive a 3 mg single dose. 
Day 2: Subjects with either no symptoms or mild symptoms on Day 2 at 3 mg will start daily home-dosing at 
3 mg on Day 3. 
Subjects with moderate or severe symptoms at 3 mg on either Day 1 or Day 2 will be considered escalation 
failures and will be discontinued from the study. 
 
3.3 
Up-Dosing 
Subjects will receive IP starting at a dose of 3 mg once daily and will gradually escalate every 
2 weeks to a maximum of 300 mg once daily, according to the Up-Dosing Schedule (Table 2).  
All first escalation doses will be administered under direct observation in the clinical research 
center (CRC) or other monitored setting (unless required by a specific institution, no distinction 
will be drawn between an investigational site, study center office, clinic, or CRC, provided the 
requirements for monitoring and emergency intervention are met by the facility). Subsequent 
doses will be dispensed to the parent/guardian and administered at home. Doses may be adjusted 
for tolerability or inter-current illness by the Investigator, except no down-dosing below 
3 mg/day is allowed.  The allowed dose levels are shown in Table 2.  Up-dosing may thereby be 
extended to a maximum of 40 weeks in order to reach 300 mg and should not exceed this period. 

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Subjects unable to escalate to 300 mg within 40 weeks will be considered escalation failures. 
Subjects able to escalate to 300 mg will continue taking the 300 mg dose for an additional 
2 weeks to ensure tolerability prior to exiting ARC007. If the subject is unable to tolerate the 
300 mg dose for the 2-week period, dosing may continue up to a maximum of 48 weeks after 
Day 1 to ensure tolerability prior to exiting the study.   
Table 2: 
Up-Dosing Schedule 
Up-Dosing Schedule 
Dose Number 
Investigational Product 
Dose, mg 
Interval (weeks) 
Percent Increase from 
Previous Dose 
1 
3 
2a 
n/a 
2 
6 
2 
100 
3 
12 
2 
100 
4 
20 
2 
67 
5 
40 
2 
100 
6 
80 
2 
100 
7 
120 
2 
50 
8 
160 
2 
33 
9 
200 
2 
25 
10 
240 
2 
20 
11 
300 
2b 
25 
a  Interval includes Day 2 of Initial Escalation. 
b  If the subject is unable to tolerate the 300 mg dose for the 2-week period, dosing may continue up to a 
maximum of 48 weeks after Day 1 to ensure tolerability prior to exiting the study. 
 
3.4 
Treatment Unblinding and Rollover to Studies ARC011 and ARC008 
The treatment assignment for each subject will be unblinded after all exit visit procedures are 
completed and all major data queries for the subject have been resolved.  For subjects 
participating in follow-on studies, both follow-on protocols must be activated at the study site 
before subjects can complete all of the exit procedures.   
Subjects who received AR101 and completed ARC007 will have the option to participate in the 
ARC011 study.  The ARC011 study is an open-label safety extension study of ARC007 to 
evaluate the safety and tolerability of 300 mg/d maintenance dosing for up to 6 months. After 
completing Study ARC011, subjects will be able to proceed to ARC008 for further maintenance 
dosing. 
Subjects who received active treatment but did not reach 300 mg/d within 40 weeks or were 
unable to tolerate 300 mg daily for 2 weeks by 48 weeks after Day 1 will not be eligible for 
enrollment in ARC011 or ARC008. 
Subjects who received placebo and completed ARC007 will be offered up-dosing and 
maintenance treatment with AR101 in the ARC008 study. In ARC008, these subjects will 

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undergo an escalation schedule identical to that for active subjects in the ARC007 study and then 
continue on maintenance dosing at 300 mg/d.  
All subjects who enter ARC008 will be allowed to continue receiving AR101 until it becomes 
commercially available or the development program is terminated. 
4. 
SELECTION AND WITHDRAWAL OF SUBJECTS 
4.1 
Inclusion Criteria 
Subjects who meet all of the following criteria are eligible: 
1. Age 4 to 17 years, inclusive 
2. A history of physician-diagnosed IgE-mediated peanut allergy that includes the onset of 
characteristic allergic signs and symptoms within two hours of known oral exposure to 
peanut or a peanut-containing food. While IgE-mediated reactions have varied 
presentations, in general characteristic allergic signs and symptoms are objective and 
affect the target organs of the skin, GI tract, upper and/or lower respiratory tract, 
cardiovascular system, or a combination (Appendix 2) 
3. Mean peanut wheal diameter on SPT of ≥ 8 mm greater than the negative saline control at 
Screening 
4. Serum IgE to peanut of ≥ 14 kUA/L at Screening 
5. Written informed consent from the subject’s parent/guardian  
6. Written assent from the subject as appropriate (eg, above the age of 7 years or the 
applicable age per local regulatory requirements) 
7. Use of effective birth control method in sexually active females of childbearing potential 
4.2 
Exclusion Criteria 
1. Subjects in whom the clinical diagnosis of peanut allergy is uncertain 
2. History of cardiovascular disease, including uncontrolled or inadequately controlled 
hypertension (see Section 5.10) 
3. Use of beta-blockers, angiotensin-converting enzyme (ACE) inhibitors, 
angiotensin-receptor blockers (ARBs), calcium channel blockers, or tricyclic 
antidepressants (see Section 5.10) 
4. History of severe or life-threatening episode of anaphylaxis or anaphylactic shock within 
60 days of screening 
5. History of EoE, other eosinophilic GI disease, chronic, recurrent, or severe 
gastroesophageal reflux disease (GERD), symptoms of dysphagia (eg, difficulty 
swallowing, food “getting stuck”), or recurrent GI symptoms of undiagnosed etiology  
6. History of a mast cell disorder, including mastocytosis, urticaria pigmentosa, chronic 
idiopathic or chronic physical urticaria beyond simple dermatographism (eg, cold 
urticaria, cholinergic urticaria), and hereditary or idiopathic angioedema 

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7. Severe persistent asthma (2007 National Heart, Lung, and Blood Institute [NHLBI] 
Criteria Steps 5 or 6, see Appendix 3) 
8. Mild or moderate persistent asthma (2007 NHLBI Criteria Steps 1 to 4), if uncontrolled 
or difficult to control as defined by any of the following: 
a. Forced expiratory volume in 1 second (FEV1) < 80% of predicted, with or without 
controller medications (only for age 6 years or greater and able to do spirometry); 
or  
b. Inhaled corticosteroid (ICS) dosing of > 500 mcg daily fluticasone (or equivalent 
ICSs based on NHLBI dosing chart); or  
c. One hospitalization in the past year prior to screening for asthma; or  
d. Emergency room (ER) visit for asthma within 6 months prior to screening 
9. History of high-dose corticosteroid use (eg, 1 to 2 mg/kg of prednisone or the equivalent 
for > 3 days) by any route of administration in any of the following manners:  
a. History of daily steroid dosing for > 1 month during the past year; or 
b. 1 steroid course in the past 3 months; or  
c. > 2 steroid courses in the past year ≥ 1 week in duration  
10. History of chronic disease (other than asthma, atopic dermatitis, or allergic rhinitis) that 
is, or is at significant risk of becoming, unstable or requiring a change in chronic 
therapeutic regimen 
11. Inability to discontinue antihistamines 5 half-lives before the screening SPT and initial 
day of escalation 
12. Lack of an available palatable vehicle food to which the subject is not additionally 
allergic  
13. Hypersensitivity to epinephrine or any of the excipients in the epinephrine auto-injector 
14. Use of omalizumab or any other monoclonal antibody therapy within the 6 months prior 
to screening or any current immunomodulatory therapy besides aeroallergen or venom 
immunotherapy or corticosteroids (see also Section 5.10)  
15. Having received at least one dose of AR101 in a previous Aimmune or Allergen 
Research Corporation study 
16. Use of other forms of peanut immunotherapy (eg, oral, sublingual, epicutaneous) within 
6 months prior to screening 
17. Participation in another clinical trial within 30 days or 5 half-lives of the IP, whichever is 
longer, prior to randomization 
18. Concurrent administration of build-up phase of immunotherapy to another allergen 
(ie, subject has not reached maintenance dosing)  
19. Pregnancy or lactation  
20. Having the same place of residence as another subject in any AR101 study 

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4.3 
Early Termination 
4.3.1 
Criteria for Early Termination 
Any subject will be prematurely terminated from additional IP exposure for the following 
reasons: 
1. Life-threatening symptoms (Consortium of Food Allergy Research [CoFAR] Grade 4; 
refer to the table in Appendix 5), including, but not limited to, anaphylaxis resulting in 
hypotension, neurological compromise, or mechanical ventilation secondary to peanut 
OIT dosing or any peanut food challenge 
2. Severe symptoms (CoFAR Grade 3; refer to the table in Appendix 5), including, but not 
limited to, those that require intensive therapy (to be determined by the Investigator, but 
may include such interventions as intravenous (IV) epinephrine, intubation, or admission 
to an intensive care unit) or those that are recurrent 
Any subject may be prematurely terminated from additional IP exposures for the following 
reasons: 
1. Poor control or persistent activation of secondary atopic disease (eg, atopic dermatitis, 
asthma)  
2. Starting any prohibited medication (Section 5.10), with no alternative medications 
available per the prescribing doctor, unless a waiver has been obtained from the Medical 
Monitor, as per Section 5.7 
3. Pregnancy  
4. Non-adherence (non-compliance) with IP dosing, as indicated by missing > 7 consecutive 
dosing days on any 1 occasion, or 3 consecutive dosing days on 3 or more occasions 
during the Up-dosing Period, as this could constitute a potential safety issue 
5. Medically-indicated circumstances (eg, as part of the treatment for inter-current AEs) that 
require missed IP dosing for > 14 consecutive days, with the exception of the voluntary 
30-day hiatus for GI-related AEs occurring at or before the 20-mg dose level  
Any subject may also be prematurely discontinued from the study if: 
1. The subject elects to withdraw consent from all future study activities, including 
follow-up. 
2. The subject is lost to follow-up (ie, no further follow-up is possible because attempts to 
reestablish contact with the subject have failed). 
3. The subject develops biopsy-documented EoE. 
4. The subject’s continued participation in the study is assessed by the Investigator to 
constitute a threat to the safety of the subject or the safe conduct of the study. 
5. The subject dies. 
6. The Sponsor discontinues the study. 

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Subjects who discontinue IP prematurely due to AEs or other safety concerns will be encouraged 
to continue their participation in follow-up safety assessments (see below). If a subject fails to 
return for scheduled visits, a documented effort must be made to determine the reason. 
4.3.2 
Follow-up of Subjects Who Discontinue Treatment 
Subjects who prematurely discontinue treatment will be brought in for an Early Discontinuation 
Visit approximately 14 days after their last dose of IP. To the extent possible, subjects will be 
monitored for safety until they come back for their Early Discontinuation Visit. 
In the event of ongoing AEs, subjects who have discontinued therapy should continue to be 
followed beyond the Early Discontinuation Visit until such time as the AE has resolved or is 
assessed to have reached a chronic stable state (a determination that may not be made sooner 
than 30 days after the Early Discontinuation Visit), whichever comes first. 
All subjects who discontinue treatment due wholly or in part to GI AEs will be instructed to 
complete the PEESS v2.0 questionnaire (Franciosi et al, 2011) monthly for 6 months. These 
subjects will also be asked to continue to fill out their daily diary for the same 6-month duration. 
Additional instructions for the follow-up of subjects who discontinue treatment due wholly or in 
part to GI AEs are provided in Section 7.3.4.2. 
4.3.3 
Subject Replacement 
No subject who undergoes early discontinuation after receiving at least 1 dose of IP will be 
replaced. 
5. 
STUDY TREATMENT 
5.1 
Formulation, Packaging, and Labeling 
The active IP, AR101, is characterized peanut allergen in the form of peanut flour, formulated 
with a bulking agent and a flow agent in pre-measured graduated doses. The capsules used in this 
study will include the following strengths: 0.5, 1, 10, 20, and 100 mg each of peanut protein.  
AR101 is characterized by high performance liquid chromatography and by specific 
enzyme-linked immunosorbent assay (ELISA) for key allergenic proteins to demonstrate 
stability and lot-to-lot consistency. Placebos, containing only excipients that are color-matched 
to the peanut flour, will be provided as matching capsules, identical to the active capsules. 
Capsules containing IP will be provided in prepackaged dosing kits. Each individual kit will 
contain 21 daily doses at a given dose level, enough to supply 2 weeks of dosing plus a 7-day 
overage to accommodate potential visit scheduling issues.  
All IP (both peanut allergen and placebo) will be packaged and labeled at the central packaging 
facility. The products will then be shipped to a drug depot where they will be labeled and 
inventoried for shipment to the clinical sites. Investigational products will be shipped by the drug 
depot to the investigational site or the investigational site’s pharmacy, according to site-specific 
institutional policies. Investigational product will then be distributed to each subject’s 
parent/guardian by study site personnel. Investigational product will be dispensed to subjects on 

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the basis of matching randomization code to ensure dosing according to their assigned treatment 
arm and dose level, without the blind being broken for the subjects or the study personnel.  
All IP will be stored in a secure location and kept refrigerated between 2°C and 8°C. Sites will 
maintain temperature logs for all refrigerators storing study drug for the duration of the study. 
5.2 
Preparation, Administration, and Dosage 
The initial escalation and the first dose at each new dose level in the up-dosing phase are to be 
administered in the CRC under the direct supervision of an appropriately credentialed healthcare 
provider and the oversight of a physician. This dose, intended for in-clinic administration, is 
removed from the dosing kit for the assigned dose level. Once a dose is removed from a dosing 
kit, the kit must be dispensed to the subject or held at the site for documented destruction or 
return to the Sponsor’s designee (as instructed); dosing kits once opened cannot be used for any 
other dosing interval or any other subject. At each clinic visit, subjects will receive a kit of 
capsules to be taken at home according to their specific dose level. The subjects will be 
instructed to document capsules taken at home using diary logs and to bring all unused capsules 
back to the clinic at the next visit. The subjects will be instructed to store the dosing kit in the 
refrigerator other than when it is removed to obtain the daily dose. 
Procedures for preparation and administration of doses given in clinic or at home are the same. 
Dose preparation is to be completed by the supervising adult. For in-clinic dosing, dose 
preparation may be performed by clinic staff or by the subject or parent/guardian under the direct 
supervision of clinic staff for the purpose of teaching and reinforcing training. The capsules 
should be pulled apart, and gently rolled between finger and thumb, followed by a light tap to the 
end of each half of the capsule to ensure full delivery of contents. The contents of the capsules 
are to be mixed with a vehicle food, such as apple sauce, yogurt, pudding, or other palatable, 
age-appropriate food. 
Care must be taken not to inhale the powder as this could provoke worsening of asthma or 
induce an allergic reaction. Investigational product may not be added to food heated above room 
temperature before consumption. The vehicle food must be one to which the subject is not 
additionally allergic. The volume of the vehicle food should be such that the entire dose can be 
consumed in a few spoonfuls. The IP should be consumed as promptly after mixing as 
practicable. If not consumed within 4 hours of mixing into a vehicle, the IP-vehicle food mixture 
should be discarded and a new dose mixed prior to consumption. If preparing a new dose is not 
feasible (eg, due to limited supply), the IP may be stored for up to 24 hours under conditions 
appropriate for the food matrix in which the IP was prepared. If there is a delay of more than 
24 hours in consumption, this IP dose is to be discarded and the process restarted with a new IP 
dose. It is recommended that each dose of IP be taken at a consistent time (within a 4-hour 
period) each day that the dose is to be taken. A target interval of ≥ 8 hours should pass between 
doses. Per Investigator judgment, a home dose may be split into 2 portions for tolerability 
reasons, further discussed in Section 6.5.5.2.  
Except for in-clinic dosing, the daily home dose should be taken as part of a meal. Dosing at the 
evening meal is recommended to permit children to be observed and supervised in the home 
setting by their parents/guardians for several hours after dosing. Subjects are to be cautioned 
against activities likely to increase allergic reactivity (eg, exercising or taking hot showers or 

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baths within 3 hours after dosing). Dosing should also not occur within 2 hours of bedtime. 
Additionally, if a subject has engaged in strenuous exercise prior to dosing, dosing should be 
delayed until signs of a hypermetabolic state (eg, flushing, sweating, rapid breathing, and/or 
rapid heart rate) have abated.  
Except as may be necessary in the course of treating an AE (see Section 6.5.5), it is crucial that 
subjects take their dose according to their assigned schedule. No attempt should be made to make 
up for a missed dose if greater than 6 hours have elapsed since usual time of dosing. 
5.3 
Drug Accountability 
Under Title 21 of the Code of Federal Regulations (21 CFR §312.62) and International Council 
for Harmonisation Good Clinical Practice Guideline (ICH E6), the Investigator is required to 
maintain adequate records of the disposition of the investigational agent, including the date and 
quantity of the drug received, to whom the drug was dispensed (subject-by-subject accounting), 
and a detailed accounting of any drug accidentally or deliberately destroyed. 
Records for receipt, storage, use, and disposition will be maintained by the study site. A drug-
dispensing log will be kept current for each subject. This log will contain the identification of 
each subject and the date and quantity of IP dispensed. 
All records regarding the disposition of the IP will be available for review by the clinical trial 
monitor. 
5.4 
Assessment of Compliance with Study Treatment and Monitoring 
Daily dosing and any reaction to at-home dosing will be recorded in diary logs. Doses of IP lost 
or destroyed at home will also be recorded in the diary logs. All unused IP should be brought 
back to the clinic with each visit for reconciliation of remaining capsules with the study diary.  
The site will provide 24-hour emergency contact information. 
5.5 
Modification of Study Treatment 
Investigational product doses may be adjusted by the study site Investigator if the subject is 
unable to tolerate their scheduled dose level. If such a dose modification occurs, the subject will 
return all unused capsules of IP during a dose adjustment visit, and be dispensed new capsules at 
the adjusted dose level. 
5.6 
Concomitant Medications 
Except as indicated in Section 5.10, all subjects may continue their usual medications during the 
study, including those taken for asthma, allergic rhinitis, and atopic dermatitis. However, they 
must be able to discontinue antihistamines and other medications that could interfere with the 
assessment of an allergic reaction 5 half-lives prior to the initial day of escalation, and SPT. 
Usual topical steroid use is permitted following SPT.  

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5.7 
Prophylactic Medications 
Although symptomatic treatments for chronic/recurrent AEs are permitted (eg, H-1 or H-2 
histamine blockers, proton pump inhibitors, or beta-adrenergic agonists) such medications 
should, in general, not be routinely started in advance of symptoms; however, exceptions can be 
granted on a case-by-case basis following a mandatory discussion between the Investigator and 
the Medical Monitor. If started, the use of these medications should be minimized, and then 
discontinued, at the earliest medically appropriate opportunity.  
5.8 
Rescue Medications 
Treatment of individual acute allergic reactions during ARC007 should be with either an 
antihistamine and/or epinephrine, along with IV fluids, beta-adrenergic agonist (eg, albuterol), 
oxygen, and/or steroids, as indicated. Subjects and parents/guardians are likely already to have 
an epinephrine auto-injector device, but for those who do not, an epinephrine auto-injector 
device will be provided. The expiry dates for the epinephrine auto-injectors should be tracked by 
the site and subject/families resupplied as necessary. Study staff must document in each subject’s 
medical record that the subject and a parent/guardian have an unexpired epinephrine 
auto-injection device and have been trained in its proper usage including injection technique.  
5.9 
Symptomatic Treatment for Chronic and/or Recurrent Adverse Events 
Symptomatic treatment for chronic/recurrent AEs is permitted (with the exception of prohibited 
medications [Section 5.10]), but should be used to supplement dose reduction, not substitute for 
it. It is advised that an attempt to withdraw symptomatic therapy be made prior to dose 
re-escalation. If unsuccessful, symptomatic therapy may be resumed and dose escalation proceed 
with the symptomatic therapy in place. 
5.10 Prohibited Medications 
• Therapeutic immunomodulatory antibodies (commercially approved by a Regulatory 
Health Authority or experimental) last used within 6 months of screening 
• Systemic corticosteroids used for any duration greater than 3 consecutive weeks 
throughout the study. If used, subjects must not be up-dosed during the 3 days after 
ceasing the administration of oral steroids 
• Beta-blockers (oral) 
• ACE inhibitors 
• ARBs 
• Calcium channel blockers 
• Tricyclic antidepressants 
During the course of the study, subjects may be at increased risk for anaphylaxis, which, in 
severe form, can result in a drop in blood pressure (BP). Additionally, the administration of 
epinephrine to treat anaphylaxis can result in a sudden rise in BP. For these reasons, the risks 
accompanying the use of any medication with known cardiovascular side effects must be 
weighed against the potential benefits of peanut OIT. This assessment must be performed for any 
medications being taken at study entry or added during the course of the study. The use of 
medication with known cardiovascular side effects during the course of the study is discouraged; 

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however, if an Investigator deems use necessary, the use must be undertaken with caution. It is 
beyond the scope of this protocol to list all drugs with cardiovascular side effects. Classes of 
drugs with a high potential for cardiovascular side effects include antipsychotics, 
cyclooxygenase-2 inhibitors (chronic use), non-steroidal anti-inflammatory drugs (chronic use), 
antiarrhythmics, antihypertensives, and antineoplastics. Before a drug with cardiovascular side 
effects is used in conjunction with OIT, the Investigator should discuss its use with a Medical 
Monitor. 
Immunomodulatory (including immunosuppressive) medications constitute another class of 
drugs whose use during the course of the study is generally prohibited. It is beyond the scope of 
this protocol to list all immunomodulatory drugs; broadly, these include drugs to treat or prevent 
transplant rejection, autoimmune disease, and certain neoplasias – examples include 
cyclosporine, tacrolimus, anti-tumor necrosis alpha drugs, and other anti-cytokine drugs. If an 
Investigator contemplates the use of a potentially immunomodulatory drug during the course of 
the study, the Investigator should discuss this with the Medical Monitor.  
6. 
STUDY PROCEDURES 
6.1 
Enrollment and Randomization 
Following signed consent and assent (as appropriate), subjects will undergo screening procedures 
as outlined in Section 6.2. Eligible subjects will be randomized 2:1 to receive either AR101 or 
placebo and enter the Initial Escalation phase when they are in their state of baseline health and 
all comorbid medical conditions are stable. Randomization will be stratified by age group (4 to 
11 years and 12 to 17 years of age) to ensure 2:1 randomization within the age groups. The 
stratified randomization will be performed using an interactive voice/web response system 
(IXRS). 
The study SOE or procedures are tabulated in Appendix 1 and are listed per visit below. 
6.2 
Screening and Baseline 
All screening procedures must be completed no later than 14 days from the signing of the 
informed consent and assent forms.  
Screening will include the following assessments/procedures: 
• Informed consent and assent, as age appropriate 
• Inclusion/exclusion criteria review including obtaining and documenting medical records 
in source documents that support the history of reaction to known oral peanut exposure 
• Medical, allergy, and dietary (food allergen exposure) history 
• Completion of the FAQLQ and the FAIM questionnaire (prior to randomization)  
• Asthma assessment by clinical history and ACT, for those subjects with a clinical history 
of asthma 
• Concomitant medications 
• Complete physical examination, including weight and height 
• Vital signs (BP, pulse rate [PR], body temperature) 

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• Peak expiratory flow rate (PEFR) or spirometry (FEV1)* (3 attempts are to be 
performed). Airflow assessment should as far as possible be measured at the same time at 
each visit.  
*Note: Only for children 6 years of age and above and able to adequately perform 
spirometry. Spirometry is to be attempted in all subjects ≥ 6 years of age. For subjects 
6 to 11 years of age, if valid spirometry results are not successfully obtained, the attempt 
is to be documented. For subjects 4 or 5 years of age, peak flow rates are to be attempted, 
but reliable performance is not required for the subject to enter the study or undergo 
study procedures at the Investigator’s discretion. The attempt must be documented, and a 
clinical assessment is required. 
• Serum pregnancy test for sexually active females of childbearing potential 
• Blood draw to collect samples for:  
o Peanut-specific IgE, total IgE, and peanut-specific IgG4 assays. The amount of blood 
to be taken for the immunoglobulin assays will be communicated from the central 
laboratory and included in the manual of procedures.  
o Complete blood cell count (CBC), obtained with the same venipuncture as the blood 
draw for the immunoglobulin assays.  
o Additional blood samples for optional exploratory immunologic studies. Note that 
these samples can be obtained with the same venipuncture as the blood draw for the 
immunoglobulin assays and CBC, but will require an additional volume of blood to 
be collected. Separate informed consent is required. 
• Optional collection of saliva sample for exploratory biomarker development (separate 
informed consent required) 
• SPT to peanut, saline, histamine, and perennial (eg, dog, cat, dust mite, cockroach) and 
seasonal pollen (eg, tree, grass, weed as per local practice) allergens 
• Completion of the Total Nasal Symptom Score Sheet in subjects with allergic rhinitis 
• AE monitoring 
• Subjects will be instructed to continue to follow a peanut-avoidant diet for the duration of 
the study. 
• Subjects and parents/guardians will additionally receive teaching about food/peanut 
allergy, according to the investigational site’s established standards. This is to include at 
a minimum the following topics (some or all of which may be addressed in a 
comprehensive anaphylaxis action plan): 
o Recognition of an allergic reaction and of the symptoms of anaphylaxis 
o Ensuring that the subject has an in-date epinephrine auto-injector and understands 
how and when to administer epinephrine 
o Requirement to go to nearest emergency facility following use of epinephrine 
auto-injector 
o Ways to minimize the risk of accidental exposure to peanut in, and outside of, the 
home (may be supplemented by referral to recognized food allergy organizations for 
access to additional learning materials) 
The laboratory values and clinical findings will serve as the baseline measures for comparison to 
subsequent measures obtained during the course of the study. 

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6.3 
Study Visits 
6.3.1 
Initial Escalation: Day 1 
The Initial Escalation Day 1 visit should occur within 21 days of the signing of the informed 
consent and assent forms. Study eligibility will be confirmed prior to proceeding with 
randomization. Randomization through the IXRS will occur on Initial Escalation Day 1 prior to 
the first dose. If the Initial Escalation is not started in this time frame, written approval to 
rescreen the subject and/or to waive any of the screening procedures must be obtained from the 
Sponsor’s Medical Monitor. 
A physician will be available at all times during the in-clinic dosing visits throughout the study. 
Subjects must be free from active wheezing or a flare of atopic disease (eg, atopic dermatitis), or 
suspected inter-current illness prior to initiating IP dose escalation. Additionally, subjects must 
be fully recovered (ie, back to their baseline state of health) from any preceding illness for at 
least 3 to 7 days, depending on the Investigator-determined severity of the illness.  
The following assessments/procedures will be performed during the Initial Escalation. 
Day 1 visit in the CRC: 
• Concomitant medication update 
• Limited physical examination 
• Diet (food allergen exposure) history update 
• Pre-dose vital sign measurements (BP, PR, body temperature) 
• PEFR (3 attempts are to be performed). Airflow assessment should be measured at 
approximately the same time for each visit. 
• Administration of IP, with dosing beginning at 0.5 mg and progressing in graduated 
doses (if tolerated) of 1, 1.5, 3, and 6 mg. Following the first dose, subsequent doses 
will be delivered at 20- to 30-minute intervals. The schedule for initial day dose 
escalation is also shown in Table 1. 
• Post-dose vital sign measurements (BP, PR) within 15 to 30 minutes post-dose, and 
prior to next dose, and at 30-minute intervals thereafter, if the time between doses is 
extended, and for the duration of the post-dose observation period. 
• Monitoring for AEs, including allergic symptoms (see below and Section 7.2) 
• Completion of the Total Nasal Symptom Score Sheet in subjects with allergic rhinitis 
(Appendix 8) 
• Peanut allergy teaching refresher (as per Section 6.2). 
Subjects may drink fluids and eat foods to which they are not allergic during the day of the initial 
day escalation procedure while they are being given the desensitization doses. At a minimum, 
subjects must be observed for 1.5 hours after completion of dose escalation, with vital sign 
measurements and assessment for signs and symptoms of allergic reaction performed every 
30 minutes. Any signs or symptoms of allergic reaction will be recorded in the case report form 
(CRF) on the appropriate Dosing Symptom/AE form. 
If Day 1 dose escalation is completed with no symptoms detected after 1.5 hours of post-dose 
observation, the subject will be able to leave the CRC. If the subject exhibited mild symptoms, 

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the duration of the observation period should be a minimum of 1 hour after resolution of the 
symptoms. For moderate symptoms, the observation period should be extended to a minimum of 
2 hours after resolution of the symptoms. And for severe symptoms, the subject should be 
observed for a minimum of 3 hours after resolution of the symptoms, either at the CRC or an 
emergency facility, as appropriate. 
Any subject deemed to have severe symptoms that include hypoxia, hypotension, or change in 
mental status, stage 3 anaphylaxis defined in Appendix 4, or who receives intensive therapy (to 
be determined by the Investigator, but may include such interventions as IV epinephrine, 
intubation, or admission to an intensive care unit) for an allergic reaction at any time should be 
discussed with the Medical Monitor and discontinued from the study. 
If dose-limiting symptoms occur at or before the 3 mg single dose, there will be no further 
dosing of IP, and the subject will be classified as an escalation failure and a non-responder for 
the purpose of primary and key secondary analyses. The subject will be asked to return to the 
CRC 14 days following the last dose of IP to undergo an Early Discontinuation Visit 
(Section 6.3.6). AEs will be evaluated from the onset until the event is resolved or medically 
stable, or until 30 days after the Early Discontinuation Visit, whichever comes first. 
If no dose-limiting symptoms occur during Day 1 dose escalation, or if dose-limiting symptoms 
occur only with the 6 mg single dose, the subject is to return to the CRC on Day 2 to confirm the 
tolerability of a single 3 mg dose of IP. 
6.3.2 
Initial Escalation: Day 2 
On Day 2 (the next consecutive day following Day 1) a single confirmatory 3 mg dose will be 
administered under medical supervision in the CRC. The only exception to Day 2 immediately 
following Day 1 is when unforeseen circumstances (eg, an inter-current illness) creates a safety 
risk to provide the next dose, consistent with the rules for missed doses. Should this occur, the 
Investigator should discuss the case with the Medical Monitor prior to administering the next 
dose. 
Subjects must be free from active wheezing, a flare of atopic disease (eg, atopic dermatitis), or 
suspected inter-current illness prior to continuing with Day 2 of the initial dose escalation.  
The following assessments/procedures will be performed during the Initial Escalation 
Day 2 visit in the CRC: 
• Concomitant medication update 
• Limited physical examination 
• Pre-dose vital sign measurement (BP, PR, body temperature) 
• PEFR (3 attempts are to be performed). Airflow assessment should, as far as possible, 
be measured at the same time at each visit 
• Oral administration of a single 3 mg dose of IP 
• Post-dose vital sign measurements (BP, PR) within 15 to 30 minutes post-dose, prior 
to discharge, and as indicated per Investigator discretion during the post-dose 

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observation period. Subjects with moderate or severe symptoms should be monitored 
at least every 30 minutes, or more frequently as indicated.  
• Monitoring for AEs, including allergic symptoms (Section 7.2). 
• Subjects will be reminded to continue to follow a peanut-avoidant diet for the duration 
of the study 
• Peanut allergy teaching refresher (as per Section 6.2) 
At a minimum, subjects must be observed for 1.5 hours after dose administration, with vital sign 
measurements and assessment for signs and symptoms of allergic reaction performed every 
30 minutes. Any signs or symptoms of allergic reaction will be recorded in the CRF on the 
appropriate Dosing Symptom/AE form. 
If Day 2 dosing is completed with no symptoms detected after 1.5 hours of post-dose 
observation, the subject will be able to leave the CRC. If the subject exhibited mild symptoms, 
the duration of the observation period should be a minimum of 1 hour after resolution of the 
symptoms. For moderate symptoms, the observation period should be extended to a minimum of 
2 hours after resolution of the symptoms. For severe symptoms, the subject should be observed 
for a minimum of 3 hours after resolution of the symptoms, either at the CRC or an emergency 
facility, as appropriate. 
Any subject deemed to have severe symptoms that include hypoxia, hypotension, or change in 
mental status (stage 3 anaphylaxis defined in Appendix 4), or who receives intensive therapy (to 
be determined by the Investigator, but may include such interventions as IV epinephrine, 
intubation, or admission to an intensive care unit) for an allergic reaction at any time should be 
discussed with the Medical Monitor and discontinued from the study. 
If dose-limiting symptoms occur on Day 2, there will be no further dosing, and the subject will 
be classified as an escalation failure and a non-responder for the purpose of statistical analyses. 
The subject will be asked to return to the CRC 14 days following the last dose of IP to undergo 
an Early Discontinuation Visit (Section 6.3.6). AEs will be evaluated from the onset until the 
event is resolved or medically stable, or until 30 days after the Early Discontinuation Visit, 
whichever comes first. 
Those subjects who tolerate the single 3 mg dose of IP on Day 2 will be dispensed a 2-week 
supply of IP at the 3 mg/d dose level. They will be instructed to continue daily oral dosing at 
home, starting the following day (Study Day 3), and to continue daily home-dosing at that dose 
level for 2 weeks until next escalation. 
On Day 3, the site is required to make telephone contact with the subject’s parent/guardian to 
enquire if any AEs (including allergic symptoms) occurred subsequent to the subject leaving the 
clinic, and to provide assistance in recording of, and responding to, any such events. 

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6.3.3 
Up-Dosing (Also Referred to as Build-up) Visits 
Up-dosing will last from a minimum of 20 weeks to a maximum of 40 weeks and comprise 
10 scheduled up-dosing visits (including the first 300 mg dose of the IP), with the potential for 
unscheduled visits for assessment of dose tolerability, dose reduction, dose re-escalation, or 
management of AEs. Subjects reaching this dose will continue in the study for an additional 
2 weeks to ensure tolerability of the 300 mg/d dose. If the subject is unable to tolerate the 
300 mg dose for the 2-week period, dosing may continue up to a maximum of 48 weeks after 
Day 1 to ensure tolerability prior to exiting the study. 
Subjects will return to the clinic every 2 weeks for up-dosing to a maximum daily dose of 
300 mg. The first dose of IP at each new dose level will be administered in the CRC under direct 
observation and medical supervision. 
Subjects must be free from active wheezing, a flare of atopic disease (eg, atopic dermatitis), or 
suspected inter-current illness prior to any dose escalation. Subjects should be maintained on 
their current, or a reduced, dose level of IP until their flare of asthma, atopic disease, or 
inter-current illness has resolved. 
Subjects should withhold their daily home dose of IP on in-clinic dosing days, but should take all 
other prescribed medications as scheduled. 
Some or all of the following assessments/procedures will be completed during up-dosing visits in 
the CRC, according to the SOE: 
• Return unused capsules to the clinic  
• Monitoring for compliance 
• Concomitant medication review 
• Limited physical examination 
• Diet (food allergen exposure) history update 
• Pre-dose vital sign measurement (BP, PR, body temperature) 
• PEFR (3 attempts are to be performed). Airflow assessment should as far as possible 
be measured at the same time at each visit. 
• IP administration under observation in the clinic 
• Post-dose vital sign measurements (BP, PR) within 15 to 30 minutes post-dose, prior 
to discharge, and at the Investigator’s discretion during the post-dose observation 
period. 
• Optional saliva collection at Week 6 Up-dosing Visit (Appendix 7) 
• Monitoring for AEs, including allergic symptoms (Section 7.2) 
• Completion of the Total Nasal Symptom Score Sheet in subjects with allergic rhinitis 
(Appendix 8) 
• Subjects will be reminded to continue to follow a peanut-avoidant diet for the duration 
of the study. 
• Take home capsules for daily dosing until next visit 
• Peanut allergy teaching refresher (as per Section 6.2) 
• Telephone follow-up call on the day after the visit 
 

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At a minimum, subjects must be observed for 1.5 hours after dose administration, with vital sign 
measurements and assessment for signs and symptoms of allergic reaction performed every 
30 minutes. Any signs or symptoms of allergic reaction will be recorded in the CRF on the 
appropriate Dosing Symptom/AE form. 
If up-dosing is completed with no symptoms detected after 1.5 hours of post-dose observation, 
the subject will be able to leave the CRC. If the subject exhibited mild symptoms, the duration of 
the observation period should be a minimum of 1 hour after resolution of the symptoms. For 
moderate symptoms, the observation period should be a minimum of 2 hours after resolution of 
the symptoms. And for severe symptoms, the subject should be observed for a minimum of 
3 hours after resolution of the symptoms, either at the CRC or an emergency facility, as 
appropriate. 
Any subject deemed to have severe symptoms that include hypoxia, hypotension, or change in 
mental status (stage 3 anaphylaxis defined in Appendix 4), or who receives intensive therapy (to 
be determined by the Investigator, but may include such interventions as IV epinephrine, 
intubation, or admission to an intensive care unit) for an allergic reaction at any time should be 
discussed with the Medical Monitor and discontinued from the study. 
On the day following in-clinic up-dosing, the site is to make telephone contact with the subject’s 
parent/guardian to inquire if any AEs (including allergic symptoms) occurred subsequent to the 
subject leaving the clinic, and to provide assistance in the recording of any such events in the 
diary. 
A dose escalation attempt may be postponed 1 to 2 weeks if, in the clinical judgment of the 
Investigator, the current dose level has not been sufficiently well tolerated to proceed to the next 
dose level. Further, if an Investigator suspects that a subject has not tolerated, or is not tolerating, 
his or her current dose level, the Investigator should have the subject return to the clinic to 
determine whether a dose reduction is warranted, and if so, the magnitude of the reduction. 
Guidelines for setting the new, lower dose are outlined in Section 6.5.5 with the dose adjustment 
depending on the severity of the dose-related symptoms. 
Subjects who require dose reduction during a 2-week dosing period will have their escalation 
schedule reset, as necessary, to maintain the new dose level for a 2-week period prior to 
attempting to re-escalate. 
Following a dose reduction, it is advised that an escalation attempt be made by 4 weeks, unless 
escalation is to be delayed further due to administration of epinephrine, as defined in Section 5.8. 
Failure to successfully escalate after 3 consecutive attempts, with each attempt spaced ≥ 2 weeks 
apart, will result in the cessation of dosing and the subject being considered an escalation failure 
and non-responder. The subject will be asked to return to the CRC 14 days following the last 
dose of IP to undergo an Early Discontinuation Visit (Section 6.3.6) and is to be followed for 
safety in the interim. 

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6.3.4 
Up-Dosing Interim (80 mg) Visit 
The 80 mg in-clinic dosing visit is the approximate midpoint (approximately 10 weeks) of the 
Up-dosing Period. At this visit the following procedures are to be performed in addition to those 
performed at the other up-dosing visits (Section 6.3.3): 
• Complete physical examination, including height and weight 
• For subjects with a clinical history of asthma, asthma assessment by clinical history and 
ACT (Appendix 3) 
• Urine pregnancy test for sexually active females of childbearing potential 
6.3.5 
End-Up-Dosing Phase Visit 
The first 300 mg in-clinic dosing visit is the end of the Up-dosing Period. At this visit the 
following procedures are to be performed in addition to those performed at the up-dosing visits 
(Section 6.3.3):  
• Complete physical examination, including height and weight 
• For subjects with a clinical history of asthma, asthma assessment by clinical history and 
ACT (Appendix 3) 
• Blood sample collection.  Collect blood samples after measuring vital signs and PEFR 
and before administration of study treatment.  These evaluations will serve as the exit 
visit screening/baseline values for the follow-on studies as applicable.   
o Peanut-specific IgE, total IgE, and peanut-specific IgG4 (immunoglobulin assays).  
o CBC, obtained with the same venipuncture as the blood draw for the 
immunoglobulin assays 
o Optional blood samples. Note that these samples can be obtained with the same 
venipuncture as the blood draw for the immunoglobulin assays and CBC, but will 
require an addition volume of blood to be collected. Separate informed consent is 
required.  
• SPT to peanut extract 
• Optional saliva collection (Appendix 7) 
6.3.6 
Exit Visit/Early Discontinuation Visit 
Subjects who tolerate their 300 mg dose for 2 weeks will have an Exit Visit per the SOE, and 
these evaluations will serve as the screening/baseline values for the follow-on studies as 
applicable.  For subjects participating in follow-on studies, both follow-on protocols must be 
activated at the study site before subjects complete all of the required ARC007 study exit 
procedures.  Certain procedures (specifically, completion of questionnaires and treatment 
unblinding) will be completed at a later unscheduled visit if necessary to accommodate IRB 
review of the follow-on protocols and shipment of open-label AR101.  Additionally, all major 
data queries must be resolved before subjects complete exit procedures and proceed to 
a follow-on study.  Blinded study treatment will continue to be dispensed to subjects until all exit 
requirements are met.   

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Subjects who fail initial escalation or up-dosing, or who prematurely discontinue treatment, will 
return to the site for an Early Discontinuation Visit that consists of the same procedures as the 
Exit Visit, except as noted below. An Early Discontinuation Visit is to occur 14 days after the 
last dose of IP. Subjects will return unused IP at this visit.  
Subjects who withdraw from ARC007 wholly or in part due to intolerable GI symptoms, who are 
not enrolled in the optional saliva study, may be approached at the time of their Early 
Discontinuation Visit to provide voluntary consent to enroll and participate in the saliva 
sub-study. If this occurs, such subjects will provide a saliva sample as part of the Early 
Discontinuation Visit and then again during post-OIT follow-up (Appendix 7). 
The following procedures will be performed at the Exit/Early Discontinuation Visit: 
• Return unused capsules to the clinic  
• Monitoring for compliance 
• Concomitant medication review 
• Complete physical examination, including weight and height 
• Diet (food allergen) history  
• Vital signs (BP, PR, body temperature) 
• PEFR (3 attempts are to be performed). Airflow assessment should, as far as possible, be 
measured at the same time at each visit 
• Urine pregnancy test for sexually active females of childbearing potential 
• Optional saliva collection for those participating in the sub-study (at Early 
Discontinuation Visit only) 
• Monitoring for AEs, including allergic symptoms (Section 7) 
• Completion of the Total Nasal Symptom Score Sheet in subjects with allergic rhinitis 
• Completion of the FAQLQ and the FAIM questionnaire after the completion of the exit 
procedures and unblinding  
o Treatment unblinding, FAQLQ, and FAIM will not be completed until both 
follow-on studies (ARC008 and ARC011) are activated at the study site, 
open-label AR101 is available, and all major queries are resolved.  The subject 
will remain on blinded study treatment until all exit procedures are performed at 
a later unscheduled visit when all other conditions are met 
• For subjects with a clinical history of asthma, asthma assessment by clinical history and 
ACT (Appendix 3) 
• Blood draw (at Early Discontinuation Visit and for subjects whose exit procedures are 
completed > 6 weeks after the 300 mg visit only) to collect samples for:  
o Peanut-specific IgE, total IgE, and peanut-specific IgG4 measurement 
(immunoglobulin assays) 
o CBC, obtained with the same venipuncture as the blood draw for the 
immunoglobulin assays 
o Optional blood draw. Note that these can be obtained with the same venipuncture 
as the blood draw for the immunoglobulin assays. Separate informed consent is 
required. 
• SPT to peanut extract 

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• Peanut allergy teaching refresher (as per Section 6.2) 
• PEESS v2.0 questionnaire (at Early Discontinuation Visit only)  
• Dispense capsules for daily dosing until next unscheduled visit (only for subjects who 
must continue double-blind treatment until all exit requirements are met) 
6.4 
Unscheduled Visits / Unscheduled Blood Draws 
The procedures performed at unscheduled visits may include any or all of those performed at 
up-dosing visits as well as PEESS v2.0 questionnaire.   
Subjects waiting for activation of follow-on protocols before completing their final exit visit 
procedures (treatment unblinding, FAQLQ, and FAIM) will continue blinded treatment and have 
an unscheduled visit every 4 weeks or sooner until all conditions are met for exiting the study.  
All exit visit procedures will be considered completed at the final unscheduled visit when 
unblinding, FAQLQ, and FAIM are completed.  If the final unscheduled visit is more than 
6 weeks after the scheduled exit visit, all exit visit procedures must be repeated.  Additionally, 
laboratory evaluations must be repeated for subjects who exit the study > 6 weeks after the 
300 mg visit, and these will serve as the screening/baseline values for the follow-on studies as 
applicable.  Subjects will then enroll in the appropriate follow-on study based on their treatment 
assignment.   
Additionally, if a subject or parent/guardian declares the intention to discontinue IP dosing, 
whether at a scheduled visit or an unscheduled visit, a blood draw should be performed to obtain 
a CBC, immunoglobulin assays, and optional blood and/or saliva samples (if the subject is 
participating in the sub-study). If a blood draw is performed at this time, it will take the place of 
the Exit Visit/Early Discontinuation Visit blood draw (Section 6.3.6). 
6.5 
Assessment and Treatment of Allergic Reactions to Peanut  
6.5.1 
Definitions of Symptom Severity 
Subjects may develop allergic symptoms during the course of OIT, similar to those seen during 
other desensitization protocols (eg, venom immunotherapy, drug desensitization, desensitization 
to aeroallergens by subcutaneous injection). The severity of the reaction will be determined on 
the basis of the Investigator’s judgment. The following definitions, developed to be consistent 
both with the PRACTALL (PRACTical issues in ALLergology Joint United States/European 
Union Initiative) consensus report and with the CoFAR grading system (table in Appendix 5) for 
allergic reactions, are provided as a general guide (Sampson et al, 2012). 
Mild symptoms: 
• Skin – limited (few) or localized hives, swelling (eg, mild lip edema), skin flushing 
(eg, few areas of faint erythema), or pruritus (mild, eg, causing occasional scratching) 
• Respiratory – rhinorrhea (eg, occasional sniffling or sneezing), nasal congestion, 
occasional cough, throat discomfort  
• Gastrointestinal – mild abdominal discomfort (including mild nausea), minor vomiting 
(typically a single episode), and/or a single episode of diarrhea 

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Moderate symptoms: 
• Skin – systemic hives (eg, numerous or widespread hives), swelling (eg, 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 
• Gastrointestinal – persistent moderate abdominal pain/cramping/nausea, more than a 
single episode of vomiting and/or diarrhea 
Severe symptoms: 
• Skin – severe generalized urticaria/angioedema/erythema  
• Respiratory – laryngeal edema, throat tightness with hoarseness, wheezing with dyspnea, 
stridor  
• Gastrointestinal – severe abdominal pain/cramping/repetitive vomiting and/or diarrhea 
• Neurological – change in mental status 
• Circulatory – clinically significant hypotension 
6.5.2 
Assessment of the Tolerability of an Individual Dose of Investigational Product 
Determination of the tolerability of any individual dose of IP should be based on an assessment 
of acute symptoms occurring in close temporal succession to dosing. 
In general, the severity of allergic symptoms elicited at a particular dose of IP will define the 
tolerability of that dose of IP. The place where there is the greatest need for clinical judgment in 
determining the tolerability of a dose is when the dose elicits mild allergic symptoms. Table 3 
illustrates the likely combinations of symptom severity and tolerability: 
Table 3: 
Allergy Symptom Severity and Investigational Product Dose Tolerability 
Symptom Severity 
Assessed Tolerability 
None 
Tolerated 
Mild, oropharyngeal symptoms only 
Tolerated 
Mild, meeting pre-defined tolerability criteria (Section 6.5.1) 
Tolerated 
Mild, not meeting pre-defined tolerability criteria (Section 6.5.1) 
Not tolerated 
Moderate (except for rare exceptions, Section 6.5.1) 
Not tolerated  
Severe 
Not tolerated 
 
In general, the severity of an allergic reaction will correspond to the maximum severity of any of 
its symptoms. 
No symptoms: If a dose elicits no symptoms, the dose will be assessed as tolerated. 
Mild symptoms: When dosing with IP elicits an acute reaction characterized by the appearance 
of only a mild symptom or symptoms, the Investigator will be required to assess whether the 

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dose was or was not tolerated. The determination of tolerability must be made on the basis of 
clinical judgment. The following are presented as guidelines for determining whether a dose 
associated with the emergence of a mild symptom or symptoms was tolerated. A dose eliciting 
only mild symptoms may be considered to be tolerated if the symptoms are:  
• Isolated to a single organ system 
• Resolve with no pharmaceutical intervention or with a single oral administration of an H1 
antihistamine  
• Do not require administration of epinephrine 
• Are not worsening in intensity or distribution over time 
• Resolve, or shows definite signs of resolving, in under 1 hour 
• Do not include objective wheezing 
Based on experience from Phase 2 study results, most acute allergic responses to dosing that are 
characterized by mild symptoms would be anticipated to meet the above criteria. If, however, an 
allergic response to dosing is characterized by mild symptoms that do not meet all of the above 
criteria (eg, has mild symptoms occurring in 2 or more organ systems, requires treatment with 
2 doses of antihistamine or 1 dose epinephrine, shows progression in severity or distribution over 
time, is protracted in duration, or includes objective wheezing), then even though the allergic 
symptoms may be mild, the dose should be assessed to be not tolerated. If a dose elicits mild 
symptoms that do not fit all of the above criteria and the dose is assessed to be tolerated, then a 
brief explanation as to why the dose was considered tolerated must be recorded in the CRF. 
Moderate symptoms: In general, if a dose elicits moderate symptoms, the dose will be assessed 
as not tolerated. There may, however, be rare occasions when a dose eliciting moderate 
symptoms could be assessed as tolerated. Generally, this would only be the case for a transient, 
self-limited (requiring no intervention and resolving completely) symptom occurring in a single 
organ system. In addition, typically the symptom would be subjective only. Any dose associated 
with moderate symptoms and assessed as tolerated must be accompanied by a brief explanation 
in the CRF as to why the dose was considered tolerated.  
Severe symptoms: If a dose elicits severe symptoms, the dose will be assessed as not tolerated. 
Whenever a dose elicits an allergic response characterized by 1 or more severe symptoms, the 
crucial decision, after adequate treatment for the allergic reaction has been administered, will be 
to determine whether the subject should continue in the study, dosing at a reduced dose level, or 
be discontinued early from the study.  
The determination of tolerability will decide the course of action to be taken in response to 
dose-related reactions (Section 6.5.3). 
6.5.3 
Assessment of the Tolerability of a Dose Level 
6.5.3.1 Assessment of Acute Symptoms Occurring After Dosing 
The assessment of the tolerability of a single dose forms the foundation for assessing the 
tolerability of a dose level during home-dosing when acute symptoms arise in close temporal 
succession to dosing. With the report of moderate or severe symptoms occurring during 
home-dosing, the dose level should be considered to be not tolerated and the subject brought to 

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the clinic the day after the emergence of such symptoms for administration of the next dose of IP 
under medical supervision. If a dose administered at home is suspected to have been not 
tolerated, even on the basis of mild symptoms, the subject should also return to the CRC for 
dosing under medical supervision at the time of the next scheduled dose.  
The recurrence of a mild symptom or symptoms over the course of several days of home-dosing 
should suggest that the dose level is not tolerated, even if each individual occurrence of 
symptoms could be assessed as tolerated on the basis of the criteria listed above. If the 
investigational site is notified of mild dose-related symptoms on 4 or more occasions during a 
single week, the subject should be brought to the CRC for dosing under direct observation for 
assessment of the tolerability of the dose level. If mild dose-related symptoms are noted on 7 or 
more occasions during a 2-week dosing interval at a given dose level, that dose level should be 
considered not tolerated and appropriate action taken (Section 6.5.5).  
Because of the reduced reliability inherent in the second-hand reporting of symptoms, 
Investigators are strongly encouraged to have subjects return to the clinic to undergo dosing 
under direct observation whenever acute allergic symptoms associated with dosing are reported.  
6.5.3.2 Assessment of Chronic/Recurrent Symptoms  
Gastrointestinal symptoms were the most common potentially allergic symptoms to occur on a 
subacute, chronic, and/or recurrent basis during Phase 2 clinical trials with AR101. Atopic 
dermatitis, seasonal allergies, or asthma are other potentially non-acute allergic reactions that 
could be brought on or exacerbated by OIT. The absence of a clear temporal relationship 
between dosing and the emergence of recurrent symptoms may help to distinguish these from 
acute dosing-related symptoms.  
If symptoms arise that suggest a chronic/recurrent reaction to IP, the dose level should be 
reduced. As with acute symptoms, the level of the dose reduction should be guided by the 
severity of the symptoms. Symptomatic treatment is permitted (Section 6.5.6), but should be 
used as a supplement to dose reduction, not a substitute for it.  
For chronic/recurrent GI symptoms, especially upper GI symptoms, Investigators are advised to 
have a low threshold for instituting a dose reduction and/or for considering early discontinuation 
of affected subjects from the study, owing to the potential for EoE.  
For subjects determined to be having dose-limiting chronic/recurrent GI symptoms during 
up-dosing, at up to and including the 20 mg/d dose level, it is advised that dosing of IP be 
suspended for 4 weeks and resumed at a dose level of 3 mg/d for a minimum of 4 weeks, with 
the first dose given in the CRC under medical supervision. If tolerated, up-dosing may resume, 
with caution, according to the usual schedule, as tolerated. (Note: The 4-week suspension of 
dosing in response to chronic/recurrent GI symptoms occurring up to and including the 20 mg/d 
level is the only protocol-specified exception to the rules for missed OIT delineated in Section 
6.6). 
For subjects who develop dose-limiting chronic/recurrent GI symptoms at the 40 mg/d dose level 
or above, dose reduction and re-escalation is to proceed as described in Section 6.5.5. 

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6.5.4 
Treatment of Acute Reactions to Peanut OIT During Initial Escalation  
The process algorithm for responding to acute allergic symptoms during OIT is shown in 
Figure 1. 
Investigator judgment will be required to determine the best course of action, with possible 
actions being the following:  
• Extending the time interval between dosing (up to an additional 30 minutes) without any 
additional treatment  
• Instituting enhanced clinical monitoring. This could include (though is not limited to) 
more frequent vital sign monitoring (including respiratory rate), auscultation, and/or the 
addition of pulse oximetry  
• Treating with antihistamine and then resuming dose escalation within 60 minutes of last 
dose, if assessed as safe 
• Treating additionally with epinephrine, beta-agonist, oxygen, IV fluids, and/or 
corticosteroids, as necessary, and discontinuing dose escalation 
• Discontinuation of desensitization protocol  
Mild symptoms: For oral/pharyngeal pruritus occurring in isolation, a specific type and 
commonly occurring mild allergic reaction, the recommended action is to advance to the next 
dose in 30 minutes (though the action taken is, as always, at the Investigator’s clinical 
discretion). 
For other mild symptoms, the action to be taken, at the Investigator’s discretion, should be to 
either:  
• Advance to next dose in 30 to 60 minutes or 
• Treat with antihistamine and then resume dose escalation within 60 minutes of last dose, 
provided that symptoms have resolved to the point where the Investigator assesses the 
subject to be safe to continue dosing (ie, having no or only minimal residual signs or 
symptoms) 
In general, if a subject requires only 1 dose of antihistamine to treat mild symptoms occurring 
during the course of the initial escalation, then the initial escalation may continue. If, however, 
the subject requires a second medication (eg, epinephrine or a beta-agonist) to treat the 
symptoms, or 2 doses of an antihistamine, the initial escalation is to be terminated and the 
subject is to receive no further OIT, even if the symptoms were assessed to be mild. Use of 
epinephrine to treat dose-related symptoms, even in the unlikely event that the symptoms are 
graded as mild, will be cause to discontinue the initial escalation.  

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Moderate symptoms: For moderate symptoms, if the symptoms are not worsening or amassing 
at a rapid pace, then a stepwise approach to treatment may be taken at the discretion of the 
Investigator. If the first action undertaken is to implement an observation period, the observation 
period should not exceed 30 minutes before either the symptoms are noted to be resolving or 
therapy is instituted. Whether treatment is initiated immediately or after an observation period, 
the subject may be treated first with antihistamines or immediately with epinephrine, as deemed 
appropriate by the Investigator. Other therapies may be added either sequentially or 
simultaneously, per Investigator judgment.  
If moderate symptoms occur at any of the doses below 6 mg (ie, up to and including 3 mg), then 
the desensitization procedure will be discontinued and the subject considered an escalation 
failure and desensitization non-responder. The decision to discontinue escalation is to be based 
solely on the determination of whether the allergic reaction was of moderate severity. Although 
it is generally the case that some form of treatment will be instituted for moderate symptoms, 
treatment is not a requirement for assessing an allergic reaction as being of moderate severity.  
Severe symptoms: For severe symptoms, the actions taken should be to discontinue the initial 
escalation and administer the appropriate rescue medications. The desensitization procedure will 
be discontinued regardless of the dose at which the severe symptom or symptoms occurred, and 
the subject will be considered an escalation failure and desensitization non-responder. 
The Medical Monitor is available to answer any questions or to assist in any decisions related to 
the study protocol.   

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Figure 1: 
Schematic for Initial Escalation Day 1 
 
 
6.5.5 
Treatment for Reactions During the Up-dosing Period: Dose Adjustment 
If a dose or dose level is assessed as not tolerated, the action taken will depend on the type and 
severity of the dose-related reaction and the Investigator’s clinical judgment.  Dosing must be at 
a dose level listed in Table 2; dosing below 3 mg/day is not allowed.  The following possible 
actions are at the Investigator’s disposal and are considered in greater detail in subsequent 
sections (Section 6.5.5.1, Section 6.5.5.2, and Figure 2): 
• Dosing the subject under medical supervision in the CRC – this is encouraged whenever 
there is question as to the tolerability of a dose level. It may be performed at the current 
dose level or at a reduced dose level, if there is already a high index of suspicion that the 
current dose level has not been tolerated.  
• Holding dose level at current level for an additional 1 to 2 weeks before attempting dose 
escalation – this may be done at the discretion of the Investigator if there is concern that 
the current dose level has not been sufficiently well tolerated to attempt up-doing to the 
next dose level.  
• Reducing dose by 1 or 2 dose levels and maintaining the reduced dose level for 
≥ 2- to 4-week period before attempting dose re-escalation – Generally, this should be the 

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action taken when a dose that has been observed in the CRC is assessed as not tolerated, 
if a dose elicits moderate or severe reactions that require no more than a single dose of 
epinephrine for treatment, or if the Investigator is convinced of the intolerability of the 
current dose level. In short, it should be considered the default action whenever a dose or 
dose level is assessed as not tolerated.  
• Reducing dose level for less than the usual 2-week period – this may be instituted as 
treatment for an inter-current AE, to aid the Investigator in determining if a dose level is 
or is not tolerated, or if a pattern of decreased IP tolerability during menses is discerned. 
The level of the reduction in dose, ranging from a 1-step reduction to a 50% reduction 
will be at the Investigator’s discretion, based on clinical judgment. The manner in which 
dose escalation may resume will depend on the level and the duration of the dose 
reduction. 
• Temporarily withholding IP dosing – this may be instituted as treatment for an inter-
current AE or to aid the Investigator in determining if a dose level is or is not tolerated, 
but the duration of withholding IP may not exceed 14 consecutive days, or the subject 
will be discontinued from the study. The manner in which dosing may resume after 
withholding dosing of IP depends on the duration for which dosing was withheld.  
• Reducing dose by 2 dose levels and maintaining the reduced dose level for at 
least 6 weeks – continuing dosing at a reduced dose level for at least 6 weeks prior to 
attempting re-escalation is mandatory if 2 doses of epinephrine are given to treat a single 
AE. In this case, discussion with the Medical Monitor is mandatory at 6 weeks, prior to 
the next up-dosing, to determine if dose escalation is warranted.  
• Stopping dosing and discontinuing the subject early from the study – this is an option that 
the subject may elect at any time and for any reason. The Investigator must discontinue 
the subject from further dosing and continuation in the trial under circumstances that 
could jeopardize the health of the subject or the integrity of the trial.  
6.5.5.1 Reactions to In-clinic Dosing 
If symptoms arise in the clinic after up-dosing, the Investigator is to determine whether or not the 
dose was tolerated (Section 6.5.3). The process algorithm for continued dosing after dose-related 
symptoms occur is described below and shown in Figure 2. 
If a subject has a dose escalation in the CRC without symptoms, the action should be to continue, 
per protocol, with daily home-dosing at the tolerated dose level and return to the CRC for the 
next scheduled dose escalation visit 2 weeks later.  
If the subject experiences only oral/pharyngeal pruritus following the administration of the first 
dose at a new dose level, the dose will generally be assessed as tolerated, and the same dose can 
be repeated the next day at home and continued throughout the 2-week home-dosing interval, 
unless other symptoms begin to develop. 
If other mild symptoms occur with the first dose at a new dose level and the dose is assessed as 
not tolerated, the action taken should be to have the subject return to the CRC the next day for 
dosing at the last tolerated dose (ie, a 1-step dose reduction) under medical supervision (if the 
subject is unable to return to the CRC on the day specified, the Investigator may initiate an 

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approximate 1 dose-level reduction at home, with the subject coming to the CRC at the earliest 
date possible).  Dosing below 3 mg/day is not allowed.  If the reduced dose is assessed as 
tolerated, the subject is to continue on that daily home dose for the ensuing 2 weeks. (See 
Section 6.5.5.2 for actions to be taken in the event that symptoms develop during home-dosing.) 
If the reduced dose is again assessed as not tolerated, the subject is to return to the CRC the next 
day for supervised dosing at a 1- or 2-step reduction in dose (per Investigator judgment, based on 
severity of reaction). If this further reduced dose is assessed as tolerated, the subject will 
continue at that dose level for daily home-dosing over the ensuing 2 weeks. If, however, the 
reduced dose is assessed as not tolerated, the subject is to be considered an escalation failure 
non-responder and will be asked to return to the CRC 14 days following their last dose of IP to 
undergo an Early Discontinuation Visit (Section 6.3.6). 
If mild symptoms occur with the first dose at a new dose level and the dose is assessed as 
tolerated, the action taken should be to repeat the same dose the next day. It is advised that the 
repeat (next day’s) dose be administered in the CRC, but it may be given at home, at the 
Investigator’s discretion. If the second dose at the new (increased) dose level is tolerated without 
symptoms, then the subject is to continue on that dose level for the requisite 2 weeks and return 
to the CRC for up-dosing at the next scheduled visit. If the dose again causes mild symptoms, 
but is assessed as tolerated, the subject may continue at that dose level or return to the last 
tolerated dose (at the Investigator’s discretion) and continue dosing at home for the next 2 weeks 
at the Investigator-determined dose level. (See Section 6.5.5.2 for actions to be taken in the event 
that symptoms develop during home-dosing.) If, following the first dose at a new dose level, the 
second dose at the new (increased) dose level is again accompanied by mild symptoms, but is 
assessed as not tolerated, the procedures outlined in the paragraph above should be followed. 
If moderate symptoms occur with the first dose at a new dose level, except for rare instances, the 
dose will be assessed as not tolerated. The action taken should be to have the subject return to 
the CRC the next day for dosing at the last tolerated dose under medical supervision.  Dosing 
below 3 mg/day is not allowed.  If this reduced dose elicits no allergic symptoms (ie, is well 
tolerated), the subject will continue on that daily home dose level for an additional 2 weeks. If 
the subject experiences mild symptoms at the reduced dose, the procedures for responding to a 
dose with mild symptoms should be followed (see above and Figure 2). If the subject 
experiences moderate symptoms at the reduced dose level, the subject should return to the CRC 
the next day and receive a further 1- or 2-step dose reduction (per Investigator judgment). If this 
reduced dose is well tolerated, it will be continued as the daily home dose for ≥ 2 weeks before 
re-escalation is attempted in the CRC. If the dose is not well tolerated, but elicits mild symptoms, 
then the treatment procedures for responding to mild symptoms should be followed (see above 
and Figure 2). If, however, the subject again experiences moderate symptoms at the reduced dose 
level, a discussion with the Medical Monitor is to ensue to reach a decision as to whether to 
continue the subject in the study.  
In the rare instance that a dose eliciting moderate symptoms is assessed as tolerated, then the 
actions taken should be the same as for a dose with mild symptoms assessed as tolerated. 
If severe symptoms occur, the action should be to treat the subject for the allergic reaction, and 
then, in consultation with the Medical Monitor, decide whether or not to discontinue the subject 
from the study. If it is determined that it is safe to allow the subject to continue in the study, the 

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subject should return to the CRC the next day for dosing at a 2-step reduction in dose under 
observation.  Dosing below 3 mg/day is not allowed.  If the subject tolerates the dose reduction 
(ie, shows no or only mild symptoms that are assessed as tolerated), then the subject is to remain 
at the reduced dose level for ≥ 2 weeks before returning to the CRC to attempt dose re-
escalation. If the subject does not tolerate the reduced dose, then the subject is to be considered 
an escalation failure non-responder. 
For specific questions related to dose escalation or continuation of the same dose that are not 
answered in the above protocol, the Medical Monitor will be available for consultation.  
6.5.5.2 Reactions to Dosing at Home 
With the occurrence of symptoms of an acute reaction to IP after home-dosing, or any acute 
allergic reaction, parents/guardians are instructed to call the study site. The Investigator must 
then determine whether or not the dose was tolerated (Section 6.5.3). Because of the reduced 
reliability inherent in the second-hand reporting of symptoms, Investigators are strongly 
encouraged to have subjects return to the clinic to undergo dosing under direct observation 
whenever acute allergic symptoms associated with dosing are reported.  
When symptoms of a dose-related allergic reaction are reported during the course of daily 
home-dosing, the Investigator must assess the severity of the reaction and whether the dose 
associated with the reaction was tolerated. The appropriate intervention will depend on the type 
and severity of symptoms (Figure 2).  
In general, moderate or severe symptoms will be considered clinically significant, and any dose 
eliciting such symptoms assessed as not tolerated; however, mild symptoms may also be 
considered clinically significant (eg, if affecting multiple organ systems, increasing in intensity, 
occurring with increasing frequency, or affecting a larger area over time) and assessed as not 
tolerated. Whenever there is question as to the clinical significance of mild signs or symptoms, 
the Investigator should have the subject return to the CRC for observed dosing under medical 
supervision.  
For home-doses assessed as not tolerated on the basis of acute dose-related symptoms, the same 
procedures described in Section 6.5.5, above, for adjusting up-dosing should be followed.  
The recurrence of mild symptoms over the course of several days of home-dosing should suggest 
that the dose level is not tolerated, even if each individual occurrence of symptoms could be 
assessed as tolerated on the basis of the criteria listed above. In this circumstance, Investigator 
judgment will be required to determine the best course of action with the possible actions being 
the following:  
• Continue with daily home-dosing at the current dose level 
• Continue the same daily dose for the rest of the 2-week interval, with the dose split into 
2 fractional doses given 8 to 12 hours apart (the 2 fractional doses need not be equal) 
• Return to the CRC for repeat dosing at the current dose level under direct observation to 
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• Return to the CRC for dosing of a previously tolerated dose level, either a 1- or 2-step 
reduction (per Investigator judgment, based on severity of reaction).  Dosing must be at a 
dose level listed in Table 2.   
• Institute the 4-week hiatus from dosing, with resumption of dosing at the 3 mg/d dose 
level, as permitted for recurrent GI symptoms occurring at or before the 20 mg dose level 
• Discontinuation of dosing, with subsequent completion of an Early Discontinuation Visit 
Any subject who discontinues up-dosing due to severe or repeated allergic reactions to IP should 
have their blood drawn for the assessment of peanut-specific immunoglobulin and CBC at, or as 
nearly as possible to, the time of the last dose but no later than at their Early Discontinuation 
Visit (Section 6.3.6). Additional assessments are to be performed per Early Discontinuation Visit 
schedule.   
Figure 2: 
Schematic for Up-dosing Period Dose Adjustment 
 
 

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Dose Adjustment in Response to Adverse Events 
At the Investigator discretion, temporary dose reductions ranging from a 1-step decrement (ie, to 
the previous dose) to approximately half of the current dose level (to the nearest feasible 
available whole dose listed in Table 2) can be instituted as part of the treatment regimen for an 
inter-current AE.  Dosing below 3 mg/day is not allowed.  Also, if a pattern of decreased 
tolerability of IP during menses is discerned, then a temporary dose reduction can be instituted 
during this time. Temporary dose reductions for inter-current AEs may be instituted as follows: 
• For dose reductions of ≤ 4 consecutive days, whether dose re-escalation is to occur at 
home or in the CRC is at the Investigator’s discretion. If the reduction in dose is 
maintained for ≤ 4 consecutive days, then the pre-reduction dose level may be resumed, 
with the biweekly escalation schedule kept unaltered.  
• If a reduction in dose is maintained for 5 to 7 consecutive days, then the subject is to 
return to the CRC to undergo dosing under medical supervision. At the Investigator’s 
discretion, the pre-reduction dose level may be resumed or dosing may continue at the 
reduced dose level. The biweekly escalation should be reset so that the subject receives 
≥ 2 consecutive weeks of treatment at the dose level assigned (either the reduced or the 
pre-reduction dose level). 
• If a reduction in dose is maintained for 8 to 14 consecutive days, then the next escalation 
attempted must be conducted in the clinic, and it should only be to 1 dose level above the 
reduced dose. If the escalation is successful, the subject should continue home-dosing for 
a minimum of 2 weeks, with his or her biweekly escalation schedule reset as necessary.  
Doses of IP may also be withheld at the Investigator’s discretion, in response to an inter-current 
AE. Doses withheld as part of the treatment for an AE constitute a special category of missed 
peanut OIT doses (Section 6.6). 
6.5.6 
Treatment for Reactions During the Up-dosing Period: Pharmacological and 
Supportive Treatments 
Treatment of acute reactions should be with either an antihistamine and/or epinephrine, along 
with IV fluids, a beta-agonist (eg, albuterol, by inhaler or nebulizer), oxygen, and/or 
corticosteroids, as indicated.  
Many mild acute allergic reactions can be transient and self-limiting, requiring no therapeutic 
intervention. Others, however, may require treatment. Generally, for mild symptoms requiring 
treatment, the subject should receive antihistamines.  
Acute allergic reactions manifesting with moderate symptoms will generally require therapeutic 
intervention, although some, even moderate, symptoms may on rare occasion be so transient as 
to require no specific treatment. Generally, for moderate symptoms requiring treatment, the 
subjects should receive antihistamines and/or epinephrine, as indicated. If there is uncertainty as 
to the severity of the reaction, administering epinephrine would be considered the most 
appropriate course of action.  

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Generally, severe symptoms will require treatment with epinephrine at a minimum. If severe 
symptoms that qualify as Stage 3 anaphylaxis (defined in Appendix 4) occur at any time, dosing 
with IP will stop and the subject will be discontinued from the study as an escalation failure 
non-responder.  
Antihistamines 
If a subject receives antihistamines only, the dose escalation can be continued. If epinephrine is 
administered, then a different course of action is to be taken.  
Epinephrine - General 
Any reaction to IP (in clinic or at home) that requires more than 2 doses of epinephrine will halt 
all further dosing of IP for the individual. The subject will be asked to return to the CRC 14 days 
following the last dose of IP to undergo an Early Discontinuation Visit (Section 6.3.6). 
Epinephrine - Clinic 
If a single administration of epinephrine is required during, or after, a dose escalation in the 
clinic, no further dosing of IP is to occur at that visit. The next dose of IP is to be reduced by 
2 dose levels and administered in the CRC, but biweekly dose escalation should continue. 
If a single administration of epinephrine is required a second consecutive time during, or after, 
1 escalation attempt, the dose should be reduced by 2 dose levels, and the subject continued at 
that dose level for 6 to 8 weeks. After 6 to 8 weeks at the reduced dose, an escalation attempt 
may be tried in clinic. 
If a single administration of epinephrine is required a third consecutive time during an escalation 
attempt, no further dosing should be attempted. Dosing in these subjects will be discontinued. 
They will be asked to return to the CRC 14 days following their last dose of IP to undergo an 
Early Discontinuation Visit (Section 6.3.6). 
Epinephrine - Home 
If a single administration of epinephrine is given during dosing at home, this epinephrine use is 
not counted as one of the uses described above, unless severe anaphylaxis is assessed to have 
occurred at home. Administration of epinephrine outside of the clinic should be followed 
immediately by the subject being taken to the nearest emergency department. The subject should 
return to clinic for an observed dose under medical supervision prior to resuming any dosing at 
home. 
6.6 
Missed OIT (Investigational Product) Doses during Up-dosing 
Missed doses of IP at any phase of the study can pose a significant risk to subjects, but the risk is 
believed to be highest during the Up-dosing Period. The algorithm for missed consecutive doses 
of IP is as follows: 
• Miss 1 to 2 doses in a row – The next dose would be at the current dose level and could 
be given at home 

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• Miss 3 to 4 doses in a row – The next dose would be the current dose and would be given 
under supervision in the CRC 
• Miss 5 to 7 doses in a row – Initiate the next dose at approximately 50% of the last 
tolerated dose (to the nearest feasible available whole dose listed in Table 2 that is ≤ 50% 
of the last tolerated dose).  Dosing below 3 mg/day is not allowed.  This dose is to be 
administered under supervision in the CRC. If tolerated, dose escalation may resume with 
dose increases of 1 dose level occurring no more frequently than weekly and generally no 
less frequently than every 4 weeks until the subject has returned to the dose level at 
which the lapse in dosing occurred. If symptoms occur, the dosing guidelines for the 
up-dosing period apply. 
• Missing > 7 consecutive days of dosing due to non-compliance (ie, for any reason other 
than treatment of an AE or an IP dispensing error) constitutes an individual stopping rule 
and the subject is to stop taking IP. The subject will be considered an escalation failure 
non-responder, and will be asked to return to the CRC 14 days following their last dose 
of IP to undergo an Early Discontinuation Visit (Section 6.3.6). 
• Additionally, excessive missed dosing, defined as 3 consecutive days of missed doses on 
3 or more occasions during the Up-dosing Period, for any reason other than treatment of 
an AE, constitutes an individual stopping rule and the subject is to stop, constitutes an 
individual stopping rule and the subject is to stop taking IP. The subject will be 
considered an escalation failure non-responder, and will be asked to return to the CRC 
14 days following their last dose of IP to undergo an Early Discontinuation Visit 
(Section 6.3.6). 
• Temporarily withholding IP dosing – this may be instituted as treatment for an 
inter-current AE or to aid the Investigator in determining if a dose level is or is not 
tolerated, but the duration of withholding IP may not exceed 14 consecutive days, or the 
subject will be discontinued from the study. The manner in which dosing may resume 
after withholding dosing of IP depends on the duration for which dosing was withheld.  
• If IP has been withheld for 8 to 14 consecutive days as treatment for an AE or due to an 
IP dispensing error, dosing may be reinitiated at approximately 25% of the last tolerated 
dose (to the nearest feasible available whole dose listed in Table 2 that is ≤ 25% of the 
last tolerated dose).  Dosing below 3 mg/day is not allowed.  The reduced dose is to be 
administered under supervision in the CRC. If tolerated, dose escalation may resume with 
dose increases of 1 dose level occurring no more frequently than weekly and no less 
frequently than every 4 weeks until the subject has returned to the dose level at which the 
lapse in dosing occurred. If symptoms occur, the dosing guidelines for the Up-dosing 
period apply. 
• If IP has been withheld for ≥ 15 consecutive days for any reason, at any point in the study 
(with the exception of a dosing hiatus instituted for chronic/recurrent GI AEs at or before 
the 20 mg dose level, as per Section 6.5.3.2), the subject will be considered an escalation 
failure non-responder, and will be asked to return to the CRC 14 days following their last 
dose of IP to undergo an Early Discontinuation Visit (Section 6.3.6). 
No attempt should be made to make up for a missed dose if greater than 6 hours have elapsed 
since usual time of dosing. 

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6.7 
Skin Prick Test 
Subjects will have SPTs performed using routine clinical procedures for food allergens 
(perennial allergens and seasonal allergens at screening only).  After the subject is off 
antihistamines for an appropriate length of time (5 half-lives of the antihistamine that is being 
used), a skin test probe is pressed through a commercial extract of an allergen into the epidermis. 
Positive (histamine) and negative (saline-glycerin) controls are placed to establish that the 
response is not blocked and to determine if there is dermatographism, respectively. 
6.8 
Visit Windows 
Strict adherence to the dosing schedule should be maintained: 
• Study visits should occur within a ± 2-day window of the scheduled visit date (ie, 2 days 
before or 2 days after the scheduled visit date)  
• The Early Discontinuation Visit is to occur 14 days after the last dose of IP where IP 
dosing has been ceased for reasons other than study completion. The permissible window 
is minus 3 days to plus 7 days. 
7. 
SAFETY MONITORING 
This section defines the types of safety events that should be reported and outlines the 
procedures for appropriately collecting, grading, recording, and reporting them. A DSMC will be 
established to monitor study safety events and will meet approximately quarterly throughout the 
study. 
7.1 
Reporting of Safety Events 
All safety events observed under this protocol are to be reported through the electronic data 
capture (EDC) system for the duration of the study. Some safety events arising under certain 
defined conditions are recorded on specific forms as follows:  
• Any allergic symptoms observed during in-clinic dosing will be recorded directly on the 
Escalation/In-Clinic Dosing form (also referred to as an IP Administration form), and are 
not to be recorded on an AE form (to avoid duplicate reporting) unless the event is 
considered an SAE. These symptoms are, however, by definition, AEs (Section 7.2) and 
will be reported as such in the database.  
• If any safety event meets the definition of an SAE (whether or not related to dosing), it 
will also be recorded on an AE/SAE form.  
• Non-serious adverse events of interest (AEIs) are reported on a non-serious AEI form and 
include anaphylaxis episodes meeting the criteria below, accidental food allergen 
exposures, GI AEs resulting in prolonged disruption of dosing, AEs associated with the 
use of epinephrine, and severe AEs (Section 7.3.4). These events will be reported to 
ProPharma Group following the same process as SAE reporting (with the exception of 
the requirement for regulatory submission). Only one form will be used per episode 
(eg, a systemic allergic reaction that meets anaphylaxis criteria in the protocol, involves 

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at least one severe symptom, and requires epinephrine use will be reported once, on either 
an SAE or non-serious AEI report form).   
7.2 
Dosing Symptoms as Adverse Events 
Although signs and symptoms of allergic reaction, especially those that are mild in severity, are 
frequent and expected occurrences in response to dose escalation during OIT, they still constitute 
AEs. As such, the start and stop times of dose-related allergic reactions, as well as any 
therapeutic interventions and relatedness to IP, will need to be recorded (Section 7.6.1).  
It is common for allergic reactions, especially allergic reactions to food allergens, to manifest 
with multiple symptoms. When multiple symptoms are noted during the same episode, it is up to 
the Investigator to determine whether one, or more than one, AE has occurred. For 
allergic / hypersensitivity reactions involving multiple symptoms, each individual symptom is to 
be entered on a separate log line on the AE eCRF. For each symptom, the AE eCRF will query 
“Is this an allergic reaction?” and the site should indicate yes/no accordingly.  
7.3 
Definitions  
7.3.1 
Adverse Event  
An AE is any untoward medical occurrence in humans, whether or not considered drug related, 
which occurs during the conduct of a clinical trial. Any change in clinical status, 
electrocardiograms, routine labs, x-rays, physical examinations, etc, that is considered clinically 
significant by the Investigator is considered an AE.  
7.3.2 
Adverse Reaction 
A suspected adverse reaction is any AE for which there is a reasonable possibility that the drug 
caused the AE. A reasonable possibility implies that there is evidence that the drug caused the 
event. 
Adverse reaction is any AE caused by the drug.  
7.3.3 
Serious Adverse Event 
An SAE is an AE that results in any of the following outcomes: 
• Death 
• Life-threatening AE (Life-threatening means that the study subject was, in the opinion of 
the Investigator or Sponsor, at immediate risk of death from the reaction as it occurred.) 
• Inpatient hospitalization or prolongation of existing hospitalization 
• Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions 
• Congenital abnormality or birth defect 
• Important medical event that may not result in one of the above outcomes, but may 
jeopardize the health of the study subject or require medical or surgical intervention to 
prevent one of the outcomes listed in the above definition of an SAE. 

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It is anticipated that the most likely cause of SAEs in this study will be anaphylaxis; however, 
not all occurrences of anaphylaxis are necessarily SAEs. Guidance for determining when 
anaphylaxis should be reported as an SAE is provided in Appendix 6. 
7.3.4 
Adverse Event of Interest 
The safety profile of OIT is well established. The Phase 2 safety experience with AR101, as 
outlined in the Investigator Brochure, is generally consistent with this profile. Nonetheless, 
5 types of AEs have particular importance in further assessment of the AR101 safety profile. 
These 5 types of AEs have been designated AEIs in ARC007: anaphylaxis events; GI AEs 
resulting in prolonged disruption of dosing; accidental food allergen exposure; AEs featuring a 
severe symptom; and AEs associated with the use of epinephrine. These events will be submitted 
to the pharmacovigilance team at ProPharma Group on a non-serious AEI form within 24 hours 
of site knowledge of the event. However, the Sponsor will not expedite reporting of AEIs to 
regulatory health authorities unless the event fulfills reportable criteria (Section 7.7.2).  
It is possible that the same event could involve some combination of AEIs (eg, epinephrine use, 
anaphylaxis, severe symptoms) and/or seriousness criteria. Should this occur, one report form 
should be used so as to not duplicate reporting. The AEI form completion guidelines will be 
provided to sites in the manual of procedures.  
The AEIs are each discussed further below.  
7.3.4.1 Anaphylaxis Event 
An anaphylaxis event is an AE that meets the definition of anaphylaxis in the 2014 position 
paper by the European Academy of Allergy and Clinical Immunology (EAACI) Food Allergy 
and Anaphylaxis Guidelines Group (Muraro et al, 2014). Accordingly, anaphylaxis is defined as 
a severe, potentially life-threatening systemic hypersensitivity reaction, characterized by being 
rapid in onset with life-threatening airway, breathing, or circulatory problems that is usually, 
though not always, associated with skin and mucosal changes. 
With respect to the inclusion of being potentially life-threatening in the definition of anaphylaxis 
and how that relates to the assessment of anaphylaxis as an SAE, reference is made to the 2012 
US Food and Drug Administration (FDA) Guidance for Industry and Investigators, Safety 
Reporting Requirements for INDs and BA/BE Studies that states, “An adverse event or 
suspected adverse reaction is considered ‘life-threatening’ if, in the view of either the 
Investigator or Sponsor, its occurrence places the patient or subject at immediate risk of death. 
It does not include an adverse event or suspected adverse reaction that, had it occurred in a more 
severe form, might have caused death.” Thus, for the reporting of anaphylaxis as an SAE, the 
severity of the reaction, assessed according to the EAACI system for grading the severity of 
anaphylactic reactions (Muraro et al, 2007), is also to be taken into account. Guidelines for when 
anaphylaxis may fulfill the seriousness criterion as an important medical event are provided in 
Appendix 4.  
When the diagnosis of anaphylaxis is made, the basis for having suspected the diagnosis must be 
documented, using the criteria established by the Second Symposium on the Definition and 

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Management of Anaphylaxis (Sampson et al, 2006). These criteria were again affirmed in the 
recently published International consensus on (ICON) anaphylaxis (Simons et al., 2014). 
7.3.4.2 Gastrointestinal AE Resulting in Prolonged Disruption of Dosing (GI AEIs) 
Gastrointestinal AEs, typically chronic/recurrent GI AEs, that result in a prolonged disruption of 
dosing will be considered AEIs and will be assessed longitudinally according to the procedures 
described below. For the purpose of delineating these AEIs, prolonged disruption of dosing is 
defined as withholding IP for > 7 days. This will include 3 categories of subjects: 
• Any subject whose dose is withheld for > 7 days due to GI AEs and resumes dosing at a 
reduced dose level 
• Any subject who develops chronic/recurrent GI AEs at or before reaching the 20-mg dose 
level and resumes dosing after a 30-day dosing hiatus 
• Any subject who permanently discontinues dosing who had experienced GI AEs 
(Section 4.3.1). 
All subjects who fall into any of these 3 categories will be asked to fill out the PEESS v2.0 
questionnaire (Franciosi et al, 2011), with the assistance of a parent/ guardian, as appropriate, 
every month for 6 months. However, it should be noted that the PEESS v2.0 was not designed to 
establish a diagnosis of EoE, and has not been validated for use in subjects with GI symptoms of 
other etiologies. Furthermore, the discriminant validity of the questionnaire has not been reported 
in either longitudinal natural history or interventional studies. For these reasons, the use of the 
PEESS v2.0 to monitor the clinical course of GI symptoms must be considered exploratory. 
Nevertheless, the PEESS v2.0 has shown good content and construct validity for all subjects 
(Franciosi et al, 2011; Martin et al, 2015), and so holds promise for being a valuable tool to 
follow the clinical course of EoE or an EoE-like immune-mediated GI syndrome. Thus, the 
PEESS v2.0, could reveal trends toward symptomatic improvement or worsening that might 
otherwise go undetected.  
Subjects who discontinue dosing prematurely due to chronic/recurrent GI AEs will be asked to 
return to the clinic for evaluation monthly for ≥ 6 months (if the subject is asymptomatic, 
telephone follow-up with the Investigator may substitute for in-clinic visit, at the Investigator’s 
discretion). If chronic/recurrent GI AEs persist beyond 6 months, subjects are to be followed 
with monthly clinic visits (telephone follow-up with an Investigator may substitute for in-clinic 
visit, at the Investigator’s discretion) until the symptoms have resolved or are assessed to have 
stabilized with optimal medical management. 
If a subject with chronic/recurrent GI AEs has not experienced complete resolution of symptoms 
within 6 weeks of discontinuation of dosing with the IP, the subject should be referred to a 
(pediatric) gastroenterologist. 
If a subject who discontinued dosing with the IP prematurely due to chronic/recurrent GI AEs is 
unable to discontinue the use of symptomatic therapies that may have been initiated to treat the 
GI AEs (eg, H1 or H2 histamine blockers or proton pump inhibitors) by 12 weeks from the time 
that IP was withdrawn, the subject should be referred to a (pediatric) gastroenterologist. 

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As is the case for any AE occurring during the study, so it is for chronic/recurrent GI AEs that 
the Investigator may, at any time, and at his or her discretion, request consultation from an 
outside physician or additional testing to assist in the diagnosis or management of the AE. 
If a subject is seen by a gastroenterologist, the investigational site is to procure records of the 
visit, as well as any test results, including those from endoscopy and endoscopic biopsy, if 
performed. These are to be retained with the subject’s source documentation.  
7.3.4.3 Accidental Food Allergen Exposure 
An accidental food allergen exposure is any known or suspected exposure to a food to which the 
subject is allergic, including peanut, whether or not it results in an AE. 
To report the occurrence of a safety event associated with accidental food ingestion, subjects will 
be instructed to contact the site study coordinator or Investigator after any known or suspected 
food allergen exposure, even if it does not cause symptoms. The subject may be asked to return 
to the site. These events will be reported as follows: 
• The non-serious AEI form will be completed for each of these events, in addition to 
events where consumption of peanut without a reaction occurs, unless:  
• The accidental food ingestion safety event meets the definition of an SAE, as defined in 
Section 7.3.3), in which case the AE form will be completed. 
If an accidental food allergen exposure does not result in an AE, no assessment of severity, 
seriousness, or relatedness is required. 
7.3.4.4 Adverse Event Featuring a Severe Symptom 
The severity of symptoms will be determined on the basis of the Investigator’s judgment. 
Severity definitions for allergic reactions to IP were developed to be consistent both with the 
PRACTALL consensus report and with the CoFAR grading system and are provided in 
Section 6.5.1 and the table in Appendix 5 as a general guide. Severe allergic AEs may include: 
• Skin – severe generalized urticaria/angioedema/erythema;  
• Respiratory – laryngeal edema, throat tightness with hoarseness, wheezing with dyspnea, 
stridor;  
• GI – severe abdominal pain/cramping/repetitive vomiting and/or diarrhea; 
• Neurological – change in mental status; 
• Circulatory – clinically significant hypotension. 
Severity of other AEs will be assigned using other grading systems as discussed in Section 7.4.  
7.3.4.5 Adverse Events Associated with Use of Epinephrine  
AEs may result in epinephrine use. Upon awareness of such an event, site staff will report it 
within 24 hours using the AEI form, independent of severity or relatedness, or whether it was 
administered in the CRC or at home. If the epinephrine was used as part of an allergic reaction 
that meets criteria for anaphylaxis, an accidental food allergen exposure, an AE featuring a 

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severe symptom, or an SAE, the use need not be reported separately. The intent of this AEI is to 
capture events that may be occurring that do not fall into one of these other categories.  
7.4 
Severity Grading  
The Investigator is to assign severity grades to AEs. Depending on the type of AE, different 
severity grading systems will be used in this study.  
• The severity grading of allergic reactions will be according to the definitions developed 
by the CoFAR group (Appendix 5).  
• The severity of anaphylactic reactions will be graded according to the EAACI system for 
grading the severity of anaphylactic reactions (Appendix 4).  
• For grading the severity of all other AEs, the National Cancer Institute’s Common 
Terminology Criteria for Adverse Events (NCI-CTCAE) system will be used. The 
purpose of using the NCI-CTCAE system is to provide standard language to describe 
AEs (toxicities) and to facilitate tabulation and analysis of the data and for assessment of 
the clinical significance of treatment-related toxicities. The NCI-CTCAE provides a term 
and a grade that closely describes the AE. Each participating site will receive copies of 
the grading scales and event descriptions.  
For AEs not included in the NCI-CTCAE listing, they are also to be graded on a scale from 
1 to 5, according to the definition provided below:  
Grade 1 
Mild 
Transient or mild discomforts (< 48 hours), no or 
minimal medical intervention/therapy required, 
hospitalization not necessary (non-prescription or 
single-use prescription therapy may be employed to 
relieve symptoms, (eg, aspirin for simple headache, 
acetaminophen for post-surgical pain) 
Grade 2 
Moderate 
Mild to moderate limitation in activity, some assistance 
may be needed; no or minimal intervention/therapy 
required, hospitalization possible 
Grade 3 
Severe 
Marked limitation in activity, some assistance usually 
required; medical intervention/therapy required, 
hospitalization possible 
Grade 4 
Life-threatening 
Extreme limitation in activity, significant assistance 
required; significant medical/therapy intervention 
required, hospitalization, or hospice care probable 
Grade 5 
Death 
Death 
 
For additional information and a printable version of the NCI-CTCAE v. 4.03 manual, consult 
the NCI-CTCAE website, http://ctep.cancer.gov/reporting/ctc.html.  

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7.4.1 
Guidelines for Determining Causality of an Adverse Event 
The Investigator will use the following question when assessing causality of an AE to IP: Is 
there a reasonable possibility that the IP caused the event? 
An affirmative answer designates the event as a suspected adverse reaction. 
7.5 
Data Safety Monitoring Committee 
Although the safety of peanut OIT overall is well established, a DSMC will monitor the study for 
safety. The DSMC will meet periodically to review accruing safety data. The committee will 
consist of individuals with extensive multicenter clinical study experience drawn from the fields 
of clinical immunology (specifically food allergies) and biostatistics. These individuals will be 
entirely independent of the conduct of the study. Further details will be provided in the DSMC 
Charter. 
7.6 
Adverse Event Collection Procedures 
Any new event or experience that was not present at Screening, or worsening of an event present 
at Screening, is considered to be an AE. Unchanged, chronic conditions are not AEs and should 
not be recorded on the AE page of the CRF. AEs will be evaluated from the onset of the event 
until the time the event is resolved or medically stable, or until 30 days after the Exit or Early 
Discontinuation Visit, whichever comes first. AEs ongoing at the time that study treatment is 
discontinued may not be determined to be medically stable until 30 days after the Exit or Early 
Discontinuation Visit has been conducted, in which case additional visits after the Exit or Early 
Discontinuation Visit may be required. For the specific case of GI-related AEIs, the need for 
additional follow-up is outlined in Section 7.3.4.2. Investigators should also report AEs 
discovered after cessation of dosing and prior to the Early Discontinuation Visit. 
AEs may be discovered through any of these methods: 
• Observing the subject 
• Questioning the subject, which should be done in an objective manner 
• Receiving an unsolicited complaint from the subject 
• Review of medical records/source documents 
• Review of home-dosing symptom diary (provided to record symptoms between visits) 
7.6.1 
Recording and Reporting Procedures 
A multi-screen AE eCRF will be used allowing all AEs to be submitted through a single 
reporting mechanism (Figure 3). Serious AEs will require additional information reported on 
additional screens within the EDC system. Source documents, with subject identifiers redacted, 
can be scanned and attached to the AE form as well. The Investigator will treat subjects 
experiencing AEs appropriately and observe them at suitable intervals until their symptoms 
resolve or their status stabilizes. 

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7.6.2 
Serious Adverse Event Recording and Reporting Procedures 
Serious AEs will be recorded on the AE CRF. All centers are obligated to report SAEs within 
24 hours of their occurrence and/or the site’s knowledge of the event to the Sponsor. The 
following attributes will be assigned:  
• Description 
• Date of onset and resolution (if known when reported) 
• Severity 
• Assessment of relatedness to test article  
• Action taken 
The Investigator will apply his/her clinical judgment to determine whether an AE is of sufficient 
severity to require that the subject be removed from treatment. If necessary, an Investigator will 
suspend any trial procedures and institute the necessary medical therapy to protect a subject from 
any immediate danger. 
Subsequent review by regulatory health authority(ies), the DSMC, IRB / EC, or the Sponsor may 
suspend further trial treatment or procedures at a site. The study Sponsor and the regulatory 
health authorities retain the authority to suspend additional enrollment and treatments for the 
entire study as applicable. 
A subject may voluntarily withdraw from treatment due to what he/she perceives as an 
intolerable AE, or for any other reason. If voluntary withdrawal is requested, the subject should 
be asked to continue (at least limited) scheduled safety evaluations, complete a study termination 
form, and be given appropriate care under medical supervision until the symptoms of any AE 
resolve or their condition becomes stable. 

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Figure 3: 
Reporting Decisions for Adverse Events 
 
1. Site to notify the site’s Principal Investigator of event(s) 
2. Site to complete and transmit an AE Form through the EDC system. Information 
regarding an SAE report must be recorded in the subject’s medical chart 
3. SAE follow-up reports should include, as applicable, hospital admittance notes, hospital 
discharge summary, clinical notes, resolution date, treatment, and any other pertinent 
information regarding the event. Reporting should not be delayed in order to provide 
these documents. 
4. In the event of a death, the AE Form must be completed and transmitted along with other 
supporting data (death certificate, medical notes, etc). 
7.7 
Serious Adverse Event Notification 
7.7.1 
Notifying the Sponsor 
Investigators will provide the Reporting Center (ProPharma Group, St. Paul, MN) with data of 
all SAEs as defined per the protocol on an ongoing basis. As noted above, the initial contact 
should be within 24 hours of site awareness of the event. 
7.7.2 
Expedited SAEs Reporting to Regulatory Health Authorities  
The sponsor’s Medical Monitor will review each SAE report and will determine whether the 
SAE must be reported to regulatory health authorities on an expedited basis. The final decision 
for disposition regarding expedited reporting to the regulatory health authorities rests with the 
sponsor’s Medical Monitor. The Sponsor will provide the DSMC and the Reporting Center with 
copies of any expedited SAE reports submitted to regulatory health authorities. 

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The Reporting Center will provide these expedited reports to the individual Investigators. Events 
that are serious, related to therapy, and unexpected will be reported to regulatory health 
authorities within 15 days or for deaths and life-threatening events within 7 days (as per 
applicable regulatory reporting requirements). 
7.7.3 
Notifying the DSMC 
The Reporting Center will provide the DSMC with listings of all SAEs on an ongoing basis. 
Furthermore, the DSMC will be informed of expedited SAE reports. Periodic reports from the 
DSMC as to the overall safety of the ongoing study, and recommendations regarding 
continuation will be sent to the Investigators for forwarding to their IRBs/ECs if requested. 
Investigational sites are instructed to report episodes of anaphylaxis within 24 hours of their 
occurrence and/or the sites being notified of the event to the Reporting Center for expedited 
review by the DSMC if the event is associated with any of the following: 
• An ER visit; 
• Hospitalization; 
• More than 2 doses of epinephrine being given as treatment for the same episode; 
• Assessment of the anaphylaxis as severe, as defined in Appendix 4. 
An initial Anaphylaxis Episode form containing the information known to the site at the time 
will be transmitted to the Reporting Center. The Reporting Center will then relay to the Sponsor 
the individual anaphylaxis reports as they are obtained. The investigational site will supplement 
the initial Anaphylaxis Episode form with additional information pertaining to the event as it 
becomes available and will forward the information to the Reporting Center. 
7.7.4 
Notifying the Institutional Review Board and Ethics Committee 
The Investigator will ensure the timely dissemination of all AE information, including expedited 
reports and DSMC safety reviews, to the IRB/EC in accordance with applicable local regulations 
and guidelines. 
7.8 
Other Safety Assessments and Precautions 
7.8.1 
Physical Examination and Vital Signs 
Physical examinations will be conducted at visits indicated in Appendix 1. Height and weight 
will also be recorded at specified visits. Vital signs will be measured, including BP, PR, and 
body temperature. Except where a complete, age-appropriate physical examination is specifically 
indicated, a limited physical exam may be performed. 
7.8.2 
Prior and Concomitant Medications 
Prior and concomitant medications will be documented in the CRF.  

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7.8.3 
Pregnancy Testing and Contraception 
7.8.3.1 Pregnancy Testing  
All sexually active female subjects of childbearing potential will undergo a serum pregnancy test 
at screening and then urine pregnancy tests at specific subsequent visits. 
7.8.3.2 Contraception 
Subjects undergoing OIT are at increased risk for experiencing allergic reactions and may be at 
increased risk for experiencing anaphylaxis. Anaphylaxis can cause a dangerous drop in BP, and 
if this were to occur during pregnancy, it could result in compromised placental perfusion and 
significant risk to the fetus. 
Pregnancy is a time when the mother’s immune system undergoes complex and incompletely 
understood changes that are believed to reduce the risk of a maternal immune reaction directed 
against the fetus. It is also a time when the fetus’s immune system is developing. Oral 
immunotherapy, at its core, entails repeated stimulation of the immune system to affect changes 
in its makeup and function. What effects OIT-induced changes in the immune system might have 
on the course of pregnancy or fetal development are currently unknown. Accordingly, sexually 
active female subjects of childbearing potential are required to practice effective birth control for 
the duration of the study.  
Sexually active female subjects are to use either:  
• A highly effective method of birth control, defined as one that results in a low failure rate 
(ie, less than 1 percent per year) when used consistently and correctly, such as implants, 
injectables, combined oral contraceptives, some intrauterine contraceptive devices, sexual 
abstinence, or a vasectomized partner; or 
• Alternatively, if a single highly effective method of birth control is not used, an effective, 
double barrier method of contraception (eg, male condom with female condom, cervical 
cap, diaphragm, or contraceptive sponge) may be used. 
7.9 
Stopping Rules 
7.9.1 
Overall Stopping Rules 
The study will be suspended at any time if a treatment-associated death occurs in a subject 
receiving AR101 active therapy, or if the second of 2 subjects is admitted to the hospital within 
6 months of the first as a direct consequence of dosing with AR101. Suspension of the study will 
entail halting the enrollment of subjects and refraining from any dose increases, but will not 
entail cessation of dosing unless so directed by the FDA, the applicable regulatory health 
authority(ies), or advised by the DSMC and agreed to by the Sponsor. The suspension will not be 
lifted and dose escalation will not be resumed until the information has been discussed with 
regulatory authorities and the regulatory authorities either concur with resumption of up-dosing 
or direct discontinuation of the study in their jurisdictions.  
The DSMC will also be continually reviewing safety data, and can also recommend, in its 
judgment, halting the study for any substantial imbalance in AEs, apart from anticipated allergic 
dosing symptoms.  

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Aimmune additionally reserves the right to discontinue the study at any time for any reason. 
The regulatory health authority(ies) and IRBs/ECs will be notified in the event of study 
discontinuation. 
7.9.2 
Individual Stopping Rules 
Individuals may stop the study at any time by withdrawing their consent if they experience 
subjectively intolerable AEs, dosing symptoms, or for any other reason. In addition, 
> 7 consecutive days of missed daily dosing due to non-compliance (ie, for any reason other than 
treatment of an AE or an IP dispensing error) constitutes an individual stopping rule. During 
Up-dosing, subjects must halt up-dosing and re-start with a reduced dose if more than 4 days of 
dosing are missed. Missing 3 or more consecutive days on 3 occasions is an individual stopping 
rule, as is missing 15 or more consecutive days of dosing for any reason, with one exception of 
the voluntary 4-week hiatus for GI AEIs occurring at or before the 20 mg dose, as specified in 
Section 6.5.3.2.  
Occurrence of any of the following will result in the cessation of dosing and the subject being 
discontinued from the study as an escalation failure non-responder, resulting in an Early 
Discontinuation Visit within 14 days:  
• Failure to accomplish up-dosing of IP after 3 attempts 
• Failure to identify a tolerated dose of IP after 3 attempts at dose reduction 
Finally, administration of 3 or more doses of epinephrine for the treatment of any dose-related 
allergic reaction in any subject is an individual stopping rule.  
8. 
OPTIONAL MECHANISTIC SUBSTUDIES 
Subjects in ARC007 are eligible to participate in the optional collection of saliva and peripheral 
blood specimens for future studies designed to better understand the biological basis and 
treatment of food allergy. The provision of these additional specimens is voluntary and does not 
affect the subject’s participation in ARC007. The parents/guardian and subject, as appropriate, 
will be asked to sign separate informed consent and assent forms to participate in this sub-study. 
The additional tubes of peripheral blood are to be collected at the same time points as the routine 
laboratory work in ARC007 and do not require additional visits or phlebotomy. The saliva 
specimens will be collected as part of an ongoing collaboration with researchers at Cincinnati 
Children’s Hospital Medical Center to analyze the salivary mRNA transcriptome of participants 
receiving OIT, as outlined further in Appendix 7.  
9. 
STATISTICAL CONSIDERATIONS 
This protocol outlines the major statistical considerations for the ARC007 study. Full details on 
the statistical methodology to be used in the analysis and data handling for this trial will be 
described in the statistical analysis plan (SAP) to be developed prior to database lock and 
statistical analysis. 
Data will be summarized using descriptive statistics within treatment group. No specific 
hypothesis testing or comparisons between the treatment groups are planned for this study. 

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Details of within-group comparisons relative to baseline values and any exploratory comparisons 
between groups will be described in the SAP. 
Descriptive statistics will be presented in the following manner: 
• Continuous data (ie, age, body weight, and height) will be summarized descriptively by 
mean, standard deviation, median, and range. 
• Categorical data (ie, sex and race) will be presented as enumerations and percentages. 
Data will be summarized by treatment group and treatment phase.  
Data will be summarized in tables for each treatment group, treatment groups combined, and 
treatment phase.  
Data will be listed for each subject.  
The end of study is defined as the date of the last visit of the last subject. 
9.1 
Analysis Populations 
The primary population of analysis for all analyses will be the safety population. The Safety 
population will consist of all subjects who receive study treatment during ARC007.  
A per-protocol population, limited to subjects who have no major protocol deviations and who 
undergo Exit Visit procedures, may be defined. Exclusions will be determined by data review 
and documented before database lock. 
Additional analysis populations may be defined in the SAP. 
9.2 
Study Endpoints 
9.2.1 
Primary Endpoint 
The primary endpoint is the frequency of TEAEs, including SAEs, during the overall study 
period. 
9.2.2 
Secondary Endpoints 
• Frequency of premature discontinuation of dosing due to AEs 
• Frequency of premature discontinuation of dosing due to chronic/recurrent GI AEs  
• Proportion of chronic/recurrent GI AEs resolving at 2, 4, and ≥ 12 weeks following 
cessation of dosing 
• Frequency of allergic reaction (hypersensitivity) AEs occurring during up-dosing, 
normalized for duration of treatment 
• Frequency of anaphylaxis as defined in the protocol  
• Frequency of use of epinephrine as a rescue medication  
• Frequency of accidental ingestion of peanut and other allergenic foods and severity of 
any resultant reactions  

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• Assessment of asthma control using the ACT questionnaire and frequency of use of 
asthma rescue medication (short acting beta-agonists) in subjects with asthma 
9.2.3 
Exploratory Endpoints 
• Changes in peanut-specific and peanut component-specific serum IgE and IgG4 levels 
• Changes in peanut SPT mean wheal diameter 
• Changes in Total Nasal Symptom Score in subjects with allergic rhinitis 
• Changes in scores of FAQLQ and the FAIM questionnaire 
9.3 
Subject and Demographic Data 
9.3.1 
Baseline Characteristics and Demographics 
Summary descriptive statistics for baseline and demographic data will be provided for all 
enrolled subjects. Baseline characteristics (body weight and height) and demographic data (age, 
race, and sex) will be collected. 
Statistical presentation for baseline and demographic characteristics may be further summarized 
by baseline peanut-specific serum IgE. 
9.3.2 
Use of Medications 
All medications used will be coded using the WHO Drug Dictionary. The number and 
percentage of subjects receiving concomitant medications or therapies will be summarized 
descriptively. 
9.3.3 
Study Disposition 
The number and percent of subjects in each analysis population will be summarized. The number 
of subjects who complete the study, discontinue prematurely, and their reason for study 
discontinuation will be tabulated. Total duration on treatment and total duration on study will 
also be summarized. 
9.3.4 
Adverse Events 
Adverse events will be coded on the basis of the Medical Dictionary for Regulatory Authorities 
terminology. Events will be tabulated by system organ classification and preferred term. Selected 
summaries will also be prepared by severity and relationship to study treatment. 
9.4 
Sample Size and Power Calculations 
ARC007 is a safety study that will add critical placebo-controlled observations to the ongoing 
safety database of AR101. As such, there are no efficacy endpoints in the study, no specific 
efficacy-related hypotheses to be tested, and no prospective sample size calculations performed 
related to the power to detect a pre-specified treatment effect size. 
A sample size of up to 500 subjects, randomized in a 2:1 ratio to AR101 or placebo, along with 
subjects enrolled in other studies in the clinical program will provide a sufficient number of 
subjects to fulfill the regulatory requirement for data on at least 600 subjects dosed for 6 months 
at 300 mg/d. 

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9.5 
Web-Based Data Collection and Management System 
Data collection will occur via an EDC system to allow easy access to enrollment 24 hours/day, 
7 days/week. Upon enrollment, a form submission schedule is generated for each subject by 
study visit that permits direct access to each electronic CRF for data entry. As data are entered, 
they are validated through range and within-form consistency checks. The Investigator will be 
required to ensure that all CRFs are completed in a timely fashion for all subjects at their site. 
9.6 
Certification in the Use of Electronic Data Entry System 
The clinic and laboratory staff will be trained in the use of the EDC system. Once certified, users 
are permitted to enter data into the production system. Access is password controlled. 
Certification for use of the EDC system will be completed via telephone and/or web-cast 
training. 
9.7 
Data Management 
Information regarding the subject's history, laboratory tests, evaluation of allergic response, and 
follow-up status will be stored and processed through the data center. Quality control procedures 
and a feedback system between the data center and the sites will be instituted to ensure the 
accuracy and completeness of the data collected. 
9.8 
Access to Data 
The investigational sites shall periodically permit authorized representatives of the IND/study 
Sponsor, and/or regulatory health authorities to examine clinical records and other source 
documents for the purpose of safety monitoring, quality assurance reviews, inspections, audits, 
and evaluations of the study progress throughout the entire study period. The Investigator is 
required by law and applicable guideline (21 CFR 312.62 and ICH E6) to keep accurate case 
records for at least 2 years after the last approval of a marketing application in an ICH region and 
until there are no pending or contemplated marketing application in an ICH region. These 
documents should be retained for a longer period however if required by the applicable local 
regulatory requirements or by an agreement with the Sponsor. 
10. 
QUALITY CONTROL AND QUALITY ASSURANCE 
10.1 Statement of Compliance 
This study will be conducted using current Good Clinical Practice (GCP), as delineated in the 
21 CFR Parts 50, 54, 56, and 312 and in the ICH E6, and according to the criteria specified in 
this study protocol. Before study initiation, the protocol and the informed consent documents 
(informed consent form and assent forms) will be reviewed and approved by an appropriate 
IRB(s)/EC(s) as well as FDA and other applicable regulatory health authority(ies). Any 
amendments to the protocol will also be approved by the Sponsor, IRBs/ECs, and submitted to 
the applicable health authorities before they are implemented. Any amendments to the consent 
materials must also be approved by the Sponsor and IRB(s)/EC(s) before they are implemented. 

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10.2 Informed Consent and Assent 
The informed consent form (ICF) is a means of providing information about the study to the 
parent/guardian of a prospective subject and allows for an informed decision about participation 
in the study. Because the study population will be comprised of children, parents or legal 
guardians will be asked to read, sign, and date an ICF before a child enters the study, takes IP, or 
undergoes any study-specific procedures. Children will sign an assent form, as required by the 
IRB/EC. Consent materials for parents/guardians who do not speak or read English will be 
translated into the appropriate language. The ICF and assent form will be reviewed to determine 
whether a revision is required whenever the protocol is amended, or new safety information 
becomes available. A copy of the ICF will be given to a prospective parent/guardian for review. 
The Investigator or designee, in the presence of a witness, will review the ICF and answer 
questions, as well as emphasize the need to avoid allergen exposure other than to IP, and the 
importance and necessity to continue exposure to IP to induce desensitization. The prospective 
subject (as age appropriate) and subject's parent/guardian will be told that being in the study is 
voluntary and that he or she may withdraw, or withdraw his/her child, from the study at any time, 
for any reason. 
10.3 Privacy and Confidentiality 
A subject's privacy and confidentiality will be respected throughout the study. Each subject will 
be assigned a sequential identification number and these numbers rather than names will be used 
to collect, store, and report subject information to the Sponsor. 
11. 
RESOURCE SHARING 
All data derived from this study are the sole property of the Sponsor and will be sent to the 
Sponsor or designee for storage and analysis. Subject data will be anonymized to maintain 
subject confidentiality. All data sets will be archived by the Sponsor or designee and may be 
made available to study investigators as well as interested, outside investigators with approval by 
the Sponsor. 
The Sponsor will require the review and provide approval where appropriate of any abstracts or 
manuscripts prepared from these data prior to their submission for publication.  
12. 
PROTOCOL DEVIATIONS 
The Investigators and site staff will conduct the study in accordance with the protocol, GCP, and 
the site’s local and country specific regulatory requirements. Any departure from the study 
design or procedures constitutes a protocol deviation.  
A major protocol deviation is a protocol deviation that may affect subjects’ rights, safety, or 
well-being and/or the completeness, accuracy, and reliability of the study data. 
A non-major protocol deviation is a protocol deviation that does not have a major impact on 
subjects’ rights, safety, or well-being, or the completeness, accuracy, and reliability of the study 
data. 

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12.1 Reporting and Managing Protocol Deviations 
The site’s Principal Investigator has the responsibility to identify, document, and report protocol 
deviations. Protocol deviations may also be identified during site monitoring visits or other 
reviews of study conduct. All protocol deviations will be reported in the clinical database. 
The Sponsor’s Medical Monitor (or designee) has the responsibility to review all protocol 
deviations periodically and to classify them as major or non-major. All major protocol deviations 
require additional documentation as directed by the Sponsor. 
Whenever applicable, corrective and preventive actions will be developed by the site and 
approved by the Sponsor, or developed by the Sponsor and communicated to the site(s) and 
implemented promptly. 

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13. 
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Med. 2012;367(15):1472; author reply 1472-1473. 
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for commercial products: relevance to food allergy. J Allergy Clin Immunol. 2001;108(3):468. 
Anagnostou K, Islam S, King Y, et al. Assessing the efficacy of oral immunotherapy for the 
desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial. 
Lancet. 2014;383(9925):1297-1304. 
Arias A, Lucendo AJ. Dietary therapies for eosinophilic esophagitis. Expert Rev Clin Immunol. 
2014;10(1):133-142. 
Avery N, King R, Knight S, Hourihane J. Assessment of quality of life in children with peanut 
allergy. Ped Allergy Immunol. 2003;14:378-382. 
Blumchen K, Ulbricht H, Staden U, et al. Oral peanut immunotherapy in children with peanut 
anaphylaxis. J Allergy Clin Immunol. 2010;126(1):83-91. 
Burks AW, Jones SM, Wood RA, et al. for the Consortium of Food Allergy Research. Oral 
immunotherapy for treatment of egg allergy in children. N Engl J Med. 2012;367:233-243. 
Franciosi JP, Hommel KA, DeBrosse CW, et al. Development of a validated patient-reported 
symptom metric for pediatric eosinophilic esophagitis: qualitative methods. BMC Gastroenterol. 
2011;1;11:126. 
Gonsalves N, Yang GY, Doerfler B, et al. Elimination diet effectively treats eosinophilic 
esophagitis in adults; food reintroduction identifies causative factors. Gastroenterology. 
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Greenhawt M, Aceves SS. Non-IgE medicated food allergy: eosinophilic esophagitis update on 
the pathogenesis, clinical features, and management of eosinophilic esophagitis in children. 
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Gupta RS, Springston EE, Smith B, et al. Parent report of physician diagnosis in pediatric food 
allergy. J Allergy Clin Immunol. 2013;131(1):150-156. 
Hofmann AM, Scurlock AM, Jones SM, et al. Safety of a peanut oral immunotherapy protocol in 
children with peanut allergy. J Allergy Clin Immunol. 2009;124(2):286-291, 291.e6. 
Jones SM, Pons L, Roberts JL, et al. Clinical efficacy and immune regulation with peanut oral 
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Joshi P, Mofidi S, Sicherer SH. Interpretation of commercial food ingredient labels by parents of 
food-allergic children. J Allergy Clin Immunol. 2002;109(6):1019-1021. 
Kagalwalla AF, Sentongo TA, Ritz S, et al. Effect of six-food elimination diet on clinical and 
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Lucendo AJ, Arias A, Tenias JM. Relation between eosinophilic esophagitis and oral 
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Maggadottir SM, Hill DA, Ruymann K, et al. Resolution of acute IgE-mediated allergy with 
development of eosinophilic esophagitis triggered by the same food. J Allergy Clin Immunol. 
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Martin LJ, Franciosi JP, Collins MH, et al. Pediatric Eosinophilic Esophagitis Symptom Scores 
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Muraro A, Roberts G, Worm M, et al. Anaphylaxis: guidelines from the European Academy of 
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Narisety SD, Skripak JM, Steele P, et al. Open-label maintenance after milk oral immunotherapy 
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Noel RJ, Putnam PE, Rothenberg ME. Eosinophilic esophagitis. N Engl J Med. 
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inhalant allergens? Asia Pac Allergy. 2012;2(4):237-241.  
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Clin Immunol. 2005;115(6):1291-1296.  
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139(2):AB257. 
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Sampson HA, Gerth van Wijk R, Bindslev-Jensen C, et al. Standardizing double-blind, placebo-
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Sampson HA, Muñoz-Furlong A, Campbell RL, et al. Second symposium on the definition and 
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Sánchez-García S, Rodríguez Del Río P, Escudero C, et al. Possible eosinophilic esophagitis 
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Spergel JM, Brown-Whitehorn TF, Cianferoni A, et al. Identification of causative foods in 
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Vickery BP, Beyer K, Burks AW, et al. Outcome of 583 entry double-blind placebo-controlled 
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predict withdrawal from peanut oral immunotherapy (OIT). J Allergy Clin Immunol. 
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reported to the US Food and Drug Administration, fiscal year 1999. J Allergy Clin Immunol. 
2002;109(6):1022-1026. 
Wasserman RL, Sugerman RW, Mireku-Akomeah N, et al. Peanut oral immunotherapy (OIT) of 
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Immunol. 2011;127(2):AB28. 
Wechsler JB, Schwartz S, Amsden K, Kagalwalla AF. Elimination diets in the management of 
eosinophilic esophagitis. J Asthma Allergy. 2014;24;7:85-94. 
Wen T, Stucke EM, Grotjan TM, et al. Molecular diagnosis of eosinophilic esophagitis by gene 
expression profiling. Gastroenterology. 2013;145(6):1289-1299. 
Wolf WA, Jerath MR, Dellon ES. De-novo onset of eosinophilic esophagitis after large volume 
allergen exposures. J Gastrointestin Liver Dis. 2013;22(2):205-208. 
Yu GP, Weldon B, Neale-May S, Nadeau KC. The safety of peanut oral immunotherapy in 
peanut-allergic subjects in a single-center trial. Int Arch Allergy Immunol. 2012;159(2):179-182.  

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Appendix 1: Schedule of Events for ARC007 
Visit 
Screening/ 
Baseline 
Initial 
Escalation 
Up-dosing Period 
Exit Visit 
Early 
Discontinuation 
Visitb 
Unscheduled 
Visitc 
Day 
1 
Day 
2 
CRC Dosing 
Interim 
(80 mg) Visit 
300 mg 
Visit 
Timing 
Day 1 within  
21 days after 
Consent/Assent 
~Every  
2 weeks for 20 
to 40 weeks 
Approximately 
Week 10 
≤ Week 40a 
14 days 
after 300 
mg Visitc 
14 days after 
last IP dose  
As needed 
Informed consent & assent 
X 
 
 
 
 
 
 
 
 
Inclusion & exclusion criteria 
X 
 
 
 
 
 
 
 
 
Medical & allergy history  
X 
 
 
 
 
 
 
 
 
Diet (food allergen) history 
X 
X 
 
X 
X 
X 
X 
X 
X 
Concomitant medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Physical examd 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Vital signs (BP, PR, temp) 
X 
Xe 
Xe 
X 
X 
X 
X 
X 
X 
PEFRf 
Xg 
X 
X 
X 
X 
X 
X 
X 
X 
Pregnancy testh 
Serum 
 
 
 
Urine 
 
Urine 
Urine 
Urine 
Blood 
draw 
Total IgE & peanut-
specific immunoglobulins 
X 
 
 
 
 
Xi 
 
X 
Xj 
CBC 
X 
 
 
 
 
Xi 
 
X 
Xj 
Optional blood sample(s)k 
X 
 
 
 
 
Xi 
 
X 
Xj 
Saliva collection, optionalk 
X 
 
 
X 
 
X 
 
Xl 
X 
Skin prick test (food).  Perennial, 
seasonal allergens at screening only 
X 
 
 
 
 
X 
X 
X 
X 
ACT 
X 
 
 
 
X 
X 
X 
X 
X 
Peanut allergy teaching 
X 
X 
X 
X 
X 
X 
X 
X 
X 
FAQLQ & FAIM questionnaire 
X 
 
 
 
 
 
Xc 
X 
Xc 
Total Nasal Symptom Scorem 
X 
X 
 
X 
X 
X 
X 
X 
X 
Monitor AEs/allergic symptoms 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Randomization in IXRS 
 
X 
 
 
 
 
 
 
 
Administration of IP at site 
 
X 
X 
X 
X 
X 
 
 
X 
Dispense/return unused IP 
 
 
X 
X 
X 
X 
X 
X 
X 
Telephone follow-upn 
 
 
X 
X 
X 
X 
 
 
X 
Monitor for compliance 
 
 
 
X 
X 
X 
X 
X 
X 
PEESS v2.0 questionnaireo 
 
 
 
 
 
 
 
X 
X 

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Abbreviations:  ACT = Asthma Control Test; AE = adverse event; BP = blood pressure; CBC = complete blood cell count; CODIT = characterized oral desensitization 
immunotherapy; CRC = clinical research center; FAIM = food allergy independent measure (questionnaire); FAQLQ = food allergy related quality of life questionnaire; 
FEV1 = forced expiratory volume in 1 second; IP = investigational product; GI = gastrointestinal; IXRS = interactive voice/web response system; PEESS = Pediatric Eosinophilic 
Esophagitis Symptom Score; PEFR = peak expiratory flow rate; PR = pulse rate; temp = body temperature.  
a) 
If the subject is unable to tolerate the 300 mg dose for the 2-week period after the End Up-dosing (300 mg) Visit, dosing may continue up to a maximum of 48 weeks after 
Day 1 to ensure tolerability prior to exiting the study. 
b) 
Subjects who discontinue dosing prematurely due to chronic/recurrent GI AEs will be asked to return to the clinic for evaluation monthly for ≥ 6 months after this visit. If the 
subject is asymptomatic, telephone follow-up with the Investigator may substitute for in-clinic visit, at the Investigator’s discretion. If chronic/recurrent GI AEs persist 
beyond 6 months, subjects will be followed with monthly clinic visits until the symptoms have resolved or are assessed to have stabilized with optimal medical management.  
c) 
Any of the procedures below may be performed.  Subjects waiting for activation of follow-on protocols before completing their final exit visit procedures will continue 
blinded treatment and have an unscheduled visit every 4 weeks or sooner until all conditions are met for exiting the study.  All exit visit procedures will be considered 
completed at the final unscheduled visit when unblinding, FAQLQ, and FAIM are completed.  If the final unscheduled visit is more than 6 weeks after the scheduled exit visit, 
all exit visit procedures must be repeated.  Additionally, laboratory evaluations must be repeated for subjects who exit the study > 6 weeks after the 300 mg visit, and these 
will serve as the baseline evaluations for the follow-on studies.  Subjects will then enroll in the appropriate follow-on study based on their treatment assignment.   
d) 
A complete physical exam (including height and weight) is required at the Screening/Baseline, the 80 mg and 300 mg up-dosing visits, Exit, and Early Discontinuation visits. 
At the Investigator’s discretion, a limited physical exam may be completed at other visits.  
e) 
BP, PR, and body temperature; BP and PR within 15 to 30 minutes post-dose, prior to the next dose, and at 30-minute intervals thereafter, if the time between doses is 
extended, and for the duration of the post-dose observation period.  
f) 
3 attempts made with the best value recorded, measured at the same time at each visit  
g) 
Peak expiratory flow rate (PEFR) or spirometry (FEV1) may be performed at the Baseline/Screening Visit 
h) 
For sexually active females of childbearing potential only 
i) 
Collect blood samples after measuring vital signs and PEFR and before administration of study treatment 
j) 
Collect blood samples after measuring vital signs and PEFR and before administration of study treatment if the unscheduled visit is > 6 weeks after the 300 mg visit and is the 
final unscheduled visit when unblinding, FAQLQ, and FAIM are completed 
k) 
For subjects for whom additional consent and assent have been provided only 
l) 
For subjects who terminate dosing and enter observational follow-up, the final sample will be collected six months after study withdrawal or as close as practicable. 
m) In subjects with allergic rhinitis only 
n) 
On the day after the visit 
o) 
To be performed every month for six months for subjects (1) for whom dose is withheld for > 7 days due to GI AEs and resumes dosing at a reduced dose level, (2) who 
develops chronic/recurrent GI AEs at or before reaching the 20-mg dose level and resumes dosing after a 30-day dosing hiatus, or (3) who permanently discontinues dosing 
who had experienced GI AEs  
 

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Appendix 2: Systems and Examples of Symptoms Involved in Acute IgE-mediated 
Reactions to Foods (Sampson et al, 2014) 
Cutaneous 
Pruritus 
Erythema/flushing 
Urticaria 
Angioedema 
Contact urticaria 
Ocular 
Pruritus 
Tearing 
Conjunctival injection 
Periorbital edema 
Respiratory tract 
Upper 
Pruritus 
Nasal congestion 
Rhinorrhea 
Sneezing 
Hoarseness 
Laryngeal edema 
Lower 
Cough 
Wheezing 
Dyspnea 
Chest tightness/pain 
Gastrointestinal 
Oral pruritus 
Oral angioedema (lips, tongue, or palate) 
Colicky abdominal pain 
Nausea 
Emesis 
Diarrhea 
Cardiovascular 
Tachycardia 
Dizziness 
Hypotension 
Loss of consciousness/fainting 
Miscellaneous 
Sense of impending doom 
Uterine cramping/contractions 

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Appendix 3: Evaluation of Asthma 
The evaluation of asthma severity will be assessed using the NHLBI classification published 
28 August 2007 as described in the table below. 
Classification 
Symptoms 
Nighttime 
Awakenings 
Lung Function 
Interference 
with Normal 
Activity 
Short Acting Beta-
agonist Use 
Intermittent 
(Step 1) 
< 2 days per 
week 
< 2 × /month 
Normal FEV1 
between 
exacerbations 
FEV1 > 80% 
predicted 
FEV1/FVC 
normal* 
None 
< 2 days /week 
Mild Persistent 
(Step 2) 
> 2 days per 
week but not 
daily 
3-4 × 
/month 
FEV1 > 80% 
predicted 
FEV1/FVC 
normal* 
Minor 
limitation 
> 2 days /week but 
not > 1 ×/day 
Moderate 
Persistent 
(Step 3 or 4) 
Daily 
> 1× /week 
but not 
nightly 
FEV1 > 60% but 
< 80% predicted 
FEV1/FVC 
reduced 5%* 
Some 
limitation 
Daily 
Severe 
Persistent 
(Step 5 or 6) 
Throughout the 
day 
Often  
7× /week 
FEV1 < 60% 
predicted 
FEV1/FVC 
reduced > 5%* 
Extremely 
limited 
Several times per 
day 
*Normal FEV1/FVC: 8-19 years of age = 85%; 20-39 years of age = 80% 

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Appendix 4: Criteria for Suspected Diagnosis, and Severity Grading, of Anaphylaxis  
Criteria for Suspected Diagnosis 
Anaphylaxis is likely when any 1 of the 3 following sets of criteria is fulfilled: 
1. Acute onset of an illness (minutes to hours) with involvement of: 
• Skin/mucosal tissue (eg, generalized hives, itch or flush, swollen lips/tongue/uvula) 
AND 
• Airway compromise (eg, dyspnea, stridor, wheeze/ bronchospasm, hypoxia, reduced 
PEFR) AND/OR 
• Reduced BP or associated symptoms (eg, hypotonia, syncope, incontinence) 
2. Two or more of the following that occur rapidly after exposure to the allergen (minutes to 
hours): 
• Skin/mucosal tissue (eg, generalized hives, itch/flush, swollen lips/tongue/uvula) 
• Airway compromise (eg, dyspnea, stridor, wheeze/bronchospasm, hypoxia, reduced 
PEFR) 
• Reduced BP or associated symptoms (eg, hypotonia, syncope, incontinence) 
• Persistent GI symptoms (eg, nausea, vomiting, crampy abdominal pain) 
3. Reduced BP after exposure to the allergen (minutes to hours): 
• Infants and children: low systolic BP (age-specific) or > 30% drop in systolic BP* 
• Adults: systolic BP < 90 mm Hg or > 30% drop from their baseline 
* Low systolic BP for children is defined as < 70 mmHg from 1 month to 1 year; less than 
(70 mmHg + [2 x age]) from 1 to 10 years; and < 90 mmHg from age 11 to 17 years. 
Note: Isolated skin or mucosal lesions following the ingestion of a food constitute a 
food-induced allergic reaction. 
Criteria for Anaphylaxis Severity Grading 
Staging System of Severity of Anaphylaxis 
Stage 
Defined by 
1. Mild (skin and subcutaneous tissues, 
GI, and/or mild respiratory) 
Flushing, urticaria, periorbital, or facial angioedema; mild 
dyspnea, wheeze, or upper respiratory symptoms; mild 
abdominal pain and/or emesis 
2. Moderate (mild symptoms + features 
suggesting moderate respiratory, 
cardiovascular or GI symptoms) 
Marked dysphagia, hoarseness, and/or stridor; shortness of 
breath, wheezing and retractions; crampy abdominal pain, 
recurrent vomiting, and/or diarrhea; and/or mild dizziness 
3. Severe (hypoxia, hypotension, or 
neurological compromise) 
Cyanosis or SpO2 < 92% at any stage; hypotension; 
confusion; collapse; loss of consciousness; or incontinence 
Criteria for diagnosis and for severity grading adapted from Muraro et al, 2007, and Muraro et al, 2014. 

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Appendix 5: Allergic Reaction Severity Grading 
The CoFAR grading system for allergic reactions is displayed in the table.  
CoFAR Specific Grading System for Allergic Reactions 
Grade 1 –  Mild 
Grade 2 –  
Moderate 
Grade 3 – Severe 
Grade 4 – Life-
Threatening 
Grade 5 
– Death 
Transient or mild 
discomforts 
(< 48 hours), no 
or minimal 
medical 
intervention/ 
therapy required. 
These symptoms 
may include 
pruritus, swelling 
or rash, 
abdominal 
discomfort, or 
other transient 
symptoms. 
Symptoms that 
produce mild to 
moderate limitation 
in activity, some 
assistance may be 
needed; no or 
minimal 
intervention/therapy 
is required. 
Hospitalization is 
possible. These 
symptoms may 
include persistent 
hives, wheezing 
without dyspnea, 
abdominal 
discomfort/ 
increased vomiting, 
or other symptoms 
Marked limitation in 
activity, some 
assistance usually 
required; medical 
intervention/therapy 
required, 
hospitalization is 
possible. Symptoms 
may include 
bronchospasm with 
dyspnea, severe 
abdominal pain, 
throat tightness with 
hoarseness, transient 
hypotension among 
others. Parenteral 
medication(s) are 
usually indicated. 
Extreme limitation in 
activity, significant 
assistance required; 
significant medical/ 
therapy. Intervention is 
required; hospitalization 
or hospice care is 
probable. Symptoms may 
include persistent 
hypotension and/or 
hypoxia with resultant 
decreased level of 
consciousness associated 
with collapse and/or 
incontinence or other life-
threatening symptoms. 
Death 
 

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Appendix 6: Guidance for Determining When an Episode of Anaphylaxis Should Be 
Reported as a Serious Adverse Event  
For an episode of anaphylaxis to be considered an SAE, the Sponsor advises that the event 
satisfies one of the outcome-based definitions of SAE specified in Section 7.3.3 of the protocol, 
with the stipulations (denoted in italics) indicated. These stipulations follow from, and are 
consistent with, the criteria for DSMC reporting (Section 7.6.2): 
1. Death – No further stipulation. 
2. Life-threatening AE (Life-threatening means that the study subject was, in the opinion of 
the Investigator or Sponsor, at immediate risk of death from the reaction as it occurred.): 
For anaphylaxis to be considered life-threatening it should be assessed to have been 
severe, as defined in Appendix 4 and of a Grade 4 allergic reaction, as defined in the 
table in Appendix 5.  
3. Inpatient hospitalization or prolongation of existing hospitalization: The hospital 
admission should not have been solely for the sake of providing an extended period of 
observation, as, for example, might be implemented to watch for a delayed or biphasic 
reaction. 
4. Persistent or significant incapacity or substantial disruption of the ability to conduct 
normal life functions: No further stipulation. 
5. Congenital abnormality or birth defect: No further stipulation. 
6. Important medical event that may not result in 1 of the above outcomes, but may 
jeopardize the health of the study subject or require medical or surgical intervention to 
prevent 1 of the outcomes listed in the above definition an SAE: 
• In general, for an anaphylactic episode to be classified as an SAE on the basis of 
being an important medical event, it should have resulted in an ER visit, and the 
ER visit should have been associated with intensive therapy. What constitutes 
intensive therapy is to be determined by the Investigator, but may include such 
interventions as IV epinephrine, intubation, or admission to an intensive care 
unit. 
• One or 2 intramuscular injections of epinephrine should ordinarily not be 
construed as intensive therapy. 
• If an Investigator assesses an episode of anaphylaxis to be an important medical 
event when the episode was of mild or moderate severity and did not require 
intensive therapy, the rationale for the assessment must be explained in detail in 
the narrative of the event. 

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Appendix 7: Exploratory Biochemical and Molecular Sub-study of Peanut-Allergic 
Children with Oral Immunotherapy-Related Gastrointestinal Symptoms  
Background 
A strong association exists between food allergy and EoE (Noel et al, 2004; Spergel et al, 2012; 
Greenhawt and Aceves, 2014). Instituting an elemental diet free of potential allergens is the most 
reliably effective treatment for spontaneously occurring EoE (Arias and Lucendo, 2014; 
Wechsler et al, 2014). In some cases of EoE, if a specific allergy-provoking food can be 
identified, then dietary avoidance of the offending food can result in resolution of the esophageal 
symptoms (Spergel et al, 2012). Alternatively, elimination from the diet of the most common 
food allergens, including milk, egg, peanut/tree nuts, soy, wheat, and shellfish/fish, can also 
result in resolution of the esophagitis (Kagalwalla et al, 2006; Gonsalves, 2012). When 
reintroduction of a suspected allergenic food is associated with the return of symptoms, this 
strongly implicates the food as a likely causative agent of the EoE (Gonsalves, 2012).  
IgE-mediated hypersensitivity to food allergens, but also aeroallergens (Alpan et al, 2012; 
Ridolo et al, 2012; Wolf et al, 2013; Rea et al, 2014), figures prominently in the pathogenesis of 
EoE, but other factors besides the induction of an immediate hypersensitivity reaction also 
appear important. One circumstance in which multiple factors pertaining to food exposure are 
controlled at the time that EoE becomes symptomatic is when EoE occurs in the setting of OIT. 
The inciting food is known, as is the amount and timing of its consumption. Moreover, EoE 
occurs only in a minority of subjects undergoing OIT. Thus, studying EoE when it arises during 
the course of OIT may provide a unique opportunity to gain insights into its pathogenesis.  
In OIT studies, GI AEs are typically prominent (Anagnostou et al, 2014; Yu et al, 2012; 
Blumchen et al, 2010; Jones et al, 2009) and account for a substantial proportion of premature 
discontinuations of study treatment (Burks et al, 2012; Varshney et al, 2011; Jones et al, 2009; 
Vickery et al, 2011). This was also observed in the completed ARC001 study and the ongoing 
ARC002 study. In the ARC001 study, 6 out of 29 subjects (21%) receiving active treatment 
discontinued prematurely. Four of the early discontinuations were attributed by the Principal 
Investigators to have been the consequence of recurrent GI AEs; and in 1 of these cases the 
diagnosis of EoE was subsequently established by endoscopic biopsy. In the other 
2 discontinuations, ≥ 1 GI AE had occurred in each subject. In the ongoing ARC002 study, an 
open-label follow-on to the ARC001 study, 3 of the 4 subjects discontinued due to GI adverse 
events (nausea, vomiting, abdominal pain) during up-dosing in part 1, and 1 subject from group 2 
discontinued due to a GI adverse event (dysphagia) during the low-dose maintenance period.  
Repeated bouts of abdominal pain and vomiting are common to both EoE and chronic/recurrent 
OIT-related GI symptoms, suggesting a common, or at least a similar, etiology in at least a 
proportion of subjects. To date, ≥ 20 occurrences of OIT-related GI AEs have been confirmed 
histopathologically to be EoE as reported in the medical literature (Lucendo et al, 2014), and in 
still other cases the symptomatology and clinical course (with or without concomitant blood 
eosinophilia) have been highly suggestive of EoE (Narisety et at, 2009; Vickery et al, 2011). 
A recent review of the literature (Lucendo et al, 2014) has indicated that the incidence of 
confirmed EoE in OIT is on the order of 3% (ranging from approximately 1% to 5%). 

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Establishing the association between OIT and the subsequent development of EoE is not always 
straight forward. The time to onset of EoE during the course of OIT may vary depending on the 
allergen and OIT regimen. Many (Wasserman et al, 2011), though not all (Hofmann et al, 2009), 
of the reported cases of EoE with peanut OIT had developed GI symptoms early in the course of 
oral desensitization, whereas with milk OIT the occurrence of EoE has tended to be after 
reintroduction of milk into the diet (Sánchez-García, 2012; Maggadottir et al, 2014). Not all EoE 
occurring during OIT is necessarily caused by the OIT, however. Food allergies often occur to 
more than 1 type of food and allergies to foods often coexist with allergies to airborne and 
contact allergens.  
Chronic GI AEs affecting participants in ARC007 have been designated as AEIs in the ARC007 
protocol. The goal of the current sub-study is to explore the biology of these GI AEIs occurring 
during this trial using a readily available and noninvasive sampling method (saliva) in an attempt 
to overcome some of the difficulties in assessing intolerable GI AEs in subjects undergoing OIT.  
Rationale for the Proposed Study 
The overall aims of this sub-study are to collect bio-specimens through a noninvasive technique, 
and to analyze them to develop a better understanding of the biochemical and molecular changes 
that occur when OIT participants develop GI AEs significant enough to require discontinuation 
of the OIT protocol. We will obtain preliminary information regarding these biological changes 
in bio-specimens from symptomatic individuals, as well as controls, using methods that have 
been developed for the study of eosinophilic GI disorders at Cincinnati Children’s Hospital 
Medical Center, Cincinnati, OH, USA.  
Specifically, this sub-study of ARC007 will enroll all willing subjects at screening, prior to 
dosing, and then collect further information from those subjects who go on to experience GI side 
effects during OIT and those subjects who do not (controls). To overcome the obstacles limiting 
traditional EoE evaluations in this context (eg, performance of an esophagogastroduodenoscopy 
[EGD]), an easily collected bio-specimen will be analyzed to determine whether patterns can be 
detected that correlate with patterns seen in other subjects with known bona fide EoE. As there 
are no known clinical predictors of EoE, all ARC007 participants will be approached about 
participating in this sub-study. Further analyses will be conducted on those subjects who develop 
GI symptoms during the course of OIT and controls who do not develop GI symptoms. While all 
subjects will provide baseline saliva specimens (collected at screening), the collection of 
esophageal specimens may provide additional supportive data. Specifically, if subjects in the 
study withdraw from OIT and undergo a clinically-indicated EGD, whenever possible, biopsy 
material will be collected from the site for further analysis, as per the ARC007 protocol.  
In addition to addressing the detection of bio-molecular signatures in subjects having AEs, it is 
possible that specific bio-molecular signatures could emerge from the planned study that 
associate with treatment success or treatment withdrawal. Thus, a possibility exists that the 
proposed bio-specimen testing could yield biomarkers predictive of an individual subject’s 
response to OIT and the collection of bio-specimens in this sub-study could facilitate these future 
analyses. 

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Known and Potential Risks and Benefits to Human Participants 
Risks 
The principal potential risk associated with this sub-study is the potential for emotional or 
psychological distress related to the discovery of uncertain information that is not itself 
diagnostic but may suggest a new clinical diagnosis (ie, EoE). To mitigate against this risk, and 
because the assays run in this sub-study are experimental, exploratory, and not part of standard 
care EoE diagnostics, the results of these studies will not be shared with participants. Clinical 
management of these individuals will be at the judgment of the site Investigator, per the current 
standard of care. The ARC007 protocol also contains specific recommendations about the 
clinical follow-up of subjects developing GI AEIs. All study candidates entering ARC007 will 
undergo an informed consent procedure detailing the potential risk of OIT-associated GI 
symptoms, including the possibility of EoE.  
There are no known physical risks to the saliva collection procedure.  
Benefits 
Individual subjects are not expected to benefit from participation in this study. Information from 
this study may help researchers to better understand peanut allergy and its relationship to EoE or 
to develop future tests or treatments to help subjects with one or both of these conditions. 
Objectives 
Primary Objective 
The primary objective is to analyze bio-molecular expression patterns in saliva samples obtained 
longitudinally from peanut-allergic participants undergoing OIT in ARC007. These studies will 
target the salivary RNA transcriptome, and if necessary further validate, with molecular-, 
cellular-, and/or protein-based approaches, the expression profile of gene pathways that are likely 
relevant to intolerable GI side effects in ARC007 subjects. 
Secondary Objectives 
The key secondary objective is to examine the relationship of the RNA expression profile to 
selected clinical variables from ARC007, including: 
• The frequency and severity of AEs related to the GI tract 
• The frequency of dosing interruptions (reductions and/or discontinuations) directly 
related to GI AEIs 
• Peripheral blood eosinophil counts 
• PEESSTM v2.0 scores  
• Immunoglobulin levels (IgE, IgG4, and their subclasses) 
Further secondary objectives include the correlation of salivary RNA transcriptome data to 
histopathologic and molecular analyses of the esophagus, when available. 

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Sub-study Design 
This is an optional sub-study in which samples will be obtained from ARC007 participants 
according to the SOE in the table presented below. Only subjects enrolled in ARC007 and 
providing additional consent for this sub-study are eligible to participate. Subjects enrolled in 
both ARC007 and this sub-study will undergo saliva collection coordinated at the designated 
ARC007 study visits. Otherwise these subjects will be treated according to the ARC007 study 
protocol. 
Sub-study Schedule of Events Exploratory Biochemical and Molecular Sub-study of 
Peanut-Allergic Children with Oral Immunotherapy-Related Gastrointestinal Symptoms 
in Study ARC007 
 
Screening Early Build-Up 
Visit 
At PEESS 
v2.0 #1 
End of Up-
Dosing Visit 
Post-OIT 
Follow-Upb 
Study Weeka 
0 
6 (± 2 wk) 
Varies 
20 
Varies  
Informed consent & assent 
X 
 
Xc 
 
 
Eligibility assessment  
X 
 
 
 
 
Saliva collection and 
packaging/shipping: 
 
 
 
 
 
No GI symptoms (controls) 
X 
X 
 
X 
 
GI symptoms (cases) 
X 
 
Xc 
 
X 
a  Minimum study weeks are shown. Actual duration may be longer depending on subject’s actual up-dosing in ARC007.  
b  For subjects who terminate dosing and enter observational follow-up, as per Section 7.3.4.2 of the ARC007 protocol. 
This sample is to be collected at the sixth monthly visit after study withdrawal or as close as practicable.  
c  Subjects withdrawing early from ARC007 with GI symptoms that were not already enrolled in this sub-study will be consented 
to enroll upon early termination. 
 
Subjects in this sub-study will undergo 3 protocol-specified collections of saliva. All subjects 
will have a baseline saliva sample collected at Screening. Because the GI AEIs are unpredictable 
and treatment-emergent, the approach to sampling post-randomization will differ by treatment 
response. Subjects who develop GI-predominant AEs that prompt their withdrawal from 
ARC007 or a protracted disruption of dosing with IP will be considered cases in this sub-study. 
The second saliva sample will be collected from cases when the first PEESS v2.0 is completed. 
The final saliva sample for cases will be collected at the end of the protocol-defined 6-month 
follow-up period for subjects that withdraw from therapy. 
Controls in this sub-study will be defined as ARC007 participants receiving OIT (active and 
placebo) who do not develop intolerable GI symptoms. Following the baseline collection, 
asymptomatic subjects will provide saliva samples at the 6-week up-dosing visit and again at the 
end of the up-dosing period.  

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This sub-study will principally involve collection, shipment, and banking of saliva samples at 
specified time points; gene expression analysis of selected salivary bio-specimens; and 
correlation with basic biometric data (eg, peripheral blood eosinophils, clinical symptom 
reports/PEESS v2.0 scores) obtained as necessary, and clinical outcome per the ARC007 
protocol. Biochemical detection of eosinophil activation products or metabolites may also be 
possible from collected samples. 
Subject participation will consist of signing an ICF approved by the IRB, EC, research ethics 
board, or like authority, and age-appropriate assent form, when indicated, as per local guidelines, 
and the provisions for bio-specimen collection and handling. 
Case Definition: ARC007 Events Triggering PEESS v2.0  
The following passage is taken from Section 7.3.4.2 of the ARC007 protocol, and serves to 
identify the case definition in this sub-study (eg, the ARC007 subjects who develop the GI AEIs 
requiring further evaluation).  
Gastrointestinal AEs, typically chronic/recurrent GI AEs, that result in a prolonged disruption of 
dosing will be considered AEIs and will be assessed longitudinally according to the procedures 
described below. For the purpose of delineating these AEIs, prolonged disruption of dosing is 
defined as withholding IP for > 7 days. This will include 3 categories of subjects: 
• Any subject whose dose is withheld for > 7 days due to GI AEs and who resumes dosing 
at a reduced dose level (Section 7.3.4.2 of the ARC007 protocol) 
• Any subject who develops chronic/recurrent GI AEs at or before reaching the 20 mg dose 
level and resumes dosing after a 30-day dosing hiatus (Section 7.3.4.2 of the ARC007 
protocol) 
• Any subject who permanently discontinues dosing who had experienced GI AEs 
(Section 4.3.2 of the ARC007 protocol) 
Subjects who fall into any of these 3 categories will be asked to fill out the PEESS v2.0 
questionnaire (Franciosi et al, 2011), with the assistance of a parent/guardian, as appropriate, 
every month for 6 months. It should, however, be noted that the PEESS v2.0 was not designed to 
establish a diagnosis of EoE, and has not been validated for use in subjects with GI symptoms of 
other etiologies. Furthermore, the discriminant validity of the questionnaire has not been reported 
in either longitudinal natural history or interventional studies. For these reasons, the use of the 
PEESS v2.0 to monitor the clinical course of GI symptoms must be considered exploratory. 
Nevertheless, the PEESS v2.0 has shown good content and construct validity (Franciosi et al, 
2011; Martin et al, 2015) and so holds promise for being a valuable tool to follow the clinical 
course of EoE or an EoE-like immune-mediated GI syndrome. Thus, the PEESS v2.0, could 
reveal trends toward symptomatic improvement or worsening that might otherwise go 
undetected. 
Exploratory Endpoints 
All endpoints in this sub-study are considered exploratory. The objective is to characterize RNA 
expression patterns in salivary specimens collected from peanut-allergic subjects who 

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participated in a study of peanut OIT and developed intolerable GI AEs that interfered with 
treatment (ie, resulted in reducing, holding, or discontinuing OIT dose levels). ARC007 subjects 
who do not develop limiting GI symptoms will also be studied as control subjects. Secondarily, 
we will also examine the associations of the salivary RNA expression changes with selected 
clinical variables and explore the within-subject correlation to RNA expression patterns observed 
in esophageal specimens, when available.  
Bioinformatic Analysis Plan for Primary and Secondary Objectives  
The bioinformatic analysis plan for the primary and secondary objectives of this study include: 
• Quality control of the genome-wide RNA sequencing data 
• Expression filter and statistical filter 
• Clustering analysis with known clinical outcomes 
• Develop an algorithm (similar to Wen et al, 2013) to quantify the oral sample signature to 
correlate with the PEESS v2.0 
• Use a portion of the samples as a training set for machine learning, then carry out the 
support vector machines (SVMs) to predict the rest of the samples. The SVM is a 
supervised learning model with associated learning algorithms that analyze data and 
recognize patterns.  
• Principle Component Analysis will be employed to globally categorize the samples, 
reduce the dimensionality for signature quantification, and aid the graphical presentation 
of the data 
Additional exploratory endpoints may include qualitative and/or quantitative comparisons to the 
patterns of bio-molecular and biochemical expression seen in subjects with spontaneously 
occurring EoE or other esophageal pathologies (historical controls). These control specimens 
will be obtained under separate protocols at the investigative laboratory.  
Criteria for Study Participation 
Inclusion Criteria 
Subjects who meet all of the following criteria are eligible for enrollment as study subjects: 
1. Participation in the ARC007 study 
2. Written informed consent from the subject’s parent/guardian 
3. Written assent the subject as appropriate (eg, above the age of 7 years) 
Exclusion Criteria 
1. Otherwise ineligible for ARC007 
Subject Termination from the Sub-study 
After enrollment, subjects may withdraw consent from this sub-study at any time. Subjects may 
also be withdrawn by the Investigator for reasons of safety or compliance.  

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Investigational Product 
No IP will be administered in the sub-study.  
Study Procedures 
The following procedures will be performed:  
1. Enrollment and Permissions 
• Obtain signatures on the IRB-approved ICF and subject’s assent. 
2. Sample Collection, Handling, and Analysis Procedures 
• Saliva is the principal bio-specimen to be collected in this study with the aid of a 
commercially available kit designed expressly for salivary RNA research purposes. 
Specific details for saliva collection will be provided to sites in a manual of procedures.  
• Blood samples for CBC, already collected in ARC007, will also be included in analyses 
relating to the secondary objectives of this sub-study. 
• Bio-specimens may be temporarily stored (no later than the next day) at investigational 
sites to facilitate batch shipping and receiving. All bio-specimens will be packaged and 
transported to the investigative laboratory in a manner compliant with all local, state, and 
federal laws and regulations, as per standard operating procedures of the shipping and 
receiving facilities. 
• Analyses will include one or more of the following:  
o Transcriptome analysis 
o EoE diagnostic panel comprising a 96-gene quantitative polymerase chain reaction 
(qPCR) array 
o Profiling of local cytokine expression  
o Targeted analysis of expression of previously identified specific candidate genes 
o Analysis of single nucleotide polymorphisms in previously identified specific 
candidate genes 
o Inflammatory pathway analysis (Ingenuity, Toppfun, or David) 
o qPCR analysis 
o Immunohistochemistry or other protein detection methods (eg, ELISA, Western blot, 
etc). 
o Mass spectrometry 
o Flow cytometry 
Lead Investigative Laboratory 
The lead investigative laboratory is the following: 
Wen Lab – Cincinnati Children’s Hospital Medical Center 
S6.405 S Building 
240 Albert Sabin Way 
Cincinnati, OH 45242 
USA 

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Permission to obtain samples of esophageal tissue from the residua (if any) of biopsy specimens 
will be obtained during the performance of routine clinical visit.  
3. Safety Monitoring 
As the study entails no treatment, there can be no treatment-emergent or treatment-related AEs in 
this sub-study. The principal risk associated with a genetic-based study is the potential for 
emotional reactions upon learning that the subject or a subject’s family member does or does not 
carry or express a gene associated with a particular condition. 
4. Statistical Considerations 
This sub-study is a pilot characterization of biochemical and bio-molecular markers in relation to 
GI side effects arising during peanut OIT in ARC007 subjects. The analyses to be conducted in 
this sub-study are all considered exploratory in nature. As such, descriptive statistical techniques 
will be utilized to characterize demographic and basic clinical variables, with standard 
assessments for normality and adjustments as necessary. Measures of correlation and 
longitudinal repeated measures will be assessed with appropriate techniques (eg, regression 
modeling) as necessary. Statistical testing for differences between treatment groups or time 
points may be assessed, but specific hypotheses are not pre-specified.  
5. Study Endpoint Assessment 
All endpoints in this study are considered exploratory and are defined in the Objectives section 
of this Appendix 7 above.  
6. Subject and Demographic Data 
Baseline Characteristics, Demographics, and Safety Data 
Baseline and demographic characteristics may be reported for each subject enrolled in the 
present study as they were obtained in ARC007. Baseline characteristics and demographic data 
could include age, race, sex, body weight, and height. Other analyses involving safety data may 
also be performed.  
Use of Medications 
There will be no medications used in this sub-study. Data from concomitant medication use in 
ARC007 related to AEs may be analyzed as part of this sub-study.  
7. Sample Size Calculations 
This is an exploratory and hypothesis-generating study involving minimal risk to subjects. No 
specific sample size calculations have been performed.  

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Appendix 8: Total Nasal Symptom Score Sheet (Example)